Title: WHO / Peds
Tags: Peds::BST::Soft_Tissue Peds::Heme::Lymphoid Peds::BST::Bone Peds::GU::Renal Peds::Neuro::Glioma Peds::GU::Germ_Cell Peds::Neuro::Ependymal Peds::Heme::Myeloid Peds::Endocrine::Thyroid Peds::Endocrine::Adrenal Peds::Neuro::Glioneuronal Peds::Neuro::Embryonal Peds::Neuro::Sellar Peds::Eye::Conjunctival_Epibulbar_Choristoma Peds::Neuro::Choroid_Plexus Peds::Head_Neck::Nasal_Chondromesenchymal_Hamartoma Peds::Neuro::Medulloblastoma Peds::Genetics::Gorlin_Syndrome Peds::Heme::Hodgkin

Q: Patients with a Juvenile Fibroadenoma typically present as adolescent girls with a rapidly growing, large breast mass (>50 mm) that, on ultrasound, classically demonstrates a benign, circumscribed solid mass with a [...] orientation.
Juvenile fibroadenoma. Ultrasound of this tumour from an 18-year-old female patient shows a well-defined, wider-than-tall, oval solid mass. The internal echoes are fairly homogeneous and there is posterior enhancement. No internal cystic spaces are present.
Juvenile fibroadenoma. Transverse ultrasound shows a macrolobulated, circumscribed, wider-than-tall hypoechoic mass within the fibroglandular breast tissue.
A: wider-than-tall
Back Extra: Juvenile Fibroadenoma
- Clinical: Juvenile fibroadenomas often present as rapid-growing, large masses (>50 mm) in adolescent girls, leading to breast distortion and asymmetry.
- Micro: Characterized by a biphasic proliferation with a cellular stroma and usual ductal hyperplasia, often with a predominant pericanalicular growth pattern.
- Ancillary: MED12 mutations are common in juvenile fibroadenomas, similar to conventional adult fibroadenomas, but with additional mutations in FLNA, DYNC2H1, and others.
Reference Gallery:
Juvenile fibroadenoma. A well-circumscribed tumour from a 17-year-old girl, with a greyish-white cut surface and slit-like spaces.
Juvenile fibroadenoma. Ultrasound of this tumour from an 18-year-old female patient shows a well-defined, wider-than-tall, oval solid mass. The internal echoes are fairly homogeneous and there is posterior enhancement. No internal cystic spaces are present.
Juvenile fibroadenoma. A predominantly pericanalicular growth pattern with a cellular stroma.
Juvenile fibroadenoma. Mixed pericanalicular and intracanalicular growth patterns.
Juvenile fibroadenoma. Cellular stroma and usual-type ductal hyperplasia in the form of gynaecomastoid epithelial tufting.
Juvenile fibroadenoma. Some juvenile fibroadenomas can have intratumoural heterogeneity, with areas featuring an increased number of glands and with a tubular arrangement resembling a tubular adenoma.
Juvenile fibroadenoma. Transverse ultrasound shows a macrolobulated, circumscribed, wider-than-tall hypoechoic mass within the fibroglandular breast tissue.

Q: Microscopically, a Juvenile Fibroadenoma is characterized by a cellular stroma and usual-type ductal hyperplasia, which often forms characteristic [...] epithelial tufts.
Juvenile fibroadenoma. Cellular stroma and usual-type ductal hyperplasia in the form of gynaecomastoid epithelial tufting.
A: gynecomastoid
Back Extra: Juvenile Fibroadenoma
- Clinical: Juvenile fibroadenomas often present as rapid-growing, large masses (>50 mm) in adolescent girls, leading to breast distortion and asymmetry.
- Micro: Characterized by a biphasic proliferation with a cellular stroma and usual ductal hyperplasia, often with a predominant pericanalicular growth pattern.
- Ancillary: MED12 mutations are common in juvenile fibroadenomas, similar to conventional adult fibroadenomas, but with additional mutations in FLNA, DYNC2H1, and others.
Reference Gallery:
Juvenile fibroadenoma. A well-circumscribed tumour from a 17-year-old girl, with a greyish-white cut surface and slit-like spaces.
Juvenile fibroadenoma. Ultrasound of this tumour from an 18-year-old female patient shows a well-defined, wider-than-tall, oval solid mass. The internal echoes are fairly homogeneous and there is posterior enhancement. No internal cystic spaces are present.
Juvenile fibroadenoma. A predominantly pericanalicular growth pattern with a cellular stroma.
Juvenile fibroadenoma. Mixed pericanalicular and intracanalicular growth patterns.
Juvenile fibroadenoma. Cellular stroma and usual-type ductal hyperplasia in the form of gynaecomastoid epithelial tufting.
Juvenile fibroadenoma. Some juvenile fibroadenomas can have intratumoural heterogeneity, with areas featuring an increased number of glands and with a tubular arrangement resembling a tubular adenoma.
Juvenile fibroadenoma. Transverse ultrasound shows a macrolobulated, circumscribed, wider-than-tall hypoechoic mass within the fibroglandular breast tissue.

Q: The biphasic proliferation in Juvenile Fibroadenoma frequently features a cellular stroma with a predominantly [...] growth pattern around the ducts.
Juvenile fibroadenoma. A predominantly pericanalicular growth pattern with a cellular stroma.
Juvenile fibroadenoma. Mixed pericanalicular and intracanalicular growth patterns.
A: pericanalicular
Back Extra: Juvenile Fibroadenoma
- Clinical: Juvenile fibroadenomas often present as rapid-growing, large masses (>50 mm) in adolescent girls, leading to breast distortion and asymmetry.
- Micro: Characterized by a biphasic proliferation with a cellular stroma and usual ductal hyperplasia, often with a predominant pericanalicular growth pattern.
- Ancillary: MED12 mutations are common in juvenile fibroadenomas, similar to conventional adult fibroadenomas, but with additional mutations in FLNA, DYNC2H1, and others.
Reference Gallery:
Juvenile fibroadenoma. A well-circumscribed tumour from a 17-year-old girl, with a greyish-white cut surface and slit-like spaces.
Juvenile fibroadenoma. Ultrasound of this tumour from an 18-year-old female patient shows a well-defined, wider-than-tall, oval solid mass. The internal echoes are fairly homogeneous and there is posterior enhancement. No internal cystic spaces are present.
Juvenile fibroadenoma. A predominantly pericanalicular growth pattern with a cellular stroma.
Juvenile fibroadenoma. Mixed pericanalicular and intracanalicular growth patterns.
Juvenile fibroadenoma. Cellular stroma and usual-type ductal hyperplasia in the form of gynaecomastoid epithelial tufting.
Juvenile fibroadenoma. Some juvenile fibroadenomas can have intratumoural heterogeneity, with areas featuring an increased number of glands and with a tubular arrangement resembling a tubular adenoma.
Juvenile fibroadenoma. Transverse ultrasound shows a macrolobulated, circumscribed, wider-than-tall hypoechoic mass within the fibroglandular breast tissue.

Q: Microscopically, Juvenile Papillomatosis is characterized by dense stroma containing multiple cysts, apocrine metaplasia, and prominent [...] (often with florid usual-type ductal hyperplasia).
Juvenile papillomatosis. A low-power scanning view of juvenile papillomatosis shows cysts, intraductal papillomas, and apocrine metaplasia within dense stroma.
Juvenile papillomatosis. Papillary apocrine hyperplasia in a cyst of juvenile papillomatosis.
Juvenile papillomatosis. A distended duct shows florid usual-type ductal hyperplasia.
A: intraductal papillomas
Back Extra: Juvenile Papillomatosis
- Clinical: Juvenile papillomatosis presents as a palpable, firm, mobile nodule, often larger and firmer than a fibroadenoma, with rare pain or nipple discharge.
- Micro: Characterized by multiple cysts, duct papillomatosis, apocrine metaplasia, and intraluminal foamy macrophages or inspissated secretions.
- Ancillary: Hotspot mutations in PIK3CA and AKT1 have been identified in cases with a family history of breast cancer, but are not specific for diagnosis.
Reference Gallery:
Juvenile papillomatosis. Ultrasound showing a retroareolar hypoechoic mass with an indistinct margin and multiple cystic areas especially at the periphery, findings that reflect the macroscopic features.
Juvenile papillomatosis. The gross appearance of juvenile papillomatosis comprises a discrete mass with cysts and intervening fibrous areas with interspersed yellowish and whitish appearances.
Juvenile papillomatosis. A low-power scanning view of juvenile papillomatosis shows cysts, intraductal papillomas, and apocrine metaplasia within dense stroma.
Juvenile papillomatosis. Papillary apocrine hyperplasia in a cyst of juvenile papillomatosis.
Juvenile papillomatosis. A distended duct shows florid usual-type ductal hyperplasia.

Q: On gross examination and ultrasound, Juvenile Papillomatosis typically presents as a discrete mass featuring intervening fibrous stroma and multiple [...], which often predominate at the periphery.
Juvenile papillomatosis. Ultrasound showing a retroareolar hypoechoic mass with an indistinct margin and multiple cystic areas especially at the periphery, findings that reflect the macroscopic features.
Juvenile papillomatosis. The gross appearance of juvenile papillomatosis comprises a discrete mass with cysts and intervening fibrous areas with interspersed yellowish and whitish appearances.
A: cysts
Back Extra: Juvenile Papillomatosis
- Clinical: Juvenile papillomatosis presents as a palpable, firm, mobile nodule, often larger and firmer than a fibroadenoma, with rare pain or nipple discharge.
- Micro: Characterized by multiple cysts, duct papillomatosis, apocrine metaplasia, and intraluminal foamy macrophages or inspissated secretions.
- Ancillary: Hotspot mutations in PIK3CA and AKT1 have been identified in cases with a family history of breast cancer, but are not specific for diagnosis.
Reference Gallery:
Juvenile papillomatosis. Ultrasound showing a retroareolar hypoechoic mass with an indistinct margin and multiple cystic areas especially at the periphery, findings that reflect the macroscopic features.
Juvenile papillomatosis. The gross appearance of juvenile papillomatosis comprises a discrete mass with cysts and intervening fibrous areas with interspersed yellowish and whitish appearances.
Juvenile papillomatosis. A low-power scanning view of juvenile papillomatosis shows cysts, intraductal papillomas, and apocrine metaplasia within dense stroma.
Juvenile papillomatosis. Papillary apocrine hyperplasia in a cyst of juvenile papillomatosis.
Juvenile papillomatosis. A distended duct shows florid usual-type ductal hyperplasia.

Q: In the spectrum of Fibroepithelial Tumors, phyllodes tumors are distinguished from fibroadenomas by their hypercellular stroma and prominent [...] stromal fronds.
Fibroepithelial tumours. Fibroadenoma. Leaf-like fronds may be seen in fibroadenomas, but they are usually not as well-developed, prominent, or diffuse as those in phyllodes tumours.
Fibroepithelial tumours. Prominent leaf-like fronds in a benign phyllodes tumour with a mildly cellular stroma.
A: leaf-like
Back Extra: Fibroepithelial Tumours
- Clinical: Fibroepithelial tumours often manifest as a palpable breast mass, with ultrasound being the preferred imaging modality in paediatric patients due to its ability to detect lesions in dense breast tissue without ionizing radiation.
- Micro: Phyllodes tumours are characterized by prominent leaf-like stromal fronds and a hypercellular stroma, distinguishing them from fibroadenomas which typically have less prominent fronds and a more cellular stroma.
- Ancillary: MED12 exon 2 mutations are frequently found in both paediatric fibroadenomas and benign phyllodes tumours, with a correlation between these mutations and stromal mitotic counts.
Reference Gallery:
Benign phyllodes tumour. A large tumour from a 19-year-old female patient, with a tan-coloured and fleshy cut surface, cleft-like spaces, and focal haemorrhage.
Benign phyllodes tumour. Ultrasound shows a well-circumscribed, round, solid mass with bulging, lobulated borders and posterior enhancement. This tumour in a 14-year-old girl shows apparent nodular compartments (stars) surrounded by slit-like cystic spaces (arrows), probably corresponding to leaf-like fronds seen microscopically.
Fibroadenoma. Intracanalicular growth pattern.
Fibroepithelial tumours. Fibroadenoma. Leaf-like fronds may be seen in fibroadenomas, but they are usually not as well-developed, prominent, or diffuse as those in phyllodes tumours.
Fibroadenoma. A more cellular stroma is often seen in paediatric fibroadenomas than in adult fibroadenomas.
Fibroepithelial tumours. Prominent leaf-like fronds in a benign phyllodes tumour with a mildly cellular stroma.
Malignant phyllodes tumour from a 15-year-old girl. A leaf-like frond is vaguely discernible with an epithelial lining capping a markedly cellular stroma.
Malignant phyllodes tumour from a 15-year-old girl. Markedly atypical stromal cells with brisk mitotic activity including atypical mitotic figures. Benign epithelial components are admixed within.

Q: Fibroepithelial Tumors are biphasic neoplasms; in malignant phyllodes tumors, it is the [...] component that exhibits marked cytologic atypia and brisk mitotic activity, while the admixed epithelial component remains benign.
Malignant phyllodes tumour from a 15-year-old girl. A leaf-like frond is vaguely discernible with an epithelial lining capping a markedly cellular stroma.
Malignant phyllodes tumour from a 15-year-old girl. Markedly atypical stromal cells with brisk mitotic activity including atypical mitotic figures. Benign epithelial components are admixed within.
A: stromal
Back Extra: Fibroepithelial Tumours
- Clinical: Fibroepithelial tumours often manifest as a palpable breast mass, with ultrasound being the preferred imaging modality in paediatric patients due to its ability to detect lesions in dense breast tissue without ionizing radiation.
- Micro: Phyllodes tumours are characterized by prominent leaf-like stromal fronds and a hypercellular stroma, distinguishing them from fibroadenomas which typically have less prominent fronds and a more cellular stroma.
- Ancillary: MED12 exon 2 mutations are frequently found in both paediatric fibroadenomas and benign phyllodes tumours, with a correlation between these mutations and stromal mitotic counts.
Reference Gallery:
Benign phyllodes tumour. A large tumour from a 19-year-old female patient, with a tan-coloured and fleshy cut surface, cleft-like spaces, and focal haemorrhage.
Benign phyllodes tumour. Ultrasound shows a well-circumscribed, round, solid mass with bulging, lobulated borders and posterior enhancement. This tumour in a 14-year-old girl shows apparent nodular compartments (stars) surrounded by slit-like cystic spaces (arrows), probably corresponding to leaf-like fronds seen microscopically.
Fibroadenoma. Intracanalicular growth pattern.
Fibroepithelial tumours. Fibroadenoma. Leaf-like fronds may be seen in fibroadenomas, but they are usually not as well-developed, prominent, or diffuse as those in phyllodes tumours.
Fibroadenoma. A more cellular stroma is often seen in paediatric fibroadenomas than in adult fibroadenomas.
Fibroepithelial tumours. Prominent leaf-like fronds in a benign phyllodes tumour with a mildly cellular stroma.
Malignant phyllodes tumour from a 15-year-old girl. A leaf-like frond is vaguely discernible with an epithelial lining capping a markedly cellular stroma.
Malignant phyllodes tumour from a 15-year-old girl. Markedly atypical stromal cells with brisk mitotic activity including atypical mitotic figures. Benign epithelial components are admixed within.

Q: Grossly, some large Fibroepithelial Tumors (such as benign phyllodes tumors) present with a tan, fleshy cut surface and characteristic [...] spaces that correspond to the prominent fronds seen microscopically.
Benign phyllodes tumour. A large tumour from a 19-year-old female patient, with a tan-coloured and fleshy cut surface, cleft-like spaces, and focal haemorrhage.
Benign phyllodes tumour. Ultrasound shows a well-circumscribed, round, solid mass with bulging, lobulated borders and posterior enhancement. This tumour in a 14-year-old girl shows apparent nodular compartments (stars) surrounded by slit-like cystic spaces (arrows), probably corresponding to leaf-like fronds seen microscopically.
A: cleft-like
Back Extra: Fibroepithelial Tumours
- Clinical: Fibroepithelial tumours often manifest as a palpable breast mass, with ultrasound being the preferred imaging modality in paediatric patients due to its ability to detect lesions in dense breast tissue without ionizing radiation.
- Micro: Phyllodes tumours are characterized by prominent leaf-like stromal fronds and a hypercellular stroma, distinguishing them from fibroadenomas which typically have less prominent fronds and a more cellular stroma.
- Ancillary: MED12 exon 2 mutations are frequently found in both paediatric fibroadenomas and benign phyllodes tumours, with a correlation between these mutations and stromal mitotic counts.
Reference Gallery:
Benign phyllodes tumour. A large tumour from a 19-year-old female patient, with a tan-coloured and fleshy cut surface, cleft-like spaces, and focal haemorrhage.
Benign phyllodes tumour. Ultrasound shows a well-circumscribed, round, solid mass with bulging, lobulated borders and posterior enhancement. This tumour in a 14-year-old girl shows apparent nodular compartments (stars) surrounded by slit-like cystic spaces (arrows), probably corresponding to leaf-like fronds seen microscopically.
Fibroadenoma. Intracanalicular growth pattern.
Fibroepithelial tumours. Fibroadenoma. Leaf-like fronds may be seen in fibroadenomas, but they are usually not as well-developed, prominent, or diffuse as those in phyllodes tumours.
Fibroadenoma. A more cellular stroma is often seen in paediatric fibroadenomas than in adult fibroadenomas.
Fibroepithelial tumours. Prominent leaf-like fronds in a benign phyllodes tumour with a mildly cellular stroma.
Malignant phyllodes tumour from a 15-year-old girl. A leaf-like frond is vaguely discernible with an epithelial lining capping a markedly cellular stroma.
Malignant phyllodes tumour from a 15-year-old girl. Markedly atypical stromal cells with brisk mitotic activity including atypical mitotic figures. Benign epithelial components are admixed within.

Q: Classic Adamantinoma is characterized by a biphasic morphology where the neoplastic [...] cells form distinct basaloid structures with peripheral palisading or tubular structures mimicking vascular channels.
Classic adamantinoma. Basaloid pattern. Neoplastic epithelial cells form basaloid structures, with peripheral palisading and spindle-shaped cells in the inner part.
Classic adamantinoma. Tubular pattern. Neoplastic epithelial cells form tubular structures mimicking vascular channels.
A: epithelial
Back Extra: Adamantinoma
- Clinical: Adamantinoma causes pain, swelling, or bowing deformity and appears as an intracortical, well-circumscribed, multilobulated lytic lesion with a soap-bubble appearance on imaging.
- Micro: Classic adamantinoma is characterized by basaloid, tubular, squamous, or spindle-shaped epithelial cells, which are positive for cytokeratin and p63.
- Ancillary: Molecular studies show recurrent copy-number gains and losses in BRAF, JAK2, KRAS, TP53, or EGFR, specific to the epithelial component of adamantinoma.
Reference Gallery:
Classic adamantinoma. Basaloid pattern. Neoplastic epithelial cells form basaloid structures, with peripheral palisading and spindle-shaped cells in the inner part.
Classic adamantinoma. Tubular pattern. Neoplastic epithelial cells form tubular structures mimicking vascular channels.
Osteofibrous dysplasia–like adamantinoma. The morphological features are similar to those of osteofibrous dysplasia (irregular trabeculae of woven bone with prominent osteoblastic rimming and fibrous stroma), with small clusters of epithelial cells.

Q: A specific variant of Adamantinoma features irregular trabeculae of woven bone with prominent osteoblastic rimming and a fibrous stroma, morphologically mimicking [...], but is distinguished by the presence of small clusters of epithelial cells.
Osteofibrous dysplasia–like adamantinoma. The morphological features are similar to those of osteofibrous dysplasia (irregular trabeculae of woven bone with prominent osteoblastic rimming and fibrous stroma), with small clusters of epithelial cells.
A: osteofibrous dysplasia
Back Extra: Adamantinoma
- Clinical: Adamantinoma causes pain, swelling, or bowing deformity and appears as an intracortical, well-circumscribed, multilobulated lytic lesion with a soap-bubble appearance on imaging.
- Micro: Classic adamantinoma is characterized by basaloid, tubular, squamous, or spindle-shaped epithelial cells, which are positive for cytokeratin and p63.
- Ancillary: Molecular studies show recurrent copy-number gains and losses in BRAF, JAK2, KRAS, TP53, or EGFR, specific to the epithelial component of adamantinoma.
Reference Gallery:
Classic adamantinoma. Basaloid pattern. Neoplastic epithelial cells form basaloid structures, with peripheral palisading and spindle-shaped cells in the inner part.
Classic adamantinoma. Tubular pattern. Neoplastic epithelial cells form tubular structures mimicking vascular channels.
Osteofibrous dysplasia–like adamantinoma. The morphological features are similar to those of osteofibrous dysplasia (irregular trabeculae of woven bone with prominent osteoblastic rimming and fibrous stroma), with small clusters of epithelial cells.

Q: Aneurysmal Bone Cyst is characterized microscopically by fibrous septa separating blood-filled spaces, which contain fibroblastic proliferation, reactive new bone formation, and numerous [...].
Aneurysmal bone cyst. The cyst wall shows fibroblastic proliferation, osteoclast-like giant cells, and new bone formation.
A: osteoclast-like giant cells
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cysts typically present with pain and swelling, and can cause neurological symptoms if located in the vertebrae.
- Micro: The lesion is characterized by blood-filled cystic spaces separated by fibrous septa with fibroblastic proliferation, osteoclast-like giant cells, and reactive woven bone.
- Ancillary: USP6 rearrangement can be detected by FISH, which is a useful diagnostic tool for confirming the presence of an aneurysmal bone cyst.
Reference Gallery:
Aneurysmal bone cyst. Whole cross-section of an aneurysmal bone cyst of the ulna in an 8-year-old boy, showing an expansile cystic lesion with multiple septations.
Aneurysmal bone cyst. The cyst wall shows fibroblastic proliferation, osteoclast-like giant cells, and new bone formation.

Q: Aneurysmal Bone Cyst typically presents grossly and radiographically as an [...] cystic lesion with multiple septations.
Aneurysmal bone cyst. Whole cross-section of an aneurysmal bone cyst of the ulna in an 8-year-old boy, showing an expansile cystic lesion with multiple septations.
A: expansile
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cysts typically present with pain and swelling, and can cause neurological symptoms if located in the vertebrae.
- Micro: The lesion is characterized by blood-filled cystic spaces separated by fibrous septa with fibroblastic proliferation, osteoclast-like giant cells, and reactive woven bone.
- Ancillary: USP6 rearrangement can be detected by FISH, which is a useful diagnostic tool for confirming the presence of an aneurysmal bone cyst.
Reference Gallery:
Aneurysmal bone cyst. Whole cross-section of an aneurysmal bone cyst of the ulna in an 8-year-old boy, showing an expansile cystic lesion with multiple septations.
Aneurysmal bone cyst. The cyst wall shows fibroblastic proliferation, osteoclast-like giant cells, and new bone formation.

Q: [...] is a primary bone lesion often driven by a characteristic USP6 gene rearrangement, prominently featuring blood-filled cystic spaces separated by fibrous septa.
Aneurysmal bone cyst. Whole cross-section of an aneurysmal bone cyst of the ulna in an 8-year-old boy, showing an expansile cystic lesion with multiple septations.
Aneurysmal bone cyst. The cyst wall shows fibroblastic proliferation, osteoclast-like giant cells, and new bone formation.
A: Aneurysmal Bone Cyst
Back Extra: Aneurysmal Bone Cyst
- Clinical: Aneurysmal bone cysts typically present with pain and swelling, and can cause neurological symptoms if located in the vertebrae.
- Micro: The lesion is characterized by blood-filled cystic spaces separated by fibrous septa with fibroblastic proliferation, osteoclast-like giant cells, and reactive woven bone.
- Ancillary: USP6 rearrangement can be detected by FISH, which is a useful diagnostic tool for confirming the presence of an aneurysmal bone cyst.
Reference Gallery:
Aneurysmal bone cyst. Whole cross-section of an aneurysmal bone cyst of the ulna in an 8-year-old boy, showing an expansile cystic lesion with multiple septations.
Aneurysmal bone cyst. The cyst wall shows fibroblastic proliferation, osteoclast-like giant cells, and new bone formation.

Q: A characteristic histologic hallmark of Bizarre Parosteal Osteochondromatous Proliferation is a disorganized mixture of hypercellular cartilage, bland spindle cells, and the formation of [...].
Bizarre parosteal osteochondromatous proliferation. A disorganized mixture of bone and cartilage, with characteristic blue bone.
Bizarre parosteal osteochondromatous proliferation. A combination of disorganized hypercellular cartilage, bland spindle cells, and bone (including blue bone).
A: blue bone
Back Extra: Bizarre Parosteal Osteochondromatous Proliferation
- Clinical: Patients typically present with a painless mass of a few months’ to several years’ duration. Radiologically, BPOP is a well-marginated ossified mass arising from the cortical bone without periosteal reaction.
- Micro: BPOP is composed of hypercellular cartilage containing enlarged, bizarre, binucleated chondrocytes, cancellous bone undergoing maturation via enchondral ossification, and spindle cell stroma.
- Ancillary: Recurrent cytogenetic abnormalities, including t(1;17)(q32;q21), inv(7)(q22q32), and inv(6)(p25q15), have been reported.
Reference Gallery:
Bizarre parosteal osteochondromatous proliferation. A disorganized mixture of bone and cartilage, with characteristic blue bone.
Bizarre parosteal osteochondromatous proliferation. A combination of disorganized hypercellular cartilage, bland spindle cells, and bone (including blue bone).
Bizarre parosteal osteochondromatous proliferation. Hypercellular cartilage containing atypical-looking chondrocytes with enlarged nuclei.
Bizarre parosteal osteochondromatous proliferation. A,B X-ray images of an exophytic and expansile cartilaginous proliferation in the proximal metaphyseal region of the humerus from a 17-year-old patient.
Bizarre parosteal osteochondromatous proliferation. A disorganized mixture of bone and cartilage.

Q: On imaging, Bizarre Parosteal Osteochondromatous Proliferation typically presents as a well-marginated, exophytic ossified mass arising from the cortical bone surface that characteristically lacks a(n) [...].
Bizarre parosteal osteochondromatous proliferation. A,B X-ray images of an exophytic and expansile cartilaginous proliferation in the proximal metaphyseal region of the humerus from a 17-year-old patient.
A: periosteal reaction
Back Extra: Bizarre Parosteal Osteochondromatous Proliferation
- Clinical: Patients typically present with a painless mass of a few months’ to several years’ duration. Radiologically, BPOP is a well-marginated ossified mass arising from the cortical bone without periosteal reaction.
- Micro: BPOP is composed of hypercellular cartilage containing enlarged, bizarre, binucleated chondrocytes, cancellous bone undergoing maturation via enchondral ossification, and spindle cell stroma.
- Ancillary: Recurrent cytogenetic abnormalities, including t(1;17)(q32;q21), inv(7)(q22q32), and inv(6)(p25q15), have been reported.
Reference Gallery:
Bizarre parosteal osteochondromatous proliferation. A disorganized mixture of bone and cartilage, with characteristic blue bone.
Bizarre parosteal osteochondromatous proliferation. A combination of disorganized hypercellular cartilage, bland spindle cells, and bone (including blue bone).
Bizarre parosteal osteochondromatous proliferation. Hypercellular cartilage containing atypical-looking chondrocytes with enlarged nuclei.
Bizarre parosteal osteochondromatous proliferation. A,B X-ray images of an exophytic and expansile cartilaginous proliferation in the proximal metaphyseal region of the humerus from a 17-year-old patient.
Bizarre parosteal osteochondromatous proliferation. A disorganized mixture of bone and cartilage.

Q: The cartilaginous component of Bizarre Parosteal Osteochondromatous Proliferation is typically hypercellular and contains enlarged, binucleated, and [...]-appearing chondrocytes.
Bizarre parosteal osteochondromatous proliferation. Hypercellular cartilage containing atypical-looking chondrocytes with enlarged nuclei.
A: bizarre
Back Extra: Bizarre Parosteal Osteochondromatous Proliferation
- Clinical: Patients typically present with a painless mass of a few months’ to several years’ duration. Radiologically, BPOP is a well-marginated ossified mass arising from the cortical bone without periosteal reaction.
- Micro: BPOP is composed of hypercellular cartilage containing enlarged, bizarre, binucleated chondrocytes, cancellous bone undergoing maturation via enchondral ossification, and spindle cell stroma.
- Ancillary: Recurrent cytogenetic abnormalities, including t(1;17)(q32;q21), inv(7)(q22q32), and inv(6)(p25q15), have been reported.
Reference Gallery:
Bizarre parosteal osteochondromatous proliferation. A disorganized mixture of bone and cartilage, with characteristic blue bone.
Bizarre parosteal osteochondromatous proliferation. A combination of disorganized hypercellular cartilage, bland spindle cells, and bone (including blue bone).
Bizarre parosteal osteochondromatous proliferation. Hypercellular cartilage containing atypical-looking chondrocytes with enlarged nuclei.
Bizarre parosteal osteochondromatous proliferation. A,B X-ray images of an exophytic and expansile cartilaginous proliferation in the proximal metaphyseal region of the humerus from a 17-year-old patient.
Bizarre parosteal osteochondromatous proliferation. A disorganized mixture of bone and cartilage.

Q: Radiographically, a Chondroblastoma classically presents as a well-defined lucent lesion that arises in the [...] of long bones.
Chondroblastoma. An anteroposterior radiograph of the right knee showing a well-defined lucent lesion in the distal femoral epiphysis (arrows).
Chondroblastoma. T1-weighted fat-saturated coronal MRI after intravenous gadolinium injection shows a well-defined, heterogeneous lesion in the epiphysis with oedema-like high signal in the adjacent marrow and soft tissues.
A: epiphysis
Back Extra: Chondroblastoma
- Clinical: Chondroblastomas often present with pain, which can be longstanding, and may be accompanied by local tenderness, joint effusion, impaired movement, and muscle atrophy.
- Micro: Histologically, chondroblastomas are characterized by sheets of ovoid to polygonal cells with distinct cytoplasmic borders, grooved nuclei, and interspersed osteoclast-like giant cells.
- Ancillary: Immunohistochemistry using an H3.3 K36M antibody shows diffuse nuclear expression in over 96% of cases, which is highly specific for this tumour.
Reference Gallery:
Chondroblastoma. An anteroposterior radiograph of the right knee showing a well-defined lucent lesion in the distal femoral epiphysis (arrows).
Chondroblastoma. T1-weighted fat-saturated coronal MRI after intravenous gadolinium injection shows a well-defined, heterogeneous lesion in the epiphysis with oedema-like high signal in the adjacent marrow and soft tissues.
Chondroblastoma. An anteroposterior radiograph of the left ankle showing a lucent lesion in the talus, subarticular to the subtalar joint. The lesion shows a sclerotic border (arrows).
Chondroblastoma. Sheets of chondroblastic cells and a central area of eosinophilic cartilaginous matrix.
Chondroblastoma. Oval to polygonal chondroblasts with well-defined cytoplasmic borders, nuclear indentations and grooves, and an osteoclast-like giant cell.
Chondroblastoma. Sheets of ovoid chondroblasts, osteoclast-like giant cells, and eosinophilic cartilaginous matrix.
Chondroblastoma. Chondroblastic cells with nuclear indentation and grooves. Chicken-wire pericellular calcification.
Chondroblastoma. H3.3 K36M antibody: diffuse nuclear expression. Note that the osteoclast-like giant cells show no expression. This antibody identifies H3-3B:c.110A>T p.K37M (K36M) mutation. The discrepancy in numbering is due to the early cleavage of the N-terminal methionine in most histones, meaning that histone sequence alterations follow their own nomenclature, which differs from Human Genome Variation Society (HGVS)-compliant numbering by omitting that first amino acid {33779999}.

Q: Histologically, a Chondroblastoma is characterized by sheets of polygonal chondroblasts with distinct cytoplasmic borders, grooved nuclei, and a classic pattern of pericellular mineralization known as [...] calcification.
Chondroblastoma. Oval to polygonal chondroblasts with well-defined cytoplasmic borders, nuclear indentations and grooves, and an osteoclast-like giant cell.
Chondroblastoma. Chondroblastic cells with nuclear indentation and grooves. Chicken-wire pericellular calcification.
A: chicken-wire
Back Extra: Chondroblastoma
- Clinical: Chondroblastomas often present with pain, which can be longstanding, and may be accompanied by local tenderness, joint effusion, impaired movement, and muscle atrophy.
- Micro: Histologically, chondroblastomas are characterized by sheets of ovoid to polygonal cells with distinct cytoplasmic borders, grooved nuclei, and interspersed osteoclast-like giant cells.
- Ancillary: Immunohistochemistry using an H3.3 K36M antibody shows diffuse nuclear expression in over 96% of cases, which is highly specific for this tumour.
Reference Gallery:
Chondroblastoma. An anteroposterior radiograph of the right knee showing a well-defined lucent lesion in the distal femoral epiphysis (arrows).
Chondroblastoma. T1-weighted fat-saturated coronal MRI after intravenous gadolinium injection shows a well-defined, heterogeneous lesion in the epiphysis with oedema-like high signal in the adjacent marrow and soft tissues.
Chondroblastoma. An anteroposterior radiograph of the left ankle showing a lucent lesion in the talus, subarticular to the subtalar joint. The lesion shows a sclerotic border (arrows).
Chondroblastoma. Sheets of chondroblastic cells and a central area of eosinophilic cartilaginous matrix.
Chondroblastoma. Oval to polygonal chondroblasts with well-defined cytoplasmic borders, nuclear indentations and grooves, and an osteoclast-like giant cell.
Chondroblastoma. Sheets of ovoid chondroblasts, osteoclast-like giant cells, and eosinophilic cartilaginous matrix.
Chondroblastoma. Chondroblastic cells with nuclear indentation and grooves. Chicken-wire pericellular calcification.
Chondroblastoma. H3.3 K36M antibody: diffuse nuclear expression. Note that the osteoclast-like giant cells show no expression. This antibody identifies H3-3B:c.110A>T p.K37M (K36M) mutation. The discrepancy in numbering is due to the early cleavage of the N-terminal methionine in most histones, meaning that histone sequence alterations follow their own nomenclature, which differs from Human Genome Variation Society (HGVS)-compliant numbering by omitting that first amino acid {33779999}.

Q: Over 96% of Chondroblastoma cases harbor a highly specific histone mutation that can be detected via immunohistochemistry, demonstrating diffuse nuclear expression of [...].
Chondroblastoma. H3.3 K36M antibody: diffuse nuclear expression. Note that the osteoclast-like giant cells show no expression. This antibody identifies H3-3B:c.110A>T p.K37M (K36M) mutation. The discrepancy in numbering is due to the early cleavage of the N-terminal methionine in most histones, meaning that histone sequence alterations follow their own nomenclature, which differs from Human Genome Variation Society (HGVS)-compliant numbering by omitting that first amino acid {33779999}.
A: H3.3 K36M
Back Extra: Chondroblastoma
- Clinical: Chondroblastomas often present with pain, which can be longstanding, and may be accompanied by local tenderness, joint effusion, impaired movement, and muscle atrophy.
- Micro: Histologically, chondroblastomas are characterized by sheets of ovoid to polygonal cells with distinct cytoplasmic borders, grooved nuclei, and interspersed osteoclast-like giant cells.
- Ancillary: Immunohistochemistry using an H3.3 K36M antibody shows diffuse nuclear expression in over 96% of cases, which is highly specific for this tumour.
Reference Gallery:
Chondroblastoma. An anteroposterior radiograph of the right knee showing a well-defined lucent lesion in the distal femoral epiphysis (arrows).
Chondroblastoma. T1-weighted fat-saturated coronal MRI after intravenous gadolinium injection shows a well-defined, heterogeneous lesion in the epiphysis with oedema-like high signal in the adjacent marrow and soft tissues.
Chondroblastoma. An anteroposterior radiograph of the left ankle showing a lucent lesion in the talus, subarticular to the subtalar joint. The lesion shows a sclerotic border (arrows).
Chondroblastoma. Sheets of chondroblastic cells and a central area of eosinophilic cartilaginous matrix.
Chondroblastoma. Oval to polygonal chondroblasts with well-defined cytoplasmic borders, nuclear indentations and grooves, and an osteoclast-like giant cell.
Chondroblastoma. Sheets of ovoid chondroblasts, osteoclast-like giant cells, and eosinophilic cartilaginous matrix.
Chondroblastoma. Chondroblastic cells with nuclear indentation and grooves. Chicken-wire pericellular calcification.
Chondroblastoma. H3.3 K36M antibody: diffuse nuclear expression. Note that the osteoclast-like giant cells show no expression. This antibody identifies H3-3B:c.110A>T p.K37M (K36M) mutation. The discrepancy in numbering is due to the early cleavage of the N-terminal methionine in most histones, meaning that histone sequence alterations follow their own nomenclature, which differs from Human Genome Variation Society (HGVS)-compliant numbering by omitting that first amino acid {33779999}.

Q: In infants presenting with a palpable mass or respiratory distress, imaging showing an expansile lytic lesion of the rib with internal chondroid matrix and fluid-fluid levels (indicating hemorrhage) is highly characteristic of [...].
Chondromesenchymal hamartoma. Axial CT shows an expansile lytic lesion involving a right posterior rib with internal chondroid matrix (arrow) and an associated extrapleural and posterior soft tissue mass (asterisks).
Chondromesenchymal hamartoma. T2-weighted sagittal MRI of a 1-year-old girl shows a large mass arising from a posterior rib with a large heterogeneous extrapleural soft tissue mass. The mass is associated with deformity of the adjacent rib (not shown) and contains multiple internal fluid-filled spaces (arrow), some of which contain fluid-fluid levels indicative of intralesional haemorrhage.
A: Chondromesenchymal Hamartoma of the Chest Wall
Back Extra: Chondromesenchymal Hamartoma of the Chest Wall
- Clinical: Infants may present with respiratory distress or a palpable mass due to rib deformation and chest wall involvement.
- Micro: Histologically, the tumor is characterized by nodules of hyaline cartilage, spindle cells, and reactive bone, often with blood-filled cystic spaces.
- Ancillary: No specific ancillary studies are required; diagnosis is made by histopathology and imaging.
Reference Gallery:
Chondromesenchymal hamartoma. Axial CT shows an expansile lytic lesion involving a right posterior rib with internal chondroid matrix (arrow) and an associated extrapleural and posterior soft tissue mass (asterisks).
Chondromesenchymal hamartoma. T2-weighted sagittal MRI of a 1-year-old girl shows a large mass arising from a posterior rib with a large heterogeneous extrapleural soft tissue mass. The mass is associated with deformity of the adjacent rib (not shown) and contains multiple internal fluid-filled spaces (arrow), some of which contain fluid-fluid levels indicative of intralesional haemorrhage.
Chondromesenchymal hamartoma. Low-power examination reveals a cystic lesion with nodules of hyaline cartilage.
Chondromesenchymal hamartoma. A nodule of cartilage with an appearance similar to that of the epiphyseal growth plate.
Chondromesenchymal hamartoma. The cyst walls are composed of a loose arrangement of bland spindled cells and multinucleated giant cells.
Chondromesenchymal hamartoma. Foci of immature bony trabeculae are also present.

Q: Microscopically, Chondromesenchymal Hamartoma of the Chest Wall is characterized by blood-filled cystic spaces, a stroma of bland spindle cells, and distinctive nodules of [...] that often resemble the epiphyseal growth plate.
Chondromesenchymal hamartoma. Low-power examination reveals a cystic lesion with nodules of hyaline cartilage.
Chondromesenchymal hamartoma. A nodule of cartilage with an appearance similar to that of the epiphyseal growth plate.
Chondromesenchymal hamartoma. The cyst walls are composed of a loose arrangement of bland spindled cells and multinucleated giant cells.
A: hyaline cartilage
Back Extra: Chondromesenchymal Hamartoma of the Chest Wall
- Clinical: Infants may present with respiratory distress or a palpable mass due to rib deformation and chest wall involvement.
- Micro: Histologically, the tumor is characterized by nodules of hyaline cartilage, spindle cells, and reactive bone, often with blood-filled cystic spaces.
- Ancillary: No specific ancillary studies are required; diagnosis is made by histopathology and imaging.
Reference Gallery:
Chondromesenchymal hamartoma. Axial CT shows an expansile lytic lesion involving a right posterior rib with internal chondroid matrix (arrow) and an associated extrapleural and posterior soft tissue mass (asterisks).
Chondromesenchymal hamartoma. T2-weighted sagittal MRI of a 1-year-old girl shows a large mass arising from a posterior rib with a large heterogeneous extrapleural soft tissue mass. The mass is associated with deformity of the adjacent rib (not shown) and contains multiple internal fluid-filled spaces (arrow), some of which contain fluid-fluid levels indicative of intralesional haemorrhage.
Chondromesenchymal hamartoma. Low-power examination reveals a cystic lesion with nodules of hyaline cartilage.
Chondromesenchymal hamartoma. A nodule of cartilage with an appearance similar to that of the epiphyseal growth plate.
Chondromesenchymal hamartoma. The cyst walls are composed of a loose arrangement of bland spindled cells and multinucleated giant cells.
Chondromesenchymal hamartoma. Foci of immature bony trabeculae are also present.

Q: Histologically, Chondromyxoid fibroma is characterized by a lobular architecture containing spindle or stellate cells in a myxoid background, with [...] characteristically concentrated at the periphery of the lobules.
Chondromyxoid fibroma. Lobular architecture. In addition to myxoid areas, areas with more hyaline cartilaginous matrix can be seen in a subset of cases.
Chondromyxoid fibroma. Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left.
A: osteoclast-like giant cells
Back Extra: Chondromyxoid fibroma
- Clinical: Chondromyxoid fibroma most frequently arises in the long bones, particularly the proximal tibia and distal femur, and can present with mild pain.
- Micro: Characterized by a lobular pattern with stellate or spindle-shaped cells in a myxoid background, and the presence of osteoclast-like giant cells at the periphery of lobules.
- Ancillary: Immunopositive for S100 and upregulation of GRM1 expression, which is absent or very low in other cartilaginous neoplasms.
Reference Gallery:
Chondromyxoid fibroma. Plain axial CT shows a large soft tissue mass arising from the right iliac wing, with bony destruction. Intralesional matrix calcifications are present.
Chondromyxoid fibroma. T1-weighted axial MRI shows that the soft tissue mass arising from the right iliac bone is isointense to skeletal muscle.
Chondromyxoid fibroma. Contrast-enhanced fat-suppressed T1-weighted axial MRI shows avid heterogeneous enhancement of the mass.
Chondromyxoid fibroma. Focal coarse calcification.
Chondromyxoid fibroma. Lobular architecture. In addition to myxoid areas, areas with more hyaline cartilaginous matrix can be seen in a subset of cases.
Chondromyxoid fibroma. Moderate nuclear enlargement may be present. The eosinophilic cytoplasmic processes are evident.
Chondromyxoid fibroma. Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left.
Chondromyxoid fibroma of the ilium. Note the yellowish-grey, relatively uniform lesion, with sharply demarcated borders and expansion of the bone.

Q: Grossly, [...] typically presents as a sharply demarcated, yellowish-gray, bone-expanding lesion, which frequently correlates with a destructive mass on CT imaging.
Chondromyxoid fibroma. Plain axial CT shows a large soft tissue mass arising from the right iliac wing, with bony destruction. Intralesional matrix calcifications are present.
Chondromyxoid fibroma of the ilium. Note the yellowish-grey, relatively uniform lesion, with sharply demarcated borders and expansion of the bone.
A: Chondromyxoid fibroma
Back Extra: Chondromyxoid fibroma
- Clinical: Chondromyxoid fibroma most frequently arises in the long bones, particularly the proximal tibia and distal femur, and can present with mild pain.
- Micro: Characterized by a lobular pattern with stellate or spindle-shaped cells in a myxoid background, and the presence of osteoclast-like giant cells at the periphery of lobules.
- Ancillary: Immunopositive for S100 and upregulation of GRM1 expression, which is absent or very low in other cartilaginous neoplasms.
Reference Gallery:
Chondromyxoid fibroma. Plain axial CT shows a large soft tissue mass arising from the right iliac wing, with bony destruction. Intralesional matrix calcifications are present.
Chondromyxoid fibroma. T1-weighted axial MRI shows that the soft tissue mass arising from the right iliac bone is isointense to skeletal muscle.
Chondromyxoid fibroma. Contrast-enhanced fat-suppressed T1-weighted axial MRI shows avid heterogeneous enhancement of the mass.
Chondromyxoid fibroma. Focal coarse calcification.
Chondromyxoid fibroma. Lobular architecture. In addition to myxoid areas, areas with more hyaline cartilaginous matrix can be seen in a subset of cases.
Chondromyxoid fibroma. Moderate nuclear enlargement may be present. The eosinophilic cytoplasmic processes are evident.
Chondromyxoid fibroma. Stellate cells embedded in a myxoid matrix are seen on the right, with more-cellular areas containing round cells and multinucleated giant cells on the left.
Chondromyxoid fibroma of the ilium. Note the yellowish-grey, relatively uniform lesion, with sharply demarcated borders and expansion of the bone.

Q: In Grade 1 Chondrosarcoma, the tumor may resemble an enchondroma cellularly, but the entrapment of pre-existing [...] is highly indicative of an infiltrative, malignant process.
Grade 1 chondrosarcoma. A mature hyaline cartilage neoplasm with cellularity not significantly different from that of enchondroma. However, pre-existing lamellar bone is entirely entrapped, indicative of a malignant process.
A: lamellar bone
Back Extra: Chondrosarcoma
- Clinical: Chondrosarcoma is the third most common primary malignancy of bone, usually arising in the fifth to seventh decades of life. In children, it is uncommon with a slight male predominance. Symptoms include localized pain, soft tissue swelling, and varying durations of clinical symptoms.
- Micro: Grade 1 chondrosarcomas show confluent sheets of well-developed hyaline cartilage with mild to moderate cellularity and minimal atypia. Higher grades (2 and 3) exhibit increasing cellularity and nuclear atypia.
- Ancillary: Molecular analysis can help differentiate chondrosarcoma from chondroblastic osteosarcoma, as chondrosarcomas frequently harbour IDH1/IDH2 mutations, which are absent in chondroblastic osteosarcoma.
Reference Gallery:
Chondrosarcoma. Plain film radiograph of a skeletally immature patient with a left proximal femoral diaphyseal lesion associated with poor margination, intralesional densities, cortical thickening, and widening of the shaft.
Chondrosarcoma. MRI confirms the proximal diaphyseal low-signal-intensity lesion seen on plain film radiographs.
Chondrosarcoma. Gross appearance of a proximal tibial chondrosarcoma with expansion into and destruction of the cortex, and with extension into the soft tissue.
Grade 1 chondrosarcoma. A mature hyaline cartilage neoplasm with cellularity not significantly different from that of enchondroma. However, pre-existing lamellar bone is entirely entrapped, indicative of a malignant process.
Grade 2 chondrosarcoma. The degree of cellularity exceeds that expected in enchondromas, outside of the digits. However, hyaline cartilage differentiation is still obvious.
Grade 3 chondrosarcoma. These tumours show the greatest cellularity of all chondrosarcomas, but the degree of hyaline cartilage differentiation begins to diminish at higher grades, with myxoid changes predominating.
Chondroblastic osteosarcoma. The principal differential diagnosis for childhood chondrosarcoma is chondroblastic osteosarcoma. The latter may show hyaline cartilage differentiation but in general tends to exhibit a greater degree of atypia relative to the cellularity.
Chondroblastic osteosarcoma. There is more variation in cellularity in chondroblastic osteosarcoma than in childhood chondrosarcoma, and the presence of osteoid production essentially confirms the diagnosis.
Grade 1 chondrosarcoma. Myxoid changes are common in low-grade chondrosarcomas and less commonly observed in enchondromas.
Grade 2 chondrosarcoma. This higher-power image illustrates that along with increasing cellularity, higher-grade tumours are also associated with nuclear atypia.

Q: A principal histologic differential diagnosis for childhood Chondrosarcoma is chondroblastic osteosarcoma, which can be definitively distinguished by the presence of malignant [...] production.
Chondroblastic osteosarcoma. The principal differential diagnosis for childhood chondrosarcoma is chondroblastic osteosarcoma. The latter may show hyaline cartilage differentiation but in general tends to exhibit a greater degree of atypia relative to the cellularity.
Chondroblastic osteosarcoma. There is more variation in cellularity in chondroblastic osteosarcoma than in childhood chondrosarcoma, and the presence of osteoid production essentially confirms the diagnosis.
A: osteoid
Back Extra: Chondrosarcoma
- Clinical: Chondrosarcoma is the third most common primary malignancy of bone, usually arising in the fifth to seventh decades of life. In children, it is uncommon with a slight male predominance. Symptoms include localized pain, soft tissue swelling, and varying durations of clinical symptoms.
- Micro: Grade 1 chondrosarcomas show confluent sheets of well-developed hyaline cartilage with mild to moderate cellularity and minimal atypia. Higher grades (2 and 3) exhibit increasing cellularity and nuclear atypia.
- Ancillary: Molecular analysis can help differentiate chondrosarcoma from chondroblastic osteosarcoma, as chondrosarcomas frequently harbour IDH1/IDH2 mutations, which are absent in chondroblastic osteosarcoma.
Reference Gallery:
Chondrosarcoma. Plain film radiograph of a skeletally immature patient with a left proximal femoral diaphyseal lesion associated with poor margination, intralesional densities, cortical thickening, and widening of the shaft.
Chondrosarcoma. MRI confirms the proximal diaphyseal low-signal-intensity lesion seen on plain film radiographs.
Chondrosarcoma. Gross appearance of a proximal tibial chondrosarcoma with expansion into and destruction of the cortex, and with extension into the soft tissue.
Grade 1 chondrosarcoma. A mature hyaline cartilage neoplasm with cellularity not significantly different from that of enchondroma. However, pre-existing lamellar bone is entirely entrapped, indicative of a malignant process.
Grade 2 chondrosarcoma. The degree of cellularity exceeds that expected in enchondromas, outside of the digits. However, hyaline cartilage differentiation is still obvious.
Grade 3 chondrosarcoma. These tumours show the greatest cellularity of all chondrosarcomas, but the degree of hyaline cartilage differentiation begins to diminish at higher grades, with myxoid changes predominating.
Chondroblastic osteosarcoma. The principal differential diagnosis for childhood chondrosarcoma is chondroblastic osteosarcoma. The latter may show hyaline cartilage differentiation but in general tends to exhibit a greater degree of atypia relative to the cellularity.
Chondroblastic osteosarcoma. There is more variation in cellularity in chondroblastic osteosarcoma than in childhood chondrosarcoma, and the presence of osteoid production essentially confirms the diagnosis.
Grade 1 chondrosarcoma. Myxoid changes are common in low-grade chondrosarcomas and less commonly observed in enchondromas.
Grade 2 chondrosarcoma. This higher-power image illustrates that along with increasing cellularity, higher-grade tumours are also associated with nuclear atypia.

Q: In high-grade (Grade 3) Chondrosarcoma, tumors exhibit the greatest cellularity, but the degree of hyaline cartilage differentiation diminishes while [...] changes begin to predominate.
Grade 3 chondrosarcoma. These tumours show the greatest cellularity of all chondrosarcomas, but the degree of hyaline cartilage differentiation begins to diminish at higher grades, with myxoid changes predominating.
A: myxoid
Back Extra: Chondrosarcoma
- Clinical: Chondrosarcoma is the third most common primary malignancy of bone, usually arising in the fifth to seventh decades of life. In children, it is uncommon with a slight male predominance. Symptoms include localized pain, soft tissue swelling, and varying durations of clinical symptoms.
- Micro: Grade 1 chondrosarcomas show confluent sheets of well-developed hyaline cartilage with mild to moderate cellularity and minimal atypia. Higher grades (2 and 3) exhibit increasing cellularity and nuclear atypia.
- Ancillary: Molecular analysis can help differentiate chondrosarcoma from chondroblastic osteosarcoma, as chondrosarcomas frequently harbour IDH1/IDH2 mutations, which are absent in chondroblastic osteosarcoma.
Reference Gallery:
Chondrosarcoma. Plain film radiograph of a skeletally immature patient with a left proximal femoral diaphyseal lesion associated with poor margination, intralesional densities, cortical thickening, and widening of the shaft.
Chondrosarcoma. MRI confirms the proximal diaphyseal low-signal-intensity lesion seen on plain film radiographs.
Chondrosarcoma. Gross appearance of a proximal tibial chondrosarcoma with expansion into and destruction of the cortex, and with extension into the soft tissue.
Grade 1 chondrosarcoma. A mature hyaline cartilage neoplasm with cellularity not significantly different from that of enchondroma. However, pre-existing lamellar bone is entirely entrapped, indicative of a malignant process.
Grade 2 chondrosarcoma. The degree of cellularity exceeds that expected in enchondromas, outside of the digits. However, hyaline cartilage differentiation is still obvious.
Grade 3 chondrosarcoma. These tumours show the greatest cellularity of all chondrosarcomas, but the degree of hyaline cartilage differentiation begins to diminish at higher grades, with myxoid changes predominating.
Chondroblastic osteosarcoma. The principal differential diagnosis for childhood chondrosarcoma is chondroblastic osteosarcoma. The latter may show hyaline cartilage differentiation but in general tends to exhibit a greater degree of atypia relative to the cellularity.
Chondroblastic osteosarcoma. There is more variation in cellularity in chondroblastic osteosarcoma than in childhood chondrosarcoma, and the presence of osteoid production essentially confirms the diagnosis.
Grade 1 chondrosarcoma. Myxoid changes are common in low-grade chondrosarcomas and less commonly observed in enchondromas.
Grade 2 chondrosarcoma. This higher-power image illustrates that along with increasing cellularity, higher-grade tumours are also associated with nuclear atypia.

Q: Microscopically, Notochordal Tumors (specifically conventional chordomas) demonstrate a characteristic lobulated architecture with an abundant myxoid matrix and large, vacuolated [...] cells.
Conventional chordoma. Classic histological appearance of conventional chordoma showing the lobulated architecture with abundant extracellular matrix.
A: physaliphorous
Back Extra: Notochordal Tumours
- Clinical: Notochordal tumours, particularly conventional chordomas, are rare paediatric bone tumours that most commonly occur in the base of the skull and upper cervical vertebrae, presenting with pain and neurological symptoms.
- Micro: Conventional chordomas show a characteristic lobulated architecture with an abundant myxoid matrix and large, physaliphorous cells, while poorly differentiated chordomas lack the myxoid matrix and show sheets of epithelioid or rhabdoid cells.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with brachyury expression being a key marker for all notochordal tumours, and loss of SMARCB1 (INI1) in poorly differentiated chordomas.
Reference Gallery:
Conventional chordoma. Sacrectomy specimen showing a large lobulated mass with a gelatinous appearance, destroying the distal sacrum and extending into soft tissue.
Conventional chordoma. Classic histological appearance of conventional chordoma showing the lobulated architecture with abundant extracellular matrix.
Poorly differentiated chordoma. Solid sheets of epithelioid cells with no extracellular myxoid matrix.
Poorly differentiated chordoma. Nuclear brachyury positivity is retained.
Benign notochordal cell tumour. Viable cancellous bone with a solid island of bland notochordal cells with no extracellular myxoid matrix.
Dedifferentiated chordoma. A conventional chordoma (upper half of the image) is juxtaposed to a high-grade pleomorphic sarcoma (lower half).
Conventional chordoma. CT of the head, without contrast, of a 6-year-old boy with a conventional chordoma of the clivus (between arrows) bilaterally involving the cavernous sinus, dorsum sellae, and retroclival epidural space.

Q: Immunohistochemistry is crucial for the diagnosis of Notochordal Tumors, as virtually all subtypes exhibit pathognomonic nuclear expression of the transcription factor [...].
Poorly differentiated chordoma. Nuclear brachyury positivity is retained.
A: brachyury
Back Extra: Notochordal Tumours
- Clinical: Notochordal tumours, particularly conventional chordomas, are rare paediatric bone tumours that most commonly occur in the base of the skull and upper cervical vertebrae, presenting with pain and neurological symptoms.
- Micro: Conventional chordomas show a characteristic lobulated architecture with an abundant myxoid matrix and large, physaliphorous cells, while poorly differentiated chordomas lack the myxoid matrix and show sheets of epithelioid or rhabdoid cells.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with brachyury expression being a key marker for all notochordal tumours, and loss of SMARCB1 (INI1) in poorly differentiated chordomas.
Reference Gallery:
Conventional chordoma. Sacrectomy specimen showing a large lobulated mass with a gelatinous appearance, destroying the distal sacrum and extending into soft tissue.
Conventional chordoma. Classic histological appearance of conventional chordoma showing the lobulated architecture with abundant extracellular matrix.
Poorly differentiated chordoma. Solid sheets of epithelioid cells with no extracellular myxoid matrix.
Poorly differentiated chordoma. Nuclear brachyury positivity is retained.
Benign notochordal cell tumour. Viable cancellous bone with a solid island of bland notochordal cells with no extracellular myxoid matrix.
Dedifferentiated chordoma. A conventional chordoma (upper half of the image) is juxtaposed to a high-grade pleomorphic sarcoma (lower half).
Conventional chordoma. CT of the head, without contrast, of a 6-year-old boy with a conventional chordoma of the clivus (between arrows) bilaterally involving the cavernous sinus, dorsum sellae, and retroclival epidural space.

Q: Malignant Notochordal Tumors (chordomas) classically arise along the axial skeleton, most commonly presenting as destructive, gelatinous masses in the skull base (clivus) and the distal spine, specifically the [...].
Conventional chordoma. Sacrectomy specimen showing a large lobulated mass with a gelatinous appearance, destroying the distal sacrum and extending into soft tissue.
Conventional chordoma. CT of the head, without contrast, of a 6-year-old boy with a conventional chordoma of the clivus (between arrows) bilaterally involving the cavernous sinus, dorsum sellae, and retroclival epidural space.
A: sacrum
Back Extra: Notochordal Tumours
- Clinical: Notochordal tumours, particularly conventional chordomas, are rare paediatric bone tumours that most commonly occur in the base of the skull and upper cervical vertebrae, presenting with pain and neurological symptoms.
- Micro: Conventional chordomas show a characteristic lobulated architecture with an abundant myxoid matrix and large, physaliphorous cells, while poorly differentiated chordomas lack the myxoid matrix and show sheets of epithelioid or rhabdoid cells.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with brachyury expression being a key marker for all notochordal tumours, and loss of SMARCB1 (INI1) in poorly differentiated chordomas.
Reference Gallery:
Conventional chordoma. Sacrectomy specimen showing a large lobulated mass with a gelatinous appearance, destroying the distal sacrum and extending into soft tissue.
Conventional chordoma. Classic histological appearance of conventional chordoma showing the lobulated architecture with abundant extracellular matrix.
Poorly differentiated chordoma. Solid sheets of epithelioid cells with no extracellular myxoid matrix.
Poorly differentiated chordoma. Nuclear brachyury positivity is retained.
Benign notochordal cell tumour. Viable cancellous bone with a solid island of bland notochordal cells with no extracellular myxoid matrix.
Dedifferentiated chordoma. A conventional chordoma (upper half of the image) is juxtaposed to a high-grade pleomorphic sarcoma (lower half).
Conventional chordoma. CT of the head, without contrast, of a 6-year-old boy with a conventional chordoma of the clivus (between arrows) bilaterally involving the cavernous sinus, dorsum sellae, and retroclival epidural space.

Q: In Enchondroma and Enchondromatosis, the presence of multiple cartilaginous tumors (e.g., Ollier disease) leads to significant bone deformities and an increased risk of secondary [...].
Ollier disease. Dorsopalmar radiograph of the left hand. Multiple enchondromas are seen in the metacarpals and phalanges. There is faint internal density in several of the tumours, but punctate matrix mineralization is inconspicuous. Expansile lesions in the proximal phalanges of the index and little fingers are consistent with subperiosteal chondromas (likely to have commenced within the cortex or deep to periosteum) and show mild diffuse density, with small punctate foci of calcification in the little finger lesion. Growth disturbance of the ulna causes mild shortening.
Ollier disease. Coronal short-tau inversion recovery (STIR) MRI of the left hand shows multiple enchondromas. Metacarpal tumours are central medullary lesions; both medullary and subperiosteal/intracortical lesions are seen in the phalanges. The tumours are lobular, and they show marked hyperintensity and thin, low-signal septations. There is marked expansile remodelling of the lesions in the proximal phalanges of the index and little finger.
Ollier disease. Multiple enchondromas are present in the metatarsal bones and phalanges.
A: chondrosarcomas
Back Extra: Enchondroma and Enchondromatosis
- Clinical: Enchondromas of the small bones may cause swellings, pain, and fracture, whereas long bone tumours are often asymptomatic. Ollier disease can lead to significant bone deformities and is associated with an increased risk of secondary chondrosarcomas.
- Micro: Enchondromas are hypocellular tumours with a multinodular or confluent architecture. The cells are embedded within a hyaline matrix, and cytological atypia and mitoses are absent. In children and in patients with enchondromatosis, enchondromas can be more cellular with open chromatin and small nucleoli.
- Ancillary: Molecular pathology is rarely used for diagnosis, but somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are common in enchondromas and enchondromatosis.
Reference Gallery:
Ollier disease. Dorsopalmar radiograph of the left hand. Multiple enchondromas are seen in the metacarpals and phalanges. There is faint internal density in several of the tumours, but punctate matrix mineralization is inconspicuous. Expansile lesions in the proximal phalanges of the index and little fingers are consistent with subperiosteal chondromas (likely to have commenced within the cortex or deep to periosteum) and show mild diffuse density, with small punctate foci of calcification in the little finger lesion. Growth disturbance of the ulna causes mild shortening.
Ollier disease. Coronal short-tau inversion recovery (STIR) MRI of the left hand shows multiple enchondromas. Metacarpal tumours are central medullary lesions; both medullary and subperiosteal/intracortical lesions are seen in the phalanges. The tumours are lobular, and they show marked hyperintensity and thin, low-signal septations. There is marked expansile remodelling of the lesions in the proximal phalanges of the index and little finger.
Ollier disease. Multiple enchondromas are present in the metatarsal bones and phalanges.
Enchondroma. Multiple cartilaginous nodules separated by bone marrow and encased by cancellous bone (a sign of slow growth). Host bone permeation is never seen in enchondromas.
Enchondroma. The chondrocytes are embedded within a hyaline matrix, with the typical finely stippled calcification. Tumour cells are located within large lacunae, in which the cytoplasm is pushed aside, forming spider-like extensions. The nuclei are small and hyperchromatic, with no visible nucleoli.
Enchondroma. Endochondral calcification is a characteristic feature. Note the necrotic chondrocytes.
Maffucci syndrome. Spindle cell and cavernous haemangioma containing multiple phleboliths within dilated vessels.

Q: Histologically, the cartilaginous nodules in Enchondroma and Enchondromatosis are separated by bone marrow and encased by cancellous bone; notably, host bone [...] is never seen.
Enchondroma. Multiple cartilaginous nodules separated by bone marrow and encased by cancellous bone (a sign of slow growth). Host bone permeation is never seen in enchondromas.
A: permeation
Back Extra: Enchondroma and Enchondromatosis
- Clinical: Enchondromas of the small bones may cause swellings, pain, and fracture, whereas long bone tumours are often asymptomatic. Ollier disease can lead to significant bone deformities and is associated with an increased risk of secondary chondrosarcomas.
- Micro: Enchondromas are hypocellular tumours with a multinodular or confluent architecture. The cells are embedded within a hyaline matrix, and cytological atypia and mitoses are absent. In children and in patients with enchondromatosis, enchondromas can be more cellular with open chromatin and small nucleoli.
- Ancillary: Molecular pathology is rarely used for diagnosis, but somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are common in enchondromas and enchondromatosis.
Reference Gallery:
Ollier disease. Dorsopalmar radiograph of the left hand. Multiple enchondromas are seen in the metacarpals and phalanges. There is faint internal density in several of the tumours, but punctate matrix mineralization is inconspicuous. Expansile lesions in the proximal phalanges of the index and little fingers are consistent with subperiosteal chondromas (likely to have commenced within the cortex or deep to periosteum) and show mild diffuse density, with small punctate foci of calcification in the little finger lesion. Growth disturbance of the ulna causes mild shortening.
Ollier disease. Coronal short-tau inversion recovery (STIR) MRI of the left hand shows multiple enchondromas. Metacarpal tumours are central medullary lesions; both medullary and subperiosteal/intracortical lesions are seen in the phalanges. The tumours are lobular, and they show marked hyperintensity and thin, low-signal septations. There is marked expansile remodelling of the lesions in the proximal phalanges of the index and little finger.
Ollier disease. Multiple enchondromas are present in the metatarsal bones and phalanges.
Enchondroma. Multiple cartilaginous nodules separated by bone marrow and encased by cancellous bone (a sign of slow growth). Host bone permeation is never seen in enchondromas.
Enchondroma. The chondrocytes are embedded within a hyaline matrix, with the typical finely stippled calcification. Tumour cells are located within large lacunae, in which the cytoplasm is pushed aside, forming spider-like extensions. The nuclei are small and hyperchromatic, with no visible nucleoli.
Enchondroma. Endochondral calcification is a characteristic feature. Note the necrotic chondrocytes.
Maffucci syndrome. Spindle cell and cavernous haemangioma containing multiple phleboliths within dilated vessels.

Q: A specific syndromic presentation of Enchondroma and Enchondromatosis is Maffucci syndrome, which is characterized by multiple enchondromas associated with spindle cell and cavernous [...].
Maffucci syndrome. Spindle cell and cavernous haemangioma containing multiple phleboliths within dilated vessels.
A: hemangiomas
Back Extra: Enchondroma and Enchondromatosis
- Clinical: Enchondromas of the small bones may cause swellings, pain, and fracture, whereas long bone tumours are often asymptomatic. Ollier disease can lead to significant bone deformities and is associated with an increased risk of secondary chondrosarcomas.
- Micro: Enchondromas are hypocellular tumours with a multinodular or confluent architecture. The cells are embedded within a hyaline matrix, and cytological atypia and mitoses are absent. In children and in patients with enchondromatosis, enchondromas can be more cellular with open chromatin and small nucleoli.
- Ancillary: Molecular pathology is rarely used for diagnosis, but somatic mutations in the isocitrate dehydrogenase genes IDH1 and IDH2 are common in enchondromas and enchondromatosis.
Reference Gallery:
Ollier disease. Dorsopalmar radiograph of the left hand. Multiple enchondromas are seen in the metacarpals and phalanges. There is faint internal density in several of the tumours, but punctate matrix mineralization is inconspicuous. Expansile lesions in the proximal phalanges of the index and little fingers are consistent with subperiosteal chondromas (likely to have commenced within the cortex or deep to periosteum) and show mild diffuse density, with small punctate foci of calcification in the little finger lesion. Growth disturbance of the ulna causes mild shortening.
Ollier disease. Coronal short-tau inversion recovery (STIR) MRI of the left hand shows multiple enchondromas. Metacarpal tumours are central medullary lesions; both medullary and subperiosteal/intracortical lesions are seen in the phalanges. The tumours are lobular, and they show marked hyperintensity and thin, low-signal septations. There is marked expansile remodelling of the lesions in the proximal phalanges of the index and little finger.
Ollier disease. Multiple enchondromas are present in the metatarsal bones and phalanges.
Enchondroma. Multiple cartilaginous nodules separated by bone marrow and encased by cancellous bone (a sign of slow growth). Host bone permeation is never seen in enchondromas.
Enchondroma. The chondrocytes are embedded within a hyaline matrix, with the typical finely stippled calcification. Tumour cells are located within large lacunae, in which the cytoplasm is pushed aside, forming spider-like extensions. The nuclei are small and hyperchromatic, with no visible nucleoli.
Enchondroma. Endochondral calcification is a characteristic feature. Note the necrotic chondrocytes.
Maffucci syndrome. Spindle cell and cavernous haemangioma containing multiple phleboliths within dilated vessels.

Q: Microscopically, Fibrous Dysplasia is characterized by a bland fibroblastic proliferation containing irregular, curvilinear trabeculae of woven bone that typically lack conspicuous [...].
Fibrous dysplasia. Irregular curvilinear trabeculae of woven bone with inconspicuous osteoblastic rimming, surrounded by a proliferation of bland-appearing spindle cells.
A: osteoblastic rimming
Q: Fibrous Dysplasia
- Clinical: Osseous deformity with associated pain and pathological fractures can occur in [...].
- Micro: Fibrous dysplasia is composed of a [...] with irregular curvilinear trabeculae of woven or (rarely) lamellar bone without conspicuous osteoblastic rimming.
- Ancillary: The detection of [...] can be useful to confirm a diagnosis of fibrous dysplasia. Common mutations include p.R201H and p.R201C.
Reference Gallery:
Fibrous dysplasia. Irregular curvilinear trabeculae of woven bone with inconspicuous osteoblastic rimming, surrounded by a proliferation of bland-appearing spindle cells.
Fibrous dysplasia. Plain radiograph of the left hip shows an eccentric circumscribed medullary lesion at the proximal femur with ground-glass density at the centre of the mass. There is endosteal scalloping. The cortex is thinned but remains intact.
Fibrous dysplasia. Fat-suppressed T2-weighted coronal MRI. The medullary lesion within the left proximal femur shows heterogeneous enhancement, which is nonspecific.
Fibrous dysplasia. Bone trabeculae with irregular osteoblastic rimming.
A: fibrous dysplasia; variably cellular proliferation of bland fibroblastic cells; GNAS mutations

Q: On plain radiography, Fibrous Dysplasia classically presents as a circumscribed medullary lesion with a [...] density, which can lead to osseous deformity, pain, and pathological fractures.
Fibrous dysplasia. Plain radiograph of the left hip shows an eccentric circumscribed medullary lesion at the proximal femur with ground-glass density at the centre of the mass. There is endosteal scalloping. The cortex is thinned but remains intact.
A: ground-glass
Q: Fibrous Dysplasia
- Clinical: Osseous deformity with associated pain and pathological fractures can occur in [...].
- Micro: Fibrous dysplasia is composed of a [...] with irregular curvilinear trabeculae of woven or (rarely) lamellar bone without conspicuous osteoblastic rimming.
- Ancillary: The detection of [...] can be useful to confirm a diagnosis of fibrous dysplasia. Common mutations include p.R201H and p.R201C.
Reference Gallery:
Fibrous dysplasia. Irregular curvilinear trabeculae of woven bone with inconspicuous osteoblastic rimming, surrounded by a proliferation of bland-appearing spindle cells.
Fibrous dysplasia. Plain radiograph of the left hip shows an eccentric circumscribed medullary lesion at the proximal femur with ground-glass density at the centre of the mass. There is endosteal scalloping. The cortex is thinned but remains intact.
Fibrous dysplasia. Fat-suppressed T2-weighted coronal MRI. The medullary lesion within the left proximal femur shows heterogeneous enhancement, which is nonspecific.
Fibrous dysplasia. Bone trabeculae with irregular osteoblastic rimming.
A: fibrous dysplasia; variably cellular proliferation of bland fibroblastic cells; GNAS mutations

Q: A lesion characterized microscopically by numerous osteoclast-like giant cells uniformly admixed with neoplastic mononuclear cells is highly characteristic of [...].
Giant cell tumour of bone. Characteristic morphology of numerous osteoclast-like giant cells, between which are the mononuclear cells.
A: Giant Cell Tumor of Bone
Back Extra: Giant Cell Tumor of Bone
- Clinical: Giant Cell Tumor of Bone (GCTB) typically presents with pain, swelling, and restricted joint movement, often lasting weeks to months.
- Micro: GCTB is characterized by numerous osteoclast-like giant cells and mononuclear cells, with a variable number of nuclei in the giant cells, some having > 50 per cell.
- Ancillary: H3-3A gene mutation, specifically H3-3A:c.103G>T p.G35W (G34W), is detected in the neoplastic stromal cells in about 96% of GCTBs.
Reference Gallery:
Giant cell tumour of bone. MRI shows a lesion with decreased signal intensity.
Giant cell tumour of bone. Characteristic morphology of numerous osteoclast-like giant cells, between which are the mononuclear cells.
Giant cell tumour of bone. Immunohistochemistry using a mutation-specific antibody for H3.3 G34W, showing diffuse positivity in the mononuclear cells. Note the absence of staining in the osteoclast-like giant cells.

Q: In Giant Cell Tumor of Bone, approximately 96% of cases harbor a highly specific [...] gene mutation, which is detected via immunohistochemistry in the neoplastic mononuclear stromal cells but is completely absent in the giant cells.
Giant cell tumour of bone. Immunohistochemistry using a mutation-specific antibody for H3.3 G34W, showing diffuse positivity in the mononuclear cells. Note the absence of staining in the osteoclast-like giant cells.
A: H3-3A (G34W)
Back Extra: Giant Cell Tumor of Bone
- Clinical: Giant Cell Tumor of Bone (GCTB) typically presents with pain, swelling, and restricted joint movement, often lasting weeks to months.
- Micro: GCTB is characterized by numerous osteoclast-like giant cells and mononuclear cells, with a variable number of nuclei in the giant cells, some having > 50 per cell.
- Ancillary: H3-3A gene mutation, specifically H3-3A:c.103G>T p.G35W (G34W), is detected in the neoplastic stromal cells in about 96% of GCTBs.
Reference Gallery:
Giant cell tumour of bone. MRI shows a lesion with decreased signal intensity.
Giant cell tumour of bone. Characteristic morphology of numerous osteoclast-like giant cells, between which are the mononuclear cells.
Giant cell tumour of bone. Immunohistochemistry using a mutation-specific antibody for H3.3 G34W, showing diffuse positivity in the mononuclear cells. Note the absence of staining in the osteoclast-like giant cells.

Q: Microscopically, mesenchymal chondrosarcoma is characterized by a classic [...] pattern, featuring hypercellular undifferentiated round cells juxtaposed with islands of mature hyaline cartilage.
Mesenchymal chondrosarcoma. The classic bimorphic pattern, with undifferentiated, mostly round tumour cells juxtaposed to a mature hyaline cartilaginous component.
Mesenchymal chondrosarcoma. High-power view of the undifferentiated tumour cells, without any distinguishing features.
A: bimorphic
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Common symptoms include pain and/or swelling. Lesions of the head and neck may be associated with headaches, visual disturbances, and vomiting.
- Micro: The lesion has a characteristic bimorphic pattern, consisting of a hypercellular round to slightly spindled undifferentiated cell population, alternating with islands of benign to low-grade hyaline cartilage.
- Ancillary: The vast majority of mesenchymal chondrosarcomas contain a relatively specific gene fusion between HEY1 and NCOA2, which are separated by only 10 Mb on chromosome 8.
Reference Gallery:
Mesenchymal chondrosarcoma. Lateral plain film radiograph of the proximal femur reveals a surface mass, causing erosion of the underlying femur, with internal flocculent calcifications.
Mesenchymal chondrosarcoma. The classic bimorphic pattern, with undifferentiated, mostly round tumour cells juxtaposed to a mature hyaline cartilaginous component.
Mesenchymal chondrosarcoma. High-power view of the undifferentiated tumour cells, without any distinguishing features.
Mesenchymal chondrosarcoma. A background haemangiopericytoma-like vascular component is usually associated with the more cellular regions.
Mesenchymal chondrosarcoma. Diffuse membranous CD99 immunopositivity is a common feature of mesenchymal chondrosarcoma.

Q: The hypercellular, undifferentiated areas of mesenchymal chondrosarcoma frequently exhibit a prominent [...]-like vascular pattern and typically show diffuse membranous immunopositivity for CD99.
Mesenchymal chondrosarcoma. A background haemangiopericytoma-like vascular component is usually associated with the more cellular regions.
Mesenchymal chondrosarcoma. Diffuse membranous CD99 immunopositivity is a common feature of mesenchymal chondrosarcoma.
A: hemangiopericytoma
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Common symptoms include pain and/or swelling. Lesions of the head and neck may be associated with headaches, visual disturbances, and vomiting.
- Micro: The lesion has a characteristic bimorphic pattern, consisting of a hypercellular round to slightly spindled undifferentiated cell population, alternating with islands of benign to low-grade hyaline cartilage.
- Ancillary: The vast majority of mesenchymal chondrosarcomas contain a relatively specific gene fusion between HEY1 and NCOA2, which are separated by only 10 Mb on chromosome 8.
Reference Gallery:
Mesenchymal chondrosarcoma. Lateral plain film radiograph of the proximal femur reveals a surface mass, causing erosion of the underlying femur, with internal flocculent calcifications.
Mesenchymal chondrosarcoma. The classic bimorphic pattern, with undifferentiated, mostly round tumour cells juxtaposed to a mature hyaline cartilaginous component.
Mesenchymal chondrosarcoma. High-power view of the undifferentiated tumour cells, without any distinguishing features.
Mesenchymal chondrosarcoma. A background haemangiopericytoma-like vascular component is usually associated with the more cellular regions.
Mesenchymal chondrosarcoma. Diffuse membranous CD99 immunopositivity is a common feature of mesenchymal chondrosarcoma.

Q: Radiographically, mesenchymal chondrosarcoma can present as a destructive, bone-eroding mass with internal [...] calcifications corresponding to its cartilaginous component.
Mesenchymal chondrosarcoma. Lateral plain film radiograph of the proximal femur reveals a surface mass, causing erosion of the underlying femur, with internal flocculent calcifications.
A: flocculent
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Common symptoms include pain and/or swelling. Lesions of the head and neck may be associated with headaches, visual disturbances, and vomiting.
- Micro: The lesion has a characteristic bimorphic pattern, consisting of a hypercellular round to slightly spindled undifferentiated cell population, alternating with islands of benign to low-grade hyaline cartilage.
- Ancillary: The vast majority of mesenchymal chondrosarcomas contain a relatively specific gene fusion between HEY1 and NCOA2, which are separated by only 10 Mb on chromosome 8.
Reference Gallery:
Mesenchymal chondrosarcoma. Lateral plain film radiograph of the proximal femur reveals a surface mass, causing erosion of the underlying femur, with internal flocculent calcifications.
Mesenchymal chondrosarcoma. The classic bimorphic pattern, with undifferentiated, mostly round tumour cells juxtaposed to a mature hyaline cartilaginous component.
Mesenchymal chondrosarcoma. High-power view of the undifferentiated tumour cells, without any distinguishing features.
Mesenchymal chondrosarcoma. A background haemangiopericytoma-like vascular component is usually associated with the more cellular regions.
Mesenchymal chondrosarcoma. Diffuse membranous CD99 immunopositivity is a common feature of mesenchymal chondrosarcoma.

Q: Histologically, Non-ossifying fibroma features bland, spindle-shaped cells characteristically arranged in a [...] pattern with scattered osteoclast-type giant cells.
Non-ossifying fibroma. Spindle cells arranged in a storiform pattern with scattered osteoclast-like giant cells and rare foamy macrophages.
A: storiform
Back Extra: Non-ossifying fibroma
- Clinical: Non-ossifying fibroma (NOF) arises in skeletally immature individuals, with a peak incidence in the second decade of life. Larger tumours can be painful and may cause pathological fractures.
- Micro: NOF consists of bland, spindle-shaped cells arranged in a storiform pattern, with scattered osteoclast-type giant cells and haemosiderin deposition.
- Ancillary: KRAS and FGFR1 mutation testing can be considered in ambiguous cases.
Reference Gallery:
Non-ossifying fibroma. Spindle cells arranged in a storiform pattern with scattered osteoclast-like giant cells and rare foamy macrophages.
Non-ossifying fibroma. Areas of haemosiderin pigment deposition.

Q: Along with a storiform spindle cell background and osteoclast-like giant cells, the microscopic appearance of a Non-ossifying fibroma typically includes the focal deposition of [...] pigment.
Non-ossifying fibroma. Areas of haemosiderin pigment deposition.
A: hemosiderin
Back Extra: Non-ossifying fibroma
- Clinical: Non-ossifying fibroma (NOF) arises in skeletally immature individuals, with a peak incidence in the second decade of life. Larger tumours can be painful and may cause pathological fractures.
- Micro: NOF consists of bland, spindle-shaped cells arranged in a storiform pattern, with scattered osteoclast-type giant cells and haemosiderin deposition.
- Ancillary: KRAS and FGFR1 mutation testing can be considered in ambiguous cases.
Reference Gallery:
Non-ossifying fibroma. Spindle cells arranged in a storiform pattern with scattered osteoclast-like giant cells and rare foamy macrophages.
Non-ossifying fibroma. Areas of haemosiderin pigment deposition.

Q: Radiographically, conventional Ossifying Fibroma typically presents as a well-defined, corticated mixed radiolucency that frequently causes [...] and minor root resorption.
Ossifying fibroma. Conventional type. A typical well-defined and corticated mixed radiolucency with patchy internal mineralization and displacement of teeth with minor root resorption (dental bitewing).
A: tooth displacement
Back Extra: Ossifying Fibroma
- Clinical: Ossifying fibromas typically present as asymptomatic bony swellings that can lead to disfigurement, tooth displacement, and root resorption.
- Micro: Histologically, ossifying fibromas show woven bone maturing to dense bone or cementum-like structures with a hypercellular stroma of spindle cells.
- Ancillary: Genetic studies show that juvenile trabecular and psammomatoid subtypes may have rearrangements involving RASAL1 and MDM2, but not GNAS mutations.
Reference Gallery:
Ossifying fibroma. Conventional type. A typical well-defined and corticated mixed radiolucency with patchy internal mineralization and displacement of teeth with minor root resorption (dental bitewing).
Ossifying fibroma. Psammomatoid subtype. A typical large radiolucent lesion with prominent expansion, well-defined margin, and minimal internal mineralization. Developing teeth are displaced (X-ray).
Ossifying fibroma. Juvenile trabecular subtype. A typical radiolucent lesion with prominent expansion and tooth displacement in a young child (dental imaging).
Ossifying fibroma. A conventional ossifying fibroma with a denser collagenous stroma than the juvenile type, with mineralization ranging from focal (shown) to dense sheets and trabeculae of relatively acellular bone.
Ossifying fibroma. High-power view of a juvenile trabecular ossifying fibroma showing disorganized woven bone with apparent atypia.
Ossifying fibroma. A psammomatoid ossifying fibroma showing numerous small, densely mineralized nodules with a thin unmineralized rim set in hypercellular fibrous tissue.
Ossifying fibroma. Juvenile trabecular ossifying fibroma. Medium-power view showing purposeless osteoid trabeculae with minimal mineralization in a cellular non-collagenous stroma.

Q: The [...] subtype of Ossifying Fibroma is characterized histologically by numerous small, densely mineralized nodules with a thin unmineralized rim, set in a hypercellular fibrous stroma.
Ossifying fibroma. A psammomatoid ossifying fibroma showing numerous small, densely mineralized nodules with a thin unmineralized rim set in hypercellular fibrous tissue.
A: psammomatoid
Back Extra: Ossifying Fibroma
- Clinical: Ossifying fibromas typically present as asymptomatic bony swellings that can lead to disfigurement, tooth displacement, and root resorption.
- Micro: Histologically, ossifying fibromas show woven bone maturing to dense bone or cementum-like structures with a hypercellular stroma of spindle cells.
- Ancillary: Genetic studies show that juvenile trabecular and psammomatoid subtypes may have rearrangements involving RASAL1 and MDM2, but not GNAS mutations.
Reference Gallery:
Ossifying fibroma. Conventional type. A typical well-defined and corticated mixed radiolucency with patchy internal mineralization and displacement of teeth with minor root resorption (dental bitewing).
Ossifying fibroma. Psammomatoid subtype. A typical large radiolucent lesion with prominent expansion, well-defined margin, and minimal internal mineralization. Developing teeth are displaced (X-ray).
Ossifying fibroma. Juvenile trabecular subtype. A typical radiolucent lesion with prominent expansion and tooth displacement in a young child (dental imaging).
Ossifying fibroma. A conventional ossifying fibroma with a denser collagenous stroma than the juvenile type, with mineralization ranging from focal (shown) to dense sheets and trabeculae of relatively acellular bone.
Ossifying fibroma. High-power view of a juvenile trabecular ossifying fibroma showing disorganized woven bone with apparent atypia.
Ossifying fibroma. A psammomatoid ossifying fibroma showing numerous small, densely mineralized nodules with a thin unmineralized rim set in hypercellular fibrous tissue.
Ossifying fibroma. Juvenile trabecular ossifying fibroma. Medium-power view showing purposeless osteoid trabeculae with minimal mineralization in a cellular non-collagenous stroma.

Q: The juvenile trabecular subtype of Ossifying Fibroma features a cellular, non-collagenous stroma containing purposeless, minimally mineralized trabeculae of [...] that can exhibit apparent atypia.
Ossifying fibroma. High-power view of a juvenile trabecular ossifying fibroma showing disorganized woven bone with apparent atypia.
Ossifying fibroma. Juvenile trabecular ossifying fibroma. Medium-power view showing purposeless osteoid trabeculae with minimal mineralization in a cellular non-collagenous stroma.
A: osteoid
Back Extra: Ossifying Fibroma
- Clinical: Ossifying fibromas typically present as asymptomatic bony swellings that can lead to disfigurement, tooth displacement, and root resorption.
- Micro: Histologically, ossifying fibromas show woven bone maturing to dense bone or cementum-like structures with a hypercellular stroma of spindle cells.
- Ancillary: Genetic studies show that juvenile trabecular and psammomatoid subtypes may have rearrangements involving RASAL1 and MDM2, but not GNAS mutations.
Reference Gallery:
Ossifying fibroma. Conventional type. A typical well-defined and corticated mixed radiolucency with patchy internal mineralization and displacement of teeth with minor root resorption (dental bitewing).
Ossifying fibroma. Psammomatoid subtype. A typical large radiolucent lesion with prominent expansion, well-defined margin, and minimal internal mineralization. Developing teeth are displaced (X-ray).
Ossifying fibroma. Juvenile trabecular subtype. A typical radiolucent lesion with prominent expansion and tooth displacement in a young child (dental imaging).
Ossifying fibroma. A conventional ossifying fibroma with a denser collagenous stroma than the juvenile type, with mineralization ranging from focal (shown) to dense sheets and trabeculae of relatively acellular bone.
Ossifying fibroma. High-power view of a juvenile trabecular ossifying fibroma showing disorganized woven bone with apparent atypia.
Ossifying fibroma. A psammomatoid ossifying fibroma showing numerous small, densely mineralized nodules with a thin unmineralized rim set in hypercellular fibrous tissue.
Ossifying fibroma. Juvenile trabecular ossifying fibroma. Medium-power view showing purposeless osteoid trabeculae with minimal mineralization in a cellular non-collagenous stroma.

Q: Clinically, [...] typically presents as an expansile, lytic bone lesion (frequently in the spine) causing pain that, unlike osteoid osteoma, is generally unresponsive to NSAIDs.
Osteoblastoma. Axial CT of the cervical spine of a 9-year-old boy demonstrates a well-lineated lytic expansile lesion with areas of radiodensity and mineralization expanding the transverse process of C6.
Osteoblastoma. Radiograph showing a well-circumscribed oval lytic lesion with reactive sclerosis involving the lateral malleolus of the fibula in a 9-year-old boy.
A: osteoblastoma
Q: Osteoblastoma
- Clinical: The most common presenting symptom of [...] is pain and swelling. NSAIDs do not typically provide pain relief.
- Micro: Histopathology of [...] shows a delicate network of haphazardly arranged trabeculae of woven bone lined by plump osteoblasts.
- Ancillary: FOS or FOSB rearrangements are detectable in the majority of [...] cases and can aid in confirming the diagnosis.
Reference Gallery:
Osteoblastoma. Axial CT of the cervical spine of a 9-year-old boy demonstrates a well-lineated lytic expansile lesion with areas of radiodensity and mineralization expanding the transverse process of C6.
Osteoblastoma. Radiograph showing a well-circumscribed oval lytic lesion with reactive sclerosis involving the lateral malleolus of the fibula in a 9-year-old boy.
Osteoblastoma. Low-power view. Note the well-defined border and absence of infiltrative growth.
Osteoblastoma. High-power view of an osteoblastoma composed of irregular trabeculae of woven bone rimmed by prominent osteoblasts, scattered osteoclasts, and intervening loose fibrovascular stroma.
Osteoblastoma. This epithelial osteoblastoma is composed of large epithelioid osteoblasts with abundant eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli.
Osteoblastoma. Nuclear expression of FOS in the osteoblastic cells.
A: osteoblastoma; osteoblastoma; osteoblastoma

Q: Microscopically, the hallmark of an osteoblastoma is a well-circumscribed network of haphazardly arranged irregular trabeculae of woven bone prominently rimmed by plump [...] within a loose fibrovascular stroma.
Osteoblastoma. Low-power view. Note the well-defined border and absence of infiltrative growth.
Osteoblastoma. High-power view of an osteoblastoma composed of irregular trabeculae of woven bone rimmed by prominent osteoblasts, scattered osteoclasts, and intervening loose fibrovascular stroma.
A: osteoblasts
Q: Osteoblastoma
- Clinical: The most common presenting symptom of [...] is pain and swelling. NSAIDs do not typically provide pain relief.
- Micro: Histopathology of [...] shows a delicate network of haphazardly arranged trabeculae of woven bone lined by plump osteoblasts.
- Ancillary: FOS or FOSB rearrangements are detectable in the majority of [...] cases and can aid in confirming the diagnosis.
Reference Gallery:
Osteoblastoma. Axial CT of the cervical spine of a 9-year-old boy demonstrates a well-lineated lytic expansile lesion with areas of radiodensity and mineralization expanding the transverse process of C6.
Osteoblastoma. Radiograph showing a well-circumscribed oval lytic lesion with reactive sclerosis involving the lateral malleolus of the fibula in a 9-year-old boy.
Osteoblastoma. Low-power view. Note the well-defined border and absence of infiltrative growth.
Osteoblastoma. High-power view of an osteoblastoma composed of irregular trabeculae of woven bone rimmed by prominent osteoblasts, scattered osteoclasts, and intervening loose fibrovascular stroma.
Osteoblastoma. This epithelial osteoblastoma is composed of large epithelioid osteoblasts with abundant eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli.
Osteoblastoma. Nuclear expression of FOS in the osteoblastic cells.
A: osteoblastoma; osteoblastoma; osteoblastoma

Q: The majority of osteoblastoma cases harbor genetic rearrangements involving [...], which can be confirmed via strong nuclear expression on immunohistochemistry.
Osteoblastoma. Nuclear expression of FOS in the osteoblastic cells.
A: FOS or FOSB
Q: Osteoblastoma
- Clinical: The most common presenting symptom of [...] is pain and swelling. NSAIDs do not typically provide pain relief.
- Micro: Histopathology of [...] shows a delicate network of haphazardly arranged trabeculae of woven bone lined by plump osteoblasts.
- Ancillary: FOS or FOSB rearrangements are detectable in the majority of [...] cases and can aid in confirming the diagnosis.
Reference Gallery:
Osteoblastoma. Axial CT of the cervical spine of a 9-year-old boy demonstrates a well-lineated lytic expansile lesion with areas of radiodensity and mineralization expanding the transverse process of C6.
Osteoblastoma. Radiograph showing a well-circumscribed oval lytic lesion with reactive sclerosis involving the lateral malleolus of the fibula in a 9-year-old boy.
Osteoblastoma. Low-power view. Note the well-defined border and absence of infiltrative growth.
Osteoblastoma. High-power view of an osteoblastoma composed of irregular trabeculae of woven bone rimmed by prominent osteoblasts, scattered osteoclasts, and intervening loose fibrovascular stroma.
Osteoblastoma. This epithelial osteoblastoma is composed of large epithelioid osteoblasts with abundant eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli.
Osteoblastoma. Nuclear expression of FOS in the osteoblastic cells.
A: osteoblastoma; osteoblastoma; osteoblastoma

Q: Radiographically and grossly, the defining hallmark of an osteochondroma is the direct continuity of the exophytic lesion's cortex and [...] with that of the underlying host bone.
Osteochondroma. An osteochondroma of the right distal femur in a 17-year-old boy. Lateral radiograph showing a pedunculated osteochondroma arising from the posterior aspect of the bone. The cortex and medulla of the lesion are continuous with those of the femur.
Osteochondroma. Cross-section through a pedunculated osteochondroma, disclosing the typical hyaline cartilaginous cap. Note the continuation with the medullary canal showing fatty marrow.
Osteochondroma. Frontal radiograph of the right knee. There is a pedunculated osteochondroma arising from the metadiaphyseal junction and projecting away from the epiphysis of the medial cortex of the left distal femur.
A: medullary cavity
Back Extra: Osteochondroma
- Clinical: Osteochondromas are usually found incidentally and symptoms are often size- and site-related. Radiographs show a bony mass, sessile or pedunculated, located at the diaphyseal-metaphyseal interface.
- Micro: The cartilage cap in osteochondromas mimics the growth plate, with disorganized endochondral ossification. The superficial chondrocytes are clustered, while those close to the bone interface become larger.
- Ancillary: Molecular analyses are not required for diagnosis, but osteochondromas are associated with biallelic inactivation of the EXT1 or EXT2 gene.
Reference Gallery:
Osteochondroma. An osteochondroma of the right distal femur in a 17-year-old boy. Lateral radiograph showing a pedunculated osteochondroma arising from the posterior aspect of the bone. The cortex and medulla of the lesion are continuous with those of the femur.
Osteochondroma. Fat-saturated proton density (PD)-weighted axial MRI through the superior aspect of the osteochondroma. The lesion contains fatty marrow (asterisk) with some oedema-like signal medially. A layer of hyperintensity is seen on the surface (arrows), consistent with a thin cartilage cap.
Osteochondroma. Classic bosselated, smooth appearance of the external surface. The tumour is covered by a translucent fibrous layer (perichondrium).
Osteochondroma. Cross-section through a pedunculated osteochondroma, disclosing the typical hyaline cartilaginous cap. Note the continuation with the medullary canal showing fatty marrow.
Osteochondroma. Hyaline cartilaginous cap composed of bland chondrocytes located in large empty lacunae, piling up at the base of the cap. Note the bone encasement at the base and the progressive chondrocyte maturation from the base to the top, with corresponding change of the matrix quality.
Osteochondroma. Frontal radiograph of the right knee. There is a pedunculated osteochondroma arising from the metadiaphyseal junction and projecting away from the epiphysis of the medial cortex of the left distal femur.

Q: Histologically, the hyaline cartilage cap of an osteochondroma morphologically mimics a normal growth plate by undergoing disorganized [...].
Osteochondroma. Hyaline cartilaginous cap composed of bland chondrocytes located in large empty lacunae, piling up at the base of the cap. Note the bone encasement at the base and the progressive chondrocyte maturation from the base to the top, with corresponding change of the matrix quality.
A: endochondral ossification
Back Extra: Osteochondroma
- Clinical: Osteochondromas are usually found incidentally and symptoms are often size- and site-related. Radiographs show a bony mass, sessile or pedunculated, located at the diaphyseal-metaphyseal interface.
- Micro: The cartilage cap in osteochondromas mimics the growth plate, with disorganized endochondral ossification. The superficial chondrocytes are clustered, while those close to the bone interface become larger.
- Ancillary: Molecular analyses are not required for diagnosis, but osteochondromas are associated with biallelic inactivation of the EXT1 or EXT2 gene.
Reference Gallery:
Osteochondroma. An osteochondroma of the right distal femur in a 17-year-old boy. Lateral radiograph showing a pedunculated osteochondroma arising from the posterior aspect of the bone. The cortex and medulla of the lesion are continuous with those of the femur.
Osteochondroma. Fat-saturated proton density (PD)-weighted axial MRI through the superior aspect of the osteochondroma. The lesion contains fatty marrow (asterisk) with some oedema-like signal medially. A layer of hyperintensity is seen on the surface (arrows), consistent with a thin cartilage cap.
Osteochondroma. Classic bosselated, smooth appearance of the external surface. The tumour is covered by a translucent fibrous layer (perichondrium).
Osteochondroma. Cross-section through a pedunculated osteochondroma, disclosing the typical hyaline cartilaginous cap. Note the continuation with the medullary canal showing fatty marrow.
Osteochondroma. Hyaline cartilaginous cap composed of bland chondrocytes located in large empty lacunae, piling up at the base of the cap. Note the bone encasement at the base and the progressive chondrocyte maturation from the base to the top, with corresponding change of the matrix quality.
Osteochondroma. Frontal radiograph of the right knee. There is a pedunculated osteochondroma arising from the metadiaphyseal junction and projecting away from the epiphysis of the medial cortex of the left distal femur.

Q: An osteochondroma is typically characterized by an outer hyaline layer that appears hyperintense on fluid-sensitive MRI and translucent on gross examination, known as the [...].
Osteochondroma. Fat-saturated proton density (PD)-weighted axial MRI through the superior aspect of the osteochondroma. The lesion contains fatty marrow (asterisk) with some oedema-like signal medially. A layer of hyperintensity is seen on the surface (arrows), consistent with a thin cartilage cap.
Osteochondroma. Classic bosselated, smooth appearance of the external surface. The tumour is covered by a translucent fibrous layer (perichondrium).
A: cartilage cap
Back Extra: Osteochondroma
- Clinical: Osteochondromas are usually found incidentally and symptoms are often size- and site-related. Radiographs show a bony mass, sessile or pedunculated, located at the diaphyseal-metaphyseal interface.
- Micro: The cartilage cap in osteochondromas mimics the growth plate, with disorganized endochondral ossification. The superficial chondrocytes are clustered, while those close to the bone interface become larger.
- Ancillary: Molecular analyses are not required for diagnosis, but osteochondromas are associated with biallelic inactivation of the EXT1 or EXT2 gene.
Reference Gallery:
Osteochondroma. An osteochondroma of the right distal femur in a 17-year-old boy. Lateral radiograph showing a pedunculated osteochondroma arising from the posterior aspect of the bone. The cortex and medulla of the lesion are continuous with those of the femur.
Osteochondroma. Fat-saturated proton density (PD)-weighted axial MRI through the superior aspect of the osteochondroma. The lesion contains fatty marrow (asterisk) with some oedema-like signal medially. A layer of hyperintensity is seen on the surface (arrows), consistent with a thin cartilage cap.
Osteochondroma. Classic bosselated, smooth appearance of the external surface. The tumour is covered by a translucent fibrous layer (perichondrium).
Osteochondroma. Cross-section through a pedunculated osteochondroma, disclosing the typical hyaline cartilaginous cap. Note the continuation with the medullary canal showing fatty marrow.
Osteochondroma. Hyaline cartilaginous cap composed of bland chondrocytes located in large empty lacunae, piling up at the base of the cap. Note the bone encasement at the base and the progressive chondrocyte maturation from the base to the top, with corresponding change of the matrix quality.
Osteochondroma. Frontal radiograph of the right knee. There is a pedunculated osteochondroma arising from the metadiaphyseal junction and projecting away from the epiphysis of the medial cortex of the left distal femur.

Q: Radiologically, Osteofibrous Dysplasia typically presents in the first two decades of life as an expansile, intracortical lesion primarily affecting the diaphysis of the [...] and/or fibula.
Osteofibrous dysplasia. Plain radiograph shows a mixed lytic and sclerotic lesion that is causing endosteal scalloping and cortical expansion of the proximal tibial diaphysis.
Osteofibrous dysplasia. Axial CT shows that the tumour is confined to the cortex of the tibia and surrounded by a rim of bone, without involvement of the medullary cavity or soft tissues.
Osteofibrous dysplasia. Axial T1 MRI demonstrates an expansile intracortical tumour causing cortical thinning, without periosteal reaction. There is no infiltration of the adjacent medullary cavity.
A: tibia
Back Extra: Osteofibrous Dysplasia
- Clinical: Osteofibrous dysplasia typically affects the first two decades of life, causing pain, swelling, or bowing deformity in the tibia and/or fibula.
- Micro: Osteofibrous dysplasia shows irregular trabeculae of woven bone with prominent osteoblastic rimming, surrounded by a fibrous stroma.
- Ancillary: FISH analysis in osteofibrous dysplasia can show trisomies of chromosomes 7, 8, and 12 in a minority of spindle-shaped cells, but these are not found in osteoblasts or osteoclasts.
Reference Gallery:
Osteofibrous dysplasia. Plain radiograph shows a mixed lytic and sclerotic lesion that is causing endosteal scalloping and cortical expansion of the proximal tibial diaphysis.
Osteofibrous dysplasia. Axial CT shows that the tumour is confined to the cortex of the tibia and surrounded by a rim of bone, without involvement of the medullary cavity or soft tissues.
Osteofibrous dysplasia. Axial T1 MRI demonstrates an expansile intracortical tumour causing cortical thinning, without periosteal reaction. There is no infiltration of the adjacent medullary cavity.
Osteofibrous dysplasia. Osteofibrous dysplasia composed of trabeculae of woven bone with osteoblastic rimming and fibrous tissue.
Osteofibrous dysplasia. Higher-power view of osteofibrous dysplasia demonstrating the woven bone with osteoblastic rimming, surrounded by spindle-shaped cells.
Osteofibrous dysplasia. Osteofibrous dysplasia shows single scattered keratin-positive stromal cells. Clusters of keratin-positive cells (as seen in osteofibrous dysplasia–like adamantinoma) are not seen.

Q: Histologically, Osteofibrous Dysplasia exhibits irregular trabeculae of woven bone surrounded by a fibrous stroma and characterized by prominent [...].
Osteofibrous dysplasia. Osteofibrous dysplasia composed of trabeculae of woven bone with osteoblastic rimming and fibrous tissue.
Osteofibrous dysplasia. Higher-power view of osteofibrous dysplasia demonstrating the woven bone with osteoblastic rimming, surrounded by spindle-shaped cells.
A: osteoblastic rimming
Back Extra: Osteofibrous Dysplasia
- Clinical: Osteofibrous dysplasia typically affects the first two decades of life, causing pain, swelling, or bowing deformity in the tibia and/or fibula.
- Micro: Osteofibrous dysplasia shows irregular trabeculae of woven bone with prominent osteoblastic rimming, surrounded by a fibrous stroma.
- Ancillary: FISH analysis in osteofibrous dysplasia can show trisomies of chromosomes 7, 8, and 12 in a minority of spindle-shaped cells, but these are not found in osteoblasts or osteoclasts.
Reference Gallery:
Osteofibrous dysplasia. Plain radiograph shows a mixed lytic and sclerotic lesion that is causing endosteal scalloping and cortical expansion of the proximal tibial diaphysis.
Osteofibrous dysplasia. Axial CT shows that the tumour is confined to the cortex of the tibia and surrounded by a rim of bone, without involvement of the medullary cavity or soft tissues.
Osteofibrous dysplasia. Axial T1 MRI demonstrates an expansile intracortical tumour causing cortical thinning, without periosteal reaction. There is no infiltration of the adjacent medullary cavity.
Osteofibrous dysplasia. Osteofibrous dysplasia composed of trabeculae of woven bone with osteoblastic rimming and fibrous tissue.
Osteofibrous dysplasia. Higher-power view of osteofibrous dysplasia demonstrating the woven bone with osteoblastic rimming, surrounded by spindle-shaped cells.
Osteofibrous dysplasia. Osteofibrous dysplasia shows single scattered keratin-positive stromal cells. Clusters of keratin-positive cells (as seen in osteofibrous dysplasia–like adamantinoma) are not seen.

Q: In Osteofibrous Dysplasia, immunohistochemical staining typically highlights single, scattered [...]-positive stromal cells, contrasting with the large cellular clusters seen in adamantinoma.
Osteofibrous dysplasia. Osteofibrous dysplasia shows single scattered keratin-positive stromal cells. Clusters of keratin-positive cells (as seen in osteofibrous dysplasia–like adamantinoma) are not seen.
A: keratin
Back Extra: Osteofibrous Dysplasia
- Clinical: Osteofibrous dysplasia typically affects the first two decades of life, causing pain, swelling, or bowing deformity in the tibia and/or fibula.
- Micro: Osteofibrous dysplasia shows irregular trabeculae of woven bone with prominent osteoblastic rimming, surrounded by a fibrous stroma.
- Ancillary: FISH analysis in osteofibrous dysplasia can show trisomies of chromosomes 7, 8, and 12 in a minority of spindle-shaped cells, but these are not found in osteoblasts or osteoclasts.
Reference Gallery:
Osteofibrous dysplasia. Plain radiograph shows a mixed lytic and sclerotic lesion that is causing endosteal scalloping and cortical expansion of the proximal tibial diaphysis.
Osteofibrous dysplasia. Axial CT shows that the tumour is confined to the cortex of the tibia and surrounded by a rim of bone, without involvement of the medullary cavity or soft tissues.
Osteofibrous dysplasia. Axial T1 MRI demonstrates an expansile intracortical tumour causing cortical thinning, without periosteal reaction. There is no infiltration of the adjacent medullary cavity.
Osteofibrous dysplasia. Osteofibrous dysplasia composed of trabeculae of woven bone with osteoblastic rimming and fibrous tissue.
Osteofibrous dysplasia. Higher-power view of osteofibrous dysplasia demonstrating the woven bone with osteoblastic rimming, surrounded by spindle-shaped cells.
Osteofibrous dysplasia. Osteofibrous dysplasia shows single scattered keratin-positive stromal cells. Clusters of keratin-positive cells (as seen in osteofibrous dysplasia–like adamantinoma) are not seen.

Q: Often presenting with nocturnal pain relieved by NSAIDs, an osteoid osteoma is characterized radiographically and histologically by a small, well-demarcated central core known as a(n) [...], which is typically surrounded by marked perilesional bone sclerosis.
Osteoid osteoma. Sagittal CT of the case shown in Fig. 18432 demonstrates a lytic intracortical lesion with marked perilesional sclerosis of the bone.
Osteoid osteoma. Low-power view showing a small intracortical and sharply demarcated nidus and surrounding sclerotic bone.
A: nidus
Q: Osteoid Osteoma
- Clinical: Osteoid osteoma typically presents with [...] that worsens at night and is often relieved by NSAIDs.
- Micro: The central portion (nidus) of the lesion contains [...] arranged around trabeculae of woven bone or osteoid.
- Ancillary: FOS gene rearrangement is a diagnostic marker found in osteoid osteoma and can be detected using [...].
Reference Gallery:
Osteoid osteoma. Lateral radiograph of the tibia of a 12-year-old boy with a history of intermittent pain. Diffuse fusiform cortical thickening and sclerosis of the tibial shaft can be seen.
Osteoid osteoma. Sagittal CT of the case shown in Fig. 18432 demonstrates a lytic intracortical lesion with marked perilesional sclerosis of the bone.
Osteoid osteoma. An intra-articular osteoid osteoma of the elbow in a 16-year-old boy who presented with local tenderness, swelling, and effusion in the elbow joint. Axial CT shows a small lucency with delicate and subtle central mineralization in the distal humerus.
Osteoid osteoma. Randomly arranged woven bone trabeculae lined by one or more layers of osteoblasts in a vascular background with osteoclast-like giant cells.
Osteoid osteoma. Low-power view showing a small intracortical and sharply demarcated nidus and surrounding sclerotic bone.
A: intermittent pain; plump osteoblasts; FOS N-terminus immunohistochemistry

Q: Microscopically, the central lesion of an osteoid osteoma consists of randomly arranged trabeculae of woven bone or osteoid lined by prominent [...] within a highly vascularized background.
Osteoid osteoma. Randomly arranged woven bone trabeculae lined by one or more layers of osteoblasts in a vascular background with osteoclast-like giant cells.
A: plump osteoblasts
Q: Osteoid Osteoma
- Clinical: Osteoid osteoma typically presents with [...] that worsens at night and is often relieved by NSAIDs.
- Micro: The central portion (nidus) of the lesion contains [...] arranged around trabeculae of woven bone or osteoid.
- Ancillary: FOS gene rearrangement is a diagnostic marker found in osteoid osteoma and can be detected using [...].
Reference Gallery:
Osteoid osteoma. Lateral radiograph of the tibia of a 12-year-old boy with a history of intermittent pain. Diffuse fusiform cortical thickening and sclerosis of the tibial shaft can be seen.
Osteoid osteoma. Sagittal CT of the case shown in Fig. 18432 demonstrates a lytic intracortical lesion with marked perilesional sclerosis of the bone.
Osteoid osteoma. An intra-articular osteoid osteoma of the elbow in a 16-year-old boy who presented with local tenderness, swelling, and effusion in the elbow joint. Axial CT shows a small lucency with delicate and subtle central mineralization in the distal humerus.
Osteoid osteoma. Randomly arranged woven bone trabeculae lined by one or more layers of osteoblasts in a vascular background with osteoclast-like giant cells.
Osteoid osteoma. Low-power view showing a small intracortical and sharply demarcated nidus and surrounding sclerotic bone.
A: intermittent pain; plump osteoblasts; FOS N-terminus immunohistochemistry

Q: The defining microscopic feature required for a diagnosis of conventional Osteosarcoma is the production of neoplastic [...] or immature bone by malignant, pleomorphic cells.
Conventional osteosarcoma. An H&E image shows an osteoblastic osteosarcoma composed of solid areas of osteoid with entrapped, deceptively bland-looking (so-called normalized) tumour cells. Note the pre-existing lamellar bone trabecula engulfed by the tumour.
Small cell osteosarcoma. Low-power H&E image showing a small cell osteosarcoma comprising small round cells and abundant lace-like osteoid.
A: osteoid
Back Extra: Osteosarcoma
- Clinical: Patients with osteosarcoma typically present with a painful mass that has been growing for several weeks or months. A pathological fracture through the mass is seen in about 15% of cases.
- Micro: Conventional osteosarcomas show neoplastic osteoid/bone production, marked pleomorphism, brisk mitotic activity, and abundant atypical mitotic figures.
- Ancillary: Immunohistochemical profiling has limited diagnostic value, but FOS immunostaining can help differentiate osteoblastic osteosarcomas from osteoblastomas.
Reference Gallery:
Conventional osteosarcoma with skip metastasis. T1-weighted MRI shows a distal femoral osteosarcoma and skip metastasis (arrow).
Conventional osteosarcoma with skip metastasis. A photograph of the posttherapy, resected tumour shows an intramedullary mass that circumferentially extends into the adjacent soft tissue, as well as skip lesions and minimal therapy-induced tumour necrosis.
Conventional osteosarcoma. An H&E image shows an osteoblastic osteosarcoma composed of solid areas of osteoid with entrapped, deceptively bland-looking (so-called normalized) tumour cells. Note the pre-existing lamellar bone trabecula engulfed by the tumour.
Conventional osteosarcoma. A gross photograph of a scapular chondroblastic osteosarcoma shows glistening grey-white cartilaginous areas.
Conventional osteosarcoma. An H&E image of a chondroblastic osteosarcoma shows malignant cartilaginous cells surrounded by a chondro-osseous matrix.
Telangiectatic osteosarcoma. T2-weighted axial MRI shows a multiloculated cystic mass with numerous fluid-fluid levels (arrows).
Telangiectatic osteosarcoma. An en bloc resection image shows an expansile haemorrhagic mass replacing the proximal femur and extending into the surrounding soft tissue.
Telangiectatic osteosarcoma. A low-power H&E image shows the aneurysmal bone cyst–like architecture of the tumour.
Telangiectatic osteosarcoma. A high-power H&E image reveals marked nuclear atypia of the tumour cells, atypical mitotic figures, and scattered multinucleated giant cells within the septa.
Conventional osteosarcoma. An H&E image shows a sclerosing osteosarcoma composed of poorly cellular, heavily mineralized, sheet-like osteoid occupying marrow spaces.
Small cell osteosarcoma. Low-power H&E image showing a small cell osteosarcoma comprising small round cells and abundant lace-like osteoid.
Small cell osteosarcoma. High-power H&E image showing a small cell osteosarcoma comprising small round cells and abundant lace-like osteoid.

Q: The telangiectatic variant of Osteosarcoma presents as a multiloculated, hemorrhagic mass with fluid-fluid levels on MRI; microscopically, it mimics an [...] but is distinguished by marked nuclear atypia within the septa.
Telangiectatic osteosarcoma. T2-weighted axial MRI shows a multiloculated cystic mass with numerous fluid-fluid levels (arrows).
Telangiectatic osteosarcoma. An en bloc resection image shows an expansile haemorrhagic mass replacing the proximal femur and extending into the surrounding soft tissue.
Telangiectatic osteosarcoma. A low-power H&E image shows the aneurysmal bone cyst–like architecture of the tumour.
A: aneurysmal bone cyst
Back Extra: Osteosarcoma
- Clinical: Patients with osteosarcoma typically present with a painful mass that has been growing for several weeks or months. A pathological fracture through the mass is seen in about 15% of cases.
- Micro: Conventional osteosarcomas show neoplastic osteoid/bone production, marked pleomorphism, brisk mitotic activity, and abundant atypical mitotic figures.
- Ancillary: Immunohistochemical profiling has limited diagnostic value, but FOS immunostaining can help differentiate osteoblastic osteosarcomas from osteoblastomas.
Reference Gallery:
Conventional osteosarcoma with skip metastasis. T1-weighted MRI shows a distal femoral osteosarcoma and skip metastasis (arrow).
Conventional osteosarcoma with skip metastasis. A photograph of the posttherapy, resected tumour shows an intramedullary mass that circumferentially extends into the adjacent soft tissue, as well as skip lesions and minimal therapy-induced tumour necrosis.
Conventional osteosarcoma. An H&E image shows an osteoblastic osteosarcoma composed of solid areas of osteoid with entrapped, deceptively bland-looking (so-called normalized) tumour cells. Note the pre-existing lamellar bone trabecula engulfed by the tumour.
Conventional osteosarcoma. A gross photograph of a scapular chondroblastic osteosarcoma shows glistening grey-white cartilaginous areas.
Conventional osteosarcoma. An H&E image of a chondroblastic osteosarcoma shows malignant cartilaginous cells surrounded by a chondro-osseous matrix.
Telangiectatic osteosarcoma. T2-weighted axial MRI shows a multiloculated cystic mass with numerous fluid-fluid levels (arrows).
Telangiectatic osteosarcoma. An en bloc resection image shows an expansile haemorrhagic mass replacing the proximal femur and extending into the surrounding soft tissue.
Telangiectatic osteosarcoma. A low-power H&E image shows the aneurysmal bone cyst–like architecture of the tumour.
Telangiectatic osteosarcoma. A high-power H&E image reveals marked nuclear atypia of the tumour cells, atypical mitotic figures, and scattered multinucleated giant cells within the septa.
Conventional osteosarcoma. An H&E image shows a sclerosing osteosarcoma composed of poorly cellular, heavily mineralized, sheet-like osteoid occupying marrow spaces.
Small cell osteosarcoma. Low-power H&E image showing a small cell osteosarcoma comprising small round cells and abundant lace-like osteoid.
Small cell osteosarcoma. High-power H&E image showing a small cell osteosarcoma comprising small round cells and abundant lace-like osteoid.

Q: When staging conventional Osteosarcoma, MRI is critical for detecting [...] metastases, which appear as distinct, separate medullary tumor foci within the same bone as the primary mass.
Conventional osteosarcoma with skip metastasis. T1-weighted MRI shows a distal femoral osteosarcoma and skip metastasis (arrow).
Conventional osteosarcoma with skip metastasis. A photograph of the posttherapy, resected tumour shows an intramedullary mass that circumferentially extends into the adjacent soft tissue, as well as skip lesions and minimal therapy-induced tumour necrosis.
A: skip
Back Extra: Osteosarcoma
- Clinical: Patients with osteosarcoma typically present with a painful mass that has been growing for several weeks or months. A pathological fracture through the mass is seen in about 15% of cases.
- Micro: Conventional osteosarcomas show neoplastic osteoid/bone production, marked pleomorphism, brisk mitotic activity, and abundant atypical mitotic figures.
- Ancillary: Immunohistochemical profiling has limited diagnostic value, but FOS immunostaining can help differentiate osteoblastic osteosarcomas from osteoblastomas.
Reference Gallery:
Conventional osteosarcoma with skip metastasis. T1-weighted MRI shows a distal femoral osteosarcoma and skip metastasis (arrow).
Conventional osteosarcoma with skip metastasis. A photograph of the posttherapy, resected tumour shows an intramedullary mass that circumferentially extends into the adjacent soft tissue, as well as skip lesions and minimal therapy-induced tumour necrosis.
Conventional osteosarcoma. An H&E image shows an osteoblastic osteosarcoma composed of solid areas of osteoid with entrapped, deceptively bland-looking (so-called normalized) tumour cells. Note the pre-existing lamellar bone trabecula engulfed by the tumour.
Conventional osteosarcoma. A gross photograph of a scapular chondroblastic osteosarcoma shows glistening grey-white cartilaginous areas.
Conventional osteosarcoma. An H&E image of a chondroblastic osteosarcoma shows malignant cartilaginous cells surrounded by a chondro-osseous matrix.
Telangiectatic osteosarcoma. T2-weighted axial MRI shows a multiloculated cystic mass with numerous fluid-fluid levels (arrows).
Telangiectatic osteosarcoma. An en bloc resection image shows an expansile haemorrhagic mass replacing the proximal femur and extending into the surrounding soft tissue.
Telangiectatic osteosarcoma. A low-power H&E image shows the aneurysmal bone cyst–like architecture of the tumour.
Telangiectatic osteosarcoma. A high-power H&E image reveals marked nuclear atypia of the tumour cells, atypical mitotic figures, and scattered multinucleated giant cells within the septa.
Conventional osteosarcoma. An H&E image shows a sclerosing osteosarcoma composed of poorly cellular, heavily mineralized, sheet-like osteoid occupying marrow spaces.
Small cell osteosarcoma. Low-power H&E image showing a small cell osteosarcoma comprising small round cells and abundant lace-like osteoid.
Small cell osteosarcoma. High-power H&E image showing a small cell osteosarcoma comprising small round cells and abundant lace-like osteoid.

Q: On radiograph, a fractured Simple Bone Cyst characteristically demonstrates the [...], which is highly suggestive of a hollow lesion.
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
A: fallen leaf sign
Back Extra: Simple Bone Cyst
- Clinical: Simple bone cysts typically present with pain, swelling, and limitation of motion, often in the proximal humerus or femur of pediatric patients.
- Micro: The cyst wall is composed of a thin layer of fibrous tissue with fibroblasts and small blood vessels, and may contain fibrin-like deposits and foamy histiocytes.
- Ancillary: MRI is useful in diagnosing simple bone cysts, showing bright T2-weighted signals.
Reference Gallery:
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.

Q: Microscopically, the wall of a Simple Bone Cyst consists of a thin layer of fibrous tissue frequently containing foamy histiocytes and [...].
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.
A: fibrin-like deposits
Back Extra: Simple Bone Cyst
- Clinical: Simple bone cysts typically present with pain, swelling, and limitation of motion, often in the proximal humerus or femur of pediatric patients.
- Micro: The cyst wall is composed of a thin layer of fibrous tissue with fibroblasts and small blood vessels, and may contain fibrin-like deposits and foamy histiocytes.
- Ancillary: MRI is useful in diagnosing simple bone cysts, showing bright T2-weighted signals.
Reference Gallery:
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.

Q: In a simple bone cyst complicated by a pathological fracture, X-rays classically reveal the [...].
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
A: fallen leaf sign
Back Extra: Simple Bone Cyst
- Clinical: Simple bone cysts often present with pain, swelling, limitation of motion, and pathological fractures, and are more common in males (M:F ratio 2:1).
- Micro: The cyst wall is composed of a thin layer of fibrous tissue containing fibroblasts, small blood vessels, and fibrin-like deposits that can calcify and ossify.
- Ancillary: MRI shows bright T2-weighted signals within the cyst, and X-rays may reveal the 'fallen leaf sign' in fractured lesions.
Reference Gallery:
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.

Q: Microscopically, the fibrous wall of a simple bone cyst frequently contains [...] that have a tendency to calcify and ossify.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
A: fibrin-like deposits
Back Extra: Simple Bone Cyst
- Clinical: Simple bone cysts often present with pain, swelling, limitation of motion, and pathological fractures, and are more common in males (M:F ratio 2:1).
- Micro: The cyst wall is composed of a thin layer of fibrous tissue containing fibroblasts, small blood vessels, and fibrin-like deposits that can calcify and ossify.
- Ancillary: MRI shows bright T2-weighted signals within the cyst, and X-rays may reveal the 'fallen leaf sign' in fractured lesions.
Reference Gallery:
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.

Q: A [...] classically presents as a hollow bone lesion that is bright on T2-weighted MRI and lined by a thin layer of fibrous tissue lacking a true epithelial lining.
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
A: simple bone cyst
Back Extra: Simple Bone Cyst
- Clinical: Simple bone cysts often present with pain, swelling, limitation of motion, and pathological fractures, and are more common in males (M:F ratio 2:1).
- Micro: The cyst wall is composed of a thin layer of fibrous tissue containing fibroblasts, small blood vessels, and fibrin-like deposits that can calcify and ossify.
- Ancillary: MRI shows bright T2-weighted signals within the cyst, and X-rays may reveal the 'fallen leaf sign' in fractured lesions.
Reference Gallery:
Simple bone cyst. X-ray demonstrating the fallen leaf sign of a fractured lesion, which when present is highly suggestive of a hollow lesion.
Simple bone cyst. The contents of the cyst are bright on T2-weighted MRI.
Simple bone cyst. The lining is composed of a thin layer of fibrous tissue containing fibroblasts and small blood vessels.
Simple bone cyst. Fibrin-like deposits are commonly found in the cyst wall.
Simple bone cyst. The fibrin-like deposits in the wall can calcify and ossify.
Simple bone cyst. Foci of foamy histiocytes are commonly found in the cyst wall.

Q: The characteristic histologic appearance of Subungual Exostosis features a thin cap of hyaline cartilage and fibrocartilage with underlying [...] ossification.
Subungual exostosis. Characteristically, a hyaline cartilaginous cap is present with underlying enchondral ossification.
Subungual exostosis. Fibrocartilage with myxoid stroma and underlying enchondral ossification is frequently present. Overlying epidermis may be seen.
A: enchondral
Back Extra: Subungual Exostosis
- Clinical: Subungual exostosis presents as a painful subungual lesion, often with nail erosion and can lead to ulceration and infection.
- Micro: Characterized by a central core of trabecular bone surrounded by a thin cap of hyaline cartilage and fibrocartilage, with underlying enchondral ossification.
- Ancillary: A recurrent chromosomal translocation, t(X;6)(q24-q26;q15-q21), is often the only change and is associated with increased expression of the IRS4 gene.
Reference Gallery:
Subungual exostosis. Characteristically, a hyaline cartilaginous cap is present with underlying enchondral ossification.
Subungual exostosis. Fibrocartilage with myxoid stroma and underlying enchondral ossification is frequently present. Overlying epidermis may be seen.
Subungual exostosis. A mature osseous mass, with a soft tissue mass surrounding it, is attached on the cortex of the distal phalanx.

Q: Subungual Exostosis typically presents as a mature osseous mass that is physically attached to the cortex of the [...].
Subungual exostosis. A mature osseous mass, with a soft tissue mass surrounding it, is attached on the cortex of the distal phalanx.
A: distal phalanx
Back Extra: Subungual Exostosis
- Clinical: Subungual exostosis presents as a painful subungual lesion, often with nail erosion and can lead to ulceration and infection.
- Micro: Characterized by a central core of trabecular bone surrounded by a thin cap of hyaline cartilage and fibrocartilage, with underlying enchondral ossification.
- Ancillary: A recurrent chromosomal translocation, t(X;6)(q24-q26;q15-q21), is often the only change and is associated with increased expression of the IRS4 gene.
Reference Gallery:
Subungual exostosis. Characteristically, a hyaline cartilaginous cap is present with underlying enchondral ossification.
Subungual exostosis. Fibrocartilage with myxoid stroma and underlying enchondral ossification is frequently present. Overlying epidermis may be seen.
Subungual exostosis. A mature osseous mass, with a soft tissue mass surrounding it, is attached on the cortex of the distal phalanx.

Q: In Vascular Tumours of Bone, the malignant subtype known as [...] is characterized microscopically by cords and nests of epithelioid cells within a myxohyaline or sclerotic stroma lacking vasoformation.
Epithelioid haemangioendothelioma of bone. The tumour consists of cords of epithelioid cells with eosinophilic cytoplasm, some containing clear vacuoles, in a sclerotic stroma.
A: epithelioid hemangioendothelioma
Back Extra: Vascular Tumours of Bone
- Clinical: Haemangiomas in children are usually symptomatic and manifest with pain and pathological fracture; tumours in the axial skeleton may cause neurological symptoms.
- Micro: Epithelioid haemangioendothelioma (EHE) is characterized by cords and nests of epithelioid cells within a myxohyaline or sclerotic stroma lacking vasoformation.
- Ancillary: 90% of Epithelioid haemangioendothelioma (EHE) cases harbour the recurrent t(1;3)(p36;q25) translocation, resulting in a WWTR1::CAMTA1 fusion.
Reference Gallery:
Haemangioma of bone. Coronal reformatted CT of a haemangioma involving two adjacent vertebral bodies in a 10-year-old child. The lesions are lytic and sclerotic and the superior vertebra has undergone a pathological compression fracture.
Haemangioma of bone. A tumour composed of cavernous, thin-walled, capillary-like spaces that are distended with blood. The vessels replace the marrow, and the pre-existing bone is preserved.
Epithelioid haemangioma of bone. Proton density (PD)-weighted MRI showing nodules of epithelioid haemangioma in the distal tibia and talus, manifesting as multiple round masses with heterogeneous signal intensity.
Epithelioid haemangioma of bone. Well-formed vessels lined by prominent epithelioid endothelial cells characterize epithelioid haemangioma.
Epithelioid haemangioma of bone. Tumour cells show strong nuclear immunohistochemical staining for FOSB.
Epithelioid haemangioendothelioma of bone. Tumour cells show strong nuclear immunohistochemical staining for CAMTA1.
Epithelioid haemangioendothelioma of bone with YAP1::TFE3 gene fusion. Large tumour cells have voluminous eosinophilic cytoplasm.
Epithelioid haemangioendothelioma of bone with YAP1::TFE3 gene fusion. Diffuse and strong immunoreactivity for TFE3.
Epithelioid haemangioendothelioma of bone. The tumour consists of cords of epithelioid cells with eosinophilic cytoplasm, some containing clear vacuoles, in a sclerotic stroma.

Q: Within the category of Vascular Tumours of Bone, up to 90% of epithelioid hemangioendothelioma (EHE) cases harbor a recurrent t(1;3)(p36;q25) translocation that results in a [CAMTA1] gene fusion, which can be confirmed with nuclear immunohistochemistry.
Epithelioid haemangioendothelioma of bone. Tumour cells show strong nuclear immunohistochemical staining for CAMTA1.
A: WWTR1
Back Extra: Vascular Tumours of Bone
- Clinical: Haemangiomas in children are usually symptomatic and manifest with pain and pathological fracture; tumours in the axial skeleton may cause neurological symptoms.
- Micro: Epithelioid haemangioendothelioma (EHE) is characterized by cords and nests of epithelioid cells within a myxohyaline or sclerotic stroma lacking vasoformation.
- Ancillary: 90% of Epithelioid haemangioendothelioma (EHE) cases harbour the recurrent t(1;3)(p36;q25) translocation, resulting in a WWTR1::CAMTA1 fusion.
Reference Gallery:
Haemangioma of bone. Coronal reformatted CT of a haemangioma involving two adjacent vertebral bodies in a 10-year-old child. The lesions are lytic and sclerotic and the superior vertebra has undergone a pathological compression fracture.
Haemangioma of bone. A tumour composed of cavernous, thin-walled, capillary-like spaces that are distended with blood. The vessels replace the marrow, and the pre-existing bone is preserved.
Epithelioid haemangioma of bone. Proton density (PD)-weighted MRI showing nodules of epithelioid haemangioma in the distal tibia and talus, manifesting as multiple round masses with heterogeneous signal intensity.
Epithelioid haemangioma of bone. Well-formed vessels lined by prominent epithelioid endothelial cells characterize epithelioid haemangioma.
Epithelioid haemangioma of bone. Tumour cells show strong nuclear immunohistochemical staining for FOSB.
Epithelioid haemangioendothelioma of bone. Tumour cells show strong nuclear immunohistochemical staining for CAMTA1.
Epithelioid haemangioendothelioma of bone with YAP1::TFE3 gene fusion. Large tumour cells have voluminous eosinophilic cytoplasm.
Epithelioid haemangioendothelioma of bone with YAP1::TFE3 gene fusion. Diffuse and strong immunoreactivity for TFE3.
Epithelioid haemangioendothelioma of bone. The tumour consists of cords of epithelioid cells with eosinophilic cytoplasm, some containing clear vacuoles, in a sclerotic stroma.

Q: When evaluating Vascular Tumours of Bone, childhood [...] in the axial skeleton frequently manifest with pain and pathological compression fractures, demonstrating a mix of lytic and sclerotic changes on imaging.
Haemangioma of bone. Coronal reformatted CT of a haemangioma involving two adjacent vertebral bodies in a 10-year-old child. The lesions are lytic and sclerotic and the superior vertebra has undergone a pathological compression fracture.
Haemangioma of bone. A tumour composed of cavernous, thin-walled, capillary-like spaces that are distended with blood. The vessels replace the marrow, and the pre-existing bone is preserved.
A: hemangiomas
Back Extra: Vascular Tumours of Bone
- Clinical: Haemangiomas in children are usually symptomatic and manifest with pain and pathological fracture; tumours in the axial skeleton may cause neurological symptoms.
- Micro: Epithelioid haemangioendothelioma (EHE) is characterized by cords and nests of epithelioid cells within a myxohyaline or sclerotic stroma lacking vasoformation.
- Ancillary: 90% of Epithelioid haemangioendothelioma (EHE) cases harbour the recurrent t(1;3)(p36;q25) translocation, resulting in a WWTR1::CAMTA1 fusion.
Reference Gallery:
Haemangioma of bone. Coronal reformatted CT of a haemangioma involving two adjacent vertebral bodies in a 10-year-old child. The lesions are lytic and sclerotic and the superior vertebra has undergone a pathological compression fracture.
Haemangioma of bone. A tumour composed of cavernous, thin-walled, capillary-like spaces that are distended with blood. The vessels replace the marrow, and the pre-existing bone is preserved.
Epithelioid haemangioma of bone. Proton density (PD)-weighted MRI showing nodules of epithelioid haemangioma in the distal tibia and talus, manifesting as multiple round masses with heterogeneous signal intensity.
Epithelioid haemangioma of bone. Well-formed vessels lined by prominent epithelioid endothelial cells characterize epithelioid haemangioma.
Epithelioid haemangioma of bone. Tumour cells show strong nuclear immunohistochemical staining for FOSB.
Epithelioid haemangioendothelioma of bone. Tumour cells show strong nuclear immunohistochemical staining for CAMTA1.
Epithelioid haemangioendothelioma of bone with YAP1::TFE3 gene fusion. Large tumour cells have voluminous eosinophilic cytoplasm.
Epithelioid haemangioendothelioma of bone with YAP1::TFE3 gene fusion. Diffuse and strong immunoreactivity for TFE3.
Epithelioid haemangioendothelioma of bone. The tumour consists of cords of epithelioid cells with eosinophilic cytoplasm, some containing clear vacuoles, in a sclerotic stroma.

Q: In Alveolar Soft Part Sarcoma, the classic histologic appearance in older children and adults consists of large, polygonal cells with abundant eosinophilic granular cytoplasm arranged in a distinct [...] growth pattern.
Alveolar soft part sarcoma. The alveolar pattern is frequent in older children and young adults. It is usually intramuscular and occurs in the buttocks and thighs.
Alveolar soft part sarcoma. Higher-power view of the alveolar pattern, which is frequent in older children and young adults. It is usually intramuscular and occurs in the buttocks and thighs.
A: alveolar
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) is a rare tumour that typically presents as a slow-growing, painless, intramuscular mass, often in the extremities, with a median age of 25 years and a female predominance.
- Micro: ASPS is characterized by large polygonal cells with eosinophilic granular cytoplasm, an eccentric vesicular nucleus, and a prominent nucleolus, arranged in an alveolar pattern. Rod-like intracytoplasmic crystalline structures may be identified by PAS with diastase resistance.
- Ancillary: The presence of the ASPSCR1::TFE3 fusion, detected by molecular studies, is highly specific and sensitive for ASPS and can help distinguish it from other TFE3-rearranged sarcomas.
Reference Gallery:
Alveolar soft part sarcoma. Solid pattern of growth in the tongue, typical in younger children.
Alveolar soft part sarcoma. Higher-power view of the solid pattern of growth in the tongue, typical in younger children.
Alveolar soft part sarcoma. The alveolar pattern is frequent in older children and young adults. It is usually intramuscular and occurs in the buttocks and thighs.
Alveolar soft part sarcoma. Higher-power view of the alveolar pattern, which is frequent in older children and young adults. It is usually intramuscular and occurs in the buttocks and thighs.
Alveolar soft part sarcoma. Non–fat-suppressed T2-weighted sagittal MRI showing a lobulated hyperintense mass within the leg muscle, with characteristic vascular signal voids at the superior and inferior poles of the mass.
Alveolar soft part sarcoma. Contrast-enhanced fat-suppressed T1-weighted sagittal MRI. The mass within the leg muscle shows heterogeneous enhancement.

Q: In younger children, Alveolar Soft Part Sarcoma frequently arises in the head and neck region (particularly the tongue) and typically exhibits a [...] histologic growth pattern rather than the typical nested architecture.
Alveolar soft part sarcoma. Solid pattern of growth in the tongue, typical in younger children.
Alveolar soft part sarcoma. Higher-power view of the solid pattern of growth in the tongue, typical in younger children.
A: solid
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) is a rare tumour that typically presents as a slow-growing, painless, intramuscular mass, often in the extremities, with a median age of 25 years and a female predominance.
- Micro: ASPS is characterized by large polygonal cells with eosinophilic granular cytoplasm, an eccentric vesicular nucleus, and a prominent nucleolus, arranged in an alveolar pattern. Rod-like intracytoplasmic crystalline structures may be identified by PAS with diastase resistance.
- Ancillary: The presence of the ASPSCR1::TFE3 fusion, detected by molecular studies, is highly specific and sensitive for ASPS and can help distinguish it from other TFE3-rearranged sarcomas.
Reference Gallery:
Alveolar soft part sarcoma. Solid pattern of growth in the tongue, typical in younger children.
Alveolar soft part sarcoma. Higher-power view of the solid pattern of growth in the tongue, typical in younger children.
Alveolar soft part sarcoma. The alveolar pattern is frequent in older children and young adults. It is usually intramuscular and occurs in the buttocks and thighs.
Alveolar soft part sarcoma. Higher-power view of the alveolar pattern, which is frequent in older children and young adults. It is usually intramuscular and occurs in the buttocks and thighs.
Alveolar soft part sarcoma. Non–fat-suppressed T2-weighted sagittal MRI showing a lobulated hyperintense mass within the leg muscle, with characteristic vascular signal voids at the superior and inferior poles of the mass.
Alveolar soft part sarcoma. Contrast-enhanced fat-suppressed T1-weighted sagittal MRI. The mass within the leg muscle shows heterogeneous enhancement.

Q: Radiologically, Alveolar Soft Part Sarcoma often presents as a hyperintense intramuscular mass on T2-weighted MRI with characteristic [...] at the poles of the mass due to its rich blood supply.
Alveolar soft part sarcoma. Non–fat-suppressed T2-weighted sagittal MRI showing a lobulated hyperintense mass within the leg muscle, with characteristic vascular signal voids at the superior and inferior poles of the mass.
Alveolar soft part sarcoma. Contrast-enhanced fat-suppressed T1-weighted sagittal MRI. The mass within the leg muscle shows heterogeneous enhancement.
A: vascular signal voids
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) is a rare tumour that typically presents as a slow-growing, painless, intramuscular mass, often in the extremities, with a median age of 25 years and a female predominance.
- Micro: ASPS is characterized by large polygonal cells with eosinophilic granular cytoplasm, an eccentric vesicular nucleus, and a prominent nucleolus, arranged in an alveolar pattern. Rod-like intracytoplasmic crystalline structures may be identified by PAS with diastase resistance.
- Ancillary: The presence of the ASPSCR1::TFE3 fusion, detected by molecular studies, is highly specific and sensitive for ASPS and can help distinguish it from other TFE3-rearranged sarcomas.
Reference Gallery:
Alveolar soft part sarcoma. Solid pattern of growth in the tongue, typical in younger children.
Alveolar soft part sarcoma. Higher-power view of the solid pattern of growth in the tongue, typical in younger children.
Alveolar soft part sarcoma. The alveolar pattern is frequent in older children and young adults. It is usually intramuscular and occurs in the buttocks and thighs.
Alveolar soft part sarcoma. Higher-power view of the alveolar pattern, which is frequent in older children and young adults. It is usually intramuscular and occurs in the buttocks and thighs.
Alveolar soft part sarcoma. Non–fat-suppressed T2-weighted sagittal MRI showing a lobulated hyperintense mass within the leg muscle, with characteristic vascular signal voids at the superior and inferior poles of the mass.
Alveolar soft part sarcoma. Contrast-enhanced fat-suppressed T1-weighted sagittal MRI. The mass within the leg muscle shows heterogeneous enhancement.

Q: Histologically, Angiomatoid Fibrous Histiocytoma is characterized by nodules of epithelioid to spindled cells, blood-filled pseudoangiomatous spaces, and a thick fibrous pseudocapsule with a prominent peripheral [...].
Angiomatoid fibrous histiocytoma. A well-circumscribed, multinodular tumour composed of fibrohistiocytic cells with a peripheral rim of lymphoid tissue resembling a metastatic lymph node deposit.
Angiomatoid fibrous histiocytoma. A central haemorrhagic cystic cavity surrounded fibrohistiocytic cells and associated with peripheral lymphoid aggregates.
A: lymphoplasmacytic cuff
Back Extra: Angiomatoid Fibrous Histiocytoma
- Clinical: Angiomatoid fibrous histiocytoma typically presents as a superficial, painless, slow-growing, and variably fluctuant soft tissue mass in children and young adults.
- Micro: The tumour is characterized by sheets or fascicles of spindled or histiocytic-like cells arranged in nodules, pseudoangiomatous spaces, and a thick fibrous pseudocapsule with lymphoplasmacytic cell cuff.
- Ancillary: Immunohistochemistry often shows positivity for SOX9 and desmin, and molecular testing reveals EWSR1::CREB1, EWSR1::ATF1, or FUS::ATF1 fusions.
Reference Gallery:
Angiomatoid fibrous histiocytoma. A well-circumscribed, multinodular tumour composed of fibrohistiocytic cells with a peripheral rim of lymphoid tissue resembling a metastatic lymph node deposit.
Angiomatoid fibrous histiocytoma. A central haemorrhagic cystic cavity surrounded fibrohistiocytic cells and associated with peripheral lymphoid aggregates.
Angiomatoid fibrous histiocytoma. A nodular tumour with adjacent lymphoid aggregates.
Angiomatoid fibrous histiocytoma. A solid nodule of epithelioid spindle cells in a syncytial pattern, with a lymphoid aggregate.
Angiomatoid fibrous histiocytoma. Tumour cells arranged in cords within a myxoid stroma.
Angiomatoid fibrous histiocytoma. Epithelioid to spindle-shaped tumour cells displaying mild nuclear pleomorphism.
Angiomatoid fibrous histiocytoma. Marked desmin immunopositivity.
Angiomatoid fibrous histiocytoma. Tumour cells displaying EWSR1 gene rearrangement in the form of single red-green split signals.

Q: Immunohistochemical staining in Angiomatoid Fibrous Histiocytoma characteristically shows positivity for SOX9 and [...].
Angiomatoid fibrous histiocytoma. Marked desmin immunopositivity.
A: desmin
Back Extra: Angiomatoid Fibrous Histiocytoma
- Clinical: Angiomatoid fibrous histiocytoma typically presents as a superficial, painless, slow-growing, and variably fluctuant soft tissue mass in children and young adults.
- Micro: The tumour is characterized by sheets or fascicles of spindled or histiocytic-like cells arranged in nodules, pseudoangiomatous spaces, and a thick fibrous pseudocapsule with lymphoplasmacytic cell cuff.
- Ancillary: Immunohistochemistry often shows positivity for SOX9 and desmin, and molecular testing reveals EWSR1::CREB1, EWSR1::ATF1, or FUS::ATF1 fusions.
Reference Gallery:
Angiomatoid fibrous histiocytoma. A well-circumscribed, multinodular tumour composed of fibrohistiocytic cells with a peripheral rim of lymphoid tissue resembling a metastatic lymph node deposit.
Angiomatoid fibrous histiocytoma. A central haemorrhagic cystic cavity surrounded fibrohistiocytic cells and associated with peripheral lymphoid aggregates.
Angiomatoid fibrous histiocytoma. A nodular tumour with adjacent lymphoid aggregates.
Angiomatoid fibrous histiocytoma. A solid nodule of epithelioid spindle cells in a syncytial pattern, with a lymphoid aggregate.
Angiomatoid fibrous histiocytoma. Tumour cells arranged in cords within a myxoid stroma.
Angiomatoid fibrous histiocytoma. Epithelioid to spindle-shaped tumour cells displaying mild nuclear pleomorphism.
Angiomatoid fibrous histiocytoma. Marked desmin immunopositivity.
Angiomatoid fibrous histiocytoma. Tumour cells displaying EWSR1 gene rearrangement in the form of single red-green split signals.

Q: Molecular testing in Angiomatoid Fibrous Histiocytoma typically demonstrates gene fusions involving CREB1 or ATF1, most commonly partnered with the [...] gene.
Angiomatoid fibrous histiocytoma. Tumour cells displaying EWSR1 gene rearrangement in the form of single red-green split signals.
A: EWSR1
Back Extra: Angiomatoid Fibrous Histiocytoma
- Clinical: Angiomatoid fibrous histiocytoma typically presents as a superficial, painless, slow-growing, and variably fluctuant soft tissue mass in children and young adults.
- Micro: The tumour is characterized by sheets or fascicles of spindled or histiocytic-like cells arranged in nodules, pseudoangiomatous spaces, and a thick fibrous pseudocapsule with lymphoplasmacytic cell cuff.
- Ancillary: Immunohistochemistry often shows positivity for SOX9 and desmin, and molecular testing reveals EWSR1::CREB1, EWSR1::ATF1, or FUS::ATF1 fusions.
Reference Gallery:
Angiomatoid fibrous histiocytoma. A well-circumscribed, multinodular tumour composed of fibrohistiocytic cells with a peripheral rim of lymphoid tissue resembling a metastatic lymph node deposit.
Angiomatoid fibrous histiocytoma. A central haemorrhagic cystic cavity surrounded fibrohistiocytic cells and associated with peripheral lymphoid aggregates.
Angiomatoid fibrous histiocytoma. A nodular tumour with adjacent lymphoid aggregates.
Angiomatoid fibrous histiocytoma. A solid nodule of epithelioid spindle cells in a syncytial pattern, with a lymphoid aggregate.
Angiomatoid fibrous histiocytoma. Tumour cells arranged in cords within a myxoid stroma.
Angiomatoid fibrous histiocytoma. Epithelioid to spindle-shaped tumour cells displaying mild nuclear pleomorphism.
Angiomatoid fibrous histiocytoma. Marked desmin immunopositivity.
Angiomatoid fibrous histiocytoma. Tumour cells displaying EWSR1 gene rearrangement in the form of single red-green split signals.

Q: In typical cutaneous Fibrous Histiocytoma, the peripheral border classically demonstrates [...] at the advancing edge, often accompanied by overlying epidermal hyperplasia.
Fibrous histiocytoma. Epidermal hyperplasia overlying the tumour, with sparing of the papillary dermis.
Fibrous histiocytoma. The tumour is characterized by a cellular proliferation of short spindled cells arranged in a haphazard manner.
Fibrous histiocytoma. Peripheral border of fibrous histiocytoma demonstrating entrapment of collagen.
A: entrapment of collagen
Back Extra: Fibrous Histiocytoma
- Clinical: Cutaneous fibrous histiocytomas (dermatofibromas) are typically elevated, red-brown or blue-black lesions, often < 10 mm in diameter.
- Micro: Aneurysmal fibrous histiocytoma is characterized by variably sized areas of haemorrhage and pseudovascular spaces lined by lesional cells.
- Ancillary: ALK gene rearrangement is frequently seen in epithelioid fibrous histiocytoma, making it a key diagnostic marker.
Reference Gallery:
Fibrous histiocytoma. Epidermal hyperplasia overlying the tumour, with sparing of the papillary dermis.
Fibrous histiocytoma. The tumour is characterized by a cellular proliferation of short spindled cells arranged in a haphazard manner.
Fibrous histiocytoma. Peripheral border of fibrous histiocytoma demonstrating entrapment of collagen.
Cellular fibrous histiocytoma. The distinctive feature of this subtype is a highly cellular proliferation of myofibroblast-like spindle cells forming a fascicular growth pattern.
Aneurysmal fibrous histiocytoma. This entity is characterized by variably sized areas of haemorrhage within the tumour.
Aneurysmal fibrous histiocytoma. Pseudovascular spaces are lined by the lesional cells. Note the background proliferation of fibroblasts and histiocytes as well as the deposition of haemosiderin pigment.
Atypical fibrous histiocytoma. In addition to the storiform proliferation with collagen trapping, numerous atypical tumour cells can be appreciated throughout the lesion.
Atypical fibrous histiocytoma. The hallmark of the entity is bizarre pleomorphic tumour cells. An atypical mitotic figure is seen near the centre of the image.
Deep fibrous histiocytoma. This example developed within the skeletal muscle.
Deep fibrous histiocytoma. Higher magnification reveals a fairly dense spindle cell tumour, with a vague storiform growth pattern, infiltrating the skeletal muscle.
Epithelioid fibrous histiocytoma. This tumour often manifests as a polypoid growth with an epidermal collarette frequently extending along the base of the lesion.
Epithelioid fibrous histiocytoma. The majority of tumours show diffuse cytoplasmic ALK positivity.

Q: The aneurysmal variant of Fibrous Histiocytoma is characterized microscopically by variably sized areas of hemorrhage and [...] that are lined by the lesional spindle cells rather than true endothelium.
Aneurysmal fibrous histiocytoma. This entity is characterized by variably sized areas of haemorrhage within the tumour.
Aneurysmal fibrous histiocytoma. Pseudovascular spaces are lined by the lesional cells. Note the background proliferation of fibroblasts and histiocytes as well as the deposition of haemosiderin pigment.
A: pseudovascular spaces
Back Extra: Fibrous Histiocytoma
- Clinical: Cutaneous fibrous histiocytomas (dermatofibromas) are typically elevated, red-brown or blue-black lesions, often < 10 mm in diameter.
- Micro: Aneurysmal fibrous histiocytoma is characterized by variably sized areas of haemorrhage and pseudovascular spaces lined by lesional cells.
- Ancillary: ALK gene rearrangement is frequently seen in epithelioid fibrous histiocytoma, making it a key diagnostic marker.
Reference Gallery:
Fibrous histiocytoma. Epidermal hyperplasia overlying the tumour, with sparing of the papillary dermis.
Fibrous histiocytoma. The tumour is characterized by a cellular proliferation of short spindled cells arranged in a haphazard manner.
Fibrous histiocytoma. Peripheral border of fibrous histiocytoma demonstrating entrapment of collagen.
Cellular fibrous histiocytoma. The distinctive feature of this subtype is a highly cellular proliferation of myofibroblast-like spindle cells forming a fascicular growth pattern.
Aneurysmal fibrous histiocytoma. This entity is characterized by variably sized areas of haemorrhage within the tumour.
Aneurysmal fibrous histiocytoma. Pseudovascular spaces are lined by the lesional cells. Note the background proliferation of fibroblasts and histiocytes as well as the deposition of haemosiderin pigment.
Atypical fibrous histiocytoma. In addition to the storiform proliferation with collagen trapping, numerous atypical tumour cells can be appreciated throughout the lesion.
Atypical fibrous histiocytoma. The hallmark of the entity is bizarre pleomorphic tumour cells. An atypical mitotic figure is seen near the centre of the image.
Deep fibrous histiocytoma. This example developed within the skeletal muscle.
Deep fibrous histiocytoma. Higher magnification reveals a fairly dense spindle cell tumour, with a vague storiform growth pattern, infiltrating the skeletal muscle.
Epithelioid fibrous histiocytoma. This tumour often manifests as a polypoid growth with an epidermal collarette frequently extending along the base of the lesion.
Epithelioid fibrous histiocytoma. The majority of tumours show diffuse cytoplasmic ALK positivity.

Q: The epithelioid variant of Fibrous Histiocytoma frequently harbors a specific gene rearrangement, rendering the tumor diffusely positive for [...] on immunohistochemistry.
Epithelioid fibrous histiocytoma. This tumour often manifests as a polypoid growth with an epidermal collarette frequently extending along the base of the lesion.
Epithelioid fibrous histiocytoma. The majority of tumours show diffuse cytoplasmic ALK positivity.
A: ALK
Back Extra: Fibrous Histiocytoma
- Clinical: Cutaneous fibrous histiocytomas (dermatofibromas) are typically elevated, red-brown or blue-black lesions, often < 10 mm in diameter.
- Micro: Aneurysmal fibrous histiocytoma is characterized by variably sized areas of haemorrhage and pseudovascular spaces lined by lesional cells.
- Ancillary: ALK gene rearrangement is frequently seen in epithelioid fibrous histiocytoma, making it a key diagnostic marker.
Reference Gallery:
Fibrous histiocytoma. Epidermal hyperplasia overlying the tumour, with sparing of the papillary dermis.
Fibrous histiocytoma. The tumour is characterized by a cellular proliferation of short spindled cells arranged in a haphazard manner.
Fibrous histiocytoma. Peripheral border of fibrous histiocytoma demonstrating entrapment of collagen.
Cellular fibrous histiocytoma. The distinctive feature of this subtype is a highly cellular proliferation of myofibroblast-like spindle cells forming a fascicular growth pattern.
Aneurysmal fibrous histiocytoma. This entity is characterized by variably sized areas of haemorrhage within the tumour.
Aneurysmal fibrous histiocytoma. Pseudovascular spaces are lined by the lesional cells. Note the background proliferation of fibroblasts and histiocytes as well as the deposition of haemosiderin pigment.
Atypical fibrous histiocytoma. In addition to the storiform proliferation with collagen trapping, numerous atypical tumour cells can be appreciated throughout the lesion.
Atypical fibrous histiocytoma. The hallmark of the entity is bizarre pleomorphic tumour cells. An atypical mitotic figure is seen near the centre of the image.
Deep fibrous histiocytoma. This example developed within the skeletal muscle.
Deep fibrous histiocytoma. Higher magnification reveals a fairly dense spindle cell tumour, with a vague storiform growth pattern, infiltrating the skeletal muscle.
Epithelioid fibrous histiocytoma. This tumour often manifests as a polypoid growth with an epidermal collarette frequently extending along the base of the lesion.
Epithelioid fibrous histiocytoma. The majority of tumours show diffuse cytoplasmic ALK positivity.

Q: Microscopically, Fibrous Histiocytoma consists of a haphazard proliferation of short spindle cells that characteristically demonstrates peripheral [...].
Fibrous histiocytoma. The tumour is characterized by a cellular proliferation of short spindled cells arranged in a haphazard manner.
Fibrous histiocytoma. Peripheral border of fibrous histiocytoma demonstrating entrapment of collagen.
A: collagen trapping
Back Extra: Fibrous Histiocytoma
- Clinical: Cutaneous fibrous histiocytomas (dermatofibromas) are elevated, red-brown or blue-black lesions < 10 mm to a few centimetres in diameter.
- Micro: Fibrous histiocytomas are composed of short spindle cells arranged in a haphazard manner, often with collagen trapping at the periphery.
- Ancillary: For epithelioid fibrous histiocytomas, demonstration of ALK overexpression by immunohistochemistry is essential.
Reference Gallery:
Fibrous histiocytoma. Epidermal hyperplasia overlying the tumour, with sparing of the papillary dermis.
Fibrous histiocytoma. The tumour is characterized by a cellular proliferation of short spindled cells arranged in a haphazard manner.
Fibrous histiocytoma. Peripheral border of fibrous histiocytoma demonstrating entrapment of collagen.
Cellular fibrous histiocytoma. The distinctive feature of this subtype is a highly cellular proliferation of myofibroblast-like spindle cells forming a fascicular growth pattern.
Aneurysmal fibrous histiocytoma. This entity is characterized by variably sized areas of haemorrhage within the tumour.
Aneurysmal fibrous histiocytoma. Pseudovascular spaces are lined by the lesional cells. Note the background proliferation of fibroblasts and histiocytes as well as the deposition of haemosiderin pigment.
Atypical fibrous histiocytoma. In addition to the storiform proliferation with collagen trapping, numerous atypical tumour cells can be appreciated throughout the lesion.
Atypical fibrous histiocytoma. The hallmark of the entity is bizarre pleomorphic tumour cells. An atypical mitotic figure is seen near the centre of the image.
Deep fibrous histiocytoma. This example developed within the skeletal muscle.
Deep fibrous histiocytoma. Higher magnification reveals a fairly dense spindle cell tumour, with a vague storiform growth pattern, infiltrating the skeletal muscle.
Epithelioid fibrous histiocytoma. This tumour often manifests as a polypoid growth with an epidermal collarette frequently extending along the base of the lesion.
Epithelioid fibrous histiocytoma. The majority of tumours show diffuse cytoplasmic ALK positivity.

Q: A classic histologic clue to the diagnosis of cutaneous Fibrous Histiocytoma is overlying epidermal hyperplasia with a clear zone that characteristically spares the [...].
Fibrous histiocytoma. Epidermal hyperplasia overlying the tumour, with sparing of the papillary dermis.
A: papillary dermis
Back Extra: Fibrous Histiocytoma
- Clinical: Cutaneous fibrous histiocytomas (dermatofibromas) are elevated, red-brown or blue-black lesions < 10 mm to a few centimetres in diameter.
- Micro: Fibrous histiocytomas are composed of short spindle cells arranged in a haphazard manner, often with collagen trapping at the periphery.
- Ancillary: For epithelioid fibrous histiocytomas, demonstration of ALK overexpression by immunohistochemistry is essential.
Reference Gallery:
Fibrous histiocytoma. Epidermal hyperplasia overlying the tumour, with sparing of the papillary dermis.
Fibrous histiocytoma. The tumour is characterized by a cellular proliferation of short spindled cells arranged in a haphazard manner.
Fibrous histiocytoma. Peripheral border of fibrous histiocytoma demonstrating entrapment of collagen.
Cellular fibrous histiocytoma. The distinctive feature of this subtype is a highly cellular proliferation of myofibroblast-like spindle cells forming a fascicular growth pattern.
Aneurysmal fibrous histiocytoma. This entity is characterized by variably sized areas of haemorrhage within the tumour.
Aneurysmal fibrous histiocytoma. Pseudovascular spaces are lined by the lesional cells. Note the background proliferation of fibroblasts and histiocytes as well as the deposition of haemosiderin pigment.
Atypical fibrous histiocytoma. In addition to the storiform proliferation with collagen trapping, numerous atypical tumour cells can be appreciated throughout the lesion.
Atypical fibrous histiocytoma. The hallmark of the entity is bizarre pleomorphic tumour cells. An atypical mitotic figure is seen near the centre of the image.
Deep fibrous histiocytoma. This example developed within the skeletal muscle.
Deep fibrous histiocytoma. Higher magnification reveals a fairly dense spindle cell tumour, with a vague storiform growth pattern, infiltrating the skeletal muscle.
Epithelioid fibrous histiocytoma. This tumour often manifests as a polypoid growth with an epidermal collarette frequently extending along the base of the lesion.
Epithelioid fibrous histiocytoma. The majority of tumours show diffuse cytoplasmic ALK positivity.

Q: The epithelioid variant of Fibrous Histiocytoma is uniquely characterized by the diagnostic overexpression of [...] on immunohistochemistry.
Epithelioid fibrous histiocytoma. This tumour often manifests as a polypoid growth with an epidermal collarette frequently extending along the base of the lesion.
Epithelioid fibrous histiocytoma. The majority of tumours show diffuse cytoplasmic ALK positivity.
A: ALK
Back Extra: Fibrous Histiocytoma
- Clinical: Cutaneous fibrous histiocytomas (dermatofibromas) are elevated, red-brown or blue-black lesions < 10 mm to a few centimetres in diameter.
- Micro: Fibrous histiocytomas are composed of short spindle cells arranged in a haphazard manner, often with collagen trapping at the periphery.
- Ancillary: For epithelioid fibrous histiocytomas, demonstration of ALK overexpression by immunohistochemistry is essential.
Reference Gallery:
Fibrous histiocytoma. Epidermal hyperplasia overlying the tumour, with sparing of the papillary dermis.
Fibrous histiocytoma. The tumour is characterized by a cellular proliferation of short spindled cells arranged in a haphazard manner.
Fibrous histiocytoma. Peripheral border of fibrous histiocytoma demonstrating entrapment of collagen.
Cellular fibrous histiocytoma. The distinctive feature of this subtype is a highly cellular proliferation of myofibroblast-like spindle cells forming a fascicular growth pattern.
Aneurysmal fibrous histiocytoma. This entity is characterized by variably sized areas of haemorrhage within the tumour.
Aneurysmal fibrous histiocytoma. Pseudovascular spaces are lined by the lesional cells. Note the background proliferation of fibroblasts and histiocytes as well as the deposition of haemosiderin pigment.
Atypical fibrous histiocytoma. In addition to the storiform proliferation with collagen trapping, numerous atypical tumour cells can be appreciated throughout the lesion.
Atypical fibrous histiocytoma. The hallmark of the entity is bizarre pleomorphic tumour cells. An atypical mitotic figure is seen near the centre of the image.
Deep fibrous histiocytoma. This example developed within the skeletal muscle.
Deep fibrous histiocytoma. Higher magnification reveals a fairly dense spindle cell tumour, with a vague storiform growth pattern, infiltrating the skeletal muscle.
Epithelioid fibrous histiocytoma. This tumour often manifests as a polypoid growth with an epidermal collarette frequently extending along the base of the lesion.
Epithelioid fibrous histiocytoma. The majority of tumours show diffuse cytoplasmic ALK positivity.

Q: A characteristic histologic finding in solid areas of Angiosarcoma is the presence of malignant cells with [...] containing red blood cells.
Angiosarcoma. Solid areas showing cells with intracytoplasmic lumina containing red blood cells.
A: intracytoplasmic lumina
Back Extra: Angiosarcoma
- Clinical: Cutaneous paediatric angiosarcomas are often unifocal, rapidly enlarging masses that can ulcerate, primarily affecting the lower extremities and head and neck.
- Micro: Angiosarcomas are infiltrative lesions with anastomosing vessels or sheets of epithelioid to spindled cells, often with high-grade nuclear features and rare marked pleomorphism.
- Ancillary: Essential diagnostic criteria include immunoreactivity for CD31 and ERG, with MYC amplification seen in radiation- and lymphoedema-associated angiosarcomas.
Reference Gallery:
Epithelioid angiosarcoma. Vasoformative channels and solid areas.
Epithelioid angiosarcoma. This tumour often has a solid, sheet-like growth pattern.
Angiosarcoma. Vasoformative tumour with epithelioid cytology and multilayering.
Angiosarcoma. Sheets of spindle cells.
Angiosarcoma. Solid areas showing cells with intracytoplasmic lumina containing red blood cells.

Q: Histologically, Angiosarcoma is typically characterized by an infiltrative proliferation of malignant endothelial cells forming complex, [...].
Epithelioid angiosarcoma. Vasoformative channels and solid areas.
Angiosarcoma. Vasoformative tumour with epithelioid cytology and multilayering.
A: anastomosing vessels
Back Extra: Angiosarcoma
- Clinical: Cutaneous paediatric angiosarcomas are often unifocal, rapidly enlarging masses that can ulcerate, primarily affecting the lower extremities and head and neck.
- Micro: Angiosarcomas are infiltrative lesions with anastomosing vessels or sheets of epithelioid to spindled cells, often with high-grade nuclear features and rare marked pleomorphism.
- Ancillary: Essential diagnostic criteria include immunoreactivity for CD31 and ERG, with MYC amplification seen in radiation- and lymphoedema-associated angiosarcomas.
Reference Gallery:
Epithelioid angiosarcoma. Vasoformative channels and solid areas.
Epithelioid angiosarcoma. This tumour often has a solid, sheet-like growth pattern.
Angiosarcoma. Vasoformative tumour with epithelioid cytology and multilayering.
Angiosarcoma. Sheets of spindle cells.
Angiosarcoma. Solid areas showing cells with intracytoplasmic lumina containing red blood cells.

Q: The presence of a highly malignant, vasoformative tumor composed of solid sheets of atypical spindle or epithelioid cells is diagnostic of [...].
Epithelioid angiosarcoma. This tumour often has a solid, sheet-like growth pattern.
Angiosarcoma. Sheets of spindle cells.
A: Angiosarcoma
Back Extra: Angiosarcoma
- Clinical: Cutaneous paediatric angiosarcomas are often unifocal, rapidly enlarging masses that can ulcerate, primarily affecting the lower extremities and head and neck.
- Micro: Angiosarcomas are infiltrative lesions with anastomosing vessels or sheets of epithelioid to spindled cells, often with high-grade nuclear features and rare marked pleomorphism.
- Ancillary: Essential diagnostic criteria include immunoreactivity for CD31 and ERG, with MYC amplification seen in radiation- and lymphoedema-associated angiosarcomas.
Reference Gallery:
Epithelioid angiosarcoma. Vasoformative channels and solid areas.
Epithelioid angiosarcoma. This tumour often has a solid, sheet-like growth pattern.
Angiosarcoma. Vasoformative tumour with epithelioid cytology and multilayering.
Angiosarcoma. Sheets of spindle cells.
Angiosarcoma. Solid areas showing cells with intracytoplasmic lumina containing red blood cells.

Q: Calcifying aponeurotic fibroma typically presents as a painless mass in the distal extremities of children and features bland spindle cells with distinctive [...].
Calcifying aponeurotic fibroma. Calcifying aponeurotic fibroma is characterized by bland spindle cells and nodular zones of calcification.
A: nodular zones of calcification
Back Extra: Calcifying aponeurotic fibroma
- Clinical: Patients typically present with a slowly growing, painless mass, most commonly in the distal extremities of children and adolescents.
- Micro: Characterized by bland spindle cells, nodular zones of calcification, and epithelioid fibroblasts. Osteoclast-type giant cells may be present.
- Ancillary: Demonstration of an FN1::EGF fusion is helpful for diagnosis, as the FN1 gene drives the inappropriate expression of EGF via its receptor, EGFR.
Reference Gallery:
Calcifying aponeurotic fibroma. Calcifying aponeurotic fibroma is characterized by bland spindle cells and nodular zones of calcification.
Calcifying aponeurotic fibroma. A nodule of calcification bordered by rounded epithelioid cells.
Calcifying aponeurotic fibroma. Calcified areas contain epithelioid fibroblasts and scattered giant cells.
Calcifying aponeurotic fibroma. Fibromatosis-like areas.

Q: Calcifying aponeurotic fibroma is characterized by central calcified areas that are characteristically bordered by rounded [...].
Calcifying aponeurotic fibroma. A nodule of calcification bordered by rounded epithelioid cells.
Calcifying aponeurotic fibroma. Calcified areas contain epithelioid fibroblasts and scattered giant cells.
A: epithelioid fibroblasts
Back Extra: Calcifying aponeurotic fibroma
- Clinical: Patients typically present with a slowly growing, painless mass, most commonly in the distal extremities of children and adolescents.
- Micro: Characterized by bland spindle cells, nodular zones of calcification, and epithelioid fibroblasts. Osteoclast-type giant cells may be present.
- Ancillary: Demonstration of an FN1::EGF fusion is helpful for diagnosis, as the FN1 gene drives the inappropriate expression of EGF via its receptor, EGFR.
Reference Gallery:
Calcifying aponeurotic fibroma. Calcifying aponeurotic fibroma is characterized by bland spindle cells and nodular zones of calcification.
Calcifying aponeurotic fibroma. A nodule of calcification bordered by rounded epithelioid cells.
Calcifying aponeurotic fibroma. Calcified areas contain epithelioid fibroblasts and scattered giant cells.
Calcifying aponeurotic fibroma. Fibromatosis-like areas.

Q: Calcifying aponeurotic fibroma contains cellular zones composed of bland spindle cells that frequently resemble [...].
Calcifying aponeurotic fibroma. Fibromatosis-like areas.
A: fibromatosis
Back Extra: Calcifying aponeurotic fibroma
- Clinical: Patients typically present with a slowly growing, painless mass, most commonly in the distal extremities of children and adolescents.
- Micro: Characterized by bland spindle cells, nodular zones of calcification, and epithelioid fibroblasts. Osteoclast-type giant cells may be present.
- Ancillary: Demonstration of an FN1::EGF fusion is helpful for diagnosis, as the FN1 gene drives the inappropriate expression of EGF via its receptor, EGFR.
Reference Gallery:
Calcifying aponeurotic fibroma. Calcifying aponeurotic fibroma is characterized by bland spindle cells and nodular zones of calcification.
Calcifying aponeurotic fibroma. A nodule of calcification bordered by rounded epithelioid cells.
Calcifying aponeurotic fibroma. Calcified areas contain epithelioid fibroblasts and scattered giant cells.
Calcifying aponeurotic fibroma. Fibromatosis-like areas.

Q: An undifferentiated round cell tumor showing moderate nuclear pleomorphism, vesicular chromatin, and variable CD99 staining, with confirmed CIC gene translocations, is diagnostic of [...].
CIC-rearranged sarcoma. Photomicrograph showing the most common pattern of CIC-rearranged sarcoma, with sheets of mildly pleomorphic round blue cells with pale cytoplasm and coarse to vesicular chromatin.
CIC-rearranged sarcoma. CD99 immunohistochemistry showing variable cytoplasmic and membranous staining in the tumour cells. The pattern is less consistent than that seen in Ewing sarcoma.
CIC::DUX4-rearranged sarcoma. Solid sheets of medium-sized cells with irregular nuclei, small nucleoli, and a thin rim of clear cytoplasm.
A: CIC-rearranged sarcoma
Back Extra: CIC-rearranged sarcoma
- Clinical: CIC-rearranged sarcomas are most common in individuals aged 25-35 years, with a slight male predominance. These tumours usually present as mass lesions with or without pain.
- Micro: The tumour cells are round to oval, with a diffuse or vaguely lobular/nodular architecture. They exhibit focal spindling, moderate nuclear pleomorphism, and vesicular nuclei with prominent nucleoli.
- Ancillary: Immunohistochemistry shows positivity for CD99 (variable), WT1 (nuclear), and ETV4. CIC gene rearrangements are detected using molecular methods, with next-generation sequencing being the most sensitive.
Reference Gallery:
CIC-rearranged sarcoma. Photomicrograph showing the most common pattern of CIC-rearranged sarcoma, with sheets of mildly pleomorphic round blue cells with pale cytoplasm and coarse to vesicular chromatin.
CIC-rearranged sarcoma. CD99 immunohistochemistry showing variable cytoplasmic and membranous staining in the tumour cells. The pattern is less consistent than that seen in Ewing sarcoma.
CIC-rearranged sarcoma. WT1 immunohistochemistry showing moderate to strong nuclear positivity in a subset of tumour cells.
CIC-rearranged sarcoma. ETV4 immunohistochemistry showing nuclear positivity in tumour cells.
CIC::DUX4-rearranged sarcoma. Solid sheets of medium-sized cells with irregular nuclei, small nucleoli, and a thin rim of clear cytoplasm.

Q: In CIC-rearranged sarcoma, immunohistochemistry classically reveals distinct nuclear positivity for ETV4 and [...].
CIC-rearranged sarcoma. WT1 immunohistochemistry showing moderate to strong nuclear positivity in a subset of tumour cells.
A: WT1
Back Extra: CIC-rearranged sarcoma
- Clinical: CIC-rearranged sarcomas are most common in individuals aged 25-35 years, with a slight male predominance. These tumours usually present as mass lesions with or without pain.
- Micro: The tumour cells are round to oval, with a diffuse or vaguely lobular/nodular architecture. They exhibit focal spindling, moderate nuclear pleomorphism, and vesicular nuclei with prominent nucleoli.
- Ancillary: Immunohistochemistry shows positivity for CD99 (variable), WT1 (nuclear), and ETV4. CIC gene rearrangements are detected using molecular methods, with next-generation sequencing being the most sensitive.
Reference Gallery:
CIC-rearranged sarcoma. Photomicrograph showing the most common pattern of CIC-rearranged sarcoma, with sheets of mildly pleomorphic round blue cells with pale cytoplasm and coarse to vesicular chromatin.
CIC-rearranged sarcoma. CD99 immunohistochemistry showing variable cytoplasmic and membranous staining in the tumour cells. The pattern is less consistent than that seen in Ewing sarcoma.
CIC-rearranged sarcoma. WT1 immunohistochemistry showing moderate to strong nuclear positivity in a subset of tumour cells.
CIC-rearranged sarcoma. ETV4 immunohistochemistry showing nuclear positivity in tumour cells.
CIC::DUX4-rearranged sarcoma. Solid sheets of medium-sized cells with irregular nuclei, small nucleoli, and a thin rim of clear cytoplasm.

Q: In CIC-rearranged sarcoma, tumor cells typically show distinct nuclear positivity for WT1 and [...] on immunohistochemistry.
CIC-rearranged sarcoma. ETV4 immunohistochemistry showing nuclear positivity in tumour cells.
A: ETV4
Back Extra: CIC-rearranged sarcoma
- Clinical: CIC-rearranged sarcomas are most common in individuals aged 25-35 years, with a slight male predominance. These tumours usually present as mass lesions with or without pain.
- Micro: The tumour cells are round to oval, with a diffuse or vaguely lobular/nodular architecture. They exhibit focal spindling, moderate nuclear pleomorphism, and vesicular nuclei with prominent nucleoli.
- Ancillary: Immunohistochemistry shows positivity for CD99 (variable), WT1 (nuclear), and ETV4. CIC gene rearrangements are detected using molecular methods, with next-generation sequencing being the most sensitive.
Reference Gallery:
CIC-rearranged sarcoma. Photomicrograph showing the most common pattern of CIC-rearranged sarcoma, with sheets of mildly pleomorphic round blue cells with pale cytoplasm and coarse to vesicular chromatin.
CIC-rearranged sarcoma. CD99 immunohistochemistry showing variable cytoplasmic and membranous staining in the tumour cells. The pattern is less consistent than that seen in Ewing sarcoma.
CIC-rearranged sarcoma. WT1 immunohistochemistry showing moderate to strong nuclear positivity in a subset of tumour cells.
CIC-rearranged sarcoma. ETV4 immunohistochemistry showing nuclear positivity in tumour cells.
CIC::DUX4-rearranged sarcoma. Solid sheets of medium-sized cells with irregular nuclei, small nucleoli, and a thin rim of clear cytoplasm.

Q: Histologically, Clear Cell Sarcoma of Soft Tissue is characterized by short fascicles and nests of cells with clear to pale cytoplasm, prominent nucleoli, and often features scattered [...] multinucleated giant cells.
Clear cell sarcoma of soft tissue. Low-power view shows a nested or fascicular architecture partitioned by thin fibrous septa.
Clear cell sarcoma of soft tissue. Tumour cells have clear to pale eosinophilic cytoplasm and prominent nucleoli.
Clear cell sarcoma of soft tissue. Scattered wreath-like multinucleated giant cells are relatively common.
A: wreath-like
Back Extra: Clear Cell Sarcoma of Soft Tissue
- Clinical: Most patients with clear cell sarcoma of soft tissue present with a palpable mass that grows insidiously over months or years, often associated with pain or tenderness.
- Micro: Characterized by short fascicles and nests of relatively uniform epithelioid or plump spindle cells with vesicular nuclei and prominent nucleoli, partitioned by dense fibrous stroma.
- Ancillary: Immunohistochemically, clear cell sarcoma of soft tissue is consistently positive for S100, SOX10, HMB45, Melan-A, and MITF; molecularly, it shows EWSR1::ATF1 fusion.
Reference Gallery:
Clear cell sarcoma of soft tissue. Low-power view shows a nested or fascicular architecture partitioned by thin fibrous septa.
Clear cell sarcoma of soft tissue. Tumour cells have clear to pale eosinophilic cytoplasm and prominent nucleoli.
Clear cell sarcoma of soft tissue. Scattered wreath-like multinucleated giant cells are relatively common.
Clear cell sarcoma of soft tissue. Tumour cells show strong and diffuse S100 expression.
Clear cell sarcoma of soft tissue. Tumour cells show consistent expression of HMB45 and other melanocytic markers.

Q: In addition to strong diffuse expression of S100 and consistent positivity for melanocytic markers (e.g., HMB45), Clear Cell Sarcoma of Soft Tissue is characteristically driven by an underlying [ATF1] gene fusion.
Clear cell sarcoma of soft tissue. Tumour cells show strong and diffuse S100 expression.
Clear cell sarcoma of soft tissue. Tumour cells show consistent expression of HMB45 and other melanocytic markers.
A: EWSR1
Back Extra: Clear Cell Sarcoma of Soft Tissue
- Clinical: Most patients with clear cell sarcoma of soft tissue present with a palpable mass that grows insidiously over months or years, often associated with pain or tenderness.
- Micro: Characterized by short fascicles and nests of relatively uniform epithelioid or plump spindle cells with vesicular nuclei and prominent nucleoli, partitioned by dense fibrous stroma.
- Ancillary: Immunohistochemically, clear cell sarcoma of soft tissue is consistently positive for S100, SOX10, HMB45, Melan-A, and MITF; molecularly, it shows EWSR1::ATF1 fusion.
Reference Gallery:
Clear cell sarcoma of soft tissue. Low-power view shows a nested or fascicular architecture partitioned by thin fibrous septa.
Clear cell sarcoma of soft tissue. Tumour cells have clear to pale eosinophilic cytoplasm and prominent nucleoli.
Clear cell sarcoma of soft tissue. Scattered wreath-like multinucleated giant cells are relatively common.
Clear cell sarcoma of soft tissue. Tumour cells show strong and diffuse S100 expression.
Clear cell sarcoma of soft tissue. Tumour cells show consistent expression of HMB45 and other melanocytic markers.

Q: A congenital hemangioma is a vascular tumor that presents fully grown at birth and is classically categorized into non-involuting and [...] subtypes.
Non-involuting congenital haemangioma. A 3-year-old boy with a dome-shaped lesion exhibiting telangiectasia and pallor.
Rapidly involuting congenital haemangioma. Newborn boy with the right medial leg bearing a bulbous lesion with shiny telangiectatic skin. The lesion was mostly involuted by 16 months of age.
A: rapidly involuting
Q: Congenital Haemangioma
- Clinical: [...] are fully grown at birth, with some subtypes showing rapid involution or no involution at all.
- Micro: [...] show lobules of capillaries with hobnailed endothelium and prominent interlobular vasculature, often with dysmorphic veins.
- Ancillary: [...] frequently have GNAQ or GNA11 mutations, and some show transient D2-40 positivity in association with neonatal thrombocytopenia.
Reference Gallery:
Non-involuting congenital haemangioma. A 3-year-old boy with a dome-shaped lesion exhibiting telangiectasia and pallor.
Non-involuting congenital haemangioma. Histology shows variably sized nodules with round and stellate capillary channels with large lumina and hobnail endothelium. There is prominent interlobular vasculature, primarily venous, including dysmorphic forms.
Rapidly involuting congenital haemangioma with fetal involution. Partial resection at 3 years shows some residual tiny capillaries, dysmorphic veins, and dilated lymphatic vessels.
Rapidly involuting congenital haemangioma. There are small lobules, prominent intralobular and perilobular vasculature, and minimally prominent endothelial cells and pericytes.
Rapidly involuting congenital haemangioma. Newborn boy with the right medial leg bearing a bulbous lesion with shiny telangiectatic skin. The lesion was mostly involuted by 16 months of age.
Rapidly involuting congenital haemangioma with fetal involution. Newborn with a large violaceous plaque at birth, which further involuted over 3 years.
A: Congenital haemangiomas; Congenital haemangiomas; Congenital haemangiomas

Q: Microscopically, a congenital hemangioma typically exhibits lobules of capillaries with a characteristic [...] endothelium, separated by prominent interlobular stroma containing dysmorphic veins.
Non-involuting congenital haemangioma. Histology shows variably sized nodules with round and stellate capillary channels with large lumina and hobnail endothelium. There is prominent interlobular vasculature, primarily venous, including dysmorphic forms.
Rapidly involuting congenital haemangioma with fetal involution. Partial resection at 3 years shows some residual tiny capillaries, dysmorphic veins, and dilated lymphatic vessels.
A: hobnail
Q: Congenital Haemangioma
- Clinical: [...] are fully grown at birth, with some subtypes showing rapid involution or no involution at all.
- Micro: [...] show lobules of capillaries with hobnailed endothelium and prominent interlobular vasculature, often with dysmorphic veins.
- Ancillary: [...] frequently have GNAQ or GNA11 mutations, and some show transient D2-40 positivity in association with neonatal thrombocytopenia.
Reference Gallery:
Non-involuting congenital haemangioma. A 3-year-old boy with a dome-shaped lesion exhibiting telangiectasia and pallor.
Non-involuting congenital haemangioma. Histology shows variably sized nodules with round and stellate capillary channels with large lumina and hobnail endothelium. There is prominent interlobular vasculature, primarily venous, including dysmorphic forms.
Rapidly involuting congenital haemangioma with fetal involution. Partial resection at 3 years shows some residual tiny capillaries, dysmorphic veins, and dilated lymphatic vessels.
Rapidly involuting congenital haemangioma. There are small lobules, prominent intralobular and perilobular vasculature, and minimally prominent endothelial cells and pericytes.
Rapidly involuting congenital haemangioma. Newborn boy with the right medial leg bearing a bulbous lesion with shiny telangiectatic skin. The lesion was mostly involuted by 16 months of age.
Rapidly involuting congenital haemangioma with fetal involution. Newborn with a large violaceous plaque at birth, which further involuted over 3 years.
A: Congenital haemangiomas; Congenital haemangiomas; Congenital haemangiomas

Q: Presenting clinically as a mass in the vulvar region or spermatic cord (often mimicking a hernia), [...] is a myxoid tumor that classically exhibits an infiltrative growth pattern into adjacent adipose tissue.
Deep angiomyxoma. Infiltration of spermatic cord adipose tissue of an 11-year-old boy by a myxoid tumour.
A: Deep Angiomyxoma
Back Extra: Deep Angiomyxoma
- Clinical: Deep angiomyxoma typically occurs in the vulva and spermatic cord, mimicking a labial cyst or a hernia.
- Micro: The tumour is characterized by bland-looking, spindled to stellate cells in a myxoid stroma with numerous blood vessels.
- Ancillary: Immunohistochemistry often shows expression of desmin, CD34, and SMA.
Reference Gallery:
Deep angiomyxoma. Infiltration of spermatic cord adipose tissue of an 11-year-old boy by a myxoid tumour.
Deep angiomyxoma. Myxoid stroma with numerous small blood vessels.
Deep angiomyxoma. The tumour is composed of bland-looking, small, spindled to stellate cells in a hypocellular myxoid matrix.
Deep angiomyxoma. Hypercellular tumour area with perivascular hyalinization.
Deep angiomyxoma. Bundles of mature smooth muscle cells are scattered in the myxoid stroma.

Q: Histologically, Deep Angiomyxoma features a hypocellular myxoid matrix containing numerous blood vessels that often demonstrate characteristic [...].
Deep angiomyxoma. Myxoid stroma with numerous small blood vessels.
Deep angiomyxoma. Hypercellular tumour area with perivascular hyalinization.
A: perivascular hyalinization
Back Extra: Deep Angiomyxoma
- Clinical: Deep angiomyxoma typically occurs in the vulva and spermatic cord, mimicking a labial cyst or a hernia.
- Micro: The tumour is characterized by bland-looking, spindled to stellate cells in a myxoid stroma with numerous blood vessels.
- Ancillary: Immunohistochemistry often shows expression of desmin, CD34, and SMA.
Reference Gallery:
Deep angiomyxoma. Infiltration of spermatic cord adipose tissue of an 11-year-old boy by a myxoid tumour.
Deep angiomyxoma. Myxoid stroma with numerous small blood vessels.
Deep angiomyxoma. The tumour is composed of bland-looking, small, spindled to stellate cells in a hypocellular myxoid matrix.
Deep angiomyxoma. Hypercellular tumour area with perivascular hyalinization.
Deep angiomyxoma. Bundles of mature smooth muscle cells are scattered in the myxoid stroma.

Q: In Deep Angiomyxoma, the myxoid stroma contains bland, spindled to stellate cells and characteristically features scattered bundles of mature [...] cells.
Deep angiomyxoma. The tumour is composed of bland-looking, small, spindled to stellate cells in a hypocellular myxoid matrix.
Deep angiomyxoma. Bundles of mature smooth muscle cells are scattered in the myxoid stroma.
A: smooth muscle
Back Extra: Deep Angiomyxoma
- Clinical: Deep angiomyxoma typically occurs in the vulva and spermatic cord, mimicking a labial cyst or a hernia.
- Micro: The tumour is characterized by bland-looking, spindled to stellate cells in a myxoid stroma with numerous blood vessels.
- Ancillary: Immunohistochemistry often shows expression of desmin, CD34, and SMA.
Reference Gallery:
Deep angiomyxoma. Infiltration of spermatic cord adipose tissue of an 11-year-old boy by a myxoid tumour.
Deep angiomyxoma. Myxoid stroma with numerous small blood vessels.
Deep angiomyxoma. The tumour is composed of bland-looking, small, spindled to stellate cells in a hypocellular myxoid matrix.
Deep angiomyxoma. Hypercellular tumour area with perivascular hyalinization.
Deep angiomyxoma. Bundles of mature smooth muscle cells are scattered in the myxoid stroma.

Q: In Dermatofibrosarcoma Protuberans, spindle cells are classically arranged in a [...] pattern and deeply infiltrate the hypodermis to create a characteristic honeycomb appearance.
Dermatofibrosarcoma protuberans. Fascicles of spindle cells arranged in a storiform pattern.
Dermatofibrosarcoma protuberans. Typical honeycomb pattern in the hypodermis.
A: storiform
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Dermatofibrosarcoma protuberans typically presents as painless, red-blue, slowly growing skin plaques or nodules, commonly located on the trunk and extremities.
- Micro: Classic DFSP features spindle cells arranged in a storiform pattern with a characteristic honeycomb appearance in the hypodermis.
- Ancillary: CD34 immunohistochemistry is positive in a majority of DFSPs, and the identification of the COL1A1::PDGFB fusion gene is important for diagnosis.
Reference Gallery:
Dermatofibrosarcoma protuberans. Superficial intradermal proliferation in a plaque-like dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. CD34 immunohistochemistry shows the horizontal orientation of tumour cells in a plaque-like dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. Fascicles of spindle cells arranged in a storiform pattern.
Dermatofibrosarcoma protuberans. Typical honeycomb pattern in the hypodermis.
Myxoid dermatofibrosarcoma protuberans. This pattern is characterized by loose myxoid stroma.
Dermatofibrosarcoma protuberans. Pigmented dendritic cells in a pigmented dermatofibrosarcoma (also known as Bednar tumour).
Fibrosarcoma. Atypical cells arranged in intersecting fascicles producing a herringbone pattern in a fibrosarcomatous dermatofibrosarcoma.
Giant cell fibroblastoma. An 8-year-old boy presented with a giant cell fibroblastoma on the right arm.
Giant cell fibroblastoma. Numerous pleomorphic cells mixed with spindle cells.
Hybrid dermatofibrosarcoma / giant cell fibroblastoma. The tumour shows an area of giant cell fibroblastoma (left) and an area of dermatofibrosarcoma (right).
Fibrosarcoma with myoid nodules. Some cases of dermatofibrosarcoma can display myoid nodules.

Q: Immunohistochemistry for Dermatofibrosarcoma Protuberans typically shows strong, diffuse positivity for [...], and molecular studies classically reveal a COL1A1::PDGFB gene fusion.
Dermatofibrosarcoma protuberans. CD34 immunohistochemistry shows the horizontal orientation of tumour cells in a plaque-like dermatofibrosarcoma protuberans.
A: CD34
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Dermatofibrosarcoma protuberans typically presents as painless, red-blue, slowly growing skin plaques or nodules, commonly located on the trunk and extremities.
- Micro: Classic DFSP features spindle cells arranged in a storiform pattern with a characteristic honeycomb appearance in the hypodermis.
- Ancillary: CD34 immunohistochemistry is positive in a majority of DFSPs, and the identification of the COL1A1::PDGFB fusion gene is important for diagnosis.
Reference Gallery:
Dermatofibrosarcoma protuberans. Superficial intradermal proliferation in a plaque-like dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. CD34 immunohistochemistry shows the horizontal orientation of tumour cells in a plaque-like dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. Fascicles of spindle cells arranged in a storiform pattern.
Dermatofibrosarcoma protuberans. Typical honeycomb pattern in the hypodermis.
Myxoid dermatofibrosarcoma protuberans. This pattern is characterized by loose myxoid stroma.
Dermatofibrosarcoma protuberans. Pigmented dendritic cells in a pigmented dermatofibrosarcoma (also known as Bednar tumour).
Fibrosarcoma. Atypical cells arranged in intersecting fascicles producing a herringbone pattern in a fibrosarcomatous dermatofibrosarcoma.
Giant cell fibroblastoma. An 8-year-old boy presented with a giant cell fibroblastoma on the right arm.
Giant cell fibroblastoma. Numerous pleomorphic cells mixed with spindle cells.
Hybrid dermatofibrosarcoma / giant cell fibroblastoma. The tumour shows an area of giant cell fibroblastoma (left) and an area of dermatofibrosarcoma (right).
Fibrosarcoma with myoid nodules. Some cases of dermatofibrosarcoma can display myoid nodules.

Q: A pigmented variant of Dermatofibrosarcoma Protuberans, characterized by the presence of melanin-laden dendritic cells among the spindle cells, is known as a [...] tumor.
Dermatofibrosarcoma protuberans. Pigmented dendritic cells in a pigmented dermatofibrosarcoma (also known as Bednar tumour).
A: Bednar
Back Extra: Dermatofibrosarcoma Protuberans
- Clinical: Dermatofibrosarcoma protuberans typically presents as painless, red-blue, slowly growing skin plaques or nodules, commonly located on the trunk and extremities.
- Micro: Classic DFSP features spindle cells arranged in a storiform pattern with a characteristic honeycomb appearance in the hypodermis.
- Ancillary: CD34 immunohistochemistry is positive in a majority of DFSPs, and the identification of the COL1A1::PDGFB fusion gene is important for diagnosis.
Reference Gallery:
Dermatofibrosarcoma protuberans. Superficial intradermal proliferation in a plaque-like dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. CD34 immunohistochemistry shows the horizontal orientation of tumour cells in a plaque-like dermatofibrosarcoma protuberans.
Dermatofibrosarcoma protuberans. Fascicles of spindle cells arranged in a storiform pattern.
Dermatofibrosarcoma protuberans. Typical honeycomb pattern in the hypodermis.
Myxoid dermatofibrosarcoma protuberans. This pattern is characterized by loose myxoid stroma.
Dermatofibrosarcoma protuberans. Pigmented dendritic cells in a pigmented dermatofibrosarcoma (also known as Bednar tumour).
Fibrosarcoma. Atypical cells arranged in intersecting fascicles producing a herringbone pattern in a fibrosarcomatous dermatofibrosarcoma.
Giant cell fibroblastoma. An 8-year-old boy presented with a giant cell fibroblastoma on the right arm.
Giant cell fibroblastoma. Numerous pleomorphic cells mixed with spindle cells.
Hybrid dermatofibrosarcoma / giant cell fibroblastoma. The tumour shows an area of giant cell fibroblastoma (left) and an area of dermatofibrosarcoma (right).
Fibrosarcoma with myoid nodules. Some cases of dermatofibrosarcoma can display myoid nodules.

Q: Histologically, Desmoid Fibromatosis is characterized by an infiltrative growth pattern of bland (myo)fibroblasts arranged in long, [...].
Desmoid fibromatosis. Tumours show an infiltrative growth pattern with extension into adjacent adipose tissue.
Desmoid fibromatosis. The tumour is composed of long sweeping fascicles of bland fibroblasts and myofibroblasts.
A: sweeping fascicles
Back Extra: Desmoid Fibromatosis
- Clinical: Desmoid fibromatosis presents as a slow-growing, deep-seated mass, predominantly in the extremities, head/neck, and trunk in children aged 6-15 years.
- Micro: Histologically, desmoid fibromatosis shows bland (myo)fibroblasts arranged in long, sweeping fascicles with an infiltrative growth pattern, often with nuclear β-catenin expression.
- Ancillary: Nuclear β-catenin expression (80% positive) and β-catenin mutations in the CTNNB1 gene (90-95% of sporadic cases) are key diagnostic markers in desmoid fibromatosis.
Reference Gallery:
Desmoid fibromatosis. Tumours show an infiltrative growth pattern with extension into adjacent adipose tissue.
Desmoid fibromatosis. The tumour is composed of long sweeping fascicles of bland fibroblasts and myofibroblasts.
Desmoid fibromatosis. Nuclear staining for β-catenin.

Q: The characteristic immunohistochemical finding in Desmoid Fibromatosis is abnormal nuclear expression of [...], which is driven by CTNNB1 mutations in most sporadic cases.
Desmoid fibromatosis. Nuclear staining for β-catenin.
A: beta-catenin
Back Extra: Desmoid Fibromatosis
- Clinical: Desmoid fibromatosis presents as a slow-growing, deep-seated mass, predominantly in the extremities, head/neck, and trunk in children aged 6-15 years.
- Micro: Histologically, desmoid fibromatosis shows bland (myo)fibroblasts arranged in long, sweeping fascicles with an infiltrative growth pattern, often with nuclear β-catenin expression.
- Ancillary: Nuclear β-catenin expression (80% positive) and β-catenin mutations in the CTNNB1 gene (90-95% of sporadic cases) are key diagnostic markers in desmoid fibromatosis.
Reference Gallery:
Desmoid fibromatosis. Tumours show an infiltrative growth pattern with extension into adjacent adipose tissue.
Desmoid fibromatosis. The tumour is composed of long sweeping fascicles of bland fibroblasts and myofibroblasts.
Desmoid fibromatosis. Nuclear staining for β-catenin.

Q: Characterized by sharply demarcated nests of undifferentiated small cells in a dense desmoplastic stroma, the [...] often exhibits central necrosis and signet-ring cell-like features.
Desmoplastic small round cell tumour. Characteristic morphology, consisting of variably sized tumour cell nests deposited in a fibromyxoid stroma.
Desmoplastic small round cell tumour. A large, centrally necrotic tumour nest.
Desmoplastic small round cell tumour. Tumour cells with signet-ring cell–like, vacuolated, and cleared-out cytoplasm.
A: desmoplastic small round cell tumor
Back Extra: Desmoplastic Small Round Cell Tumour
- Clinical: Desmoplastic small round cell tumour (DSRCT) typically presents with widespread abdominal/peritoneal involvement, causing pain, abdominal distention, and a palpable mass.
- Micro: DSRCT is characterized by sharply demarcated nests of undifferentiated small cells in a desmoplastic stroma, often with necrosis and signet-ring cell–like features.
- Ancillary: Immunohistochemically, DSRCTs show a polyphenotypic profile, positive for desmin, cytokeratins, and EMA, and the presence of the EWSR1::WT1 fusion transcript.
Reference Gallery:
Desmoplastic small round cell tumour. Characteristic morphology, consisting of variably sized tumour cell nests deposited in a fibromyxoid stroma.
Desmoplastic small round cell tumour. Solid growth pattern with large confluent sheets of cells.
Desmoplastic small round cell tumour. Undifferentiated small cells with minimal nuclear pleomorphism.
Desmoplastic small round cell tumour. Marked cytological atypia and pronounced nuclear pleomorphism.
Desmoplastic small round cell tumour. A large, centrally necrotic tumour nest.
Desmoplastic small round cell tumour. Tumour cells with signet-ring cell–like, vacuolated, and cleared-out cytoplasm.
Desmoplastic small round cell tumour. Epithelial features with gland formation.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against cytokeratin.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against C-terminal WT1.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against desmin.
Desmoplastic small round cell tumour. Contrast-enhanced axial CT shows one of the largest masses in the pelvic cavity, which is heterogeneous in enhancement. The mass abuts the urinary bladder anteriorly and compresses onto the contrast-filled rectum posteriorly.

Q: A desmoplastic small round cell tumor typically displays a polyphenotypic immunohistochemical profile (positive for desmin and cytokeratins) and harbors the highly specific [WT1] fusion transcript.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against cytokeratin.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against C-terminal WT1.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against desmin.
A: EWSR1
Back Extra: Desmoplastic Small Round Cell Tumour
- Clinical: Desmoplastic small round cell tumour (DSRCT) typically presents with widespread abdominal/peritoneal involvement, causing pain, abdominal distention, and a palpable mass.
- Micro: DSRCT is characterized by sharply demarcated nests of undifferentiated small cells in a desmoplastic stroma, often with necrosis and signet-ring cell–like features.
- Ancillary: Immunohistochemically, DSRCTs show a polyphenotypic profile, positive for desmin, cytokeratins, and EMA, and the presence of the EWSR1::WT1 fusion transcript.
Reference Gallery:
Desmoplastic small round cell tumour. Characteristic morphology, consisting of variably sized tumour cell nests deposited in a fibromyxoid stroma.
Desmoplastic small round cell tumour. Solid growth pattern with large confluent sheets of cells.
Desmoplastic small round cell tumour. Undifferentiated small cells with minimal nuclear pleomorphism.
Desmoplastic small round cell tumour. Marked cytological atypia and pronounced nuclear pleomorphism.
Desmoplastic small round cell tumour. A large, centrally necrotic tumour nest.
Desmoplastic small round cell tumour. Tumour cells with signet-ring cell–like, vacuolated, and cleared-out cytoplasm.
Desmoplastic small round cell tumour. Epithelial features with gland formation.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against cytokeratin.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against C-terminal WT1.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against desmin.
Desmoplastic small round cell tumour. Contrast-enhanced axial CT shows one of the largest masses in the pelvic cavity, which is heterogeneous in enhancement. The mass abuts the urinary bladder anteriorly and compresses onto the contrast-filled rectum posteriorly.

Q: Clinically, a desmoplastic small round cell tumor typically presents with pain, distention, and widespread, bulky masses predominantly involving the [...] cavity.
Desmoplastic small round cell tumour. Contrast-enhanced axial CT shows one of the largest masses in the pelvic cavity, which is heterogeneous in enhancement. The mass abuts the urinary bladder anteriorly and compresses onto the contrast-filled rectum posteriorly.
A: peritoneal
Back Extra: Desmoplastic Small Round Cell Tumour
- Clinical: Desmoplastic small round cell tumour (DSRCT) typically presents with widespread abdominal/peritoneal involvement, causing pain, abdominal distention, and a palpable mass.
- Micro: DSRCT is characterized by sharply demarcated nests of undifferentiated small cells in a desmoplastic stroma, often with necrosis and signet-ring cell–like features.
- Ancillary: Immunohistochemically, DSRCTs show a polyphenotypic profile, positive for desmin, cytokeratins, and EMA, and the presence of the EWSR1::WT1 fusion transcript.
Reference Gallery:
Desmoplastic small round cell tumour. Characteristic morphology, consisting of variably sized tumour cell nests deposited in a fibromyxoid stroma.
Desmoplastic small round cell tumour. Solid growth pattern with large confluent sheets of cells.
Desmoplastic small round cell tumour. Undifferentiated small cells with minimal nuclear pleomorphism.
Desmoplastic small round cell tumour. Marked cytological atypia and pronounced nuclear pleomorphism.
Desmoplastic small round cell tumour. A large, centrally necrotic tumour nest.
Desmoplastic small round cell tumour. Tumour cells with signet-ring cell–like, vacuolated, and cleared-out cytoplasm.
Desmoplastic small round cell tumour. Epithelial features with gland formation.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against cytokeratin.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against C-terminal WT1.
Desmoplastic small round cell tumour. Immunohistochemical signal obtained with an antibody directed against desmin.
Desmoplastic small round cell tumour. Contrast-enhanced axial CT shows one of the largest masses in the pelvic cavity, which is heterogeneous in enhancement. The mass abuts the urinary bladder anteriorly and compresses onto the contrast-filled rectum posteriorly.

Q: To firmly establish the diagnosis of an EBV-associated smooth muscle tumor, it is essential to demonstrate the presence of the virus within the tumor nuclei using [...].
EBV-associated smooth muscle tumour. A specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing EBV-encoded small RNA (EBER) expression in tumour cells.
A: EBER in situ hybridization
Back Extra: EBV-associated smooth muscle tumour
- Clinical: Symptoms are related to the site of involvement, such as neurological symptoms for CNS tumours, abdominal pain for intestinal cases, and cyanosis or infection for endobronchial cases.
- Micro: Tumours show short interlacing fascicles of spindle cells with eosinophilic cytoplasm and blunt-ended nuclei, often intermingled with areas of small to medium-sized cells.
- Ancillary: EBER in situ hybridization is essential for diagnosing EBV-associated smooth muscle tumours and confirming EBV infection.
Reference Gallery:
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing aortic involvement.
EBV-associated smooth muscle tumour. A specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing EBV-encoded small RNA (EBER) expression in tumour cells.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing liver involvement.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing adrenal gland involvement.
EBV-associated smooth muscle tumour. A densely cellular area with interconnecting fascicles of spindle cells.
EBV-associated smooth muscle tumour. Characteristic small to medium-sized cells associated with a rich vascular network.
EBV-associated smooth muscle tumour. The tumour shows spindle cells in fascicles intermingled with areas composed of small to medium-sized cells.

Q: Histologically, an EBV-associated smooth muscle tumor features short interlacing fascicles of spindle cells with blunt-ended nuclei, characteristically intermingled with distinct areas of [...].
EBV-associated smooth muscle tumour. A densely cellular area with interconnecting fascicles of spindle cells.
EBV-associated smooth muscle tumour. The tumour shows spindle cells in fascicles intermingled with areas composed of small to medium-sized cells.
A: small to medium-sized cells
Back Extra: EBV-associated smooth muscle tumour
- Clinical: Symptoms are related to the site of involvement, such as neurological symptoms for CNS tumours, abdominal pain for intestinal cases, and cyanosis or infection for endobronchial cases.
- Micro: Tumours show short interlacing fascicles of spindle cells with eosinophilic cytoplasm and blunt-ended nuclei, often intermingled with areas of small to medium-sized cells.
- Ancillary: EBER in situ hybridization is essential for diagnosing EBV-associated smooth muscle tumours and confirming EBV infection.
Reference Gallery:
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing aortic involvement.
EBV-associated smooth muscle tumour. A specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing EBV-encoded small RNA (EBER) expression in tumour cells.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing liver involvement.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing adrenal gland involvement.
EBV-associated smooth muscle tumour. A densely cellular area with interconnecting fascicles of spindle cells.
EBV-associated smooth muscle tumour. Characteristic small to medium-sized cells associated with a rich vascular network.
EBV-associated smooth muscle tumour. The tumour shows spindle cells in fascicles intermingled with areas composed of small to medium-sized cells.

Q: In severely immunocompromised patients, an EBV-associated smooth muscle tumor frequently exhibits a rapidly progressive and [...] clinical presentation, simultaneously involving multiple atypical gross sites such as the aorta, liver, and adrenal glands.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing aortic involvement.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing liver involvement.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing adrenal gland involvement.
A: multifocal
Back Extra: EBV-associated smooth muscle tumour
- Clinical: Symptoms are related to the site of involvement, such as neurological symptoms for CNS tumours, abdominal pain for intestinal cases, and cyanosis or infection for endobronchial cases.
- Micro: Tumours show short interlacing fascicles of spindle cells with eosinophilic cytoplasm and blunt-ended nuclei, often intermingled with areas of small to medium-sized cells.
- Ancillary: EBER in situ hybridization is essential for diagnosing EBV-associated smooth muscle tumours and confirming EBV infection.
Reference Gallery:
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing aortic involvement.
EBV-associated smooth muscle tumour. A specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing EBV-encoded small RNA (EBER) expression in tumour cells.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing liver involvement.
EBV-associated smooth muscle tumour. A gross specimen from a 3-year-old boy with NK-cell immunodeficiency and rapidly progressive multifocal and multicentric EBV-associated smooth muscle tumours, showing adrenal gland involvement.
EBV-associated smooth muscle tumour. A densely cellular area with interconnecting fascicles of spindle cells.
EBV-associated smooth muscle tumour. Characteristic small to medium-sized cells associated with a rich vascular network.
EBV-associated smooth muscle tumour. The tumour shows spindle cells in fascicles intermingled with areas composed of small to medium-sized cells.

Q: The defining histologic feature of an Ectomesenchymoma is the intermingled admixture of neuroectodermal elements (e.g., ganglion cells or neuroblasts) and [...].
Ectomesenchymoma. Round and spindled rhabdomyosarcomatous cells intermingled with ganglioneuroblastic elements.
Ectomesenchymoma. Individual ganglion cells exist in a spindle cell rhabdomyosarcomatous background.
A: rhabdomyosarcoma
Back Extra: Ectomesenchymoma
- Clinical: Ectomesenchymoma most commonly presents as a deep or superficial soft tissue mass in the pelvis, urogenital organs, and intra-abdominal/retroperitoneal soft tissue, with a predilection for infants and children aged < 5 years.
- Micro: The tumor is characterized by intermingled areas of rhabdomyosarcoma and neuroectodermal elements, including ganglion cells and neuroblastic components.
- Ancillary: Cytogenetic findings in ectomesenchymoma often show trisomies of chromosomes 2, 8, and 11, and frequent HRAS mutations, similar to those found in embryonal rhabdomyosarcoma.
Reference Gallery:
Ectomesenchymoma. Round and spindled rhabdomyosarcomatous cells intermingled with ganglioneuroblastic elements.
Ectomesenchymoma. Myogenin immunostaining highlights rhabdomyosarcomatous elements.
Ectomesenchymoma. Individual ganglion cells exist in a spindle cell rhabdomyosarcomatous background.
Ectomesenchymoma. Postchemotherapy ectomesenchymoma shows retained scattered ganglion cells and rhabdomyoblasts in oedematous and neuromatous stroma.

Q: Because Ectomesenchymoma contains areas of skeletal muscle differentiation, its malignant mesenchymal component can be highlighted by strong nuclear immunostaining for [...].
Ectomesenchymoma. Myogenin immunostaining highlights rhabdomyosarcomatous elements.
A: myogenin
Back Extra: Ectomesenchymoma
- Clinical: Ectomesenchymoma most commonly presents as a deep or superficial soft tissue mass in the pelvis, urogenital organs, and intra-abdominal/retroperitoneal soft tissue, with a predilection for infants and children aged < 5 years.
- Micro: The tumor is characterized by intermingled areas of rhabdomyosarcoma and neuroectodermal elements, including ganglion cells and neuroblastic components.
- Ancillary: Cytogenetic findings in ectomesenchymoma often show trisomies of chromosomes 2, 8, and 11, and frequent HRAS mutations, similar to those found in embryonal rhabdomyosarcoma.
Reference Gallery:
Ectomesenchymoma. Round and spindled rhabdomyosarcomatous cells intermingled with ganglioneuroblastic elements.
Ectomesenchymoma. Myogenin immunostaining highlights rhabdomyosarcomatous elements.
Ectomesenchymoma. Individual ganglion cells exist in a spindle cell rhabdomyosarcomatous background.
Ectomesenchymoma. Postchemotherapy ectomesenchymoma shows retained scattered ganglion cells and rhabdomyoblasts in oedematous and neuromatous stroma.

Q: The classic microscopic appearance of Epithelioid Hemangioendothelioma consists of cords of bland epithelioid tumor cells in a myxohyaline stroma, with many cells showing [...] that may contain red blood cells.
Epithelioid haemangioendothelioma. High-power image showing uniform epithelioid cells arranged in cords. Some of the neoplastic cells have intracytoplasmic vacuoles containing erythrocytes.
Epithelioid haemangioendothelioma. Cords and clusters of epithelioid endothelial cells with cytoplasmic vacuoles, which may or may not contain red blood cells, within a myxohyaline stroma.
A: intracytoplasmic vacuoles
Back Extra: Epithelioid Hemangioendothelioma
- Clinical: Epithelioid Hemangioendothelioma (EHE) often presents as a painful mass in soft tissues, with a high incidence of multiorgan disease in children.
- Micro: EHE is characterized by cords and nests of bland epithelioid tumour cells with round nuclei and eosinophilic cytoplasm in a myxohyaline stroma. Intracytoplasmic vacuoles may contain red blood cells.
- Ancillary: Molecular confirmation of WWTR1::CAMTA1 or YAP1::TFE3 fusions is essential for diagnosis.
Reference Gallery:
Epithelioid haemangioendothelioma. Cords and nests of epithelioid endothelial cells in a myxohyaline stroma.
Epithelioid haemangioendothelioma. High-power image showing uniform epithelioid cells arranged in cords. Some of the neoplastic cells have intracytoplasmic vacuoles containing erythrocytes.
Epithelioid haemangioendothelioma. Nuclear immunoreactivity for CAMTA1.
Epithelioid haemangioendothelioma. A case showing angiocentric growth with luminal occlusion.
Epithelioid haemangioendothelioma. Multifocal and focally confluent tan-white round masses in the liver.
Epithelioid haemangioendothelioma. Cords and clusters of epithelioid endothelial cells with cytoplasmic vacuoles, which may or may not contain red blood cells, within a myxohyaline stroma.

Q: The majority of Epithelioid Hemangioendothelioma cases harbor a WWTR1::CAMTA1 gene fusion, which can be diagnostically confirmed by diffuse nuclear immunohistochemical staining for [...].
Epithelioid haemangioendothelioma. Nuclear immunoreactivity for CAMTA1.
A: CAMTA1
Back Extra: Epithelioid Hemangioendothelioma
- Clinical: Epithelioid Hemangioendothelioma (EHE) often presents as a painful mass in soft tissues, with a high incidence of multiorgan disease in children.
- Micro: EHE is characterized by cords and nests of bland epithelioid tumour cells with round nuclei and eosinophilic cytoplasm in a myxohyaline stroma. Intracytoplasmic vacuoles may contain red blood cells.
- Ancillary: Molecular confirmation of WWTR1::CAMTA1 or YAP1::TFE3 fusions is essential for diagnosis.
Reference Gallery:
Epithelioid haemangioendothelioma. Cords and nests of epithelioid endothelial cells in a myxohyaline stroma.
Epithelioid haemangioendothelioma. High-power image showing uniform epithelioid cells arranged in cords. Some of the neoplastic cells have intracytoplasmic vacuoles containing erythrocytes.
Epithelioid haemangioendothelioma. Nuclear immunoreactivity for CAMTA1.
Epithelioid haemangioendothelioma. A case showing angiocentric growth with luminal occlusion.
Epithelioid haemangioendothelioma. Multifocal and focally confluent tan-white round masses in the liver.
Epithelioid haemangioendothelioma. Cords and clusters of epithelioid endothelial cells with cytoplasmic vacuoles, which may or may not contain red blood cells, within a myxohyaline stroma.

Q: Histologically, [...] is characterized by a lobular proliferation of well-formed blood vessels lined by plump endothelial cells with abundant eosinophilic cytoplasm, frequently accompanied by an inflammatory infiltrate of lymphocytes and eosinophils.
Epithelioid haemangioma. Lobular proliferation of vessels with surrounding inflammatory infiltrate composed of lymphocytes and eosinophils.
Epithelioid haemangioma. The vessels are lined by epithelioid endothelial cells with abundant eosinophilic cytoplasm.
A: Epithelioid Haemangioma
Back Extra: Epithelioid Haemangioma
- Clinical: Patients with cutaneous epithelioid haemangiomas present with one or multiple erythematous to violaceous papules or nodules, commonly on the lower extremities in children.
- Micro: Epithelioid haemangioma is characterized by a lobular proliferation of well-formed blood vessels lined by endothelial cells with enlarged vesicular nuclei and abundant eosinophilic cytoplasm.
- Ancillary: FOS or FOSB rearrangements are identified in approximately half of all cases, leading to prolonged activation or upregulation of these transcription factors.
Reference Gallery:
Epithelioid haemangioma. Lobular proliferation of vessels with surrounding inflammatory infiltrate composed of lymphocytes and eosinophils.
Epithelioid haemangioma. The vessels are lined by epithelioid endothelial cells with abundant eosinophilic cytoplasm.
Epithelioid haemangioma. In the cellular subtype of epithelioid haemangioma, vasoformative channels are less apparent and the inflammatory infiltrate is typically sparse to absent.
Epithelioid haemangioma. Intravascular subtype showing intravascular proliferation of vessels lined by epithelioid endothelial cells arising in a pre-existing vein.

Q: Molecular testing in Epithelioid Haemangioma reveals that approximately half of all cases are driven by recurrent gene rearrangements involving [...], leading to the prolonged activation of these transcription factors.
Epithelioid haemangioma. The vessels are lined by epithelioid endothelial cells with abundant eosinophilic cytoplasm.
Epithelioid haemangioma. In the cellular subtype of epithelioid haemangioma, vasoformative channels are less apparent and the inflammatory infiltrate is typically sparse to absent.
A: FOS or FOSB
Back Extra: Epithelioid Haemangioma
- Clinical: Patients with cutaneous epithelioid haemangiomas present with one or multiple erythematous to violaceous papules or nodules, commonly on the lower extremities in children.
- Micro: Epithelioid haemangioma is characterized by a lobular proliferation of well-formed blood vessels lined by endothelial cells with enlarged vesicular nuclei and abundant eosinophilic cytoplasm.
- Ancillary: FOS or FOSB rearrangements are identified in approximately half of all cases, leading to prolonged activation or upregulation of these transcription factors.
Reference Gallery:
Epithelioid haemangioma. Lobular proliferation of vessels with surrounding inflammatory infiltrate composed of lymphocytes and eosinophils.
Epithelioid haemangioma. The vessels are lined by epithelioid endothelial cells with abundant eosinophilic cytoplasm.
Epithelioid haemangioma. In the cellular subtype of epithelioid haemangioma, vasoformative channels are less apparent and the inflammatory infiltrate is typically sparse to absent.
Epithelioid haemangioma. Intravascular subtype showing intravascular proliferation of vessels lined by epithelioid endothelial cells arising in a pre-existing vein.

Q: The [...] subtype of Epithelioid Haemangioma is characterized by an intraluminal proliferation of vessels lined by epithelioid endothelial cells that arises directly within a pre-existing vein.
Epithelioid haemangioma. Intravascular subtype showing intravascular proliferation of vessels lined by epithelioid endothelial cells arising in a pre-existing vein.
A: intravascular
Back Extra: Epithelioid Haemangioma
- Clinical: Patients with cutaneous epithelioid haemangiomas present with one or multiple erythematous to violaceous papules or nodules, commonly on the lower extremities in children.
- Micro: Epithelioid haemangioma is characterized by a lobular proliferation of well-formed blood vessels lined by endothelial cells with enlarged vesicular nuclei and abundant eosinophilic cytoplasm.
- Ancillary: FOS or FOSB rearrangements are identified in approximately half of all cases, leading to prolonged activation or upregulation of these transcription factors.
Reference Gallery:
Epithelioid haemangioma. Lobular proliferation of vessels with surrounding inflammatory infiltrate composed of lymphocytes and eosinophils.
Epithelioid haemangioma. The vessels are lined by epithelioid endothelial cells with abundant eosinophilic cytoplasm.
Epithelioid haemangioma. In the cellular subtype of epithelioid haemangioma, vasoformative channels are less apparent and the inflammatory infiltrate is typically sparse to absent.
Epithelioid haemangioma. Intravascular subtype showing intravascular proliferation of vessels lined by epithelioid endothelial cells arising in a pre-existing vein.

Q: Histologically, the classic type of Epithelioid Sarcoma typically forms cellular nodules with central necrosis, creating a characteristic [...] growth pattern.
Classic-type epithelioid sarcoma. Low-power view of multiple nodules with central necrosis (pseudogranulomatous growth pattern) in the dermis.
A: pseudogranulomatous
Back Extra: Epithelioid Sarcoma
- Clinical: Epithelioid sarcoma (ES) typically presents as slow-growing, painless, firm, superficially located nodules, often resulting in non-healing skin ulcers.
- Micro: Classic ES shows cellular nodules with central necrosis and a pseudogranulomatous pattern, while proximal ES has a multinodular growth of large rhabdoid and pleomorphic cells.
- Ancillary: ES is characterized by loss of SMARCB1 (INI1) expression, diffuse expression of cytokeratin (CAM5.2), and strong membranous CD34 expression.
Reference Gallery:
Classic-type epithelioid sarcoma. Low-power view of multiple nodules with central necrosis (pseudogranulomatous growth pattern) in the dermis.
Classic-type epithelioid sarcoma. Epithelioid tumour cells with abundant eosinophilic cytoplasm, arranged in sheets.
Classic-type epithelioid sarcoma. Spindle-shaped tumour cells arranged in fascicles.
Proximal-type epithelioid sarcoma. Low-power view showing a multinodular growth pattern.
Proximal-type epithelioid sarcoma. Pleomorphic epithelioid tumour cells with abundant eosinophilic cytoplasm and enlarged vesicular nuclei with prominent nucleoli.
Proximal-type epithelioid sarcoma. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and eccentrically located vesicular nuclei.
Classic-type epithelioid sarcoma. Diffuse expression of cytokeratin (CAM5.2).
Classic-type epithelioid sarcoma. Diffuse and strong membranous expression of CD34.
Classic-type epithelioid sarcoma. Unexpected nuclear expression of ERG.
Classic-type epithelioid sarcoma. Complete loss of SMARCB1 (INI1) nuclear expression in the neoplastic cells (endothelial cells being the internal controls).
Epithelioid sarcoma. A small nodular lesion within the dermis of a finger of a 7-year-old girl.
Epithelioid sarcoma. A small nodular lesion within the dermis of a finger of a 7-year-old girl. The cells are large and epithelioid with vesicular nuclei and evident nucleoli.

Q: The proximal type of Epithelioid Sarcoma frequently features large, pleomorphic cells with glassy intracytoplasmic hyaline inclusions and eccentric nuclei, known as [...] cells.
Proximal-type epithelioid sarcoma. Pleomorphic epithelioid tumour cells with abundant eosinophilic cytoplasm and enlarged vesicular nuclei with prominent nucleoli.
Proximal-type epithelioid sarcoma. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and eccentrically located vesicular nuclei.
A: rhabdoid
Back Extra: Epithelioid Sarcoma
- Clinical: Epithelioid sarcoma (ES) typically presents as slow-growing, painless, firm, superficially located nodules, often resulting in non-healing skin ulcers.
- Micro: Classic ES shows cellular nodules with central necrosis and a pseudogranulomatous pattern, while proximal ES has a multinodular growth of large rhabdoid and pleomorphic cells.
- Ancillary: ES is characterized by loss of SMARCB1 (INI1) expression, diffuse expression of cytokeratin (CAM5.2), and strong membranous CD34 expression.
Reference Gallery:
Classic-type epithelioid sarcoma. Low-power view of multiple nodules with central necrosis (pseudogranulomatous growth pattern) in the dermis.
Classic-type epithelioid sarcoma. Epithelioid tumour cells with abundant eosinophilic cytoplasm, arranged in sheets.
Classic-type epithelioid sarcoma. Spindle-shaped tumour cells arranged in fascicles.
Proximal-type epithelioid sarcoma. Low-power view showing a multinodular growth pattern.
Proximal-type epithelioid sarcoma. Pleomorphic epithelioid tumour cells with abundant eosinophilic cytoplasm and enlarged vesicular nuclei with prominent nucleoli.
Proximal-type epithelioid sarcoma. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and eccentrically located vesicular nuclei.
Classic-type epithelioid sarcoma. Diffuse expression of cytokeratin (CAM5.2).
Classic-type epithelioid sarcoma. Diffuse and strong membranous expression of CD34.
Classic-type epithelioid sarcoma. Unexpected nuclear expression of ERG.
Classic-type epithelioid sarcoma. Complete loss of SMARCB1 (INI1) nuclear expression in the neoplastic cells (endothelial cells being the internal controls).
Epithelioid sarcoma. A small nodular lesion within the dermis of a finger of a 7-year-old girl.
Epithelioid sarcoma. A small nodular lesion within the dermis of a finger of a 7-year-old girl. The cells are large and epithelioid with vesicular nuclei and evident nucleoli.

Q: A defining immunohistochemical hallmark of Epithelioid Sarcoma is the complete loss of [...] nuclear expression, with retained expression in background endothelial cells.
Classic-type epithelioid sarcoma. Complete loss of SMARCB1 (INI1) nuclear expression in the neoplastic cells (endothelial cells being the internal controls).
A: SMARCB1 (INI1)
Back Extra: Epithelioid Sarcoma
- Clinical: Epithelioid sarcoma (ES) typically presents as slow-growing, painless, firm, superficially located nodules, often resulting in non-healing skin ulcers.
- Micro: Classic ES shows cellular nodules with central necrosis and a pseudogranulomatous pattern, while proximal ES has a multinodular growth of large rhabdoid and pleomorphic cells.
- Ancillary: ES is characterized by loss of SMARCB1 (INI1) expression, diffuse expression of cytokeratin (CAM5.2), and strong membranous CD34 expression.
Reference Gallery:
Classic-type epithelioid sarcoma. Low-power view of multiple nodules with central necrosis (pseudogranulomatous growth pattern) in the dermis.
Classic-type epithelioid sarcoma. Epithelioid tumour cells with abundant eosinophilic cytoplasm, arranged in sheets.
Classic-type epithelioid sarcoma. Spindle-shaped tumour cells arranged in fascicles.
Proximal-type epithelioid sarcoma. Low-power view showing a multinodular growth pattern.
Proximal-type epithelioid sarcoma. Pleomorphic epithelioid tumour cells with abundant eosinophilic cytoplasm and enlarged vesicular nuclei with prominent nucleoli.
Proximal-type epithelioid sarcoma. Aggregates of rhabdoid cells with glassy intracytoplasmic hyaline inclusions and eccentrically located vesicular nuclei.
Classic-type epithelioid sarcoma. Diffuse expression of cytokeratin (CAM5.2).
Classic-type epithelioid sarcoma. Diffuse and strong membranous expression of CD34.
Classic-type epithelioid sarcoma. Unexpected nuclear expression of ERG.
Classic-type epithelioid sarcoma. Complete loss of SMARCB1 (INI1) nuclear expression in the neoplastic cells (endothelial cells being the internal controls).
Epithelioid sarcoma. A small nodular lesion within the dermis of a finger of a 7-year-old girl.
Epithelioid sarcoma. A small nodular lesion within the dermis of a finger of a 7-year-old girl. The cells are large and epithelioid with vesicular nuclei and evident nucleoli.

Q: Immunohistochemistry for Ewing Sarcoma characteristically demonstrates strong, diffuse, and membranous staining for [...].
Ewing sarcoma. CD99 staining typically shows a strong diffuse and membranous pattern of reactivity.
A: CD99
Back Extra: Ewing Sarcoma
- Clinical: Ewing sarcoma typically presents with localized pain and a palpable mass; bony tumours may cause pathological fractures. B symptoms are rare except in advanced disease.
- Micro: Ewing sarcoma features solid sheets of small round cells with round nuclei, finely granular chromatin, and scant cytoplasm. Necrosis is common.
- Ancillary: CD99 immunohistochemistry is strongly and diffusely membranous in Ewing sarcoma, and molecular confirmation of EWSR1::ETS fusions is critical.
Reference Gallery:
Ewing sarcoma. Classic morphology. The tumour cells are spread out in a patternless sheet. Note the variably clear cytoplasm of individual tumour cells. A zone of necrosis is present in the lower part of the field.
Ewing sarcoma. Atypical histology. This tumour has cells and nuclei of a larger size, nuclear contour irregularities including some spindling, and coarser chromatin. Scattered areas of karyorrhexis are present.
Ewing sarcoma. Neuroectodermal differentiation. This example has pseudorosettes.
Ewing sarcoma. Cytological smear. The smear is cellular and the tumour cells are dyscohesive. They have round nuclei, dispersed chromatin, inconspicuous nucleoli, and scant cytoplasm. Apoptotic cells and karyorrhectic debris can also be seen in the background.
Ewing sarcoma. CD99 staining typically shows a strong diffuse and membranous pattern of reactivity.
Bone Ewing sarcoma. T2-weighted fat-suppressed axial MRI shows a T2-hyperintense extraosseous soft tissue mass. The periosteum is elevated by the tumour, which erodes into the underlying cortex.
Bone Ewing sarcoma. Contrast-enhanced T1-weighted fat-suppressed axial MRI shows avid enhancement of the extraosseous soft tissue as well as the intraosseous component.
Ewing sarcoma. Sheets and nests of uniform small round cells with a moderate amount of eosinophilic cytoplasm and oval nuclei with delicate chromatin.
Adamantinoma-like Ewing sarcoma. Nested and lobulated architecture with peripheral palisading and hyalinized stroma.
Adamantinoma-like Ewing sarcoma. Focal formation of compact keratin pearls.
Adamantinoma-like Ewing sarcoma. Diffuse cytokeratin AE1/AE3 positivity.

Q: Histologically, Ewing Sarcoma classically presents as patternless solid sheets of uniform [...] with finely granular chromatin, scant (often variably clear) cytoplasm, and frequent necrosis.
Ewing sarcoma. Classic morphology. The tumour cells are spread out in a patternless sheet. Note the variably clear cytoplasm of individual tumour cells. A zone of necrosis is present in the lower part of the field.
Ewing sarcoma. Sheets and nests of uniform small round cells with a moderate amount of eosinophilic cytoplasm and oval nuclei with delicate chromatin.
A: small round cells
Back Extra: Ewing Sarcoma
- Clinical: Ewing sarcoma typically presents with localized pain and a palpable mass; bony tumours may cause pathological fractures. B symptoms are rare except in advanced disease.
- Micro: Ewing sarcoma features solid sheets of small round cells with round nuclei, finely granular chromatin, and scant cytoplasm. Necrosis is common.
- Ancillary: CD99 immunohistochemistry is strongly and diffusely membranous in Ewing sarcoma, and molecular confirmation of EWSR1::ETS fusions is critical.
Reference Gallery:
Ewing sarcoma. Classic morphology. The tumour cells are spread out in a patternless sheet. Note the variably clear cytoplasm of individual tumour cells. A zone of necrosis is present in the lower part of the field.
Ewing sarcoma. Atypical histology. This tumour has cells and nuclei of a larger size, nuclear contour irregularities including some spindling, and coarser chromatin. Scattered areas of karyorrhexis are present.
Ewing sarcoma. Neuroectodermal differentiation. This example has pseudorosettes.
Ewing sarcoma. Cytological smear. The smear is cellular and the tumour cells are dyscohesive. They have round nuclei, dispersed chromatin, inconspicuous nucleoli, and scant cytoplasm. Apoptotic cells and karyorrhectic debris can also be seen in the background.
Ewing sarcoma. CD99 staining typically shows a strong diffuse and membranous pattern of reactivity.
Bone Ewing sarcoma. T2-weighted fat-suppressed axial MRI shows a T2-hyperintense extraosseous soft tissue mass. The periosteum is elevated by the tumour, which erodes into the underlying cortex.
Bone Ewing sarcoma. Contrast-enhanced T1-weighted fat-suppressed axial MRI shows avid enhancement of the extraosseous soft tissue as well as the intraosseous component.
Ewing sarcoma. Sheets and nests of uniform small round cells with a moderate amount of eosinophilic cytoplasm and oval nuclei with delicate chromatin.
Adamantinoma-like Ewing sarcoma. Nested and lobulated architecture with peripheral palisading and hyalinized stroma.
Adamantinoma-like Ewing sarcoma. Focal formation of compact keratin pearls.
Adamantinoma-like Ewing sarcoma. Diffuse cytokeratin AE1/AE3 positivity.

Q: In cases of Ewing Sarcoma exhibiting neuroectodermal differentiation, the tumor cells may arrange radially to form [...].
Ewing sarcoma. Neuroectodermal differentiation. This example has pseudorosettes.
A: pseudorosettes
Back Extra: Ewing Sarcoma
- Clinical: Ewing sarcoma typically presents with localized pain and a palpable mass; bony tumours may cause pathological fractures. B symptoms are rare except in advanced disease.
- Micro: Ewing sarcoma features solid sheets of small round cells with round nuclei, finely granular chromatin, and scant cytoplasm. Necrosis is common.
- Ancillary: CD99 immunohistochemistry is strongly and diffusely membranous in Ewing sarcoma, and molecular confirmation of EWSR1::ETS fusions is critical.
Reference Gallery:
Ewing sarcoma. Classic morphology. The tumour cells are spread out in a patternless sheet. Note the variably clear cytoplasm of individual tumour cells. A zone of necrosis is present in the lower part of the field.
Ewing sarcoma. Atypical histology. This tumour has cells and nuclei of a larger size, nuclear contour irregularities including some spindling, and coarser chromatin. Scattered areas of karyorrhexis are present.
Ewing sarcoma. Neuroectodermal differentiation. This example has pseudorosettes.
Ewing sarcoma. Cytological smear. The smear is cellular and the tumour cells are dyscohesive. They have round nuclei, dispersed chromatin, inconspicuous nucleoli, and scant cytoplasm. Apoptotic cells and karyorrhectic debris can also be seen in the background.
Ewing sarcoma. CD99 staining typically shows a strong diffuse and membranous pattern of reactivity.
Bone Ewing sarcoma. T2-weighted fat-suppressed axial MRI shows a T2-hyperintense extraosseous soft tissue mass. The periosteum is elevated by the tumour, which erodes into the underlying cortex.
Bone Ewing sarcoma. Contrast-enhanced T1-weighted fat-suppressed axial MRI shows avid enhancement of the extraosseous soft tissue as well as the intraosseous component.
Ewing sarcoma. Sheets and nests of uniform small round cells with a moderate amount of eosinophilic cytoplasm and oval nuclei with delicate chromatin.
Adamantinoma-like Ewing sarcoma. Nested and lobulated architecture with peripheral palisading and hyalinized stroma.
Adamantinoma-like Ewing sarcoma. Focal formation of compact keratin pearls.
Adamantinoma-like Ewing sarcoma. Diffuse cytokeratin AE1/AE3 positivity.

Q: Microscopically, EWSR1::SMAD3-rearranged fibroblastic tumor typically displays a biphasic architecture with central hyalinized areas that characteristically contain dystrophic [...].
EWSR1::SMAD3-rearranged fibroblastic tumour. Transition zone of the hypercellular periphery to the less cellular central area.
EWSR1::SMAD3-rearranged fibroblastic tumour. High-power view of a hyaline area showing dystrophic calcification.
A: calcification
Back Extra: EWSR1::SMAD3-rearranged fibroblastic tumour
- Clinical: Patients typically present with a superficial, often slow-growing lesion at the distal extremities, mainly in acral sites, with a strong female preponderance.
- Micro: The tumour shows a nodular or multinodular growth pattern with infiltrative margins, a biphasic appearance, and calcification in hyalinized areas.
- Ancillary: Consistent ERG expression and detection of the EWSR1::SMAD3 fusion gene by RT-PCR or FISH are required for diagnosis.
Reference Gallery:
EWSR1::SMAD3-rearranged fibroblastic tumour. Low-power view shows the infiltration into subcutaneous fat, and the fascicular architecture.
EWSR1::SMAD3-rearranged fibroblastic tumour. Transition zone of the hypercellular periphery to the less cellular central area.
EWSR1::SMAD3-rearranged fibroblastic tumour. High-power view of a hyaline area showing dystrophic calcification.
EWSR1::SMAD3-rearranged fibroblastic tumour. Diagram showing the EWSR1 (exon 7) fusion with SMAD3 (exon 5) and the domains of the fusion oncoprotein.

Q: At low power, EWSR1::SMAD3-rearranged fibroblastic tumor frequently exhibits a fascicular architecture and an infiltrative growth pattern extending into the underlying [...].
EWSR1::SMAD3-rearranged fibroblastic tumour. Low-power view shows the infiltration into subcutaneous fat, and the fascicular architecture.
A: subcutaneous fat
Back Extra: EWSR1::SMAD3-rearranged fibroblastic tumour
- Clinical: Patients typically present with a superficial, often slow-growing lesion at the distal extremities, mainly in acral sites, with a strong female preponderance.
- Micro: The tumour shows a nodular or multinodular growth pattern with infiltrative margins, a biphasic appearance, and calcification in hyalinized areas.
- Ancillary: Consistent ERG expression and detection of the EWSR1::SMAD3 fusion gene by RT-PCR or FISH are required for diagnosis.
Reference Gallery:
EWSR1::SMAD3-rearranged fibroblastic tumour. Low-power view shows the infiltration into subcutaneous fat, and the fascicular architecture.
EWSR1::SMAD3-rearranged fibroblastic tumour. Transition zone of the hypercellular periphery to the less cellular central area.
EWSR1::SMAD3-rearranged fibroblastic tumour. High-power view of a hyaline area showing dystrophic calcification.
EWSR1::SMAD3-rearranged fibroblastic tumour. Diagram showing the EWSR1 (exon 7) fusion with SMAD3 (exon 5) and the domains of the fusion oncoprotein.

Q: The defining molecular alteration of EWSR1::SMAD3-rearranged fibroblastic tumor is a fusion gene typically involving EWSR1 (exon 7) and [...] (exon 5).
EWSR1::SMAD3-rearranged fibroblastic tumour. Diagram showing the EWSR1 (exon 7) fusion with SMAD3 (exon 5) and the domains of the fusion oncoprotein.
A: SMAD3
Back Extra: EWSR1::SMAD3-rearranged fibroblastic tumour
- Clinical: Patients typically present with a superficial, often slow-growing lesion at the distal extremities, mainly in acral sites, with a strong female preponderance.
- Micro: The tumour shows a nodular or multinodular growth pattern with infiltrative margins, a biphasic appearance, and calcification in hyalinized areas.
- Ancillary: Consistent ERG expression and detection of the EWSR1::SMAD3 fusion gene by RT-PCR or FISH are required for diagnosis.
Reference Gallery:
EWSR1::SMAD3-rearranged fibroblastic tumour. Low-power view shows the infiltration into subcutaneous fat, and the fascicular architecture.
EWSR1::SMAD3-rearranged fibroblastic tumour. Transition zone of the hypercellular periphery to the less cellular central area.
EWSR1::SMAD3-rearranged fibroblastic tumour. High-power view of a hyaline area showing dystrophic calcification.
EWSR1::SMAD3-rearranged fibroblastic tumour. Diagram showing the EWSR1 (exon 7) fusion with SMAD3 (exon 5) and the domains of the fusion oncoprotein.

Q: The hallmark histologic feature of an extrarenal rhabdoid tumor is the presence of discohesive cells with eccentric vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm containing glassy [...].
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. The rhabdoid cells show a discohesive growth pattern.
A: hyaline inclusions
Back Extra: Extrarenal Rhabdoid Tumour
- Clinical: Extrarenal Rhabdoid Tumour primarily affects infants and children, presenting as a rapidly enlarging soft tissue mass.
- Micro: Characteristic rhabdoid cells with large vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm containing hyaline inclusions.
- Ancillary: Loss of expression of SMARCB1 (INI1) is a key diagnostic feature in Extrarenal Rhabdoid Tumour.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. The rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. A proliferation of undifferentiated small round cells, which is often observed in liver tumours.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) is observed in the vascular endothelial cells and inflammatory cells (internal control) but is completely absent in the neoplastic cells.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin (CAM5.2), which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Nuclear expression of SALL4.
Extrarenal rhabdoid tumour. Chromosomal microarray analysis of an extrarenal rhabdoid tumour. Overlapping deletions in chromosome 22 result in homozygous loss of SMARCB1.
Extrarenal rhabdoid tumour. Contrast-enhanced axial CT showing a large heterogeneously enhancing mass arising from the urinary bladder. The imaging features are nonspecific.

Q: The defining diagnostic molecular feature of an extrarenal rhabdoid tumor is the complete loss of expression of the tumor suppressor [...], which can be demonstrated via immunohistochemistry or chromosomal microarray.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) is observed in the vascular endothelial cells and inflammatory cells (internal control) but is completely absent in the neoplastic cells.
Extrarenal rhabdoid tumour. Chromosomal microarray analysis of an extrarenal rhabdoid tumour. Overlapping deletions in chromosome 22 result in homozygous loss of SMARCB1.
A: SMARCB1 (INI1)
Back Extra: Extrarenal Rhabdoid Tumour
- Clinical: Extrarenal Rhabdoid Tumour primarily affects infants and children, presenting as a rapidly enlarging soft tissue mass.
- Micro: Characteristic rhabdoid cells with large vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm containing hyaline inclusions.
- Ancillary: Loss of expression of SMARCB1 (INI1) is a key diagnostic feature in Extrarenal Rhabdoid Tumour.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. The rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. A proliferation of undifferentiated small round cells, which is often observed in liver tumours.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) is observed in the vascular endothelial cells and inflammatory cells (internal control) but is completely absent in the neoplastic cells.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin (CAM5.2), which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Nuclear expression of SALL4.
Extrarenal rhabdoid tumour. Chromosomal microarray analysis of an extrarenal rhabdoid tumour. Overlapping deletions in chromosome 22 result in homozygous loss of SMARCB1.
Extrarenal rhabdoid tumour. Contrast-enhanced axial CT showing a large heterogeneously enhancing mass arising from the urinary bladder. The imaging features are nonspecific.

Q: In an extrarenal rhabdoid tumor, the characteristic cytoplasmic hyaline inclusions show strong, dot-like immunoreactivity for [...] (e.g., CAM5.2).
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin (CAM5.2), which is confined to the inclusions.
A: keratin
Back Extra: Extrarenal Rhabdoid Tumour
- Clinical: Extrarenal Rhabdoid Tumour primarily affects infants and children, presenting as a rapidly enlarging soft tissue mass.
- Micro: Characteristic rhabdoid cells with large vesicular nuclei, prominent nucleoli, and eosinophilic cytoplasm containing hyaline inclusions.
- Ancillary: Loss of expression of SMARCB1 (INI1) is a key diagnostic feature in Extrarenal Rhabdoid Tumour.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. The rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. A proliferation of undifferentiated small round cells, which is often observed in liver tumours.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) is observed in the vascular endothelial cells and inflammatory cells (internal control) but is completely absent in the neoplastic cells.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin (CAM5.2), which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Nuclear expression of SALL4.
Extrarenal rhabdoid tumour. Chromosomal microarray analysis of an extrarenal rhabdoid tumour. Overlapping deletions in chromosome 22 result in homozygous loss of SMARCB1.
Extrarenal rhabdoid tumour. Contrast-enhanced axial CT showing a large heterogeneously enhancing mass arising from the urinary bladder. The imaging features are nonspecific.

Q: Microscopically, an extrarenal rhabdoid tumor is characterized by discohesive cells with large vesicular nuclei, prominent nucleoli, and abundant eosinophilic cytoplasm that frequently contains [...].
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. The rhabdoid cells show a discohesive growth pattern.
A: glassy juxtanuclear inclusions
Q: Extrarenal Rhabdoid Tumour
- Clinical: Most patients with [...] present with a rapidly enlarging soft tissue mass; clinical symptoms depend on the primary organ involved.
- Micro: [...] are characterized by rhabdoid cells with large vesicular nuclei, prominent nucleoli, and abundant cytoplasm, often with juxtanuclear inclusions.
- Ancillary: Key ancillary studies for [...] include loss of SMARCB1 (INI1) expression and homozygous inactivation of the SMARCB1 gene.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. The rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. A proliferation of undifferentiated small round cells, which is often observed in liver tumours.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) is observed in the vascular endothelial cells and inflammatory cells (internal control) but is completely absent in the neoplastic cells.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin (CAM5.2), which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Nuclear expression of SALL4.
Extrarenal rhabdoid tumour. Chromosomal microarray analysis of an extrarenal rhabdoid tumour. Overlapping deletions in chromosome 22 result in homozygous loss of SMARCB1.
Extrarenal rhabdoid tumour. Contrast-enhanced axial CT showing a large heterogeneously enhancing mass arising from the urinary bladder. The imaging features are nonspecific.
A: extrarenal rhabdoid tumour; Extrarenal rhabdoid tumours; extrarenal rhabdoid tumours

Q: A defining molecular and immunohistochemical hallmark of an extrarenal rhabdoid tumor is the complete loss of [...] expression in neoplastic cells, while retained in background non-neoplastic cells.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) is observed in the vascular endothelial cells and inflammatory cells (internal control) but is completely absent in the neoplastic cells.
Extrarenal rhabdoid tumour. Chromosomal microarray analysis of an extrarenal rhabdoid tumour. Overlapping deletions in chromosome 22 result in homozygous loss of SMARCB1.
A: SMARCB1 (INI1)
Q: Extrarenal Rhabdoid Tumour
- Clinical: Most patients with [...] present with a rapidly enlarging soft tissue mass; clinical symptoms depend on the primary organ involved.
- Micro: [...] are characterized by rhabdoid cells with large vesicular nuclei, prominent nucleoli, and abundant cytoplasm, often with juxtanuclear inclusions.
- Ancillary: Key ancillary studies for [...] include loss of SMARCB1 (INI1) expression and homozygous inactivation of the SMARCB1 gene.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. The rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. A proliferation of undifferentiated small round cells, which is often observed in liver tumours.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) is observed in the vascular endothelial cells and inflammatory cells (internal control) but is completely absent in the neoplastic cells.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin (CAM5.2), which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Nuclear expression of SALL4.
Extrarenal rhabdoid tumour. Chromosomal microarray analysis of an extrarenal rhabdoid tumour. Overlapping deletions in chromosome 22 result in homozygous loss of SMARCB1.
Extrarenal rhabdoid tumour. Contrast-enhanced axial CT showing a large heterogeneously enhancing mass arising from the urinary bladder. The imaging features are nonspecific.
A: extrarenal rhabdoid tumour; Extrarenal rhabdoid tumours; extrarenal rhabdoid tumours

Q: In an extrarenal rhabdoid tumor, immunohistochemical staining for keratin (e.g., CAM5.2) characteristically shows strong immunoreactivity that is uniquely localized to the [...].
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin (CAM5.2), which is confined to the inclusions.
A: cytoplasmic inclusions
Q: Extrarenal Rhabdoid Tumour
- Clinical: Most patients with [...] present with a rapidly enlarging soft tissue mass; clinical symptoms depend on the primary organ involved.
- Micro: [...] are characterized by rhabdoid cells with large vesicular nuclei, prominent nucleoli, and abundant cytoplasm, often with juxtanuclear inclusions.
- Ancillary: Key ancillary studies for [...] include loss of SMARCB1 (INI1) expression and homozygous inactivation of the SMARCB1 gene.
Reference Gallery:
Extrarenal rhabdoid tumour. Characteristic rhabdoid cells with eosinophilic cytoplasm containing glassy inclusion-like bodies, eccentric vesicular nuclei, and prominent nucleoli.
Extrarenal rhabdoid tumour. The rhabdoid cells show a discohesive growth pattern.
Extrarenal rhabdoid tumour. A proliferation of undifferentiated small round cells, which is often observed in liver tumours.
Extrarenal rhabdoid tumour. Positive nuclear expression of SMARCB1 (INI1) is observed in the vascular endothelial cells and inflammatory cells (internal control) but is completely absent in the neoplastic cells.
Extrarenal rhabdoid tumour. Strong positive cytoplasmic immunoreactivity for keratin (CAM5.2), which is confined to the inclusions.
Extrarenal rhabdoid tumour. Focal membranous positivity for EMA.
Extrarenal rhabdoid tumour. Nuclear expression of SALL4.
Extrarenal rhabdoid tumour. Chromosomal microarray analysis of an extrarenal rhabdoid tumour. Overlapping deletions in chromosome 22 result in homozygous loss of SMARCB1.
Extrarenal rhabdoid tumour. Contrast-enhanced axial CT showing a large heterogeneously enhancing mass arising from the urinary bladder. The imaging features are nonspecific.
A: extrarenal rhabdoid tumour; Extrarenal rhabdoid tumours; extrarenal rhabdoid tumours

Q: Early (active) phase lesions of Fibrodysplasia ossificans progressiva initially consist of a nonspecific, vascular, loose fibrous proliferation that progressively matures into cartilage and eventually undergoes [...].
Fibrodysplasia ossificans progressiva. Early (active) phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Resting-phase example in the patient shown in Fig. <<18735>>, 9 months later. Right back mass.
A: endochondral ossification
Back Extra: Fibrodysplasia ossificans progressiva
- Clinical: Fibrodysplasia ossificans progressiva (FOP) is associated with congenital malformations of the great toes and cervical–vertebral fusions, with episodes of painful soft tissue swelling and progressive ossification.
- Micro: Early lesions of FOP are nonspecific vascular loose fibrous tissue proliferations that mature into cartilage and endochondral ossification.
- Ancillary: Molecular testing is necessary to demonstrate a germline mutation of ACVR1, which encodes a BMP receptor.
Reference Gallery:
Fibrodysplasia ossificans progressiva. Early (active) phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Early (active) phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Early (active)-phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Early (active)-phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Resting-phase example in the patient shown in Fig. <<18735>>, 9 months later. Right back mass.
Fibrodysplasia ossificans progressiva. Resting-phase example in the patient shown in Fig. <<18735>>, 9 months later. Right back mass.

Q: Molecular testing in Fibrodysplasia ossificans progressiva is utilized to demonstrate a characteristic germline mutation in the [...] gene, which encodes a bone morphogenetic protein (BMP) receptor.
Fibrodysplasia ossificans progressiva. Early (active) phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Resting-phase example in the patient shown in Fig. <<18735>>, 9 months later. Right back mass.
A: ACVR1
Back Extra: Fibrodysplasia ossificans progressiva
- Clinical: Fibrodysplasia ossificans progressiva (FOP) is associated with congenital malformations of the great toes and cervical–vertebral fusions, with episodes of painful soft tissue swelling and progressive ossification.
- Micro: Early lesions of FOP are nonspecific vascular loose fibrous tissue proliferations that mature into cartilage and endochondral ossification.
- Ancillary: Molecular testing is necessary to demonstrate a germline mutation of ACVR1, which encodes a BMP receptor.
Reference Gallery:
Fibrodysplasia ossificans progressiva. Early (active) phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Early (active) phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Early (active)-phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Early (active)-phase example in the left scapular soft tissues of a 1-year-old boy.
Fibrodysplasia ossificans progressiva. Resting-phase example in the patient shown in Fig. <<18735>>, 9 months later. Right back mass.
Fibrodysplasia ossificans progressiva. Resting-phase example in the patient shown in Fig. <<18735>>, 9 months later. Right back mass.

Q: Histologically, Fibroma of Tendon Sheath typically consists of circumscribed fascicles of bland fibroblasts in a dense collagenous stroma with characteristic [...] blood vessels.
Fibroma of tendon sheath. Bland, nodular spindle cell lesion arising from tendon.
Fibroma of tendon sheath. Bland spindle cell fascicles with slit-like blood vessels.
A: slit-like
Back Extra: Fibroma of Tendon Sheath
- Clinical: Fibroma of tendon sheath (FOTS) is a slow-growing, painless nodule, usually found on the finger tendons, particularly the thumb, index finger, and middle finger, and rarely in the knee, elbow, or wrist.
- Micro: Histological examination of FOTS reveals a circumscribed arrangement of bland fibroblasts and myofibroblasts in a densely collagenous or hyalinized stroma with characteristic slit-like blood vessels.
- Ancillary: Chromosome 11q rearrangements have been identified in 2 cases of FOTS, and there are increasing reports of FOTS-like tumours harbouring genetic alterations of USP6, better classified as nodular fasciitis.
Reference Gallery:
Fibroma of tendon sheath. Bland, nodular spindle cell lesion arising from tendon.
Fibroma of tendon sheath. Bland spindle cell fascicles with slit-like blood vessels.
Fibroma of tendon Sheath. CD34 decorates the slit-like blood vessels within this lesion and the surrounding dermal collagen, but the lesional fibroblasts are negative.

Q: In Fibroma of Tendon Sheath, an immunohistochemical stain for [...] highlights the characteristic slit-like blood vessels, while the surrounding lesional fibroblasts remain negative.
Fibroma of tendon Sheath. CD34 decorates the slit-like blood vessels within this lesion and the surrounding dermal collagen, but the lesional fibroblasts are negative.
A: CD34
Back Extra: Fibroma of Tendon Sheath
- Clinical: Fibroma of tendon sheath (FOTS) is a slow-growing, painless nodule, usually found on the finger tendons, particularly the thumb, index finger, and middle finger, and rarely in the knee, elbow, or wrist.
- Micro: Histological examination of FOTS reveals a circumscribed arrangement of bland fibroblasts and myofibroblasts in a densely collagenous or hyalinized stroma with characteristic slit-like blood vessels.
- Ancillary: Chromosome 11q rearrangements have been identified in 2 cases of FOTS, and there are increasing reports of FOTS-like tumours harbouring genetic alterations of USP6, better classified as nodular fasciitis.
Reference Gallery:
Fibroma of tendon sheath. Bland, nodular spindle cell lesion arising from tendon.
Fibroma of tendon sheath. Bland spindle cell fascicles with slit-like blood vessels.
Fibroma of tendon Sheath. CD34 decorates the slit-like blood vessels within this lesion and the surrounding dermal collagen, but the lesional fibroblasts are negative.

Q: In Fibromatosis colli, infants typically present within the first few weeks of life with a neck mass located specifically within the [...] muscle.
Fibromatosis colli. Colour Doppler ultrasound image (right side of neck). There is a heterogeneous hyperechoic fusiform mass along the right sternocleidomastoid muscle.
A: sternocleidomastoid
Back Extra: Fibromatosis colli
- Clinical: Fibromatosis colli often presents as a mass in the sternocleidomastoid muscle within 2–4 weeks of birth, with potential progression to torticollis and plagiocephaly.
- Micro: Histologically, fibromatosis colli shows a paucicellular, bland, fibroblastic proliferation entrapping skeletal muscle fibers with reactive and regenerative changes.
- Ancillary: Ultrasound is the preferred imaging method, demonstrating an isoechoic to hypoechoic, solid, well-defined ovoid mass in the sternocleidomastoid muscle.
Reference Gallery:
Fibromatosis colli. Skeletal muscle fibres with reactive, regenerative changes, entrapped by collagen fibres and fibroblasts.
Fibromatosis colli. A bland, fibroblastic spindle cell processes arranged in fascicles infiltrates skeletal muscle (left).
Fibromatosis colli. Colour Doppler ultrasound image (right side of neck). There is a heterogeneous hyperechoic fusiform mass along the right sternocleidomastoid muscle.

Q: Histologically, Fibromatosis colli is characterized by a bland, paucicellular fibroblastic proliferation that characteristically entraps [...].
Fibromatosis colli. Skeletal muscle fibres with reactive, regenerative changes, entrapped by collagen fibres and fibroblasts.
Fibromatosis colli. A bland, fibroblastic spindle cell processes arranged in fascicles infiltrates skeletal muscle (left).
A: skeletal muscle fibers
Back Extra: Fibromatosis colli
- Clinical: Fibromatosis colli often presents as a mass in the sternocleidomastoid muscle within 2–4 weeks of birth, with potential progression to torticollis and plagiocephaly.
- Micro: Histologically, fibromatosis colli shows a paucicellular, bland, fibroblastic proliferation entrapping skeletal muscle fibers with reactive and regenerative changes.
- Ancillary: Ultrasound is the preferred imaging method, demonstrating an isoechoic to hypoechoic, solid, well-defined ovoid mass in the sternocleidomastoid muscle.
Reference Gallery:
Fibromatosis colli. Skeletal muscle fibres with reactive, regenerative changes, entrapped by collagen fibres and fibroblasts.
Fibromatosis colli. A bland, fibroblastic spindle cell processes arranged in fascicles infiltrates skeletal muscle (left).
Fibromatosis colli. Colour Doppler ultrasound image (right side of neck). There is a heterogeneous hyperechoic fusiform mass along the right sternocleidomastoid muscle.

Q: The characteristic histologic finding in Fibrous Hamartoma of Infancy is a [...] pattern consisting of bland fibroblastic fascicles, mature adipose tissue, and myxoid nodules of primitive mesenchymal cells.
Fibrous hamartoma of infancy. Characteristic triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view showing the triphasic pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
A: triphasic
Back Extra: Fibrous Hamartoma of Infancy
- Clinical: Fibrous hamartoma of infancy typically presents as a painless solitary subcutaneous mass in infants and young children.
- Micro: The characteristic triphasic pattern of fibrous hamartoma of infancy includes fascicles of bland fibroblastic/myofibroblastic cells, mature adipose tissue, and myxoid nodules containing primitive mesenchymal cells.
- Ancillary: CD34 immunohistochemistry is positive in areas resembling giant cell fibroblastoma in fibrous hamartoma of infancy.
Reference Gallery:
Fibrous hamartoma of infancy. Characteristic triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view showing the triphasic pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Giant cell fibroblastoma–like areas with abundant collagen forming slit-like spaces lined by flattened tumour cells.
Fibrous hamartoma of infancy. CD34 immunohistochemistry highlights giant cell fibroblastoma–like areas.

Q: In Fibrous Hamartoma of Infancy, areas that histologically resemble giant cell fibroblastoma are characteristically positive for the immunohistochemical marker [...].
Fibrous hamartoma of infancy. Giant cell fibroblastoma–like areas with abundant collagen forming slit-like spaces lined by flattened tumour cells.
Fibrous hamartoma of infancy. CD34 immunohistochemistry highlights giant cell fibroblastoma–like areas.
A: CD34
Back Extra: Fibrous Hamartoma of Infancy
- Clinical: Fibrous hamartoma of infancy typically presents as a painless solitary subcutaneous mass in infants and young children.
- Micro: The characteristic triphasic pattern of fibrous hamartoma of infancy includes fascicles of bland fibroblastic/myofibroblastic cells, mature adipose tissue, and myxoid nodules containing primitive mesenchymal cells.
- Ancillary: CD34 immunohistochemistry is positive in areas resembling giant cell fibroblastoma in fibrous hamartoma of infancy.
Reference Gallery:
Fibrous hamartoma of infancy. Characteristic triphasic organoid pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view showing the triphasic pattern with bundles of fibroblastic spindle cells, mature adipose tissue, and nodules of primitive mesenchyme.
Fibrous hamartoma of infancy. Giant cell fibroblastoma–like areas with abundant collagen forming slit-like spaces lined by flattened tumour cells.
Fibrous hamartoma of infancy. CD34 immunohistochemistry highlights giant cell fibroblastoma–like areas.

Q: Microscopically, Gardner Fibroma is characterized by haphazardly arranged coarse collagen bundles and prominent clefts, creating a characteristic [...].
Gardner fibroma. Dense collagen bundles and sparse bland fibroblasts intermingle in this cracked-collagen pattern.
A: cracking artifact
Back Extra: Gardner Fibroma
- Clinical: Gardner fibroma (GF) is a painless plaque/mass, typically diagnosed in young children (aged < 10 years), including neonates.
- Micro: GF exhibits haphazardly arranged coarse collagen bundles interspersed with bland spindled fibroblasts and prominent clefts (cracking artefact).
- Ancillary: GF is associated with germline and somatic APC mutations, often showing nuclear β-catenin staining.
Reference Gallery:
Gardner fibroma. Dense collagen bundles and sparse bland fibroblasts intermingle in this cracked-collagen pattern.
Gardner fibroma. Entrapped neurovascular bundle, typical of Gardner fibroma.
Gardner fibroma. This Gardner fibroma (left) is associated with a desmoid tumour (right) in a patient with an APC mutation.
Gardner fibroma. Nuclear staining for β-catenin is demonstrated in this tumour.

Q: Immunohistochemistry for Gardner Fibroma typically demonstrates positive [...] staining due to its underlying genetic driver.
Gardner fibroma. Nuclear staining for β-catenin is demonstrated in this tumour.
A: nuclear β-catenin
Back Extra: Gardner Fibroma
- Clinical: Gardner fibroma (GF) is a painless plaque/mass, typically diagnosed in young children (aged < 10 years), including neonates.
- Micro: GF exhibits haphazardly arranged coarse collagen bundles interspersed with bland spindled fibroblasts and prominent clefts (cracking artefact).
- Ancillary: GF is associated with germline and somatic APC mutations, often showing nuclear β-catenin staining.
Reference Gallery:
Gardner fibroma. Dense collagen bundles and sparse bland fibroblasts intermingle in this cracked-collagen pattern.
Gardner fibroma. Entrapped neurovascular bundle, typical of Gardner fibroma.
Gardner fibroma. This Gardner fibroma (left) is associated with a desmoid tumour (right) in a patient with an APC mutation.
Gardner fibroma. Nuclear staining for β-catenin is demonstrated in this tumour.

Q: Gardner Fibroma is strongly associated with germline and somatic mutations in the [...] gene, predisposing patients to concurrent or subsequent desmoid tumors.
Gardner fibroma. This Gardner fibroma (left) is associated with a desmoid tumour (right) in a patient with an APC mutation.
A: APC
Back Extra: Gardner Fibroma
- Clinical: Gardner fibroma (GF) is a painless plaque/mass, typically diagnosed in young children (aged < 10 years), including neonates.
- Micro: GF exhibits haphazardly arranged coarse collagen bundles interspersed with bland spindled fibroblasts and prominent clefts (cracking artefact).
- Ancillary: GF is associated with germline and somatic APC mutations, often showing nuclear β-catenin staining.
Reference Gallery:
Gardner fibroma. Dense collagen bundles and sparse bland fibroblasts intermingle in this cracked-collagen pattern.
Gardner fibroma. Entrapped neurovascular bundle, typical of Gardner fibroma.
Gardner fibroma. This Gardner fibroma (left) is associated with a desmoid tumour (right) in a patient with an APC mutation.
Gardner fibroma. Nuclear staining for β-catenin is demonstrated in this tumour.

Q: In Paediatric Gastrointestinal Stromal Tumour, the characteristic architecture consists of bands of muscularis propria separating tumor nodules, creating a distinct [...] or plexiform pattern.
Gastrointestinal stromal tumour. This tumour arose in the body of the stomach of a girl in her second decade of life. Note the plexiform growth pattern.
Gastrointestinal stromal tumour. A multinodular architecture is characteristic of gastrointestinal stromal tumours in children, the majority of which are succinate dehydrogenase–deficient.
Gastrointestinal stromal tumour. Bands of muscularis propria separate nodules of tumour in succinate dehydrogenase–deficient gastrointestinal stromal tumours.
A: multinodular
Back Extra: Paediatric Gastrointestinal Stromal Tumour
- Clinical: Children with Paediatric Gastrointestinal Stromal Tumour (GIST) often present with symptoms related to gastric mucosal ulceration, such as acute and chronic gastrointestinal bleeding, abdominal pain, and an abdominal mass.
- Micro: SDH-deficient GISTs in children show a characteristic multinodular architecture, with bands of muscularis propria separating nodules of tumour, and a plexiform pattern of mural involvement.
- Ancillary: Loss of SDHB expression by immunohistochemistry is a critical hallmark for diagnosing succinate dehydrogenase (SDH)-deficient Paediatric Gastrointestinal Stromal Tumour (GIST).
Reference Gallery:
Gastrointestinal stromal tumour. Lymph node metastasis is a common finding for gastrointestinal stromal tumours in the paediatric population.
Gastrointestinal stromal tumour. This tumour arose in the body of the stomach of a girl in her second decade of life. Note the plexiform growth pattern.
Gastrointestinal stromal tumour. A multinodular architecture is characteristic of gastrointestinal stromal tumours in children, the majority of which are succinate dehydrogenase–deficient.
Gastrointestinal stromal tumour. Bands of muscularis propria separate nodules of tumour in succinate dehydrogenase–deficient gastrointestinal stromal tumours.
Gastrointestinal stromal tumour. Most gastrointestinal stromal tumours in children show epithelioid morphology. Note the uniform cytology, abundant pale eosinophilic cytoplasm, and syncytial growth pattern.
Gastrointestinal stromal tumour. By immunohistochemistry, the tumour cells show strong and diffuse expression of KIT (CD117).
Gastrointestinal stromal tumour. The tumour cells in this succinate dehydrogenase–deficient gastrointestinal stromal tumour show a loss of staining for SDHB. Note the granular (mitochondrial) pattern of staining in endothelial cells, which serves as an internal control.
Paediatric gastrointestinal stromal tumour. Contrast-enhanced axial CT shows a large exophytic mass with heterogeneous enhancement arising from the small bowel loops.

Q: The critical immunohistochemical hallmark for diagnosing succinate dehydrogenase (SDH)-deficient Paediatric Gastrointestinal Stromal Tumour is the loss of [...] expression, which contrasts with the retained granular (mitochondrial) staining in internal control endothelial cells.
Gastrointestinal stromal tumour. The tumour cells in this succinate dehydrogenase–deficient gastrointestinal stromal tumour show a loss of staining for SDHB. Note the granular (mitochondrial) pattern of staining in endothelial cells, which serves as an internal control.
A: SDHB
Back Extra: Paediatric Gastrointestinal Stromal Tumour
- Clinical: Children with Paediatric Gastrointestinal Stromal Tumour (GIST) often present with symptoms related to gastric mucosal ulceration, such as acute and chronic gastrointestinal bleeding, abdominal pain, and an abdominal mass.
- Micro: SDH-deficient GISTs in children show a characteristic multinodular architecture, with bands of muscularis propria separating nodules of tumour, and a plexiform pattern of mural involvement.
- Ancillary: Loss of SDHB expression by immunohistochemistry is a critical hallmark for diagnosing succinate dehydrogenase (SDH)-deficient Paediatric Gastrointestinal Stromal Tumour (GIST).
Reference Gallery:
Gastrointestinal stromal tumour. Lymph node metastasis is a common finding for gastrointestinal stromal tumours in the paediatric population.
Gastrointestinal stromal tumour. This tumour arose in the body of the stomach of a girl in her second decade of life. Note the plexiform growth pattern.
Gastrointestinal stromal tumour. A multinodular architecture is characteristic of gastrointestinal stromal tumours in children, the majority of which are succinate dehydrogenase–deficient.
Gastrointestinal stromal tumour. Bands of muscularis propria separate nodules of tumour in succinate dehydrogenase–deficient gastrointestinal stromal tumours.
Gastrointestinal stromal tumour. Most gastrointestinal stromal tumours in children show epithelioid morphology. Note the uniform cytology, abundant pale eosinophilic cytoplasm, and syncytial growth pattern.
Gastrointestinal stromal tumour. By immunohistochemistry, the tumour cells show strong and diffuse expression of KIT (CD117).
Gastrointestinal stromal tumour. The tumour cells in this succinate dehydrogenase–deficient gastrointestinal stromal tumour show a loss of staining for SDHB. Note the granular (mitochondrial) pattern of staining in endothelial cells, which serves as an internal control.
Paediatric gastrointestinal stromal tumour. Contrast-enhanced axial CT shows a large exophytic mass with heterogeneous enhancement arising from the small bowel loops.

Q: Unlike the typical adult spindle cell variants, most cases of Paediatric Gastrointestinal Stromal Tumour display [...] morphology, featuring uniform cytology with abundant pale eosinophilic cytoplasm and a syncytial growth pattern.
Gastrointestinal stromal tumour. Most gastrointestinal stromal tumours in children show epithelioid morphology. Note the uniform cytology, abundant pale eosinophilic cytoplasm, and syncytial growth pattern.
A: epithelioid
Back Extra: Paediatric Gastrointestinal Stromal Tumour
- Clinical: Children with Paediatric Gastrointestinal Stromal Tumour (GIST) often present with symptoms related to gastric mucosal ulceration, such as acute and chronic gastrointestinal bleeding, abdominal pain, and an abdominal mass.
- Micro: SDH-deficient GISTs in children show a characteristic multinodular architecture, with bands of muscularis propria separating nodules of tumour, and a plexiform pattern of mural involvement.
- Ancillary: Loss of SDHB expression by immunohistochemistry is a critical hallmark for diagnosing succinate dehydrogenase (SDH)-deficient Paediatric Gastrointestinal Stromal Tumour (GIST).
Reference Gallery:
Gastrointestinal stromal tumour. Lymph node metastasis is a common finding for gastrointestinal stromal tumours in the paediatric population.
Gastrointestinal stromal tumour. This tumour arose in the body of the stomach of a girl in her second decade of life. Note the plexiform growth pattern.
Gastrointestinal stromal tumour. A multinodular architecture is characteristic of gastrointestinal stromal tumours in children, the majority of which are succinate dehydrogenase–deficient.
Gastrointestinal stromal tumour. Bands of muscularis propria separate nodules of tumour in succinate dehydrogenase–deficient gastrointestinal stromal tumours.
Gastrointestinal stromal tumour. Most gastrointestinal stromal tumours in children show epithelioid morphology. Note the uniform cytology, abundant pale eosinophilic cytoplasm, and syncytial growth pattern.
Gastrointestinal stromal tumour. By immunohistochemistry, the tumour cells show strong and diffuse expression of KIT (CD117).
Gastrointestinal stromal tumour. The tumour cells in this succinate dehydrogenase–deficient gastrointestinal stromal tumour show a loss of staining for SDHB. Note the granular (mitochondrial) pattern of staining in endothelial cells, which serves as an internal control.
Paediatric gastrointestinal stromal tumour. Contrast-enhanced axial CT shows a large exophytic mass with heterogeneous enhancement arising from the small bowel loops.

Q: A well-circumscribed, painful cutaneous nodule reveals solid sheets and nests of uniform, round cells with bland chromatin surrounding capillary-sized vessels. These morphologic features are characteristic of a [...].
Classic glomus tumour. A well-circumscribed tumour composed of solid sheets of monomorphic glomus cells.
Classic glomus tumour. Glomus cells are uniform and show round nuclei, bland chromatin, and minimal mitotic activity.
A: Glomus Tumor and Glomuvenous Malformation
Back Extra: Glomus Tumor and Glomuvenous Malformation
- Clinical: Cutaneous classic glomus tumours (cGTs) manifest as single, small blue-red nodules with paroxysmal pain, often triggered by cold exposure or minor tactile stimulation.
- Micro: cGTs are composed of sheets, nests, and trabeculae of monomorphic glomus cells in a hyalinized or myxoid stroma with branching capillary-sized vessels.
- Ancillary: GTs harbour recurrent NOTCH-family gene rearrangements, with MIR143 fusions with NOTCH1, NOTCH2, or NOTCH3 present in over 50% of cases.
Reference Gallery:
Classic glomus tumour. A well-circumscribed tumour composed of solid sheets of monomorphic glomus cells.
Classic glomus tumour. Glomus cells are uniform and show round nuclei, bland chromatin, and minimal mitotic activity.

Q: In a Glomus Tumor and Glomuvenous Malformation, the classic microscopic appearance features branching capillary-sized vessels surrounded by solid sheets and nests of uniform, [...] with round nuclei and minimal mitotic activity.
Classic glomus tumour. A well-circumscribed tumour composed of solid sheets of monomorphic glomus cells.
Classic glomus tumour. Glomus cells are uniform and show round nuclei, bland chromatin, and minimal mitotic activity.
A: monomorphic glomus cells
Back Extra: Glomus Tumor and Glomuvenous Malformation
- Clinical: Cutaneous classic glomus tumours (cGTs) manifest as single, small blue-red nodules with paroxysmal pain, often triggered by cold exposure or minor tactile stimulation.
- Micro: cGTs are composed of sheets, nests, and trabeculae of monomorphic glomus cells in a hyalinized or myxoid stroma with branching capillary-sized vessels.
- Ancillary: GTs harbour recurrent NOTCH-family gene rearrangements, with MIR143 fusions with NOTCH1, NOTCH2, or NOTCH3 present in over 50% of cases.
Reference Gallery:
Classic glomus tumour. A well-circumscribed tumour composed of solid sheets of monomorphic glomus cells.
Classic glomus tumour. Glomus cells are uniform and show round nuclei, bland chromatin, and minimal mitotic activity.

Q: Morphologically, Granular Cell Tumor typically presents as sheets, nests, and trabeculae of large, monotonous epithelioid to polygonal cells with characteristic intensely eosinophilic, [...] cytoplasm.
Granular cell tumour. A cutaneous, deep dermal nodular lesion composed of cells with abundant granular pale eosinophilic cytoplasm and nuclei with finely dispersed chromatin. The cells are arranged in a solid pattern.
Granular cell tumour. A cutaneous, deep dermal nodular lesion composed of cells with abundant granular pale eosinophilic cytoplasm and nuclei with finely dispersed chromatin. The cells are arranged in a solid pattern.
A: granular
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours are rare in children, typically affecting the deep dermis and subcutaneous tissue, particularly of the head and neck, trunk, and proximal extremities.
- Micro: Granular cell tumour is characterized by sheets, nests, and trabeculae of large, monotonous epithelioid to polygonal cells with intensely eosinophilic, granular cytoplasm.
- Ancillary: Granular cell tumours are generally reactive for S100, SOX10, nestin, inhibin, and calretinin. Loss-of-function mutations affecting the V-ATPase accessory genes, ATP6AP1 and ATP6AP2, are found in 72% of cases.
Reference Gallery:
Granular cell tumour. A cutaneous, deep dermal nodular lesion composed of cells with abundant granular pale eosinophilic cytoplasm and nuclei with finely dispersed chromatin. The cells are arranged in a solid pattern.
Granular cell tumour. A cutaneous, deep dermal nodular lesion composed of cells with abundant granular pale eosinophilic cytoplasm and nuclei with finely dispersed chromatin. The cells are arranged in a solid pattern.
Granular cell tumour. A cutaneous, deep dermal nodular lesion composed of cells with abundant granular pale eosinophilic cytoplasm and nuclei with finely dispersed chromatin. Melanocytic markers are negative.
Granular cell tumour. A cutaneous, deep dermal nodular lesion. The cells are arranged in a solid pattern and S100 is strongly and diffusely positive.

Q: Immunohistochemically, a Granular Cell Tumor characteristically demonstrates strong and diffuse reactivity for the neural crest marker [...] (along with SOX10), reflecting its neural/Schwannian differentiation.
Granular cell tumour. A cutaneous, deep dermal nodular lesion. The cells are arranged in a solid pattern and S100 is strongly and diffusely positive.
A: S100
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours are rare in children, typically affecting the deep dermis and subcutaneous tissue, particularly of the head and neck, trunk, and proximal extremities.
- Micro: Granular cell tumour is characterized by sheets, nests, and trabeculae of large, monotonous epithelioid to polygonal cells with intensely eosinophilic, granular cytoplasm.
- Ancillary: Granular cell tumours are generally reactive for S100, SOX10, nestin, inhibin, and calretinin. Loss-of-function mutations affecting the V-ATPase accessory genes, ATP6AP1 and ATP6AP2, are found in 72% of cases.
Reference Gallery:
Granular cell tumour. A cutaneous, deep dermal nodular lesion composed of cells with abundant granular pale eosinophilic cytoplasm and nuclei with finely dispersed chromatin. The cells are arranged in a solid pattern.
Granular cell tumour. A cutaneous, deep dermal nodular lesion composed of cells with abundant granular pale eosinophilic cytoplasm and nuclei with finely dispersed chromatin. The cells are arranged in a solid pattern.
Granular cell tumour. A cutaneous, deep dermal nodular lesion composed of cells with abundant granular pale eosinophilic cytoplasm and nuclei with finely dispersed chromatin. Melanocytic markers are negative.
Granular cell tumour. A cutaneous, deep dermal nodular lesion. The cells are arranged in a solid pattern and S100 is strongly and diffusely positive.

Q: In Inclusion Body Infantile Digital Fibromatosis, the spindled myofibroblastic cells characteristically contain pale-pink to red [...].
Inclusion body fibromatosis. Bland spindle cells contain pink, round cytoplasmic inclusions.
A: intracytoplasmic inclusions
Back Extra: Inclusion Body Infantile Digital Fibromatosis
- Clinical: Inclusion Body Infantile Digital Fibromatosis typically presents as painless, dome-shaped to polypoid cutaneous lesions in children under 5 years, most often during the first year of life.
- Micro: The lesions are composed of spindled myofibroblastic cells arranged in fascicles, with characteristic pale-pink to red intracytoplasmic inclusions that stain red with trichrome stain.
- Ancillary: Intracytoplasmic inclusions are positive for SMA, calponin, and sometimes caldesmon, which can aid in the diagnosis.
Reference Gallery:
Inclusion body fibromatosis. This dermal-based nodular tumour is composed of spindle cells arranged in fascicles, surrounding skin adnexal structures.
Inclusion body fibromatosis. Bland spindle cells contain pink, round cytoplasmic inclusions.
Inclusion body fibromatosis. Intracytoplasmic inclusions stain bright red with a trichrome stain.
Infantile digital fibromatosis. Plump reactive fibroblasts may be seen within the dermis in the context of the myofibroblastic proliferation.

Q: The characteristic intracytoplasmic inclusions of Inclusion Body Infantile Digital Fibromatosis are highlighted in bright red by a [...] stain.
Inclusion body fibromatosis. Intracytoplasmic inclusions stain bright red with a trichrome stain.
A: trichrome
Back Extra: Inclusion Body Infantile Digital Fibromatosis
- Clinical: Inclusion Body Infantile Digital Fibromatosis typically presents as painless, dome-shaped to polypoid cutaneous lesions in children under 5 years, most often during the first year of life.
- Micro: The lesions are composed of spindled myofibroblastic cells arranged in fascicles, with characteristic pale-pink to red intracytoplasmic inclusions that stain red with trichrome stain.
- Ancillary: Intracytoplasmic inclusions are positive for SMA, calponin, and sometimes caldesmon, which can aid in the diagnosis.
Reference Gallery:
Inclusion body fibromatosis. This dermal-based nodular tumour is composed of spindle cells arranged in fascicles, surrounding skin adnexal structures.
Inclusion body fibromatosis. Bland spindle cells contain pink, round cytoplasmic inclusions.
Inclusion body fibromatosis. Intracytoplasmic inclusions stain bright red with a trichrome stain.
Infantile digital fibromatosis. Plump reactive fibroblasts may be seen within the dermis in the context of the myofibroblastic proliferation.

Q: A painless, dermal-based nodular tumor on the digits of a young child featuring myofibroblastic spindle cells with round, pink inclusions is pathognomonic for [...].
Inclusion body fibromatosis. This dermal-based nodular tumour is composed of spindle cells arranged in fascicles, surrounding skin adnexal structures.
Inclusion body fibromatosis. Bland spindle cells contain pink, round cytoplasmic inclusions.
A: Inclusion Body Infantile Digital Fibromatosis
Back Extra: Inclusion Body Infantile Digital Fibromatosis
- Clinical: Inclusion Body Infantile Digital Fibromatosis typically presents as painless, dome-shaped to polypoid cutaneous lesions in children under 5 years, most often during the first year of life.
- Micro: The lesions are composed of spindled myofibroblastic cells arranged in fascicles, with characteristic pale-pink to red intracytoplasmic inclusions that stain red with trichrome stain.
- Ancillary: Intracytoplasmic inclusions are positive for SMA, calponin, and sometimes caldesmon, which can aid in the diagnosis.
Reference Gallery:
Inclusion body fibromatosis. This dermal-based nodular tumour is composed of spindle cells arranged in fascicles, surrounding skin adnexal structures.
Inclusion body fibromatosis. Bland spindle cells contain pink, round cytoplasmic inclusions.
Inclusion body fibromatosis. Intracytoplasmic inclusions stain bright red with a trichrome stain.
Infantile digital fibromatosis. Plump reactive fibroblasts may be seen within the dermis in the context of the myofibroblastic proliferation.

Q: The classic molecular drivers of Infantile Fibrosarcoma are gene fusions or activating alterations involving the receptor tyrosine kinase pathway, most commonly the [...] gene family (classically ETV6::NTRK3).
Infantile fibrosarcoma. Immunohistochemistry with a pan-TRK antibody shows cytoplasmic expression in a tumour with TPM3::NTRK1 fusion.
Infantile fibrosarcoma. Immunohistochemistry with a pan-TRK antibody shows cytoplasmic expression in a tumour with TPM3::NTRK1 fusion.
A: NTRK
Q: Infantile Fibrosarcoma
- Clinical: Patients with [...] typically present with a painless mass or exophytic nodule, and rapid growth may occur. Approximately one-third of cases are congenital.
- Micro: [...] is a cellular, monomorphic neoplasm composed of primitive, ovoid/round to spindled cells, arranged in compact sheets or long fascicles, often with a haemangiopericytoma-like vascular pattern.
- Ancillary: [...] is characterized by fusions or activating alterations of receptor tyrosine kinase pathway genes, such as ETV6::NTRK3, NTRK1, NTRK2, NTRK3, RET, MET, and BRAF.
Reference Gallery:
Infantile fibrosarcoma. Immunohistochemistry with a pan-TRK antibody shows cytoplasmic expression in a tumour with TPM3::NTRK1 fusion.
Infantile fibrosarcoma. Long intersecting fascicles or a herringbone pattern of growth (TPR::NTRK1).
Infantile fibrosarcoma. Primitive stellate cells within a myxoid stroma (ETV6::NTRK3).
Infantile fibrosarcoma. An example with a cellular, ovoid to round cell pattern (EML4::NTRK3).
Infantile fibrosarcoma. Infantile fibrosarcoma infiltrating between skeletal muscle bundles (TPM3::NTRK1).
Infantile fibrosarcoma. Immunohistochemistry with a pan-TRK antibody shows cytoplasmic expression in a tumour with TPM3::NTRK1 fusion.
Infantile fibrosarcoma. A tumour in a newborn infant, deforming the plantar region.
Infantile fibrosarcoma. The tumour is densely cellular and shows the characteristic herringbone pattern (ETV6::NTRK3 fusion–positive).
Infantile fibrosarcoma. T1-weighted axial MRI of the left axilla shows a huge well-defined mass that is slightly hyperintense to adjacent muscle. The intralesional vascular flow due to the vasculature component may be observed in this tumour.
Infantile fibrosarcoma. T2-weighted sagittal MRI of the left axilla. This tumour is hyperintense compared with adjacent muscles and there are multiple internal cystic or necrotic components.
Infantile fibrosarcoma. Contrast-enhanced T1-weighted coronal MRI of the left axilla. This tumour shows heterogeneous enhancement with non-enhanced cystic or necrotic portions.
A: infantile fibrosarcoma; Infantile fibrosarcoma; Infantile fibrosarcoma

Q: Histologically, Infantile Fibrosarcoma features primitive, ovoid to spindled cells arranged in long, intersecting fascicles that frequently form a characteristic [...] growth pattern.
Infantile fibrosarcoma. Long intersecting fascicles or a herringbone pattern of growth (TPR::NTRK1).
Infantile fibrosarcoma. The tumour is densely cellular and shows the characteristic herringbone pattern (ETV6::NTRK3 fusion–positive).
A: herringbone
Q: Infantile Fibrosarcoma
- Clinical: Patients with [...] typically present with a painless mass or exophytic nodule, and rapid growth may occur. Approximately one-third of cases are congenital.
- Micro: [...] is a cellular, monomorphic neoplasm composed of primitive, ovoid/round to spindled cells, arranged in compact sheets or long fascicles, often with a haemangiopericytoma-like vascular pattern.
- Ancillary: [...] is characterized by fusions or activating alterations of receptor tyrosine kinase pathway genes, such as ETV6::NTRK3, NTRK1, NTRK2, NTRK3, RET, MET, and BRAF.
Reference Gallery:
Infantile fibrosarcoma. Immunohistochemistry with a pan-TRK antibody shows cytoplasmic expression in a tumour with TPM3::NTRK1 fusion.
Infantile fibrosarcoma. Long intersecting fascicles or a herringbone pattern of growth (TPR::NTRK1).
Infantile fibrosarcoma. Primitive stellate cells within a myxoid stroma (ETV6::NTRK3).
Infantile fibrosarcoma. An example with a cellular, ovoid to round cell pattern (EML4::NTRK3).
Infantile fibrosarcoma. Infantile fibrosarcoma infiltrating between skeletal muscle bundles (TPM3::NTRK1).
Infantile fibrosarcoma. Immunohistochemistry with a pan-TRK antibody shows cytoplasmic expression in a tumour with TPM3::NTRK1 fusion.
Infantile fibrosarcoma. A tumour in a newborn infant, deforming the plantar region.
Infantile fibrosarcoma. The tumour is densely cellular and shows the characteristic herringbone pattern (ETV6::NTRK3 fusion–positive).
Infantile fibrosarcoma. T1-weighted axial MRI of the left axilla shows a huge well-defined mass that is slightly hyperintense to adjacent muscle. The intralesional vascular flow due to the vasculature component may be observed in this tumour.
Infantile fibrosarcoma. T2-weighted sagittal MRI of the left axilla. This tumour is hyperintense compared with adjacent muscles and there are multiple internal cystic or necrotic components.
Infantile fibrosarcoma. Contrast-enhanced T1-weighted coronal MRI of the left axilla. This tumour shows heterogeneous enhancement with non-enhanced cystic or necrotic portions.
A: infantile fibrosarcoma; Infantile fibrosarcoma; Infantile fibrosarcoma

Q: Clinically, Infantile Fibrosarcoma typically presents as a rapidly growing, painless mass or exophytic nodule, with approximately one-third of cases being [...] (present at birth).
Infantile fibrosarcoma. A tumour in a newborn infant, deforming the plantar region.
Infantile fibrosarcoma. T1-weighted axial MRI of the left axilla shows a huge well-defined mass that is slightly hyperintense to adjacent muscle. The intralesional vascular flow due to the vasculature component may be observed in this tumour.
A: congenital
Q: Infantile Fibrosarcoma
- Clinical: Patients with [...] typically present with a painless mass or exophytic nodule, and rapid growth may occur. Approximately one-third of cases are congenital.
- Micro: [...] is a cellular, monomorphic neoplasm composed of primitive, ovoid/round to spindled cells, arranged in compact sheets or long fascicles, often with a haemangiopericytoma-like vascular pattern.
- Ancillary: [...] is characterized by fusions or activating alterations of receptor tyrosine kinase pathway genes, such as ETV6::NTRK3, NTRK1, NTRK2, NTRK3, RET, MET, and BRAF.
Reference Gallery:
Infantile fibrosarcoma. Immunohistochemistry with a pan-TRK antibody shows cytoplasmic expression in a tumour with TPM3::NTRK1 fusion.
Infantile fibrosarcoma. Long intersecting fascicles or a herringbone pattern of growth (TPR::NTRK1).
Infantile fibrosarcoma. Primitive stellate cells within a myxoid stroma (ETV6::NTRK3).
Infantile fibrosarcoma. An example with a cellular, ovoid to round cell pattern (EML4::NTRK3).
Infantile fibrosarcoma. Infantile fibrosarcoma infiltrating between skeletal muscle bundles (TPM3::NTRK1).
Infantile fibrosarcoma. Immunohistochemistry with a pan-TRK antibody shows cytoplasmic expression in a tumour with TPM3::NTRK1 fusion.
Infantile fibrosarcoma. A tumour in a newborn infant, deforming the plantar region.
Infantile fibrosarcoma. The tumour is densely cellular and shows the characteristic herringbone pattern (ETV6::NTRK3 fusion–positive).
Infantile fibrosarcoma. T1-weighted axial MRI of the left axilla shows a huge well-defined mass that is slightly hyperintense to adjacent muscle. The intralesional vascular flow due to the vasculature component may be observed in this tumour.
Infantile fibrosarcoma. T2-weighted sagittal MRI of the left axilla. This tumour is hyperintense compared with adjacent muscles and there are multiple internal cystic or necrotic components.
Infantile fibrosarcoma. Contrast-enhanced T1-weighted coronal MRI of the left axilla. This tumour shows heterogeneous enhancement with non-enhanced cystic or necrotic portions.
A: infantile fibrosarcoma; Infantile fibrosarcoma; Infantile fibrosarcoma

Q: Histologically, Hepatic Infantile Haemangioma features complex anastomosing sinusoid-like channels lined by bland endothelial cells that characteristically exhibit immunoreactivity for [...].
Hepatic infantile haemangioma. Histology shows complex anastomosing vascular/sinusoidal channels and pseudopapillae with foci of endothelial redundancy and rare mitotic figures. Solid areas, endothelial atypia, necrosis, and atypical mitoses are absent.
Hepatic infantile haemangioma. Tumour cells are immunoreactive for GLUT1.
A: GLUT1
Back Extra: Hepatic Infantile Haemangioma
- Clinical: Hepatic infantile haemangioma (HIH) is the most common hepatic mesenchymal tumour in children, often associated with the female sex, multigestational pregnancy, low birth weight, and prematurity. Clinical features include hepatomegaly, abdominal enlargement, and abdominal compartment syndrome.
- Micro: Histologically, HIH is characterized by anastomosing, sinusoid-like channels lined by flattened or minimally plump endothelial cells. Entrapped bile ducts and hepatocytes may also be present.
- Ancillary: Diagnostic criteria include wide, anastomosing, sinusoid-like channels with mostly small and bland GLUT1-immunopositive endothelial cells. Moderate to marked endothelial atypia, solid spindled or epithelioid foci, necrosis, and variability in GLUT1 endothelial immunoexpression suggest transition into angiosarcoma.
Reference Gallery:
Hepatic infantile haemangioma. Liver explant from a 3-month-old with abdominal compartment syndrome, showing multiple lesions.
Hepatic infantile haemangioma. The cut section of a liver explant from a 3-month-old with abdominal compartment syndrome shows a cholestatic liver with diffuse tan-white, occasionally coalescing masses.
Hepatic infantile haemangioma. Histology shows complex anastomosing vascular/sinusoidal channels and pseudopapillae with foci of endothelial redundancy and rare mitotic figures. Solid areas, endothelial atypia, necrosis, and atypical mitoses are absent.
Hepatic infantile haemangioma. Tumour cells are immunoreactive for GLUT1.
Hepatic infantile haemangioma. Fat-saturated T2-weighted axial MRI showing numerous well-defined hyperintense nodules in the liver.

Q: The most common hepatic mesenchymal tumor in children, often presenting with hepatomegaly and numerous well-defined hyperintense nodules on T2-weighted MRI, is [...].
Hepatic infantile haemangioma. Liver explant from a 3-month-old with abdominal compartment syndrome, showing multiple lesions.
Hepatic infantile haemangioma. The cut section of a liver explant from a 3-month-old with abdominal compartment syndrome shows a cholestatic liver with diffuse tan-white, occasionally coalescing masses.
Hepatic infantile haemangioma. Fat-saturated T2-weighted axial MRI showing numerous well-defined hyperintense nodules in the liver.
A: Hepatic Infantile Haemangioma
Back Extra: Hepatic Infantile Haemangioma
- Clinical: Hepatic infantile haemangioma (HIH) is the most common hepatic mesenchymal tumour in children, often associated with the female sex, multigestational pregnancy, low birth weight, and prematurity. Clinical features include hepatomegaly, abdominal enlargement, and abdominal compartment syndrome.
- Micro: Histologically, HIH is characterized by anastomosing, sinusoid-like channels lined by flattened or minimally plump endothelial cells. Entrapped bile ducts and hepatocytes may also be present.
- Ancillary: Diagnostic criteria include wide, anastomosing, sinusoid-like channels with mostly small and bland GLUT1-immunopositive endothelial cells. Moderate to marked endothelial atypia, solid spindled or epithelioid foci, necrosis, and variability in GLUT1 endothelial immunoexpression suggest transition into angiosarcoma.
Reference Gallery:
Hepatic infantile haemangioma. Liver explant from a 3-month-old with abdominal compartment syndrome, showing multiple lesions.
Hepatic infantile haemangioma. The cut section of a liver explant from a 3-month-old with abdominal compartment syndrome shows a cholestatic liver with diffuse tan-white, occasionally coalescing masses.
Hepatic infantile haemangioma. Histology shows complex anastomosing vascular/sinusoidal channels and pseudopapillae with foci of endothelial redundancy and rare mitotic figures. Solid areas, endothelial atypia, necrosis, and atypical mitoses are absent.
Hepatic infantile haemangioma. Tumour cells are immunoreactive for GLUT1.
Hepatic infantile haemangioma. Fat-saturated T2-weighted axial MRI showing numerous well-defined hyperintense nodules in the liver.

Q: An elevated, red, well-defined vascular lesion appearing in the newborn period that typically undergoes gradual involution over several years is characteristic of [...].
Infantile haemangioma. A 10-month-old infant with several elevated, red, well-defined lesions. Two are shown, the nuchal one with a healing ulceration.
A: infantile hemangioma
Back Extra: Infantile Hemangioma
- Clinical: Infantile Hemangioma typically appears in the newborn period and reaches its peak size by around 10 months of age, then gradually involutes over several years.
- Micro: In the proliferative phase, the lesion is characterized by closely approximated capillaries with plump endothelial cells and pericytes, which become less prominent during involution.
- Ancillary: GLUT1 immunoreactivity is a key diagnostic marker, showing intense and diffuse cytoplasmic staining in endothelial cells during the proliferative phase.
Reference Gallery:
Infantile haemangioma. A 10-month-old infant with several elevated, red, well-defined lesions. Two are shown, the nuchal one with a healing ulceration.
Infantile haemangioma. A proliferative-phase lesion with closely approximated capillaries, mostly inconspicuous lumina, and uniform plump endothelial cells and pericytes.
Infantile haemangioma. An involutional-phase lesion in a 2-year-old, characterized by larger channels, flattened endothelial cells and pericytes, a thick basement membrane, and channels separated by a delicate collagenous stroma containing mast cells.
Infantile haemangioma. Intense GLUT1 immunoreactivity of the entire endothelial cytoplasm in a proliferative-phase lesion.
Reticular infantile haemangioma. A 3-week-old girl with an extraordinarily extensive dark-red reticular lesion of the lower extremities, perineum, and buttocks, in association with sacral dysgenesis (LUMBAR syndrome [lower body haemangioma, urogenital abnormalities/ulceration, myelopathy, bony deformities, anorectal malformations/arterial anomalies, and renal anomalies]).
Reticular infantile haemangioma. Relatively inconspicuous dermal capillary channels in the infant shown in Fig. <<19725>>.
Reticular infantile haemangioma. The lesional vessels are delineated by GLUT1 endothelial immunopositivity.

Q: A highly specific diagnostic immunohistochemical marker for Infantile Hemangioma is [...], which shows intense and diffuse cytoplasmic staining in the lesional endothelial cells.
Infantile haemangioma. Intense GLUT1 immunoreactivity of the entire endothelial cytoplasm in a proliferative-phase lesion.
Reticular infantile haemangioma. The lesional vessels are delineated by GLUT1 endothelial immunopositivity.
A: GLUT1
Back Extra: Infantile Hemangioma
- Clinical: Infantile Hemangioma typically appears in the newborn period and reaches its peak size by around 10 months of age, then gradually involutes over several years.
- Micro: In the proliferative phase, the lesion is characterized by closely approximated capillaries with plump endothelial cells and pericytes, which become less prominent during involution.
- Ancillary: GLUT1 immunoreactivity is a key diagnostic marker, showing intense and diffuse cytoplasmic staining in endothelial cells during the proliferative phase.
Reference Gallery:
Infantile haemangioma. A 10-month-old infant with several elevated, red, well-defined lesions. Two are shown, the nuchal one with a healing ulceration.
Infantile haemangioma. A proliferative-phase lesion with closely approximated capillaries, mostly inconspicuous lumina, and uniform plump endothelial cells and pericytes.
Infantile haemangioma. An involutional-phase lesion in a 2-year-old, characterized by larger channels, flattened endothelial cells and pericytes, a thick basement membrane, and channels separated by a delicate collagenous stroma containing mast cells.
Infantile haemangioma. Intense GLUT1 immunoreactivity of the entire endothelial cytoplasm in a proliferative-phase lesion.
Reticular infantile haemangioma. A 3-week-old girl with an extraordinarily extensive dark-red reticular lesion of the lower extremities, perineum, and buttocks, in association with sacral dysgenesis (LUMBAR syndrome [lower body haemangioma, urogenital abnormalities/ulceration, myelopathy, bony deformities, anorectal malformations/arterial anomalies, and renal anomalies]).
Reticular infantile haemangioma. Relatively inconspicuous dermal capillary channels in the infant shown in Fig. <<19725>>.
Reticular infantile haemangioma. The lesional vessels are delineated by GLUT1 endothelial immunopositivity.

Q: In the proliferative phase of an Infantile Hemangioma, the lesion is microscopically characterized by closely approximated capillaries with inconspicuous lumina that are lined by uniform, [...] and pericytes.
Infantile haemangioma. A proliferative-phase lesion with closely approximated capillaries, mostly inconspicuous lumina, and uniform plump endothelial cells and pericytes.
A: plump endothelial cells
Back Extra: Infantile Hemangioma
- Clinical: Infantile Hemangioma typically appears in the newborn period and reaches its peak size by around 10 months of age, then gradually involutes over several years.
- Micro: In the proliferative phase, the lesion is characterized by closely approximated capillaries with plump endothelial cells and pericytes, which become less prominent during involution.
- Ancillary: GLUT1 immunoreactivity is a key diagnostic marker, showing intense and diffuse cytoplasmic staining in endothelial cells during the proliferative phase.
Reference Gallery:
Infantile haemangioma. A 10-month-old infant with several elevated, red, well-defined lesions. Two are shown, the nuchal one with a healing ulceration.
Infantile haemangioma. A proliferative-phase lesion with closely approximated capillaries, mostly inconspicuous lumina, and uniform plump endothelial cells and pericytes.
Infantile haemangioma. An involutional-phase lesion in a 2-year-old, characterized by larger channels, flattened endothelial cells and pericytes, a thick basement membrane, and channels separated by a delicate collagenous stroma containing mast cells.
Infantile haemangioma. Intense GLUT1 immunoreactivity of the entire endothelial cytoplasm in a proliferative-phase lesion.
Reticular infantile haemangioma. A 3-week-old girl with an extraordinarily extensive dark-red reticular lesion of the lower extremities, perineum, and buttocks, in association with sacral dysgenesis (LUMBAR syndrome [lower body haemangioma, urogenital abnormalities/ulceration, myelopathy, bony deformities, anorectal malformations/arterial anomalies, and renal anomalies]).
Reticular infantile haemangioma. Relatively inconspicuous dermal capillary channels in the infant shown in Fig. <<19725>>.
Reticular infantile haemangioma. The lesional vessels are delineated by GLUT1 endothelial immunopositivity.

Q: A mesenchymal neoplasm characterized by a proliferation of spindled myofibroblasts admixed with a variable lymphoplasmacytic infiltrate, which frequently harbors an ALK gene rearrangement, is diagnosed as [...].
Inflammatory myofibroblastic tumour. The myxoid pattern consists of plump or spindled myofibroblasts with vesicular nuclei in an oedematous, myxoid stroma with abundant blood vessels, lymphocytes, plasma cells, and macrophages, mimicking granulation tissue. This tumour arose in the abdomen of a 4-month-old and contained a RANBP2::ALK fusion.
Inflammatory myofibroblastic tumour. The hypercellular pattern is composed of compact fascicular spindle cells with collagenous stroma and a lymphoplasmacytic infiltrate. This tumour contains a TPM4::ALK gene fusion.
A: Inflammatory Myofibroblastic Tumor
Back Extra: Inflammatory Myofibroblastic Tumor
- Clinical: Inflammatory Myofibroblastic Tumor (IMT) primarily affects children and young adults, causing symptoms such as abdominal pain, gastrointestinal obstruction, or bleeding in abdominal cases, and cough, chest pain, and dyspnoea in pulmonary cases.
- Micro: IMT is characterized by a proliferation of spindled and elongated fibroblastic-myofibroblastic cells with a variable inflammatory infiltrate. Common patterns include myxoid, hypercellular, and epithelioid, often combined within a single tumour.
- Ancillary: ALK immunohistochemistry is positive in 50-60% of IMT cases and correlates with ALK gene rearrangement. Molecular assays, including FISH and RNA-based fusion assays, are recommended for diagnosis.
Reference Gallery:
Inflammatory myofibroblastic tumour. An example with FN1::ROS1 fusion in the lung of a 2-month-old boy who presented with features of bronchial obstruction and cyst formation.
Inflammatory myofibroblastic tumour. The myxoid pattern consists of plump or spindled myofibroblasts with vesicular nuclei in an oedematous, myxoid stroma with abundant blood vessels, lymphocytes, plasma cells, and macrophages, mimicking granulation tissue. This tumour arose in the abdomen of a 4-month-old and contained a RANBP2::ALK fusion.
Inflammatory myofibroblastic tumour. The hypercellular pattern is composed of compact fascicular spindle cells with collagenous stroma and a lymphoplasmacytic infiltrate. This tumour contains a TPM4::ALK gene fusion.
Inflammatory myofibroblastic tumour. Tumour cells are predominantly epithelioid, in the context of a myxoid stroma with interspersed inflammatory cells, in this tumour with RANBP2::ALK fusion in an infant.
Inflammatory myofibroblastic tumour. ALK immunostaining shows granular and dot-like cytoplasmic staining.
Epithelioid inflammatory myofibroblastic tumour. An example from the bowel shows a myxoid background with a mixed inflammatory infiltrate and aggregates of large epithelioid cells.
Epithelioid inflammatory myofibroblastic tumour. At higher power, the tumour cells show large vesicular nuclei with single prominent nucleoli, and abundant cytoplasm.
Inflammatory myofibroblastic tumour of lung. Contrast-enhanced axial CT shows a single lobulated mass with heterogeneous enhancement at the lower lobe of the left lung.

Q: Approximately 50-60% of Inflammatory Myofibroblastic Tumor cases exhibit a specific gene rearrangement that can be detected via positive immunohistochemistry for [...].
Inflammatory myofibroblastic tumour. ALK immunostaining shows granular and dot-like cytoplasmic staining.
A: ALK
Back Extra: Inflammatory Myofibroblastic Tumor
- Clinical: Inflammatory Myofibroblastic Tumor (IMT) primarily affects children and young adults, causing symptoms such as abdominal pain, gastrointestinal obstruction, or bleeding in abdominal cases, and cough, chest pain, and dyspnoea in pulmonary cases.
- Micro: IMT is characterized by a proliferation of spindled and elongated fibroblastic-myofibroblastic cells with a variable inflammatory infiltrate. Common patterns include myxoid, hypercellular, and epithelioid, often combined within a single tumour.
- Ancillary: ALK immunohistochemistry is positive in 50-60% of IMT cases and correlates with ALK gene rearrangement. Molecular assays, including FISH and RNA-based fusion assays, are recommended for diagnosis.
Reference Gallery:
Inflammatory myofibroblastic tumour. An example with FN1::ROS1 fusion in the lung of a 2-month-old boy who presented with features of bronchial obstruction and cyst formation.
Inflammatory myofibroblastic tumour. The myxoid pattern consists of plump or spindled myofibroblasts with vesicular nuclei in an oedematous, myxoid stroma with abundant blood vessels, lymphocytes, plasma cells, and macrophages, mimicking granulation tissue. This tumour arose in the abdomen of a 4-month-old and contained a RANBP2::ALK fusion.
Inflammatory myofibroblastic tumour. The hypercellular pattern is composed of compact fascicular spindle cells with collagenous stroma and a lymphoplasmacytic infiltrate. This tumour contains a TPM4::ALK gene fusion.
Inflammatory myofibroblastic tumour. Tumour cells are predominantly epithelioid, in the context of a myxoid stroma with interspersed inflammatory cells, in this tumour with RANBP2::ALK fusion in an infant.
Inflammatory myofibroblastic tumour. ALK immunostaining shows granular and dot-like cytoplasmic staining.
Epithelioid inflammatory myofibroblastic tumour. An example from the bowel shows a myxoid background with a mixed inflammatory infiltrate and aggregates of large epithelioid cells.
Epithelioid inflammatory myofibroblastic tumour. At higher power, the tumour cells show large vesicular nuclei with single prominent nucleoli, and abundant cytoplasm.
Inflammatory myofibroblastic tumour of lung. Contrast-enhanced axial CT shows a single lobulated mass with heterogeneous enhancement at the lower lobe of the left lung.

Q: The histological architecture of Inflammatory Myofibroblastic Tumor can show myxoid or hypercellular features, as well as an [...] pattern characterized by large, plump cells with vesicular nuclei and prominent nucleoli.
Epithelioid inflammatory myofibroblastic tumour. An example from the bowel shows a myxoid background with a mixed inflammatory infiltrate and aggregates of large epithelioid cells.
Epithelioid inflammatory myofibroblastic tumour. At higher power, the tumour cells show large vesicular nuclei with single prominent nucleoli, and abundant cytoplasm.
A: epithelioid
Back Extra: Inflammatory Myofibroblastic Tumor
- Clinical: Inflammatory Myofibroblastic Tumor (IMT) primarily affects children and young adults, causing symptoms such as abdominal pain, gastrointestinal obstruction, or bleeding in abdominal cases, and cough, chest pain, and dyspnoea in pulmonary cases.
- Micro: IMT is characterized by a proliferation of spindled and elongated fibroblastic-myofibroblastic cells with a variable inflammatory infiltrate. Common patterns include myxoid, hypercellular, and epithelioid, often combined within a single tumour.
- Ancillary: ALK immunohistochemistry is positive in 50-60% of IMT cases and correlates with ALK gene rearrangement. Molecular assays, including FISH and RNA-based fusion assays, are recommended for diagnosis.
Reference Gallery:
Inflammatory myofibroblastic tumour. An example with FN1::ROS1 fusion in the lung of a 2-month-old boy who presented with features of bronchial obstruction and cyst formation.
Inflammatory myofibroblastic tumour. The myxoid pattern consists of plump or spindled myofibroblasts with vesicular nuclei in an oedematous, myxoid stroma with abundant blood vessels, lymphocytes, plasma cells, and macrophages, mimicking granulation tissue. This tumour arose in the abdomen of a 4-month-old and contained a RANBP2::ALK fusion.
Inflammatory myofibroblastic tumour. The hypercellular pattern is composed of compact fascicular spindle cells with collagenous stroma and a lymphoplasmacytic infiltrate. This tumour contains a TPM4::ALK gene fusion.
Inflammatory myofibroblastic tumour. Tumour cells are predominantly epithelioid, in the context of a myxoid stroma with interspersed inflammatory cells, in this tumour with RANBP2::ALK fusion in an infant.
Inflammatory myofibroblastic tumour. ALK immunostaining shows granular and dot-like cytoplasmic staining.
Epithelioid inflammatory myofibroblastic tumour. An example from the bowel shows a myxoid background with a mixed inflammatory infiltrate and aggregates of large epithelioid cells.
Epithelioid inflammatory myofibroblastic tumour. At higher power, the tumour cells show large vesicular nuclei with single prominent nucleoli, and abundant cytoplasm.
Inflammatory myofibroblastic tumour of lung. Contrast-enhanced axial CT shows a single lobulated mass with heterogeneous enhancement at the lower lobe of the left lung.

Q: A benign, slow-growing soft tissue tumor that is characteristically hypocellular with bland cells in an abundant myxoid stroma, often seen adjacent to or infiltrating surrounding skeletal muscle fibers, is classically an [...].
Intramuscular myxoma. A hypocellular lesion from the neck of a 12-year-old boy. Note the surrounding skeletal muscle fibres.
Intramuscular myxoma. Higher-power view of a myxoma showing a hypocellular lesion with small, regular spindle cells in a myxoid background.
A: Intramuscular/Juxta-Articular Myxoma
Back Extra: Intramuscular/Juxta-Articular Myxoma
- Clinical: Intramuscular/juxta-articular myxomas are typically slow-growing, solitary, and can be painless or painful masses. MRI shows high T2 and low T1 signal intensity.
- Micro: These lesions are hypocellular with uniform, bland spindle to stellate cells in an abundant myxoid stroma. Cystic and frothy changes may be present.
- Ancillary: Immunohistochemistry shows variable staining with CD34 and SMA. GNAS mutations are reported in adults but not in children.
Reference Gallery:
Intramuscular myxoma. A hypocellular lesion from the neck of a 12-year-old boy. Note the surrounding skeletal muscle fibres.
Intramuscular myxoma. Higher-power view of a myxoma showing a hypocellular lesion with small, regular spindle cells in a myxoid background.

Q: Histologically, the characteristic cellular features of an Intramuscular/Juxta-Articular Myxoma include bland, uniform [...] cells set within a markedly hypocellular and abundant myxoid stroma.
Intramuscular myxoma. Higher-power view of a myxoma showing a hypocellular lesion with small, regular spindle cells in a myxoid background.
A: spindle to stellate
Back Extra: Intramuscular/Juxta-Articular Myxoma
- Clinical: Intramuscular/juxta-articular myxomas are typically slow-growing, solitary, and can be painless or painful masses. MRI shows high T2 and low T1 signal intensity.
- Micro: These lesions are hypocellular with uniform, bland spindle to stellate cells in an abundant myxoid stroma. Cystic and frothy changes may be present.
- Ancillary: Immunohistochemistry shows variable staining with CD34 and SMA. GNAS mutations are reported in adults but not in children.
Reference Gallery:
Intramuscular myxoma. A hypocellular lesion from the neck of a 12-year-old boy. Note the surrounding skeletal muscle fibres.
Intramuscular myxoma. Higher-power view of a myxoma showing a hypocellular lesion with small, regular spindle cells in a myxoid background.

Q: The clinical presentation of slow-growing papular and nodular skin lesions (such as those on the ear lobe), combined with joint contractures and gingival hyperplasia, is highly characteristic of [...].
Juvenile hyaline fibromatosis. Ear lobe lesion in a 15-month-old girl with infantile hyaline fibromatosis.
A: Juvenile Hyaline Fibromatosis
Back Extra: Juvenile Hyaline Fibromatosis
- Clinical: Juvenile hyaline fibromatosis manifests with slow-growing papular and nodular skin lesions, joint contractures, gingival hyperplasia, and osteopenia.
- Micro: Histopathology shows plump to spindled uniform fibroblasts and abundant extracellular eosinophilic, non-fibrillar hyaline material, staining strongly with PAS and diastase-resistant.
- Ancillary: Molecular testing for a germline mutation of ANTXR2 is essential for diagnosis.
Reference Gallery:
Juvenile hyaline fibromatosis. Ear lobe lesion in a 15-month-old girl with infantile hyaline fibromatosis.
Juvenile hyaline fibromatosis. Skin with atrophy of the epidermis and hyalinization of the papillary dermis with a chondroid appearance.
Juvenile hyaline fibromatosis. Skin with atrophy of the epidermis and with a hyaline amorphous substance replacing the papillary dermis.
Juvenile hyaline fibromatosis. Hyalinization of the dermis with a chondroid appearance.

Q: Microscopically, Juvenile Hyaline Fibromatosis is characterized by uniform, plump to spindled fibroblasts embedded in an abundant, extracellular [...] material that replaces the dermis and frequently imparts a chondroid appearance.
Juvenile hyaline fibromatosis. Skin with atrophy of the epidermis and hyalinization of the papillary dermis with a chondroid appearance.
Juvenile hyaline fibromatosis. Skin with atrophy of the epidermis and with a hyaline amorphous substance replacing the papillary dermis.
Juvenile hyaline fibromatosis. Hyalinization of the dermis with a chondroid appearance.
A: hyaline
Back Extra: Juvenile Hyaline Fibromatosis
- Clinical: Juvenile hyaline fibromatosis manifests with slow-growing papular and nodular skin lesions, joint contractures, gingival hyperplasia, and osteopenia.
- Micro: Histopathology shows plump to spindled uniform fibroblasts and abundant extracellular eosinophilic, non-fibrillar hyaline material, staining strongly with PAS and diastase-resistant.
- Ancillary: Molecular testing for a germline mutation of ANTXR2 is essential for diagnosis.
Reference Gallery:
Juvenile hyaline fibromatosis. Ear lobe lesion in a 15-month-old girl with infantile hyaline fibromatosis.
Juvenile hyaline fibromatosis. Skin with atrophy of the epidermis and hyalinization of the papillary dermis with a chondroid appearance.
Juvenile hyaline fibromatosis. Skin with atrophy of the epidermis and with a hyaline amorphous substance replacing the papillary dermis.
Juvenile hyaline fibromatosis. Hyalinization of the dermis with a chondroid appearance.

Q: Microscopically, Kaposi Sarcoma is classically characterized by a proliferation of spindle cells that form characteristic [...] containing intraluminal erythrocytes.
Kaposi sarcoma. Proliferation of spindle cells with slit-like spaces at the periphery with erythrocytes in the lumen. Mitoses are easily seen.
A: slit-like spaces
Back Extra: Kaposi Sarcoma
- Clinical: In children, Kaposi sarcoma can present with rapidly progressive lymphadenopathy and visceral involvement, often without cutaneous lesions, posing a diagnostic challenge.
- Micro: Kaposi sarcoma is characterized by proliferating spindle cells forming slit-like spaces with intraluminal erythrocytes, mitoses, and areas of necrosis.
- Ancillary: Detection of KSHV/HHV8 by PCR and immunohistochemistry for LANA confirms the diagnosis of Kaposi sarcoma.
Reference Gallery:
Kaposi sarcoma. An intestinal lesion in transplantation-related Kaposi sarcoma.
Kaposi sarcoma. Proliferation of spindle cells with slit-like spaces at the periphery with erythrocytes in the lumen. Mitoses are easily seen.
Kaposi sarcoma. Peripheral area of a lymph node, with almost complete effacement of the architecture. Angioproliferation is more obvious, with larger (in comparison with the normal vessels) and congestive lumina.
Kaposi sarcoma. Small bowel with a submucosal nodular lesion showing central necrosis, cellular debris, and hyaline globules.
Kaposi sarcoma. A well-demarcated lesion in the liver parenchyma, without a pseudocapsule.

Q: In pediatric or transplant-associated cases, Kaposi Sarcoma poses a diagnostic challenge as it frequently presents with rapidly progressive lymphadenopathy and [...] involvement (e.g., intestinal or hepatic), often in the absence of cutaneous lesions.
Kaposi sarcoma. An intestinal lesion in transplantation-related Kaposi sarcoma.
Kaposi sarcoma. Peripheral area of a lymph node, with almost complete effacement of the architecture. Angioproliferation is more obvious, with larger (in comparison with the normal vessels) and congestive lumina.
Kaposi sarcoma. A well-demarcated lesion in the liver parenchyma, without a pseudocapsule.
A: visceral
Back Extra: Kaposi Sarcoma
- Clinical: In children, Kaposi sarcoma can present with rapidly progressive lymphadenopathy and visceral involvement, often without cutaneous lesions, posing a diagnostic challenge.
- Micro: Kaposi sarcoma is characterized by proliferating spindle cells forming slit-like spaces with intraluminal erythrocytes, mitoses, and areas of necrosis.
- Ancillary: Detection of KSHV/HHV8 by PCR and immunohistochemistry for LANA confirms the diagnosis of Kaposi sarcoma.
Reference Gallery:
Kaposi sarcoma. An intestinal lesion in transplantation-related Kaposi sarcoma.
Kaposi sarcoma. Proliferation of spindle cells with slit-like spaces at the periphery with erythrocytes in the lumen. Mitoses are easily seen.
Kaposi sarcoma. Peripheral area of a lymph node, with almost complete effacement of the architecture. Angioproliferation is more obvious, with larger (in comparison with the normal vessels) and congestive lumina.
Kaposi sarcoma. Small bowel with a submucosal nodular lesion showing central necrosis, cellular debris, and hyaline globules.
Kaposi sarcoma. A well-demarcated lesion in the liver parenchyma, without a pseudocapsule.

Q: On histologic examination, nodular lesions of Kaposi Sarcoma can exhibit central necrosis, cellular debris, and characteristic eosinophilic [...].
Kaposi sarcoma. Small bowel with a submucosal nodular lesion showing central necrosis, cellular debris, and hyaline globules.
A: hyaline globules
Back Extra: Kaposi Sarcoma
- Clinical: In children, Kaposi sarcoma can present with rapidly progressive lymphadenopathy and visceral involvement, often without cutaneous lesions, posing a diagnostic challenge.
- Micro: Kaposi sarcoma is characterized by proliferating spindle cells forming slit-like spaces with intraluminal erythrocytes, mitoses, and areas of necrosis.
- Ancillary: Detection of KSHV/HHV8 by PCR and immunohistochemistry for LANA confirms the diagnosis of Kaposi sarcoma.
Reference Gallery:
Kaposi sarcoma. An intestinal lesion in transplantation-related Kaposi sarcoma.
Kaposi sarcoma. Proliferation of spindle cells with slit-like spaces at the periphery with erythrocytes in the lumen. Mitoses are easily seen.
Kaposi sarcoma. Peripheral area of a lymph node, with almost complete effacement of the architecture. Angioproliferation is more obvious, with larger (in comparison with the normal vessels) and congestive lumina.
Kaposi sarcoma. Small bowel with a submucosal nodular lesion showing central necrosis, cellular debris, and hyaline globules.
Kaposi sarcoma. A well-demarcated lesion in the liver parenchyma, without a pseudocapsule.

Q: Histologically, [...] is a lobulated tumor characterized by a spectrum of adipocyte maturation (ranging from primitive spindled mesenchymal cells to lipoblasts and mature adipocytes) separated by fibrovascular septa.
Lipoblastoma. Lipoblasts, variably mature adipocytes, primitive spindled mesenchymal cells, and multinucleated floret cells are intermixed in this tumour.
Lipoblastoma. The tumour shows predominant lipoblasts, with evidence of a spectrum of maturation.
Lipoblastoma. A spectrum of adipocyte maturity, myxoid matrix, and fibrovascular septa constitute this classic lipoblastoma.
A: Lipoblastoma/Lipoblastomatosis
Back Extra: Lipoblastoma/Lipoblastomatosis
- Clinical: Lipoblastoma is typically a superficial, circumscribed tumour that clinically simulates a lipoma or a vascular malformation. Lipoblastomatosis is more infiltrative and can compress adjacent structures.
- Micro: Lipoblastoma is a lobulated tumour comprising sheets of adipocytes showing a spectrum of maturation, ranging from primitive stellate or spindled mesenchymal cells to multivacuolated or small signet-ring lipoblasts through to mature adipocytes, separated by fibrovascular septa.
- Ancillary: Molecular studies may reveal PLAG1 rearrangements or copy-number gain. PLAG1 nuclear immunohistochemical staining can be useful, especially in less differentiated tumours, but its concordance with molecular studies is < 60% and sensitivity is about 50%.
Reference Gallery:
Lipoblastoma. Lipoblasts, variably mature adipocytes, primitive spindled mesenchymal cells, and multinucleated floret cells are intermixed in this tumour.
Lipoblastoma. The tumour is composed of predominantly mature adipocytes with scattered lipoblasts. There are thin fibrous septa.
Lipoblastoma. The tumour shows predominant lipoblasts, with evidence of a spectrum of maturation.
Lipoblastoma. A spectrum of adipocyte maturity, myxoid matrix, and fibrovascular septa constitute this classic lipoblastoma.
Lipoblastoma. Contrast-enhanced axial CT shows a lobular fat-density mass with internal septations in the anterior abdomen, displacing the adjacent small bowel loops.

Q: On contrast-enhanced CT, [...] typically appears as a lobular fat-density mass with internal septations that may compress or displace adjacent structures (e.g., small bowel loops).
Lipoblastoma. Contrast-enhanced axial CT shows a lobular fat-density mass with internal septations in the anterior abdomen, displacing the adjacent small bowel loops.
A: Lipoblastoma/Lipoblastomatosis
Back Extra: Lipoblastoma/Lipoblastomatosis
- Clinical: Lipoblastoma is typically a superficial, circumscribed tumour that clinically simulates a lipoma or a vascular malformation. Lipoblastomatosis is more infiltrative and can compress adjacent structures.
- Micro: Lipoblastoma is a lobulated tumour comprising sheets of adipocytes showing a spectrum of maturation, ranging from primitive stellate or spindled mesenchymal cells to multivacuolated or small signet-ring lipoblasts through to mature adipocytes, separated by fibrovascular septa.
- Ancillary: Molecular studies may reveal PLAG1 rearrangements or copy-number gain. PLAG1 nuclear immunohistochemical staining can be useful, especially in less differentiated tumours, but its concordance with molecular studies is < 60% and sensitivity is about 50%.
Reference Gallery:
Lipoblastoma. Lipoblasts, variably mature adipocytes, primitive spindled mesenchymal cells, and multinucleated floret cells are intermixed in this tumour.
Lipoblastoma. The tumour is composed of predominantly mature adipocytes with scattered lipoblasts. There are thin fibrous septa.
Lipoblastoma. The tumour shows predominant lipoblasts, with evidence of a spectrum of maturation.
Lipoblastoma. A spectrum of adipocyte maturity, myxoid matrix, and fibrovascular septa constitute this classic lipoblastoma.
Lipoblastoma. Contrast-enhanced axial CT shows a lobular fat-density mass with internal septations in the anterior abdomen, displacing the adjacent small bowel loops.

Q: Microscopically, Lipofibromatosis features mature adipose tissue that is traversed by cellular fascicles of uniform [...].
Lipofibromatosis. Mature adipose tissue is traversed by cellular fascicles of spindle cells with uniform fibroblasts.
A: spindle cells
Back Extra: Lipofibromatosis
- Clinical: Lipofibromatosis typically manifests as a slowly growing subcutaneous mass, more common in boys and often congenital.
- Micro: LPF is characterized by an admixture of mature fat, fascicles of bland spindled cells, and lipoblast-like cells.
- Ancillary: Detection of the FN1::EGF gene fusion can be helpful in diagnosis, suggesting activation of the PI3K/AKT/mTOR pathway.
Reference Gallery:
Lipofibromatosis. The fibroblastic cells show a uniform appearance, with a subset showing intracytoplasmic vacuolization resembling univacuolated or bivacuolated lipoblasts.
Lipofibromatosis. Mature adipose tissue is traversed by cellular fascicles of spindle cells with uniform fibroblasts.
Lipofibromatosis. Lipofibromatosis typically involves subcutaneous adipose tissue and can also involve skeletal muscle.

Q: In Lipofibromatosis, the uniform fibroblastic cells often show intracytoplasmic vacuolization that mimics univacuolated or bivacuolated [...].
Lipofibromatosis. The fibroblastic cells show a uniform appearance, with a subset showing intracytoplasmic vacuolization resembling univacuolated or bivacuolated lipoblasts.
A: lipoblasts
Back Extra: Lipofibromatosis
- Clinical: Lipofibromatosis typically manifests as a slowly growing subcutaneous mass, more common in boys and often congenital.
- Micro: LPF is characterized by an admixture of mature fat, fascicles of bland spindled cells, and lipoblast-like cells.
- Ancillary: Detection of the FN1::EGF gene fusion can be helpful in diagnosis, suggesting activation of the PI3K/AKT/mTOR pathway.
Reference Gallery:
Lipofibromatosis. The fibroblastic cells show a uniform appearance, with a subset showing intracytoplasmic vacuolization resembling univacuolated or bivacuolated lipoblasts.
Lipofibromatosis. Mature adipose tissue is traversed by cellular fascicles of spindle cells with uniform fibroblasts.
Lipofibromatosis. Lipofibromatosis typically involves subcutaneous adipose tissue and can also involve skeletal muscle.

Q: Clinically and histologically, Lipofibromatosis presents as a subcutaneous mass that can frequently extend to involve the underlying [...].
Lipofibromatosis. Lipofibromatosis typically involves subcutaneous adipose tissue and can also involve skeletal muscle.
A: skeletal muscle
Back Extra: Lipofibromatosis
- Clinical: Lipofibromatosis typically manifests as a slowly growing subcutaneous mass, more common in boys and often congenital.
- Micro: LPF is characterized by an admixture of mature fat, fascicles of bland spindled cells, and lipoblast-like cells.
- Ancillary: Detection of the FN1::EGF gene fusion can be helpful in diagnosis, suggesting activation of the PI3K/AKT/mTOR pathway.
Reference Gallery:
Lipofibromatosis. The fibroblastic cells show a uniform appearance, with a subset showing intracytoplasmic vacuolization resembling univacuolated or bivacuolated lipoblasts.
Lipofibromatosis. Mature adipose tissue is traversed by cellular fascicles of spindle cells with uniform fibroblasts.
Lipofibromatosis. Lipofibromatosis typically involves subcutaneous adipose tissue and can also involve skeletal muscle.

Q: Histologically, Lipomatosis is characterized by the diffuse, infiltrative overgrowth of [...] into regional structures (such as skeletal muscle) without features of malignancy.
PTEN hamartoma of soft tissue. This lesion displays the classic pattern of intramuscular lipomatosis, with mature adipocytes infiltrating skeletal muscle.
PTEN hamartoma of soft tissue. Adipose tissue, vascular malformation, and entrapped skeletal muscle fibres constitute part of this hamartomatous lesion.
A: mature adipose tissue
Back Extra: Lipomatosis
- Clinical: Lipomatosis often presents with infiltrative overgrowth of mature adipose tissue, which can affect various regions including the face, trunk, and extremities.
- Micro: Microscopically, lipomatosis shows overgrowth of mature adipose tissue, often infiltrating regional tissues without features of malignancy.
- Ancillary: Germline, mosaic, or somatic mutations in PIK3CA, PTEN, and other genes in the PI3K/PTEN/AKT/TSC/mTORC1 pathway are implicated in the pathogenesis of lipomatosis.
Reference Gallery:
PTEN hamartoma of soft tissue. This lesion displays the classic pattern of intramuscular lipomatosis, with mature adipocytes infiltrating skeletal muscle.
PTEN hamartoma of soft tissue. Adipose tissue, vascular malformation, and entrapped skeletal muscle fibres constitute part of this hamartomatous lesion.
Fibroadipose vascular anomaly. Lobules of dilated back-to-back venous channels are surrounded by fibroadipose tissue in this example.
Fibroadipose vascular anomaly. Fibroadipose tissue infiltrates skeletal muscle, and prominent malformed arteries can be seen on the right.
Lipomatosis. Axial T1-weighted image shows infiltrative growth of fatty tissue within the thoracic cavity, which is of the same signal intensity as the subcutaneous fat. The fat tissue wraps around the heart.
Lipomatosis. Coronal T1-weighted image shows the infiltrative fatty tissue within the thorax and anterior abdomen, which is of the same signal intensity as the subcutaneous fat. There is no definite surrounding capsule.

Q: On T1-weighted MRI, thoracic or abdominal Lipomatosis typically presents as an infiltrative mass that lacks a true capsule and shares the exact same signal intensity as normal [...].
Lipomatosis. Axial T1-weighted image shows infiltrative growth of fatty tissue within the thoracic cavity, which is of the same signal intensity as the subcutaneous fat. The fat tissue wraps around the heart.
Lipomatosis. Coronal T1-weighted image shows the infiltrative fatty tissue within the thorax and anterior abdomen, which is of the same signal intensity as the subcutaneous fat. There is no definite surrounding capsule.
A: subcutaneous fat
Back Extra: Lipomatosis
- Clinical: Lipomatosis often presents with infiltrative overgrowth of mature adipose tissue, which can affect various regions including the face, trunk, and extremities.
- Micro: Microscopically, lipomatosis shows overgrowth of mature adipose tissue, often infiltrating regional tissues without features of malignancy.
- Ancillary: Germline, mosaic, or somatic mutations in PIK3CA, PTEN, and other genes in the PI3K/PTEN/AKT/TSC/mTORC1 pathway are implicated in the pathogenesis of lipomatosis.
Reference Gallery:
PTEN hamartoma of soft tissue. This lesion displays the classic pattern of intramuscular lipomatosis, with mature adipocytes infiltrating skeletal muscle.
PTEN hamartoma of soft tissue. Adipose tissue, vascular malformation, and entrapped skeletal muscle fibres constitute part of this hamartomatous lesion.
Fibroadipose vascular anomaly. Lobules of dilated back-to-back venous channels are surrounded by fibroadipose tissue in this example.
Fibroadipose vascular anomaly. Fibroadipose tissue infiltrates skeletal muscle, and prominent malformed arteries can be seen on the right.
Lipomatosis. Axial T1-weighted image shows infiltrative growth of fatty tissue within the thoracic cavity, which is of the same signal intensity as the subcutaneous fat. The fat tissue wraps around the heart.
Lipomatosis. Coronal T1-weighted image shows the infiltrative fatty tissue within the thorax and anterior abdomen, which is of the same signal intensity as the subcutaneous fat. There is no definite surrounding capsule.

Q: The pathogenesis of Lipomatosis is frequently driven by mutations in the PI3K/AKT/mTOR pathway, including the PIK3CA gene and the [...] gene (the latter often associated with soft tissue hamartomas).
PTEN hamartoma of soft tissue. This lesion displays the classic pattern of intramuscular lipomatosis, with mature adipocytes infiltrating skeletal muscle.
A: PTEN
Back Extra: Lipomatosis
- Clinical: Lipomatosis often presents with infiltrative overgrowth of mature adipose tissue, which can affect various regions including the face, trunk, and extremities.
- Micro: Microscopically, lipomatosis shows overgrowth of mature adipose tissue, often infiltrating regional tissues without features of malignancy.
- Ancillary: Germline, mosaic, or somatic mutations in PIK3CA, PTEN, and other genes in the PI3K/PTEN/AKT/TSC/mTORC1 pathway are implicated in the pathogenesis of lipomatosis.
Reference Gallery:
PTEN hamartoma of soft tissue. This lesion displays the classic pattern of intramuscular lipomatosis, with mature adipocytes infiltrating skeletal muscle.
PTEN hamartoma of soft tissue. Adipose tissue, vascular malformation, and entrapped skeletal muscle fibres constitute part of this hamartomatous lesion.
Fibroadipose vascular anomaly. Lobules of dilated back-to-back venous channels are surrounded by fibroadipose tissue in this example.
Fibroadipose vascular anomaly. Fibroadipose tissue infiltrates skeletal muscle, and prominent malformed arteries can be seen on the right.
Lipomatosis. Axial T1-weighted image shows infiltrative growth of fatty tissue within the thoracic cavity, which is of the same signal intensity as the subcutaneous fat. The fat tissue wraps around the heart.
Lipomatosis. Coronal T1-weighted image shows the infiltrative fatty tissue within the thorax and anterior abdomen, which is of the same signal intensity as the subcutaneous fat. There is no definite surrounding capsule.

Q: The myxoid variant of Liposarcoma characteristically features lipoblasts with indented nuclei and a delicate, arborizing [...] capillary network within a myxoid stroma.
Myxoid liposarcoma. Myxoid liposarcoma in a 12-year-old boy, lower extremity. There are myxoid areas and a delicate plexiform vascular pattern.
Myxoid liposarcoma. Typical lipoblasts with indented nuclei.
Myxoid liposarcoma. Myxoid stroma with a plexiform, delicately arborizing capillary network.
A: plexiform
Back Extra: Liposarcoma
- Clinical: Liposarcomas in children are usually large, deep-seated, painless soft tissue masses, with a female predominance. Myxoid liposarcoma is the most common subtype.
- Micro: Myxoid liposarcomas show myxoid areas with a delicate plexiform vascular pattern and lipoblasts with indented nuclei.
- Ancillary: FISH analysis for DDIT3 rearrangement is diagnostic for myxoid liposarcoma, distinguishing it from other myxoid tumors.
Reference Gallery:
Paediatric myxoid liposarcoma. FISH analysis using a break-apart probe for DDIT3. Split red and green signals indicate a rearrangement of DDIT3, characteristic of myxoid liposarcoma.
Myxoid liposarcoma. Myxoid liposarcoma in a 12-year-old boy, lower extremity. There are myxoid areas and a delicate plexiform vascular pattern.
Myxoid liposarcoma. Typical lipoblasts with indented nuclei.
Myxoid liposarcoma. A microcystic/pulmonary oedema-like pattern.
Myxoid liposarcoma. Myxoid stroma with a plexiform, delicately arborizing capillary network.
Myxoid pleomorphic liposarcoma. Admixture of myxoid liposarcoma–like and pleomorphic liposarcoma–like areas.
Myxoid pleomorphic liposarcoma. Myxoid liposarcoma–like areas in myxoid pleomorphic liposarcoma composed of myxoid matrix, scattered lipoblasts, and a delicate capillary network.
Myxoid pleomorphic liposarcoma. Pleomorphic liposarcoma–like areas with severe cytological atypia and pleomorphic lipoblasts.

Q: To distinguish myxoid Liposarcoma from other myxoid soft tissue tumors, FISH analysis is highly diagnostic when it demonstrates a characteristic rearrangement involving the [...] gene.
Paediatric myxoid liposarcoma. FISH analysis using a break-apart probe for DDIT3. Split red and green signals indicate a rearrangement of DDIT3, characteristic of myxoid liposarcoma.
A: DDIT3
Back Extra: Liposarcoma
- Clinical: Liposarcomas in children are usually large, deep-seated, painless soft tissue masses, with a female predominance. Myxoid liposarcoma is the most common subtype.
- Micro: Myxoid liposarcomas show myxoid areas with a delicate plexiform vascular pattern and lipoblasts with indented nuclei.
- Ancillary: FISH analysis for DDIT3 rearrangement is diagnostic for myxoid liposarcoma, distinguishing it from other myxoid tumors.
Reference Gallery:
Paediatric myxoid liposarcoma. FISH analysis using a break-apart probe for DDIT3. Split red and green signals indicate a rearrangement of DDIT3, characteristic of myxoid liposarcoma.
Myxoid liposarcoma. Myxoid liposarcoma in a 12-year-old boy, lower extremity. There are myxoid areas and a delicate plexiform vascular pattern.
Myxoid liposarcoma. Typical lipoblasts with indented nuclei.
Myxoid liposarcoma. A microcystic/pulmonary oedema-like pattern.
Myxoid liposarcoma. Myxoid stroma with a plexiform, delicately arborizing capillary network.
Myxoid pleomorphic liposarcoma. Admixture of myxoid liposarcoma–like and pleomorphic liposarcoma–like areas.
Myxoid pleomorphic liposarcoma. Myxoid liposarcoma–like areas in myxoid pleomorphic liposarcoma composed of myxoid matrix, scattered lipoblasts, and a delicate capillary network.
Myxoid pleomorphic liposarcoma. Pleomorphic liposarcoma–like areas with severe cytological atypia and pleomorphic lipoblasts.

Q: The stroma in myxoid Liposarcoma frequently pools to form microcystic spaces, resulting in an architectural appearance classically described as a [...] pattern.
Myxoid liposarcoma. A microcystic/pulmonary oedema-like pattern.
A: pulmonary edema-like
Back Extra: Liposarcoma
- Clinical: Liposarcomas in children are usually large, deep-seated, painless soft tissue masses, with a female predominance. Myxoid liposarcoma is the most common subtype.
- Micro: Myxoid liposarcomas show myxoid areas with a delicate plexiform vascular pattern and lipoblasts with indented nuclei.
- Ancillary: FISH analysis for DDIT3 rearrangement is diagnostic for myxoid liposarcoma, distinguishing it from other myxoid tumors.
Reference Gallery:
Paediatric myxoid liposarcoma. FISH analysis using a break-apart probe for DDIT3. Split red and green signals indicate a rearrangement of DDIT3, characteristic of myxoid liposarcoma.
Myxoid liposarcoma. Myxoid liposarcoma in a 12-year-old boy, lower extremity. There are myxoid areas and a delicate plexiform vascular pattern.
Myxoid liposarcoma. Typical lipoblasts with indented nuclei.
Myxoid liposarcoma. A microcystic/pulmonary oedema-like pattern.
Myxoid liposarcoma. Myxoid stroma with a plexiform, delicately arborizing capillary network.
Myxoid pleomorphic liposarcoma. Admixture of myxoid liposarcoma–like and pleomorphic liposarcoma–like areas.
Myxoid pleomorphic liposarcoma. Myxoid liposarcoma–like areas in myxoid pleomorphic liposarcoma composed of myxoid matrix, scattered lipoblasts, and a delicate capillary network.
Myxoid pleomorphic liposarcoma. Pleomorphic liposarcoma–like areas with severe cytological atypia and pleomorphic lipoblasts.

Q: Clinically presenting as a rapidly growing, erythematous, bleeding polypoid lesion, [...] is a common vascular proliferation often found on the head, neck, or distal extremities.
Lobular capillary haemangioma (pyogenic granuloma). An erythematous polypoid lesion in the neck.
A: Lobular Capillary Hemangioma (Pyogenic Granuloma)
Back Extra: Lobular Capillary Hemangioma (Pyogenic Granuloma)
- Clinical: Rapidly growing, solitary, erythematous, dome-shaped or pedunculated papules that bleed easily, often found on the head and neck or distal extremities.
- Micro: Lobules of capillaries in an oedematous stroma, lined by bland endothelial cells and surrounded by SMA-positive pericytes, with frequent ulceration and an epidermal collarette.
- Ancillary: Not typically required; diagnosis is usually made by clinical and histological features.
Reference Gallery:
Lobular capillary haemangioma (pyogenic granuloma). Ulcerated lobular capillary haemangioma with epidermal collarette.
Lobular capillary haemangioma (pyogenic granuloma). Lobules of capillary vessels separated by fibrous septa.
Lobular capillary haemangioma (pyogenic granuloma). Capillaries are lined by bland endothelial cells and surrounded by pericytes.
Lobular capillary haemangioma (pyogenic granuloma). An erythematous polypoid lesion in the neck.

Q: A classic low-power microscopic feature of Lobular Capillary Hemangioma (Pyogenic Granuloma) is a polypoid, often ulcerated mass flanked by an inward growth of the adjacent epithelium, termed an [...].
Lobular capillary haemangioma (pyogenic granuloma). Ulcerated lobular capillary haemangioma with epidermal collarette.
A: epidermal collarette
Back Extra: Lobular Capillary Hemangioma (Pyogenic Granuloma)
- Clinical: Rapidly growing, solitary, erythematous, dome-shaped or pedunculated papules that bleed easily, often found on the head and neck or distal extremities.
- Micro: Lobules of capillaries in an oedematous stroma, lined by bland endothelial cells and surrounded by SMA-positive pericytes, with frequent ulceration and an epidermal collarette.
- Ancillary: Not typically required; diagnosis is usually made by clinical and histological features.
Reference Gallery:
Lobular capillary haemangioma (pyogenic granuloma). Ulcerated lobular capillary haemangioma with epidermal collarette.
Lobular capillary haemangioma (pyogenic granuloma). Lobules of capillary vessels separated by fibrous septa.
Lobular capillary haemangioma (pyogenic granuloma). Capillaries are lined by bland endothelial cells and surrounded by pericytes.
Lobular capillary haemangioma (pyogenic granuloma). An erythematous polypoid lesion in the neck.

Q: Microscopically, Lobular Capillary Hemangioma (Pyogenic Granuloma) is characterized by distinct [...] of capillaries lined by bland endothelial cells and separated by fibrous septa within an edematous stroma.
Lobular capillary haemangioma (pyogenic granuloma). Lobules of capillary vessels separated by fibrous septa.
Lobular capillary haemangioma (pyogenic granuloma). Capillaries are lined by bland endothelial cells and surrounded by pericytes.
A: lobules
Back Extra: Lobular Capillary Hemangioma (Pyogenic Granuloma)
- Clinical: Rapidly growing, solitary, erythematous, dome-shaped or pedunculated papules that bleed easily, often found on the head and neck or distal extremities.
- Micro: Lobules of capillaries in an oedematous stroma, lined by bland endothelial cells and surrounded by SMA-positive pericytes, with frequent ulceration and an epidermal collarette.
- Ancillary: Not typically required; diagnosis is usually made by clinical and histological features.
Reference Gallery:
Lobular capillary haemangioma (pyogenic granuloma). Ulcerated lobular capillary haemangioma with epidermal collarette.
Lobular capillary haemangioma (pyogenic granuloma). Lobules of capillary vessels separated by fibrous septa.
Lobular capillary haemangioma (pyogenic granuloma). Capillaries are lined by bland endothelial cells and surrounded by pericytes.
Lobular capillary haemangioma (pyogenic granuloma). An erythematous polypoid lesion in the neck.

Q: Histologically, Low-grade fibromyxoid sarcoma / sclerosing epithelioid fibrosarcoma classically demonstrates an abrupt transition between densely collagenous and [...] stroma, containing uniform spindle to stellate cells arranged in whorls and short fascicles.
Low-grade fibromyxoid sarcoma. In this example of paediatric low-grade fibromyxoid sarcoma, uniform spindle and stellate cells are distributed within a myxoid/myxocollagenous and collagenous stroma. The demarcation between stromal components is typically abrupt. Vascularity is quite prominent, with variably sized (frequently arteriole-sized) vessels and focal perivascular sclerosis.
Low-grade fibromyxoid sarcoma. There is demarcation between the more hypercellular areas of tumour and those with moderate cellularity. The tumour is disposed in short fascicles and whorls, and vascularity is prominent.
A: myxoid
Back Extra: Low-grade fibromyxoid sarcoma / sclerosing epithelioid fibrosarcoma
- Clinical: Patients typically present with a painless mass, and most low-grade fibromyxoid sarcomas in patients < 21 years are < 50 mm in size, localized, and without nodal or distant metastases.
- Micro: Alternating collagenous and myxoid areas, with spindle and stellate cells arranged in whorls or short fascicles, and minimal atypia.
- Ancillary: Strong diffuse cytoplasmic MUC4 expression is highly sensitive and specific for low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma.
Reference Gallery:
Low-grade fibromyxoid sarcoma. This lobulated paediatric low-grade fibromyxoid sarcoma is in the deeper dermis / subcutis. Superficial tumours are more common in children.
Low-grade fibromyxoid sarcoma. In this example of paediatric low-grade fibromyxoid sarcoma, uniform spindle and stellate cells are distributed within a myxoid/myxocollagenous and collagenous stroma. The demarcation between stromal components is typically abrupt. Vascularity is quite prominent, with variably sized (frequently arteriole-sized) vessels and focal perivascular sclerosis.
Low-grade fibromyxoid sarcoma. There is demarcation between the more hypercellular areas of tumour and those with moderate cellularity. The tumour is disposed in short fascicles and whorls, and vascularity is prominent.
Low-grade fibromyxoid sarcoma. Low-grade fibromyxoid sarcoma typically lacks atypia. Here, uniform cells with ovoid, somewhat angulated, nuclei and fibrillary cytoplasm are dispersed within moderately collagenous stroma.
Low-grade fibromyxoid sarcoma. A densely collagenized area with epithelioid cells, resembling sclerosing epithelioid fibrosarcoma.
Low-grade fibromyxoid sarcoma. Macroscopic appearance of a low-grade fibromyxoid sarcoma in the upper back of a 14-year-old boy.
Low-grade fibromyxoid sarcoma. The cut surface appears pale, gelatinous, and vaguely multinodular.
Low-grade fibromyxoid sarcoma. Fascicles of elongated cells in continuity with myxoid areas.
Low-grade fibromyxoid sarcoma. The cells show minimal atypia, and the nuclei have finely dispersed chromatin.
Low-grade fibromyxoid sarcoma. MUC4 is strongly and diffusely positive.
Low-grade fibromyxoid sarcoma. Contrast-enhanced axial CT showing a well-defined large right thoracic mass with density lower than that of adjacent skeletal muscles. It has poor heterogeneous enhancement and causes compression of the heart.
Low-grade fibromyxoid sarcoma. Contrast-enhanced coronal CT reformatted image showing a paucity of intralesional enhancement within the large mass in right hemithorax, causing compression of the heart and a mediastinal shift.

Q: Within the morphologic spectrum of Low-grade fibromyxoid sarcoma / sclerosing epithelioid fibrosarcoma, areas may become densely collagenized and feature nests or cords of [...] cells, bridging the presentation toward the sclerosing variant.
Low-grade fibromyxoid sarcoma. A densely collagenized area with epithelioid cells, resembling sclerosing epithelioid fibrosarcoma.
A: epithelioid
Back Extra: Low-grade fibromyxoid sarcoma / sclerosing epithelioid fibrosarcoma
- Clinical: Patients typically present with a painless mass, and most low-grade fibromyxoid sarcomas in patients < 21 years are < 50 mm in size, localized, and without nodal or distant metastases.
- Micro: Alternating collagenous and myxoid areas, with spindle and stellate cells arranged in whorls or short fascicles, and minimal atypia.
- Ancillary: Strong diffuse cytoplasmic MUC4 expression is highly sensitive and specific for low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma.
Reference Gallery:
Low-grade fibromyxoid sarcoma. This lobulated paediatric low-grade fibromyxoid sarcoma is in the deeper dermis / subcutis. Superficial tumours are more common in children.
Low-grade fibromyxoid sarcoma. In this example of paediatric low-grade fibromyxoid sarcoma, uniform spindle and stellate cells are distributed within a myxoid/myxocollagenous and collagenous stroma. The demarcation between stromal components is typically abrupt. Vascularity is quite prominent, with variably sized (frequently arteriole-sized) vessels and focal perivascular sclerosis.
Low-grade fibromyxoid sarcoma. There is demarcation between the more hypercellular areas of tumour and those with moderate cellularity. The tumour is disposed in short fascicles and whorls, and vascularity is prominent.
Low-grade fibromyxoid sarcoma. Low-grade fibromyxoid sarcoma typically lacks atypia. Here, uniform cells with ovoid, somewhat angulated, nuclei and fibrillary cytoplasm are dispersed within moderately collagenous stroma.
Low-grade fibromyxoid sarcoma. A densely collagenized area with epithelioid cells, resembling sclerosing epithelioid fibrosarcoma.
Low-grade fibromyxoid sarcoma. Macroscopic appearance of a low-grade fibromyxoid sarcoma in the upper back of a 14-year-old boy.
Low-grade fibromyxoid sarcoma. The cut surface appears pale, gelatinous, and vaguely multinodular.
Low-grade fibromyxoid sarcoma. Fascicles of elongated cells in continuity with myxoid areas.
Low-grade fibromyxoid sarcoma. The cells show minimal atypia, and the nuclei have finely dispersed chromatin.
Low-grade fibromyxoid sarcoma. MUC4 is strongly and diffusely positive.
Low-grade fibromyxoid sarcoma. Contrast-enhanced axial CT showing a well-defined large right thoracic mass with density lower than that of adjacent skeletal muscles. It has poor heterogeneous enhancement and causes compression of the heart.
Low-grade fibromyxoid sarcoma. Contrast-enhanced coronal CT reformatted image showing a paucity of intralesional enhancement within the large mass in right hemithorax, causing compression of the heart and a mediastinal shift.

Q: A highly sensitive and specific immunohistochemical marker for the diagnosis of Low-grade fibromyxoid sarcoma / sclerosing epithelioid fibrosarcoma is strong, diffuse cytoplasmic expression of [...].
Low-grade fibromyxoid sarcoma. MUC4 is strongly and diffusely positive.
A: MUC4
Back Extra: Low-grade fibromyxoid sarcoma / sclerosing epithelioid fibrosarcoma
- Clinical: Patients typically present with a painless mass, and most low-grade fibromyxoid sarcomas in patients < 21 years are < 50 mm in size, localized, and without nodal or distant metastases.
- Micro: Alternating collagenous and myxoid areas, with spindle and stellate cells arranged in whorls or short fascicles, and minimal atypia.
- Ancillary: Strong diffuse cytoplasmic MUC4 expression is highly sensitive and specific for low-grade fibromyxoid sarcoma and sclerosing epithelioid fibrosarcoma.
Reference Gallery:
Low-grade fibromyxoid sarcoma. This lobulated paediatric low-grade fibromyxoid sarcoma is in the deeper dermis / subcutis. Superficial tumours are more common in children.
Low-grade fibromyxoid sarcoma. In this example of paediatric low-grade fibromyxoid sarcoma, uniform spindle and stellate cells are distributed within a myxoid/myxocollagenous and collagenous stroma. The demarcation between stromal components is typically abrupt. Vascularity is quite prominent, with variably sized (frequently arteriole-sized) vessels and focal perivascular sclerosis.
Low-grade fibromyxoid sarcoma. There is demarcation between the more hypercellular areas of tumour and those with moderate cellularity. The tumour is disposed in short fascicles and whorls, and vascularity is prominent.
Low-grade fibromyxoid sarcoma. Low-grade fibromyxoid sarcoma typically lacks atypia. Here, uniform cells with ovoid, somewhat angulated, nuclei and fibrillary cytoplasm are dispersed within moderately collagenous stroma.
Low-grade fibromyxoid sarcoma. A densely collagenized area with epithelioid cells, resembling sclerosing epithelioid fibrosarcoma.
Low-grade fibromyxoid sarcoma. Macroscopic appearance of a low-grade fibromyxoid sarcoma in the upper back of a 14-year-old boy.
Low-grade fibromyxoid sarcoma. The cut surface appears pale, gelatinous, and vaguely multinodular.
Low-grade fibromyxoid sarcoma. Fascicles of elongated cells in continuity with myxoid areas.
Low-grade fibromyxoid sarcoma. The cells show minimal atypia, and the nuclei have finely dispersed chromatin.
Low-grade fibromyxoid sarcoma. MUC4 is strongly and diffusely positive.
Low-grade fibromyxoid sarcoma. Contrast-enhanced axial CT showing a well-defined large right thoracic mass with density lower than that of adjacent skeletal muscles. It has poor heterogeneous enhancement and causes compression of the heart.
Low-grade fibromyxoid sarcoma. Contrast-enhanced coronal CT reformatted image showing a paucity of intralesional enhancement within the large mass in right hemithorax, causing compression of the heart and a mediastinal shift.

Q: A characteristic immunohistochemical finding in Low-grade myofibroblastic sarcoma is strong SMA expression, which frequently displays a distinct [...] accentuation.
Low-grade myofibroblastic tumour. The tumour shows multifocal strong SMA expression, with frequent subplasmalemmal accentuation.
A: subplasmalemmal
Back Extra: Low-grade myofibroblastic sarcoma
- Clinical: Patients with low-grade myofibroblastic sarcoma typically present with an enlarging mass, rarely associated with pain.
- Micro: The tumour is composed of spindle cells with elongated vesicular nuclei and palely eosinophilic cytoplasm, often in a collagenous stroma, with focal atypia and scattered mitotic activity.
- Ancillary: Immunohistochemistry shows strong SMA expression, often with subplasmalemmal accentuation, and focal nuclear atypia is key for diagnosis.
Reference Gallery:
Low-grade myofibroblastic tumour. The tumour is composed of long fascicles of spindle cells with elongated vesicular nuclei and palely eosinophilic cytoplasm, in a collagenous stroma. These tumours can have a bland appearance in many foci, mimicking other myofibroblastic neoplasms such as fibromatosis or nodular fasciitis.
Low-grade myofibroblastic tumour. At higher magnification, tumours frequently show features reminiscent of myofibroblasts, with elongated vesicular nuclei, frequent small nucleoli, and eosinophilic cytoplasm. Atypia is focal and mild, and there is scattered mitotic activity.
Low-grade myofibroblastic tumour. The tumour shows multifocal strong SMA expression, with frequent subplasmalemmal accentuation.

Q: Microscopically, Low-grade myofibroblastic sarcoma features fascicles of spindle cells in a collagenous stroma. A key finding that distinguishes this tumor from benign mimics (such as fibromatosis or nodular fasciitis) is the presence of scattered mitotic activity and focal [...].
Low-grade myofibroblastic tumour. The tumour is composed of long fascicles of spindle cells with elongated vesicular nuclei and palely eosinophilic cytoplasm, in a collagenous stroma. These tumours can have a bland appearance in many foci, mimicking other myofibroblastic neoplasms such as fibromatosis or nodular fasciitis.
Low-grade myofibroblastic tumour. At higher magnification, tumours frequently show features reminiscent of myofibroblasts, with elongated vesicular nuclei, frequent small nucleoli, and eosinophilic cytoplasm. Atypia is focal and mild, and there is scattered mitotic activity.
A: nuclear atypia
Back Extra: Low-grade myofibroblastic sarcoma
- Clinical: Patients with low-grade myofibroblastic sarcoma typically present with an enlarging mass, rarely associated with pain.
- Micro: The tumour is composed of spindle cells with elongated vesicular nuclei and palely eosinophilic cytoplasm, often in a collagenous stroma, with focal atypia and scattered mitotic activity.
- Ancillary: Immunohistochemistry shows strong SMA expression, often with subplasmalemmal accentuation, and focal nuclear atypia is key for diagnosis.
Reference Gallery:
Low-grade myofibroblastic tumour. The tumour is composed of long fascicles of spindle cells with elongated vesicular nuclei and palely eosinophilic cytoplasm, in a collagenous stroma. These tumours can have a bland appearance in many foci, mimicking other myofibroblastic neoplasms such as fibromatosis or nodular fasciitis.
Low-grade myofibroblastic tumour. At higher magnification, tumours frequently show features reminiscent of myofibroblasts, with elongated vesicular nuclei, frequent small nucleoli, and eosinophilic cytoplasm. Atypia is focal and mild, and there is scattered mitotic activity.
Low-grade myofibroblastic tumour. The tumour shows multifocal strong SMA expression, with frequent subplasmalemmal accentuation.

Q: A biopsy of an enlarging, painful soft tissue mass in a teenager reveals fascicles of spindle cells with tapered, wavy, hyperchromatic nuclei and patchy S100 expression. This presentation strongly suggests a diagnosis of [...].
Malignant peripheral nerve sheath tumour. This lesion of the dorsum of the left foot of a 9-year-old boy appears fleshy, pale, and relatively well defined. It measures 80 × 60 × 60 mm, extends into the subcutaneous tissue and skeletal muscle, and focally infiltrates the periosteum of the talus.
Malignant peripheral nerve sheath tumour. The neoplastic cells feature tapered, wavy, hyperchromatic nuclei.
A: Malignant Peripheral Nerve Sheath Tumor
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant peripheral nerve sheath tumours (MPNSTs) in children are rare, typically affecting teenagers and presenting as enlarging, painful soft tissue masses.
- Micro: MPNSTs often show fascicles of spindle cells with tapered, wavy, hyperchromatic nuclei, perivascular cell condensation, and geographical necrosis.
- Ancillary: Immunostaining for S100 is patchy or focal in about 50% of conventional MPNSTs, and SOX10 is expressed in 70–84% of cases.
Reference Gallery:
Malignant peripheral nerve sheath tumour. This lesion of the dorsum of the left foot of a 9-year-old boy appears fleshy, pale, and relatively well defined. It measures 80 × 60 × 60 mm, extends into the subcutaneous tissue and skeletal muscle, and focally infiltrates the periosteum of the talus.
Malignant peripheral nerve sheath tumour. The tumour consists of fascicles of spindle cells with perivascular condensation.
Malignant peripheral nerve sheath tumour. The neoplastic cells feature tapered, wavy, hyperchromatic nuclei.
Malignant peripheral nerve sheath tumour. The tumour shows geographical necrosis with a perivascular-sparing pattern.
Malignant triton tumour. The tumour is composed of long fascicles of spindle cells with scattered rhabdomyoblasts.
Malignant peripheral nerve sheath tumour. The tumour shows heterologous glands.
Malignant peripheral nerve sheath tumour. The tumour shows loss of H3 p.K27me3 in the presence of an appropriate positive internal control (blood vessel).
Epithelioid malignant peripheral nerve sheath tumour. The neoplastic cells show abundant eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli.
Epithelioid malignant peripheral nerve sheath tumour. The tumour shows loss of SMARCB1 (INI1) in the presence of an appropriate positive control.
Malignant peripheral nerve sheath tumour. T2-weighted fat-suppressed sagittal MRI shows a heterogeneous T2-hyperintense mass with intratumoural cystic areas.

Q: In Malignant Peripheral Nerve Sheath Tumor, the conventional spindle cell morphology often demonstrates densely packed cells around vessels (perivascular condensation) alongside extensive areas of cell death known as [...].
Malignant peripheral nerve sheath tumour. The tumour consists of fascicles of spindle cells with perivascular condensation.
Malignant peripheral nerve sheath tumour. The tumour shows geographical necrosis with a perivascular-sparing pattern.
A: geographical necrosis
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant peripheral nerve sheath tumours (MPNSTs) in children are rare, typically affecting teenagers and presenting as enlarging, painful soft tissue masses.
- Micro: MPNSTs often show fascicles of spindle cells with tapered, wavy, hyperchromatic nuclei, perivascular cell condensation, and geographical necrosis.
- Ancillary: Immunostaining for S100 is patchy or focal in about 50% of conventional MPNSTs, and SOX10 is expressed in 70–84% of cases.
Reference Gallery:
Malignant peripheral nerve sheath tumour. This lesion of the dorsum of the left foot of a 9-year-old boy appears fleshy, pale, and relatively well defined. It measures 80 × 60 × 60 mm, extends into the subcutaneous tissue and skeletal muscle, and focally infiltrates the periosteum of the talus.
Malignant peripheral nerve sheath tumour. The tumour consists of fascicles of spindle cells with perivascular condensation.
Malignant peripheral nerve sheath tumour. The neoplastic cells feature tapered, wavy, hyperchromatic nuclei.
Malignant peripheral nerve sheath tumour. The tumour shows geographical necrosis with a perivascular-sparing pattern.
Malignant triton tumour. The tumour is composed of long fascicles of spindle cells with scattered rhabdomyoblasts.
Malignant peripheral nerve sheath tumour. The tumour shows heterologous glands.
Malignant peripheral nerve sheath tumour. The tumour shows loss of H3 p.K27me3 in the presence of an appropriate positive internal control (blood vessel).
Epithelioid malignant peripheral nerve sheath tumour. The neoplastic cells show abundant eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli.
Epithelioid malignant peripheral nerve sheath tumour. The tumour shows loss of SMARCB1 (INI1) in the presence of an appropriate positive control.
Malignant peripheral nerve sheath tumour. T2-weighted fat-suppressed sagittal MRI shows a heterogeneous T2-hyperintense mass with intratumoural cystic areas.

Q: To confirm the diagnosis of Myoepithelial Tumor of Soft Tissue, immunohistochemistry typically demonstrates characteristic co-expression of S100 and [...] (e.g., keratin and EMA).
Myoepithelial carcinoma of soft tissue. Most cases show positivity for keratin (pankeratin shown).
Myoepithelial carcinoma of soft tissue. S100 is frequently positive.
A: epithelial markers
Back Extra: Myoepithelial Tumour of Soft Tissue
- Clinical: Myoepithelial tumours of soft tissue present as painless, palpable masses, with 20% arising in children and a higher likelihood of being malignant in this age group.
- Micro: These tumours show multinodular growth with variably myxoid, collagenous, or hyalinized stroma, and a mixture of spindle and epithelioid cells.
- Ancillary: The diagnosis is confirmed by the expression of both epithelial markers (keratin, EMA) and S100, with EWSR1 gene rearrangements present in about 50% of cases.
Reference Gallery:
Myoepithelial tumour of soft tissue. Lobulated growth with reticular, trabecular, nested patterns and a hyalinized and myxoid stroma.
Myoepithelial tumour of soft tissue. Epithelioid and spindle cells arranged in trabeculae.
Myoepithelioma. Epithelioid and spindle cells with variably eosinophilic or cleared cytoplasm, without cytological atypia.
Myoepithelial tumour of soft tissue. Cartilaginous (and/or osseous) differentiation is seen in about 10% of cases.
Myoepithelial carcinoma of soft tissue. Solid growth of tumour cells with nuclear atypia and readily identified nucleoli.
Myoepithelial carcinoma of soft tissue. Some tumours may show a densely sclerotic stroma with nested growth of epithelioid cells with frequently clear cytoplasm.
Myoepithelial carcinoma of soft tissue. Most cases show positivity for keratin (pankeratin shown).
Myoepithelial carcinoma of soft tissue. S100 is frequently positive.

Q: Histologically, Myoepithelial Tumor of Soft Tissue often displays a multinodular growth pattern composed of a mixture of epithelioid and [...] cells set within a variably myxoid, collagenous, or hyalinized stroma.
Myoepithelial tumour of soft tissue. Lobulated growth with reticular, trabecular, nested patterns and a hyalinized and myxoid stroma.
Myoepithelial tumour of soft tissue. Epithelioid and spindle cells arranged in trabeculae.
Myoepithelioma. Epithelioid and spindle cells with variably eosinophilic or cleared cytoplasm, without cytological atypia.
A: spindle
Back Extra: Myoepithelial Tumour of Soft Tissue
- Clinical: Myoepithelial tumours of soft tissue present as painless, palpable masses, with 20% arising in children and a higher likelihood of being malignant in this age group.
- Micro: These tumours show multinodular growth with variably myxoid, collagenous, or hyalinized stroma, and a mixture of spindle and epithelioid cells.
- Ancillary: The diagnosis is confirmed by the expression of both epithelial markers (keratin, EMA) and S100, with EWSR1 gene rearrangements present in about 50% of cases.
Reference Gallery:
Myoepithelial tumour of soft tissue. Lobulated growth with reticular, trabecular, nested patterns and a hyalinized and myxoid stroma.
Myoepithelial tumour of soft tissue. Epithelioid and spindle cells arranged in trabeculae.
Myoepithelioma. Epithelioid and spindle cells with variably eosinophilic or cleared cytoplasm, without cytological atypia.
Myoepithelial tumour of soft tissue. Cartilaginous (and/or osseous) differentiation is seen in about 10% of cases.
Myoepithelial carcinoma of soft tissue. Solid growth of tumour cells with nuclear atypia and readily identified nucleoli.
Myoepithelial carcinoma of soft tissue. Some tumours may show a densely sclerotic stroma with nested growth of epithelioid cells with frequently clear cytoplasm.
Myoepithelial carcinoma of soft tissue. Most cases show positivity for keratin (pankeratin shown).
Myoepithelial carcinoma of soft tissue. S100 is frequently positive.

Q: In addition to its classic mixed cell population, approximately 10% of cases of Myoepithelial Tumor of Soft Tissue can exhibit focal [...] or osseous differentiation.
Myoepithelial tumour of soft tissue. Cartilaginous (and/or osseous) differentiation is seen in about 10% of cases.
A: cartilaginous
Back Extra: Myoepithelial Tumour of Soft Tissue
- Clinical: Myoepithelial tumours of soft tissue present as painless, palpable masses, with 20% arising in children and a higher likelihood of being malignant in this age group.
- Micro: These tumours show multinodular growth with variably myxoid, collagenous, or hyalinized stroma, and a mixture of spindle and epithelioid cells.
- Ancillary: The diagnosis is confirmed by the expression of both epithelial markers (keratin, EMA) and S100, with EWSR1 gene rearrangements present in about 50% of cases.
Reference Gallery:
Myoepithelial tumour of soft tissue. Lobulated growth with reticular, trabecular, nested patterns and a hyalinized and myxoid stroma.
Myoepithelial tumour of soft tissue. Epithelioid and spindle cells arranged in trabeculae.
Myoepithelioma. Epithelioid and spindle cells with variably eosinophilic or cleared cytoplasm, without cytological atypia.
Myoepithelial tumour of soft tissue. Cartilaginous (and/or osseous) differentiation is seen in about 10% of cases.
Myoepithelial carcinoma of soft tissue. Solid growth of tumour cells with nuclear atypia and readily identified nucleoli.
Myoepithelial carcinoma of soft tissue. Some tumours may show a densely sclerotic stroma with nested growth of epithelioid cells with frequently clear cytoplasm.
Myoepithelial carcinoma of soft tissue. Most cases show positivity for keratin (pankeratin shown).
Myoepithelial carcinoma of soft tissue. S100 is frequently positive.

Q: In the spectrum of the tumors Myofibroma and Myopericytoma, myopericytoma is characteristically formed by bland round to ovoid cells arranged in a [...] pattern.
Myopericytoma. Myopericytoma is characterized by a proliferation of round to ovoid cells arranged in a concentric perivascular pattern.
Myopericytoma. The neoplastic cells of myopericytoma express SMA.
A: concentric perivascular
Back Extra: Myofibroma and Myopericytoma
- Clinical: Myofibroma and myopericytoma typically present as painless, reddish nodules in children and adolescents, with myofibroma being the most frequent fibroblastic tumour in this age group.
- Micro: Myofibroma exhibits a biphasic pattern with spindle cells and more primitive round cells, while myopericytoma shows a proliferation of bland cells arranged in a concentric perivascular pattern.
- Ancillary: SRF rearrangements and PDGFRB mutations are key findings in myofibroma, while PDGFRB mutations and NOTCH gene rearrangements are important in myopericytoma.
Reference Gallery:
Myopericytoma. Myopericytoma is characterized by a proliferation of round to ovoid cells arranged in a concentric perivascular pattern.
Myopericytoma. The neoplastic cells of myopericytoma express SMA.
Myofibroma. A 17-year-old girl presented with a myofibroma in the soft tissue around the parotid gland.
Myofibroma. Biphasic cell population: spindle cells arranged in fascicles, and more primitive round cells associated with thin-walled vessels.
Myofibroma. Infarction areas can be observed (left).
Myofibroma. Intersecting fascicles of spindle cells and elongated thin-walled vessels.
Myofibroma. Cellular myofibroma with calcifications, harbouring an SRF::RELA fusion.
Myofibroma. SRF rearrangement in a cellular myofibroma (FISH analysis with SRF probe).
Myofibroma. Haemangiopericytoma-like pattern and round cells bulging into the vascular lumen.
Myofibroma. A PDGFRB mutation is often identified in myofibroma. This case harbours PDGFRB p.N666K.

Q: When evaluating the tumors Myofibroma and Myopericytoma, myofibroma classically exhibits a [...] histologic pattern, consisting of fascicular spindle cells and primitive round cells associated with thin-walled vessels.
Myofibroma. Biphasic cell population: spindle cells arranged in fascicles, and more primitive round cells associated with thin-walled vessels.
Myofibroma. Intersecting fascicles of spindle cells and elongated thin-walled vessels.
A: biphasic
Back Extra: Myofibroma and Myopericytoma
- Clinical: Myofibroma and myopericytoma typically present as painless, reddish nodules in children and adolescents, with myofibroma being the most frequent fibroblastic tumour in this age group.
- Micro: Myofibroma exhibits a biphasic pattern with spindle cells and more primitive round cells, while myopericytoma shows a proliferation of bland cells arranged in a concentric perivascular pattern.
- Ancillary: SRF rearrangements and PDGFRB mutations are key findings in myofibroma, while PDGFRB mutations and NOTCH gene rearrangements are important in myopericytoma.
Reference Gallery:
Myopericytoma. Myopericytoma is characterized by a proliferation of round to ovoid cells arranged in a concentric perivascular pattern.
Myopericytoma. The neoplastic cells of myopericytoma express SMA.
Myofibroma. A 17-year-old girl presented with a myofibroma in the soft tissue around the parotid gland.
Myofibroma. Biphasic cell population: spindle cells arranged in fascicles, and more primitive round cells associated with thin-walled vessels.
Myofibroma. Infarction areas can be observed (left).
Myofibroma. Intersecting fascicles of spindle cells and elongated thin-walled vessels.
Myofibroma. Cellular myofibroma with calcifications, harbouring an SRF::RELA fusion.
Myofibroma. SRF rearrangement in a cellular myofibroma (FISH analysis with SRF probe).
Myofibroma. Haemangiopericytoma-like pattern and round cells bulging into the vascular lumen.
Myofibroma. A PDGFRB mutation is often identified in myofibroma. This case harbours PDGFRB p.N666K.

Q: In the molecular workup of Myofibroma and Myopericytoma, myofibromas frequently harbor PDGFRB mutations and gene rearrangements involving [...].
Myofibroma. SRF rearrangement in a cellular myofibroma (FISH analysis with SRF probe).
Myofibroma. A PDGFRB mutation is often identified in myofibroma. This case harbours PDGFRB p.N666K.
A: SRF
Back Extra: Myofibroma and Myopericytoma
- Clinical: Myofibroma and myopericytoma typically present as painless, reddish nodules in children and adolescents, with myofibroma being the most frequent fibroblastic tumour in this age group.
- Micro: Myofibroma exhibits a biphasic pattern with spindle cells and more primitive round cells, while myopericytoma shows a proliferation of bland cells arranged in a concentric perivascular pattern.
- Ancillary: SRF rearrangements and PDGFRB mutations are key findings in myofibroma, while PDGFRB mutations and NOTCH gene rearrangements are important in myopericytoma.
Reference Gallery:
Myopericytoma. Myopericytoma is characterized by a proliferation of round to ovoid cells arranged in a concentric perivascular pattern.
Myopericytoma. The neoplastic cells of myopericytoma express SMA.
Myofibroma. A 17-year-old girl presented with a myofibroma in the soft tissue around the parotid gland.
Myofibroma. Biphasic cell population: spindle cells arranged in fascicles, and more primitive round cells associated with thin-walled vessels.
Myofibroma. Infarction areas can be observed (left).
Myofibroma. Intersecting fascicles of spindle cells and elongated thin-walled vessels.
Myofibroma. Cellular myofibroma with calcifications, harbouring an SRF::RELA fusion.
Myofibroma. SRF rearrangement in a cellular myofibroma (FISH analysis with SRF probe).
Myofibroma. Haemangiopericytoma-like pattern and round cells bulging into the vascular lumen.
Myofibroma. A PDGFRB mutation is often identified in myofibroma. This case harbours PDGFRB p.N666K.

Q: Microscopically, a Neurofibroma is characterized by bland spindle cells with thin, wavy nuclei embedded in a myxoid stroma containing dense collagen bundles often described as having a [...] appearance.
Diffuse neurofibroma. Lesion from the soft tissues of the elbow of an 11-year-old. The lesion shows the wavy appearance of proliferating Schwann cells and associated non-neoplastic elements.
Diffuse neurofibroma. Higher magnification of the example shown in Fig. 23699. Note the lack of pleomorphism or atypia, the rare mitotic figure of normal morphology, and the characteristic elongated shape of the nuclei of neoplastic Schwann cells.
A: "shredded carrot"
Back Extra: Neurofibroma
- Clinical: Neurofibromas are the most common peripheral nerve sheath tumours, often asymptomatic and usually present as a mass.
- Micro: Neurofibromas are characterized by cytologically bland spindle cells with thin, wavy nuclei in a myxoid stroma, often described as 'shredded carrots'.
- Ancillary: S100 and SOX10 immunohistochemistry are strongly positive in neoplastic Schwann cell nuclei, highlighting the neural crest origin.
Reference Gallery:
Diffuse neurofibroma. Low-power view of a diffuse neurofibroma from the elbow of an 11-year-old. The lesion is characteristically bland and homogeneous.
Diffuse neurofibroma. Lesion from the soft tissues of the elbow of an 11-year-old. The lesion shows the wavy appearance of proliferating Schwann cells and associated non-neoplastic elements.
Diffuse neurofibroma. Higher magnification of the example shown in Fig. 23699. Note the lack of pleomorphism or atypia, the rare mitotic figure of normal morphology, and the characteristic elongated shape of the nuclei of neoplastic Schwann cells.
Diffuse neurofibroma. S100 immunohistochemistry showing a strong and diffuse pattern of nuclear and cytoplasmic staining.
Diffuse neurofibroma. SOX10 immunohistochemistry is strongly positive in the neoplastic Schwann cell nuclei, consistent with their neural crest origin.
Plexiform neurofibroma. A large mesenteric mass from an 18-year-old patient with neurofibromatosis type 1.
Plexiform neurofibroma. Higher-magnification view of Fig. 23703. Note the separate nodules of loose components with prominent myxoid change.
Plexiform neurofibroma. The neoplastic Schwann cells show no atypia or mitotic activity. There is prominent myxoid change.
Plexiform neurofibroma. S100 immunohistochemistry highlights the plexiform pattern in this neurofibroma from the left forearm of a 16-year-old child.
Neurofibroma. T2-weighted coronal MRI shows a well-defined mass infiltrating the entire sciatic nerve trunk, extending from the right buttock down to the right thigh. The tumour is of high T2 signal intensity relative to surrounding muscle. There is no perilesional oedema-like zone. The tumour is static in size.
Neurofibroma. Contrast-enhanced T1-weighted coronal MRI shows that the infiltrative tumour along the right sciatic nerve is homogeneously enhanced, with no intratumoural cystic lesion or evidence of peripheral enhancement. The latter is indicative of malignant change.

Q: To highlight the neural crest origin of the neoplastic Schwann cells in a Neurofibroma, immunohistochemistry is characteristically strongly positive for S100 and [...].
Diffuse neurofibroma. S100 immunohistochemistry showing a strong and diffuse pattern of nuclear and cytoplasmic staining.
Diffuse neurofibroma. SOX10 immunohistochemistry is strongly positive in the neoplastic Schwann cell nuclei, consistent with their neural crest origin.
A: SOX10
Back Extra: Neurofibroma
- Clinical: Neurofibromas are the most common peripheral nerve sheath tumours, often asymptomatic and usually present as a mass.
- Micro: Neurofibromas are characterized by cytologically bland spindle cells with thin, wavy nuclei in a myxoid stroma, often described as 'shredded carrots'.
- Ancillary: S100 and SOX10 immunohistochemistry are strongly positive in neoplastic Schwann cell nuclei, highlighting the neural crest origin.
Reference Gallery:
Diffuse neurofibroma. Low-power view of a diffuse neurofibroma from the elbow of an 11-year-old. The lesion is characteristically bland and homogeneous.
Diffuse neurofibroma. Lesion from the soft tissues of the elbow of an 11-year-old. The lesion shows the wavy appearance of proliferating Schwann cells and associated non-neoplastic elements.
Diffuse neurofibroma. Higher magnification of the example shown in Fig. 23699. Note the lack of pleomorphism or atypia, the rare mitotic figure of normal morphology, and the characteristic elongated shape of the nuclei of neoplastic Schwann cells.
Diffuse neurofibroma. S100 immunohistochemistry showing a strong and diffuse pattern of nuclear and cytoplasmic staining.
Diffuse neurofibroma. SOX10 immunohistochemistry is strongly positive in the neoplastic Schwann cell nuclei, consistent with their neural crest origin.
Plexiform neurofibroma. A large mesenteric mass from an 18-year-old patient with neurofibromatosis type 1.
Plexiform neurofibroma. Higher-magnification view of Fig. 23703. Note the separate nodules of loose components with prominent myxoid change.
Plexiform neurofibroma. The neoplastic Schwann cells show no atypia or mitotic activity. There is prominent myxoid change.
Plexiform neurofibroma. S100 immunohistochemistry highlights the plexiform pattern in this neurofibroma from the left forearm of a 16-year-old child.
Neurofibroma. T2-weighted coronal MRI shows a well-defined mass infiltrating the entire sciatic nerve trunk, extending from the right buttock down to the right thigh. The tumour is of high T2 signal intensity relative to surrounding muscle. There is no perilesional oedema-like zone. The tumour is static in size.
Neurofibroma. Contrast-enhanced T1-weighted coronal MRI shows that the infiltrative tumour along the right sciatic nerve is homogeneously enhanced, with no intratumoural cystic lesion or evidence of peripheral enhancement. The latter is indicative of malignant change.

Q: The plexiform variant of Neurofibroma, which classically presents as multiple expanded nerve fascicles grossly and separate myxoid nodules microscopically, is virtually pathognomonic for the syndrome [...].
Plexiform neurofibroma. A large mesenteric mass from an 18-year-old patient with neurofibromatosis type 1.
Plexiform neurofibroma. Higher-magnification view of Fig. 23703. Note the separate nodules of loose components with prominent myxoid change.
A: neurofibromatosis type 1
Back Extra: Neurofibroma
- Clinical: Neurofibromas are the most common peripheral nerve sheath tumours, often asymptomatic and usually present as a mass.
- Micro: Neurofibromas are characterized by cytologically bland spindle cells with thin, wavy nuclei in a myxoid stroma, often described as 'shredded carrots'.
- Ancillary: S100 and SOX10 immunohistochemistry are strongly positive in neoplastic Schwann cell nuclei, highlighting the neural crest origin.
Reference Gallery:
Diffuse neurofibroma. Low-power view of a diffuse neurofibroma from the elbow of an 11-year-old. The lesion is characteristically bland and homogeneous.
Diffuse neurofibroma. Lesion from the soft tissues of the elbow of an 11-year-old. The lesion shows the wavy appearance of proliferating Schwann cells and associated non-neoplastic elements.
Diffuse neurofibroma. Higher magnification of the example shown in Fig. 23699. Note the lack of pleomorphism or atypia, the rare mitotic figure of normal morphology, and the characteristic elongated shape of the nuclei of neoplastic Schwann cells.
Diffuse neurofibroma. S100 immunohistochemistry showing a strong and diffuse pattern of nuclear and cytoplasmic staining.
Diffuse neurofibroma. SOX10 immunohistochemistry is strongly positive in the neoplastic Schwann cell nuclei, consistent with their neural crest origin.
Plexiform neurofibroma. A large mesenteric mass from an 18-year-old patient with neurofibromatosis type 1.
Plexiform neurofibroma. Higher-magnification view of Fig. 23703. Note the separate nodules of loose components with prominent myxoid change.
Plexiform neurofibroma. The neoplastic Schwann cells show no atypia or mitotic activity. There is prominent myxoid change.
Plexiform neurofibroma. S100 immunohistochemistry highlights the plexiform pattern in this neurofibroma from the left forearm of a 16-year-old child.
Neurofibroma. T2-weighted coronal MRI shows a well-defined mass infiltrating the entire sciatic nerve trunk, extending from the right buttock down to the right thigh. The tumour is of high T2 signal intensity relative to surrounding muscle. There is no perilesional oedema-like zone. The tumour is static in size.
Neurofibroma. Contrast-enhanced T1-weighted coronal MRI shows that the infiltrative tumour along the right sciatic nerve is homogeneously enhanced, with no intratumoural cystic lesion or evidence of peripheral enhancement. The latter is indicative of malignant change.

Q: Histologically, Nodular fasciitis is classically described as having a [...] appearance, featuring loose intersecting fascicles of plump myofibroblasts, extravasated erythrocytes, and microcysts.
Nodular fasciitis. Characteristic tissue culture–like appearance with extravasated erythrocytes, and a microcyst (middle right).
A: tissue culture-like
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis typically presents as a rapidly growing, self-limiting lesion, commonly in the upper extremities and head and neck regions.
- Micro: Characterized by loose intersecting fascicles of plump, bland myofibroblasts with a myxoid stroma, microcysts, and osteoclast-like giant cells.
- Ancillary: Immunohistochemistry shows positivity for SMA and MSA, and molecular studies often reveal USP6 gene rearrangements.
Reference Gallery:
Nodular fasciitis. Characteristic tissue culture–like appearance with extravasated erythrocytes, and a microcyst (middle right).
Nodular fasciitis. Osteoclast-like giant cells are frequently encountered.
Myositis ossificans. Axial CT of a 3-year-old girl with a large round mass in the deep soft tissues of the pelvis, with irregular circular radiodensity with central radiolucency.
Myositis ossificans. The peripheral portion of the lesion is delineated by well-formed mineralized trabeculae of bone. Centrally the bone merges with unmineralized, broad, poorly formed interconnecting trabeculae that are rimmed by osteoblasts. The intertrabecular space is filled with spindle cells enmeshed in a myxoid stroma.
Myositis ossificans. Primitive-appearing trabeculae of bone associated with osteoblasts and fascicles of spindle cells in a myxoid stroma.
Myositis ossificans. The central portion is composed of fascicles of spindle cells that have elongate nuclei, fine chromatin, conspicuous nucleoli, and eosinophilic cytoplasm. Typical mitoses are present and the stroma is myxoid.
Fibro-osseous tumour. This consists of fascicles of spindles enmeshed in a myxoid stroma alternating with irregular linear trabeculae of woven bone.
Fibro-osseous tumour. The woven bone is associated with plump osteoblasts and the spindle cells are oriented in intersecting fascicles.
Proliferative myositis. Skeletal muscle cells are splayed apart by the proliferating cells.
Proliferative myositis. The lesional cells are large and polyhedral, with vesicular nuclei, prominent nucleoli, and abundant eccentric amphophilic cytoplasm. Note the myxoid stroma and extravasated red blood cells.
Cranial fasciitis. CT shows a mass in the soft tissue in the occipital region.

Q: In addition to a myxoid stroma and plump myofibroblasts, the microscopic appearance of Nodular fasciitis frequently features scattered [...].
Nodular fasciitis. Osteoclast-like giant cells are frequently encountered.
A: osteoclast-like giant cells
Back Extra: Nodular Fasciitis
- Clinical: Nodular fasciitis typically presents as a rapidly growing, self-limiting lesion, commonly in the upper extremities and head and neck regions.
- Micro: Characterized by loose intersecting fascicles of plump, bland myofibroblasts with a myxoid stroma, microcysts, and osteoclast-like giant cells.
- Ancillary: Immunohistochemistry shows positivity for SMA and MSA, and molecular studies often reveal USP6 gene rearrangements.
Reference Gallery:
Nodular fasciitis. Characteristic tissue culture–like appearance with extravasated erythrocytes, and a microcyst (middle right).
Nodular fasciitis. Osteoclast-like giant cells are frequently encountered.
Myositis ossificans. Axial CT of a 3-year-old girl with a large round mass in the deep soft tissues of the pelvis, with irregular circular radiodensity with central radiolucency.
Myositis ossificans. The peripheral portion of the lesion is delineated by well-formed mineralized trabeculae of bone. Centrally the bone merges with unmineralized, broad, poorly formed interconnecting trabeculae that are rimmed by osteoblasts. The intertrabecular space is filled with spindle cells enmeshed in a myxoid stroma.
Myositis ossificans. Primitive-appearing trabeculae of bone associated with osteoblasts and fascicles of spindle cells in a myxoid stroma.
Myositis ossificans. The central portion is composed of fascicles of spindle cells that have elongate nuclei, fine chromatin, conspicuous nucleoli, and eosinophilic cytoplasm. Typical mitoses are present and the stroma is myxoid.
Fibro-osseous tumour. This consists of fascicles of spindles enmeshed in a myxoid stroma alternating with irregular linear trabeculae of woven bone.
Fibro-osseous tumour. The woven bone is associated with plump osteoblasts and the spindle cells are oriented in intersecting fascicles.
Proliferative myositis. Skeletal muscle cells are splayed apart by the proliferating cells.
Proliferative myositis. The lesional cells are large and polyhedral, with vesicular nuclei, prominent nucleoli, and abundant eccentric amphophilic cytoplasm. Note the myxoid stroma and extravasated red blood cells.
Cranial fasciitis. CT shows a mass in the soft tissue in the occipital region.

Q: In Papillary Intralymphatic Angioendothelioma and Retiform Haemangioendothelioma, the papillary intralymphatic variant is histologically characterized by dilated spaces with glomeruloid proliferations and a distinct [...] hobnail endothelium.
Papillary intralymphatic angioendothelioma. Typically there are lymphatic features of intraluminal proteinaceous fluid, stromal and intraluminal lymphocytes, and undulating endothelium with a matchstick-like hobnail endothelium.
Papillary intralymphatic angioendothelioma. Intraluminal tufting and glomeruloid proliferation.
A: matchstick-like
Back Extra: Papillary Intralymphatic Angioendothelioma and Retiform Haemangioendothelioma
- Clinical: Papillary intralymphatic angioendothelioma (PILA) and retiform haemangioendothelioma (RHE) manifest as slow-growing, cutaneous, pink-violaceous nodules or plaques, often in children and young adults.
- Micro: PILA is characterized by columnar, matchstick-like endothelial cells with intraluminal tufting and glomeruloid endothelial proliferations in dilated lymphatic spaces. RHE shows a densely sclerotic stroma and an arborizing pattern resembling rete testis.
- Ancillary: Both PILA and RHE stain for lymphatic markers (PILA: podoplanin [D2-40], PROX1, VEGFR3; RHE: PROX1, occasionally D2-40) and endothelial markers (CD31, CD34, ERG).
Reference Gallery:
Papillary intralymphatic angioendothelioma. Typically there are lymphatic features of intraluminal proteinaceous fluid, stromal and intraluminal lymphocytes, and undulating endothelium with a matchstick-like hobnail endothelium.
Papillary intralymphatic angioendothelioma. Intraluminal tufting and glomeruloid proliferation.
Papillary intralymphatic angioendothelioma. VEGFR3 reactivity in cells lining vascular spaces.
Retiform haemangioendothelioma. Sclerotic stroma that imparts a rete testis–like appearance.

Q: In Papillary Intralymphatic Angioendothelioma and Retiform Haemangioendothelioma, the retiform variant features an arborizing vascular pattern within a densely sclerotic stroma that characteristically resembles the [...].
Retiform haemangioendothelioma. Sclerotic stroma that imparts a rete testis–like appearance.
A: rete testis
Back Extra: Papillary Intralymphatic Angioendothelioma and Retiform Haemangioendothelioma
- Clinical: Papillary intralymphatic angioendothelioma (PILA) and retiform haemangioendothelioma (RHE) manifest as slow-growing, cutaneous, pink-violaceous nodules or plaques, often in children and young adults.
- Micro: PILA is characterized by columnar, matchstick-like endothelial cells with intraluminal tufting and glomeruloid endothelial proliferations in dilated lymphatic spaces. RHE shows a densely sclerotic stroma and an arborizing pattern resembling rete testis.
- Ancillary: Both PILA and RHE stain for lymphatic markers (PILA: podoplanin [D2-40], PROX1, VEGFR3; RHE: PROX1, occasionally D2-40) and endothelial markers (CD31, CD34, ERG).
Reference Gallery:
Papillary intralymphatic angioendothelioma. Typically there are lymphatic features of intraluminal proteinaceous fluid, stromal and intraluminal lymphocytes, and undulating endothelium with a matchstick-like hobnail endothelium.
Papillary intralymphatic angioendothelioma. Intraluminal tufting and glomeruloid proliferation.
Papillary intralymphatic angioendothelioma. VEGFR3 reactivity in cells lining vascular spaces.
Retiform haemangioendothelioma. Sclerotic stroma that imparts a rete testis–like appearance.

Q: Immunohistochemistry in Papillary Intralymphatic Angioendothelioma and Retiform Haemangioendothelioma highlights endothelial markers as well as lymphatic markers like PROX1, podoplanin (D2-40), and [...].
Papillary intralymphatic angioendothelioma. VEGFR3 reactivity in cells lining vascular spaces.
A: VEGFR3
Back Extra: Papillary Intralymphatic Angioendothelioma and Retiform Haemangioendothelioma
- Clinical: Papillary intralymphatic angioendothelioma (PILA) and retiform haemangioendothelioma (RHE) manifest as slow-growing, cutaneous, pink-violaceous nodules or plaques, often in children and young adults.
- Micro: PILA is characterized by columnar, matchstick-like endothelial cells with intraluminal tufting and glomeruloid endothelial proliferations in dilated lymphatic spaces. RHE shows a densely sclerotic stroma and an arborizing pattern resembling rete testis.
- Ancillary: Both PILA and RHE stain for lymphatic markers (PILA: podoplanin [D2-40], PROX1, VEGFR3; RHE: PROX1, occasionally D2-40) and endothelial markers (CD31, CD34, ERG).
Reference Gallery:
Papillary intralymphatic angioendothelioma. Typically there are lymphatic features of intraluminal proteinaceous fluid, stromal and intraluminal lymphocytes, and undulating endothelium with a matchstick-like hobnail endothelium.
Papillary intralymphatic angioendothelioma. Intraluminal tufting and glomeruloid proliferation.
Papillary intralymphatic angioendothelioma. VEGFR3 reactivity in cells lining vascular spaces.
Retiform haemangioendothelioma. Sclerotic stroma that imparts a rete testis–like appearance.

Q: Histologically, a [...] characteristically consists of epithelioid or spindle cells with clear to granular cytoplasm arranged in a perivascular location around a rich capillary network.
PEComa. An example of a PEComa made up of spindle cells with clear, elongated cytoplasm arranged in fascicles around a capillary network.
PEComa. This tumour consists of epithelioid cells with predominant granular eosinophilic cytoplasm, round nuclei, and small nucleoli, arranged in nests around a capillary network.
A: PEComa
Back Extra: PEComa
- Clinical: PEComas can present at various sites, including the genital areas, falciform ligament/ligamentum teres, kidney, and intestinal wall. Intra-abdominal tumours may cause acute abdominal symptoms.
- Micro: Histologically, PEComas consist of epithelioid cells with a clear to granular cytoplasm, round to oval nuclei, and a typical perivascular location. Spindle cells with clear, elongated cytoplasm may also be present.
- Ancillary: Loss of heterozygosity involving the TSC2 or TSC1 locus is found in PEComas. Variable immunoreactivity for HMB45, cathepsin K, and muscle markers (actin, calponin, desmin).
Reference Gallery:
PEComa. An example of a PEComa made up of spindle cells with clear, elongated cytoplasm arranged in fascicles around a capillary network.
PEComa. This tumour consists of epithelioid cells with predominant granular eosinophilic cytoplasm, round nuclei, and small nucleoli, arranged in nests around a capillary network.
PEComa. Patchy HMB45 immunoreactivity (A) and diffuse strong expression of cathepsin K (B) in the epithelioid cells of a PEComa.
PEComa. An example of a PEComa made up of epithelioid cells with melanin pigment.
PEComa. Plain axial CT shows a well-circumscribed mass at the right suprarenal region. The mass is isodense to the paraspinal muscle, with internal calcifications.
PEComa. Contrast-enhanced axial CT shows heterogeneous enhancement of the mass, with internal areas of necrosis. The mass compresses onto the adjacent structures including the inferior vena cava, pancreatic head, and liver. Note there are multiple liver metastases.

Q: By immunohistochemistry, a PEComa classically co-expresses melanocytic markers (e.g., HMB45), smooth muscle markers, and typically shows strong, diffuse positivity for [...].
PEComa. Patchy HMB45 immunoreactivity (A) and diffuse strong expression of cathepsin K (B) in the epithelioid cells of a PEComa.
A: cathepsin K
Back Extra: PEComa
- Clinical: PEComas can present at various sites, including the genital areas, falciform ligament/ligamentum teres, kidney, and intestinal wall. Intra-abdominal tumours may cause acute abdominal symptoms.
- Micro: Histologically, PEComas consist of epithelioid cells with a clear to granular cytoplasm, round to oval nuclei, and a typical perivascular location. Spindle cells with clear, elongated cytoplasm may also be present.
- Ancillary: Loss of heterozygosity involving the TSC2 or TSC1 locus is found in PEComas. Variable immunoreactivity for HMB45, cathepsin K, and muscle markers (actin, calponin, desmin).
Reference Gallery:
PEComa. An example of a PEComa made up of spindle cells with clear, elongated cytoplasm arranged in fascicles around a capillary network.
PEComa. This tumour consists of epithelioid cells with predominant granular eosinophilic cytoplasm, round nuclei, and small nucleoli, arranged in nests around a capillary network.
PEComa. Patchy HMB45 immunoreactivity (A) and diffuse strong expression of cathepsin K (B) in the epithelioid cells of a PEComa.
PEComa. An example of a PEComa made up of epithelioid cells with melanin pigment.
PEComa. Plain axial CT shows a well-circumscribed mass at the right suprarenal region. The mass is isodense to the paraspinal muscle, with internal calcifications.
PEComa. Contrast-enhanced axial CT shows heterogeneous enhancement of the mass, with internal areas of necrosis. The mass compresses onto the adjacent structures including the inferior vena cava, pancreatic head, and liver. Note there are multiple liver metastases.

Q: Reflecting their expression of melanocytic markers, the epithelioid cells of a PEComa may occasionally contain visible intracellular [...] pigment on routine H&E staining.
PEComa. An example of a PEComa made up of epithelioid cells with melanin pigment.
A: melanin
Back Extra: PEComa
- Clinical: PEComas can present at various sites, including the genital areas, falciform ligament/ligamentum teres, kidney, and intestinal wall. Intra-abdominal tumours may cause acute abdominal symptoms.
- Micro: Histologically, PEComas consist of epithelioid cells with a clear to granular cytoplasm, round to oval nuclei, and a typical perivascular location. Spindle cells with clear, elongated cytoplasm may also be present.
- Ancillary: Loss of heterozygosity involving the TSC2 or TSC1 locus is found in PEComas. Variable immunoreactivity for HMB45, cathepsin K, and muscle markers (actin, calponin, desmin).
Reference Gallery:
PEComa. An example of a PEComa made up of spindle cells with clear, elongated cytoplasm arranged in fascicles around a capillary network.
PEComa. This tumour consists of epithelioid cells with predominant granular eosinophilic cytoplasm, round nuclei, and small nucleoli, arranged in nests around a capillary network.
PEComa. Patchy HMB45 immunoreactivity (A) and diffuse strong expression of cathepsin K (B) in the epithelioid cells of a PEComa.
PEComa. An example of a PEComa made up of epithelioid cells with melanin pigment.
PEComa. Plain axial CT shows a well-circumscribed mass at the right suprarenal region. The mass is isodense to the paraspinal muscle, with internal calcifications.
PEComa. Contrast-enhanced axial CT shows heterogeneous enhancement of the mass, with internal areas of necrosis. The mass compresses onto the adjacent structures including the inferior vena cava, pancreatic head, and liver. Note there are multiple liver metastases.

Q: Histologically, Paediatric NTRK-rearranged spindle cell neoplasm features haphazardly arranged monomorphic spindle cells that frequently exhibit stromal and [...].
Paediatric NTRK-rearranged spindle cell neoplasm. Infantile fibrosarcoma–like tumour (NTRK3) with perivascular hyalinosis.
Paediatric NTRK-rearranged spindle cell neoplasm. Monomorphic ovoid to spindle cells infiltrating through subcutaneous adipose tissue.
A: perivascular hyalinization
Back Extra: Paediatric NTRK-rearranged spindle cell neoplasm
- Clinical: Patients most frequently present with a palpable mass, most commonly in the superficial soft tissues of the extremities, with a wide age distribution (median: 19 years).
- Micro: Characterized by haphazardly arranged primitive/monomorphic spindle cells, with possible stromal and perivascular hyalinization.
- Ancillary: Essential diagnostic criteria include fusions or activating alterations of receptor tyrosine kinase pathway genes (e.g., NTRK1, NTRK2, NTRK3, RET, RAF1, BRAF).
Reference Gallery:
Paediatric NTRK-rearranged spindle cell neoplasm. Low-power view showing diffuse, band-like growth within the dermis involving subcutaneous adipose tissue.
Paediatric NTRK-rearranged spindle cell neoplasm. Diffuse growth with focal fat entrapment and mixed chronic inflammation.
Paediatric NTRK-rearranged spindle cell neoplasm. CD34 expression.
Paediatric NTRK-rearranged spindle cell neoplasm. S100 expression.
Paediatric NTRK-rearranged spindle cell neoplasm. Pan-TRK positivity.
Paediatric NTRK-rearranged spindle cell neoplasm. Infantile fibrosarcoma–like tumour (NTRK3) with perivascular hyalinosis.
Paediatric NTRK-rearranged spindle cell neoplasm. Monomorphic ovoid to spindle cells infiltrating through subcutaneous adipose tissue.

Q: Along with frequent CD34 and S100 co-expression, Paediatric NTRK-rearranged spindle cell neoplasm is driven by kinase alterations that can often be detected immunohistochemically by diffuse [...] positivity.
Paediatric NTRK-rearranged spindle cell neoplasm. CD34 expression.
Paediatric NTRK-rearranged spindle cell neoplasm. S100 expression.
Paediatric NTRK-rearranged spindle cell neoplasm. Pan-TRK positivity.
A: Pan-TRK
Back Extra: Paediatric NTRK-rearranged spindle cell neoplasm
- Clinical: Patients most frequently present with a palpable mass, most commonly in the superficial soft tissues of the extremities, with a wide age distribution (median: 19 years).
- Micro: Characterized by haphazardly arranged primitive/monomorphic spindle cells, with possible stromal and perivascular hyalinization.
- Ancillary: Essential diagnostic criteria include fusions or activating alterations of receptor tyrosine kinase pathway genes (e.g., NTRK1, NTRK2, NTRK3, RET, RAF1, BRAF).
Reference Gallery:
Paediatric NTRK-rearranged spindle cell neoplasm. Low-power view showing diffuse, band-like growth within the dermis involving subcutaneous adipose tissue.
Paediatric NTRK-rearranged spindle cell neoplasm. Diffuse growth with focal fat entrapment and mixed chronic inflammation.
Paediatric NTRK-rearranged spindle cell neoplasm. CD34 expression.
Paediatric NTRK-rearranged spindle cell neoplasm. S100 expression.
Paediatric NTRK-rearranged spindle cell neoplasm. Pan-TRK positivity.
Paediatric NTRK-rearranged spindle cell neoplasm. Infantile fibrosarcoma–like tumour (NTRK3) with perivascular hyalinosis.
Paediatric NTRK-rearranged spindle cell neoplasm. Monomorphic ovoid to spindle cells infiltrating through subcutaneous adipose tissue.

Q: At low power, Paediatric NTRK-rearranged spindle cell neoplasm often involves the dermis and subcutis, demonstrating a diffuse growth pattern with focal [...].
Paediatric NTRK-rearranged spindle cell neoplasm. Low-power view showing diffuse, band-like growth within the dermis involving subcutaneous adipose tissue.
Paediatric NTRK-rearranged spindle cell neoplasm. Diffuse growth with focal fat entrapment and mixed chronic inflammation.
A: fat entrapment
Back Extra: Paediatric NTRK-rearranged spindle cell neoplasm
- Clinical: Patients most frequently present with a palpable mass, most commonly in the superficial soft tissues of the extremities, with a wide age distribution (median: 19 years).
- Micro: Characterized by haphazardly arranged primitive/monomorphic spindle cells, with possible stromal and perivascular hyalinization.
- Ancillary: Essential diagnostic criteria include fusions or activating alterations of receptor tyrosine kinase pathway genes (e.g., NTRK1, NTRK2, NTRK3, RET, RAF1, BRAF).
Reference Gallery:
Paediatric NTRK-rearranged spindle cell neoplasm. Low-power view showing diffuse, band-like growth within the dermis involving subcutaneous adipose tissue.
Paediatric NTRK-rearranged spindle cell neoplasm. Diffuse growth with focal fat entrapment and mixed chronic inflammation.
Paediatric NTRK-rearranged spindle cell neoplasm. CD34 expression.
Paediatric NTRK-rearranged spindle cell neoplasm. S100 expression.
Paediatric NTRK-rearranged spindle cell neoplasm. Pan-TRK positivity.
Paediatric NTRK-rearranged spindle cell neoplasm. Infantile fibrosarcoma–like tumour (NTRK3) with perivascular hyalinosis.
Paediatric NTRK-rearranged spindle cell neoplasm. Monomorphic ovoid to spindle cells infiltrating through subcutaneous adipose tissue.

Q: Microscopically, soft tissue Perineurioma typically exhibits a storiform or [...] growth pattern consisting of spindle cells with delicate processes within a collagenous stroma.
Perineurioma. The tumour shows spindle cells with delicate processes, arranged in a vaguely whorled pattern.
A: whorled
Back Extra: Perineurioma
- Clinical: Intraneural perineuriomas often present with progressive muscle weakness, while soft tissue perineuriomas present as nonspecific masses.
- Micro: Soft tissue perineurioma exhibits a storiform or whorled growth pattern with spindle cells and a collagenous stroma.
- Ancillary: Tumour cells in perineuriomas are consistently positive for EMA and may also express GLUT1 and CD34.
Reference Gallery:
Perineurioma. The tumour shows spindle cells with delicate processes, arranged in a vaguely whorled pattern.
Perineurioma. Cells are positive for EMA.
Perineurioma. Cells are positive for GLUT1.

Q: Immunohistochemically, the neoplastic spindle cells in Perineurioma are consistently positive for [...], which helps confirm the diagnosis.
Perineurioma. Cells are positive for EMA.
A: EMA
Back Extra: Perineurioma
- Clinical: Intraneural perineuriomas often present with progressive muscle weakness, while soft tissue perineuriomas present as nonspecific masses.
- Micro: Soft tissue perineurioma exhibits a storiform or whorled growth pattern with spindle cells and a collagenous stroma.
- Ancillary: Tumour cells in perineuriomas are consistently positive for EMA and may also express GLUT1 and CD34.
Reference Gallery:
Perineurioma. The tumour shows spindle cells with delicate processes, arranged in a vaguely whorled pattern.
Perineurioma. Cells are positive for EMA.
Perineurioma. Cells are positive for GLUT1.

Q: In addition to EMA and CD34, the tumor cells of Perineurioma frequently show immunohistochemical positivity for [...].
Perineurioma. Cells are positive for GLUT1.
A: GLUT1
Back Extra: Perineurioma
- Clinical: Intraneural perineuriomas often present with progressive muscle weakness, while soft tissue perineuriomas present as nonspecific masses.
- Micro: Soft tissue perineurioma exhibits a storiform or whorled growth pattern with spindle cells and a collagenous stroma.
- Ancillary: Tumour cells in perineuriomas are consistently positive for EMA and may also express GLUT1 and CD34.
Reference Gallery:
Perineurioma. The tumour shows spindle cells with delicate processes, arranged in a vaguely whorled pattern.
Perineurioma. Cells are positive for EMA.
Perineurioma. Cells are positive for GLUT1.

Q: Histologically, Phosphaturic Mesenchymal Tumor is characterized by fibroblast-like spindle cells and prominent dilated blood vessels, often surrounded by a characteristic primitive [...] matrix.
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumour in the jaw of a 9-year-old patient. Lobules of primitive chondroid matrix and rich vascularity are distinctive features.
Phosphaturic mesenchymal tumour. Spindle cells adjacent to a primitive chondroid area. Dilated blood vessels are present.
Phosphaturic mesenchymal tumour. Primitive chondroid material with incipient calcification and spindle cells surrounding dilated blood vessels.
A: chondroid
Back Extra: Phosphaturic Mesenchymal Tumor
- Clinical: Phosphaturic Mesenchymal Tumor (PMT) often presents with longstanding osteomalacia, severe hypophosphataemia, and increased FGF23 levels.
- Micro: PMT is characterized by fibroblast-like spindle mesenchymal cells in a hyalinized matrix, with areas of chondroid and osseous metaplasia, and rich vascularization.
- Ancillary: Immunohistochemical stains for CD56, ERG, FGFR1, SATB2, and SSTR2A are positive in PMT, and FN1::FGFR1 or FN1::FGF1 fusions are confirmatory.
Reference Gallery:
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumour in the jaw of a 9-year-old patient. Lobules of primitive chondroid matrix and rich vascularity are distinctive features.
Phosphaturic mesenchymal tumour. Spindle cells adjacent to a primitive chondroid area. Dilated blood vessels are present.
Phosphaturic mesenchymal tumour. Primitive chondroid material with incipient calcification and spindle cells surrounding dilated blood vessels.

Q: A spindle cell neoplasm characterized histologically by a primitive chondroid matrix and rich vascularity, which clinically causes severe hypophosphatemia and osteomalacia via paraneoplastic FGF23 secretion, is the [...].
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumour in the jaw of a 9-year-old patient. Lobules of primitive chondroid matrix and rich vascularity are distinctive features.
Phosphaturic mesenchymal tumour. Spindle cells adjacent to a primitive chondroid area. Dilated blood vessels are present.
Phosphaturic mesenchymal tumour. Primitive chondroid material with incipient calcification and spindle cells surrounding dilated blood vessels.
A: Phosphaturic Mesenchymal Tumor
Back Extra: Phosphaturic Mesenchymal Tumor
- Clinical: Phosphaturic Mesenchymal Tumor (PMT) often presents with longstanding osteomalacia, severe hypophosphataemia, and increased FGF23 levels.
- Micro: PMT is characterized by fibroblast-like spindle mesenchymal cells in a hyalinized matrix, with areas of chondroid and osseous metaplasia, and rich vascularization.
- Ancillary: Immunohistochemical stains for CD56, ERG, FGFR1, SATB2, and SSTR2A are positive in PMT, and FN1::FGFR1 or FN1::FGF1 fusions are confirmatory.
Reference Gallery:
Phosphaturic mesenchymal tumour. Phosphaturic mesenchymal tumour in the jaw of a 9-year-old patient. Lobules of primitive chondroid matrix and rich vascularity are distinctive features.
Phosphaturic mesenchymal tumour. Spindle cells adjacent to a primitive chondroid area. Dilated blood vessels are present.
Phosphaturic mesenchymal tumour. Primitive chondroid material with incipient calcification and spindle cells surrounding dilated blood vessels.

Q: Microscopically, the characteristic architectural pattern of Plantar/Palmar Fibromatoses is a [...] arrangement of proliferating spindle cells.
Plantar fibromatosis. Low-power view reveals a nodular arrangement of spindle cells.
A: nodular
Back Extra: Plantar/Palmar Fibromatoses
- Clinical: Palmar fibromatosis often presents as contractures, swelling, or a painless nodular mass. Plantar fibromatosis usually presents as asymptomatic nodules.
- Micro: Microscopically, these tumours are composed of a nodular arrangement of spindle cells, with mitotic activity but no atypical mitoses.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of palmar/plantar fibromatoses.
Reference Gallery:
Plantar fibromatosis. Low-power view reveals a nodular arrangement of spindle cells.

Q: In Plantar/Palmar Fibromatoses, the proliferating spindle cells may exhibit mitotic activity, but they characteristically lack [...].
Plantar fibromatosis. Low-power view reveals a nodular arrangement of spindle cells.
A: atypical mitoses
Back Extra: Plantar/Palmar Fibromatoses
- Clinical: Palmar fibromatosis often presents as contractures, swelling, or a painless nodular mass. Plantar fibromatosis usually presents as asymptomatic nodules.
- Micro: Microscopically, these tumours are composed of a nodular arrangement of spindle cells, with mitotic activity but no atypical mitoses.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of palmar/plantar fibromatoses.
Reference Gallery:
Plantar fibromatosis. Low-power view reveals a nodular arrangement of spindle cells.

Q: Microscopically, the distinct nodules in Plexiform Fibrohistiocytic Tumor are composed of bland histiocytoid cells admixed with multinucleated [...] giant cells.
Plexiform fibrohistiocytic tumour. The nodules are composed of bland and uniform histiocytoid cells with admixed osteoclast-like, multinucleated giant cells.
A: osteoclast-like
Back Extra: Plexiform Fibrohistiocytic Tumour
- Clinical: Plexiform Fibrohistiocytic Tumour (PFHT) is a rare dermal and subcutaneous neoplasm, commonly presenting as a slow-growing tumour or plaque, predominantly in children and young adults, with a slight female predominance.
- Micro: PFHT is characterized by a plexiform or multinodular arrangement of nodules of histiocytoid cells with admixed multinucleated osteoclastic-like giant cells, connected by fascicles of spindled fibroblastic/myofibroblastic cells.
- Ancillary: Diagnostic molecular pathology is not clinically relevant for PFHT.
Reference Gallery:
Plexiform fibrohistiocytic tumour. The nodules are composed of bland and uniform histiocytoid cells with admixed osteoclast-like, multinucleated giant cells.
Plexiform fibrohistiocytic tumour. Bland spindle cell / fibroblastic component.
Plexiform fibrohistiocytic tumour. This example is composed of nodules of histiocytoid cells and intervening fascicles of spindle cells arranged in a plexiform architecture.
Plexiform fibrohistiocytic tumour. Infiltrative tumour growth at the junction of the dermis and subcutaneous adipose tissue.

Q: The characteristic architecture of Plexiform Fibrohistiocytic Tumor consists of a [...] or multinodular arrangement of histiocytoid nodules connected by fascicles of spindled fibroblastic cells.
Plexiform fibrohistiocytic tumour. Bland spindle cell / fibroblastic component.
Plexiform fibrohistiocytic tumour. This example is composed of nodules of histiocytoid cells and intervening fascicles of spindle cells arranged in a plexiform architecture.
A: plexiform
Back Extra: Plexiform Fibrohistiocytic Tumour
- Clinical: Plexiform Fibrohistiocytic Tumour (PFHT) is a rare dermal and subcutaneous neoplasm, commonly presenting as a slow-growing tumour or plaque, predominantly in children and young adults, with a slight female predominance.
- Micro: PFHT is characterized by a plexiform or multinodular arrangement of nodules of histiocytoid cells with admixed multinucleated osteoclastic-like giant cells, connected by fascicles of spindled fibroblastic/myofibroblastic cells.
- Ancillary: Diagnostic molecular pathology is not clinically relevant for PFHT.
Reference Gallery:
Plexiform fibrohistiocytic tumour. The nodules are composed of bland and uniform histiocytoid cells with admixed osteoclast-like, multinucleated giant cells.
Plexiform fibrohistiocytic tumour. Bland spindle cell / fibroblastic component.
Plexiform fibrohistiocytic tumour. This example is composed of nodules of histiocytoid cells and intervening fascicles of spindle cells arranged in a plexiform architecture.
Plexiform fibrohistiocytic tumour. Infiltrative tumour growth at the junction of the dermis and subcutaneous adipose tissue.

Q: Histologically, Plexiform Fibrohistiocytic Tumor typically exhibits an infiltrative growth pattern localized at the junction of the dermis and [...] adipose tissue.
Plexiform fibrohistiocytic tumour. Infiltrative tumour growth at the junction of the dermis and subcutaneous adipose tissue.
A: subcutaneous
Back Extra: Plexiform Fibrohistiocytic Tumour
- Clinical: Plexiform Fibrohistiocytic Tumour (PFHT) is a rare dermal and subcutaneous neoplasm, commonly presenting as a slow-growing tumour or plaque, predominantly in children and young adults, with a slight female predominance.
- Micro: PFHT is characterized by a plexiform or multinodular arrangement of nodules of histiocytoid cells with admixed multinucleated osteoclastic-like giant cells, connected by fascicles of spindled fibroblastic/myofibroblastic cells.
- Ancillary: Diagnostic molecular pathology is not clinically relevant for PFHT.
Reference Gallery:
Plexiform fibrohistiocytic tumour. The nodules are composed of bland and uniform histiocytoid cells with admixed osteoclast-like, multinucleated giant cells.
Plexiform fibrohistiocytic tumour. Bland spindle cell / fibroblastic component.
Plexiform fibrohistiocytic tumour. This example is composed of nodules of histiocytoid cells and intervening fascicles of spindle cells arranged in a plexiform architecture.
Plexiform fibrohistiocytic tumour. Infiltrative tumour growth at the junction of the dermis and subcutaneous adipose tissue.

Q: Histologically, Pseudomyogenic Hemangioendothelioma is characterized by fascicles of plump spindle cells with bright eosinophilic cytoplasm that mimic [...], often accompanied by intratumoral neutrophils.
Pseudomyogenic haemangioendothelioma. Fascicles of plump spindle cells with eosinophilic cytoplasm. Prominences of intratumoural neutrophils are a common finding.
Pseudomyogenic haemangioendothelioma. The spindle cells may contain bright eosinophilic cytoplasm, mimicking rhabdomyoblasts.
A: rhabdomyoblasts
Back Extra: Pseudomyogenic Hemangioendothelioma
- Clinical: Pseudomyogenic Hemangioendothelioma typically presents as painful or painless cutaneous and subcutaneous nodules, often multifocal, with involvement of multiple tissue planes.
- Micro: The tumour is composed of sheets and fascicles of plump spindle cells with eosinophilic cytoplasm, mimicking rhabdomyoblasts, and may contain a myxoid stroma and neutrophils.
- Ancillary: Diffuse expression of keratins (AE1/AE3) and endothelial markers (FLI1, ERG), positive CD31, and FOSB gene fusion are key diagnostic features.
Reference Gallery:
Pseudomyogenic haemangioendothelioma. A skin lesion infiltrating into the subcutis. Note the overlying epidermal hyperplasia.
Pseudomyogenic haemangioendothelioma. An intramuscular tumour infiltrating between muscle fibres.
Pseudomyogenic haemangioendothelioma. Fascicles of plump spindle cells with eosinophilic cytoplasm. Prominences of intratumoural neutrophils are a common finding.
Pseudomyogenic haemangioendothelioma. The spindle cells may contain bright eosinophilic cytoplasm, mimicking rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. A focus of tumour in the tibia. This patient also had cutaneous and intramuscular lesions.
Pseudomyogenic haemangioendothelioma. This tibial lesion shows a loose fascicular architecture and scant myxoid stroma. The spindle and epithelioid cells contain eosinophilic cytoplasm.
Pseudomyogenic haemangioendothelioma. Immunohistochemistry for keratins (with AE1/AE3) is typically strongly and diffusely positive.
Pseudomyogenic haemangioendothelioma. Expression of FOSB reflects the presence of a FOSB gene fusion.

Q: Immunohistochemically, Pseudomyogenic Hemangioendothelioma uniquely co-expresses endothelial markers (e.g., ERG, FLI1) and keratins (AE1/AE3), and is defined molecularly by a [...] gene fusion.
Pseudomyogenic haemangioendothelioma. Immunohistochemistry for keratins (with AE1/AE3) is typically strongly and diffusely positive.
Pseudomyogenic haemangioendothelioma. Expression of FOSB reflects the presence of a FOSB gene fusion.
A: FOSB
Back Extra: Pseudomyogenic Hemangioendothelioma
- Clinical: Pseudomyogenic Hemangioendothelioma typically presents as painful or painless cutaneous and subcutaneous nodules, often multifocal, with involvement of multiple tissue planes.
- Micro: The tumour is composed of sheets and fascicles of plump spindle cells with eosinophilic cytoplasm, mimicking rhabdomyoblasts, and may contain a myxoid stroma and neutrophils.
- Ancillary: Diffuse expression of keratins (AE1/AE3) and endothelial markers (FLI1, ERG), positive CD31, and FOSB gene fusion are key diagnostic features.
Reference Gallery:
Pseudomyogenic haemangioendothelioma. A skin lesion infiltrating into the subcutis. Note the overlying epidermal hyperplasia.
Pseudomyogenic haemangioendothelioma. An intramuscular tumour infiltrating between muscle fibres.
Pseudomyogenic haemangioendothelioma. Fascicles of plump spindle cells with eosinophilic cytoplasm. Prominences of intratumoural neutrophils are a common finding.
Pseudomyogenic haemangioendothelioma. The spindle cells may contain bright eosinophilic cytoplasm, mimicking rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. A focus of tumour in the tibia. This patient also had cutaneous and intramuscular lesions.
Pseudomyogenic haemangioendothelioma. This tibial lesion shows a loose fascicular architecture and scant myxoid stroma. The spindle and epithelioid cells contain eosinophilic cytoplasm.
Pseudomyogenic haemangioendothelioma. Immunohistochemistry for keratins (with AE1/AE3) is typically strongly and diffusely positive.
Pseudomyogenic haemangioendothelioma. Expression of FOSB reflects the presence of a FOSB gene fusion.

Q: A vascular tumor that characteristically presents as painful or painless multifocal nodules involving multiple tissue planes (e.g., skin, skeletal muscle, and bone in the same region) is [...].
Pseudomyogenic haemangioendothelioma. A skin lesion infiltrating into the subcutis. Note the overlying epidermal hyperplasia.
Pseudomyogenic haemangioendothelioma. An intramuscular tumour infiltrating between muscle fibres.
Pseudomyogenic haemangioendothelioma. A focus of tumour in the tibia. This patient also had cutaneous and intramuscular lesions.
A: Pseudomyogenic Hemangioendothelioma
Back Extra: Pseudomyogenic Hemangioendothelioma
- Clinical: Pseudomyogenic Hemangioendothelioma typically presents as painful or painless cutaneous and subcutaneous nodules, often multifocal, with involvement of multiple tissue planes.
- Micro: The tumour is composed of sheets and fascicles of plump spindle cells with eosinophilic cytoplasm, mimicking rhabdomyoblasts, and may contain a myxoid stroma and neutrophils.
- Ancillary: Diffuse expression of keratins (AE1/AE3) and endothelial markers (FLI1, ERG), positive CD31, and FOSB gene fusion are key diagnostic features.
Reference Gallery:
Pseudomyogenic haemangioendothelioma. A skin lesion infiltrating into the subcutis. Note the overlying epidermal hyperplasia.
Pseudomyogenic haemangioendothelioma. An intramuscular tumour infiltrating between muscle fibres.
Pseudomyogenic haemangioendothelioma. Fascicles of plump spindle cells with eosinophilic cytoplasm. Prominences of intratumoural neutrophils are a common finding.
Pseudomyogenic haemangioendothelioma. The spindle cells may contain bright eosinophilic cytoplasm, mimicking rhabdomyoblasts.
Pseudomyogenic haemangioendothelioma. A focus of tumour in the tibia. This patient also had cutaneous and intramuscular lesions.
Pseudomyogenic haemangioendothelioma. This tibial lesion shows a loose fascicular architecture and scant myxoid stroma. The spindle and epithelioid cells contain eosinophilic cytoplasm.
Pseudomyogenic haemangioendothelioma. Immunohistochemistry for keratins (with AE1/AE3) is typically strongly and diffusely positive.
Pseudomyogenic haemangioendothelioma. Expression of FOSB reflects the presence of a FOSB gene fusion.

Q: Microscopically, a Benign triton tumor / neuromuscular choristoma is characterized by intraneural elements enclosed within the perineural sheath that are intercalated with haphazardly arranged bundles of mature [...].
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
A: skeletal muscle
Back Extra: Benign triton tumour / neuromuscular choristoma
- Clinical: Patients with benign triton tumour / neuromuscular choristoma often present with progressive pain or features of peripheral neuropathy/plexopathy, and may have limb atrophy and superimposed desmoid fibromatosis.
- Micro: Haphazardly arranged bundles of mature skeletal muscle with cross-striations are intercalated between intraneural elements, and the myogenic component expresses desmin and myogenin.
- Ancillary: The presence of CTNNB1 exon 3 (p.T41A and p.S45F) mutations supports the diagnosis of benign triton tumour / neuromuscular choristoma.
Reference Gallery:
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
Neuromuscular choristoma. Immunostaining for S100 (red) and desmin (brown) highlights Schwann cells and skeletal muscle fibres with evident cross-striations, respectively.

Q: To confirm the admixed tissue components in a Benign triton tumor / neuromuscular choristoma, immunohistochemical staining demonstrates Schwann cells positive for S100 and mature, cross-striated muscle fibers positive for [...].
Neuromuscular choristoma. Immunostaining for S100 (red) and desmin (brown) highlights Schwann cells and skeletal muscle fibres with evident cross-striations, respectively.
A: desmin
Back Extra: Benign triton tumour / neuromuscular choristoma
- Clinical: Patients with benign triton tumour / neuromuscular choristoma often present with progressive pain or features of peripheral neuropathy/plexopathy, and may have limb atrophy and superimposed desmoid fibromatosis.
- Micro: Haphazardly arranged bundles of mature skeletal muscle with cross-striations are intercalated between intraneural elements, and the myogenic component expresses desmin and myogenin.
- Ancillary: The presence of CTNNB1 exon 3 (p.T41A and p.S45F) mutations supports the diagnosis of benign triton tumour / neuromuscular choristoma.
Reference Gallery:
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
Neuromuscular choristoma. Immunostaining for S100 (red) and desmin (brown) highlights Schwann cells and skeletal muscle fibres with evident cross-striations, respectively.

Q: A peripheral nerve lesion consisting of haphazardly admixed neural elements and mature striated muscle fibers, which may harbor CTNNB1 exon 3 mutations, is diagnostic of a [...].
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
A: Benign triton tumor / neuromuscular choristoma
Back Extra: Benign triton tumour / neuromuscular choristoma
- Clinical: Patients with benign triton tumour / neuromuscular choristoma often present with progressive pain or features of peripheral neuropathy/plexopathy, and may have limb atrophy and superimposed desmoid fibromatosis.
- Micro: Haphazardly arranged bundles of mature skeletal muscle with cross-striations are intercalated between intraneural elements, and the myogenic component expresses desmin and myogenin.
- Ancillary: The presence of CTNNB1 exon 3 (p.T41A and p.S45F) mutations supports the diagnosis of benign triton tumour / neuromuscular choristoma.
Reference Gallery:
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
Neuromuscular choristoma. The tumour shows mature neural tissue and skeletal muscle fibres enclosed in the perineural sheath.
Neuromuscular choristoma. Immunostaining for S100 (red) and desmin (brown) highlights Schwann cells and skeletal muscle fibres with evident cross-striations, respectively.

Q: The fetal (myxoid) variant of a rhabdomyoma is a benign skeletal muscle tumor that can present as a polypoid mass in infants and classically features primitive spindle cells and [...] enmeshed in a myxoid stroma.
Rhabdomyoma. A polypoid mass arising from the vulva of a 2-month-old girl.
Fetal rhabdomyoma. The tumour is composed of alternating myotubes and primitive cells enmeshed in a myxoid stroma.
A: myotubes
Back Extra: Rhabdomyoma
- Clinical: Extracardiac rhabdomyomas present as growing masses in the head and neck region, often in the posterior auricular region, and can cause proptosis, decreased vision, airway obstruction, or hoarseness.
- Micro: The classic fetal (myxoid) type of rhabdomyoma contains primitive spindle cells with indistinct cytoplasm arranged in irregular bundles within a myxoid background, interspersed with immature skeletal muscle fibres.
- Ancillary: Inactivating germline mutations in PTCH1 and dysregulation of hedgehog signalling are key genetic underpinnings in the pathogenesis of rhabdomyomas.
Reference Gallery:
Rhabdomyoma. A polypoid mass arising from the vulva of a 2-month-old girl.
Fetal rhabdomyoma. The tumour is composed of alternating myotubes and primitive cells enmeshed in a myxoid stroma.
Rhabdomyoma. An example of fetal rhabdomyoma, with increased numbers of primitive cells that have uniform cytological features and no mitotic activity.
Rhabdomyoma. This example of the intermediate form of fetal rhabdomyoma contains closely packed myocytes and lacks a myxoid stroma. The cells are uniform and without atypia or mitoses.
Fetal rhabdomyoma. Myogenin expression in intermediate-type fetal rhabdomyoma.
Fetal rhabdomyoma. Desmin highlights focal cross-striations.

Q: To confirm skeletal muscle differentiation in a rhabdomyoma, immunohistochemistry shows nuclear positivity for myogenin, while a [...] stain typically highlights focal cross-striations.
Fetal rhabdomyoma. Myogenin expression in intermediate-type fetal rhabdomyoma.
Fetal rhabdomyoma. Desmin highlights focal cross-striations.
A: desmin
Back Extra: Rhabdomyoma
- Clinical: Extracardiac rhabdomyomas present as growing masses in the head and neck region, often in the posterior auricular region, and can cause proptosis, decreased vision, airway obstruction, or hoarseness.
- Micro: The classic fetal (myxoid) type of rhabdomyoma contains primitive spindle cells with indistinct cytoplasm arranged in irregular bundles within a myxoid background, interspersed with immature skeletal muscle fibres.
- Ancillary: Inactivating germline mutations in PTCH1 and dysregulation of hedgehog signalling are key genetic underpinnings in the pathogenesis of rhabdomyomas.
Reference Gallery:
Rhabdomyoma. A polypoid mass arising from the vulva of a 2-month-old girl.
Fetal rhabdomyoma. The tumour is composed of alternating myotubes and primitive cells enmeshed in a myxoid stroma.
Rhabdomyoma. An example of fetal rhabdomyoma, with increased numbers of primitive cells that have uniform cytological features and no mitotic activity.
Rhabdomyoma. This example of the intermediate form of fetal rhabdomyoma contains closely packed myocytes and lacks a myxoid stroma. The cells are uniform and without atypia or mitoses.
Fetal rhabdomyoma. Myogenin expression in intermediate-type fetal rhabdomyoma.
Fetal rhabdomyoma. Desmin highlights focal cross-striations.

Q: Unlike the classic myxoid type, the intermediate variant of a fetal rhabdomyoma is composed of uniform, closely packed myocytes and characteristically lacks a [...].
Rhabdomyoma. This example of the intermediate form of fetal rhabdomyoma contains closely packed myocytes and lacks a myxoid stroma. The cells are uniform and without atypia or mitoses.
A: myxoid stroma
Back Extra: Rhabdomyoma
- Clinical: Extracardiac rhabdomyomas present as growing masses in the head and neck region, often in the posterior auricular region, and can cause proptosis, decreased vision, airway obstruction, or hoarseness.
- Micro: The classic fetal (myxoid) type of rhabdomyoma contains primitive spindle cells with indistinct cytoplasm arranged in irregular bundles within a myxoid background, interspersed with immature skeletal muscle fibres.
- Ancillary: Inactivating germline mutations in PTCH1 and dysregulation of hedgehog signalling are key genetic underpinnings in the pathogenesis of rhabdomyomas.
Reference Gallery:
Rhabdomyoma. A polypoid mass arising from the vulva of a 2-month-old girl.
Fetal rhabdomyoma. The tumour is composed of alternating myotubes and primitive cells enmeshed in a myxoid stroma.
Rhabdomyoma. An example of fetal rhabdomyoma, with increased numbers of primitive cells that have uniform cytological features and no mitotic activity.
Rhabdomyoma. This example of the intermediate form of fetal rhabdomyoma contains closely packed myocytes and lacks a myxoid stroma. The cells are uniform and without atypia or mitoses.
Fetal rhabdomyoma. Myogenin expression in intermediate-type fetal rhabdomyoma.
Fetal rhabdomyoma. Desmin highlights focal cross-striations.

Q: Embryonal rhabdomyosarcoma arising from mucosal surfaces often has a gross grape-like (botryoid) appearance and microscopically shows a subepithelial condensation of tumor cells known as the [...].
Botryoid embryonal rhabdomyosarcoma. Macroscopic appearance of mucosal-based embryonal rhabdomyosarcoma with a grape-like (botryoid) or polypoid appearance.
Botryoid embryonal rhabdomyosarcoma. Low-power examination of a mucosal-based botryoid embryonal rhabdomyosarcoma shows hypocellular polypoid masses with tumour condensation beneath the epithelial lining (cambium layer).
A: cambium layer
Back Extra: Rhabdomyosarcoma
- Clinical: Embryonal rhabdomyosarcomas often present with site-specific symptoms, such as proptosis in orbital tumours or bladder obstruction in genitourinary tumours.
- Micro: Embryonal rhabdomyosarcoma shows a mix of primitive mesenchymal cells and differentiating rhabdomyoblasts, while alveolar rhabdomyosarcoma has a more uniform appearance with sheets of round cells.
- Ancillary: PAX3::FOXO1 or PAX7::FOXO1 translocations are characteristic of alveolar rhabdomyosarcoma, and MYOD1 p.L122R mutations are associated with a poor prognosis in sclerosing rhabdomyosarcoma.
Reference Gallery:
Botryoid embryonal rhabdomyosarcoma. Macroscopic appearance of mucosal-based embryonal rhabdomyosarcoma with a grape-like (botryoid) or polypoid appearance.
Botryoid embryonal rhabdomyosarcoma. Low-power examination of a mucosal-based botryoid embryonal rhabdomyosarcoma shows hypocellular polypoid masses with tumour condensation beneath the epithelial lining (cambium layer).
Embryonal rhabdomyosarcoma, dense pattern. Embryonal rhabdomyosarcoma may be poorly differentiated, with sheets of densely packed ovoid to slightly angulated cells.
Spindle cell rhabdomyosarcoma with differentiation. The pure spindled pattern of rhabdomyosarcoma often shows at least focal cytodifferentiation with well-formed myotubes, most frequently seen in infants with VGLL2::NCOA2 gene rearrangements.
Embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma shows nuclear heterogeneity, with coarse chromatin and multiple small nucleoli. Mitotic figures are readily identified.
Spindle cell rhabdomyosarcoma. On high-power magnification, spindle cell rhabdomyosarcoma shows a uniform proliferation of elongate, ovoid cells with coarse chromatin and small nucleoli.
Embryonal rhabdomyosarcoma. Most embryonal rhabdomyosarcomas show only patchy or moderate nuclear staining for myogenin (MYF4).
Orbital embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma frequently arises in the orbit, where a large mass may result in proptosis.
Alveolar rhabdomyosarcoma. The solid pattern of alveolar rhabdomyosarcoma consists of sheets of homogeneous round cells, which may mimic lymphoma.
Sclerosing rhabdomyosarcoma. The sclerosing pattern of rhabdomyosarcoma consists of uniform round cells arranged in cords separated by a densely hyalinized stroma.
Typical embryonal rhabdomyosarcoma with differentiation. At least focal cytodifferentiation is often seen, characterized by tails of eosinophilic cytoplasm (strap cells).
Alveolar rhabdomyosarcoma (PAX3::FOXO1-positive case). Fibrovascular septa are lined by a single layer of tumour cells, and differentiating rhabdomyoblasts are seen.

Q: Alveolar rhabdomyosarcoma often exhibits distinctive fibrovascular septa and is characteristically driven by translocations involving PAX7 or [FOXO1].
Alveolar rhabdomyosarcoma. The solid pattern of alveolar rhabdomyosarcoma consists of sheets of homogeneous round cells, which may mimic lymphoma.
Alveolar rhabdomyosarcoma (PAX3::FOXO1-positive case). Fibrovascular septa are lined by a single layer of tumour cells, and differentiating rhabdomyoblasts are seen.
A: PAX3
Back Extra: Rhabdomyosarcoma
- Clinical: Embryonal rhabdomyosarcomas often present with site-specific symptoms, such as proptosis in orbital tumours or bladder obstruction in genitourinary tumours.
- Micro: Embryonal rhabdomyosarcoma shows a mix of primitive mesenchymal cells and differentiating rhabdomyoblasts, while alveolar rhabdomyosarcoma has a more uniform appearance with sheets of round cells.
- Ancillary: PAX3::FOXO1 or PAX7::FOXO1 translocations are characteristic of alveolar rhabdomyosarcoma, and MYOD1 p.L122R mutations are associated with a poor prognosis in sclerosing rhabdomyosarcoma.
Reference Gallery:
Botryoid embryonal rhabdomyosarcoma. Macroscopic appearance of mucosal-based embryonal rhabdomyosarcoma with a grape-like (botryoid) or polypoid appearance.
Botryoid embryonal rhabdomyosarcoma. Low-power examination of a mucosal-based botryoid embryonal rhabdomyosarcoma shows hypocellular polypoid masses with tumour condensation beneath the epithelial lining (cambium layer).
Embryonal rhabdomyosarcoma, dense pattern. Embryonal rhabdomyosarcoma may be poorly differentiated, with sheets of densely packed ovoid to slightly angulated cells.
Spindle cell rhabdomyosarcoma with differentiation. The pure spindled pattern of rhabdomyosarcoma often shows at least focal cytodifferentiation with well-formed myotubes, most frequently seen in infants with VGLL2::NCOA2 gene rearrangements.
Embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma shows nuclear heterogeneity, with coarse chromatin and multiple small nucleoli. Mitotic figures are readily identified.
Spindle cell rhabdomyosarcoma. On high-power magnification, spindle cell rhabdomyosarcoma shows a uniform proliferation of elongate, ovoid cells with coarse chromatin and small nucleoli.
Embryonal rhabdomyosarcoma. Most embryonal rhabdomyosarcomas show only patchy or moderate nuclear staining for myogenin (MYF4).
Orbital embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma frequently arises in the orbit, where a large mass may result in proptosis.
Alveolar rhabdomyosarcoma. The solid pattern of alveolar rhabdomyosarcoma consists of sheets of homogeneous round cells, which may mimic lymphoma.
Sclerosing rhabdomyosarcoma. The sclerosing pattern of rhabdomyosarcoma consists of uniform round cells arranged in cords separated by a densely hyalinized stroma.
Typical embryonal rhabdomyosarcoma with differentiation. At least focal cytodifferentiation is often seen, characterized by tails of eosinophilic cytoplasm (strap cells).
Alveolar rhabdomyosarcoma (PAX3::FOXO1-positive case). Fibrovascular septa are lined by a single layer of tumour cells, and differentiating rhabdomyoblasts are seen.

Q: In cases of embryonal rhabdomyosarcoma showing focal cytodifferentiation, pathologists often identify differentiating rhabdomyoblasts with tails of brightly eosinophilic cytoplasm, termed [...].
Typical embryonal rhabdomyosarcoma with differentiation. At least focal cytodifferentiation is often seen, characterized by tails of eosinophilic cytoplasm (strap cells).
A: strap cells
Back Extra: Rhabdomyosarcoma
- Clinical: Embryonal rhabdomyosarcomas often present with site-specific symptoms, such as proptosis in orbital tumours or bladder obstruction in genitourinary tumours.
- Micro: Embryonal rhabdomyosarcoma shows a mix of primitive mesenchymal cells and differentiating rhabdomyoblasts, while alveolar rhabdomyosarcoma has a more uniform appearance with sheets of round cells.
- Ancillary: PAX3::FOXO1 or PAX7::FOXO1 translocations are characteristic of alveolar rhabdomyosarcoma, and MYOD1 p.L122R mutations are associated with a poor prognosis in sclerosing rhabdomyosarcoma.
Reference Gallery:
Botryoid embryonal rhabdomyosarcoma. Macroscopic appearance of mucosal-based embryonal rhabdomyosarcoma with a grape-like (botryoid) or polypoid appearance.
Botryoid embryonal rhabdomyosarcoma. Low-power examination of a mucosal-based botryoid embryonal rhabdomyosarcoma shows hypocellular polypoid masses with tumour condensation beneath the epithelial lining (cambium layer).
Embryonal rhabdomyosarcoma, dense pattern. Embryonal rhabdomyosarcoma may be poorly differentiated, with sheets of densely packed ovoid to slightly angulated cells.
Spindle cell rhabdomyosarcoma with differentiation. The pure spindled pattern of rhabdomyosarcoma often shows at least focal cytodifferentiation with well-formed myotubes, most frequently seen in infants with VGLL2::NCOA2 gene rearrangements.
Embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma shows nuclear heterogeneity, with coarse chromatin and multiple small nucleoli. Mitotic figures are readily identified.
Spindle cell rhabdomyosarcoma. On high-power magnification, spindle cell rhabdomyosarcoma shows a uniform proliferation of elongate, ovoid cells with coarse chromatin and small nucleoli.
Embryonal rhabdomyosarcoma. Most embryonal rhabdomyosarcomas show only patchy or moderate nuclear staining for myogenin (MYF4).
Orbital embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma frequently arises in the orbit, where a large mass may result in proptosis.
Alveolar rhabdomyosarcoma. The solid pattern of alveolar rhabdomyosarcoma consists of sheets of homogeneous round cells, which may mimic lymphoma.
Sclerosing rhabdomyosarcoma. The sclerosing pattern of rhabdomyosarcoma consists of uniform round cells arranged in cords separated by a densely hyalinized stroma.
Typical embryonal rhabdomyosarcoma with differentiation. At least focal cytodifferentiation is often seen, characterized by tails of eosinophilic cytoplasm (strap cells).
Alveolar rhabdomyosarcoma (PAX3::FOXO1-positive case). Fibrovascular septa are lined by a single layer of tumour cells, and differentiating rhabdomyoblasts are seen.

Q: Within the category of Round Cell Sarcoma with EWSR1::Non-ETS Fusions, tumors that present as destructive bone lesions and show small to medium-sized cells with clear cytoplasm arranged in cords and nests typically harbor a fusion involving the [...] gene.
Round cell sarcoma with EWSR1::NFATC2 fusion. This sarcoma arose in the diaphysis of the humerus of a 19-year-old male patient. The tumour shows cortical destruction and focal soft tissue extension.
Round cell sarcoma with EWSR1::NFATC2 fusion. A high-power image of an NFATC2-rearranged sarcoma showing medium-sized round cells with clear cytoplasm arranged in cords/nests. There is prominent fibrohyaline stroma.
A: NFATC2
Back Extra: Round Cell Sarcoma with EWSR1::Non-ETS Fusions
- Clinical: EWSR1/FUS::NFATC2 sarcomas typically manifest as painful, locally destructive bone lesions or as primary soft tissue tumours, while EWSR1::PATZ1 sarcomas manifest as isolated soft tissue masses.
- Micro: EWSR1/FUS::NFATC2 sarcomas show small to medium-sized round and/or spindled cells with clear cytoplasm arranged in cords, nests, and trabeculae, while EWSR1::PATZ1 sarcomas show small round and/or spindled cells with fibrous stroma.
- Ancillary: The EWSR1::NFATC2 fusion is best detected by sequence-based fusion assays, and the EWSR1::PATZ1 fusion is best detected using the same method due to its intrachromosomal paracentric inversion.
Reference Gallery:
Round cell sarcoma with EWSR1::NFATC2 fusion. This sarcoma arose in the diaphysis of the humerus of a 19-year-old male patient. The tumour shows cortical destruction and focal soft tissue extension.
Round cell sarcoma with EWSR1::NFATC2 fusion. NFATC2-rearranged sarcoma infiltrates and destroys bone. In this case from a 19-year-old male patient, the fibrous component is quite prominent.
Round cell sarcoma with EWSR1::NFATC2 fusion. A high-power image of an NFATC2-rearranged sarcoma showing medium-sized round cells with clear cytoplasm arranged in cords/nests. There is prominent fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This tumour is composed of a round cell population admixed with a fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This tumour is composed of a monotonous population of cells with small to medium-sized round nuclei and scant cytoplasm, embedded in a fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This case displays a predominant solid aspect made up of a mixture of round to spindled cells within a delicate fibrous stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. Sometimes the tumour may show a solid, haphazard proliferation of cells with round to elongated nuclei with scant intervening stroma. Tumour nuclei are slightly hyperchromatic but monotonous with regular contours, in keeping with the context of translocation-related sarcoma.
Round cell sarcoma with EWSR1::PATZ1 fusion. Break-apart FISH with an EWSR1 probe (green: telomeric [3′]; red: centromeric [5′]). A small gap separating the probes can be seen in the tumour cells. PATZ1 rearrangement is notoriously difficult to detect by break-apart FISH because it involves an intrachromosomal paracentric inversion.

Q: In Round Cell Sarcoma with EWSR1::Non-ETS Fusions, the EWSR1::PATZ1 fusion is notoriously difficult to detect by break-apart FISH because the genetic rearrangement involves an [...].
Round cell sarcoma with EWSR1::PATZ1 fusion. Break-apart FISH with an EWSR1 probe (green: telomeric [3′]; red: centromeric [5′]). A small gap separating the probes can be seen in the tumour cells. PATZ1 rearrangement is notoriously difficult to detect by break-apart FISH because it involves an intrachromosomal paracentric inversion.
A: intrachromosomal paracentric inversion
Back Extra: Round Cell Sarcoma with EWSR1::Non-ETS Fusions
- Clinical: EWSR1/FUS::NFATC2 sarcomas typically manifest as painful, locally destructive bone lesions or as primary soft tissue tumours, while EWSR1::PATZ1 sarcomas manifest as isolated soft tissue masses.
- Micro: EWSR1/FUS::NFATC2 sarcomas show small to medium-sized round and/or spindled cells with clear cytoplasm arranged in cords, nests, and trabeculae, while EWSR1::PATZ1 sarcomas show small round and/or spindled cells with fibrous stroma.
- Ancillary: The EWSR1::NFATC2 fusion is best detected by sequence-based fusion assays, and the EWSR1::PATZ1 fusion is best detected using the same method due to its intrachromosomal paracentric inversion.
Reference Gallery:
Round cell sarcoma with EWSR1::NFATC2 fusion. This sarcoma arose in the diaphysis of the humerus of a 19-year-old male patient. The tumour shows cortical destruction and focal soft tissue extension.
Round cell sarcoma with EWSR1::NFATC2 fusion. NFATC2-rearranged sarcoma infiltrates and destroys bone. In this case from a 19-year-old male patient, the fibrous component is quite prominent.
Round cell sarcoma with EWSR1::NFATC2 fusion. A high-power image of an NFATC2-rearranged sarcoma showing medium-sized round cells with clear cytoplasm arranged in cords/nests. There is prominent fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This tumour is composed of a round cell population admixed with a fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This tumour is composed of a monotonous population of cells with small to medium-sized round nuclei and scant cytoplasm, embedded in a fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This case displays a predominant solid aspect made up of a mixture of round to spindled cells within a delicate fibrous stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. Sometimes the tumour may show a solid, haphazard proliferation of cells with round to elongated nuclei with scant intervening stroma. Tumour nuclei are slightly hyperchromatic but monotonous with regular contours, in keeping with the context of translocation-related sarcoma.
Round cell sarcoma with EWSR1::PATZ1 fusion. Break-apart FISH with an EWSR1 probe (green: telomeric [3′]; red: centromeric [5′]). A small gap separating the probes can be seen in the tumour cells. PATZ1 rearrangement is notoriously difficult to detect by break-apart FISH because it involves an intrachromosomal paracentric inversion.

Q: Within the spectrum of Round Cell Sarcoma with EWSR1::Non-ETS Fusions, the subtype that frequently presents as an isolated soft tissue mass composed of monotonous round-to-spindled cells in a prominent fibrohyaline stroma is characterized by a fusion involving the [...] gene.
Round cell sarcoma with EWSR1::PATZ1 fusion. This tumour is composed of a monotonous population of cells with small to medium-sized round nuclei and scant cytoplasm, embedded in a fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This case displays a predominant solid aspect made up of a mixture of round to spindled cells within a delicate fibrous stroma.
A: PATZ1
Back Extra: Round Cell Sarcoma with EWSR1::Non-ETS Fusions
- Clinical: EWSR1/FUS::NFATC2 sarcomas typically manifest as painful, locally destructive bone lesions or as primary soft tissue tumours, while EWSR1::PATZ1 sarcomas manifest as isolated soft tissue masses.
- Micro: EWSR1/FUS::NFATC2 sarcomas show small to medium-sized round and/or spindled cells with clear cytoplasm arranged in cords, nests, and trabeculae, while EWSR1::PATZ1 sarcomas show small round and/or spindled cells with fibrous stroma.
- Ancillary: The EWSR1::NFATC2 fusion is best detected by sequence-based fusion assays, and the EWSR1::PATZ1 fusion is best detected using the same method due to its intrachromosomal paracentric inversion.
Reference Gallery:
Round cell sarcoma with EWSR1::NFATC2 fusion. This sarcoma arose in the diaphysis of the humerus of a 19-year-old male patient. The tumour shows cortical destruction and focal soft tissue extension.
Round cell sarcoma with EWSR1::NFATC2 fusion. NFATC2-rearranged sarcoma infiltrates and destroys bone. In this case from a 19-year-old male patient, the fibrous component is quite prominent.
Round cell sarcoma with EWSR1::NFATC2 fusion. A high-power image of an NFATC2-rearranged sarcoma showing medium-sized round cells with clear cytoplasm arranged in cords/nests. There is prominent fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This tumour is composed of a round cell population admixed with a fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This tumour is composed of a monotonous population of cells with small to medium-sized round nuclei and scant cytoplasm, embedded in a fibrohyaline stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. This case displays a predominant solid aspect made up of a mixture of round to spindled cells within a delicate fibrous stroma.
Round cell sarcoma with EWSR1::PATZ1 fusion. Sometimes the tumour may show a solid, haphazard proliferation of cells with round to elongated nuclei with scant intervening stroma. Tumour nuclei are slightly hyperchromatic but monotonous with regular contours, in keeping with the context of translocation-related sarcoma.
Round cell sarcoma with EWSR1::PATZ1 fusion. Break-apart FISH with an EWSR1 probe (green: telomeric [3′]; red: centromeric [5′]). A small gap separating the probes can be seen in the tumour cells. PATZ1 rearrangement is notoriously difficult to detect by break-apart FISH because it involves an intrachromosomal paracentric inversion.

Q: Microscopically, Sarcoma with BCOR Genetic Alterations typically consists of primitive, small, round to ovoid tumor cells that characteristically feature pale nuclei with [...] set within a rich capillary network.
Sarcoma with BCOR::CCNB3 fusion. Cells show typical nuclear features with finely dispersed chromatin.
Sarcoma with BCOR::CCNB3 fusion. Characteristic delicate vascular pattern.
Sarcoma with BCOR::CCNB3 fusion. Characteristic pale nuclei with finely dispersed chromatin.
A: finely dispersed chromatin
Back Extra: Sarcoma with BCOR Genetic Alterations
- Clinical: Sarcoma with BCOR Genetic Alterations commonly presents with pain (in 65% of cases) and swelling (in 40%).
- Micro: The tumour is characterized by primitive, small, round to slightly elongated cells with finely dispersed chromatin and a rich capillary network.
- Ancillary: Diagnosis is confirmed by strong and diffuse nuclear BCOR immunopositivity and detection of BCOR gene rearrangements or ITDs.
Reference Gallery:
Sarcoma with BCOR::CCNB3 fusion. Varying morphology, with plump, short, spindled and stellate cells juxtaposed to monotonous small primitive cells with eosinophilic cytoplasm.
Sarcoma with BCOR::CCNB3 fusion. Intraosseous tumour composed of small primitive ovoid cells arranged in sheets and vague fascicles.
Sarcoma with BCOR::CCNB3 fusion. A cellular tumour composed of round to ovoid cells forming poorly defined cell nests supported by a rich network of thin branching vessels.
Sarcoma with BCOR::CCNB3 fusion. A tumour with lower cellularity and more prominent myxoid stroma showing cells arranged in cord-like structures with focal clustering of cells.
Sarcoma with BCOR::CCNB3 fusion. A tumour with plump and stellate cells and prominent myxoid stroma with microcyst formation.
Sarcoma with BCOR::CCNB3 fusion. The lesion shown in Fig. <<19754>> is densely cellular, with round to slightly elongated cells.
Sarcoma with BCOR::CCNB3 fusion. Tumour cells show diffuse positive nuclear immunostaining for BCOR.
Sarcoma with BCOR::CCNB3 fusion. Cells show typical nuclear features with finely dispersed chromatin.
Sarcoma with BCOR::CCNB3 fusion. Characteristic delicate vascular pattern.
Sarcoma with BCOR::CCNB3 fusion. Sarcoma with abundant myxoid stroma and small aggregates of round epithelioid cells in a 5-month-old baby.
Sarcoma with BCOR::CCNB3 fusion. Characteristic pale nuclei with finely dispersed chromatin.

Q: The diagnosis of Sarcoma with BCOR Genetic Alterations is confirmed by detecting gene rearrangements or internal tandem duplications (ITDs), along with strong and diffuse nuclear immunohistochemical positivity for [...].
Sarcoma with BCOR::CCNB3 fusion. Tumour cells show diffuse positive nuclear immunostaining for BCOR.
A: BCOR
Back Extra: Sarcoma with BCOR Genetic Alterations
- Clinical: Sarcoma with BCOR Genetic Alterations commonly presents with pain (in 65% of cases) and swelling (in 40%).
- Micro: The tumour is characterized by primitive, small, round to slightly elongated cells with finely dispersed chromatin and a rich capillary network.
- Ancillary: Diagnosis is confirmed by strong and diffuse nuclear BCOR immunopositivity and detection of BCOR gene rearrangements or ITDs.
Reference Gallery:
Sarcoma with BCOR::CCNB3 fusion. Varying morphology, with plump, short, spindled and stellate cells juxtaposed to monotonous small primitive cells with eosinophilic cytoplasm.
Sarcoma with BCOR::CCNB3 fusion. Intraosseous tumour composed of small primitive ovoid cells arranged in sheets and vague fascicles.
Sarcoma with BCOR::CCNB3 fusion. A cellular tumour composed of round to ovoid cells forming poorly defined cell nests supported by a rich network of thin branching vessels.
Sarcoma with BCOR::CCNB3 fusion. A tumour with lower cellularity and more prominent myxoid stroma showing cells arranged in cord-like structures with focal clustering of cells.
Sarcoma with BCOR::CCNB3 fusion. A tumour with plump and stellate cells and prominent myxoid stroma with microcyst formation.
Sarcoma with BCOR::CCNB3 fusion. The lesion shown in Fig. <<19754>> is densely cellular, with round to slightly elongated cells.
Sarcoma with BCOR::CCNB3 fusion. Tumour cells show diffuse positive nuclear immunostaining for BCOR.
Sarcoma with BCOR::CCNB3 fusion. Cells show typical nuclear features with finely dispersed chromatin.
Sarcoma with BCOR::CCNB3 fusion. Characteristic delicate vascular pattern.
Sarcoma with BCOR::CCNB3 fusion. Sarcoma with abundant myxoid stroma and small aggregates of round epithelioid cells in a 5-month-old baby.
Sarcoma with BCOR::CCNB3 fusion. Characteristic pale nuclei with finely dispersed chromatin.

Q: Hybrid nerve sheath tumor characteristically exhibits a biphasic histologic pattern featuring a loose, hypocellular matrix that surrounds solid [...] nodules.
Hybrid neurofibroma/schwannoma. An example showing a solid schwannomatous nodule surrounded by loose, hypocellular, neurofibromatous tumour.
A: schwannomatous
Back Extra: Hybrid Nerve Sheath Tumour
- Clinical: Hybrid nerve sheath tumours are rare, occurring as painless masses in subcutaneous tissue or dermis, and may cause pain or neurological deficits if involving large peripheral nerves or spinal nerves.
- Micro: The microscopic appearance includes a mix of Schwann cells and perineurial cells, often forming a biphasic pattern with schwannomatous nodules within a neurofibroma-like matrix.
- Ancillary: Immunohistochemistry is crucial for identifying the different components, with S100 highlighting Schwann cells and EMA marking perineurial cells.
Reference Gallery:
Hybrid neurofibroma/schwannoma. An example showing a solid schwannomatous nodule surrounded by loose, hypocellular, neurofibromatous tumour.

Q: Hybrid nerve sheath tumor often presents with a biphasic pattern where solid schwannomatous nodules are set within a loose, hypocellular [...] matrix.
Hybrid neurofibroma/schwannoma. An example showing a solid schwannomatous nodule surrounded by loose, hypocellular, neurofibromatous tumour.
A: neurofibromatous
Back Extra: Hybrid Nerve Sheath Tumour
- Clinical: Hybrid nerve sheath tumours are rare, occurring as painless masses in subcutaneous tissue or dermis, and may cause pain or neurological deficits if involving large peripheral nerves or spinal nerves.
- Micro: The microscopic appearance includes a mix of Schwann cells and perineurial cells, often forming a biphasic pattern with schwannomatous nodules within a neurofibroma-like matrix.
- Ancillary: Immunohistochemistry is crucial for identifying the different components, with S100 highlighting Schwann cells and EMA marking perineurial cells.
Reference Gallery:
Hybrid neurofibroma/schwannoma. An example showing a solid schwannomatous nodule surrounded by loose, hypocellular, neurofibromatous tumour.

Q: Histologically, a Schwannoma is a spindle cell tumor exhibiting biphasic architecture with hypercellular Antoni A and hypocellular Antoni B areas, often featuring characteristic nuclear palisading around anucleate fibrillary processes known as [...].
Schwannoma. Low-power view of a schwannoma from the soft tissues in the hand of a 12-year-old patient. Note the encapsulation of the tumour and the prominent Verocay bodies.
Schwannoma. Higher magnification of a schwannoma from the soft tissues in the foot of a 12-year-old girl. Observe the nuclear palisading.
A: Verocay bodies
Back Extra: Schwannoma
- Clinical: Schwannomas are slow-growing, often asymptomatic masses, typically found incidentally on imaging. Patients with spinal schwannomas may experience sensory or motor symptoms, while those with vestibular schwannomas often present with hearing loss and vertigo.
- Micro: Schwannomas are encapsulated spindle cell tumours, predominantly composed of Antoni A tissue (compact areas with nuclear palisading) and Antoni B tissue (loosely arranged foci with histiocytes and hyalinized blood vessels).
- Ancillary: Essential for diagnosis are classic schwannoma histopathology (Antoni A or B areas) and extensive S100 or SOX10 expression. Hyalinized blood vessels and Verocay bodies are also characteristic.
Reference Gallery:
Schwannoma. Macroscopic appearance of a schwannoma in the plantar soft tissues of a 12-year-old. Note the encapsulated appearance with a white to yellow homogeneous and non-haemorrhagic cut surface.
Schwannoma. Low-power view of a schwannoma from the soft tissues in the hand of a 12-year-old patient. Note the encapsulation of the tumour and the prominent Verocay bodies.
Schwannoma. S100 immunohistochemistry shows a diffuse staining pattern in this case from the foot of a 12-year-old girl.
Schwannoma. SOX10 immunohistochemistry shows strong staining in this example from the hand of a 12-year-old boy.
Schwannoma. Higher magnification of a schwannoma from the soft tissues in the foot of a 12-year-old girl. Observe the nuclear palisading.

Q: Immunohistochemistry for a Schwannoma characteristically demonstrates diffuse, strong positivity for neural crest markers SOX10 and [...].
Schwannoma. S100 immunohistochemistry shows a diffuse staining pattern in this case from the foot of a 12-year-old girl.
Schwannoma. SOX10 immunohistochemistry shows strong staining in this example from the hand of a 12-year-old boy.
A: S100
Back Extra: Schwannoma
- Clinical: Schwannomas are slow-growing, often asymptomatic masses, typically found incidentally on imaging. Patients with spinal schwannomas may experience sensory or motor symptoms, while those with vestibular schwannomas often present with hearing loss and vertigo.
- Micro: Schwannomas are encapsulated spindle cell tumours, predominantly composed of Antoni A tissue (compact areas with nuclear palisading) and Antoni B tissue (loosely arranged foci with histiocytes and hyalinized blood vessels).
- Ancillary: Essential for diagnosis are classic schwannoma histopathology (Antoni A or B areas) and extensive S100 or SOX10 expression. Hyalinized blood vessels and Verocay bodies are also characteristic.
Reference Gallery:
Schwannoma. Macroscopic appearance of a schwannoma in the plantar soft tissues of a 12-year-old. Note the encapsulated appearance with a white to yellow homogeneous and non-haemorrhagic cut surface.
Schwannoma. Low-power view of a schwannoma from the soft tissues in the hand of a 12-year-old patient. Note the encapsulation of the tumour and the prominent Verocay bodies.
Schwannoma. S100 immunohistochemistry shows a diffuse staining pattern in this case from the foot of a 12-year-old girl.
Schwannoma. SOX10 immunohistochemistry shows strong staining in this example from the hand of a 12-year-old boy.
Schwannoma. Higher magnification of a schwannoma from the soft tissues in the foot of a 12-year-old girl. Observe the nuclear palisading.

Q: Macroscopically, a Schwannoma typically presents as a slow-growing, solid mass that is well-[...] with a white-to-yellow homogeneous cut surface, helping distinguish it from most neurofibromas.
Schwannoma. Macroscopic appearance of a schwannoma in the plantar soft tissues of a 12-year-old. Note the encapsulated appearance with a white to yellow homogeneous and non-haemorrhagic cut surface.
A: encapsulated
Back Extra: Schwannoma
- Clinical: Schwannomas are slow-growing, often asymptomatic masses, typically found incidentally on imaging. Patients with spinal schwannomas may experience sensory or motor symptoms, while those with vestibular schwannomas often present with hearing loss and vertigo.
- Micro: Schwannomas are encapsulated spindle cell tumours, predominantly composed of Antoni A tissue (compact areas with nuclear palisading) and Antoni B tissue (loosely arranged foci with histiocytes and hyalinized blood vessels).
- Ancillary: Essential for diagnosis are classic schwannoma histopathology (Antoni A or B areas) and extensive S100 or SOX10 expression. Hyalinized blood vessels and Verocay bodies are also characteristic.
Reference Gallery:
Schwannoma. Macroscopic appearance of a schwannoma in the plantar soft tissues of a 12-year-old. Note the encapsulated appearance with a white to yellow homogeneous and non-haemorrhagic cut surface.
Schwannoma. Low-power view of a schwannoma from the soft tissues in the hand of a 12-year-old patient. Note the encapsulation of the tumour and the prominent Verocay bodies.
Schwannoma. S100 immunohistochemistry shows a diffuse staining pattern in this case from the foot of a 12-year-old girl.
Schwannoma. SOX10 immunohistochemistry shows strong staining in this example from the hand of a 12-year-old boy.
Schwannoma. Higher magnification of a schwannoma from the soft tissues in the foot of a 12-year-old girl. Observe the nuclear palisading.

Q: A patient presenting with a classic clinical triad of nasal obstruction, prominent epistaxis, and a distinct nasopharyngeal mass on imaging is highly characteristic of [...].
Sinonasal angiofibroma. This axial CT shows a large, soft tissue–density mass emanating from the nasopharynx and filling the nasal cavity as it expands anteriorly.
Sinonasal angiofibroma. T1-weighted coronal MRI shows a large mass filling the nasopharynx and nasal cavity and expanding into the orbit and soft tissues of the face. It is not uncommon for this benign tumour to grow quite large.
A: Sinonasal Angiofibroma
Back Extra: Sinonasal Angiofibroma
- Clinical: Sinonasal Angiofibroma presents with a classic triad of nasal obstruction, epistaxis, and a nasopharyngeal mass, often over a prolonged symptom duration.
- Micro: The stroma of Sinonasal Angiofibroma is composed of bipolar or stellate fibroblastic cells, with a highly vascularized background of variably sized blood vessels.
- Ancillary: Aberrant nuclear β-catenin expression is seen in most Sinonasal Angiofibromas, and somatic mutations in the CTNNB1 gene are present in 75% of cases.
Reference Gallery:
Sinonasal angiofibroma. The tumour shows a highly vascularized fibrovascular proliferation covered by respiratory mucosa.
Sinonasal angiofibroma. In some areas of the neoplasm, the walls of dilated and communicating vessels are replaced by neoplastic cells.
Sinonasal angiofibroma. Variably sized blood vessels ranging from thin-walled to focally or diffusely thickened muscular vessels are embedded in a loose cellular to densely collagenized fibrous stroma.
Sinonasal angiofibroma. Vascularity. A variety of vessel types and sizes constitute angiofibroma, with circumferential smooth muscle, pads of smooth muscle, and a complete lack of smooth muscle around the vessels. The stroma shows increased cellularity and collagen deposition.
Sinonasal angiofibroma. Embolic material. Angiofibroma showing several different sizes and types of vessels within a fibrous connective tissue stroma. Embolic material (right) is noted: a sign of preoperative embolization of the tumour.
Sinonasal angiofibroma. Cellularity. Angiofibroma showing a variably cellular stroma, with bipolar to stellate spindled cells set within a collagenized background. Patulous to compressed vessels are present. Atypia and mitoses are absent.
Sinonasal angiofibroma. The neoplastic stromal cells show strong nuclear expression of AR.
Sinonasal angiofibroma. Nuclear β-catenin is strongly expressed in the neoplastic stromal cells.
Sinonasal angiofibroma. This axial CT shows a large, soft tissue–density mass emanating from the nasopharynx and filling the nasal cavity as it expands anteriorly.
Sinonasal angiofibroma. T1-weighted coronal MRI shows a large mass filling the nasopharynx and nasal cavity and expanding into the orbit and soft tissues of the face. It is not uncommon for this benign tumour to grow quite large.
Sinonasal angiofibroma. Sagittal CT demonstrates a large mass arising from the upper nasopharynx and filling the nasal cavity. Bone remodelling is noted, along with a mixed signal.

Q: Histologically, the stroma of Sinonasal Angiofibroma features a highly vascularized background of variably sized blood vessels interspersed with characteristic [...] fibroblastic cells.
Sinonasal angiofibroma. Variably sized blood vessels ranging from thin-walled to focally or diffusely thickened muscular vessels are embedded in a loose cellular to densely collagenized fibrous stroma.
Sinonasal angiofibroma. Cellularity. Angiofibroma showing a variably cellular stroma, with bipolar to stellate spindled cells set within a collagenized background. Patulous to compressed vessels are present. Atypia and mitoses are absent.
A: bipolar or stellate
Back Extra: Sinonasal Angiofibroma
- Clinical: Sinonasal Angiofibroma presents with a classic triad of nasal obstruction, epistaxis, and a nasopharyngeal mass, often over a prolonged symptom duration.
- Micro: The stroma of Sinonasal Angiofibroma is composed of bipolar or stellate fibroblastic cells, with a highly vascularized background of variably sized blood vessels.
- Ancillary: Aberrant nuclear β-catenin expression is seen in most Sinonasal Angiofibromas, and somatic mutations in the CTNNB1 gene are present in 75% of cases.
Reference Gallery:
Sinonasal angiofibroma. The tumour shows a highly vascularized fibrovascular proliferation covered by respiratory mucosa.
Sinonasal angiofibroma. In some areas of the neoplasm, the walls of dilated and communicating vessels are replaced by neoplastic cells.
Sinonasal angiofibroma. Variably sized blood vessels ranging from thin-walled to focally or diffusely thickened muscular vessels are embedded in a loose cellular to densely collagenized fibrous stroma.
Sinonasal angiofibroma. Vascularity. A variety of vessel types and sizes constitute angiofibroma, with circumferential smooth muscle, pads of smooth muscle, and a complete lack of smooth muscle around the vessels. The stroma shows increased cellularity and collagen deposition.
Sinonasal angiofibroma. Embolic material. Angiofibroma showing several different sizes and types of vessels within a fibrous connective tissue stroma. Embolic material (right) is noted: a sign of preoperative embolization of the tumour.
Sinonasal angiofibroma. Cellularity. Angiofibroma showing a variably cellular stroma, with bipolar to stellate spindled cells set within a collagenized background. Patulous to compressed vessels are present. Atypia and mitoses are absent.
Sinonasal angiofibroma. The neoplastic stromal cells show strong nuclear expression of AR.
Sinonasal angiofibroma. Nuclear β-catenin is strongly expressed in the neoplastic stromal cells.
Sinonasal angiofibroma. This axial CT shows a large, soft tissue–density mass emanating from the nasopharynx and filling the nasal cavity as it expands anteriorly.
Sinonasal angiofibroma. T1-weighted coronal MRI shows a large mass filling the nasopharynx and nasal cavity and expanding into the orbit and soft tissues of the face. It is not uncommon for this benign tumour to grow quite large.
Sinonasal angiofibroma. Sagittal CT demonstrates a large mass arising from the upper nasopharynx and filling the nasal cavity. Bone remodelling is noted, along with a mixed signal.

Q: In Sinonasal Angiofibroma, the neoplastic stromal cells characteristically show aberrant nuclear expression of [...] (driven by CTNNB1 somatic mutations) alongside androgen receptor (AR) positivity.
Sinonasal angiofibroma. The neoplastic stromal cells show strong nuclear expression of AR.
Sinonasal angiofibroma. Nuclear β-catenin is strongly expressed in the neoplastic stromal cells.
A: β-catenin
Back Extra: Sinonasal Angiofibroma
- Clinical: Sinonasal Angiofibroma presents with a classic triad of nasal obstruction, epistaxis, and a nasopharyngeal mass, often over a prolonged symptom duration.
- Micro: The stroma of Sinonasal Angiofibroma is composed of bipolar or stellate fibroblastic cells, with a highly vascularized background of variably sized blood vessels.
- Ancillary: Aberrant nuclear β-catenin expression is seen in most Sinonasal Angiofibromas, and somatic mutations in the CTNNB1 gene are present in 75% of cases.
Reference Gallery:
Sinonasal angiofibroma. The tumour shows a highly vascularized fibrovascular proliferation covered by respiratory mucosa.
Sinonasal angiofibroma. In some areas of the neoplasm, the walls of dilated and communicating vessels are replaced by neoplastic cells.
Sinonasal angiofibroma. Variably sized blood vessels ranging from thin-walled to focally or diffusely thickened muscular vessels are embedded in a loose cellular to densely collagenized fibrous stroma.
Sinonasal angiofibroma. Vascularity. A variety of vessel types and sizes constitute angiofibroma, with circumferential smooth muscle, pads of smooth muscle, and a complete lack of smooth muscle around the vessels. The stroma shows increased cellularity and collagen deposition.
Sinonasal angiofibroma. Embolic material. Angiofibroma showing several different sizes and types of vessels within a fibrous connective tissue stroma. Embolic material (right) is noted: a sign of preoperative embolization of the tumour.
Sinonasal angiofibroma. Cellularity. Angiofibroma showing a variably cellular stroma, with bipolar to stellate spindled cells set within a collagenized background. Patulous to compressed vessels are present. Atypia and mitoses are absent.
Sinonasal angiofibroma. The neoplastic stromal cells show strong nuclear expression of AR.
Sinonasal angiofibroma. Nuclear β-catenin is strongly expressed in the neoplastic stromal cells.
Sinonasal angiofibroma. This axial CT shows a large, soft tissue–density mass emanating from the nasopharynx and filling the nasal cavity as it expands anteriorly.
Sinonasal angiofibroma. T1-weighted coronal MRI shows a large mass filling the nasopharynx and nasal cavity and expanding into the orbit and soft tissues of the face. It is not uncommon for this benign tumour to grow quite large.
Sinonasal angiofibroma. Sagittal CT demonstrates a large mass arising from the upper nasopharynx and filling the nasal cavity. Bone remodelling is noted, along with a mixed signal.

Q: Histologically, Sinonasal Tract Myxoma features a hypocellular proliferation of spindled or stellate cells set within a myxoid stroma that characteristically contains [...] blood vessels.
Sinonasal myxoma. The lesion is characterized by cells with elongated, slender cytoplasm and without atypia, interspersed in an abundant myxoid stroma containing curvilinear blood vessels.
A: curvilinear
Back Extra: Sinonasal Tract Myxoma
- Clinical: Sinonasal myxoma presents as a slow-growing nasolabial swelling, commonly in children under 3 years old, with a slight male predominance.
- Micro: The lesion is characterized by a hypocellular proliferation of spindled, stellate, or round cells within a myxoid stroma containing curvilinear blood vessels and fine collagen bands.
- Ancillary: Immunohistochemistry shows variable positivity for SMA and diffuse nuclear staining for β-catenin.
Reference Gallery:
Sinonasal myxoma. The lesion is characterized by cells with elongated, slender cytoplasm and without atypia, interspersed in an abundant myxoid stroma containing curvilinear blood vessels.
Sinonasal myxoma. There is diffuse nuclear staining for β-catenin.

Q: By immunohistochemistry, Sinonasal Tract Myxoma characteristically exhibits diffuse nuclear staining for [...].
Sinonasal myxoma. There is diffuse nuclear staining for β-catenin.
A: β-catenin
Back Extra: Sinonasal Tract Myxoma
- Clinical: Sinonasal myxoma presents as a slow-growing nasolabial swelling, commonly in children under 3 years old, with a slight male predominance.
- Micro: The lesion is characterized by a hypocellular proliferation of spindled, stellate, or round cells within a myxoid stroma containing curvilinear blood vessels and fine collagen bands.
- Ancillary: Immunohistochemistry shows variable positivity for SMA and diffuse nuclear staining for β-catenin.
Reference Gallery:
Sinonasal myxoma. The lesion is characterized by cells with elongated, slender cytoplasm and without atypia, interspersed in an abundant myxoid stroma containing curvilinear blood vessels.
Sinonasal myxoma. There is diffuse nuclear staining for β-catenin.

Q: In Solitary Circumscribed Neuroma, the lesion is typically composed of bland, spindle-shaped cells with wavy nuclei in a fibrous stroma, often forming fascicles that demonstrate [...].
Solitary circumscribed neuroma. Higher magnification reveals banal spindle cells with focal palisading, set in a fibrous stroma.
A: focal palisading
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary Circumscribed Neuroma is a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly found on the face, particularly the nose, forehead, and lips.
- Micro: The lesion is composed of bland spindle-shaped cells with wavy nuclei in a background of hyalinized collagen, forming well-developed fascicles with focal palisading and artefactual clefting.
- Ancillary: Lesional Schwann cells show diffuse S100 positivity, and the peripheral capsule is highlighted by perineurial markers such as EMA and GLUT1.
Reference Gallery:
Solitary circumscribed neuroma. Higher magnification reveals banal spindle cells with focal palisading, set in a fibrous stroma.
Solitary circumscribed neuroma. Lesional Schwann cells stain diffusely positively with S100.
Solitary circumscribed neuroma. NFP is expressed by variable numbers of small intratumoural axons.
Solitary circumscribed neuroma. EMA staining highlights perineurial cells in the capsule.

Q: In Solitary Circumscribed Neuroma, immunohistochemistry demonstrates diffusely S100-positive Schwann cells intermixed with numerous small intratumoral axons that are highlighted by [...] (NFP).
Solitary circumscribed neuroma. Lesional Schwann cells stain diffusely positively with S100.
Solitary circumscribed neuroma. NFP is expressed by variable numbers of small intratumoural axons.
A: neurofilament protein
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary Circumscribed Neuroma is a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly found on the face, particularly the nose, forehead, and lips.
- Micro: The lesion is composed of bland spindle-shaped cells with wavy nuclei in a background of hyalinized collagen, forming well-developed fascicles with focal palisading and artefactual clefting.
- Ancillary: Lesional Schwann cells show diffuse S100 positivity, and the peripheral capsule is highlighted by perineurial markers such as EMA and GLUT1.
Reference Gallery:
Solitary circumscribed neuroma. Higher magnification reveals banal spindle cells with focal palisading, set in a fibrous stroma.
Solitary circumscribed neuroma. Lesional Schwann cells stain diffusely positively with S100.
Solitary circumscribed neuroma. NFP is expressed by variable numbers of small intratumoural axons.
Solitary circumscribed neuroma. EMA staining highlights perineurial cells in the capsule.

Q: The well-developed peripheral capsule of a Solitary Circumscribed Neuroma is composed of perineurial cells, which can be confirmed using an immunostain for [...] (EMA).
Solitary circumscribed neuroma. EMA staining highlights perineurial cells in the capsule.
A: epithelial membrane antigen
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary Circumscribed Neuroma is a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly found on the face, particularly the nose, forehead, and lips.
- Micro: The lesion is composed of bland spindle-shaped cells with wavy nuclei in a background of hyalinized collagen, forming well-developed fascicles with focal palisading and artefactual clefting.
- Ancillary: Lesional Schwann cells show diffuse S100 positivity, and the peripheral capsule is highlighted by perineurial markers such as EMA and GLUT1.
Reference Gallery:
Solitary circumscribed neuroma. Higher magnification reveals banal spindle cells with focal palisading, set in a fibrous stroma.
Solitary circumscribed neuroma. Lesional Schwann cells stain diffusely positively with S100.
Solitary circumscribed neuroma. NFP is expressed by variable numbers of small intratumoural axons.
Solitary circumscribed neuroma. EMA staining highlights perineurial cells in the capsule.

Q: [...] is a cutaneous or subcutaneous tumor that characteristically presents with well-demarcated myxoid lobules, bland spindle cells, and curvilinear vasculature.
Superficial angiomyxoma. The tumour typically shows a well-demarcated growth of myxoid lobules.
Superficial angiomyxoma. The tumour is characteristically composed of bland spindle cells and curvilinear vasculature set within a copious myxoid matrix.
A: Superficial Angiomyxoma
Back Extra: Superficial Angiomyxoma
- Clinical: Superficial angiomyxomas are rare in children, typically presenting as painless cutaneous or subcutaneous papules or nodules, often found in the genital and head/neck regions.
- Micro: Histologically, superficial angiomyxoma is characterized by bland-looking spindled to stellate cells in a myxoid stroma with capillary-like vessels and a lobular/multinodular appearance.
- Ancillary: CD34 is diffusely expressed in superficial angiomyxoma.
Reference Gallery:
Superficial angiomyxoma. The tumour typically shows a well-demarcated growth of myxoid lobules.
Superficial angiomyxoma. The tumour is characteristically composed of bland spindle cells and curvilinear vasculature set within a copious myxoid matrix.

Q: Superficial Angiomyxoma characteristically exhibits a well-demarcated, [...] or multinodular growth pattern of bland spindle cells set within a copious myxoid stroma.
Superficial angiomyxoma. The tumour typically shows a well-demarcated growth of myxoid lobules.
A: lobular
Back Extra: Superficial Angiomyxoma
- Clinical: Superficial angiomyxomas are rare in children, typically presenting as painless cutaneous or subcutaneous papules or nodules, often found in the genital and head/neck regions.
- Micro: Histologically, superficial angiomyxoma is characterized by bland-looking spindled to stellate cells in a myxoid stroma with capillary-like vessels and a lobular/multinodular appearance.
- Ancillary: CD34 is diffusely expressed in superficial angiomyxoma.
Reference Gallery:
Superficial angiomyxoma. The tumour typically shows a well-demarcated growth of myxoid lobules.
Superficial angiomyxoma. The tumour is characteristically composed of bland spindle cells and curvilinear vasculature set within a copious myxoid matrix.

Q: Superficial Angiomyxoma contains bland spindle cells and thin, capillary-like vessels that characteristically exhibit a [...] architecture.
Superficial angiomyxoma. The tumour is characteristically composed of bland spindle cells and curvilinear vasculature set within a copious myxoid matrix.
A: curvilinear
Back Extra: Superficial Angiomyxoma
- Clinical: Superficial angiomyxomas are rare in children, typically presenting as painless cutaneous or subcutaneous papules or nodules, often found in the genital and head/neck regions.
- Micro: Histologically, superficial angiomyxoma is characterized by bland-looking spindled to stellate cells in a myxoid stroma with capillary-like vessels and a lobular/multinodular appearance.
- Ancillary: CD34 is diffusely expressed in superficial angiomyxoma.
Reference Gallery:
Superficial angiomyxoma. The tumour typically shows a well-demarcated growth of myxoid lobules.
Superficial angiomyxoma. The tumour is characteristically composed of bland spindle cells and curvilinear vasculature set within a copious myxoid matrix.

Q: In Synovial Sarcoma, the classic biphasic variant is histologically characterized by a dual population consisting of a spindle cell component and an [...] (or glandular) component.
Synovial sarcoma. Biphasic synovial sarcoma with a glandular component and a spindle cell component.
A: epithelial
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma often presents as a slow-growing mass, typically in the deep soft tissues of the extremities near large joints, with or without pain.
- Micro: Synovial sarcoma can exhibit monophasic, biphasic, or poorly differentiated histological patterns, with the biphasic variant showing both spindle and epithelial components.
- Ancillary: Immunohistochemical markers such as SS18::SSX fusion protein, TLE1, BCL2, CD99, and EMA are crucial for diagnosing synovial sarcoma.
Reference Gallery:
Synovial sarcoma. Biphasic synovial sarcoma with a glandular component and a spindle cell component.
Synovial sarcoma. Monophasic synovial sarcoma with fascicles of monomorphic blue spindle cells.
Synovial sarcoma. Monophasic synovial sarcoma with high cellularity and mitotic activity.
Synovial sarcoma. Poorly differentiated synovial sarcoma with primitive round cells.
Synovial sarcoma. Multifocal EMA expression.
Synovial sarcoma. Diffuse strong SS18::SSX immunostaining of tumour cell nuclei.
Synovial sarcoma. Loss of SMARCB1 (INI1) expression.
Synovial sarcoma. Fat-suppressed T2-weighted sagittal MRI showing a T2-hyperintense lobular mass at the ventral aspect of the wrist, with areas of interspersed dark signal representing calcifications.
Synovial sarcoma. Fat-suppressed T1-weighted postcontrast sagittal MRI showing avid enhancement of the mass over the ventral aspect of the wrist, as well as evidence of multiple non-enhancing septations.

Q: The defining molecular alteration in Synovial Sarcoma, which can be detected via highly specific, strong nuclear immunohistochemical staining, is the [SSX] fusion protein.
Synovial sarcoma. Diffuse strong SS18::SSX immunostaining of tumour cell nuclei.
A: SS18
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma often presents as a slow-growing mass, typically in the deep soft tissues of the extremities near large joints, with or without pain.
- Micro: Synovial sarcoma can exhibit monophasic, biphasic, or poorly differentiated histological patterns, with the biphasic variant showing both spindle and epithelial components.
- Ancillary: Immunohistochemical markers such as SS18::SSX fusion protein, TLE1, BCL2, CD99, and EMA are crucial for diagnosing synovial sarcoma.
Reference Gallery:
Synovial sarcoma. Biphasic synovial sarcoma with a glandular component and a spindle cell component.
Synovial sarcoma. Monophasic synovial sarcoma with fascicles of monomorphic blue spindle cells.
Synovial sarcoma. Monophasic synovial sarcoma with high cellularity and mitotic activity.
Synovial sarcoma. Poorly differentiated synovial sarcoma with primitive round cells.
Synovial sarcoma. Multifocal EMA expression.
Synovial sarcoma. Diffuse strong SS18::SSX immunostaining of tumour cell nuclei.
Synovial sarcoma. Loss of SMARCB1 (INI1) expression.
Synovial sarcoma. Fat-suppressed T2-weighted sagittal MRI showing a T2-hyperintense lobular mass at the ventral aspect of the wrist, with areas of interspersed dark signal representing calcifications.
Synovial sarcoma. Fat-suppressed T1-weighted postcontrast sagittal MRI showing avid enhancement of the mass over the ventral aspect of the wrist, as well as evidence of multiple non-enhancing septations.

Q: The monophasic variant of Synovial Sarcoma typically presents without distinct glandular formation and is instead composed of highly cellular fascicles of monomorphic blue [...] cells.
Synovial sarcoma. Monophasic synovial sarcoma with fascicles of monomorphic blue spindle cells.
Synovial sarcoma. Monophasic synovial sarcoma with high cellularity and mitotic activity.
A: spindle
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma often presents as a slow-growing mass, typically in the deep soft tissues of the extremities near large joints, with or without pain.
- Micro: Synovial sarcoma can exhibit monophasic, biphasic, or poorly differentiated histological patterns, with the biphasic variant showing both spindle and epithelial components.
- Ancillary: Immunohistochemical markers such as SS18::SSX fusion protein, TLE1, BCL2, CD99, and EMA are crucial for diagnosing synovial sarcoma.
Reference Gallery:
Synovial sarcoma. Biphasic synovial sarcoma with a glandular component and a spindle cell component.
Synovial sarcoma. Monophasic synovial sarcoma with fascicles of monomorphic blue spindle cells.
Synovial sarcoma. Monophasic synovial sarcoma with high cellularity and mitotic activity.
Synovial sarcoma. Poorly differentiated synovial sarcoma with primitive round cells.
Synovial sarcoma. Multifocal EMA expression.
Synovial sarcoma. Diffuse strong SS18::SSX immunostaining of tumour cell nuclei.
Synovial sarcoma. Loss of SMARCB1 (INI1) expression.
Synovial sarcoma. Fat-suppressed T2-weighted sagittal MRI showing a T2-hyperintense lobular mass at the ventral aspect of the wrist, with areas of interspersed dark signal representing calcifications.
Synovial sarcoma. Fat-suppressed T1-weighted postcontrast sagittal MRI showing avid enhancement of the mass over the ventral aspect of the wrist, as well as evidence of multiple non-enhancing septations.

Q: Microscopically, the localized type of Tenosynovial Giant Cell Tumor typically contains an admixture of small histiocyte-like cells, larger mononuclear cells, and [...].
Tenosynovial giant cell tumour. Localized type showing an admixture of small histiocyte-like cells, larger mononuclear cells, and osteoclast-like giant cells.
A: osteoclast-like giant cells
Back Extra: Tenosynovial Giant Cell Tumour
- Clinical: Patients with tenosynovial giant cell tumour typically present with swelling, pain, and reduced range of motion.
- Micro: The localized type often contains an admixture of small histiocyte-like cells, larger mononuclear cells, and osteoclast-like giant cells.
- Ancillary: Cytogenetic studies often reveal a translocation of CSF1, encoding colony stimulating factor 1.
Reference Gallery:
Tenosynovial giant cell tumour. Diffuse type showing villous architecture.
Tenosynovial giant cell tumour. Localized type showing an admixture of small histiocyte-like cells, larger mononuclear cells, and osteoclast-like giant cells.
Tenosynovial giant cell tumour. Collections of foamy histiocytes are common in the localized type.
Tenosynovial giant cell tumour. Giant cells may be absent or extremely rare in the diffuse type. The cytoplasm of larger mononuclear cells often contains a peripheral rim of haemosiderin.

Q: In the diffuse type of Tenosynovial Giant Cell Tumor, giant cells may be rare, and the cytoplasm of larger mononuclear cells often contains a characteristic peripheral rim of [...].
Tenosynovial giant cell tumour. Giant cells may be absent or extremely rare in the diffuse type. The cytoplasm of larger mononuclear cells often contains a peripheral rim of haemosiderin.
A: hemosiderin
Back Extra: Tenosynovial Giant Cell Tumour
- Clinical: Patients with tenosynovial giant cell tumour typically present with swelling, pain, and reduced range of motion.
- Micro: The localized type often contains an admixture of small histiocyte-like cells, larger mononuclear cells, and osteoclast-like giant cells.
- Ancillary: Cytogenetic studies often reveal a translocation of CSF1, encoding colony stimulating factor 1.
Reference Gallery:
Tenosynovial giant cell tumour. Diffuse type showing villous architecture.
Tenosynovial giant cell tumour. Localized type showing an admixture of small histiocyte-like cells, larger mononuclear cells, and osteoclast-like giant cells.
Tenosynovial giant cell tumour. Collections of foamy histiocytes are common in the localized type.
Tenosynovial giant cell tumour. Giant cells may be absent or extremely rare in the diffuse type. The cytoplasm of larger mononuclear cells often contains a peripheral rim of haemosiderin.

Q: The diffuse type of Tenosynovial Giant Cell Tumor often displays a characteristic [...] architecture upon histologic examination.
Tenosynovial giant cell tumour. Diffuse type showing villous architecture.
A: villous
Back Extra: Tenosynovial Giant Cell Tumour
- Clinical: Patients with tenosynovial giant cell tumour typically present with swelling, pain, and reduced range of motion.
- Micro: The localized type often contains an admixture of small histiocyte-like cells, larger mononuclear cells, and osteoclast-like giant cells.
- Ancillary: Cytogenetic studies often reveal a translocation of CSF1, encoding colony stimulating factor 1.
Reference Gallery:
Tenosynovial giant cell tumour. Diffuse type showing villous architecture.
Tenosynovial giant cell tumour. Localized type showing an admixture of small histiocyte-like cells, larger mononuclear cells, and osteoclast-like giant cells.
Tenosynovial giant cell tumour. Collections of foamy histiocytes are common in the localized type.
Tenosynovial giant cell tumour. Giant cells may be absent or extremely rare in the diffuse type. The cytoplasm of larger mononuclear cells often contains a peripheral rim of haemosiderin.

Q: In the spectrum of Tufted Angioma and Kaposiform Haemangioendothelioma, the classic histologic appearance of tufted angioma features well-circumscribed vascular tufts in the dermis and subcutaneous tissue arranged in a characteristic [...].
Tufted angioma. Low-power view showing small vascular tufts involving the dermis and extending to the subcutaneous tissue in a cannonball pattern.
A: "cannonball" pattern
Back Extra: Tufted Angioma and Kaposiform Haemangioendothelioma
- Clinical: Tufted angioma (TA) presents with a pink or red-purple cutaneous macule or infiltrated plaque, often in the skin and subcutis. Kaposiform haemangioendothelioma (KHE) presents with a poorly defined, large, bulging, indurated purple-red tumour, commonly associated with Kasabach–Merritt phenomenon (KMP).
- Micro: Kaposiform haemangioendothelioma (KHE) shows vascular tufts similar to tufted angioma (TA) but with larger, coalescing nodules and more prominent spindled endothelial cells forming slit-like lumina with microthrombi.
- Ancillary: Immunohistochemistry (IHC) for both TA and KHE shows strong positivity for panendothelial markers (CD31, CD34, ERG) and lymphatic markers (podoplanin, LYVE1, PROX1).
Reference Gallery:
Kaposiform haemangioendothelioma. A large tumour involving the abdominal wall of a newborn with associated Kasabach–Merritt phenomenon. Note the ecchymotic skin surrounding the mass.
Kaposiform haemangioendothelioma. Residual lesion after resolution of Kasabach–Merritt phenomenon (same case as shown in Fig. 20084).
Tufted angioma. A congenital red-purple plaque in the forearm of a newborn.
Tufted angioma. Low-power view showing small vascular tufts involving the dermis and extending to the subcutaneous tissue in a cannonball pattern.
Tufted angioma. Some dilated lymphatic channels are seen in the dermis between the tufts.
Tufted angioma. Some lymphatic vessels form crescents around the vascular tufts.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Core biopsy of a Kaposiform haemangioendothelioma showing a solid, vaguely lobular mass, with some fibrous septa and an increased number of dilated lymphatic vessels.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Extensive areas of spindle cells forming slit-like lumina.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Extensive thrombosis can be seen in cases associated with Kasabach–Merritt phenomenon.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. CD61 is helpful to highlight the presence of microthrombi.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Focal expression of podoplanin is noted in the periphery of the lobules.
Kaposiform haemangioendothelioma. T2-weighted axial MRI of the mid-abdomen shows an extensive, poorly defined infiltrative hyperintense lesion involving the right posterior pararenal space, right abdominal wall muscles, and right back muscles with an anteriorly displaced right kidney. The subcutaneous fat reticulation might represent lymphoedema, which is commonly found in infiltrative Kaposiform haemangioendothelioma accompanied by Kasabach–Merritt phenomenon.

Q: Within the spectrum of Tufted Angioma and Kaposiform Haemangioendothelioma, large, infiltrative tumors (especially in infants) are classically complicated by profound thrombocytopenia and consumptive coagulopathy, a clinical presentation known as the [...].
Kaposiform haemangioendothelioma. A large tumour involving the abdominal wall of a newborn with associated Kasabach–Merritt phenomenon. Note the ecchymotic skin surrounding the mass.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Extensive thrombosis can be seen in cases associated with Kasabach–Merritt phenomenon.
A: Kasabach-Merritt phenomenon
Back Extra: Tufted Angioma and Kaposiform Haemangioendothelioma
- Clinical: Tufted angioma (TA) presents with a pink or red-purple cutaneous macule or infiltrated plaque, often in the skin and subcutis. Kaposiform haemangioendothelioma (KHE) presents with a poorly defined, large, bulging, indurated purple-red tumour, commonly associated with Kasabach–Merritt phenomenon (KMP).
- Micro: Kaposiform haemangioendothelioma (KHE) shows vascular tufts similar to tufted angioma (TA) but with larger, coalescing nodules and more prominent spindled endothelial cells forming slit-like lumina with microthrombi.
- Ancillary: Immunohistochemistry (IHC) for both TA and KHE shows strong positivity for panendothelial markers (CD31, CD34, ERG) and lymphatic markers (podoplanin, LYVE1, PROX1).
Reference Gallery:
Kaposiform haemangioendothelioma. A large tumour involving the abdominal wall of a newborn with associated Kasabach–Merritt phenomenon. Note the ecchymotic skin surrounding the mass.
Kaposiform haemangioendothelioma. Residual lesion after resolution of Kasabach–Merritt phenomenon (same case as shown in Fig. 20084).
Tufted angioma. A congenital red-purple plaque in the forearm of a newborn.
Tufted angioma. Low-power view showing small vascular tufts involving the dermis and extending to the subcutaneous tissue in a cannonball pattern.
Tufted angioma. Some dilated lymphatic channels are seen in the dermis between the tufts.
Tufted angioma. Some lymphatic vessels form crescents around the vascular tufts.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Core biopsy of a Kaposiform haemangioendothelioma showing a solid, vaguely lobular mass, with some fibrous septa and an increased number of dilated lymphatic vessels.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Extensive areas of spindle cells forming slit-like lumina.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Extensive thrombosis can be seen in cases associated with Kasabach–Merritt phenomenon.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. CD61 is helpful to highlight the presence of microthrombi.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Focal expression of podoplanin is noted in the periphery of the lobules.
Kaposiform haemangioendothelioma. T2-weighted axial MRI of the mid-abdomen shows an extensive, poorly defined infiltrative hyperintense lesion involving the right posterior pararenal space, right abdominal wall muscles, and right back muscles with an anteriorly displaced right kidney. The subcutaneous fat reticulation might represent lymphoedema, which is commonly found in infiltrative Kaposiform haemangioendothelioma accompanied by Kasabach–Merritt phenomenon.

Q: Histologically, the kaposiform variant of Tufted Angioma and Kaposiform Haemangioendothelioma is characterized by coalescing nodules of prominent spindled endothelial cells that form distinctive [...] often containing microthrombi.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Extensive areas of spindle cells forming slit-like lumina.
A: slit-like lumina
Back Extra: Tufted Angioma and Kaposiform Haemangioendothelioma
- Clinical: Tufted angioma (TA) presents with a pink or red-purple cutaneous macule or infiltrated plaque, often in the skin and subcutis. Kaposiform haemangioendothelioma (KHE) presents with a poorly defined, large, bulging, indurated purple-red tumour, commonly associated with Kasabach–Merritt phenomenon (KMP).
- Micro: Kaposiform haemangioendothelioma (KHE) shows vascular tufts similar to tufted angioma (TA) but with larger, coalescing nodules and more prominent spindled endothelial cells forming slit-like lumina with microthrombi.
- Ancillary: Immunohistochemistry (IHC) for both TA and KHE shows strong positivity for panendothelial markers (CD31, CD34, ERG) and lymphatic markers (podoplanin, LYVE1, PROX1).
Reference Gallery:
Kaposiform haemangioendothelioma. A large tumour involving the abdominal wall of a newborn with associated Kasabach–Merritt phenomenon. Note the ecchymotic skin surrounding the mass.
Kaposiform haemangioendothelioma. Residual lesion after resolution of Kasabach–Merritt phenomenon (same case as shown in Fig. 20084).
Tufted angioma. A congenital red-purple plaque in the forearm of a newborn.
Tufted angioma. Low-power view showing small vascular tufts involving the dermis and extending to the subcutaneous tissue in a cannonball pattern.
Tufted angioma. Some dilated lymphatic channels are seen in the dermis between the tufts.
Tufted angioma. Some lymphatic vessels form crescents around the vascular tufts.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Core biopsy of a Kaposiform haemangioendothelioma showing a solid, vaguely lobular mass, with some fibrous septa and an increased number of dilated lymphatic vessels.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Extensive areas of spindle cells forming slit-like lumina.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Extensive thrombosis can be seen in cases associated with Kasabach–Merritt phenomenon.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. CD61 is helpful to highlight the presence of microthrombi.
Kaposiform haemangioendothelioma with Kasabach–Merritt phenomenon. Focal expression of podoplanin is noted in the periphery of the lobules.
Kaposiform haemangioendothelioma. T2-weighted axial MRI of the mid-abdomen shows an extensive, poorly defined infiltrative hyperintense lesion involving the right posterior pararenal space, right abdominal wall muscles, and right back muscles with an anteriorly displaced right kidney. The subcutaneous fat reticulation might represent lymphoedema, which is commonly found in infiltrative Kaposiform haemangioendothelioma accompanied by Kasabach–Merritt phenomenon.

Q: [...] is a high-grade tumor that inherently lacks an identifiable lineage and typically exhibits pleomorphic, spindle cell, or epithelioid morphologic patterns.
Undifferentiated sarcoma. Undifferentiated pleomorphic sarcoma.
Undifferentiated sarcoma. Undifferentiated spindle cell sarcoma.
Undifferentiated sarcoma. Unddifferentiated epithelioid cell sarcoma.
A: Undifferentiated Sarcoma
Back Extra: Undifferentiated Sarcoma
- Clinical: Undifferentiated sarcomas are high-grade tumours often presenting with rapid growth, commonly in the head and neck region in the paediatric population.
- Micro: The three main subtypes are pleomorphic, spindle cell, and epithelioid, all lacking an identifiable line of differentiation and often showing high mitotic activity and necrosis.
- Ancillary: Molecular studies show no recurrent genetic abnormalities, but common targets of deletions include CDKN2A, CDKN2B, PTEN, TP53, and RB1.
Reference Gallery:
Undifferentiated sarcoma. Undifferentiated pleomorphic sarcoma.
Undifferentiated sarcoma. Undifferentiated spindle cell sarcoma.
Undifferentiated sarcoma. Unddifferentiated epithelioid cell sarcoma.

Q: In cases of Undifferentiated Sarcoma, despite showing high-grade features such as high mitotic activity and necrosis, the tumor cells characteristically lack any identifiable line of [...].
Undifferentiated sarcoma. Undifferentiated pleomorphic sarcoma.
Undifferentiated sarcoma. Undifferentiated spindle cell sarcoma.
Undifferentiated sarcoma. Unddifferentiated epithelioid cell sarcoma.
A: differentiation
Back Extra: Undifferentiated Sarcoma
- Clinical: Undifferentiated sarcomas are high-grade tumours often presenting with rapid growth, commonly in the head and neck region in the paediatric population.
- Micro: The three main subtypes are pleomorphic, spindle cell, and epithelioid, all lacking an identifiable line of differentiation and often showing high mitotic activity and necrosis.
- Ancillary: Molecular studies show no recurrent genetic abnormalities, but common targets of deletions include CDKN2A, CDKN2B, PTEN, TP53, and RB1.
Reference Gallery:
Undifferentiated sarcoma. Undifferentiated pleomorphic sarcoma.
Undifferentiated sarcoma. Undifferentiated spindle cell sarcoma.
Undifferentiated sarcoma. Unddifferentiated epithelioid cell sarcoma.

Q: Histologically, an Arteriovenous Malformation features large, tortuous arteries and veins where some vessels appear to be of [...], frequently accompanied by a small-caliber capillary-like component.
Arteriovenous malformation. Large tortuous thick-walled vessels in the dermis and hypodermis.
Arteriovenous malformation. A typical lesion with large tortuous vessels, some of indeterminate lineage, along with a small-calibre component in the middle of the field.
Arteriovenous malformation. The small-calibre component has a capillary-like appearance.
A: indeterminate lineage
Back Extra: Arteriovenous Malformation
- Clinical: Arteriovenous malformations (AVMs) often present as warm, red lesions that can cause pain, ulceration, and bleeding. They may be present at birth or develop during childhood.
- Micro: AVMs are characterized by large, tortuous arteries and veins, with some vessels appearing indeterminate in lineage. There is often a small-calibre component with a capillary-like appearance.
- Ancillary: Diagnosis is supported by imaging and the presence of somatic MAP2K1 mutations. For associated syndromes (PWS, CM-AVM, HHT), germline mutations in RASA1, EPHB4, ENG, ACVRL1, GDF2, or SMAD4 may be identified.
Reference Gallery:
Arteriovenous malformation. Swelling and cutaneous stain of the cheek in a 5-year-old girl.
Arteriovenous malformation. Large tortuous thick-walled vessels in the dermis and hypodermis.
Arteriovenous malformation. A typical lesion with large tortuous vessels, some of indeterminate lineage, along with a small-calibre component in the middle of the field.
Arteriovenous malformation. The small-calibre component has a capillary-like appearance.
Parkes Weber syndrome. Overgrown extremity and diffuse capillary stain in a 1-year-old girl with germline RASA1 mutation.
Parkes Weber syndrome. Enlarged arteries and veins in the hypodermis.
Arteriovenous malformation. Minimal enlargement of dermal arteries and veins on the biopsy of one of 27 capillary stains on the trunk and extremities of a 2-year-old girl with germline RASA1 mutation.
Hereditary haemorrhagic telangiectasia. Arteriovenous malformation of the left upper lobe of the lung, with massive dilatation of pulmonary arteries and veins, in a 9-month-old boy with a family history of hereditary haemorrhagic telangiectasia. Thrombi (white arrows) and white coils (black arrows) are seen in the pulmonary arteries.
Hereditary haemorrhagic telangiectasia. Arteriovenous malformation of the colon, with large dysmorphic vascular channels in all layers, in a 4-year-old girl with arteriovenous malformation in the brain stem and a family history of hereditary haemorrhagic telangiectasia.
Arteriovenous malformations. Fat-suppressed T2-weighted coronal MRI showing multiple serpentine structures with flow voids around the wrist and hand region, corresponding to enlarged feeding arteries and draining veins. Note the absence of a well-defined mass.

Q: On T2-weighted MRI, an Arteriovenous Malformation typically demonstrates multiple serpentine structures with [...] (representing enlarged feeding and draining vessels), notably lacking a well-defined soft tissue mass.
Arteriovenous malformations. Fat-suppressed T2-weighted coronal MRI showing multiple serpentine structures with flow voids around the wrist and hand region, corresponding to enlarged feeding arteries and draining veins. Note the absence of a well-defined mass.
A: flow voids
Back Extra: Arteriovenous Malformation
- Clinical: Arteriovenous malformations (AVMs) often present as warm, red lesions that can cause pain, ulceration, and bleeding. They may be present at birth or develop during childhood.
- Micro: AVMs are characterized by large, tortuous arteries and veins, with some vessels appearing indeterminate in lineage. There is often a small-calibre component with a capillary-like appearance.
- Ancillary: Diagnosis is supported by imaging and the presence of somatic MAP2K1 mutations. For associated syndromes (PWS, CM-AVM, HHT), germline mutations in RASA1, EPHB4, ENG, ACVRL1, GDF2, or SMAD4 may be identified.
Reference Gallery:
Arteriovenous malformation. Swelling and cutaneous stain of the cheek in a 5-year-old girl.
Arteriovenous malformation. Large tortuous thick-walled vessels in the dermis and hypodermis.
Arteriovenous malformation. A typical lesion with large tortuous vessels, some of indeterminate lineage, along with a small-calibre component in the middle of the field.
Arteriovenous malformation. The small-calibre component has a capillary-like appearance.
Parkes Weber syndrome. Overgrown extremity and diffuse capillary stain in a 1-year-old girl with germline RASA1 mutation.
Parkes Weber syndrome. Enlarged arteries and veins in the hypodermis.
Arteriovenous malformation. Minimal enlargement of dermal arteries and veins on the biopsy of one of 27 capillary stains on the trunk and extremities of a 2-year-old girl with germline RASA1 mutation.
Hereditary haemorrhagic telangiectasia. Arteriovenous malformation of the left upper lobe of the lung, with massive dilatation of pulmonary arteries and veins, in a 9-month-old boy with a family history of hereditary haemorrhagic telangiectasia. Thrombi (white arrows) and white coils (black arrows) are seen in the pulmonary arteries.
Hereditary haemorrhagic telangiectasia. Arteriovenous malformation of the colon, with large dysmorphic vascular channels in all layers, in a 4-year-old girl with arteriovenous malformation in the brain stem and a family history of hereditary haemorrhagic telangiectasia.
Arteriovenous malformations. Fat-suppressed T2-weighted coronal MRI showing multiple serpentine structures with flow voids around the wrist and hand region, corresponding to enlarged feeding arteries and draining veins. Note the absence of a well-defined mass.

Q: Visceral Arteriovenous Malformations (e.g., massive dilation of pulmonary arteries and veins or dysmorphic channels in the colon) are a hallmark of [...], a syndrome caused by mutations in genes such as ENG or ACVRL1.
Hereditary haemorrhagic telangiectasia. Arteriovenous malformation of the left upper lobe of the lung, with massive dilatation of pulmonary arteries and veins, in a 9-month-old boy with a family history of hereditary haemorrhagic telangiectasia. Thrombi (white arrows) and white coils (black arrows) are seen in the pulmonary arteries.
Hereditary haemorrhagic telangiectasia. Arteriovenous malformation of the colon, with large dysmorphic vascular channels in all layers, in a 4-year-old girl with arteriovenous malformation in the brain stem and a family history of hereditary haemorrhagic telangiectasia.
A: Hereditary Hemorrhagic Telangiectasia
Back Extra: Arteriovenous Malformation
- Clinical: Arteriovenous malformations (AVMs) often present as warm, red lesions that can cause pain, ulceration, and bleeding. They may be present at birth or develop during childhood.
- Micro: AVMs are characterized by large, tortuous arteries and veins, with some vessels appearing indeterminate in lineage. There is often a small-calibre component with a capillary-like appearance.
- Ancillary: Diagnosis is supported by imaging and the presence of somatic MAP2K1 mutations. For associated syndromes (PWS, CM-AVM, HHT), germline mutations in RASA1, EPHB4, ENG, ACVRL1, GDF2, or SMAD4 may be identified.
Reference Gallery:
Arteriovenous malformation. Swelling and cutaneous stain of the cheek in a 5-year-old girl.
Arteriovenous malformation. Large tortuous thick-walled vessels in the dermis and hypodermis.
Arteriovenous malformation. A typical lesion with large tortuous vessels, some of indeterminate lineage, along with a small-calibre component in the middle of the field.
Arteriovenous malformation. The small-calibre component has a capillary-like appearance.
Parkes Weber syndrome. Overgrown extremity and diffuse capillary stain in a 1-year-old girl with germline RASA1 mutation.
Parkes Weber syndrome. Enlarged arteries and veins in the hypodermis.
Arteriovenous malformation. Minimal enlargement of dermal arteries and veins on the biopsy of one of 27 capillary stains on the trunk and extremities of a 2-year-old girl with germline RASA1 mutation.
Hereditary haemorrhagic telangiectasia. Arteriovenous malformation of the left upper lobe of the lung, with massive dilatation of pulmonary arteries and veins, in a 9-month-old boy with a family history of hereditary haemorrhagic telangiectasia. Thrombi (white arrows) and white coils (black arrows) are seen in the pulmonary arteries.
Hereditary haemorrhagic telangiectasia. Arteriovenous malformation of the colon, with large dysmorphic vascular channels in all layers, in a 4-year-old girl with arteriovenous malformation in the brain stem and a family history of hereditary haemorrhagic telangiectasia.
Arteriovenous malformations. Fat-suppressed T2-weighted coronal MRI showing multiple serpentine structures with flow voids around the wrist and hand region, corresponding to enlarged feeding arteries and draining veins. Note the absence of a well-defined mass.

Q: In the context of Intramuscular Vascular Anomalies, intramuscular [...] microscopically demonstrate a spongiform arrangement of closely apposed, dysmorphic channels of varying caliber with minimal interposed skeletal muscle.
Intramuscular venous malformation. Closely apposed malformed venous channels of varying calibre, structure, and arrangement.
Intramuscular venous malformation. Large venous channels in the vastus intermedius muscle from a 10-year-old boy.
A: venous malformations
Back Extra: Intramuscular Vascular Anomalies
- Clinical: Localized discomfort is a prime symptom, particularly with fast-flow vascular anomalies (FAVA).
- Micro: Intramuscular venous malformations (VM) are characterized by spongiform, variably sized, dysmorphic venous channels with minimal interposed skeletal muscle or fibroadipose tissue.
- Ancillary: Identification of somatic mutations (TEK, PIK3CA, MAP2K1, KRAS) and germline and/or somatic mutations (RASA1, EPHB4, PTEN) can help in diagnosing intramuscular vascular anomalies.
Reference Gallery:
Intramuscular fast-flow vascular anomaly. There is abundant capillary proliferation and a thick-walled draining channel among skeletal muscle fibres.
Intramuscular fibroadipose vascular anomaly. Vascular nodules, grey fibrous streaks, and abundant fat form a mass in the vastus lateralis of a 15-year-old boy.
Intramuscular PTEN hamartoma of soft tissue. Predominantly intramuscular masses in the left thigh and calf of a 7-year-old girl with cutaneous stains.
Intramuscular PTEN hamartoma of soft tissue. Nodular vascular zones embedded in a moderate amount of fat in a paraspinal mass from a 16-year-old boy. There is focal necrosis from preoperative embolization.
Intramuscular PTEN hamartoma of soft tissue. There are enlarged arteries, complex draining venous channels, small nodular myxoid foci with arterial arborization, fibrofatty stroma, and lymphoid aggregates.
Intramuscular PTEN hamartoma of soft tissue. There is also a large focus of muscularized indeterminate-type vessels.
Intramuscular fibroadipose vascular anomaly. Skeletal muscle is infiltrated by thin-walled back-to-back venous clusters, fibrous tissue, fat, and lymphoid aggregates.
Intramuscular venous malformation. Closely apposed malformed venous channels of varying calibre, structure, and arrangement.
Intramuscular venous malformation. Large venous channels in the vastus intermedius muscle from a 10-year-old boy.
Intramuscular arteriovenous malformation. A mass in the musculature of the right anterior leg of a 1-year-old girl with Parkes Weber syndrome and lesional RASA1 mutation. There are multiple capillary stains in the overgrown right extremity, one in the left thigh, and others subsequently developing on the torso and neck.
Intramuscular arteriovenous malformation. Biopsy of the musculature of the right leg showing infiltration by numerous prominent arteries and several dysmorphic veins.

Q: A painful subtype of Intramuscular Vascular Anomalies known as a [...] (FAVA) microscopically shows skeletal muscle infiltrated by thin-walled venous clusters, abundant fat, dense fibrous tissue, and lymphoid aggregates.
Intramuscular fibroadipose vascular anomaly. Vascular nodules, grey fibrous streaks, and abundant fat form a mass in the vastus lateralis of a 15-year-old boy.
Intramuscular fibroadipose vascular anomaly. Skeletal muscle is infiltrated by thin-walled back-to-back venous clusters, fibrous tissue, fat, and lymphoid aggregates.
A: fibroadipose vascular anomaly
Back Extra: Intramuscular Vascular Anomalies
- Clinical: Localized discomfort is a prime symptom, particularly with fast-flow vascular anomalies (FAVA).
- Micro: Intramuscular venous malformations (VM) are characterized by spongiform, variably sized, dysmorphic venous channels with minimal interposed skeletal muscle or fibroadipose tissue.
- Ancillary: Identification of somatic mutations (TEK, PIK3CA, MAP2K1, KRAS) and germline and/or somatic mutations (RASA1, EPHB4, PTEN) can help in diagnosing intramuscular vascular anomalies.
Reference Gallery:
Intramuscular fast-flow vascular anomaly. There is abundant capillary proliferation and a thick-walled draining channel among skeletal muscle fibres.
Intramuscular fibroadipose vascular anomaly. Vascular nodules, grey fibrous streaks, and abundant fat form a mass in the vastus lateralis of a 15-year-old boy.
Intramuscular PTEN hamartoma of soft tissue. Predominantly intramuscular masses in the left thigh and calf of a 7-year-old girl with cutaneous stains.
Intramuscular PTEN hamartoma of soft tissue. Nodular vascular zones embedded in a moderate amount of fat in a paraspinal mass from a 16-year-old boy. There is focal necrosis from preoperative embolization.
Intramuscular PTEN hamartoma of soft tissue. There are enlarged arteries, complex draining venous channels, small nodular myxoid foci with arterial arborization, fibrofatty stroma, and lymphoid aggregates.
Intramuscular PTEN hamartoma of soft tissue. There is also a large focus of muscularized indeterminate-type vessels.
Intramuscular fibroadipose vascular anomaly. Skeletal muscle is infiltrated by thin-walled back-to-back venous clusters, fibrous tissue, fat, and lymphoid aggregates.
Intramuscular venous malformation. Closely apposed malformed venous channels of varying calibre, structure, and arrangement.
Intramuscular venous malformation. Large venous channels in the vastus intermedius muscle from a 10-year-old boy.
Intramuscular arteriovenous malformation. A mass in the musculature of the right anterior leg of a 1-year-old girl with Parkes Weber syndrome and lesional RASA1 mutation. There are multiple capillary stains in the overgrown right extremity, one in the left thigh, and others subsequently developing on the torso and neck.
Intramuscular arteriovenous malformation. Biopsy of the musculature of the right leg showing infiltration by numerous prominent arteries and several dysmorphic veins.

Q: When evaluating Intramuscular Vascular Anomalies, the microscopic finding of complex draining veins, small nodular myxoid foci with arterial arborization, fibrofatty stroma, and lymphoid aggregates is characteristic of an intramuscular [...] of soft tissue.
Intramuscular PTEN hamartoma of soft tissue. There are enlarged arteries, complex draining venous channels, small nodular myxoid foci with arterial arborization, fibrofatty stroma, and lymphoid aggregates.
Intramuscular PTEN hamartoma of soft tissue. There is also a large focus of muscularized indeterminate-type vessels.
A: PTEN hamartoma
Back Extra: Intramuscular Vascular Anomalies
- Clinical: Localized discomfort is a prime symptom, particularly with fast-flow vascular anomalies (FAVA).
- Micro: Intramuscular venous malformations (VM) are characterized by spongiform, variably sized, dysmorphic venous channels with minimal interposed skeletal muscle or fibroadipose tissue.
- Ancillary: Identification of somatic mutations (TEK, PIK3CA, MAP2K1, KRAS) and germline and/or somatic mutations (RASA1, EPHB4, PTEN) can help in diagnosing intramuscular vascular anomalies.
Reference Gallery:
Intramuscular fast-flow vascular anomaly. There is abundant capillary proliferation and a thick-walled draining channel among skeletal muscle fibres.
Intramuscular fibroadipose vascular anomaly. Vascular nodules, grey fibrous streaks, and abundant fat form a mass in the vastus lateralis of a 15-year-old boy.
Intramuscular PTEN hamartoma of soft tissue. Predominantly intramuscular masses in the left thigh and calf of a 7-year-old girl with cutaneous stains.
Intramuscular PTEN hamartoma of soft tissue. Nodular vascular zones embedded in a moderate amount of fat in a paraspinal mass from a 16-year-old boy. There is focal necrosis from preoperative embolization.
Intramuscular PTEN hamartoma of soft tissue. There are enlarged arteries, complex draining venous channels, small nodular myxoid foci with arterial arborization, fibrofatty stroma, and lymphoid aggregates.
Intramuscular PTEN hamartoma of soft tissue. There is also a large focus of muscularized indeterminate-type vessels.
Intramuscular fibroadipose vascular anomaly. Skeletal muscle is infiltrated by thin-walled back-to-back venous clusters, fibrous tissue, fat, and lymphoid aggregates.
Intramuscular venous malformation. Closely apposed malformed venous channels of varying calibre, structure, and arrangement.
Intramuscular venous malformation. Large venous channels in the vastus intermedius muscle from a 10-year-old boy.
Intramuscular arteriovenous malformation. A mass in the musculature of the right anterior leg of a 1-year-old girl with Parkes Weber syndrome and lesional RASA1 mutation. There are multiple capillary stains in the overgrown right extremity, one in the left thigh, and others subsequently developing on the torso and neck.
Intramuscular arteriovenous malformation. Biopsy of the musculature of the right leg showing infiltration by numerous prominent arteries and several dysmorphic veins.

Q: Presenting clinically as red to black papules with a scaly or verrucous surface, [...] microscopically features ectatic superficial vessels.
Angiokeratoma. Clinical appearance.
A: Angiokeratoma
Back Extra: Angiokeratoma
- Clinical: Angiokeratoma presents as red to black papules, 2-5 mm in size, with a scaly or verrucous surface.
- Micro: Histologically, angiokeratoma is characterized by ectatic thin-walled vessels in the superficial dermis and variable epidermal hyperplasia.
- Ancillary: CD31 and D2-40 are positive in the vascular endothelium of angiokeratoma.
Reference Gallery:
Angiokeratoma. Clinical appearance.
Angiokeratoma. Vessels abutting epidermis that is variably thick.
Angiokeratoma. CD31 is positive in vascular endothelium by immunohistochemistry.
Angiokeratoma. D2-40 is positive by immunohistochemistry.
Angiokeratoma. Exophytic lesion with ectatic vessels showing a thrombus.

Q: Histologically, Angiokeratoma is characterized by thin-walled, ectatic [...] in the superficial dermis intimately abutting a variably hyperplastic epidermis.
Angiokeratoma. Vessels abutting epidermis that is variably thick.
Angiokeratoma. Exophytic lesion with ectatic vessels showing a thrombus.
A: vessels
Back Extra: Angiokeratoma
- Clinical: Angiokeratoma presents as red to black papules, 2-5 mm in size, with a scaly or verrucous surface.
- Micro: Histologically, angiokeratoma is characterized by ectatic thin-walled vessels in the superficial dermis and variable epidermal hyperplasia.
- Ancillary: CD31 and D2-40 are positive in the vascular endothelium of angiokeratoma.
Reference Gallery:
Angiokeratoma. Clinical appearance.
Angiokeratoma. Vessels abutting epidermis that is variably thick.
Angiokeratoma. CD31 is positive in vascular endothelium by immunohistochemistry.
Angiokeratoma. D2-40 is positive by immunohistochemistry.
Angiokeratoma. Exophytic lesion with ectatic vessels showing a thrombus.

Q: By immunohistochemistry, the endothelial lining of the superficial vascular channels in Angiokeratoma is characteristically positive for CD31 and [...].
Angiokeratoma. CD31 is positive in vascular endothelium by immunohistochemistry.
Angiokeratoma. D2-40 is positive by immunohistochemistry.
A: D2-40
Back Extra: Angiokeratoma
- Clinical: Angiokeratoma presents as red to black papules, 2-5 mm in size, with a scaly or verrucous surface.
- Micro: Histologically, angiokeratoma is characterized by ectatic thin-walled vessels in the superficial dermis and variable epidermal hyperplasia.
- Ancillary: CD31 and D2-40 are positive in the vascular endothelium of angiokeratoma.
Reference Gallery:
Angiokeratoma. Clinical appearance.
Angiokeratoma. Vessels abutting epidermis that is variably thick.
Angiokeratoma. CD31 is positive in vascular endothelium by immunohistochemistry.
Angiokeratoma. D2-40 is positive by immunohistochemistry.
Angiokeratoma. Exophytic lesion with ectatic vessels showing a thrombus.

Q: Clinically presenting as a port-wine stain, a [...] microscopically exhibits dilated dermal capillaries and postcapillary venules.
Capillary malformation. Numerous dilated vessels with fibromuscular walls in the lip of a 22-year-old woman with facial capillary malformation and Sturge–Weber syndrome.
Capillary malformation. Extensive capillary stain of the left lower extremity in a 1-year-old girl with Klippel–Trénaunay syndrome with lymphatic malformation, several small haemorrhagic lymphatic vesicles, and diffuse subcutaneous fibroadipocytic overgrowth.
A: Capillary Malformation
Back Extra: Capillary Malformation
- Clinical: Capillary malformations (CMs) are most commonly located in the head and neck region, but they also occur on the trunk and extremities. Facial port-wine stains are typically unilateral and can be associated with Sturge–Weber syndrome or Klippel–Trénaunay syndrome.
- Micro: Microscopic findings include dilated capillaries and postcapillary venules, sometimes with larger channels and stromal fibrosis.
- Ancillary: molecular genetics studies often reveal GNAQ or PIK3CA mutations, which can help in diagnosis and prognosis.
Reference Gallery:
Capillary malformation. Right facial capillary malformation in an 11-month-old boy with Sturge–Weber syndrome showing minimal ectasia of dermal capillary-venular vasculature.
Capillary malformation. Numerous dilated vessels with fibromuscular walls in the lip of a 22-year-old woman with facial capillary malformation and Sturge–Weber syndrome.
Capillary malformation. Extensive capillary stain of the left lower extremity in a 1-year-old girl with Klippel–Trénaunay syndrome with lymphatic malformation, several small haemorrhagic lymphatic vesicles, and diffuse subcutaneous fibroadipocytic overgrowth.
Capillary malformation. Capillary stain with dilatation of dermal venules and veins in a 25-year-old man with Klippel–Trénaunay syndrome. Barium sulfate (brown) is present in vessel lumina after injection into the vein of Servelle in a postoperative specimen.

Q: A unilateral facial Capillary Malformation is classically associated with [...] syndrome, which shows minimal to prominent dermal vascular ectasia.
Capillary malformation. Right facial capillary malformation in an 11-month-old boy with Sturge–Weber syndrome showing minimal ectasia of dermal capillary-venular vasculature.
Capillary malformation. Numerous dilated vessels with fibromuscular walls in the lip of a 22-year-old woman with facial capillary malformation and Sturge–Weber syndrome.
A: Sturge-Weber
Back Extra: Capillary Malformation
- Clinical: Capillary malformations (CMs) are most commonly located in the head and neck region, but they also occur on the trunk and extremities. Facial port-wine stains are typically unilateral and can be associated with Sturge–Weber syndrome or Klippel–Trénaunay syndrome.
- Micro: Microscopic findings include dilated capillaries and postcapillary venules, sometimes with larger channels and stromal fibrosis.
- Ancillary: molecular genetics studies often reveal GNAQ or PIK3CA mutations, which can help in diagnosis and prognosis.
Reference Gallery:
Capillary malformation. Right facial capillary malformation in an 11-month-old boy with Sturge–Weber syndrome showing minimal ectasia of dermal capillary-venular vasculature.
Capillary malformation. Numerous dilated vessels with fibromuscular walls in the lip of a 22-year-old woman with facial capillary malformation and Sturge–Weber syndrome.
Capillary malformation. Extensive capillary stain of the left lower extremity in a 1-year-old girl with Klippel–Trénaunay syndrome with lymphatic malformation, several small haemorrhagic lymphatic vesicles, and diffuse subcutaneous fibroadipocytic overgrowth.
Capillary malformation. Capillary stain with dilatation of dermal venules and veins in a 25-year-old man with Klippel–Trénaunay syndrome. Barium sulfate (brown) is present in vessel lumina after injection into the vein of Servelle in a postoperative specimen.

Q: An extensive lower extremity Capillary Malformation accompanied by lymphatic malformations and soft tissue overgrowth is characteristic of [...] syndrome.
Capillary malformation. Extensive capillary stain of the left lower extremity in a 1-year-old girl with Klippel–Trénaunay syndrome with lymphatic malformation, several small haemorrhagic lymphatic vesicles, and diffuse subcutaneous fibroadipocytic overgrowth.
Capillary malformation. Capillary stain with dilatation of dermal venules and veins in a 25-year-old man with Klippel–Trénaunay syndrome. Barium sulfate (brown) is present in vessel lumina after injection into the vein of Servelle in a postoperative specimen.
A: Klippel-Trenaunay
Back Extra: Capillary Malformation
- Clinical: Capillary malformations (CMs) are most commonly located in the head and neck region, but they also occur on the trunk and extremities. Facial port-wine stains are typically unilateral and can be associated with Sturge–Weber syndrome or Klippel–Trénaunay syndrome.
- Micro: Microscopic findings include dilated capillaries and postcapillary venules, sometimes with larger channels and stromal fibrosis.
- Ancillary: molecular genetics studies often reveal GNAQ or PIK3CA mutations, which can help in diagnosis and prognosis.
Reference Gallery:
Capillary malformation. Right facial capillary malformation in an 11-month-old boy with Sturge–Weber syndrome showing minimal ectasia of dermal capillary-venular vasculature.
Capillary malformation. Numerous dilated vessels with fibromuscular walls in the lip of a 22-year-old woman with facial capillary malformation and Sturge–Weber syndrome.
Capillary malformation. Extensive capillary stain of the left lower extremity in a 1-year-old girl with Klippel–Trénaunay syndrome with lymphatic malformation, several small haemorrhagic lymphatic vesicles, and diffuse subcutaneous fibroadipocytic overgrowth.
Capillary malformation. Capillary stain with dilatation of dermal venules and veins in a 25-year-old man with Klippel–Trénaunay syndrome. Barium sulfate (brown) is present in vessel lumina after injection into the vein of Servelle in a postoperative specimen.

Q: In Lymphatic Anomalies, the malformed lymphatic channels are lined by endothelium that is characteristically immunopositive for PROX1 and [...].
Common lymphatic malformation. Lymphatic channels vary in size, shape, and muscularization, with lumina either empty or containing protein or macrophages. Dispersed lymphoid aggregates are present.
Kaposiform lymphangiomatosis. There is moderate immunopositivity for D2-40 in spindled lymphatic endothelial cells and vicinal lymphatic vessels.
A: D2-40
Lymphatic Anomalies
- Clinical: Children with lymphatic anomalies often present with localized or regional swelling, cutaneous vesicles, or serous cavity effusions.
- Micro: Lymphatic anomalies display malformed lymphatic channels with irregularly muscularized walls, and the lymphatic endothelium is immunopositive for D2-40 and PROX1.
- Ancillary: Identification of mutations, particularly in PIK3CA or NRAS, can help in diagnosing lymphatic anomalies.
Reference Gallery:
Common lymphatic malformation. Thin-walled macrocystic and microcystic spaces in a partial resection of an extensive lesion of the left chest wall, neck, and mediastinum in a 2-year-old boy.
Common lymphatic malformation. Lymphatic channels vary in size, shape, and muscularization, with lumina either empty or containing protein or macrophages. Dispersed lymphoid aggregates are present.
Generalized lymphatic anomaly. Dysmorphic lymphatic vessels show mostly fibrous walls and a primitive anastomotic pattern. A few lymphoid aggregates are present.
Kaposiform lymphangiomatosis. There are malformed dilated lymphatic channels and peripheral cellular clusters.
Kaposiform lymphangiomatosis. Solid clusters show spindled haemosiderotic lymphatic endothelial cells with interspersed erythrocytes.
Kaposiform lymphangiomatosis. There is moderate immunopositivity for D2-40 in spindled lymphatic endothelial cells and vicinal lymphatic vessels.
Lymphatic malformation. Fat-suppressed T2-weighted axial MRI shows a well-defined, multilobulated, septated mass anterior to the left jaw, which is markedly hyperintense relative to the muscles.
Lymphatic malformation. Fat-suppressed T1-weighted contrast-enhanced axial MRI shows mild rim and septal enhancement of the mass but no enhancement of the central lymph-filled spaces.

Q: On MRI, Lymphatic Anomalies characteristically present as a well-defined, multilobulated mass with fluid-filled spaces that are markedly hyperintense on T2-weighted imaging and show [...] on T1-weighted contrast studies.
Lymphatic malformation. Fat-suppressed T2-weighted axial MRI shows a well-defined, multilobulated, septated mass anterior to the left jaw, which is markedly hyperintense relative to the muscles.
Lymphatic malformation. Fat-suppressed T1-weighted contrast-enhanced axial MRI shows mild rim and septal enhancement of the mass but no enhancement of the central lymph-filled spaces.
A: rim and septal enhancement
Lymphatic Anomalies
- Clinical: Children with lymphatic anomalies often present with localized or regional swelling, cutaneous vesicles, or serous cavity effusions.
- Micro: Lymphatic anomalies display malformed lymphatic channels with irregularly muscularized walls, and the lymphatic endothelium is immunopositive for D2-40 and PROX1.
- Ancillary: Identification of mutations, particularly in PIK3CA or NRAS, can help in diagnosing lymphatic anomalies.
Reference Gallery:
Common lymphatic malformation. Thin-walled macrocystic and microcystic spaces in a partial resection of an extensive lesion of the left chest wall, neck, and mediastinum in a 2-year-old boy.
Common lymphatic malformation. Lymphatic channels vary in size, shape, and muscularization, with lumina either empty or containing protein or macrophages. Dispersed lymphoid aggregates are present.
Generalized lymphatic anomaly. Dysmorphic lymphatic vessels show mostly fibrous walls and a primitive anastomotic pattern. A few lymphoid aggregates are present.
Kaposiform lymphangiomatosis. There are malformed dilated lymphatic channels and peripheral cellular clusters.
Kaposiform lymphangiomatosis. Solid clusters show spindled haemosiderotic lymphatic endothelial cells with interspersed erythrocytes.
Kaposiform lymphangiomatosis. There is moderate immunopositivity for D2-40 in spindled lymphatic endothelial cells and vicinal lymphatic vessels.
Lymphatic malformation. Fat-suppressed T2-weighted axial MRI shows a well-defined, multilobulated, septated mass anterior to the left jaw, which is markedly hyperintense relative to the muscles.
Lymphatic malformation. Fat-suppressed T1-weighted contrast-enhanced axial MRI shows mild rim and septal enhancement of the mass but no enhancement of the central lymph-filled spaces.

Q: Microscopically, Lymphatic Anomalies display malformed, dilated lymphatic channels with irregularly muscularized or fibrous walls, frequently accompanied by scattered [...].
Common lymphatic malformation. Lymphatic channels vary in size, shape, and muscularization, with lumina either empty or containing protein or macrophages. Dispersed lymphoid aggregates are present.
Generalized lymphatic anomaly. Dysmorphic lymphatic vessels show mostly fibrous walls and a primitive anastomotic pattern. A few lymphoid aggregates are present.
A: lymphoid aggregates
Lymphatic Anomalies
- Clinical: Children with lymphatic anomalies often present with localized or regional swelling, cutaneous vesicles, or serous cavity effusions.
- Micro: Lymphatic anomalies display malformed lymphatic channels with irregularly muscularized walls, and the lymphatic endothelium is immunopositive for D2-40 and PROX1.
- Ancillary: Identification of mutations, particularly in PIK3CA or NRAS, can help in diagnosing lymphatic anomalies.
Reference Gallery:
Common lymphatic malformation. Thin-walled macrocystic and microcystic spaces in a partial resection of an extensive lesion of the left chest wall, neck, and mediastinum in a 2-year-old boy.
Common lymphatic malformation. Lymphatic channels vary in size, shape, and muscularization, with lumina either empty or containing protein or macrophages. Dispersed lymphoid aggregates are present.
Generalized lymphatic anomaly. Dysmorphic lymphatic vessels show mostly fibrous walls and a primitive anastomotic pattern. A few lymphoid aggregates are present.
Kaposiform lymphangiomatosis. There are malformed dilated lymphatic channels and peripheral cellular clusters.
Kaposiform lymphangiomatosis. Solid clusters show spindled haemosiderotic lymphatic endothelial cells with interspersed erythrocytes.
Kaposiform lymphangiomatosis. There is moderate immunopositivity for D2-40 in spindled lymphatic endothelial cells and vicinal lymphatic vessels.
Lymphatic malformation. Fat-suppressed T2-weighted axial MRI shows a well-defined, multilobulated, septated mass anterior to the left jaw, which is markedly hyperintense relative to the muscles.
Lymphatic malformation. Fat-suppressed T1-weighted contrast-enhanced axial MRI shows mild rim and septal enhancement of the mass but no enhancement of the central lymph-filled spaces.

Q: Microscopically, common Venous Malformations consist of dysmorphic venous channels of varying caliber that frequently contain organizing [...].
Common venous malformation. A mass in the hand and distal forearm of a 6-year-old boy, accompanied by a bluish tinge and dilated dermal veins.
Common venous malformation. Dysmorphic veins and organizing thrombi of varying age.
A: thrombi
Back Extra: Venous Malformations
- Clinical: Venous malformations (CVM) present as soft, compressible masses with a bluish tint, often involving subcutaneous fat, dermis, and underlying soft tissue. Blue rubber bleb naevus syndrome (BRBNS) and verrucous venous malformation (VVM) are specific variants with distinct clinical presentations.
- Micro: Abnormal venous channels in CVM vary in number, calibre, shape, and muscularization, often containing organizing thrombi. VVM shows verrucous epidermis and small vessels throughout the dermis and hypodermis, with thickened vascular walls.
- Ancillary: Demonstration of mutations in TEK, PIK3CA, or MAP2K1 can help confirm the type of venous malformation. These mutations upregulate PI3K/AKT/mTOR and RAS/MAPK signalling pathways, which are crucial for angiogenesis and vasculogenesis.
Reference Gallery:
Common venous malformation. A mass in the hand and distal forearm of a 6-year-old boy, accompanied by a bluish tinge and dilated dermal veins.
Common venous malformation. Dysmorphic veins and organizing thrombi of varying age.
Blue rubber bleb naevus syndrome. Typical disseminated small, raised, blue lesions in a 20-year-old woman.
Blue rubber bleb naevus syndrome. A 9-month-old boy with a congenital massive bleb in the sacral region and several small cutaneous lesions elsewhere, including one on the left lateral thigh.
Blue rubber bleb naevus syndrome. A shin lesion from a 1-month-old infant showing several large and minimally muscularized dermal venous channels.
Glomuvenous malformation. Subcutaneous large and irregularly muscularized venous channels with complex lumina in a penile lesion of a 10-year-old boy.
Glomuvenous malformation. Round glomus cells merging with mural smooth muscle in an abnormal vein.
Verrucous venous malformation. A 12-year-old girl with congenital, linearly distributed, grouped, verrucous, maroon lesions, after multiple excisions.
Verrucous venous malformation. Verrucous epidermis and small vessels throughout the dermis and hypodermis.
Verrucous venous malformation. Thickened vascular walls with multilamellated basement membrane.
Verrucous venous malformation. Focal endothelial immunopositivity for GLUT1.
Venous malformation. Fat-suppressed T2-weighted coronal MRI shows the extent of the venous malformation, which appears as a hyperintense, multilobulated, septated mass involving the subcutaneous tissue and muscles of the right upper extremity and right chest wall.

Q: A distinct variant of Venous Malformations that presents with widely disseminated small, raised, blue cutaneous lesions is known as [...].
Blue rubber bleb naevus syndrome. Typical disseminated small, raised, blue lesions in a 20-year-old woman.
Blue rubber bleb naevus syndrome. A shin lesion from a 1-month-old infant showing several large and minimally muscularized dermal venous channels.
A: blue rubber bleb nevus syndrome
Back Extra: Venous Malformations
- Clinical: Venous malformations (CVM) present as soft, compressible masses with a bluish tint, often involving subcutaneous fat, dermis, and underlying soft tissue. Blue rubber bleb naevus syndrome (BRBNS) and verrucous venous malformation (VVM) are specific variants with distinct clinical presentations.
- Micro: Abnormal venous channels in CVM vary in number, calibre, shape, and muscularization, often containing organizing thrombi. VVM shows verrucous epidermis and small vessels throughout the dermis and hypodermis, with thickened vascular walls.
- Ancillary: Demonstration of mutations in TEK, PIK3CA, or MAP2K1 can help confirm the type of venous malformation. These mutations upregulate PI3K/AKT/mTOR and RAS/MAPK signalling pathways, which are crucial for angiogenesis and vasculogenesis.
Reference Gallery:
Common venous malformation. A mass in the hand and distal forearm of a 6-year-old boy, accompanied by a bluish tinge and dilated dermal veins.
Common venous malformation. Dysmorphic veins and organizing thrombi of varying age.
Blue rubber bleb naevus syndrome. Typical disseminated small, raised, blue lesions in a 20-year-old woman.
Blue rubber bleb naevus syndrome. A 9-month-old boy with a congenital massive bleb in the sacral region and several small cutaneous lesions elsewhere, including one on the left lateral thigh.
Blue rubber bleb naevus syndrome. A shin lesion from a 1-month-old infant showing several large and minimally muscularized dermal venous channels.
Glomuvenous malformation. Subcutaneous large and irregularly muscularized venous channels with complex lumina in a penile lesion of a 10-year-old boy.
Glomuvenous malformation. Round glomus cells merging with mural smooth muscle in an abnormal vein.
Verrucous venous malformation. A 12-year-old girl with congenital, linearly distributed, grouped, verrucous, maroon lesions, after multiple excisions.
Verrucous venous malformation. Verrucous epidermis and small vessels throughout the dermis and hypodermis.
Verrucous venous malformation. Thickened vascular walls with multilamellated basement membrane.
Verrucous venous malformation. Focal endothelial immunopositivity for GLUT1.
Venous malformation. Fat-suppressed T2-weighted coronal MRI shows the extent of the venous malformation, which appears as a hyperintense, multilobulated, septated mass involving the subcutaneous tissue and muscles of the right upper extremity and right chest wall.

Q: The [...] variant of Venous Malformations clinically presents as linearly distributed maroon lesions and microscopically features an acanthotic epidermis overlying small dermal vessels with thickened walls.
Verrucous venous malformation. A 12-year-old girl with congenital, linearly distributed, grouped, verrucous, maroon lesions, after multiple excisions.
Verrucous venous malformation. Verrucous epidermis and small vessels throughout the dermis and hypodermis.
Verrucous venous malformation. Thickened vascular walls with multilamellated basement membrane.
A: verrucous
Back Extra: Venous Malformations
- Clinical: Venous malformations (CVM) present as soft, compressible masses with a bluish tint, often involving subcutaneous fat, dermis, and underlying soft tissue. Blue rubber bleb naevus syndrome (BRBNS) and verrucous venous malformation (VVM) are specific variants with distinct clinical presentations.
- Micro: Abnormal venous channels in CVM vary in number, calibre, shape, and muscularization, often containing organizing thrombi. VVM shows verrucous epidermis and small vessels throughout the dermis and hypodermis, with thickened vascular walls.
- Ancillary: Demonstration of mutations in TEK, PIK3CA, or MAP2K1 can help confirm the type of venous malformation. These mutations upregulate PI3K/AKT/mTOR and RAS/MAPK signalling pathways, which are crucial for angiogenesis and vasculogenesis.
Reference Gallery:
Common venous malformation. A mass in the hand and distal forearm of a 6-year-old boy, accompanied by a bluish tinge and dilated dermal veins.
Common venous malformation. Dysmorphic veins and organizing thrombi of varying age.
Blue rubber bleb naevus syndrome. Typical disseminated small, raised, blue lesions in a 20-year-old woman.
Blue rubber bleb naevus syndrome. A 9-month-old boy with a congenital massive bleb in the sacral region and several small cutaneous lesions elsewhere, including one on the left lateral thigh.
Blue rubber bleb naevus syndrome. A shin lesion from a 1-month-old infant showing several large and minimally muscularized dermal venous channels.
Glomuvenous malformation. Subcutaneous large and irregularly muscularized venous channels with complex lumina in a penile lesion of a 10-year-old boy.
Glomuvenous malformation. Round glomus cells merging with mural smooth muscle in an abnormal vein.
Verrucous venous malformation. A 12-year-old girl with congenital, linearly distributed, grouped, verrucous, maroon lesions, after multiple excisions.
Verrucous venous malformation. Verrucous epidermis and small vessels throughout the dermis and hypodermis.
Verrucous venous malformation. Thickened vascular walls with multilamellated basement membrane.
Verrucous venous malformation. Focal endothelial immunopositivity for GLUT1.
Venous malformation. Fat-suppressed T2-weighted coronal MRI shows the extent of the venous malformation, which appears as a hyperintense, multilobulated, septated mass involving the subcutaneous tissue and muscles of the right upper extremity and right chest wall.

Q: In an Adrenal Cortical Tumor, histologic features such as marked pleomorphism, frequent atypical mitoses, and true tumor [...] strongly suggest a malignant course (carcinoma).
Adrenal cortical carcinoma. The mass is grossly well circumscribed. The cut surface shows areas of haemorrhage and necrosis.
Adrenal cortical carcinoma. High-grade adrenal cortical carcinoma with an atypical mitotic figure and apoptotic body.
Adrenal cortical carcinoma. True tumour necrosis.
A: necrosis
Back Extra: Adrenal Cortical Tumor
- Clinical: Adrenal cortical tumours are most often detected due to endocrinopathies such as virilization, Cushing syndrome, and feminization, with non-functioning tumours being less common and often diagnosed incidentally.
- Micro: Adrenal cortical adenomas typically have a nested or trabecular architecture with uniform cells, while carcinomas show marked pleomorphism, mitotic activity, and necrosis.
- Ancillary: Immunohistochemical markers such as α-inhibin, melan-A, and SF1 are positive in adrenal cortical tumours, while chromogranin is negative. A Ki-67 proliferation index > 15% suggests a malignant course.
Reference Gallery:
Adrenal cortical tumours. Overall genomic landscape of paediatric adrenal cortical tumours showing the association between clinical, pathological, and molecular attributes, with identification of three groups. A The upper panel details the clinicopathological features of 19 patients. The middle panel details the genetic alterations, including essential molecular features. The lower panel displays the expression of selected cell-cycle genes. B Kaplan–Meier analysis of group 1 tumours as compared with the other groups combined.
Adrenal cortical tumours. Circos plots demonstrating the overall association between pathological features and the degree of genetic alterations. Accumulation of genetic alterations is associated with increasing tumour weight and aggressive tumour phenotype.
Adrenal cortical carcinoma. The mass is grossly well circumscribed. The cut surface shows areas of haemorrhage and necrosis.
Adrenal cortical tumour. This tumour shows a mixture of lipid-rich and lipid-poor cells with nuclear pleomorphism.
Adrenal cortical tumour. High-grade adrenal cortical carcinoma with small-cell features and mitotic figures.
Adrenal cortical tumour. This tumour shows abundant eosinophilic cytoplasm, occasional mitotic figures, and nuclear pleomorphism.
Adrenal cortical carcinoma. High-grade adrenal cortical carcinoma with an atypical mitotic figure and apoptotic body.
Adrenal cortical carcinoma. True tumour necrosis.
Adrenal cortical tumour. Immunoreactivity for α-inhibin, which commonly shows a mosaic pattern of staining.
Adrenal cortical carcinoma. Immunoreactivity for melan-A.
Adrenal cortical carcinoma. Immunoreactivity for SF1.
Adrenal cortical carcinoma. Immunoreactivity for Ki-67. A Ki-67 proliferation index of < 10% predicts a benign course, whereas > 15% predicts a malignant course.

Q: An Adrenal Cortical Tumor is typically negative for chromogranin but characteristically positive for immunohistochemical markers such as melan-A, SF1, and [...].
Adrenal cortical tumour. Immunoreactivity for α-inhibin, which commonly shows a mosaic pattern of staining.
Adrenal cortical carcinoma. Immunoreactivity for melan-A.
Adrenal cortical carcinoma. Immunoreactivity for SF1.
A: α-inhibin
Back Extra: Adrenal Cortical Tumor
- Clinical: Adrenal cortical tumours are most often detected due to endocrinopathies such as virilization, Cushing syndrome, and feminization, with non-functioning tumours being less common and often diagnosed incidentally.
- Micro: Adrenal cortical adenomas typically have a nested or trabecular architecture with uniform cells, while carcinomas show marked pleomorphism, mitotic activity, and necrosis.
- Ancillary: Immunohistochemical markers such as α-inhibin, melan-A, and SF1 are positive in adrenal cortical tumours, while chromogranin is negative. A Ki-67 proliferation index > 15% suggests a malignant course.
Reference Gallery:
Adrenal cortical tumours. Overall genomic landscape of paediatric adrenal cortical tumours showing the association between clinical, pathological, and molecular attributes, with identification of three groups. A The upper panel details the clinicopathological features of 19 patients. The middle panel details the genetic alterations, including essential molecular features. The lower panel displays the expression of selected cell-cycle genes. B Kaplan–Meier analysis of group 1 tumours as compared with the other groups combined.
Adrenal cortical tumours. Circos plots demonstrating the overall association between pathological features and the degree of genetic alterations. Accumulation of genetic alterations is associated with increasing tumour weight and aggressive tumour phenotype.
Adrenal cortical carcinoma. The mass is grossly well circumscribed. The cut surface shows areas of haemorrhage and necrosis.
Adrenal cortical tumour. This tumour shows a mixture of lipid-rich and lipid-poor cells with nuclear pleomorphism.
Adrenal cortical tumour. High-grade adrenal cortical carcinoma with small-cell features and mitotic figures.
Adrenal cortical tumour. This tumour shows abundant eosinophilic cytoplasm, occasional mitotic figures, and nuclear pleomorphism.
Adrenal cortical carcinoma. High-grade adrenal cortical carcinoma with an atypical mitotic figure and apoptotic body.
Adrenal cortical carcinoma. True tumour necrosis.
Adrenal cortical tumour. Immunoreactivity for α-inhibin, which commonly shows a mosaic pattern of staining.
Adrenal cortical carcinoma. Immunoreactivity for melan-A.
Adrenal cortical carcinoma. Immunoreactivity for SF1.
Adrenal cortical carcinoma. Immunoreactivity for Ki-67. A Ki-67 proliferation index of < 10% predicts a benign course, whereas > 15% predicts a malignant course.

Q: To help predict the clinical behavior of an Adrenal Cortical Tumor, an immunohistochemical [...] proliferation index of > 15% is indicative of a malignant course.
Adrenal cortical carcinoma. Immunoreactivity for Ki-67. A Ki-67 proliferation index of < 10% predicts a benign course, whereas > 15% predicts a malignant course.
A: Ki-67
Back Extra: Adrenal Cortical Tumor
- Clinical: Adrenal cortical tumours are most often detected due to endocrinopathies such as virilization, Cushing syndrome, and feminization, with non-functioning tumours being less common and often diagnosed incidentally.
- Micro: Adrenal cortical adenomas typically have a nested or trabecular architecture with uniform cells, while carcinomas show marked pleomorphism, mitotic activity, and necrosis.
- Ancillary: Immunohistochemical markers such as α-inhibin, melan-A, and SF1 are positive in adrenal cortical tumours, while chromogranin is negative. A Ki-67 proliferation index > 15% suggests a malignant course.
Reference Gallery:
Adrenal cortical tumours. Overall genomic landscape of paediatric adrenal cortical tumours showing the association between clinical, pathological, and molecular attributes, with identification of three groups. A The upper panel details the clinicopathological features of 19 patients. The middle panel details the genetic alterations, including essential molecular features. The lower panel displays the expression of selected cell-cycle genes. B Kaplan–Meier analysis of group 1 tumours as compared with the other groups combined.
Adrenal cortical tumours. Circos plots demonstrating the overall association between pathological features and the degree of genetic alterations. Accumulation of genetic alterations is associated with increasing tumour weight and aggressive tumour phenotype.
Adrenal cortical carcinoma. The mass is grossly well circumscribed. The cut surface shows areas of haemorrhage and necrosis.
Adrenal cortical tumour. This tumour shows a mixture of lipid-rich and lipid-poor cells with nuclear pleomorphism.
Adrenal cortical tumour. High-grade adrenal cortical carcinoma with small-cell features and mitotic figures.
Adrenal cortical tumour. This tumour shows abundant eosinophilic cytoplasm, occasional mitotic figures, and nuclear pleomorphism.
Adrenal cortical carcinoma. High-grade adrenal cortical carcinoma with an atypical mitotic figure and apoptotic body.
Adrenal cortical carcinoma. True tumour necrosis.
Adrenal cortical tumour. Immunoreactivity for α-inhibin, which commonly shows a mosaic pattern of staining.
Adrenal cortical carcinoma. Immunoreactivity for melan-A.
Adrenal cortical carcinoma. Immunoreactivity for SF1.
Adrenal cortical carcinoma. Immunoreactivity for Ki-67. A Ki-67 proliferation index of < 10% predicts a benign course, whereas > 15% predicts a malignant course.

Q: Histologically, Neuroendocrine Tumors characteristically exhibit an insular, nested, or trabecular architecture with polygonal cells containing finely granular, [...] chromatin.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The PanNET shows trabeculae and a cord-like growth pattern with fibrotic stroma.
A: stippled ("salt-and-pepper")
Back Extra: Neuroendocrine Tumours
- Clinical: The clinical presentation of neuroendocrine tumours (NETs) depends on their site of origin and hormonal activity. Symptoms can include hypoglycaemia due to insulinoma, gastrin excess due to gastrinoma, and carcinoid syndrome due to metastatic small bowel NET.
- Micro: Histologically, most NETs have an insular/nested architecture with polygonal cells and stippled chromatin (salt-and-pepper nuclei). The tumour cells express INSM1, synaptophysin, chromogranins, and keratins.
- Ancillary: Tumour cells are variably positive for insulin gene enhancer protein ISL1, PDX1, PAX6, polyclonal PAX8, and CDX2. Immunostaining for hormones can help differentiate between MEN1 and other rare manifestations.
Reference Gallery:
Structural and functional imaging studies in a paediatric age–onset metastatic insulin-producing well-differentiated pancreatic neuroendocrine tumour (PanNET). An 11-year-old child presented with an insulin-producing well-differentiated PanNET with low-grade proliferative features (G1 NET; insulinoma). Subsequently, the patient developed progressive symptoms related to the insulinoma and was found to have diffuse miliary hypervascular liver metastases in association with massive peritumoural steatosis. The metastatic disease was difficult to see on CT (A) and MRI (B; in-phase and out-of-phase T1 sequence images are shown), as well as on initial 68Ga-DOTATOC PET-CT imaging (C), because of the small size of the tumour deposits. The interim liver biopsy showed only steatosis. During follow-up, the largest metastatic tumour deposit did show uptake using 68Ga-exendin PET-CT (GLP-1–targeted PET) (D). Arrows indicate the dominant metastatic tumour deposit in different imaging modalities.
Pancreatic neuroendocrine tumour (PanNET). Gross findings of a paediatric age–onset PanNET.
Bronchial/pulmonary neuroendocrine tumour (NET). Gross findings of a paediatric age–onset bronchial/pulmonary NET.
Ileal enterochromaffin (EC)-cell neuroendocrine tumour (NET). An ileal EC-cell well-differentiated NET in a 17-year-old girl.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). Liver metastasis in a paediatric patient with a primary ileal EC-cell NET.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The PanNET shows trabeculae and a cord-like growth pattern with fibrotic stroma.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for chromogranin A.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for CAM5.2 and shows angioinvasion, lymphatic invasion, and perineural invasion (arrow).
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The Ki-67 index is 14.8% in hotspots.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae (chromogranin A).

Q: Immunohistochemical staining in Neuroendocrine Tumors typically demonstrates strong, diffuse positivity for broad neuroendocrine markers such as synaptophysin, INSM1, and [...].
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for chromogranin A.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae (chromogranin A).
A: chromogranin
Back Extra: Neuroendocrine Tumours
- Clinical: The clinical presentation of neuroendocrine tumours (NETs) depends on their site of origin and hormonal activity. Symptoms can include hypoglycaemia due to insulinoma, gastrin excess due to gastrinoma, and carcinoid syndrome due to metastatic small bowel NET.
- Micro: Histologically, most NETs have an insular/nested architecture with polygonal cells and stippled chromatin (salt-and-pepper nuclei). The tumour cells express INSM1, synaptophysin, chromogranins, and keratins.
- Ancillary: Tumour cells are variably positive for insulin gene enhancer protein ISL1, PDX1, PAX6, polyclonal PAX8, and CDX2. Immunostaining for hormones can help differentiate between MEN1 and other rare manifestations.
Reference Gallery:
Structural and functional imaging studies in a paediatric age–onset metastatic insulin-producing well-differentiated pancreatic neuroendocrine tumour (PanNET). An 11-year-old child presented with an insulin-producing well-differentiated PanNET with low-grade proliferative features (G1 NET; insulinoma). Subsequently, the patient developed progressive symptoms related to the insulinoma and was found to have diffuse miliary hypervascular liver metastases in association with massive peritumoural steatosis. The metastatic disease was difficult to see on CT (A) and MRI (B; in-phase and out-of-phase T1 sequence images are shown), as well as on initial 68Ga-DOTATOC PET-CT imaging (C), because of the small size of the tumour deposits. The interim liver biopsy showed only steatosis. During follow-up, the largest metastatic tumour deposit did show uptake using 68Ga-exendin PET-CT (GLP-1–targeted PET) (D). Arrows indicate the dominant metastatic tumour deposit in different imaging modalities.
Pancreatic neuroendocrine tumour (PanNET). Gross findings of a paediatric age–onset PanNET.
Bronchial/pulmonary neuroendocrine tumour (NET). Gross findings of a paediatric age–onset bronchial/pulmonary NET.
Ileal enterochromaffin (EC)-cell neuroendocrine tumour (NET). An ileal EC-cell well-differentiated NET in a 17-year-old girl.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). Liver metastasis in a paediatric patient with a primary ileal EC-cell NET.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The PanNET shows trabeculae and a cord-like growth pattern with fibrotic stroma.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for chromogranin A.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for CAM5.2 and shows angioinvasion, lymphatic invasion, and perineural invasion (arrow).
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The Ki-67 index is 14.8% in hotspots.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae (chromogranin A).

Q: When small bowel Neuroendocrine Tumors metastasize to the liver, bypassing hepatic first-pass metabolism, patients may classically present with [...], characterized by cutaneous flushing and diarrhea.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). Liver metastasis in a paediatric patient with a primary ileal EC-cell NET.
A: carcinoid syndrome
Back Extra: Neuroendocrine Tumours
- Clinical: The clinical presentation of neuroendocrine tumours (NETs) depends on their site of origin and hormonal activity. Symptoms can include hypoglycaemia due to insulinoma, gastrin excess due to gastrinoma, and carcinoid syndrome due to metastatic small bowel NET.
- Micro: Histologically, most NETs have an insular/nested architecture with polygonal cells and stippled chromatin (salt-and-pepper nuclei). The tumour cells express INSM1, synaptophysin, chromogranins, and keratins.
- Ancillary: Tumour cells are variably positive for insulin gene enhancer protein ISL1, PDX1, PAX6, polyclonal PAX8, and CDX2. Immunostaining for hormones can help differentiate between MEN1 and other rare manifestations.
Reference Gallery:
Structural and functional imaging studies in a paediatric age–onset metastatic insulin-producing well-differentiated pancreatic neuroendocrine tumour (PanNET). An 11-year-old child presented with an insulin-producing well-differentiated PanNET with low-grade proliferative features (G1 NET; insulinoma). Subsequently, the patient developed progressive symptoms related to the insulinoma and was found to have diffuse miliary hypervascular liver metastases in association with massive peritumoural steatosis. The metastatic disease was difficult to see on CT (A) and MRI (B; in-phase and out-of-phase T1 sequence images are shown), as well as on initial 68Ga-DOTATOC PET-CT imaging (C), because of the small size of the tumour deposits. The interim liver biopsy showed only steatosis. During follow-up, the largest metastatic tumour deposit did show uptake using 68Ga-exendin PET-CT (GLP-1–targeted PET) (D). Arrows indicate the dominant metastatic tumour deposit in different imaging modalities.
Pancreatic neuroendocrine tumour (PanNET). Gross findings of a paediatric age–onset PanNET.
Bronchial/pulmonary neuroendocrine tumour (NET). Gross findings of a paediatric age–onset bronchial/pulmonary NET.
Ileal enterochromaffin (EC)-cell neuroendocrine tumour (NET). An ileal EC-cell well-differentiated NET in a 17-year-old girl.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). Liver metastasis in a paediatric patient with a primary ileal EC-cell NET.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The PanNET shows trabeculae and a cord-like growth pattern with fibrotic stroma.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for chromogranin A.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for CAM5.2 and shows angioinvasion, lymphatic invasion, and perineural invasion (arrow).
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The Ki-67 index is 14.8% in hotspots.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae (chromogranin A).

Q: Microscopically, Phaeochromocytoma typically exhibits a nested [...] pattern composed of tumor cells resembling normal chromaffin cells with basophilic to amphophilic granular cytoplasm.
Conventional cytomorphology in paediatric phaeochromocytoma. Like in adults, conventional phaeochromocytomas in children consist of tumour cells resembling normal chromaffin cells that display basophilic to amphophilic cytoplasmic granularity. The cells in this example show mild nuclear pleomorphism and occasional nuclear pseudoinclusions, which can also be seen in adrenal cortical carcinomas.
A: Zellballen
Back Extra: Phaeochromocytoma
- Clinical: Symptoms of paediatric phaeochromocytoma often include hypertension, headache, and diaphoresis, with sustained rather than episodic manifestations.
- Micro: Most paediatric phaeochromocytomas exhibit a nested Zellballen pattern, with tumour cells resembling normal chromaffin cells and displaying basophilic to amphophilic granular cytoplasm.
- Ancillary: Immunohistochemical staining for chromogranin A, synaptophysin, and DBH is positive in phaeochromocytomas, while staining for keratins is negative.
Reference Gallery:
Conventional cytomorphology in paediatric phaeochromocytoma. Like in adults, conventional phaeochromocytomas in children consist of tumour cells resembling normal chromaffin cells that display basophilic to amphophilic cytoplasmic granularity. The cells in this example show mild nuclear pleomorphism and occasional nuclear pseudoinclusions, which can also be seen in adrenal cortical carcinomas.
SDH-related paediatric phaeochromocytoma. Cytoplasmic eosinophilia and/or intracytoplasmic vacuoles are variably noted.
Adrenal gland from a patient with paediatric-onset multiple endocrine neoplasia type 2A syndrome with a microphaeochromocytoma arising in the background of adrenal medullary hyperplasia. Arrows indicate a microtumour in the background of expanded (hyperplastic) adrenal medulla.
Gross findings in a paediatric phaeochromocytoma. The cut surface of the adrenal gland shows a phaeochromocytoma.
Adrenal phaeochromocytoma. Iobenguane (metaiodobenzylguanidine; 123I-MIBG) scintigraphy shows bilateral uptake in both adrenal tumours.
Adrenal phaeochromocytoma. Clear cell change in a phaeochromocytoma should not be mistaken for an adrenal cortical neoplasm. The spectrum of clear cell change varies in phaeochromocytomas. This composite photomicrograph illustrates an example of diffuse zona fasciculata–like clear cell change in a von Hippel–Lindau syndrome–related phaeochromocytoma.
Adrenal phaeochromocytoma. Biomarkers of phaeochromocytomas. The tumour cells are strongly and diffusely positive for chromogranin A.
Adrenal phaeochromocytoma. MRI studies show a heterogeneous adrenal tumour (arrow).
Adrenal phaeochromocytoma. SDHB is a crucial molecular immunohistochemistry biomarker in the detection of SDH-related pathogenesis. Loss of SDHB immunoreactivity is regarded as a surrogate biomarker for SDH gene–related tumours, with a loss of cytoplasmic granular staining being a sign of succinate dehydrogenase immunodeficiency. The presence of positive staining in endothelial cells is an obligatory endogenous control.
Adrenal phaeochromocytoma. Intratumoural sustentacular cells in a paediatric phaeochromocytoma. Tumours show intertumoural and intratumoural variations in sustentacular cells (S100-positive and SOX10-positive), ranging from a well-developed sustentacular cell network (shown here) to sustentacular cells that are reduced or disorganized.
Adrenal phaeochromocytoma. T2-weighted MRI shows a hyperintense tumour (arrow) in a patient with a family history of von Hippel–Lindau syndrome.
Phaeochromocytoma. Contrast-enhanced axial CT shows a large mass in the left adrenal gland, which is posterior to the pancreatic tail, with marked contrast enhancement and well-defined internal cystic change.

Q: Immunohistochemical staining in Phaeochromocytoma is characteristically strongly and diffusely positive for neuroendocrine markers such as synaptophysin and [...], while remaining negative for keratins.
Adrenal phaeochromocytoma. Biomarkers of phaeochromocytomas. The tumour cells are strongly and diffusely positive for chromogranin A.
A: chromogranin A
Back Extra: Phaeochromocytoma
- Clinical: Symptoms of paediatric phaeochromocytoma often include hypertension, headache, and diaphoresis, with sustained rather than episodic manifestations.
- Micro: Most paediatric phaeochromocytomas exhibit a nested Zellballen pattern, with tumour cells resembling normal chromaffin cells and displaying basophilic to amphophilic granular cytoplasm.
- Ancillary: Immunohistochemical staining for chromogranin A, synaptophysin, and DBH is positive in phaeochromocytomas, while staining for keratins is negative.
Reference Gallery:
Conventional cytomorphology in paediatric phaeochromocytoma. Like in adults, conventional phaeochromocytomas in children consist of tumour cells resembling normal chromaffin cells that display basophilic to amphophilic cytoplasmic granularity. The cells in this example show mild nuclear pleomorphism and occasional nuclear pseudoinclusions, which can also be seen in adrenal cortical carcinomas.
SDH-related paediatric phaeochromocytoma. Cytoplasmic eosinophilia and/or intracytoplasmic vacuoles are variably noted.
Adrenal gland from a patient with paediatric-onset multiple endocrine neoplasia type 2A syndrome with a microphaeochromocytoma arising in the background of adrenal medullary hyperplasia. Arrows indicate a microtumour in the background of expanded (hyperplastic) adrenal medulla.
Gross findings in a paediatric phaeochromocytoma. The cut surface of the adrenal gland shows a phaeochromocytoma.
Adrenal phaeochromocytoma. Iobenguane (metaiodobenzylguanidine; 123I-MIBG) scintigraphy shows bilateral uptake in both adrenal tumours.
Adrenal phaeochromocytoma. Clear cell change in a phaeochromocytoma should not be mistaken for an adrenal cortical neoplasm. The spectrum of clear cell change varies in phaeochromocytomas. This composite photomicrograph illustrates an example of diffuse zona fasciculata–like clear cell change in a von Hippel–Lindau syndrome–related phaeochromocytoma.
Adrenal phaeochromocytoma. Biomarkers of phaeochromocytomas. The tumour cells are strongly and diffusely positive for chromogranin A.
Adrenal phaeochromocytoma. MRI studies show a heterogeneous adrenal tumour (arrow).
Adrenal phaeochromocytoma. SDHB is a crucial molecular immunohistochemistry biomarker in the detection of SDH-related pathogenesis. Loss of SDHB immunoreactivity is regarded as a surrogate biomarker for SDH gene–related tumours, with a loss of cytoplasmic granular staining being a sign of succinate dehydrogenase immunodeficiency. The presence of positive staining in endothelial cells is an obligatory endogenous control.
Adrenal phaeochromocytoma. Intratumoural sustentacular cells in a paediatric phaeochromocytoma. Tumours show intertumoural and intratumoural variations in sustentacular cells (S100-positive and SOX10-positive), ranging from a well-developed sustentacular cell network (shown here) to sustentacular cells that are reduced or disorganized.
Adrenal phaeochromocytoma. T2-weighted MRI shows a hyperintense tumour (arrow) in a patient with a family history of von Hippel–Lindau syndrome.
Phaeochromocytoma. Contrast-enhanced axial CT shows a large mass in the left adrenal gland, which is posterior to the pancreatic tail, with marked contrast enhancement and well-defined internal cystic change.

Q: In Phaeochromocytoma, the neoplastic cells are characteristically surrounded by an intratumoral network of sustentacular cells, which highlight positively for S100 and [...].
Adrenal phaeochromocytoma. Intratumoural sustentacular cells in a paediatric phaeochromocytoma. Tumours show intertumoural and intratumoural variations in sustentacular cells (S100-positive and SOX10-positive), ranging from a well-developed sustentacular cell network (shown here) to sustentacular cells that are reduced or disorganized.
A: SOX10
Back Extra: Phaeochromocytoma
- Clinical: Symptoms of paediatric phaeochromocytoma often include hypertension, headache, and diaphoresis, with sustained rather than episodic manifestations.
- Micro: Most paediatric phaeochromocytomas exhibit a nested Zellballen pattern, with tumour cells resembling normal chromaffin cells and displaying basophilic to amphophilic granular cytoplasm.
- Ancillary: Immunohistochemical staining for chromogranin A, synaptophysin, and DBH is positive in phaeochromocytomas, while staining for keratins is negative.
Reference Gallery:
Conventional cytomorphology in paediatric phaeochromocytoma. Like in adults, conventional phaeochromocytomas in children consist of tumour cells resembling normal chromaffin cells that display basophilic to amphophilic cytoplasmic granularity. The cells in this example show mild nuclear pleomorphism and occasional nuclear pseudoinclusions, which can also be seen in adrenal cortical carcinomas.
SDH-related paediatric phaeochromocytoma. Cytoplasmic eosinophilia and/or intracytoplasmic vacuoles are variably noted.
Adrenal gland from a patient with paediatric-onset multiple endocrine neoplasia type 2A syndrome with a microphaeochromocytoma arising in the background of adrenal medullary hyperplasia. Arrows indicate a microtumour in the background of expanded (hyperplastic) adrenal medulla.
Gross findings in a paediatric phaeochromocytoma. The cut surface of the adrenal gland shows a phaeochromocytoma.
Adrenal phaeochromocytoma. Iobenguane (metaiodobenzylguanidine; 123I-MIBG) scintigraphy shows bilateral uptake in both adrenal tumours.
Adrenal phaeochromocytoma. Clear cell change in a phaeochromocytoma should not be mistaken for an adrenal cortical neoplasm. The spectrum of clear cell change varies in phaeochromocytomas. This composite photomicrograph illustrates an example of diffuse zona fasciculata–like clear cell change in a von Hippel–Lindau syndrome–related phaeochromocytoma.
Adrenal phaeochromocytoma. Biomarkers of phaeochromocytomas. The tumour cells are strongly and diffusely positive for chromogranin A.
Adrenal phaeochromocytoma. MRI studies show a heterogeneous adrenal tumour (arrow).
Adrenal phaeochromocytoma. SDHB is a crucial molecular immunohistochemistry biomarker in the detection of SDH-related pathogenesis. Loss of SDHB immunoreactivity is regarded as a surrogate biomarker for SDH gene–related tumours, with a loss of cytoplasmic granular staining being a sign of succinate dehydrogenase immunodeficiency. The presence of positive staining in endothelial cells is an obligatory endogenous control.
Adrenal phaeochromocytoma. Intratumoural sustentacular cells in a paediatric phaeochromocytoma. Tumours show intertumoural and intratumoural variations in sustentacular cells (S100-positive and SOX10-positive), ranging from a well-developed sustentacular cell network (shown here) to sustentacular cells that are reduced or disorganized.
Adrenal phaeochromocytoma. T2-weighted MRI shows a hyperintense tumour (arrow) in a patient with a family history of von Hippel–Lindau syndrome.
Phaeochromocytoma. Contrast-enhanced axial CT shows a large mass in the left adrenal gland, which is posterior to the pancreatic tail, with marked contrast enhancement and well-defined internal cystic change.

Q: The classic histologic pattern seen in Parasympathetic Paraganglioma (Head and Neck Paraganglioma) consists of prominent nests of clear to eosinophilic tumor cells surrounded by an intricate vascular network, a morphology termed [...] architecture.
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for S100 (nuclear and cytoplasmic). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.
Carotid body paraganglioma. The relative levels of expression of neuroendocrine markers in this apparently sporadic carotid body paraganglioma are similar to those generally seen in other head and neck parasympathetic paragangliomas: synaptophysin (seen here) shows the strongest expression, followed by chromogranin A and tyrosine hydroxylase.
A: Zellballen
Back Extra: Parasympathetic Paraganglioma (Head and Neck Paraganglioma)
- Clinical: Parasympathetic paragangliomas are typically discovered incidentally or through genetic testing in families with known histories. Only about 4% are biochemically functional, producing predominantly dopamine and/or 3-methoxytyramine.
- Micro: Carotid body paragangliomas exhibit a Zellballen architecture with clear cells and well-developed, sometimes cavernous, blood vessels. Sustentacular cells are inconspicuous with H&E stains.
- Ancillary: Immunohistochemical staining for neuroendocrine markers (synaptophysin, chromogranin A, tyrosine hydroxylase) and S100 is helpful. SDHB mutations are associated with a higher risk of metastasis and other tumours.
Reference Gallery:
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. T2-weighted MRI showed a hypervascular tumour in the bifurcation of the carotid artery.
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. To assess potential surgical options, CT angiography was performed, further demarcating the lesion, which was deemed unresectable because of the encasement of the internal and external carotid.
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. To exclude metastases, a 68Ga-DOTATOC PET-CT image was acquired, showing bright labelling consistent with intense expression of SSRT. Genetic testing showed a germline SDHD mutation.
Carotid body paraganglioma. The spongy cut surface (shown here) of this sporadic paraganglioma corresponds to cavernous blood vessels that communicated with vessels in the tumour capsule.
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for S100 (nuclear and cytoplasmic). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.
Carotid body paraganglioma. The relative levels of expression of neuroendocrine markers in this apparently sporadic carotid body paraganglioma are similar to those generally seen in other head and neck parasympathetic paragangliomas: synaptophysin (seen here) shows the strongest expression, followed by chromogranin A and tyrosine hydroxylase.
SDHB-related carotid body paraganglioma. This fibrotic SDHB-mutated paraganglioma encases the carotid artery and extends to the resection margins. The tumour was removed in an en bloc resection followed by a synthetic carotid artery graft. The patient, who was 22 years old when the tumour was discovered, has a germline SDHB mutation.
SDHB-related carotid body paraganglioma. Areas with a nested Zellballen pattern are present focally at the periphery of the tumour, but the tumour mostly consists of small cells with solid and infiltrative growth. The patient, who was 22 years old when the tumour was discovered, has a germline SDHB mutation.
Local recurrence of a carotid body paraganglioma. This neck mass was discovered on follow-up scanning in a patient with a germline SDHB mutation who had an ipsilateral sclerotic infiltrating paraganglioma resected 4 years earlier. The lesion was 4–8 mm in diameter and protruded from the lumen of a vein.
Local recurrence of a carotid body paraganglioma. This neck mass was discovered on follow-up scanning in a patient with a germline SDHB mutation who had an ipsilateral sclerotic infiltrating paraganglioma resected 4 years earlier. Unlike the initial tumour, which for the most part was highly cellular and consisted of small cells with infiltrative and solid growth patterns and extremely rare sustentacular cells, this tumour consisted of larger cells with relatively well-formed nests and readily identified sustentacular cells (immunohistochemical stain for S100).
SDHB-related paraganglioma in the neck. This neck paraganglioma from an adolescent boy with an SDHB mutation and a history of gastrointestinal stromal tumour has prominent vacuoles and slightly eosinophilic cytoplasm, which is often seen in association with SDHB mutation. In this case there is abundant cytoplasm but the Zellballen pattern is poorly formed.
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for SOX10 (nuclear). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.

Q: In Parasympathetic Paraganglioma (Head and Neck Paraganglioma), the inconspicuous sustentacular cells located at the periphery of the Zellballen nests are classically highlighted by immunohistochemical stains for SOX10 and [...].
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for S100 (nuclear and cytoplasmic). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for SOX10 (nuclear). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.
A: S100
Back Extra: Parasympathetic Paraganglioma (Head and Neck Paraganglioma)
- Clinical: Parasympathetic paragangliomas are typically discovered incidentally or through genetic testing in families with known histories. Only about 4% are biochemically functional, producing predominantly dopamine and/or 3-methoxytyramine.
- Micro: Carotid body paragangliomas exhibit a Zellballen architecture with clear cells and well-developed, sometimes cavernous, blood vessels. Sustentacular cells are inconspicuous with H&E stains.
- Ancillary: Immunohistochemical staining for neuroendocrine markers (synaptophysin, chromogranin A, tyrosine hydroxylase) and S100 is helpful. SDHB mutations are associated with a higher risk of metastasis and other tumours.
Reference Gallery:
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. T2-weighted MRI showed a hypervascular tumour in the bifurcation of the carotid artery.
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. To assess potential surgical options, CT angiography was performed, further demarcating the lesion, which was deemed unresectable because of the encasement of the internal and external carotid.
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. To exclude metastases, a 68Ga-DOTATOC PET-CT image was acquired, showing bright labelling consistent with intense expression of SSRT. Genetic testing showed a germline SDHD mutation.
Carotid body paraganglioma. The spongy cut surface (shown here) of this sporadic paraganglioma corresponds to cavernous blood vessels that communicated with vessels in the tumour capsule.
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for S100 (nuclear and cytoplasmic). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.
Carotid body paraganglioma. The relative levels of expression of neuroendocrine markers in this apparently sporadic carotid body paraganglioma are similar to those generally seen in other head and neck parasympathetic paragangliomas: synaptophysin (seen here) shows the strongest expression, followed by chromogranin A and tyrosine hydroxylase.
SDHB-related carotid body paraganglioma. This fibrotic SDHB-mutated paraganglioma encases the carotid artery and extends to the resection margins. The tumour was removed in an en bloc resection followed by a synthetic carotid artery graft. The patient, who was 22 years old when the tumour was discovered, has a germline SDHB mutation.
SDHB-related carotid body paraganglioma. Areas with a nested Zellballen pattern are present focally at the periphery of the tumour, but the tumour mostly consists of small cells with solid and infiltrative growth. The patient, who was 22 years old when the tumour was discovered, has a germline SDHB mutation.
Local recurrence of a carotid body paraganglioma. This neck mass was discovered on follow-up scanning in a patient with a germline SDHB mutation who had an ipsilateral sclerotic infiltrating paraganglioma resected 4 years earlier. The lesion was 4–8 mm in diameter and protruded from the lumen of a vein.
Local recurrence of a carotid body paraganglioma. This neck mass was discovered on follow-up scanning in a patient with a germline SDHB mutation who had an ipsilateral sclerotic infiltrating paraganglioma resected 4 years earlier. Unlike the initial tumour, which for the most part was highly cellular and consisted of small cells with infiltrative and solid growth patterns and extremely rare sustentacular cells, this tumour consisted of larger cells with relatively well-formed nests and readily identified sustentacular cells (immunohistochemical stain for S100).
SDHB-related paraganglioma in the neck. This neck paraganglioma from an adolescent boy with an SDHB mutation and a history of gastrointestinal stromal tumour has prominent vacuoles and slightly eosinophilic cytoplasm, which is often seen in association with SDHB mutation. In this case there is abundant cytoplasm but the Zellballen pattern is poorly formed.
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for SOX10 (nuclear). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.

Q: In Parasympathetic Paraganglioma (Head and Neck Paraganglioma), tumors associated with germline mutations in the [...] gene frequently exhibit a solid or infiltrative growth pattern and carry a higher risk of metastasis.
SDHB-related carotid body paraganglioma. This fibrotic SDHB-mutated paraganglioma encases the carotid artery and extends to the resection margins. The tumour was removed in an en bloc resection followed by a synthetic carotid artery graft. The patient, who was 22 years old when the tumour was discovered, has a germline SDHB mutation.
SDHB-related carotid body paraganglioma. Areas with a nested Zellballen pattern are present focally at the periphery of the tumour, but the tumour mostly consists of small cells with solid and infiltrative growth. The patient, who was 22 years old when the tumour was discovered, has a germline SDHB mutation.
A: SDHB
Back Extra: Parasympathetic Paraganglioma (Head and Neck Paraganglioma)
- Clinical: Parasympathetic paragangliomas are typically discovered incidentally or through genetic testing in families with known histories. Only about 4% are biochemically functional, producing predominantly dopamine and/or 3-methoxytyramine.
- Micro: Carotid body paragangliomas exhibit a Zellballen architecture with clear cells and well-developed, sometimes cavernous, blood vessels. Sustentacular cells are inconspicuous with H&E stains.
- Ancillary: Immunohistochemical staining for neuroendocrine markers (synaptophysin, chromogranin A, tyrosine hydroxylase) and S100 is helpful. SDHB mutations are associated with a higher risk of metastasis and other tumours.
Reference Gallery:
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. T2-weighted MRI showed a hypervascular tumour in the bifurcation of the carotid artery.
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. To assess potential surgical options, CT angiography was performed, further demarcating the lesion, which was deemed unresectable because of the encasement of the internal and external carotid.
Carotid body paraganglioma. Classic anatomical and functional imaging characteristics in a 19-year-old patient. To exclude metastases, a 68Ga-DOTATOC PET-CT image was acquired, showing bright labelling consistent with intense expression of SSRT. Genetic testing showed a germline SDHD mutation.
Carotid body paraganglioma. The spongy cut surface (shown here) of this sporadic paraganglioma corresponds to cavernous blood vessels that communicated with vessels in the tumour capsule.
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for S100 (nuclear and cytoplasmic). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.
Carotid body paraganglioma. The relative levels of expression of neuroendocrine markers in this apparently sporadic carotid body paraganglioma are similar to those generally seen in other head and neck parasympathetic paragangliomas: synaptophysin (seen here) shows the strongest expression, followed by chromogranin A and tyrosine hydroxylase.
SDHB-related carotid body paraganglioma. This fibrotic SDHB-mutated paraganglioma encases the carotid artery and extends to the resection margins. The tumour was removed in an en bloc resection followed by a synthetic carotid artery graft. The patient, who was 22 years old when the tumour was discovered, has a germline SDHB mutation.
SDHB-related carotid body paraganglioma. Areas with a nested Zellballen pattern are present focally at the periphery of the tumour, but the tumour mostly consists of small cells with solid and infiltrative growth. The patient, who was 22 years old when the tumour was discovered, has a germline SDHB mutation.
Local recurrence of a carotid body paraganglioma. This neck mass was discovered on follow-up scanning in a patient with a germline SDHB mutation who had an ipsilateral sclerotic infiltrating paraganglioma resected 4 years earlier. The lesion was 4–8 mm in diameter and protruded from the lumen of a vein.
Local recurrence of a carotid body paraganglioma. This neck mass was discovered on follow-up scanning in a patient with a germline SDHB mutation who had an ipsilateral sclerotic infiltrating paraganglioma resected 4 years earlier. Unlike the initial tumour, which for the most part was highly cellular and consisted of small cells with infiltrative and solid growth patterns and extremely rare sustentacular cells, this tumour consisted of larger cells with relatively well-formed nests and readily identified sustentacular cells (immunohistochemical stain for S100).
SDHB-related paraganglioma in the neck. This neck paraganglioma from an adolescent boy with an SDHB mutation and a history of gastrointestinal stromal tumour has prominent vacuoles and slightly eosinophilic cytoplasm, which is often seen in association with SDHB mutation. In this case there is abundant cytoplasm but the Zellballen pattern is poorly formed.
Carotid body paraganglioma. Prominent, well-formed nests of clear tumour cells are highlighted by immunohistochemical staining for SOX10 (nuclear). Note the intratumoural variation in density of sustentacular cells, with a gradient in this case from periphery to centre. A small nerve outside the tumour is present in the lower-right corner.

Q: In Sympathetic Paraganglioma, the characteristic microscopic finding consists of small nests of neuroendocrine cells surrounded by a delicate fibrovascular stroma, a pattern known as [...].
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including sharply defined tumour cell nests (Zellballen pattern).
A: Zellballen
Back Extra: Sympathetic Paraganglioma
- Clinical: Sympathetic paragangliomas predominantly occur in the abdomen, retroperitoneum, pelvis, and thorax, with a median age of presentation in paediatric patients being 11.6 to 13.3 years.
- Micro: Tumours are arranged in small nests (Zellballen) of neuroendocrine cells with basophilic, amphophilic, or clear cytoplasm, surrounded by a delicate fibrovascular stroma.
- Ancillary: Essential diagnostic features include Zellballen or nested architecture, stippled nuclear chromatin, and neuroendocrine histology. Immunohistochemistry for SDHB and other relevant biomarkers is also important.
Reference Gallery:
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT (shown here) showed a small midline paraganglioma.
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. Whole-body MIBG scan (shown here) showed a small midline paraganglioma.
Abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT and whole-body MIBG scan showed a small midline paraganglioma, which had varied histological patterns including irregular nests and cords of cells with prominent intervening sclerosis (shown here). Intratumoural heterogeneity was also observed with respect to several immunohistochemical markers.
Abdominal paraganglioma. Staining of a resected paraganglioma for SSTR2A can be useful as a preliminary test to assess whether functional imaging or treatment with radiolabelled somatostatin analogues would be suitable to screen for or treat metastases. Most sympathetic paragangliomas express SSTR2A. However, intratumoural heterogeneity can be marked, like in this example.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, a uniformly positive immunohistochemical stain for GATA3 shows characteristic nuclear staining in a paraganglioma and in two neurons in an adjacent normal ganglion at the bottom of the image.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, highly variable staining for tyrosine hydroxylase can be seen.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the large fleshy nodules with central necrosis in the tumour shown here, which are putative risk factors for metastasis. This tumour also had a diffuse growth pattern and high cellularity.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the bulging nodule and cystic change in the tumour shown here.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background. This solid growth pattern with high cellularity was associated with tumour necrosis and coarse nodularity; all these features are putative risk factors for metastasis.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including sharply defined tumour cell nests (Zellballen pattern).
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including clear cells with patchy degenerative changes.

Q: Hereditary Sympathetic Paragangliomas that present as multicentric tumors or show an increased risk for metastasis are classically associated with germline mutations in [...].
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the large fleshy nodules with central necrosis in the tumour shown here, which are putative risk factors for metastasis. This tumour also had a diffuse growth pattern and high cellularity.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the bulging nodule and cystic change in the tumour shown here.
A: SDHB
Back Extra: Sympathetic Paraganglioma
- Clinical: Sympathetic paragangliomas predominantly occur in the abdomen, retroperitoneum, pelvis, and thorax, with a median age of presentation in paediatric patients being 11.6 to 13.3 years.
- Micro: Tumours are arranged in small nests (Zellballen) of neuroendocrine cells with basophilic, amphophilic, or clear cytoplasm, surrounded by a delicate fibrovascular stroma.
- Ancillary: Essential diagnostic features include Zellballen or nested architecture, stippled nuclear chromatin, and neuroendocrine histology. Immunohistochemistry for SDHB and other relevant biomarkers is also important.
Reference Gallery:
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT (shown here) showed a small midline paraganglioma.
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. Whole-body MIBG scan (shown here) showed a small midline paraganglioma.
Abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT and whole-body MIBG scan showed a small midline paraganglioma, which had varied histological patterns including irregular nests and cords of cells with prominent intervening sclerosis (shown here). Intratumoural heterogeneity was also observed with respect to several immunohistochemical markers.
Abdominal paraganglioma. Staining of a resected paraganglioma for SSTR2A can be useful as a preliminary test to assess whether functional imaging or treatment with radiolabelled somatostatin analogues would be suitable to screen for or treat metastases. Most sympathetic paragangliomas express SSTR2A. However, intratumoural heterogeneity can be marked, like in this example.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, a uniformly positive immunohistochemical stain for GATA3 shows characteristic nuclear staining in a paraganglioma and in two neurons in an adjacent normal ganglion at the bottom of the image.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, highly variable staining for tyrosine hydroxylase can be seen.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the large fleshy nodules with central necrosis in the tumour shown here, which are putative risk factors for metastasis. This tumour also had a diffuse growth pattern and high cellularity.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the bulging nodule and cystic change in the tumour shown here.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background. This solid growth pattern with high cellularity was associated with tumour necrosis and coarse nodularity; all these features are putative risk factors for metastasis.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including sharply defined tumour cell nests (Zellballen pattern).
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including clear cells with patchy degenerative changes.

Q: In Sympathetic Paraganglioma, immunohistochemistry frequently demonstrates uniform nuclear positivity for the transcription factor [...], whereas functional markers like tyrosine hydroxylase can be highly variable and focal.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, a uniformly positive immunohistochemical stain for GATA3 shows characteristic nuclear staining in a paraganglioma and in two neurons in an adjacent normal ganglion at the bottom of the image.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, highly variable staining for tyrosine hydroxylase can be seen.
A: GATA3
Back Extra: Sympathetic Paraganglioma
- Clinical: Sympathetic paragangliomas predominantly occur in the abdomen, retroperitoneum, pelvis, and thorax, with a median age of presentation in paediatric patients being 11.6 to 13.3 years.
- Micro: Tumours are arranged in small nests (Zellballen) of neuroendocrine cells with basophilic, amphophilic, or clear cytoplasm, surrounded by a delicate fibrovascular stroma.
- Ancillary: Essential diagnostic features include Zellballen or nested architecture, stippled nuclear chromatin, and neuroendocrine histology. Immunohistochemistry for SDHB and other relevant biomarkers is also important.
Reference Gallery:
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT (shown here) showed a small midline paraganglioma.
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. Whole-body MIBG scan (shown here) showed a small midline paraganglioma.
Abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT and whole-body MIBG scan showed a small midline paraganglioma, which had varied histological patterns including irregular nests and cords of cells with prominent intervening sclerosis (shown here). Intratumoural heterogeneity was also observed with respect to several immunohistochemical markers.
Abdominal paraganglioma. Staining of a resected paraganglioma for SSTR2A can be useful as a preliminary test to assess whether functional imaging or treatment with radiolabelled somatostatin analogues would be suitable to screen for or treat metastases. Most sympathetic paragangliomas express SSTR2A. However, intratumoural heterogeneity can be marked, like in this example.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, a uniformly positive immunohistochemical stain for GATA3 shows characteristic nuclear staining in a paraganglioma and in two neurons in an adjacent normal ganglion at the bottom of the image.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, highly variable staining for tyrosine hydroxylase can be seen.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the large fleshy nodules with central necrosis in the tumour shown here, which are putative risk factors for metastasis. This tumour also had a diffuse growth pattern and high cellularity.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the bulging nodule and cystic change in the tumour shown here.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background. This solid growth pattern with high cellularity was associated with tumour necrosis and coarse nodularity; all these features are putative risk factors for metastasis.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including sharply defined tumour cell nests (Zellballen pattern).
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including clear cells with patchy degenerative changes.

Q: Microscopically, a Sympathetic Paraganglioma classically features small nests of neuroendocrine cells surrounded by a delicate fibrovascular stroma, an arrangement known as the [...] pattern.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including sharply defined tumour cell nests (Zellballen pattern).
A: Zellballen
Back Extra: Sympathetic Paraganglioma
- Clinical: Sympathetic paragangliomas are often found in the abdomen, retroperitoneum, pelvis, and thorax, with about 50% of pediatric cases being phaeochromocytomas.
- Micro: Tumours are arranged in small nests (Zellballen) of neuroendocrine cells separated by a delicate fibrovascular stroma, often with basophilic, amphophilic, or clear cytoplasm.
- Ancillary: Immunohistochemistry for SDHB and other relevant biomarkers is considered in selected cases, and biochemical testing for metanephrines is essential for diagnosis.
Reference Gallery:
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT (shown here) showed a small midline paraganglioma.
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. Whole-body MIBG scan (shown here) showed a small midline paraganglioma.
Abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT and whole-body MIBG scan showed a small midline paraganglioma, which had varied histological patterns including irregular nests and cords of cells with prominent intervening sclerosis (shown here). Intratumoural heterogeneity was also observed with respect to several immunohistochemical markers.
Abdominal paraganglioma. Staining of a resected paraganglioma for SSTR2A can be useful as a preliminary test to assess whether functional imaging or treatment with radiolabelled somatostatin analogues would be suitable to screen for or treat metastases. Most sympathetic paragangliomas express SSTR2A. However, intratumoural heterogeneity can be marked, like in this example.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, a uniformly positive immunohistochemical stain for GATA3 shows characteristic nuclear staining in a paraganglioma and in two neurons in an adjacent normal ganglion at the bottom of the image.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, highly variable staining for tyrosine hydroxylase can be seen.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the large fleshy nodules with central necrosis in the tumour shown here, which are putative risk factors for metastasis. This tumour also had a diffuse growth pattern and high cellularity.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the bulging nodule and cystic change in the tumour shown here.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background. This solid growth pattern with high cellularity was associated with tumour necrosis and coarse nodularity; all these features are putative risk factors for metastasis.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including sharply defined tumour cell nests (Zellballen pattern).
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including clear cells with patchy degenerative changes.

Q: In patients with a Sympathetic Paraganglioma, germline mutations in the [...] gene are strongly associated with multicentric tumors and a significantly increased risk of metastasis.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the large fleshy nodules with central necrosis in the tumour shown here, which are putative risk factors for metastasis. This tumour also had a diffuse growth pattern and high cellularity.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background. This solid growth pattern with high cellularity was associated with tumour necrosis and coarse nodularity; all these features are putative risk factors for metastasis.
A: SDHB
Back Extra: Sympathetic Paraganglioma
- Clinical: Sympathetic paragangliomas are often found in the abdomen, retroperitoneum, pelvis, and thorax, with about 50% of pediatric cases being phaeochromocytomas.
- Micro: Tumours are arranged in small nests (Zellballen) of neuroendocrine cells separated by a delicate fibrovascular stroma, often with basophilic, amphophilic, or clear cytoplasm.
- Ancillary: Immunohistochemistry for SDHB and other relevant biomarkers is considered in selected cases, and biochemical testing for metanephrines is essential for diagnosis.
Reference Gallery:
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT (shown here) showed a small midline paraganglioma.
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. Whole-body MIBG scan (shown here) showed a small midline paraganglioma.
Abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT and whole-body MIBG scan showed a small midline paraganglioma, which had varied histological patterns including irregular nests and cords of cells with prominent intervening sclerosis (shown here). Intratumoural heterogeneity was also observed with respect to several immunohistochemical markers.
Abdominal paraganglioma. Staining of a resected paraganglioma for SSTR2A can be useful as a preliminary test to assess whether functional imaging or treatment with radiolabelled somatostatin analogues would be suitable to screen for or treat metastases. Most sympathetic paragangliomas express SSTR2A. However, intratumoural heterogeneity can be marked, like in this example.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, a uniformly positive immunohistochemical stain for GATA3 shows characteristic nuclear staining in a paraganglioma and in two neurons in an adjacent normal ganglion at the bottom of the image.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, highly variable staining for tyrosine hydroxylase can be seen.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the large fleshy nodules with central necrosis in the tumour shown here, which are putative risk factors for metastasis. This tumour also had a diffuse growth pattern and high cellularity.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the bulging nodule and cystic change in the tumour shown here.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background. This solid growth pattern with high cellularity was associated with tumour necrosis and coarse nodularity; all these features are putative risk factors for metastasis.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including sharply defined tumour cell nests (Zellballen pattern).
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including clear cells with patchy degenerative changes.

Q: In a Sympathetic Paraganglioma, the expression of functional markers can be highly variable and heterogeneous; for instance, immunohistochemical staining for [...] often shows focal and weak positivity compared to the diffuse expression of transcription factors.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, highly variable staining for tyrosine hydroxylase can be seen.
A: tyrosine hydroxylase
Back Extra: Sympathetic Paraganglioma
- Clinical: Sympathetic paragangliomas are often found in the abdomen, retroperitoneum, pelvis, and thorax, with about 50% of pediatric cases being phaeochromocytomas.
- Micro: Tumours are arranged in small nests (Zellballen) of neuroendocrine cells separated by a delicate fibrovascular stroma, often with basophilic, amphophilic, or clear cytoplasm.
- Ancillary: Immunohistochemistry for SDHB and other relevant biomarkers is considered in selected cases, and biochemical testing for metanephrines is essential for diagnosis.
Reference Gallery:
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT (shown here) showed a small midline paraganglioma.
Anatomical and functional imaging in a patient with abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. Whole-body MIBG scan (shown here) showed a small midline paraganglioma.
Abdominal paraganglioma. The patient was a 13-year-old girl in a family with a known SDHB mutation; two older family members had already developed paragangliomas. Genetic testing confirmed that she also carried the mutation. Biochemical testing for metanephrines was negative. CT and whole-body MIBG scan showed a small midline paraganglioma, which had varied histological patterns including irregular nests and cords of cells with prominent intervening sclerosis (shown here). Intratumoural heterogeneity was also observed with respect to several immunohistochemical markers.
Abdominal paraganglioma. Staining of a resected paraganglioma for SSTR2A can be useful as a preliminary test to assess whether functional imaging or treatment with radiolabelled somatostatin analogues would be suitable to screen for or treat metastases. Most sympathetic paragangliomas express SSTR2A. However, intratumoural heterogeneity can be marked, like in this example.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, a uniformly positive immunohistochemical stain for GATA3 shows characteristic nuclear staining in a paraganglioma and in two neurons in an adjacent normal ganglion at the bottom of the image.
Abdominal paraganglioma. Sympathetic paragangliomas can show intratumoural heterogeneity with respect to biomarker expression, varying with both the type of marker and individual tumour. Transcription factors are often diffusely expressed, whereas expression of functional markers can be focal and weak. Here, highly variable staining for tyrosine hydroxylase can be seen.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the large fleshy nodules with central necrosis in the tumour shown here, which are putative risk factors for metastasis. This tumour also had a diffuse growth pattern and high cellularity.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance. Note the bulging nodule and cystic change in the tumour shown here.
Multicentric paragangliomas. This patient with a hereditary SDHB mutation was screened for tumours in her early twenties. By that time, she had already developed three paragangliomas (34–47 mm) adjacent to her lumbar vertebrae, each with a somewhat different gross appearance.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background. This solid growth pattern with high cellularity was associated with tumour necrosis and coarse nodularity; all these features are putative risk factors for metastasis.
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including sharply defined tumour cell nests (Zellballen pattern).
Histological findings in multicentric paragangliomas. Multiple histological patterns can be found in synchronous paragangliomas with the same genetic background, including clear cells with patchy degenerative changes.

Q: Microscopically, Neuroendocrine Tumours (NETs) frequently exhibit an insular, nested, or trabecular architecture with polygonal cells possessing characteristic stippled chromatin, classically described as [...] nuclei.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The PanNET shows trabeculae and a cord-like growth pattern with fibrotic stroma.
A: salt-and-pepper
Back Extra: Neuroendocrine Tumours (NETs)
- Clinical: Neuroendocrine Tumours (NETs) can present with hormone excess symptoms, such as hypoglycaemia due to insulinoma, gastrin excess due to gastrinoma, and carcinoid syndrome due to metastatic small bowel NET.
- Micro: Neuroendocrine Tumours (NETs) typically exhibit an insular/nested architecture with polygonal cells, smooth nuclear contours, and stippled chromatin (salt-and-pepper nuclei).
- Ancillary: Immunohistochemistry for Neuroendocrine Tumours (NETs) shows expression of INSM1, synaptophysin, chromogranins, and keratins, with additional markers like TTF1, serotonin, and calcitonin in pulmonary NETs.
Reference Gallery:
Structural and functional imaging studies in a paediatric age–onset metastatic insulin-producing well-differentiated pancreatic neuroendocrine tumour (PanNET). An 11-year-old child presented with an insulin-producing well-differentiated PanNET with low-grade proliferative features (G1 NET; insulinoma). Subsequently, the patient developed progressive symptoms related to the insulinoma and was found to have diffuse miliary hypervascular liver metastases in association with massive peritumoural steatosis. The metastatic disease was difficult to see on CT (A) and MRI (B; in-phase and out-of-phase T1 sequence images are shown), as well as on initial 68Ga-DOTATOC PET-CT imaging (C), because of the small size of the tumour deposits. The interim liver biopsy showed only steatosis. During follow-up, the largest metastatic tumour deposit did show uptake using 68Ga-exendin PET-CT (GLP-1–targeted PET) (D). Arrows indicate the dominant metastatic tumour deposit in different imaging modalities.
Pancreatic neuroendocrine tumour (PanNET). Gross findings of a paediatric age–onset PanNET.
Bronchial/pulmonary neuroendocrine tumour (NET). Gross findings of a paediatric age–onset bronchial/pulmonary NET.
Ileal enterochromaffin (EC)-cell neuroendocrine tumour (NET). An ileal EC-cell well-differentiated NET in a 17-year-old girl.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae (chromogranin A).
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). Liver metastasis in a paediatric patient with a primary ileal EC-cell NET.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). The tumour is positive for chromogranin A.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). The tumour is positive for serotonin (shown here), as well as for CAM5.2 and CDX2. The immunohistochemical findings are consistent with a midgut EC-cell origin.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The PanNET shows trabeculae and a cord-like growth pattern with fibrotic stroma.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for chromogranin A.

Q: Immunohistochemistry for Neuroendocrine Tumours (NETs) classically demonstrates strong expression of neuroendocrine markers such as INSM1, synaptophysin, and [...].
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). The tumour is positive for chromogranin A.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for chromogranin A.
A: chromogranin
Back Extra: Neuroendocrine Tumours (NETs)
- Clinical: Neuroendocrine Tumours (NETs) can present with hormone excess symptoms, such as hypoglycaemia due to insulinoma, gastrin excess due to gastrinoma, and carcinoid syndrome due to metastatic small bowel NET.
- Micro: Neuroendocrine Tumours (NETs) typically exhibit an insular/nested architecture with polygonal cells, smooth nuclear contours, and stippled chromatin (salt-and-pepper nuclei).
- Ancillary: Immunohistochemistry for Neuroendocrine Tumours (NETs) shows expression of INSM1, synaptophysin, chromogranins, and keratins, with additional markers like TTF1, serotonin, and calcitonin in pulmonary NETs.
Reference Gallery:
Structural and functional imaging studies in a paediatric age–onset metastatic insulin-producing well-differentiated pancreatic neuroendocrine tumour (PanNET). An 11-year-old child presented with an insulin-producing well-differentiated PanNET with low-grade proliferative features (G1 NET; insulinoma). Subsequently, the patient developed progressive symptoms related to the insulinoma and was found to have diffuse miliary hypervascular liver metastases in association with massive peritumoural steatosis. The metastatic disease was difficult to see on CT (A) and MRI (B; in-phase and out-of-phase T1 sequence images are shown), as well as on initial 68Ga-DOTATOC PET-CT imaging (C), because of the small size of the tumour deposits. The interim liver biopsy showed only steatosis. During follow-up, the largest metastatic tumour deposit did show uptake using 68Ga-exendin PET-CT (GLP-1–targeted PET) (D). Arrows indicate the dominant metastatic tumour deposit in different imaging modalities.
Pancreatic neuroendocrine tumour (PanNET). Gross findings of a paediatric age–onset PanNET.
Bronchial/pulmonary neuroendocrine tumour (NET). Gross findings of a paediatric age–onset bronchial/pulmonary NET.
Ileal enterochromaffin (EC)-cell neuroendocrine tumour (NET). An ileal EC-cell well-differentiated NET in a 17-year-old girl.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae (chromogranin A).
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). Liver metastasis in a paediatric patient with a primary ileal EC-cell NET.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). The tumour is positive for chromogranin A.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). The tumour is positive for serotonin (shown here), as well as for CAM5.2 and CDX2. The immunohistochemical findings are consistent with a midgut EC-cell origin.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The PanNET shows trabeculae and a cord-like growth pattern with fibrotic stroma.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for chromogranin A.

Q: Functional Neuroendocrine Tumours (NETs) can present with symptoms of hormone excess, such as an insulinoma leading to profound [...] or a metastatic midgut tumor causing carcinoid syndrome.
Structural and functional imaging studies in a paediatric age–onset metastatic insulin-producing well-differentiated pancreatic neuroendocrine tumour (PanNET). An 11-year-old child presented with an insulin-producing well-differentiated PanNET with low-grade proliferative features (G1 NET; insulinoma). Subsequently, the patient developed progressive symptoms related to the insulinoma and was found to have diffuse miliary hypervascular liver metastases in association with massive peritumoural steatosis. The metastatic disease was difficult to see on CT (A) and MRI (B; in-phase and out-of-phase T1 sequence images are shown), as well as on initial 68Ga-DOTATOC PET-CT imaging (C), because of the small size of the tumour deposits. The interim liver biopsy showed only steatosis. During follow-up, the largest metastatic tumour deposit did show uptake using 68Ga-exendin PET-CT (GLP-1–targeted PET) (D). Arrows indicate the dominant metastatic tumour deposit in different imaging modalities.
A: hypoglycemia
Back Extra: Neuroendocrine Tumours (NETs)
- Clinical: Neuroendocrine Tumours (NETs) can present with hormone excess symptoms, such as hypoglycaemia due to insulinoma, gastrin excess due to gastrinoma, and carcinoid syndrome due to metastatic small bowel NET.
- Micro: Neuroendocrine Tumours (NETs) typically exhibit an insular/nested architecture with polygonal cells, smooth nuclear contours, and stippled chromatin (salt-and-pepper nuclei).
- Ancillary: Immunohistochemistry for Neuroendocrine Tumours (NETs) shows expression of INSM1, synaptophysin, chromogranins, and keratins, with additional markers like TTF1, serotonin, and calcitonin in pulmonary NETs.
Reference Gallery:
Structural and functional imaging studies in a paediatric age–onset metastatic insulin-producing well-differentiated pancreatic neuroendocrine tumour (PanNET). An 11-year-old child presented with an insulin-producing well-differentiated PanNET with low-grade proliferative features (G1 NET; insulinoma). Subsequently, the patient developed progressive symptoms related to the insulinoma and was found to have diffuse miliary hypervascular liver metastases in association with massive peritumoural steatosis. The metastatic disease was difficult to see on CT (A) and MRI (B; in-phase and out-of-phase T1 sequence images are shown), as well as on initial 68Ga-DOTATOC PET-CT imaging (C), because of the small size of the tumour deposits. The interim liver biopsy showed only steatosis. During follow-up, the largest metastatic tumour deposit did show uptake using 68Ga-exendin PET-CT (GLP-1–targeted PET) (D). Arrows indicate the dominant metastatic tumour deposit in different imaging modalities.
Pancreatic neuroendocrine tumour (PanNET). Gross findings of a paediatric age–onset PanNET.
Bronchial/pulmonary neuroendocrine tumour (NET). Gross findings of a paediatric age–onset bronchial/pulmonary NET.
Ileal enterochromaffin (EC)-cell neuroendocrine tumour (NET). An ileal EC-cell well-differentiated NET in a 17-year-old girl.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving the bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae.
Histological features in a paediatric age–onset bronchopulmonary neuroendocrine tumour (NET). The tumour consists of a well-differentiated NET involving bronchus and adjacent lung parenchyma. The tumour shows a mixed growth pattern including nests, sheets, and trabeculae (chromogranin A).
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). Liver metastasis in a paediatric patient with a primary ileal EC-cell NET.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). The tumour is positive for chromogranin A.
Metastatic well-differentiated enterochromaffin (EC)-cell neuroendocrine tumour (NET). The tumour is positive for serotonin (shown here), as well as for CAM5.2 and CDX2. The immunohistochemical findings are consistent with a midgut EC-cell origin.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The PanNET shows trabeculae and a cord-like growth pattern with fibrotic stroma.
Sporadic well-differentiated pancreatic neuroendocrine tumour (PanNET) with intermediate-grade proliferative features (G2 NET) in a 12-year-old child. The tumour is diffusely positive for chromogranin A.

Q: A Parathyroid Adenoma associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome characteristically demonstrates a loss of immunohistochemical nuclear expression for [...].
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. Complete loss of nuclear expression of parafibromin in all neoplastic cells. The presence of the prerequisite internal positive control in non-neoplastic endothelial and stromal cells is emphasized.
Parathyroid adenoma. There is normal nuclear expression of parafibromin in this tumour not associated with hyperparathyroidism–jaw tumour syndrome.
A: parafibromin
Q: Parathyroid Adenoma
- Clinical: Children are more likely to be symptomatic with marked hypercalcemia and hypercalciuria in [...].
- Micro: [...] is typically composed of chief cells with a reduction or absence of stromal fat, and may contain oxyphilic and water-clear cells.
- Ancillary: Loss of immunohistochemical expression of [...] is seen in parathyroid adenomas associated with hyperparathyroidism–jaw tumour syndrome (HPT-JT).
Reference Gallery:
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. This tumour demonstrates the typical sheet-like architecture, eosinophilic cell type, prominent vasculature, and microcystic change of parathyroid tumours associated with hyperparathyroidism–jaw tumour syndrome.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. There is eosinophilic cytoplasm with perinuclear cytoplasmic clearing, nuclear enlargement (often with preserved N:C ratios), and some multinucleation.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. Complete loss of nuclear expression of parafibromin in all neoplastic cells. The presence of the prerequisite internal positive control in non-neoplastic endothelial and stromal cells is emphasized.
Parathyroid adenoma. There is normal nuclear expression of parafibromin in this tumour not associated with hyperparathyroidism–jaw tumour syndrome.
A: Parathyroid Adenoma; Parathyroid Adenoma; parafibromin

Q: Microscopically, a Parathyroid Adenoma is typically composed of sheets of chief cells and is characterized by a marked reduction or absence of normal [...].
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. This tumour demonstrates the typical sheet-like architecture, eosinophilic cell type, prominent vasculature, and microcystic change of parathyroid tumours associated with hyperparathyroidism–jaw tumour syndrome.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. There is eosinophilic cytoplasm with perinuclear cytoplasmic clearing, nuclear enlargement (often with preserved N:C ratios), and some multinucleation.
A: stromal fat
Q: Parathyroid Adenoma
- Clinical: Children are more likely to be symptomatic with marked hypercalcemia and hypercalciuria in [...].
- Micro: [...] is typically composed of chief cells with a reduction or absence of stromal fat, and may contain oxyphilic and water-clear cells.
- Ancillary: Loss of immunohistochemical expression of [...] is seen in parathyroid adenomas associated with hyperparathyroidism–jaw tumour syndrome (HPT-JT).
Reference Gallery:
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. This tumour demonstrates the typical sheet-like architecture, eosinophilic cell type, prominent vasculature, and microcystic change of parathyroid tumours associated with hyperparathyroidism–jaw tumour syndrome.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. There is eosinophilic cytoplasm with perinuclear cytoplasmic clearing, nuclear enlargement (often with preserved N:C ratios), and some multinucleation.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. Complete loss of nuclear expression of parafibromin in all neoplastic cells. The presence of the prerequisite internal positive control in non-neoplastic endothelial and stromal cells is emphasized.
Parathyroid adenoma. There is normal nuclear expression of parafibromin in this tumour not associated with hyperparathyroidism–jaw tumour syndrome.
A: Parathyroid Adenoma; Parathyroid Adenoma; parafibromin

Q: A distinct morphological variant of Parathyroid Adenoma characterized by a sheet-like growth pattern, prominent vasculature, and eosinophilic cells with perinuclear clearing is classically associated with [...].
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. This tumour demonstrates the typical sheet-like architecture, eosinophilic cell type, prominent vasculature, and microcystic change of parathyroid tumours associated with hyperparathyroidism–jaw tumour syndrome.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. There is eosinophilic cytoplasm with perinuclear cytoplasmic clearing, nuclear enlargement (often with preserved N:C ratios), and some multinucleation.
A: hyperparathyroidism-jaw tumor syndrome
Q: Parathyroid Adenoma
- Clinical: Children with [...] are more likely to present with marked hypercalcaemia and hypercalciuria compared to adults, and the condition is often hereditary or syndromic.
- Micro: [...] often show a sheet-like growth pattern, eosinophilic cell type, and prominent vasculature, especially in cases associated with hyperparathyroidism–jaw tumour syndrome.
- Ancillary: Immunohistochemistry for [...] is particularly useful in identifying parathyroid adenomas associated with hyperparathyroidism–jaw tumour syndrome (HPT-JT), showing loss of nuclear expression.
Reference Gallery:
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. This tumour demonstrates the typical sheet-like architecture, eosinophilic cell type, prominent vasculature, and microcystic change of parathyroid tumours associated with hyperparathyroidism–jaw tumour syndrome.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. There is eosinophilic cytoplasm with perinuclear cytoplasmic clearing, nuclear enlargement (often with preserved N:C ratios), and some multinucleation.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. Complete loss of nuclear expression of parafibromin in all neoplastic cells. The presence of the prerequisite internal positive control in non-neoplastic endothelial and stromal cells is emphasized.
Parathyroid adenoma. There is normal nuclear expression of parafibromin in this tumour not associated with hyperparathyroidism–jaw tumour syndrome.
A: parathyroid adenoma; Parathyroid adenomas; parafibromin

Q: In the evaluation of a Parathyroid Adenoma, complete loss of nuclear expression of [...] on immunohistochemistry strongly indicates an association with hyperparathyroidism-jaw tumor syndrome.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. Complete loss of nuclear expression of parafibromin in all neoplastic cells. The presence of the prerequisite internal positive control in non-neoplastic endothelial and stromal cells is emphasized.
Parathyroid adenoma. There is normal nuclear expression of parafibromin in this tumour not associated with hyperparathyroidism–jaw tumour syndrome.
A: parafibromin
Q: Parathyroid Adenoma
- Clinical: Children with [...] are more likely to present with marked hypercalcaemia and hypercalciuria compared to adults, and the condition is often hereditary or syndromic.
- Micro: [...] often show a sheet-like growth pattern, eosinophilic cell type, and prominent vasculature, especially in cases associated with hyperparathyroidism–jaw tumour syndrome.
- Ancillary: Immunohistochemistry for [...] is particularly useful in identifying parathyroid adenomas associated with hyperparathyroidism–jaw tumour syndrome (HPT-JT), showing loss of nuclear expression.
Reference Gallery:
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. This tumour demonstrates the typical sheet-like architecture, eosinophilic cell type, prominent vasculature, and microcystic change of parathyroid tumours associated with hyperparathyroidism–jaw tumour syndrome.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. There is eosinophilic cytoplasm with perinuclear cytoplasmic clearing, nuclear enlargement (often with preserved N:C ratios), and some multinucleation.
Parafibromin-deficient (hyperparathyroidism–jaw tumour type) parathyroid adenoma. Complete loss of nuclear expression of parafibromin in all neoplastic cells. The presence of the prerequisite internal positive control in non-neoplastic endothelial and stromal cells is emphasized.
Parathyroid adenoma. There is normal nuclear expression of parafibromin in this tumour not associated with hyperparathyroidism–jaw tumour syndrome.
A: parathyroid adenoma; Parathyroid adenomas; parafibromin

Q: A distinctive microscopic feature of Cribriform Morular Thyroid Carcinoma is the admixture of cribriform and papillary architecture interspersed with characteristic [...].
Cribriform morular thyroid carcinoma. Cribriform architecture, with irregularly shaped follicular structures devoid of colloid, interspersed with morular areas. Inset: Scattered optically clear nuclei within morules, caused by the accumulation of biotin.
Cribriform morular thyroid carcinoma. There is a morule in the upper left and cribriform tubular growth in the lower right.
A: squamoid morulae
Back Extra: Cribriform Morular Thyroid Carcinoma
- Clinical: Cribriform Morular Thyroid Carcinoma is most commonly found in young women, with 89% of cases occurring in individuals aged < 40 years. It can present as a painless mass, hoarseness, or dysphagia.
- Micro: The tumour shows a distinctive admixture of growth patterns, including cribriform, follicular, papillary, trabecular, and solid patterns, with squamoid morulae and papillae lined by tall, cuboidal, or pseudostratified cells.
- Ancillary: Characteristic aberrant nuclear and cytoplasmic β-catenin staining is a hallmark of Cribriform Morular Thyroid Carcinoma, reflecting constitutive WNT/β-catenin pathway activation.
Reference Gallery:
Cribriform morular thyroid carcinoma. Cribriform architecture, with irregularly shaped follicular structures devoid of colloid, interspersed with morular areas. Inset: Scattered optically clear nuclei within morules, caused by the accumulation of biotin.
Cribriform morular thyroid carcinoma. Non-morular area showing oval, overlapping grooved nuclei.
Cribriform morular thyroid carcinoma. β-catenin immunohistochemistry, showing strong nuclear and moderate cytoplasmic reactivity in both follicular and morular cells.
Cribriform morular thyroid carcinoma. This tumour is diffusely positive for ER.
Cribriform morular thyroid carcinoma. β-catenin immunostaining shows characteristic aberrant immunopositivity in the nuclei and in the cytoplasm of the tumour cells.
Cribriform morular thyroid carcinoma. The tumour is positive for thyroid transcription factor 1 (TTF1) by immunostaining, except for the morules (arrows).
Cribriform morular thyroid carcinoma. There is a morule in the upper left and cribriform tubular growth in the lower right.
Cribriform morular thyroid carcinoma. Papillae and pseudopapillae are lined by tall, cuboidal, or pseudostratified columnar cells. Tubular follicles lacking colloid are seen.
Cribriform morular thyroid carcinoma. The cribriform structures lack intervening fibrous stroma and merge with tubular follicles that lack colloid.
Cribriform morular thyroid carcinoma. These tumours are usually circumscribed or encapsulated, but they can have fibrous bands imparting a multilobulated appearance.
Cribriform morular thyroid carcinoma. The morular component is positive for CK5.
Cribriform morular thyroid carcinoma. Immunostaining for CD5 highlights the morular component of these tumours, as well as scattered CD5-positive T lymphocytes.

Q: The hallmark immunohistochemical finding in Cribriform Morular Thyroid Carcinoma, reflecting constitutive WNT pathway activation, is aberrant nuclear and cytoplasmic staining for [...].
Cribriform morular thyroid carcinoma. β-catenin immunohistochemistry, showing strong nuclear and moderate cytoplasmic reactivity in both follicular and morular cells.
Cribriform morular thyroid carcinoma. β-catenin immunostaining shows characteristic aberrant immunopositivity in the nuclei and in the cytoplasm of the tumour cells.
A: β-catenin
Back Extra: Cribriform Morular Thyroid Carcinoma
- Clinical: Cribriform Morular Thyroid Carcinoma is most commonly found in young women, with 89% of cases occurring in individuals aged < 40 years. It can present as a painless mass, hoarseness, or dysphagia.
- Micro: The tumour shows a distinctive admixture of growth patterns, including cribriform, follicular, papillary, trabecular, and solid patterns, with squamoid morulae and papillae lined by tall, cuboidal, or pseudostratified cells.
- Ancillary: Characteristic aberrant nuclear and cytoplasmic β-catenin staining is a hallmark of Cribriform Morular Thyroid Carcinoma, reflecting constitutive WNT/β-catenin pathway activation.
Reference Gallery:
Cribriform morular thyroid carcinoma. Cribriform architecture, with irregularly shaped follicular structures devoid of colloid, interspersed with morular areas. Inset: Scattered optically clear nuclei within morules, caused by the accumulation of biotin.
Cribriform morular thyroid carcinoma. Non-morular area showing oval, overlapping grooved nuclei.
Cribriform morular thyroid carcinoma. β-catenin immunohistochemistry, showing strong nuclear and moderate cytoplasmic reactivity in both follicular and morular cells.
Cribriform morular thyroid carcinoma. This tumour is diffusely positive for ER.
Cribriform morular thyroid carcinoma. β-catenin immunostaining shows characteristic aberrant immunopositivity in the nuclei and in the cytoplasm of the tumour cells.
Cribriform morular thyroid carcinoma. The tumour is positive for thyroid transcription factor 1 (TTF1) by immunostaining, except for the morules (arrows).
Cribriform morular thyroid carcinoma. There is a morule in the upper left and cribriform tubular growth in the lower right.
Cribriform morular thyroid carcinoma. Papillae and pseudopapillae are lined by tall, cuboidal, or pseudostratified columnar cells. Tubular follicles lacking colloid are seen.
Cribriform morular thyroid carcinoma. The cribriform structures lack intervening fibrous stroma and merge with tubular follicles that lack colloid.
Cribriform morular thyroid carcinoma. These tumours are usually circumscribed or encapsulated, but they can have fibrous bands imparting a multilobulated appearance.
Cribriform morular thyroid carcinoma. The morular component is positive for CK5.
Cribriform morular thyroid carcinoma. Immunostaining for CD5 highlights the morular component of these tumours, as well as scattered CD5-positive T lymphocytes.

Q: In Cribriform Morular Thyroid Carcinoma, the morular areas frequently contain scattered optically clear nuclei, which is caused by the accumulation of [...].
Cribriform morular thyroid carcinoma. Cribriform architecture, with irregularly shaped follicular structures devoid of colloid, interspersed with morular areas. Inset: Scattered optically clear nuclei within morules, caused by the accumulation of biotin.
A: biotin
Back Extra: Cribriform Morular Thyroid Carcinoma
- Clinical: Cribriform Morular Thyroid Carcinoma is most commonly found in young women, with 89% of cases occurring in individuals aged < 40 years. It can present as a painless mass, hoarseness, or dysphagia.
- Micro: The tumour shows a distinctive admixture of growth patterns, including cribriform, follicular, papillary, trabecular, and solid patterns, with squamoid morulae and papillae lined by tall, cuboidal, or pseudostratified cells.
- Ancillary: Characteristic aberrant nuclear and cytoplasmic β-catenin staining is a hallmark of Cribriform Morular Thyroid Carcinoma, reflecting constitutive WNT/β-catenin pathway activation.
Reference Gallery:
Cribriform morular thyroid carcinoma. Cribriform architecture, with irregularly shaped follicular structures devoid of colloid, interspersed with morular areas. Inset: Scattered optically clear nuclei within morules, caused by the accumulation of biotin.
Cribriform morular thyroid carcinoma. Non-morular area showing oval, overlapping grooved nuclei.
Cribriform morular thyroid carcinoma. β-catenin immunohistochemistry, showing strong nuclear and moderate cytoplasmic reactivity in both follicular and morular cells.
Cribriform morular thyroid carcinoma. This tumour is diffusely positive for ER.
Cribriform morular thyroid carcinoma. β-catenin immunostaining shows characteristic aberrant immunopositivity in the nuclei and in the cytoplasm of the tumour cells.
Cribriform morular thyroid carcinoma. The tumour is positive for thyroid transcription factor 1 (TTF1) by immunostaining, except for the morules (arrows).
Cribriform morular thyroid carcinoma. There is a morule in the upper left and cribriform tubular growth in the lower right.
Cribriform morular thyroid carcinoma. Papillae and pseudopapillae are lined by tall, cuboidal, or pseudostratified columnar cells. Tubular follicles lacking colloid are seen.
Cribriform morular thyroid carcinoma. The cribriform structures lack intervening fibrous stroma and merge with tubular follicles that lack colloid.
Cribriform morular thyroid carcinoma. These tumours are usually circumscribed or encapsulated, but they can have fibrous bands imparting a multilobulated appearance.
Cribriform morular thyroid carcinoma. The morular component is positive for CK5.
Cribriform morular thyroid carcinoma. Immunostaining for CD5 highlights the morular component of these tumours, as well as scattered CD5-positive T lymphocytes.

Q: Grossly and microscopically, a Follicular Adenoma of the Thyroid is characteristically well-circumscribed and demarcated from the surrounding benign parenchyma by a thin fibrous [...].
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
A: capsule
Back Extra: Follicular Adenoma of the Thyroid
- Clinical: Follicular adenomas of the thyroid typically present as solitary or dominant palpable masses, with compressive symptoms in about 15% of cases.
- Micro: Follicular adenomas are well-circumscribed and encapsulated, often showing a mixture of microfollicles and macrofollicles with bland, monomorphic nuclei.
- Ancillary: Immunohistochemistry shows reactivity for thyroglobulin, TTF1, and PAX8, but negative for calcitonin and PTH. Galectin-3 can be expressed in up to 30% of benign lesions.
Reference Gallery:
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. There are multiple encapsulated tan-white follicular adenomas in a multinodular background in this patient with PTEN hamartoma tumour syndrome.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
Follicular adenoma. The nuclei are bland and monomorphic and have round to ovid nucleoli with condensed chromatin. The nuclei should not deviate much from those in the adjacent normal tissue, seen here as a compressed follicle.
Follicular adenoma with papillary architecture. Like conventional follicular adenomas, those with papillary architecture are demarcated from the surrounding thyroid by a capsule but often show cystic change and a pseudopapillary architecture, reminiscent of a hyperplastic nodule. These are fairly common in adolescents.
Follicular adenoma (FA) with papillary architecture. The pseudopapillae seen in FA with papillary architecture show cuboidal to columnar cells with bland ovoid nuclei, similar to those seen in typical FA, and are polarized towards the basement membrane without much stratification or overlap. In contrast to the fibrovascular cores of true papillae seen in conventional papillary thyroid carcinoma, these papillae often show follicles within. The cytoplasm is often somewhat oncocytic. Hyperfunctioning adenomas may show some overlap with FA with papillary architecture but often show more vacuolated cytoplasm and scalloped colloid.
Follicular adenoma in a background of thyroiditis. This example shows a prominent microfollicular pattern and is notably spared by the lymphocytic infiltrates, which is typically the case for neoplasms in a thyroiditis background.
Thyroid follicular adenoma. The Pap-stained smear is cellular, with limited colloid. The follicular cells are arranged in tight follicles and have round nuclei.

Q: Cytologically and histologically, the cells composing a Follicular Adenoma of the Thyroid arrange in microfollicles or macrofollicles and exhibit uniformly [...] nuclei with condensed chromatin, completely lacking the nuclear atypia seen in papillary thyroid carcinoma.
Follicular adenoma. The nuclei are bland and monomorphic and have round to ovid nucleoli with condensed chromatin. The nuclei should not deviate much from those in the adjacent normal tissue, seen here as a compressed follicle.
Thyroid follicular adenoma. The Pap-stained smear is cellular, with limited colloid. The follicular cells are arranged in tight follicles and have round nuclei.
A: bland and monomorphic
Back Extra: Follicular Adenoma of the Thyroid
- Clinical: Follicular adenomas of the thyroid typically present as solitary or dominant palpable masses, with compressive symptoms in about 15% of cases.
- Micro: Follicular adenomas are well-circumscribed and encapsulated, often showing a mixture of microfollicles and macrofollicles with bland, monomorphic nuclei.
- Ancillary: Immunohistochemistry shows reactivity for thyroglobulin, TTF1, and PAX8, but negative for calcitonin and PTH. Galectin-3 can be expressed in up to 30% of benign lesions.
Reference Gallery:
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. There are multiple encapsulated tan-white follicular adenomas in a multinodular background in this patient with PTEN hamartoma tumour syndrome.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
Follicular adenoma. The nuclei are bland and monomorphic and have round to ovid nucleoli with condensed chromatin. The nuclei should not deviate much from those in the adjacent normal tissue, seen here as a compressed follicle.
Follicular adenoma with papillary architecture. Like conventional follicular adenomas, those with papillary architecture are demarcated from the surrounding thyroid by a capsule but often show cystic change and a pseudopapillary architecture, reminiscent of a hyperplastic nodule. These are fairly common in adolescents.
Follicular adenoma (FA) with papillary architecture. The pseudopapillae seen in FA with papillary architecture show cuboidal to columnar cells with bland ovoid nuclei, similar to those seen in typical FA, and are polarized towards the basement membrane without much stratification or overlap. In contrast to the fibrovascular cores of true papillae seen in conventional papillary thyroid carcinoma, these papillae often show follicles within. The cytoplasm is often somewhat oncocytic. Hyperfunctioning adenomas may show some overlap with FA with papillary architecture but often show more vacuolated cytoplasm and scalloped colloid.
Follicular adenoma in a background of thyroiditis. This example shows a prominent microfollicular pattern and is notably spared by the lymphocytic infiltrates, which is typically the case for neoplasms in a thyroiditis background.
Thyroid follicular adenoma. The Pap-stained smear is cellular, with limited colloid. The follicular cells are arranged in tight follicles and have round nuclei.

Q: A distinct morphological variant of Follicular Adenoma of the Thyroid frequently seen in adolescents can exhibit cystic change and a [...] architecture, which differs from conventional papillary thyroid carcinoma by lacking true fibrovascular cores.
Follicular adenoma with papillary architecture. Like conventional follicular adenomas, those with papillary architecture are demarcated from the surrounding thyroid by a capsule but often show cystic change and a pseudopapillary architecture, reminiscent of a hyperplastic nodule. These are fairly common in adolescents.
Follicular adenoma (FA) with papillary architecture. The pseudopapillae seen in FA with papillary architecture show cuboidal to columnar cells with bland ovoid nuclei, similar to those seen in typical FA, and are polarized towards the basement membrane without much stratification or overlap. In contrast to the fibrovascular cores of true papillae seen in conventional papillary thyroid carcinoma, these papillae often show follicles within. The cytoplasm is often somewhat oncocytic. Hyperfunctioning adenomas may show some overlap with FA with papillary architecture but often show more vacuolated cytoplasm and scalloped colloid.
A: pseudopapillary
Back Extra: Follicular Adenoma of the Thyroid
- Clinical: Follicular adenomas of the thyroid typically present as solitary or dominant palpable masses, with compressive symptoms in about 15% of cases.
- Micro: Follicular adenomas are well-circumscribed and encapsulated, often showing a mixture of microfollicles and macrofollicles with bland, monomorphic nuclei.
- Ancillary: Immunohistochemistry shows reactivity for thyroglobulin, TTF1, and PAX8, but negative for calcitonin and PTH. Galectin-3 can be expressed in up to 30% of benign lesions.
Reference Gallery:
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. There are multiple encapsulated tan-white follicular adenomas in a multinodular background in this patient with PTEN hamartoma tumour syndrome.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
Follicular adenoma. The nuclei are bland and monomorphic and have round to ovid nucleoli with condensed chromatin. The nuclei should not deviate much from those in the adjacent normal tissue, seen here as a compressed follicle.
Follicular adenoma with papillary architecture. Like conventional follicular adenomas, those with papillary architecture are demarcated from the surrounding thyroid by a capsule but often show cystic change and a pseudopapillary architecture, reminiscent of a hyperplastic nodule. These are fairly common in adolescents.
Follicular adenoma (FA) with papillary architecture. The pseudopapillae seen in FA with papillary architecture show cuboidal to columnar cells with bland ovoid nuclei, similar to those seen in typical FA, and are polarized towards the basement membrane without much stratification or overlap. In contrast to the fibrovascular cores of true papillae seen in conventional papillary thyroid carcinoma, these papillae often show follicles within. The cytoplasm is often somewhat oncocytic. Hyperfunctioning adenomas may show some overlap with FA with papillary architecture but often show more vacuolated cytoplasm and scalloped colloid.
Follicular adenoma in a background of thyroiditis. This example shows a prominent microfollicular pattern and is notably spared by the lymphocytic infiltrates, which is typically the case for neoplasms in a thyroiditis background.
Thyroid follicular adenoma. The Pap-stained smear is cellular, with limited colloid. The follicular cells are arranged in tight follicles and have round nuclei.

Q: An encapsulated, well-demarcated benign neoplasm composed of varying follicular architectures with bland nuclei, strictly lacking capsular or vascular invasion, is best diagnosed as a [...].
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
A: Follicular Adenoma of the Thyroid
Follicular Adenoma of the Thyroid
- Clinical: The majority of Follicular Adenomas of the Thyroid manifest as solitary or dominant palpable masses, often with a smooth, well-defined border on ultrasound.
- Micro: Follicular Adenomas of the Thyroid are well-circumscribed and encapsulated, with a mixture of microfollicular and macrofollicular patterns and bland, monomorphic nuclei.
- Ancillary: Immunohistochemistry shows reactivity for thyroglobulin, TTF1, and PAX8, aiding in the diagnosis of Follicular Adenomas of the Thyroid.
Reference Gallery:
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. There are multiple encapsulated tan-white follicular adenomas in a multinodular background in this patient with PTEN hamartoma tumour syndrome.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
Follicular adenoma. The nuclei are bland and monomorphic and have round to ovoid nucleoli with condensed chromatin. The nuclei should not deviate much from those in the adjacent normal tissue, seen here as a compressed follicle.
Follicular adenoma with papillary architecture. Like conventional follicular adenomas, those with papillary architecture are demarcated from the surrounding thyroid by a capsule but often show cystic change and a pseudopapillary architecture, reminiscent of a hyperplastic nodule. These are fairly common in adolescents.
Follicular adenoma (FA) with papillary architecture. The pseudopapillae seen in FA with papillary architecture show cuboidal to columnar cells with bland ovoid nuclei, similar to those seen in typical FA, and are polarized towards the basement membrane without much stratification or overlap. In contrast to the fibrovascular cores of true papillae seen in conventional papillary thyroid carcinoma, these papillae often show follicles within. The cytoplasm is often somewhat oncocytic. Hyperfunctioning adenomas may show some overlap with FA with papillary architecture but often show more vacuolated cytoplasm and scalloped colloid.
Follicular adenoma in a background of thyroiditis. This example shows a prominent microfollicular pattern and is notably spared by the lymphocytic infiltrates, which is typically the case for neoplasms in a thyroiditis background.
Thyroid follicular adenoma. The Pap-stained smear is cellular, with limited colloid. The follicular cells are arranged in tight follicles and have round nuclei.

Q: Grossly and microscopically, a Follicular Adenoma of the Thyroid is structurally defined by the presence of a well-formed, intact fibrous [...] that completely separates the uniform neoplastic proliferation from the adjacent normal parenchyma.
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
A: capsule
Follicular Adenoma of the Thyroid
- Clinical: The majority of Follicular Adenomas of the Thyroid manifest as solitary or dominant palpable masses, often with a smooth, well-defined border on ultrasound.
- Micro: Follicular Adenomas of the Thyroid are well-circumscribed and encapsulated, with a mixture of microfollicular and macrofollicular patterns and bland, monomorphic nuclei.
- Ancillary: Immunohistochemistry shows reactivity for thyroglobulin, TTF1, and PAX8, aiding in the diagnosis of Follicular Adenomas of the Thyroid.
Reference Gallery:
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. There are multiple encapsulated tan-white follicular adenomas in a multinodular background in this patient with PTEN hamartoma tumour syndrome.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
Follicular adenoma. The nuclei are bland and monomorphic and have round to ovoid nucleoli with condensed chromatin. The nuclei should not deviate much from those in the adjacent normal tissue, seen here as a compressed follicle.
Follicular adenoma with papillary architecture. Like conventional follicular adenomas, those with papillary architecture are demarcated from the surrounding thyroid by a capsule but often show cystic change and a pseudopapillary architecture, reminiscent of a hyperplastic nodule. These are fairly common in adolescents.
Follicular adenoma (FA) with papillary architecture. The pseudopapillae seen in FA with papillary architecture show cuboidal to columnar cells with bland ovoid nuclei, similar to those seen in typical FA, and are polarized towards the basement membrane without much stratification or overlap. In contrast to the fibrovascular cores of true papillae seen in conventional papillary thyroid carcinoma, these papillae often show follicles within. The cytoplasm is often somewhat oncocytic. Hyperfunctioning adenomas may show some overlap with FA with papillary architecture but often show more vacuolated cytoplasm and scalloped colloid.
Follicular adenoma in a background of thyroiditis. This example shows a prominent microfollicular pattern and is notably spared by the lymphocytic infiltrates, which is typically the case for neoplasms in a thyroiditis background.
Thyroid follicular adenoma. The Pap-stained smear is cellular, with limited colloid. The follicular cells are arranged in tight follicles and have round nuclei.

Q: In contrast to the optically clear and grooved nuclei of papillary thyroid carcinoma, the nuclei in a Follicular Adenoma of the Thyroid are characteristically round to ovoid, bland, and [...].
Follicular adenoma. The nuclei are bland and monomorphic and have round to ovoid nucleoli with condensed chromatin. The nuclei should not deviate much from those in the adjacent normal tissue, seen here as a compressed follicle.
Thyroid follicular adenoma. The Pap-stained smear is cellular, with limited colloid. The follicular cells are arranged in tight follicles and have round nuclei.
A: monomorphic
Follicular Adenoma of the Thyroid
- Clinical: The majority of Follicular Adenomas of the Thyroid manifest as solitary or dominant palpable masses, often with a smooth, well-defined border on ultrasound.
- Micro: Follicular Adenomas of the Thyroid are well-circumscribed and encapsulated, with a mixture of microfollicular and macrofollicular patterns and bland, monomorphic nuclei.
- Ancillary: Immunohistochemistry shows reactivity for thyroglobulin, TTF1, and PAX8, aiding in the diagnosis of Follicular Adenomas of the Thyroid.
Reference Gallery:
Follicular adenoma. This example is encapsulated and well delineated from the adjacent thyroid parenchyma and shows a homogeneous light-pink to tan cut surface.
Follicular adenoma. There are multiple encapsulated tan-white follicular adenomas in a multinodular background in this patient with PTEN hamartoma tumour syndrome.
Follicular adenoma. This example demonstrates a thin capsule that imparts separation from the surrounding parenchyma. It is composed of a mixture of microfollicles and macrofollicles, and it is overall more cellular and distinct from the surrounding thyroid.
Follicular adenoma. The nuclei are bland and monomorphic and have round to ovoid nucleoli with condensed chromatin. The nuclei should not deviate much from those in the adjacent normal tissue, seen here as a compressed follicle.
Follicular adenoma with papillary architecture. Like conventional follicular adenomas, those with papillary architecture are demarcated from the surrounding thyroid by a capsule but often show cystic change and a pseudopapillary architecture, reminiscent of a hyperplastic nodule. These are fairly common in adolescents.
Follicular adenoma (FA) with papillary architecture. The pseudopapillae seen in FA with papillary architecture show cuboidal to columnar cells with bland ovoid nuclei, similar to those seen in typical FA, and are polarized towards the basement membrane without much stratification or overlap. In contrast to the fibrovascular cores of true papillae seen in conventional papillary thyroid carcinoma, these papillae often show follicles within. The cytoplasm is often somewhat oncocytic. Hyperfunctioning adenomas may show some overlap with FA with papillary architecture but often show more vacuolated cytoplasm and scalloped colloid.
Follicular adenoma in a background of thyroiditis. This example shows a prominent microfollicular pattern and is notably spared by the lymphocytic infiltrates, which is typically the case for neoplasms in a thyroiditis background.
Thyroid follicular adenoma. The Pap-stained smear is cellular, with limited colloid. The follicular cells are arranged in tight follicles and have round nuclei.

Q: Microscopically, Medullary Thyroid Carcinoma can exhibit solid, cribriform, or follicular growth patterns composed of round and spindle cells, and is classically associated with an [...] stroma.
Medullary thyroid carcinoma. Medullary thyroid carcinoma showing an admixture of round and spindle cells with minimal atypia, in a solid, cribriform, and follicular growth pattern.
FNAB cytology of medullary thyroid carcinoma. Romanowsky-stained smear showing cellular dyscohesion, anisocytosis, binucleation/multinucleation, and small intracytoplasmic vacuoles. Inset: Coarse amyloid fragment.
A: amyloid
Q: Medullary Thyroid Carcinoma
- Clinical: In hereditary medullary thyroid carcinoma ([...]), the tumour often presents in the second decade of life with painless thyroid nodules or cervical lymphadenopathy, and can be associated with multiple endocrine neoplasia type 2 (MEN2).
- Micro: Medullary thyroid carcinoma ([...]) can show a variety of patterns, including solid, cribriform, and follicular growth with minimal atypia, and is often associated with amyloid stroma.
- Ancillary: Immunohistochemistry for calcitonin, chromogranin, and CEA is crucial in diagnosing medullary thyroid carcinoma ([...]).
Reference Gallery:
RET gene/protein. Diagram demonstrating the protein domains, most common germline pathogenic sequence variants in multiple endocrine neoplasia syndromes, and relative risks for aggressive carcinomas.
Medullary thyroid carcinoma. Ultrasound image of the thyroid of a syndromic patient. Bilateral sonographically abnormal thyroid nodules are present in this patient with a RET p.G533C germline variant: longitudinal greyscale sonography reveals a dominant left-lobe hypoechoic solid 12 mm nodule (yellow arrow) and a similar subcentimetre right-lobe nodule (inset), both containing dystrophic calcifications (red arrows).
Medullary thyroid carcinoma. Longitudinal colour Doppler sonography of the thyroid of a syndromic patient. In a patient with a RET p.V804M germline pathogenic sequence variant, longitudinal colour Doppler sonography shows flow within a hypoechoic 13 mm nodule, confirming its solid composition.
Outer surface of a prophylactic thyroidectomy. Prophylactic total thyroidectomy in a 3-year-old girl with multiple endocrine neoplasia type 2. The total weight of the gland was 1.53 g. The greatest dimension (longitudinal) of the right lobe was 21 mm and that of the left lobe was 17 mm. Microscopically, C-cell hyperplasia was identified.
Cut surface of a total thyroidectomy in a syndromic patient. Total thyroidectomy in an 11-year-old boy with known multiple endocrine neoplasia type 2 and clinically suspected medullary thyroid carcinoma. The total weight of the gland was 10.3 g. The greatest dimension (longitudinal) of the right lobe was 35 mm and that of the left lobe was 22 mm. A 19 mm tumour was present in the right upper-mid lobe and a 3 mm tumour was in the left upper lobe.
Medullary thyroid carcinoma. Medullary thyroid carcinoma showing an admixture of round and spindle cells with minimal atypia, in a solid, cribriform, and follicular growth pattern.
Primary C-cell hyperplasia. C cells line and fill follicles, but there is no destructive invasion.
Primary C-cell hyperplasia. Calcitonin staining highlights primary C-cell hyperplasia in a prophylactic thyroidectomy in a syndromic child.
FNAB cytology of medullary thyroid carcinoma. Pap-stained alcohol-fixed smear showing vaguely cohesive cells with round to oval nuclei with finely stippled chromatin and small nucleoli. Inset: Spindled cells.
FNAB cytology of medullary thyroid carcinoma. Romanowsky-stained smear showing cellular dyscohesion, anisocytosis, binucleation/multinucleation, and small intracytoplasmic vacuoles. Inset: Coarse amyloid fragment.
Medullary thyroid carcinoma. Many different patterns of growth can be seen in a medullary thyroid carcinoma, including a cribriform pattern, showing apoptosis in the centre.
Medullary thyroid carcinoma. A pseudopapillary architecture can be seen in some tumours, showing areas of necrosis.
A: MTC; MTC; MTC

Q: Hereditary cases of Medullary Thyroid Carcinoma are strongly associated with germline pathogenic variants in the RET gene, manifesting as part of [...] syndromes.
RET gene/protein. Diagram demonstrating the protein domains, most common germline pathogenic sequence variants in multiple endocrine neoplasia syndromes, and relative risks for aggressive carcinomas.
Cut surface of a total thyroidectomy in a syndromic patient. Total thyroidectomy in an 11-year-old boy with known multiple endocrine neoplasia type 2 and clinically suspected medullary thyroid carcinoma. The total weight of the gland was 10.3 g. The greatest dimension (longitudinal) of the right lobe was 35 mm and that of the left lobe was 22 mm. A 19 mm tumour was present in the right upper-mid lobe and a 3 mm tumour was in the left upper lobe.
A: multiple endocrine neoplasia type 2 (MEN2)
Q: Medullary Thyroid Carcinoma
- Clinical: In hereditary medullary thyroid carcinoma ([...]), the tumour often presents in the second decade of life with painless thyroid nodules or cervical lymphadenopathy, and can be associated with multiple endocrine neoplasia type 2 (MEN2).
- Micro: Medullary thyroid carcinoma ([...]) can show a variety of patterns, including solid, cribriform, and follicular growth with minimal atypia, and is often associated with amyloid stroma.
- Ancillary: Immunohistochemistry for calcitonin, chromogranin, and CEA is crucial in diagnosing medullary thyroid carcinoma ([...]).
Reference Gallery:
RET gene/protein. Diagram demonstrating the protein domains, most common germline pathogenic sequence variants in multiple endocrine neoplasia syndromes, and relative risks for aggressive carcinomas.
Medullary thyroid carcinoma. Ultrasound image of the thyroid of a syndromic patient. Bilateral sonographically abnormal thyroid nodules are present in this patient with a RET p.G533C germline variant: longitudinal greyscale sonography reveals a dominant left-lobe hypoechoic solid 12 mm nodule (yellow arrow) and a similar subcentimetre right-lobe nodule (inset), both containing dystrophic calcifications (red arrows).
Medullary thyroid carcinoma. Longitudinal colour Doppler sonography of the thyroid of a syndromic patient. In a patient with a RET p.V804M germline pathogenic sequence variant, longitudinal colour Doppler sonography shows flow within a hypoechoic 13 mm nodule, confirming its solid composition.
Outer surface of a prophylactic thyroidectomy. Prophylactic total thyroidectomy in a 3-year-old girl with multiple endocrine neoplasia type 2. The total weight of the gland was 1.53 g. The greatest dimension (longitudinal) of the right lobe was 21 mm and that of the left lobe was 17 mm. Microscopically, C-cell hyperplasia was identified.
Cut surface of a total thyroidectomy in a syndromic patient. Total thyroidectomy in an 11-year-old boy with known multiple endocrine neoplasia type 2 and clinically suspected medullary thyroid carcinoma. The total weight of the gland was 10.3 g. The greatest dimension (longitudinal) of the right lobe was 35 mm and that of the left lobe was 22 mm. A 19 mm tumour was present in the right upper-mid lobe and a 3 mm tumour was in the left upper lobe.
Medullary thyroid carcinoma. Medullary thyroid carcinoma showing an admixture of round and spindle cells with minimal atypia, in a solid, cribriform, and follicular growth pattern.
Primary C-cell hyperplasia. C cells line and fill follicles, but there is no destructive invasion.
Primary C-cell hyperplasia. Calcitonin staining highlights primary C-cell hyperplasia in a prophylactic thyroidectomy in a syndromic child.
FNAB cytology of medullary thyroid carcinoma. Pap-stained alcohol-fixed smear showing vaguely cohesive cells with round to oval nuclei with finely stippled chromatin and small nucleoli. Inset: Spindled cells.
FNAB cytology of medullary thyroid carcinoma. Romanowsky-stained smear showing cellular dyscohesion, anisocytosis, binucleation/multinucleation, and small intracytoplasmic vacuoles. Inset: Coarse amyloid fragment.
Medullary thyroid carcinoma. Many different patterns of growth can be seen in a medullary thyroid carcinoma, including a cribriform pattern, showing apoptosis in the centre.
Medullary thyroid carcinoma. A pseudopapillary architecture can be seen in some tumours, showing areas of necrosis.
A: MTC; MTC; MTC

Q: Medullary Thyroid Carcinoma arises from parafollicular C-cells; prophylactic thyroidectomies in syndromic patients often reveal the precursor lesion, primary C-cell hyperplasia, which is strongly positive for [...] by immunohistochemistry.
Primary C-cell hyperplasia. C cells line and fill follicles, but there is no destructive invasion.
Primary C-cell hyperplasia. Calcitonin staining highlights primary C-cell hyperplasia in a prophylactic thyroidectomy in a syndromic child.
A: calcitonin
Q: Medullary Thyroid Carcinoma
- Clinical: In hereditary medullary thyroid carcinoma ([...]), the tumour often presents in the second decade of life with painless thyroid nodules or cervical lymphadenopathy, and can be associated with multiple endocrine neoplasia type 2 (MEN2).
- Micro: Medullary thyroid carcinoma ([...]) can show a variety of patterns, including solid, cribriform, and follicular growth with minimal atypia, and is often associated with amyloid stroma.
- Ancillary: Immunohistochemistry for calcitonin, chromogranin, and CEA is crucial in diagnosing medullary thyroid carcinoma ([...]).
Reference Gallery:
RET gene/protein. Diagram demonstrating the protein domains, most common germline pathogenic sequence variants in multiple endocrine neoplasia syndromes, and relative risks for aggressive carcinomas.
Medullary thyroid carcinoma. Ultrasound image of the thyroid of a syndromic patient. Bilateral sonographically abnormal thyroid nodules are present in this patient with a RET p.G533C germline variant: longitudinal greyscale sonography reveals a dominant left-lobe hypoechoic solid 12 mm nodule (yellow arrow) and a similar subcentimetre right-lobe nodule (inset), both containing dystrophic calcifications (red arrows).
Medullary thyroid carcinoma. Longitudinal colour Doppler sonography of the thyroid of a syndromic patient. In a patient with a RET p.V804M germline pathogenic sequence variant, longitudinal colour Doppler sonography shows flow within a hypoechoic 13 mm nodule, confirming its solid composition.
Outer surface of a prophylactic thyroidectomy. Prophylactic total thyroidectomy in a 3-year-old girl with multiple endocrine neoplasia type 2. The total weight of the gland was 1.53 g. The greatest dimension (longitudinal) of the right lobe was 21 mm and that of the left lobe was 17 mm. Microscopically, C-cell hyperplasia was identified.
Cut surface of a total thyroidectomy in a syndromic patient. Total thyroidectomy in an 11-year-old boy with known multiple endocrine neoplasia type 2 and clinically suspected medullary thyroid carcinoma. The total weight of the gland was 10.3 g. The greatest dimension (longitudinal) of the right lobe was 35 mm and that of the left lobe was 22 mm. A 19 mm tumour was present in the right upper-mid lobe and a 3 mm tumour was in the left upper lobe.
Medullary thyroid carcinoma. Medullary thyroid carcinoma showing an admixture of round and spindle cells with minimal atypia, in a solid, cribriform, and follicular growth pattern.
Primary C-cell hyperplasia. C cells line and fill follicles, but there is no destructive invasion.
Primary C-cell hyperplasia. Calcitonin staining highlights primary C-cell hyperplasia in a prophylactic thyroidectomy in a syndromic child.
FNAB cytology of medullary thyroid carcinoma. Pap-stained alcohol-fixed smear showing vaguely cohesive cells with round to oval nuclei with finely stippled chromatin and small nucleoli. Inset: Spindled cells.
FNAB cytology of medullary thyroid carcinoma. Romanowsky-stained smear showing cellular dyscohesion, anisocytosis, binucleation/multinucleation, and small intracytoplasmic vacuoles. Inset: Coarse amyloid fragment.
Medullary thyroid carcinoma. Many different patterns of growth can be seen in a medullary thyroid carcinoma, including a cribriform pattern, showing apoptosis in the centre.
Medullary thyroid carcinoma. A pseudopapillary architecture can be seen in some tumours, showing areas of necrosis.
A: MTC; MTC; MTC

Q: The classic histopathologic finding in Medullary Thyroid Carcinoma is a proliferation of round, plasmacytoid, and spindle-shaped cells associated with an extracellular stroma composed of [...].
Medullary thyroid carcinoma. Medullary thyroid carcinoma showing an admixture of round and spindle cells with minimal atypia, in a solid, cribriform, and follicular growth pattern.
FNAB cytology of medullary thyroid carcinoma. Romanowsky-stained smear showing cellular dyscohesion, anisocytosis, binucleation/multinucleation, and small intracytoplasmic vacuoles. Inset: Coarse amyloid fragment.
A: amyloid
Back Extra: Medullary Thyroid Carcinoma
- Clinical: Medullary thyroid carcinoma (MTC) often presents as a painless thyroid nodule or cervical lymphadenopathy. Serum levels of calcitonin are a key diagnostic marker.
- Micro: Histopathology of MTC shows a variety of growth patterns including solid, trabecular, and cribriform, with frequent presence of amyloid stroma.
- Ancillary: Immunohistochemistry is critical for diagnosing MTC, with positive markers including calcitonin, CGRP, synaptophysin, chromogranins, and CEA.
Reference Gallery:
Medullary thyroid carcinoma. Ultrasound image of the thyroid of a syndromic patient. Bilateral sonographically abnormal thyroid nodules are present in this patient with a RET p.G533C germline variant: longitudinal greyscale sonography reveals a dominant left-lobe hypoechoic solid 12 mm nodule (yellow arrow) and a similar subcentimetre right-lobe nodule (inset), both containing dystrophic calcifications (red arrows).
Medullary thyroid carcinoma. Longitudinal colour Doppler sonography of the thyroid of a syndromic patient. In a patient with a RET p.V804M germline pathogenic sequence variant, longitudinal colour Doppler sonography shows flow within a hypoechoic 13 mm nodule, confirming its solid composition.
Outer surface of a prophylactic thyroidectomy. Prophylactic total thyroidectomy in a 3-year-old girl with multiple endocrine neoplasia type 2. The total weight of the gland was 1.53 g. The greatest dimension (longitudinal) of the right lobe was 21 mm and that of the left lobe was 17 mm. Microscopically, C-cell hyperplasia was identified.
Cut surface of a total thyroidectomy in a syndromic patient. Total thyroidectomy in an 11-year-old boy with known multiple endocrine neoplasia type 2 and clinically suspected medullary thyroid carcinoma. The total weight of the gland was 10.3 g. The greatest dimension (longitudinal) of the right lobe was 35 mm and that of the left lobe was 22 mm. A 19 mm tumour was present in the right upper-mid lobe and a 3 mm tumour was in the left upper lobe.
Medullary thyroid carcinoma. Medullary thyroid carcinoma showing an admixture of round and spindle cells with minimal atypia, in a solid, cribriform, and follicular growth pattern.
Primary C-cell hyperplasia. C cells line and fill follicles, but there is no destructive invasion.
Primary C-cell hyperplasia. Calcitonin staining highlights primary C-cell hyperplasia in a prophylactic thyroidectomy in a syndromic child.
FNAB cytology of medullary thyroid carcinoma. Pap-stained alcohol-fixed smear showing vaguely cohesive cells with round to oval nuclei with finely stippled chromatin and small nucleoli. Inset: Spindled cells.
FNAB cytology of medullary thyroid carcinoma. Romanowsky-stained smear showing cellular dyscohesion, anisocytosis, binucleation/multinucleation, and small intracytoplasmic vacuoles. Inset: Coarse amyloid fragment.
Medullary thyroid carcinoma. Many different patterns of growth can be seen in a medullary thyroid carcinoma, including a cribriform pattern, showing apoptosis in the centre.
Medullary thyroid carcinoma. A pseudopapillary architecture can be seen in some tumours, showing areas of necrosis.

Q: In familial syndromes like MEN2, prophylactic thyroidectomies are performed to prevent Medullary Thyroid Carcinoma, frequently revealing the precursor lesion known as primary [...].
Outer surface of a prophylactic thyroidectomy. Prophylactic total thyroidectomy in a 3-year-old girl with multiple endocrine neoplasia type 2. The total weight of the gland was 1.53 g. The greatest dimension (longitudinal) of the right lobe was 21 mm and that of the left lobe was 17 mm. Microscopically, C-cell hyperplasia was identified.
Primary C-cell hyperplasia. C cells line and fill follicles, but there is no destructive invasion.
Primary C-cell hyperplasia. Calcitonin staining highlights primary C-cell hyperplasia in a prophylactic thyroidectomy in a syndromic child.
A: C-cell hyperplasia
Back Extra: Medullary Thyroid Carcinoma
- Clinical: Medullary thyroid carcinoma (MTC) often presents as a painless thyroid nodule or cervical lymphadenopathy. Serum levels of calcitonin are a key diagnostic marker.
- Micro: Histopathology of MTC shows a variety of growth patterns including solid, trabecular, and cribriform, with frequent presence of amyloid stroma.
- Ancillary: Immunohistochemistry is critical for diagnosing MTC, with positive markers including calcitonin, CGRP, synaptophysin, chromogranins, and CEA.
Reference Gallery:
Medullary thyroid carcinoma. Ultrasound image of the thyroid of a syndromic patient. Bilateral sonographically abnormal thyroid nodules are present in this patient with a RET p.G533C germline variant: longitudinal greyscale sonography reveals a dominant left-lobe hypoechoic solid 12 mm nodule (yellow arrow) and a similar subcentimetre right-lobe nodule (inset), both containing dystrophic calcifications (red arrows).
Medullary thyroid carcinoma. Longitudinal colour Doppler sonography of the thyroid of a syndromic patient. In a patient with a RET p.V804M germline pathogenic sequence variant, longitudinal colour Doppler sonography shows flow within a hypoechoic 13 mm nodule, confirming its solid composition.
Outer surface of a prophylactic thyroidectomy. Prophylactic total thyroidectomy in a 3-year-old girl with multiple endocrine neoplasia type 2. The total weight of the gland was 1.53 g. The greatest dimension (longitudinal) of the right lobe was 21 mm and that of the left lobe was 17 mm. Microscopically, C-cell hyperplasia was identified.
Cut surface of a total thyroidectomy in a syndromic patient. Total thyroidectomy in an 11-year-old boy with known multiple endocrine neoplasia type 2 and clinically suspected medullary thyroid carcinoma. The total weight of the gland was 10.3 g. The greatest dimension (longitudinal) of the right lobe was 35 mm and that of the left lobe was 22 mm. A 19 mm tumour was present in the right upper-mid lobe and a 3 mm tumour was in the left upper lobe.
Medullary thyroid carcinoma. Medullary thyroid carcinoma showing an admixture of round and spindle cells with minimal atypia, in a solid, cribriform, and follicular growth pattern.
Primary C-cell hyperplasia. C cells line and fill follicles, but there is no destructive invasion.
Primary C-cell hyperplasia. Calcitonin staining highlights primary C-cell hyperplasia in a prophylactic thyroidectomy in a syndromic child.
FNAB cytology of medullary thyroid carcinoma. Pap-stained alcohol-fixed smear showing vaguely cohesive cells with round to oval nuclei with finely stippled chromatin and small nucleoli. Inset: Spindled cells.
FNAB cytology of medullary thyroid carcinoma. Romanowsky-stained smear showing cellular dyscohesion, anisocytosis, binucleation/multinucleation, and small intracytoplasmic vacuoles. Inset: Coarse amyloid fragment.
Medullary thyroid carcinoma. Many different patterns of growth can be seen in a medullary thyroid carcinoma, including a cribriform pattern, showing apoptosis in the centre.
Medullary thyroid carcinoma. A pseudopapillary architecture can be seen in some tumours, showing areas of necrosis.

Q: Familial cases of Medullary Thyroid Carcinoma, such as those seen in MEN2 syndromes, are typically driven by germline pathogenic variants in the [...] proto-oncogene.
Medullary thyroid carcinoma. Ultrasound image of the thyroid of a syndromic patient. Bilateral sonographically abnormal thyroid nodules are present in this patient with a RET p.G533C germline variant: longitudinal greyscale sonography reveals a dominant left-lobe hypoechoic solid 12 mm nodule (yellow arrow) and a similar subcentimetre right-lobe nodule (inset), both containing dystrophic calcifications (red arrows).
Medullary thyroid carcinoma. Longitudinal colour Doppler sonography of the thyroid of a syndromic patient. In a patient with a RET p.V804M germline pathogenic sequence variant, longitudinal colour Doppler sonography shows flow within a hypoechoic 13 mm nodule, confirming its solid composition.
A: RET
Back Extra: Medullary Thyroid Carcinoma
- Clinical: Medullary thyroid carcinoma (MTC) often presents as a painless thyroid nodule or cervical lymphadenopathy. Serum levels of calcitonin are a key diagnostic marker.
- Micro: Histopathology of MTC shows a variety of growth patterns including solid, trabecular, and cribriform, with frequent presence of amyloid stroma.
- Ancillary: Immunohistochemistry is critical for diagnosing MTC, with positive markers including calcitonin, CGRP, synaptophysin, chromogranins, and CEA.
Reference Gallery:
Medullary thyroid carcinoma. Ultrasound image of the thyroid of a syndromic patient. Bilateral sonographically abnormal thyroid nodules are present in this patient with a RET p.G533C germline variant: longitudinal greyscale sonography reveals a dominant left-lobe hypoechoic solid 12 mm nodule (yellow arrow) and a similar subcentimetre right-lobe nodule (inset), both containing dystrophic calcifications (red arrows).
Medullary thyroid carcinoma. Longitudinal colour Doppler sonography of the thyroid of a syndromic patient. In a patient with a RET p.V804M germline pathogenic sequence variant, longitudinal colour Doppler sonography shows flow within a hypoechoic 13 mm nodule, confirming its solid composition.
Outer surface of a prophylactic thyroidectomy. Prophylactic total thyroidectomy in a 3-year-old girl with multiple endocrine neoplasia type 2. The total weight of the gland was 1.53 g. The greatest dimension (longitudinal) of the right lobe was 21 mm and that of the left lobe was 17 mm. Microscopically, C-cell hyperplasia was identified.
Cut surface of a total thyroidectomy in a syndromic patient. Total thyroidectomy in an 11-year-old boy with known multiple endocrine neoplasia type 2 and clinically suspected medullary thyroid carcinoma. The total weight of the gland was 10.3 g. The greatest dimension (longitudinal) of the right lobe was 35 mm and that of the left lobe was 22 mm. A 19 mm tumour was present in the right upper-mid lobe and a 3 mm tumour was in the left upper lobe.
Medullary thyroid carcinoma. Medullary thyroid carcinoma showing an admixture of round and spindle cells with minimal atypia, in a solid, cribriform, and follicular growth pattern.
Primary C-cell hyperplasia. C cells line and fill follicles, but there is no destructive invasion.
Primary C-cell hyperplasia. Calcitonin staining highlights primary C-cell hyperplasia in a prophylactic thyroidectomy in a syndromic child.
FNAB cytology of medullary thyroid carcinoma. Pap-stained alcohol-fixed smear showing vaguely cohesive cells with round to oval nuclei with finely stippled chromatin and small nucleoli. Inset: Spindled cells.
FNAB cytology of medullary thyroid carcinoma. Romanowsky-stained smear showing cellular dyscohesion, anisocytosis, binucleation/multinucleation, and small intracytoplasmic vacuoles. Inset: Coarse amyloid fragment.
Medullary thyroid carcinoma. Many different patterns of growth can be seen in a medullary thyroid carcinoma, including a cribriform pattern, showing apoptosis in the centre.
Medullary thyroid carcinoma. A pseudopapillary architecture can be seen in some tumours, showing areas of necrosis.

Q: The classic microscopic nuclear features of Papillary Thyroid Carcinoma include open, ground-glass chromatin, longitudinal grooves, and frequent [...].
Classic papillary thyroid carcinoma. Nuclei exhibit open, ground-glass chromatin, with frequent intranuclear cytoplasmic inclusions.
Cytology of classic papillary thyroid carcinoma (liquid-based cytology). Enlarged, oval, overlapping nuclei with pale chromatin, longitudinal grooves, and intranuclear pseudoinclusions (Pap stain).
A: intranuclear pseudoinclusions
Back Extra: Papillary Thyroid Carcinoma
- Clinical: Papillary thyroid carcinoma (PTC) typically presents as an asymptomatic nodule or cervical lymphadenopathy, often detected incidentally.
- Micro: Classic PTC is characterized by well-formed papillary structures with central fibrovascular cores, and nuclear features such as enlarged, grooved nuclei with ground-glass chromatin and intranuclear pseudoinclusions.
- Ancillary: Immunohistochemistry for thyroid transcription factor 1 (TTF1), PAX8, and thyroglobulin is positive in PTC, and the BRAF p.V600E mutation can be detected using the VE1 antibody with high sensitivity and specificity.
Reference Gallery:
Papillary thyroid carcinoma. Gross appearance shows an irregular, infiltrative, off-white tumour. The coarse granular appearance reflects the presence of papillary structures.
Classic papillary thyroid carcinoma. Papillary structures with fibrovascular cores lined by cells with oval, pale, overlapping nuclei.
Classic papillary thyroid carcinoma. Nuclei exhibit open, ground-glass chromatin, with frequent intranuclear cytoplasmic inclusions.
Cytology of classic papillary thyroid carcinoma. Well-formed papillary structure with central fibrovascular core and finger-like papillary projections (Pap stain).
Cytology of classic papillary thyroid carcinoma. Flat, monolayered syncytial sheet of follicular cells with enlarged, oval, overlapping, grooved nuclei; powdery chromatin; and small nucleoli (Pap stain).
Cytology of classic papillary thyroid carcinoma (liquid-based cytology). Enlarged, oval, overlapping nuclei with pale chromatin, longitudinal grooves, and intranuclear pseudoinclusions (Pap stain).
Diffuse sclerosing papillary thyroid carcinoma. Squamous morule with cells arranged in a swirling manner. Note the prominent lymphoid infiltrate.
Solid/trabecular papillary thyroid carcinoma. Solid islands of tumour cells with discernible microfollicular formations within the islands. A delicate but prominent vascular network is seen.
Solid/trabecular papillary thyroid carcinoma. Nuclear features of papillary thyroid carcinoma are preserved, with well-formed nuclear pseudoinclusions.
Tall cell papillary thyroid carcinoma. Tall columnar cells, two to three times taller than wide, showing abundant eosinophilic cytoplasm.
Papillary thyroid carcinoma. Gross appearance of a papillary thyroid carcinoma of a predominantly cystic nature, with intraluminal papillary protrusions.
Encapsulated papillary thyroid carcinoma. Gross appearance shows a relatively circumscribed encapsulated nodule with a fleshy, solid cut surface. This pattern is more common in the follicular variant of papillary thyroid carcinoma. Note the area of capsular invasion at the 3 to 6 o’clock position, with new secondary capsule formation.

Q: Classic Papillary Thyroid Carcinoma is architecturally characterized by well-formed papillary structures that contain central [...] and are lined by cells with overlapping nuclei.
Classic papillary thyroid carcinoma. Papillary structures with fibrovascular cores lined by cells with oval, pale, overlapping nuclei.
Cytology of classic papillary thyroid carcinoma. Well-formed papillary structure with central fibrovascular core and finger-like papillary projections (Pap stain).
A: fibrovascular cores
Back Extra: Papillary Thyroid Carcinoma
- Clinical: Papillary thyroid carcinoma (PTC) typically presents as an asymptomatic nodule or cervical lymphadenopathy, often detected incidentally.
- Micro: Classic PTC is characterized by well-formed papillary structures with central fibrovascular cores, and nuclear features such as enlarged, grooved nuclei with ground-glass chromatin and intranuclear pseudoinclusions.
- Ancillary: Immunohistochemistry for thyroid transcription factor 1 (TTF1), PAX8, and thyroglobulin is positive in PTC, and the BRAF p.V600E mutation can be detected using the VE1 antibody with high sensitivity and specificity.
Reference Gallery:
Papillary thyroid carcinoma. Gross appearance shows an irregular, infiltrative, off-white tumour. The coarse granular appearance reflects the presence of papillary structures.
Classic papillary thyroid carcinoma. Papillary structures with fibrovascular cores lined by cells with oval, pale, overlapping nuclei.
Classic papillary thyroid carcinoma. Nuclei exhibit open, ground-glass chromatin, with frequent intranuclear cytoplasmic inclusions.
Cytology of classic papillary thyroid carcinoma. Well-formed papillary structure with central fibrovascular core and finger-like papillary projections (Pap stain).
Cytology of classic papillary thyroid carcinoma. Flat, monolayered syncytial sheet of follicular cells with enlarged, oval, overlapping, grooved nuclei; powdery chromatin; and small nucleoli (Pap stain).
Cytology of classic papillary thyroid carcinoma (liquid-based cytology). Enlarged, oval, overlapping nuclei with pale chromatin, longitudinal grooves, and intranuclear pseudoinclusions (Pap stain).
Diffuse sclerosing papillary thyroid carcinoma. Squamous morule with cells arranged in a swirling manner. Note the prominent lymphoid infiltrate.
Solid/trabecular papillary thyroid carcinoma. Solid islands of tumour cells with discernible microfollicular formations within the islands. A delicate but prominent vascular network is seen.
Solid/trabecular papillary thyroid carcinoma. Nuclear features of papillary thyroid carcinoma are preserved, with well-formed nuclear pseudoinclusions.
Tall cell papillary thyroid carcinoma. Tall columnar cells, two to three times taller than wide, showing abundant eosinophilic cytoplasm.
Papillary thyroid carcinoma. Gross appearance of a papillary thyroid carcinoma of a predominantly cystic nature, with intraluminal papillary protrusions.
Encapsulated papillary thyroid carcinoma. Gross appearance shows a relatively circumscribed encapsulated nodule with a fleshy, solid cut surface. This pattern is more common in the follicular variant of papillary thyroid carcinoma. Note the area of capsular invasion at the 3 to 6 o’clock position, with new secondary capsule formation.

Q: On macroscopic examination, classic Papillary Thyroid Carcinoma often presents as an irregular, infiltrative, off-white tumor with a coarse, granular cut surface that reflects the presence of underlying [...].
Papillary thyroid carcinoma. Gross appearance shows an irregular, infiltrative, off-white tumour. The coarse granular appearance reflects the presence of papillary structures.
A: papillary structures
Back Extra: Papillary Thyroid Carcinoma
- Clinical: Papillary thyroid carcinoma (PTC) typically presents as an asymptomatic nodule or cervical lymphadenopathy, often detected incidentally.
- Micro: Classic PTC is characterized by well-formed papillary structures with central fibrovascular cores, and nuclear features such as enlarged, grooved nuclei with ground-glass chromatin and intranuclear pseudoinclusions.
- Ancillary: Immunohistochemistry for thyroid transcription factor 1 (TTF1), PAX8, and thyroglobulin is positive in PTC, and the BRAF p.V600E mutation can be detected using the VE1 antibody with high sensitivity and specificity.
Reference Gallery:
Papillary thyroid carcinoma. Gross appearance shows an irregular, infiltrative, off-white tumour. The coarse granular appearance reflects the presence of papillary structures.
Classic papillary thyroid carcinoma. Papillary structures with fibrovascular cores lined by cells with oval, pale, overlapping nuclei.
Classic papillary thyroid carcinoma. Nuclei exhibit open, ground-glass chromatin, with frequent intranuclear cytoplasmic inclusions.
Cytology of classic papillary thyroid carcinoma. Well-formed papillary structure with central fibrovascular core and finger-like papillary projections (Pap stain).
Cytology of classic papillary thyroid carcinoma. Flat, monolayered syncytial sheet of follicular cells with enlarged, oval, overlapping, grooved nuclei; powdery chromatin; and small nucleoli (Pap stain).
Cytology of classic papillary thyroid carcinoma (liquid-based cytology). Enlarged, oval, overlapping nuclei with pale chromatin, longitudinal grooves, and intranuclear pseudoinclusions (Pap stain).
Diffuse sclerosing papillary thyroid carcinoma. Squamous morule with cells arranged in a swirling manner. Note the prominent lymphoid infiltrate.
Solid/trabecular papillary thyroid carcinoma. Solid islands of tumour cells with discernible microfollicular formations within the islands. A delicate but prominent vascular network is seen.
Solid/trabecular papillary thyroid carcinoma. Nuclear features of papillary thyroid carcinoma are preserved, with well-formed nuclear pseudoinclusions.
Tall cell papillary thyroid carcinoma. Tall columnar cells, two to three times taller than wide, showing abundant eosinophilic cytoplasm.
Papillary thyroid carcinoma. Gross appearance of a papillary thyroid carcinoma of a predominantly cystic nature, with intraluminal papillary protrusions.
Encapsulated papillary thyroid carcinoma. Gross appearance shows a relatively circumscribed encapsulated nodule with a fleshy, solid cut surface. This pattern is more common in the follicular variant of papillary thyroid carcinoma. Note the area of capsular invasion at the 3 to 6 o’clock position, with new secondary capsule formation.

Q: [...] is a biphasic thyroid neoplasm characterized by a lobulated pattern of long, sweeping fascicles of spindle cells that merge into complex glandular structures and cleft-like spaces containing basophilic mucosubstance.
Thyroid spindle epithelial tumour with thymus-like elements. A highly cellular tumour with a lobulated growth pattern. Even at this low magnification it is evident that there are interspersed reticulated spaces, some apparently empty and some containing basophilic mucosubstance.
Thyroid spindle epithelial tumour with thymus-like elements. The biphasic tumour comprises long, sweeping fascicles of spindle cells merging into complex glandular structures. Basophilic mucosubstance is present in the reticulated spaces among the spindle cells as well as the glandular lumina.
Thyroid spindle epithelial tumour with thymus-like elements. Fascicles of spindle cells merge into elongated glandular structures, some with a glomeruloid appearance. The glandular structures are lined by uniform cuboidal to low columnar cells.
A: Spindle Epithelial Tumor with Thymus-Like Elements
Back Extra: Spindle Epithelial Tumour with Thymus-Like Elements
- Clinical: SETTLE typically presents as a painless thyroid mass, with potential for metastasis to the lung, lymph node, kidney, and liver.
- Micro: The tumour is highly cellular with a lobulated pattern, comprising long fascicles of spindle cells merging into glandular structures and cleft-like spaces containing basophilic mucosubstances.
- Ancillary: Both spindled and glandular cells show diffuse positivity for pancytokeratin and p40, and are negative for thyroglobulin, calcitonin, and TTF1.
Reference Gallery:
Thyroid spindle epithelial tumour with thymus-like elements. A highly cellular tumour with a lobulated growth pattern. Even at this low magnification it is evident that there are interspersed reticulated spaces, some apparently empty and some containing basophilic mucosubstance.
Thyroid spindle epithelial tumour with thymus-like elements. The biphasic tumour comprises long, sweeping fascicles of spindle cells merging into complex glandular structures. Basophilic mucosubstance is present in the reticulated spaces among the spindle cells as well as the glandular lumina.
Thyroid spindle epithelial tumour with thymus-like elements. Fascicles of spindle cells merge into elongated glandular structures, some with a glomeruloid appearance. The glandular structures are lined by uniform cuboidal to low columnar cells.
Thyroid spindle epithelial tumour with thymus-like elements. The spindle cells appear uniform and have elongated, bland-looking nuclei.
Thyroid spindle epithelial tumour with thymus-like elements. All the spindle cells and the cuboidal epithelial cells are immunopositive for pancytokeratin.
Thyroid spindle epithelial tumour with thymus-like elements. Both the spindle cells (right) and the cuboidal epithelial cells (left) are extensively immunopositive for p40.
Spindle epithelial tumour with thymus-like elements, metastatic to the kidney. Residual renal parenchyma is seen (right). The metastatic tumour (left) comprises spindle cells in fascicles, interspersed with reticulated spaces.

Q: A key immunohistochemical feature of Spindle Epithelial Tumor with Thymus-Like Elements is that both the spindled and epithelial components show diffuse positivity for pancytokeratin and [...], while remaining negative for thyroid-specific markers like thyroglobulin and TTF1.
Thyroid spindle epithelial tumour with thymus-like elements. All the spindle cells and the cuboidal epithelial cells are immunopositive for pancytokeratin.
Thyroid spindle epithelial tumour with thymus-like elements. Both the spindle cells (right) and the cuboidal epithelial cells (left) are extensively immunopositive for p40.
A: p40
Back Extra: Spindle Epithelial Tumour with Thymus-Like Elements
- Clinical: SETTLE typically presents as a painless thyroid mass, with potential for metastasis to the lung, lymph node, kidney, and liver.
- Micro: The tumour is highly cellular with a lobulated pattern, comprising long fascicles of spindle cells merging into glandular structures and cleft-like spaces containing basophilic mucosubstances.
- Ancillary: Both spindled and glandular cells show diffuse positivity for pancytokeratin and p40, and are negative for thyroglobulin, calcitonin, and TTF1.
Reference Gallery:
Thyroid spindle epithelial tumour with thymus-like elements. A highly cellular tumour with a lobulated growth pattern. Even at this low magnification it is evident that there are interspersed reticulated spaces, some apparently empty and some containing basophilic mucosubstance.
Thyroid spindle epithelial tumour with thymus-like elements. The biphasic tumour comprises long, sweeping fascicles of spindle cells merging into complex glandular structures. Basophilic mucosubstance is present in the reticulated spaces among the spindle cells as well as the glandular lumina.
Thyroid spindle epithelial tumour with thymus-like elements. Fascicles of spindle cells merge into elongated glandular structures, some with a glomeruloid appearance. The glandular structures are lined by uniform cuboidal to low columnar cells.
Thyroid spindle epithelial tumour with thymus-like elements. The spindle cells appear uniform and have elongated, bland-looking nuclei.
Thyroid spindle epithelial tumour with thymus-like elements. All the spindle cells and the cuboidal epithelial cells are immunopositive for pancytokeratin.
Thyroid spindle epithelial tumour with thymus-like elements. Both the spindle cells (right) and the cuboidal epithelial cells (left) are extensively immunopositive for p40.
Spindle epithelial tumour with thymus-like elements, metastatic to the kidney. Residual renal parenchyma is seen (right). The metastatic tumour (left) comprises spindle cells in fascicles, interspersed with reticulated spaces.

Q: Microscopically, Spindle Epithelial Tumor with Thymus-like Elements features a lobulated architecture with a characteristic [...] pattern, where long fascicles of bland spindle cells merge into complex glandular structures.
Thyroid spindle epithelial tumour with thymus-like elements. The biphasic tumour comprises long, sweeping fascicles of spindle cells merging into complex glandular structures. Basophilic mucosubstance is present in the reticulated spaces among the spindle cells as well as the glandular lumina.
Thyroid spindle epithelial tumour with thymus-like elements. Fascicles of spindle cells merge into elongated glandular structures, some with a glomeruloid appearance. The glandular structures are lined by uniform cuboidal to low columnar cells.
A: biphasic
Back Extra: Spindle Epithelial Tumour with Thymus-like Elements
- Clinical: Spindle Epithelial Tumour with Thymus-like Elements (SETTLE) typically presents as a painless thyroid mass, with a cold thyroid scan and heterogeneous density on CT.
- Micro: SETTLE is characterized by a lobulated architecture with a biphasic pattern of spindle cells merging into glandular structures and interspersed cleft-like spaces containing mucosubstances.
- Ancillary: Both spindle and glandular cells are positive for pancytokeratin and p40, but negative for thyroglobulin, calcitonin, and TTF1.
Reference Gallery:
Thyroid spindle epithelial tumour with thymus-like elements. A highly cellular tumour with a lobulated growth pattern. Even at this low magnification it is evident that there are interspersed reticulated spaces, some apparently empty and some containing basophilic mucosubstance.
Thyroid spindle epithelial tumour with thymus-like elements. The biphasic tumour comprises long, sweeping fascicles of spindle cells merging into complex glandular structures. Basophilic mucosubstance is present in the reticulated spaces among the spindle cells as well as the glandular lumina.
Thyroid spindle epithelial tumour with thymus-like elements. Fascicles of spindle cells merge into elongated glandular structures, some with a glomeruloid appearance. The glandular structures are lined by uniform cuboidal to low columnar cells.
Thyroid spindle epithelial tumour with thymus-like elements. The spindle cells appear uniform and have elongated, bland-looking nuclei.
Thyroid spindle epithelial tumour with thymus-like elements. All the spindle cells and the cuboidal epithelial cells are immunopositive for pancytokeratin.
Thyroid spindle epithelial tumour with thymus-like elements. Both the spindle cells (right) and the cuboidal epithelial cells (left) are extensively immunopositive for p40.
Spindle epithelial tumour with thymus-like elements, metastatic to the kidney. Residual renal parenchyma is seen (right). The metastatic tumour (left) comprises spindle cells in fascicles, interspersed with reticulated spaces.

Q: In Spindle Epithelial Tumor with Thymus-like Elements, both the spindle and epithelial components lack expression of thyroid markers (e.g., thyroglobulin, TTF1) but demonstrate strong diagnostic immunopositivity for pancytokeratin and [...].
Thyroid spindle epithelial tumour with thymus-like elements. All the spindle cells and the cuboidal epithelial cells are immunopositive for pancytokeratin.
Thyroid spindle epithelial tumour with thymus-like elements. Both the spindle cells (right) and the cuboidal epithelial cells (left) are extensively immunopositive for p40.
A: p40
Back Extra: Spindle Epithelial Tumour with Thymus-like Elements
- Clinical: Spindle Epithelial Tumour with Thymus-like Elements (SETTLE) typically presents as a painless thyroid mass, with a cold thyroid scan and heterogeneous density on CT.
- Micro: SETTLE is characterized by a lobulated architecture with a biphasic pattern of spindle cells merging into glandular structures and interspersed cleft-like spaces containing mucosubstances.
- Ancillary: Both spindle and glandular cells are positive for pancytokeratin and p40, but negative for thyroglobulin, calcitonin, and TTF1.
Reference Gallery:
Thyroid spindle epithelial tumour with thymus-like elements. A highly cellular tumour with a lobulated growth pattern. Even at this low magnification it is evident that there are interspersed reticulated spaces, some apparently empty and some containing basophilic mucosubstance.
Thyroid spindle epithelial tumour with thymus-like elements. The biphasic tumour comprises long, sweeping fascicles of spindle cells merging into complex glandular structures. Basophilic mucosubstance is present in the reticulated spaces among the spindle cells as well as the glandular lumina.
Thyroid spindle epithelial tumour with thymus-like elements. Fascicles of spindle cells merge into elongated glandular structures, some with a glomeruloid appearance. The glandular structures are lined by uniform cuboidal to low columnar cells.
Thyroid spindle epithelial tumour with thymus-like elements. The spindle cells appear uniform and have elongated, bland-looking nuclei.
Thyroid spindle epithelial tumour with thymus-like elements. All the spindle cells and the cuboidal epithelial cells are immunopositive for pancytokeratin.
Thyroid spindle epithelial tumour with thymus-like elements. Both the spindle cells (right) and the cuboidal epithelial cells (left) are extensively immunopositive for p40.
Spindle epithelial tumour with thymus-like elements, metastatic to the kidney. Residual renal parenchyma is seen (right). The metastatic tumour (left) comprises spindle cells in fascicles, interspersed with reticulated spaces.

Q: A lobulated thyroid tumor showing a biphasic proliferation of spindle cells merging into complex, sometimes glomeruloid, glandular structures with interspersed basophilic mucosubstance is highly diagnostic of [...].
Thyroid spindle epithelial tumour with thymus-like elements. A highly cellular tumour with a lobulated growth pattern. Even at this low magnification it is evident that there are interspersed reticulated spaces, some apparently empty and some containing basophilic mucosubstance.
Thyroid spindle epithelial tumour with thymus-like elements. Fascicles of spindle cells merge into elongated glandular structures, some with a glomeruloid appearance. The glandular structures are lined by uniform cuboidal to low columnar cells.
A: Spindle Epithelial Tumor with Thymus-like Elements
Back Extra: Spindle Epithelial Tumour with Thymus-like Elements
- Clinical: Spindle Epithelial Tumour with Thymus-like Elements (SETTLE) typically presents as a painless thyroid mass, with a cold thyroid scan and heterogeneous density on CT.
- Micro: SETTLE is characterized by a lobulated architecture with a biphasic pattern of spindle cells merging into glandular structures and interspersed cleft-like spaces containing mucosubstances.
- Ancillary: Both spindle and glandular cells are positive for pancytokeratin and p40, but negative for thyroglobulin, calcitonin, and TTF1.
Reference Gallery:
Thyroid spindle epithelial tumour with thymus-like elements. A highly cellular tumour with a lobulated growth pattern. Even at this low magnification it is evident that there are interspersed reticulated spaces, some apparently empty and some containing basophilic mucosubstance.
Thyroid spindle epithelial tumour with thymus-like elements. The biphasic tumour comprises long, sweeping fascicles of spindle cells merging into complex glandular structures. Basophilic mucosubstance is present in the reticulated spaces among the spindle cells as well as the glandular lumina.
Thyroid spindle epithelial tumour with thymus-like elements. Fascicles of spindle cells merge into elongated glandular structures, some with a glomeruloid appearance. The glandular structures are lined by uniform cuboidal to low columnar cells.
Thyroid spindle epithelial tumour with thymus-like elements. The spindle cells appear uniform and have elongated, bland-looking nuclei.
Thyroid spindle epithelial tumour with thymus-like elements. All the spindle cells and the cuboidal epithelial cells are immunopositive for pancytokeratin.
Thyroid spindle epithelial tumour with thymus-like elements. Both the spindle cells (right) and the cuboidal epithelial cells (left) are extensively immunopositive for p40.
Spindle epithelial tumour with thymus-like elements, metastatic to the kidney. Residual renal parenchyma is seen (right). The metastatic tumour (left) comprises spindle cells in fascicles, interspersed with reticulated spaces.

Q: Clinically and microscopically, elevated variants of [...] frequently enclose solid and cystic rests of conjunctival epithelium that contain luminal proteinaceous concretions.
Compound naevus. Conjunctival subepithelial cystic naevus. A circumscribed, pigmented, mildly elevated lesion with prominent cysts in the bulbar conjunctiva and a minimally dilated feeder vessel.
Compound naevus. The lesion is dominated by dilated cystic rests of conjunctival epithelium, which contain luminal proteinaceous concretions.
A: Conjunctival Junctional, Compound, and Subepithelial Naevi
Back Extra: Conjunctival Junctional, Compound, and Subepithelial Naevi
- Clinical: Conjunctival naevocellular naevi are well-circumscribed, brown to tan-coloured lesions that can be flat (junctional) or elevated (compound and subepithelial).
- Micro: In compound naevi, naevocytes are symmetrically arranged both within the epithelium and in the substantia propria, often enclosing solid and cystic rests of conjunctival epithelium.
- Ancillary: Immunohistochemistry shows positivity for S100, SOX10, MITF, and Melan-A, with HMB45 being positive in the junctional component.
Reference Gallery:
Conjunctival junctional naevus. A circumscribed, lightly pigmented, flat lesion in the bulbar conjunctiva, not associated with feeder/intrinsic vessels or cysts.
Conjunctival junctional naevus. Focally confluent nests of naevoid melanocytes are present at the epithelium–substantia propria junction.
Compound naevus. Conjunctival subepithelial cystic naevus. A circumscribed, pigmented, mildly elevated lesion with prominent cysts in the bulbar conjunctiva and a minimally dilated feeder vessel.
Compound naevus. Melan-A immunostaining highlights the bland melanocytes.
Compound naevus. The lesion is dominated by dilated cystic rests of conjunctival epithelium, which contain luminal proteinaceous concretions.
Compound naevus. Variably pigmented naevus nests surround the conjunctival epithelial rests.
Conjunctival subepithelial naevus. A circumscribed, pigmented, mildly elevated lesion with prominent cysts in the bulbar conjunctiva and a minimally dilated feeder vessel.
Conjunctival subepithelial naevus. The lesion is dominated by dilated cystic rests of conjunctival epithelium, which contain luminal proteinaceous concretions.
Conjunctival subepithelial naevus. Variably pigmented nests of naevus cells surround the conjunctival epithelial rests.
Conjunctival subepithelial naevus. Bland cytological features.

Q: In Conjunctival Junctional, Compound, and Subepithelial Naevi, the flat junctional variants are characterized by nests of nevocytes located strictly at the [...] junction.
Conjunctival junctional naevus. A circumscribed, lightly pigmented, flat lesion in the bulbar conjunctiva, not associated with feeder/intrinsic vessels or cysts.
Conjunctival junctional naevus. Focally confluent nests of naevoid melanocytes are present at the epithelium–substantia propria junction.
A: epithelium-substantia propria
Back Extra: Conjunctival Junctional, Compound, and Subepithelial Naevi
- Clinical: Conjunctival naevocellular naevi are well-circumscribed, brown to tan-coloured lesions that can be flat (junctional) or elevated (compound and subepithelial).
- Micro: In compound naevi, naevocytes are symmetrically arranged both within the epithelium and in the substantia propria, often enclosing solid and cystic rests of conjunctival epithelium.
- Ancillary: Immunohistochemistry shows positivity for S100, SOX10, MITF, and Melan-A, with HMB45 being positive in the junctional component.
Reference Gallery:
Conjunctival junctional naevus. A circumscribed, lightly pigmented, flat lesion in the bulbar conjunctiva, not associated with feeder/intrinsic vessels or cysts.
Conjunctival junctional naevus. Focally confluent nests of naevoid melanocytes are present at the epithelium–substantia propria junction.
Compound naevus. Conjunctival subepithelial cystic naevus. A circumscribed, pigmented, mildly elevated lesion with prominent cysts in the bulbar conjunctiva and a minimally dilated feeder vessel.
Compound naevus. Melan-A immunostaining highlights the bland melanocytes.
Compound naevus. The lesion is dominated by dilated cystic rests of conjunctival epithelium, which contain luminal proteinaceous concretions.
Compound naevus. Variably pigmented naevus nests surround the conjunctival epithelial rests.
Conjunctival subepithelial naevus. A circumscribed, pigmented, mildly elevated lesion with prominent cysts in the bulbar conjunctiva and a minimally dilated feeder vessel.
Conjunctival subepithelial naevus. The lesion is dominated by dilated cystic rests of conjunctival epithelium, which contain luminal proteinaceous concretions.
Conjunctival subepithelial naevus. Variably pigmented nests of naevus cells surround the conjunctival epithelial rests.
Conjunctival subepithelial naevus. Bland cytological features.

Q: In Conjunctival Junctional, Compound, and Subepithelial Naevi, the melanocytes demonstrate immunohistochemical positivity for S100, SOX10, MITF, and [...] (shown here highlighting the bland cells), while HMB45 is typically restricted to the junctional component.
Compound naevus. Melan-A immunostaining highlights the bland melanocytes.
A: Melan-A
Back Extra: Conjunctival Junctional, Compound, and Subepithelial Naevi
- Clinical: Conjunctival naevocellular naevi are well-circumscribed, brown to tan-coloured lesions that can be flat (junctional) or elevated (compound and subepithelial).
- Micro: In compound naevi, naevocytes are symmetrically arranged both within the epithelium and in the substantia propria, often enclosing solid and cystic rests of conjunctival epithelium.
- Ancillary: Immunohistochemistry shows positivity for S100, SOX10, MITF, and Melan-A, with HMB45 being positive in the junctional component.
Reference Gallery:
Conjunctival junctional naevus. A circumscribed, lightly pigmented, flat lesion in the bulbar conjunctiva, not associated with feeder/intrinsic vessels or cysts.
Conjunctival junctional naevus. Focally confluent nests of naevoid melanocytes are present at the epithelium–substantia propria junction.
Compound naevus. Conjunctival subepithelial cystic naevus. A circumscribed, pigmented, mildly elevated lesion with prominent cysts in the bulbar conjunctiva and a minimally dilated feeder vessel.
Compound naevus. Melan-A immunostaining highlights the bland melanocytes.
Compound naevus. The lesion is dominated by dilated cystic rests of conjunctival epithelium, which contain luminal proteinaceous concretions.
Compound naevus. Variably pigmented naevus nests surround the conjunctival epithelial rests.
Conjunctival subepithelial naevus. A circumscribed, pigmented, mildly elevated lesion with prominent cysts in the bulbar conjunctiva and a minimally dilated feeder vessel.
Conjunctival subepithelial naevus. The lesion is dominated by dilated cystic rests of conjunctival epithelium, which contain luminal proteinaceous concretions.
Conjunctival subepithelial naevus. Variably pigmented nests of naevus cells surround the conjunctival epithelial rests.
Conjunctival subepithelial naevus. Bland cytological features.

Q: A prominent histological feature of an Epibulbar Choristoma (specifically the dermoid type) is the presence of wiry collagen fibers and [...] (e.g., hair follicles and sebaceous glands) beneath a keratinized squamous epithelium.
Epibulbar choristoma. Dermoid. An inferotemporal epibulbar tumour with cilia in a 12-year-old girl.
Epibulbar choristoma. Epibulbar dermoid. Histopathological analysis of the excised lesion shows a tumour covered by keratinized squamous epithelium. The tumour is composed of wiry collagen fibres. Hair follicles with adjacent sebaceous glands are present.
A: dermal appendages
Back Extra: Epibulbar Choristoma
- Clinical: Epibulbar choristomas are typically located in the superior or inferior temporal quadrants and can involve the cornea. They may be bilateral in syndromic patients.
- Micro: Dermoids are composed of keratinized squamous epithelium, dermal appendages, and wiry collagen fibres. Dermolipomas additionally contain a large amount of adipose tissue.
- Ancillary: Not relevant; diagnosis is based on clinical and histopathological findings.
Reference Gallery:
Epibulbar choristoma. Dermoid. An inferotemporal epibulbar tumour with cilia in a 12-year-old girl.
Epibulbar choristoma. Dermolipoma. A whitish-yellowish lesion in the temporal quadrant of one eye of a 15-year-old boy.
Epibulbar choristoma. Epibulbar dermoid. Histopathological analysis of the excised lesion shows a tumour covered by keratinized squamous epithelium. The tumour is composed of wiry collagen fibres. Hair follicles with adjacent sebaceous glands are present.
Epibulbar choristoma. Dermolipoma. The tumour is covered by non-keratinized squamous epithelium and is composed of wiry collagen fibres with a large amount of mature adipose tissue.
Epibulbar choristoma. Complex choristoma. The lesion contains ectopic lacrimal gland, cartilage, adipose tissue, and fibrous tissue.

Q: The dermolipoma variant of an Epibulbar Choristoma is classically distinguished from a simple dermoid by the histological presence of a large amount of mature [...].
Epibulbar choristoma. Dermolipoma. A whitish-yellowish lesion in the temporal quadrant of one eye of a 15-year-old boy.
Epibulbar choristoma. Dermolipoma. The tumour is covered by non-keratinized squamous epithelium and is composed of wiry collagen fibres with a large amount of mature adipose tissue.
A: adipose tissue
Back Extra: Epibulbar Choristoma
- Clinical: Epibulbar choristomas are typically located in the superior or inferior temporal quadrants and can involve the cornea. They may be bilateral in syndromic patients.
- Micro: Dermoids are composed of keratinized squamous epithelium, dermal appendages, and wiry collagen fibres. Dermolipomas additionally contain a large amount of adipose tissue.
- Ancillary: Not relevant; diagnosis is based on clinical and histopathological findings.
Reference Gallery:
Epibulbar choristoma. Dermoid. An inferotemporal epibulbar tumour with cilia in a 12-year-old girl.
Epibulbar choristoma. Dermolipoma. A whitish-yellowish lesion in the temporal quadrant of one eye of a 15-year-old boy.
Epibulbar choristoma. Epibulbar dermoid. Histopathological analysis of the excised lesion shows a tumour covered by keratinized squamous epithelium. The tumour is composed of wiry collagen fibres. Hair follicles with adjacent sebaceous glands are present.
Epibulbar choristoma. Dermolipoma. The tumour is covered by non-keratinized squamous epithelium and is composed of wiry collagen fibres with a large amount of mature adipose tissue.
Epibulbar choristoma. Complex choristoma. The lesion contains ectopic lacrimal gland, cartilage, adipose tissue, and fibrous tissue.

Q: A complex Epibulbar Choristoma is characterized histologically by the presence of varied ectopic elements, classically including adipose tissue, fibrous tissue, ectopic lacrimal gland, and [...].
Epibulbar choristoma. Complex choristoma. The lesion contains ectopic lacrimal gland, cartilage, adipose tissue, and fibrous tissue.
A: cartilage
Back Extra: Epibulbar Choristoma
- Clinical: Epibulbar choristomas are typically located in the superior or inferior temporal quadrants and can involve the cornea. They may be bilateral in syndromic patients.
- Micro: Dermoids are composed of keratinized squamous epithelium, dermal appendages, and wiry collagen fibres. Dermolipomas additionally contain a large amount of adipose tissue.
- Ancillary: Not relevant; diagnosis is based on clinical and histopathological findings.
Reference Gallery:
Epibulbar choristoma. Dermoid. An inferotemporal epibulbar tumour with cilia in a 12-year-old girl.
Epibulbar choristoma. Dermolipoma. A whitish-yellowish lesion in the temporal quadrant of one eye of a 15-year-old boy.
Epibulbar choristoma. Epibulbar dermoid. Histopathological analysis of the excised lesion shows a tumour covered by keratinized squamous epithelium. The tumour is composed of wiry collagen fibres. Hair follicles with adjacent sebaceous glands are present.
Epibulbar choristoma. Dermolipoma. The tumour is covered by non-keratinized squamous epithelium and is composed of wiry collagen fibres with a large amount of mature adipose tissue.
Epibulbar choristoma. Complex choristoma. The lesion contains ectopic lacrimal gland, cartilage, adipose tissue, and fibrous tissue.

Q: A firm, nodular, whitish mass in the superotemporal conjunctiva that demonstrates localized episcleral calcification on CT imaging is characteristic of a(n) [...].
Epibulbar osseous choristoma. A firm, nodular, whitish mass can be seen in the superotemporal conjunctiva.
Epibulbar osseous choristoma. A firm, nodular, whitish mass can be seen in the superotemporal conjunctiva.
Epibulbar osseous choristoma. Transverse CT showing bone in the temporal episclera of the right eye. The calcified choristoma is clearly visible anterior to the eye.
A: Epibulbar Osseous Choristoma
Back Extra: Epibulbar Osseous Choristoma
- Clinical: Patients with epibulbar osseous choristoma present with a yellow, orange, pink, or white subconjunctival mass that is firm and may be multinodular, extending from the equator to the superotemporal fornix.
- Micro: The lesion is composed of compact lamellar bone with normal osteocytes and Haversian canals, surrounded by dense fibrous tissue (periosteum) and an internal osteogenic layer.
- Ancillary: CT imaging shows calcified bone in the episclera, which helps in the diagnosis of epibulbar osseous choristoma.
Reference Gallery:
Epibulbar osseous choristoma. A firm, nodular, whitish mass can be seen in the superotemporal conjunctiva.
Epibulbar osseous choristoma. A firm, nodular, whitish mass can be seen in the superotemporal conjunctiva.
Epibulbar osseous choristoma. The lesion is composed of compact lamellar bone surrounded by periosteum.
Epibulbar osseous choristoma. Transverse CT showing bone in the temporal episclera of the right eye. The calcified choristoma is clearly visible anterior to the eye.

Q: Histologically, an Epibulbar Osseous Choristoma is defined by the presence of ectopic, compact [...] with normal osteocytes and Haversian canals, typically surrounded by a dense fibrous periosteum.
Epibulbar osseous choristoma. The lesion is composed of compact lamellar bone surrounded by periosteum.
A: lamellar bone
Back Extra: Epibulbar Osseous Choristoma
- Clinical: Patients with epibulbar osseous choristoma present with a yellow, orange, pink, or white subconjunctival mass that is firm and may be multinodular, extending from the equator to the superotemporal fornix.
- Micro: The lesion is composed of compact lamellar bone with normal osteocytes and Haversian canals, surrounded by dense fibrous tissue (periosteum) and an internal osteogenic layer.
- Ancillary: CT imaging shows calcified bone in the episclera, which helps in the diagnosis of epibulbar osseous choristoma.
Reference Gallery:
Epibulbar osseous choristoma. A firm, nodular, whitish mass can be seen in the superotemporal conjunctiva.
Epibulbar osseous choristoma. A firm, nodular, whitish mass can be seen in the superotemporal conjunctiva.
Epibulbar osseous choristoma. The lesion is composed of compact lamellar bone surrounded by periosteum.
Epibulbar osseous choristoma. Transverse CT showing bone in the temporal episclera of the right eye. The calcified choristoma is clearly visible anterior to the eye.

Q: In Diffuse Choroidal Neurofibroma and Ganglioneuroma, a distinctive histologic finding is the presence of [...], which are composed of concentric Schwann cell processes.
Diffuse choroidal neurofibroma. Ovoid bodies composed of concentric Schwann cell processes are typical of diffuse choroidal neurofibroma.
Choroidal neurofibroma in neurofibromatosis type 1. Electron microscopy shows ovoid bodies, composed of elongated cells with Schwann cell properties, including a fragmented basal lamina.
A: ovoid bodies
Back Extra: Diffuse Choroidal Neurofibroma and Ganglioneuroma
- Clinical: Patients with diffuse choroidal neurofibroma and ganglioneuroma may present with a pale, diffuse choroidal mass and are often associated with neurofibromatosis type 1 (NF1).
- Micro: Histopathology shows a haphazard proliferation of Schwann cells, fibroblasts, and choroidal melanocytes, with ovoid bodies composed of concentric Schwann cell processes being distinctive.
- Ancillary: NF1 gene inactivation is expected in patients with NF1, while PTEN mutations may be seen in the very rare cases associated with Cowden syndrome.
Reference Gallery:
Diffuse choroidal neurofibroma. The trabecular meshwork is hypercellular, due to involvement by the diffuse neurofibroma.
Diffuse choroidal neurofibroma. A dysmorphic, hypoplastic ciliary body associated with a diffuse choroidal neurofibroma.
Diffuse choroidal neurofibroma. Bland spindle cells replace the normal architecture of the choroid.
Diffuse choroidal neurofibroma. The diffuse neurofibroma involves a scleral canal, traversing the sclera from the upper left to the lower right of the image. The choroidal component is towards the top of the image.
Diffuse choroidal neurofibroma. Ovoid bodies composed of concentric Schwann cell processes are typical of diffuse choroidal neurofibroma.
Abnormal ganglion cells. Aggregates of ganglion cells in association with a neurofibroma component may be seen in some instances, where the term “ganglioneuroma” may be more suitable. For ganglioneuroma images, see <<16.0.0.5>>Ganglioneuroma (p. XXX).
Choroidal neurofibroma in neurofibromatosis type 1. Uveal neurofibromas typically cause diffuse expansion of the choroid.
Choroidal neurofibroma in neurofibromatosis type 1. Electron microscopy shows ovoid bodies, composed of elongated cells with Schwann cell properties, including a fragmented basal lamina.
Diffuse choroidal neurofibroma. Marked thickening of the choroid with extrascleral extension around ciliary nerves.
Diffuse choroidal neurofibroma. Marked thickening of the iris and ciliary body with iris neovascularization and obliteration of the anterior chamber angle.

Q: Patients with Diffuse Choroidal Neurofibroma and Ganglioneuroma typically present with diffuse choroidal expansion and are most strongly associated with [...].
Choroidal neurofibroma in neurofibromatosis type 1. Uveal neurofibromas typically cause diffuse expansion of the choroid.
Diffuse choroidal neurofibroma. Marked thickening of the choroid with extrascleral extension around ciliary nerves.
A: neurofibromatosis type 1
Back Extra: Diffuse Choroidal Neurofibroma and Ganglioneuroma
- Clinical: Patients with diffuse choroidal neurofibroma and ganglioneuroma may present with a pale, diffuse choroidal mass and are often associated with neurofibromatosis type 1 (NF1).
- Micro: Histopathology shows a haphazard proliferation of Schwann cells, fibroblasts, and choroidal melanocytes, with ovoid bodies composed of concentric Schwann cell processes being distinctive.
- Ancillary: NF1 gene inactivation is expected in patients with NF1, while PTEN mutations may be seen in the very rare cases associated with Cowden syndrome.
Reference Gallery:
Diffuse choroidal neurofibroma. The trabecular meshwork is hypercellular, due to involvement by the diffuse neurofibroma.
Diffuse choroidal neurofibroma. A dysmorphic, hypoplastic ciliary body associated with a diffuse choroidal neurofibroma.
Diffuse choroidal neurofibroma. Bland spindle cells replace the normal architecture of the choroid.
Diffuse choroidal neurofibroma. The diffuse neurofibroma involves a scleral canal, traversing the sclera from the upper left to the lower right of the image. The choroidal component is towards the top of the image.
Diffuse choroidal neurofibroma. Ovoid bodies composed of concentric Schwann cell processes are typical of diffuse choroidal neurofibroma.
Abnormal ganglion cells. Aggregates of ganglion cells in association with a neurofibroma component may be seen in some instances, where the term “ganglioneuroma” may be more suitable. For ganglioneuroma images, see <<16.0.0.5>>Ganglioneuroma (p. XXX).
Choroidal neurofibroma in neurofibromatosis type 1. Uveal neurofibromas typically cause diffuse expansion of the choroid.
Choroidal neurofibroma in neurofibromatosis type 1. Electron microscopy shows ovoid bodies, composed of elongated cells with Schwann cell properties, including a fragmented basal lamina.
Diffuse choroidal neurofibroma. Marked thickening of the choroid with extrascleral extension around ciliary nerves.
Diffuse choroidal neurofibroma. Marked thickening of the iris and ciliary body with iris neovascularization and obliteration of the anterior chamber angle.

Q: The diagnosis of Diffuse Choroidal Neurofibroma and Ganglioneuroma is most suitable when the typical haphazard spindle cell proliferation is accompanied by aggregates of abnormal [...].
Diffuse choroidal neurofibroma. Bland spindle cells replace the normal architecture of the choroid.
Abnormal ganglion cells. Aggregates of ganglion cells in association with a neurofibroma component may be seen in some instances, where the term “ganglioneuroma” may be more suitable. For ganglioneuroma images, see <<16.0.0.5>>Ganglioneuroma (p. XXX).
A: ganglion cells
Back Extra: Diffuse Choroidal Neurofibroma and Ganglioneuroma
- Clinical: Patients with diffuse choroidal neurofibroma and ganglioneuroma may present with a pale, diffuse choroidal mass and are often associated with neurofibromatosis type 1 (NF1).
- Micro: Histopathology shows a haphazard proliferation of Schwann cells, fibroblasts, and choroidal melanocytes, with ovoid bodies composed of concentric Schwann cell processes being distinctive.
- Ancillary: NF1 gene inactivation is expected in patients with NF1, while PTEN mutations may be seen in the very rare cases associated with Cowden syndrome.
Reference Gallery:
Diffuse choroidal neurofibroma. The trabecular meshwork is hypercellular, due to involvement by the diffuse neurofibroma.
Diffuse choroidal neurofibroma. A dysmorphic, hypoplastic ciliary body associated with a diffuse choroidal neurofibroma.
Diffuse choroidal neurofibroma. Bland spindle cells replace the normal architecture of the choroid.
Diffuse choroidal neurofibroma. The diffuse neurofibroma involves a scleral canal, traversing the sclera from the upper left to the lower right of the image. The choroidal component is towards the top of the image.
Diffuse choroidal neurofibroma. Ovoid bodies composed of concentric Schwann cell processes are typical of diffuse choroidal neurofibroma.
Abnormal ganglion cells. Aggregates of ganglion cells in association with a neurofibroma component may be seen in some instances, where the term “ganglioneuroma” may be more suitable. For ganglioneuroma images, see <<16.0.0.5>>Ganglioneuroma (p. XXX).
Choroidal neurofibroma in neurofibromatosis type 1. Uveal neurofibromas typically cause diffuse expansion of the choroid.
Choroidal neurofibroma in neurofibromatosis type 1. Electron microscopy shows ovoid bodies, composed of elongated cells with Schwann cell properties, including a fragmented basal lamina.
Diffuse choroidal neurofibroma. Marked thickening of the choroid with extrascleral extension around ciliary nerves.
Diffuse choroidal neurofibroma. Marked thickening of the iris and ciliary body with iris neovascularization and obliteration of the anterior chamber angle.

Q: Microscopically, Inflamed Juvenile Conjunctival Naevus is characterized by a distinctive [...] or triangular architecture with prominent lymphocytic inflammation and epithelial inclusions.
Inflamed juvenile conjunctival naevus. This section shows the architecture of the juvenile inflamed conjunctival naevus that resembles a V. The central portion is thicker, with the stromal component of melanocytes and epithelial inclusions with inflammation. The periphery contains the junctional/epithelial component and is thinner.
Inflamed juvenile conjunctival naevus. The epithelial inclusions and epithelial cysts in the stroma are associated with naevomelanocytes in their walls. Lymphocytes, plasma cells, and some eosinophils are seen in between the epithelial inclusions and the melanocytic nests.
A: V-shaped
Back Extra: Inflamed Juvenile Conjunctival Naevus
- Clinical: Inflamed juvenile conjunctival naevus (IJCN) is an elevated, well-circumscribed, usually amelanotic nodular lesion that may appear orange/red due to vascularization and increased pigmentation.
- Micro: IJCN shows a triangular or V-shaped architecture with prominent lymphocytic inflammation, cystic and solid epithelial rests, and PAS-positive material in the cystic cavities.
- Ancillary: NRAS p.Q61R mutations are more common than BRAF p.V600E mutations in IJCN, and immunostaining for CD45, CD3, and CD20 reveals a mixed population of B and T cells.
Reference Gallery:
Inflamed juvenile conjunctival naevus. Eosinophils are seen in the stroma and in the conjunctival epithelium containing the nest of melanocytes.
Inflamed juvenile conjunctival naevus. PAS staining highlights the goblet cells in the epithelial inclusions and the PAS-positive material filling the cystic cavities that together with the inflammatory infiltrate contribute to the growth of the lesion.
Inflamed juvenile conjunctival naevus. This section shows the architecture of the juvenile inflamed conjunctival naevus that resembles a V. The central portion is thicker, with the stromal component of melanocytes and epithelial inclusions with inflammation. The periphery contains the junctional/epithelial component and is thinner.
Inflamed juvenile conjunctival naevus. The epithelial inclusions and epithelial cysts in the stroma are associated with naevomelanocytes in their walls. Lymphocytes, plasma cells, and some eosinophils are seen in between the epithelial inclusions and the melanocytic nests.
Inflamed juvenile conjunctival naevus. This overview of the naevus immunostained with a panmelanocytic marker highlights the nests (and single cells) of melanocytes associated with the epithelial inclusions, and the cysts separated by the inflammatory component (melan-A immunohistochemistry with DAB chromogen).
Inflamed juvenile conjunctival naevus. Epithelial-associated nests of naevomelanocytes are positive for HMB45 (cytoplasmic, red chromogen staining), while nests of melanocytes in the stroma are negative. Inflammatory cells and proliferative epithelial cells are highlighted by Ki-67 (MIB1) immunostaining (nuclear, brown DAB chromogen staining).

Q: In Inflamed Juvenile Conjunctival Naevus, [...] staining highlights the goblet cells within epithelial inclusions and the material filling the cystic cavities.
Inflamed juvenile conjunctival naevus. PAS staining highlights the goblet cells in the epithelial inclusions and the PAS-positive material filling the cystic cavities that together with the inflammatory infiltrate contribute to the growth of the lesion.
A: PAS
Back Extra: Inflamed Juvenile Conjunctival Naevus
- Clinical: Inflamed juvenile conjunctival naevus (IJCN) is an elevated, well-circumscribed, usually amelanotic nodular lesion that may appear orange/red due to vascularization and increased pigmentation.
- Micro: IJCN shows a triangular or V-shaped architecture with prominent lymphocytic inflammation, cystic and solid epithelial rests, and PAS-positive material in the cystic cavities.
- Ancillary: NRAS p.Q61R mutations are more common than BRAF p.V600E mutations in IJCN, and immunostaining for CD45, CD3, and CD20 reveals a mixed population of B and T cells.
Reference Gallery:
Inflamed juvenile conjunctival naevus. Eosinophils are seen in the stroma and in the conjunctival epithelium containing the nest of melanocytes.
Inflamed juvenile conjunctival naevus. PAS staining highlights the goblet cells in the epithelial inclusions and the PAS-positive material filling the cystic cavities that together with the inflammatory infiltrate contribute to the growth of the lesion.
Inflamed juvenile conjunctival naevus. This section shows the architecture of the juvenile inflamed conjunctival naevus that resembles a V. The central portion is thicker, with the stromal component of melanocytes and epithelial inclusions with inflammation. The periphery contains the junctional/epithelial component and is thinner.
Inflamed juvenile conjunctival naevus. The epithelial inclusions and epithelial cysts in the stroma are associated with naevomelanocytes in their walls. Lymphocytes, plasma cells, and some eosinophils are seen in between the epithelial inclusions and the melanocytic nests.
Inflamed juvenile conjunctival naevus. This overview of the naevus immunostained with a panmelanocytic marker highlights the nests (and single cells) of melanocytes associated with the epithelial inclusions, and the cysts separated by the inflammatory component (melan-A immunohistochemistry with DAB chromogen).
Inflamed juvenile conjunctival naevus. Epithelial-associated nests of naevomelanocytes are positive for HMB45 (cytoplasmic, red chromogen staining), while nests of melanocytes in the stroma are negative. Inflammatory cells and proliferative epithelial cells are highlighted by Ki-67 (MIB1) immunostaining (nuclear, brown DAB chromogen staining).

Q: In Inflamed Juvenile Conjunctival Naevus, epithelial-associated nests of nevomelanocytes are characteristically positive for [...], while nests in the deeper stroma are negative.
Inflamed juvenile conjunctival naevus. Epithelial-associated nests of naevomelanocytes are positive for HMB45 (cytoplasmic, red chromogen staining), while nests of melanocytes in the stroma are negative. Inflammatory cells and proliferative epithelial cells are highlighted by Ki-67 (MIB1) immunostaining (nuclear, brown DAB chromogen staining).
A: HMB45
Back Extra: Inflamed Juvenile Conjunctival Naevus
- Clinical: Inflamed juvenile conjunctival naevus (IJCN) is an elevated, well-circumscribed, usually amelanotic nodular lesion that may appear orange/red due to vascularization and increased pigmentation.
- Micro: IJCN shows a triangular or V-shaped architecture with prominent lymphocytic inflammation, cystic and solid epithelial rests, and PAS-positive material in the cystic cavities.
- Ancillary: NRAS p.Q61R mutations are more common than BRAF p.V600E mutations in IJCN, and immunostaining for CD45, CD3, and CD20 reveals a mixed population of B and T cells.
Reference Gallery:
Inflamed juvenile conjunctival naevus. Eosinophils are seen in the stroma and in the conjunctival epithelium containing the nest of melanocytes.
Inflamed juvenile conjunctival naevus. PAS staining highlights the goblet cells in the epithelial inclusions and the PAS-positive material filling the cystic cavities that together with the inflammatory infiltrate contribute to the growth of the lesion.
Inflamed juvenile conjunctival naevus. This section shows the architecture of the juvenile inflamed conjunctival naevus that resembles a V. The central portion is thicker, with the stromal component of melanocytes and epithelial inclusions with inflammation. The periphery contains the junctional/epithelial component and is thinner.
Inflamed juvenile conjunctival naevus. The epithelial inclusions and epithelial cysts in the stroma are associated with naevomelanocytes in their walls. Lymphocytes, plasma cells, and some eosinophils are seen in between the epithelial inclusions and the melanocytic nests.
Inflamed juvenile conjunctival naevus. This overview of the naevus immunostained with a panmelanocytic marker highlights the nests (and single cells) of melanocytes associated with the epithelial inclusions, and the cysts separated by the inflammatory component (melan-A immunohistochemistry with DAB chromogen).
Inflamed juvenile conjunctival naevus. Epithelial-associated nests of naevomelanocytes are positive for HMB45 (cytoplasmic, red chromogen staining), while nests of melanocytes in the stroma are negative. Inflammatory cells and proliferative epithelial cells are highlighted by Ki-67 (MIB1) immunostaining (nuclear, brown DAB chromogen staining).

Q: A Lisch Nodule (Iris Hamartoma) presents clinically as small, bilateral, minimally elevated iris nodules that serve as a major diagnostic criterion for [...].
Lisch nodules. Slit-lamp photograph of an iris featuring multiple small but variably sized tan/brown nodules.
A: Neurofibromatosis Type 1 (NF1)
Back Extra: Lisch Nodule (Iris Hamartoma)
- Clinical: Lisch nodules are small, bilateral, minimally elevated iris nodules that usually appear in early childhood (~2 years) and are a diagnostic criterion for Neurofibromatosis Type 1 (NF1).
- Micro: Microscopically, Lisch nodules are composed of bland spindle-shaped melanocytes arranged haphazardly on the anterior face of the iris, with no prominent nucleoli or mitotic figures.
- Ancillary: Immunohistochemical confirmation with S100 staining is essential to confirm the melanocytic lineage of the cells in Lisch nodules.
Reference Gallery:
Lisch nodule (iris hamartoma). S100 immunohistochemistry of the bland spindle melanocytes (cytoplasmic and nuclear staining).
Lisch nodule (iris hamartoma). Iris tissue showing a Lisch nodule. It is composed of bland spindle-shaped melanocytes on the iris surface and within the underlying superficial iris stroma.
Lisch nodules. Slit-lamp photograph of an iris featuring multiple small but variably sized tan/brown nodules.

Q: Microscopically, a Lisch Nodule (Iris Hamartoma) is characterized by a haphazard proliferation of bland, spindle-shaped [...] located on the anterior face of the iris.
Lisch nodule (iris hamartoma). Iris tissue showing a Lisch nodule. It is composed of bland spindle-shaped melanocytes on the iris surface and within the underlying superficial iris stroma.
A: melanocytes
Back Extra: Lisch Nodule (Iris Hamartoma)
- Clinical: Lisch nodules are small, bilateral, minimally elevated iris nodules that usually appear in early childhood (~2 years) and are a diagnostic criterion for Neurofibromatosis Type 1 (NF1).
- Micro: Microscopically, Lisch nodules are composed of bland spindle-shaped melanocytes arranged haphazardly on the anterior face of the iris, with no prominent nucleoli or mitotic figures.
- Ancillary: Immunohistochemical confirmation with S100 staining is essential to confirm the melanocytic lineage of the cells in Lisch nodules.
Reference Gallery:
Lisch nodule (iris hamartoma). S100 immunohistochemistry of the bland spindle melanocytes (cytoplasmic and nuclear staining).
Lisch nodule (iris hamartoma). Iris tissue showing a Lisch nodule. It is composed of bland spindle-shaped melanocytes on the iris surface and within the underlying superficial iris stroma.
Lisch nodules. Slit-lamp photograph of an iris featuring multiple small but variably sized tan/brown nodules.

Q: Immunohistochemical analysis of a Lisch Nodule (Iris Hamartoma) typically reveals strong cytoplasmic and nuclear positivity for [...], confirming the neural crest lineage of the constituent spindle cells.
Lisch nodule (iris hamartoma). S100 immunohistochemistry of the bland spindle melanocytes (cytoplasmic and nuclear staining).
A: S100
Back Extra: Lisch Nodule (Iris Hamartoma)
- Clinical: Lisch nodules are small, bilateral, minimally elevated iris nodules that usually appear in early childhood (~2 years) and are a diagnostic criterion for Neurofibromatosis Type 1 (NF1).
- Micro: Microscopically, Lisch nodules are composed of bland spindle-shaped melanocytes arranged haphazardly on the anterior face of the iris, with no prominent nucleoli or mitotic figures.
- Ancillary: Immunohistochemical confirmation with S100 staining is essential to confirm the melanocytic lineage of the cells in Lisch nodules.
Reference Gallery:
Lisch nodule (iris hamartoma). S100 immunohistochemistry of the bland spindle melanocytes (cytoplasmic and nuclear staining).
Lisch nodule (iris hamartoma). Iris tissue showing a Lisch nodule. It is composed of bland spindle-shaped melanocytes on the iris surface and within the underlying superficial iris stroma.
Lisch nodules. Slit-lamp photograph of an iris featuring multiple small but variably sized tan/brown nodules.

Q: Microscopically, a ciliary body medulloepithelioma features thick bands of polarized neuroepithelium resembling embryonic medullary epithelium, often forming a characteristic net-like [...] pattern.
Ciliary body medulloepithelioma. There are thick bands of polarized epithelium resembling medullary epithelium, and a diktyomatous pattern comprising thinner epithelial strands. Pools of hyaluronic acid surround neuroepithelial elements.
A: diktyomatous
Back Extra: Medulloepithelioma
- Clinical: Patients with medulloepithelioma often present with visual loss, leukocoria, strabismus, or a red and painful eye.
- Micro: The tumour is composed of anastomosing cords, bands, and ribbons of polarized neuroepithelial cells resembling embryonic medullary epithelium, often with intralesional cystoid spaces.
- Ancillary: Immunoreactivity for LIN28A is specific for medulloepithelioma and correlates with aggressive behavior.
Reference Gallery:
Ciliary body medulloepithelioma. A tumour on the inner surface of the ciliary body. Intralesional cysts and a neoplastic cyclitic membrane are present.
Teratoid ciliary body medulloepithelioma. A teratoid tumour on the inner surface of the ciliary body contains foci of hyaline cartilage and multiple cystoid spaces.
Ciliary body medulloepithelioma. There are thick bands of polarized epithelium resembling medullary epithelium, and a diktyomatous pattern comprising thinner epithelial strands. Pools of hyaluronic acid surround neuroepithelial elements.
Teratoid ciliary body medulloepithelioma. Neuroepithelial elements are surrounded by myxoid matrix. A focus of hyaline cartilage is present in this teratoid tumour.

Q: The teratoid variant of ciliary body medulloepithelioma is morphologically distinguished from the non-teratoid type by the presence of heterologous elements, most commonly foci of [...].
Teratoid ciliary body medulloepithelioma. A teratoid tumour on the inner surface of the ciliary body contains foci of hyaline cartilage and multiple cystoid spaces.
Teratoid ciliary body medulloepithelioma. Neuroepithelial elements are surrounded by myxoid matrix. A focus of hyaline cartilage is present in this teratoid tumour.
A: hyaline cartilage
Back Extra: Medulloepithelioma
- Clinical: Patients with medulloepithelioma often present with visual loss, leukocoria, strabismus, or a red and painful eye.
- Micro: The tumour is composed of anastomosing cords, bands, and ribbons of polarized neuroepithelial cells resembling embryonic medullary epithelium, often with intralesional cystoid spaces.
- Ancillary: Immunoreactivity for LIN28A is specific for medulloepithelioma and correlates with aggressive behavior.
Reference Gallery:
Ciliary body medulloepithelioma. A tumour on the inner surface of the ciliary body. Intralesional cysts and a neoplastic cyclitic membrane are present.
Teratoid ciliary body medulloepithelioma. A teratoid tumour on the inner surface of the ciliary body contains foci of hyaline cartilage and multiple cystoid spaces.
Ciliary body medulloepithelioma. There are thick bands of polarized epithelium resembling medullary epithelium, and a diktyomatous pattern comprising thinner epithelial strands. Pools of hyaluronic acid surround neuroepithelial elements.
Teratoid ciliary body medulloepithelioma. Neuroepithelial elements are surrounded by myxoid matrix. A focus of hyaline cartilage is present in this teratoid tumour.

Q: Histologically, Pilocytic Astrocytoma of the Optic Nerve is characterized by bland spindled cells with long, hair-like processes and characteristic thick, eosinophilic structures known as [...].
Pilocytic astrocytoma of the optic nerve. Rosenthal fibres and bland spindled cells characterize the tumour within the optic nerve.
A: Rosenthal fibers
Back Extra: Pilocytic Astrocytoma of the Optic Nerve
- Clinical: Pilocytic astrocytomas of the optic nerve can cause visual loss, endocrinopathies, hypothalamic dysfunction, and disfiguring proptosis.
- Micro: Characterized by cells with long, fine, hair-like processes, round to spindle-shaped nuclei, Rosenthal fibres, and eosinophilic granular bodies.
- Ancillary: Most optic nerve pilocytic astrocytomas have MAPK-activating mutations, including BRAF fusions and point mutations.
Reference Gallery:
Pilocytic astrocytoma of the optic nerve. A GFAP stain highlights the expansion of the optic nerve parenchyma by glioma cells.
Pilocytic astrocytoma of the optic nerve. Rosenthal fibres and bland spindled cells characterize the tumour within the optic nerve.
Pilocytic astrocytoma of the optic nerve. There is hypercellularity and atypia in the parenchyma of the nerve.
Pilocytic astrocytoma of the optic nerve. Note the expansion of the optic nerve parenchyma and massive extension into the meninges.

Q: A classic histologic feature of Pilocytic Astrocytoma of the Optic Nerve is the marked expansion of the optic nerve parenchyma, which is strongly highlighted by the glial immunohistochemical marker [...].
Pilocytic astrocytoma of the optic nerve. A GFAP stain highlights the expansion of the optic nerve parenchyma by glioma cells.
A: GFAP
Back Extra: Pilocytic Astrocytoma of the Optic Nerve
- Clinical: Pilocytic astrocytomas of the optic nerve can cause visual loss, endocrinopathies, hypothalamic dysfunction, and disfiguring proptosis.
- Micro: Characterized by cells with long, fine, hair-like processes, round to spindle-shaped nuclei, Rosenthal fibres, and eosinophilic granular bodies.
- Ancillary: Most optic nerve pilocytic astrocytomas have MAPK-activating mutations, including BRAF fusions and point mutations.
Reference Gallery:
Pilocytic astrocytoma of the optic nerve. A GFAP stain highlights the expansion of the optic nerve parenchyma by glioma cells.
Pilocytic astrocytoma of the optic nerve. Rosenthal fibres and bland spindled cells characterize the tumour within the optic nerve.
Pilocytic astrocytoma of the optic nerve. There is hypercellularity and atypia in the parenchyma of the nerve.
Pilocytic astrocytoma of the optic nerve. Note the expansion of the optic nerve parenchyma and massive extension into the meninges.

Q: In Pilocytic Astrocytoma of the Optic Nerve, the tumor expands the optic nerve parenchyma and characteristically shows massive extension into the surrounding [...].
Pilocytic astrocytoma of the optic nerve. Note the expansion of the optic nerve parenchyma and massive extension into the meninges.
A: meninges
Back Extra: Pilocytic Astrocytoma of the Optic Nerve
- Clinical: Pilocytic astrocytomas of the optic nerve can cause visual loss, endocrinopathies, hypothalamic dysfunction, and disfiguring proptosis.
- Micro: Characterized by cells with long, fine, hair-like processes, round to spindle-shaped nuclei, Rosenthal fibres, and eosinophilic granular bodies.
- Ancillary: Most optic nerve pilocytic astrocytomas have MAPK-activating mutations, including BRAF fusions and point mutations.
Reference Gallery:
Pilocytic astrocytoma of the optic nerve. A GFAP stain highlights the expansion of the optic nerve parenchyma by glioma cells.
Pilocytic astrocytoma of the optic nerve. Rosenthal fibres and bland spindled cells characterize the tumour within the optic nerve.
Pilocytic astrocytoma of the optic nerve. There is hypercellularity and atypia in the parenchyma of the nerve.
Pilocytic astrocytoma of the optic nerve. Note the expansion of the optic nerve parenchyma and massive extension into the meninges.

Q: Clinically, Phakomatous Choristoma presents as a congenital, firm, slowly growing subcutaneous mass most typically located in the [...].
Phakomatous choristoma. A congenital mass involves the medial lower eyelid.
A: medial lower eyelid
Back Extra: Phakomatous Choristoma
- Clinical: Patients present with a smooth, firm, slowly growing subcutaneous mass in the medial lower eyelid, already present at birth. Phakomatous choristoma is extremely rare, with < 30 cases reported worldwide.
- Micro: The histological appearance consists of desmoplastic-like stroma with islands of cuboid to polygonal cells surrounded by a thick layer of eosinophilic, amorphic, PAS-positive material analogous to lens capsule. Bladder/Wedl-like cells and psammomatous calcification may also be present.
- Ancillary: Not relevant; the diagnosis is primarily based on histological examination.
Reference Gallery:
Phakomatous choristoma. The histological picture exhibits lens epithelial cells surrounded by amorphic eosinophilic material.
Phakomatous choristoma. The PAS reaction highlights a PAS-positive membrane surrounding the epithelial cells.
Phakomatous choristoma. A congenital mass involves the medial lower eyelid.

Q: The histologic hallmark of Phakomatous Choristoma consists of epithelial cell islands surrounded by a thick, eosinophilic, PAS-positive material analogous to the [...].
Phakomatous choristoma. The histological picture exhibits lens epithelial cells surrounded by amorphic eosinophilic material.
Phakomatous choristoma. The PAS reaction highlights a PAS-positive membrane surrounding the epithelial cells.
A: lens capsule
Back Extra: Phakomatous Choristoma
- Clinical: Patients present with a smooth, firm, slowly growing subcutaneous mass in the medial lower eyelid, already present at birth. Phakomatous choristoma is extremely rare, with < 30 cases reported worldwide.
- Micro: The histological appearance consists of desmoplastic-like stroma with islands of cuboid to polygonal cells surrounded by a thick layer of eosinophilic, amorphic, PAS-positive material analogous to lens capsule. Bladder/Wedl-like cells and psammomatous calcification may also be present.
- Ancillary: Not relevant; the diagnosis is primarily based on histological examination.
Reference Gallery:
Phakomatous choristoma. The histological picture exhibits lens epithelial cells surrounded by amorphic eosinophilic material.
Phakomatous choristoma. The PAS reaction highlights a PAS-positive membrane surrounding the epithelial cells.
Phakomatous choristoma. A congenital mass involves the medial lower eyelid.

Q: The classic clinical presenting signs of retinoblastoma include strabismus and [...] (an abnormal white pupillary reflex).
Leukocoria. White pupillary reflex from the left eye.
Retinoblastoma. Colour fundus photograph showing a white macular tumour in the right eye, with localized subretinal seeding and subretinal fluid.
A: leukocoria
Q: Retinoblastoma
- Clinical: Leukocoria (white pupillary reflex) and squint are common presenting signs of [...].
- Micro: [...] is composed of primitive neuroblastic cells with Flexner–Wintersteiner and Homer Wright rosettes, and often shows geographical necrosis and calcification.
- Ancillary: MRI is used to exclude extraocular extension and brain involvement in [...], but histopathology remains the gold standard for assessing high-risk features.
Reference Gallery:
Leukocoria. White pupillary reflex from the left eye.
Retinoblastoma. Colour fundus photograph showing a white macular tumour in the right eye, with localized subretinal seeding and subretinal fluid.
Retinoblastoma. Colour fundus photograph showing a retinoblastoma with extensive diffuse vitreous seeding that appears as floating spheres and dust in the vitreous.
Retinoblastoma in the left eye. On T1-weighted MRI the tumour is brighter than the vitreous.
Retinoblastoma in the left eye. On T2-weighted MRI the tumour is darker than the vitreous.
Retinoblastoma. Exophytic retinoblastoma with associated retinal detachment and subretinal gelatinous yellow fluid. The tan-grey tumour is covered by the retina and has bright white calcifications.
Retinoblastoma. Vitreous seeds in endophytic retinoblastoma. Sphere-type retinoblastoma tumour seeds show central bright white cores with a translucent solid periphery. In between the spheres there are areas of dust-type seeds. These seeds are in the anterior vitreous in front of the ciliary body pars plicata.
Retinoblastoma. Extensively necrotic retinoblastoma. The intraocular tissues and tumour show extensive necrosis with remote haemorrhage and condensation bands of vitreous with tumour. The retina and tumour vessels are engorged. Necrotic debris is present in the anterior chamber.
Grossing of an eye with retinoblastoma. After obtaining the superior calotte (seen to the left) through an anterior–posterior cut in this right eye, the remainder of the eye shows the optic nerve intact just under the plane of the section.
Grossing of an eye with retinoblastoma. Each calotte (cap) obtained is further sectioned in an anterior–posterior direction to be submitted on edge for histological sectioning.
Grossing of an eye with retinoblastoma. The entire eye with the tumour is submitted in three tall cassettes. The pupil–optic nerve section and the two calottes (on edge to allow the examination of most of the choroidal surface) are seen in these cassettes. The cross-section of the optic nerve margin should be submitted in a separate cassette.
Retinoblastoma. Indeterminate growth pattern and massive choroidal invasion. This retinoblastoma is mostly exophytic but there is diffuse central obliteration of the vitreous cavity showing areas of haemorrhage (inferior left) and central calcification. There is massive replacement of the inferior choroid around the optic nerve (15 mm at the base) by the tumour.
A: retinoblastoma; Retinoblastoma; retinoblastoma

Q: On gross examination, retinoblastoma characteristically presents as an intraocular tumor with extensive geographical necrosis and bright white [...].
Retinoblastoma. Exophytic retinoblastoma with associated retinal detachment and subretinal gelatinous yellow fluid. The tan-grey tumour is covered by the retina and has bright white calcifications.
Retinoblastoma. Extensively necrotic retinoblastoma. The intraocular tissues and tumour show extensive necrosis with remote haemorrhage and condensation bands of vitreous with tumour. The retina and tumour vessels are engorged. Necrotic debris is present in the anterior chamber.
A: calcifications
Q: Retinoblastoma
- Clinical: Leukocoria (white pupillary reflex) and squint are common presenting signs of [...].
- Micro: [...] is composed of primitive neuroblastic cells with Flexner–Wintersteiner and Homer Wright rosettes, and often shows geographical necrosis and calcification.
- Ancillary: MRI is used to exclude extraocular extension and brain involvement in [...], but histopathology remains the gold standard for assessing high-risk features.
Reference Gallery:
Leukocoria. White pupillary reflex from the left eye.
Retinoblastoma. Colour fundus photograph showing a white macular tumour in the right eye, with localized subretinal seeding and subretinal fluid.
Retinoblastoma. Colour fundus photograph showing a retinoblastoma with extensive diffuse vitreous seeding that appears as floating spheres and dust in the vitreous.
Retinoblastoma in the left eye. On T1-weighted MRI the tumour is brighter than the vitreous.
Retinoblastoma in the left eye. On T2-weighted MRI the tumour is darker than the vitreous.
Retinoblastoma. Exophytic retinoblastoma with associated retinal detachment and subretinal gelatinous yellow fluid. The tan-grey tumour is covered by the retina and has bright white calcifications.
Retinoblastoma. Vitreous seeds in endophytic retinoblastoma. Sphere-type retinoblastoma tumour seeds show central bright white cores with a translucent solid periphery. In between the spheres there are areas of dust-type seeds. These seeds are in the anterior vitreous in front of the ciliary body pars plicata.
Retinoblastoma. Extensively necrotic retinoblastoma. The intraocular tissues and tumour show extensive necrosis with remote haemorrhage and condensation bands of vitreous with tumour. The retina and tumour vessels are engorged. Necrotic debris is present in the anterior chamber.
Grossing of an eye with retinoblastoma. After obtaining the superior calotte (seen to the left) through an anterior–posterior cut in this right eye, the remainder of the eye shows the optic nerve intact just under the plane of the section.
Grossing of an eye with retinoblastoma. Each calotte (cap) obtained is further sectioned in an anterior–posterior direction to be submitted on edge for histological sectioning.
Grossing of an eye with retinoblastoma. The entire eye with the tumour is submitted in three tall cassettes. The pupil–optic nerve section and the two calottes (on edge to allow the examination of most of the choroidal surface) are seen in these cassettes. The cross-section of the optic nerve margin should be submitted in a separate cassette.
Retinoblastoma. Indeterminate growth pattern and massive choroidal invasion. This retinoblastoma is mostly exophytic but there is diffuse central obliteration of the vitreous cavity showing areas of haemorrhage (inferior left) and central calcification. There is massive replacement of the inferior choroid around the optic nerve (15 mm at the base) by the tumour.
A: retinoblastoma; Retinoblastoma; retinoblastoma

Q: At higher magnification, the uniform cells of a Retinocytoma characteristically exhibit round nuclei, speckled chromatin, and [...] cytoplasm, making the tumor notably less basophilic overall than a retinoblastoma.
Retinocytoma. A juxtapapillary retinocytoma is present next to the optic nerve (ON). The tumour effaces the retina deep to the nerve fibre layer. It is cellular but not nearly as basophilic as a retinoblastoma. An oval area of dystrophic calcium is noted on the right.
Retinocytoma. A higher-magnification view shows cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin.
A: eosinophilic
Back Extra: Retinocytoma
- Clinical: Most retinocytomas are unilateral and can be detected during screening in families with known retinoblastoma or incidentally. They are semitranslucent and surrounded by mild to moderate pigmentary changes.
- Micro: Retinocytomas consist of a uniform population of cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin. Fleurettes are characteristic, and dystrophic calcification is common.
- Ancillary: Retinocytomas generally harbour biallelic loss of the RB1 gene but have less aneuploidy and secondary mutations compared to retinoblastoma. They do not express Ki-67 or p53.
Reference Gallery:
Retinocytoma. A juxtapapillary retinocytoma is present next to the optic nerve (ON). The tumour effaces the retina deep to the nerve fibre layer. It is cellular but not nearly as basophilic as a retinoblastoma. An oval area of dystrophic calcium is noted on the right.
Retinocytoma. A higher-magnification view shows cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin.

Q: On histologic examination, a Retinocytoma commonly features dense, oval areas of [...] interspersed within the cellular tumor.
Retinocytoma. A juxtapapillary retinocytoma is present next to the optic nerve (ON). The tumour effaces the retina deep to the nerve fibre layer. It is cellular but not nearly as basophilic as a retinoblastoma. An oval area of dystrophic calcium is noted on the right.
A: dystrophic calcification
Back Extra: Retinocytoma
- Clinical: Most retinocytomas are unilateral and can be detected during screening in families with known retinoblastoma or incidentally. They are semitranslucent and surrounded by mild to moderate pigmentary changes.
- Micro: Retinocytomas consist of a uniform population of cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin. Fleurettes are characteristic, and dystrophic calcification is common.
- Ancillary: Retinocytomas generally harbour biallelic loss of the RB1 gene but have less aneuploidy and secondary mutations compared to retinoblastoma. They do not express Ki-67 or p53.
Reference Gallery:
Retinocytoma. A juxtapapillary retinocytoma is present next to the optic nerve (ON). The tumour effaces the retina deep to the nerve fibre layer. It is cellular but not nearly as basophilic as a retinoblastoma. An oval area of dystrophic calcium is noted on the right.
Retinocytoma. A higher-magnification view shows cells with eosinophilic cytoplasm, round nuclei, and speckled chromatin.

Q: In Beckwith-Wiedemann Syndrome, the kidneys of affected infants often exhibit [...], which serve as precursor lesions to Wilms tumor.
Perilobar nephrogenic rests. These are in the kidney of a young child with Beckwith–Wiedemann syndrome.
A: perilobar nephrogenic rests
Back Extra: Beckwith-Wiedemann Syndrome
- Clinical: Beckwith-Wiedemann syndrome (BWS) predisposes primarily to nephroblastoma and hepatoblastoma, with differential diagnoses including Costello, Malan, Perlman, and Simpson–Golabi–Behmel syndromes.
- Micro: Perilobar nephrogenic rests are seen in the kidneys of infants and young children with BWS and are considered precursor lesions of Wilms tumour.
- Ancillary: Molecular analyses include methylation at imprinting loci, mutation screening of CDKN1C, and copy-number analysis at 11p15.5, with possible mosaicism requiring analysis of different tissues.
Reference Gallery:
Perilobar nephrogenic rests. These are in the kidney of a young child with Beckwith–Wiedemann syndrome.
Medullary ray nodules. These are seen in the kidneys of patients with Wilms tumour and Beckwith–Wiedemann syndrome.

Q: Microscopic evaluation of the kidneys in patients with Beckwith-Wiedemann Syndrome and Wilms tumor may reveal distinct lesions known as [...].
Medullary ray nodules. These are seen in the kidneys of patients with Wilms tumour and Beckwith–Wiedemann syndrome.
A: medullary ray nodules
Back Extra: Beckwith-Wiedemann Syndrome
- Clinical: Beckwith-Wiedemann syndrome (BWS) predisposes primarily to nephroblastoma and hepatoblastoma, with differential diagnoses including Costello, Malan, Perlman, and Simpson–Golabi–Behmel syndromes.
- Micro: Perilobar nephrogenic rests are seen in the kidneys of infants and young children with BWS and are considered precursor lesions of Wilms tumour.
- Ancillary: Molecular analyses include methylation at imprinting loci, mutation screening of CDKN1C, and copy-number analysis at 11p15.5, with possible mosaicism requiring analysis of different tissues.
Reference Gallery:
Perilobar nephrogenic rests. These are in the kidney of a young child with Beckwith–Wiedemann syndrome.
Medullary ray nodules. These are seen in the kidneys of patients with Wilms tumour and Beckwith–Wiedemann syndrome.

Q: Histologically, glioblastomas arising in patients with Constitutional Mismatch Repair Deficiency Syndrome frequently exhibit severe nuclear pleomorphism and bizarre, multinucleated [...].
Glioblastoma arising in the setting of constitutional mismatch repair deficiency syndrome (CMMRD). Glioblastomas arising in this setting often demonstrate severe nuclear pleomorphism with bizarre and multinucleated giant cells.
A: giant cells
Back Extra: Constitutional Mismatch Repair Deficiency Syndrome
- Clinical: Children with Constitutional Mismatch Repair Deficiency Syndrome (CMMRD) often develop ultrahypermutated malignant gliomas, CNS embryonal tumours, and a variety of other cancers during childhood and early adulthood.
- Micro: Glioblastomas in CMMRD show severe nuclear pleomorphism, bizarre multinucleated giant cells, or sheets of primitive small blue cells.
- Ancillary: IHC shows loss of expression of the inactivated mismatch repair protein (and its heterodimer) in both tumour and normal tissue in > 90% of CMMRD-associated cancers.
Reference Gallery:
Glioblastoma arising in the setting of constitutional mismatch repair deficiency syndrome (CMMRD). Glioblastomas arising in this setting often demonstrate severe nuclear pleomorphism with bizarre and multinucleated giant cells.
Representative imaging of replication repair–deficient glioblastomas. T1-weighted postcontrast MRI of a patient with constitutional mismatch repair deficiency syndrome with a homozygous MSH2 pathogenic germline variant. Note two synchronous tumours (arrows). Both tumours had secondary somatic mutations and ultrahypermutation, one involving POLE and one involving POLD1.
Glioblastoma arising in the setting of constitutional mismatch repair deficiency syndrome (CMMRD). This glioblastoma in the cerebral hemispheres of a child with CMMRD demonstrates a complete absence of PMS2 protein both in tumour cells and in normal cells, resulting from biallelic inactivation of the PMS2 mismatch repair gene in the germline of this patient.
Representative imaging of replication repair–deficient glioblastomas. A FLAIR sequence of a patient with Lynch syndrome and MLH1 heterozygous pathogenic germline variant. This gliomatosis-like pattern is typical for somatic mutation in IDH1 and hypermutation.

Q: In Constitutional Mismatch Repair Deficiency Syndrome, immunohistochemistry for the affected mismatch repair protein (e.g., PMS2) reveals a characteristic loss of expression in [...], reflecting the germline biallelic inactivation.
Glioblastoma arising in the setting of constitutional mismatch repair deficiency syndrome (CMMRD). This glioblastoma in the cerebral hemispheres of a child with CMMRD demonstrates a complete absence of PMS2 protein both in tumour cells and in normal cells, resulting from biallelic inactivation of the PMS2 mismatch repair gene in the germline of this patient.
A: both tumor and normal cells
Back Extra: Constitutional Mismatch Repair Deficiency Syndrome
- Clinical: Children with Constitutional Mismatch Repair Deficiency Syndrome (CMMRD) often develop ultrahypermutated malignant gliomas, CNS embryonal tumours, and a variety of other cancers during childhood and early adulthood.
- Micro: Glioblastomas in CMMRD show severe nuclear pleomorphism, bizarre multinucleated giant cells, or sheets of primitive small blue cells.
- Ancillary: IHC shows loss of expression of the inactivated mismatch repair protein (and its heterodimer) in both tumour and normal tissue in > 90% of CMMRD-associated cancers.
Reference Gallery:
Glioblastoma arising in the setting of constitutional mismatch repair deficiency syndrome (CMMRD). Glioblastomas arising in this setting often demonstrate severe nuclear pleomorphism with bizarre and multinucleated giant cells.
Representative imaging of replication repair–deficient glioblastomas. T1-weighted postcontrast MRI of a patient with constitutional mismatch repair deficiency syndrome with a homozygous MSH2 pathogenic germline variant. Note two synchronous tumours (arrows). Both tumours had secondary somatic mutations and ultrahypermutation, one involving POLE and one involving POLD1.
Glioblastoma arising in the setting of constitutional mismatch repair deficiency syndrome (CMMRD). This glioblastoma in the cerebral hemispheres of a child with CMMRD demonstrates a complete absence of PMS2 protein both in tumour cells and in normal cells, resulting from biallelic inactivation of the PMS2 mismatch repair gene in the germline of this patient.
Representative imaging of replication repair–deficient glioblastomas. A FLAIR sequence of a patient with Lynch syndrome and MLH1 heterozygous pathogenic germline variant. This gliomatosis-like pattern is typical for somatic mutation in IDH1 and hypermutation.

Q: Children and young adults with Constitutional Mismatch Repair Deficiency Syndrome have a high risk of developing ultrahypermutated malignant [...] (e.g., glioblastomas), which can present as synchronous CNS tumors on MRI.
Representative imaging of replication repair–deficient glioblastomas. T1-weighted postcontrast MRI of a patient with constitutional mismatch repair deficiency syndrome with a homozygous MSH2 pathogenic germline variant. Note two synchronous tumours (arrows). Both tumours had secondary somatic mutations and ultrahypermutation, one involving POLE and one involving POLD1.
A: gliomas
Back Extra: Constitutional Mismatch Repair Deficiency Syndrome
- Clinical: Children with Constitutional Mismatch Repair Deficiency Syndrome (CMMRD) often develop ultrahypermutated malignant gliomas, CNS embryonal tumours, and a variety of other cancers during childhood and early adulthood.
- Micro: Glioblastomas in CMMRD show severe nuclear pleomorphism, bizarre multinucleated giant cells, or sheets of primitive small blue cells.
- Ancillary: IHC shows loss of expression of the inactivated mismatch repair protein (and its heterodimer) in both tumour and normal tissue in > 90% of CMMRD-associated cancers.
Reference Gallery:
Glioblastoma arising in the setting of constitutional mismatch repair deficiency syndrome (CMMRD). Glioblastomas arising in this setting often demonstrate severe nuclear pleomorphism with bizarre and multinucleated giant cells.
Representative imaging of replication repair–deficient glioblastomas. T1-weighted postcontrast MRI of a patient with constitutional mismatch repair deficiency syndrome with a homozygous MSH2 pathogenic germline variant. Note two synchronous tumours (arrows). Both tumours had secondary somatic mutations and ultrahypermutation, one involving POLE and one involving POLD1.
Glioblastoma arising in the setting of constitutional mismatch repair deficiency syndrome (CMMRD). This glioblastoma in the cerebral hemispheres of a child with CMMRD demonstrates a complete absence of PMS2 protein both in tumour cells and in normal cells, resulting from biallelic inactivation of the PMS2 mismatch repair gene in the germline of this patient.
Representative imaging of replication repair–deficient glioblastomas. A FLAIR sequence of a patient with Lynch syndrome and MLH1 heterozygous pathogenic germline variant. This gliomatosis-like pattern is typical for somatic mutation in IDH1 and hypermutation.

Q: In DICER1 Syndrome, patients frequently develop characteristic ovarian neoplasms known as [...], which often display a lobular growth pattern with dark-staining cells centrally and paler cells at the periphery.
Sertoli–Leydig cell tumour. An example with intermediate differentiation. These tumours often grow in cellular lobules, as seen in this picture. The lobules are usually predominantly composed of dark-staining Sertoli cells, with fewer Leydig cells. The latter are often conspicuous at the periphery of the lobules, as seen to some degree in this picture at the 3 o’clock position.
Sertoli–Leydig cell tumour. DICER1-related Sertoli–Leydig cell tumours are usually poorly differentiated, solid and cystic, and pale tan.
A: Sertoli-Leydig cell tumors
Back Extra: DICER1 Syndrome
- Clinical: Patients with DICER1 syndrome are at increased risk for tumours in the lungs, kidneys, thyroid, sinonasal tract, ovaries, uterine cervix, liver, gastrointestinal tract, eyes, and brain.
- Micro: Sertoli–Leydig cell tumours in DICER1 syndrome are often moderately to poorly differentiated and may show a lobular growth pattern with dark-staining Sertoli cells and fewer Leydig cells at the periphery.
- Ancillary: Diagnosis of DICER1 syndrome is confirmed by the presence of heterozygous germline loss-of-function pathogenic variants in the DICER1 gene.
Reference Gallery:
Differentiated thyroid carcinoma (DTC) arising in DICER1 syndrome. The diagnosis of thyroid carcinoma in DICER1 syndrome should be restricted to lesions showing invasive growth. Here, a follicular carcinoma shows mushrooming growth into the adjacent thyroid.
Differentiated thyroid carcinoma (DTC) arising in DICER1 syndrome. The DTCs arising in DICER1 syndrome usually demonstrate a follicular or solid architecture. The nuclei may show subtle nuclear atypia.
Sertoli–Leydig cell tumour. An example with intermediate differentiation. These tumours often grow in cellular lobules, as seen in this picture. The lobules are usually predominantly composed of dark-staining Sertoli cells, with fewer Leydig cells. The latter are often conspicuous at the periphery of the lobules, as seen to some degree in this picture at the 3 o’clock position.
Thyroblastoma. This is an underrecognized DICER1-associated tumour with primitive thyroid follicles surrounded by primitive spindle cell stroma, mimicking thyroid in development.
Sertoli–Leydig cell tumour. DICER1-related Sertoli–Leydig cell tumours are usually poorly differentiated, solid and cystic, and pale tan.
DICER1-related pleuropulmonary blastoma. Type I cysts are lined by epithelial cells beneath which lie primitive mesenchymal tumour cells.
Pleuropulmonary blastoma. Type I cysts in pleuropulmonary blastoma are lined by keratin-positive epithelial cells.

Q: A highly specific pediatric lung malignancy classically associated with DICER1 Syndrome is the [...], which frequently features Type I cysts lined by epithelial cells with an underlying layer of primitive mesenchymal cells.
DICER1-related pleuropulmonary blastoma. Type I cysts are lined by epithelial cells beneath which lie primitive mesenchymal tumour cells.
Pleuropulmonary blastoma. Type I cysts in pleuropulmonary blastoma are lined by keratin-positive epithelial cells.
A: pleuropulmonary blastoma
Back Extra: DICER1 Syndrome
- Clinical: Patients with DICER1 syndrome are at increased risk for tumours in the lungs, kidneys, thyroid, sinonasal tract, ovaries, uterine cervix, liver, gastrointestinal tract, eyes, and brain.
- Micro: Sertoli–Leydig cell tumours in DICER1 syndrome are often moderately to poorly differentiated and may show a lobular growth pattern with dark-staining Sertoli cells and fewer Leydig cells at the periphery.
- Ancillary: Diagnosis of DICER1 syndrome is confirmed by the presence of heterozygous germline loss-of-function pathogenic variants in the DICER1 gene.
Reference Gallery:
Differentiated thyroid carcinoma (DTC) arising in DICER1 syndrome. The diagnosis of thyroid carcinoma in DICER1 syndrome should be restricted to lesions showing invasive growth. Here, a follicular carcinoma shows mushrooming growth into the adjacent thyroid.
Differentiated thyroid carcinoma (DTC) arising in DICER1 syndrome. The DTCs arising in DICER1 syndrome usually demonstrate a follicular or solid architecture. The nuclei may show subtle nuclear atypia.
Sertoli–Leydig cell tumour. An example with intermediate differentiation. These tumours often grow in cellular lobules, as seen in this picture. The lobules are usually predominantly composed of dark-staining Sertoli cells, with fewer Leydig cells. The latter are often conspicuous at the periphery of the lobules, as seen to some degree in this picture at the 3 o’clock position.
Thyroblastoma. This is an underrecognized DICER1-associated tumour with primitive thyroid follicles surrounded by primitive spindle cell stroma, mimicking thyroid in development.
Sertoli–Leydig cell tumour. DICER1-related Sertoli–Leydig cell tumours are usually poorly differentiated, solid and cystic, and pale tan.
DICER1-related pleuropulmonary blastoma. Type I cysts are lined by epithelial cells beneath which lie primitive mesenchymal tumour cells.
Pleuropulmonary blastoma. Type I cysts in pleuropulmonary blastoma are lined by keratin-positive epithelial cells.

Q: An underrecognized thyroid neoplasm strongly associated with DICER1 Syndrome that features primitive thyroid follicles surrounded by a primitive spindle cell stroma (mimicking the developing thyroid) is the [...].
Thyroblastoma. This is an underrecognized DICER1-associated tumour with primitive thyroid follicles surrounded by primitive spindle cell stroma, mimicking thyroid in development.
A: thyroblastoma
Back Extra: DICER1 Syndrome
- Clinical: Patients with DICER1 syndrome are at increased risk for tumours in the lungs, kidneys, thyroid, sinonasal tract, ovaries, uterine cervix, liver, gastrointestinal tract, eyes, and brain.
- Micro: Sertoli–Leydig cell tumours in DICER1 syndrome are often moderately to poorly differentiated and may show a lobular growth pattern with dark-staining Sertoli cells and fewer Leydig cells at the periphery.
- Ancillary: Diagnosis of DICER1 syndrome is confirmed by the presence of heterozygous germline loss-of-function pathogenic variants in the DICER1 gene.
Reference Gallery:
Differentiated thyroid carcinoma (DTC) arising in DICER1 syndrome. The diagnosis of thyroid carcinoma in DICER1 syndrome should be restricted to lesions showing invasive growth. Here, a follicular carcinoma shows mushrooming growth into the adjacent thyroid.
Differentiated thyroid carcinoma (DTC) arising in DICER1 syndrome. The DTCs arising in DICER1 syndrome usually demonstrate a follicular or solid architecture. The nuclei may show subtle nuclear atypia.
Sertoli–Leydig cell tumour. An example with intermediate differentiation. These tumours often grow in cellular lobules, as seen in this picture. The lobules are usually predominantly composed of dark-staining Sertoli cells, with fewer Leydig cells. The latter are often conspicuous at the periphery of the lobules, as seen to some degree in this picture at the 3 o’clock position.
Thyroblastoma. This is an underrecognized DICER1-associated tumour with primitive thyroid follicles surrounded by primitive spindle cell stroma, mimicking thyroid in development.
Sertoli–Leydig cell tumour. DICER1-related Sertoli–Leydig cell tumours are usually poorly differentiated, solid and cystic, and pale tan.
DICER1-related pleuropulmonary blastoma. Type I cysts are lined by epithelial cells beneath which lie primitive mesenchymal tumour cells.
Pleuropulmonary blastoma. Type I cysts in pleuropulmonary blastoma are lined by keratin-positive epithelial cells.

Q: In classic Familial Adenomatous Polyposis, the gross examination of the large bowel typically reveals numerous adenomatous polyps, usually numbering greater than [...].
Familial adenomatous polyposis. Colectomy specimen from a teenager with an APC mutation, showing the classic appearance of the resected colon, with several hundred polypoid lesions.
A: 100
Back Extra: Familial Adenomatous Polyposis
- Clinical: In the gastrointestinal tract, Classic FAP is characterized by numerous (usually > 100 and as many as several thousand) adenomatous polyps of the large bowel, with a near-100% risk of developing colorectal adenocarcinoma by age 45 if not treated.
- Micro: Large bowel polyps are almost always classic adenomas of varying type (tubular, tubulovillous, or villous), grade (low or high), and size, similar to sporadic adenomas. Monocryptal and oligocryptal adenomas are characteristic.
- Ancillary: The presence of a pathogenic germline APC mutation is the gold standard for FAP diagnosis. Immunohistochemistry reveals nuclear expression of β-catenin in desmoid tumours.
Reference Gallery:
Familial adenomatous polyposis. Colectomy specimen from a teenager with an APC mutation, showing the classic appearance of the resected colon, with several hundred polypoid lesions.
Hepatoblastoma. Liver explant from an 18-month-old boy with hepatoblastoma status after chemotherapy and with multiple β-catenin–activated adenomas, who was found to have a germline APC mutation.

Q: The gold standard for confirming the diagnosis of Familial Adenomatous Polyposis is the identification of a pathogenic germline mutation in the [...] gene.
Familial adenomatous polyposis. Colectomy specimen from a teenager with an APC mutation, showing the classic appearance of the resected colon, with several hundred polypoid lesions.
Hepatoblastoma. Liver explant from an 18-month-old boy with hepatoblastoma status after chemotherapy and with multiple β-catenin–activated adenomas, who was found to have a germline APC mutation.
A: APC
Back Extra: Familial Adenomatous Polyposis
- Clinical: In the gastrointestinal tract, Classic FAP is characterized by numerous (usually > 100 and as many as several thousand) adenomatous polyps of the large bowel, with a near-100% risk of developing colorectal adenocarcinoma by age 45 if not treated.
- Micro: Large bowel polyps are almost always classic adenomas of varying type (tubular, tubulovillous, or villous), grade (low or high), and size, similar to sporadic adenomas. Monocryptal and oligocryptal adenomas are characteristic.
- Ancillary: The presence of a pathogenic germline APC mutation is the gold standard for FAP diagnosis. Immunohistochemistry reveals nuclear expression of β-catenin in desmoid tumours.
Reference Gallery:
Familial adenomatous polyposis. Colectomy specimen from a teenager with an APC mutation, showing the classic appearance of the resected colon, with several hundred polypoid lesions.
Hepatoblastoma. Liver explant from an 18-month-old boy with hepatoblastoma status after chemotherapy and with multiple β-catenin–activated adenomas, who was found to have a germline APC mutation.

Q: Infants and young children with Familial Adenomatous Polyposis have a significantly increased risk of developing [...], a rare childhood liver tumor.
Hepatoblastoma. Liver explant from an 18-month-old boy with hepatoblastoma status after chemotherapy and with multiple β-catenin–activated adenomas, who was found to have a germline APC mutation.
A: hepatoblastoma
Back Extra: Familial Adenomatous Polyposis
- Clinical: In the gastrointestinal tract, Classic FAP is characterized by numerous (usually > 100 and as many as several thousand) adenomatous polyps of the large bowel, with a near-100% risk of developing colorectal adenocarcinoma by age 45 if not treated.
- Micro: Large bowel polyps are almost always classic adenomas of varying type (tubular, tubulovillous, or villous), grade (low or high), and size, similar to sporadic adenomas. Monocryptal and oligocryptal adenomas are characteristic.
- Ancillary: The presence of a pathogenic germline APC mutation is the gold standard for FAP diagnosis. Immunohistochemistry reveals nuclear expression of β-catenin in desmoid tumours.
Reference Gallery:
Familial adenomatous polyposis. Colectomy specimen from a teenager with an APC mutation, showing the classic appearance of the resected colon, with several hundred polypoid lesions.
Hepatoblastoma. Liver explant from an 18-month-old boy with hepatoblastoma status after chemotherapy and with multiple β-catenin–activated adenomas, who was found to have a germline APC mutation.

Q: The algorithmic testing for Lynch Syndrome in colorectal cancer involves checking for high microsatellite instability (MSI), typically identified by the loss of nuclear immunohistochemical staining for [...] proteins (e.g., MLH1, PMS2, MSH2, MSH6).
Lynch syndrome. A suggested algorithm for colorectal cancer tumour testing for Lynch syndrome. MMR, mismatch repair; MSI, microsatellite instability.
A: mismatch repair
Back Extra: Lynch Syndrome
- Clinical: Lynch syndrome is characterized by a predisposition to a wide variety of cancers, often arising in young people, including colon, rectum, endometrium, stomach, and more.
- Micro: The typical histological features in CRC with MSI include tumour-infiltrating lymphocytes, Crohn-like peritumoural lymphocytic reaction, poor differentiation, and mucinous and signet-ring cell features.
- Ancillary: IHC shows loss of nuclear staining for mismatch repair proteins (MLH1, PMS2, MSH2, MSH6), indicating MSI and suggesting the most likely involved gene.
Reference Gallery:
Lynch syndrome. A segment of proximal ascending colon with a large (110 mm) polypoid mass (tumour) adjacent to several tan-pink mucosal nodules of 2–3 mm (superficial lymphoid aggregates on histology, not shown here) in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma.
Lynch syndrome. Cross-section of a tumour in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma. The tumour demonstrates a white cut surface abutting the serosal surface.
Lynch syndrome. A tumour in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma. The tumour comprises sheets of poorly differentiated tumour cells with basophilic cytoplasm, increased N:C ratio, irregular nuclear contours, and conspicuous nucleoli. Numerous mitotic figures are present.
Lynch syndrome. A suggested algorithm for colorectal cancer tumour testing for Lynch syndrome. MMR, mismatch repair; MSI, microsatellite instability.

Q: Patients with Lynch Syndrome are strongly predisposed to a variety of early-onset malignancies, most classically presenting with right-sided, large polypoid [...] carcinomas alongside a high risk of endometrial cancer.
Lynch syndrome. A segment of proximal ascending colon with a large (110 mm) polypoid mass (tumour) adjacent to several tan-pink mucosal nodules of 2–3 mm (superficial lymphoid aggregates on histology, not shown here) in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma.
Lynch syndrome. Cross-section of a tumour in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma. The tumour demonstrates a white cut surface abutting the serosal surface.
A: colorectal
Back Extra: Lynch Syndrome
- Clinical: Lynch syndrome is characterized by a predisposition to a wide variety of cancers, often arising in young people, including colon, rectum, endometrium, stomach, and more.
- Micro: The typical histological features in CRC with MSI include tumour-infiltrating lymphocytes, Crohn-like peritumoural lymphocytic reaction, poor differentiation, and mucinous and signet-ring cell features.
- Ancillary: IHC shows loss of nuclear staining for mismatch repair proteins (MLH1, PMS2, MSH2, MSH6), indicating MSI and suggesting the most likely involved gene.
Reference Gallery:
Lynch syndrome. A segment of proximal ascending colon with a large (110 mm) polypoid mass (tumour) adjacent to several tan-pink mucosal nodules of 2–3 mm (superficial lymphoid aggregates on histology, not shown here) in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma.
Lynch syndrome. Cross-section of a tumour in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma. The tumour demonstrates a white cut surface abutting the serosal surface.
Lynch syndrome. A tumour in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma. The tumour comprises sheets of poorly differentiated tumour cells with basophilic cytoplasm, increased N:C ratio, irregular nuclear contours, and conspicuous nucleoli. Numerous mitotic figures are present.
Lynch syndrome. A suggested algorithm for colorectal cancer tumour testing for Lynch syndrome. MMR, mismatch repair; MSI, microsatellite instability.

Q: A right-sided colonic adenocarcinoma exhibiting solid sheets of cells with poor differentiation, prominent nucleoli, and numerous mitoses in an unusually young patient should raise strong clinical suspicion for [...].
Lynch syndrome. A segment of proximal ascending colon with a large (110 mm) polypoid mass (tumour) adjacent to several tan-pink mucosal nodules of 2–3 mm (superficial lymphoid aggregates on histology, not shown here) in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma.
Lynch syndrome. A tumour in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma. The tumour comprises sheets of poorly differentiated tumour cells with basophilic cytoplasm, increased N:C ratio, irregular nuclear contours, and conspicuous nucleoli. Numerous mitotic figures are present.
A: Lynch Syndrome
Back Extra: Lynch Syndrome
- Clinical: Lynch syndrome is characterized by a predisposition to a wide variety of cancers, often arising in young people, including colon, rectum, endometrium, stomach, and more.
- Micro: The typical histological features in CRC with MSI include tumour-infiltrating lymphocytes, Crohn-like peritumoural lymphocytic reaction, poor differentiation, and mucinous and signet-ring cell features.
- Ancillary: IHC shows loss of nuclear staining for mismatch repair proteins (MLH1, PMS2, MSH2, MSH6), indicating MSI and suggesting the most likely involved gene.
Reference Gallery:
Lynch syndrome. A segment of proximal ascending colon with a large (110 mm) polypoid mass (tumour) adjacent to several tan-pink mucosal nodules of 2–3 mm (superficial lymphoid aggregates on histology, not shown here) in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma.
Lynch syndrome. Cross-section of a tumour in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma. The tumour demonstrates a white cut surface abutting the serosal surface.
Lynch syndrome. A tumour in a 16-year-old with Lynch syndrome who underwent a subtotal colectomy for a colonic adenocarcinoma. The tumour comprises sheets of poorly differentiated tumour cells with basophilic cytoplasm, increased N:C ratio, irregular nuclear contours, and conspicuous nucleoli. Numerous mitotic figures are present.
Lynch syndrome. A suggested algorithm for colorectal cancer tumour testing for Lynch syndrome. MMR, mismatch repair; MSI, microsatellite instability.

Q: The most frequent clinical manifestations of Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) include odontogenic keratocysts and [...].
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). A Numerous basal cell carcinomas in the head and neck area and upper trunk. B Multiple bifid ribs.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Multiple odontogenic keratocysts are highlighted by the presence of displaced teeth.
A: multiple basal cell carcinomas
Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
- Clinical: Multiple basal cell carcinomas and odontogenic keratocysts are the most frequent manifestations of Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).
- Micro: NBCCS-associated odontogenic keratocysts are typically multifocal and develop in younger patients, with features such as basal budding and microcysts in the wall.
- Ancillary: A comprehensive mutation analysis of PTCH1 and SUFU is essential for diagnosing Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).
Reference Gallery:
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). A Numerous basal cell carcinomas in the head and neck area and upper trunk. B Multiple bifid ribs.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Multiple odontogenic keratocysts are highlighted by the presence of displaced teeth.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Palmar pitting can be extremely subtle; it is easier to detect in less-clean hands, because dirt tends to become trapped in the pits.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome): odontogenic keratocyst. Scanning magnification shows a squamous lined cyst.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome): odontogenic keratocyst. Higher magnification shows expansion of the basal and parabasal layers and parakeratosis.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Hedgehog (HH) signalling pathway. Normal HH signalling and aberrant HH signalling in naevoid basal cell carcinoma syndrome (NBCCS). A In the normal HH signalling pathway, in the presence of the sonic hedgehog signalling protein (SHH), PTCH1 suppresses smoothened (SMO), which in turn allows SUFU to inhibit GLI transcription factors; in the absence of SHH, SMO is released from inhibition by PTCH1 and translocates to the cytosol, where it inhibits SUFU, thereby relieving inhibition of GLI transcription factors. B In NBCCS, PTCH1 mutations lead to constitutive activation of GLI transcription factors; in rare NBCCS cases, SMO mutations (which are common in sporadic basal cell carcinoma) or SUFU mutations may lead to the same result.

Q: Unlike sporadic cases, the odontogenic keratocysts associated with Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) are characteristically [...] and typically present in younger patients, with microscopic features like basal budding.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Multiple odontogenic keratocysts are highlighted by the presence of displaced teeth.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome): odontogenic keratocyst. Scanning magnification shows a squamous lined cyst.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome): odontogenic keratocyst. Higher magnification shows expansion of the basal and parabasal layers and parakeratosis.
A: multifocal
Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
- Clinical: Multiple basal cell carcinomas and odontogenic keratocysts are the most frequent manifestations of Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).
- Micro: NBCCS-associated odontogenic keratocysts are typically multifocal and develop in younger patients, with features such as basal budding and microcysts in the wall.
- Ancillary: A comprehensive mutation analysis of PTCH1 and SUFU is essential for diagnosing Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).
Reference Gallery:
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). A Numerous basal cell carcinomas in the head and neck area and upper trunk. B Multiple bifid ribs.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Multiple odontogenic keratocysts are highlighted by the presence of displaced teeth.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Palmar pitting can be extremely subtle; it is easier to detect in less-clean hands, because dirt tends to become trapped in the pits.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome): odontogenic keratocyst. Scanning magnification shows a squamous lined cyst.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome): odontogenic keratocyst. Higher magnification shows expansion of the basal and parabasal layers and parakeratosis.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Hedgehog (HH) signalling pathway. Normal HH signalling and aberrant HH signalling in naevoid basal cell carcinoma syndrome (NBCCS). A In the normal HH signalling pathway, in the presence of the sonic hedgehog signalling protein (SHH), PTCH1 suppresses smoothened (SMO), which in turn allows SUFU to inhibit GLI transcription factors; in the absence of SHH, SMO is released from inhibition by PTCH1 and translocates to the cytosol, where it inhibits SUFU, thereby relieving inhibition of GLI transcription factors. B In NBCCS, PTCH1 mutations lead to constitutive activation of GLI transcription factors; in rare NBCCS cases, SMO mutations (which are common in sporadic basal cell carcinoma) or SUFU mutations may lead to the same result.

Q: The pathogenesis of Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome) involves aberrant Hedgehog signaling, and molecular diagnosis often requires mutation analysis of SUFU and [...].
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Hedgehog (HH) signalling pathway. Normal HH signalling and aberrant HH signalling in naevoid basal cell carcinoma syndrome (NBCCS). A In the normal HH signalling pathway, in the presence of the sonic hedgehog signalling protein (SHH), PTCH1 suppresses smoothened (SMO), which in turn allows SUFU to inhibit GLI transcription factors; in the absence of SHH, SMO is released from inhibition by PTCH1 and translocates to the cytosol, where it inhibits SUFU, thereby relieving inhibition of GLI transcription factors. B In NBCCS, PTCH1 mutations lead to constitutive activation of GLI transcription factors; in rare NBCCS cases, SMO mutations (which are common in sporadic basal cell carcinoma) or SUFU mutations may lead to the same result.
A: PTCH1
Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome)
- Clinical: Multiple basal cell carcinomas and odontogenic keratocysts are the most frequent manifestations of Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).
- Micro: NBCCS-associated odontogenic keratocysts are typically multifocal and develop in younger patients, with features such as basal budding and microcysts in the wall.
- Ancillary: A comprehensive mutation analysis of PTCH1 and SUFU is essential for diagnosing Naevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).
Reference Gallery:
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). A Numerous basal cell carcinomas in the head and neck area and upper trunk. B Multiple bifid ribs.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Multiple odontogenic keratocysts are highlighted by the presence of displaced teeth.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Palmar pitting can be extremely subtle; it is easier to detect in less-clean hands, because dirt tends to become trapped in the pits.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome): odontogenic keratocyst. Scanning magnification shows a squamous lined cyst.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome): odontogenic keratocyst. Higher magnification shows expansion of the basal and parabasal layers and parakeratosis.
Naevoid basal cell carcinoma syndrome (Gorlin syndrome). Hedgehog (HH) signalling pathway. Normal HH signalling and aberrant HH signalling in naevoid basal cell carcinoma syndrome (NBCCS). A In the normal HH signalling pathway, in the presence of the sonic hedgehog signalling protein (SHH), PTCH1 suppresses smoothened (SMO), which in turn allows SUFU to inhibit GLI transcription factors; in the absence of SHH, SMO is released from inhibition by PTCH1 and translocates to the cytosol, where it inhibits SUFU, thereby relieving inhibition of GLI transcription factors. B In NBCCS, PTCH1 mutations lead to constitutive activation of GLI transcription factors; in rare NBCCS cases, SMO mutations (which are common in sporadic basal cell carcinoma) or SUFU mutations may lead to the same result.

Q: The defining genetic feature of Li-Fraumeni Syndrome is an inherited germline mutation in the [...] tumor suppressor gene, predisposing patients to a broad spectrum of early-onset malignancies, including osteosarcomas and breast cancers.
Li–Fraumeni syndrome. TP53 mutations. The vast majority of mutations are missense sequence alterations.
Li–Fraumeni syndrome. Osteosarcoma of the femur.
A: TP53
Back Extra: Li-Fraumeni Syndrome
- Clinical: Li-Fraumeni Syndrome (LFS) is characterized by the early onset of a broad spectrum of cancers, including brain tumours, adrenocortical carcinomas, soft tissue sarcomas, and osteosarcomas in childhood, and malignant breast tumours in adults.
- Micro: Brain tumours in children with LFS are mainly sonic hedgehog medulloblastomas, IDH-wildtype high-grade gliomas, and choroid plexus carcinomas.
- Ancillary: Candidates for TP53 germline testing are identified on the basis of the 2015 Chompret criteria and the recommendations of the National Comprehensive Cancer Network (NCCN).
Reference Gallery:
Li–Fraumeni syndrome. TP53 mutations. The vast majority of mutations are missense sequence alterations.
Li–Fraumeni syndrome. Osteosarcoma of the femur.
Li–Fraumeni syndrome. Contrast-enhanced axial CT shows a mixed solid-cystic tumour over the right frontal region. There is marked contrast enhancement of the solid component, associated with mass effect and midline shift. This was confirmed to be a high-grade glioma.
Li–Fraumeni syndrome. Contrast-enhanced T1-weighted axial MRI of the patient shown in Fig. 28529, 2 years after resection of the first high-grade glioma in the right frontal region, showing local recurrence with an avidly enhancing mass.

Q: In Li-Fraumeni Syndrome, the characteristic high-grade gliomas that develop in childhood are primarily [...] molecularly, and present as part of a classic brain tumor spectrum alongside sonic hedgehog medulloblastomas and choroid plexus carcinomas.
Li–Fraumeni syndrome. Contrast-enhanced axial CT shows a mixed solid-cystic tumour over the right frontal region. There is marked contrast enhancement of the solid component, associated with mass effect and midline shift. This was confirmed to be a high-grade glioma.
Li–Fraumeni syndrome. Contrast-enhanced T1-weighted axial MRI of the patient shown in Fig. 28529, 2 years after resection of the first high-grade glioma in the right frontal region, showing local recurrence with an avidly enhancing mass.
A: IDH-wildtype
Back Extra: Li-Fraumeni Syndrome
- Clinical: Li-Fraumeni Syndrome (LFS) is characterized by the early onset of a broad spectrum of cancers, including brain tumours, adrenocortical carcinomas, soft tissue sarcomas, and osteosarcomas in childhood, and malignant breast tumours in adults.
- Micro: Brain tumours in children with LFS are mainly sonic hedgehog medulloblastomas, IDH-wildtype high-grade gliomas, and choroid plexus carcinomas.
- Ancillary: Candidates for TP53 germline testing are identified on the basis of the 2015 Chompret criteria and the recommendations of the National Comprehensive Cancer Network (NCCN).
Reference Gallery:
Li–Fraumeni syndrome. TP53 mutations. The vast majority of mutations are missense sequence alterations.
Li–Fraumeni syndrome. Osteosarcoma of the femur.
Li–Fraumeni syndrome. Contrast-enhanced axial CT shows a mixed solid-cystic tumour over the right frontal region. There is marked contrast enhancement of the solid component, associated with mass effect and midline shift. This was confirmed to be a high-grade glioma.
Li–Fraumeni syndrome. Contrast-enhanced T1-weighted axial MRI of the patient shown in Fig. 28529, 2 years after resection of the first high-grade glioma in the right frontal region, showing local recurrence with an avidly enhancing mass.

Q: Children with Neurofibromatosis Type 1 classically exhibit multiple [...] macules, along with Lisch nodules and cutaneous neurofibromas.
Neurofibromatosis type 1. Multiple café-au-lait spots on the back of a child with neurofibromatosis type 1.
Neurofibromatosis type 1. Left arm of an adult with neurofibromatosis type 1, showing cutaneous neurofibromas.
A: café-au-lait
Back Extra: Neurofibromatosis Type 1
- Clinical: Children with Neurofibromatosis Type 1 often exhibit multiple café-au-lait macules, Lisch nodules, and cutaneous neurofibromas.
- Micro: Nerve sheath tumours in NF1 are predominantly neurofibromas, which may contain cells of the haematopoietic lineage (e.g., histiocytes and mast cells).
- Ancillary: A pathogenic NF1 variant is detected in 95% of people with Neurofibromatosis Type 1, and MEK inhibitors are approved for symptomatic, inoperable plexiform neurofibromas in children aged 2–18 years.
Reference Gallery:
Neurofibromatosis type 1. Multiple café-au-lait spots on the back of a child with neurofibromatosis type 1.
Neurofibromatosis type 1. Left arm of an adult with neurofibromatosis type 1, showing cutaneous neurofibromas.
Neurofibromatosis type 1. T2-weighted axial MRI showing multiple focal areas of signal intensity (previously known as “unidentified bright objects”) present in the basal ganglia and thalamic nuclei (arrows). These are common CNS findings in neurofibromatosis type 1.
Neurofibromatosis type 1. FLAIR MRI showing increased signal intensity at the optic chiasm (short arrow) and bilateral optic radiations (long arrows) consistent with optic pathway glioma / pilocytic astrocytoma.
Neurofibromatosis type 1. T2-weighted axial MRI showing left sphenoid wing dysplasia (arrow) and mild protrusion of the left eye globe.
Pilocytic astrocytoma. The most common brain tumour in patients with neurofibromatosis type 1 is pilocytic astrocytoma, which is frequently located in association with the optic nerve (asterisks).
Low-grade astrocytoma with subependymal giant cell astrocytoma–like morphology. A variety of gliomas may also affect patients with neurofibromatosis type 1, including low-grade astrocytomas that are difficult to classify, occasionally demonstrating subependymal giant cell astrocytoma–like morphology.
Glioblastoma. Overtly malignant tumours usually afflict adult patients and may contain infiltration, mitotic activity, and palisading necrosis typical of glioblastoma.
Neurofibromatosis type 1–associated high-grade glioma. ATRX mutations lead to loss of ATRX protein staining by immunohistochemistry, with preservation in blood vessels and other non-neoplastic cells.

Q: The most common brain tumor affecting patients with Neurofibromatosis Type 1 is a(n) [...], which is frequently associated with the optic nerve.
Neurofibromatosis type 1. FLAIR MRI showing increased signal intensity at the optic chiasm (short arrow) and bilateral optic radiations (long arrows) consistent with optic pathway glioma / pilocytic astrocytoma.
Pilocytic astrocytoma. The most common brain tumour in patients with neurofibromatosis type 1 is pilocytic astrocytoma, which is frequently located in association with the optic nerve (asterisks).
A: pilocytic astrocytoma
Back Extra: Neurofibromatosis Type 1
- Clinical: Children with Neurofibromatosis Type 1 often exhibit multiple café-au-lait macules, Lisch nodules, and cutaneous neurofibromas.
- Micro: Nerve sheath tumours in NF1 are predominantly neurofibromas, which may contain cells of the haematopoietic lineage (e.g., histiocytes and mast cells).
- Ancillary: A pathogenic NF1 variant is detected in 95% of people with Neurofibromatosis Type 1, and MEK inhibitors are approved for symptomatic, inoperable plexiform neurofibromas in children aged 2–18 years.
Reference Gallery:
Neurofibromatosis type 1. Multiple café-au-lait spots on the back of a child with neurofibromatosis type 1.
Neurofibromatosis type 1. Left arm of an adult with neurofibromatosis type 1, showing cutaneous neurofibromas.
Neurofibromatosis type 1. T2-weighted axial MRI showing multiple focal areas of signal intensity (previously known as “unidentified bright objects”) present in the basal ganglia and thalamic nuclei (arrows). These are common CNS findings in neurofibromatosis type 1.
Neurofibromatosis type 1. FLAIR MRI showing increased signal intensity at the optic chiasm (short arrow) and bilateral optic radiations (long arrows) consistent with optic pathway glioma / pilocytic astrocytoma.
Neurofibromatosis type 1. T2-weighted axial MRI showing left sphenoid wing dysplasia (arrow) and mild protrusion of the left eye globe.
Pilocytic astrocytoma. The most common brain tumour in patients with neurofibromatosis type 1 is pilocytic astrocytoma, which is frequently located in association with the optic nerve (asterisks).
Low-grade astrocytoma with subependymal giant cell astrocytoma–like morphology. A variety of gliomas may also affect patients with neurofibromatosis type 1, including low-grade astrocytomas that are difficult to classify, occasionally demonstrating subependymal giant cell astrocytoma–like morphology.
Glioblastoma. Overtly malignant tumours usually afflict adult patients and may contain infiltration, mitotic activity, and palisading necrosis typical of glioblastoma.
Neurofibromatosis type 1–associated high-grade glioma. ATRX mutations lead to loss of ATRX protein staining by immunohistochemistry, with preservation in blood vessels and other non-neoplastic cells.

Q: A common MRI finding in patients with Neurofibromatosis Type 1 is multiple focal areas of T2 signal intensity in the basal ganglia and thalamus, historically known as [...].
Neurofibromatosis type 1. T2-weighted axial MRI showing multiple focal areas of signal intensity (previously known as “unidentified bright objects”) present in the basal ganglia and thalamic nuclei (arrows). These are common CNS findings in neurofibromatosis type 1.
A: unidentified bright objects
Back Extra: Neurofibromatosis Type 1
- Clinical: Children with Neurofibromatosis Type 1 often exhibit multiple café-au-lait macules, Lisch nodules, and cutaneous neurofibromas.
- Micro: Nerve sheath tumours in NF1 are predominantly neurofibromas, which may contain cells of the haematopoietic lineage (e.g., histiocytes and mast cells).
- Ancillary: A pathogenic NF1 variant is detected in 95% of people with Neurofibromatosis Type 1, and MEK inhibitors are approved for symptomatic, inoperable plexiform neurofibromas in children aged 2–18 years.
Reference Gallery:
Neurofibromatosis type 1. Multiple café-au-lait spots on the back of a child with neurofibromatosis type 1.
Neurofibromatosis type 1. Left arm of an adult with neurofibromatosis type 1, showing cutaneous neurofibromas.
Neurofibromatosis type 1. T2-weighted axial MRI showing multiple focal areas of signal intensity (previously known as “unidentified bright objects”) present in the basal ganglia and thalamic nuclei (arrows). These are common CNS findings in neurofibromatosis type 1.
Neurofibromatosis type 1. FLAIR MRI showing increased signal intensity at the optic chiasm (short arrow) and bilateral optic radiations (long arrows) consistent with optic pathway glioma / pilocytic astrocytoma.
Neurofibromatosis type 1. T2-weighted axial MRI showing left sphenoid wing dysplasia (arrow) and mild protrusion of the left eye globe.
Pilocytic astrocytoma. The most common brain tumour in patients with neurofibromatosis type 1 is pilocytic astrocytoma, which is frequently located in association with the optic nerve (asterisks).
Low-grade astrocytoma with subependymal giant cell astrocytoma–like morphology. A variety of gliomas may also affect patients with neurofibromatosis type 1, including low-grade astrocytomas that are difficult to classify, occasionally demonstrating subependymal giant cell astrocytoma–like morphology.
Glioblastoma. Overtly malignant tumours usually afflict adult patients and may contain infiltration, mitotic activity, and palisading necrosis typical of glioblastoma.
Neurofibromatosis type 1–associated high-grade glioma. ATRX mutations lead to loss of ATRX protein staining by immunohistochemistry, with preservation in blood vessels and other non-neoplastic cells.

Q: The hallmark radiographic and clinical finding in Neurofibromatosis Type 2 is the presence of bilateral [...].
Neurofibromatosis type 2 schwannomas. MRI of bilateral vestibular schwannomas, the hallmark of neurofibromatosis type 2. When large, vestibular schwannomas may compress the brain stem.
A: vestibular schwannomas
Back Extra: Neurofibromatosis Type 2
- Clinical: Patients with neurofibromatosis type 2 often present with bilateral vestibular schwannomas, which can cause hearing loss, tinnitus, or imbalance.
- Micro: NF2 schwannomas often have a multilobular (cluster-of-grapes) appearance and may entrap seventh cranial nerve fibres.
- Ancillary: A pathogenic sequence variant of the NF2 gene is detected in 70–90% of patients with neurofibromatosis type 2.
Reference Gallery:
Schwannoma/meningioma. A collision tumour of schwannoma (lower half) and meningioma (upper half) is characteristic of neurofibromatosis type 2.
Schwannoma/meningioma. The meningioma component is highlighted with PR immunostaining.
Schwannoma/meningioma. The schwannoma component is highlighted with S100 immunostaining.
Other lesions in neurofibromatosis type 2. A Schwann cell tumourlet embedded in a peripheral nerve.
Neurofibromatosis type 2 schwannomas. MRI of bilateral vestibular schwannomas, the hallmark of neurofibromatosis type 2. When large, vestibular schwannomas may compress the brain stem.
Cutaneous schwannoma. Cutaneous schwannoma is a common manifestation in children with neurofibromatosis type 2 and is often associated with a raised pigmented lesion of the skin (neurofibromatosis type 2 plaque).
Cutaneous schwannoma. S100 immunostaining highlighting a cutaneous plexiform schwannoma.
Neurofibromatosis type 2 schwannoma. A mosaic pattern of SMARCB1 (INI1) staining is common in syndromic (neurofibromatosis type 2 and schwannomatosis) schwannomas.
Other lesions in neurofibromatosis type 2. Meningioangiomatosis histologically consists of an intracortical proliferation of small capillaries with a cuff of perivascular meningothelial cells, separated by brain parenchyma. In neurofibromatosis type 2, most cases are asymptomatic.
Plexiform schwannoma. A, B MRI showing a large plexiform schwannoma in a patient with neurofibromatosis type 2.
Plexiform schwannoma. Multiple nerve fascicles are expanded and replaced by tumour, a pattern similar to that of a plexiform neurofibroma.
Plexiform schwannoma. Examination at high magnification shows the typical histological features of schwannoma, including Verocay bodies.

Q: A characteristic histologic finding in Neurofibromatosis Type 2 is a collision tumor comprising both a meningioma and a [...].
Schwannoma/meningioma. A collision tumour of schwannoma (lower half) and meningioma (upper half) is characteristic of neurofibromatosis type 2.
Schwannoma/meningioma. The meningioma component is highlighted with PR immunostaining.
Schwannoma/meningioma. The schwannoma component is highlighted with S100 immunostaining.
A: schwannoma
Back Extra: Neurofibromatosis Type 2
- Clinical: Patients with neurofibromatosis type 2 often present with bilateral vestibular schwannomas, which can cause hearing loss, tinnitus, or imbalance.
- Micro: NF2 schwannomas often have a multilobular (cluster-of-grapes) appearance and may entrap seventh cranial nerve fibres.
- Ancillary: A pathogenic sequence variant of the NF2 gene is detected in 70–90% of patients with neurofibromatosis type 2.
Reference Gallery:
Schwannoma/meningioma. A collision tumour of schwannoma (lower half) and meningioma (upper half) is characteristic of neurofibromatosis type 2.
Schwannoma/meningioma. The meningioma component is highlighted with PR immunostaining.
Schwannoma/meningioma. The schwannoma component is highlighted with S100 immunostaining.
Other lesions in neurofibromatosis type 2. A Schwann cell tumourlet embedded in a peripheral nerve.
Neurofibromatosis type 2 schwannomas. MRI of bilateral vestibular schwannomas, the hallmark of neurofibromatosis type 2. When large, vestibular schwannomas may compress the brain stem.
Cutaneous schwannoma. Cutaneous schwannoma is a common manifestation in children with neurofibromatosis type 2 and is often associated with a raised pigmented lesion of the skin (neurofibromatosis type 2 plaque).
Cutaneous schwannoma. S100 immunostaining highlighting a cutaneous plexiform schwannoma.
Neurofibromatosis type 2 schwannoma. A mosaic pattern of SMARCB1 (INI1) staining is common in syndromic (neurofibromatosis type 2 and schwannomatosis) schwannomas.
Other lesions in neurofibromatosis type 2. Meningioangiomatosis histologically consists of an intracortical proliferation of small capillaries with a cuff of perivascular meningothelial cells, separated by brain parenchyma. In neurofibromatosis type 2, most cases are asymptomatic.
Plexiform schwannoma. A, B MRI showing a large plexiform schwannoma in a patient with neurofibromatosis type 2.
Plexiform schwannoma. Multiple nerve fascicles are expanded and replaced by tumour, a pattern similar to that of a plexiform neurofibroma.
Plexiform schwannoma. Examination at high magnification shows the typical histological features of schwannoma, including Verocay bodies.

Q: Tumors arising in the setting of Neurofibromatosis Type 2 often exhibit a characteristic [...] pattern of SMARCB1 (INI1) immunostaining.
Neurofibromatosis type 2 schwannoma. A mosaic pattern of SMARCB1 (INI1) staining is common in syndromic (neurofibromatosis type 2 and schwannomatosis) schwannomas.
A: mosaic
Back Extra: Neurofibromatosis Type 2
- Clinical: Patients with neurofibromatosis type 2 often present with bilateral vestibular schwannomas, which can cause hearing loss, tinnitus, or imbalance.
- Micro: NF2 schwannomas often have a multilobular (cluster-of-grapes) appearance and may entrap seventh cranial nerve fibres.
- Ancillary: A pathogenic sequence variant of the NF2 gene is detected in 70–90% of patients with neurofibromatosis type 2.
Reference Gallery:
Schwannoma/meningioma. A collision tumour of schwannoma (lower half) and meningioma (upper half) is characteristic of neurofibromatosis type 2.
Schwannoma/meningioma. The meningioma component is highlighted with PR immunostaining.
Schwannoma/meningioma. The schwannoma component is highlighted with S100 immunostaining.
Other lesions in neurofibromatosis type 2. A Schwann cell tumourlet embedded in a peripheral nerve.
Neurofibromatosis type 2 schwannomas. MRI of bilateral vestibular schwannomas, the hallmark of neurofibromatosis type 2. When large, vestibular schwannomas may compress the brain stem.
Cutaneous schwannoma. Cutaneous schwannoma is a common manifestation in children with neurofibromatosis type 2 and is often associated with a raised pigmented lesion of the skin (neurofibromatosis type 2 plaque).
Cutaneous schwannoma. S100 immunostaining highlighting a cutaneous plexiform schwannoma.
Neurofibromatosis type 2 schwannoma. A mosaic pattern of SMARCB1 (INI1) staining is common in syndromic (neurofibromatosis type 2 and schwannomatosis) schwannomas.
Other lesions in neurofibromatosis type 2. Meningioangiomatosis histologically consists of an intracortical proliferation of small capillaries with a cuff of perivascular meningothelial cells, separated by brain parenchyma. In neurofibromatosis type 2, most cases are asymptomatic.
Plexiform schwannoma. A, B MRI showing a large plexiform schwannoma in a patient with neurofibromatosis type 2.
Plexiform schwannoma. Multiple nerve fascicles are expanded and replaced by tumour, a pattern similar to that of a plexiform neurofibroma.
Plexiform schwannoma. Examination at high magnification shows the typical histological features of schwannoma, including Verocay bodies.

Q: Heritable Retinoblastoma Syndrome is characterized by the loss of both alleles of the [...] tumor suppressor gene, often resulting from inheritance from a heterozygote followed by a second somatic mutation.
Retinoblastoma syndrome. Heritable retinoblastoma results from inheritance from a heterozygote or from somatic mosaicism, with both cases leading to the loss of both alleles. In sporadic cases, both alleles are lost by mutation. Chr, chromosome; RB, retinoblastoma.
A: RB1
Back Extra: Retinoblastoma Syndrome
- Clinical: Children with heritable Retinoblastoma Syndrome develop ocular retinoblastoma between 0 and 5 years of age, with a median age of 10 months, and have a 5% risk of developing trilateral retinoblastoma.
- Micro: The histological features of the intracranial tumour in trilateral retinoblastoma are identical to those of retinoblastoma, with poorly demarcated, soft, and friable tumours.
- Ancillary: Identification of the specific RB1 gene variant and genetic counselling are crucial for patients with Retinoblastoma Syndrome, especially in the context of intracranial retinoblastoma.
Reference Gallery:
Retinoblastoma syndrome. Heritable retinoblastoma results from inheritance from a heterozygote or from somatic mosaicism, with both cases leading to the loss of both alleles. In sporadic cases, both alleles are lost by mutation. Chr, chromosome; RB, retinoblastoma.

Q: An increased risk of developing mesothelioma, uveal melanoma, cutaneous melanoma, renal cell carcinoma, and meningiomas is characteristic of [...].
BAP1 tumour predisposition syndrome. Associated meningioma.
A: BAP1 Tumor Predisposition Syndrome
Back Extra: BAP1 Tumour Predisposition Syndrome
- Clinical: BAP1 germline pathogenic variant carriers have an increased risk of developing mesothelioma, uveal melanoma, cutaneous melanoma, renal cell carcinoma, and meningioma.
- Micro: BAP1-inactivated melanocytic tumours in the skin are composed of intradermal melanocytes with varying degrees of atypia, often showing loss of nuclear BAP1 expression on immunohistochemistry.
- Ancillary: Genetic testing, including BAP1 genetic sequencing and deletion/duplication analysis, is essential for confirming the diagnosis of BAP1 tumour predisposition syndrome.
Reference Gallery:
BAP1 tumour predisposition syndrome. Associated meningioma.

Q: In addition to melanomas, mesotheliomas, and renal cell carcinomas, patients with BAP1 Tumor Predisposition Syndrome have an increased risk of developing CNS neoplasms, most notably [...].
BAP1 tumour predisposition syndrome. Associated meningioma.
A: meningiomas
Back Extra: BAP1 Tumour Predisposition Syndrome
- Clinical: BAP1 germline pathogenic variant carriers have an increased risk of developing mesothelioma, uveal melanoma, cutaneous melanoma, renal cell carcinoma, and meningioma.
- Micro: BAP1-inactivated melanocytic tumours in the skin are composed of intradermal melanocytes with varying degrees of atypia, often showing loss of nuclear BAP1 expression on immunohistochemistry.
- Ancillary: Genetic testing, including BAP1 genetic sequencing and deletion/duplication analysis, is essential for confirming the diagnosis of BAP1 tumour predisposition syndrome.
Reference Gallery:
BAP1 tumour predisposition syndrome. Associated meningioma.

Q: Histologically, tumors associated with Rhabdoid Tumor Predisposition Syndrome exhibit large, irregular nuclei with vesicular chromatin and [...].
CNS atypical teratoid/rhabdoid tumour. The tumour nuclei are large and irregular, many with vesicular chromatin and prominent nucleoli. Mitotic figures and apoptotic bodies are numerous.
A: prominent nucleoli
Back Extra: Rhabdoid Tumour Predisposition Syndrome
- Clinical: The median age of tumour onset in patients with Rhabdoid Tumour Predisposition Syndrome is younger than that in patients with sporadic tumours.
- Micro: RTPS-associated tumours are histopathologically similar to their sporadic counterparts, with large and irregular tumour nuclei, vesicular chromatin, and prominent nucleoli.
- Ancillary: Loss of immunohistochemical staining for SMARCB1 (INI1) or SMARCA4 (BRG1) identifies tumours associated with RTPS1 and RTPS2, respectively.
Reference Gallery:
CNS atypical teratoid/rhabdoid tumour. The tumour nuclei are large and irregular, many with vesicular chromatin and prominent nucleoli. Mitotic figures and apoptotic bodies are numerous.
CNS atypical teratoid/rhabdoid tumour. SMARCB1 (INI1) expression is lost in neoplastic cells.

Q: Tumors associated with type 1 Rhabdoid Tumor Predisposition Syndrome characteristically demonstrate a loss of immunohistochemical staining for [...].
CNS atypical teratoid/rhabdoid tumour. SMARCB1 (INI1) expression is lost in neoplastic cells.
A: SMARCB1 (INI1)
Back Extra: Rhabdoid Tumour Predisposition Syndrome
- Clinical: The median age of tumour onset in patients with Rhabdoid Tumour Predisposition Syndrome is younger than that in patients with sporadic tumours.
- Micro: RTPS-associated tumours are histopathologically similar to their sporadic counterparts, with large and irregular tumour nuclei, vesicular chromatin, and prominent nucleoli.
- Ancillary: Loss of immunohistochemical staining for SMARCB1 (INI1) or SMARCA4 (BRG1) identifies tumours associated with RTPS1 and RTPS2, respectively.
Reference Gallery:
CNS atypical teratoid/rhabdoid tumour. The tumour nuclei are large and irregular, many with vesicular chromatin and prominent nucleoli. Mitotic figures and apoptotic bodies are numerous.
CNS atypical teratoid/rhabdoid tumour. SMARCB1 (INI1) expression is lost in neoplastic cells.

Q: In Rothmund-Thomson Syndrome, the characteristic chronic skin manifestation that features a combination of skin atrophy, telangiectasia, and marbleized hypo- and hyperpigmentation is known as [...].
Rothmund–Thomson syndrome. Poikiloderma. Extensor surface of the lower leg demonstrating the chronic phase, with skin atrophy, marbleized mixed hypopigmentation, and hyperpigmentation with telangiectasia.
A: poikiloderma
Back Extra: Rothmund-Thomson Syndrome
- Clinical: Characterized by an erythematous rash that starts on the cheeks in infancy, spreading to the extremities, and eventually developing into poikiloderma with hypopigmentation, hyperpigmentation, telangiectasia, and atrophy.
- Micro: Histopathological features include hyperkeratosis, epidermal atrophy, intraepidermal dyskeratotic cells, basal cell vacuolization, melanin incontinence, and prominent superficial dermal vessels.
- Ancillary: Molecular testing for biallelic pathogenic variants in the RECQL4 gene confirms RTS type 2, while mutations in ANAPC1 are associated with RTS type 1.
Reference Gallery:
Rothmund–Thomson syndrome. Poikiloderma. Extensor surface of the lower leg demonstrating the chronic phase, with skin atrophy, marbleized mixed hypopigmentation, and hyperpigmentation with telangiectasia.
Rothmund–Thomson syndrome. Radial ray defect manifesting as a missing thumb.
Rothmund–Thomson syndrome, Baller–Gerold syndrome, and RAPADILINO syndrome. The overlapping clinical features of Rothmund–Thomson syndrome, Baller–Gerold syndrome, and RAPADILINO syndrome (radial ray malformations, patella and palate abnormalities, diarrhoea and dislocated joints, limb abnormalities and little size, slender nose, and normal intelligence; associated with RECQL4 pathogenic variants).
Rothmund–Thomson syndrome. Histopathological features of poikiloderma characteristically seen in Rothmund–Thomson syndrome, with prominent superficial dermal vessels, minimal basal cell vacuolization, and intraepidermal dyskeratotic cells.
Rothmund–Thomson syndrome. Osteoblastic osteosarcoma, the most common malignancy seen in Rothmund–Thomson syndrome, displays pleomorphic osteoblasts and eosinophilic malignant osteoid.

Q: Type 2 Rothmund-Thomson Syndrome, which carries a high risk for developing osteosarcoma and shares overlapping features with Baller-Gerold and RAPADILINO syndromes, is caused by biallelic pathogenic variants in the [...] gene.
Rothmund–Thomson syndrome, Baller–Gerold syndrome, and RAPADILINO syndrome. The overlapping clinical features of Rothmund–Thomson syndrome, Baller–Gerold syndrome, and RAPADILINO syndrome (radial ray malformations, patella and palate abnormalities, diarrhoea and dislocated joints, limb abnormalities and little size, slender nose, and normal intelligence; associated with RECQL4 pathogenic variants).
Rothmund–Thomson syndrome. Osteoblastic osteosarcoma, the most common malignancy seen in Rothmund–Thomson syndrome, displays pleomorphic osteoblasts and eosinophilic malignant osteoid.
A: RECQL4
Back Extra: Rothmund-Thomson Syndrome
- Clinical: Characterized by an erythematous rash that starts on the cheeks in infancy, spreading to the extremities, and eventually developing into poikiloderma with hypopigmentation, hyperpigmentation, telangiectasia, and atrophy.
- Micro: Histopathological features include hyperkeratosis, epidermal atrophy, intraepidermal dyskeratotic cells, basal cell vacuolization, melanin incontinence, and prominent superficial dermal vessels.
- Ancillary: Molecular testing for biallelic pathogenic variants in the RECQL4 gene confirms RTS type 2, while mutations in ANAPC1 are associated with RTS type 1.
Reference Gallery:
Rothmund–Thomson syndrome. Poikiloderma. Extensor surface of the lower leg demonstrating the chronic phase, with skin atrophy, marbleized mixed hypopigmentation, and hyperpigmentation with telangiectasia.
Rothmund–Thomson syndrome. Radial ray defect manifesting as a missing thumb.
Rothmund–Thomson syndrome, Baller–Gerold syndrome, and RAPADILINO syndrome. The overlapping clinical features of Rothmund–Thomson syndrome, Baller–Gerold syndrome, and RAPADILINO syndrome (radial ray malformations, patella and palate abnormalities, diarrhoea and dislocated joints, limb abnormalities and little size, slender nose, and normal intelligence; associated with RECQL4 pathogenic variants).
Rothmund–Thomson syndrome. Histopathological features of poikiloderma characteristically seen in Rothmund–Thomson syndrome, with prominent superficial dermal vessels, minimal basal cell vacuolization, and intraepidermal dyskeratotic cells.
Rothmund–Thomson syndrome. Osteoblastic osteosarcoma, the most common malignancy seen in Rothmund–Thomson syndrome, displays pleomorphic osteoblasts and eosinophilic malignant osteoid.

Q: Microscopically, the skin lesions in Rothmund-Thomson Syndrome demonstrate epidermal atrophy, prominent superficial dermal vessels, minimal basal cell vacuolization, and scattered [...].
Rothmund–Thomson syndrome. Histopathological features of poikiloderma characteristically seen in Rothmund–Thomson syndrome, with prominent superficial dermal vessels, minimal basal cell vacuolization, and intraepidermal dyskeratotic cells.
A: intraepidermal dyskeratotic cells
Back Extra: Rothmund-Thomson Syndrome
- Clinical: Characterized by an erythematous rash that starts on the cheeks in infancy, spreading to the extremities, and eventually developing into poikiloderma with hypopigmentation, hyperpigmentation, telangiectasia, and atrophy.
- Micro: Histopathological features include hyperkeratosis, epidermal atrophy, intraepidermal dyskeratotic cells, basal cell vacuolization, melanin incontinence, and prominent superficial dermal vessels.
- Ancillary: Molecular testing for biallelic pathogenic variants in the RECQL4 gene confirms RTS type 2, while mutations in ANAPC1 are associated with RTS type 1.
Reference Gallery:
Rothmund–Thomson syndrome. Poikiloderma. Extensor surface of the lower leg demonstrating the chronic phase, with skin atrophy, marbleized mixed hypopigmentation, and hyperpigmentation with telangiectasia.
Rothmund–Thomson syndrome. Radial ray defect manifesting as a missing thumb.
Rothmund–Thomson syndrome, Baller–Gerold syndrome, and RAPADILINO syndrome. The overlapping clinical features of Rothmund–Thomson syndrome, Baller–Gerold syndrome, and RAPADILINO syndrome (radial ray malformations, patella and palate abnormalities, diarrhoea and dislocated joints, limb abnormalities and little size, slender nose, and normal intelligence; associated with RECQL4 pathogenic variants).
Rothmund–Thomson syndrome. Histopathological features of poikiloderma characteristically seen in Rothmund–Thomson syndrome, with prominent superficial dermal vessels, minimal basal cell vacuolization, and intraepidermal dyskeratotic cells.
Rothmund–Thomson syndrome. Osteoblastic osteosarcoma, the most common malignancy seen in Rothmund–Thomson syndrome, displays pleomorphic osteoblasts and eosinophilic malignant osteoid.

Q: Microscopic examination of CNS tubers in Tuberous Sclerosis reveals a disorganized cortex with markedly enlarged, dysmorphic neurons and characteristic [...], which have abundant eosinophilic cytoplasm and prominent nucleoli.
Tuberous sclerosis. Cortical tuber with dysmorphic enlarged neurons embedded in a densely fibrillary background.
Tuberous sclerosis. Balloon cells, with eosinophilic cytoplasm, large nuclei, and prominent nucleoli, dispersed in the white matter.
A: balloon cells
Back Extra: Tuberous Sclerosis
- Clinical: Cardiac rhabdomyomas are often a presenting feature in newborns and infants aged < 2 years, and 80-90% of patients with tuberous sclerosis experience intractable epilepsy.
- Micro: CNS tubers in tuberous sclerosis consist of disorganized cortex with dysmorphic, markedly enlarged neurons, balloon cells, dense fibrillary gliosis, and calcification.
- Ancillary: Genetic testing to identify pathogenic variants of TSC1 or TSC2 is recommended when tuberous sclerosis is suspected but cannot be clinically confirmed.
Reference Gallery:
Tuberous sclerosis. Gross autopsy section from a patient with tuberous sclerosis illustrates axially cut cerebral hemispheric parenchyma with multiple subependymal nodules in the lateral and third ventricles (arrows).
Tuberous sclerosis. Gross image of the brain from a 57-year-old man showing an unusual tuber in the cerebellar hemisphere with extensive calcification.
Tuberous sclerosis. Postcontrast T1-weighted axial MRI demonstrates two small enhancing subependymal nodules along the right caudate nucleus (arrows).
Tuberous sclerosis. T2-weighted coronal MRI demonstrates a minimally expansile hyperintense lesion in the left frontal white matter compatible with a cortical/subcortical tuber (arrow).
Tuberous sclerosis. Cortical tuber with dysmorphic enlarged neurons embedded in a densely fibrillary background.
Tuberous sclerosis. Cortical tuber with large neuronal cells highlighted by NeuN.
Tuberous sclerosis. Balloon cells, with eosinophilic cytoplasm, large nuclei, and prominent nucleoli, dispersed in the white matter.
Tuberous sclerosis. Cortical tuber showing a balloon cell with a ganglion-like nucleus and strong immunoreactivity for S100.
Tuberous sclerosis. T2-weighted axial MRI showing multiple tiny T2-hypointense, calcified subependymal nodules (arrows) along the lining of bilateral lateral ventricles.
Tuberous sclerosis. Contrast-enhanced T1-weighted axial MRI showing an enhancing mass (arrow) near the foramen of Monro. It was subsequently confirmed to be a subependymal giant cell astrocytoma.

Q: A classic macroscopic and radiologic finding in Tuberous Sclerosis is the presence of multiple, often calcified [...] lining the lateral ventricles.
Tuberous sclerosis. Gross autopsy section from a patient with tuberous sclerosis illustrates axially cut cerebral hemispheric parenchyma with multiple subependymal nodules in the lateral and third ventricles (arrows).
Tuberous sclerosis. T2-weighted axial MRI showing multiple tiny T2-hypointense, calcified subependymal nodules (arrows) along the lining of bilateral lateral ventricles.
A: subependymal nodules
Back Extra: Tuberous Sclerosis
- Clinical: Cardiac rhabdomyomas are often a presenting feature in newborns and infants aged < 2 years, and 80-90% of patients with tuberous sclerosis experience intractable epilepsy.
- Micro: CNS tubers in tuberous sclerosis consist of disorganized cortex with dysmorphic, markedly enlarged neurons, balloon cells, dense fibrillary gliosis, and calcification.
- Ancillary: Genetic testing to identify pathogenic variants of TSC1 or TSC2 is recommended when tuberous sclerosis is suspected but cannot be clinically confirmed.
Reference Gallery:
Tuberous sclerosis. Gross autopsy section from a patient with tuberous sclerosis illustrates axially cut cerebral hemispheric parenchyma with multiple subependymal nodules in the lateral and third ventricles (arrows).
Tuberous sclerosis. Gross image of the brain from a 57-year-old man showing an unusual tuber in the cerebellar hemisphere with extensive calcification.
Tuberous sclerosis. Postcontrast T1-weighted axial MRI demonstrates two small enhancing subependymal nodules along the right caudate nucleus (arrows).
Tuberous sclerosis. T2-weighted coronal MRI demonstrates a minimally expansile hyperintense lesion in the left frontal white matter compatible with a cortical/subcortical tuber (arrow).
Tuberous sclerosis. Cortical tuber with dysmorphic enlarged neurons embedded in a densely fibrillary background.
Tuberous sclerosis. Cortical tuber with large neuronal cells highlighted by NeuN.
Tuberous sclerosis. Balloon cells, with eosinophilic cytoplasm, large nuclei, and prominent nucleoli, dispersed in the white matter.
Tuberous sclerosis. Cortical tuber showing a balloon cell with a ganglion-like nucleus and strong immunoreactivity for S100.
Tuberous sclerosis. T2-weighted axial MRI showing multiple tiny T2-hypointense, calcified subependymal nodules (arrows) along the lining of bilateral lateral ventricles.
Tuberous sclerosis. Contrast-enhanced T1-weighted axial MRI showing an enhancing mass (arrow) near the foramen of Monro. It was subsequently confirmed to be a subependymal giant cell astrocytoma.

Q: Patients with Tuberous Sclerosis typically harbor pathogenic variants in the TSC1 or TSC2 genes; in the CNS, this can lead to the development of an enhancing mass near the foramen of Monro known as a [...].
Tuberous sclerosis. Contrast-enhanced T1-weighted axial MRI showing an enhancing mass (arrow) near the foramen of Monro. It was subsequently confirmed to be a subependymal giant cell astrocytoma.
A: subependymal giant cell astrocytoma
Back Extra: Tuberous Sclerosis
- Clinical: Cardiac rhabdomyomas are often a presenting feature in newborns and infants aged < 2 years, and 80-90% of patients with tuberous sclerosis experience intractable epilepsy.
- Micro: CNS tubers in tuberous sclerosis consist of disorganized cortex with dysmorphic, markedly enlarged neurons, balloon cells, dense fibrillary gliosis, and calcification.
- Ancillary: Genetic testing to identify pathogenic variants of TSC1 or TSC2 is recommended when tuberous sclerosis is suspected but cannot be clinically confirmed.
Reference Gallery:
Tuberous sclerosis. Gross autopsy section from a patient with tuberous sclerosis illustrates axially cut cerebral hemispheric parenchyma with multiple subependymal nodules in the lateral and third ventricles (arrows).
Tuberous sclerosis. Gross image of the brain from a 57-year-old man showing an unusual tuber in the cerebellar hemisphere with extensive calcification.
Tuberous sclerosis. Postcontrast T1-weighted axial MRI demonstrates two small enhancing subependymal nodules along the right caudate nucleus (arrows).
Tuberous sclerosis. T2-weighted coronal MRI demonstrates a minimally expansile hyperintense lesion in the left frontal white matter compatible with a cortical/subcortical tuber (arrow).
Tuberous sclerosis. Cortical tuber with dysmorphic enlarged neurons embedded in a densely fibrillary background.
Tuberous sclerosis. Cortical tuber with large neuronal cells highlighted by NeuN.
Tuberous sclerosis. Balloon cells, with eosinophilic cytoplasm, large nuclei, and prominent nucleoli, dispersed in the white matter.
Tuberous sclerosis. Cortical tuber showing a balloon cell with a ganglion-like nucleus and strong immunoreactivity for S100.
Tuberous sclerosis. T2-weighted axial MRI showing multiple tiny T2-hypointense, calcified subependymal nodules (arrows) along the lining of bilateral lateral ventricles.
Tuberous sclerosis. Contrast-enhanced T1-weighted axial MRI showing an enhancing mass (arrow) near the foramen of Monro. It was subsequently confirmed to be a subependymal giant cell astrocytoma.

Q: A key diagnostic feature of Hereditary Phaeochromocytoma-Paraganglioma Syndromes is the immunohistochemical loss of [...] in tumor cells, while demonstrating intact stromal positivity.
SDH-related paraganglioma. A lack of cytoplasmic SDHB with intact stromal positivity indicates SDH-related disease.
SDH-related paraganglioma. Familial head and neck paraganglioma immunostained for SDHB, showing succinate dehydrogenase deficiency, with granular cytoplasmic staining of endothelial cells and completely negative tumour cells.
A: SDHB
Back Extra: Hereditary Phaeochromocytoma-Paraganglioma Syndromes
- Clinical: Hereditary Phaeochromocytoma-Paraganglioma Syndromes can present with symptoms of catecholamine excess, such as sweating, palpitations, and hypertension.
- Micro: These syndromes often show a pseudorosette pattern and can have cells with clear or vacuolated eosinophilic cytoplasm.
- Ancillary: Immunohistochemistry showing loss of SDHB in tumour cells and intact stromal positivity is a key diagnostic feature.
Reference Gallery:
Familial paraganglioma syndromes caused by SDH mutations. Paragangliomas in familial paraganglioma syndrome. Multiple para-aortic and pelvic paragangliomas (arrows) are identified with 68Ga-DOTATATE PET-CT in a patient with a pathogenic germline SDHB mutation.
SDH-related paraganglioma. These tumours often have abundant granular eosinophilic cytoplasm.
SDH-related paraganglioma. The tumours express cytoplasmic tyrosine hydroxylase.
SDH-related paraganglioma. A lack of cytoplasmic SDHB with intact stromal positivity indicates SDH-related disease.
SDH-related paraganglioma. Tumours associated with a pseudohypoxia pathway alteration also express inhibin.
SDH-related paraganglioma. Familial head and neck paraganglioma immunostained for SDHB, showing succinate dehydrogenase deficiency, with granular cytoplasmic staining of endothelial cells and completely negative tumour cells.
Familial paraganglioma syndromes caused by SDH mutations. Biochemical and genetic clusters of paragangliomas.

Q: Patients with Hereditary Phaeochromocytoma-Paraganglioma Syndromes often harbor pathogenic germline [...] mutations, which can present clinically with symptoms of catecholamine excess and multiple para-aortic or pelvic paragangliomas on PET-CT imaging.
Familial paraganglioma syndromes caused by SDH mutations. Paragangliomas in familial paraganglioma syndrome. Multiple para-aortic and pelvic paragangliomas (arrows) are identified with 68Ga-DOTATATE PET-CT in a patient with a pathogenic germline SDHB mutation.
A: SDH
Back Extra: Hereditary Phaeochromocytoma-Paraganglioma Syndromes
- Clinical: Hereditary Phaeochromocytoma-Paraganglioma Syndromes can present with symptoms of catecholamine excess, such as sweating, palpitations, and hypertension.
- Micro: These syndromes often show a pseudorosette pattern and can have cells with clear or vacuolated eosinophilic cytoplasm.
- Ancillary: Immunohistochemistry showing loss of SDHB in tumour cells and intact stromal positivity is a key diagnostic feature.
Reference Gallery:
Familial paraganglioma syndromes caused by SDH mutations. Paragangliomas in familial paraganglioma syndrome. Multiple para-aortic and pelvic paragangliomas (arrows) are identified with 68Ga-DOTATATE PET-CT in a patient with a pathogenic germline SDHB mutation.
SDH-related paraganglioma. These tumours often have abundant granular eosinophilic cytoplasm.
SDH-related paraganglioma. The tumours express cytoplasmic tyrosine hydroxylase.
SDH-related paraganglioma. A lack of cytoplasmic SDHB with intact stromal positivity indicates SDH-related disease.
SDH-related paraganglioma. Tumours associated with a pseudohypoxia pathway alteration also express inhibin.
SDH-related paraganglioma. Familial head and neck paraganglioma immunostained for SDHB, showing succinate dehydrogenase deficiency, with granular cytoplasmic staining of endothelial cells and completely negative tumour cells.
Familial paraganglioma syndromes caused by SDH mutations. Biochemical and genetic clusters of paragangliomas.

Q: In Von Hippel-Lindau Syndrome, patients may develop endolymphatic sac tumors (ELSTs). These tumors can histologically mimic choroid plexus papillomas but are definitively distinguished by characteristic [...], which can be confirmed on neuroimaging.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. The histopathology is reminiscent of choroid plexus papilloma, but the bone invasion essentially excludes that diagnosis.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. The histopathology is reminiscent of choroid plexus papilloma, but the bone invasion essentially excludes that diagnosis.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. CT of the tumour shown in Fig. 20207 shows destruction of the temporal bone, which essentially excludes the diagnostic consideration of choroid plexus papilloma.
A: bone invasion
Back Extra: Von Hippel-Lindau Syndrome
- Clinical: Retinal haemangioblastomas often manifest earlier than renal cell carcinoma, offering an early diagnosis opportunity in patients with Von Hippel-Lindau syndrome.
- Micro: Histopathology of VHL-associated tumours is similar to sporadic tumours, but endolymphatic sac tumours (ELSTs) may mimic choroid plexus papillomas, necessitating neuroimaging to confirm bone invasion.
- Ancillary: Genetic testing for VHL germline sequence variants is crucial for confirming the diagnosis of Von Hippel-Lindau syndrome.
Reference Gallery:
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. This contrast-enhancing tumour (seen here by postcontrast T1-weighted MRI) arose in the cerebellopontine angle and was therefore resected by a neurosurgeon.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. The histopathology is reminiscent of choroid plexus papilloma, but the bone invasion essentially excludes that diagnosis.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. The histopathology is reminiscent of choroid plexus papilloma, but the bone invasion essentially excludes that diagnosis.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. CT of the tumour shown in Fig. 20207 shows destruction of the temporal bone, which essentially excludes the diagnostic consideration of choroid plexus papilloma.
Von Hippel–Lindau syndrome pathogenesis. A The β domain of VHL protein (pVHL) interacts with HIF1α, whereas the α domain interacts with other partners of the VHL complex. In von Hippel–Lindau syndrome, alterations in the α domain prevent the formation of a functional VHL complex. B In normoxia, the VHL complex binds to HIF1α and promotes ubiquitination and proteasomal degradation in an oxygen-dependent manner. In hypoxia, binding of VHL protein to HIF1α is impaired, resulting in an accumulation of HIF1α and increased activation of target genes. In von Hippel–Lindau syndrome, HIF1α accumulation results from failed binding of HIF1α to the dysfunctional VHL complex. C HIF accumulation in haemangioblastoma stroma tumour cells leads to altered gene expression of HIF-responsive genes and results in increased vascularization due to angiogenesis and vasculogenesis, cyst formation due to increased vascular permeability, metabolic adaptation, growth stimulation, extramedullary haematopoiesis, and lipid deposition (clear cell phenotype).

Q: The pathogenesis of Von Hippel-Lindau Syndrome involves a dysfunctional VHL complex that fails to promote the ubiquitination and proteasomal degradation of [...], leading to its accumulation, altered gene expression, and increased angiogenesis.
Von Hippel–Lindau syndrome pathogenesis. A The β domain of VHL protein (pVHL) interacts with HIF1α, whereas the α domain interacts with other partners of the VHL complex. In von Hippel–Lindau syndrome, alterations in the α domain prevent the formation of a functional VHL complex. B In normoxia, the VHL complex binds to HIF1α and promotes ubiquitination and proteasomal degradation in an oxygen-dependent manner. In hypoxia, binding of VHL protein to HIF1α is impaired, resulting in an accumulation of HIF1α and increased activation of target genes. In von Hippel–Lindau syndrome, HIF1α accumulation results from failed binding of HIF1α to the dysfunctional VHL complex. C HIF accumulation in haemangioblastoma stroma tumour cells leads to altered gene expression of HIF-responsive genes and results in increased vascularization due to angiogenesis and vasculogenesis, cyst formation due to increased vascular permeability, metabolic adaptation, growth stimulation, extramedullary haematopoiesis, and lipid deposition (clear cell phenotype).
A: hypoxia-inducible factor 1-alpha (HIF1α)
Back Extra: Von Hippel-Lindau Syndrome
- Clinical: Retinal haemangioblastomas often manifest earlier than renal cell carcinoma, offering an early diagnosis opportunity in patients with Von Hippel-Lindau syndrome.
- Micro: Histopathology of VHL-associated tumours is similar to sporadic tumours, but endolymphatic sac tumours (ELSTs) may mimic choroid plexus papillomas, necessitating neuroimaging to confirm bone invasion.
- Ancillary: Genetic testing for VHL germline sequence variants is crucial for confirming the diagnosis of Von Hippel-Lindau syndrome.
Reference Gallery:
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. This contrast-enhancing tumour (seen here by postcontrast T1-weighted MRI) arose in the cerebellopontine angle and was therefore resected by a neurosurgeon.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. The histopathology is reminiscent of choroid plexus papilloma, but the bone invasion essentially excludes that diagnosis.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. The histopathology is reminiscent of choroid plexus papilloma, but the bone invasion essentially excludes that diagnosis.
Endolymphatic sac tumour in a patient with von Hippel–Lindau syndrome. CT of the tumour shown in Fig. 20207 shows destruction of the temporal bone, which essentially excludes the diagnostic consideration of choroid plexus papilloma.
Von Hippel–Lindau syndrome pathogenesis. A The β domain of VHL protein (pVHL) interacts with HIF1α, whereas the α domain interacts with other partners of the VHL complex. In von Hippel–Lindau syndrome, alterations in the α domain prevent the formation of a functional VHL complex. B In normoxia, the VHL complex binds to HIF1α and promotes ubiquitination and proteasomal degradation in an oxygen-dependent manner. In hypoxia, binding of VHL protein to HIF1α is impaired, resulting in an accumulation of HIF1α and increased activation of target genes. In von Hippel–Lindau syndrome, HIF1α accumulation results from failed binding of HIF1α to the dysfunctional VHL complex. C HIF accumulation in haemangioblastoma stroma tumour cells leads to altered gene expression of HIF-responsive genes and results in increased vascularization due to angiogenesis and vasculogenesis, cyst formation due to increased vascular permeability, metabolic adaptation, growth stimulation, extramedullary haematopoiesis, and lipid deposition (clear cell phenotype).

Q: The 'W' in WAGR Syndrome stands for [...], which often presents on ultrasound as a circumscribed hypoechoic renal mass.
WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies, and a range of developmental delays). Greyscale ultrasound of a patient with WAGR syndrome shows a fairly well-circumscribed hypoechoic mass in the middle region of the left kidney, which was subsequently confirmed to be a Wilms tumour.
A: Wilms tumor
Back Extra: WAGR Syndrome
- Clinical: WAGR syndrome is diagnosed at birth based on the presence of aniridia, and confirmed by cytogenetics or microarray demonstrating deletion at 11p13.
- Micro: Histologically, WAGR syndrome is associated with stromal features and mixed Wilms tumour, with frequent intralobar nephrogenic rests.
- Ancillary: Diagnosis is confirmed by high-resolution cytogenetics or microarray demonstrating interstitial deletion on chromosome 11p13.
Reference Gallery:
Intralobar nephrogenic rest. An intralobar nephrogenic rest, rich in stroma and with small cysts, blending with the surrounding renal parenchyma.
WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies, and a range of developmental delays). Greyscale ultrasound of a patient with WAGR syndrome shows a fairly well-circumscribed hypoechoic mass in the middle region of the left kidney, which was subsequently confirmed to be a Wilms tumour.

Q: Histologically, WAGR Syndrome is frequently associated with stroma-rich precursor lesions that blend with the surrounding renal parenchyma, known as [...].
Intralobar nephrogenic rest. An intralobar nephrogenic rest, rich in stroma and with small cysts, blending with the surrounding renal parenchyma.
A: intralobar nephrogenic rests
Back Extra: WAGR Syndrome
- Clinical: WAGR syndrome is diagnosed at birth based on the presence of aniridia, and confirmed by cytogenetics or microarray demonstrating deletion at 11p13.
- Micro: Histologically, WAGR syndrome is associated with stromal features and mixed Wilms tumour, with frequent intralobar nephrogenic rests.
- Ancillary: Diagnosis is confirmed by high-resolution cytogenetics or microarray demonstrating interstitial deletion on chromosome 11p13.
Reference Gallery:
Intralobar nephrogenic rest. An intralobar nephrogenic rest, rich in stroma and with small cysts, blending with the surrounding renal parenchyma.
WAGR syndrome (Wilms tumour, aniridia, genitourinary anomalies, and a range of developmental delays). Greyscale ultrasound of a patient with WAGR syndrome shows a fairly well-circumscribed hypoechoic mass in the middle region of the left kidney, which was subsequently confirmed to be a Wilms tumour.

Q: Patients with Xeroderma Pigmentosum exhibit severe sun sensitivity and a high risk of early-onset skin cancers due to inherited defects in the [...] pathway.
Xeroderma pigmentosum (XP). A 9-month-old girl with XP complementation group D (XPD) with severe blistering erythema of the cheeks following minimal sun exposure. Note the sparing of her forehead and eyes, which were protected by a hat. B A 2-year-old girl with XP complementation group C (XPC) who did not sunburn easily but developed multiple hyperpigmented macules on her face. A rapidly growing keratoacanthoma or other squamous cell carcinoma grew on her upper lip and a precancerous lesion appeared on her forehead. C A 23-year-old northern African man with XPC with numerous hyperpigmented macules on his face. A nodular basal cell carcinoma is present on his left nasal root and a pigmented basal cell carcinoma on his left cheek. His eyes show corneal scarring from unprotected sun exposure. D A 35-year-old man with XP complementation group A (XPA) with neurological degeneration. He has numerous hyperpigmented macules on the sun-exposed areas of his face and neck. Progressive sensorineural deafness necessitates the use of a hearing aid.
The nucleotide excision repair pathway. Transcription-coupled repair removes damage from actively transcribed genes, and global genome repair removes damage from the remainder of the genome. In global genome repair, DNA damage such as ultraviolet (UV) radiation-induced cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4 PPs) is recognized by proteins including the DDB2 (XPE) and XPC gene products. In transcription-coupled repair, the lesion appears to block the progress of RNA polymerase II (RNAPII) in a process involving the ERCC8 (CSA) and ERCC6 (CSB) gene products. Following initial damage recognition, the two pathways converge. The XPB (ERCC3) and XPD (ERCC2) helicases unwind the DNA region surrounding the lesion, along with the XPA and ERCC5 (XPG) gene products and replication protein A (RPA). The XPF and XPG (ERCC5) endonucleases perform incisions to excise the lesion in a fragment of B30 nucleotides. The resulting gap is filled via de novo DNA synthesis. If any individual part of this highly coordinated system is mutated, the entire pathway fails to function normally. Mutations in the genes shown in rounded rectangles have been associated with clinical disease. DNA pol ε/δ, DNA polymerase ε/δ; PCNA, proliferating cell nuclear antigen; RF-C, replication factor C.
A: nucleotide excision repair
Back Extra: Xeroderma Pigmentosum
- Clinical: Patients with Xeroderma Pigmentosum (XP) exhibit severe sun sensitivity, numerous hyperpigmented macules, and a high risk of developing skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma.
- Micro: The histopathology of tumours in Xeroderma Pigmentosum (XP) is similar to that of sporadic counterparts.
- Ancillary: DNA sequencing of XPA and other relevant genes is essential for the diagnosis of Xeroderma Pigmentosum (XP).
Reference Gallery:
Xeroderma pigmentosum (XP). A 9-month-old girl with XP complementation group D (XPD) with severe blistering erythema of the cheeks following minimal sun exposure. Note the sparing of her forehead and eyes, which were protected by a hat. B A 2-year-old girl with XP complementation group C (XPC) who did not sunburn easily but developed multiple hyperpigmented macules on her face. A rapidly growing keratoacanthoma or other squamous cell carcinoma grew on her upper lip and a precancerous lesion appeared on her forehead. C A 23-year-old northern African man with XPC with numerous hyperpigmented macules on his face. A nodular basal cell carcinoma is present on his left nasal root and a pigmented basal cell carcinoma on his left cheek. His eyes show corneal scarring from unprotected sun exposure. D A 35-year-old man with XP complementation group A (XPA) with neurological degeneration. He has numerous hyperpigmented macules on the sun-exposed areas of his face and neck. Progressive sensorineural deafness necessitates the use of a hearing aid.
Skin cancer in the setting of xeroderma pigmentosum (XP). The graphs show the proportions of non-melanoma skin cancer cases (A) and melanoma cases (B) first diagnosed within each of the age groups indicated, among patients with XP (black bars) and in the general population of the USA (grey bars); individuals with both non-melanoma skin cancer and melanoma are included in both graphs. The median age at first diagnosis of non-melanoma skin cancer was 9 years among the patients with XP versus 67 years in the general population. The median age at first diagnosis of melanoma was 22 years among the patients with XP versus 55 years in the general population.
The nucleotide excision repair pathway. Transcription-coupled repair removes damage from actively transcribed genes, and global genome repair removes damage from the remainder of the genome. In global genome repair, DNA damage such as ultraviolet (UV) radiation-induced cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4 PPs) is recognized by proteins including the DDB2 (XPE) and XPC gene products. In transcription-coupled repair, the lesion appears to block the progress of RNA polymerase II (RNAPII) in a process involving the ERCC8 (CSA) and ERCC6 (CSB) gene products. Following initial damage recognition, the two pathways converge. The XPB (ERCC3) and XPD (ERCC2) helicases unwind the DNA region surrounding the lesion, along with the XPA and ERCC5 (XPG) gene products and replication protein A (RPA). The XPF and XPG (ERCC5) endonucleases perform incisions to excise the lesion in a fragment of B30 nucleotides. The resulting gap is filled via de novo DNA synthesis. If any individual part of this highly coordinated system is mutated, the entire pathway fails to function normally. Mutations in the genes shown in rounded rectangles have been associated with clinical disease. DNA pol ε/δ, DNA polymerase ε/δ; PCNA, proliferating cell nuclear antigen; RF-C, replication factor C.

Q: Diagnosis of Xeroderma Pigmentosum is often confirmed via DNA sequencing of relevant genes (e.g., XPA through XPG), which are essential for recognizing and excising UV-induced [...] and 6-4 photoproducts from DNA.
The nucleotide excision repair pathway. Transcription-coupled repair removes damage from actively transcribed genes, and global genome repair removes damage from the remainder of the genome. In global genome repair, DNA damage such as ultraviolet (UV) radiation-induced cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4 PPs) is recognized by proteins including the DDB2 (XPE) and XPC gene products. In transcription-coupled repair, the lesion appears to block the progress of RNA polymerase II (RNAPII) in a process involving the ERCC8 (CSA) and ERCC6 (CSB) gene products. Following initial damage recognition, the two pathways converge. The XPB (ERCC3) and XPD (ERCC2) helicases unwind the DNA region surrounding the lesion, along with the XPA and ERCC5 (XPG) gene products and replication protein A (RPA). The XPF and XPG (ERCC5) endonucleases perform incisions to excise the lesion in a fragment of B30 nucleotides. The resulting gap is filled via de novo DNA synthesis. If any individual part of this highly coordinated system is mutated, the entire pathway fails to function normally. Mutations in the genes shown in rounded rectangles have been associated with clinical disease. DNA pol ε/δ, DNA polymerase ε/δ; PCNA, proliferating cell nuclear antigen; RF-C, replication factor C.
A: cyclobutane pyrimidine dimers
Back Extra: Xeroderma Pigmentosum
- Clinical: Patients with Xeroderma Pigmentosum (XP) exhibit severe sun sensitivity, numerous hyperpigmented macules, and a high risk of developing skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma.
- Micro: The histopathology of tumours in Xeroderma Pigmentosum (XP) is similar to that of sporadic counterparts.
- Ancillary: DNA sequencing of XPA and other relevant genes is essential for the diagnosis of Xeroderma Pigmentosum (XP).
Reference Gallery:
Xeroderma pigmentosum (XP). A 9-month-old girl with XP complementation group D (XPD) with severe blistering erythema of the cheeks following minimal sun exposure. Note the sparing of her forehead and eyes, which were protected by a hat. B A 2-year-old girl with XP complementation group C (XPC) who did not sunburn easily but developed multiple hyperpigmented macules on her face. A rapidly growing keratoacanthoma or other squamous cell carcinoma grew on her upper lip and a precancerous lesion appeared on her forehead. C A 23-year-old northern African man with XPC with numerous hyperpigmented macules on his face. A nodular basal cell carcinoma is present on his left nasal root and a pigmented basal cell carcinoma on his left cheek. His eyes show corneal scarring from unprotected sun exposure. D A 35-year-old man with XP complementation group A (XPA) with neurological degeneration. He has numerous hyperpigmented macules on the sun-exposed areas of his face and neck. Progressive sensorineural deafness necessitates the use of a hearing aid.
Skin cancer in the setting of xeroderma pigmentosum (XP). The graphs show the proportions of non-melanoma skin cancer cases (A) and melanoma cases (B) first diagnosed within each of the age groups indicated, among patients with XP (black bars) and in the general population of the USA (grey bars); individuals with both non-melanoma skin cancer and melanoma are included in both graphs. The median age at first diagnosis of non-melanoma skin cancer was 9 years among the patients with XP versus 67 years in the general population. The median age at first diagnosis of melanoma was 22 years among the patients with XP versus 55 years in the general population.
The nucleotide excision repair pathway. Transcription-coupled repair removes damage from actively transcribed genes, and global genome repair removes damage from the remainder of the genome. In global genome repair, DNA damage such as ultraviolet (UV) radiation-induced cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4 PPs) is recognized by proteins including the DDB2 (XPE) and XPC gene products. In transcription-coupled repair, the lesion appears to block the progress of RNA polymerase II (RNAPII) in a process involving the ERCC8 (CSA) and ERCC6 (CSB) gene products. Following initial damage recognition, the two pathways converge. The XPB (ERCC3) and XPD (ERCC2) helicases unwind the DNA region surrounding the lesion, along with the XPA and ERCC5 (XPG) gene products and replication protein A (RPA). The XPF and XPG (ERCC5) endonucleases perform incisions to excise the lesion in a fragment of B30 nucleotides. The resulting gap is filled via de novo DNA synthesis. If any individual part of this highly coordinated system is mutated, the entire pathway fails to function normally. Mutations in the genes shown in rounded rectangles have been associated with clinical disease. DNA pol ε/δ, DNA polymerase ε/δ; PCNA, proliferating cell nuclear antigen; RF-C, replication factor C.

Q: A pediatric patient presenting with severe sun-induced blistering erythema, numerous hyperpigmented macules, and early-onset skin cancers (e.g., basal cell carcinoma, squamous cell carcinoma, and melanoma) should be highly suspected of having [...].
Xeroderma pigmentosum (XP). A 9-month-old girl with XP complementation group D (XPD) with severe blistering erythema of the cheeks following minimal sun exposure. Note the sparing of her forehead and eyes, which were protected by a hat. B A 2-year-old girl with XP complementation group C (XPC) who did not sunburn easily but developed multiple hyperpigmented macules on her face. A rapidly growing keratoacanthoma or other squamous cell carcinoma grew on her upper lip and a precancerous lesion appeared on her forehead. C A 23-year-old northern African man with XPC with numerous hyperpigmented macules on his face. A nodular basal cell carcinoma is present on his left nasal root and a pigmented basal cell carcinoma on his left cheek. His eyes show corneal scarring from unprotected sun exposure. D A 35-year-old man with XP complementation group A (XPA) with neurological degeneration. He has numerous hyperpigmented macules on the sun-exposed areas of his face and neck. Progressive sensorineural deafness necessitates the use of a hearing aid.
Skin cancer in the setting of xeroderma pigmentosum (XP). The graphs show the proportions of non-melanoma skin cancer cases (A) and melanoma cases (B) first diagnosed within each of the age groups indicated, among patients with XP (black bars) and in the general population of the USA (grey bars); individuals with both non-melanoma skin cancer and melanoma are included in both graphs. The median age at first diagnosis of non-melanoma skin cancer was 9 years among the patients with XP versus 67 years in the general population. The median age at first diagnosis of melanoma was 22 years among the patients with XP versus 55 years in the general population.
A: Xeroderma Pigmentosum
Back Extra: Xeroderma Pigmentosum
- Clinical: Patients with Xeroderma Pigmentosum (XP) exhibit severe sun sensitivity, numerous hyperpigmented macules, and a high risk of developing skin cancers, including basal cell carcinoma, squamous cell carcinoma, and melanoma.
- Micro: The histopathology of tumours in Xeroderma Pigmentosum (XP) is similar to that of sporadic counterparts.
- Ancillary: DNA sequencing of XPA and other relevant genes is essential for the diagnosis of Xeroderma Pigmentosum (XP).
Reference Gallery:
Xeroderma pigmentosum (XP). A 9-month-old girl with XP complementation group D (XPD) with severe blistering erythema of the cheeks following minimal sun exposure. Note the sparing of her forehead and eyes, which were protected by a hat. B A 2-year-old girl with XP complementation group C (XPC) who did not sunburn easily but developed multiple hyperpigmented macules on her face. A rapidly growing keratoacanthoma or other squamous cell carcinoma grew on her upper lip and a precancerous lesion appeared on her forehead. C A 23-year-old northern African man with XPC with numerous hyperpigmented macules on his face. A nodular basal cell carcinoma is present on his left nasal root and a pigmented basal cell carcinoma on his left cheek. His eyes show corneal scarring from unprotected sun exposure. D A 35-year-old man with XP complementation group A (XPA) with neurological degeneration. He has numerous hyperpigmented macules on the sun-exposed areas of his face and neck. Progressive sensorineural deafness necessitates the use of a hearing aid.
Skin cancer in the setting of xeroderma pigmentosum (XP). The graphs show the proportions of non-melanoma skin cancer cases (A) and melanoma cases (B) first diagnosed within each of the age groups indicated, among patients with XP (black bars) and in the general population of the USA (grey bars); individuals with both non-melanoma skin cancer and melanoma are included in both graphs. The median age at first diagnosis of non-melanoma skin cancer was 9 years among the patients with XP versus 67 years in the general population. The median age at first diagnosis of melanoma was 22 years among the patients with XP versus 55 years in the general population.
The nucleotide excision repair pathway. Transcription-coupled repair removes damage from actively transcribed genes, and global genome repair removes damage from the remainder of the genome. In global genome repair, DNA damage such as ultraviolet (UV) radiation-induced cyclobutane pyrimidine dimers (CPDs) and 6–4 photoproducts (6–4 PPs) is recognized by proteins including the DDB2 (XPE) and XPC gene products. In transcription-coupled repair, the lesion appears to block the progress of RNA polymerase II (RNAPII) in a process involving the ERCC8 (CSA) and ERCC6 (CSB) gene products. Following initial damage recognition, the two pathways converge. The XPB (ERCC3) and XPD (ERCC2) helicases unwind the DNA region surrounding the lesion, along with the XPA and ERCC5 (XPG) gene products and replication protein A (RPA). The XPF and XPG (ERCC5) endonucleases perform incisions to excise the lesion in a fragment of B30 nucleotides. The resulting gap is filled via de novo DNA synthesis. If any individual part of this highly coordinated system is mutated, the entire pathway fails to function normally. Mutations in the genes shown in rounded rectangles have been associated with clinical disease. DNA pol ε/δ, DNA polymerase ε/δ; PCNA, proliferating cell nuclear antigen; RF-C, replication factor C.

Q: Microscopic examination of an Appendiceal Neuroendocrine Tumour (NET) characteristically shows uniform polygonal tumor cells arranged in large nests, frequently demonstrating a classic [...] pattern.
Appendiceal neuroendocrine tumour (NET). Low-power view. The tumour features the classic Zellballen pattern of neuroendocrine neoplasia.
Appendiceal neuroendocrine tumour (NET). Typical nested pattern of NET in the appendix of a 10-year-old child.
A: Zellballen
Back Extra: Appendiceal Neuroendocrine Tumour (NET)
- Clinical: Most patients (85%) present with acute appendicitis, with the tumour incidentally detected during pathological evaluation of the appendectomy specimen.
- Micro: Paediatric appendiceal NETs are composed of uniform polygonal tumour cells arranged in large nests, often with peripheral nuclear palisading and luminal formations.
- Ancillary: Essential markers include synaptophysin and chromogranin A or B, with a classic Zellballen pattern.
Reference Gallery:
Appendiceal neuroendocrine tumour (NET). Macroscopic image from a 10-year-old. Most of the tumour is intraluminal. The tumour replaces most of the mucosa and penetrates through the wall layers, focally reaching the mesoappendix.
Appendiceal neuroendocrine tumour (NET). Low-power view. The tumour features the classic Zellballen pattern of neuroendocrine neoplasia.
Appendiceal neuroendocrine tumour (NET). Typical nested pattern of NET in the appendix of a 10-year-old child.
Appendiceal neuroendocrine tumour (NET). Higher-magnification view of a NET in the appendix of a 10-year-old child.
Appendiceal neuroendocrine tumour (NET). High-power view of a NET in the appendix of a child. The chromatin pattern is classically stippled, without prominent nucleoli.
Appendiceal neuroendocrine tumour (NET). Synaptophysin staining is consistently positive in NETs of the appendix.
Diagnosis not found. Legend text not found

Q: At high magnification, the tumor cells in an Appendiceal Neuroendocrine Tumour (NET) typically display a finely granular, [...] chromatin pattern without prominent nucleoli.
Appendiceal neuroendocrine tumour (NET). Higher-magnification view of a NET in the appendix of a 10-year-old child.
Appendiceal neuroendocrine tumour (NET). High-power view of a NET in the appendix of a child. The chromatin pattern is classically stippled, without prominent nucleoli.
A: stippled
Back Extra: Appendiceal Neuroendocrine Tumour (NET)
- Clinical: Most patients (85%) present with acute appendicitis, with the tumour incidentally detected during pathological evaluation of the appendectomy specimen.
- Micro: Paediatric appendiceal NETs are composed of uniform polygonal tumour cells arranged in large nests, often with peripheral nuclear palisading and luminal formations.
- Ancillary: Essential markers include synaptophysin and chromogranin A or B, with a classic Zellballen pattern.
Reference Gallery:
Appendiceal neuroendocrine tumour (NET). Macroscopic image from a 10-year-old. Most of the tumour is intraluminal. The tumour replaces most of the mucosa and penetrates through the wall layers, focally reaching the mesoappendix.
Appendiceal neuroendocrine tumour (NET). Low-power view. The tumour features the classic Zellballen pattern of neuroendocrine neoplasia.
Appendiceal neuroendocrine tumour (NET). Typical nested pattern of NET in the appendix of a 10-year-old child.
Appendiceal neuroendocrine tumour (NET). Higher-magnification view of a NET in the appendix of a 10-year-old child.
Appendiceal neuroendocrine tumour (NET). High-power view of a NET in the appendix of a child. The chromatin pattern is classically stippled, without prominent nucleoli.
Appendiceal neuroendocrine tumour (NET). Synaptophysin staining is consistently positive in NETs of the appendix.
Diagnosis not found. Legend text not found

Q: Immunohistochemical evaluation of an Appendiceal Neuroendocrine Tumour (NET) will consistently demonstrate diffuse positivity for essential neuroendocrine markers, including chromogranin and [...].
Appendiceal neuroendocrine tumour (NET). Synaptophysin staining is consistently positive in NETs of the appendix.
A: synaptophysin
Back Extra: Appendiceal Neuroendocrine Tumour (NET)
- Clinical: Most patients (85%) present with acute appendicitis, with the tumour incidentally detected during pathological evaluation of the appendectomy specimen.
- Micro: Paediatric appendiceal NETs are composed of uniform polygonal tumour cells arranged in large nests, often with peripheral nuclear palisading and luminal formations.
- Ancillary: Essential markers include synaptophysin and chromogranin A or B, with a classic Zellballen pattern.
Reference Gallery:
Appendiceal neuroendocrine tumour (NET). Macroscopic image from a 10-year-old. Most of the tumour is intraluminal. The tumour replaces most of the mucosa and penetrates through the wall layers, focally reaching the mesoappendix.
Appendiceal neuroendocrine tumour (NET). Low-power view. The tumour features the classic Zellballen pattern of neuroendocrine neoplasia.
Appendiceal neuroendocrine tumour (NET). Typical nested pattern of NET in the appendix of a 10-year-old child.
Appendiceal neuroendocrine tumour (NET). Higher-magnification view of a NET in the appendix of a 10-year-old child.
Appendiceal neuroendocrine tumour (NET). High-power view of a NET in the appendix of a child. The chromatin pattern is classically stippled, without prominent nucleoli.
Appendiceal neuroendocrine tumour (NET). Synaptophysin staining is consistently positive in NETs of the appendix.
Diagnosis not found. Legend text not found

Q: Morphologically, a calcifying nested stromal-epithelial tumor is characterized by nests of epithelioid and spindle cells within a cellular stroma, frequently accompanied by characteristic [...] and occasional osseous metaplasia.
Calcifying nested stromal-epithelial tumour. Psammomatous calcifications are often seen, sometimes with osseous metaplasia.
Calcifying nested stromal-epithelial tumour. The tumour is composed of nests of epithelioid and spindle cells surrounded by cellular stroma.
A: psammomatous calcifications
Back Extra: Calcifying Nested Stromal-Epithelial Tumour
- Clinical: Calcifying Nested Stromal-Epithelial Tumour is often discovered incidentally, sometimes with a history of a calcified hepatic nodule. It can present with abdominal pain, a palpable mass, or Cushing syndrome in about 20% of cases.
- Micro: The tumour is characterized by nests of epithelioid and spindle cells surrounded by a cellular stroma, with psammomatous calcifications and occasional ossification.
- Ancillary: Immunohistochemistry shows positivity for broad-spectrum keratins, WT1, and aberrant β-catenin staining. The stromal spindle cells are positive for SMA.
Reference Gallery:
Calcifying nested stromal-epithelial tumour. Psammomatous calcifications are often seen, sometimes with osseous metaplasia.
Calcifying nested stromal-epithelial tumour. The tumour is composed of nests of epithelioid and spindle cells surrounded by cellular stroma.
Calcifying nested stromal-epithelial tumour. The tumour cells contain irregular nuclei with fine chromatin, variably prominent small nucleoli, and abundant pale eosinophilic cytoplasm.
Calcifying nested stromal-epithelial tumour. Immunohistochemistry for β-catenin shows aberrant cytoplasmic and nuclear staining. Note the normal membranous staining in the surrounding bile ducts.
Calcifying nested stromal-epithelial tumour. Cross-section of the tumour showing a pale yellowish-tan cut surface with focal cystic change and calcifications at the periphery.

Q: In a calcifying nested stromal-epithelial tumor, immunohistochemistry characteristically demonstrates aberrant nuclear and cytoplasmic expression of [...].
Calcifying nested stromal-epithelial tumour. Immunohistochemistry for β-catenin shows aberrant cytoplasmic and nuclear staining. Note the normal membranous staining in the surrounding bile ducts.
A: β-catenin
Back Extra: Calcifying Nested Stromal-Epithelial Tumour
- Clinical: Calcifying Nested Stromal-Epithelial Tumour is often discovered incidentally, sometimes with a history of a calcified hepatic nodule. It can present with abdominal pain, a palpable mass, or Cushing syndrome in about 20% of cases.
- Micro: The tumour is characterized by nests of epithelioid and spindle cells surrounded by a cellular stroma, with psammomatous calcifications and occasional ossification.
- Ancillary: Immunohistochemistry shows positivity for broad-spectrum keratins, WT1, and aberrant β-catenin staining. The stromal spindle cells are positive for SMA.
Reference Gallery:
Calcifying nested stromal-epithelial tumour. Psammomatous calcifications are often seen, sometimes with osseous metaplasia.
Calcifying nested stromal-epithelial tumour. The tumour is composed of nests of epithelioid and spindle cells surrounded by cellular stroma.
Calcifying nested stromal-epithelial tumour. The tumour cells contain irregular nuclei with fine chromatin, variably prominent small nucleoli, and abundant pale eosinophilic cytoplasm.
Calcifying nested stromal-epithelial tumour. Immunohistochemistry for β-catenin shows aberrant cytoplasmic and nuclear staining. Note the normal membranous staining in the surrounding bile ducts.
Calcifying nested stromal-epithelial tumour. Cross-section of the tumour showing a pale yellowish-tan cut surface with focal cystic change and calcifications at the periphery.

Q: On macroscopic examination, a calcifying nested stromal-epithelial tumor typically exhibits a pale yellowish-tan cut surface with focal cystic change and characteristic peripheral [...].
Calcifying nested stromal-epithelial tumour. Cross-section of the tumour showing a pale yellowish-tan cut surface with focal cystic change and calcifications at the periphery.
A: calcifications
Back Extra: Calcifying Nested Stromal-Epithelial Tumour
- Clinical: Calcifying Nested Stromal-Epithelial Tumour is often discovered incidentally, sometimes with a history of a calcified hepatic nodule. It can present with abdominal pain, a palpable mass, or Cushing syndrome in about 20% of cases.
- Micro: The tumour is characterized by nests of epithelioid and spindle cells surrounded by a cellular stroma, with psammomatous calcifications and occasional ossification.
- Ancillary: Immunohistochemistry shows positivity for broad-spectrum keratins, WT1, and aberrant β-catenin staining. The stromal spindle cells are positive for SMA.
Reference Gallery:
Calcifying nested stromal-epithelial tumour. Psammomatous calcifications are often seen, sometimes with osseous metaplasia.
Calcifying nested stromal-epithelial tumour. The tumour is composed of nests of epithelioid and spindle cells surrounded by cellular stroma.
Calcifying nested stromal-epithelial tumour. The tumour cells contain irregular nuclei with fine chromatin, variably prominent small nucleoli, and abundant pale eosinophilic cytoplasm.
Calcifying nested stromal-epithelial tumour. Immunohistochemistry for β-catenin shows aberrant cytoplasmic and nuclear staining. Note the normal membranous staining in the surrounding bile ducts.
Calcifying nested stromal-epithelial tumour. Cross-section of the tumour showing a pale yellowish-tan cut surface with focal cystic change and calcifications at the periphery.

Q: In Hepatic Congenital Haemangioma, the plump to hobnailed endothelial cells are characteristically immunonegative for [...], helping distinguish this tumor from infantile hemangiomas.
Hepatic rapidly involuting congenital haemangioma. High-power view of the periphery demonstrates aggregates or lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes.
Hepatic rapidly involuting congenital haemangioma. GLUT1 is negative within the endothelial cells. Red blood cells serve as the internal control.
Hepatic non-involuting congenital haemangioma. This example is from a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. Higher magnification highlights lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes. Endothelial cells lack pleomorphism and endothelial redundancy. Solid areas are absent. GLUT1 (not shown here) was negative.
A: GLUT1
Back Extra: Hepatic Congenital Haemangioma
- Clinical: Hepatic congenital haemangioma (HCH) is primarily asymptomatic, often found incidentally on prenatal ultrasound or in infancy. Some cases may present with hepatomegaly, thrombocytopenia, and mild hypofibrinogenaemia.
- Micro: HCH is composed of variably sized aggregates or lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes. Central necrosis, macrophages, dystrophic calcification, and chronic inflammatory cells are frequently observed.
- Ancillary: Lesional endothelial cells are immunoreactive for CD31, CD34, and WT1, and immunonegative for GLUT1. Missense mutations affecting the glutamine at amino acid position 209 (Q209) in GNAQ and GNA11 are common.
Reference Gallery:
Hepatic rapidly involuting congenital haemangioma. High-power view of the periphery demonstrates aggregates or lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes.
Hepatic rapidly involuting congenital haemangioma. GLUT1 is negative within the endothelial cells. Red blood cells serve as the internal control.
Hepatic non-involuting congenital haemangioma. A solitary, diffusely red-brown mottled vascular lesion within the left lobe of the liver in a 17-month-old.
Hepatic non-involuting congenital haemangioma. This example is from a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. Left lateral segmentectomy demonstrates an unencapsulated hepatic lesion composed of vascular channels tracking along hepatic sinusoids.
Hepatic non-involuting congenital haemangioma. This example is from a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. Higher magnification highlights lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes. Endothelial cells lack pleomorphism and endothelial redundancy. Solid areas are absent. GLUT1 (not shown here) was negative.
Hepatic non-involuting congenital haemangioma. Lip lesion in a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. The lip lesion shows similar histology to the hepatic lesions.
Hepatic rapidly involuting congenital haemangioma. Liver resection showing a vascular lesion with dilated central vascular channels surrounded by a rim of calcification.
Hepatic rapidly involuting congenital haemangioma. Liver resection of an ovoid mass with large areas of central necrosis, haemorrhage, and fibrosis.
Hepatic congenital haemangioma. Contrast-enhanced axial CT showing a large hepatic tumour with an intense centripetal pattern of enhancement; the centre is not completely enhanced due to central necrosis.

Q: Gross and histologic examination of a rapidly involuting Hepatic Congenital Haemangioma frequently reveals large areas of central [...], along with hemorrhage, fibrosis, and dystrophic calcification.
Hepatic rapidly involuting congenital haemangioma. Liver resection showing a vascular lesion with dilated central vascular channels surrounded by a rim of calcification.
Hepatic rapidly involuting congenital haemangioma. Liver resection of an ovoid mass with large areas of central necrosis, haemorrhage, and fibrosis.
A: necrosis
Back Extra: Hepatic Congenital Haemangioma
- Clinical: Hepatic congenital haemangioma (HCH) is primarily asymptomatic, often found incidentally on prenatal ultrasound or in infancy. Some cases may present with hepatomegaly, thrombocytopenia, and mild hypofibrinogenaemia.
- Micro: HCH is composed of variably sized aggregates or lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes. Central necrosis, macrophages, dystrophic calcification, and chronic inflammatory cells are frequently observed.
- Ancillary: Lesional endothelial cells are immunoreactive for CD31, CD34, and WT1, and immunonegative for GLUT1. Missense mutations affecting the glutamine at amino acid position 209 (Q209) in GNAQ and GNA11 are common.
Reference Gallery:
Hepatic rapidly involuting congenital haemangioma. High-power view of the periphery demonstrates aggregates or lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes.
Hepatic rapidly involuting congenital haemangioma. GLUT1 is negative within the endothelial cells. Red blood cells serve as the internal control.
Hepatic non-involuting congenital haemangioma. A solitary, diffusely red-brown mottled vascular lesion within the left lobe of the liver in a 17-month-old.
Hepatic non-involuting congenital haemangioma. This example is from a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. Left lateral segmentectomy demonstrates an unencapsulated hepatic lesion composed of vascular channels tracking along hepatic sinusoids.
Hepatic non-involuting congenital haemangioma. This example is from a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. Higher magnification highlights lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes. Endothelial cells lack pleomorphism and endothelial redundancy. Solid areas are absent. GLUT1 (not shown here) was negative.
Hepatic non-involuting congenital haemangioma. Lip lesion in a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. The lip lesion shows similar histology to the hepatic lesions.
Hepatic rapidly involuting congenital haemangioma. Liver resection showing a vascular lesion with dilated central vascular channels surrounded by a rim of calcification.
Hepatic rapidly involuting congenital haemangioma. Liver resection of an ovoid mass with large areas of central necrosis, haemorrhage, and fibrosis.
Hepatic congenital haemangioma. Contrast-enhanced axial CT showing a large hepatic tumour with an intense centripetal pattern of enhancement; the centre is not completely enhanced due to central necrosis.

Q: On contrast-enhanced CT, a Hepatic Congenital Haemangioma classically demonstrates an intense [...] pattern of enhancement, often with an unenhanced center.
Hepatic congenital haemangioma. Contrast-enhanced axial CT showing a large hepatic tumour with an intense centripetal pattern of enhancement; the centre is not completely enhanced due to central necrosis.
A: centripetal
Back Extra: Hepatic Congenital Haemangioma
- Clinical: Hepatic congenital haemangioma (HCH) is primarily asymptomatic, often found incidentally on prenatal ultrasound or in infancy. Some cases may present with hepatomegaly, thrombocytopenia, and mild hypofibrinogenaemia.
- Micro: HCH is composed of variably sized aggregates or lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes. Central necrosis, macrophages, dystrophic calcification, and chronic inflammatory cells are frequently observed.
- Ancillary: Lesional endothelial cells are immunoreactive for CD31, CD34, and WT1, and immunonegative for GLUT1. Missense mutations affecting the glutamine at amino acid position 209 (Q209) in GNAQ and GNA11 are common.
Reference Gallery:
Hepatic rapidly involuting congenital haemangioma. High-power view of the periphery demonstrates aggregates or lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes.
Hepatic rapidly involuting congenital haemangioma. GLUT1 is negative within the endothelial cells. Red blood cells serve as the internal control.
Hepatic non-involuting congenital haemangioma. A solitary, diffusely red-brown mottled vascular lesion within the left lobe of the liver in a 17-month-old.
Hepatic non-involuting congenital haemangioma. This example is from a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. Left lateral segmentectomy demonstrates an unencapsulated hepatic lesion composed of vascular channels tracking along hepatic sinusoids.
Hepatic non-involuting congenital haemangioma. This example is from a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. Higher magnification highlights lobules of capillary-type channels lined by plump to hobnailed endothelial cells and pericytes. Endothelial cells lack pleomorphism and endothelial redundancy. Solid areas are absent. GLUT1 (not shown here) was negative.
Hepatic non-involuting congenital haemangioma. Lip lesion in a 2-year-old child with two hepatic lesions measuring 42 mm and 5 mm, the larger of which was identified on antenatal Doppler ultrasound. The lip lesion shows similar histology to the hepatic lesions.
Hepatic rapidly involuting congenital haemangioma. Liver resection showing a vascular lesion with dilated central vascular channels surrounded by a rim of calcification.
Hepatic rapidly involuting congenital haemangioma. Liver resection of an ovoid mass with large areas of central necrosis, haemorrhage, and fibrosis.
Hepatic congenital haemangioma. Contrast-enhanced axial CT showing a large hepatic tumour with an intense centripetal pattern of enhancement; the centre is not completely enhanced due to central necrosis.

Q: Microscopically, Embryonal Sarcoma of the Liver is composed of pleomorphic spindle and stellate cells in a myxoid stroma, often containing characteristic PASD-positive [...].
Embryonal sarcoma of the liver. The tumour is composed of medium to large spindle and stellate cells embedded in a myxoid stroma. The nuclei are pleomorphic and hyperchromatic and the cytoplasm is often eosinophilic. Mitotic figures are numerous.
Embryonal sarcoma of the liver. PASD staining highlights the intracytoplasmic globules.
A: intracytoplasmic globules
Back Extra: Embryonal Sarcoma of the Liver
- Clinical: Patients with Embryonal Sarcoma of the Liver typically present with a rapidly growing, palpable abdominal mass, abdominal pain, and swelling. Serum AFP levels are not elevated.
- Micro: Embryonal Sarcoma of the Liver is composed of medium to large spindle and stellate cells in a myxoid stroma, with pleomorphic and hyperchromatic nuclei and eosinophilic cytoplasm. Intracytoplasmic globules and numerous mitotic figures are characteristic.
- Ancillary: Immunohistochemically, Embryonal Sarcoma of the Liver is positive for vimentin, α1-antitrypsin, and desmin, with nuclear p53 positivity. C19MC hyperexpression and TP53 mutation or loss are common molecular findings.
Reference Gallery:
Embryonal sarcoma of the liver. The tumour is composed of medium to large spindle and stellate cells embedded in a myxoid stroma. The nuclei are pleomorphic and hyperchromatic and the cytoplasm is often eosinophilic. Mitotic figures are numerous.
Embryonal sarcoma of the liver. Entrapped liver tissue can be seen at the periphery of the tumour.
Embryonal sarcoma of the liver. The tumour cells are strongly positive for desmin.
Embryonal sarcoma of the liver. PASD staining highlights the intracytoplasmic globules.
Embryonal sarcoma of the liver. Gross image of a posttherapy explant showing a predominantly necrotic tumour abutting the large vessels in the medial aspect of the liver.
Embryonal sarcoma of the liver. Contrast-enhanced axial CT shows a large hepatic mass showing predominantly water attenuation, consistent with the myxoid stroma. Enhancement is limited to the septa and periphery.

Q: Immunohistochemically, the tumor cells of Embryonal Sarcoma of the Liver characteristically demonstrate strong positivity for the intermediate filament [...].
Embryonal sarcoma of the liver. The tumour cells are strongly positive for desmin.
A: desmin
Back Extra: Embryonal Sarcoma of the Liver
- Clinical: Patients with Embryonal Sarcoma of the Liver typically present with a rapidly growing, palpable abdominal mass, abdominal pain, and swelling. Serum AFP levels are not elevated.
- Micro: Embryonal Sarcoma of the Liver is composed of medium to large spindle and stellate cells in a myxoid stroma, with pleomorphic and hyperchromatic nuclei and eosinophilic cytoplasm. Intracytoplasmic globules and numerous mitotic figures are characteristic.
- Ancillary: Immunohistochemically, Embryonal Sarcoma of the Liver is positive for vimentin, α1-antitrypsin, and desmin, with nuclear p53 positivity. C19MC hyperexpression and TP53 mutation or loss are common molecular findings.
Reference Gallery:
Embryonal sarcoma of the liver. The tumour is composed of medium to large spindle and stellate cells embedded in a myxoid stroma. The nuclei are pleomorphic and hyperchromatic and the cytoplasm is often eosinophilic. Mitotic figures are numerous.
Embryonal sarcoma of the liver. Entrapped liver tissue can be seen at the periphery of the tumour.
Embryonal sarcoma of the liver. The tumour cells are strongly positive for desmin.
Embryonal sarcoma of the liver. PASD staining highlights the intracytoplasmic globules.
Embryonal sarcoma of the liver. Gross image of a posttherapy explant showing a predominantly necrotic tumour abutting the large vessels in the medial aspect of the liver.
Embryonal sarcoma of the liver. Contrast-enhanced axial CT shows a large hepatic mass showing predominantly water attenuation, consistent with the myxoid stroma. Enhancement is limited to the septa and periphery.

Q: Radiologically, Embryonal Sarcoma of the Liver often appears on contrast-enhanced CT as a large mass with predominantly water attenuation due to its prominent [...] stroma.
Embryonal sarcoma of the liver. Contrast-enhanced axial CT shows a large hepatic mass showing predominantly water attenuation, consistent with the myxoid stroma. Enhancement is limited to the septa and periphery.
A: myxoid
Back Extra: Embryonal Sarcoma of the Liver
- Clinical: Patients with Embryonal Sarcoma of the Liver typically present with a rapidly growing, palpable abdominal mass, abdominal pain, and swelling. Serum AFP levels are not elevated.
- Micro: Embryonal Sarcoma of the Liver is composed of medium to large spindle and stellate cells in a myxoid stroma, with pleomorphic and hyperchromatic nuclei and eosinophilic cytoplasm. Intracytoplasmic globules and numerous mitotic figures are characteristic.
- Ancillary: Immunohistochemically, Embryonal Sarcoma of the Liver is positive for vimentin, α1-antitrypsin, and desmin, with nuclear p53 positivity. C19MC hyperexpression and TP53 mutation or loss are common molecular findings.
Reference Gallery:
Embryonal sarcoma of the liver. The tumour is composed of medium to large spindle and stellate cells embedded in a myxoid stroma. The nuclei are pleomorphic and hyperchromatic and the cytoplasm is often eosinophilic. Mitotic figures are numerous.
Embryonal sarcoma of the liver. Entrapped liver tissue can be seen at the periphery of the tumour.
Embryonal sarcoma of the liver. The tumour cells are strongly positive for desmin.
Embryonal sarcoma of the liver. PASD staining highlights the intracytoplasmic globules.
Embryonal sarcoma of the liver. Gross image of a posttherapy explant showing a predominantly necrotic tumour abutting the large vessels in the medial aspect of the liver.
Embryonal sarcoma of the liver. Contrast-enhanced axial CT shows a large hepatic mass showing predominantly water attenuation, consistent with the myxoid stroma. Enhancement is limited to the septa and periphery.

Q: Microscopically, [...] is characterized by a multinodular, biphasic growth pattern consisting of bland spindle cells and epithelial nodules that frequently form rosettes.
Gastroblastoma. A vaguely biphasic tumour arising in the wall of the gastric antrum.
Gastroblastoma. An epithelial cell nodule surrounded by bland spindle cells.
Gastroblastoma. Epithelial cells forming small rosettes.
A: gastroblastoma
Gastroblastoma
- Clinical: Patients with Gastroblastoma typically present with nonspecific abdominal pain or discomfort, and may have a palpable abdominal mass, gastrointestinal bleeding, and anemia.
- Micro: Gastroblastoma has a multinodular growth pattern with mesenchymal and epithelial components, often forming rosettes with eosinophilic secretions.
- Ancillary: The characteristic GLI1 staining and the presence of the MALAT1::GLI1 fusion gene are key diagnostic features of Gastroblastoma.
Reference Gallery:
Gastroblastoma. A vaguely biphasic tumour arising in the wall of the gastric antrum.
Gastroblastoma. An epithelial cell nodule surrounded by bland spindle cells.
Gastroblastoma. Epithelial cells forming small rosettes.
Gastroblastoma. Strong diffuse nuclear and cytoplasmic staining for GLI1.

Q: A key diagnostic feature of gastroblastoma is the presence of the MALAT1::GLI1 fusion gene, which corresponds to strong, diffuse nuclear and cytoplasmic immunostaining for [...].
Gastroblastoma. Strong diffuse nuclear and cytoplasmic staining for GLI1.
A: GLI1
Gastroblastoma
- Clinical: Patients with Gastroblastoma typically present with nonspecific abdominal pain or discomfort, and may have a palpable abdominal mass, gastrointestinal bleeding, and anemia.
- Micro: Gastroblastoma has a multinodular growth pattern with mesenchymal and epithelial components, often forming rosettes with eosinophilic secretions.
- Ancillary: The characteristic GLI1 staining and the presence of the MALAT1::GLI1 fusion gene are key diagnostic features of Gastroblastoma.
Reference Gallery:
Gastroblastoma. A vaguely biphasic tumour arising in the wall of the gastric antrum.
Gastroblastoma. An epithelial cell nodule surrounded by bland spindle cells.
Gastroblastoma. Epithelial cells forming small rosettes.
Gastroblastoma. Strong diffuse nuclear and cytoplasmic staining for GLI1.

Q: Hepatic Angiosarcoma manifests in early childhood as a rapidly enlarging liver mass that grossly demonstrates a large, tan tumor with central areas of [...] and necrosis.
Hepatic angiosarcoma. This resection from a 4-year-old with multifocal hepatic infantile haemangiomas, a rapidly enlarging liver mass, and a new lung mass shows a large, tan, ovoid to round mass with central areas of haemorrhage and necrosis.
A: hemorrhage
Back Extra: Hepatic Angiosarcoma
- Clinical: Hepatic Angiosarcoma manifests in early childhood with symptoms such as abdominal pain, jaundice, and a rapidly enlarging liver mass.
- Micro: Solid foci with markedly atypical, pleomorphic, spindled to epithelioid endothelial cells and readily identified mitoses are characteristic of Hepatic Angiosarcoma.
- Ancillary: ROS1 rearrangements and activating RAS mutations are common in Hepatic Angiosarcoma.
Reference Gallery:
Hepatic angiosarcoma. This resection from a 4-year-old with multifocal hepatic infantile haemangiomas, a rapidly enlarging liver mass, and a new lung mass shows a large, tan, ovoid to round mass with central areas of haemorrhage and necrosis.
Hepatic angiosarcoma. This example is from a 4-year-old with multifocal hepatic infantile haemangiomas, a rapidly enlarging liver mass, and a new lung mass. Scattered foci of solid areas show sheets of spindled endothelial cells with several mitotic figures.
Hepatic angiosarcoma. Lung metastasis showing a solid, cellular mass composed of pleomorphic epithelioid to focally spindled endothelial cells with numerous mitoses.
Hepatic angiosarcoma. Tumour cells are immunoreactive for GLUT1.

Q: The solid foci of Hepatic Angiosarcoma typically consist of markedly atypical, pleomorphic, [...] endothelial cells with readily identified mitoses.
Hepatic angiosarcoma. This example is from a 4-year-old with multifocal hepatic infantile haemangiomas, a rapidly enlarging liver mass, and a new lung mass. Scattered foci of solid areas show sheets of spindled endothelial cells with several mitotic figures.
Hepatic angiosarcoma. Lung metastasis showing a solid, cellular mass composed of pleomorphic epithelioid to focally spindled endothelial cells with numerous mitoses.
A: spindled to epithelioid
Back Extra: Hepatic Angiosarcoma
- Clinical: Hepatic Angiosarcoma manifests in early childhood with symptoms such as abdominal pain, jaundice, and a rapidly enlarging liver mass.
- Micro: Solid foci with markedly atypical, pleomorphic, spindled to epithelioid endothelial cells and readily identified mitoses are characteristic of Hepatic Angiosarcoma.
- Ancillary: ROS1 rearrangements and activating RAS mutations are common in Hepatic Angiosarcoma.
Reference Gallery:
Hepatic angiosarcoma. This resection from a 4-year-old with multifocal hepatic infantile haemangiomas, a rapidly enlarging liver mass, and a new lung mass shows a large, tan, ovoid to round mass with central areas of haemorrhage and necrosis.
Hepatic angiosarcoma. This example is from a 4-year-old with multifocal hepatic infantile haemangiomas, a rapidly enlarging liver mass, and a new lung mass. Scattered foci of solid areas show sheets of spindled endothelial cells with several mitotic figures.
Hepatic angiosarcoma. Lung metastasis showing a solid, cellular mass composed of pleomorphic epithelioid to focally spindled endothelial cells with numerous mitoses.
Hepatic angiosarcoma. Tumour cells are immunoreactive for GLUT1.

Q: Ancillary testing in Hepatic Angiosarcoma frequently reveals ROS1 rearrangements or RAS mutations, and the tumor cells typically show diagnostic immunoreactivity for [...].
Hepatic angiosarcoma. Tumour cells are immunoreactive for GLUT1.
A: GLUT1
Back Extra: Hepatic Angiosarcoma
- Clinical: Hepatic Angiosarcoma manifests in early childhood with symptoms such as abdominal pain, jaundice, and a rapidly enlarging liver mass.
- Micro: Solid foci with markedly atypical, pleomorphic, spindled to epithelioid endothelial cells and readily identified mitoses are characteristic of Hepatic Angiosarcoma.
- Ancillary: ROS1 rearrangements and activating RAS mutations are common in Hepatic Angiosarcoma.
Reference Gallery:
Hepatic angiosarcoma. This resection from a 4-year-old with multifocal hepatic infantile haemangiomas, a rapidly enlarging liver mass, and a new lung mass shows a large, tan, ovoid to round mass with central areas of haemorrhage and necrosis.
Hepatic angiosarcoma. This example is from a 4-year-old with multifocal hepatic infantile haemangiomas, a rapidly enlarging liver mass, and a new lung mass. Scattered foci of solid areas show sheets of spindled endothelial cells with several mitotic figures.
Hepatic angiosarcoma. Lung metastasis showing a solid, cellular mass composed of pleomorphic epithelioid to focally spindled endothelial cells with numerous mitoses.
Hepatic angiosarcoma. Tumour cells are immunoreactive for GLUT1.

Q: The well-differentiated fetal pattern of Hepatoblastoma is histologically characterized by uniform polygonal cells lacking mitotic activity that form a classic [...] cell pattern.
Well-differentiated fetal hepatoblastoma. The uniform polygonal cells show a light and dark cell pattern and no mitotic activity.
A: light and dark
Back Extra: Hepatoblastoma
- Clinical: Hepatoblastoma (HBL) is most commonly seen in children aged 6 months to 5 years, presenting with an abdominal mass and elevated AFP levels.
- Micro: Well-differentiated fetal hepatoblastoma is characterized by uniform polygonal cells with a light and dark cell pattern and no mitotic activity.
- Ancillary: About 90% of hepatoblastomas carry CTNNB1 mutations, and immunohistochemistry for β-catenin and glypican-3 (GPC3) can be useful in diagnosis.
Reference Gallery:
Well-differentiated fetal hepatoblastoma. The uniform polygonal cells show a light and dark cell pattern and no mitotic activity.
Well-differentiated fetal hepatoblastoma. Strong nuclear β-catenin staining is present.
Well-differentiated fetal hepatoblastoma. Fine granular glypican-3 (GPC3) immunostaining staining is seen in the cells of well-differentiated fetal hepatoblastoma.
Well-differentiated fetal hepatoblastoma. Glutamine synthetase (GS) staining in the same case, showing strong cytoplasmic staining.
Hepatoblastoma. Crowded fetal pattern. An area with monotonous polygonal cells with increased N:C ratios and round nuclei. Note the extramedullary haematopoiesis.
Hepatoblastoma. Crowded fetal pattern showing fetal cells with larger nuclei and mitoses.
Hepatoblastoma. Embryonal hepatoblastoma with a small cell undifferentiated component, cells with scant cytoplasm and oval to angulated nuclei, and a focus of small cells in the upper quadrant.
Hepatoblastoma. Mixed hepatoblastoma showing the epithelial fetal pattern, osteoid, and blastema.
Hepatocellular neoplasm NOS. Biopsy of a lesion composed of primitive cells, some with angulated nuclei, but with an acinar arrangement, mimicking hepatocellular carcinoma.
Hepatocellular neoplasm NOS. There is nuclear β-catenin staining in almost every tumour cell.
PRETEXT staging. An illustration of pretreatment extent of disease (PRETEXT) staging as determined by the involvement of contiguous segments of liver.
Hepatoblastoma. Axial CT image obtained in the arterial phase of enhancement, showing a circumscribed, heterogeneously enhanced mass in the right lobe of the liver, displacing the gallbladder.

Q: Approximately 90% of Hepatoblastoma cases harbor mutations in the [...] gene, which is diagnostically supported by strong nuclear immunohistochemical staining for β-catenin.
Well-differentiated fetal hepatoblastoma. Strong nuclear β-catenin staining is present.
A: CTNNB1
Back Extra: Hepatoblastoma
- Clinical: Hepatoblastoma (HBL) is most commonly seen in children aged 6 months to 5 years, presenting with an abdominal mass and elevated AFP levels.
- Micro: Well-differentiated fetal hepatoblastoma is characterized by uniform polygonal cells with a light and dark cell pattern and no mitotic activity.
- Ancillary: About 90% of hepatoblastomas carry CTNNB1 mutations, and immunohistochemistry for β-catenin and glypican-3 (GPC3) can be useful in diagnosis.
Reference Gallery:
Well-differentiated fetal hepatoblastoma. The uniform polygonal cells show a light and dark cell pattern and no mitotic activity.
Well-differentiated fetal hepatoblastoma. Strong nuclear β-catenin staining is present.
Well-differentiated fetal hepatoblastoma. Fine granular glypican-3 (GPC3) immunostaining staining is seen in the cells of well-differentiated fetal hepatoblastoma.
Well-differentiated fetal hepatoblastoma. Glutamine synthetase (GS) staining in the same case, showing strong cytoplasmic staining.
Hepatoblastoma. Crowded fetal pattern. An area with monotonous polygonal cells with increased N:C ratios and round nuclei. Note the extramedullary haematopoiesis.
Hepatoblastoma. Crowded fetal pattern showing fetal cells with larger nuclei and mitoses.
Hepatoblastoma. Embryonal hepatoblastoma with a small cell undifferentiated component, cells with scant cytoplasm and oval to angulated nuclei, and a focus of small cells in the upper quadrant.
Hepatoblastoma. Mixed hepatoblastoma showing the epithelial fetal pattern, osteoid, and blastema.
Hepatocellular neoplasm NOS. Biopsy of a lesion composed of primitive cells, some with angulated nuclei, but with an acinar arrangement, mimicking hepatocellular carcinoma.
Hepatocellular neoplasm NOS. There is nuclear β-catenin staining in almost every tumour cell.
PRETEXT staging. An illustration of pretreatment extent of disease (PRETEXT) staging as determined by the involvement of contiguous segments of liver.
Hepatoblastoma. Axial CT image obtained in the arterial phase of enhancement, showing a circumscribed, heterogeneously enhanced mass in the right lobe of the liver, displacing the gallbladder.

Q: The mixed epithelial and mesenchymal subtype of Hepatoblastoma is characterized by the presence of heterologous mesenchymal elements, most classically presenting as [...] mixed with fetal and blastemal components.
Hepatoblastoma. Mixed hepatoblastoma showing the epithelial fetal pattern, osteoid, and blastema.
A: osteoid
Back Extra: Hepatoblastoma
- Clinical: Hepatoblastoma (HBL) is most commonly seen in children aged 6 months to 5 years, presenting with an abdominal mass and elevated AFP levels.
- Micro: Well-differentiated fetal hepatoblastoma is characterized by uniform polygonal cells with a light and dark cell pattern and no mitotic activity.
- Ancillary: About 90% of hepatoblastomas carry CTNNB1 mutations, and immunohistochemistry for β-catenin and glypican-3 (GPC3) can be useful in diagnosis.
Reference Gallery:
Well-differentiated fetal hepatoblastoma. The uniform polygonal cells show a light and dark cell pattern and no mitotic activity.
Well-differentiated fetal hepatoblastoma. Strong nuclear β-catenin staining is present.
Well-differentiated fetal hepatoblastoma. Fine granular glypican-3 (GPC3) immunostaining staining is seen in the cells of well-differentiated fetal hepatoblastoma.
Well-differentiated fetal hepatoblastoma. Glutamine synthetase (GS) staining in the same case, showing strong cytoplasmic staining.
Hepatoblastoma. Crowded fetal pattern. An area with monotonous polygonal cells with increased N:C ratios and round nuclei. Note the extramedullary haematopoiesis.
Hepatoblastoma. Crowded fetal pattern showing fetal cells with larger nuclei and mitoses.
Hepatoblastoma. Embryonal hepatoblastoma with a small cell undifferentiated component, cells with scant cytoplasm and oval to angulated nuclei, and a focus of small cells in the upper quadrant.
Hepatoblastoma. Mixed hepatoblastoma showing the epithelial fetal pattern, osteoid, and blastema.
Hepatocellular neoplasm NOS. Biopsy of a lesion composed of primitive cells, some with angulated nuclei, but with an acinar arrangement, mimicking hepatocellular carcinoma.
Hepatocellular neoplasm NOS. There is nuclear β-catenin staining in almost every tumour cell.
PRETEXT staging. An illustration of pretreatment extent of disease (PRETEXT) staging as determined by the involvement of contiguous segments of liver.
Hepatoblastoma. Axial CT image obtained in the arterial phase of enhancement, showing a circumscribed, heterogeneously enhanced mass in the right lobe of the liver, displacing the gallbladder.

Q: The classic histological appearance of Mesenchymal Hamartoma of the Liver features a loose connective tissue stroma with tortuous, branched bile ducts that often demonstrate a [...] pattern.
Mesenchymal hamartoma. Dilated and branched ductal structures in a loose mesenchymal stroma containing bland spindle-shaped cells.
Mesenchymal hamartoma. Liver biopsy showing CK7 staining of the abnormal ductal structures, which are partly in a ductal plate arrangement.
A: ductal plate malformation
Back Extra: Mesenchymal Hamartoma of the Liver
- Clinical: Mesenchymal hamartoma of the liver typically presents with abdominal distension and an upper abdominal mass, with pain being a rare feature.
- Micro: The lesion is characterized by a loose connective tissue stroma with tortuous and branched bile ducts, often showing a ductal plate malformation pattern.
- Ancillary: Immunohistochemistry shows spindle cells positive for vimentin, actin, and desmin (focal), while ducts stain positively for CK7 and CK19.
Reference Gallery:
Mesenchymal hamartoma. A well-circumscribed tumour with solid and cystic areas.
Mesenchymal hamartoma. The cyst wall of this tumour is composed of a composite mixture of loose connective tissue, malformed bile ducts, hepatocyte islands, and dilated vessels.
Mesenchymal hamartoma. Higher-magnification image of the cyst wall showing a mixture of stromal and epithelial components and the inner surface of the cyst devoid of any lining cells.
Mesenchymal hamartoma. Solid tumour area featuring lobulated islands of haphazardly arranged loose connective tissue and bile ducts separated by hepatocytic parenchyma.
Mesenchymal hamartoma. Dilated and branched ductal structures in a loose mesenchymal stroma containing bland spindle-shaped cells.
Mesenchymal hamartoma. Dilated bile ducts surrounded by a concentric cuff of collagenous tissue.
Mesenchymal hamartoma. Dense collagenized stroma arranged concentrically around bile ducts.
Mesenchymal hamartoma. Liver biopsy showing an abnormal mixture of mesenchymal tissue and epithelial components.
Mesenchymal hamartoma. Liver biopsy showing CK7 staining of the abnormal ductal structures, which are partly in a ductal plate arrangement.

Q: A well-circumscribed hepatic tumor presenting with both solid and cystic areas, characterized histologically by a composite mixture of loose connective tissue, malformed bile ducts, and hepatocyte islands, is highly indicative of [...].
Mesenchymal hamartoma. A well-circumscribed tumour with solid and cystic areas.
Mesenchymal hamartoma. The cyst wall of this tumour is composed of a composite mixture of loose connective tissue, malformed bile ducts, hepatocyte islands, and dilated vessels.
A: Mesenchymal Hamartoma of the Liver
Back Extra: Mesenchymal Hamartoma of the Liver
- Clinical: Mesenchymal hamartoma of the liver typically presents with abdominal distension and an upper abdominal mass, with pain being a rare feature.
- Micro: The lesion is characterized by a loose connective tissue stroma with tortuous and branched bile ducts, often showing a ductal plate malformation pattern.
- Ancillary: Immunohistochemistry shows spindle cells positive for vimentin, actin, and desmin (focal), while ducts stain positively for CK7 and CK19.
Reference Gallery:
Mesenchymal hamartoma. A well-circumscribed tumour with solid and cystic areas.
Mesenchymal hamartoma. The cyst wall of this tumour is composed of a composite mixture of loose connective tissue, malformed bile ducts, hepatocyte islands, and dilated vessels.
Mesenchymal hamartoma. Higher-magnification image of the cyst wall showing a mixture of stromal and epithelial components and the inner surface of the cyst devoid of any lining cells.
Mesenchymal hamartoma. Solid tumour area featuring lobulated islands of haphazardly arranged loose connective tissue and bile ducts separated by hepatocytic parenchyma.
Mesenchymal hamartoma. Dilated and branched ductal structures in a loose mesenchymal stroma containing bland spindle-shaped cells.
Mesenchymal hamartoma. Dilated bile ducts surrounded by a concentric cuff of collagenous tissue.
Mesenchymal hamartoma. Dense collagenized stroma arranged concentrically around bile ducts.
Mesenchymal hamartoma. Liver biopsy showing an abnormal mixture of mesenchymal tissue and epithelial components.
Mesenchymal hamartoma. Liver biopsy showing CK7 staining of the abnormal ductal structures, which are partly in a ductal plate arrangement.

Q: In Mesenchymal Hamartoma of the Liver, immunohistochemistry of the abnormal, tortuous ductal structures demonstrates strong epithelial positivity for CK19 and [...].
Mesenchymal hamartoma. Liver biopsy showing CK7 staining of the abnormal ductal structures, which are partly in a ductal plate arrangement.
A: CK7
Back Extra: Mesenchymal Hamartoma of the Liver
- Clinical: Mesenchymal hamartoma of the liver typically presents with abdominal distension and an upper abdominal mass, with pain being a rare feature.
- Micro: The lesion is characterized by a loose connective tissue stroma with tortuous and branched bile ducts, often showing a ductal plate malformation pattern.
- Ancillary: Immunohistochemistry shows spindle cells positive for vimentin, actin, and desmin (focal), while ducts stain positively for CK7 and CK19.
Reference Gallery:
Mesenchymal hamartoma. A well-circumscribed tumour with solid and cystic areas.
Mesenchymal hamartoma. The cyst wall of this tumour is composed of a composite mixture of loose connective tissue, malformed bile ducts, hepatocyte islands, and dilated vessels.
Mesenchymal hamartoma. Higher-magnification image of the cyst wall showing a mixture of stromal and epithelial components and the inner surface of the cyst devoid of any lining cells.
Mesenchymal hamartoma. Solid tumour area featuring lobulated islands of haphazardly arranged loose connective tissue and bile ducts separated by hepatocytic parenchyma.
Mesenchymal hamartoma. Dilated and branched ductal structures in a loose mesenchymal stroma containing bland spindle-shaped cells.
Mesenchymal hamartoma. Dilated bile ducts surrounded by a concentric cuff of collagenous tissue.
Mesenchymal hamartoma. Dense collagenized stroma arranged concentrically around bile ducts.
Mesenchymal hamartoma. Liver biopsy showing an abnormal mixture of mesenchymal tissue and epithelial components.
Mesenchymal hamartoma. Liver biopsy showing CK7 staining of the abnormal ductal structures, which are partly in a ductal plate arrangement.

Q: Histologically, Pancreatic Acinar Cell Carcinoma is a highly cellular tumor with scant fibrous stroma that characteristically shows diffuse, strong immunohistochemical positivity for acinar markers such as trypsin and [...].
Pancreatic acinar cell carcinoma. A At low magnification, pancreatic acinar cell carcinoma shows solid and lobular growth and appears highly cellular, with scant fibrous stroma. B This case shows a solid pattern of growth characterized by large sheets of cells that have large nuclei with dispersed chromatin and prominent nucleoli. Only rare lumina are observed. Tumour cells are diffusely and strongly positive for BCL10 (C) and more focally positive for AFP (D), which was also elevated in the serum in this 10-year-old patient.
Pancreatic acinar cell carcinoma. This example, observed in a 1-year-old boy presenting with Cushing syndrome, shows a mixed architectural pattern including solid and acinar/glandular features in some areas (A) and trabeculae in others (B). Tumour cells are immunoreactive for trypsin (C) and focally immunoreactive for ACTH (D).
A: BCL10
Back Extra: Pancreatic Acinar Cell Carcinoma
- Clinical: Pancreatic Acinar Cell Carcinoma often presents with vague symptoms such as abdominal pain, swelling, and nausea. Serum AFP levels are elevated in pediatric patients.
- Micro: The tumor shows a highly cellular appearance with scant fibrous stroma, and cells may exhibit acinar, solid, or trabecular patterns.
- Ancillary: Immunohistochemistry is crucial, showing strong positivity for BCL10 and focal positivity for AFP and ACTH in cases presenting with Cushing syndrome.
Reference Gallery:
Pancreatic acinar cell carcinoma. A At low magnification, pancreatic acinar cell carcinoma shows solid and lobular growth and appears highly cellular, with scant fibrous stroma. B This case shows a solid pattern of growth characterized by large sheets of cells that have large nuclei with dispersed chromatin and prominent nucleoli. Only rare lumina are observed. Tumour cells are diffusely and strongly positive for BCL10 (C) and more focally positive for AFP (D), which was also elevated in the serum in this 10-year-old patient.
Pancreatic acinar cell carcinoma. This example, observed in a 1-year-old boy presenting with Cushing syndrome, shows a mixed architectural pattern including solid and acinar/glandular features in some areas (A) and trabeculae in others (B). Tumour cells are immunoreactive for trypsin (C) and focally immunoreactive for ACTH (D).

Q: Pediatric patients with Pancreatic Acinar Cell Carcinoma may present with elevated serum levels of [...], which can also be demonstrated focally within the tumor via immunohistochemistry.
Pancreatic acinar cell carcinoma. A At low magnification, pancreatic acinar cell carcinoma shows solid and lobular growth and appears highly cellular, with scant fibrous stroma. B This case shows a solid pattern of growth characterized by large sheets of cells that have large nuclei with dispersed chromatin and prominent nucleoli. Only rare lumina are observed. Tumour cells are diffusely and strongly positive for BCL10 (C) and more focally positive for AFP (D), which was also elevated in the serum in this 10-year-old patient.
A: alpha-fetoprotein (AFP)
Back Extra: Pancreatic Acinar Cell Carcinoma
- Clinical: Pancreatic Acinar Cell Carcinoma often presents with vague symptoms such as abdominal pain, swelling, and nausea. Serum AFP levels are elevated in pediatric patients.
- Micro: The tumor shows a highly cellular appearance with scant fibrous stroma, and cells may exhibit acinar, solid, or trabecular patterns.
- Ancillary: Immunohistochemistry is crucial, showing strong positivity for BCL10 and focal positivity for AFP and ACTH in cases presenting with Cushing syndrome.
Reference Gallery:
Pancreatic acinar cell carcinoma. A At low magnification, pancreatic acinar cell carcinoma shows solid and lobular growth and appears highly cellular, with scant fibrous stroma. B This case shows a solid pattern of growth characterized by large sheets of cells that have large nuclei with dispersed chromatin and prominent nucleoli. Only rare lumina are observed. Tumour cells are diffusely and strongly positive for BCL10 (C) and more focally positive for AFP (D), which was also elevated in the serum in this 10-year-old patient.
Pancreatic acinar cell carcinoma. This example, observed in a 1-year-old boy presenting with Cushing syndrome, shows a mixed architectural pattern including solid and acinar/glandular features in some areas (A) and trabeculae in others (B). Tumour cells are immunoreactive for trypsin (C) and focally immunoreactive for ACTH (D).

Q: Rarely, pediatric cases of Pancreatic Acinar Cell Carcinoma can present with Cushing syndrome due to ectopic tumor secretion and focal immunoreactivity for [...].
Pancreatic acinar cell carcinoma. This example, observed in a 1-year-old boy presenting with Cushing syndrome, shows a mixed architectural pattern including solid and acinar/glandular features in some areas (A) and trabeculae in others (B). Tumour cells are immunoreactive for trypsin (C) and focally immunoreactive for ACTH (D).
A: ACTH
Back Extra: Pancreatic Acinar Cell Carcinoma
- Clinical: Pancreatic Acinar Cell Carcinoma often presents with vague symptoms such as abdominal pain, swelling, and nausea. Serum AFP levels are elevated in pediatric patients.
- Micro: The tumor shows a highly cellular appearance with scant fibrous stroma, and cells may exhibit acinar, solid, or trabecular patterns.
- Ancillary: Immunohistochemistry is crucial, showing strong positivity for BCL10 and focal positivity for AFP and ACTH in cases presenting with Cushing syndrome.
Reference Gallery:
Pancreatic acinar cell carcinoma. A At low magnification, pancreatic acinar cell carcinoma shows solid and lobular growth and appears highly cellular, with scant fibrous stroma. B This case shows a solid pattern of growth characterized by large sheets of cells that have large nuclei with dispersed chromatin and prominent nucleoli. Only rare lumina are observed. Tumour cells are diffusely and strongly positive for BCL10 (C) and more focally positive for AFP (D), which was also elevated in the serum in this 10-year-old patient.
Pancreatic acinar cell carcinoma. This example, observed in a 1-year-old boy presenting with Cushing syndrome, shows a mixed architectural pattern including solid and acinar/glandular features in some areas (A) and trabeculae in others (B). Tumour cells are immunoreactive for trypsin (C) and focally immunoreactive for ACTH (D).

Q: A germ cell tumor consisting of a biphasic proliferation of mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts in a prominently hemorrhagic background is characteristic of [...].
Choriocarcinoma. Panoramic view of an area of haemorrhage and necrosis with foci of choriocarcinoma from a 17-year-old patient.
Choriocarcinoma. Cytotrophoblastic and syncytiotrophoblastic cells in a haemorrhagic background, characteristic of choriocarcinoma.
A: Choriocarcinoma (Non-Gestational)
Back Extra: Choriocarcinoma (Non-Gestational)
- Clinical: Choriocarcinoma often presents with signs or symptoms of distant metastasis, such as haemoptysis, abdominal mass, neurological dysfunction, anaemia, or hypotension.
- Micro: Choriocarcinoma is characterized by mononucleated trophoblasts (cytotrophoblasts and intermediate trophoblasts) and multinucleated syncytiotrophoblasts in a haemorrhagic background.
- Ancillary: Immunohistochemistry shows strong positivity for β-hCG, and isochromosome 12p is a key diagnostic finding.
Reference Gallery:
Choriocarcinoma. Panoramic view of an area of haemorrhage and necrosis with foci of choriocarcinoma from a 17-year-old patient.
Choriocarcinoma. Cytotrophoblastic and syncytiotrophoblastic cells in a haemorrhagic background, characteristic of choriocarcinoma.
Choriocarcinoma. Cytotrophoblast with multiple mitoses in a focus of choriocarcinoma.
Choriocarcinoma. Immunohistochemistry is strongly positive for β-hCG in choriocarcinoma.

Q: In Choriocarcinoma (Non-Gestational), immunohistochemical stains will demonstrate strong, characteristic positivity for [...].
Choriocarcinoma. Immunohistochemistry is strongly positive for β-hCG in choriocarcinoma.
A: β-hCG
Back Extra: Choriocarcinoma (Non-Gestational)
- Clinical: Choriocarcinoma often presents with signs or symptoms of distant metastasis, such as haemoptysis, abdominal mass, neurological dysfunction, anaemia, or hypotension.
- Micro: Choriocarcinoma is characterized by mononucleated trophoblasts (cytotrophoblasts and intermediate trophoblasts) and multinucleated syncytiotrophoblasts in a haemorrhagic background.
- Ancillary: Immunohistochemistry shows strong positivity for β-hCG, and isochromosome 12p is a key diagnostic finding.
Reference Gallery:
Choriocarcinoma. Panoramic view of an area of haemorrhage and necrosis with foci of choriocarcinoma from a 17-year-old patient.
Choriocarcinoma. Cytotrophoblastic and syncytiotrophoblastic cells in a haemorrhagic background, characteristic of choriocarcinoma.
Choriocarcinoma. Cytotrophoblast with multiple mitoses in a focus of choriocarcinoma.
Choriocarcinoma. Immunohistochemistry is strongly positive for β-hCG in choriocarcinoma.

Q: Histologically, the glandular pattern of Embryonal Carcinoma is typically composed of highly pleomorphic tumor cells that may be admixed with [...].
Embryonal carcinoma. The glandular pattern of embryonal carcinoma is composed of pleomorphic tumour cells and syncytiotrophoblastic giant cells.
A: syncytiotrophoblastic giant cells
Back Extra: Embryonal Carcinoma
- Clinical: Embryonal carcinoma is the second most common testicular germ cell tumour after seminoma, presenting as a testicular mass with potential metastatic disease in 10% of cases.
- Micro: Embryonal carcinoma cells are epithelioid with vesicular nuclei, dense amphophilic cytoplasm, and prominent mitoses and apoptosis.
- Ancillary: Isochromosome 12p and increased gains of 12p are diagnostic findings that help differentiate embryonal carcinoma from non-germ cell malignancies.
Reference Gallery:
Embryonal carcinoma. The glandular pattern of embryonal carcinoma is composed of pleomorphic tumour cells and syncytiotrophoblastic giant cells.
Embryonal carcinoma. SOX2 stains embryonal carcinoma in a nuclear pattern.

Q: By immunohistochemistry, Embryonal Carcinoma characteristically demonstrates positive nuclear staining for [...].
Embryonal carcinoma. SOX2 stains embryonal carcinoma in a nuclear pattern.
A: SOX2
Back Extra: Embryonal Carcinoma
- Clinical: Embryonal carcinoma is the second most common testicular germ cell tumour after seminoma, presenting as a testicular mass with potential metastatic disease in 10% of cases.
- Micro: Embryonal carcinoma cells are epithelioid with vesicular nuclei, dense amphophilic cytoplasm, and prominent mitoses and apoptosis.
- Ancillary: Isochromosome 12p and increased gains of 12p are diagnostic findings that help differentiate embryonal carcinoma from non-germ cell malignancies.
Reference Gallery:
Embryonal carcinoma. The glandular pattern of embryonal carcinoma is composed of pleomorphic tumour cells and syncytiotrophoblastic giant cells.
Embryonal carcinoma. SOX2 stains embryonal carcinoma in a nuclear pattern.

Q: Histologically, an Extragonadal Teratoma contains derivatives from multiple embryonic lineages; however, sacrococcygeal variants frequently feature primitive rosettes composed of [...] tissue.
Extragonadal teratoma. Histology from a mediastinal teratoma in a premature newborn (29th gestational week) showing various tissue types (respiratory and intestinal epithelium, acinic proliferations, a small cartilage island, and a few predominantly immature neuroepithelial elements).
Extragonadal teratoma. Histology from a sacrococcygeal teratoma in a fetus (25th gestational week) showing a focus of immature neuroepithelial tissue.
A: immature neuroepithelial
Back Extra: Extragonadal Teratoma
- Clinical: Congenital teratomas typically manifest in utero, often detected by sonography as a solid or mixed cystic and solid mass. Large lesions are associated with an increased risk of fetal demise and perinatal mortality.
- Micro: Teratomas contain tissues derived from all three germ cell layers (ectoderm, mesoderm, and endoderm). Immature tissue components, such as primitive neuroectodermal rosettes, are common in sacrococcygeal teratomas (SCT).
- Ancillary: Elevated hCG levels in neonates are physiologically normal and do not correlate with the presence of yolk sac tumor (YST) components.
Reference Gallery:
Extragonadal teratoma. Neonate with a large sacrococcygeal teratoma.
Extragonadal teratoma. Induced abortion of a fetus with a rapidly growing cervical teratoma (22nd gestational week).
Extragonadal teratoma. Cut surface of a mediastinal teratoma with solid and cystic areas.
Extragonadal teratoma. Histology from a mediastinal teratoma in a premature newborn (29th gestational week) showing various tissue types (respiratory and intestinal epithelium, acinic proliferations, a small cartilage island, and a few predominantly immature neuroepithelial elements).
Extragonadal teratoma. Histology from a resected sacrococcygeal teratoma in a newborn showing mature elements (brain tissue, a cyst with papillary epithelial proliferation, and fat tissue islands, in a dense collagenous stroma).
Extragonadal teratoma. Histology from a sacrococcygeal teratoma in a fetus (25th gestational week) showing a focus of immature neuroepithelial tissue.

Q: The most common anatomic location for a congenital Extragonadal Teratoma is the [...] region, which typically presents as a large, mixed solid and cystic mass in neonates.
Extragonadal teratoma. Neonate with a large sacrococcygeal teratoma.
A: sacrococcygeal
Back Extra: Extragonadal Teratoma
- Clinical: Congenital teratomas typically manifest in utero, often detected by sonography as a solid or mixed cystic and solid mass. Large lesions are associated with an increased risk of fetal demise and perinatal mortality.
- Micro: Teratomas contain tissues derived from all three germ cell layers (ectoderm, mesoderm, and endoderm). Immature tissue components, such as primitive neuroectodermal rosettes, are common in sacrococcygeal teratomas (SCT).
- Ancillary: Elevated hCG levels in neonates are physiologically normal and do not correlate with the presence of yolk sac tumor (YST) components.
Reference Gallery:
Extragonadal teratoma. Neonate with a large sacrococcygeal teratoma.
Extragonadal teratoma. Induced abortion of a fetus with a rapidly growing cervical teratoma (22nd gestational week).
Extragonadal teratoma. Cut surface of a mediastinal teratoma with solid and cystic areas.
Extragonadal teratoma. Histology from a mediastinal teratoma in a premature newborn (29th gestational week) showing various tissue types (respiratory and intestinal epithelium, acinic proliferations, a small cartilage island, and a few predominantly immature neuroepithelial elements).
Extragonadal teratoma. Histology from a resected sacrococcygeal teratoma in a newborn showing mature elements (brain tissue, a cyst with papillary epithelial proliferation, and fat tissue islands, in a dense collagenous stroma).
Extragonadal teratoma. Histology from a sacrococcygeal teratoma in a fetus (25th gestational week) showing a focus of immature neuroepithelial tissue.

Q: By definition, the microscopic diagnosis of a classic Extragonadal Teratoma requires the identification of tissue components derived from all three [...] (ectoderm, mesoderm, and endoderm).
Extragonadal teratoma. Histology from a mediastinal teratoma in a premature newborn (29th gestational week) showing various tissue types (respiratory and intestinal epithelium, acinic proliferations, a small cartilage island, and a few predominantly immature neuroepithelial elements).
Extragonadal teratoma. Histology from a resected sacrococcygeal teratoma in a newborn showing mature elements (brain tissue, a cyst with papillary epithelial proliferation, and fat tissue islands, in a dense collagenous stroma).
A: germ cell layers
Back Extra: Extragonadal Teratoma
- Clinical: Congenital teratomas typically manifest in utero, often detected by sonography as a solid or mixed cystic and solid mass. Large lesions are associated with an increased risk of fetal demise and perinatal mortality.
- Micro: Teratomas contain tissues derived from all three germ cell layers (ectoderm, mesoderm, and endoderm). Immature tissue components, such as primitive neuroectodermal rosettes, are common in sacrococcygeal teratomas (SCT).
- Ancillary: Elevated hCG levels in neonates are physiologically normal and do not correlate with the presence of yolk sac tumor (YST) components.
Reference Gallery:
Extragonadal teratoma. Neonate with a large sacrococcygeal teratoma.
Extragonadal teratoma. Induced abortion of a fetus with a rapidly growing cervical teratoma (22nd gestational week).
Extragonadal teratoma. Cut surface of a mediastinal teratoma with solid and cystic areas.
Extragonadal teratoma. Histology from a mediastinal teratoma in a premature newborn (29th gestational week) showing various tissue types (respiratory and intestinal epithelium, acinic proliferations, a small cartilage island, and a few predominantly immature neuroepithelial elements).
Extragonadal teratoma. Histology from a resected sacrococcygeal teratoma in a newborn showing mature elements (brain tissue, a cyst with papillary epithelial proliferation, and fat tissue islands, in a dense collagenous stroma).
Extragonadal teratoma. Histology from a sacrococcygeal teratoma in a fetus (25th gestational week) showing a focus of immature neuroepithelial tissue.

Q: Histologically, Germinoma/Dysgerminoma/Seminoma is characterized by uniform pale cells with clear cytoplasm and crisp cell membranes, typically arranged in nests that are separated by delicate fibrovascular septa containing a prominent infiltrate of [...].
Germinoma/dysgerminoma/seminoma. High-power view showing tumour cells with clear cytoplasm, crisp cytoplasmic membranes, and polygonal nuclei.
Germinoma/dysgerminoma/seminoma. Overview showing the diffuse arrangement of pale cells interrupted by fibrovascular septa containing lymphocytes.
A: lymphocytes
Back Extra: Germinoma/Dysgerminoma/Seminoma
- Clinical: Germinoma/Dysgerminoma/Seminoma can present with a testicular mass, visual disturbances, and endocrine disorders depending on the anatomical location.
- Micro: These tumours show a diffuse arrangement of pale cells with clear cytoplasm, crisp cytoplasmic membranes, and polygonal nuclei, often interrupted by fibrovascular septa containing lymphocytes.
- Ancillary: Immunohistochemically, germinomas are positive for KIT (CD117), OCT3/4, SALL4, SOX17, and podoplanin, and typically show 12p alterations (isochromosome 12p, 12p gains).
Reference Gallery:
Germinoma/dysgerminoma/seminoma. High-power view showing tumour cells with clear cytoplasm, crisp cytoplasmic membranes, and polygonal nuclei.
Germinoma/dysgerminoma/seminoma. Overview showing the diffuse arrangement of pale cells interrupted by fibrovascular septa containing lymphocytes.
Germinoma. MRI showing a sellar germ cell tumour.
Germinoma/dysgerminoma/seminoma with syncytiotrophoblast cells. β-hCG staining highlights clusters of syncytiotrophoblast cells. The germinoma/dysgerminoma/seminoma tumour cells are negative.
Germinoma/dysgerminoma/seminoma with syncytiotrophoblast cells. OCT3/4 staining highlights the germinoma/dysgerminoma/seminoma tumour cells. The syncytiotrophoblast cells are negative.
Seminoma. Pale, lobular cut surface.
Postpubertal germ cell tumour. FISH showing 12p gain and isochromosome 12p (circle).
Cytology of germinoma. Smear preparation with large tumour cells in a homogeneous and tigroid background.
Germinoma/dysgerminoma/seminoma. This example shows admixed multinucleated syncytiotrophoblast cells.
Germinoma. T1-weighted sagittal MRI shows a poorly defined heterogeneous isointense to hypointense mass (extent marked by the two arrows) at the sellar and suprasellar region. Note the loss of the normal T1 bright spot of the posterior pituitary gland.
Germinoma. Contrast-enhanced T1-weighted sagittal MRI shows moderate enhancement of the tumour, the extent of which is shown by the two arrows.

Q: Cytogenetic analysis (such as FISH) of postpubertal Germinoma/Dysgerminoma/Seminoma frequently reveals a characteristic [...] or corresponding genetic gains in the short arm of this chromosome.
Postpubertal germ cell tumour. FISH showing 12p gain and isochromosome 12p (circle).
A: isochromosome 12p
Back Extra: Germinoma/Dysgerminoma/Seminoma
- Clinical: Germinoma/Dysgerminoma/Seminoma can present with a testicular mass, visual disturbances, and endocrine disorders depending on the anatomical location.
- Micro: These tumours show a diffuse arrangement of pale cells with clear cytoplasm, crisp cytoplasmic membranes, and polygonal nuclei, often interrupted by fibrovascular septa containing lymphocytes.
- Ancillary: Immunohistochemically, germinomas are positive for KIT (CD117), OCT3/4, SALL4, SOX17, and podoplanin, and typically show 12p alterations (isochromosome 12p, 12p gains).
Reference Gallery:
Germinoma/dysgerminoma/seminoma. High-power view showing tumour cells with clear cytoplasm, crisp cytoplasmic membranes, and polygonal nuclei.
Germinoma/dysgerminoma/seminoma. Overview showing the diffuse arrangement of pale cells interrupted by fibrovascular septa containing lymphocytes.
Germinoma. MRI showing a sellar germ cell tumour.
Germinoma/dysgerminoma/seminoma with syncytiotrophoblast cells. β-hCG staining highlights clusters of syncytiotrophoblast cells. The germinoma/dysgerminoma/seminoma tumour cells are negative.
Germinoma/dysgerminoma/seminoma with syncytiotrophoblast cells. OCT3/4 staining highlights the germinoma/dysgerminoma/seminoma tumour cells. The syncytiotrophoblast cells are negative.
Seminoma. Pale, lobular cut surface.
Postpubertal germ cell tumour. FISH showing 12p gain and isochromosome 12p (circle).
Cytology of germinoma. Smear preparation with large tumour cells in a homogeneous and tigroid background.
Germinoma/dysgerminoma/seminoma. This example shows admixed multinucleated syncytiotrophoblast cells.
Germinoma. T1-weighted sagittal MRI shows a poorly defined heterogeneous isointense to hypointense mass (extent marked by the two arrows) at the sellar and suprasellar region. Note the loss of the normal T1 bright spot of the posterior pituitary gland.
Germinoma. Contrast-enhanced T1-weighted sagittal MRI shows moderate enhancement of the tumour, the extent of which is shown by the two arrows.

Q: On cytologic smear preparations, Germinoma/Dysgerminoma/Seminoma classically demonstrates large tumor cells set against a characteristic, stripped or [...] background.
Cytology of germinoma. Smear preparation with large tumour cells in a homogeneous and tigroid background.
A: tigroid
Back Extra: Germinoma/Dysgerminoma/Seminoma
- Clinical: Germinoma/Dysgerminoma/Seminoma can present with a testicular mass, visual disturbances, and endocrine disorders depending on the anatomical location.
- Micro: These tumours show a diffuse arrangement of pale cells with clear cytoplasm, crisp cytoplasmic membranes, and polygonal nuclei, often interrupted by fibrovascular septa containing lymphocytes.
- Ancillary: Immunohistochemically, germinomas are positive for KIT (CD117), OCT3/4, SALL4, SOX17, and podoplanin, and typically show 12p alterations (isochromosome 12p, 12p gains).
Reference Gallery:
Germinoma/dysgerminoma/seminoma. High-power view showing tumour cells with clear cytoplasm, crisp cytoplasmic membranes, and polygonal nuclei.
Germinoma/dysgerminoma/seminoma. Overview showing the diffuse arrangement of pale cells interrupted by fibrovascular septa containing lymphocytes.
Germinoma. MRI showing a sellar germ cell tumour.
Germinoma/dysgerminoma/seminoma with syncytiotrophoblast cells. β-hCG staining highlights clusters of syncytiotrophoblast cells. The germinoma/dysgerminoma/seminoma tumour cells are negative.
Germinoma/dysgerminoma/seminoma with syncytiotrophoblast cells. OCT3/4 staining highlights the germinoma/dysgerminoma/seminoma tumour cells. The syncytiotrophoblast cells are negative.
Seminoma. Pale, lobular cut surface.
Postpubertal germ cell tumour. FISH showing 12p gain and isochromosome 12p (circle).
Cytology of germinoma. Smear preparation with large tumour cells in a homogeneous and tigroid background.
Germinoma/dysgerminoma/seminoma. This example shows admixed multinucleated syncytiotrophoblast cells.
Germinoma. T1-weighted sagittal MRI shows a poorly defined heterogeneous isointense to hypointense mass (extent marked by the two arrows) at the sellar and suprasellar region. Note the loss of the normal T1 bright spot of the posterior pituitary gland.
Germinoma. Contrast-enhanced T1-weighted sagittal MRI shows moderate enhancement of the tumour, the extent of which is shown by the two arrows.

Q: In Immature Teratoma, the defining microscopic finding is the presence of immature [...] tissue, which often forms primitive neural tubules and rosettes with hyperchromatic nuclei.
Immature teratoma. The immature neuroectodermal tissue forms primitive neural tubules lined by cells with increased N:C ratios. The nuclei are enlarged and hyperchromatic. Mitotic figures and apoptotic bodies are present.
A: neuroectodermal
Back Extra: Immature Teratoma
- Clinical: Immature teratoma usually manifests as a pelvic mass, and elevated serum AFP should prompt more extensive sampling to rule out a component of yolk sac tumor.
- Micro: Immature teratoma contains variable amounts of immature neuroectodermal tissue, often forming primitive neural tubules and rosettes with hyperchromatic nuclei and increased mitotic activity.
- Ancillary: Grading is based on the number of low-power microscopic fields containing aggregated amounts of immature neuroectoderm, and any foci of yolk sac tumor should be quantified in the pathology report.
Reference Gallery:
Immature teratoma. The extent of immature neuroectodermal tissue in this case is consistent with grade 1.
Immature teratoma. The immature neuroectodermal tissue forms primitive neural tubules lined by cells with increased N:C ratios. The nuclei are enlarged and hyperchromatic. Mitotic figures and apoptotic bodies are present.
Immature teratoma. The extent of immature neuroectodermal tissue in this case is consistent with grade 3.
Immature teratoma, ovarian. Contrast-enhanced axial CT shows a heterogeneous mixed solid-cystic pelvic mass containing calcifications (dense material) and punctate foci of fat (very low density material).

Q: The histologic grade of an Immature Teratoma is directly determined by the aggregated amount of immature [...] present across low-power microscopic fields.
Immature teratoma. The extent of immature neuroectodermal tissue in this case is consistent with grade 1.
Immature teratoma. The extent of immature neuroectodermal tissue in this case is consistent with grade 3.
A: neuroectoderm
Back Extra: Immature Teratoma
- Clinical: Immature teratoma usually manifests as a pelvic mass, and elevated serum AFP should prompt more extensive sampling to rule out a component of yolk sac tumor.
- Micro: Immature teratoma contains variable amounts of immature neuroectodermal tissue, often forming primitive neural tubules and rosettes with hyperchromatic nuclei and increased mitotic activity.
- Ancillary: Grading is based on the number of low-power microscopic fields containing aggregated amounts of immature neuroectoderm, and any foci of yolk sac tumor should be quantified in the pathology report.
Reference Gallery:
Immature teratoma. The extent of immature neuroectodermal tissue in this case is consistent with grade 1.
Immature teratoma. The immature neuroectodermal tissue forms primitive neural tubules lined by cells with increased N:C ratios. The nuclei are enlarged and hyperchromatic. Mitotic figures and apoptotic bodies are present.
Immature teratoma. The extent of immature neuroectodermal tissue in this case is consistent with grade 3.
Immature teratoma, ovarian. Contrast-enhanced axial CT shows a heterogeneous mixed solid-cystic pelvic mass containing calcifications (dense material) and punctate foci of fat (very low density material).

Q: Radiographically, an ovarian Immature Teratoma typically appears on CT imaging as a heterogeneous mixed solid-cystic pelvic mass that contains dense calcifications and punctate foci of very low-density [...].
Immature teratoma, ovarian. Contrast-enhanced axial CT shows a heterogeneous mixed solid-cystic pelvic mass containing calcifications (dense material) and punctate foci of fat (very low density material).
A: fat
Back Extra: Immature Teratoma
- Clinical: Immature teratoma usually manifests as a pelvic mass, and elevated serum AFP should prompt more extensive sampling to rule out a component of yolk sac tumor.
- Micro: Immature teratoma contains variable amounts of immature neuroectodermal tissue, often forming primitive neural tubules and rosettes with hyperchromatic nuclei and increased mitotic activity.
- Ancillary: Grading is based on the number of low-power microscopic fields containing aggregated amounts of immature neuroectoderm, and any foci of yolk sac tumor should be quantified in the pathology report.
Reference Gallery:
Immature teratoma. The extent of immature neuroectodermal tissue in this case is consistent with grade 1.
Immature teratoma. The immature neuroectodermal tissue forms primitive neural tubules lined by cells with increased N:C ratios. The nuclei are enlarged and hyperchromatic. Mitotic figures and apoptotic bodies are present.
Immature teratoma. The extent of immature neuroectodermal tissue in this case is consistent with grade 3.
Immature teratoma, ovarian. Contrast-enhanced axial CT shows a heterogeneous mixed solid-cystic pelvic mass containing calcifications (dense material) and punctate foci of fat (very low density material).

Q: Microscopically, Intratubular Germ Cell Neoplasia (Male Gonadal) consists of atypical cells with clear cytoplasm and large, angulated nuclei located in the spermatogonial niche, typically arranged in a single layer resembling a [...].
Early germ cell neoplasia in situ. The encircled tubule shows within the spermatogonial niches a clonal expansion of germ cells with enlarged nuclei (arrow), coexpressing OCT4 (nuclear, brown) and TSPY (membranous, blue), arranged as the beginning of a string of beads, characterizing this lesion as early germ cell neoplasia in situ. The other tubules show germ cells in the niches expressing TSPY with and without OCT4. The morphology in these tubules is still compatible with pre–germ cell neoplasia in situ. Inset: For comparison, full-blown germ cell neoplasia in situ is shown, in which all tumour cells express OCT4 (and in this case also TSPY, but this is not essential).
A: string of beads
Intratubular Germ Cell Neoplasia (Male Gonadal)
- Clinical: Adults with Intratubular Germ Cell Neoplasia (Male Gonadal) are usually symptomless or present with mild testicular pain and relatively small testes (6–12 mL).
- Micro: Intratubular Germ Cell Neoplasia (Male Gonadal) consists of atypical cells resembling gonocytes with ample clear cytoplasm and large (10–11 µm) angulated nuclei, typically located in the niche of spermatogonia, in one layer resembling a string of beads.
- Ancillary: Immunohistochemical markers such as OCT4 and KIT are crucial for diagnosing Intratubular Germ Cell Neoplasia (Male Gonadal).
Reference Gallery:
Ultrasound pattern of microlithiasis in testis. Sonogram showing testicular microlithiasis with numerous intratesticular echogenic foci, 1–2 mm in diameter. This speckled appearance is characteristic of testicular microlithiasis. Inset: Microscopy of microlith.
Early germ cell neoplasia in situ. The encircled tubule shows within the spermatogonial niches a clonal expansion of germ cells with enlarged nuclei (arrow), coexpressing OCT4 (nuclear, brown) and TSPY (membranous, blue), arranged as the beginning of a string of beads, characterizing this lesion as early germ cell neoplasia in situ. The other tubules show germ cells in the niches expressing TSPY with and without OCT4. The morphology in these tubules is still compatible with pre–germ cell neoplasia in situ. Inset: For comparison, full-blown germ cell neoplasia in situ is shown, in which all tumour cells express OCT4 (and in this case also TSPY, but this is not essential).
Testicular germ cell neoplasia in situ. KITLG is diffusely expressed, mostly (but not exclusively) in a granular pattern in the Sertoli cells of tubules containing germ cell neoplasia in situ.
Floating germ cell neoplasia in situ cells. Progression to independence from Sertoli cells allows germ cell neoplasia in situ cells to leave the spermatogonial niches, get stacked in multiple layers (open arrowheads), float within the tubules (arrows), and colonize adjacent normal tubules (solid arrowheads) by reoccupying spermatogonial niches.
Host response clears germ cell neoplasia in situ over time. Parenchyma of seminoma in an elderly patient. The host response has almost completely wiped out the seminoma. It has also virtually cleared germ cell neoplasia in situ from the tubules, which have become entirely fibrotic in the process.

Q: Immunohistochemistry is crucial for confirming the diagnosis of Intratubular Germ Cell Neoplasia (Male Gonadal), as the atypical germ cells characteristically demonstrate strong positivity for KIT and [...].
Early germ cell neoplasia in situ. The encircled tubule shows within the spermatogonial niches a clonal expansion of germ cells with enlarged nuclei (arrow), coexpressing OCT4 (nuclear, brown) and TSPY (membranous, blue), arranged as the beginning of a string of beads, characterizing this lesion as early germ cell neoplasia in situ. The other tubules show germ cells in the niches expressing TSPY with and without OCT4. The morphology in these tubules is still compatible with pre–germ cell neoplasia in situ. Inset: For comparison, full-blown germ cell neoplasia in situ is shown, in which all tumour cells express OCT4 (and in this case also TSPY, but this is not essential).
A: OCT4
Intratubular Germ Cell Neoplasia (Male Gonadal)
- Clinical: Adults with Intratubular Germ Cell Neoplasia (Male Gonadal) are usually symptomless or present with mild testicular pain and relatively small testes (6–12 mL).
- Micro: Intratubular Germ Cell Neoplasia (Male Gonadal) consists of atypical cells resembling gonocytes with ample clear cytoplasm and large (10–11 µm) angulated nuclei, typically located in the niche of spermatogonia, in one layer resembling a string of beads.
- Ancillary: Immunohistochemical markers such as OCT4 and KIT are crucial for diagnosing Intratubular Germ Cell Neoplasia (Male Gonadal).
Reference Gallery:
Ultrasound pattern of microlithiasis in testis. Sonogram showing testicular microlithiasis with numerous intratesticular echogenic foci, 1–2 mm in diameter. This speckled appearance is characteristic of testicular microlithiasis. Inset: Microscopy of microlith.
Early germ cell neoplasia in situ. The encircled tubule shows within the spermatogonial niches a clonal expansion of germ cells with enlarged nuclei (arrow), coexpressing OCT4 (nuclear, brown) and TSPY (membranous, blue), arranged as the beginning of a string of beads, characterizing this lesion as early germ cell neoplasia in situ. The other tubules show germ cells in the niches expressing TSPY with and without OCT4. The morphology in these tubules is still compatible with pre–germ cell neoplasia in situ. Inset: For comparison, full-blown germ cell neoplasia in situ is shown, in which all tumour cells express OCT4 (and in this case also TSPY, but this is not essential).
Testicular germ cell neoplasia in situ. KITLG is diffusely expressed, mostly (but not exclusively) in a granular pattern in the Sertoli cells of tubules containing germ cell neoplasia in situ.
Floating germ cell neoplasia in situ cells. Progression to independence from Sertoli cells allows germ cell neoplasia in situ cells to leave the spermatogonial niches, get stacked in multiple layers (open arrowheads), float within the tubules (arrows), and colonize adjacent normal tubules (solid arrowheads) by reoccupying spermatogonial niches.
Host response clears germ cell neoplasia in situ over time. Parenchyma of seminoma in an elderly patient. The host response has almost completely wiped out the seminoma. It has also virtually cleared germ cell neoplasia in situ from the tubules, which have become entirely fibrotic in the process.

Q: A testicular mass in a young male showing a heterogeneous histologic mixture of components, such as embryonal carcinoma, teratoma, and yolk sac tumor, is diagnostic of a [...].
Malignant mixed germ cell tumour. An area of embryonal carcinoma in the tumour shown in Fig. 23829 from a 17-year-old boy with multiple copies of isochromosome 12p.
Malignant mixed germ cell tumour. Teratomatous component represented by intestinal glandular structures in an 18-year-old male patient.
A: Malignant Mixed Germ Cell Tumor
Back Extra: Malignant Mixed Germ Cell Tumour
- Clinical: Malignant Mixed Germ Cell Tumours (MMGCTs) are the majority of non-seminomatous testicular tumours, often presenting with elevated tumour markers and potential metastases.
- Micro: Histopathological features of MMGCTs include a mix of components such as yolk sac tumour, embryonal carcinoma, and teratoma, with the yolk sac tumour component often missed.
- Ancillary: Diagnosis involves immunohistochemistry for markers like OCT3/4, PLAP, AFP, hCG, and glypican-3 (GPC3).
Reference Gallery:
Malignant mixed germ cell tumour. Orchiectomy specimen from a 17-year-old boy.
Malignant mixed germ cell tumour. Cut surface shows a multicystic and fleshy tumour with multifocal haemorrhage replacing most of the testicular parenchyma in this example from a 17-year-old boy.
Malignant mixed germ cell tumour. A Schiller–Duval body in an area of yolk sac tumour from an orchiectomy specimen from a 17-year-old patient. Cytogenetic analysis revealed two copies of the short arm of chromosome 12 (isochromosome 12p), along with four copies of chromosome 12, resulting in five or six copies of 12p and other chromosomal abnormalities.
Malignant mixed germ cell tumour. An area of embryonal carcinoma in the tumour shown in Fig. 23829 from a 17-year-old boy with multiple copies of isochromosome 12p.
Malignant mixed germ cell tumour. A focus of seminoma at the borderline with the testicular parenchyma showing seminiferous tubules with germ cell neoplasia in situ. This example is from an 18-year-old male patient.
Malignant mixed germ cell tumour. Teratomatous component represented by intestinal glandular structures in an 18-year-old male patient.
Malignant mixed germ cell tumour. Peritumoural testicular parenchyma showing seminiferous tubules with the classic appearance of germ cell neoplasia in situ. This is from the 17-year-old boy with multiple copies of isochromosome 12p (see Fig. 23829).
Malignant mixed germ cell tumour. A yolk sac tumour area is highlighted by glypican-3 (GPC3) immunohistochemistry in this example from a 17-year-old boy.
Malignant mixed germ cell tumour. Contrast-enhanced axial CT shows a mixed solid and cystic mass with irregular enhancing fibrovascular septa.

Q: In a Malignant Mixed Germ Cell Tumor, the often-overlooked yolk sac component can be highlighted using immunohistochemistry for [...].
Malignant mixed germ cell tumour. A yolk sac tumour area is highlighted by glypican-3 (GPC3) immunohistochemistry in this example from a 17-year-old boy.
A: glypican-3 (GPC3)
Back Extra: Malignant Mixed Germ Cell Tumour
- Clinical: Malignant Mixed Germ Cell Tumours (MMGCTs) are the majority of non-seminomatous testicular tumours, often presenting with elevated tumour markers and potential metastases.
- Micro: Histopathological features of MMGCTs include a mix of components such as yolk sac tumour, embryonal carcinoma, and teratoma, with the yolk sac tumour component often missed.
- Ancillary: Diagnosis involves immunohistochemistry for markers like OCT3/4, PLAP, AFP, hCG, and glypican-3 (GPC3).
Reference Gallery:
Malignant mixed germ cell tumour. Orchiectomy specimen from a 17-year-old boy.
Malignant mixed germ cell tumour. Cut surface shows a multicystic and fleshy tumour with multifocal haemorrhage replacing most of the testicular parenchyma in this example from a 17-year-old boy.
Malignant mixed germ cell tumour. A Schiller–Duval body in an area of yolk sac tumour from an orchiectomy specimen from a 17-year-old patient. Cytogenetic analysis revealed two copies of the short arm of chromosome 12 (isochromosome 12p), along with four copies of chromosome 12, resulting in five or six copies of 12p and other chromosomal abnormalities.
Malignant mixed germ cell tumour. An area of embryonal carcinoma in the tumour shown in Fig. 23829 from a 17-year-old boy with multiple copies of isochromosome 12p.
Malignant mixed germ cell tumour. A focus of seminoma at the borderline with the testicular parenchyma showing seminiferous tubules with germ cell neoplasia in situ. This example is from an 18-year-old male patient.
Malignant mixed germ cell tumour. Teratomatous component represented by intestinal glandular structures in an 18-year-old male patient.
Malignant mixed germ cell tumour. Peritumoural testicular parenchyma showing seminiferous tubules with the classic appearance of germ cell neoplasia in situ. This is from the 17-year-old boy with multiple copies of isochromosome 12p (see Fig. 23829).
Malignant mixed germ cell tumour. A yolk sac tumour area is highlighted by glypican-3 (GPC3) immunohistochemistry in this example from a 17-year-old boy.
Malignant mixed germ cell tumour. Contrast-enhanced axial CT shows a mixed solid and cystic mass with irregular enhancing fibrovascular septa.

Q: Microscopic examination of a Malignant Mixed Germ Cell Tumor may reveal a yolk sac component characterized by pathognomonic glomeruloid structures known as [...].
Malignant mixed germ cell tumour. A Schiller–Duval body in an area of yolk sac tumour from an orchiectomy specimen from a 17-year-old patient. Cytogenetic analysis revealed two copies of the short arm of chromosome 12 (isochromosome 12p), along with four copies of chromosome 12, resulting in five or six copies of 12p and other chromosomal abnormalities.
A: Schiller-Duval bodies
Back Extra: Malignant Mixed Germ Cell Tumour
- Clinical: Malignant Mixed Germ Cell Tumours (MMGCTs) are the majority of non-seminomatous testicular tumours, often presenting with elevated tumour markers and potential metastases.
- Micro: Histopathological features of MMGCTs include a mix of components such as yolk sac tumour, embryonal carcinoma, and teratoma, with the yolk sac tumour component often missed.
- Ancillary: Diagnosis involves immunohistochemistry for markers like OCT3/4, PLAP, AFP, hCG, and glypican-3 (GPC3).
Reference Gallery:
Malignant mixed germ cell tumour. Orchiectomy specimen from a 17-year-old boy.
Malignant mixed germ cell tumour. Cut surface shows a multicystic and fleshy tumour with multifocal haemorrhage replacing most of the testicular parenchyma in this example from a 17-year-old boy.
Malignant mixed germ cell tumour. A Schiller–Duval body in an area of yolk sac tumour from an orchiectomy specimen from a 17-year-old patient. Cytogenetic analysis revealed two copies of the short arm of chromosome 12 (isochromosome 12p), along with four copies of chromosome 12, resulting in five or six copies of 12p and other chromosomal abnormalities.
Malignant mixed germ cell tumour. An area of embryonal carcinoma in the tumour shown in Fig. 23829 from a 17-year-old boy with multiple copies of isochromosome 12p.
Malignant mixed germ cell tumour. A focus of seminoma at the borderline with the testicular parenchyma showing seminiferous tubules with germ cell neoplasia in situ. This example is from an 18-year-old male patient.
Malignant mixed germ cell tumour. Teratomatous component represented by intestinal glandular structures in an 18-year-old male patient.
Malignant mixed germ cell tumour. Peritumoural testicular parenchyma showing seminiferous tubules with the classic appearance of germ cell neoplasia in situ. This is from the 17-year-old boy with multiple copies of isochromosome 12p (see Fig. 23829).
Malignant mixed germ cell tumour. A yolk sac tumour area is highlighted by glypican-3 (GPC3) immunohistochemistry in this example from a 17-year-old boy.
Malignant mixed germ cell tumour. Contrast-enhanced axial CT shows a mixed solid and cystic mass with irregular enhancing fibrovascular septa.

Q: Mature cystic teratoma characteristically exhibits cysts lined by stratified squamous epithelium with associated [...].
Mature cystic teratoma. Gross specimen showing cut surface with abundant sebaceous material and hair.
Mature cystic teratoma, testis. A stratified squamous epithelial lining with associated pilosebaceous units lines a cyst. The adjacent testis of this teenage boy shows normal seminiferous tubules.
A: pilosebaceous units
Back Extra: Mature Cystic Teratoma
- Clinical: Mature cystic teratoma is a type I germ cell tumour that presents with abdominal pain or a mass, and is commonly detected in the testes of paediatric patients aged 1.5–2.5 years.
- Micro: The microscopic features of mature cystic teratoma include ectodermal derivatives (squamous epithelium, neuroectoderm), mesodermal derivatives (adipose tissue, bone, cartilage, smooth muscle), and endodermal derivatives (gastrointestinal and respiratory epithelium).
- Ancillary: While ancillary studies are not typically necessary for diagnosis, imaging such as CT can help identify the presence of a Rokitansky nodule and foci of calcification and fat within the mass.
Reference Gallery:
Mature cystic teratoma. Gross specimen showing cut surface with abundant sebaceous material and hair.
Mature cystic teratoma, testis. Dilated and tubular glands are embedded in a smooth muscle stroma. There was no cytological atypia in this prepubertal-type teratoma from a teenage boy.
Mature cystic teratoma, testis. A stratified squamous epithelial lining with associated pilosebaceous units lines a cyst. The adjacent testis of this teenage boy shows normal seminiferous tubules.
Mature cystic teratoma, testis. Higher-magnification view of the case shown in Fig. 18259.
Mature cystic teratoma, ovary. A prominent lipogranulomatous reaction, as shown here, can be associated with ruptured squamous elements.
Mature cystic teratoma, ovary. The choroid plexus, as in this example, may be associated with glial components.
Mature cystic teratoma, ovary. A nodule of cartilage is noted adjacent to smooth muscle and adipose tissue.
Mature cystic teratoma. Contrast-enhanced axial CT shows a large cystic mass with a focal enhancing soft tissue protuberance, known as the Rokitansky nodule. Within the nodule, there are multiple foci of calcification and a focus of very low density suggestive of fat.
Mature cystic teratoma. Contrast-enhanced coronal reformatted CT shows a large cystic mass in the central abdomen displacing the bowel loops. There is a focal Rokitansky nodule containing multiple internal foci of calcifications. Additional foci of very low density suggestive of a fat component are also evident within the mass.

Q: In mature cystic teratoma, contrast-enhanced CT often demonstrates a cystic mass containing fat and calcifications, along with a focal enhancing soft tissue protuberance known as a [...].
Mature cystic teratoma. Contrast-enhanced axial CT shows a large cystic mass with a focal enhancing soft tissue protuberance, known as the Rokitansky nodule. Within the nodule, there are multiple foci of calcification and a focus of very low density suggestive of fat.
Mature cystic teratoma. Contrast-enhanced coronal reformatted CT shows a large cystic mass in the central abdomen displacing the bowel loops. There is a focal Rokitansky nodule containing multiple internal foci of calcifications. Additional foci of very low density suggestive of a fat component are also evident within the mass.
A: Rokitansky nodule
Back Extra: Mature Cystic Teratoma
- Clinical: Mature cystic teratoma is a type I germ cell tumour that presents with abdominal pain or a mass, and is commonly detected in the testes of paediatric patients aged 1.5–2.5 years.
- Micro: The microscopic features of mature cystic teratoma include ectodermal derivatives (squamous epithelium, neuroectoderm), mesodermal derivatives (adipose tissue, bone, cartilage, smooth muscle), and endodermal derivatives (gastrointestinal and respiratory epithelium).
- Ancillary: While ancillary studies are not typically necessary for diagnosis, imaging such as CT can help identify the presence of a Rokitansky nodule and foci of calcification and fat within the mass.
Reference Gallery:
Mature cystic teratoma. Gross specimen showing cut surface with abundant sebaceous material and hair.
Mature cystic teratoma, testis. Dilated and tubular glands are embedded in a smooth muscle stroma. There was no cytological atypia in this prepubertal-type teratoma from a teenage boy.
Mature cystic teratoma, testis. A stratified squamous epithelial lining with associated pilosebaceous units lines a cyst. The adjacent testis of this teenage boy shows normal seminiferous tubules.
Mature cystic teratoma, testis. Higher-magnification view of the case shown in Fig. 18259.
Mature cystic teratoma, ovary. A prominent lipogranulomatous reaction, as shown here, can be associated with ruptured squamous elements.
Mature cystic teratoma, ovary. The choroid plexus, as in this example, may be associated with glial components.
Mature cystic teratoma, ovary. A nodule of cartilage is noted adjacent to smooth muscle and adipose tissue.
Mature cystic teratoma. Contrast-enhanced axial CT shows a large cystic mass with a focal enhancing soft tissue protuberance, known as the Rokitansky nodule. Within the nodule, there are multiple foci of calcification and a focus of very low density suggestive of fat.
Mature cystic teratoma. Contrast-enhanced coronal reformatted CT shows a large cystic mass in the central abdomen displacing the bowel loops. There is a focal Rokitansky nodule containing multiple internal foci of calcifications. Additional foci of very low density suggestive of a fat component are also evident within the mass.

Q: A prominent [...] giant cell reaction can be seen in mature cystic teratoma when the squamous elements rupture into the surrounding stroma.
Mature cystic teratoma, ovary. A prominent lipogranulomatous reaction, as shown here, can be associated with ruptured squamous elements.
A: lipogranulomatous
Back Extra: Mature Cystic Teratoma
- Clinical: Mature cystic teratoma is a type I germ cell tumour that presents with abdominal pain or a mass, and is commonly detected in the testes of paediatric patients aged 1.5–2.5 years.
- Micro: The microscopic features of mature cystic teratoma include ectodermal derivatives (squamous epithelium, neuroectoderm), mesodermal derivatives (adipose tissue, bone, cartilage, smooth muscle), and endodermal derivatives (gastrointestinal and respiratory epithelium).
- Ancillary: While ancillary studies are not typically necessary for diagnosis, imaging such as CT can help identify the presence of a Rokitansky nodule and foci of calcification and fat within the mass.
Reference Gallery:
Mature cystic teratoma. Gross specimen showing cut surface with abundant sebaceous material and hair.
Mature cystic teratoma, testis. Dilated and tubular glands are embedded in a smooth muscle stroma. There was no cytological atypia in this prepubertal-type teratoma from a teenage boy.
Mature cystic teratoma, testis. A stratified squamous epithelial lining with associated pilosebaceous units lines a cyst. The adjacent testis of this teenage boy shows normal seminiferous tubules.
Mature cystic teratoma, testis. Higher-magnification view of the case shown in Fig. 18259.
Mature cystic teratoma, ovary. A prominent lipogranulomatous reaction, as shown here, can be associated with ruptured squamous elements.
Mature cystic teratoma, ovary. The choroid plexus, as in this example, may be associated with glial components.
Mature cystic teratoma, ovary. A nodule of cartilage is noted adjacent to smooth muscle and adipose tissue.
Mature cystic teratoma. Contrast-enhanced axial CT shows a large cystic mass with a focal enhancing soft tissue protuberance, known as the Rokitansky nodule. Within the nodule, there are multiple foci of calcification and a focus of very low density suggestive of fat.
Mature cystic teratoma. Contrast-enhanced coronal reformatted CT shows a large cystic mass in the central abdomen displacing the bowel loops. There is a focal Rokitansky nodule containing multiple internal foci of calcifications. Additional foci of very low density suggestive of a fat component are also evident within the mass.

Q: A prominent variant of Monodermal Teratoma (Female Gonadal) is struma ovarii, which is composed of [...] filled with colloid and can rarely present with clinical hyperthyroidism.
Struma ovarii. The tumour is composed of thyroid follicles filled with colloid.
Struma ovarii. Higher-power magnification of the case shown in Fig. 19044. The follicles are lined by low cuboidal cells with round and small nuclei without atypia. Colloid is evident within the follicles.
A: thyroid follicles
Back Extra: Monodermal Teratoma (Female Gonadal)
- Clinical: Patients with Monodermal Teratoma (Female Gonadal), especially struma ovarii, may present with signs and symptoms of a pelvic mass, ascites, and in rare cases, hyperthyroidism.
- Micro: Monodermal cystic teratomas are characterized by cysts lined by benign keratinizing squamous epithelium or neuroectodermal tissues, often lined by ependymal cells with a glial matrix.
- Ancillary: Immunohistochemistry for thyroglobulin, thyroid transcription factor 1 (TTF1), and PAX8 is positive in struma ovarii, while neuroendocrine markers are positive in carcinoids.
Reference Gallery:
Struma ovarii. The tumour is composed of thyroid follicles filled with colloid.
Struma ovarii. Higher-power magnification of the case shown in Fig. 19044. The follicles are lined by low cuboidal cells with round and small nuclei without atypia. Colloid is evident within the follicles.
Monodermal cystic teratoma. This neuroectodermal cyst is lined by low cuboidal ependymal-type cells with cilia, and the stroma is composed of a glial matrix.
Squamous cell carcinoma arising within a mature cystic teratoma. Haphazardly arranged nests of squamous cell carcinoma with variable size and shape infiltrate the underlying stroma. The lining of the mature cystic teratoma is present at the top of the photograph.

Q: The neuroectodermal cystic variant of Monodermal Teratoma (Female Gonadal) is characteristically lined by ciliated [...] cells resting on a prominent glial matrix.
Monodermal cystic teratoma. This neuroectodermal cyst is lined by low cuboidal ependymal-type cells with cilia, and the stroma is composed of a glial matrix.
A: ependymal
Back Extra: Monodermal Teratoma (Female Gonadal)
- Clinical: Patients with Monodermal Teratoma (Female Gonadal), especially struma ovarii, may present with signs and symptoms of a pelvic mass, ascites, and in rare cases, hyperthyroidism.
- Micro: Monodermal cystic teratomas are characterized by cysts lined by benign keratinizing squamous epithelium or neuroectodermal tissues, often lined by ependymal cells with a glial matrix.
- Ancillary: Immunohistochemistry for thyroglobulin, thyroid transcription factor 1 (TTF1), and PAX8 is positive in struma ovarii, while neuroendocrine markers are positive in carcinoids.
Reference Gallery:
Struma ovarii. The tumour is composed of thyroid follicles filled with colloid.
Struma ovarii. Higher-power magnification of the case shown in Fig. 19044. The follicles are lined by low cuboidal cells with round and small nuclei without atypia. Colloid is evident within the follicles.
Monodermal cystic teratoma. This neuroectodermal cyst is lined by low cuboidal ependymal-type cells with cilia, and the stroma is composed of a glial matrix.
Squamous cell carcinoma arising within a mature cystic teratoma. Haphazardly arranged nests of squamous cell carcinoma with variable size and shape infiltrate the underlying stroma. The lining of the mature cystic teratoma is present at the top of the photograph.

Q: A [...] is a germ cell tumor characterized by an admixture of mature and immature somatic-type tissues derived from all three germ layers (e.g., squamous epithelium, cartilage, and glandular tissue).
Teratoma, postpubertal-type. This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
Teratoma, postpubertal-type. Squamous epithelial and glandular tissue, fibrous stroma, adipose tissue, and glial proliferation (lower right).
A: Postpubertal-Type Teratoma
Back Extra: Postpubertal-Type Teratoma
- Clinical: Postpubertal-Type Teratomas can present in various locations, including the gonad, mediastinum, sacrococcygeal region, and head and neck, with symptoms depending on the location such as hydrocephalus, intracranial hypertension, and ocular paralysis.
- Micro: These tumors are characterized by the presence of mature and immature somatic-type tissues derived from ectoderm, endoderm, and mesoderm, often showing organoid arrangements with glandular and mesenchymal elements.
- Ancillary: Differentiation from prepubertal-type teratomas is crucial, with postpubertal teratomas typically showing more mature and adult-type tissue elements, and the presence of somatic-type malignancy is a key finding.
Reference Gallery:
Teratoma, postpubertal-type. Mixed teratomatous elements with embryonic-type neuroectodermal components.
Teratoma, postpubertal-type. This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
Teratoma, postpubertal-type. Cartilage and glandular tissue are seen in this teratoma. The cartilage appears hypercellular and shows prominent cellular atypia.
Teratoma, postpubertal-type. Glandular epithelium showing goblet cells. The surrounding spindle cell stroma is predominantly aggregating around the glands.
Teratoma, postpubertal-type. This example shows mature cartilage and an embryonal-type neuroectodermal component.
Teratoma, postpubertal-type. A single gland is surrounded by highly cellular spindle cell stroma in a myxoid matrix.
Teratoma, postpubertal-type. Mature glandular elements with mild nuclear atypia and pleomorphism. Note the syncytiotrophoblast with intracytoplasmic red blood cells and the spindle cell stroma displaying variable cellularity.
Teratoma, postpubertal-type. Periglandular stromal cuffing. Both mesenchymal and epithelial components show nuclear atypia.
Teratoma, postpubertal-type. Rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular and mesenchymal component with prominent rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (low-power view).
Teratoma, postpubertal-type. Squamous epithelial and glandular tissue, fibrous stroma, adipose tissue, and glial proliferation (lower right).

Q: In a Postpubertal-Type Teratoma, the spindle cell stroma can display cytologic atypia and characteristically aggregate around epithelial glands, a pattern known as periglandular [...].
Teratoma, postpubertal-type. Glandular epithelium showing goblet cells. The surrounding spindle cell stroma is predominantly aggregating around the glands.
Teratoma, postpubertal-type. Periglandular stromal cuffing. Both mesenchymal and epithelial components show nuclear atypia.
A: stromal cuffing
Back Extra: Postpubertal-Type Teratoma
- Clinical: Postpubertal-Type Teratomas can present in various locations, including the gonad, mediastinum, sacrococcygeal region, and head and neck, with symptoms depending on the location such as hydrocephalus, intracranial hypertension, and ocular paralysis.
- Micro: These tumors are characterized by the presence of mature and immature somatic-type tissues derived from ectoderm, endoderm, and mesoderm, often showing organoid arrangements with glandular and mesenchymal elements.
- Ancillary: Differentiation from prepubertal-type teratomas is crucial, with postpubertal teratomas typically showing more mature and adult-type tissue elements, and the presence of somatic-type malignancy is a key finding.
Reference Gallery:
Teratoma, postpubertal-type. Mixed teratomatous elements with embryonic-type neuroectodermal components.
Teratoma, postpubertal-type. This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
Teratoma, postpubertal-type. Cartilage and glandular tissue are seen in this teratoma. The cartilage appears hypercellular and shows prominent cellular atypia.
Teratoma, postpubertal-type. Glandular epithelium showing goblet cells. The surrounding spindle cell stroma is predominantly aggregating around the glands.
Teratoma, postpubertal-type. This example shows mature cartilage and an embryonal-type neuroectodermal component.
Teratoma, postpubertal-type. A single gland is surrounded by highly cellular spindle cell stroma in a myxoid matrix.
Teratoma, postpubertal-type. Mature glandular elements with mild nuclear atypia and pleomorphism. Note the syncytiotrophoblast with intracytoplasmic red blood cells and the spindle cell stroma displaying variable cellularity.
Teratoma, postpubertal-type. Periglandular stromal cuffing. Both mesenchymal and epithelial components show nuclear atypia.
Teratoma, postpubertal-type. Rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular and mesenchymal component with prominent rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (low-power view).
Teratoma, postpubertal-type. Squamous epithelial and glandular tissue, fibrous stroma, adipose tissue, and glial proliferation (lower right).

Q: Histologic sections of a Postpubertal-Type Teratoma frequently reveal primitive, immature neural elements, classified as embryonic-type [...] components, alongside mature tissues.
Teratoma, postpubertal-type. Mixed teratomatous elements with embryonic-type neuroectodermal components.
Teratoma, postpubertal-type. This example shows mature cartilage and an embryonal-type neuroectodermal component.
A: neuroectodermal
Back Extra: Postpubertal-Type Teratoma
- Clinical: Postpubertal-Type Teratomas can present in various locations, including the gonad, mediastinum, sacrococcygeal region, and head and neck, with symptoms depending on the location such as hydrocephalus, intracranial hypertension, and ocular paralysis.
- Micro: These tumors are characterized by the presence of mature and immature somatic-type tissues derived from ectoderm, endoderm, and mesoderm, often showing organoid arrangements with glandular and mesenchymal elements.
- Ancillary: Differentiation from prepubertal-type teratomas is crucial, with postpubertal teratomas typically showing more mature and adult-type tissue elements, and the presence of somatic-type malignancy is a key finding.
Reference Gallery:
Teratoma, postpubertal-type. Mixed teratomatous elements with embryonic-type neuroectodermal components.
Teratoma, postpubertal-type. This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
Teratoma, postpubertal-type. Cartilage and glandular tissue are seen in this teratoma. The cartilage appears hypercellular and shows prominent cellular atypia.
Teratoma, postpubertal-type. Glandular epithelium showing goblet cells. The surrounding spindle cell stroma is predominantly aggregating around the glands.
Teratoma, postpubertal-type. This example shows mature cartilage and an embryonal-type neuroectodermal component.
Teratoma, postpubertal-type. A single gland is surrounded by highly cellular spindle cell stroma in a myxoid matrix.
Teratoma, postpubertal-type. Mature glandular elements with mild nuclear atypia and pleomorphism. Note the syncytiotrophoblast with intracytoplasmic red blood cells and the spindle cell stroma displaying variable cellularity.
Teratoma, postpubertal-type. Periglandular stromal cuffing. Both mesenchymal and epithelial components show nuclear atypia.
Teratoma, postpubertal-type. Rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular and mesenchymal component with prominent rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (low-power view).
Teratoma, postpubertal-type. Squamous epithelial and glandular tissue, fibrous stroma, adipose tissue, and glial proliferation (lower right).

Q: Microscopically, Prepubertal-Type Testicular Teratoma is characterized by well-differentiated tissues from one or more germ cell layers (e.g., cartilage, glandular epithelium, glial tissue) that characteristically lacks [...].
Prepubertal-type teratoma. This prepubertal-type teratoma occurring in a child includes glandular epithelium, cartilage, spindle cell stroma, and focal smooth muscle.
Prepubertal-type teratoma. This prepubertal-type teratoma includes cysts with glandular epithelium, glial tissue (left), and focal pigmented epithelium (right).
A: cytological atypia
Back Extra: Prepubertal-Type Testicular Teratoma
- Clinical: Prepubertal-type testicular teratomas typically present as lumps in boys under 6 years of age, often discovered by patients or parents, and are usually at least partially cystic on ultrasound.
- Micro: These teratomas lack cytological atypia and are composed of well-differentiated elements from one or more germinal layers, often arranged in an organoid pattern.
- Ancillary: Molecular investigations show that prepubertal-type teratomas are diploid and lack the genetic abnormalities typically seen in postpubertal-type teratomas, such as isochromosome 12p gain.
Reference Gallery:
Prepubertal-type teratoma. The tumour shows solid and cystic areas in the testis of a 17-year-old boy. FISH hybridization for isochromosome 12p was negative.
Prepubertal-type teratoma. This prepubertal-type teratoma occurring in a child includes glandular epithelium, cartilage, spindle cell stroma, and focal smooth muscle.
Prepubertal-type teratoma. This prepubertal-type teratoma includes cysts with glandular epithelium, glial tissue (left), and focal pigmented epithelium (right).
Epidermoid cyst. An epidermoid cyst occurring in the postpubertal testis is considered a form of prepubertal-type teratoma. This example includes a single cyst lined by keratinizing squamous epithelium, associated with normal seminiferous tubules.

Q: Unlike postpubertal-type tumors, molecular investigations of Prepubertal-Type Testicular Teratoma reveal a diploid genome that characteristically lacks [...] gain.
Prepubertal-type teratoma. The tumour shows solid and cystic areas in the testis of a 17-year-old boy. FISH hybridization for isochromosome 12p was negative.
A: isochromosome 12p
Back Extra: Prepubertal-Type Testicular Teratoma
- Clinical: Prepubertal-type testicular teratomas typically present as lumps in boys under 6 years of age, often discovered by patients or parents, and are usually at least partially cystic on ultrasound.
- Micro: These teratomas lack cytological atypia and are composed of well-differentiated elements from one or more germinal layers, often arranged in an organoid pattern.
- Ancillary: Molecular investigations show that prepubertal-type teratomas are diploid and lack the genetic abnormalities typically seen in postpubertal-type teratomas, such as isochromosome 12p gain.
Reference Gallery:
Prepubertal-type teratoma. The tumour shows solid and cystic areas in the testis of a 17-year-old boy. FISH hybridization for isochromosome 12p was negative.
Prepubertal-type teratoma. This prepubertal-type teratoma occurring in a child includes glandular epithelium, cartilage, spindle cell stroma, and focal smooth muscle.
Prepubertal-type teratoma. This prepubertal-type teratoma includes cysts with glandular epithelium, glial tissue (left), and focal pigmented epithelium (right).
Epidermoid cyst. An epidermoid cyst occurring in the postpubertal testis is considered a form of prepubertal-type teratoma. This example includes a single cyst lined by keratinizing squamous epithelium, associated with normal seminiferous tubules.

Q: A testicular epidermoid cyst, which is typically a single cyst lined by keratinizing squamous epithelium, is classified as a monodermal form of [...].
Epidermoid cyst. An epidermoid cyst occurring in the postpubertal testis is considered a form of prepubertal-type teratoma. This example includes a single cyst lined by keratinizing squamous epithelium, associated with normal seminiferous tubules.
A: Prepubertal-Type Testicular Teratoma
Back Extra: Prepubertal-Type Testicular Teratoma
- Clinical: Prepubertal-type testicular teratomas typically present as lumps in boys under 6 years of age, often discovered by patients or parents, and are usually at least partially cystic on ultrasound.
- Micro: These teratomas lack cytological atypia and are composed of well-differentiated elements from one or more germinal layers, often arranged in an organoid pattern.
- Ancillary: Molecular investigations show that prepubertal-type teratomas are diploid and lack the genetic abnormalities typically seen in postpubertal-type teratomas, such as isochromosome 12p gain.
Reference Gallery:
Prepubertal-type teratoma. The tumour shows solid and cystic areas in the testis of a 17-year-old boy. FISH hybridization for isochromosome 12p was negative.
Prepubertal-type teratoma. This prepubertal-type teratoma occurring in a child includes glandular epithelium, cartilage, spindle cell stroma, and focal smooth muscle.
Prepubertal-type teratoma. This prepubertal-type teratoma includes cysts with glandular epithelium, glial tissue (left), and focal pigmented epithelium (right).
Epidermoid cyst. An epidermoid cyst occurring in the postpubertal testis is considered a form of prepubertal-type teratoma. This example includes a single cyst lined by keratinizing squamous epithelium, associated with normal seminiferous tubules.

Q: Histologic examination of Yolk Sac Tumor characteristically reveals [...], which are often accompanied by intracytoplasmic eosinophilic hyaline globules and band-like intercellular deposits of basement membrane.
Yolk sac tumour. Classic Schiller–Duval body surrounded by cells with intracytoplasmic eosinophilic globules.
Yolk sac tumour. At higher magnification, the intracellular globular globules and band-like intercellular deposits of basement membrane (parietal differentiation) are clearly seen.
A: Schiller-Duval bodies
Back Extra: Yolk Sac Tumor
- Clinical: Yolk Sac Tumor predominantly affects prepubertal males, with a median age of 16-20 months, and rarely arises beyond 6 years of age.
- Micro: Yolk Sac Tumor is characterized by the presence of intracytoplasmic and extracellular hyaline globules, band-like intercellular deposits of basement membrane, and Schiller–Duval bodies.
- Ancillary: Immunohistochemistry for AFP, SALL4, and glypican-3 (GPC3) is highly specific for Yolk Sac Tumor.
Reference Gallery:
Pure yolk sac tumour. Orchiectomy specimen from an 18-year-old patient with Down syndrome.
Pure yolk sac tumour. Cut surface of the orchiectomy specimen from the 18-year-old patient with Down syndrome shown in Fig. <<22975>>.
Yolk sac tumour. Classic Schiller–Duval body surrounded by cells with intracytoplasmic eosinophilic globules.
Yolk sac tumour. At higher magnification, the intracellular globular globules and band-like intercellular deposits of basement membrane (parietal differentiation) are clearly seen.
Yolk sac tumour. Strong nuclear staining for SALL4.
Yolk sac tumour. Strong staining for AE1/AE3.
Yolk sac tumour. Positive immunohistochemistry for glypican-3 (GPC3).
Yolk sac tumour. Contrast-enhanced axial CT shows a heterogeneous anterior mediastinal mass abutting the ascending aorta and pulmonary trunk. A cystic component is noted within the mass and there is no calcification.

Q: In addition to SALL4 and alpha-fetoprotein (AFP), Yolk Sac Tumor characteristically demonstrates highly specific, positive immunohistochemical staining for [...].
Yolk sac tumour. Strong nuclear staining for SALL4.
Yolk sac tumour. Positive immunohistochemistry for glypican-3 (GPC3).
A: glypican-3
Back Extra: Yolk Sac Tumor
- Clinical: Yolk Sac Tumor predominantly affects prepubertal males, with a median age of 16-20 months, and rarely arises beyond 6 years of age.
- Micro: Yolk Sac Tumor is characterized by the presence of intracytoplasmic and extracellular hyaline globules, band-like intercellular deposits of basement membrane, and Schiller–Duval bodies.
- Ancillary: Immunohistochemistry for AFP, SALL4, and glypican-3 (GPC3) is highly specific for Yolk Sac Tumor.
Reference Gallery:
Pure yolk sac tumour. Orchiectomy specimen from an 18-year-old patient with Down syndrome.
Pure yolk sac tumour. Cut surface of the orchiectomy specimen from the 18-year-old patient with Down syndrome shown in Fig. <<22975>>.
Yolk sac tumour. Classic Schiller–Duval body surrounded by cells with intracytoplasmic eosinophilic globules.
Yolk sac tumour. At higher magnification, the intracellular globular globules and band-like intercellular deposits of basement membrane (parietal differentiation) are clearly seen.
Yolk sac tumour. Strong nuclear staining for SALL4.
Yolk sac tumour. Strong staining for AE1/AE3.
Yolk sac tumour. Positive immunohistochemistry for glypican-3 (GPC3).
Yolk sac tumour. Contrast-enhanced axial CT shows a heterogeneous anterior mediastinal mass abutting the ascending aorta and pulmonary trunk. A cystic component is noted within the mass and there is no calcification.

Q: Presenting grossly as a well-circumscribed yellow nodule, [...] typically features a lobulated histologic pattern with macrocystic and microcystic areas.
Juvenile granulosa cell tumour of the testis. A well-circumscribed solid nodule with a yellow cut surface.
Juvenile granulosa cell tumour of the testis. Overview of the multicystic appearance.
A: Juvenile Granulosa Cell Tumor of the Testis
Back Extra: Juvenile Granulosa Cell Tumour of the Testis
- Clinical: Almost all patients with Juvenile Granulosa Cell Tumour of the Testis present with a testicular mass or testicular enlargement, and hormonal changes like gynaecomastia or premature puberty are extremely rare.
- Micro: Histomorphologically, a lobulated pattern with macrocystic and microcystic areas is characteristic. The tumour cells are polygonal with sometimes vacuolated or eosinophilic cytoplasm, embedded in a fibrous or fibromyxoid stroma.
- Ancillary: Juvenile Granulosa Cell Tumour of the Testis shares a common immunophenotype with other sex cord stromal tumours, expressing SF1, calretinin, inhibin, SOX9, WT1, and FOXL2.
Reference Gallery:
Juvenile granulosa cell tumour of the testis. A well-circumscribed solid nodule with a yellow cut surface.
Juvenile granulosa cell tumour of the testis. Overview of the multicystic appearance.
Juvenile granulosa cell tumour of the testis. Solid area with a lobular growth pattern and microcysts containing basophilic fluid.

Q: Histologically, Juvenile Granulosa Cell Tumor of the Testis is highly characterized by a solid and lobular growth pattern containing microcysts filled with [...].
Juvenile granulosa cell tumour of the testis. Solid area with a lobular growth pattern and microcysts containing basophilic fluid.
A: basophilic fluid
Back Extra: Juvenile Granulosa Cell Tumour of the Testis
- Clinical: Almost all patients with Juvenile Granulosa Cell Tumour of the Testis present with a testicular mass or testicular enlargement, and hormonal changes like gynaecomastia or premature puberty are extremely rare.
- Micro: Histomorphologically, a lobulated pattern with macrocystic and microcystic areas is characteristic. The tumour cells are polygonal with sometimes vacuolated or eosinophilic cytoplasm, embedded in a fibrous or fibromyxoid stroma.
- Ancillary: Juvenile Granulosa Cell Tumour of the Testis shares a common immunophenotype with other sex cord stromal tumours, expressing SF1, calretinin, inhibin, SOX9, WT1, and FOXL2.
Reference Gallery:
Juvenile granulosa cell tumour of the testis. A well-circumscribed solid nodule with a yellow cut surface.
Juvenile granulosa cell tumour of the testis. Overview of the multicystic appearance.
Juvenile granulosa cell tumour of the testis. Solid area with a lobular growth pattern and microcysts containing basophilic fluid.

Q: The VCL::ALK variant of ALK-rearranged renal cell carcinoma is strongly associated with sickle cell trait and characteristically displays striking cytoplasmic vacuolization interspersed with scattered [...].
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate striking cytoplasmic vacuolization.
Renal cell carcinoma with VCL::ALK gene fusion. There are numerous sickled erythrocytes scattered among the vacuolated neoplastic cells.
A: sickled erythrocytes
Back Extra: ALK-rearranged renal cell carcinoma
- Clinical: ALK-rearranged renal cell carcinomas are associated with young patients and those with sickle cell trait. They have no specific clinical features.
- Micro: The neoplastic cells often have a distinctive morphology, including eosinophilic cytoplasm, cytoplasmic vacuolization, and the presence of sickled erythrocytes.
- Ancillary: ALK labeling and demonstration of ALK rearrangement are crucial for diagnosis, while SMARCB1 protein is typically retained.
Reference Gallery:
Renal cell carcinoma with VCL::ALK gene fusion. The neoplasm is well delineated from the native kidney by the fibrous capsule to the right.
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate striking cytoplasmic vacuolization.
Renal cell carcinoma with VCL::ALK gene fusion. There are numerous sickled erythrocytes scattered among the vacuolated neoplastic cells.
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate diffuse cytoplasmic immunoreactivity for ALK protein by immunohistochemistry.
Renal cell carcinoma with EML4::ALK gene fusion. The neoplastic cells form glands and cribriform structures within an oedematous, desmoplastic stroma. The native kidney is to the left.
Renal cell carcinoma with EML4::ALK gene fusion. The morphology is that of a nondescript high-grade adenocarcinoma with desmoplastic stroma.

Q: The EML4::ALK variant of ALK-rearranged renal cell carcinoma typically presents as a nondescript, high-grade adenocarcinoma that forms glands and cribriform structures embedded within an [...] stroma.
Renal cell carcinoma with EML4::ALK gene fusion. The neoplastic cells form glands and cribriform structures within an oedematous, desmoplastic stroma. The native kidney is to the left.
Renal cell carcinoma with EML4::ALK gene fusion. The morphology is that of a nondescript high-grade adenocarcinoma with desmoplastic stroma.
A: edematous, desmoplastic
Back Extra: ALK-rearranged renal cell carcinoma
- Clinical: ALK-rearranged renal cell carcinomas are associated with young patients and those with sickle cell trait. They have no specific clinical features.
- Micro: The neoplastic cells often have a distinctive morphology, including eosinophilic cytoplasm, cytoplasmic vacuolization, and the presence of sickled erythrocytes.
- Ancillary: ALK labeling and demonstration of ALK rearrangement are crucial for diagnosis, while SMARCB1 protein is typically retained.
Reference Gallery:
Renal cell carcinoma with VCL::ALK gene fusion. The neoplasm is well delineated from the native kidney by the fibrous capsule to the right.
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate striking cytoplasmic vacuolization.
Renal cell carcinoma with VCL::ALK gene fusion. There are numerous sickled erythrocytes scattered among the vacuolated neoplastic cells.
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate diffuse cytoplasmic immunoreactivity for ALK protein by immunohistochemistry.
Renal cell carcinoma with EML4::ALK gene fusion. The neoplastic cells form glands and cribriform structures within an oedematous, desmoplastic stroma. The native kidney is to the left.
Renal cell carcinoma with EML4::ALK gene fusion. The morphology is that of a nondescript high-grade adenocarcinoma with desmoplastic stroma.

Q: Ancillary testing for ALK-rearranged renal cell carcinoma reveals diffuse cytoplasmic immunoreactivity for the [...] protein, while expression of the SMARCB1 protein is typically retained.
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate diffuse cytoplasmic immunoreactivity for ALK protein by immunohistochemistry.
A: ALK
Back Extra: ALK-rearranged renal cell carcinoma
- Clinical: ALK-rearranged renal cell carcinomas are associated with young patients and those with sickle cell trait. They have no specific clinical features.
- Micro: The neoplastic cells often have a distinctive morphology, including eosinophilic cytoplasm, cytoplasmic vacuolization, and the presence of sickled erythrocytes.
- Ancillary: ALK labeling and demonstration of ALK rearrangement are crucial for diagnosis, while SMARCB1 protein is typically retained.
Reference Gallery:
Renal cell carcinoma with VCL::ALK gene fusion. The neoplasm is well delineated from the native kidney by the fibrous capsule to the right.
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate striking cytoplasmic vacuolization.
Renal cell carcinoma with VCL::ALK gene fusion. There are numerous sickled erythrocytes scattered among the vacuolated neoplastic cells.
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate diffuse cytoplasmic immunoreactivity for ALK protein by immunohistochemistry.
Renal cell carcinoma with EML4::ALK gene fusion. The neoplastic cells form glands and cribriform structures within an oedematous, desmoplastic stroma. The native kidney is to the left.
Renal cell carcinoma with EML4::ALK gene fusion. The morphology is that of a nondescript high-grade adenocarcinoma with desmoplastic stroma.

Q: Anaplastic Sarcoma of the Kidney: Histologically, this tumor features a multipatterned architecture with spindle cell areas, blastema-like regions, marked anaplasia, and distinct nodules of [...].
Anaplastic sarcoma of the kidney. A spindle cell component of the tumour.
Anaplastic sarcoma of the kidney. An island of malignant cartilage is one of the key features.
Anaplastic sarcoma of the kidney. Blastema-like areas.
A: malignant cartilage
Back Extra: Anaplastic Sarcoma of the Kidney
- Clinical: Anaplastic Sarcoma of the Kidney (ASK) typically presents as a large renal mass, often causing flank pain and haematuria, with a median age of presentation at 9.4 years.
- Micro: Histologically, ASK is characterized by a multipatterned sarcoma with spindle cell areas, blastema-like areas, and malignant cartilage nodules, often with marked anaplasia.
- Ancillary: ASK is associated with biallelic DICER1 loss-of-function and missense RNase IIIb pathogenic variants, which are key to its diagnosis.
Reference Gallery:
Anaplastic sarcoma of the kidney. A spindle cell component of the tumour.
Anaplastic sarcoma of the kidney. Marked diffuse anaplasia in the stromal component.
Anaplastic sarcoma of the kidney. An island of malignant cartilage is one of the key features.
Anaplastic sarcoma of the kidney. A cystic component of the tumour, closely resembling cystic nephroma.
Anaplastic sarcoma of the kidney. Blastema-like areas.
Anaplastic sarcoma of the kidney. Cystic areas.
Anaplastic sarcoma of the kidney. Spindle cell area.

Q: Anaplastic Sarcoma of the Kidney: This pediatric renal tumor is genetically characterized by biallelic loss-of-function and missense RNase IIIb pathogenic variants in the [...] gene.
Anaplastic sarcoma of the kidney. Marked diffuse anaplasia in the stromal component.
A: DICER1
Back Extra: Anaplastic Sarcoma of the Kidney
- Clinical: Anaplastic Sarcoma of the Kidney (ASK) typically presents as a large renal mass, often causing flank pain and haematuria, with a median age of presentation at 9.4 years.
- Micro: Histologically, ASK is characterized by a multipatterned sarcoma with spindle cell areas, blastema-like areas, and malignant cartilage nodules, often with marked anaplasia.
- Ancillary: ASK is associated with biallelic DICER1 loss-of-function and missense RNase IIIb pathogenic variants, which are key to its diagnosis.
Reference Gallery:
Anaplastic sarcoma of the kidney. A spindle cell component of the tumour.
Anaplastic sarcoma of the kidney. Marked diffuse anaplasia in the stromal component.
Anaplastic sarcoma of the kidney. An island of malignant cartilage is one of the key features.
Anaplastic sarcoma of the kidney. A cystic component of the tumour, closely resembling cystic nephroma.
Anaplastic sarcoma of the kidney. Blastema-like areas.
Anaplastic sarcoma of the kidney. Cystic areas.
Anaplastic sarcoma of the kidney. Spindle cell area.

Q: Anaplastic Sarcoma of the Kidney: As suggested by its name, a key diagnostic histologic feature is the presence of marked diffuse [...] within the stromal component.
Anaplastic sarcoma of the kidney. Marked diffuse anaplasia in the stromal component.
A: anaplasia
Back Extra: Anaplastic Sarcoma of the Kidney
- Clinical: Anaplastic Sarcoma of the Kidney (ASK) typically presents as a large renal mass, often causing flank pain and haematuria, with a median age of presentation at 9.4 years.
- Micro: Histologically, ASK is characterized by a multipatterned sarcoma with spindle cell areas, blastema-like areas, and malignant cartilage nodules, often with marked anaplasia.
- Ancillary: ASK is associated with biallelic DICER1 loss-of-function and missense RNase IIIb pathogenic variants, which are key to its diagnosis.
Reference Gallery:
Anaplastic sarcoma of the kidney. A spindle cell component of the tumour.
Anaplastic sarcoma of the kidney. Marked diffuse anaplasia in the stromal component.
Anaplastic sarcoma of the kidney. An island of malignant cartilage is one of the key features.
Anaplastic sarcoma of the kidney. A cystic component of the tumour, closely resembling cystic nephroma.
Anaplastic sarcoma of the kidney. Blastema-like areas.
Anaplastic sarcoma of the kidney. Cystic areas.
Anaplastic sarcoma of the kidney. Spindle cell area.

Q: The classic histologic pattern of Clear Cell Sarcoma of the Kidney features ovoid tumor cells arranged in broad trabeculae or nests, separated by distinctive, delicate [...].
Clear cell sarcoma of the kidney. Classic areas feature ovoid tumour cells with variably clear nuclei and cytoplasm; note the delicate branching vasculature.
A: arborizing fibrovascular septa
Back Extra: Clear Cell Sarcoma of the Kidney
- Clinical: Clear cell sarcoma of the kidney (CCSK) typically presents with an abdominal mass, distension, pain, or gross hematuria, and is most common in children under 3 years of age with a male predominance.
- Micro: The classic histological pattern of CCSK includes ovoid tumour cells with clear nuclei and cytoplasm, arranged in broad trabeculae or nests, with distinctive arborizing fibrovascular septa.
- Ancillary: Immunohistochemistry shows strong and diffuse nuclear staining for cyclin D1 and BCOR, which are key markers for diagnosing CCSK.
Reference Gallery:
Clear cell sarcoma of the kidney. Gross examination shows a well-circumscribed fleshy mass.
Clear cell sarcoma of the kidney. Classic areas feature ovoid tumour cells with variably clear nuclei and cytoplasm; note the delicate branching vasculature.
Clear cell sarcoma of the kidney. Cellular areas feature overlapping of the nuclei.
Clear cell sarcoma of the kidney. Myxoid areas show increased extracellular matrix. Cyst formation is possible.
Clear cell sarcoma of the kidney. Sclerosing areas show deposits of eosinophilic hyalinized material that may resemble osteoid.
Clear cell sarcoma of the kidney. Epithelioid areas feature tumour cells arranged as tubules or trabeculae.
Clear cell sarcoma of the kidney. Palisading areas resemble Verocay bodies of schwannomas.
Clear cell sarcoma of the kidney. Spindled areas feature fascicular groups of elongated tumour cells, resembling a spindle cell sarcoma.
Clear cell sarcoma of the kidney. Anaplasia may rarely occur in clear cell sarcoma of the kidney and is defined as for nephroblastoma.
Clear cell sarcoma of the kidney. Tumour cell nuclei stain for cyclin D1 in a strong and diffuse pattern. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Tumour cell nuclei stain for BCOR in a strong and diffuse pattern. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Contrast-enhanced axial CT showing a large heterogeneous enhancing mass (predominantly a central large fluid space with enhancing septa). The tumour crosses the midline and markedly displaces the pancreas and its adjacent splenic vein.

Q: Immunohistochemistry for Clear Cell Sarcoma of the Kidney characteristically demonstrates strong and diffuse nuclear staining for cyclin D1 and [...].
Clear cell sarcoma of the kidney. Tumour cell nuclei stain for cyclin D1 in a strong and diffuse pattern. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Tumour cell nuclei stain for BCOR in a strong and diffuse pattern. Note that vascular endothelial cells are negative.
A: BCOR
Back Extra: Clear Cell Sarcoma of the Kidney
- Clinical: Clear cell sarcoma of the kidney (CCSK) typically presents with an abdominal mass, distension, pain, or gross hematuria, and is most common in children under 3 years of age with a male predominance.
- Micro: The classic histological pattern of CCSK includes ovoid tumour cells with clear nuclei and cytoplasm, arranged in broad trabeculae or nests, with distinctive arborizing fibrovascular septa.
- Ancillary: Immunohistochemistry shows strong and diffuse nuclear staining for cyclin D1 and BCOR, which are key markers for diagnosing CCSK.
Reference Gallery:
Clear cell sarcoma of the kidney. Gross examination shows a well-circumscribed fleshy mass.
Clear cell sarcoma of the kidney. Classic areas feature ovoid tumour cells with variably clear nuclei and cytoplasm; note the delicate branching vasculature.
Clear cell sarcoma of the kidney. Cellular areas feature overlapping of the nuclei.
Clear cell sarcoma of the kidney. Myxoid areas show increased extracellular matrix. Cyst formation is possible.
Clear cell sarcoma of the kidney. Sclerosing areas show deposits of eosinophilic hyalinized material that may resemble osteoid.
Clear cell sarcoma of the kidney. Epithelioid areas feature tumour cells arranged as tubules or trabeculae.
Clear cell sarcoma of the kidney. Palisading areas resemble Verocay bodies of schwannomas.
Clear cell sarcoma of the kidney. Spindled areas feature fascicular groups of elongated tumour cells, resembling a spindle cell sarcoma.
Clear cell sarcoma of the kidney. Anaplasia may rarely occur in clear cell sarcoma of the kidney and is defined as for nephroblastoma.
Clear cell sarcoma of the kidney. Tumour cell nuclei stain for cyclin D1 in a strong and diffuse pattern. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Tumour cell nuclei stain for BCOR in a strong and diffuse pattern. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Contrast-enhanced axial CT showing a large heterogeneous enhancing mass (predominantly a central large fluid space with enhancing septa). The tumour crosses the midline and markedly displaces the pancreas and its adjacent splenic vein.

Q: In Eosinophilic Solid and Cystic Renal Cell Carcinoma, the neoplastic cells characteristically display voluminous eosinophilic cytoplasm containing highly specific [...].
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated and have particularly voluminous eosinophilic cytoplasm.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells characteristically demonstrate basophilic cytoplasmic stippling.
A: basophilic cytoplasmic stippling
Back Extra: Eosinophilic Solid and Cystic Renal Cell Carcinoma
- Clinical: Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) was originally described in women but has also been reported in children and men, with a reported age range of 14–75 years.
- Micro: ESC-RCCs are typically unencapsulated, with a solid and cystic architecture. The neoplastic cells are polygonal with voluminous eosinophilic cytoplasm and basophilic cytoplasmic stippling.
- Ancillary: Identification of biallelic somatic mutations in TSC1 or TSC2, along with focal or diffuse CK20 positivity, is diagnostic of ESC-RCC.
Reference Gallery:
Eosinophilic solid and cystic renal cell carcinoma. At low power, this well-delineated neoplasm demonstrates both cystic and solid architecture.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasm has a predominantly solid architecture and cysts containing pale-pink proteinaceous fluid.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated and have particularly voluminous eosinophilic cytoplasm.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells characteristically demonstrate basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasms occasionally demonstrate a papillary architecture.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasms typically demonstrate patchy but intense single-cell immunoreactivity for CK20.

Q: The diagnosis of Eosinophilic Solid and Cystic Renal Cell Carcinoma is supported by patchy but intense single-cell immunoreactivity for [...].
Eosinophilic solid and cystic renal cell carcinoma. The neoplasms typically demonstrate patchy but intense single-cell immunoreactivity for CK20.
A: CK20
Back Extra: Eosinophilic Solid and Cystic Renal Cell Carcinoma
- Clinical: Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) was originally described in women but has also been reported in children and men, with a reported age range of 14–75 years.
- Micro: ESC-RCCs are typically unencapsulated, with a solid and cystic architecture. The neoplastic cells are polygonal with voluminous eosinophilic cytoplasm and basophilic cytoplasmic stippling.
- Ancillary: Identification of biallelic somatic mutations in TSC1 or TSC2, along with focal or diffuse CK20 positivity, is diagnostic of ESC-RCC.
Reference Gallery:
Eosinophilic solid and cystic renal cell carcinoma. At low power, this well-delineated neoplasm demonstrates both cystic and solid architecture.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasm has a predominantly solid architecture and cysts containing pale-pink proteinaceous fluid.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated and have particularly voluminous eosinophilic cytoplasm.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells characteristically demonstrate basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasms occasionally demonstrate a papillary architecture.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasms typically demonstrate patchy but intense single-cell immunoreactivity for CK20.

Q: Eosinophilic Solid and Cystic Renal Cell Carcinoma is genetically characterized by diagnostic biallelic somatic mutations in the [...] genes.
Eosinophilic solid and cystic renal cell carcinoma. At low power, this well-delineated neoplasm demonstrates both cystic and solid architecture.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasm has a predominantly solid architecture and cysts containing pale-pink proteinaceous fluid.
A: TSC1 or TSC2
Back Extra: Eosinophilic Solid and Cystic Renal Cell Carcinoma
- Clinical: Eosinophilic solid and cystic renal cell carcinoma (ESC-RCC) was originally described in women but has also been reported in children and men, with a reported age range of 14–75 years.
- Micro: ESC-RCCs are typically unencapsulated, with a solid and cystic architecture. The neoplastic cells are polygonal with voluminous eosinophilic cytoplasm and basophilic cytoplasmic stippling.
- Ancillary: Identification of biallelic somatic mutations in TSC1 or TSC2, along with focal or diffuse CK20 positivity, is diagnostic of ESC-RCC.
Reference Gallery:
Eosinophilic solid and cystic renal cell carcinoma. At low power, this well-delineated neoplasm demonstrates both cystic and solid architecture.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasm has a predominantly solid architecture and cysts containing pale-pink proteinaceous fluid.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated and have particularly voluminous eosinophilic cytoplasm.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells characteristically demonstrate basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasms occasionally demonstrate a papillary architecture.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasms typically demonstrate patchy but intense single-cell immunoreactivity for CK20.

Q: Microscopic examination of Malignant Rhabdoid Tumor of the Kidney classically reveals a diffuse growth pattern of large, pleomorphic cells with prominent nucleoli and characteristic pink [...].
Malignant rhabdoid tumour of the kidney. Diffuse growth pattern of tumour cells.
Malignant rhabdoid tumour of the kidney. High-power view showing the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions in some cells.
A: cytoplasmic inclusions
Back Extra: Malignant Rhabdoid Tumour of the Kidney
- Clinical: Malignant Rhabdoid Tumour of the Kidney (MRTK) typically presents in infants and young children, with a mean/median age of 1 year, and often presents with haematuria and/or an abdominal mass.
- Micro: MRTK is characterized by large, pleomorphic cells with prominent nucleoli, pink cytoplasmic inclusions, and a diffuse infiltrative growth pattern with abundant necrosis.
- Ancillary: The diagnosis of MRTK is confirmed by the loss of nuclear SMARCB1 (INI1) staining in tumour cells, with complementary genetic analysis showing SMARCB1 or SMARCA4 mutations.
Reference Gallery:
Malignant rhabdoid tumour of the kidney. Diffuse growth pattern of tumour cells.
Malignant rhabdoid tumour of the kidney. High-power view showing the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions in some cells.
Malignant rhabdoid tumour of the kidney. Absence of SMARCB1 (INI1) immunostaining in tumour cells, with retention in normal cells (which serve as an internal positive control).
Malignant rhabdoid tumour of the kidney. Contrast-enhanced axial CT showing a heterogeneous mass with an indistinct margin in the central portion of the left kidney, with invasion to the renal pelvis and extracapsular spread with encasement of the renal vessels, aorta, and inferior vena cava. There is an associated enlargement of retroperitoneal lymph nodes.
Malignant rhabdoid tumour of the kidney. Contrast-enhanced coronal reformatted CT showing a heterogeneous mass arising from the lower pole of the left kidney, with extracapsular spread and encasement of the renal vessels, aorta, and inferior vena cava. There is obstructive dilatation of the upper pole calyces.

Q: The diagnosis of Malignant Rhabdoid Tumor of the Kidney is immunohistochemically confirmed by the pathognomonic loss of nuclear staining for [...].
Malignant rhabdoid tumour of the kidney. Absence of SMARCB1 (INI1) immunostaining in tumour cells, with retention in normal cells (which serve as an internal positive control).
A: SMARCB1 (INI1)
Back Extra: Malignant Rhabdoid Tumour of the Kidney
- Clinical: Malignant Rhabdoid Tumour of the Kidney (MRTK) typically presents in infants and young children, with a mean/median age of 1 year, and often presents with haematuria and/or an abdominal mass.
- Micro: MRTK is characterized by large, pleomorphic cells with prominent nucleoli, pink cytoplasmic inclusions, and a diffuse infiltrative growth pattern with abundant necrosis.
- Ancillary: The diagnosis of MRTK is confirmed by the loss of nuclear SMARCB1 (INI1) staining in tumour cells, with complementary genetic analysis showing SMARCB1 or SMARCA4 mutations.
Reference Gallery:
Malignant rhabdoid tumour of the kidney. Diffuse growth pattern of tumour cells.
Malignant rhabdoid tumour of the kidney. High-power view showing the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions in some cells.
Malignant rhabdoid tumour of the kidney. Absence of SMARCB1 (INI1) immunostaining in tumour cells, with retention in normal cells (which serve as an internal positive control).
Malignant rhabdoid tumour of the kidney. Contrast-enhanced axial CT showing a heterogeneous mass with an indistinct margin in the central portion of the left kidney, with invasion to the renal pelvis and extracapsular spread with encasement of the renal vessels, aorta, and inferior vena cava. There is an associated enlargement of retroperitoneal lymph nodes.
Malignant rhabdoid tumour of the kidney. Contrast-enhanced coronal reformatted CT showing a heterogeneous mass arising from the lower pole of the left kidney, with extracapsular spread and encasement of the renal vessels, aorta, and inferior vena cava. There is obstructive dilatation of the upper pole calyces.

Q: The classic type of [...] is the most common renal tumor in the first 3 months of life and is characterized microscopically by interlacing fascicles of spindle cells, thin-walled vascular spaces, and an irregular tumor-kidney interface with entrapped normal renal parenchyma.
Mesoblastic nephroma. Classic-type mesoblastic nephroma composed of interlacing fascicles of spindled cells and thin-walled vascular spaces.
Mesoblastic nephroma. The tumour–kidney interface is irregular, with many islands of entrapped normal renal parenchyma.
A: mesoblastic nephroma
Back Extra: Mesoblastic Nephroma
- Clinical: Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life, presenting with an abdominal mass, hypertension, or haematuria.
- Micro: Classic type MN is characterized by intermingling fascicles of spindle cells and thin-walled vascular spaces, while the cellular type shows plump cells in a sheet-like pattern.
- Ancillary: Cellular MN often has a t(12;15)(p13;q25) translocation, leading to the ETV6::NTRK3 gene fusion, which can be detected by immunohistochemistry using a pan-TRK antibody.
Reference Gallery:
Mesoblastic nephroma. Classic-type mesoblastic nephroma composed of interlacing fascicles of spindled cells and thin-walled vascular spaces.
Mesoblastic nephroma. The tumour–kidney interface is irregular, with many islands of entrapped normal renal parenchyma.
Mesoblastic nephroma. Cellular type, composed of densely packed plump cells growing in a sheet-like pattern.
Mesoblastic nephroma. The tumour–kidney border in the cellular type is sharp, despite the absence of the capsule.
Mesoblastic nephroma. Mixed type, composed of cellular areas (upper part of the figure) that are sharply demarcated from the classic type.
Mesoblastic nephroma. Renal sinus infiltration by tumour, which is very common because no capsule is present.
Congenital mesoblastic nephroma. Contrast-enhanced axial CT shows a fairly homogeneous mass with predominantly peripheral enhancement at the anterior region of the left kidney extending to the renal hilum but without invasion of the renal vessels.

Q: Often harboring a t(12;15) ETV6::NTRK3 gene fusion, the cellular type of [...] is microscopically composed of densely packed plump cells growing in a sheet-like pattern with a sharp tumor-kidney border despite the lack of a fibrous capsule.
Mesoblastic nephroma. Cellular type, composed of densely packed plump cells growing in a sheet-like pattern.
Mesoblastic nephroma. The tumour–kidney border in the cellular type is sharp, despite the absence of the capsule.
A: mesoblastic nephroma
Back Extra: Mesoblastic Nephroma
- Clinical: Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life, presenting with an abdominal mass, hypertension, or haematuria.
- Micro: Classic type MN is characterized by intermingling fascicles of spindle cells and thin-walled vascular spaces, while the cellular type shows plump cells in a sheet-like pattern.
- Ancillary: Cellular MN often has a t(12;15)(p13;q25) translocation, leading to the ETV6::NTRK3 gene fusion, which can be detected by immunohistochemistry using a pan-TRK antibody.
Reference Gallery:
Mesoblastic nephroma. Classic-type mesoblastic nephroma composed of interlacing fascicles of spindled cells and thin-walled vascular spaces.
Mesoblastic nephroma. The tumour–kidney interface is irregular, with many islands of entrapped normal renal parenchyma.
Mesoblastic nephroma. Cellular type, composed of densely packed plump cells growing in a sheet-like pattern.
Mesoblastic nephroma. The tumour–kidney border in the cellular type is sharp, despite the absence of the capsule.
Mesoblastic nephroma. Mixed type, composed of cellular areas (upper part of the figure) that are sharply demarcated from the classic type.
Mesoblastic nephroma. Renal sinus infiltration by tumour, which is very common because no capsule is present.
Congenital mesoblastic nephroma. Contrast-enhanced axial CT shows a fairly homogeneous mass with predominantly peripheral enhancement at the anterior region of the left kidney extending to the renal hilum but without invasion of the renal vessels.

Q: On contrast-enhanced CT, a congenital [...] typically presents in early infancy as a fairly homogeneous mass with predominantly peripheral enhancement that may extend to the renal hilum without invading the renal vessels.
Congenital mesoblastic nephroma. Contrast-enhanced axial CT shows a fairly homogeneous mass with predominantly peripheral enhancement at the anterior region of the left kidney extending to the renal hilum but without invasion of the renal vessels.
A: mesoblastic nephroma
Back Extra: Mesoblastic Nephroma
- Clinical: Mesoblastic nephroma (MN) is the most common renal tumour in the first 3 months of life, presenting with an abdominal mass, hypertension, or haematuria.
- Micro: Classic type MN is characterized by intermingling fascicles of spindle cells and thin-walled vascular spaces, while the cellular type shows plump cells in a sheet-like pattern.
- Ancillary: Cellular MN often has a t(12;15)(p13;q25) translocation, leading to the ETV6::NTRK3 gene fusion, which can be detected by immunohistochemistry using a pan-TRK antibody.
Reference Gallery:
Mesoblastic nephroma. Classic-type mesoblastic nephroma composed of interlacing fascicles of spindled cells and thin-walled vascular spaces.
Mesoblastic nephroma. The tumour–kidney interface is irregular, with many islands of entrapped normal renal parenchyma.
Mesoblastic nephroma. Cellular type, composed of densely packed plump cells growing in a sheet-like pattern.
Mesoblastic nephroma. The tumour–kidney border in the cellular type is sharp, despite the absence of the capsule.
Mesoblastic nephroma. Mixed type, composed of cellular areas (upper part of the figure) that are sharply demarcated from the classic type.
Mesoblastic nephroma. Renal sinus infiltration by tumour, which is very common because no capsule is present.
Congenital mesoblastic nephroma. Contrast-enhanced axial CT shows a fairly homogeneous mass with predominantly peripheral enhancement at the anterior region of the left kidney extending to the renal hilum but without invasion of the renal vessels.

Q: A renal neoplasm characterized by a biphasic morphology—comprising a bland spindle cell stromal component and a primitive epithelial component—is the [...].
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, and an epithelial nodule that is identical to metanephric adenoma is present at the upper right. Note the unencapsulated border with the native kidney at the top of the image.
Metanephric adenofibroma. The metanephric stromal tumour component on the left is composed of bland spindle cells, and the metanephric adenoma component composed of primitive but mitotically inactive tubules is to the right.
Metanephric adenofibroma. The bland spindle cell stromal component is at the bottom, and the primitive but mitotically inactive epithelial component is at the top.
A: Metanephric Adenofibroma
Q: Metanephric Adenofibroma
- Clinical: Patients with [...] present with polycythaemia in 4 of 14 cases and haematuria in 3 of 14 cases.
- Micro: The [...] is characterized by a biphasic morphology with a spindle cell stromal component and an epithelial component.
- Ancillary: [...] mutations are characteristic of metanephric adenofibroma and other metanephric neoplasms.
Reference Gallery:
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, and an epithelial nodule that is identical to metanephric adenoma is present at the upper right. Note the unencapsulated border with the native kidney at the top of the image.
Metanephric adenofibroma. The metanephric stromal tumour component on the left is composed of bland spindle cells, and the metanephric adenoma component composed of primitive but mitotically inactive tubules is to the right.
Metanephric adenofibroma. The bland spindle cell stromal component is at the bottom, and the primitive but mitotically inactive epithelial component is at the top.
A: metanephric adenofibroma; metanephric adenofibroma; BRAF p.V600E

Q: The histopathologic hallmark of Metanephric Adenofibroma is a highly characteristic [...] morphology, which features an intimate mixture of spindle cell stroma and primitive epithelial tubules.
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, and an epithelial nodule that is identical to metanephric adenoma is present at the upper right. Note the unencapsulated border with the native kidney at the top of the image.
Metanephric adenofibroma. The metanephric stromal tumour component on the left is composed of bland spindle cells, and the metanephric adenoma component composed of primitive but mitotically inactive tubules is to the right.
Metanephric adenofibroma. The bland spindle cell stromal component is at the bottom, and the primitive but mitotically inactive epithelial component is at the top.
A: biphasic
Q: Metanephric Adenofibroma
- Clinical: Patients with [...] present with polycythaemia in 4 of 14 cases and haematuria in 3 of 14 cases.
- Micro: The [...] is characterized by a biphasic morphology with a spindle cell stromal component and an epithelial component.
- Ancillary: [...] mutations are characteristic of metanephric adenofibroma and other metanephric neoplasms.
Reference Gallery:
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, and an epithelial nodule that is identical to metanephric adenoma is present at the upper right. Note the unencapsulated border with the native kidney at the top of the image.
Metanephric adenofibroma. The metanephric stromal tumour component on the left is composed of bland spindle cells, and the metanephric adenoma component composed of primitive but mitotically inactive tubules is to the right.
Metanephric adenofibroma. The bland spindle cell stromal component is at the bottom, and the primitive but mitotically inactive epithelial component is at the top.
A: metanephric adenofibroma; metanephric adenofibroma; BRAF p.V600E

Q: Microscopically, Metanephric Adenoma consists of small, uniform, embryonic-appearing cells forming branching tubules in an edematous stroma, often creating a characteristic [...] appearance.
Metanephric adenoma. The neoplasm is unencapsulated and directly abuts the native kidney to the right. The neoplasm is composed of cuboidal cells with primitive basophilic nuclei and minimal cytoplasm, forming small tubules. Mitotic activity is not evident. A psammoma body is noted at the lower right.
Metanephric adenoma. The stroma is oedematous and contains branching tubules and tubulopapillary structures, creating a fingerprint-like appearance.
A: fingerprint-like
Back Extra: Metanephric Adenoma
- Clinical: Approximately 50% of cases are identified incidentally. Common presenting symptoms include abdominal pain and haematuria.
- Micro: Composed of small, uniform, embryonic-appearing cells forming small tubules in a hyalinized, oedematous stroma. Psammoma bodies are common.
- Ancillary: Diffuse nuclear immunoreactivity for WT1 protein and positivity for BRAF p.V600E mutation are characteristic.
Reference Gallery:
Metanephric adenoma. The neoplasm is unencapsulated and directly abuts the native kidney to the right. The neoplasm is composed of cuboidal cells with primitive basophilic nuclei and minimal cytoplasm, forming small tubules. Mitotic activity is not evident. A psammoma body is noted at the lower right.
Metanephric adenoma. The stroma is oedematous and contains branching tubules and tubulopapillary structures, creating a fingerprint-like appearance.
Metanephric adenoma. Tumours with more prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and absence of stromal foam cells are clues to the diagnosis of metanephric adenoma.
Metanephric adenoma. Metanephric adenomas typically demonstrate diffuse nuclear immunoreactivity for WT1 protein.

Q: When Metanephric Adenoma displays prominent papillary architecture, it can mimic low-grade papillary renal cell carcinoma; however, it is distinguished by hyperchromatic primitive nuclei and the absence of stromal [...].
Metanephric adenoma. Tumours with more prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and absence of stromal foam cells are clues to the diagnosis of metanephric adenoma.
A: foam cells
Back Extra: Metanephric Adenoma
- Clinical: Approximately 50% of cases are identified incidentally. Common presenting symptoms include abdominal pain and haematuria.
- Micro: Composed of small, uniform, embryonic-appearing cells forming small tubules in a hyalinized, oedematous stroma. Psammoma bodies are common.
- Ancillary: Diffuse nuclear immunoreactivity for WT1 protein and positivity for BRAF p.V600E mutation are characteristic.
Reference Gallery:
Metanephric adenoma. The neoplasm is unencapsulated and directly abuts the native kidney to the right. The neoplasm is composed of cuboidal cells with primitive basophilic nuclei and minimal cytoplasm, forming small tubules. Mitotic activity is not evident. A psammoma body is noted at the lower right.
Metanephric adenoma. The stroma is oedematous and contains branching tubules and tubulopapillary structures, creating a fingerprint-like appearance.
Metanephric adenoma. Tumours with more prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and absence of stromal foam cells are clues to the diagnosis of metanephric adenoma.
Metanephric adenoma. Metanephric adenomas typically demonstrate diffuse nuclear immunoreactivity for WT1 protein.

Q: Ancillary testing for Metanephric Adenoma is characteristically positive for the BRAF p.V600E mutation and shows diffuse nuclear immunoreactivity for [...].
Metanephric adenoma. Metanephric adenomas typically demonstrate diffuse nuclear immunoreactivity for WT1 protein.
A: WT1
Back Extra: Metanephric Adenoma
- Clinical: Approximately 50% of cases are identified incidentally. Common presenting symptoms include abdominal pain and haematuria.
- Micro: Composed of small, uniform, embryonic-appearing cells forming small tubules in a hyalinized, oedematous stroma. Psammoma bodies are common.
- Ancillary: Diffuse nuclear immunoreactivity for WT1 protein and positivity for BRAF p.V600E mutation are characteristic.
Reference Gallery:
Metanephric adenoma. The neoplasm is unencapsulated and directly abuts the native kidney to the right. The neoplasm is composed of cuboidal cells with primitive basophilic nuclei and minimal cytoplasm, forming small tubules. Mitotic activity is not evident. A psammoma body is noted at the lower right.
Metanephric adenoma. The stroma is oedematous and contains branching tubules and tubulopapillary structures, creating a fingerprint-like appearance.
Metanephric adenoma. Tumours with more prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and absence of stromal foam cells are clues to the diagnosis of metanephric adenoma.
Metanephric adenoma. Metanephric adenomas typically demonstrate diffuse nuclear immunoreactivity for WT1 protein.

Q: Macroscopically, metanephric stromal tumor typically presents as a fibrous mass centered in the renal medulla with a characteristic [...] border interfacing with the native kidney.
Metanephric stromal tumour. This is a fibrous neoplasm, centred in the medulla of this bivalved kidney. Note the scalloped border with the native kidney.
A: scalloped
Back Extra: Metanephric Stromal Tumour
- Clinical: Patients with metanephric stromal tumour typically present with an abdominal mass, although haematuria is not rare.
- Micro: Characterized by spindle-shaped cells forming concentric, onion-skin like rings around entrapped renal tubules and blood vessels.
- Ancillary: Most metanephric stromal tumours harbour BRAF p.V600E mutations, which can aid in differentiation from other renal tumours.
Reference Gallery:
Metanephric stromal tumour. This is a fibrous neoplasm, centred in the medulla of this bivalved kidney. Note the scalloped border with the native kidney.
Metanephric stromal tumour. Metanephric stromal tumours are composed of bland spindle cells and have a scalloped border with the native kidney. Native renal tubules are present within the lesion.
Metanephric stromal tumour. Neoplastic spindle cells encircle entrapped native tubules in a concentric fashion, yielding an onion-skin pattern.
Metanephric stromal tumour. Glomeruli entrapped within a metanephric stromal tumour frequently demonstrate florid juxtaglomerular cell hyperplasia. This may result in hyperreninism.
Metanephric stromal tumour. The neoplastic cells are bland and have indistinct cytoplasmic processes within a fibromyxoid stroma. Note the striking juxtaglomerular cell hyperplasia in the entrapped glomerulus at the lower right.
Metanephric stromal tumour. Arterioles within and occasionally outside of a metanephric stromal tumour frequently demonstrate angiodysplasia. Compared to the normal arterial wall (lower right), the majority of this arterial wall is markedly thickened and has undergone myxoid degeneration. The normally spindle-shaped smooth muscle cells have become epithelioid. These vessels can rupture, leading to haemorrhage.

Q: A characteristic microscopic feature of metanephric stromal tumor is the presence of bland spindle cells forming concentric, [...] rings around entrapped native renal tubules and blood vessels.
Metanephric stromal tumour. Metanephric stromal tumours are composed of bland spindle cells and have a scalloped border with the native kidney. Native renal tubules are present within the lesion.
Metanephric stromal tumour. Neoplastic spindle cells encircle entrapped native tubules in a concentric fashion, yielding an onion-skin pattern.
A: onion-skin
Back Extra: Metanephric Stromal Tumour
- Clinical: Patients with metanephric stromal tumour typically present with an abdominal mass, although haematuria is not rare.
- Micro: Characterized by spindle-shaped cells forming concentric, onion-skin like rings around entrapped renal tubules and blood vessels.
- Ancillary: Most metanephric stromal tumours harbour BRAF p.V600E mutations, which can aid in differentiation from other renal tumours.
Reference Gallery:
Metanephric stromal tumour. This is a fibrous neoplasm, centred in the medulla of this bivalved kidney. Note the scalloped border with the native kidney.
Metanephric stromal tumour. Metanephric stromal tumours are composed of bland spindle cells and have a scalloped border with the native kidney. Native renal tubules are present within the lesion.
Metanephric stromal tumour. Neoplastic spindle cells encircle entrapped native tubules in a concentric fashion, yielding an onion-skin pattern.
Metanephric stromal tumour. Glomeruli entrapped within a metanephric stromal tumour frequently demonstrate florid juxtaglomerular cell hyperplasia. This may result in hyperreninism.
Metanephric stromal tumour. The neoplastic cells are bland and have indistinct cytoplasmic processes within a fibromyxoid stroma. Note the striking juxtaglomerular cell hyperplasia in the entrapped glomerulus at the lower right.
Metanephric stromal tumour. Arterioles within and occasionally outside of a metanephric stromal tumour frequently demonstrate angiodysplasia. Compared to the normal arterial wall (lower right), the majority of this arterial wall is markedly thickened and has undergone myxoid degeneration. The normally spindle-shaped smooth muscle cells have become epithelioid. These vessels can rupture, leading to haemorrhage.

Q: Entrapped glomeruli within a metanephric stromal tumor frequently demonstrate florid [...] hyperplasia, which may result in clinical hyperreninism.
Metanephric stromal tumour. Glomeruli entrapped within a metanephric stromal tumour frequently demonstrate florid juxtaglomerular cell hyperplasia. This may result in hyperreninism.
Metanephric stromal tumour. The neoplastic cells are bland and have indistinct cytoplasmic processes within a fibromyxoid stroma. Note the striking juxtaglomerular cell hyperplasia in the entrapped glomerulus at the lower right.
A: juxtaglomerular cell
Back Extra: Metanephric Stromal Tumour
- Clinical: Patients with metanephric stromal tumour typically present with an abdominal mass, although haematuria is not rare.
- Micro: Characterized by spindle-shaped cells forming concentric, onion-skin like rings around entrapped renal tubules and blood vessels.
- Ancillary: Most metanephric stromal tumours harbour BRAF p.V600E mutations, which can aid in differentiation from other renal tumours.
Reference Gallery:
Metanephric stromal tumour. This is a fibrous neoplasm, centred in the medulla of this bivalved kidney. Note the scalloped border with the native kidney.
Metanephric stromal tumour. Metanephric stromal tumours are composed of bland spindle cells and have a scalloped border with the native kidney. Native renal tubules are present within the lesion.
Metanephric stromal tumour. Neoplastic spindle cells encircle entrapped native tubules in a concentric fashion, yielding an onion-skin pattern.
Metanephric stromal tumour. Glomeruli entrapped within a metanephric stromal tumour frequently demonstrate florid juxtaglomerular cell hyperplasia. This may result in hyperreninism.
Metanephric stromal tumour. The neoplastic cells are bland and have indistinct cytoplasmic processes within a fibromyxoid stroma. Note the striking juxtaglomerular cell hyperplasia in the entrapped glomerulus at the lower right.
Metanephric stromal tumour. Arterioles within and occasionally outside of a metanephric stromal tumour frequently demonstrate angiodysplasia. Compared to the normal arterial wall (lower right), the majority of this arterial wall is markedly thickened and has undergone myxoid degeneration. The normally spindle-shaped smooth muscle cells have become epithelioid. These vessels can rupture, leading to haemorrhage.

Q: Microscopically, Nephroblastoma classically exhibits a triphasic pattern consisting of epithelial, stromal, and [...] components.
Nephroblastoma. This example is composed of closely mixed blastemal and epithelial components.
Nephroblastoma. This nephroblastoma is composed of the blastemal component only (nodular appearance).
Nephroblastoma. The stromal component with heterologous elements, including cartilage and skeletal muscle.
A: blastemal
Back Extra: Nephroblastoma
- Clinical: Patients with nephroblastoma usually present with an abdominal mass and may have symptoms like abdominal pain, haematuria, hypertension, and anaemia.
- Micro: Nephroblastoma typically consists of blastemal, epithelial, and stromal components. Focal and diffuse anaplasia significantly affect prognosis.
- Ancillary: WT1, IGF2, TP53, MYCN, and 1q gain are important molecular markers in nephroblastoma, each with specific prognostic implications.
Reference Gallery:
Nephroblastoma. This example is composed of closely mixed blastemal and epithelial components.
Nephroblastoma. This nephroblastoma is composed of the epithelial component only (monophasic).
Nephroblastoma. This nephroblastoma is composed of the blastemal component only (nodular appearance).
Anaplastic nephroblastoma. Diffuse anaplasia with markedly enlarged and hyperchromatic nuclei and enlarged multipolar, atypical mitoses.
Anaplastic nephroblastoma. Focal anaplasia surrounded by chemotherapy-induced changes.
Nephrogenic rests. A perilobar nephrogenic rest showing sclerosing and a hyperplastic rest.
Nephrogenic rests. An intralobar nephrogenic rest mingling with the normal renal parenchyma.
Nephrogenic rests. Perilobar hyperplastic nephroblastomatosis.
Nephroblastoma. The stromal component with heterologous elements, including cartilage and skeletal muscle.
Nephroblastoma. FISH showing chromosome 1q gain.
Nephroblastoma. Aniridia.
Anaplasia cell. H&E staining.

Q: In Nephroblastoma, the presence of focal or diffuse [...] (characterized by markedly enlarged, hyperchromatic nuclei and atypical multipolar mitoses) significantly worsens the prognosis.
Anaplastic nephroblastoma. Diffuse anaplasia with markedly enlarged and hyperchromatic nuclei and enlarged multipolar, atypical mitoses.
Anaplastic nephroblastoma. Focal anaplasia surrounded by chemotherapy-induced changes.
Anaplasia cell. H&E staining.
A: anaplasia
Back Extra: Nephroblastoma
- Clinical: Patients with nephroblastoma usually present with an abdominal mass and may have symptoms like abdominal pain, haematuria, hypertension, and anaemia.
- Micro: Nephroblastoma typically consists of blastemal, epithelial, and stromal components. Focal and diffuse anaplasia significantly affect prognosis.
- Ancillary: WT1, IGF2, TP53, MYCN, and 1q gain are important molecular markers in nephroblastoma, each with specific prognostic implications.
Reference Gallery:
Nephroblastoma. This example is composed of closely mixed blastemal and epithelial components.
Nephroblastoma. This nephroblastoma is composed of the epithelial component only (monophasic).
Nephroblastoma. This nephroblastoma is composed of the blastemal component only (nodular appearance).
Anaplastic nephroblastoma. Diffuse anaplasia with markedly enlarged and hyperchromatic nuclei and enlarged multipolar, atypical mitoses.
Anaplastic nephroblastoma. Focal anaplasia surrounded by chemotherapy-induced changes.
Nephrogenic rests. A perilobar nephrogenic rest showing sclerosing and a hyperplastic rest.
Nephrogenic rests. An intralobar nephrogenic rest mingling with the normal renal parenchyma.
Nephrogenic rests. Perilobar hyperplastic nephroblastomatosis.
Nephroblastoma. The stromal component with heterologous elements, including cartilage and skeletal muscle.
Nephroblastoma. FISH showing chromosome 1q gain.
Nephroblastoma. Aniridia.
Anaplasia cell. H&E staining.

Q: Fluorescence in situ hybridization (FISH) can be used to detect the gain of chromosome [...], an important adverse molecular prognostic marker in Nephroblastoma.
Nephroblastoma. FISH showing chromosome 1q gain.
A: 1q
Back Extra: Nephroblastoma
- Clinical: Patients with nephroblastoma usually present with an abdominal mass and may have symptoms like abdominal pain, haematuria, hypertension, and anaemia.
- Micro: Nephroblastoma typically consists of blastemal, epithelial, and stromal components. Focal and diffuse anaplasia significantly affect prognosis.
- Ancillary: WT1, IGF2, TP53, MYCN, and 1q gain are important molecular markers in nephroblastoma, each with specific prognostic implications.
Reference Gallery:
Nephroblastoma. This example is composed of closely mixed blastemal and epithelial components.
Nephroblastoma. This nephroblastoma is composed of the epithelial component only (monophasic).
Nephroblastoma. This nephroblastoma is composed of the blastemal component only (nodular appearance).
Anaplastic nephroblastoma. Diffuse anaplasia with markedly enlarged and hyperchromatic nuclei and enlarged multipolar, atypical mitoses.
Anaplastic nephroblastoma. Focal anaplasia surrounded by chemotherapy-induced changes.
Nephrogenic rests. A perilobar nephrogenic rest showing sclerosing and a hyperplastic rest.
Nephrogenic rests. An intralobar nephrogenic rest mingling with the normal renal parenchyma.
Nephrogenic rests. Perilobar hyperplastic nephroblastomatosis.
Nephroblastoma. The stromal component with heterologous elements, including cartilage and skeletal muscle.
Nephroblastoma. FISH showing chromosome 1q gain.
Nephroblastoma. Aniridia.
Anaplasia cell. H&E staining.

Q: A pediatric renal mass presenting with gross hematuria shows a characteristic biphasic histologic appearance consisting of spindle cells and [...] cells. This is diagnostic of Ossifying Renal Tumor of Infancy.
Ossifying renal tumour of infancy. High-power view of the calcified part with osteoblastic cells.
Ossifying renal tumour of infancy. High-power view showing the spindle cell component.
A: osteoblast-like
Back Extra: Ossifying Renal Tumor of Infancy
- Clinical: Patients with Ossifying Renal Tumor of Infancy (ORTI) typically present with gross hematuria and a calcified mass seen on imaging.
- Micro: ORTIs are composed of osteoblast-like cells and spindle cells, with the former often immunopositive for EMA and vimentin.
- Ancillary: Clonal trisomy 4 has been identified as a recurrent molecular abnormality in ORTIs.
Reference Gallery:
Ossifying renal tumour of infancy. Low-power view showing the relationship of the tumour to the kidney and calyces.
Ossifying renal tumour of infancy. High-power view of the calcified part with osteoblastic cells.
Ossifying renal tumour of infancy. High-power view showing the spindle cell component.

Q: A pediatric patient presents with a calcified renal mass and gross hematuria. Microscopically, the lesion consists of a calcified component with osteoblastic cells and a distinct spindle cell population. This classic presentation describes [...].
Ossifying renal tumour of infancy. Low-power view showing the relationship of the tumour to the kidney and calyces.
Ossifying renal tumour of infancy. High-power view of the calcified part with osteoblastic cells.
Ossifying renal tumour of infancy. High-power view showing the spindle cell component.
A: Ossifying Renal Tumor of Infancy
Back Extra: Ossifying Renal Tumor of Infancy
- Clinical: Patients with Ossifying Renal Tumor of Infancy (ORTI) typically present with gross hematuria and a calcified mass seen on imaging.
- Micro: ORTIs are composed of osteoblast-like cells and spindle cells, with the former often immunopositive for EMA and vimentin.
- Ancillary: Clonal trisomy 4 has been identified as a recurrent molecular abnormality in ORTIs.
Reference Gallery:
Ossifying renal tumour of infancy. Low-power view showing the relationship of the tumour to the kidney and calyces.
Ossifying renal tumour of infancy. High-power view of the calcified part with osteoblastic cells.
Ossifying renal tumour of infancy. High-power view showing the spindle cell component.

Q: Histologically, Paediatric Cystic Nephroma is characterized by cysts lined by flattened, cuboidal, or hobnail epithelium, and importantly lacks [...] within the septa.
Paediatric cystic nephroma. There are mature tubules within the septa, but no blastema.
Paediatric cystic nephroma. The cysts are lined with a hobnail epithelium.
Paediatric cystic nephroma. The cysts are lined with a flat epithelium.
A: blastema
Back Extra: Paediatric Cystic Nephroma
- Clinical: Paediatric cystic nephroma may present as a palpable abdominal mass and is often associated with germline DICER1 mutations.
- Micro: The tumour is composed of cysts separated by septa lined with flattened, cuboidal, or hobnail epithelium, with no blastema present.
- Ancillary: Germline analysis of tumour-specific DICER1 mutations can aid in diagnosis.
Reference Gallery:
Paediatric cystic nephroma. There are mature tubules within the septa, but no blastema.
Paediatric cystic nephroma. The cysts are lined with a hobnail epithelium.
Paediatric cystic nephroma. The cysts are lined with a flat epithelium.
Paediatric cystic nephroma. Ultrasound shows a well-circumscribed multiseptated cystic mass. The cysts are anechoic with no nodular solid components.
Paediatric cystic nephroma. Contrast-enhanced axial CT shows an encapsulated multiseptated cystic mass. The cysts are isoattenuating or slightly hyperattenuating relative to water. The capsule and septa are mildly enhancing. Herniation of the tumour into the collecting system is a characteristic feature.

Q: Patients diagnosed with Paediatric Cystic Nephroma often present with a multiseptated cystic mass and are frequently associated with germline mutations in the [...] gene.
Paediatric cystic nephroma. Ultrasound shows a well-circumscribed multiseptated cystic mass. The cysts are anechoic with no nodular solid components.
Paediatric cystic nephroma. Contrast-enhanced axial CT shows an encapsulated multiseptated cystic mass. The cysts are isoattenuating or slightly hyperattenuating relative to water. The capsule and septa are mildly enhancing. Herniation of the tumour into the collecting system is a characteristic feature.
A: DICER1
Back Extra: Paediatric Cystic Nephroma
- Clinical: Paediatric cystic nephroma may present as a palpable abdominal mass and is often associated with germline DICER1 mutations.
- Micro: The tumour is composed of cysts separated by septa lined with flattened, cuboidal, or hobnail epithelium, with no blastema present.
- Ancillary: Germline analysis of tumour-specific DICER1 mutations can aid in diagnosis.
Reference Gallery:
Paediatric cystic nephroma. There are mature tubules within the septa, but no blastema.
Paediatric cystic nephroma. The cysts are lined with a hobnail epithelium.
Paediatric cystic nephroma. The cysts are lined with a flat epithelium.
Paediatric cystic nephroma. Ultrasound shows a well-circumscribed multiseptated cystic mass. The cysts are anechoic with no nodular solid components.
Paediatric cystic nephroma. Contrast-enhanced axial CT shows an encapsulated multiseptated cystic mass. The cysts are isoattenuating or slightly hyperattenuating relative to water. The capsule and septa are mildly enhancing. Herniation of the tumour into the collecting system is a characteristic feature.

Q: A characteristic radiologic finding of Paediatric Cystic Nephroma on contrast-enhanced CT is the [...] of the multiseptated cystic tumor into the collecting system.
Paediatric cystic nephroma. Contrast-enhanced axial CT shows an encapsulated multiseptated cystic mass. The cysts are isoattenuating or slightly hyperattenuating relative to water. The capsule and septa are mildly enhancing. Herniation of the tumour into the collecting system is a characteristic feature.
A: herniation
Back Extra: Paediatric Cystic Nephroma
- Clinical: Paediatric cystic nephroma may present as a palpable abdominal mass and is often associated with germline DICER1 mutations.
- Micro: The tumour is composed of cysts separated by septa lined with flattened, cuboidal, or hobnail epithelium, with no blastema present.
- Ancillary: Germline analysis of tumour-specific DICER1 mutations can aid in diagnosis.
Reference Gallery:
Paediatric cystic nephroma. There are mature tubules within the septa, but no blastema.
Paediatric cystic nephroma. The cysts are lined with a hobnail epithelium.
Paediatric cystic nephroma. The cysts are lined with a flat epithelium.
Paediatric cystic nephroma. Ultrasound shows a well-circumscribed multiseptated cystic mass. The cysts are anechoic with no nodular solid components.
Paediatric cystic nephroma. Contrast-enhanced axial CT shows an encapsulated multiseptated cystic mass. The cysts are isoattenuating or slightly hyperattenuating relative to water. The capsule and septa are mildly enhancing. Herniation of the tumour into the collecting system is a characteristic feature.

Q: Microscopically, the characteristic variable-sized cystic spaces of Peritoneal Inclusion Cysts are classically lined by a single layer of bland, flat, or cuboidal [...] cells.
Peritoneal inclusion cysts. Cysts of variable size, lined by bland, flat and cuboidal mesothelial cells.
Peritoneal inclusion cysts. Cystic spaces lined by bland, flat and cuboidal mesothelial cells.
A: mesothelial
Back Extra: Peritoneal Inclusion Cysts
- Clinical: Peritoneal inclusion cysts can present with abdominal or pelvic pain, abdominal distension, or as an inguinal hernia.
- Micro: Peritoneal inclusion cysts are lined by a single layer of bland, flat or cuboidal mesothelial cells, with occasional metaplastic or reactive changes.
- Ancillary: Immunohistochemistry shows positivity for mesothelial markers such as calretinin and CK5/6, with variable positivity for PAX8, ER, and PR.
Reference Gallery:
Peritoneal inclusion cysts. Cysts of variable size, lined by bland, flat and cuboidal mesothelial cells.
Peritoneal inclusion cysts. Cystic spaces lined by bland, flat and cuboidal mesothelial cells.

Q: Histologically, the presence of cystic spaces lined by a single layer of bland, flat, or cuboidal mesothelial cells with occasional reactive changes is the hallmark of [...].
Peritoneal inclusion cysts. Cysts of variable size, lined by bland, flat and cuboidal mesothelial cells.
Peritoneal inclusion cysts. Cystic spaces lined by bland, flat and cuboidal mesothelial cells.
A: Peritoneal Inclusion Cysts
Back Extra: Peritoneal Inclusion Cysts
- Clinical: Peritoneal inclusion cysts can present with abdominal or pelvic pain, abdominal distension, or as an inguinal hernia.
- Micro: Peritoneal inclusion cysts are lined by a single layer of bland, flat or cuboidal mesothelial cells, with occasional metaplastic or reactive changes.
- Ancillary: Immunohistochemistry shows positivity for mesothelial markers such as calretinin and CK5/6, with variable positivity for PAX8, ER, and PR.
Reference Gallery:
Peritoneal inclusion cysts. Cysts of variable size, lined by bland, flat and cuboidal mesothelial cells.
Peritoneal inclusion cysts. Cystic spaces lined by bland, flat and cuboidal mesothelial cells.

Q: Histologically, the TFE3-rearranged variant of Renal Cell Carcinoma with MiT Translocations classically demonstrates a papillary pattern containing numerous [...].
TFE3-rearranged renal cell carcinoma. Papillary pattern with many psammoma bodies.
A: psammoma bodies
Back Extra: Renal Cell Carcinoma with MiT Translocations
- Clinical: Renal cell carcinoma with MiT translocations tends to affect young people, with a median age of approximately 30 years, and prior exposure to cytotoxic chemotherapy is a risk factor.
- Micro: TFE3-rearranged RCC shows a papillary pattern with many psammoma bodies, while TFEB-rearranged RCC exhibits a biphasic pattern with nests of larger epithelioid cells and smaller cells.
- Ancillary: Immunohistochemistry (IHC) is crucial for diagnosis, with TFE3-rearranged RCC showing strong nuclear TFE3 staining and TFEB-rearranged RCC showing strong nuclear TFEB staining.
Reference Gallery:
Renal cell carcinoma with MiT translocations. TFEB-rearranged renal cell carcinoma. Neoplasia with a biphasic appearance, with larger epithelioid cells at the periphery of the nests and smaller cells clustered in the centre.
TFEB-rearranged renal cell carcinoma. Strong diffuse nuclear staining for TFEB in tumour cells, but not in the stroma.
TFEB-rearranged renal cell carcinoma. Characteristic focal HMB45 immunohistochemical staining.
TFE3-rearranged renal cell carcinoma. Papillary pattern with many psammoma bodies.
TFE3-rearranged renal cell carcinoma. The gross appearance is a well-circumscribed tumour with a tan-yellow cut surface, focal haemorrhage, and necrosis.
Renal cell carcinoma with MiT translocations. TFE3-rearranged renal cell carcinoma. Typical FISH image of a dual-colour break-apart TFE3 (Xp11.2) locus from a female patient.
TFE3-rearranged renal cell carcinoma. Macroscopic appearance with focal haemorrhage.
TFEB-rearranged renal cell carcinoma. The tumour cells show nuclear and cytoplasmic labelling for TFEB.
Renal cell carcinoma with MiT translocations. TFEB-rearranged renal cell carcinoma. Typical image of dual-colour break-apart FISH for the TFEB (6p21) locus.
TFE3-rearranged renal cell carcinoma. Eosinophilic and clear cell components are present.
TFE3-rearranged renal cell carcinoma. At higher power, there is patchy, fine to slightly coarse cytoplasmic melanin pigmentation.
TFE3-rearranged renal cell carcinoma. This example has a solid histological pattern.

Q: The TFEB-rearranged variant of Renal Cell Carcinoma with MiT Translocations often exhibits a characteristic biphasic pattern consisting of nests with larger epithelioid cells at the periphery and [...] clustered in the center.
Renal cell carcinoma with MiT translocations. TFEB-rearranged renal cell carcinoma. Neoplasia with a biphasic appearance, with larger epithelioid cells at the periphery of the nests and smaller cells clustered in the centre.
A: smaller cells
Back Extra: Renal Cell Carcinoma with MiT Translocations
- Clinical: Renal cell carcinoma with MiT translocations tends to affect young people, with a median age of approximately 30 years, and prior exposure to cytotoxic chemotherapy is a risk factor.
- Micro: TFE3-rearranged RCC shows a papillary pattern with many psammoma bodies, while TFEB-rearranged RCC exhibits a biphasic pattern with nests of larger epithelioid cells and smaller cells.
- Ancillary: Immunohistochemistry (IHC) is crucial for diagnosis, with TFE3-rearranged RCC showing strong nuclear TFE3 staining and TFEB-rearranged RCC showing strong nuclear TFEB staining.
Reference Gallery:
Renal cell carcinoma with MiT translocations. TFEB-rearranged renal cell carcinoma. Neoplasia with a biphasic appearance, with larger epithelioid cells at the periphery of the nests and smaller cells clustered in the centre.
TFEB-rearranged renal cell carcinoma. Strong diffuse nuclear staining for TFEB in tumour cells, but not in the stroma.
TFEB-rearranged renal cell carcinoma. Characteristic focal HMB45 immunohistochemical staining.
TFE3-rearranged renal cell carcinoma. Papillary pattern with many psammoma bodies.
TFE3-rearranged renal cell carcinoma. The gross appearance is a well-circumscribed tumour with a tan-yellow cut surface, focal haemorrhage, and necrosis.
Renal cell carcinoma with MiT translocations. TFE3-rearranged renal cell carcinoma. Typical FISH image of a dual-colour break-apart TFE3 (Xp11.2) locus from a female patient.
TFE3-rearranged renal cell carcinoma. Macroscopic appearance with focal haemorrhage.
TFEB-rearranged renal cell carcinoma. The tumour cells show nuclear and cytoplasmic labelling for TFEB.
Renal cell carcinoma with MiT translocations. TFEB-rearranged renal cell carcinoma. Typical image of dual-colour break-apart FISH for the TFEB (6p21) locus.
TFE3-rearranged renal cell carcinoma. Eosinophilic and clear cell components are present.
TFE3-rearranged renal cell carcinoma. At higher power, there is patchy, fine to slightly coarse cytoplasmic melanin pigmentation.
TFE3-rearranged renal cell carcinoma. This example has a solid histological pattern.

Q: To confirm the specific subtype of Renal Cell Carcinoma with MiT Translocations, immunohistochemistry is utilized to detect strong, diffuse nuclear staining for either [...].
TFEB-rearranged renal cell carcinoma. Strong diffuse nuclear staining for TFEB in tumour cells, but not in the stroma.
TFEB-rearranged renal cell carcinoma. The tumour cells show nuclear and cytoplasmic labelling for TFEB.
A: TFE3 or TFEB
Back Extra: Renal Cell Carcinoma with MiT Translocations
- Clinical: Renal cell carcinoma with MiT translocations tends to affect young people, with a median age of approximately 30 years, and prior exposure to cytotoxic chemotherapy is a risk factor.
- Micro: TFE3-rearranged RCC shows a papillary pattern with many psammoma bodies, while TFEB-rearranged RCC exhibits a biphasic pattern with nests of larger epithelioid cells and smaller cells.
- Ancillary: Immunohistochemistry (IHC) is crucial for diagnosis, with TFE3-rearranged RCC showing strong nuclear TFE3 staining and TFEB-rearranged RCC showing strong nuclear TFEB staining.
Reference Gallery:
Renal cell carcinoma with MiT translocations. TFEB-rearranged renal cell carcinoma. Neoplasia with a biphasic appearance, with larger epithelioid cells at the periphery of the nests and smaller cells clustered in the centre.
TFEB-rearranged renal cell carcinoma. Strong diffuse nuclear staining for TFEB in tumour cells, but not in the stroma.
TFEB-rearranged renal cell carcinoma. Characteristic focal HMB45 immunohistochemical staining.
TFE3-rearranged renal cell carcinoma. Papillary pattern with many psammoma bodies.
TFE3-rearranged renal cell carcinoma. The gross appearance is a well-circumscribed tumour with a tan-yellow cut surface, focal haemorrhage, and necrosis.
Renal cell carcinoma with MiT translocations. TFE3-rearranged renal cell carcinoma. Typical FISH image of a dual-colour break-apart TFE3 (Xp11.2) locus from a female patient.
TFE3-rearranged renal cell carcinoma. Macroscopic appearance with focal haemorrhage.
TFEB-rearranged renal cell carcinoma. The tumour cells show nuclear and cytoplasmic labelling for TFEB.
Renal cell carcinoma with MiT translocations. TFEB-rearranged renal cell carcinoma. Typical image of dual-colour break-apart FISH for the TFEB (6p21) locus.
TFE3-rearranged renal cell carcinoma. Eosinophilic and clear cell components are present.
TFE3-rearranged renal cell carcinoma. At higher power, there is patchy, fine to slightly coarse cytoplasmic melanin pigmentation.
TFE3-rearranged renal cell carcinoma. This example has a solid histological pattern.

Q: In Renal Ewing Sarcoma, the microscopic appearance classically consists of a highly cellular tumor composed of uniform [...] with scant cytoplasm.
Renal Ewing sarcoma. Low-power view showing the tumour in relation to the kidney.
Renal Ewing sarcoma. High-power view showing the typical appearance of Ewing sarcoma with uniform small round cells with little cytoplasm and slightly nodular growth.
A: small round cells
Back Extra: Renal Ewing Sarcoma
- Clinical: The classic presentation of Renal Ewing Sarcoma often includes haematuria, pain, and a palpable mass, though these symptoms are not specific.
- Micro: Microscopically, Renal Ewing Sarcoma shows a highly cellular tumor composed of small cells with little cytoplasm, organized in sheets and possibly rosettes.
- Ancillary: The diagnosis of Renal Ewing Sarcoma is confirmed by diffuse strong membranous CD99 expression and nuclear NKX2-2 staining in ≥ 5% of tumor cells.
Reference Gallery:
Renal Ewing sarcoma. Low-power view showing the tumour in relation to the kidney.
Renal Ewing sarcoma. High-power view showing the typical appearance of Ewing sarcoma with uniform small round cells with little cytoplasm and slightly nodular growth.
Renal Ewing sarcoma. Strong diffuse membranous CD99 immunostaining of tumour cells.
Renal Ewing sarcoma. Strong diffuse nuclear NKX2-2 immunostaining of tumour cells.

Q: The diagnosis of Renal Ewing Sarcoma is characteristically supported by strong, diffuse membranous immunohistochemical expression of [...].
Renal Ewing sarcoma. Strong diffuse membranous CD99 immunostaining of tumour cells.
A: CD99
Back Extra: Renal Ewing Sarcoma
- Clinical: The classic presentation of Renal Ewing Sarcoma often includes haematuria, pain, and a palpable mass, though these symptoms are not specific.
- Micro: Microscopically, Renal Ewing Sarcoma shows a highly cellular tumor composed of small cells with little cytoplasm, organized in sheets and possibly rosettes.
- Ancillary: The diagnosis of Renal Ewing Sarcoma is confirmed by diffuse strong membranous CD99 expression and nuclear NKX2-2 staining in ≥ 5% of tumor cells.
Reference Gallery:
Renal Ewing sarcoma. Low-power view showing the tumour in relation to the kidney.
Renal Ewing sarcoma. High-power view showing the typical appearance of Ewing sarcoma with uniform small round cells with little cytoplasm and slightly nodular growth.
Renal Ewing sarcoma. Strong diffuse membranous CD99 immunostaining of tumour cells.
Renal Ewing sarcoma. Strong diffuse nuclear NKX2-2 immunostaining of tumour cells.

Q: In addition to membranous markers, Renal Ewing Sarcoma frequently demonstrates diffuse nuclear immunostaining for [...].
Renal Ewing sarcoma. Strong diffuse nuclear NKX2-2 immunostaining of tumour cells.
A: NKX2-2
Back Extra: Renal Ewing Sarcoma
- Clinical: The classic presentation of Renal Ewing Sarcoma often includes haematuria, pain, and a palpable mass, though these symptoms are not specific.
- Micro: Microscopically, Renal Ewing Sarcoma shows a highly cellular tumor composed of small cells with little cytoplasm, organized in sheets and possibly rosettes.
- Ancillary: The diagnosis of Renal Ewing Sarcoma is confirmed by diffuse strong membranous CD99 expression and nuclear NKX2-2 staining in ≥ 5% of tumor cells.
Reference Gallery:
Renal Ewing sarcoma. Low-power view showing the tumour in relation to the kidney.
Renal Ewing sarcoma. High-power view showing the typical appearance of Ewing sarcoma with uniform small round cells with little cytoplasm and slightly nodular growth.
Renal Ewing sarcoma. Strong diffuse membranous CD99 immunostaining of tumour cells.
Renal Ewing sarcoma. Strong diffuse nuclear NKX2-2 immunostaining of tumour cells.

Q: SMARCB1-deficient renal medullary carcinoma is predominantly seen in young patients with a history of [...] or hemoglobin SC disease.
Renal medullary carcinoma. Extravasated red blood cells within the neoplasm demonstrate sickling.
A: sickle cell trait
Back Extra: SMARCB1-deficient renal medullary carcinoma
- Clinical: SMARCB1-deficient renal medullary carcinoma typically presents with haematuria, flank pain, and an abdominal mass, and is more common in patients with sickle cell trait or haemoglobin SC disease.
- Micro: Histologically, the neoplastic cells form cords and tubules within a desmoplastic stroma, often demonstrating a cribriform or adenoid cystic carcinoma-like appearance.
- Ancillary: Immunohistochemistry shows a loss of SMARCB1 (INI1) in the neoplastic cells, while surrounding stromal cells retain normal SMARCB1 expression.
Reference Gallery:
Renal medullary carcinoma. The neoplastic cells form cords and tubules within an oedematous desmoplastic stroma. Native kidney is present to the left.
Renal medullary carcinoma. The neoplasm has a cribriform architecture, reminiscent of adenoid cystic carcinoma.
Renal medullary carcinoma. The neoplastic cells are vacuolated and form cords in a desmoplastic stroma. They permeate the kidney, surrounding a native glomerulus at the upper left.
Renal medullary carcinoma. Extravasated red blood cells within the neoplasm demonstrate sickling.
Renal medullary carcinoma. The renal medullary carcinoma cells in this lymph node metastasis have a rhabdoid phenotype. They demonstrate vesicular chromatin, prominent nucleoli, and hyaline intracytoplasmic inclusions.
Renal medullary carcinoma. The neoplastic cells demonstrate a loss of SMARCB1 (INI1). The surrounding non-neoplastic stromal cells demonstrate appropriate nuclear immunoreactivity.

Q: Histologically, SMARCB1-deficient renal medullary carcinoma frequently exhibits a cribriform architecture within a desmoplastic stroma, remarkably reminiscent of [...].
Renal medullary carcinoma. The neoplasm has a cribriform architecture, reminiscent of adenoid cystic carcinoma.
A: adenoid cystic carcinoma
Back Extra: SMARCB1-deficient renal medullary carcinoma
- Clinical: SMARCB1-deficient renal medullary carcinoma typically presents with haematuria, flank pain, and an abdominal mass, and is more common in patients with sickle cell trait or haemoglobin SC disease.
- Micro: Histologically, the neoplastic cells form cords and tubules within a desmoplastic stroma, often demonstrating a cribriform or adenoid cystic carcinoma-like appearance.
- Ancillary: Immunohistochemistry shows a loss of SMARCB1 (INI1) in the neoplastic cells, while surrounding stromal cells retain normal SMARCB1 expression.
Reference Gallery:
Renal medullary carcinoma. The neoplastic cells form cords and tubules within an oedematous desmoplastic stroma. Native kidney is present to the left.
Renal medullary carcinoma. The neoplasm has a cribriform architecture, reminiscent of adenoid cystic carcinoma.
Renal medullary carcinoma. The neoplastic cells are vacuolated and form cords in a desmoplastic stroma. They permeate the kidney, surrounding a native glomerulus at the upper left.
Renal medullary carcinoma. Extravasated red blood cells within the neoplasm demonstrate sickling.
Renal medullary carcinoma. The renal medullary carcinoma cells in this lymph node metastasis have a rhabdoid phenotype. They demonstrate vesicular chromatin, prominent nucleoli, and hyaline intracytoplasmic inclusions.
Renal medullary carcinoma. The neoplastic cells demonstrate a loss of SMARCB1 (INI1). The surrounding non-neoplastic stromal cells demonstrate appropriate nuclear immunoreactivity.

Q: Immunohistochemistry in SMARCB1-deficient renal medullary carcinoma confirms the diagnosis by showing a characteristic loss of [...] (SMARCB1) in the tumor cells, with retained nuclear expression in background stromal cells.
Renal medullary carcinoma. The neoplastic cells demonstrate a loss of SMARCB1 (INI1). The surrounding non-neoplastic stromal cells demonstrate appropriate nuclear immunoreactivity.
A: INI1
Back Extra: SMARCB1-deficient renal medullary carcinoma
- Clinical: SMARCB1-deficient renal medullary carcinoma typically presents with haematuria, flank pain, and an abdominal mass, and is more common in patients with sickle cell trait or haemoglobin SC disease.
- Micro: Histologically, the neoplastic cells form cords and tubules within a desmoplastic stroma, often demonstrating a cribriform or adenoid cystic carcinoma-like appearance.
- Ancillary: Immunohistochemistry shows a loss of SMARCB1 (INI1) in the neoplastic cells, while surrounding stromal cells retain normal SMARCB1 expression.
Reference Gallery:
Renal medullary carcinoma. The neoplastic cells form cords and tubules within an oedematous desmoplastic stroma. Native kidney is present to the left.
Renal medullary carcinoma. The neoplasm has a cribriform architecture, reminiscent of adenoid cystic carcinoma.
Renal medullary carcinoma. The neoplastic cells are vacuolated and form cords in a desmoplastic stroma. They permeate the kidney, surrounding a native glomerulus at the upper left.
Renal medullary carcinoma. Extravasated red blood cells within the neoplasm demonstrate sickling.
Renal medullary carcinoma. The renal medullary carcinoma cells in this lymph node metastasis have a rhabdoid phenotype. They demonstrate vesicular chromatin, prominent nucleoli, and hyaline intracytoplasmic inclusions.
Renal medullary carcinoma. The neoplastic cells demonstrate a loss of SMARCB1 (INI1). The surrounding non-neoplastic stromal cells demonstrate appropriate nuclear immunoreactivity.

Q: Microscopically, Condyloma acuminatum frequently demonstrates squamous hyperplasia, papillomatosis, and the characteristic presence of virally altered cells with irregular chromatin and perinuclear clearing known as [...].
Vulvar condyloma, genital seborrhoeic keratosis. This still image from a whole slide scan shows squamous hyperplasia with elongated rete pegs and keratin horn cysts.
Vulvar condyloma, seborrhoeic keratosis–like. High-magnification view demonstrates parakeratosis atop squamous hyperplasia. An embedded keratin horn cyst is seen in the mid-lower epidermis. Scattered koilocytes are also noted (nuclear chromatin irregularities with perinuclear clearing). PCR was positive for HPV6.
A: koilocytes
Q: Condyloma acuminatum
- Clinical: Most cases of [...] in children are acquired through non-sexual routes such as vertical transmission, autoinoculation, or shared personal items.
- Micro: [...] shows squamous hyperplasia, papillomatosis, and koilocytosis with elongated rete pegs and keratin horn cysts.
- Ancillary: Typing of HPV by sequencing is helpful for confirming the presence of [...]. p16INK4a staining can also be used to differentiate between high-grade and low-grade squamous intraepithelial lesions.
Reference Gallery:
Paediatric genital condyloma. Preoperative photograph of a 2-year-old girl with congenitally acquired condyloma of the vulva, grossly and microscopically a genital seborrhoeic keratosis subtype. PCR was positive for HPV6.
Paediatric genital condyloma. This 5-year-old girl was subjected to repeated sexual assault by her mother’s boyfriend and presented with persistent “scratching of her private parts”. The clinical photo shows multiple exophytic papillomatous lesions of the labia majora.
Vulvar condyloma, genital seborrhoeic keratosis. This still image from a whole slide scan shows squamous hyperplasia with elongated rete pegs and keratin horn cysts.
Vulvar condyloma, seborrhoeic keratosis–like. High-magnification view demonstrates parakeratosis atop squamous hyperplasia. An embedded keratin horn cyst is seen in the mid-lower epidermis. Scattered koilocytes are also noted (nuclear chromatin irregularities with perinuclear clearing). PCR was positive for HPV6.
A: condyloma acuminatum; Condyloma acuminatum; condyloma acuminatum

Q: In pediatric patients, the presentation of multiple exophytic, papillomatous lesions on the genitalia is characteristic of [...], a condition usually acquired via non-sexual routes (e.g., vertical transmission) but which occasionally warrants evaluation for potential sexual abuse.
Paediatric genital condyloma. Preoperative photograph of a 2-year-old girl with congenitally acquired condyloma of the vulva, grossly and microscopically a genital seborrhoeic keratosis subtype. PCR was positive for HPV6.
Paediatric genital condyloma. This 5-year-old girl was subjected to repeated sexual assault by her mother’s boyfriend and presented with persistent “scratching of her private parts”. The clinical photo shows multiple exophytic papillomatous lesions of the labia majora.
A: Condyloma acuminatum
Q: Condyloma acuminatum
- Clinical: Most cases of [...] in children are acquired through non-sexual routes such as vertical transmission, autoinoculation, or shared personal items.
- Micro: [...] shows squamous hyperplasia, papillomatosis, and koilocytosis with elongated rete pegs and keratin horn cysts.
- Ancillary: Typing of HPV by sequencing is helpful for confirming the presence of [...]. p16INK4a staining can also be used to differentiate between high-grade and low-grade squamous intraepithelial lesions.
Reference Gallery:
Paediatric genital condyloma. Preoperative photograph of a 2-year-old girl with congenitally acquired condyloma of the vulva, grossly and microscopically a genital seborrhoeic keratosis subtype. PCR was positive for HPV6.
Paediatric genital condyloma. This 5-year-old girl was subjected to repeated sexual assault by her mother’s boyfriend and presented with persistent “scratching of her private parts”. The clinical photo shows multiple exophytic papillomatous lesions of the labia majora.
Vulvar condyloma, genital seborrhoeic keratosis. This still image from a whole slide scan shows squamous hyperplasia with elongated rete pegs and keratin horn cysts.
Vulvar condyloma, seborrhoeic keratosis–like. High-magnification view demonstrates parakeratosis atop squamous hyperplasia. An embedded keratin horn cyst is seen in the mid-lower epidermis. Scattered koilocytes are also noted (nuclear chromatin irregularities with perinuclear clearing). PCR was positive for HPV6.
A: condyloma acuminatum; Condyloma acuminatum; condyloma acuminatum

Q: Microscopically, a(n) [...] is defined by an admixture of female-directed elements (e.g., granulosa cells forming variably sized follicles) and male-directed elements (e.g., solid lobules of Sertoli cells and clusters of pink Leydig cells).
Gynandroblastoma. Gynandroblastoma composed of Sertoli–Leydig cell tumour (left) and adult granulosa cell tumour (right).
A: gynandroblastoma
Q: Gynandroblastoma
- Clinical: Patients with [...] can present with abdominal pain or distension and androgenic symptoms, and the median age at presentation is 24.5–28 years.
- Micro: [...] is characterized by deep purple solid lobules of Sertoli cells, small clusters of Leydig cells with abundant pink cytoplasm, and pale nodules containing small clusters of cells and variably sized follicles.
- Ancillary: [...] often shows biallelic DICER1 loss-of-function and missense RNase IIIb mutations, which are essential for confirming the diagnosis.
Reference Gallery:
Gynandroblastoma. Gynandroblastoma composed of Sertoli–Leydig cell tumour (left) and adult granulosa cell tumour (right).
Gynandroblastoma. Gynandroblastoma composed of juvenile granulosa cell tumour (shown here) and moderately differentiated Sertoli–Leydig cell tumour with heterologous intestinal mucinous differentiation (shown in Fig. 37643).
Gynandroblastoma. Gynandroblastoma composed of juvenile granulosa cell tumour (shown in Fig. 37642) and moderately differentiated Sertoli–Leydig cell tumour with heterologous intestinal mucinous differentiation (shown here).
A: gynandroblastoma; Gynandroblastoma; Gynandroblastoma

Q: In a gynandroblastoma, the female-directed component can be an adult or juvenile granulosa cell tumor, while the male-directed Sertoli-Leydig component may occasionally exhibit [...] elements, such as intestinal mucinous glands.
Gynandroblastoma. Gynandroblastoma composed of juvenile granulosa cell tumour (shown here) and moderately differentiated Sertoli–Leydig cell tumour with heterologous intestinal mucinous differentiation (shown in Fig. 37643).
Gynandroblastoma. Gynandroblastoma composed of juvenile granulosa cell tumour (shown in Fig. 37642) and moderately differentiated Sertoli–Leydig cell tumour with heterologous intestinal mucinous differentiation (shown here).
A: heterologous
Q: Gynandroblastoma
- Clinical: Patients with [...] can present with abdominal pain or distension and androgenic symptoms, and the median age at presentation is 24.5–28 years.
- Micro: [...] is characterized by deep purple solid lobules of Sertoli cells, small clusters of Leydig cells with abundant pink cytoplasm, and pale nodules containing small clusters of cells and variably sized follicles.
- Ancillary: [...] often shows biallelic DICER1 loss-of-function and missense RNase IIIb mutations, which are essential for confirming the diagnosis.
Reference Gallery:
Gynandroblastoma. Gynandroblastoma composed of Sertoli–Leydig cell tumour (left) and adult granulosa cell tumour (right).
Gynandroblastoma. Gynandroblastoma composed of juvenile granulosa cell tumour (shown here) and moderately differentiated Sertoli–Leydig cell tumour with heterologous intestinal mucinous differentiation (shown in Fig. 37643).
Gynandroblastoma. Gynandroblastoma composed of juvenile granulosa cell tumour (shown in Fig. 37642) and moderately differentiated Sertoli–Leydig cell tumour with heterologous intestinal mucinous differentiation (shown here).
A: gynandroblastoma; Gynandroblastoma; Gynandroblastoma

Q: Patients with Juvenile Granulosa Cell Tumor of the Ovary often present with a pelvic mass and [...] effects, which can manifest clinically as precocious pseudopuberty and radiologically as endometrial thickening.
Juvenile granulosa cell tumour of the ovary. Contrast axial CT showing a large, almost completely cystic mass arising from the pelvis of a prepubertal girl.
Juvenile granulosa cell tumour of the ovary. Contrast axial CT showing a poorly enhancing solid component at the uppermost aspect of the cystic mass. Note there is endometrial thickening within the uterus as a result of the estrogenic effect.
A: estrogenic
Back Extra: Juvenile Granulosa Cell Tumor of the Ovary
- Clinical: Patients with Juvenile Granulosa Cell Tumor of the Ovary often present with a pelvic mass and estrogenic effects, including precocious pseudopuberty and menstrual disturbances.
- Micro: Histologically, the tumour shows a nodular or diffuse growth pattern with interspersed follicles and cells with round, vesicular nuclei and abundant pale or eosinophilic cytoplasm.
- Ancillary: Genetic testing may reveal activating alterations in AKT1 and GNAS, and somatic mosaic IDH1 and IDH2 mutations in cases associated with Ollier disease or Maffucci syndrome.
Reference Gallery:
Juvenile granulosa cell tumour. The tumour has a predominantly nodular, solid, yellow cut surface with focal cystic and haemorrhagic areas.
Juvenile granulosa cell tumour. Low-magnification view showing nodular tumour architecture with variably sized follicle-like spaces.
Juvenile granulosa cell tumour. Predominantly solid growth pattern with small follicle-like spaces (upper part of image). The cells have eosinophilic or focally vacuolated cytoplasm.
Juvenile granulosa cell tumour. High-magnification view showing mitotic activity and apoptosis.
Juvenile granulosa cell tumour of the ovary. Contrast axial CT showing a large, almost completely cystic mass arising from the pelvis of a prepubertal girl.
Juvenile granulosa cell tumour of the ovary. Contrast axial CT showing a poorly enhancing solid component at the uppermost aspect of the cystic mass. Note there is endometrial thickening within the uterus as a result of the estrogenic effect.

Q: Histologically, Juvenile Granulosa Cell Tumor of the Ovary characteristically exhibits a nodular growth pattern with interspersed [...] and neoplastic cells containing round, vesicular nuclei with abundant eosinophilic cytoplasm.
Juvenile granulosa cell tumour. Low-magnification view showing nodular tumour architecture with variably sized follicle-like spaces.
Juvenile granulosa cell tumour. Predominantly solid growth pattern with small follicle-like spaces (upper part of image). The cells have eosinophilic or focally vacuolated cytoplasm.
A: follicle-like spaces
Back Extra: Juvenile Granulosa Cell Tumor of the Ovary
- Clinical: Patients with Juvenile Granulosa Cell Tumor of the Ovary often present with a pelvic mass and estrogenic effects, including precocious pseudopuberty and menstrual disturbances.
- Micro: Histologically, the tumour shows a nodular or diffuse growth pattern with interspersed follicles and cells with round, vesicular nuclei and abundant pale or eosinophilic cytoplasm.
- Ancillary: Genetic testing may reveal activating alterations in AKT1 and GNAS, and somatic mosaic IDH1 and IDH2 mutations in cases associated with Ollier disease or Maffucci syndrome.
Reference Gallery:
Juvenile granulosa cell tumour. The tumour has a predominantly nodular, solid, yellow cut surface with focal cystic and haemorrhagic areas.
Juvenile granulosa cell tumour. Low-magnification view showing nodular tumour architecture with variably sized follicle-like spaces.
Juvenile granulosa cell tumour. Predominantly solid growth pattern with small follicle-like spaces (upper part of image). The cells have eosinophilic or focally vacuolated cytoplasm.
Juvenile granulosa cell tumour. High-magnification view showing mitotic activity and apoptosis.
Juvenile granulosa cell tumour of the ovary. Contrast axial CT showing a large, almost completely cystic mass arising from the pelvis of a prepubertal girl.
Juvenile granulosa cell tumour of the ovary. Contrast axial CT showing a poorly enhancing solid component at the uppermost aspect of the cystic mass. Note there is endometrial thickening within the uterus as a result of the estrogenic effect.

Q: Grossly, Juvenile Granulosa Cell Tumor of the Ovary frequently presents as a nodular mass with a prominently [...] cut surface, corresponding to the lipid-rich, luteinized cytoplasm of the neoplastic cells, often mixed with cystic and hemorrhagic areas.
Juvenile granulosa cell tumour. The tumour has a predominantly nodular, solid, yellow cut surface with focal cystic and haemorrhagic areas.
A: yellow
Back Extra: Juvenile Granulosa Cell Tumor of the Ovary
- Clinical: Patients with Juvenile Granulosa Cell Tumor of the Ovary often present with a pelvic mass and estrogenic effects, including precocious pseudopuberty and menstrual disturbances.
- Micro: Histologically, the tumour shows a nodular or diffuse growth pattern with interspersed follicles and cells with round, vesicular nuclei and abundant pale or eosinophilic cytoplasm.
- Ancillary: Genetic testing may reveal activating alterations in AKT1 and GNAS, and somatic mosaic IDH1 and IDH2 mutations in cases associated with Ollier disease or Maffucci syndrome.
Reference Gallery:
Juvenile granulosa cell tumour. The tumour has a predominantly nodular, solid, yellow cut surface with focal cystic and haemorrhagic areas.
Juvenile granulosa cell tumour. Low-magnification view showing nodular tumour architecture with variably sized follicle-like spaces.
Juvenile granulosa cell tumour. Predominantly solid growth pattern with small follicle-like spaces (upper part of image). The cells have eosinophilic or focally vacuolated cytoplasm.
Juvenile granulosa cell tumour. High-magnification view showing mitotic activity and apoptosis.
Juvenile granulosa cell tumour of the ovary. Contrast axial CT showing a large, almost completely cystic mass arising from the pelvis of a prepubertal girl.
Juvenile granulosa cell tumour of the ovary. Contrast axial CT showing a poorly enhancing solid component at the uppermost aspect of the cystic mass. Note there is endometrial thickening within the uterus as a result of the estrogenic effect.

Q: Histologically, a papillary cystadenoma is characterized by complex tubulopapillary growth with distinctive [...] within the papillary cores.
Papillary cystadenoma. Complex papillary structures with hyalinized stromal cores.
Papillary cystadenoma. Tubulopapillary architecture with cuboidal cells that have clear to eosinophilic cytoplasm and stromal hyalinization.
A: stromal hyalinization
Back Extra: Papillary Cystadenoma
- Clinical: Patients may present with abdominal pain, though it is often an incidental finding in children. Most cases are associated with von Hippel–Lindau syndrome.
- Micro: Characterized by complex tubulopapillary growth with stromal hyalinization. Cells are non-ciliated and cuboidal with minimal clear to eosinophilic cytoplasm.
- Ancillary: Immunohistochemistry shows positivity for CK7, PAX8, PAX2, and CD10. WT1 and calretinin are variably positive; ER and PR are negative.
Reference Gallery:
Papillary cystadenoma. Complex papillary structures with hyalinized stromal cores.
Papillary cystadenoma. Tubulopapillary architecture with cuboidal cells that have clear to eosinophilic cytoplasm and stromal hyalinization.

Q: The complex architecture of a papillary cystadenoma is lined by non-ciliated, cuboidal cells that typically feature minimal [...] cytoplasm.
Papillary cystadenoma. Tubulopapillary architecture with cuboidal cells that have clear to eosinophilic cytoplasm and stromal hyalinization.
A: clear to eosinophilic
Back Extra: Papillary Cystadenoma
- Clinical: Patients may present with abdominal pain, though it is often an incidental finding in children. Most cases are associated with von Hippel–Lindau syndrome.
- Micro: Characterized by complex tubulopapillary growth with stromal hyalinization. Cells are non-ciliated and cuboidal with minimal clear to eosinophilic cytoplasm.
- Ancillary: Immunohistochemistry shows positivity for CK7, PAX8, PAX2, and CD10. WT1 and calretinin are variably positive; ER and PR are negative.
Reference Gallery:
Papillary cystadenoma. Complex papillary structures with hyalinized stromal cores.
Papillary cystadenoma. Tubulopapillary architecture with cuboidal cells that have clear to eosinophilic cytoplasm and stromal hyalinization.

Q: Microscopically, Mesonephric Remnants and Hyperplasia are characterized by small to medium-sized tubules lined by bland cuboidal cells that contain characteristic [...].
Mesonephric remnants. Mesonephric remnants in the lateral cervical wall are composed of simple tubules lined by bland cuboidal epithelium with characteristic eosinophilic luminal secretions.
Mesonephric remnants. Mesonephric remnants are composed of bland cuboidal cells with pale eosinophilic cytoplasm and nuclei with fine chromatin.
A: eosinophilic luminal secretions
Back Extra: Mesonephric Remnants and Hyperplasia
- Clinical: Mesonephric remnants and hyperplasia are usually incidental findings but may rarely present with abnormal cervical cytology or as a mass.
- Micro: Mesonephric remnants and hyperplasia are characterized by small to medium-sized tubules lined by cuboidal cells with fine chromatin and eosinophilic luminal secretions.
- Ancillary: Immunohistochemistry shows positivity for CD10 (luminal/apical), calretinin, GATA3, TTF1, and PAX8, while ER, PR, and p16 are negative.
Reference Gallery:
Mesonephric remnants. Mesonephric remnants in the lateral cervical wall are composed of simple tubules lined by bland cuboidal epithelium with characteristic eosinophilic luminal secretions.
Mesonephric remnants. Mesonephric remnants are composed of bland cuboidal cells with pale eosinophilic cytoplasm and nuclei with fine chromatin.

Q: [...] is an often incidental cervical finding composed of simple tubules lined by bland cuboidal epithelium with pale eosinophilic cytoplasm and fine chromatin.
Mesonephric remnants. Mesonephric remnants in the lateral cervical wall are composed of simple tubules lined by bland cuboidal epithelium with characteristic eosinophilic luminal secretions.
Mesonephric remnants. Mesonephric remnants are composed of bland cuboidal cells with pale eosinophilic cytoplasm and nuclei with fine chromatin.
A: Mesonephric Remnants and Hyperplasia
Back Extra: Mesonephric Remnants and Hyperplasia
- Clinical: Mesonephric remnants and hyperplasia are usually incidental findings but may rarely present with abnormal cervical cytology or as a mass.
- Micro: Mesonephric remnants and hyperplasia are characterized by small to medium-sized tubules lined by cuboidal cells with fine chromatin and eosinophilic luminal secretions.
- Ancillary: Immunohistochemistry shows positivity for CD10 (luminal/apical), calretinin, GATA3, TTF1, and PAX8, while ER, PR, and p16 are negative.
Reference Gallery:
Mesonephric remnants. Mesonephric remnants in the lateral cervical wall are composed of simple tubules lined by bland cuboidal epithelium with characteristic eosinophilic luminal secretions.
Mesonephric remnants. Mesonephric remnants are composed of bland cuboidal cells with pale eosinophilic cytoplasm and nuclei with fine chromatin.

Q: A benign vaginal lesion classically presenting with bleeding in prepubertal girls (aged 2–5 years) that histologically features branching fibrovascular cores lined by bland cuboidal to columnar epithelium is known as [...].
Müllerian papilloma. Papillary structures with branching fibrovascular cores are covered by cuboidal to columnar epithelium.
Müllerian papilloma. The columnar epithelial lining over the papillae displays bland nuclear features.
A: Müllerian papilloma
Back Extra: Müllerian papilloma
- Clinical: Most patients present with vaginal bleeding, and these lesions are found predominantly in prepubertal girls, typically aged 2–5 years.
- Micro: Müllerian papillomas have a papillary architecture with branching fibrovascular stromal cores lined by cuboidal or columnar epithelium with bland nuclei and no cytological atypia.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of Müllerian papilloma.
Reference Gallery:
Müllerian papilloma. Papillary structures with branching fibrovascular cores are covered by cuboidal to columnar epithelium.
Müllerian papilloma. The columnar epithelial lining over the papillae displays bland nuclear features.

Q: Bilateral cases of Ovarian Fibroma are relatively uncommon but occur frequently in young patients with [...] syndrome.
Ovarian fibroma in Gorlin syndrome. External appearance of an ovarian fibroma from a 15-year-old girl.
Ovarian fibroma in Gorlin syndrome. Cut surface of an ovarian fibroma from a 15-year-old girl.
A: Gorlin
Back Extra: Ovarian Fibroma
- Clinical: Most cases are unilateral, but bilateral cases occur occasionally, especially in young patients with Gorlin syndrome. Symptoms often include an ovarian mass, and less frequently, hormonal manifestations or Meigs syndrome (ascites and pleural effusion).
- Micro: Characterized by intersecting fascicles of spindle to ovoid cells with bland nuclei within a variably collagenous, hyalinized stroma. Calcifications and eosinophilic hyaline globules may be present.
- Ancillary: Cytogenetic studies often show trisomy and/or tetrasomy of chromosome 12, as well as imbalances of chromosomes 4 and 9. Loss of heterozygosity at the PTCH1 locus and at the STK11 locus is frequent in both hereditary and sporadic cases.
Reference Gallery:
Ovarian fibroma in Gorlin syndrome. External appearance of an ovarian fibroma from a 15-year-old girl.
Ovarian fibroma in Gorlin syndrome. Cut surface of an ovarian fibroma from a 15-year-old girl.
Ovarian fibroma in Gorlin syndrome. Intersecting fascicles of spindle cells and focal calcifications.
Ovarian fibroma in Gorlin syndrome. Spindle and ovoid cells are surrounded by collagen bundles.
Ovarian fibroma in Gorlin syndrome. This example (the same case as shown in Fig. 18397) shows densely packed spindle cells without marked atypia or mitotic figures.

Q: The characteristic microscopic appearance of an Ovarian Fibroma involves intersecting fascicles of bland [...] cells set within a variably collagenous stroma, occasionally with focal calcifications.
Ovarian fibroma in Gorlin syndrome. Intersecting fascicles of spindle cells and focal calcifications.
Ovarian fibroma in Gorlin syndrome. Spindle and ovoid cells are surrounded by collagen bundles.
Ovarian fibroma in Gorlin syndrome. This example (the same case as shown in Fig. 18397) shows densely packed spindle cells without marked atypia or mitotic figures.
A: spindle
Back Extra: Ovarian Fibroma
- Clinical: Most cases are unilateral, but bilateral cases occur occasionally, especially in young patients with Gorlin syndrome. Symptoms often include an ovarian mass, and less frequently, hormonal manifestations or Meigs syndrome (ascites and pleural effusion).
- Micro: Characterized by intersecting fascicles of spindle to ovoid cells with bland nuclei within a variably collagenous, hyalinized stroma. Calcifications and eosinophilic hyaline globules may be present.
- Ancillary: Cytogenetic studies often show trisomy and/or tetrasomy of chromosome 12, as well as imbalances of chromosomes 4 and 9. Loss of heterozygosity at the PTCH1 locus and at the STK11 locus is frequent in both hereditary and sporadic cases.
Reference Gallery:
Ovarian fibroma in Gorlin syndrome. External appearance of an ovarian fibroma from a 15-year-old girl.
Ovarian fibroma in Gorlin syndrome. Cut surface of an ovarian fibroma from a 15-year-old girl.
Ovarian fibroma in Gorlin syndrome. Intersecting fascicles of spindle cells and focal calcifications.
Ovarian fibroma in Gorlin syndrome. Spindle and ovoid cells are surrounded by collagen bundles.
Ovarian fibroma in Gorlin syndrome. This example (the same case as shown in Fig. 18397) shows densely packed spindle cells without marked atypia or mitotic figures.

Q: Poorly differentiated Sertoli-Leydig cell tumors often have a solid, fleshy, tan-yellow gross appearance and microscopically consist of diffuse sheets of immature, [...] Sertoli cells.
Sertoli–Leydig cell tumour, poorly differentiated. The cut surface shows a predominantly solid, fleshy, tan-yellow cut surface with focal haemorrhage.
Sertoli–Leydig cell tumour. A poorly differentiated example, composed of diffuse sheets of immature, sarcomatoid Sertoli cells resembling primitive gonadal stroma.
A: sarcomatoid
Back Extra: Sertoli-Leydig Cell Tumour
- Clinical: Sertoli-Leydig Cell Tumours may present with pelvic pain, a pelvic mass, or androgenic manifestations such as hirsutism and clitoromegaly.
- Micro: Poorly differentiated Sertoli-Leydig Cell Tumours consist of diffuse sheets of immature, sarcomatoid Sertoli cells with moderate to marked nuclear atypia and conspicuous mitotic figures.
- Ancillary: Sertoli cells in Sertoli-Leydig Cell Tumours are typically positive for vimentin, pancytokeratin, and sex cord markers (α-inhibin, calretinin, SF1, WT1, and FOXL2).
Reference Gallery:
Sertoli–Leydig cell tumour, poorly differentiated. The cut surface shows a predominantly solid, fleshy, tan-yellow cut surface with focal haemorrhage.
Sertoli–Leydig cell tumour. A moderately differentiated tumour in a young patient with DICER1 syndrome. The tumour is composed of compressed basophilic Sertoli cell tubules and scattered small clusters of eosinophilic Leydig cells.
Sertoli–Leydig cell tumour. A moderately differentiated tumour in a young patient with DICER1 syndrome.
Sertoli–Leydig cell tumour. A poorly differentiated example, composed of diffuse sheets of immature, sarcomatoid Sertoli cells resembling primitive gonadal stroma.
Sertoli–Leydig cell tumour. The tumour contains heterologous mucinous epithelium surrounded by immature Sertoli cells and rare Leydig cell clusters.
Sertoli–Leydig cell tumour. Retiform subtype, in which the tumour cells form anastomosing, slit-like, irregular spaces resembling the rete testis.

Q: A moderately differentiated Sertoli-Leydig cell tumor is composed of compressed basophilic Sertoli cell tubules and clusters of eosinophilic Leydig cells, and may clinically present with [...] manifestations (e.g., hirsutism, clitoromegaly).
Sertoli–Leydig cell tumour. A moderately differentiated tumour in a young patient with DICER1 syndrome. The tumour is composed of compressed basophilic Sertoli cell tubules and scattered small clusters of eosinophilic Leydig cells.
A: androgenic
Back Extra: Sertoli-Leydig Cell Tumour
- Clinical: Sertoli-Leydig Cell Tumours may present with pelvic pain, a pelvic mass, or androgenic manifestations such as hirsutism and clitoromegaly.
- Micro: Poorly differentiated Sertoli-Leydig Cell Tumours consist of diffuse sheets of immature, sarcomatoid Sertoli cells with moderate to marked nuclear atypia and conspicuous mitotic figures.
- Ancillary: Sertoli cells in Sertoli-Leydig Cell Tumours are typically positive for vimentin, pancytokeratin, and sex cord markers (α-inhibin, calretinin, SF1, WT1, and FOXL2).
Reference Gallery:
Sertoli–Leydig cell tumour, poorly differentiated. The cut surface shows a predominantly solid, fleshy, tan-yellow cut surface with focal haemorrhage.
Sertoli–Leydig cell tumour. A moderately differentiated tumour in a young patient with DICER1 syndrome. The tumour is composed of compressed basophilic Sertoli cell tubules and scattered small clusters of eosinophilic Leydig cells.
Sertoli–Leydig cell tumour. A moderately differentiated tumour in a young patient with DICER1 syndrome.
Sertoli–Leydig cell tumour. A poorly differentiated example, composed of diffuse sheets of immature, sarcomatoid Sertoli cells resembling primitive gonadal stroma.
Sertoli–Leydig cell tumour. The tumour contains heterologous mucinous epithelium surrounded by immature Sertoli cells and rare Leydig cell clusters.
Sertoli–Leydig cell tumour. Retiform subtype, in which the tumour cells form anastomosing, slit-like, irregular spaces resembling the rete testis.

Q: The retiform variant of Sertoli-Leydig cell tumor features anastomosing, slit-like, irregular spaces microscopically that resemble the [...].
Sertoli–Leydig cell tumour. Retiform subtype, in which the tumour cells form anastomosing, slit-like, irregular spaces resembling the rete testis.
A: rete testis
Back Extra: Sertoli-Leydig Cell Tumour
- Clinical: Sertoli-Leydig Cell Tumours may present with pelvic pain, a pelvic mass, or androgenic manifestations such as hirsutism and clitoromegaly.
- Micro: Poorly differentiated Sertoli-Leydig Cell Tumours consist of diffuse sheets of immature, sarcomatoid Sertoli cells with moderate to marked nuclear atypia and conspicuous mitotic figures.
- Ancillary: Sertoli cells in Sertoli-Leydig Cell Tumours are typically positive for vimentin, pancytokeratin, and sex cord markers (α-inhibin, calretinin, SF1, WT1, and FOXL2).
Reference Gallery:
Sertoli–Leydig cell tumour, poorly differentiated. The cut surface shows a predominantly solid, fleshy, tan-yellow cut surface with focal haemorrhage.
Sertoli–Leydig cell tumour. A moderately differentiated tumour in a young patient with DICER1 syndrome. The tumour is composed of compressed basophilic Sertoli cell tubules and scattered small clusters of eosinophilic Leydig cells.
Sertoli–Leydig cell tumour. A moderately differentiated tumour in a young patient with DICER1 syndrome.
Sertoli–Leydig cell tumour. A poorly differentiated example, composed of diffuse sheets of immature, sarcomatoid Sertoli cells resembling primitive gonadal stroma.
Sertoli–Leydig cell tumour. The tumour contains heterologous mucinous epithelium surrounded by immature Sertoli cells and rare Leydig cell clusters.
Sertoli–Leydig cell tumour. Retiform subtype, in which the tumour cells form anastomosing, slit-like, irregular spaces resembling the rete testis.

Q: A defining microscopic feature of Sclerosing Stromal Tumor is its [...] architecture, characterized by cellular nodules separated by edematous or collagenous stroma.
Sclerosing stromal tumour. Cellular pseudolobules separated by densely collagenous to focally oedematous stroma. Note the conspicuous haemangiopericytoma-like vessels.
A: pseudolobular
Back Extra: Sclerosing Stromal Tumour
- Clinical: Patients with Sclerosing Stromal Tumour often present with menstrual abnormalities, abnormal uterine bleeding, or abdominal pain.
- Micro: Sclerosing Stromal Tumour is characterized by a pseudolobular appearance with a prominent vasculature, composed of thin-walled dilated vessels and an admixture of epithelioid and spindled cells.
- Ancillary: GLI2 rearrangements are detected in > 80% of Sclerosing Stromal Tumours, with the FHL2::GLI2 fusion being present in > 60% of cases.
Reference Gallery:
Sclerosing stromal tumour. Cellular pseudolobules separated by densely collagenous to focally oedematous stroma. Note the conspicuous haemangiopericytoma-like vessels.
Sclerosing stromal tumour. A nodule composed of an admixture of epithelioid and spindled cells.

Q: The cellular nodules of Sclerosing Stromal Tumor characteristically contain a prominent hemangiopericytoma-like vasculature and an admixture of [...] cells.
Sclerosing stromal tumour. Cellular pseudolobules separated by densely collagenous to focally oedematous stroma. Note the conspicuous haemangiopericytoma-like vessels.
Sclerosing stromal tumour. A nodule composed of an admixture of epithelioid and spindled cells.
A: epithelioid and spindled
Back Extra: Sclerosing Stromal Tumour
- Clinical: Patients with Sclerosing Stromal Tumour often present with menstrual abnormalities, abnormal uterine bleeding, or abdominal pain.
- Micro: Sclerosing Stromal Tumour is characterized by a pseudolobular appearance with a prominent vasculature, composed of thin-walled dilated vessels and an admixture of epithelioid and spindled cells.
- Ancillary: GLI2 rearrangements are detected in > 80% of Sclerosing Stromal Tumours, with the FHL2::GLI2 fusion being present in > 60% of cases.
Reference Gallery:
Sclerosing stromal tumour. Cellular pseudolobules separated by densely collagenous to focally oedematous stroma. Note the conspicuous haemangiopericytoma-like vessels.
Sclerosing stromal tumour. A nodule composed of an admixture of epithelioid and spindled cells.

Q: In Sex Cord Tumor with Annular Tubules, the characteristic histologic finding consists of interconnecting nests of cells with pale cytoplasm and radially arranged nuclei encircling central [...].
Sex cord tumour with annular tubules. Complex interconnecting tubules are separated by relatively scant fibrovascular stroma.
Sex cord tumour with annular tubules. The tubules are lined by cells with uniform, radially arranged nuclei and abundant pale cytoplasm encircling basement membrane–like material.
A: hyaline basement membrane-like material
Back Extra: Sex Cord Tumour with Annular Tubules
- Clinical: Sex cord tumour with annular tubules (SCTAT) can present as an incidental finding in Peutz–Jeghers syndrome (PJS) or with nonspecific symptoms including estrogenic effects in non-syndromic cases.
- Micro: Characterized by variably sized, rounded nests of tubules that encircle hyaline basement membrane–like material, with cells showing pale cytoplasm and radially arranged nuclei.
- Ancillary: Tumour cells are typically positive for calretinin, WT1, inhibin, SF1, FOXL2, and CD56, and negative for EMA and CD10.
Reference Gallery:
Sex cord tumour with annular tubules. Non-syndromic tumour with a predominantly solid, yellow, and focally nodular cut surface.
Sex cord tumour with annular tubules. Complex interconnecting tubules are separated by relatively scant fibrovascular stroma.
Sex cord tumour with annular tubules. The tubules are lined by cells with uniform, radially arranged nuclei and abundant pale cytoplasm encircling basement membrane–like material.

Q: Sex Cord Tumor with Annular Tubules frequently presents as an incidental finding in patients with [...], whereas non-syndromic cases typically manifest with estrogenic effects and exhibit a solid, yellow gross appearance.
Sex cord tumour with annular tubules. Non-syndromic tumour with a predominantly solid, yellow, and focally nodular cut surface.
A: Peutz-Jeghers syndrome
Back Extra: Sex Cord Tumour with Annular Tubules
- Clinical: Sex cord tumour with annular tubules (SCTAT) can present as an incidental finding in Peutz–Jeghers syndrome (PJS) or with nonspecific symptoms including estrogenic effects in non-syndromic cases.
- Micro: Characterized by variably sized, rounded nests of tubules that encircle hyaline basement membrane–like material, with cells showing pale cytoplasm and radially arranged nuclei.
- Ancillary: Tumour cells are typically positive for calretinin, WT1, inhibin, SF1, FOXL2, and CD56, and negative for EMA and CD10.
Reference Gallery:
Sex cord tumour with annular tubules. Non-syndromic tumour with a predominantly solid, yellow, and focally nodular cut surface.
Sex cord tumour with annular tubules. Complex interconnecting tubules are separated by relatively scant fibrovascular stroma.
Sex cord tumour with annular tubules. The tubules are lined by cells with uniform, radially arranged nuclei and abundant pale cytoplasm encircling basement membrane–like material.

Q: The defining molecular abnormality in Small Cell Carcinoma of the Ovary, Hypercalcemic Type is an inactivating mutation resulting in the highly sensitive and specific immunohistochemical loss of [...] (and often SMARCA2) expression in the tumor cells.
Small cell carcinoma of the ovary, hypercalcaemic type. SMARCA4 (BRG1) immunohistochemistry showing a loss of expression in the tumour cells and retained expression in endothelial and stromal cells. Dual loss of SMARCA4 and SMARCA2 (BRM) is highly sensitive and specific for this tumour.
A: SMARCA4
Back Extra: Small Cell Carcinoma of the Ovary, Hypercalcaemic Type
- Clinical: Two-thirds of patients present with paraneoplastic hypercalcaemia, and the tumour is most common in young women and children.
- Micro: Tumour cells are small, round to ovoid with scant cytoplasm and brisk mitotic activity. Large cells with eccentric nuclei and dense cytoplasm are also present in about half of the cases.
- Ancillary: Inactivating mutations in SMARCA4 are nearly universal, and immunohistochemistry shows loss of SMARCA4 and SMARCA2 expression in tumour cells.
Reference Gallery:
Small cell carcinoma of the ovary, hypercalcaemic type. Small nests of tumour cells separated by minimal fibrous stroma. The tumour cells are round to oval, with occasional prominent nucleoli and chromocentres and with scant cytoplasm.
Small cell carcinoma of the ovary, hypercalcaemic type. Comparison between the small cell (lower right) and large cell (remaining area) morphology. The large cells often show larger, open nuclei with vesicular chromatin and prominent nucleoli. Abundant eosinophilic cytoplasm is present, and cellular borders can occasionally be delineated.
Small cell carcinoma of the ovary, hypercalcaemic type. The large-cell regions occasionally contain rhabdoid cells with eccentric nuclei, prominent nucleoli, and dense to glassy eosinophilic cytoplasmic inclusions that displace the nucleus.
Small cell carcinoma of the ovary, hypercalcaemic type. A focus of benign mucinous epithelium (right) within the small-cell component.
Small cell carcinoma of the ovary, hypercalcaemic type. SMARCA4 (BRG1) immunohistochemistry showing a loss of expression in the tumour cells and retained expression in endothelial and stromal cells. Dual loss of SMARCA4 and SMARCA2 (BRM) is highly sensitive and specific for this tumour.

Q: Microscopically, Small Cell Carcinoma of the Ovary, Hypercalcemic Type consists of small, round to oval tumor cells with scant cytoplasm, often admixed with large cells exhibiting a distinctive [...] morphology characterized by eccentric nuclei and dense, glassy eosinophilic cytoplasmic inclusions.
Small cell carcinoma of the ovary, hypercalcaemic type. Small nests of tumour cells separated by minimal fibrous stroma. The tumour cells are round to oval, with occasional prominent nucleoli and chromocentres and with scant cytoplasm.
Small cell carcinoma of the ovary, hypercalcaemic type. Comparison between the small cell (lower right) and large cell (remaining area) morphology. The large cells often show larger, open nuclei with vesicular chromatin and prominent nucleoli. Abundant eosinophilic cytoplasm is present, and cellular borders can occasionally be delineated.
Small cell carcinoma of the ovary, hypercalcaemic type. The large-cell regions occasionally contain rhabdoid cells with eccentric nuclei, prominent nucleoli, and dense to glassy eosinophilic cytoplasmic inclusions that displace the nucleus.
A: rhabdoid
Back Extra: Small Cell Carcinoma of the Ovary, Hypercalcaemic Type
- Clinical: Two-thirds of patients present with paraneoplastic hypercalcaemia, and the tumour is most common in young women and children.
- Micro: Tumour cells are small, round to ovoid with scant cytoplasm and brisk mitotic activity. Large cells with eccentric nuclei and dense cytoplasm are also present in about half of the cases.
- Ancillary: Inactivating mutations in SMARCA4 are nearly universal, and immunohistochemistry shows loss of SMARCA4 and SMARCA2 expression in tumour cells.
Reference Gallery:
Small cell carcinoma of the ovary, hypercalcaemic type. Small nests of tumour cells separated by minimal fibrous stroma. The tumour cells are round to oval, with occasional prominent nucleoli and chromocentres and with scant cytoplasm.
Small cell carcinoma of the ovary, hypercalcaemic type. Comparison between the small cell (lower right) and large cell (remaining area) morphology. The large cells often show larger, open nuclei with vesicular chromatin and prominent nucleoli. Abundant eosinophilic cytoplasm is present, and cellular borders can occasionally be delineated.
Small cell carcinoma of the ovary, hypercalcaemic type. The large-cell regions occasionally contain rhabdoid cells with eccentric nuclei, prominent nucleoli, and dense to glassy eosinophilic cytoplasmic inclusions that displace the nucleus.
Small cell carcinoma of the ovary, hypercalcaemic type. A focus of benign mucinous epithelium (right) within the small-cell component.
Small cell carcinoma of the ovary, hypercalcaemic type. SMARCA4 (BRG1) immunohistochemistry showing a loss of expression in the tumour cells and retained expression in endothelial and stromal cells. Dual loss of SMARCA4 and SMARCA2 (BRM) is highly sensitive and specific for this tumour.

Q: Histologically, Acinic cell carcinoma is characterized by cells that display serous acinar differentiation and contain prominent, basophilic [...] within their cytoplasm.
Acinic cell carcinoma. High-power view showing numerous blue cytoplasmic granules in the acinar cells. Secretory vacuoles are noted.
Acinic cell carcinoma. Acinar differentiation is seen as small blue granules in the cytoplasm. There is an overall fenestrated tumour pattern.
A: secretory granules
Back Extra: Acinic Cell Carcinoma
- Clinical: Acinic cell carcinoma typically presents as a slow-growing mass in the parotid gland, with a higher incidence in females and children in their second decade of life.
- Micro: The tumour is characterized by serous acinar cells with cytoplasmic granules, often arranged in solid, microcystic, macrocystic, follicular, papillary, and cystic patterns.
- Ancillary: Immunohistochemistry shows positivity for amylase, α1-antitrypsin, lactoferrin, and lysozyme, and molecular studies reveal a recurrent rearrangement, t(4;9)(q13;q31), involving the NR4A3 gene.
Reference Gallery:
Acinic cell carcinoma. Low-power view demonstrates an infiltrative tumour with areas of cystic degeneration. A lymph node is noted at the lower left.
Acinic cell carcinoma. High-power view showing numerous blue cytoplasmic granules in the acinar cells. Secretory vacuoles are noted.
Acinic cell carcinoma. A more solid pattern is noted in this example, but serous acinar differentiation is still easily identified.
Acinic cell carcinoma. Acinar differentiation is seen as small blue granules in the cytoplasm. There is an overall fenestrated tumour pattern.
Acinic cell carcinoma. A Romanowsky (Diff-Quik)-stained cellular smear with cohesive clusters and sheets of serous acinar cells without ducts. Numerous naked tumour nuclei are in the background, created when fragile cytoplasm is stripped away.
Acinic cell carcinoma. High-power view of a Romanowsky (Diff-Quik)-stained FNAB smear showing a cohesive cluster of serous acinar cells. These are large, uniform cells with round, centrally placed nuclei and cytoplasmic azurophilic serous granules.

Q: On fine-needle aspiration (FNA) smears, Acinic cell carcinoma typically reveals cohesive clusters of serous acinar cells accompanied by numerous background [...], resulting from the stripping of fragile cytoplasm.
Acinic cell carcinoma. A Romanowsky (Diff-Quik)-stained cellular smear with cohesive clusters and sheets of serous acinar cells without ducts. Numerous naked tumour nuclei are in the background, created when fragile cytoplasm is stripped away.
Acinic cell carcinoma. High-power view of a Romanowsky (Diff-Quik)-stained FNAB smear showing a cohesive cluster of serous acinar cells. These are large, uniform cells with round, centrally placed nuclei and cytoplasmic azurophilic serous granules.
A: naked tumor nuclei
Back Extra: Acinic Cell Carcinoma
- Clinical: Acinic cell carcinoma typically presents as a slow-growing mass in the parotid gland, with a higher incidence in females and children in their second decade of life.
- Micro: The tumour is characterized by serous acinar cells with cytoplasmic granules, often arranged in solid, microcystic, macrocystic, follicular, papillary, and cystic patterns.
- Ancillary: Immunohistochemistry shows positivity for amylase, α1-antitrypsin, lactoferrin, and lysozyme, and molecular studies reveal a recurrent rearrangement, t(4;9)(q13;q31), involving the NR4A3 gene.
Reference Gallery:
Acinic cell carcinoma. Low-power view demonstrates an infiltrative tumour with areas of cystic degeneration. A lymph node is noted at the lower left.
Acinic cell carcinoma. High-power view showing numerous blue cytoplasmic granules in the acinar cells. Secretory vacuoles are noted.
Acinic cell carcinoma. A more solid pattern is noted in this example, but serous acinar differentiation is still easily identified.
Acinic cell carcinoma. Acinar differentiation is seen as small blue granules in the cytoplasm. There is an overall fenestrated tumour pattern.
Acinic cell carcinoma. A Romanowsky (Diff-Quik)-stained cellular smear with cohesive clusters and sheets of serous acinar cells without ducts. Numerous naked tumour nuclei are in the background, created when fragile cytoplasm is stripped away.
Acinic cell carcinoma. High-power view of a Romanowsky (Diff-Quik)-stained FNAB smear showing a cohesive cluster of serous acinar cells. These are large, uniform cells with round, centrally placed nuclei and cytoplasmic azurophilic serous granules.

Q: A slow-growing parotid gland tumor that displays prominent serous acinar differentiation and harbors a recurrent t(4;9)(q13;q31) translocation involving the NR4A3 gene is classic for [...].
Acinic cell carcinoma. High-power view showing numerous blue cytoplasmic granules in the acinar cells. Secretory vacuoles are noted.
Acinic cell carcinoma. A more solid pattern is noted in this example, but serous acinar differentiation is still easily identified.
A: Acinic cell carcinoma
Back Extra: Acinic Cell Carcinoma
- Clinical: Acinic cell carcinoma typically presents as a slow-growing mass in the parotid gland, with a higher incidence in females and children in their second decade of life.
- Micro: The tumour is characterized by serous acinar cells with cytoplasmic granules, often arranged in solid, microcystic, macrocystic, follicular, papillary, and cystic patterns.
- Ancillary: Immunohistochemistry shows positivity for amylase, α1-antitrypsin, lactoferrin, and lysozyme, and molecular studies reveal a recurrent rearrangement, t(4;9)(q13;q31), involving the NR4A3 gene.
Reference Gallery:
Acinic cell carcinoma. Low-power view demonstrates an infiltrative tumour with areas of cystic degeneration. A lymph node is noted at the lower left.
Acinic cell carcinoma. High-power view showing numerous blue cytoplasmic granules in the acinar cells. Secretory vacuoles are noted.
Acinic cell carcinoma. A more solid pattern is noted in this example, but serous acinar differentiation is still easily identified.
Acinic cell carcinoma. Acinar differentiation is seen as small blue granules in the cytoplasm. There is an overall fenestrated tumour pattern.
Acinic cell carcinoma. A Romanowsky (Diff-Quik)-stained cellular smear with cohesive clusters and sheets of serous acinar cells without ducts. Numerous naked tumour nuclei are in the background, created when fragile cytoplasm is stripped away.
Acinic cell carcinoma. High-power view of a Romanowsky (Diff-Quik)-stained FNAB smear showing a cohesive cluster of serous acinar cells. These are large, uniform cells with round, centrally placed nuclei and cytoplasmic azurophilic serous granules.

Q: In Central Giant Cell Granuloma, the characteristic histologic finding is clusters of [...] set within a bland spindle cell stroma with frequent hemorrhage.
Giant cell granuloma. Clusters of multinucleated giant cells in a bland spindle cell stroma with haemorrhage.
A: multinucleated osteoclast-like giant cells
Back Extra: Central Giant Cell Granuloma
- Clinical: Central giant cell granulomas are usually asymptomatic but can present with pain, jaw expansion, or paraesthesia. They are often identified as expansile radiolucencies on routine dental radiographs.
- Micro: The lesion is characterized by clusters of multinucleated osteoclast-like giant cells in a bland spindle cell stroma with haemorrhage. Osteoid or woven bone may be present.
- Ancillary: TRPV4, KRAS, and FGFR1 mutations are reported in sporadic cases, while PTPN11 mutations are associated with Noonan-like/multiple giant cell lesion syndrome.
Reference Gallery:
Giant cell granuloma. Coronal CT showing a rounded, multilocular, and markedly expansile radiolucent lesion displacing teeth. There is patchy cortical erosion in a background of mixed dentition.
Giant cell granuloma. Clusters of multinucleated giant cells in a bland spindle cell stroma with haemorrhage.

Q: On dental radiographs or CT imaging, Central Giant Cell Granuloma typically presents as a multilocular and markedly [...] lesion that frequently displaces adjacent teeth and causes cortical erosion.
Giant cell granuloma. Coronal CT showing a rounded, multilocular, and markedly expansile radiolucent lesion displacing teeth. There is patchy cortical erosion in a background of mixed dentition.
A: expansile radiolucent
Back Extra: Central Giant Cell Granuloma
- Clinical: Central giant cell granulomas are usually asymptomatic but can present with pain, jaw expansion, or paraesthesia. They are often identified as expansile radiolucencies on routine dental radiographs.
- Micro: The lesion is characterized by clusters of multinucleated osteoclast-like giant cells in a bland spindle cell stroma with haemorrhage. Osteoid or woven bone may be present.
- Ancillary: TRPV4, KRAS, and FGFR1 mutations are reported in sporadic cases, while PTPN11 mutations are associated with Noonan-like/multiple giant cell lesion syndrome.
Reference Gallery:
Giant cell granuloma. Coronal CT showing a rounded, multilocular, and markedly expansile radiolucent lesion displacing teeth. There is patchy cortical erosion in a background of mixed dentition.
Giant cell granuloma. Clusters of multinucleated giant cells in a bland spindle cell stroma with haemorrhage.

Q: Clinically, Congenital Granular Cell Epulis most commonly presents as a polypoid mass on the anterior alveolar ridge of [...].
Congenital granular cell epulis. A polypoid mass in the anterior mandible of a newborn girl.
Congenital granular cell epulis. A gross photograph demonstrates a polypoid mass with a tan, smooth, homogeneous surface.
A: newborn females
Back Extra: Congenital Granular Cell Epulis
- Clinical: Congenital granular cell epulis is a polypoid, sessile, or pedunculated mass with a smooth, mucosal-coloured surface, usually < 20 mm, and is more common in females (M:F ratio: 1:7–10).
- Micro: The tumour is composed of sheets and nests of polygonal cells with eosinophilic, granular cytoplasm and prominent cell membranes, and lacks mitotic activity.
- Ancillary: Tumour cells are negative for S100 and/or SOX10, but positive for CD68, NSE, and vimentin.
Reference Gallery:
Congenital granular cell epulis. A polypoid mass in the anterior mandible of a newborn girl.
Congenital granular cell epulis. Uniform atrophic epithelium overlying sheets of tightly packed, medium-sized to large homogeneous polygonal cells with abundant eosinophilic granular cytoplasm, replacing the subepithelial stroma.
Congenital granular cell epulis. Cells have abundant eosinophilic granular cytoplasm and basophilic eccentric nuclei. Mitoses are absent but a background vascularity is seen.
Congenital granular cell epulis. A gross photograph demonstrates a polypoid mass with a tan, smooth, homogeneous surface.
Congenital granular cell epulis. High-power view shows numerous granules in polygonal cells with small, eccentrically placed nuclei. This is similar to conventional granular cell tumour but lacks S100 immunoreactivity.

Q: Histologically, Congenital Granular Cell Epulis is characterized by sheets of polygonal cells with abundant, [...] cytoplasm and eccentric nuclei, completely lacking mitotic activity.
Congenital granular cell epulis. Uniform atrophic epithelium overlying sheets of tightly packed, medium-sized to large homogeneous polygonal cells with abundant eosinophilic granular cytoplasm, replacing the subepithelial stroma.
Congenital granular cell epulis. Cells have abundant eosinophilic granular cytoplasm and basophilic eccentric nuclei. Mitoses are absent but a background vascularity is seen.
A: eosinophilic granular
Back Extra: Congenital Granular Cell Epulis
- Clinical: Congenital granular cell epulis is a polypoid, sessile, or pedunculated mass with a smooth, mucosal-coloured surface, usually < 20 mm, and is more common in females (M:F ratio: 1:7–10).
- Micro: The tumour is composed of sheets and nests of polygonal cells with eosinophilic, granular cytoplasm and prominent cell membranes, and lacks mitotic activity.
- Ancillary: Tumour cells are negative for S100 and/or SOX10, but positive for CD68, NSE, and vimentin.
Reference Gallery:
Congenital granular cell epulis. A polypoid mass in the anterior mandible of a newborn girl.
Congenital granular cell epulis. Uniform atrophic epithelium overlying sheets of tightly packed, medium-sized to large homogeneous polygonal cells with abundant eosinophilic granular cytoplasm, replacing the subepithelial stroma.
Congenital granular cell epulis. Cells have abundant eosinophilic granular cytoplasm and basophilic eccentric nuclei. Mitoses are absent but a background vascularity is seen.
Congenital granular cell epulis. A gross photograph demonstrates a polypoid mass with a tan, smooth, homogeneous surface.
Congenital granular cell epulis. High-power view shows numerous granules in polygonal cells with small, eccentrically placed nuclei. This is similar to conventional granular cell tumour but lacks S100 immunoreactivity.

Q: To distinguish Congenital Granular Cell Epulis from a conventional granular cell tumor, immunohistochemistry will show that the epulis is characteristically negative for [...].
Congenital granular cell epulis. High-power view shows numerous granules in polygonal cells with small, eccentrically placed nuclei. This is similar to conventional granular cell tumour but lacks S100 immunoreactivity.
A: S100
Back Extra: Congenital Granular Cell Epulis
- Clinical: Congenital granular cell epulis is a polypoid, sessile, or pedunculated mass with a smooth, mucosal-coloured surface, usually < 20 mm, and is more common in females (M:F ratio: 1:7–10).
- Micro: The tumour is composed of sheets and nests of polygonal cells with eosinophilic, granular cytoplasm and prominent cell membranes, and lacks mitotic activity.
- Ancillary: Tumour cells are negative for S100 and/or SOX10, but positive for CD68, NSE, and vimentin.
Reference Gallery:
Congenital granular cell epulis. A polypoid mass in the anterior mandible of a newborn girl.
Congenital granular cell epulis. Uniform atrophic epithelium overlying sheets of tightly packed, medium-sized to large homogeneous polygonal cells with abundant eosinophilic granular cytoplasm, replacing the subepithelial stroma.
Congenital granular cell epulis. Cells have abundant eosinophilic granular cytoplasm and basophilic eccentric nuclei. Mitoses are absent but a background vascularity is seen.
Congenital granular cell epulis. A gross photograph demonstrates a polypoid mass with a tan, smooth, homogeneous surface.
Congenital granular cell epulis. High-power view shows numerous granules in polygonal cells with small, eccentrically placed nuclei. This is similar to conventional granular cell tumour but lacks S100 immunoreactivity.

Q: Histologically, melanotic neuroectodermal tumor of infancy features a classic biphasic population of small primitive neuroblastic cells and larger [...]-producing epithelial cells.
Melanotic neuroectodermal tumour of infancy. Aggregates of tumour cells separated by fibrous stroma. There are small blue cells, with larger epithelial cells at the periphery, some of which contain melanin pigment.
Melanotic neuroectodermal tumour of infancy. High-power view of small neuroblast-like cells with hyperchromatic nuclei and scant cytoplasm, which are associated with larger epithelial cells with vesicular nuclei and cytoplasmic pigment.
A: melanin
Back Extra: Melanotic Neuroectodermal Tumour of Infancy
- Clinical: Melanotic neuroectodermal tumour of infancy typically presents as a sessile, painless, rapidly enlarging mass in the upper alveolus, causing facial deformity and feeding disruption.
- Micro: The tumour is characterized by a biphasic population of small neuroblastic cells and larger melanin-producing epithelial cells arranged in alveolar nests, cords, and trabeculae.
- Ancillary: Immunohistochemistry shows both small and large tumour cells expressing vimentin and synaptophysin, with large cells additionally expressing pancytokeratin, HMB45, and melan-A.
Reference Gallery:
Melanotic neuroectodermal tumour of infancy. The small neuroblast-like cells are highlighted with synaptophysin, but the melanin-containing epithelial cells are not.
Melanotic neuroectodermal tumour of infancy. Epithelial cells at the periphery of the tumour cell nests are highlighted by HMB45.
Melanotic neuroectodermal tumour of infancy. Small primitive cells with associated larger epithelioid cells.
Melanotic neuroectodermal tumour of infancy. Aggregates of tumour cells separated by fibrous stroma. There are small blue cells, with larger epithelial cells at the periphery, some of which contain melanin pigment.
Melanotic neuroectodermal tumour of infancy. High-power view of small neuroblast-like cells with hyperchromatic nuclei and scant cytoplasm, which are associated with larger epithelial cells with vesicular nuclei and cytoplasmic pigment.

Q: In melanotic neuroectodermal tumor of infancy, the large epithelial cells at the periphery of the nests characteristically express melanocytic markers such as [...], while the small neuroblast-like cells are highlighted by synaptophysin.
Melanotic neuroectodermal tumour of infancy. The small neuroblast-like cells are highlighted with synaptophysin, but the melanin-containing epithelial cells are not.
Melanotic neuroectodermal tumour of infancy. Epithelial cells at the periphery of the tumour cell nests are highlighted by HMB45.
A: HMB45
Back Extra: Melanotic Neuroectodermal Tumour of Infancy
- Clinical: Melanotic neuroectodermal tumour of infancy typically presents as a sessile, painless, rapidly enlarging mass in the upper alveolus, causing facial deformity and feeding disruption.
- Micro: The tumour is characterized by a biphasic population of small neuroblastic cells and larger melanin-producing epithelial cells arranged in alveolar nests, cords, and trabeculae.
- Ancillary: Immunohistochemistry shows both small and large tumour cells expressing vimentin and synaptophysin, with large cells additionally expressing pancytokeratin, HMB45, and melan-A.
Reference Gallery:
Melanotic neuroectodermal tumour of infancy. The small neuroblast-like cells are highlighted with synaptophysin, but the melanin-containing epithelial cells are not.
Melanotic neuroectodermal tumour of infancy. Epithelial cells at the periphery of the tumour cell nests are highlighted by HMB45.
Melanotic neuroectodermal tumour of infancy. Small primitive cells with associated larger epithelioid cells.
Melanotic neuroectodermal tumour of infancy. Aggregates of tumour cells separated by fibrous stroma. There are small blue cells, with larger epithelial cells at the periphery, some of which contain melanin pigment.
Melanotic neuroectodermal tumour of infancy. High-power view of small neuroblast-like cells with hyperchromatic nuclei and scant cytoplasm, which are associated with larger epithelial cells with vesicular nuclei and cytoplasmic pigment.

Q: [...] is a salivary gland malignancy classically characterized by a variable histologic mixture of epidermoid, intermediate, and mucinous cells.
Mucoepidermoid carcinoma. The cyst lining is represented by numerous mucous cells.
Mucoepidermoid carcinoma. An intermediate-grade soft palate tumour showing predominantly microcystic and solid growth with an abundance of epidermoid cells. Tumour nests vary in size and shape and infiltrate around an arteriole.
A: Mucoepidermoid Carcinoma
Back Extra: Mucoepidermoid Carcinoma
- Clinical: Patients usually present with a solitary painless mass or mucosal ulceration, which is present for a mean duration of about 1 year. MEC is the most common salivary gland malignancy in paediatric patients, affecting adolescents (median ages: 12–15 years) with no sex predilection.
- Micro: The tumour is composed of epidermoid, intermediate, and mucinous cells in varying proportions. The mucinous cells contain intracytoplasmic mucin compressing a peripherally located nucleus. The epidermoid cells are polygonal, have abundant eosinophilic or clear cytoplasm, and (rarely) may show small foci of overt keratinization.
- Ancillary: The presence of MAML2 rearrangements is an important diagnostic marker for Mucoepidermoid Carcinoma. Mucicarmine or PAS stains highlight mucous cells, and immunohistochemically, clusters of epidermoid cells are highlighted by p63, p40, and CK5/6, whereas CEA(m) and EMA (MUC1) highlight mucocytes.
Reference Gallery:
Mucoepidermoid carcinoma. The cyst lining is represented by numerous mucous cells.
Mucoepidermoid carcinoma. An intermediate-grade soft palate tumour showing predominantly microcystic and solid growth with an abundance of epidermoid cells. Tumour nests vary in size and shape and infiltrate around an arteriole.
Mucoepidermoid carcinoma. MAML2 translocation FISH. Examples of neoplastic cells with one rearranged and one normal MAML2 signal. The MAML2 gene without rearrangement is characterized by an overlapping pair of green and red signals (resulting in yellow). The rearranged MAML2 gene is characterized by separate green and red signals.

Q: The defining molecular driver in the majority of Mucoepidermoid Carcinoma cases is a genetic rearrangement involving the [...] gene.
Mucoepidermoid carcinoma. MAML2 translocation FISH. Examples of neoplastic cells with one rearranged and one normal MAML2 signal. The MAML2 gene without rearrangement is characterized by an overlapping pair of green and red signals (resulting in yellow). The rearranged MAML2 gene is characterized by separate green and red signals.
A: MAML2
Back Extra: Mucoepidermoid Carcinoma
- Clinical: Patients usually present with a solitary painless mass or mucosal ulceration, which is present for a mean duration of about 1 year. MEC is the most common salivary gland malignancy in paediatric patients, affecting adolescents (median ages: 12–15 years) with no sex predilection.
- Micro: The tumour is composed of epidermoid, intermediate, and mucinous cells in varying proportions. The mucinous cells contain intracytoplasmic mucin compressing a peripherally located nucleus. The epidermoid cells are polygonal, have abundant eosinophilic or clear cytoplasm, and (rarely) may show small foci of overt keratinization.
- Ancillary: The presence of MAML2 rearrangements is an important diagnostic marker for Mucoepidermoid Carcinoma. Mucicarmine or PAS stains highlight mucous cells, and immunohistochemically, clusters of epidermoid cells are highlighted by p63, p40, and CK5/6, whereas CEA(m) and EMA (MUC1) highlight mucocytes.
Reference Gallery:
Mucoepidermoid carcinoma. The cyst lining is represented by numerous mucous cells.
Mucoepidermoid carcinoma. An intermediate-grade soft palate tumour showing predominantly microcystic and solid growth with an abundance of epidermoid cells. Tumour nests vary in size and shape and infiltrate around an arteriole.
Mucoepidermoid carcinoma. MAML2 translocation FISH. Examples of neoplastic cells with one rearranged and one normal MAML2 signal. The MAML2 gene without rearrangement is characterized by an overlapping pair of green and red signals (resulting in yellow). The rearranged MAML2 gene is characterized by separate green and red signals.

Q: Nasal Chondromesenchymal Hamartoma is a locally destructive tumor (which may show intracranial extension on CT) that is frequently associated with pleuropulmonary blastoma syndrome due to mutations in the [...] gene.
Nasal chondromesenchymal hamartoma. Coronal CT showing a destructive sinonasal tract mass with intracranial extension.
A: DICER1
Back Extra: Nasal Chondromesenchymal Hamartoma
- Clinical: Symptoms include nasal obstruction, a mass, and ophthalmological findings. Tumours may erode into the cranial cavity and are often associated with DICER1 pleuropulmonary blastoma syndrome.
- Micro: Histologically, the lesion shows well-demarcated nodules of immature to mature cartilage in a myxoid to spindle cell stroma. Osteoclast-like giant cells and fibro-osseous proliferation may be present.
- Ancillary: S100 and SOX9 immunohistochemistry highlight the cartilaginous portions, while DICER1 genetic testing is recommended due to the association with DICER1 mutations.
Reference Gallery:
Nasal chondromesenchymal hamartoma. Coronal CT showing a destructive sinonasal tract mass with intracranial extension.
Nasal chondromesenchymal hamartoma. Low-power view shows immature cartilage and stroma in a background of minor mucoserous glands.
Nasal chondromesenchymal hamartoma. Intermediate-power view demonstrates immature islands of cartilage in a cellular background stroma.
Nasal chondromesenchymal hamartoma. High-power view shows immature cartilage in a cellular stroma showing mild nuclear pleomorphism. Extravasated erythrocytes are noted with focal cystic changes.
Nasal chondromesenchymal hamartoma. Bone, immature cartilage, and a cellular spindled cell stroma are noted in this hamartoma.
Nasal chondromesenchymal hamartoma. S100 strongly highlights the nuclei and cytoplasm of the cartilaginous portions of the hamartoma. (The minor mucoserous gland is a good internal control.)

Q: Histologically, Nasal Chondromesenchymal Hamartoma is characterized by well-demarcated nodules of immature to mature [...] admixed with a cellular myxoid to spindle cell stroma.
Nasal chondromesenchymal hamartoma. Low-power view shows immature cartilage and stroma in a background of minor mucoserous glands.
Nasal chondromesenchymal hamartoma. Intermediate-power view demonstrates immature islands of cartilage in a cellular background stroma.
Nasal chondromesenchymal hamartoma. Bone, immature cartilage, and a cellular spindled cell stroma are noted in this hamartoma.
A: cartilage
Back Extra: Nasal Chondromesenchymal Hamartoma
- Clinical: Symptoms include nasal obstruction, a mass, and ophthalmological findings. Tumours may erode into the cranial cavity and are often associated with DICER1 pleuropulmonary blastoma syndrome.
- Micro: Histologically, the lesion shows well-demarcated nodules of immature to mature cartilage in a myxoid to spindle cell stroma. Osteoclast-like giant cells and fibro-osseous proliferation may be present.
- Ancillary: S100 and SOX9 immunohistochemistry highlight the cartilaginous portions, while DICER1 genetic testing is recommended due to the association with DICER1 mutations.
Reference Gallery:
Nasal chondromesenchymal hamartoma. Coronal CT showing a destructive sinonasal tract mass with intracranial extension.
Nasal chondromesenchymal hamartoma. Low-power view shows immature cartilage and stroma in a background of minor mucoserous glands.
Nasal chondromesenchymal hamartoma. Intermediate-power view demonstrates immature islands of cartilage in a cellular background stroma.
Nasal chondromesenchymal hamartoma. High-power view shows immature cartilage in a cellular stroma showing mild nuclear pleomorphism. Extravasated erythrocytes are noted with focal cystic changes.
Nasal chondromesenchymal hamartoma. Bone, immature cartilage, and a cellular spindled cell stroma are noted in this hamartoma.
Nasal chondromesenchymal hamartoma. S100 strongly highlights the nuclei and cytoplasm of the cartilaginous portions of the hamartoma. (The minor mucoserous gland is a good internal control.)

Q: In Nasal Chondromesenchymal Hamartoma, the cartilaginous portions of the tumor are characteristically highlighted by SOX9 and [...] on immunohistochemistry.
Nasal chondromesenchymal hamartoma. S100 strongly highlights the nuclei and cytoplasm of the cartilaginous portions of the hamartoma. (The minor mucoserous gland is a good internal control.)
A: S100
Back Extra: Nasal Chondromesenchymal Hamartoma
- Clinical: Symptoms include nasal obstruction, a mass, and ophthalmological findings. Tumours may erode into the cranial cavity and are often associated with DICER1 pleuropulmonary blastoma syndrome.
- Micro: Histologically, the lesion shows well-demarcated nodules of immature to mature cartilage in a myxoid to spindle cell stroma. Osteoclast-like giant cells and fibro-osseous proliferation may be present.
- Ancillary: S100 and SOX9 immunohistochemistry highlight the cartilaginous portions, while DICER1 genetic testing is recommended due to the association with DICER1 mutations.
Reference Gallery:
Nasal chondromesenchymal hamartoma. Coronal CT showing a destructive sinonasal tract mass with intracranial extension.
Nasal chondromesenchymal hamartoma. Low-power view shows immature cartilage and stroma in a background of minor mucoserous glands.
Nasal chondromesenchymal hamartoma. Intermediate-power view demonstrates immature islands of cartilage in a cellular background stroma.
Nasal chondromesenchymal hamartoma. High-power view shows immature cartilage in a cellular stroma showing mild nuclear pleomorphism. Extravasated erythrocytes are noted with focal cystic changes.
Nasal chondromesenchymal hamartoma. Bone, immature cartilage, and a cellular spindled cell stroma are noted in this hamartoma.
Nasal chondromesenchymal hamartoma. S100 strongly highlights the nuclei and cytoplasm of the cartilaginous portions of the hamartoma. (The minor mucoserous gland is a good internal control.)

Q: A pathognomonic clinical finding of a Nasal Dermoid Cyst is the presence of a midline nasal pit with [...].
Nasal dermoid cyst. Protruding hair on the nasal dorsum (arrow).
Nasal dermoid cyst. Inflamed dermoid cyst (arrowheads) and nasal pit (arrow).
A: protruding hair
Back Extra: Nasal Dermoid Cyst
- Clinical: A sinus may be visible centrally over the nasal mass or adjacent to the mass. A nasal pit with protruding hair is pathognomonic. Progressive enlargement can cause facial skeletal deformities.
- Micro: The cyst and sinus are lined by keratinizing stratified squamous epithelium with dermal appendages, including hair follicles, hair shafts, sweat, and sebaceous glands.
- Ancillary: Preoperative imaging is crucial to detect intracranial extensions, present in 10–20% of cases.
Reference Gallery:
Nasal dermoid cyst. Protruding hair on the nasal dorsum (arrow).
Nasal dermoid cyst. Inflamed dermoid cyst (arrowheads) and nasal pit (arrow).
Nasal dermoid cyst. Longitudinally sectioned dermoid sinus lined by keratinizing stratified squamous mucosa with numerous dermal hair follicles. The lumen contains hair shafts and laminated keratin debris.
Nasal dermoid cyst. Cross-section of dermoid sinus lined by keratinizing stratified squamous mucosa associated with numerous dermal appendages including hair follicles, sebaceous glands, and sweat glands. Hair fragments are present within the lumen.
Nasal dermoid cyst. Higher-magnification view showing numerous dermal pilosebaceous units and cross-sectioned hair shafts within the lumen.

Q: Microscopically, a Nasal Dermoid Cyst is characterized by a cyst or sinus tract lined by keratinizing stratified squamous epithelium that uniquely contains [...] (such as hair follicles, sweat glands, and sebaceous glands).
Nasal dermoid cyst. Longitudinally sectioned dermoid sinus lined by keratinizing stratified squamous mucosa with numerous dermal hair follicles. The lumen contains hair shafts and laminated keratin debris.
Nasal dermoid cyst. Cross-section of dermoid sinus lined by keratinizing stratified squamous mucosa associated with numerous dermal appendages including hair follicles, sebaceous glands, and sweat glands. Hair fragments are present within the lumen.
Nasal dermoid cyst. Higher-magnification view showing numerous dermal pilosebaceous units and cross-sectioned hair shafts within the lumen.
A: dermal appendages
Back Extra: Nasal Dermoid Cyst
- Clinical: A sinus may be visible centrally over the nasal mass or adjacent to the mass. A nasal pit with protruding hair is pathognomonic. Progressive enlargement can cause facial skeletal deformities.
- Micro: The cyst and sinus are lined by keratinizing stratified squamous epithelium with dermal appendages, including hair follicles, hair shafts, sweat, and sebaceous glands.
- Ancillary: Preoperative imaging is crucial to detect intracranial extensions, present in 10–20% of cases.
Reference Gallery:
Nasal dermoid cyst. Protruding hair on the nasal dorsum (arrow).
Nasal dermoid cyst. Inflamed dermoid cyst (arrowheads) and nasal pit (arrow).
Nasal dermoid cyst. Longitudinally sectioned dermoid sinus lined by keratinizing stratified squamous mucosa with numerous dermal hair follicles. The lumen contains hair shafts and laminated keratin debris.
Nasal dermoid cyst. Cross-section of dermoid sinus lined by keratinizing stratified squamous mucosa associated with numerous dermal appendages including hair follicles, sebaceous glands, and sweat glands. Hair fragments are present within the lumen.
Nasal dermoid cyst. Higher-magnification view showing numerous dermal pilosebaceous units and cross-sectioned hair shafts within the lumen.

Q: In Nasopharyngeal dermoid, the classic histological appearance consists of an outer layer of stratified squamous epithelium associated with underlying [...] (e.g., hair follicles and sebaceous glands).
Nasopharyngeal dermoid. Stratified squamous epithelium with hair follicles and sebaceous glands.
A: cutaneous adnexal structures
Back Extra: Nasopharyngeal dermoid
- Clinical: Babies and newborns may present with observable difficulties in breathing, swallowing, or eating due to an often pedunculated mass variably obstructing the nasopharynx.
- Micro: Nasopharyngeal dermoids may be polypoid, solid, or cystic, showing stratified squamous epithelium associated with cutaneous adnexal structures such as hair follicles and sebaceous glands, sometimes creating a hairy polyp, and often with cartilage.
- Ancillary: Not clinically relevant
Reference Gallery:
Nasopharyngeal dermoid. Stratified squamous epithelium with hair follicles and sebaceous glands.

Q: Due to the prominent hair follicles and sebaceous glands seen histologically, a Nasopharyngeal dermoid in a newborn is sometimes descriptively referred to as a [...].
Nasopharyngeal dermoid. Stratified squamous epithelium with hair follicles and sebaceous glands.
A: hairy polyp
Back Extra: Nasopharyngeal dermoid
- Clinical: Babies and newborns may present with observable difficulties in breathing, swallowing, or eating due to an often pedunculated mass variably obstructing the nasopharynx.
- Micro: Nasopharyngeal dermoids may be polypoid, solid, or cystic, showing stratified squamous epithelium associated with cutaneous adnexal structures such as hair follicles and sebaceous glands, sometimes creating a hairy polyp, and often with cartilage.
- Ancillary: Not clinically relevant
Reference Gallery:
Nasopharyngeal dermoid. Stratified squamous epithelium with hair follicles and sebaceous glands.

Q: In Nasopharyngeal Carcinoma, ancillary testing with in situ hybridization for [...] is almost invariably positive.
Metastatic nasopharyngeal carcinoma in lymph node. In a metastatic carcinoma of uncertain origin, positive labelling for EBV-encoded small RNA (EBER) strongly suggests a nasopharyngeal primary.
A: EBV-encoded small RNA (EBER)
Back Extra: Nasopharyngeal Carcinoma
- Clinical: Nasopharyngeal carcinoma often presents with unilateral or bilateral upper cervical lymphadenopathy, nasal obstruction, epistaxis, and hearing impairment.
- Micro: Histologically, the tumour comprises solid sheets, irregular islands, and trabeculae, often intermingled with lymphocytes and plasma cells.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is almost invariably positive in nasopharyngeal carcinoma.
Reference Gallery:
Nasopharyngeal carcinoma. Biopsy of the nasopharynx shows the tumour beneath an intact epithelium.
Nasopharyngeal carcinoma. Undifferentiated carcinoma characterized by large tumour cells that have indistinct cell borders and crowded nuclei with vesicular chromatin and prominent nucleoli.
Nasopharyngeal carcinoma. In undifferentiated carcinoma, the tumour cells can be spindly, forming sweeping fascicles.
Nasopharyngeal carcinoma with subtle tumour involvement. A biopsy shows a dense infiltrate of small lymphocytes and plasma cells, but the carcinoma cells can barely be appreciated.
Nasopharyngeal carcinoma with subtle tumour involvement. Immunostaining for cytokeratin may highlight a surprising number of carcinoma cells.
Metastatic nasopharyngeal carcinoma in lymph node. The node shows extensive replacement by sheets of carcinoma cells.
Metastatic nasopharyngeal carcinoma in lymph node. The carcinoma cells have a syncytial appearance, with vesicular nuclei and prominent nucleoli.
Metastatic nasopharyngeal carcinoma in lymph node. In this example, the carcinoma cells are intimately intermingled with lymphocytes, plasma cells, and eosinophils, mimicking Hodgkin lymphoma.
Metastatic nasopharyngeal carcinoma in lymph node. In a metastatic carcinoma of uncertain origin, positive labelling for EBV-encoded small RNA (EBER) strongly suggests a nasopharyngeal primary.
Nasopharyngeal carcinoma. T2-weighted fat-suppressed axial MRI shows mildly hyperintense mucosal thickening over the roof of the nasopharynx and a large metastatic right retropharyngeal node.
Nasopharyngeal carcinoma. Contrast-enhanced T1-weighted axial MRI shows heterogeneous enhancement of both the primary nasopharynx carcinoma and the large right retropharyngeal node.

Q: Histologically, the undifferentiated variant of Nasopharyngeal Carcinoma features prominent infiltration by lymphocytes and plasma cells, along with large tumor cells that have indistinct cell borders, often described as having a [...] appearance.
Nasopharyngeal carcinoma. Undifferentiated carcinoma characterized by large tumour cells that have indistinct cell borders and crowded nuclei with vesicular chromatin and prominent nucleoli.
Metastatic nasopharyngeal carcinoma in lymph node. The carcinoma cells have a syncytial appearance, with vesicular nuclei and prominent nucleoli.
Metastatic nasopharyngeal carcinoma in lymph node. In this example, the carcinoma cells are intimately intermingled with lymphocytes, plasma cells, and eosinophils, mimicking Hodgkin lymphoma.
A: syncytial
Back Extra: Nasopharyngeal Carcinoma
- Clinical: Nasopharyngeal carcinoma often presents with unilateral or bilateral upper cervical lymphadenopathy, nasal obstruction, epistaxis, and hearing impairment.
- Micro: Histologically, the tumour comprises solid sheets, irregular islands, and trabeculae, often intermingled with lymphocytes and plasma cells.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is almost invariably positive in nasopharyngeal carcinoma.
Reference Gallery:
Nasopharyngeal carcinoma. Biopsy of the nasopharynx shows the tumour beneath an intact epithelium.
Nasopharyngeal carcinoma. Undifferentiated carcinoma characterized by large tumour cells that have indistinct cell borders and crowded nuclei with vesicular chromatin and prominent nucleoli.
Nasopharyngeal carcinoma. In undifferentiated carcinoma, the tumour cells can be spindly, forming sweeping fascicles.
Nasopharyngeal carcinoma with subtle tumour involvement. A biopsy shows a dense infiltrate of small lymphocytes and plasma cells, but the carcinoma cells can barely be appreciated.
Nasopharyngeal carcinoma with subtle tumour involvement. Immunostaining for cytokeratin may highlight a surprising number of carcinoma cells.
Metastatic nasopharyngeal carcinoma in lymph node. The node shows extensive replacement by sheets of carcinoma cells.
Metastatic nasopharyngeal carcinoma in lymph node. The carcinoma cells have a syncytial appearance, with vesicular nuclei and prominent nucleoli.
Metastatic nasopharyngeal carcinoma in lymph node. In this example, the carcinoma cells are intimately intermingled with lymphocytes, plasma cells, and eosinophils, mimicking Hodgkin lymphoma.
Metastatic nasopharyngeal carcinoma in lymph node. In a metastatic carcinoma of uncertain origin, positive labelling for EBV-encoded small RNA (EBER) strongly suggests a nasopharyngeal primary.
Nasopharyngeal carcinoma. T2-weighted fat-suppressed axial MRI shows mildly hyperintense mucosal thickening over the roof of the nasopharynx and a large metastatic right retropharyngeal node.
Nasopharyngeal carcinoma. Contrast-enhanced T1-weighted axial MRI shows heterogeneous enhancement of both the primary nasopharynx carcinoma and the large right retropharyngeal node.

Q: A head and neck tumor presenting clinically with epistaxis and prominent cervical lymphadenopathy, and radiographically as a mucosal mass over the roof of the nasopharynx, is highly characteristic of [...].
Nasopharyngeal carcinoma. T2-weighted fat-suppressed axial MRI shows mildly hyperintense mucosal thickening over the roof of the nasopharynx and a large metastatic right retropharyngeal node.
Nasopharyngeal carcinoma. Contrast-enhanced T1-weighted axial MRI shows heterogeneous enhancement of both the primary nasopharynx carcinoma and the large right retropharyngeal node.
A: Nasopharyngeal Carcinoma
Back Extra: Nasopharyngeal Carcinoma
- Clinical: Nasopharyngeal carcinoma often presents with unilateral or bilateral upper cervical lymphadenopathy, nasal obstruction, epistaxis, and hearing impairment.
- Micro: Histologically, the tumour comprises solid sheets, irregular islands, and trabeculae, often intermingled with lymphocytes and plasma cells.
- Ancillary: In situ hybridization for EBV-encoded small RNA (EBER) is almost invariably positive in nasopharyngeal carcinoma.
Reference Gallery:
Nasopharyngeal carcinoma. Biopsy of the nasopharynx shows the tumour beneath an intact epithelium.
Nasopharyngeal carcinoma. Undifferentiated carcinoma characterized by large tumour cells that have indistinct cell borders and crowded nuclei with vesicular chromatin and prominent nucleoli.
Nasopharyngeal carcinoma. In undifferentiated carcinoma, the tumour cells can be spindly, forming sweeping fascicles.
Nasopharyngeal carcinoma with subtle tumour involvement. A biopsy shows a dense infiltrate of small lymphocytes and plasma cells, but the carcinoma cells can barely be appreciated.
Nasopharyngeal carcinoma with subtle tumour involvement. Immunostaining for cytokeratin may highlight a surprising number of carcinoma cells.
Metastatic nasopharyngeal carcinoma in lymph node. The node shows extensive replacement by sheets of carcinoma cells.
Metastatic nasopharyngeal carcinoma in lymph node. The carcinoma cells have a syncytial appearance, with vesicular nuclei and prominent nucleoli.
Metastatic nasopharyngeal carcinoma in lymph node. In this example, the carcinoma cells are intimately intermingled with lymphocytes, plasma cells, and eosinophils, mimicking Hodgkin lymphoma.
Metastatic nasopharyngeal carcinoma in lymph node. In a metastatic carcinoma of uncertain origin, positive labelling for EBV-encoded small RNA (EBER) strongly suggests a nasopharyngeal primary.
Nasopharyngeal carcinoma. T2-weighted fat-suppressed axial MRI shows mildly hyperintense mucosal thickening over the roof of the nasopharynx and a large metastatic right retropharyngeal node.
Nasopharyngeal carcinoma. Contrast-enhanced T1-weighted axial MRI shows heterogeneous enhancement of both the primary nasopharynx carcinoma and the large right retropharyngeal node.

Q: Histologically, NUT Carcinoma frequently presents as infiltrative nests of primitive, undifferentiated round cells with numerous foci of [...].
NUT carcinoma. Infiltrative nests of undifferentiated, monotonous round cells with numerous foci of abrupt keratinization.
A: abrupt keratinization
Back Extra: NUT Carcinoma
- Clinical: NUT Carcinoma presents with nonspecific symptoms and is locally aggressive with a high metastatic rate, often seen in children and young adults.
- Micro: Characterized by infiltrative nests and sheets of primitive-appearing, medium-sized undifferentiated cells with high mitotic counts and frequent necrosis.
- Ancillary: Diagnosis is confirmed by demonstration of NUTM1 rearrangement, with a dot-like nuclear pattern on NUT immunohistochemistry.
Reference Gallery:
NUT carcinoma. Infiltrative nests of undifferentiated, monotonous round cells with numerous foci of abrupt keratinization.
NUT carcinoma. Diffuse, dot-like immunostaining with NUT monoclonal antibody is diagnostic for NUT carcinoma.
NUT carcinoma. This large sinonasal NUT carcinoma shows aggressive behaviour, with growth into the brain and orbit.

Q: The diagnostic immunohistochemical hallmark of NUT Carcinoma is a diffuse, [...] staining pattern with the NUT monoclonal antibody.
NUT carcinoma. Diffuse, dot-like immunostaining with NUT monoclonal antibody is diagnostic for NUT carcinoma.
A: dot-like nuclear
Back Extra: NUT Carcinoma
- Clinical: NUT Carcinoma presents with nonspecific symptoms and is locally aggressive with a high metastatic rate, often seen in children and young adults.
- Micro: Characterized by infiltrative nests and sheets of primitive-appearing, medium-sized undifferentiated cells with high mitotic counts and frequent necrosis.
- Ancillary: Diagnosis is confirmed by demonstration of NUTM1 rearrangement, with a dot-like nuclear pattern on NUT immunohistochemistry.
Reference Gallery:
NUT carcinoma. Infiltrative nests of undifferentiated, monotonous round cells with numerous foci of abrupt keratinization.
NUT carcinoma. Diffuse, dot-like immunostaining with NUT monoclonal antibody is diagnostic for NUT carcinoma.
NUT carcinoma. This large sinonasal NUT carcinoma shows aggressive behaviour, with growth into the brain and orbit.

Q: NUT Carcinoma is a highly aggressive neoplasm of children and young adults that classically arises in midline locations, such as the [...] tract, often exhibiting destructive local growth into structures like the brain and orbit.
NUT carcinoma. This large sinonasal NUT carcinoma shows aggressive behaviour, with growth into the brain and orbit.
A: sinonasal
Back Extra: NUT Carcinoma
- Clinical: NUT Carcinoma presents with nonspecific symptoms and is locally aggressive with a high metastatic rate, often seen in children and young adults.
- Micro: Characterized by infiltrative nests and sheets of primitive-appearing, medium-sized undifferentiated cells with high mitotic counts and frequent necrosis.
- Ancillary: Diagnosis is confirmed by demonstration of NUTM1 rearrangement, with a dot-like nuclear pattern on NUT immunohistochemistry.
Reference Gallery:
NUT carcinoma. Infiltrative nests of undifferentiated, monotonous round cells with numerous foci of abrupt keratinization.
NUT carcinoma. Diffuse, dot-like immunostaining with NUT monoclonal antibody is diagnostic for NUT carcinoma.
NUT carcinoma. This large sinonasal NUT carcinoma shows aggressive behaviour, with growth into the brain and orbit.

Q: Among Odontogenic Tumors, the microscopic finding of islands of loose, stellate reticulum-like epithelium surrounded by a basophilic, peripheral palisaded basal layer of columnar cells is characteristic of an [...].
Ameloblastoma, follicular pattern. Central islands of loose, stellate, reticulum-like epithelium surrounded by a basophilic peripheral palisaded basal layer of columnar ameloblastic cells. There is focal acanthomatous change, and multiple small cysts are seen forming within the epithelium.
Plexiform ameloblastoma. A meshwork of strands of epithelium with peripheral ameloblast-like cells.
A: ameloblastoma
Q: Odontogenic Tumours
- Clinical: Most patients with [...] present with jaw swelling, expansion of the jaw, asymmetry, or displacement of teeth. Imaging includes plain radiographs, CT, or cone beam CT.
- Micro: Ameloblastoma shows islands of loose, stellate reticulum-like epithelium surrounded by a basophilic peripheral palisaded basal layer of columnar ameloblastic cells. Cystic change within the epithelium is common.
- Ancillary: Differential diagnoses for [...] include other odontogenic cysts and neoplasms, such as dentigerous cyst, keratocystic odontogenic tumour, and odontogenic myxoma.
Reference Gallery:
Ameloblastoma. A typical multilocular, scalloped, radiolucent expansile lesion with partial cortication extending from the coronoid notch to the posterior body of the mandible, with cortical perforation and a displaced developing tooth and minor tooth root resorption (plain radiograph).
Ameloblastoma, follicular pattern. Central islands of loose, stellate, reticulum-like epithelium surrounded by a basophilic peripheral palisaded basal layer of columnar ameloblastic cells. There is focal acanthomatous change, and multiple small cysts are seen forming within the epithelium.
Ameloblastic fibroma. A radiolucent posterior maxilla lesion displacing the crown of a developing tooth superiorly and surrounded by a thin expanded cortical bone layer. There is displacement of forming teeth anteriorly (plain radiograph).
Odontoma. A corticated mixed radiolucency containing discrete denticles of enamel and dentin, radiopaque mesially and distally, with little cortical expansion but a prominent central unmineralized portion that has not yet matured (plain radiograph).
Odontoma, complex pattern. Typical complex odontoma decalcified section showing a band of tubular dentin inferiorly and eosinophilic enamel matrix on its upper surface, together with a disorganized mass of strands of odontogenic epithelium showing ameloblastic and stellate reticulum differentiation.
Odontogenic myxoma. Axial CT showing an expanding mass affecting the maxillary alveolus anteriorly and laterally. The lesion is radiolucent but has irregular thin bony septa at right angles to the cortex, with focal cortical destruction.
Odontogenic myxoma. Periphery of an odontogenic myxoma showing microscopic cortical perforation. The sparsely cellular myxoid lesion is contained by the periosteum at the top, with permeative spread around residual bone trabecula and into medullary areas.
Odontogenic keratocyst. A multilocular radiolucency extending from the mid-ramus to the premolar region with minimal expansion of the inferior cortex. There is peripheral cortication and little displacement of the associated teeth, which do not show root resorption (plain radiograph).
Odontogenic keratocyst. Non-inflamed cyst lining, showing a flat basement membrane with palisaded basal cells, a thin epithelium, and a corrugated, parakeratinized refractile luminal surface.
Ameloblastic fibroma. Strands of epithelium with cuboidal or slightly elongate basophilic basal epithelium without stellate reticulum, lying in a highly cellular uniform fibroblastic stroma. Note the absence of matrix and calcified tissue.
Plexiform ameloblastoma. A meshwork of strands of epithelium with peripheral ameloblast-like cells.
A: odontogenic tumours; odontogenic tumours

Q: Patients with Odontogenic Tumors often present with jaw swelling and asymmetry; radiographically, an [...] classically appears as a multilocular, scalloped, radiolucent expansile lesion that can cause cortical perforation and displace developing teeth.
Ameloblastoma. A typical multilocular, scalloped, radiolucent expansile lesion with partial cortication extending from the coronoid notch to the posterior body of the mandible, with cortical perforation and a displaced developing tooth and minor tooth root resorption (plain radiograph).
A: ameloblastoma
Q: Odontogenic Tumours
- Clinical: Most patients with [...] present with jaw swelling, expansion of the jaw, asymmetry, or displacement of teeth. Imaging includes plain radiographs, CT, or cone beam CT.
- Micro: Ameloblastoma shows islands of loose, stellate reticulum-like epithelium surrounded by a basophilic peripheral palisaded basal layer of columnar ameloblastic cells. Cystic change within the epithelium is common.
- Ancillary: Differential diagnoses for [...] include other odontogenic cysts and neoplasms, such as dentigerous cyst, keratocystic odontogenic tumour, and odontogenic myxoma.
Reference Gallery:
Ameloblastoma. A typical multilocular, scalloped, radiolucent expansile lesion with partial cortication extending from the coronoid notch to the posterior body of the mandible, with cortical perforation and a displaced developing tooth and minor tooth root resorption (plain radiograph).
Ameloblastoma, follicular pattern. Central islands of loose, stellate, reticulum-like epithelium surrounded by a basophilic peripheral palisaded basal layer of columnar ameloblastic cells. There is focal acanthomatous change, and multiple small cysts are seen forming within the epithelium.
Ameloblastic fibroma. A radiolucent posterior maxilla lesion displacing the crown of a developing tooth superiorly and surrounded by a thin expanded cortical bone layer. There is displacement of forming teeth anteriorly (plain radiograph).
Odontoma. A corticated mixed radiolucency containing discrete denticles of enamel and dentin, radiopaque mesially and distally, with little cortical expansion but a prominent central unmineralized portion that has not yet matured (plain radiograph).
Odontoma, complex pattern. Typical complex odontoma decalcified section showing a band of tubular dentin inferiorly and eosinophilic enamel matrix on its upper surface, together with a disorganized mass of strands of odontogenic epithelium showing ameloblastic and stellate reticulum differentiation.
Odontogenic myxoma. Axial CT showing an expanding mass affecting the maxillary alveolus anteriorly and laterally. The lesion is radiolucent but has irregular thin bony septa at right angles to the cortex, with focal cortical destruction.
Odontogenic myxoma. Periphery of an odontogenic myxoma showing microscopic cortical perforation. The sparsely cellular myxoid lesion is contained by the periosteum at the top, with permeative spread around residual bone trabecula and into medullary areas.
Odontogenic keratocyst. A multilocular radiolucency extending from the mid-ramus to the premolar region with minimal expansion of the inferior cortex. There is peripheral cortication and little displacement of the associated teeth, which do not show root resorption (plain radiograph).
Odontogenic keratocyst. Non-inflamed cyst lining, showing a flat basement membrane with palisaded basal cells, a thin epithelium, and a corrugated, parakeratinized refractile luminal surface.
Ameloblastic fibroma. Strands of epithelium with cuboidal or slightly elongate basophilic basal epithelium without stellate reticulum, lying in a highly cellular uniform fibroblastic stroma. Note the absence of matrix and calcified tissue.
Plexiform ameloblastoma. A meshwork of strands of epithelium with peripheral ameloblast-like cells.
A: odontogenic tumours; odontogenic tumours

Q: In the differential diagnosis of Odontogenic Tumors, the [...] is a critical cystic lesion distinguished microscopically by a flat basement membrane, palisaded basal cells, and a distinctive corrugated, parakeratinized luminal surface.
Odontogenic keratocyst. A multilocular radiolucency extending from the mid-ramus to the premolar region with minimal expansion of the inferior cortex. There is peripheral cortication and little displacement of the associated teeth, which do not show root resorption (plain radiograph).
Odontogenic keratocyst. Non-inflamed cyst lining, showing a flat basement membrane with palisaded basal cells, a thin epithelium, and a corrugated, parakeratinized refractile luminal surface.
A: odontogenic keratocyst
Q: Odontogenic Tumours
- Clinical: Most patients with [...] present with jaw swelling, expansion of the jaw, asymmetry, or displacement of teeth. Imaging includes plain radiographs, CT, or cone beam CT.
- Micro: Ameloblastoma shows islands of loose, stellate reticulum-like epithelium surrounded by a basophilic peripheral palisaded basal layer of columnar ameloblastic cells. Cystic change within the epithelium is common.
- Ancillary: Differential diagnoses for [...] include other odontogenic cysts and neoplasms, such as dentigerous cyst, keratocystic odontogenic tumour, and odontogenic myxoma.
Reference Gallery:
Ameloblastoma. A typical multilocular, scalloped, radiolucent expansile lesion with partial cortication extending from the coronoid notch to the posterior body of the mandible, with cortical perforation and a displaced developing tooth and minor tooth root resorption (plain radiograph).
Ameloblastoma, follicular pattern. Central islands of loose, stellate, reticulum-like epithelium surrounded by a basophilic peripheral palisaded basal layer of columnar ameloblastic cells. There is focal acanthomatous change, and multiple small cysts are seen forming within the epithelium.
Ameloblastic fibroma. A radiolucent posterior maxilla lesion displacing the crown of a developing tooth superiorly and surrounded by a thin expanded cortical bone layer. There is displacement of forming teeth anteriorly (plain radiograph).
Odontoma. A corticated mixed radiolucency containing discrete denticles of enamel and dentin, radiopaque mesially and distally, with little cortical expansion but a prominent central unmineralized portion that has not yet matured (plain radiograph).
Odontoma, complex pattern. Typical complex odontoma decalcified section showing a band of tubular dentin inferiorly and eosinophilic enamel matrix on its upper surface, together with a disorganized mass of strands of odontogenic epithelium showing ameloblastic and stellate reticulum differentiation.
Odontogenic myxoma. Axial CT showing an expanding mass affecting the maxillary alveolus anteriorly and laterally. The lesion is radiolucent but has irregular thin bony septa at right angles to the cortex, with focal cortical destruction.
Odontogenic myxoma. Periphery of an odontogenic myxoma showing microscopic cortical perforation. The sparsely cellular myxoid lesion is contained by the periosteum at the top, with permeative spread around residual bone trabecula and into medullary areas.
Odontogenic keratocyst. A multilocular radiolucency extending from the mid-ramus to the premolar region with minimal expansion of the inferior cortex. There is peripheral cortication and little displacement of the associated teeth, which do not show root resorption (plain radiograph).
Odontogenic keratocyst. Non-inflamed cyst lining, showing a flat basement membrane with palisaded basal cells, a thin epithelium, and a corrugated, parakeratinized refractile luminal surface.
Ameloblastic fibroma. Strands of epithelium with cuboidal or slightly elongate basophilic basal epithelium without stellate reticulum, lying in a highly cellular uniform fibroblastic stroma. Note the absence of matrix and calcified tissue.
Plexiform ameloblastoma. A meshwork of strands of epithelium with peripheral ameloblast-like cells.
A: odontogenic tumours; odontogenic tumours

Q: Histologically, Pleomorphic Adenoma is characterized by the biphasic blending of epithelial and myoepithelial cells with a distinct [...] stroma.
Pleomorphic adenoma. The blending of the chondromesenchymal stroma with the epithelial and myoepithelial components is shown. Fibrous bands are present.
Pleomorphic adenoma. Abundant chondroid material blends with the epithelial-myoepithelial proliferation of a pleomorphic adenoma.
A: chondromesenchymal
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic adenoma (PA) typically presents as a slow-growing, asymptomatic, discrete mass in the parotid gland.
- Micro: Histologically, PAs show a wide variety of features, including blending of epithelial, myoepithelial, and chondromesenchymal components.
- Ancillary: PLAG1 rearrangements, detectable by FISH, are found in about 80-90% of PAs.
Reference Gallery:
Pleomorphic adenoma. A 9-year-old girl demonstrates an intact mucosa overlying a left palate mass.
Pleomorphic adenoma. A well-circumscribed and encapsulated pleomorphic adenoma is noted in the parotid gland tissue.
Pleomorphic adenoma. The blending of the chondromesenchymal stroma with the epithelial and myoepithelial components is shown. Fibrous bands are present.
Pleomorphic adenoma. Abundant chondroid material blends with the epithelial-myoepithelial proliferation of a pleomorphic adenoma.
Pleomorphic adenoma. The stroma-rich pattern is shown here, with only limited epithelial-myoepithelial elements present.
Pleomorphic adenoma. The fibrillar stroma stains a deep magenta in this Romanowsky (Diff-Quik)-stained smear with embedded plasmacytoid epithelial elements.
Pleomorphic adenoma. There is a fibrillar quality to the myxoid matrix material seen in this Pap-stained smear, with embedded myoepithelial cells.
Pleomorphic adenoma. G-banded karyotype from a patient with a pleomorphic adenoma showing a reciprocal translocation, t(8;14)(q12;q32). PLAG1 rearrangement is detected in metaphase (upper right) and interphase (lower right) cells using dual-colour break-apart probes (green, 5′ PLAG1; red, 3′ PLAG1). Arrows indicate der(8) and der(14) chromosomes.
Pleomorphic adenoma. A clinical photograph showing a smooth, rounded mass in the region of the parotid gland.

Q: Approximately 80-90% of Pleomorphic Adenoma cases harbor a recurrent genetic rearrangement involving the [...] gene, which can be detected by FISH.
Pleomorphic adenoma. G-banded karyotype from a patient with a pleomorphic adenoma showing a reciprocal translocation, t(8;14)(q12;q32). PLAG1 rearrangement is detected in metaphase (upper right) and interphase (lower right) cells using dual-colour break-apart probes (green, 5′ PLAG1; red, 3′ PLAG1). Arrows indicate der(8) and der(14) chromosomes.
A: PLAG1
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic adenoma (PA) typically presents as a slow-growing, asymptomatic, discrete mass in the parotid gland.
- Micro: Histologically, PAs show a wide variety of features, including blending of epithelial, myoepithelial, and chondromesenchymal components.
- Ancillary: PLAG1 rearrangements, detectable by FISH, are found in about 80-90% of PAs.
Reference Gallery:
Pleomorphic adenoma. A 9-year-old girl demonstrates an intact mucosa overlying a left palate mass.
Pleomorphic adenoma. A well-circumscribed and encapsulated pleomorphic adenoma is noted in the parotid gland tissue.
Pleomorphic adenoma. The blending of the chondromesenchymal stroma with the epithelial and myoepithelial components is shown. Fibrous bands are present.
Pleomorphic adenoma. Abundant chondroid material blends with the epithelial-myoepithelial proliferation of a pleomorphic adenoma.
Pleomorphic adenoma. The stroma-rich pattern is shown here, with only limited epithelial-myoepithelial elements present.
Pleomorphic adenoma. The fibrillar stroma stains a deep magenta in this Romanowsky (Diff-Quik)-stained smear with embedded plasmacytoid epithelial elements.
Pleomorphic adenoma. There is a fibrillar quality to the myxoid matrix material seen in this Pap-stained smear, with embedded myoepithelial cells.
Pleomorphic adenoma. G-banded karyotype from a patient with a pleomorphic adenoma showing a reciprocal translocation, t(8;14)(q12;q32). PLAG1 rearrangement is detected in metaphase (upper right) and interphase (lower right) cells using dual-colour break-apart probes (green, 5′ PLAG1; red, 3′ PLAG1). Arrows indicate der(8) and der(14) chromosomes.
Pleomorphic adenoma. A clinical photograph showing a smooth, rounded mass in the region of the parotid gland.

Q: Typically presenting as a slow-growing, asymptomatic, well-circumscribed mass in the parotid gland, [...] is the most common benign salivary gland tumor.
Pleomorphic adenoma. A well-circumscribed and encapsulated pleomorphic adenoma is noted in the parotid gland tissue.
Pleomorphic adenoma. A clinical photograph showing a smooth, rounded mass in the region of the parotid gland.
A: Pleomorphic Adenoma
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic adenoma (PA) typically presents as a slow-growing, asymptomatic, discrete mass in the parotid gland.
- Micro: Histologically, PAs show a wide variety of features, including blending of epithelial, myoepithelial, and chondromesenchymal components.
- Ancillary: PLAG1 rearrangements, detectable by FISH, are found in about 80-90% of PAs.
Reference Gallery:
Pleomorphic adenoma. A 9-year-old girl demonstrates an intact mucosa overlying a left palate mass.
Pleomorphic adenoma. A well-circumscribed and encapsulated pleomorphic adenoma is noted in the parotid gland tissue.
Pleomorphic adenoma. The blending of the chondromesenchymal stroma with the epithelial and myoepithelial components is shown. Fibrous bands are present.
Pleomorphic adenoma. Abundant chondroid material blends with the epithelial-myoepithelial proliferation of a pleomorphic adenoma.
Pleomorphic adenoma. The stroma-rich pattern is shown here, with only limited epithelial-myoepithelial elements present.
Pleomorphic adenoma. The fibrillar stroma stains a deep magenta in this Romanowsky (Diff-Quik)-stained smear with embedded plasmacytoid epithelial elements.
Pleomorphic adenoma. There is a fibrillar quality to the myxoid matrix material seen in this Pap-stained smear, with embedded myoepithelial cells.
Pleomorphic adenoma. G-banded karyotype from a patient with a pleomorphic adenoma showing a reciprocal translocation, t(8;14)(q12;q32). PLAG1 rearrangement is detected in metaphase (upper right) and interphase (lower right) cells using dual-colour break-apart probes (green, 5′ PLAG1; red, 3′ PLAG1). Arrows indicate der(8) and der(14) chromosomes.
Pleomorphic adenoma. A clinical photograph showing a smooth, rounded mass in the region of the parotid gland.

Q: Patients with Sialoblastoma typically present in the [...] period with a painless facial swelling, frequently involving the parotid gland.
Sialoblastoma. MRI of the head of a 2-month-old boy with a 30 × 30 mm left parotid, well-defined, lobulated mass. At birth, the mass was 10 mm in size (not shown here).
Sialoblastoma. CT of the head of the boy shown in Fig. <<19635>> at 5 months of age. The mass has grown considerably and protrudes from the left side of the face.
A: neonatal
Back Extra: Sialoblastoma
- Clinical: Patients present with painless facial swelling, often diagnosed in the neonatal period, with rare cases showing nerve involvement or skin ulceration.
- Micro: Sialoblastoma typically shows solid organoid nests of primitive basaloid epithelial cells with scant cytoplasm and round to oval vesicular nuclei, separated by dense fibrous stroma.
- Ancillary: Immunohistochemistry shows reactivity for SOX10, p63, nuclear β-catenin, and KIT (CD117), and variably for cytokeratins including CK5/6, CK7, and CK19, along with SMA and calponin.
Reference Gallery:
Sialoblastoma. Low-power view. The tumour is composed of solid organoid nests of primitive basaloid epithelial cells, separated by scant fibrous stroma.
Sialoblastoma. Tumour cells exhibit round to oval nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Occasional differentiated ducts are noted within the tumour nests.
Sialoblastoma. MRI of the head of a 2-month-old boy with a 30 × 30 mm left parotid, well-defined, lobulated mass. At birth, the mass was 10 mm in size (not shown here).
Sialoblastoma. CT of the head of the boy shown in Fig. <<19635>> at 5 months of age. The mass has grown considerably and protrudes from the left side of the face.
Sialoblastoma. Sialoblastoma composed of solid organoid nests of tumour cells with a primitive basaloid appearance.
Sialoblastoma. Tumour cells show round to oval vesicular nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Differentiated ductules (arrows) are present around and within the nests. Occasional mitoses are observed.
Sialoblastoma. p63 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.
Sialoblastoma. CK19 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.
Sialoblastoma. CK7 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.

Q: Microscopically, Sialoblastoma is classically characterized by solid organoid nests of primitive [...] epithelial cells separated by a dense fibrous stroma.
Sialoblastoma. Low-power view. The tumour is composed of solid organoid nests of primitive basaloid epithelial cells, separated by scant fibrous stroma.
Sialoblastoma. Sialoblastoma composed of solid organoid nests of tumour cells with a primitive basaloid appearance.
Sialoblastoma. Tumour cells show round to oval vesicular nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Differentiated ductules (arrows) are present around and within the nests. Occasional mitoses are observed.
A: basaloid
Back Extra: Sialoblastoma
- Clinical: Patients present with painless facial swelling, often diagnosed in the neonatal period, with rare cases showing nerve involvement or skin ulceration.
- Micro: Sialoblastoma typically shows solid organoid nests of primitive basaloid epithelial cells with scant cytoplasm and round to oval vesicular nuclei, separated by dense fibrous stroma.
- Ancillary: Immunohistochemistry shows reactivity for SOX10, p63, nuclear β-catenin, and KIT (CD117), and variably for cytokeratins including CK5/6, CK7, and CK19, along with SMA and calponin.
Reference Gallery:
Sialoblastoma. Low-power view. The tumour is composed of solid organoid nests of primitive basaloid epithelial cells, separated by scant fibrous stroma.
Sialoblastoma. Tumour cells exhibit round to oval nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Occasional differentiated ducts are noted within the tumour nests.
Sialoblastoma. MRI of the head of a 2-month-old boy with a 30 × 30 mm left parotid, well-defined, lobulated mass. At birth, the mass was 10 mm in size (not shown here).
Sialoblastoma. CT of the head of the boy shown in Fig. <<19635>> at 5 months of age. The mass has grown considerably and protrudes from the left side of the face.
Sialoblastoma. Sialoblastoma composed of solid organoid nests of tumour cells with a primitive basaloid appearance.
Sialoblastoma. Tumour cells show round to oval vesicular nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Differentiated ductules (arrows) are present around and within the nests. Occasional mitoses are observed.
Sialoblastoma. p63 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.
Sialoblastoma. CK19 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.
Sialoblastoma. CK7 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.

Q: Immunohistochemistry in Sialoblastoma demonstrates primitive tumor cells with strong nuclear reactivity for [...], consistent with myoepithelial differentiation.
Sialoblastoma. p63 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.
A: p63
Back Extra: Sialoblastoma
- Clinical: Patients present with painless facial swelling, often diagnosed in the neonatal period, with rare cases showing nerve involvement or skin ulceration.
- Micro: Sialoblastoma typically shows solid organoid nests of primitive basaloid epithelial cells with scant cytoplasm and round to oval vesicular nuclei, separated by dense fibrous stroma.
- Ancillary: Immunohistochemistry shows reactivity for SOX10, p63, nuclear β-catenin, and KIT (CD117), and variably for cytokeratins including CK5/6, CK7, and CK19, along with SMA and calponin.
Reference Gallery:
Sialoblastoma. Low-power view. The tumour is composed of solid organoid nests of primitive basaloid epithelial cells, separated by scant fibrous stroma.
Sialoblastoma. Tumour cells exhibit round to oval nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Occasional differentiated ducts are noted within the tumour nests.
Sialoblastoma. MRI of the head of a 2-month-old boy with a 30 × 30 mm left parotid, well-defined, lobulated mass. At birth, the mass was 10 mm in size (not shown here).
Sialoblastoma. CT of the head of the boy shown in Fig. <<19635>> at 5 months of age. The mass has grown considerably and protrudes from the left side of the face.
Sialoblastoma. Sialoblastoma composed of solid organoid nests of tumour cells with a primitive basaloid appearance.
Sialoblastoma. Tumour cells show round to oval vesicular nuclei with single small nucleoli and scant, poorly outlined cytoplasm. Differentiated ductules (arrows) are present around and within the nests. Occasional mitoses are observed.
Sialoblastoma. p63 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.
Sialoblastoma. CK19 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.
Sialoblastoma. CK7 immunostaining. Tumour cells are strongly immunoreactive for p63 (nuclear) and CK19 (cytoplasmic), consistent with a myoepithelial differentiation. Differentiated ductules (arrows) are negative for p63 and weakly positive for CK19. Expression of CK7 is only present in the differentiated ductules.

Q: Clinically, Squamous Papilloma and Papillomatosis typically presents as painless, soft nodules with a pedunculated base and a characteristic [...] surface.
Squamous papilloma. A clinical photograph of a papillary, fleshy-coloured, pedunculated tumour of the soft palate.
A: cauliflower-like
Back Extra: Squamous Papilloma and Papillomatosis
- Clinical: Squamous papillomas present as painless, soft nodules with a pedunculated base, often with a cauliflower-like surface.
- Micro: Histologically, squamous papillomas show multiple papillary projections lined by thickened squamous epithelium with koilocytic atypia.
- Ancillary: HPV genotyping can help distinguish between episomal and integrated patterns, which may be relevant in recurrent respiratory papillomatosis (RRP).
Reference Gallery:
Squamous papilloma. A clinical photograph of a papillary, fleshy-coloured, pedunculated tumour of the soft palate.
Squamous papilloma. Histologically, there are multiple papillary projections lined by thickened epithelium with luminal cells showing koilocytic changes.
Squamous papilloma. High-power view shows thickened epithelium with orderly maturation to the surface. Crenated nuclei with perinuclear haloes and sharp cell borders are characteristic of koilocytic change in squamous papilloma.

Q: On microscopic examination, Squamous Papilloma and Papillomatosis shows multiple papillary projections of thickened squamous epithelium exhibiting [...] atypia, characterized by cells with crenated nuclei and perinuclear halos.
Squamous papilloma. Histologically, there are multiple papillary projections lined by thickened epithelium with luminal cells showing koilocytic changes.
Squamous papilloma. High-power view shows thickened epithelium with orderly maturation to the surface. Crenated nuclei with perinuclear haloes and sharp cell borders are characteristic of koilocytic change in squamous papilloma.
A: koilocytic
Back Extra: Squamous Papilloma and Papillomatosis
- Clinical: Squamous papillomas present as painless, soft nodules with a pedunculated base, often with a cauliflower-like surface.
- Micro: Histologically, squamous papillomas show multiple papillary projections lined by thickened squamous epithelium with koilocytic atypia.
- Ancillary: HPV genotyping can help distinguish between episomal and integrated patterns, which may be relevant in recurrent respiratory papillomatosis (RRP).
Reference Gallery:
Squamous papilloma. A clinical photograph of a papillary, fleshy-coloured, pedunculated tumour of the soft palate.
Squamous papilloma. Histologically, there are multiple papillary projections lined by thickened epithelium with luminal cells showing koilocytic changes.
Squamous papilloma. High-power view shows thickened epithelium with orderly maturation to the surface. Crenated nuclei with perinuclear haloes and sharp cell borders are characteristic of koilocytic change in squamous papilloma.

Q: Histologically, White Sponge Nevus is characterized by shaggy hyperparakeratosis, acanthosis with spinous layer vacuolation, and characteristic bright [...] representing keratin tonofilaments.
White sponge naevus. Prominent hyperparakeratosis and acanthosis with spinous cell layer vacuolation.
White sponge naevus. High-power view of bright eosinophilic perinuclear condensation in some of the cells in the spinous layer.
A: eosinophilic perinuclear condensation
Back Extra: White Sponge Naevus
- Clinical: White sponge naevus presents as non-tender, filmy-white, mildly wrinkled to velvety patches or plaques, which become more prominent during puberty and persist throughout life.
- Micro: Histologically, the condition shows shaggy hyperparakeratosis and acanthosis with vacuolation of the spinous layer and bright eosinophilic perinuclear condensation representing keratin tonofilaments.
- Ancillary: Mutations in KRT4 and KRT13, responsible for the production of keratin proteins, are associated with the condition, which is inherited in an autosomal dominant pattern with reduced penetrance.
Reference Gallery:
White sponge naevus. Prominent hyperparakeratosis and acanthosis with spinous cell layer vacuolation.
White sponge naevus. High-power view of bright eosinophilic perinuclear condensation in some of the cells in the spinous layer.
White sponge naevus. Buccal mucosa with white, adherent, velvety to folded plaques.

Q: Clinically, [...] presents as non-tender, filmy-white, mildly wrinkled to velvety mucosal plaques that typically become more prominent during puberty and persist throughout life.
White sponge naevus. Buccal mucosa with white, adherent, velvety to folded plaques.
A: White Sponge Nevus
Back Extra: White Sponge Naevus
- Clinical: White sponge naevus presents as non-tender, filmy-white, mildly wrinkled to velvety patches or plaques, which become more prominent during puberty and persist throughout life.
- Micro: Histologically, the condition shows shaggy hyperparakeratosis and acanthosis with vacuolation of the spinous layer and bright eosinophilic perinuclear condensation representing keratin tonofilaments.
- Ancillary: Mutations in KRT4 and KRT13, responsible for the production of keratin proteins, are associated with the condition, which is inherited in an autosomal dominant pattern with reduced penetrance.
Reference Gallery:
White sponge naevus. Prominent hyperparakeratosis and acanthosis with spinous cell layer vacuolation.
White sponge naevus. High-power view of bright eosinophilic perinuclear condensation in some of the cells in the spinous layer.
White sponge naevus. Buccal mucosa with white, adherent, velvety to folded plaques.

Q: Microscopically, large round to oval histiocytes with complex nuclear contours and moderately abundant eosinophilic cytoplasm are the hallmark of [...].
Langerhans cell histiocytosis. Round to oval histiocytes with complex nuclear contours and moderately abundant eosinophilic cytoplasm.
A: Langerhans Cell Histiocytosis
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Older children and adults with single-system LCH (SS-LCH) often present with painful or painless osteolytic lesions of the bone cortex and/or vertebra plana.
- Micro: LCH is characterized by large (10–25 µm) round to oval histiocytes with a complex nuclear contour and moderately abundant eosinophilic cytoplasm.
- Ancillary: BRAF p.V600E mutations are highly prevalent in LCH and are associated with an increased risk of relapse and poor clinical outcomes.
Reference Gallery:
Langerhans cell histiocytosis. Round to oval histiocytes with complex nuclear contours and moderately abundant eosinophilic cytoplasm.
Langerhans cell histiocytosis. CD1a stain with surface staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD207 (langerin) stain with granular cytoplasmic staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD68 (PGM1) immunohistochemistry with Golgi/cytoplasmic dot staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. Cutaneous Langerhans cell histiocytosis with crusted red-brown papules with collarettes of scale.
Langerhans cell histiocytosis and related disorders. Langerhans cell histiocytosis expressing BRAF p.V600E (VE1 immunostain) in the cytoplasm with diffuse dark granular staining.
Vertebra plana in Langerhans cell histiocytosis. Midline sagittal T1-weighted postcontrast MRI with fat suppression shows collapse of the T6 vertebral body (white arrow). There is diffuse enhancement of the vertebral body and paraspinal soft tissue component (yellow arrow). Posteriorly protruding components efface the anterior thecal sac and mildly distort the spinal cord (blue arrow).
Juvenile xanthogranuloma family. The histopathology of both juvenile xanthogranuloma and Erdheim–Chester disease can show a cellular infiltrate of plump epithelioid cells with a variable number of Touton giant cells.
Juvenile xanthogranuloma family. Monomorphic cellular infiltrate of small cells with finely vacuolated cytoplasm.
Juvenile xanthogranuloma family. The CD163 stain highlights lesional histiocytes with surface staining in xanthogranuloma lesions of both juvenile xanthogranuloma and Erdheim–Chester disease.
Juvenile xanthogranuloma family. The factor XIIIa stain highlights lesional histiocytes with cytoplasmic staining in both juvenile xanthogranuloma and Erdheim–Chester disease, with less staining in highly lipidized cells.
Rosai–Dorfman disease. Staining for S100 highlights the large Rosai–Dorfman cells in the sinus of the lymph node with frequent emperipolesis.

Q: In single-system Langerhans Cell Histiocytosis, patients often present with osteolytic bone lesions that can cause complete collapse of a vertebral body, a radiographic finding known as [...].
Vertebra plana in Langerhans cell histiocytosis. Midline sagittal T1-weighted postcontrast MRI with fat suppression shows collapse of the T6 vertebral body (white arrow). There is diffuse enhancement of the vertebral body and paraspinal soft tissue component (yellow arrow). Posteriorly protruding components efface the anterior thecal sac and mildly distort the spinal cord (blue arrow).
A: vertebra plana
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Older children and adults with single-system LCH (SS-LCH) often present with painful or painless osteolytic lesions of the bone cortex and/or vertebra plana.
- Micro: LCH is characterized by large (10–25 µm) round to oval histiocytes with a complex nuclear contour and moderately abundant eosinophilic cytoplasm.
- Ancillary: BRAF p.V600E mutations are highly prevalent in LCH and are associated with an increased risk of relapse and poor clinical outcomes.
Reference Gallery:
Langerhans cell histiocytosis. Round to oval histiocytes with complex nuclear contours and moderately abundant eosinophilic cytoplasm.
Langerhans cell histiocytosis. CD1a stain with surface staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD207 (langerin) stain with granular cytoplasmic staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD68 (PGM1) immunohistochemistry with Golgi/cytoplasmic dot staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. Cutaneous Langerhans cell histiocytosis with crusted red-brown papules with collarettes of scale.
Langerhans cell histiocytosis and related disorders. Langerhans cell histiocytosis expressing BRAF p.V600E (VE1 immunostain) in the cytoplasm with diffuse dark granular staining.
Vertebra plana in Langerhans cell histiocytosis. Midline sagittal T1-weighted postcontrast MRI with fat suppression shows collapse of the T6 vertebral body (white arrow). There is diffuse enhancement of the vertebral body and paraspinal soft tissue component (yellow arrow). Posteriorly protruding components efface the anterior thecal sac and mildly distort the spinal cord (blue arrow).
Juvenile xanthogranuloma family. The histopathology of both juvenile xanthogranuloma and Erdheim–Chester disease can show a cellular infiltrate of plump epithelioid cells with a variable number of Touton giant cells.
Juvenile xanthogranuloma family. Monomorphic cellular infiltrate of small cells with finely vacuolated cytoplasm.
Juvenile xanthogranuloma family. The CD163 stain highlights lesional histiocytes with surface staining in xanthogranuloma lesions of both juvenile xanthogranuloma and Erdheim–Chester disease.
Juvenile xanthogranuloma family. The factor XIIIa stain highlights lesional histiocytes with cytoplasmic staining in both juvenile xanthogranuloma and Erdheim–Chester disease, with less staining in highly lipidized cells.
Rosai–Dorfman disease. Staining for S100 highlights the large Rosai–Dorfman cells in the sinus of the lymph node with frequent emperipolesis.

Q: The [...] mutation is highly prevalent in Langerhans Cell Histiocytosis, which can be demonstrated via VE1 immunostaining and correlates with increased relapse risk.
Langerhans cell histiocytosis and related disorders. Langerhans cell histiocytosis expressing BRAF p.V600E (VE1 immunostain) in the cytoplasm with diffuse dark granular staining.
A: BRAF p.V600E
Back Extra: Langerhans Cell Histiocytosis
- Clinical: Older children and adults with single-system LCH (SS-LCH) often present with painful or painless osteolytic lesions of the bone cortex and/or vertebra plana.
- Micro: LCH is characterized by large (10–25 µm) round to oval histiocytes with a complex nuclear contour and moderately abundant eosinophilic cytoplasm.
- Ancillary: BRAF p.V600E mutations are highly prevalent in LCH and are associated with an increased risk of relapse and poor clinical outcomes.
Reference Gallery:
Langerhans cell histiocytosis. Round to oval histiocytes with complex nuclear contours and moderately abundant eosinophilic cytoplasm.
Langerhans cell histiocytosis. CD1a stain with surface staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD207 (langerin) stain with granular cytoplasmic staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. CD68 (PGM1) immunohistochemistry with Golgi/cytoplasmic dot staining of Langerhans cell histiocytosis cells.
Langerhans cell histiocytosis. Cutaneous Langerhans cell histiocytosis with crusted red-brown papules with collarettes of scale.
Langerhans cell histiocytosis and related disorders. Langerhans cell histiocytosis expressing BRAF p.V600E (VE1 immunostain) in the cytoplasm with diffuse dark granular staining.
Vertebra plana in Langerhans cell histiocytosis. Midline sagittal T1-weighted postcontrast MRI with fat suppression shows collapse of the T6 vertebral body (white arrow). There is diffuse enhancement of the vertebral body and paraspinal soft tissue component (yellow arrow). Posteriorly protruding components efface the anterior thecal sac and mildly distort the spinal cord (blue arrow).
Juvenile xanthogranuloma family. The histopathology of both juvenile xanthogranuloma and Erdheim–Chester disease can show a cellular infiltrate of plump epithelioid cells with a variable number of Touton giant cells.
Juvenile xanthogranuloma family. Monomorphic cellular infiltrate of small cells with finely vacuolated cytoplasm.
Juvenile xanthogranuloma family. The CD163 stain highlights lesional histiocytes with surface staining in xanthogranuloma lesions of both juvenile xanthogranuloma and Erdheim–Chester disease.
Juvenile xanthogranuloma family. The factor XIIIa stain highlights lesional histiocytes with cytoplasmic staining in both juvenile xanthogranuloma and Erdheim–Chester disease, with less staining in highly lipidized cells.
Rosai–Dorfman disease. Staining for S100 highlights the large Rosai–Dorfman cells in the sinus of the lymph node with frequent emperipolesis.

Q: The hallmark diagnostic cells in Classic Hodgkin Lymphoma are [...], which typically feature bilobed or multilobed nuclei with prominent nucleoli and a clear halo.
Tumour cell types in classic Hodgkin lymphoma. Binucleated Reed–Sternberg cell.
Tumour cell types in classic Hodgkin lymphoma. Multinucleated Reed–Sternberg cells.
A: Reed-Sternberg cells
Back Extra: Classic Hodgkin Lymphoma
- Clinical: Patients with Classic Hodgkin Lymphoma often present with peripheral lymphadenopathy, B symptoms (fever, night sweats, weight loss), and occasionally superior vena cava syndrome due to mediastinal involvement.
- Micro: The hallmark cells in Classic Hodgkin Lymphoma are Reed-Sternberg cells, characterized by bilobed or multilobed nuclei with a prominent nucleolus and a clear halo. Mononuclear variants (Hodgkin cells) and mummified cells (apoptotic) are also observed.
- Ancillary: Immunohistochemically, Reed-Sternberg cells in Classic Hodgkin Lymphoma are typically CD30+ and CD15+, with variable PAX5 expression and negative for B-cell markers like CD19 and CD20.
Reference Gallery:
Classic Hodgkin lymphoma. Nodular sclerosis classic Hodgkin lymphoma with a thickened capsule and sclerotic areas.
Classic Hodgkin lymphoma. Mixed-cellularity classic Hodgkin lymphoma with a diffuse, mottled infiltrate and a thin capsule.
Tumour cell types in classic Hodgkin lymphoma. Binucleated Reed–Sternberg cell.
Tumour cell types in classic Hodgkin lymphoma. Mononuclear Hodgkin cell.
Tumour cell types in classic Hodgkin lymphoma. Multinucleated Reed–Sternberg cells.
Tumour cell types in classic Hodgkin lymphoma. Mummified (apoptotic) Hodgkin cell.
Immunohistochemistry in classic Hodgkin lymphoma. Strong CD30 expression in Hodgkin cells.
Immunohistochemistry in classic Hodgkin lymphoma. Variable CD15 expression in Hodgkin cells, with scattered strong staining in smaller granulocytes.
Immunohistochemistry in classic Hodgkin lymphoma. Weakly PAX5-staining Hodgkin cells.
Immunohistochemistry in classic Hodgkin lymphoma. Reactive CD3-expressing T cells surrounding a Hodgkin cell.
Classic Hodgkin lymphoma. Contrast-enhanced axial CT image shows a large, hypoattenuating, non-homogeneously enhancing anterior mediastinal mass. Note that the trachea is compressed and the great vessels are encased and displaced.
Classic Hodgkin lymphoma. Fusion FDG PET-CT axial image demonstrates intense tracer uptake by the mass.

Q: Immunohistochemically, the neoplastic cells in Classic Hodgkin Lymphoma are characteristically positive for [...] and typically show weak, variable expression of PAX5.
Immunohistochemistry in classic Hodgkin lymphoma. Strong CD30 expression in Hodgkin cells.
Immunohistochemistry in classic Hodgkin lymphoma. Variable CD15 expression in Hodgkin cells, with scattered strong staining in smaller granulocytes.
A: CD30 and CD15
Back Extra: Classic Hodgkin Lymphoma
- Clinical: Patients with Classic Hodgkin Lymphoma often present with peripheral lymphadenopathy, B symptoms (fever, night sweats, weight loss), and occasionally superior vena cava syndrome due to mediastinal involvement.
- Micro: The hallmark cells in Classic Hodgkin Lymphoma are Reed-Sternberg cells, characterized by bilobed or multilobed nuclei with a prominent nucleolus and a clear halo. Mononuclear variants (Hodgkin cells) and mummified cells (apoptotic) are also observed.
- Ancillary: Immunohistochemically, Reed-Sternberg cells in Classic Hodgkin Lymphoma are typically CD30+ and CD15+, with variable PAX5 expression and negative for B-cell markers like CD19 and CD20.
Reference Gallery:
Classic Hodgkin lymphoma. Nodular sclerosis classic Hodgkin lymphoma with a thickened capsule and sclerotic areas.
Classic Hodgkin lymphoma. Mixed-cellularity classic Hodgkin lymphoma with a diffuse, mottled infiltrate and a thin capsule.
Tumour cell types in classic Hodgkin lymphoma. Binucleated Reed–Sternberg cell.
Tumour cell types in classic Hodgkin lymphoma. Mononuclear Hodgkin cell.
Tumour cell types in classic Hodgkin lymphoma. Multinucleated Reed–Sternberg cells.
Tumour cell types in classic Hodgkin lymphoma. Mummified (apoptotic) Hodgkin cell.
Immunohistochemistry in classic Hodgkin lymphoma. Strong CD30 expression in Hodgkin cells.
Immunohistochemistry in classic Hodgkin lymphoma. Variable CD15 expression in Hodgkin cells, with scattered strong staining in smaller granulocytes.
Immunohistochemistry in classic Hodgkin lymphoma. Weakly PAX5-staining Hodgkin cells.
Immunohistochemistry in classic Hodgkin lymphoma. Reactive CD3-expressing T cells surrounding a Hodgkin cell.
Classic Hodgkin lymphoma. Contrast-enhanced axial CT image shows a large, hypoattenuating, non-homogeneously enhancing anterior mediastinal mass. Note that the trachea is compressed and the great vessels are encased and displaced.
Classic Hodgkin lymphoma. Fusion FDG PET-CT axial image demonstrates intense tracer uptake by the mass.

Q: Along with the classic diagnostic cells, the tumor microenvironment in Classic Hodgkin Lymphoma also contains mononuclear variants known as [...] and apoptotic variants known as mummified cells.
Tumour cell types in classic Hodgkin lymphoma. Mononuclear Hodgkin cell.
Tumour cell types in classic Hodgkin lymphoma. Mummified (apoptotic) Hodgkin cell.
A: Hodgkin cells
Back Extra: Classic Hodgkin Lymphoma
- Clinical: Patients with Classic Hodgkin Lymphoma often present with peripheral lymphadenopathy, B symptoms (fever, night sweats, weight loss), and occasionally superior vena cava syndrome due to mediastinal involvement.
- Micro: The hallmark cells in Classic Hodgkin Lymphoma are Reed-Sternberg cells, characterized by bilobed or multilobed nuclei with a prominent nucleolus and a clear halo. Mononuclear variants (Hodgkin cells) and mummified cells (apoptotic) are also observed.
- Ancillary: Immunohistochemically, Reed-Sternberg cells in Classic Hodgkin Lymphoma are typically CD30+ and CD15+, with variable PAX5 expression and negative for B-cell markers like CD19 and CD20.
Reference Gallery:
Classic Hodgkin lymphoma. Nodular sclerosis classic Hodgkin lymphoma with a thickened capsule and sclerotic areas.
Classic Hodgkin lymphoma. Mixed-cellularity classic Hodgkin lymphoma with a diffuse, mottled infiltrate and a thin capsule.
Tumour cell types in classic Hodgkin lymphoma. Binucleated Reed–Sternberg cell.
Tumour cell types in classic Hodgkin lymphoma. Mononuclear Hodgkin cell.
Tumour cell types in classic Hodgkin lymphoma. Multinucleated Reed–Sternberg cells.
Tumour cell types in classic Hodgkin lymphoma. Mummified (apoptotic) Hodgkin cell.
Immunohistochemistry in classic Hodgkin lymphoma. Strong CD30 expression in Hodgkin cells.
Immunohistochemistry in classic Hodgkin lymphoma. Variable CD15 expression in Hodgkin cells, with scattered strong staining in smaller granulocytes.
Immunohistochemistry in classic Hodgkin lymphoma. Weakly PAX5-staining Hodgkin cells.
Immunohistochemistry in classic Hodgkin lymphoma. Reactive CD3-expressing T cells surrounding a Hodgkin cell.
Classic Hodgkin lymphoma. Contrast-enhanced axial CT image shows a large, hypoattenuating, non-homogeneously enhancing anterior mediastinal mass. Note that the trachea is compressed and the great vessels are encased and displaced.
Classic Hodgkin lymphoma. Fusion FDG PET-CT axial image demonstrates intense tracer uptake by the mass.

Q: The characteristic large, multilobulated blastic tumor cells scattered throughout the vague nodules in Nodular Lymphocyte-Predominant Hodgkin Lymphoma are known as [...].
Nodular lymphocyte-predominant Hodgkin lymphoma. Vaguely nodular infiltrate of small lymphocytes with scattered large LP cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Typical multilobulated lymphocyte-predominant cell.
A: lymphocyte-predominant (LP) cells
Q: Nodular Lymphocyte-Predominant Hodgkin Lymphoma
- Clinical: Most patients with [...] present with limited disease (stage I or II) and an indolent course. B symptoms, bulky disease, or a mediastinal mass are unusual.
- Micro: The lymph node architecture is partly or totally replaced by large, vague nodules that lack germinal centres, containing CD21-positive follicular dendritic cell meshworks with scattered large blastic tumour cells ([...]).
- Ancillary: Immunohistochemistry shows strong expression of B-cell markers such as [...], CD79a, and PAX5 in LP cells, and frequent CD30 expression in up to 28% of cases.
Reference Gallery:
Nodular lymphocyte-predominant Hodgkin lymphoma. Vaguely nodular infiltrate of small lymphocytes with scattered large LP cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. Differential diagnosis: expanded follicle with a progressively transformed germinal centre invaded by small mantle B cells and in the background reactive follicular hyperplasia.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Typical multilobulated lymphocyte-predominant cell.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Nodular follicular dendritic cell meshworks highlighted by CD21.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Scattered strongly staining OCT2-positive lymphocyte-predominant cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. PD1 highlights the rosettes of PD1-expressing T follicular helper (TFH) cells around a lymphocyte-predominant cell.
A: Nodular Lymphocyte-Predominant Hodgkin Lymphoma; LP cells; CD20

Q: The vague nodules in Nodular Lymphocyte-Predominant Hodgkin Lymphoma lack true germinal centers but characteristically contain expanded follicular dendritic cell meshworks, which can be highlighted by the immunohistochemical stain [...].
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Nodular follicular dendritic cell meshworks highlighted by CD21.
A: CD21
Q: Nodular Lymphocyte-Predominant Hodgkin Lymphoma
- Clinical: Most patients with [...] present with limited disease (stage I or II) and an indolent course. B symptoms, bulky disease, or a mediastinal mass are unusual.
- Micro: The lymph node architecture is partly or totally replaced by large, vague nodules that lack germinal centres, containing CD21-positive follicular dendritic cell meshworks with scattered large blastic tumour cells ([...]).
- Ancillary: Immunohistochemistry shows strong expression of B-cell markers such as [...], CD79a, and PAX5 in LP cells, and frequent CD30 expression in up to 28% of cases.
Reference Gallery:
Nodular lymphocyte-predominant Hodgkin lymphoma. Vaguely nodular infiltrate of small lymphocytes with scattered large LP cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. Differential diagnosis: expanded follicle with a progressively transformed germinal centre invaded by small mantle B cells and in the background reactive follicular hyperplasia.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Typical multilobulated lymphocyte-predominant cell.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Nodular follicular dendritic cell meshworks highlighted by CD21.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Scattered strongly staining OCT2-positive lymphocyte-predominant cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. PD1 highlights the rosettes of PD1-expressing T follicular helper (TFH) cells around a lymphocyte-predominant cell.
A: Nodular Lymphocyte-Predominant Hodgkin Lymphoma; LP cells; CD20

Q: In Nodular Lymphocyte-Predominant Hodgkin Lymphoma, the neoplastic LP cells are characteristically surrounded by rosettes of T follicular helper (TFH) cells, which can be highlighted by immunohistochemistry for [...].
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. PD1 highlights the rosettes of PD1-expressing T follicular helper (TFH) cells around a lymphocyte-predominant cell.
A: PD-1
Q: Nodular Lymphocyte-Predominant Hodgkin Lymphoma
- Clinical: Most patients with [...] present with limited disease (stage I or II) and an indolent course. B symptoms, bulky disease, or a mediastinal mass are unusual.
- Micro: The lymph node architecture is partly or totally replaced by large, vague nodules that lack germinal centres, containing CD21-positive follicular dendritic cell meshworks with scattered large blastic tumour cells ([...]).
- Ancillary: Immunohistochemistry shows strong expression of B-cell markers such as [...], CD79a, and PAX5 in LP cells, and frequent CD30 expression in up to 28% of cases.
Reference Gallery:
Nodular lymphocyte-predominant Hodgkin lymphoma. Vaguely nodular infiltrate of small lymphocytes with scattered large LP cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. Differential diagnosis: expanded follicle with a progressively transformed germinal centre invaded by small mantle B cells and in the background reactive follicular hyperplasia.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Typical multilobulated lymphocyte-predominant cell.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Nodular follicular dendritic cell meshworks highlighted by CD21.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. Scattered strongly staining OCT2-positive lymphocyte-predominant cells.
Nodular lymphocyte-predominant Hodgkin lymphoma. Morphology and immunohistochemistry. PD1 highlights the rosettes of PD1-expressing T follicular helper (TFH) cells around a lymphocyte-predominant cell.
A: Nodular Lymphocyte-Predominant Hodgkin Lymphoma; LP cells; CD20

Q: In HIV-Associated Lymphoproliferative Disorders, the microscopic appearance of [...] typically consists of sheets of large lymphoid cells with prominent nucleoli, frequent mitoses, and a plasmacytoid or plasmablastic cytoplasm.
Diffuse large B-cell lymphoma. There are sheets of large lymphoid cells with round or oval nuclei, prominent and often central nucleoli, and plasmacytoid cytoplasm.
A: diffuse large B-cell lymphoma
Back Extra: HIV-Associated Lymphoproliferative Disorders
- Clinical: Children with HIV-associated lymphoproliferative disorders often present with systemic B symptoms, such as fever, and site-specific symptoms like headache and seizures for CNS involvement.
- Micro: Diffuse large B-cell lymphoma in HIV shows sheets of large cells with prominent nucleoli, frequent mitoses, and a plasmablastic appearance.
- Ancillary: Burkitt lymphoma in HIV is characterized by MYC translocations and a high Ki-67 proliferation index, often reaching 100%.
Reference Gallery:
Diffuse large B-cell lymphoma. There are sheets of large lymphoid cells with round or oval nuclei, prominent and often central nucleoli, and plasmacytoid cytoplasm.
Diffuse large B-cell lymphoma. Primary from the CNS. Large pleomorphic malignant lymphoid cells with prominent nucleoli are seen cuffing a vascular channel and infiltrating the brain parenchyma.
Classic Hodgkin lymphoma. There are numerous Reed–Sternberg and mononuclear Hodgkin cells. The background includes small lymphocytes, plasma cells, and histiocytes.
Polymorphic lymphoid proliferation. There is a mixture of small lymphocytes, plasma cells, and large immunoblasts with prominent nucleoli. Despite the mixed population, a clonal IG gene rearrangement was identified in an oligoclonal background. Similar proliferations are seen after transplantation and in other abnormal immune states.

Q: Site-specific symptoms like headaches and seizures in HIV-Associated Lymphoproliferative Disorders can indicate primary CNS involvement, which is microscopically characterized by pleomorphic malignant cells classically cuffing [...] within the brain parenchyma.
Diffuse large B-cell lymphoma. Primary from the CNS. Large pleomorphic malignant lymphoid cells with prominent nucleoli are seen cuffing a vascular channel and infiltrating the brain parenchyma.
A: vascular channels
Back Extra: HIV-Associated Lymphoproliferative Disorders
- Clinical: Children with HIV-associated lymphoproliferative disorders often present with systemic B symptoms, such as fever, and site-specific symptoms like headache and seizures for CNS involvement.
- Micro: Diffuse large B-cell lymphoma in HIV shows sheets of large cells with prominent nucleoli, frequent mitoses, and a plasmablastic appearance.
- Ancillary: Burkitt lymphoma in HIV is characterized by MYC translocations and a high Ki-67 proliferation index, often reaching 100%.
Reference Gallery:
Diffuse large B-cell lymphoma. There are sheets of large lymphoid cells with round or oval nuclei, prominent and often central nucleoli, and plasmacytoid cytoplasm.
Diffuse large B-cell lymphoma. Primary from the CNS. Large pleomorphic malignant lymphoid cells with prominent nucleoli are seen cuffing a vascular channel and infiltrating the brain parenchyma.
Classic Hodgkin lymphoma. There are numerous Reed–Sternberg and mononuclear Hodgkin cells. The background includes small lymphocytes, plasma cells, and histiocytes.
Polymorphic lymphoid proliferation. There is a mixture of small lymphocytes, plasma cells, and large immunoblasts with prominent nucleoli. Despite the mixed population, a clonal IG gene rearrangement was identified in an oligoclonal background. Similar proliferations are seen after transplantation and in other abnormal immune states.

Q: Some HIV-Associated Lymphoproliferative Disorders present as a [...] lymphoid proliferation, demonstrating a distinctly mixed population of small lymphocytes, plasma cells, and large immunoblasts with prominent nucleoli.
Polymorphic lymphoid proliferation. There is a mixture of small lymphocytes, plasma cells, and large immunoblasts with prominent nucleoli. Despite the mixed population, a clonal IG gene rearrangement was identified in an oligoclonal background. Similar proliferations are seen after transplantation and in other abnormal immune states.
A: polymorphic
Back Extra: HIV-Associated Lymphoproliferative Disorders
- Clinical: Children with HIV-associated lymphoproliferative disorders often present with systemic B symptoms, such as fever, and site-specific symptoms like headache and seizures for CNS involvement.
- Micro: Diffuse large B-cell lymphoma in HIV shows sheets of large cells with prominent nucleoli, frequent mitoses, and a plasmablastic appearance.
- Ancillary: Burkitt lymphoma in HIV is characterized by MYC translocations and a high Ki-67 proliferation index, often reaching 100%.
Reference Gallery:
Diffuse large B-cell lymphoma. There are sheets of large lymphoid cells with round or oval nuclei, prominent and often central nucleoli, and plasmacytoid cytoplasm.
Diffuse large B-cell lymphoma. Primary from the CNS. Large pleomorphic malignant lymphoid cells with prominent nucleoli are seen cuffing a vascular channel and infiltrating the brain parenchyma.
Classic Hodgkin lymphoma. There are numerous Reed–Sternberg and mononuclear Hodgkin cells. The background includes small lymphocytes, plasma cells, and histiocytes.
Polymorphic lymphoid proliferation. There is a mixture of small lymphocytes, plasma cells, and large immunoblasts with prominent nucleoli. Despite the mixed population, a clonal IG gene rearrangement was identified in an oligoclonal background. Similar proliferations are seen after transplantation and in other abnormal immune states.

Q: In polymorphic Posttransplant Lymphoproliferative Disorders, the underlying lymphoid architecture is typically effaced by a heterogeneous population of small lymphocytes, plasma cells, and prominent large cells with smooth chromatin and basophilic cytoplasm known as [...].
Polymorphic posttransplant lymphoproliferative disorder. Diffuse effacement of the tonsillar architecture with expansion of the interfollicular regions by a heterogeneous lymphoplasmacytic population, with vague nodularity.
Polymorphic posttransplant lymphoproliferative disorder. A Giemsa-stained imprint highlights interspersed immunoblastic cells, which are large and bear smooth chromatin and basophilic cytoplasm.
Polymorphic posttransplant lymphoproliferative disorder. The full morphological spectrum of B cells is seen, from round lymphocytes with mature, condensed chromatin to immunoblast-like and plasmacytic cells.
A: immunoblasts
Back Extra: Posttransplant Lymphoproliferative Disorders
- Clinical: The most important predictor of Posttransplant Lymphoproliferative Disorders (PTLDs) is EBV seronegativity of the recipient, particularly in kidney and heart transplants.
- Micro: Polymorphic PTLD is characterized by effacement of the underlying lymphoid organ architecture by a heterogeneous population of small and medium-sized lymphocytes, immunoblasts, and plasma cells.
- Ancillary: EBV-encoded small RNA (EBER) in situ hybridization is positive in numerous cells in polymorphic PTLD, and clonality analysis is useful in distinguishing between non-destructive (ND-PTLD) and monomorphic (M-PTLD) types.
Reference Gallery:
Polymorphic posttransplant lymphoproliferative disorder. Diffuse effacement of the tonsillar architecture with expansion of the interfollicular regions by a heterogeneous lymphoplasmacytic population, with vague nodularity.
Polymorphic posttransplant lymphoproliferative disorder. A Giemsa-stained imprint highlights interspersed immunoblastic cells, which are large and bear smooth chromatin and basophilic cytoplasm.
Polymorphic posttransplant lymphoproliferative disorder. EBV-encoded small RNA (EBER) in situ hybridization: EBER positivity among cells of all sizes, including a few large immunoblasts scattered throughout. The heterogeneous EBER pattern is typical in polymorphic posttransplant lymphoproliferative disorder in children.
Polymorphic posttransplant lymphoproliferative disorder. The full morphological spectrum of B cells is seen, from round lymphocytes with mature, condensed chromatin to immunoblast-like and plasmacytic cells.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. This example is composed of mature plasma cells with uniform small round nuclei and the characteristic clockface chromatin pattern. A few intermingled small lymphocytes correspond to mature T cells. The range of B-cell maturity is absent (as expected in monomorphic patterns).
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. CD138 staining shows a sheet-like plasma cell population expanding and distorting the underlying tonsillar architecture. EBV-encoded small RNA (EBER) (not shown) was negative in this case and is a feature somewhat enhanced in plasma cell posttransplant lymphoproliferative disorder.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. Plasma cells are kappa light chain–restricted.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. There are a few lambda plasma cells in the background.

Q: A major risk factor for Posttransplant Lymphoproliferative Disorders is recipient seronegativity for Epstein-Barr virus (EBV), and tissue evaluation of the polymorphic subtype typically demonstrates a heterogeneous pattern of positivity for [...] by in situ hybridization.
Polymorphic posttransplant lymphoproliferative disorder. EBV-encoded small RNA (EBER) in situ hybridization: EBER positivity among cells of all sizes, including a few large immunoblasts scattered throughout. The heterogeneous EBER pattern is typical in polymorphic posttransplant lymphoproliferative disorder in children.
A: EBV-encoded small RNA (EBER)
Back Extra: Posttransplant Lymphoproliferative Disorders
- Clinical: The most important predictor of Posttransplant Lymphoproliferative Disorders (PTLDs) is EBV seronegativity of the recipient, particularly in kidney and heart transplants.
- Micro: Polymorphic PTLD is characterized by effacement of the underlying lymphoid organ architecture by a heterogeneous population of small and medium-sized lymphocytes, immunoblasts, and plasma cells.
- Ancillary: EBV-encoded small RNA (EBER) in situ hybridization is positive in numerous cells in polymorphic PTLD, and clonality analysis is useful in distinguishing between non-destructive (ND-PTLD) and monomorphic (M-PTLD) types.
Reference Gallery:
Polymorphic posttransplant lymphoproliferative disorder. Diffuse effacement of the tonsillar architecture with expansion of the interfollicular regions by a heterogeneous lymphoplasmacytic population, with vague nodularity.
Polymorphic posttransplant lymphoproliferative disorder. A Giemsa-stained imprint highlights interspersed immunoblastic cells, which are large and bear smooth chromatin and basophilic cytoplasm.
Polymorphic posttransplant lymphoproliferative disorder. EBV-encoded small RNA (EBER) in situ hybridization: EBER positivity among cells of all sizes, including a few large immunoblasts scattered throughout. The heterogeneous EBER pattern is typical in polymorphic posttransplant lymphoproliferative disorder in children.
Polymorphic posttransplant lymphoproliferative disorder. The full morphological spectrum of B cells is seen, from round lymphocytes with mature, condensed chromatin to immunoblast-like and plasmacytic cells.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. This example is composed of mature plasma cells with uniform small round nuclei and the characteristic clockface chromatin pattern. A few intermingled small lymphocytes correspond to mature T cells. The range of B-cell maturity is absent (as expected in monomorphic patterns).
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. CD138 staining shows a sheet-like plasma cell population expanding and distorting the underlying tonsillar architecture. EBV-encoded small RNA (EBER) (not shown) was negative in this case and is a feature somewhat enhanced in plasma cell posttransplant lymphoproliferative disorder.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. Plasma cells are kappa light chain–restricted.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. There are a few lambda plasma cells in the background.

Q: Unlike polymorphic variants, monomorphic Posttransplant Lymphoproliferative Disorders lack a full B-cell maturation spectrum and can present as a plasma cell neoplasm characterized by sheets of CD138+ cells with definitive [...].
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. This example is composed of mature plasma cells with uniform small round nuclei and the characteristic clockface chromatin pattern. A few intermingled small lymphocytes correspond to mature T cells. The range of B-cell maturity is absent (as expected in monomorphic patterns).
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. CD138 staining shows a sheet-like plasma cell population expanding and distorting the underlying tonsillar architecture. EBV-encoded small RNA (EBER) (not shown) was negative in this case and is a feature somewhat enhanced in plasma cell posttransplant lymphoproliferative disorder.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. Plasma cells are kappa light chain–restricted.
A: light chain restriction
Back Extra: Posttransplant Lymphoproliferative Disorders
- Clinical: The most important predictor of Posttransplant Lymphoproliferative Disorders (PTLDs) is EBV seronegativity of the recipient, particularly in kidney and heart transplants.
- Micro: Polymorphic PTLD is characterized by effacement of the underlying lymphoid organ architecture by a heterogeneous population of small and medium-sized lymphocytes, immunoblasts, and plasma cells.
- Ancillary: EBV-encoded small RNA (EBER) in situ hybridization is positive in numerous cells in polymorphic PTLD, and clonality analysis is useful in distinguishing between non-destructive (ND-PTLD) and monomorphic (M-PTLD) types.
Reference Gallery:
Polymorphic posttransplant lymphoproliferative disorder. Diffuse effacement of the tonsillar architecture with expansion of the interfollicular regions by a heterogeneous lymphoplasmacytic population, with vague nodularity.
Polymorphic posttransplant lymphoproliferative disorder. A Giemsa-stained imprint highlights interspersed immunoblastic cells, which are large and bear smooth chromatin and basophilic cytoplasm.
Polymorphic posttransplant lymphoproliferative disorder. EBV-encoded small RNA (EBER) in situ hybridization: EBER positivity among cells of all sizes, including a few large immunoblasts scattered throughout. The heterogeneous EBER pattern is typical in polymorphic posttransplant lymphoproliferative disorder in children.
Polymorphic posttransplant lymphoproliferative disorder. The full morphological spectrum of B cells is seen, from round lymphocytes with mature, condensed chromatin to immunoblast-like and plasmacytic cells.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. This example is composed of mature plasma cells with uniform small round nuclei and the characteristic clockface chromatin pattern. A few intermingled small lymphocytes correspond to mature T cells. The range of B-cell maturity is absent (as expected in monomorphic patterns).
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. CD138 staining shows a sheet-like plasma cell population expanding and distorting the underlying tonsillar architecture. EBV-encoded small RNA (EBER) (not shown) was negative in this case and is a feature somewhat enhanced in plasma cell posttransplant lymphoproliferative disorder.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. Plasma cells are kappa light chain–restricted.
Monomorphic posttransplant lymphoproliferative disorder – plasma cell neoplasm. There are a few lambda plasma cells in the background.

Q: In Aggressive NK-cell leukemia, the neoplastic cells are characteristically positive for CD56 and show nearly uniform positivity for [...] via EBER in situ hybridization.
Aggressive NK-cell leukaemia. In situ hybridization for EBV-encoded small RNA (EBER) highlights the neoplastic cells in the bone marrow biopsy. The nuclear atypia in this example is striking.
Aggressive NK-cell leukaemia. Neoplastic cells show strong immunoreactivity for CD56.
A: Epstein-Barr virus (EBV)
Back Extra: Aggressive NK-Cell Leukaemia
- Clinical: Patients with Aggressive NK-Cell Leukaemia often present with constitutional symptoms such as fever, leukaemic spread, and multiorgan failure.
- Micro: Bone marrow and extramedullary sites show infiltration by monomorphic cells with pleomorphic nuclei and apoptotic bodies.
- Ancillary: Neoplastic cells are typically CD2+, CD3ε+, CD56+, and positive for cytotoxic markers, with EBV-encoded small RNA (EBER) positivity.
Reference Gallery:
Aggressive NK-cell leukaemia. In situ hybridization for EBV-encoded small RNA (EBER) highlights the neoplastic cells in the bone marrow biopsy. The nuclear atypia in this example is striking.
Aggressive NK-cell leukaemia complicated by haemophagocytic syndrome. The marrow biopsy shows neoplastic cells with substantial nuclear pleomorphism and irregular nuclear foldings. There are admixed histiocytes with phagocytosed red blood cells.
Aggressive NK-cell leukaemia. The neoplastic cells in this marrow aspirate smear show substantial nuclear pleomorphism. Histiocytes with phagocytosed red blood cells are apparent.
Aggressive NK-cell leukaemia. In this blood smear, the neoplastic cells are very similar to normal large granular lymphocytes.
Aggressive NK-cell leukaemia. In the peripheral blood, the neoplastic cells in this case have basophilic cytoplasm and nuclei with open chromatin and distinct nucleoli. Azurophilic granules can be seen in the cytoplasm.
Aggressive NK-cell leukaemia. The neoplastic cells are negative for surface CD3, whereas the normal T lymphocytes are positive.
Aggressive NK-cell leukaemia. Neoplastic cells show strong immunoreactivity for CD56.
Aggressive NK-cell leukaemia. Lymph node. The neoplastic cells appear monotonous and have round nuclei. There are many interspersed apoptotic bodies.

Q: A severe clinical complication frequently observed in patients with Aggressive NK-cell leukemia is secondary [...], which can be identified morphologically by benign histiocytes engulfing red blood cells within the bone marrow.
Aggressive NK-cell leukaemia complicated by haemophagocytic syndrome. The marrow biopsy shows neoplastic cells with substantial nuclear pleomorphism and irregular nuclear foldings. There are admixed histiocytes with phagocytosed red blood cells.
Aggressive NK-cell leukaemia. The neoplastic cells in this marrow aspirate smear show substantial nuclear pleomorphism. Histiocytes with phagocytosed red blood cells are apparent.
A: hemophagocytic syndrome
Back Extra: Aggressive NK-Cell Leukaemia
- Clinical: Patients with Aggressive NK-Cell Leukaemia often present with constitutional symptoms such as fever, leukaemic spread, and multiorgan failure.
- Micro: Bone marrow and extramedullary sites show infiltration by monomorphic cells with pleomorphic nuclei and apoptotic bodies.
- Ancillary: Neoplastic cells are typically CD2+, CD3ε+, CD56+, and positive for cytotoxic markers, with EBV-encoded small RNA (EBER) positivity.
Reference Gallery:
Aggressive NK-cell leukaemia. In situ hybridization for EBV-encoded small RNA (EBER) highlights the neoplastic cells in the bone marrow biopsy. The nuclear atypia in this example is striking.
Aggressive NK-cell leukaemia complicated by haemophagocytic syndrome. The marrow biopsy shows neoplastic cells with substantial nuclear pleomorphism and irregular nuclear foldings. There are admixed histiocytes with phagocytosed red blood cells.
Aggressive NK-cell leukaemia. The neoplastic cells in this marrow aspirate smear show substantial nuclear pleomorphism. Histiocytes with phagocytosed red blood cells are apparent.
Aggressive NK-cell leukaemia. In this blood smear, the neoplastic cells are very similar to normal large granular lymphocytes.
Aggressive NK-cell leukaemia. In the peripheral blood, the neoplastic cells in this case have basophilic cytoplasm and nuclei with open chromatin and distinct nucleoli. Azurophilic granules can be seen in the cytoplasm.
Aggressive NK-cell leukaemia. The neoplastic cells are negative for surface CD3, whereas the normal T lymphocytes are positive.
Aggressive NK-cell leukaemia. Neoplastic cells show strong immunoreactivity for CD56.
Aggressive NK-cell leukaemia. Lymph node. The neoplastic cells appear monotonous and have round nuclei. There are many interspersed apoptotic bodies.

Q: On a peripheral blood smear in Aggressive NK-cell leukemia, the neoplastic cells often resemble normal large granular lymphocytes and feature basophilic cytoplasm containing distinct [...].
Aggressive NK-cell leukaemia. In this blood smear, the neoplastic cells are very similar to normal large granular lymphocytes.
Aggressive NK-cell leukaemia. In the peripheral blood, the neoplastic cells in this case have basophilic cytoplasm and nuclei with open chromatin and distinct nucleoli. Azurophilic granules can be seen in the cytoplasm.
A: azurophilic granules
Back Extra: Aggressive NK-Cell Leukaemia
- Clinical: Patients with Aggressive NK-Cell Leukaemia often present with constitutional symptoms such as fever, leukaemic spread, and multiorgan failure.
- Micro: Bone marrow and extramedullary sites show infiltration by monomorphic cells with pleomorphic nuclei and apoptotic bodies.
- Ancillary: Neoplastic cells are typically CD2+, CD3ε+, CD56+, and positive for cytotoxic markers, with EBV-encoded small RNA (EBER) positivity.
Reference Gallery:
Aggressive NK-cell leukaemia. In situ hybridization for EBV-encoded small RNA (EBER) highlights the neoplastic cells in the bone marrow biopsy. The nuclear atypia in this example is striking.
Aggressive NK-cell leukaemia complicated by haemophagocytic syndrome. The marrow biopsy shows neoplastic cells with substantial nuclear pleomorphism and irregular nuclear foldings. There are admixed histiocytes with phagocytosed red blood cells.
Aggressive NK-cell leukaemia. The neoplastic cells in this marrow aspirate smear show substantial nuclear pleomorphism. Histiocytes with phagocytosed red blood cells are apparent.
Aggressive NK-cell leukaemia. In this blood smear, the neoplastic cells are very similar to normal large granular lymphocytes.
Aggressive NK-cell leukaemia. In the peripheral blood, the neoplastic cells in this case have basophilic cytoplasm and nuclei with open chromatin and distinct nucleoli. Azurophilic granules can be seen in the cytoplasm.
Aggressive NK-cell leukaemia. The neoplastic cells are negative for surface CD3, whereas the normal T lymphocytes are positive.
Aggressive NK-cell leukaemia. Neoplastic cells show strong immunoreactivity for CD56.
Aggressive NK-cell leukaemia. Lymph node. The neoplastic cells appear monotonous and have round nuclei. There are many interspersed apoptotic bodies.

Q: In ALK-positive large B-cell lymphoma, the tumor is characteristically composed of monomorphic large cells with [...] features, displaying a round pale nucleus, a large central nucleolus, and abundant basophilic cytoplasm.
ALK-positive large B-cell lymphoma. Immunoblastic and plasmablastic features of monomorphic neoplastic cells with a round pale nucleus and a large central nucleolus.
A: plasmablastic or immunoblastic
Back Extra: ALK-positive large B-cell lymphoma
- Clinical: Patients usually present with localized or generalized lymphadenopathy and B symptoms (bone marrow symptoms) in more than half of the cases. The average age at presentation is 12–13 years.
- Micro: The tumours are composed of monomorphic large plasmablastic or immunoblastic cells with a round pale nucleus, a large central nucleolus, and abundant basophilic cytoplasm.
- Ancillary: Most cases show restricted granular cytoplasmic ALK staining, characteristic of the CLTC::ALK fusion. Immunohistochemical positivity for ALK is sufficient for diagnosis.
Reference Gallery:
ALK-positive large B-cell lymphoma. Immunoblastic and plasmablastic features of monomorphic neoplastic cells with a round pale nucleus and a large central nucleolus.
ALK-positive large B-cell lymphoma. ALK1 staining shows granular cytoplasmic ALK expression in this case associated with TSPYL2 (CTCL)::ALK translocation.
ALK-positive large B-cell lymphoma. The tumour cells strongly express EMA.
ALK-positive large B-cell lymphoma. Strong cytoplasmic expression of IgA by tumour cells.

Q: The diagnosis of ALK-positive large B-cell lymphoma is supported by immunohistochemical positivity showing restricted granular cytoplasmic [...] staining, which is characteristic of the CLTC::ALK fusion.
ALK-positive large B-cell lymphoma. ALK1 staining shows granular cytoplasmic ALK expression in this case associated with TSPYL2 (CTCL)::ALK translocation.
A: ALK
Back Extra: ALK-positive large B-cell lymphoma
- Clinical: Patients usually present with localized or generalized lymphadenopathy and B symptoms (bone marrow symptoms) in more than half of the cases. The average age at presentation is 12–13 years.
- Micro: The tumours are composed of monomorphic large plasmablastic or immunoblastic cells with a round pale nucleus, a large central nucleolus, and abundant basophilic cytoplasm.
- Ancillary: Most cases show restricted granular cytoplasmic ALK staining, characteristic of the CLTC::ALK fusion. Immunohistochemical positivity for ALK is sufficient for diagnosis.
Reference Gallery:
ALK-positive large B-cell lymphoma. Immunoblastic and plasmablastic features of monomorphic neoplastic cells with a round pale nucleus and a large central nucleolus.
ALK-positive large B-cell lymphoma. ALK1 staining shows granular cytoplasmic ALK expression in this case associated with TSPYL2 (CTCL)::ALK translocation.
ALK-positive large B-cell lymphoma. The tumour cells strongly express EMA.
ALK-positive large B-cell lymphoma. Strong cytoplasmic expression of IgA by tumour cells.

Q: In ALK-positive Anaplastic Large Cell Lymphoma, the characteristic neoplastic cells are known as [...], which feature a horseshoe-shaped or kidney-shaped nucleus and a prominent Golgi complex.
ALK-positive anaplastic large cell lymphoma. Cerebrospinal fluid cytology shows large neoplastic cells with a kidney-shaped nucleus and a prominent Golgi complex.
ALK-positive anaplastic large cell lymphoma. Morphological features of the common subtype with a predominant population of large cells with abundant cytoplasm, and hallmark cells characterized by their kidney-shaped nucleus (arrows).
A: hallmark cells
Back Extra: ALK-positive Anaplastic Large Cell Lymphoma
- Clinical: ALK-positive Anaplastic Large Cell Lymphoma (ALK+ ALCL) accounts for 15% of all paediatric non-Hodgkin lymphomas, with advanced disease (stage III–IV) and B symptoms commonly present at diagnosis.
- Micro: ALK+ ALCLs often grow in a cohesive manner within sinuses in lymph nodes, with characteristic hallmark cells having a horseshoe-shaped nucleus and a perinuclear eosinophilic region.
- Ancillary: Malignant cells are strongly positive for CD30 and often coexpress EMA and clusterin. They express an ALK fusion protein, and commonly show loss of pan-T-cell antigens (CD3 and CD5).
Reference Gallery:
ALK-positive anaplastic large cell lymphoma. Cerebrospinal fluid cytology shows large neoplastic cells with a kidney-shaped nucleus and a prominent Golgi complex.
ALK-positive anaplastic large cell lymphoma. Tumour cells show strong and homogeneous positivity for CD30.
ALK-positive anaplastic large cell lymphoma. Tumour cells show strong and homogeneous positivity for CD43.
ALK-positive anaplastic large cell lymphoma. Two distinct subtypes can coexist on a single biopsy. In this composite subtype, ALK1 staining clearly underlines a small-cell area (left) and a common subtype area (right) with larger tumour cells.
ALK-positive anaplastic large cell lymphoma. Nuclear, nucleolar, and cytoplasmic staining is observed in tumours associated with the t(2;5) translocation (ALK1 staining).
ALK-positive anaplastic large cell lymphoma. In tumours associated with the t(2;3)(p23;q21) translocation, ALK1 staining is restricted to the cytoplasm (TFG::ALK fusion protein).
ALK-positive anaplastic large cell lymphoma. Morphological features of the common subtype with a predominant population of large cells with abundant cytoplasm, and hallmark cells characterized by their kidney-shaped nucleus (arrows).
ALK-positive anaplastic large cell lymphoma. In the small cell subtype, hallmark cells (arrowhead) are rare, while small cells with irregular nuclei (arrow) are predominant.
ALK-positive anaplastic large cell lymphoma. In the lymphohistiocytic subtype, a large number of reactive histiocytes (arrowhead) outnumbers neoplastic cells (arrow) and may lead to misdiagnosis as a reactive lesion.
ALK-positive anaplastic large cell lymphoma. In the small cell subtype, hallmark cells often cluster around blood vessels (perivascular pattern, arrows) (ALK1 staining).
ALK-positive anaplastic large cell lymphoma. ALK signalling pathways activated downstream of the NPM1::ALK protein. The AKT/mTOR, JAK/STAT, MAPK, and PLCγ pathways are the major pathways activated downstream NPM::ALK protein, leading to the survival and proliferation of tumour cells. However, STAT3 seems to be the major effector of ALK oncogenic activity.
ALK-positive anaplastic large cell lymphoma. Subcellular distribution of ALK fusion proteins. Tumours associated with t(2;5) express NPM1::ALK protein and show a characteristic cytoplasmic, nuclear, and nucleolar staining that can be explained by the formation of homodimers and heterodimers: wildtype NPM1 provides nuclear localization signals (NLSs) whereby the NPM1::ALK protein can enter the nucleus. On the other hand, the formation of NPM1::ALK homodimers retained in the cytoplasm mimics ligand binding and is responsible for the oncogenic activation of the ALK catalytic domain. In the variant translocations, ALK partners lack nuclear localization signals but their oligomerization domain located in their amino-terminal portion could induce dimerization of the chimeric proteins and activation of the ALK catalytic domain. Both homodimers and heterodimers are restricted to the cytoplasm.

Q: Immunohistochemically, the tumor cells in ALK-positive Anaplastic Large Cell Lymphoma exhibit strong, homogeneous positivity for [...].
ALK-positive anaplastic large cell lymphoma. Tumour cells show strong and homogeneous positivity for CD30.
A: CD30
Back Extra: ALK-positive Anaplastic Large Cell Lymphoma
- Clinical: ALK-positive Anaplastic Large Cell Lymphoma (ALK+ ALCL) accounts for 15% of all paediatric non-Hodgkin lymphomas, with advanced disease (stage III–IV) and B symptoms commonly present at diagnosis.
- Micro: ALK+ ALCLs often grow in a cohesive manner within sinuses in lymph nodes, with characteristic hallmark cells having a horseshoe-shaped nucleus and a perinuclear eosinophilic region.
- Ancillary: Malignant cells are strongly positive for CD30 and often coexpress EMA and clusterin. They express an ALK fusion protein, and commonly show loss of pan-T-cell antigens (CD3 and CD5).
Reference Gallery:
ALK-positive anaplastic large cell lymphoma. Cerebrospinal fluid cytology shows large neoplastic cells with a kidney-shaped nucleus and a prominent Golgi complex.
ALK-positive anaplastic large cell lymphoma. Tumour cells show strong and homogeneous positivity for CD30.
ALK-positive anaplastic large cell lymphoma. Tumour cells show strong and homogeneous positivity for CD43.
ALK-positive anaplastic large cell lymphoma. Two distinct subtypes can coexist on a single biopsy. In this composite subtype, ALK1 staining clearly underlines a small-cell area (left) and a common subtype area (right) with larger tumour cells.
ALK-positive anaplastic large cell lymphoma. Nuclear, nucleolar, and cytoplasmic staining is observed in tumours associated with the t(2;5) translocation (ALK1 staining).
ALK-positive anaplastic large cell lymphoma. In tumours associated with the t(2;3)(p23;q21) translocation, ALK1 staining is restricted to the cytoplasm (TFG::ALK fusion protein).
ALK-positive anaplastic large cell lymphoma. Morphological features of the common subtype with a predominant population of large cells with abundant cytoplasm, and hallmark cells characterized by their kidney-shaped nucleus (arrows).
ALK-positive anaplastic large cell lymphoma. In the small cell subtype, hallmark cells (arrowhead) are rare, while small cells with irregular nuclei (arrow) are predominant.
ALK-positive anaplastic large cell lymphoma. In the lymphohistiocytic subtype, a large number of reactive histiocytes (arrowhead) outnumbers neoplastic cells (arrow) and may lead to misdiagnosis as a reactive lesion.
ALK-positive anaplastic large cell lymphoma. In the small cell subtype, hallmark cells often cluster around blood vessels (perivascular pattern, arrows) (ALK1 staining).
ALK-positive anaplastic large cell lymphoma. ALK signalling pathways activated downstream of the NPM1::ALK protein. The AKT/mTOR, JAK/STAT, MAPK, and PLCγ pathways are the major pathways activated downstream NPM::ALK protein, leading to the survival and proliferation of tumour cells. However, STAT3 seems to be the major effector of ALK oncogenic activity.
ALK-positive anaplastic large cell lymphoma. Subcellular distribution of ALK fusion proteins. Tumours associated with t(2;5) express NPM1::ALK protein and show a characteristic cytoplasmic, nuclear, and nucleolar staining that can be explained by the formation of homodimers and heterodimers: wildtype NPM1 provides nuclear localization signals (NLSs) whereby the NPM1::ALK protein can enter the nucleus. On the other hand, the formation of NPM1::ALK homodimers retained in the cytoplasm mimics ligand binding and is responsible for the oncogenic activation of the ALK catalytic domain. In the variant translocations, ALK partners lack nuclear localization signals but their oligomerization domain located in their amino-terminal portion could induce dimerization of the chimeric proteins and activation of the ALK catalytic domain. Both homodimers and heterodimers are restricted to the cytoplasm.

Q: In cases of ALK-positive Anaplastic Large Cell Lymphoma driven by the classic t(2;5) translocation (NPM1::ALK), ALK immunostaining typically shows both cytoplasmic and [...] positivity.
ALK-positive anaplastic large cell lymphoma. Nuclear, nucleolar, and cytoplasmic staining is observed in tumours associated with the t(2;5) translocation (ALK1 staining).
A: nuclear
Back Extra: ALK-positive Anaplastic Large Cell Lymphoma
- Clinical: ALK-positive Anaplastic Large Cell Lymphoma (ALK+ ALCL) accounts for 15% of all paediatric non-Hodgkin lymphomas, with advanced disease (stage III–IV) and B symptoms commonly present at diagnosis.
- Micro: ALK+ ALCLs often grow in a cohesive manner within sinuses in lymph nodes, with characteristic hallmark cells having a horseshoe-shaped nucleus and a perinuclear eosinophilic region.
- Ancillary: Malignant cells are strongly positive for CD30 and often coexpress EMA and clusterin. They express an ALK fusion protein, and commonly show loss of pan-T-cell antigens (CD3 and CD5).
Reference Gallery:
ALK-positive anaplastic large cell lymphoma. Cerebrospinal fluid cytology shows large neoplastic cells with a kidney-shaped nucleus and a prominent Golgi complex.
ALK-positive anaplastic large cell lymphoma. Tumour cells show strong and homogeneous positivity for CD30.
ALK-positive anaplastic large cell lymphoma. Tumour cells show strong and homogeneous positivity for CD43.
ALK-positive anaplastic large cell lymphoma. Two distinct subtypes can coexist on a single biopsy. In this composite subtype, ALK1 staining clearly underlines a small-cell area (left) and a common subtype area (right) with larger tumour cells.
ALK-positive anaplastic large cell lymphoma. Nuclear, nucleolar, and cytoplasmic staining is observed in tumours associated with the t(2;5) translocation (ALK1 staining).
ALK-positive anaplastic large cell lymphoma. In tumours associated with the t(2;3)(p23;q21) translocation, ALK1 staining is restricted to the cytoplasm (TFG::ALK fusion protein).
ALK-positive anaplastic large cell lymphoma. Morphological features of the common subtype with a predominant population of large cells with abundant cytoplasm, and hallmark cells characterized by their kidney-shaped nucleus (arrows).
ALK-positive anaplastic large cell lymphoma. In the small cell subtype, hallmark cells (arrowhead) are rare, while small cells with irregular nuclei (arrow) are predominant.
ALK-positive anaplastic large cell lymphoma. In the lymphohistiocytic subtype, a large number of reactive histiocytes (arrowhead) outnumbers neoplastic cells (arrow) and may lead to misdiagnosis as a reactive lesion.
ALK-positive anaplastic large cell lymphoma. In the small cell subtype, hallmark cells often cluster around blood vessels (perivascular pattern, arrows) (ALK1 staining).
ALK-positive anaplastic large cell lymphoma. ALK signalling pathways activated downstream of the NPM1::ALK protein. The AKT/mTOR, JAK/STAT, MAPK, and PLCγ pathways are the major pathways activated downstream NPM::ALK protein, leading to the survival and proliferation of tumour cells. However, STAT3 seems to be the major effector of ALK oncogenic activity.
ALK-positive anaplastic large cell lymphoma. Subcellular distribution of ALK fusion proteins. Tumours associated with t(2;5) express NPM1::ALK protein and show a characteristic cytoplasmic, nuclear, and nucleolar staining that can be explained by the formation of homodimers and heterodimers: wildtype NPM1 provides nuclear localization signals (NLSs) whereby the NPM1::ALK protein can enter the nucleus. On the other hand, the formation of NPM1::ALK homodimers retained in the cytoplasm mimics ligand binding and is responsible for the oncogenic activation of the ALK catalytic domain. In the variant translocations, ALK partners lack nuclear localization signals but their oligomerization domain located in their amino-terminal portion could induce dimerization of the chimeric proteins and activation of the ALK catalytic domain. Both homodimers and heterodimers are restricted to the cytoplasm.

Q: Microscopically, B-lymphoblastic leukaemia/lymphoma is characterized by dense bone marrow replacement by small to medium-sized mononuclear cells with finely dispersed chromatin and scant cytoplasm, consistent with [...].
B-lymphoblastic leukaemia. Bone marrow core biopsy section shows sheets of small to medium-sized mononuclear cells with finely dispersed chromatin, small to indistinct nucleoli, and scant cytoplasm, consistent with blasts.
B-lymphoblastic leukaemia. L1 morphology. Bone marrow aspirate smear (Wright–Giemsa stain) shows extensive replacement by small to medium-sized blasts with round to slightly irregular nuclei, slightly condensed chromatin, indistinct nucleoli, and scant cytoplasm, consistent with lymphoblasts.
A: lymphoblasts
Back Extra: B-lymphoblastic leukaemia/lymphoma
- Clinical: Patients with B-lymphoblastic leukaemia/lymphoma can present with symptoms of cytopenias, bone pain, and/or extramedullary masses.
- Micro: Bone marrow and mass biopsies show dense infiltrate of small to medium-sized mononuclear cells consistent with blasts, often with a starry-sky pattern in skin involvement.
- Ancillary: Essential criteria for B-ALL include ≥ 20% B-cell lymphoblasts by flow cytometry, positive for B-cell lineage markers (CD19, CD22, cCD79a, and/or PAX5) and markers of immaturity (TdT, CD34, and/or CD10).
Reference Gallery:
B-lymphoblastic leukaemia. Bone marrow core biopsy section shows sheets of small to medium-sized mononuclear cells with finely dispersed chromatin, small to indistinct nucleoli, and scant cytoplasm, consistent with blasts.
B-lymphoblastic leukaemia. L1 morphology. Bone marrow aspirate smear (Wright–Giemsa stain) shows extensive replacement by small to medium-sized blasts with round to slightly irregular nuclei, slightly condensed chromatin, indistinct nucleoli, and scant cytoplasm, consistent with lymphoblasts.
B-lymphoblastic leukaemia. L2 morphology and granules. Bone marrow aspirate smear (Wright–Giemsa stain) shows extensive replacement by medium-sized to large blasts with round to slightly irregular nuclei, fine chromatin, small to prominent nucleoli, and moderate cytoplasm with granules, morphologically consistent with myeloblasts, but the immunophenotype shows a B-cell lineage.
Philadelphia chromosome–like B-lymphoblastic leukaemia. Flow cytometry of bone marrow cells shows a large population of CD19+, CD10+, CD34+ B-cell lymphoblasts (red population) with partial expression of CD36, an immunophenotype associated with both BCR::ABL1+ and BCR::ABL1-like B-lymphoblastic leukaemias. Cytogenetic studies show ABL1 fusion (not BCR::ABL1). The yellow population (P5) represents erythroid cells.
Minimal residual disease of B-lymphoblastic leukaemia with t(4;11) during treatment. Patient with B-lymphoblastic leukaemia with t(4;11) at day 15 of induction chemotherapy. No blasts are morphologically identified on bone marrow aspirate smears. Flow-based minimal residual disease analysis of 1 million events shows 0.28% abnormal B-cell lymphoblasts that are CD19+, CD34+ (subset), and CD15+. Both CD34− (P5) and CD34+ (P4) B cells are leukaemic cells (gates CD20 and CD19). Normal regenerating B cells (haematogones) have an immunophenotypic profile defined by gates P9, P13, and P17.

Q: The essential diagnostic criteria for B-lymphoblastic leukaemia/lymphoma require demonstrating ≥ [...] B-cell lymphoblasts by flow cytometry or morphologic examination, which typically co-express B-lineage markers (e.g., CD19, PAX5) and immaturity markers (e.g., TdT, CD34).
Philadelphia chromosome–like B-lymphoblastic leukaemia. Flow cytometry of bone marrow cells shows a large population of CD19+, CD10+, CD34+ B-cell lymphoblasts (red population) with partial expression of CD36, an immunophenotype associated with both BCR::ABL1+ and BCR::ABL1-like B-lymphoblastic leukaemias. Cytogenetic studies show ABL1 fusion (not BCR::ABL1). The yellow population (P5) represents erythroid cells.
A: 20%
Back Extra: B-lymphoblastic leukaemia/lymphoma
- Clinical: Patients with B-lymphoblastic leukaemia/lymphoma can present with symptoms of cytopenias, bone pain, and/or extramedullary masses.
- Micro: Bone marrow and mass biopsies show dense infiltrate of small to medium-sized mononuclear cells consistent with blasts, often with a starry-sky pattern in skin involvement.
- Ancillary: Essential criteria for B-ALL include ≥ 20% B-cell lymphoblasts by flow cytometry, positive for B-cell lineage markers (CD19, CD22, cCD79a, and/or PAX5) and markers of immaturity (TdT, CD34, and/or CD10).
Reference Gallery:
B-lymphoblastic leukaemia. Bone marrow core biopsy section shows sheets of small to medium-sized mononuclear cells with finely dispersed chromatin, small to indistinct nucleoli, and scant cytoplasm, consistent with blasts.
B-lymphoblastic leukaemia. L1 morphology. Bone marrow aspirate smear (Wright–Giemsa stain) shows extensive replacement by small to medium-sized blasts with round to slightly irregular nuclei, slightly condensed chromatin, indistinct nucleoli, and scant cytoplasm, consistent with lymphoblasts.
B-lymphoblastic leukaemia. L2 morphology and granules. Bone marrow aspirate smear (Wright–Giemsa stain) shows extensive replacement by medium-sized to large blasts with round to slightly irregular nuclei, fine chromatin, small to prominent nucleoli, and moderate cytoplasm with granules, morphologically consistent with myeloblasts, but the immunophenotype shows a B-cell lineage.
Philadelphia chromosome–like B-lymphoblastic leukaemia. Flow cytometry of bone marrow cells shows a large population of CD19+, CD10+, CD34+ B-cell lymphoblasts (red population) with partial expression of CD36, an immunophenotype associated with both BCR::ABL1+ and BCR::ABL1-like B-lymphoblastic leukaemias. Cytogenetic studies show ABL1 fusion (not BCR::ABL1). The yellow population (P5) represents erythroid cells.
Minimal residual disease of B-lymphoblastic leukaemia with t(4;11) during treatment. Patient with B-lymphoblastic leukaemia with t(4;11) at day 15 of induction chemotherapy. No blasts are morphologically identified on bone marrow aspirate smears. Flow-based minimal residual disease analysis of 1 million events shows 0.28% abnormal B-cell lymphoblasts that are CD19+, CD34+ (subset), and CD15+. Both CD34− (P5) and CD34+ (P4) B cells are leukaemic cells (gates CD20 and CD19). Normal regenerating B cells (haematogones) have an immunophenotypic profile defined by gates P9, P13, and P17.

Q: While typical B-lymphoblastic leukaemia/lymphoma presents with small to medium blasts, L2 morphology variants can show larger blasts with prominent nucleoli and cytoplasmic granules, morphologically mimicking [...].
B-lymphoblastic leukaemia. L2 morphology and granules. Bone marrow aspirate smear (Wright–Giemsa stain) shows extensive replacement by medium-sized to large blasts with round to slightly irregular nuclei, fine chromatin, small to prominent nucleoli, and moderate cytoplasm with granules, morphologically consistent with myeloblasts, but the immunophenotype shows a B-cell lineage.
A: myeloblasts
Back Extra: B-lymphoblastic leukaemia/lymphoma
- Clinical: Patients with B-lymphoblastic leukaemia/lymphoma can present with symptoms of cytopenias, bone pain, and/or extramedullary masses.
- Micro: Bone marrow and mass biopsies show dense infiltrate of small to medium-sized mononuclear cells consistent with blasts, often with a starry-sky pattern in skin involvement.
- Ancillary: Essential criteria for B-ALL include ≥ 20% B-cell lymphoblasts by flow cytometry, positive for B-cell lineage markers (CD19, CD22, cCD79a, and/or PAX5) and markers of immaturity (TdT, CD34, and/or CD10).
Reference Gallery:
B-lymphoblastic leukaemia. Bone marrow core biopsy section shows sheets of small to medium-sized mononuclear cells with finely dispersed chromatin, small to indistinct nucleoli, and scant cytoplasm, consistent with blasts.
B-lymphoblastic leukaemia. L1 morphology. Bone marrow aspirate smear (Wright–Giemsa stain) shows extensive replacement by small to medium-sized blasts with round to slightly irregular nuclei, slightly condensed chromatin, indistinct nucleoli, and scant cytoplasm, consistent with lymphoblasts.
B-lymphoblastic leukaemia. L2 morphology and granules. Bone marrow aspirate smear (Wright–Giemsa stain) shows extensive replacement by medium-sized to large blasts with round to slightly irregular nuclei, fine chromatin, small to prominent nucleoli, and moderate cytoplasm with granules, morphologically consistent with myeloblasts, but the immunophenotype shows a B-cell lineage.
Philadelphia chromosome–like B-lymphoblastic leukaemia. Flow cytometry of bone marrow cells shows a large population of CD19+, CD10+, CD34+ B-cell lymphoblasts (red population) with partial expression of CD36, an immunophenotype associated with both BCR::ABL1+ and BCR::ABL1-like B-lymphoblastic leukaemias. Cytogenetic studies show ABL1 fusion (not BCR::ABL1). The yellow population (P5) represents erythroid cells.
Minimal residual disease of B-lymphoblastic leukaemia with t(4;11) during treatment. Patient with B-lymphoblastic leukaemia with t(4;11) at day 15 of induction chemotherapy. No blasts are morphologically identified on bone marrow aspirate smears. Flow-based minimal residual disease analysis of 1 million events shows 0.28% abnormal B-cell lymphoblasts that are CD19+, CD34+ (subset), and CD15+. Both CD34− (P5) and CD34+ (P4) B cells are leukaemic cells (gates CD20 and CD19). Normal regenerating B cells (haematogones) have an immunophenotypic profile defined by gates P9, P13, and P17.

Q: Histologically, Burkitt Lymphoma is characterized by a diffuse, monomorphic population of medium-sized cells with a characteristic [...] pattern imparted by interspersed tingible-body macrophages.
Burkitt lymphoma. Histopathology with dense sheets of monomorphic blasts, cohesive growth, and a starry-sky pattern.
A: starry-sky
Back Extra: Burkitt Lymphoma
- Clinical: Burkitt lymphoma often presents with rapidly growing masses, and symptoms are mass-related. It can also present as acute leukaemia with ≥ 25% neoplastic cells in bone marrow smears.
- Micro: Histologically, Burkitt lymphoma is characterized by a diffuse monomorphic population of medium-sized cells with a starry-sky pattern due to the presence of tingible-body macrophages.
- Ancillary: The immunophenotype of Burkitt lymphoma is homogeneous, with strong expression of CD20, CD10, and a high Ki-67 index (usually close to 100%).
Reference Gallery:
Burkitt lymphoma. Sporadic Burkitt lymphoma growing as an abdominal mass.
Burkitt lymphoma. Histopathology with dense sheets of monomorphic blasts, cohesive growth, and a starry-sky pattern.
Burkitt lymphoma. Loss of cohesive growth and starry-sky pattern in poorly fixed areas of the tumour.
Burkitt lymphoma. Histology with monomorphic small/medium-sized blasts, a narrow rim of cytoplasm, and few nucleoli.
Burkitt lymphoma. Strong and abundant expression of CD20.
Burkitt lymphoma. Strong and abundant expression of CD10.
Burkitt lymphoma. BCL2 protein expression is negative or only faintly positive (less intense than in reactive T cells).
Burkitt lymphoma. Cytology with vacuolated blasts (known as L3 morphology).
Burkitt lymphoma. High proliferation index, with virtually all neoplastic nuclei being positive for Ki-67 in well-preserved tissue areas.
Burkitt lymphoma. FISH of IGH::MYC with the locus-specific identifier (LSI) IGH / MYC / CEP 8 tri-colour dual fusion FISH probe. Double fusion signals (yellow) confirm MYC and IGH translocation; chromosome 8 signals (aqua) are also visible.
Burkitt lymphoma. Contrast-enhanced axial CT image shows a large, poorly enhancing mass arising from the left mandible associated with bony destruction.

Q: Immunophenotypically, Burkitt Lymphoma demonstrates strong expression of CD20 and CD10, along with an exceptionally high Ki-67 proliferation index approaching [...]%.
Burkitt lymphoma. High proliferation index, with virtually all neoplastic nuclei being positive for Ki-67 in well-preserved tissue areas.
A: 100
Back Extra: Burkitt Lymphoma
- Clinical: Burkitt lymphoma often presents with rapidly growing masses, and symptoms are mass-related. It can also present as acute leukaemia with ≥ 25% neoplastic cells in bone marrow smears.
- Micro: Histologically, Burkitt lymphoma is characterized by a diffuse monomorphic population of medium-sized cells with a starry-sky pattern due to the presence of tingible-body macrophages.
- Ancillary: The immunophenotype of Burkitt lymphoma is homogeneous, with strong expression of CD20, CD10, and a high Ki-67 index (usually close to 100%).
Reference Gallery:
Burkitt lymphoma. Sporadic Burkitt lymphoma growing as an abdominal mass.
Burkitt lymphoma. Histopathology with dense sheets of monomorphic blasts, cohesive growth, and a starry-sky pattern.
Burkitt lymphoma. Loss of cohesive growth and starry-sky pattern in poorly fixed areas of the tumour.
Burkitt lymphoma. Histology with monomorphic small/medium-sized blasts, a narrow rim of cytoplasm, and few nucleoli.
Burkitt lymphoma. Strong and abundant expression of CD20.
Burkitt lymphoma. Strong and abundant expression of CD10.
Burkitt lymphoma. BCL2 protein expression is negative or only faintly positive (less intense than in reactive T cells).
Burkitt lymphoma. Cytology with vacuolated blasts (known as L3 morphology).
Burkitt lymphoma. High proliferation index, with virtually all neoplastic nuclei being positive for Ki-67 in well-preserved tissue areas.
Burkitt lymphoma. FISH of IGH::MYC with the locus-specific identifier (LSI) IGH / MYC / CEP 8 tri-colour dual fusion FISH probe. Double fusion signals (yellow) confirm MYC and IGH translocation; chromosome 8 signals (aqua) are also visible.
Burkitt lymphoma. Contrast-enhanced axial CT image shows a large, poorly enhancing mass arising from the left mandible associated with bony destruction.

Q: On cytologic preparations, the neoplastic blasts of Burkitt Lymphoma characteristically feature prominent cytoplasmic vacuoles, historically referred to as [...] morphology.
Burkitt lymphoma. Cytology with vacuolated blasts (known as L3 morphology).
A: L3
Back Extra: Burkitt Lymphoma
- Clinical: Burkitt lymphoma often presents with rapidly growing masses, and symptoms are mass-related. It can also present as acute leukaemia with ≥ 25% neoplastic cells in bone marrow smears.
- Micro: Histologically, Burkitt lymphoma is characterized by a diffuse monomorphic population of medium-sized cells with a starry-sky pattern due to the presence of tingible-body macrophages.
- Ancillary: The immunophenotype of Burkitt lymphoma is homogeneous, with strong expression of CD20, CD10, and a high Ki-67 index (usually close to 100%).
Reference Gallery:
Burkitt lymphoma. Sporadic Burkitt lymphoma growing as an abdominal mass.
Burkitt lymphoma. Histopathology with dense sheets of monomorphic blasts, cohesive growth, and a starry-sky pattern.
Burkitt lymphoma. Loss of cohesive growth and starry-sky pattern in poorly fixed areas of the tumour.
Burkitt lymphoma. Histology with monomorphic small/medium-sized blasts, a narrow rim of cytoplasm, and few nucleoli.
Burkitt lymphoma. Strong and abundant expression of CD20.
Burkitt lymphoma. Strong and abundant expression of CD10.
Burkitt lymphoma. BCL2 protein expression is negative or only faintly positive (less intense than in reactive T cells).
Burkitt lymphoma. Cytology with vacuolated blasts (known as L3 morphology).
Burkitt lymphoma. High proliferation index, with virtually all neoplastic nuclei being positive for Ki-67 in well-preserved tissue areas.
Burkitt lymphoma. FISH of IGH::MYC with the locus-specific identifier (LSI) IGH / MYC / CEP 8 tri-colour dual fusion FISH probe. Double fusion signals (yellow) confirm MYC and IGH translocation; chromosome 8 signals (aqua) are also visible.
Burkitt lymphoma. Contrast-enhanced axial CT image shows a large, poorly enhancing mass arising from the left mandible associated with bony destruction.

Q: Within the spectrum of Primary cutaneous CD30-positive T-cell lymphoproliferative disorders, [...] classically presents clinically as waxing and waning papular lesions.
Lymphomatoid papulosis. Papule in a child.
A: lymphomatoid papulosis
Back Extra: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders
- Clinical: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders include Lymphomatoid papulosis (LyP) and Cutaneous anaplastic large cell lymphoma (C-ALCL), with LyP presenting as waxing and waning papular lesions.
- Micro: LyP can present as various histological types, including Type A with a wedge-shaped dermal infiltrate and Type C with large pleomorphic lymphocytes.
- Ancillary: TR gene rearrangement is useful for determining clonality in C-ALCL and LyP, and DUSP22::IRF4 rearrangement is seen in selected cases of C-ALCL and a subtype of LyP.
Reference Gallery:
Lymphomatoid papulosis. Papule in a child.
Lymphomatoid papulosis. CD30 expression.
Lymphomatoid papulosis. Low-power view showing wedge-shaped dermal infiltration.
Lymphomatoid papulosis. Mixed inflammatory infiltrate, with prominent eosinophils and atypical mononuclear cells.
Lymphomatoid papulosis. The atypical cells are positive for CD2 by immunohistochemistry.
Lymphomatoid papulosis. CD3 immunohistochemistry.

Q: In Primary cutaneous CD30-positive T-cell lymphoproliferative disorders, specifically Type A lymphomatoid papulosis, low-power histology reveals a characteristic [...] dermal infiltrate containing atypical cells and mixed inflammation.
Lymphomatoid papulosis. Low-power view showing wedge-shaped dermal infiltration.
Lymphomatoid papulosis. Mixed inflammatory infiltrate, with prominent eosinophils and atypical mononuclear cells.
A: wedge-shaped
Back Extra: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders
- Clinical: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders include Lymphomatoid papulosis (LyP) and Cutaneous anaplastic large cell lymphoma (C-ALCL), with LyP presenting as waxing and waning papular lesions.
- Micro: LyP can present as various histological types, including Type A with a wedge-shaped dermal infiltrate and Type C with large pleomorphic lymphocytes.
- Ancillary: TR gene rearrangement is useful for determining clonality in C-ALCL and LyP, and DUSP22::IRF4 rearrangement is seen in selected cases of C-ALCL and a subtype of LyP.
Reference Gallery:
Lymphomatoid papulosis. Papule in a child.
Lymphomatoid papulosis. CD30 expression.
Lymphomatoid papulosis. Low-power view showing wedge-shaped dermal infiltration.
Lymphomatoid papulosis. Mixed inflammatory infiltrate, with prominent eosinophils and atypical mononuclear cells.
Lymphomatoid papulosis. The atypical cells are positive for CD2 by immunohistochemistry.
Lymphomatoid papulosis. CD3 immunohistochemistry.

Q: By definition, the large pleomorphic atypical cells in Primary cutaneous CD30-positive T-cell lymphoproliferative disorders strongly express [...] by immunohistochemistry.
Lymphomatoid papulosis. CD30 expression.
A: CD30
Back Extra: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders
- Clinical: Primary cutaneous CD30-positive T-cell lymphoproliferative disorders include Lymphomatoid papulosis (LyP) and Cutaneous anaplastic large cell lymphoma (C-ALCL), with LyP presenting as waxing and waning papular lesions.
- Micro: LyP can present as various histological types, including Type A with a wedge-shaped dermal infiltrate and Type C with large pleomorphic lymphocytes.
- Ancillary: TR gene rearrangement is useful for determining clonality in C-ALCL and LyP, and DUSP22::IRF4 rearrangement is seen in selected cases of C-ALCL and a subtype of LyP.
Reference Gallery:
Lymphomatoid papulosis. Papule in a child.
Lymphomatoid papulosis. CD30 expression.
Lymphomatoid papulosis. Low-power view showing wedge-shaped dermal infiltration.
Lymphomatoid papulosis. Mixed inflammatory infiltrate, with prominent eosinophils and atypical mononuclear cells.
Lymphomatoid papulosis. The atypical cells are positive for CD2 by immunohistochemistry.
Lymphomatoid papulosis. CD3 immunohistochemistry.

Q: Histologically, Diffuse Large B-Cell Lymphoma, NOS typically effaces the underlying tissue architecture with dense sheets of [...] cells that can exhibit highly variable morphologic features (e.g., centroblastic, blastoid, or plasmablastic).
Diffuse large B-cell lymphoma. A tonsil showing centroblastic cytology.
Diffuse large B-cell lymphoma. A CNS diffuse large B-cell lymphoma with blastoid cytology.
Diffuse large B-cell lymphoma. A lymph node with plasmablastic cytology.
A: blastic
Back Extra: Diffuse Large B-Cell Lymphoma, NOS
- Clinical: The majority of patients present with localized disease, B symptoms are detected in about 20% of patients, and the median age at diagnosis is 11 years.
- Micro: The tissue architecture is effaced by dense sheets of blastic cells, and a starry-sky pattern may be present but is not common. Morphology may be very variable, especially in localized subtypes such as CNS or bone lymphomas.
- Ancillary: B-cell markers such as CD20, CD19, and CD79a are expressed, and the vast majority of cases express germinal-centre markers such as CD10 and BCL6.
Reference Gallery:
Diffuse large B-cell lymphoma. A tonsil showing centroblastic cytology.
Diffuse large B-cell lymphoma. A case in the ileum with smaller blasts and a centrocytoid appearance.
Diffuse large B-cell lymphoma. A CNS diffuse large B-cell lymphoma with blastoid cytology.
Diffuse large B-cell lymphoma. A case occurring in bone with clear cell cytology.
Diffuse large B-cell lymphoma. A lymph node with plasmablastic cytology.
Diffuse large B-cell lymphoma. The large cells stain positively for CD20, consistent with their B-cell origin.
Diffuse large B-cell lymphoma. Nuclei negative for Ki-67 can be easily detected, and proliferation is thus lower, as it is in Burkitt lymphoma.

Q: Immunohistochemical evaluation of Diffuse Large B-Cell Lymphoma, NOS demonstrates strong positivity for pan-B-cell markers, most notably diffuse membranous staining for [...].
Diffuse large B-cell lymphoma. The large cells stain positively for CD20, consistent with their B-cell origin.
A: CD20
Back Extra: Diffuse Large B-Cell Lymphoma, NOS
- Clinical: The majority of patients present with localized disease, B symptoms are detected in about 20% of patients, and the median age at diagnosis is 11 years.
- Micro: The tissue architecture is effaced by dense sheets of blastic cells, and a starry-sky pattern may be present but is not common. Morphology may be very variable, especially in localized subtypes such as CNS or bone lymphomas.
- Ancillary: B-cell markers such as CD20, CD19, and CD79a are expressed, and the vast majority of cases express germinal-centre markers such as CD10 and BCL6.
Reference Gallery:
Diffuse large B-cell lymphoma. A tonsil showing centroblastic cytology.
Diffuse large B-cell lymphoma. A case in the ileum with smaller blasts and a centrocytoid appearance.
Diffuse large B-cell lymphoma. A CNS diffuse large B-cell lymphoma with blastoid cytology.
Diffuse large B-cell lymphoma. A case occurring in bone with clear cell cytology.
Diffuse large B-cell lymphoma. A lymph node with plasmablastic cytology.
Diffuse large B-cell lymphoma. The large cells stain positively for CD20, consistent with their B-cell origin.
Diffuse large B-cell lymphoma. Nuclei negative for Ki-67 can be easily detected, and proliferation is thus lower, as it is in Burkitt lymphoma.

Q: While both are aggressive neoplasms, the [...] proliferation index in Diffuse Large B-Cell Lymphoma, NOS is characteristically lower than the nearly 100% fraction observed in Burkitt lymphoma.
Diffuse large B-cell lymphoma. Nuclei negative for Ki-67 can be easily detected, and proliferation is thus lower, as it is in Burkitt lymphoma.
A: Ki-67
Back Extra: Diffuse Large B-Cell Lymphoma, NOS
- Clinical: The majority of patients present with localized disease, B symptoms are detected in about 20% of patients, and the median age at diagnosis is 11 years.
- Micro: The tissue architecture is effaced by dense sheets of blastic cells, and a starry-sky pattern may be present but is not common. Morphology may be very variable, especially in localized subtypes such as CNS or bone lymphomas.
- Ancillary: B-cell markers such as CD20, CD19, and CD79a are expressed, and the vast majority of cases express germinal-centre markers such as CD10 and BCL6.
Reference Gallery:
Diffuse large B-cell lymphoma. A tonsil showing centroblastic cytology.
Diffuse large B-cell lymphoma. A case in the ileum with smaller blasts and a centrocytoid appearance.
Diffuse large B-cell lymphoma. A CNS diffuse large B-cell lymphoma with blastoid cytology.
Diffuse large B-cell lymphoma. A case occurring in bone with clear cell cytology.
Diffuse large B-cell lymphoma. A lymph node with plasmablastic cytology.
Diffuse large B-cell lymphoma. The large cells stain positively for CD20, consistent with their B-cell origin.
Diffuse large B-cell lymphoma. Nuclei negative for Ki-67 can be easily detected, and proliferation is thus lower, as it is in Burkitt lymphoma.

Q: Characterized by scattered large atypical B-cells that resemble Hodgkin Reed-Sternberg (HRS) cells or immunoblasts within a reactive background of small lymphocytes and histiocytes, and showing EBER positivity, this diagnosis is [...].
EBV-positive large B-cell lymphoma. There are scattered large atypical cells in a background of small lymphocytes and histiocytes.
EBV-positive large B-cell lymphoma. EBV-encoded small RNA (EBER) is positive in the large cells.
A: EBV-positive diffuse large B-cell lymphoma
Back Extra: EBV-positive diffuse large B-cell lymphoma
- Clinical: Patients with EBV-positive diffuse large B-cell lymphoma may present with low- or high-stage disease, and EBV serology and serum EBV viral load are recommended for workup and monitoring.
- Micro: The large atypical cells in EBV-positive diffuse large B-cell lymphoma can resemble HRS cells or immunoblasts, and are often seen in a background of small lymphocytes and histiocytes.
- Ancillary: The neoplastic cells are positive for CD20, CD79, PAX5, OCT2, and BOB1, and show EBV-encoded small RNA (EBER) and LMP1 positivity, consistent with type II EBV latency.
Reference Gallery:
EBV-positive large B-cell lymphoma. There are scattered large atypical cells in a background of small lymphocytes and histiocytes.
EBV-positive large B-cell lymphoma. The large atypical cells are strongly positive for CD20.
EBV-positive large B-cell lymphoma. EBV-encoded small RNA (EBER) is positive in the large cells.
EBV-positive large B-cell lymphoma. LMP1 is positive in the large cells.

Q: In EBV-positive diffuse large B-cell lymphoma, the neoplastic cells demonstrate a retained B-cell program (e.g., strong CD20 positivity) and typically express EBER and LMP1, reflecting a [...] EBV latency pattern.
EBV-positive large B-cell lymphoma. The large atypical cells are strongly positive for CD20.
EBV-positive large B-cell lymphoma. EBV-encoded small RNA (EBER) is positive in the large cells.
EBV-positive large B-cell lymphoma. LMP1 is positive in the large cells.
A: type II
Back Extra: EBV-positive diffuse large B-cell lymphoma
- Clinical: Patients with EBV-positive diffuse large B-cell lymphoma may present with low- or high-stage disease, and EBV serology and serum EBV viral load are recommended for workup and monitoring.
- Micro: The large atypical cells in EBV-positive diffuse large B-cell lymphoma can resemble HRS cells or immunoblasts, and are often seen in a background of small lymphocytes and histiocytes.
- Ancillary: The neoplastic cells are positive for CD20, CD79, PAX5, OCT2, and BOB1, and show EBV-encoded small RNA (EBER) and LMP1 positivity, consistent with type II EBV latency.
Reference Gallery:
EBV-positive large B-cell lymphoma. There are scattered large atypical cells in a background of small lymphocytes and histiocytes.
EBV-positive large B-cell lymphoma. The large atypical cells are strongly positive for CD20.
EBV-positive large B-cell lymphoma. EBV-encoded small RNA (EBER) is positive in the large cells.
EBV-positive large B-cell lymphoma. LMP1 is positive in the large cells.

Q: In Hepatosplenic T-cell lymphoma, atypical lymphoid cells characteristically infiltrate the [...] of the liver, which can be highlighted on PAS staining.
Hepatosplenic T-cell lymphoma. PAS staining shows dilated hepatic sinusoids containing numerous atypical lymphoid cells with medium-sized nuclei and a thin rim of pale cytoplasm.
A: sinusoids
Back Extra: Hepatosplenic T-cell lymphoma
- Clinical: Patients with Hepatosplenic T-cell lymphoma (HSTL) typically present with hepatosplenomegaly, systemic symptoms, and marked thrombocytopenia, often with anaemia and leukopenia.
- Micro: HSTL cells are typically monotonous, with medium-sized nuclei, small inconspicuous nucleoli, and a rim of pale cytoplasm. They involve the cords and sinuses of the splenic red pulp and the sinusoids of the liver.
- Ancillary: The neoplastic cells have a mature, non-activated cytotoxic T-cell phenotype, with aberrations. They are CD3+, CD5−, CD4−, CD8−/+, CD56+/−, and usually TCRγδ+.
Reference Gallery:
Hepatosplenic T-cell lymphoma. PAS staining shows dilated hepatic sinusoids containing numerous atypical lymphoid cells with medium-sized nuclei and a thin rim of pale cytoplasm.
Hepatosplenic T-cell lymphoma. CD3 is diffusely positive in the atypical lymphoid population.
Hepatosplenic T-cell lymphoma. Giemsa staining highlights the irregular profile of nuclei and inconspicuous nucleoli.

Q: Immunohistochemistry in Hepatosplenic T-cell lymphoma characteristically demonstrates diffuse positivity for the pan-T-cell marker [...] within the atypical lymphoid population.
Hepatosplenic T-cell lymphoma. CD3 is diffusely positive in the atypical lymphoid population.
A: CD3
Back Extra: Hepatosplenic T-cell lymphoma
- Clinical: Patients with Hepatosplenic T-cell lymphoma (HSTL) typically present with hepatosplenomegaly, systemic symptoms, and marked thrombocytopenia, often with anaemia and leukopenia.
- Micro: HSTL cells are typically monotonous, with medium-sized nuclei, small inconspicuous nucleoli, and a rim of pale cytoplasm. They involve the cords and sinuses of the splenic red pulp and the sinusoids of the liver.
- Ancillary: The neoplastic cells have a mature, non-activated cytotoxic T-cell phenotype, with aberrations. They are CD3+, CD5−, CD4−, CD8−/+, CD56+/−, and usually TCRγδ+.
Reference Gallery:
Hepatosplenic T-cell lymphoma. PAS staining shows dilated hepatic sinusoids containing numerous atypical lymphoid cells with medium-sized nuclei and a thin rim of pale cytoplasm.
Hepatosplenic T-cell lymphoma. CD3 is diffusely positive in the atypical lymphoid population.
Hepatosplenic T-cell lymphoma. Giemsa staining highlights the irregular profile of nuclei and inconspicuous nucleoli.

Q: A patient presenting with hepatosplenomegaly, systemic symptoms, marked thrombocytopenia, and anemia, whose biopsy reveals monotonous lymphoid cells with irregular nuclei and inconspicuous nucleoli on Giemsa stain, likely has [...].
Hepatosplenic T-cell lymphoma. Giemsa staining highlights the irregular profile of nuclei and inconspicuous nucleoli.
A: Hepatosplenic T-cell lymphoma
Back Extra: Hepatosplenic T-cell lymphoma
- Clinical: Patients with Hepatosplenic T-cell lymphoma (HSTL) typically present with hepatosplenomegaly, systemic symptoms, and marked thrombocytopenia, often with anaemia and leukopenia.
- Micro: HSTL cells are typically monotonous, with medium-sized nuclei, small inconspicuous nucleoli, and a rim of pale cytoplasm. They involve the cords and sinuses of the splenic red pulp and the sinusoids of the liver.
- Ancillary: The neoplastic cells have a mature, non-activated cytotoxic T-cell phenotype, with aberrations. They are CD3+, CD5−, CD4−, CD8−/+, CD56+/−, and usually TCRγδ+.
Reference Gallery:
Hepatosplenic T-cell lymphoma. PAS staining shows dilated hepatic sinusoids containing numerous atypical lymphoid cells with medium-sized nuclei and a thin rim of pale cytoplasm.
Hepatosplenic T-cell lymphoma. CD3 is diffusely positive in the atypical lymphoid population.
Hepatosplenic T-cell lymphoma. Giemsa staining highlights the irregular profile of nuclei and inconspicuous nucleoli.

Q: Morphologically, High-grade B-cell lymphoma with 11q aberration may be indistinguishable from [...], showing medium-sized blasts and a starry-sky pattern, though it often has more cellular pleomorphism.
High-grade B-cell lymphoma with 11q aberration. Morphology showing medium-sized blasts with slightly polymorphic nuclei and a starry-sky pattern.
A: Burkitt lymphoma
Back Extra: High-grade B-cell lymphoma with 11q aberration
- Clinical: High-grade B-cell lymphoma with 11q aberration presents with mass-related symptoms and lacks B symptoms. It may occur in immunocompromised patients.
- Micro: Morphologically, it may be indistinguishable from Burkitt lymphoma but can show more cellular pleomorphism, variation in nuclear shape, and larger nucleoli. The starry-sky pattern may be absent.
- Ancillary: Diagnosis is confirmed by the detection of the characteristic 11q gain/loss pattern using high-resolution array-based comparative genomic hybridization or FISH.
Reference Gallery:
High-grade B-cell lymphoma with 11q aberration. Morphology showing medium-sized blasts with slightly polymorphic nuclei and a starry-sky pattern.
High-grade B-cell lymphoma with 11q aberration. FISH showing alteration of 11q.

Q: The diagnosis of High-grade B-cell lymphoma with 11q aberration is confirmed by the detection of the characteristic 11q gain/loss pattern using high-resolution array-based comparative genomic hybridization or [...].
High-grade B-cell lymphoma with 11q aberration. FISH showing alteration of 11q.
A: FISH
Back Extra: High-grade B-cell lymphoma with 11q aberration
- Clinical: High-grade B-cell lymphoma with 11q aberration presents with mass-related symptoms and lacks B symptoms. It may occur in immunocompromised patients.
- Micro: Morphologically, it may be indistinguishable from Burkitt lymphoma but can show more cellular pleomorphism, variation in nuclear shape, and larger nucleoli. The starry-sky pattern may be absent.
- Ancillary: Diagnosis is confirmed by the detection of the characteristic 11q gain/loss pattern using high-resolution array-based comparative genomic hybridization or FISH.
Reference Gallery:
High-grade B-cell lymphoma with 11q aberration. Morphology showing medium-sized blasts with slightly polymorphic nuclei and a starry-sky pattern.
High-grade B-cell lymphoma with 11q aberration. FISH showing alteration of 11q.

Q: Clinically, patients with Hydroa vacciniforme lymphoproliferative disorder present with recurrent papulovesicular eruptions on sun-exposed areas that typically progress to blisters, ulcers, and [...].
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated with haemorrhagic crusts and pitted scars.
A: varioliform atrophic scars
Back Extra: Hydroa vacciniforme lymphoproliferative disorder
- Clinical: Classic HV-LPD is characterized by recurrent papulovesicular eruptions on sun-exposed areas, which can progress to blisters, ulcers, and varioliform atrophic scars.
- Micro: Histopathology shows epidermal reticular degeneration, intraepidermal spongiotic vesiculation, and a perivascular and periadnexal lymphocytic infiltrate.
- Ancillary: Most cases show clonal rearrangements of the TR genes and positive in situ hybridization for EBV-encoded small RNA (EBER).
Reference Gallery:
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated with haemorrhagic crusts and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around the adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia.
Hydroa vacciniforme lymphoproliferative disorder. The atypical infiltrate surrounds blood vessels with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. Atypical cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).

Q: A characteristic histopathologic finding in Hydroa vacciniforme lymphoproliferative disorder is a perivascular and periadnexal lymphocytic infiltrate with angiodestructive features and overlying intraepidermal [...].
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around the adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation.
Hydroa vacciniforme lymphoproliferative disorder. The atypical infiltrate surrounds blood vessels with angiodestructive features.
A: spongiotic vesiculation
Back Extra: Hydroa vacciniforme lymphoproliferative disorder
- Clinical: Classic HV-LPD is characterized by recurrent papulovesicular eruptions on sun-exposed areas, which can progress to blisters, ulcers, and varioliform atrophic scars.
- Micro: Histopathology shows epidermal reticular degeneration, intraepidermal spongiotic vesiculation, and a perivascular and periadnexal lymphocytic infiltrate.
- Ancillary: Most cases show clonal rearrangements of the TR genes and positive in situ hybridization for EBV-encoded small RNA (EBER).
Reference Gallery:
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated with haemorrhagic crusts and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around the adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia.
Hydroa vacciniforme lymphoproliferative disorder. The atypical infiltrate surrounds blood vessels with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. Atypical cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).

Q: The pathogenesis of Hydroa vacciniforme lymphoproliferative disorder is strongly linked to a specific viral infection, with the atypical lymphoid cells characteristically demonstrating diffuse positivity for [...] by in situ hybridization.
Hydroa vacciniforme lymphoproliferative disorder. Atypical cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).
A: EBV-encoded small RNA (EBER)
Back Extra: Hydroa vacciniforme lymphoproliferative disorder
- Clinical: Classic HV-LPD is characterized by recurrent papulovesicular eruptions on sun-exposed areas, which can progress to blisters, ulcers, and varioliform atrophic scars.
- Micro: Histopathology shows epidermal reticular degeneration, intraepidermal spongiotic vesiculation, and a perivascular and periadnexal lymphocytic infiltrate.
- Ancillary: Most cases show clonal rearrangements of the TR genes and positive in situ hybridization for EBV-encoded small RNA (EBER).
Reference Gallery:
Hydroa vacciniforme lymphoproliferative disorder. The lesions are located in sun-exposed and non–sun-exposed areas. The skin exhibits a papulovesicular eruption. Many of the lesions are ulcerated with haemorrhagic crusts and pitted scars.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate predominates in the dermis. The infiltrate is mainly located around the adnexa and blood vessels. There is an intraepidermal spongiotic vesiculation.
Hydroa vacciniforme lymphoproliferative disorder. The lymphoid infiltrate, which can be of T-cell or NK-cell lineage, is composed of small to medium-sized cells without atypia.
Hydroa vacciniforme lymphoproliferative disorder. The atypical infiltrate surrounds blood vessels with angiodestructive features.
Hydroa vacciniforme lymphoproliferative disorder. Atypical cells are positive for EBV, as demonstrated by in situ hybridization for EBV-encoded small RNA (EBER).

Q: A pediatric patient presenting with localized tonsillar enlargement, no B symptoms, and morphology ranging from expansive follicles to cohesive sheets of centroblastic cells is characteristic of [...].
Large B-cell lymphoma with IRF4 rearrangement. Infiltration of the tonsil with expansive large follicles.
Large B-cell lymphoma with IRF4 rearrangement. The cytology in this case is centroblastic. A starry-sky pattern is not observed.
A: Large B-cell lymphoma with IRF4 rearrangement
Back Extra: Large B-cell lymphoma with IRF4 rearrangement
- Clinical: The most common presentation is localized tonsillar enlargement or isolated lymphadenopathy without B symptoms, primarily in patients aged < 18 years.
- Micro: Morphology can be diffuse, follicular and diffuse, or purely follicular, with large, round follicles lacking the serpiginous configuration of pediatric-type follicular lymphoma.
- Ancillary: Immunohistochemistry shows a mature B-cell phenotype with strong expression of IRF4 (MUM1) and a high proliferation index; molecular studies often reveal IRF4 rearrangements.
Reference Gallery:
Large B-cell lymphoma with IRF4 rearrangement. Infiltration of the tonsil with expansive large follicles.
Large B-cell lymphoma with IRF4 rearrangement. Cytology shows cohesive sheets of large cells with apparent nucleoli.
Large B-cell lymphoma with IRF4 rearrangement. Cells infiltrating the ileum, with a diffuse growth pattern.
Large B-cell lymphoma with IRF4 rearrangement. The cytology in this case is centroblastic. A starry-sky pattern is not observed.
Large B-cell lymphoma with IRF4 rearrangement. FISH with a break-apart assay for the DUSP22::IRF4 gene locus showing split signals indicating IRF4 gene rearrangement.

Q: Molecular confirmation of Large B-cell lymphoma with IRF4 rearrangement is often achieved using a FISH break-apart assay, which demonstrates split signals at the [IRF4] gene locus.
Large B-cell lymphoma with IRF4 rearrangement. FISH with a break-apart assay for the DUSP22::IRF4 gene locus showing split signals indicating IRF4 gene rearrangement.
A: DUSP22
Back Extra: Large B-cell lymphoma with IRF4 rearrangement
- Clinical: The most common presentation is localized tonsillar enlargement or isolated lymphadenopathy without B symptoms, primarily in patients aged < 18 years.
- Micro: Morphology can be diffuse, follicular and diffuse, or purely follicular, with large, round follicles lacking the serpiginous configuration of pediatric-type follicular lymphoma.
- Ancillary: Immunohistochemistry shows a mature B-cell phenotype with strong expression of IRF4 (MUM1) and a high proliferation index; molecular studies often reveal IRF4 rearrangements.
Reference Gallery:
Large B-cell lymphoma with IRF4 rearrangement. Infiltration of the tonsil with expansive large follicles.
Large B-cell lymphoma with IRF4 rearrangement. Cytology shows cohesive sheets of large cells with apparent nucleoli.
Large B-cell lymphoma with IRF4 rearrangement. Cells infiltrating the ileum, with a diffuse growth pattern.
Large B-cell lymphoma with IRF4 rearrangement. The cytology in this case is centroblastic. A starry-sky pattern is not observed.
Large B-cell lymphoma with IRF4 rearrangement. FISH with a break-apart assay for the DUSP22::IRF4 gene locus showing split signals indicating IRF4 gene rearrangement.

Q: When exhibiting a follicular growth pattern, Large B-cell lymphoma with IRF4 rearrangement features large, round follicles that lack the characteristic [...] configuration seen in pediatric-type follicular lymphoma.
Large B-cell lymphoma with IRF4 rearrangement. Infiltration of the tonsil with expansive large follicles.
A: serpiginous
Back Extra: Large B-cell lymphoma with IRF4 rearrangement
- Clinical: The most common presentation is localized tonsillar enlargement or isolated lymphadenopathy without B symptoms, primarily in patients aged < 18 years.
- Micro: Morphology can be diffuse, follicular and diffuse, or purely follicular, with large, round follicles lacking the serpiginous configuration of pediatric-type follicular lymphoma.
- Ancillary: Immunohistochemistry shows a mature B-cell phenotype with strong expression of IRF4 (MUM1) and a high proliferation index; molecular studies often reveal IRF4 rearrangements.
Reference Gallery:
Large B-cell lymphoma with IRF4 rearrangement. Infiltration of the tonsil with expansive large follicles.
Large B-cell lymphoma with IRF4 rearrangement. Cytology shows cohesive sheets of large cells with apparent nucleoli.
Large B-cell lymphoma with IRF4 rearrangement. Cells infiltrating the ileum, with a diffuse growth pattern.
Large B-cell lymphoma with IRF4 rearrangement. The cytology in this case is centroblastic. A starry-sky pattern is not observed.
Large B-cell lymphoma with IRF4 rearrangement. FISH with a break-apart assay for the DUSP22::IRF4 gene locus showing split signals indicating IRF4 gene rearrangement.

Q: Microscopic examination of Lymphomatoid Granulomatosis typically demonstrates a lymphohistiocytic infiltrate with a characteristic [...] growth pattern, often leading to necrosis of the vessel wall.
Lymphomatoid granulomatosis, grade 2. Large hyperchromatic atypical lymphoid cells within a necrotic vessel wall.
A: angiocentric and angiodestructive
Back Extra: Lymphomatoid Granulomatosis
- Clinical: Initial symptoms often include cough/dyspnoea, neurological symptoms, hepatosplenomegaly, and lymphadenopathy, which are more frequent in children.
- Micro: Characterized by a lymphohistiocytic infiltrate with an angiocentric and angiodestructive growth pattern, often with central necrosis.
- Ancillary: Large atypical cells are positive for CD20 and EBV by in situ hybridization using EBER probes, and there is variable expression of CD30.
Reference Gallery:
Lymphomatoid granulomatosis, grade 2. Large hyperchromatic atypical lymphoid cells within a necrotic vessel wall.
Lymphomatoid granulomatosis, grade 2. CD20 immunohistochemistry highlights large B cells.
Lymphomatoid granulomatosis, grade 2. The large cells are positive for EBV by in situ hybridization using an EBV-encoded small RNA (EBER) probe.
Lymphomatoid granulomatosis, grade 2. Numerous EBV-positive cells by in situ hybridization are present within the vessel wall.

Q: In Lymphomatoid Granulomatosis, the large, atypical B-cells (which express CD20) are characteristically positive for [...] by in situ hybridization using EBER probes.
Lymphomatoid granulomatosis, grade 2. CD20 immunohistochemistry highlights large B cells.
Lymphomatoid granulomatosis, grade 2. The large cells are positive for EBV by in situ hybridization using an EBV-encoded small RNA (EBER) probe.
Lymphomatoid granulomatosis, grade 2. Numerous EBV-positive cells by in situ hybridization are present within the vessel wall.
A: Epstein-Barr virus (EBV)
Back Extra: Lymphomatoid Granulomatosis
- Clinical: Initial symptoms often include cough/dyspnoea, neurological symptoms, hepatosplenomegaly, and lymphadenopathy, which are more frequent in children.
- Micro: Characterized by a lymphohistiocytic infiltrate with an angiocentric and angiodestructive growth pattern, often with central necrosis.
- Ancillary: Large atypical cells are positive for CD20 and EBV by in situ hybridization using EBER probes, and there is variable expression of CD30.
Reference Gallery:
Lymphomatoid granulomatosis, grade 2. Large hyperchromatic atypical lymphoid cells within a necrotic vessel wall.
Lymphomatoid granulomatosis, grade 2. CD20 immunohistochemistry highlights large B cells.
Lymphomatoid granulomatosis, grade 2. The large cells are positive for EBV by in situ hybridization using an EBV-encoded small RNA (EBER) probe.
Lymphomatoid granulomatosis, grade 2. Numerous EBV-positive cells by in situ hybridization are present within the vessel wall.

Q: Morphologically, a tumor diagnosed as Mediastinal Grey Zone Lymphoma exhibits a transitional or mixed appearance, featuring areas that resemble diffuse large B-cell lymphoma and areas that resemble [...].
Grey zone lymphoma. An area closely resembling diffuse large B-cell lymphoma.
Grey zone lymphoma. An area closely resembling classic Hodgkin lymphoma.
A: classic Hodgkin lymphoma
Back Extra: Mediastinal Grey Zone Lymphoma
- Clinical: Patients with Mediastinal Grey Zone Lymphoma often present with a large mediastinal mass, and the condition is more common in young adults (20-40 years) with a male predominance.
- Micro: The tumour is composed of pleomorphic cells with confluent, sheet-like growth, and may show a mix of features resembling both classic Hodgkin lymphoma and diffuse large B-cell lymphoma.
- Ancillary: Immunohistochemistry shows strong expression of CD20, PAX5, and other B-cell markers, with variable CD30 and CD15 expression, and frequent EBV negativity.
Reference Gallery:
Grey zone lymphoma. An area closely resembling diffuse large B-cell lymphoma.
Grey zone lymphoma. An area closely resembling classic Hodgkin lymphoma.
Grey zone lymphoma. CD30 is more strongly expressed in the classic Hodgkin lymphoma–like areas than in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD15 expression is restricted to the classic Hodgkin lymphoma–like areas.
Grey zone lymphoma. Intense CD20 staining both in the classic Hodgkin lymphoma–like areas and in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD19 is more strongly expressed in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD23 stains only Hodgkin lymphoma cells but is negative in the diffuse large B-cell lymphoma areas. In both its components, the tumour was positive for CD22, PAX5, BOB1, OCT2, and CD200 (not shown).
Grey zone lymphoma. CD79 positivity in classic Hodgkin lymphoma–like cells and diffuse large B-cell lymphoma–like areas.

Q: Unlike typical classic Hodgkin lymphoma, Mediastinal Grey Zone Lymphoma is characterized by intense, widespread immunohistochemical staining for the B-cell marker [...] throughout both components of the tumor.
Grey zone lymphoma. Intense CD20 staining both in the classic Hodgkin lymphoma–like areas and in the diffuse large B-cell lymphoma–like areas.
A: CD20
Back Extra: Mediastinal Grey Zone Lymphoma
- Clinical: Patients with Mediastinal Grey Zone Lymphoma often present with a large mediastinal mass, and the condition is more common in young adults (20-40 years) with a male predominance.
- Micro: The tumour is composed of pleomorphic cells with confluent, sheet-like growth, and may show a mix of features resembling both classic Hodgkin lymphoma and diffuse large B-cell lymphoma.
- Ancillary: Immunohistochemistry shows strong expression of CD20, PAX5, and other B-cell markers, with variable CD30 and CD15 expression, and frequent EBV negativity.
Reference Gallery:
Grey zone lymphoma. An area closely resembling diffuse large B-cell lymphoma.
Grey zone lymphoma. An area closely resembling classic Hodgkin lymphoma.
Grey zone lymphoma. CD30 is more strongly expressed in the classic Hodgkin lymphoma–like areas than in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD15 expression is restricted to the classic Hodgkin lymphoma–like areas.
Grey zone lymphoma. Intense CD20 staining both in the classic Hodgkin lymphoma–like areas and in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD19 is more strongly expressed in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD23 stains only Hodgkin lymphoma cells but is negative in the diffuse large B-cell lymphoma areas. In both its components, the tumour was positive for CD22, PAX5, BOB1, OCT2, and CD200 (not shown).
Grey zone lymphoma. CD79 positivity in classic Hodgkin lymphoma–like cells and diffuse large B-cell lymphoma–like areas.

Q: In Mediastinal Grey Zone Lymphoma, the expression of the activation marker [...] is variable and typically much stronger in the classic Hodgkin lymphoma-like areas than in the diffuse large B-cell lymphoma-like areas.
Grey zone lymphoma. CD30 is more strongly expressed in the classic Hodgkin lymphoma–like areas than in the diffuse large B-cell lymphoma–like areas.
A: CD30
Back Extra: Mediastinal Grey Zone Lymphoma
- Clinical: Patients with Mediastinal Grey Zone Lymphoma often present with a large mediastinal mass, and the condition is more common in young adults (20-40 years) with a male predominance.
- Micro: The tumour is composed of pleomorphic cells with confluent, sheet-like growth, and may show a mix of features resembling both classic Hodgkin lymphoma and diffuse large B-cell lymphoma.
- Ancillary: Immunohistochemistry shows strong expression of CD20, PAX5, and other B-cell markers, with variable CD30 and CD15 expression, and frequent EBV negativity.
Reference Gallery:
Grey zone lymphoma. An area closely resembling diffuse large B-cell lymphoma.
Grey zone lymphoma. An area closely resembling classic Hodgkin lymphoma.
Grey zone lymphoma. CD30 is more strongly expressed in the classic Hodgkin lymphoma–like areas than in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD15 expression is restricted to the classic Hodgkin lymphoma–like areas.
Grey zone lymphoma. Intense CD20 staining both in the classic Hodgkin lymphoma–like areas and in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD19 is more strongly expressed in the diffuse large B-cell lymphoma–like areas.
Grey zone lymphoma. CD23 stains only Hodgkin lymphoma cells but is negative in the diffuse large B-cell lymphoma areas. In both its components, the tumour was positive for CD22, PAX5, BOB1, OCT2, and CD200 (not shown).
Grey zone lymphoma. CD79 positivity in classic Hodgkin lymphoma–like cells and diffuse large B-cell lymphoma–like areas.

Q: In Mycosis Fungoides, the neoplastic lymphocytes classically align along the basal layer and exhibit highly irregular, convoluted [...] nuclei.
Mycosis fungoides. At high power, lymphoid cells are aligned along the basal layer and show cerebriform nuclei.
Mycosis fungoides. Intraepithelial lymphocytes show a pale perinuclear halo and mildly hyperchromic nuclei with an irregular profile. There is no spongiosis.
A: cerebriform
Back Extra: Mycosis Fungoides
- Clinical: Mycosis fungoides in children is rare and often presents as hypopigmented patches and plaques, with a good prognosis and rare progression to advanced stages.
- Micro: Histopathology shows a predominantly dermal, band-like, perivascular, and periadnexal infiltrate of small lymphocytes with cerebriform nuclei and intraepidermal Pautrier microabscesses.
- Ancillary: Immunohistochemistry reveals a T-helper immunophenotype (CD3+, CD4+, CD5+, CD7−, CD8−) with characteristic clonal TR gene rearrangements.
Reference Gallery:
Mycosis fungoides. Skin with junctional and intraepidermal lymphocytic infiltrate.
Mycosis fungoides. At high power, lymphoid cells are aligned along the basal layer and show cerebriform nuclei.
Mycosis fungoides. Immunostaining shows diffuse positivity of lymphoid cells for CD3.
Mycosis fungoides. Immunostaining shows a prevalent population of CD8+ cells.
Mycosis fungoides. Immunostaining shows that CD5 expression is preserved in the clonal CD8+ population.
Mycosis fungoides. Immunostaining shows that CD7 expression is reduced in the clonal CD8+ population.
Mycosis fungoides. Immunostaining shows that CD4 is positive in a minority of cells.
Mycosis fungoides. Dermal, mostly perivascular, superficial lymphocytic infiltrate, with intraepidermal lymphocytes. Epidermis shows minimal hyperkeratosis.
Mycosis fungoides. Intraepithelial lymphocytes show a pale perinuclear halo and mildly hyperchromic nuclei with an irregular profile. There is no spongiosis.
Mycosis fungoides. Intraepithelial lymphocytes show a pale perinuclear halo and mildly hyperchromic nuclei with an irregular profile. There is no spongiosis.
Mycosis fungoides. CD3 (shown here) and CD4 immunostaining highlights the T-helper immunophenotype of the lesion.
Mycosis fungoides. CD4 (shown here) and CD3 immunostaining highlights the T-helper immunophenotype of the lesion.

Q: The classic immunophenotype of Mycosis Fungoides consists of mature T-helper cells that are strongly positive for CD3 and [...], often with an aberrant loss of CD7 expression.
Mycosis fungoides. CD3 (shown here) and CD4 immunostaining highlights the T-helper immunophenotype of the lesion.
Mycosis fungoides. CD4 (shown here) and CD3 immunostaining highlights the T-helper immunophenotype of the lesion.
A: CD4
Back Extra: Mycosis Fungoides
- Clinical: Mycosis fungoides in children is rare and often presents as hypopigmented patches and plaques, with a good prognosis and rare progression to advanced stages.
- Micro: Histopathology shows a predominantly dermal, band-like, perivascular, and periadnexal infiltrate of small lymphocytes with cerebriform nuclei and intraepidermal Pautrier microabscesses.
- Ancillary: Immunohistochemistry reveals a T-helper immunophenotype (CD3+, CD4+, CD5+, CD7−, CD8−) with characteristic clonal TR gene rearrangements.
Reference Gallery:
Mycosis fungoides. Skin with junctional and intraepidermal lymphocytic infiltrate.
Mycosis fungoides. At high power, lymphoid cells are aligned along the basal layer and show cerebriform nuclei.
Mycosis fungoides. Immunostaining shows diffuse positivity of lymphoid cells for CD3.
Mycosis fungoides. Immunostaining shows a prevalent population of CD8+ cells.
Mycosis fungoides. Immunostaining shows that CD5 expression is preserved in the clonal CD8+ population.
Mycosis fungoides. Immunostaining shows that CD7 expression is reduced in the clonal CD8+ population.
Mycosis fungoides. Immunostaining shows that CD4 is positive in a minority of cells.
Mycosis fungoides. Dermal, mostly perivascular, superficial lymphocytic infiltrate, with intraepidermal lymphocytes. Epidermis shows minimal hyperkeratosis.
Mycosis fungoides. Intraepithelial lymphocytes show a pale perinuclear halo and mildly hyperchromic nuclei with an irregular profile. There is no spongiosis.
Mycosis fungoides. Intraepithelial lymphocytes show a pale perinuclear halo and mildly hyperchromic nuclei with an irregular profile. There is no spongiosis.
Mycosis fungoides. CD3 (shown here) and CD4 immunostaining highlights the T-helper immunophenotype of the lesion.
Mycosis fungoides. CD4 (shown here) and CD3 immunostaining highlights the T-helper immunophenotype of the lesion.

Q: The presence of atypical T-lymphocytes migrating into the epidermis to form intraepidermal collections known as Pautrier microabscesses is a pathognomonic histologic finding in [...].
Mycosis fungoides. Skin with junctional and intraepidermal lymphocytic infiltrate.
Mycosis fungoides. Dermal, mostly perivascular, superficial lymphocytic infiltrate, with intraepidermal lymphocytes. Epidermis shows minimal hyperkeratosis.
A: Mycosis Fungoides
Back Extra: Mycosis Fungoides
- Clinical: Mycosis fungoides in children is rare and often presents as hypopigmented patches and plaques, with a good prognosis and rare progression to advanced stages.
- Micro: Histopathology shows a predominantly dermal, band-like, perivascular, and periadnexal infiltrate of small lymphocytes with cerebriform nuclei and intraepidermal Pautrier microabscesses.
- Ancillary: Immunohistochemistry reveals a T-helper immunophenotype (CD3+, CD4+, CD5+, CD7−, CD8−) with characteristic clonal TR gene rearrangements.
Reference Gallery:
Mycosis fungoides. Skin with junctional and intraepidermal lymphocytic infiltrate.
Mycosis fungoides. At high power, lymphoid cells are aligned along the basal layer and show cerebriform nuclei.
Mycosis fungoides. Immunostaining shows diffuse positivity of lymphoid cells for CD3.
Mycosis fungoides. Immunostaining shows a prevalent population of CD8+ cells.
Mycosis fungoides. Immunostaining shows that CD5 expression is preserved in the clonal CD8+ population.
Mycosis fungoides. Immunostaining shows that CD7 expression is reduced in the clonal CD8+ population.
Mycosis fungoides. Immunostaining shows that CD4 is positive in a minority of cells.
Mycosis fungoides. Dermal, mostly perivascular, superficial lymphocytic infiltrate, with intraepidermal lymphocytes. Epidermis shows minimal hyperkeratosis.
Mycosis fungoides. Intraepithelial lymphocytes show a pale perinuclear halo and mildly hyperchromic nuclei with an irregular profile. There is no spongiosis.
Mycosis fungoides. Intraepithelial lymphocytes show a pale perinuclear halo and mildly hyperchromic nuclei with an irregular profile. There is no spongiosis.
Mycosis fungoides. CD3 (shown here) and CD4 immunostaining highlights the T-helper immunophenotype of the lesion.
Mycosis fungoides. CD4 (shown here) and CD3 immunostaining highlights the T-helper immunophenotype of the lesion.

Q: In Paediatric Nodal Marginal Zone Lymphoma, the lymph node architecture is partially effaced by expanded pale marginal zones, often featuring hyperplastic follicles that morphologically resemble [...] (PTGC).
Typical features of paediatric nodal marginal zone lymphoma. Hyperplastic follicles resembling progressive transformation of germinal centres with expanded paler marginal zones. Some reactive germinal centres are also still present.
Paediatric nodal marginal zone lymphoma. At low magnification, the retained organoid architecture is seen, with follicles and pale, markedly expanded interfollicular areas.
A: progressive transformation of germinal centers
Back Extra: Paediatric Nodal Marginal Zone Lymphoma
- Clinical: Patients with Paediatric Nodal Marginal Zone Lymphoma (PNMZL) usually present with localized stage I/II disease, peripheral lymphadenopathy, and normal serum LDH levels.
- Micro: The lymph node architecture in PNMZL is partially effaced by an interfollicular proliferation with markedly expanded pale marginal zones and attenuated sinuses.
- Ancillary: Essential ancillary studies for PNMZL include the detection of clonal rearrangements of IGH and IGK genes and the presence of CD43-positive B cells.
Reference Gallery:
Paediatric nodal marginal zone lymphoma. Pale marginal zone cells partially disrupt follicle mantles with follicular colonization.
Paediatric nodal marginal zone lymphoma. There is a spectrum of small to medium-sized cells with cleared cytoplasm and some intermingled large cells.
Typical features of paediatric nodal marginal zone lymphoma. Hyperplastic follicles resembling progressive transformation of germinal centres with expanded paler marginal zones. Some reactive germinal centres are also still present.
Typical features of paediatric nodal marginal zone lymphoma. CD20 stains follicles and perifollicular and interfollicular B cells.
Typical features of paediatric nodal marginal zone lymphoma. IgD-positive mantle cells penetrating the germinal centres. There is infiltration at the periphery by marginal zone cells.
Typical features of paediatric nodal marginal zone lymphoma. Remnants of reactive germinal centres are highlighted by the presence of CD10-positive B cells.
Typical features of paediatric nodal marginal zone lymphoma. Remnants of reactive germinal centres are highlighted by the presence of BCL2-negative B cells.
Typical features of paediatric nodal marginal zone lymphoma. Residual germinal centre follicles contain abundant PD1+ T cells.
Paediatric nodal marginal zone lymphoma. Detection of IGH and IGK gene rearrangements. A dominant peak (red arrow) of PCR products of identical size, indicating a clonal expansion within a polyclonal background, is evident in the IGH-FR1 and IGH-FR2 reactions (shown here), as well as in the IGK-DE amplification.
Paediatric nodal marginal zone lymphoma. Detection of IGH and IGK gene rearrangements by gene scan. A dominant peak (red arrow) of PCR products of identical size, indicating a clonal expansion within a polyclonal background, is evident in the IGK-DE amplification (shown here), as well as in the IGH-FR1 and IGH-FR2 reactions.
Paediatric nodal marginal zone lymphoma. At low magnification, the retained organoid architecture is seen, with follicles and pale, markedly expanded interfollicular areas.

Q: A critical ancillary finding used to confirm Paediatric Nodal Marginal Zone Lymphoma is the PCR detection of clonal [...] gene rearrangements.
Paediatric nodal marginal zone lymphoma. Detection of IGH and IGK gene rearrangements. A dominant peak (red arrow) of PCR products of identical size, indicating a clonal expansion within a polyclonal background, is evident in the IGH-FR1 and IGH-FR2 reactions (shown here), as well as in the IGK-DE amplification.
Paediatric nodal marginal zone lymphoma. Detection of IGH and IGK gene rearrangements by gene scan. A dominant peak (red arrow) of PCR products of identical size, indicating a clonal expansion within a polyclonal background, is evident in the IGK-DE amplification (shown here), as well as in the IGH-FR1 and IGH-FR2 reactions.
A: IGH and IGK
Back Extra: Paediatric Nodal Marginal Zone Lymphoma
- Clinical: Patients with Paediatric Nodal Marginal Zone Lymphoma (PNMZL) usually present with localized stage I/II disease, peripheral lymphadenopathy, and normal serum LDH levels.
- Micro: The lymph node architecture in PNMZL is partially effaced by an interfollicular proliferation with markedly expanded pale marginal zones and attenuated sinuses.
- Ancillary: Essential ancillary studies for PNMZL include the detection of clonal rearrangements of IGH and IGK genes and the presence of CD43-positive B cells.
Reference Gallery:
Paediatric nodal marginal zone lymphoma. Pale marginal zone cells partially disrupt follicle mantles with follicular colonization.
Paediatric nodal marginal zone lymphoma. There is a spectrum of small to medium-sized cells with cleared cytoplasm and some intermingled large cells.
Typical features of paediatric nodal marginal zone lymphoma. Hyperplastic follicles resembling progressive transformation of germinal centres with expanded paler marginal zones. Some reactive germinal centres are also still present.
Typical features of paediatric nodal marginal zone lymphoma. CD20 stains follicles and perifollicular and interfollicular B cells.
Typical features of paediatric nodal marginal zone lymphoma. IgD-positive mantle cells penetrating the germinal centres. There is infiltration at the periphery by marginal zone cells.
Typical features of paediatric nodal marginal zone lymphoma. Remnants of reactive germinal centres are highlighted by the presence of CD10-positive B cells.
Typical features of paediatric nodal marginal zone lymphoma. Remnants of reactive germinal centres are highlighted by the presence of BCL2-negative B cells.
Typical features of paediatric nodal marginal zone lymphoma. Residual germinal centre follicles contain abundant PD1+ T cells.
Paediatric nodal marginal zone lymphoma. Detection of IGH and IGK gene rearrangements. A dominant peak (red arrow) of PCR products of identical size, indicating a clonal expansion within a polyclonal background, is evident in the IGH-FR1 and IGH-FR2 reactions (shown here), as well as in the IGK-DE amplification.
Paediatric nodal marginal zone lymphoma. Detection of IGH and IGK gene rearrangements by gene scan. A dominant peak (red arrow) of PCR products of identical size, indicating a clonal expansion within a polyclonal background, is evident in the IGK-DE amplification (shown here), as well as in the IGH-FR1 and IGH-FR2 reactions.
Paediatric nodal marginal zone lymphoma. At low magnification, the retained organoid architecture is seen, with follicles and pale, markedly expanded interfollicular areas.

Q: A characteristic histologic feature of Paediatric Nodal Marginal Zone Lymphoma is the partial disruption of follicle mantles by pale marginal zone cells, resulting in a distinct pattern known as [...].
Paediatric nodal marginal zone lymphoma. Pale marginal zone cells partially disrupt follicle mantles with follicular colonization.
A: follicular colonization
Back Extra: Paediatric Nodal Marginal Zone Lymphoma
- Clinical: Patients with Paediatric Nodal Marginal Zone Lymphoma (PNMZL) usually present with localized stage I/II disease, peripheral lymphadenopathy, and normal serum LDH levels.
- Micro: The lymph node architecture in PNMZL is partially effaced by an interfollicular proliferation with markedly expanded pale marginal zones and attenuated sinuses.
- Ancillary: Essential ancillary studies for PNMZL include the detection of clonal rearrangements of IGH and IGK genes and the presence of CD43-positive B cells.
Reference Gallery:
Paediatric nodal marginal zone lymphoma. Pale marginal zone cells partially disrupt follicle mantles with follicular colonization.
Paediatric nodal marginal zone lymphoma. There is a spectrum of small to medium-sized cells with cleared cytoplasm and some intermingled large cells.
Typical features of paediatric nodal marginal zone lymphoma. Hyperplastic follicles resembling progressive transformation of germinal centres with expanded paler marginal zones. Some reactive germinal centres are also still present.
Typical features of paediatric nodal marginal zone lymphoma. CD20 stains follicles and perifollicular and interfollicular B cells.
Typical features of paediatric nodal marginal zone lymphoma. IgD-positive mantle cells penetrating the germinal centres. There is infiltration at the periphery by marginal zone cells.
Typical features of paediatric nodal marginal zone lymphoma. Remnants of reactive germinal centres are highlighted by the presence of CD10-positive B cells.
Typical features of paediatric nodal marginal zone lymphoma. Remnants of reactive germinal centres are highlighted by the presence of BCL2-negative B cells.
Typical features of paediatric nodal marginal zone lymphoma. Residual germinal centre follicles contain abundant PD1+ T cells.
Paediatric nodal marginal zone lymphoma. Detection of IGH and IGK gene rearrangements. A dominant peak (red arrow) of PCR products of identical size, indicating a clonal expansion within a polyclonal background, is evident in the IGH-FR1 and IGH-FR2 reactions (shown here), as well as in the IGK-DE amplification.
Paediatric nodal marginal zone lymphoma. Detection of IGH and IGK gene rearrangements by gene scan. A dominant peak (red arrow) of PCR products of identical size, indicating a clonal expansion within a polyclonal background, is evident in the IGK-DE amplification (shown here), as well as in the IGH-FR1 and IGH-FR2 reactions.
Paediatric nodal marginal zone lymphoma. At low magnification, the retained organoid architecture is seen, with follicles and pale, markedly expanded interfollicular areas.

Q: Histologically, Paediatric-type follicular lymphoma is characterized by expansile follicles surrounded by a rim of reactive tissue, producing a characteristic [...] appearance.
Paediatric-type follicular lymphoma. CD20 highlights the pure follicular architecture with expansile follicles, giving a node-in-node appearance at low power, with a rim of reactive lymph node tissue.
A: "node-in-node"
Back Extra: Paediatric-type follicular lymphoma
- Clinical: Paediatric-type follicular lymphoma (PTFL) typically presents with single painless lymph node enlargement in the head and neck region, most commonly in adolescent males.
- Micro: PTFL is characterized by a pure follicular growth pattern with atypical, enlarged follicles and a rim of reactive lymph node tissue, often described as a 'node-in-node' appearance.
- Ancillary: Neoplastic cells in PTFL are positive for B-cell markers (CD20, CD79a, PAX5) and germinal-center markers (CD10, BCL6), with a high proliferation index (> 30%) and negative for BCL2.
Reference Gallery:
Paediatric-type follicular lymphoma. CD20 highlights the pure follicular architecture with expansile follicles, giving a node-in-node appearance at low power, with a rim of reactive lymph node tissue.
Paediatric-type follicular lymphoma. CD10 is confined to the follicles and spares the interfollicular areas.
Paediatric-type follicular lymphoma. Comparison of paediatric-type follicular lymphoma (left) and reactive lymph node (right). The follicles of paediatric-type follicular lymphoma lack zonation and the mantle is thinned; tingible-body macrophages are present.
Paediatric-type follicular lymphoma. High-power view shows medium-sized cells with small nucleoli.

Q: Microscopically, the neoplastic follicles of Paediatric-type follicular lymphoma are distinguished from reactive follicles by an attenuated mantle zone and a lack of [...], despite retaining tingible-body macrophages.
Paediatric-type follicular lymphoma. Comparison of paediatric-type follicular lymphoma (left) and reactive lymph node (right). The follicles of paediatric-type follicular lymphoma lack zonation and the mantle is thinned; tingible-body macrophages are present.
Paediatric-type follicular lymphoma. High-power view shows medium-sized cells with small nucleoli.
A: zonation
Back Extra: Paediatric-type follicular lymphoma
- Clinical: Paediatric-type follicular lymphoma (PTFL) typically presents with single painless lymph node enlargement in the head and neck region, most commonly in adolescent males.
- Micro: PTFL is characterized by a pure follicular growth pattern with atypical, enlarged follicles and a rim of reactive lymph node tissue, often described as a 'node-in-node' appearance.
- Ancillary: Neoplastic cells in PTFL are positive for B-cell markers (CD20, CD79a, PAX5) and germinal-center markers (CD10, BCL6), with a high proliferation index (> 30%) and negative for BCL2.
Reference Gallery:
Paediatric-type follicular lymphoma. CD20 highlights the pure follicular architecture with expansile follicles, giving a node-in-node appearance at low power, with a rim of reactive lymph node tissue.
Paediatric-type follicular lymphoma. CD10 is confined to the follicles and spares the interfollicular areas.
Paediatric-type follicular lymphoma. Comparison of paediatric-type follicular lymphoma (left) and reactive lymph node (right). The follicles of paediatric-type follicular lymphoma lack zonation and the mantle is thinned; tingible-body macrophages are present.
Paediatric-type follicular lymphoma. High-power view shows medium-sized cells with small nucleoli.

Q: Histologically, Peripheral T-cell lymphoma NOS often presents with a variable inflammatory background intermixed with atypical, [...] that have irregular nuclei.
Peripheral T-cell lymphoma NOS. An example in a patient with Nijmegen breakage syndrome with epithelioid cell reaction, eosinophils, and scattered large pleomorphic blasts.
Peripheral T-cell lymphoma NOS. Medium-sized polymorphic blasts.
A: medium-sized polymorphic cells
Back Extra: Peripheral T-cell lymphoma NOS
- Clinical: The clinical features of Peripheral T-cell lymphoma NOS are often related to the tumor site and extent, with B symptoms typically not present even at advanced stages.
- Micro: The microscopic appearance includes medium-sized polymorphic cells with irregular nuclei and a variable number of inflammatory cells mixed in the tissue.
- Ancillary: CD3 is usually positive, and TdT should be negative; any expression of TdT suggests lymphoblastic lymphoma.
Reference Gallery:
Peripheral T-cell lymphoma NOS. An example in a patient with Nijmegen breakage syndrome with epithelioid cell reaction, eosinophils, and scattered large pleomorphic blasts.
Peripheral T-cell lymphoma NOS. Positive staining for CD3.
Peripheral T-cell lymphoma NOS. Medium-sized polymorphic blasts.

Q: Immunohistochemical evaluation of Peripheral T-cell lymphoma NOS typically demonstrates diffuse, positive staining for the pan-T-cell marker [...].
Peripheral T-cell lymphoma NOS. Positive staining for CD3.
A: CD3
Back Extra: Peripheral T-cell lymphoma NOS
- Clinical: The clinical features of Peripheral T-cell lymphoma NOS are often related to the tumor site and extent, with B symptoms typically not present even at advanced stages.
- Micro: The microscopic appearance includes medium-sized polymorphic cells with irregular nuclei and a variable number of inflammatory cells mixed in the tissue.
- Ancillary: CD3 is usually positive, and TdT should be negative; any expression of TdT suggests lymphoblastic lymphoma.
Reference Gallery:
Peripheral T-cell lymphoma NOS. An example in a patient with Nijmegen breakage syndrome with epithelioid cell reaction, eosinophils, and scattered large pleomorphic blasts.
Peripheral T-cell lymphoma NOS. Positive staining for CD3.
Peripheral T-cell lymphoma NOS. Medium-sized polymorphic blasts.

Q: In Plasmablastic Lymphoma, the tumor cells characteristically express terminal B-cell differentiation markers (e.g., IRF4/MUM1, CD38, CD138) but are almost universally negative for the mature B-cell marker [...].
Plasmablastic lymphoma. CD20 expression is negative in virtually all cells. Only isolated positive cells may be seen.
Plasmablastic lymphoma. IRF4 (MUM1) expression is a constant feature, together with the expression of terminal B-cell differentiation markers such as Blimp1, CD38, and CD138.
A: CD20
Back Extra: Plasmablastic Lymphoma
- Clinical: Plasmablastic lymphoma in children often involves extranodal sites such as the nasal/oral cavity, skin and soft tissue, digestive system, and CNS, with a male predilection and a mean age of 10 years.
- Micro: The tumor is characterized by a diffuse infiltration of large immunoblasts and plasmablasts, with a prominent starry-sky pattern and common mitotic figures.
- Ancillary: MYC protein expression is consistently found, and EBV-encoded small RNA (EBER) is positive in virtually all paediatric cases, aiding in diagnosis.
Reference Gallery:
Plasmablastic lymphoma. Diffuse neoplastic proliferation of immunoblastic and plasmablastic lymphoid cells. Scattered histiocytes and reactive lymphocytes are seen.
Plasmablastic lymphoma. Morphological detail showing large cells with a high N:C ratio, vesicular chromatin, and prominent nucleoli. Abundant mitoses are seen.
Plasmablastic lymphoma. MYC positivity by immunohistochemistry is seen in almost every case. The proportion of positive cells correlates with the presence of MYC gene rearrangements.
Plasmablastic lymphoma. CD20 expression is negative in virtually all cells. Only isolated positive cells may be seen.
Plasmablastic lymphoma. IRF4 (MUM1) expression is a constant feature, together with the expression of terminal B-cell differentiation markers such as Blimp1, CD38, and CD138.
Plasmablastic lymphoma. The proliferation index as measured with Ki-67 is very high (close to 100%).
Plasmablastic lymphoma. EBV can be demonstrated in the vast majority of immunodeficiency-associated cases. EBV-encoded small RNA (EBER) is required because of the EBV latency pattern.
Plasmablastic lymphoma. FISH analysis with a MYC break-apart probe shows a rearranged pattern in most of the cells.

Q: The vast majority of immunodeficiency-associated and pediatric cases of Plasmablastic Lymphoma are driven by [...], which is consistently demonstrated using EBER in situ hybridization.
Plasmablastic lymphoma. EBV can be demonstrated in the vast majority of immunodeficiency-associated cases. EBV-encoded small RNA (EBER) is required because of the EBV latency pattern.
A: Epstein-Barr virus (EBV)
Back Extra: Plasmablastic Lymphoma
- Clinical: Plasmablastic lymphoma in children often involves extranodal sites such as the nasal/oral cavity, skin and soft tissue, digestive system, and CNS, with a male predilection and a mean age of 10 years.
- Micro: The tumor is characterized by a diffuse infiltration of large immunoblasts and plasmablasts, with a prominent starry-sky pattern and common mitotic figures.
- Ancillary: MYC protein expression is consistently found, and EBV-encoded small RNA (EBER) is positive in virtually all paediatric cases, aiding in diagnosis.
Reference Gallery:
Plasmablastic lymphoma. Diffuse neoplastic proliferation of immunoblastic and plasmablastic lymphoid cells. Scattered histiocytes and reactive lymphocytes are seen.
Plasmablastic lymphoma. Morphological detail showing large cells with a high N:C ratio, vesicular chromatin, and prominent nucleoli. Abundant mitoses are seen.
Plasmablastic lymphoma. MYC positivity by immunohistochemistry is seen in almost every case. The proportion of positive cells correlates with the presence of MYC gene rearrangements.
Plasmablastic lymphoma. CD20 expression is negative in virtually all cells. Only isolated positive cells may be seen.
Plasmablastic lymphoma. IRF4 (MUM1) expression is a constant feature, together with the expression of terminal B-cell differentiation markers such as Blimp1, CD38, and CD138.
Plasmablastic lymphoma. The proliferation index as measured with Ki-67 is very high (close to 100%).
Plasmablastic lymphoma. EBV can be demonstrated in the vast majority of immunodeficiency-associated cases. EBV-encoded small RNA (EBER) is required because of the EBV latency pattern.
Plasmablastic lymphoma. FISH analysis with a MYC break-apart probe shows a rearranged pattern in most of the cells.

Q: Plasmablastic Lymphoma consistently demonstrates strong nuclear positivity for MYC protein by immunohistochemistry, which closely correlates with the presence of [...] detected by FISH analysis.
Plasmablastic lymphoma. MYC positivity by immunohistochemistry is seen in almost every case. The proportion of positive cells correlates with the presence of MYC gene rearrangements.
Plasmablastic lymphoma. FISH analysis with a MYC break-apart probe shows a rearranged pattern in most of the cells.
A: MYC gene rearrangements
Back Extra: Plasmablastic Lymphoma
- Clinical: Plasmablastic lymphoma in children often involves extranodal sites such as the nasal/oral cavity, skin and soft tissue, digestive system, and CNS, with a male predilection and a mean age of 10 years.
- Micro: The tumor is characterized by a diffuse infiltration of large immunoblasts and plasmablasts, with a prominent starry-sky pattern and common mitotic figures.
- Ancillary: MYC protein expression is consistently found, and EBV-encoded small RNA (EBER) is positive in virtually all paediatric cases, aiding in diagnosis.
Reference Gallery:
Plasmablastic lymphoma. Diffuse neoplastic proliferation of immunoblastic and plasmablastic lymphoid cells. Scattered histiocytes and reactive lymphocytes are seen.
Plasmablastic lymphoma. Morphological detail showing large cells with a high N:C ratio, vesicular chromatin, and prominent nucleoli. Abundant mitoses are seen.
Plasmablastic lymphoma. MYC positivity by immunohistochemistry is seen in almost every case. The proportion of positive cells correlates with the presence of MYC gene rearrangements.
Plasmablastic lymphoma. CD20 expression is negative in virtually all cells. Only isolated positive cells may be seen.
Plasmablastic lymphoma. IRF4 (MUM1) expression is a constant feature, together with the expression of terminal B-cell differentiation markers such as Blimp1, CD38, and CD138.
Plasmablastic lymphoma. The proliferation index as measured with Ki-67 is very high (close to 100%).
Plasmablastic lymphoma. EBV can be demonstrated in the vast majority of immunodeficiency-associated cases. EBV-encoded small RNA (EBER) is required because of the EBV latency pattern.
Plasmablastic lymphoma. FISH analysis with a MYC break-apart probe shows a rearranged pattern in most of the cells.

Q: A young female presenting with airway obstruction due to a large, intensely FDG-avid anterior mediastinal mass on imaging is classic for [...].
Primary mediastinal large B-cell lymphoma. Contrast-enhanced axial CT image shows a lobular, heterogeneously enhancing soft tissue mass involving both prevascular and visceral spaces, which encases the bilateral main bronchi.
Primary mediastinal large B-cell lymphoma. Fusion FDG PET-CT axial image shows intense tracer uptake by the mass.
A: Primary Mediastinal Large B-Cell Lymphoma
Back Extra: Primary Mediastinal Large B-Cell Lymphoma
- Clinical: Primary mediastinal large B-cell lymphoma (PMBCL) often presents with symptoms of airway obstruction and effusions, and is more common in adolescents and young adults, with a slight female predominance in European populations.
- Micro: The histopathology of PMBCL shows a diffuse growth pattern with large cells forming clusters or sheets, often with a distinctive fibrosis made up of irregular collagen bands.
- Ancillary: PMBCL typically expresses CD20, CD30 (weak and heterogeneous), IRF4 (MUM1), and CD23, and frequently shows copy-number gains and amplifications in the 9p24.1 region, leading to overexpression of PDL1 and PDL2.
Reference Gallery:
Primary mediastinal large B-cell lymphoma. CT of a patient with a primary mediastinal (thymic) large B-cell lymphoma.
Primary mediastinal (thymic) large B-cell lymphoma. Histopathology of a typical case showing a centroblast-like morphology.
Primary mediastinal (thymic) large B-cell lymphoma. Strong and diffuse expression of CD20.
Primary mediastinal (thymic) large B-cell lymphoma. Variable expression of CD23.
Primary mediastinal (thymic) large B-cell lymphoma. Typical example showing sheets of blasts with clear or pale eosinophilic cytoplasm, with accompanying sclerosis and infiltration of the skeletal muscle of the chest wall.
Primary mediastinal (thymic) large B-cell lymphoma. Variable expression of CD23.
Primary mediastinal large B-cell lymphoma. Contrast-enhanced axial CT image shows a lobular, heterogeneously enhancing soft tissue mass involving both prevascular and visceral spaces, which encases the bilateral main bronchi.
Primary mediastinal large B-cell lymphoma. Fusion FDG PET-CT axial image shows intense tracer uptake by the mass.

Q: The histopathology of Primary Mediastinal Large B-Cell Lymphoma often demonstrates sheets of large blasts with clear or pale eosinophilic cytoplasm, accompanied by distinctive compartmentalizing bands of [...].
Primary mediastinal (thymic) large B-cell lymphoma. Histopathology of a typical case showing a centroblast-like morphology.
Primary mediastinal (thymic) large B-cell lymphoma. Typical example showing sheets of blasts with clear or pale eosinophilic cytoplasm, with accompanying sclerosis and infiltration of the skeletal muscle of the chest wall.
A: sclerosis
Back Extra: Primary Mediastinal Large B-Cell Lymphoma
- Clinical: Primary mediastinal large B-cell lymphoma (PMBCL) often presents with symptoms of airway obstruction and effusions, and is more common in adolescents and young adults, with a slight female predominance in European populations.
- Micro: The histopathology of PMBCL shows a diffuse growth pattern with large cells forming clusters or sheets, often with a distinctive fibrosis made up of irregular collagen bands.
- Ancillary: PMBCL typically expresses CD20, CD30 (weak and heterogeneous), IRF4 (MUM1), and CD23, and frequently shows copy-number gains and amplifications in the 9p24.1 region, leading to overexpression of PDL1 and PDL2.
Reference Gallery:
Primary mediastinal large B-cell lymphoma. CT of a patient with a primary mediastinal (thymic) large B-cell lymphoma.
Primary mediastinal (thymic) large B-cell lymphoma. Histopathology of a typical case showing a centroblast-like morphology.
Primary mediastinal (thymic) large B-cell lymphoma. Strong and diffuse expression of CD20.
Primary mediastinal (thymic) large B-cell lymphoma. Variable expression of CD23.
Primary mediastinal (thymic) large B-cell lymphoma. Typical example showing sheets of blasts with clear or pale eosinophilic cytoplasm, with accompanying sclerosis and infiltration of the skeletal muscle of the chest wall.
Primary mediastinal (thymic) large B-cell lymphoma. Variable expression of CD23.
Primary mediastinal large B-cell lymphoma. Contrast-enhanced axial CT image shows a lobular, heterogeneously enhancing soft tissue mass involving both prevascular and visceral spaces, which encases the bilateral main bronchi.
Primary mediastinal large B-cell lymphoma. Fusion FDG PET-CT axial image shows intense tracer uptake by the mass.

Q: Immunohistochemistry in Primary Mediastinal Large B-Cell Lymphoma reveals strong, diffuse expression of the B-cell marker CD20 alongside variable but characteristic expression of [...].
Primary mediastinal (thymic) large B-cell lymphoma. Strong and diffuse expression of CD20.
Primary mediastinal (thymic) large B-cell lymphoma. Variable expression of CD23.
A: CD23
Back Extra: Primary Mediastinal Large B-Cell Lymphoma
- Clinical: Primary mediastinal large B-cell lymphoma (PMBCL) often presents with symptoms of airway obstruction and effusions, and is more common in adolescents and young adults, with a slight female predominance in European populations.
- Micro: The histopathology of PMBCL shows a diffuse growth pattern with large cells forming clusters or sheets, often with a distinctive fibrosis made up of irregular collagen bands.
- Ancillary: PMBCL typically expresses CD20, CD30 (weak and heterogeneous), IRF4 (MUM1), and CD23, and frequently shows copy-number gains and amplifications in the 9p24.1 region, leading to overexpression of PDL1 and PDL2.
Reference Gallery:
Primary mediastinal large B-cell lymphoma. CT of a patient with a primary mediastinal (thymic) large B-cell lymphoma.
Primary mediastinal (thymic) large B-cell lymphoma. Histopathology of a typical case showing a centroblast-like morphology.
Primary mediastinal (thymic) large B-cell lymphoma. Strong and diffuse expression of CD20.
Primary mediastinal (thymic) large B-cell lymphoma. Variable expression of CD23.
Primary mediastinal (thymic) large B-cell lymphoma. Typical example showing sheets of blasts with clear or pale eosinophilic cytoplasm, with accompanying sclerosis and infiltration of the skeletal muscle of the chest wall.
Primary mediastinal (thymic) large B-cell lymphoma. Variable expression of CD23.
Primary mediastinal large B-cell lymphoma. Contrast-enhanced axial CT image shows a lobular, heterogeneously enhancing soft tissue mass involving both prevascular and visceral spaces, which encases the bilateral main bronchi.
Primary mediastinal large B-cell lymphoma. Fusion FDG PET-CT axial image shows intense tracer uptake by the mass.

Q: A characteristic histologic feature of Subcutaneous Panniculitis-like T-cell Lymphoma is the [...] of individual adipocytes by medium-sized, atypical lymphoid cells.
Subcutaneous panniculitis-like T-cell lymphoma. Medium-sized lymphoid cells surround single adipocytes. Histiocytes are also present.
Subcutaneous panniculitis-like T-cell lymphoma. Uniform hyperchromatic lymphoid cells infiltrate the subcutaneous fat lobules, with the characteristic rimming of single adipocytes.
A: rimming
Back Extra: Subcutaneous Panniculitis-like T-cell Lymphoma
- Clinical: Patients typically present with multiple subcutaneous nodules or deep plaques, most frequently on the extremities or trunk, and systemic symptoms in approximately 60% of cases.
- Micro: SPTCL shows a dense panniculitis-like infiltrate involving the subcutaneous fat lobules, with medium-sized lymphoid cells that rim individual adipocytes and are often admixed with numerous histiocytes.
- Ancillary: The lymphoma cells have a mature αβ T-cell phenotype (CD3+ and usually CD8+), with expression of cytotoxic molecules including granzyme B, perforin, and TIA1.
Reference Gallery:
Subcutaneous panniculitis-like T-cell lymphoma. Medium-sized lymphoid cells surround single adipocytes. Histiocytes are also present.
Subcutaneous panniculitis-like T-cell lymphoma. CD8 immunohistochemistry highlights tumour cells.
Subcutaneous panniculitis-like T-cell lymphoma. Uniform hyperchromatic lymphoid cells infiltrate the subcutaneous fat lobules.
Subcutaneous panniculitis-like T-cell lymphoma. The cells are CD3-positive.
Subcutaneous panniculitis-like T-cell lymphoma. The cells express βF1.
Subcutaneous panniculitis-like T-cell lymphoma. Uniform hyperchromatic lymphoid cells infiltrate the subcutaneous fat lobules, with the characteristic rimming of single adipocytes.
Subcutaneous panniculitis-like T-cell lymphoma. Uniform hyperchromatic lymphoid cells infiltrate the subcutaneous fat lobules, with the characteristic rimming of single adipocytes.
Subcutaneous panniculitis-like T-cell lymphoma. Positive perforin immunohistochemistry.

Q: By immunohistochemistry, the neoplastic cells of Subcutaneous Panniculitis-like T-cell Lymphoma demonstrate a mature $\alpha\beta$ T-cell phenotype that is characteristically positive for CD3, cytotoxic molecules (e.g., perforin), and [...].
Subcutaneous panniculitis-like T-cell lymphoma. CD8 immunohistochemistry highlights tumour cells.
Subcutaneous panniculitis-like T-cell lymphoma. The cells are CD3-positive.
Subcutaneous panniculitis-like T-cell lymphoma. Positive perforin immunohistochemistry.
A: CD8
Back Extra: Subcutaneous Panniculitis-like T-cell Lymphoma
- Clinical: Patients typically present with multiple subcutaneous nodules or deep plaques, most frequently on the extremities or trunk, and systemic symptoms in approximately 60% of cases.
- Micro: SPTCL shows a dense panniculitis-like infiltrate involving the subcutaneous fat lobules, with medium-sized lymphoid cells that rim individual adipocytes and are often admixed with numerous histiocytes.
- Ancillary: The lymphoma cells have a mature αβ T-cell phenotype (CD3+ and usually CD8+), with expression of cytotoxic molecules including granzyme B, perforin, and TIA1.
Reference Gallery:
Subcutaneous panniculitis-like T-cell lymphoma. Medium-sized lymphoid cells surround single adipocytes. Histiocytes are also present.
Subcutaneous panniculitis-like T-cell lymphoma. CD8 immunohistochemistry highlights tumour cells.
Subcutaneous panniculitis-like T-cell lymphoma. Uniform hyperchromatic lymphoid cells infiltrate the subcutaneous fat lobules.
Subcutaneous panniculitis-like T-cell lymphoma. The cells are CD3-positive.
Subcutaneous panniculitis-like T-cell lymphoma. The cells express βF1.
Subcutaneous panniculitis-like T-cell lymphoma. Uniform hyperchromatic lymphoid cells infiltrate the subcutaneous fat lobules, with the characteristic rimming of single adipocytes.
Subcutaneous panniculitis-like T-cell lymphoma. Uniform hyperchromatic lymphoid cells infiltrate the subcutaneous fat lobules, with the characteristic rimming of single adipocytes.
Subcutaneous panniculitis-like T-cell lymphoma. Positive perforin immunohistochemistry.

Q: In Systemic EBV-positive T-cell lymphoma of childhood, the neoplastic lymphocytes typically exhibit a cytotoxic T-cell phenotype, being strongly positive for CD8 and TIA1, and are uniformly positive for [...] by in situ hybridization.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. Double staining for CD8 (brown) and by in situ hybridization for EBV-encoded small RNA (EBER) (black) shows that many CD8+ cells are positive for EBV RNA.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. In situ hybridization shows that the neoplastic cells are positive for EBV-encoded small RNA (EBER).
A: EBV-encoded small RNA (EBER)
Back Extra: Systemic EBV-positive T-cell lymphoma of childhood
- Clinical: Systemic EBV-positive T-cell lymphoma of childhood presents with symptoms of infectious mononucleosis, hepatosplenomegaly, and liver failure, and is often complicated by hemophagocytic syndrome.
- Micro: The lymph nodes show preserved architecture with expanded interfollicular areas containing small to large atypical lymphocytes, with prominent apoptosis and frequent mitoses.
- Ancillary: The neoplastic cells are CD8+, TIA1+, and positive for EBV-encoded small RNA (EBER).
Reference Gallery:
Systemic EBV-positive T-cell lymphoma of childhood. Small lymph node with relatively preserved architecture, with residual regressive follicles and an expanded interfollicular area.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating lymphocytes are CD8+
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The interfollicular infiltrate is polymorphic, with small cells lacking cytological atypia intermingled with some relatively large cells with irregular nuclei and prominent nucleoli.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. Double staining for CD8 (brown) and by in situ hybridization for EBV-encoded small RNA (EBER) (black) shows that many CD8+ cells are positive for EBV RNA.
Systemic EBV-positive T-cell lymphoma of childhood. The lymph node shows partial preservation of the architecture, with residual follicles with regressive germinal centres and expansion of the interfollicular area by large atypical cells with clear cytoplasm.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating lymphocytes are predominantly large cells with irregular nuclei and several prominent nucleoli, and with abundant clear cytoplasm. Prominent apoptosis and frequent mitosis are observed.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating cells are CD8+
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. In situ hybridization shows that the neoplastic cells are positive for EBV-encoded small RNA (EBER).
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. Some atypical cells are positive for LMP1.
Systemic EBV-positive T-cell lymphoma of childhood. The spleen shows a depleted white pulp with congestive red pulp.
Systemic EBV-positive T-cell lymphoma of childhood. Spleen. In situ hybridization for EBV-encoded small RNA (EBER) demonstrates a mild sinusoidal infiltrate positive for EBV RNA.
Systemic EBV-positive T-cell lymphoma of childhood. The spleen shows a subtle sinusoidal lymphoid infiltrate with striking haemophagocytosis.

Q: Clinically, Systemic EBV-positive T-cell lymphoma of childhood frequently presents with fulminant infectious mononucleosis-like symptoms and is often complicated by a rapidly fatal [...].
Systemic EBV-positive T-cell lymphoma of childhood. The spleen shows a subtle sinusoidal lymphoid infiltrate with striking haemophagocytosis.
A: hemophagocytic syndrome
Back Extra: Systemic EBV-positive T-cell lymphoma of childhood
- Clinical: Systemic EBV-positive T-cell lymphoma of childhood presents with symptoms of infectious mononucleosis, hepatosplenomegaly, and liver failure, and is often complicated by hemophagocytic syndrome.
- Micro: The lymph nodes show preserved architecture with expanded interfollicular areas containing small to large atypical lymphocytes, with prominent apoptosis and frequent mitoses.
- Ancillary: The neoplastic cells are CD8+, TIA1+, and positive for EBV-encoded small RNA (EBER).
Reference Gallery:
Systemic EBV-positive T-cell lymphoma of childhood. Small lymph node with relatively preserved architecture, with residual regressive follicles and an expanded interfollicular area.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating lymphocytes are CD8+
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The interfollicular infiltrate is polymorphic, with small cells lacking cytological atypia intermingled with some relatively large cells with irregular nuclei and prominent nucleoli.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. Double staining for CD8 (brown) and by in situ hybridization for EBV-encoded small RNA (EBER) (black) shows that many CD8+ cells are positive for EBV RNA.
Systemic EBV-positive T-cell lymphoma of childhood. The lymph node shows partial preservation of the architecture, with residual follicles with regressive germinal centres and expansion of the interfollicular area by large atypical cells with clear cytoplasm.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating lymphocytes are predominantly large cells with irregular nuclei and several prominent nucleoli, and with abundant clear cytoplasm. Prominent apoptosis and frequent mitosis are observed.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating cells are CD8+
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. In situ hybridization shows that the neoplastic cells are positive for EBV-encoded small RNA (EBER).
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. Some atypical cells are positive for LMP1.
Systemic EBV-positive T-cell lymphoma of childhood. The spleen shows a depleted white pulp with congestive red pulp.
Systemic EBV-positive T-cell lymphoma of childhood. Spleen. In situ hybridization for EBV-encoded small RNA (EBER) demonstrates a mild sinusoidal infiltrate positive for EBV RNA.
Systemic EBV-positive T-cell lymphoma of childhood. The spleen shows a subtle sinusoidal lymphoid infiltrate with striking haemophagocytosis.

Q: Histologically, the lymph node architecture in Systemic EBV-positive T-cell lymphoma of childhood is typically partially preserved, with small to large atypical lymphocytes characteristically expanding the [...] areas alongside prominent apoptosis and frequent mitoses.
Systemic EBV-positive T-cell lymphoma of childhood. Small lymph node with relatively preserved architecture, with residual regressive follicles and an expanded interfollicular area.
Systemic EBV-positive T-cell lymphoma of childhood. The lymph node shows partial preservation of the architecture, with residual follicles with regressive germinal centres and expansion of the interfollicular area by large atypical cells with clear cytoplasm.
A: interfollicular
Back Extra: Systemic EBV-positive T-cell lymphoma of childhood
- Clinical: Systemic EBV-positive T-cell lymphoma of childhood presents with symptoms of infectious mononucleosis, hepatosplenomegaly, and liver failure, and is often complicated by hemophagocytic syndrome.
- Micro: The lymph nodes show preserved architecture with expanded interfollicular areas containing small to large atypical lymphocytes, with prominent apoptosis and frequent mitoses.
- Ancillary: The neoplastic cells are CD8+, TIA1+, and positive for EBV-encoded small RNA (EBER).
Reference Gallery:
Systemic EBV-positive T-cell lymphoma of childhood. Small lymph node with relatively preserved architecture, with residual regressive follicles and an expanded interfollicular area.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating lymphocytes are CD8+
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The interfollicular infiltrate is polymorphic, with small cells lacking cytological atypia intermingled with some relatively large cells with irregular nuclei and prominent nucleoli.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. Double staining for CD8 (brown) and by in situ hybridization for EBV-encoded small RNA (EBER) (black) shows that many CD8+ cells are positive for EBV RNA.
Systemic EBV-positive T-cell lymphoma of childhood. The lymph node shows partial preservation of the architecture, with residual follicles with regressive germinal centres and expansion of the interfollicular area by large atypical cells with clear cytoplasm.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating lymphocytes are predominantly large cells with irregular nuclei and several prominent nucleoli, and with abundant clear cytoplasm. Prominent apoptosis and frequent mitosis are observed.
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. The infiltrating cells are CD8+
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. In situ hybridization shows that the neoplastic cells are positive for EBV-encoded small RNA (EBER).
Systemic EBV-positive T-cell lymphoma of childhood. Lymph node. Some atypical cells are positive for LMP1.
Systemic EBV-positive T-cell lymphoma of childhood. The spleen shows a depleted white pulp with congestive red pulp.
Systemic EBV-positive T-cell lymphoma of childhood. Spleen. In situ hybridization for EBV-encoded small RNA (EBER) demonstrates a mild sinusoidal infiltrate positive for EBV RNA.
Systemic EBV-positive T-cell lymphoma of childhood. The spleen shows a subtle sinusoidal lymphoid infiltrate with striking haemophagocytosis.

Q: Patients with [...] often present with an anterior mediastinal mass and biopsies showing a dense infiltrate of small to medium-sized blasts with fine chromatin and characteristic nuclear convolutions.
T-lymphoblastic leukaemia/lymphoma. Cytospin of pleural fluid (Wright–Giemsa stain) from a patient with an anterior mediastinal mass and pleural effusion shows medium-sized to large mononuclear cells with irregular nuclei, fine to condensed chromatin, small to indistinct nucleoli, moderate cytoplasm, and cytoplasmic vacuoles (findings more typical of transformed mature lymphocytes). Flow cytometry shows that these are T-cell lymphoblasts. Bone marrow involvement is not known at this time point.
T-lymphoblastic lymphoma. Mediastinal mass core needle biopsy shows sheets of medium-sized mononuclear cells with fine chromatin, inconspicuous nucleoli, nuclear convolutions, and scant cytoplasm. Accompanying bone marrow aspirate smears were negative.
A: T- and NK-lymphoblastic leukaemia/lymphoma
Q: T- and NK-lymphoblastic leukaemia/lymphoma
- Clinical: Patients with [...] often present with cytopenias, bone pain, and/or an anterior mediastinal mass, which can cause respiratory distress.
- Micro: In [...], bone marrow and mass biopsies show a dense infiltrate of small to medium-sized mononuclear cells with fine chromatin and nuclear convolutions, often with a starry-sky appearance.
- Ancillary: CD3 (cytoplasmic or surface) is the gold standard for diagnosing [...]. TdT and CD34 are commonly expressed, and NOTCH1 activating mutations are associated with better outcomes.
Reference Gallery:
T-lymphoblastic leukaemia/lymphoma. Cytospin of pleural fluid (Wright–Giemsa stain) from a patient with an anterior mediastinal mass and pleural effusion shows medium-sized to large mononuclear cells with irregular nuclei, fine to condensed chromatin, small to indistinct nucleoli, moderate cytoplasm, and cytoplasmic vacuoles (findings more typical of transformed mature lymphocytes). Flow cytometry shows that these are T-cell lymphoblasts. Bone marrow involvement is not known at this time point.
T-lymphoblastic lymphoma. Mediastinal mass core needle biopsy shows sheets of medium-sized mononuclear cells with fine chromatin, inconspicuous nucleoli, nuclear convolutions, and scant cytoplasm. Accompanying bone marrow aspirate smears were negative.
T-lymphoblastic lymphoma. Paraffin immunohistochemistry shows that the tumour cells are CD1a+. They are also CD3+, TdT+ (subset), and CD34− (not shown).
Minimal residual disease of T-lymphoblastic leukaemia. No blasts were morphologically identified on a bone marrow aspirate smear in a patient with T-lymphoblastic leukaemia at day 15 of induction chemotherapy. However, flow-based minimal residual disease analysis of 750,000 events shows 1.36% T-cell lymphoblasts (red population) that are positive for both cCD3 (gate P4) and CD34 (gate P7). Normal bone marrow aspirates do not have T-cell lymphoblasts.
A: T- and NK-lymphoblastic leukaemia/lymphoma; T- and NK-lymphoblastic leukaemia/lymphoma; T- and NK-lymphoblastic leukaemia/lymphoma

Q: In T- and NK-lymphoblastic leukaemia/lymphoma, the gold standard for lineage assignment is the expression of cytoplasmic or surface [...], which is often accompanied by immaturity markers like TdT and CD34.
T-lymphoblastic lymphoma. Paraffin immunohistochemistry shows that the tumour cells are CD1a+. They are also CD3+, TdT+ (subset), and CD34− (not shown).
Minimal residual disease of T-lymphoblastic leukaemia. No blasts were morphologically identified on a bone marrow aspirate smear in a patient with T-lymphoblastic leukaemia at day 15 of induction chemotherapy. However, flow-based minimal residual disease analysis of 750,000 events shows 1.36% T-cell lymphoblasts (red population) that are positive for both cCD3 (gate P4) and CD34 (gate P7). Normal bone marrow aspirates do not have T-cell lymphoblasts.
A: CD3
Q: T- and NK-lymphoblastic leukaemia/lymphoma
- Clinical: Patients with [...] often present with cytopenias, bone pain, and/or an anterior mediastinal mass, which can cause respiratory distress.
- Micro: In [...], bone marrow and mass biopsies show a dense infiltrate of small to medium-sized mononuclear cells with fine chromatin and nuclear convolutions, often with a starry-sky appearance.
- Ancillary: CD3 (cytoplasmic or surface) is the gold standard for diagnosing [...]. TdT and CD34 are commonly expressed, and NOTCH1 activating mutations are associated with better outcomes.
Reference Gallery:
T-lymphoblastic leukaemia/lymphoma. Cytospin of pleural fluid (Wright–Giemsa stain) from a patient with an anterior mediastinal mass and pleural effusion shows medium-sized to large mononuclear cells with irregular nuclei, fine to condensed chromatin, small to indistinct nucleoli, moderate cytoplasm, and cytoplasmic vacuoles (findings more typical of transformed mature lymphocytes). Flow cytometry shows that these are T-cell lymphoblasts. Bone marrow involvement is not known at this time point.
T-lymphoblastic lymphoma. Mediastinal mass core needle biopsy shows sheets of medium-sized mononuclear cells with fine chromatin, inconspicuous nucleoli, nuclear convolutions, and scant cytoplasm. Accompanying bone marrow aspirate smears were negative.
T-lymphoblastic lymphoma. Paraffin immunohistochemistry shows that the tumour cells are CD1a+. They are also CD3+, TdT+ (subset), and CD34− (not shown).
Minimal residual disease of T-lymphoblastic leukaemia. No blasts were morphologically identified on a bone marrow aspirate smear in a patient with T-lymphoblastic leukaemia at day 15 of induction chemotherapy. However, flow-based minimal residual disease analysis of 750,000 events shows 1.36% T-cell lymphoblasts (red population) that are positive for both cCD3 (gate P4) and CD34 (gate P7). Normal bone marrow aspirates do not have T-cell lymphoblasts.
A: T- and NK-lymphoblastic leukaemia/lymphoma; T- and NK-lymphoblastic leukaemia/lymphoma; T- and NK-lymphoblastic leukaemia/lymphoma

Q: A defining diagnostic criterion for Acute Myeloid Leukaemia (AML) Defined by Differentiation is the identification of at least [...] blasts (or blast equivalents) among the nucleated cells in the bone marrow or peripheral blood.
Acute myeloid leukaemia (AML) without maturation. Blasts are intermediate in size, with pale basophilic cytoplasm, fine lacy chromatin, and one or two prominent nucleoli (Wright–Giemsa stain).
A: 20%
Back Extra: Acute Myeloid Leukaemia (AML) Defined by Differentiation
- Clinical: Signs and symptoms of Acute Myeloid Leukaemia (AML) Defined by Differentiation include fever, bone pain, fatigue, petechial rash, bruising, and bleeding.
- Micro: By definition, blasts or blast equivalents account for ≥ 20% of the nucleated cells in the bone marrow and/or peripheral blood. The bone marrow is hypercellular with abundant blasts.
- Ancillary: Essential diagnostic criteria include identification of ≥ 20% blasts in the bone marrow or blood, evidence of myeloid derivation, and absence of definitive T-cell or B-cell differentiation by immunophenotyping.
Reference Gallery:
Acute megakaryoblastic leukaemia. Bone marrow aspirate smear showing a collection of large blasts with basophilic cytoplasm and cytoplasmic blebs.
Acute myeloid leukaemia (AML) without maturation. Blasts are intermediate in size, with pale basophilic cytoplasm, fine lacy chromatin, and one or two prominent nucleoli (Wright–Giemsa stain).
Acute myelomonocytic leukaemia. Blasts are intermediate in size to large and have pale basophilic cytoplasm with fine azurophilic granules. Promonocytes have irregularly folded and convoluted nuclei with overlapping nuclear folds, fine delicate chromatin, and one or two nucleoli (bone marrow aspirate, Wright–Giemsa stain).

Q: Morphologically, the bone marrow in Acute Myeloid Leukaemia (AML) Defined by Differentiation is characteristically hypercellular due to an abundant accumulation of immature myeloid precursors known as [...].
Acute megakaryoblastic leukaemia. Bone marrow aspirate smear showing a collection of large blasts with basophilic cytoplasm and cytoplasmic blebs.
Acute myelomonocytic leukaemia. Blasts are intermediate in size to large and have pale basophilic cytoplasm with fine azurophilic granules. Promonocytes have irregularly folded and convoluted nuclei with overlapping nuclear folds, fine delicate chromatin, and one or two nucleoli (bone marrow aspirate, Wright–Giemsa stain).
A: blasts
Back Extra: Acute Myeloid Leukaemia (AML) Defined by Differentiation
- Clinical: Signs and symptoms of Acute Myeloid Leukaemia (AML) Defined by Differentiation include fever, bone pain, fatigue, petechial rash, bruising, and bleeding.
- Micro: By definition, blasts or blast equivalents account for ≥ 20% of the nucleated cells in the bone marrow and/or peripheral blood. The bone marrow is hypercellular with abundant blasts.
- Ancillary: Essential diagnostic criteria include identification of ≥ 20% blasts in the bone marrow or blood, evidence of myeloid derivation, and absence of definitive T-cell or B-cell differentiation by immunophenotyping.
Reference Gallery:
Acute megakaryoblastic leukaemia. Bone marrow aspirate smear showing a collection of large blasts with basophilic cytoplasm and cytoplasmic blebs.
Acute myeloid leukaemia (AML) without maturation. Blasts are intermediate in size, with pale basophilic cytoplasm, fine lacy chromatin, and one or two prominent nucleoli (Wright–Giemsa stain).
Acute myelomonocytic leukaemia. Blasts are intermediate in size to large and have pale basophilic cytoplasm with fine azurophilic granules. Promonocytes have irregularly folded and convoluted nuclei with overlapping nuclear folds, fine delicate chromatin, and one or two nucleoli (bone marrow aspirate, Wright–Giemsa stain).

Q: In Acute Myeloid Leukaemia with Defining Genetic Abnormalities, cases harboring a KMT2A rearrangement (e.g., t(10;11)) frequently exhibit prominent monocytic or [...] differentiation on bone marrow aspirate smears and immunostains.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(10;11), here showing monocytic differentiation.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(10;11), showing megakaryoblastic differentiation.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. AML with t(10;11), showing megakaryoblastic differentiation (CD61 stain).
A: megakaryoblastic
Back Extra: Acute Myeloid Leukaemia with Defining Genetic Abnormalities
- Clinical: Patients with Acute Myeloid Leukaemia (AML) with defining genetic abnormalities often present with acute leukaemia, including hyperleukocytosis and specific syndromes.
- Micro: Histopathology of AML with defining genetic abnormalities reveals increased blasts with specific morphological features, such as megakaryoblastic differentiation in AML with CBFA2T3::GLIS2 fusion.
- Ancillary: Cytogenetic and molecular studies, including G-banding, FISH, PCR, and next-generation sequencing, are essential for identifying specific genetic abnormalities and fusion partners in AML.
Reference Gallery:
Acute myeloid leukaemia (AML) with defining genetic abnormalities. Frequency and co-occurrence of mutations in paediatric AML.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. G-banding showing t(6;11).
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(6;11).
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(10;11), here showing monocytic differentiation.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(10;11), showing megakaryoblastic differentiation.
Acute myeloid leukaemia (AML) with ETV6 fusion. Bone marrow aspirate smear.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. FACS plot showing expression of NG2 and CD15 in AML with t(10;11).
Acute myeloid leukaemia (AML) with ETV6 fusion. FISH (using an ETV6 break-apart probe) of a case with MNX1::ETV6 fusion.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. AML with t(10;11), showing megakaryoblastic differentiation (CD61 stain).

Q: In pediatric cases of Acute Myeloid Leukaemia with Defining Genetic Abnormalities, the presence of the CBFA2T3::GLIS2 fusion is strongly associated with the characteristic [...] immunophenotype on flow cytometry.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
A: RAM
Back Extra: Acute Myeloid Leukaemia with Defining Genetic Abnormalities
- Clinical: Patients with Acute Myeloid Leukaemia (AML) with defining genetic abnormalities often present with acute leukaemia, including hyperleukocytosis and specific syndromes.
- Micro: Histopathology of AML with defining genetic abnormalities reveals increased blasts with specific morphological features, such as megakaryoblastic differentiation in AML with CBFA2T3::GLIS2 fusion.
- Ancillary: Cytogenetic and molecular studies, including G-banding, FISH, PCR, and next-generation sequencing, are essential for identifying specific genetic abnormalities and fusion partners in AML.
Reference Gallery:
Acute myeloid leukaemia (AML) with defining genetic abnormalities. Frequency and co-occurrence of mutations in paediatric AML.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. G-banding showing t(6;11).
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(6;11).
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(10;11), here showing monocytic differentiation.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(10;11), showing megakaryoblastic differentiation.
Acute myeloid leukaemia (AML) with ETV6 fusion. Bone marrow aspirate smear.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. FACS plot showing expression of NG2 and CD15 in AML with t(10;11).
Acute myeloid leukaemia (AML) with ETV6 fusion. FISH (using an ETV6 break-apart probe) of a case with MNX1::ETV6 fusion.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. AML with t(10;11), showing megakaryoblastic differentiation (CD61 stain).

Q: The diagnostic workup for Acute Myeloid Leukaemia with Defining Genetic Abnormalities often employs FISH break-apart probes to identify specific structural variants, such as the [...] gene fusion.
Acute myeloid leukaemia (AML) with ETV6 fusion. FISH (using an ETV6 break-apart probe) of a case with MNX1::ETV6 fusion.
A: ETV6
Back Extra: Acute Myeloid Leukaemia with Defining Genetic Abnormalities
- Clinical: Patients with Acute Myeloid Leukaemia (AML) with defining genetic abnormalities often present with acute leukaemia, including hyperleukocytosis and specific syndromes.
- Micro: Histopathology of AML with defining genetic abnormalities reveals increased blasts with specific morphological features, such as megakaryoblastic differentiation in AML with CBFA2T3::GLIS2 fusion.
- Ancillary: Cytogenetic and molecular studies, including G-banding, FISH, PCR, and next-generation sequencing, are essential for identifying specific genetic abnormalities and fusion partners in AML.
Reference Gallery:
Acute myeloid leukaemia (AML) with defining genetic abnormalities. Frequency and co-occurrence of mutations in paediatric AML.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. G-banding showing t(6;11).
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(6;11).
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(10;11), here showing monocytic differentiation.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. Smear of AML with t(10;11), showing megakaryoblastic differentiation.
Acute myeloid leukaemia (AML) with ETV6 fusion. Bone marrow aspirate smear.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. FACS plot showing expression of NG2 and CD15 in AML with t(10;11).
Acute myeloid leukaemia (AML) with ETV6 fusion. FISH (using an ETV6 break-apart probe) of a case with MNX1::ETV6 fusion.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with CBFA2T3::GLIS2 fusion. FACS plot showing the RAM immunophenotype often associated with this abnormality.
Acute myeloid leukaemia (AML) with KMT2A rearrangement. AML with t(10;11), showing megakaryoblastic differentiation (CD61 stain).

Q: A characteristic histologic finding in Myelodysplastic syndrome with excess blasts is the presence of abnormal foci of immature myeloid precursors, which can be prominently highlighted on a bone marrow biopsy using a [...] immunostain.
Myelodysplastic syndrome with excess blasts. Bone marrow section containing a focus of immature myeloid precursors.
Myelodysplastic syndrome with excess blasts. Bone marrow biopsy showing foci of immature cells that stain positively for CD34.
A: CD34
Back Extra: Myelodysplastic syndrome with excess blasts
- Clinical: The most common symptoms are malaise, fever, and bleeding due to peripheral blood cytopenias.
- Micro: Disruption of red cell colony formation and abnormal localization of immature granulocytic cells are characteristic histological features.
- Ancillary: Somatic mutations in the RAS pathway, transcription factors, and epigenetic modifiers are commonly seen, with monosomy 7 being the most frequent chromosomal aberration.
Reference Gallery:
Myelodysplastic syndrome with excess blasts. Bone marrow section containing a focus of immature myeloid precursors.
Myelodysplastic syndrome with excess blasts. Bone marrow biopsy showing foci of immature cells that stain positively for CD34.
Myelodysplastic syndrome with excess blasts. Bone marrow aspirate smear showing normoblasts with multinuclearity, nuclear budding, and megaloblastoid changes, as well as myeloid precursors with hypogranularity.

Q: Bone marrow aspirate smears in Myelodysplastic syndrome with excess blasts show prominent multilineage dysplasia, including megaloblastoid changes and nuclear budding in normoblasts, along with characteristic [...] in the myeloid precursors.
Myelodysplastic syndrome with excess blasts. Bone marrow aspirate smear showing normoblasts with multinuclearity, nuclear budding, and megaloblastoid changes, as well as myeloid precursors with hypogranularity.
A: hypogranularity
Back Extra: Myelodysplastic syndrome with excess blasts
- Clinical: The most common symptoms are malaise, fever, and bleeding due to peripheral blood cytopenias.
- Micro: Disruption of red cell colony formation and abnormal localization of immature granulocytic cells are characteristic histological features.
- Ancillary: Somatic mutations in the RAS pathway, transcription factors, and epigenetic modifiers are commonly seen, with monosomy 7 being the most frequent chromosomal aberration.
Reference Gallery:
Myelodysplastic syndrome with excess blasts. Bone marrow section containing a focus of immature myeloid precursors.
Myelodysplastic syndrome with excess blasts. Bone marrow biopsy showing foci of immature cells that stain positively for CD34.
Myelodysplastic syndrome with excess blasts. Bone marrow aspirate smear showing normoblasts with multinuclearity, nuclear budding, and megaloblastoid changes, as well as myeloid precursors with hypogranularity.

Q: In Chronic Myeloid Leukemia (CML), molecular testing (FISH or RT-PCR) is essential to identify the pathognomonic [ABL1] fusion gene, which is critical for diagnosis and monitoring response to targeted therapy.
Chronic myeloid leukaemia (CML). Exons and intronic breakpoints of the ABL1 and BCR genes (blue horizontal arrows) and the corresponding fusion proteins. In the BCR gene, the most frequently observed major breakpoint cluster region (M-bcr), the less frequently observed minor breakpoint cluster region (m-bcr), and the rarely observed micro breakpoint cluster region (µ-bcr) can produce eight mRNA fusion transcripts and translated proteins due to alternate splicing of exon 2 of the ABL1 gene and due to two internal breakpoints in introns 13 and 14 of the BCR gene (note: length of exons and introns not to scale). In addition, three variant breakpoint cluster regions (v-bcr; blue vertical arrows) have been described rarely or only once. ABL1b is a pseudogene and is spliced out frequently.
A: BCR
Back Extra: Chronic Myeloid Leukemia (CML)
- Clinical: Paediatric patients with CML usually present with chronic-phase CML (CML-CP), characterized by symptoms such as fever, bleeding, fatigue, and bone pain. Splenomegaly and higher leukocyte and platelet counts are also common.
- Micro: In chronic-phase CML, the bone marrow shows hypercellularity and markedly increased myelopoiesis, with predominant myelocytes, promyelocytes, and segmented neutrophils. Micromegakaryocytes with hypolobated nuclei and increased eosinophils are common.
- Ancillary: Molecular tests (FISH or RT-PCR) are essential to identify the BCR::ABL1 fusion gene, which is crucial for monitoring response to TKI treatment. Flow cytometry is important for detecting mixed phenotypes in CML-BP.
Reference Gallery:
Chronic myeloid leukaemia (CML). Exons and intronic breakpoints of the ABL1 and BCR genes (blue horizontal arrows) and the corresponding fusion proteins. In the BCR gene, the most frequently observed major breakpoint cluster region (M-bcr), the less frequently observed minor breakpoint cluster region (m-bcr), and the rarely observed micro breakpoint cluster region (µ-bcr) can produce eight mRNA fusion transcripts and translated proteins due to alternate splicing of exon 2 of the ABL1 gene and due to two internal breakpoints in introns 13 and 14 of the BCR gene (note: length of exons and introns not to scale). In addition, three variant breakpoint cluster regions (v-bcr; blue vertical arrows) have been described rarely or only once. ABL1b is a pseudogene and is spliced out frequently.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. Smear from bone marrow aspirate. A non-lobulated micromegakaryocyte with cytoplasm showing mature staining properties and a granular structure. The average cell diameter is < 25 μm. Dysplastic megakaryocytic features (namely hypolobation) and micromegakaryocytes are consistently seen in all paediatric patients with CML.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. An increased number of eosinophils (arrows) can be found at all stages of maturation in most paediatric patients with CML. The number of basophils (arrowheads) in chronic-phase CML is usually slightly increased, but in advanced CML, marked and sometimes even excessive basophilia is a key laboratory finding.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. Smear from bone marrow aspirate. Hypersegmented neutrophils (arrow: a nucleus with > 4 segments) can be detected frequently in chronic-phase CML because of the prolonged lifetime of the mature granulocytes. Immature and mature eosinophils (arrowheads) may also show basophilic granules and are termed “harlequin cells” by some authors.
Chronic myeloid leukaemia (CML), BCR::ABL1. CML in the chronic phase at diagnosis (bone marrow trephine biopsy). Histology demonstrates increased and left-shifted granulopoiesis. In such cases, there is an accompanying proliferation of eosinophils and eosinophilic precursors, a reduction of erythropoiesis, and an accumulation of small, non-lobulated megakaryocytes.

Q: The bone marrow in the chronic phase of Chronic Myeloid Leukemia (CML) typically exhibits marked hypercellularity, left-shifted granulopoiesis, and characteristic small, hypolobated or non-lobulated [...].
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. Smear from bone marrow aspirate. A non-lobulated micromegakaryocyte with cytoplasm showing mature staining properties and a granular structure. The average cell diameter is < 25 μm. Dysplastic megakaryocytic features (namely hypolobation) and micromegakaryocytes are consistently seen in all paediatric patients with CML.
Chronic myeloid leukaemia (CML), BCR::ABL1. CML in the chronic phase at diagnosis (bone marrow trephine biopsy). Histology demonstrates increased and left-shifted granulopoiesis. In such cases, there is an accompanying proliferation of eosinophils and eosinophilic precursors, a reduction of erythropoiesis, and an accumulation of small, non-lobulated megakaryocytes.
A: micromegakaryocytes
Back Extra: Chronic Myeloid Leukemia (CML)
- Clinical: Paediatric patients with CML usually present with chronic-phase CML (CML-CP), characterized by symptoms such as fever, bleeding, fatigue, and bone pain. Splenomegaly and higher leukocyte and platelet counts are also common.
- Micro: In chronic-phase CML, the bone marrow shows hypercellularity and markedly increased myelopoiesis, with predominant myelocytes, promyelocytes, and segmented neutrophils. Micromegakaryocytes with hypolobated nuclei and increased eosinophils are common.
- Ancillary: Molecular tests (FISH or RT-PCR) are essential to identify the BCR::ABL1 fusion gene, which is crucial for monitoring response to TKI treatment. Flow cytometry is important for detecting mixed phenotypes in CML-BP.
Reference Gallery:
Chronic myeloid leukaemia (CML). Exons and intronic breakpoints of the ABL1 and BCR genes (blue horizontal arrows) and the corresponding fusion proteins. In the BCR gene, the most frequently observed major breakpoint cluster region (M-bcr), the less frequently observed minor breakpoint cluster region (m-bcr), and the rarely observed micro breakpoint cluster region (µ-bcr) can produce eight mRNA fusion transcripts and translated proteins due to alternate splicing of exon 2 of the ABL1 gene and due to two internal breakpoints in introns 13 and 14 of the BCR gene (note: length of exons and introns not to scale). In addition, three variant breakpoint cluster regions (v-bcr; blue vertical arrows) have been described rarely or only once. ABL1b is a pseudogene and is spliced out frequently.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. Smear from bone marrow aspirate. A non-lobulated micromegakaryocyte with cytoplasm showing mature staining properties and a granular structure. The average cell diameter is < 25 μm. Dysplastic megakaryocytic features (namely hypolobation) and micromegakaryocytes are consistently seen in all paediatric patients with CML.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. An increased number of eosinophils (arrows) can be found at all stages of maturation in most paediatric patients with CML. The number of basophils (arrowheads) in chronic-phase CML is usually slightly increased, but in advanced CML, marked and sometimes even excessive basophilia is a key laboratory finding.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. Smear from bone marrow aspirate. Hypersegmented neutrophils (arrow: a nucleus with > 4 segments) can be detected frequently in chronic-phase CML because of the prolonged lifetime of the mature granulocytes. Immature and mature eosinophils (arrowheads) may also show basophilic granules and are termed “harlequin cells” by some authors.
Chronic myeloid leukaemia (CML), BCR::ABL1. CML in the chronic phase at diagnosis (bone marrow trephine biopsy). Histology demonstrates increased and left-shifted granulopoiesis. In such cases, there is an accompanying proliferation of eosinophils and eosinophilic precursors, a reduction of erythropoiesis, and an accumulation of small, non-lobulated megakaryocytes.

Q: Bone marrow aspirate smears in Chronic Myeloid Leukemia (CML) demonstrate markedly increased myelopoiesis that is frequently accompanied by a characteristic absolute increase in both eosinophils and [...].
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. An increased number of eosinophils (arrows) can be found at all stages of maturation in most paediatric patients with CML. The number of basophils (arrowheads) in chronic-phase CML is usually slightly increased, but in advanced CML, marked and sometimes even excessive basophilia is a key laboratory finding.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. Smear from bone marrow aspirate. Hypersegmented neutrophils (arrow: a nucleus with > 4 segments) can be detected frequently in chronic-phase CML because of the prolonged lifetime of the mature granulocytes. Immature and mature eosinophils (arrowheads) may also show basophilic granules and are termed “harlequin cells” by some authors.
A: basophils
Back Extra: Chronic Myeloid Leukemia (CML)
- Clinical: Paediatric patients with CML usually present with chronic-phase CML (CML-CP), characterized by symptoms such as fever, bleeding, fatigue, and bone pain. Splenomegaly and higher leukocyte and platelet counts are also common.
- Micro: In chronic-phase CML, the bone marrow shows hypercellularity and markedly increased myelopoiesis, with predominant myelocytes, promyelocytes, and segmented neutrophils. Micromegakaryocytes with hypolobated nuclei and increased eosinophils are common.
- Ancillary: Molecular tests (FISH or RT-PCR) are essential to identify the BCR::ABL1 fusion gene, which is crucial for monitoring response to TKI treatment. Flow cytometry is important for detecting mixed phenotypes in CML-BP.
Reference Gallery:
Chronic myeloid leukaemia (CML). Exons and intronic breakpoints of the ABL1 and BCR genes (blue horizontal arrows) and the corresponding fusion proteins. In the BCR gene, the most frequently observed major breakpoint cluster region (M-bcr), the less frequently observed minor breakpoint cluster region (m-bcr), and the rarely observed micro breakpoint cluster region (µ-bcr) can produce eight mRNA fusion transcripts and translated proteins due to alternate splicing of exon 2 of the ABL1 gene and due to two internal breakpoints in introns 13 and 14 of the BCR gene (note: length of exons and introns not to scale). In addition, three variant breakpoint cluster regions (v-bcr; blue vertical arrows) have been described rarely or only once. ABL1b is a pseudogene and is spliced out frequently.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. Smear from bone marrow aspirate. A non-lobulated micromegakaryocyte with cytoplasm showing mature staining properties and a granular structure. The average cell diameter is < 25 μm. Dysplastic megakaryocytic features (namely hypolobation) and micromegakaryocytes are consistently seen in all paediatric patients with CML.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. An increased number of eosinophils (arrows) can be found at all stages of maturation in most paediatric patients with CML. The number of basophils (arrowheads) in chronic-phase CML is usually slightly increased, but in advanced CML, marked and sometimes even excessive basophilia is a key laboratory finding.
Chronic myeloid leukaemia (CML) in the chronic phase at diagnosis. Smear from bone marrow aspirate. Hypersegmented neutrophils (arrow: a nucleus with > 4 segments) can be detected frequently in chronic-phase CML because of the prolonged lifetime of the mature granulocytes. Immature and mature eosinophils (arrowheads) may also show basophilic granules and are termed “harlequin cells” by some authors.
Chronic myeloid leukaemia (CML), BCR::ABL1. CML in the chronic phase at diagnosis (bone marrow trephine biopsy). Histology demonstrates increased and left-shifted granulopoiesis. In such cases, there is an accompanying proliferation of eosinophils and eosinophilic precursors, a reduction of erythropoiesis, and an accumulation of small, non-lobulated megakaryocytes.

Q: Peripheral blood smears showing abnormal monocytes with cytoplasmic vacuoles alongside a hypercellular bone marrow with a less prominent monocyte compartment in a young child are characteristic of [...].
Juvenile myelomonocytic leukaemia. Peripheral blood smear showing abnormal monocytes with cytoplasmic vacuoles and a myeloblast.
Juvenile myelomonocytic leukaemia. The bone marrow aspirate smear usually reflects the changes noted in blood but the monocyte compartment is generally less prominent.
A: Juvenile Myelomonocytic Leukemia
Q: Juvenile Myelomonocytic Leukemia
- Clinical: Children with [...] often present with hepatosplenomegaly, lymphadenopathy, and skin lesions.
- Micro: The bone marrow in [...] is hypercellular with granulocytic proliferation and a less prominent monocyte compartment.
- Ancillary: Cytogenetic studies in [...] show a normal karyotype in 65% of cases, with monosomy 7 in about 25%.
Reference Gallery:
Juvenile myelomonocytic leukaemia. Peripheral blood smear showing abnormal monocytes with cytoplasmic vacuoles and a myeloblast.
Juvenile myelomonocytic leukaemia. The bone marrow aspirate smear usually reflects the changes noted in blood but the monocyte compartment is generally less prominent.
Juvenile myelomonocytic leukaemia. Schema of the RAS signalling pathway, with gene mutations contributing to juvenile myelomonocytic leukaemia shown in red. Percentages are calculated from juvenile myelomonocytic leukaemia patient series from Japan, North America, and Europe.
A: Juvenile Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

Q: The pathogenesis of Juvenile Myelomonocytic Leukemia is fundamentally driven by gene mutations involving the [...] signaling pathway.
Juvenile myelomonocytic leukaemia. Schema of the RAS signalling pathway, with gene mutations contributing to juvenile myelomonocytic leukaemia shown in red. Percentages are calculated from juvenile myelomonocytic leukaemia patient series from Japan, North America, and Europe.
A: RAS
Q: Juvenile Myelomonocytic Leukemia
- Clinical: Children with [...] often present with hepatosplenomegaly, lymphadenopathy, and skin lesions.
- Micro: The bone marrow in [...] is hypercellular with granulocytic proliferation and a less prominent monocyte compartment.
- Ancillary: Cytogenetic studies in [...] show a normal karyotype in 65% of cases, with monosomy 7 in about 25%.
Reference Gallery:
Juvenile myelomonocytic leukaemia. Peripheral blood smear showing abnormal monocytes with cytoplasmic vacuoles and a myeloblast.
Juvenile myelomonocytic leukaemia. The bone marrow aspirate smear usually reflects the changes noted in blood but the monocyte compartment is generally less prominent.
Juvenile myelomonocytic leukaemia. Schema of the RAS signalling pathway, with gene mutations contributing to juvenile myelomonocytic leukaemia shown in red. Percentages are calculated from juvenile myelomonocytic leukaemia patient series from Japan, North America, and Europe.
A: Juvenile Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

Q: Histologically, cutaneous Mastocytosis is characterized by an increased number of mast cells in the dermis, which are frequently admixed with [...].
Maculopapular cutaneous mastocytosis / urticaria pigmentosa. Yellow patches were noted on the left forearm of a 1-year-old boy. Pink-orange papules were present on the boy’s midback, and a subtle perivascular and interstitial infiltrate of mast cells and eosinophils was found on punch biopsy. The overlying epidermis shows basal keratinocytic hyperpigmentation.
Mastocytosis. Cutaneous mastocytosis with predominant infiltration of promastocytes. Histological examination of a solitary lesion on the trunk of a 13-year-old boy showed numerous mast cells with bilobed and multilobed nuclei in the dermis, accompanied by some eosinophils. No recurrence was noted after surgical removal of the lesion.
A: eosinophils
Back Extra: Mastocytosis
- Clinical: In children, the most common form of mastocytosis is maculopapular cutaneous mastocytosis, characterized by brown, yellow, or pale red papules, plaques, and/or nodules.
- Micro: Histologically, cutaneous mastocytosis shows increased numbers of mast cells in the dermis, often forming groups with admixed eosinophils. The epidermis may be hyperpigmented.
- Ancillary: The KIT p.D816V mutation, detected in peripheral blood or bone marrow using high-sensitivity PCR, is a minor criterion for diagnosing systemic mastocytosis.
Reference Gallery:
Mastocytoma. A 12-week-old boy presented with an isolated 12 mm red-brown nodule on his right temple. A punch biopsy shows a dense infiltrate of large mononuclear cells filling the papillary and reticular dermis.
Maculopapular cutaneous mastocytosis / urticaria pigmentosa. Yellow patches were noted on the left forearm of a 1-year-old boy. Punch biopsy shows a perivascular infiltrate of mast cells in the papillary dermis.
Maculopapular cutaneous mastocytosis / urticaria pigmentosa. Yellow patches were noted on the left forearm of a 1-year-old boy. Pink-orange papules were present on the boy’s midback, and a subtle perivascular and interstitial infiltrate of mast cells and eosinophils was found on punch biopsy. The overlying epidermis shows basal keratinocytic hyperpigmentation.
Indolent systemic mastocytosis. A 3-year-old girl presented with cutaneous mastocytosis, absolute lymphopenia, elevated serum tryptase (60 µg/L), and KIT p.D816V mutation in peripheral blood using a high sensitivity PCR assay. A bone marrow aspirate shows rare (<1%) spindle-shaped mast cells, which by flow cytometry (data not shown) demonstrated aberrant expression of CD2 and CD25. Normal granulopoiesis, erythropoiesis, haematogones, and an eosinophil are also present (Wright–Giemsa stain).
Gastrointestinal systemic mastocytosis. A 5-year-old girl presented with diarrhea and abdominal pain necessitating repeat visits to the emergency room. Colon biopsy shows a dense, band-like infiltrate of mast cells within the lamina propria, surrounded by an intense eosinophilic infiltrate.
Mastocytosis. Mastocytoma. A yellowish nodule with an orange-peel surface and recurrent blisters on the back of an infant.
Mastocytosis. Maculopapular cutaneous mastocytosis, monomorphic type. Small brown macules and papules (similar to the characteristic lesions of mastocytosis in adults) on the trunk of an infant.
Mastocytosis. Maculopapular cutaneous mastocytosis, polymorphic type. Large, confluent, reddish macules on the trunk of an infant. These lesions are rarely seen in adults.
Mastocytosis. Diffuse cutaneous mastocytosis. This infant has erythroderma and infiltrated skin, with multiple blisters from minimal rubbing of the skin against the linens.
Mastocytosis. Cutaneous mastocytosis with predominant infiltration of promastocytes. Histological examination of a solitary lesion on the trunk of a 13-year-old boy showed numerous mast cells with bilobed and multilobed nuclei in the dermis, accompanied by some eosinophils. No recurrence was noted after surgical removal of the lesion.
Mastocytosis. Cutaneous mastocytosis with predominant infiltration of promastocytes. Histological examination of a solitary lesion on the trunk of a 13-year-old boy showed mast cells that were strongly reactive for KIT (CD117).
Indolent systemic mastocytosis. A 3-year-old girl presented with cutaneous mastocytosis, absolute lymphopenia, elevated serum tryptase (60 µg/L), and KIT p.D816V mutation in peripheral blood using a high sensitivity PCR assay. Bone marrow biopsy showed a normocellular marrow with rare multifocal mast cell aggregates and increased interstitial mast cells, occupying 10% of cellular marrow, best demonstrated by immunohistochemical staining for KIT (CD117) (shown here), CD25, and tryptase.

Q: A minor diagnostic criterion for systemic Mastocytosis is the detection of the [...] mutation in peripheral blood or bone marrow.
Indolent systemic mastocytosis. A 3-year-old girl presented with cutaneous mastocytosis, absolute lymphopenia, elevated serum tryptase (60 µg/L), and KIT p.D816V mutation in peripheral blood using a high sensitivity PCR assay. A bone marrow aspirate shows rare (<1%) spindle-shaped mast cells, which by flow cytometry (data not shown) demonstrated aberrant expression of CD2 and CD25. Normal granulopoiesis, erythropoiesis, haematogones, and an eosinophil are also present (Wright–Giemsa stain).
Indolent systemic mastocytosis. A 3-year-old girl presented with cutaneous mastocytosis, absolute lymphopenia, elevated serum tryptase (60 µg/L), and KIT p.D816V mutation in peripheral blood using a high sensitivity PCR assay. Bone marrow biopsy showed a normocellular marrow with rare multifocal mast cell aggregates and increased interstitial mast cells, occupying 10% of cellular marrow, best demonstrated by immunohistochemical staining for KIT (CD117) (shown here), CD25, and tryptase.
A: KIT p.D816V
Back Extra: Mastocytosis
- Clinical: In children, the most common form of mastocytosis is maculopapular cutaneous mastocytosis, characterized by brown, yellow, or pale red papules, plaques, and/or nodules.
- Micro: Histologically, cutaneous mastocytosis shows increased numbers of mast cells in the dermis, often forming groups with admixed eosinophils. The epidermis may be hyperpigmented.
- Ancillary: The KIT p.D816V mutation, detected in peripheral blood or bone marrow using high-sensitivity PCR, is a minor criterion for diagnosing systemic mastocytosis.
Reference Gallery:
Mastocytoma. A 12-week-old boy presented with an isolated 12 mm red-brown nodule on his right temple. A punch biopsy shows a dense infiltrate of large mononuclear cells filling the papillary and reticular dermis.
Maculopapular cutaneous mastocytosis / urticaria pigmentosa. Yellow patches were noted on the left forearm of a 1-year-old boy. Punch biopsy shows a perivascular infiltrate of mast cells in the papillary dermis.
Maculopapular cutaneous mastocytosis / urticaria pigmentosa. Yellow patches were noted on the left forearm of a 1-year-old boy. Pink-orange papules were present on the boy’s midback, and a subtle perivascular and interstitial infiltrate of mast cells and eosinophils was found on punch biopsy. The overlying epidermis shows basal keratinocytic hyperpigmentation.
Indolent systemic mastocytosis. A 3-year-old girl presented with cutaneous mastocytosis, absolute lymphopenia, elevated serum tryptase (60 µg/L), and KIT p.D816V mutation in peripheral blood using a high sensitivity PCR assay. A bone marrow aspirate shows rare (<1%) spindle-shaped mast cells, which by flow cytometry (data not shown) demonstrated aberrant expression of CD2 and CD25. Normal granulopoiesis, erythropoiesis, haematogones, and an eosinophil are also present (Wright–Giemsa stain).
Gastrointestinal systemic mastocytosis. A 5-year-old girl presented with diarrhea and abdominal pain necessitating repeat visits to the emergency room. Colon biopsy shows a dense, band-like infiltrate of mast cells within the lamina propria, surrounded by an intense eosinophilic infiltrate.
Mastocytosis. Mastocytoma. A yellowish nodule with an orange-peel surface and recurrent blisters on the back of an infant.
Mastocytosis. Maculopapular cutaneous mastocytosis, monomorphic type. Small brown macules and papules (similar to the characteristic lesions of mastocytosis in adults) on the trunk of an infant.
Mastocytosis. Maculopapular cutaneous mastocytosis, polymorphic type. Large, confluent, reddish macules on the trunk of an infant. These lesions are rarely seen in adults.
Mastocytosis. Diffuse cutaneous mastocytosis. This infant has erythroderma and infiltrated skin, with multiple blisters from minimal rubbing of the skin against the linens.
Mastocytosis. Cutaneous mastocytosis with predominant infiltration of promastocytes. Histological examination of a solitary lesion on the trunk of a 13-year-old boy showed numerous mast cells with bilobed and multilobed nuclei in the dermis, accompanied by some eosinophils. No recurrence was noted after surgical removal of the lesion.
Mastocytosis. Cutaneous mastocytosis with predominant infiltration of promastocytes. Histological examination of a solitary lesion on the trunk of a 13-year-old boy showed mast cells that were strongly reactive for KIT (CD117).
Indolent systemic mastocytosis. A 3-year-old girl presented with cutaneous mastocytosis, absolute lymphopenia, elevated serum tryptase (60 µg/L), and KIT p.D816V mutation in peripheral blood using a high sensitivity PCR assay. Bone marrow biopsy showed a normocellular marrow with rare multifocal mast cell aggregates and increased interstitial mast cells, occupying 10% of cellular marrow, best demonstrated by immunohistochemical staining for KIT (CD117) (shown here), CD25, and tryptase.

Q: In children, the most common clinical variant of Mastocytosis is characterized by brown, yellow, or pale red papules and plaques, and is formally known as [...].
Mastocytosis. Maculopapular cutaneous mastocytosis, monomorphic type. Small brown macules and papules (similar to the characteristic lesions of mastocytosis in adults) on the trunk of an infant.
Mastocytosis. Maculopapular cutaneous mastocytosis, polymorphic type. Large, confluent, reddish macules on the trunk of an infant. These lesions are rarely seen in adults.
A: maculopapular cutaneous mastocytosis
Back Extra: Mastocytosis
- Clinical: In children, the most common form of mastocytosis is maculopapular cutaneous mastocytosis, characterized by brown, yellow, or pale red papules, plaques, and/or nodules.
- Micro: Histologically, cutaneous mastocytosis shows increased numbers of mast cells in the dermis, often forming groups with admixed eosinophils. The epidermis may be hyperpigmented.
- Ancillary: The KIT p.D816V mutation, detected in peripheral blood or bone marrow using high-sensitivity PCR, is a minor criterion for diagnosing systemic mastocytosis.
Reference Gallery:
Mastocytoma. A 12-week-old boy presented with an isolated 12 mm red-brown nodule on his right temple. A punch biopsy shows a dense infiltrate of large mononuclear cells filling the papillary and reticular dermis.
Maculopapular cutaneous mastocytosis / urticaria pigmentosa. Yellow patches were noted on the left forearm of a 1-year-old boy. Punch biopsy shows a perivascular infiltrate of mast cells in the papillary dermis.
Maculopapular cutaneous mastocytosis / urticaria pigmentosa. Yellow patches were noted on the left forearm of a 1-year-old boy. Pink-orange papules were present on the boy’s midback, and a subtle perivascular and interstitial infiltrate of mast cells and eosinophils was found on punch biopsy. The overlying epidermis shows basal keratinocytic hyperpigmentation.
Indolent systemic mastocytosis. A 3-year-old girl presented with cutaneous mastocytosis, absolute lymphopenia, elevated serum tryptase (60 µg/L), and KIT p.D816V mutation in peripheral blood using a high sensitivity PCR assay. A bone marrow aspirate shows rare (<1%) spindle-shaped mast cells, which by flow cytometry (data not shown) demonstrated aberrant expression of CD2 and CD25. Normal granulopoiesis, erythropoiesis, haematogones, and an eosinophil are also present (Wright–Giemsa stain).
Gastrointestinal systemic mastocytosis. A 5-year-old girl presented with diarrhea and abdominal pain necessitating repeat visits to the emergency room. Colon biopsy shows a dense, band-like infiltrate of mast cells within the lamina propria, surrounded by an intense eosinophilic infiltrate.
Mastocytosis. Mastocytoma. A yellowish nodule with an orange-peel surface and recurrent blisters on the back of an infant.
Mastocytosis. Maculopapular cutaneous mastocytosis, monomorphic type. Small brown macules and papules (similar to the characteristic lesions of mastocytosis in adults) on the trunk of an infant.
Mastocytosis. Maculopapular cutaneous mastocytosis, polymorphic type. Large, confluent, reddish macules on the trunk of an infant. These lesions are rarely seen in adults.
Mastocytosis. Diffuse cutaneous mastocytosis. This infant has erythroderma and infiltrated skin, with multiple blisters from minimal rubbing of the skin against the linens.
Mastocytosis. Cutaneous mastocytosis with predominant infiltration of promastocytes. Histological examination of a solitary lesion on the trunk of a 13-year-old boy showed numerous mast cells with bilobed and multilobed nuclei in the dermis, accompanied by some eosinophils. No recurrence was noted after surgical removal of the lesion.
Mastocytosis. Cutaneous mastocytosis with predominant infiltration of promastocytes. Histological examination of a solitary lesion on the trunk of a 13-year-old boy showed mast cells that were strongly reactive for KIT (CD117).
Indolent systemic mastocytosis. A 3-year-old girl presented with cutaneous mastocytosis, absolute lymphopenia, elevated serum tryptase (60 µg/L), and KIT p.D816V mutation in peripheral blood using a high sensitivity PCR assay. Bone marrow biopsy showed a normocellular marrow with rare multifocal mast cell aggregates and increased interstitial mast cells, occupying 10% of cellular marrow, best demonstrated by immunohistochemical staining for KIT (CD117) (shown here), CD25, and tryptase.

Q: In the setting of Myeloid Neoplasms Associated with Germline Predisposition, patients with familial platelet disorder typically demonstrate bone marrow megakaryodyspoiesis characterized by >10% [...].
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Scattered and rare focal aggregates of dysplastic megakaryocytes.
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. CD61 immunohistochemistry highlights small mononuclear megakaryocytes (intense staining of moderate cytoplasm) and increased megakaryoblasts (dim staining with scant cytoplasm).
A: small, hypolobated megakaryocytes
Back Extra: Myeloid Neoplasms Associated with Germline Predisposition
- Clinical: Myeloid neoplasms associated with germline predisposition can present with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML).
- Micro: Familial platelet disorder with associated myeloid malignancy shows megakaryodyspoiesis, characterized by > 10% small, hypolobated megakaryocytes.
- Ancillary: Diagnosis of myeloid neoplasms associated with germline predisposition often requires genetic testing and specific laboratory studies such as chromosomal breakage tests for Fanconi anaemia.
Reference Gallery:
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Wright-stained haemodiluted bone marrow aspirate smear with mostly dysplastic erythroid precursors.
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Bone marrow biopsy with variable cellularity (overall hypocellular).
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Scattered and rare focal aggregates of dysplastic megakaryocytes.
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. CD61 immunohistochemistry highlights small mononuclear megakaryocytes (intense staining of moderate cytoplasm) and increased megakaryoblasts (dim staining with scant cytoplasm).
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. Wright-stained bone marrow aspirate smear with an absence of neutrophils and increased eosinophils.
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. Wright-stained bone marrow aspirate smear with rare focal collection of immature myeloid precursors. Blasts are < 5% and there is a normal bone marrow karyotype.
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. PAS-stained bone marrow biopsy with normal cellularity, peritrabecular myeloid precursor expansion, an absence of neutrophils, and normal erythroid and megakaryocytic maturation.
Myeloid dysplastic syndrome (MDS) in Fanconi anaemia (FA). Spectrum of haematological conditions in patients with FA, and a diagnostic algorithm based on laboratory results. BM, bone marrow; FA-AIP, cytogenetic aberration of indeterminate potential in a patient with FA; FA-AML, acute myeloid leukaemia in a patient with FA; FA-BMF, bone marrow failure in a patient with FA with a normal blast percentage and normal cytogenetics; FA-MDS–EB, MDS with excess blasts in a patient with FA; FA-MDS–non-EB, MDS without excess blasts in a patient with FA; PB, peripheral blood. *In cases with rapid rise in bone marrow cellularity, FA-MDS must be considered.

Q: The diagnostic evaluation of Myeloid Neoplasms Associated with Germline Predisposition often requires specific genetic and laboratory studies, such as the use of [...] to diagnose underlying Fanconi anemia.
Myeloid dysplastic syndrome (MDS) in Fanconi anaemia (FA). Spectrum of haematological conditions in patients with FA, and a diagnostic algorithm based on laboratory results. BM, bone marrow; FA-AIP, cytogenetic aberration of indeterminate potential in a patient with FA; FA-AML, acute myeloid leukaemia in a patient with FA; FA-BMF, bone marrow failure in a patient with FA with a normal blast percentage and normal cytogenetics; FA-MDS–EB, MDS with excess blasts in a patient with FA; FA-MDS–non-EB, MDS without excess blasts in a patient with FA; PB, peripheral blood. *In cases with rapid rise in bone marrow cellularity, FA-MDS must be considered.
A: chromosomal breakage tests
Back Extra: Myeloid Neoplasms Associated with Germline Predisposition
- Clinical: Myeloid neoplasms associated with germline predisposition can present with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML).
- Micro: Familial platelet disorder with associated myeloid malignancy shows megakaryodyspoiesis, characterized by > 10% small, hypolobated megakaryocytes.
- Ancillary: Diagnosis of myeloid neoplasms associated with germline predisposition often requires genetic testing and specific laboratory studies such as chromosomal breakage tests for Fanconi anaemia.
Reference Gallery:
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Wright-stained haemodiluted bone marrow aspirate smear with mostly dysplastic erythroid precursors.
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Bone marrow biopsy with variable cellularity (overall hypocellular).
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Scattered and rare focal aggregates of dysplastic megakaryocytes.
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. CD61 immunohistochemistry highlights small mononuclear megakaryocytes (intense staining of moderate cytoplasm) and increased megakaryoblasts (dim staining with scant cytoplasm).
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. Wright-stained bone marrow aspirate smear with an absence of neutrophils and increased eosinophils.
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. Wright-stained bone marrow aspirate smear with rare focal collection of immature myeloid precursors. Blasts are < 5% and there is a normal bone marrow karyotype.
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. PAS-stained bone marrow biopsy with normal cellularity, peritrabecular myeloid precursor expansion, an absence of neutrophils, and normal erythroid and megakaryocytic maturation.
Myeloid dysplastic syndrome (MDS) in Fanconi anaemia (FA). Spectrum of haematological conditions in patients with FA, and a diagnostic algorithm based on laboratory results. BM, bone marrow; FA-AIP, cytogenetic aberration of indeterminate potential in a patient with FA; FA-AML, acute myeloid leukaemia in a patient with FA; FA-BMF, bone marrow failure in a patient with FA with a normal blast percentage and normal cytogenetics; FA-MDS–EB, MDS with excess blasts in a patient with FA; FA-MDS–non-EB, MDS without excess blasts in a patient with FA; PB, peripheral blood. *In cases with rapid rise in bone marrow cellularity, FA-MDS must be considered.

Q: In the spectrum of Myeloid Neoplasms Associated with Germline Predisposition, a bone marrow evaluation showing an absence of neutrophils and a compensatory increase in eosinophils without evidence of acute myeloid leukemia (AML) is characteristic of [...].
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. Wright-stained bone marrow aspirate smear with an absence of neutrophils and increased eosinophils.
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. PAS-stained bone marrow biopsy with normal cellularity, peritrabecular myeloid precursor expansion, an absence of neutrophils, and normal erythroid and megakaryocytic maturation.
A: severe congenital neutropenia
Back Extra: Myeloid Neoplasms Associated with Germline Predisposition
- Clinical: Myeloid neoplasms associated with germline predisposition can present with aplastic anaemia, myelodysplastic syndrome (MDS), and acute myeloid leukaemia (AML).
- Micro: Familial platelet disorder with associated myeloid malignancy shows megakaryodyspoiesis, characterized by > 10% small, hypolobated megakaryocytes.
- Ancillary: Diagnosis of myeloid neoplasms associated with germline predisposition often requires genetic testing and specific laboratory studies such as chromosomal breakage tests for Fanconi anaemia.
Reference Gallery:
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Wright-stained haemodiluted bone marrow aspirate smear with mostly dysplastic erythroid precursors.
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Bone marrow biopsy with variable cellularity (overall hypocellular).
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. Scattered and rare focal aggregates of dysplastic megakaryocytes.
Myeloid dysplastic syndrome in familial platelet disorder with associated myeloid malignancy. CD61 immunohistochemistry highlights small mononuclear megakaryocytes (intense staining of moderate cytoplasm) and increased megakaryoblasts (dim staining with scant cytoplasm).
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. Wright-stained bone marrow aspirate smear with an absence of neutrophils and increased eosinophils.
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. Wright-stained bone marrow aspirate smear with rare focal collection of immature myeloid precursors. Blasts are < 5% and there is a normal bone marrow karyotype.
Severe congenital neutropenia. Bone marrow from a 2-year-old patient on chronic G-CSF therapy with a decreasing absolute neutrophil count and no evidence of acute myeloid leukaemia (AML) / myeloid dysplastic syndrome. PAS-stained bone marrow biopsy with normal cellularity, peritrabecular myeloid precursor expansion, an absence of neutrophils, and normal erythroid and megakaryocytic maturation.
Myeloid dysplastic syndrome (MDS) in Fanconi anaemia (FA). Spectrum of haematological conditions in patients with FA, and a diagnostic algorithm based on laboratory results. BM, bone marrow; FA-AIP, cytogenetic aberration of indeterminate potential in a patient with FA; FA-AML, acute myeloid leukaemia in a patient with FA; FA-BMF, bone marrow failure in a patient with FA with a normal blast percentage and normal cytogenetics; FA-MDS–EB, MDS with excess blasts in a patient with FA; FA-MDS–non-EB, MDS without excess blasts in a patient with FA; PB, peripheral blood. *In cases with rapid rise in bone marrow cellularity, FA-MDS must be considered.

Q: In Myeloid Proliferations Associated with Down Syndrome, neonates may present with hepatosplenomegaly, a vesiculopapular rash, and peripheral blood blasts with abnormal megakaryocytic features, representing a phase called [...].
Transient abnormal myelopoiesis. A low-power view of a blood film with many blasts.
Transient abnormal myelopoiesis. A higher-power view of a blood film with blasts, including one that is partially differentiated towards an abnormal megakaryocyte and a megakaryocyte fragment (i.e. a huge platelet, larger than a red cell).
A: transient abnormal myelopoiesis
Back Extra: Myeloid Proliferations Associated with Down Syndrome
- Clinical: Transient abnormal myelopoiesis (TAM) often presents with hepatomegaly, splenomegaly, and a vesiculopapular skin rash in neonates with Down syndrome.
- Micro: Myeloid leukaemia associated with Down syndrome (ML-DS) is characterized by infiltration of the bone marrow with blasts, often expressing megakaryocytic markers.
- Ancillary: Detection of exon 2 or 3 GATA1 mutations in peripheral blood blasts is crucial for diagnosing transient abnormal myelopoiesis (TAM) and myeloid leukaemia associated with Down syndrome (ML-DS).
Reference Gallery:
Transient abnormal myelopoiesis. A low-power view of a blood film with many blasts.
Transient abnormal myelopoiesis. A higher-power view of a blood film with blasts, including one that is partially differentiated towards an abnormal megakaryocyte and a megakaryocyte fragment (i.e. a huge platelet, larger than a red cell).
Myeloid (megakaryoblastic) leukaemia in Down syndrome. The cells are CD42-positive in this preparation, consistent with megakaryoblasts.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. The densely cellular bone marrow has a prominent blastic component and a dense reticulin network. Blasts are positive for KIT (CD117) in this preparation, consistent with megakaryoblasts.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. There is a densely cellular bone marrow with a dense reticulin network.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. There is a densely cellular bone marrow with a prominent blastic component.

Q: In the leukemic phase of Myeloid Proliferations Associated with Down Syndrome, the bone marrow is typically infiltrated by megakaryoblasts that express characteristic markers such as KIT (CD117) and [...].
Myeloid (megakaryoblastic) leukaemia in Down syndrome. The cells are CD42-positive in this preparation, consistent with megakaryoblasts.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. The densely cellular bone marrow has a prominent blastic component and a dense reticulin network. Blasts are positive for KIT (CD117) in this preparation, consistent with megakaryoblasts.
A: CD42
Back Extra: Myeloid Proliferations Associated with Down Syndrome
- Clinical: Transient abnormal myelopoiesis (TAM) often presents with hepatomegaly, splenomegaly, and a vesiculopapular skin rash in neonates with Down syndrome.
- Micro: Myeloid leukaemia associated with Down syndrome (ML-DS) is characterized by infiltration of the bone marrow with blasts, often expressing megakaryocytic markers.
- Ancillary: Detection of exon 2 or 3 GATA1 mutations in peripheral blood blasts is crucial for diagnosing transient abnormal myelopoiesis (TAM) and myeloid leukaemia associated with Down syndrome (ML-DS).
Reference Gallery:
Transient abnormal myelopoiesis. A low-power view of a blood film with many blasts.
Transient abnormal myelopoiesis. A higher-power view of a blood film with blasts, including one that is partially differentiated towards an abnormal megakaryocyte and a megakaryocyte fragment (i.e. a huge platelet, larger than a red cell).
Myeloid (megakaryoblastic) leukaemia in Down syndrome. The cells are CD42-positive in this preparation, consistent with megakaryoblasts.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. The densely cellular bone marrow has a prominent blastic component and a dense reticulin network. Blasts are positive for KIT (CD117) in this preparation, consistent with megakaryoblasts.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. There is a densely cellular bone marrow with a dense reticulin network.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. There is a densely cellular bone marrow with a prominent blastic component.

Q: In Myeloid Proliferations Associated with Down Syndrome, the densely cellular bone marrow infiltrated by megakaryoblasts classically exhibits a prominent [...].
Myeloid (megakaryoblastic) leukaemia in Down syndrome. There is a densely cellular bone marrow with a dense reticulin network.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. There is a densely cellular bone marrow with a prominent blastic component.
A: reticulin network
Back Extra: Myeloid Proliferations Associated with Down Syndrome
- Clinical: Transient abnormal myelopoiesis (TAM) often presents with hepatomegaly, splenomegaly, and a vesiculopapular skin rash in neonates with Down syndrome.
- Micro: Myeloid leukaemia associated with Down syndrome (ML-DS) is characterized by infiltration of the bone marrow with blasts, often expressing megakaryocytic markers.
- Ancillary: Detection of exon 2 or 3 GATA1 mutations in peripheral blood blasts is crucial for diagnosing transient abnormal myelopoiesis (TAM) and myeloid leukaemia associated with Down syndrome (ML-DS).
Reference Gallery:
Transient abnormal myelopoiesis. A low-power view of a blood film with many blasts.
Transient abnormal myelopoiesis. A higher-power view of a blood film with blasts, including one that is partially differentiated towards an abnormal megakaryocyte and a megakaryocyte fragment (i.e. a huge platelet, larger than a red cell).
Myeloid (megakaryoblastic) leukaemia in Down syndrome. The cells are CD42-positive in this preparation, consistent with megakaryoblasts.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. The densely cellular bone marrow has a prominent blastic component and a dense reticulin network. Blasts are positive for KIT (CD117) in this preparation, consistent with megakaryoblasts.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. There is a densely cellular bone marrow with a dense reticulin network.
Myeloid (megakaryoblastic) leukaemia in Down syndrome. There is a densely cellular bone marrow with a prominent blastic component.

Q: In Refractory Cytopenia of Childhood, bone marrow biopsies typically exhibit a patchy distribution of hematopoiesis and overall [...].
Refractory cytopenia of childhood. Bone marrow biopsy show hypoplasia and patchy distribution of haematopoiesis, in particular erythropoiesis.
A: hypoplasia
Back Extra: Refractory Cytopenia of Childhood
- Clinical: Refractory cytopenia of childhood (RCC) often presents with symptoms such as bleeding, fever, and malaise, with common findings of cytopenia, particularly thrombocytopenia and anemia.
- Micro: In RCC, bone marrow biopsies typically show hypoplasia or patchy distribution of hematopoiesis, with dysplasia in myeloid lineages and abnormal erythroid precursors.
- Ancillary: Monosomy 7 is the most common cytogenetic abnormality in RCC and is associated with a higher risk of progression to advanced MDS or AML.
Reference Gallery:
Refractory cytopenia of childhood. Bone marrow biopsy show hypoplasia and patchy distribution of haematopoiesis, in particular erythropoiesis.
Refractory cytopenia of childhood. Bone marrow biopsy shows a cluster of proerythroblasts without maturation.
Refractory cytopenia of childhood. Bone marrow biopsy shows dysplasia of megakaryocytes with small, non-lobated nuclei or separated nuclei on CD42b immunohistochemistry.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing an erythroid precursor with abnormal nuclear segmentation, nuclear bridges, and megaloblastoid changes.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing a small megakaryocyte with a round nucleus.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing an erythroid precursor with double nuclei.

Q: In Refractory Cytopenia of Childhood, megakaryocytic dysplasia frequently manifests as small cells with non-lobated nuclei, which can be highlighted using [...] immunohistochemistry.
Refractory cytopenia of childhood. Bone marrow biopsy shows dysplasia of megakaryocytes with small, non-lobated nuclei or separated nuclei on CD42b immunohistochemistry.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing a small megakaryocyte with a round nucleus.
A: CD42b
Back Extra: Refractory Cytopenia of Childhood
- Clinical: Refractory cytopenia of childhood (RCC) often presents with symptoms such as bleeding, fever, and malaise, with common findings of cytopenia, particularly thrombocytopenia and anemia.
- Micro: In RCC, bone marrow biopsies typically show hypoplasia or patchy distribution of hematopoiesis, with dysplasia in myeloid lineages and abnormal erythroid precursors.
- Ancillary: Monosomy 7 is the most common cytogenetic abnormality in RCC and is associated with a higher risk of progression to advanced MDS or AML.
Reference Gallery:
Refractory cytopenia of childhood. Bone marrow biopsy show hypoplasia and patchy distribution of haematopoiesis, in particular erythropoiesis.
Refractory cytopenia of childhood. Bone marrow biopsy shows a cluster of proerythroblasts without maturation.
Refractory cytopenia of childhood. Bone marrow biopsy shows dysplasia of megakaryocytes with small, non-lobated nuclei or separated nuclei on CD42b immunohistochemistry.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing an erythroid precursor with abnormal nuclear segmentation, nuclear bridges, and megaloblastoid changes.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing a small megakaryocyte with a round nucleus.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing an erythroid precursor with double nuclei.

Q: In Refractory Cytopenia of Childhood, bone marrow aspirates often demonstrate marked dysplasia in [...] precursors, exhibiting features such as abnormal nuclear segmentation, nuclear bridges, and double nuclei.
Refractory cytopenia of childhood. Bone marrow biopsy shows a cluster of proerythroblasts without maturation.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing an erythroid precursor with abnormal nuclear segmentation, nuclear bridges, and megaloblastoid changes.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing an erythroid precursor with double nuclei.
A: erythroid
Back Extra: Refractory Cytopenia of Childhood
- Clinical: Refractory cytopenia of childhood (RCC) often presents with symptoms such as bleeding, fever, and malaise, with common findings of cytopenia, particularly thrombocytopenia and anemia.
- Micro: In RCC, bone marrow biopsies typically show hypoplasia or patchy distribution of hematopoiesis, with dysplasia in myeloid lineages and abnormal erythroid precursors.
- Ancillary: Monosomy 7 is the most common cytogenetic abnormality in RCC and is associated with a higher risk of progression to advanced MDS or AML.
Reference Gallery:
Refractory cytopenia of childhood. Bone marrow biopsy show hypoplasia and patchy distribution of haematopoiesis, in particular erythropoiesis.
Refractory cytopenia of childhood. Bone marrow biopsy shows a cluster of proerythroblasts without maturation.
Refractory cytopenia of childhood. Bone marrow biopsy shows dysplasia of megakaryocytes with small, non-lobated nuclei or separated nuclei on CD42b immunohistochemistry.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing an erythroid precursor with abnormal nuclear segmentation, nuclear bridges, and megaloblastoid changes.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing a small megakaryocyte with a round nucleus.
Refractory cytopenia of childhood. Bone marrow aspirate smear showing an erythroid precursor with double nuclei.

Q: Histologically, Atypical Choroid Plexus Papilloma is characterized by an otherwise well-differentiated papillary tumor with increased [...] (≥ 1 mitosis/mm² or ≥ 2 mitoses/10 HPF).
Atypical choroid plexus papilloma. Increased mitotic activity in an otherwise well-differentiated papillary tumour.
A: mitotic activity
Back Extra: Atypical Choroid Plexus Papilloma
- Clinical: Atypical choroid plexus papillomas often present with hydrocephalus and raised intracranial pressure, and have been reported with metastasis at diagnosis in 17% of cases.
- Micro: Atypical choroid plexus papilloma is characterized by increased mitotic activity (≥ 1 mitosis/mm² or ≥ 2 mitoses/10 HPF).
- Ancillary: Genome-wide chromosomal copy-number analysis can demonstrate characteristic hyperploidy, which aids in differentiating from choroid plexus carcinoma.
Reference Gallery:
Atypical choroid plexus papilloma. Increased mitotic activity in an otherwise well-differentiated papillary tumour.
Atypical choroid plexus papilloma. Increased proliferative activity (Ki-67 immunohistochemistry).

Q: An intraventricular papillary tumor presenting with hydrocephalus that demonstrates elevated Ki-67 proliferation and ≥ 2 mitoses/10 HPF is best classified as [...].
Atypical choroid plexus papilloma. Increased mitotic activity in an otherwise well-differentiated papillary tumour.
Atypical choroid plexus papilloma. Increased proliferative activity (Ki-67 immunohistochemistry).
A: Atypical Choroid Plexus Papilloma
Back Extra: Atypical Choroid Plexus Papilloma
- Clinical: Atypical choroid plexus papillomas often present with hydrocephalus and raised intracranial pressure, and have been reported with metastasis at diagnosis in 17% of cases.
- Micro: Atypical choroid plexus papilloma is characterized by increased mitotic activity (≥ 1 mitosis/mm² or ≥ 2 mitoses/10 HPF).
- Ancillary: Genome-wide chromosomal copy-number analysis can demonstrate characteristic hyperploidy, which aids in differentiating from choroid plexus carcinoma.
Reference Gallery:
Atypical choroid plexus papilloma. Increased mitotic activity in an otherwise well-differentiated papillary tumour.
Atypical choroid plexus papilloma. Increased proliferative activity (Ki-67 immunohistochemistry).

Q: Choroid plexus carcinoma typically arises in the [...] of young children, often presenting as a large, contrast-enhancing tumor that causes hydrocephalus.
Choroid plexus carcinoma. This T1-weighted coronal MRI of a 5-year-old girl shows a contrast-enhancing tumour related to the lateral ventricle.
Choroid plexus carcinoma. A large choroid plexus carcinoma in the lateral ventricle with extensive invasion of brain tissue.
A: lateral ventricles
Back Extra: Choroid Plexus Carcinoma
- Clinical: Choroid plexus carcinomas often cause hydrocephalus, increased intracranial pressure, and symptoms like nausea and vomiting due to their location in the ventricles.
- Micro: Choroid plexus carcinomas exhibit increased cellularity, nuclear pleomorphism, and frequent mitotic figures, often with necrosis and invasion into the brain parenchyma.
- Ancillary: Immunohistochemistry shows positivity for cytokeratins and transthyretin, with a high Ki-67 index, and TP53 mutations are common.
Reference Gallery:
Choroid plexus carcinoma. Increased cellularity, nuclear pleomorphism, and mitotic activity.
Choroid plexus carcinoma. Immunohistochemistry for cytokeratin is positive.
Choroid plexus carcinoma. Immunohistochemisty for transthyretin (prealbumin).
Choroid plexus carcinoma. Ki-67 immunohistochemical staining shows high proliferative activity.
Choroid plexus carcinoma. Cytokeratin-positive choroid plexus carcinoma is shown invading the brain parenchyma.
Choroid plexus carcinoma. Choroid plexus carcinoma is shown invading GFAP-positive brain parenchyma.
Choroid plexus carcinoma. This T1-weighted coronal MRI of a 5-year-old girl shows a contrast-enhancing tumour related to the lateral ventricle.
Choroid plexus carcinoma. Axial T2-weighted MRI of a 5-year-old girl.
Choroid plexus carcinoma. Touch preparation shows epithelioid cells with pleomorphism.
Choroid plexus carcinoma. A large choroid plexus carcinoma in the lateral ventricle with extensive invasion of brain tissue.

Q: A key microscopic feature of choroid plexus carcinoma is the presence of atypical cells with frequent mitoses and frank [...], which can be highlighted by GFAP staining of adjacent normal tissue.
Choroid plexus carcinoma. Increased cellularity, nuclear pleomorphism, and mitotic activity.
Choroid plexus carcinoma. Cytokeratin-positive choroid plexus carcinoma is shown invading the brain parenchyma.
Choroid plexus carcinoma. Choroid plexus carcinoma is shown invading GFAP-positive brain parenchyma.
A: invasion into the brain parenchyma
Back Extra: Choroid Plexus Carcinoma
- Clinical: Choroid plexus carcinomas often cause hydrocephalus, increased intracranial pressure, and symptoms like nausea and vomiting due to their location in the ventricles.
- Micro: Choroid plexus carcinomas exhibit increased cellularity, nuclear pleomorphism, and frequent mitotic figures, often with necrosis and invasion into the brain parenchyma.
- Ancillary: Immunohistochemistry shows positivity for cytokeratins and transthyretin, with a high Ki-67 index, and TP53 mutations are common.
Reference Gallery:
Choroid plexus carcinoma. Increased cellularity, nuclear pleomorphism, and mitotic activity.
Choroid plexus carcinoma. Immunohistochemistry for cytokeratin is positive.
Choroid plexus carcinoma. Immunohistochemisty for transthyretin (prealbumin).
Choroid plexus carcinoma. Ki-67 immunohistochemical staining shows high proliferative activity.
Choroid plexus carcinoma. Cytokeratin-positive choroid plexus carcinoma is shown invading the brain parenchyma.
Choroid plexus carcinoma. Choroid plexus carcinoma is shown invading GFAP-positive brain parenchyma.
Choroid plexus carcinoma. This T1-weighted coronal MRI of a 5-year-old girl shows a contrast-enhancing tumour related to the lateral ventricle.
Choroid plexus carcinoma. Axial T2-weighted MRI of a 5-year-old girl.
Choroid plexus carcinoma. Touch preparation shows epithelioid cells with pleomorphism.
Choroid plexus carcinoma. A large choroid plexus carcinoma in the lateral ventricle with extensive invasion of brain tissue.

Q: Immunohistochemical evaluation of choroid plexus carcinoma typically demonstrates an elevated Ki-67 index and tumor cells that are positive for cytokeratins and [...].
Choroid plexus carcinoma. Immunohistochemistry for cytokeratin is positive.
Choroid plexus carcinoma. Immunohistochemisty for transthyretin (prealbumin).
Choroid plexus carcinoma. Ki-67 immunohistochemical staining shows high proliferative activity.
A: transthyretin
Back Extra: Choroid Plexus Carcinoma
- Clinical: Choroid plexus carcinomas often cause hydrocephalus, increased intracranial pressure, and symptoms like nausea and vomiting due to their location in the ventricles.
- Micro: Choroid plexus carcinomas exhibit increased cellularity, nuclear pleomorphism, and frequent mitotic figures, often with necrosis and invasion into the brain parenchyma.
- Ancillary: Immunohistochemistry shows positivity for cytokeratins and transthyretin, with a high Ki-67 index, and TP53 mutations are common.
Reference Gallery:
Choroid plexus carcinoma. Increased cellularity, nuclear pleomorphism, and mitotic activity.
Choroid plexus carcinoma. Immunohistochemistry for cytokeratin is positive.
Choroid plexus carcinoma. Immunohistochemisty for transthyretin (prealbumin).
Choroid plexus carcinoma. Ki-67 immunohistochemical staining shows high proliferative activity.
Choroid plexus carcinoma. Cytokeratin-positive choroid plexus carcinoma is shown invading the brain parenchyma.
Choroid plexus carcinoma. Choroid plexus carcinoma is shown invading GFAP-positive brain parenchyma.
Choroid plexus carcinoma. This T1-weighted coronal MRI of a 5-year-old girl shows a contrast-enhancing tumour related to the lateral ventricle.
Choroid plexus carcinoma. Axial T2-weighted MRI of a 5-year-old girl.
Choroid plexus carcinoma. Touch preparation shows epithelioid cells with pleomorphism.
Choroid plexus carcinoma. A large choroid plexus carcinoma in the lateral ventricle with extensive invasion of brain tissue.

Q: On imaging and gross examination, a Choroid Plexus Papilloma typically presents as an enhancing, [...]-like intraventricular mass that often causes hydrocephalus.
Choroid plexus papilloma. Sagittal, contrast-enhanced, T1-weighted MRI shows a strongly enhancing, cauliflower-like mass in the third ventricle of a 22-month-old girl.
Choroid plexus papilloma. Intraoperative endoscopic view of a choroid plexus papilloma.
A: cauliflower
Back Extra: Choroid Plexus Papilloma
- Clinical: Choroid plexus papillomas are most often located in the lateral ventricles, followed by the fourth and third ventricles. Hydrocephalus and increased intracranial pressure are common features.
- Micro: The histopathology shows a well-developed papillary pattern with a single layer of uniform cuboidal to columnar epithelial cells, and very low or absent mitotic activity.
- Ancillary: Immunohistochemistry is positive for cytokeratins, vimentin, and S100, with membranous staining for the potassium channel Kir7.1 and transthyretin.
Reference Gallery:
Choroid plexus papilloma. Sagittal, contrast-enhanced, T1-weighted MRI shows a strongly enhancing, cauliflower-like mass in the third ventricle of a 22-month-old girl.
Choroid plexus papilloma. Intraoperative endoscopic view of a choroid plexus papilloma.
Choroid plexus papilloma. Papillary pattern with a single layer of monomorphic cuboidal cells.
Choroid plexus papilloma. Immunohistochemistry for S100.
Choroid plexus papilloma. Immunohistochemistry for transthyretin (prealbumin).
Choroid plexus papilloma cells in cerebrospinal fluid. Immunohistochemistry for the potassium channel Kir7.1.
Choroid plexus papilloma. Immunohistochemistry for the potassium channel Kir7.1 shows typical membranous labelling of the apical surface of tumour cells.

Q: Histologically, a Choroid Plexus Papilloma features a well-developed papillary pattern lined by a single layer of uniform [...] epithelial cells with very low or absent mitotic activity.
Choroid plexus papilloma. Papillary pattern with a single layer of monomorphic cuboidal cells.
A: cuboidal to columnar
Back Extra: Choroid Plexus Papilloma
- Clinical: Choroid plexus papillomas are most often located in the lateral ventricles, followed by the fourth and third ventricles. Hydrocephalus and increased intracranial pressure are common features.
- Micro: The histopathology shows a well-developed papillary pattern with a single layer of uniform cuboidal to columnar epithelial cells, and very low or absent mitotic activity.
- Ancillary: Immunohistochemistry is positive for cytokeratins, vimentin, and S100, with membranous staining for the potassium channel Kir7.1 and transthyretin.
Reference Gallery:
Choroid plexus papilloma. Sagittal, contrast-enhanced, T1-weighted MRI shows a strongly enhancing, cauliflower-like mass in the third ventricle of a 22-month-old girl.
Choroid plexus papilloma. Intraoperative endoscopic view of a choroid plexus papilloma.
Choroid plexus papilloma. Papillary pattern with a single layer of monomorphic cuboidal cells.
Choroid plexus papilloma. Immunohistochemistry for S100.
Choroid plexus papilloma. Immunohistochemistry for transthyretin (prealbumin).
Choroid plexus papilloma cells in cerebrospinal fluid. Immunohistochemistry for the potassium channel Kir7.1.
Choroid plexus papilloma. Immunohistochemistry for the potassium channel Kir7.1 shows typical membranous labelling of the apical surface of tumour cells.

Q: In addition to S100 and transthyretin, immunohistochemistry for a Choroid Plexus Papilloma characteristically shows apical membranous staining for the potassium channel [...].
Choroid plexus papilloma. Immunohistochemistry for S100.
Choroid plexus papilloma. Immunohistochemistry for transthyretin (prealbumin).
Choroid plexus papilloma. Immunohistochemistry for the potassium channel Kir7.1 shows typical membranous labelling of the apical surface of tumour cells.
A: Kir7.1
Back Extra: Choroid Plexus Papilloma
- Clinical: Choroid plexus papillomas are most often located in the lateral ventricles, followed by the fourth and third ventricles. Hydrocephalus and increased intracranial pressure are common features.
- Micro: The histopathology shows a well-developed papillary pattern with a single layer of uniform cuboidal to columnar epithelial cells, and very low or absent mitotic activity.
- Ancillary: Immunohistochemistry is positive for cytokeratins, vimentin, and S100, with membranous staining for the potassium channel Kir7.1 and transthyretin.
Reference Gallery:
Choroid plexus papilloma. Sagittal, contrast-enhanced, T1-weighted MRI shows a strongly enhancing, cauliflower-like mass in the third ventricle of a 22-month-old girl.
Choroid plexus papilloma. Intraoperative endoscopic view of a choroid plexus papilloma.
Choroid plexus papilloma. Papillary pattern with a single layer of monomorphic cuboidal cells.
Choroid plexus papilloma. Immunohistochemistry for S100.
Choroid plexus papilloma. Immunohistochemistry for transthyretin (prealbumin).
Choroid plexus papilloma cells in cerebrospinal fluid. Immunohistochemistry for the potassium channel Kir7.1.
Choroid plexus papilloma. Immunohistochemistry for the potassium channel Kir7.1 shows typical membranous labelling of the apical surface of tumour cells.

Q: In Atypical Teratoid/Rhabdoid Tumor, the hallmark histologic finding is the presence of [...], which are characterized by eccentric vesicular nuclei, prominent nucleoli, and abundant pale eosinophilic cytoplasm.
Atypical teratoid/rhabdoid tumour. Rhabdoid cells of varying size with vesicular nuclei, prominent nucleoli, and pale eosinophilic cytoplasm.
Atypical teratoid/rhabdoid tumour. Leptomeningeal tumour spread. Cerebrospinal fluid cytology shows large tumour cells with rhabdoid features (extensive cytoplasm with eccentric nuclei). May–Grünwald–Giemsa staining.
A: rhabdoid cells
Back Extra: Atypical Teratoid/Rhabdoid Tumor
- Clinical: Atypical teratoid/rhabdoid tumour (AT/RT) commonly presents with nonspecific signs such as lethargy, vomiting, and failure to thrive, especially in infants.
- Micro: AT/RTs are characterized by a mixture of poorly differentiated cells, rhabdoid cells, and areas of mesenchymal and epithelial differentiation.
- Ancillary: Loss of nuclear SMARCB1 (INI1) expression is a highly sensitive marker for diagnosing AT/RT.
Reference Gallery:
Atypical teratoid/rhabdoid tumour (AT/RT) consensus subtypes. Summary of demographic and molecular features of AT/RT subtypes.
Atypical teratoid/rhabdoid tumour. Tumour with multiple haemorrhagic areas, arising in the right cerebellopontine angle.
Atypical teratoid/rhabdoid tumour. Axial T2-weighted MRI demonstrating tumour heterogeneity.
Atypical teratoid/rhabdoid tumour. Axial T1-weighted MRI.
Atypical teratoid/rhabdoid tumour. Rhabdoid cells of varying size with vesicular nuclei, prominent nucleoli, and pale eosinophilic cytoplasm.
Atypical teratoid/rhabdoid tumour. Lesions composed of small embryonal cells without typical rhabdoid cells raise the diagnostic possibility of other CNS embryonal tumours.
Atypical teratoid/rhabdoid tumour. Mesenchymal area composed of loosely arranged elongated cells.
Atypical teratoid/rhabdoid tumour. Compact area with fascicular growth pattern.
Atypical teratoid/rhabdoid tumour. Loss of nuclear immunoreactivity for SMARCB1 in tumour cells, with retained expression in endothelial cells.
Atypical teratoid/rhabdoid tumour. SMA positivity.
Atypical teratoid/rhabdoid tumour. Patchy expression of EMA.
Atypical teratoid/rhabdoid tumour. Leptomeningeal tumour spread. Cerebrospinal fluid cytology shows large tumour cells with rhabdoid features (extensive cytoplasm with eccentric nuclei). May–Grünwald–Giemsa staining.

Q: A defining diagnostic feature of Atypical Teratoid/Rhabdoid Tumor is the immunohistochemical loss of nuclear expression for [...] in tumor cells, with retained expression in endothelial and inflammatory cells.
Atypical teratoid/rhabdoid tumour. Loss of nuclear immunoreactivity for SMARCB1 in tumour cells, with retained expression in endothelial cells.
A: SMARCB1 (INI1)
Back Extra: Atypical Teratoid/Rhabdoid Tumor
- Clinical: Atypical teratoid/rhabdoid tumour (AT/RT) commonly presents with nonspecific signs such as lethargy, vomiting, and failure to thrive, especially in infants.
- Micro: AT/RTs are characterized by a mixture of poorly differentiated cells, rhabdoid cells, and areas of mesenchymal and epithelial differentiation.
- Ancillary: Loss of nuclear SMARCB1 (INI1) expression is a highly sensitive marker for diagnosing AT/RT.
Reference Gallery:
Atypical teratoid/rhabdoid tumour (AT/RT) consensus subtypes. Summary of demographic and molecular features of AT/RT subtypes.
Atypical teratoid/rhabdoid tumour. Tumour with multiple haemorrhagic areas, arising in the right cerebellopontine angle.
Atypical teratoid/rhabdoid tumour. Axial T2-weighted MRI demonstrating tumour heterogeneity.
Atypical teratoid/rhabdoid tumour. Axial T1-weighted MRI.
Atypical teratoid/rhabdoid tumour. Rhabdoid cells of varying size with vesicular nuclei, prominent nucleoli, and pale eosinophilic cytoplasm.
Atypical teratoid/rhabdoid tumour. Lesions composed of small embryonal cells without typical rhabdoid cells raise the diagnostic possibility of other CNS embryonal tumours.
Atypical teratoid/rhabdoid tumour. Mesenchymal area composed of loosely arranged elongated cells.
Atypical teratoid/rhabdoid tumour. Compact area with fascicular growth pattern.
Atypical teratoid/rhabdoid tumour. Loss of nuclear immunoreactivity for SMARCB1 in tumour cells, with retained expression in endothelial cells.
Atypical teratoid/rhabdoid tumour. SMA positivity.
Atypical teratoid/rhabdoid tumour. Patchy expression of EMA.
Atypical teratoid/rhabdoid tumour. Leptomeningeal tumour spread. Cerebrospinal fluid cytology shows large tumour cells with rhabdoid features (extensive cytoplasm with eccentric nuclei). May–Grünwald–Giemsa staining.

Q: A pediatric patient presents with a large, partly solid and partly cystic brain mass on MRI. Histology reveals sheets of densely packed, poorly differentiated cells with a high nuclear-to-cytoplasmic ratio and brisk mitotic activity. If comprehensive molecular testing (such as genome-wide methylation profiling) is performed but fails to match a recognized World Health Organization category, the diagnosis is a(n) [...].
CNS embryonal tumour. Postcontrast, T1-weighted MRI showing a large, partly solid, partly cystic tumour in the left frontal lobe of an infant. This is the same patient of whom the histology and copy-number variation profile are shown in Fig. #36360 and Fig. #36361.
CNS embryonal tumour. CNS embryonal tumour (from the same patient shown in Fig. #36359) consisting of densely packed, small, poorly differentiated cells with a high mitotic count. RNA sequencing revealed a BRD4::CREBBP fusion gene. Methylation profiling did not result in a match using the brain tumour classifier available at https://www.molecularneuropathology.org.
CNS embryonal tumour. The copy-number variation profile of the tumour in Fig. #36359 and Fig. #36360 (derived from genome-wide methylome analysis) did not reveal large chromosomal gains or losses. The tumour was classified as CNS embryonal tumour not elsewhere classified (NEC).
A: CNS embryonal tumor NEC/NOS
Back Extra: CNS Embryonal Tumour NEC/NOS
- Clinical: Patients with CNS embryonal tumours generally present acutely with symptoms of raised intracranial pressure, epilepsy, or focal neurological deficits.
- Micro: CNS embryonal tumours are characterized by sheets of densely packed, immature cells with a high N:C ratio, round, oval, or angulated hyperchromatic nuclei, and high mitotic activity.
- Ancillary: The neoplastic cells in CNS embryonal tumours are variably immunopositive for synaptophysin and OLIG2 and demonstrate a high Ki-67 proliferation index.
Reference Gallery:
CNS embryonal tumour. Postcontrast, T1-weighted MRI showing a large, partly solid, partly cystic tumour in the left frontal lobe of an infant. This is the same patient of whom the histology and copy-number variation profile are shown in Fig. #36360 and Fig. #36361.
CNS embryonal tumour. CNS embryonal tumour (from the same patient shown in Fig. #36359) consisting of densely packed, small, poorly differentiated cells with a high mitotic count. RNA sequencing revealed a BRD4::CREBBP fusion gene. Methylation profiling did not result in a match using the brain tumour classifier available at https://www.molecularneuropathology.org.
CNS embryonal tumour. The copy-number variation profile of the tumour in Fig. #36359 and Fig. #36360 (derived from genome-wide methylome analysis) did not reveal large chromosomal gains or losses. The tumour was classified as CNS embryonal tumour not elsewhere classified (NEC).

Q: A rare embryonal tumor primarily occurring in childhood that exhibits poorly differentiated cells in a neuropil-like matrix, strong OLIG2 positivity, and widespread TTF1 expression is known as [...].
CNS neuroblastoma, FOXR2-activated. Axial T2-weighted image showing a large, partially cystic mass involving the right parietal lobe (left).
CNS neuroblastoma, FOXR2-activated. Neurocytic and neuroblastic cells are set in a neuropil-like matrix.
A: CNS Neuroblastoma, FOXR2-Activated
Q: CNS Neuroblastoma, FOXR2-Activated
- Clinical: [...] CNS neuroblastoma is a rare, recently described tumour occurring primarily in childhood, often with a slight female preponderance.
- Micro: The tumour consists of sheets of poorly differentiated cells with a high N:C ratio, round, oval, or angulated hyperchromatic nuclei, and abundant mitotic activity. Areas of necrosis and Homer Wright rosettes may be evident.
- Ancillary: Immunohistochemistry shows strong OLIG2 immunolabelling and a high Ki-67 proliferation index. Widespread synaptophysin and TTF1 immunoreactivities may also be present.
Reference Gallery:
CNS neuroblastoma, FOXR2-activated. Axial T2-weighted image showing a large, partially cystic mass involving the right parietal lobe (left).
CNS neuroblastoma, FOXR2-activated. Some tumours show focal ganglion cell formation (ganglioneuroblastoma phenotype).
CNS neuroblastoma, FOXR2-activated. Neurocytic and neuroblastic cells are set in a neuropil-like matrix.
CNS neuroblastoma, FOXR2-activated. Postcontrast T1-weighted image showing thickening and enhancement of overlying meninges as well as inhomogeneous enhancement of solid tumour components.
CNS neuroblastoma, FOXR2-activated. Typically, there is patchy immunoreactivity for synaptophysin, although expression is widespread in this example.
CNS neuroblastoma, FOXR2-activated. Extensive and strong OLIG2 immunolabelling is present in tumour cell nuclei.
CNS neuroblastoma, FOXR2-activated. The Ki-67 proliferation index is high.
CNS neuroblastoma, FOXR2-activated. Widespread and strong immunoreactivity for thyroid transcription factor 1 (TTF1, also called NKX2-1) may be found.
A: FOXR2-activated

Q: An unusual and highly specific immunohistochemical profile for CNS Neuroblastoma, FOXR2-Activated is the strong, widespread nuclear co-expression of OLIG2 and [...] (also known as NKX2-1).
CNS neuroblastoma, FOXR2-activated. Extensive and strong OLIG2 immunolabelling is present in tumour cell nuclei.
CNS neuroblastoma, FOXR2-activated. Widespread and strong immunoreactivity for thyroid transcription factor 1 (TTF1, also called NKX2-1) may be found.
A: TTF1
Q: CNS Neuroblastoma, FOXR2-Activated
- Clinical: [...] CNS neuroblastoma is a rare, recently described tumour occurring primarily in childhood, often with a slight female preponderance.
- Micro: The tumour consists of sheets of poorly differentiated cells with a high N:C ratio, round, oval, or angulated hyperchromatic nuclei, and abundant mitotic activity. Areas of necrosis and Homer Wright rosettes may be evident.
- Ancillary: Immunohistochemistry shows strong OLIG2 immunolabelling and a high Ki-67 proliferation index. Widespread synaptophysin and TTF1 immunoreactivities may also be present.
Reference Gallery:
CNS neuroblastoma, FOXR2-activated. Axial T2-weighted image showing a large, partially cystic mass involving the right parietal lobe (left).
CNS neuroblastoma, FOXR2-activated. Some tumours show focal ganglion cell formation (ganglioneuroblastoma phenotype).
CNS neuroblastoma, FOXR2-activated. Neurocytic and neuroblastic cells are set in a neuropil-like matrix.
CNS neuroblastoma, FOXR2-activated. Postcontrast T1-weighted image showing thickening and enhancement of overlying meninges as well as inhomogeneous enhancement of solid tumour components.
CNS neuroblastoma, FOXR2-activated. Typically, there is patchy immunoreactivity for synaptophysin, although expression is widespread in this example.
CNS neuroblastoma, FOXR2-activated. Extensive and strong OLIG2 immunolabelling is present in tumour cell nuclei.
CNS neuroblastoma, FOXR2-activated. The Ki-67 proliferation index is high.
CNS neuroblastoma, FOXR2-activated. Widespread and strong immunoreactivity for thyroid transcription factor 1 (TTF1, also called NKX2-1) may be found.
A: FOXR2-activated

Q: In CNS Neuroblastoma, FOXR2-Activated, some tumors exhibit a ganglioneuroblastoma phenotype characterized microscopically by focal [...] formation.
CNS neuroblastoma, FOXR2-activated. Some tumours show focal ganglion cell formation (ganglioneuroblastoma phenotype).
A: ganglion cell
Q: CNS Neuroblastoma, FOXR2-Activated
- Clinical: [...] CNS neuroblastoma is a rare, recently described tumour occurring primarily in childhood, often with a slight female preponderance.
- Micro: The tumour consists of sheets of poorly differentiated cells with a high N:C ratio, round, oval, or angulated hyperchromatic nuclei, and abundant mitotic activity. Areas of necrosis and Homer Wright rosettes may be evident.
- Ancillary: Immunohistochemistry shows strong OLIG2 immunolabelling and a high Ki-67 proliferation index. Widespread synaptophysin and TTF1 immunoreactivities may also be present.
Reference Gallery:
CNS neuroblastoma, FOXR2-activated. Axial T2-weighted image showing a large, partially cystic mass involving the right parietal lobe (left).
CNS neuroblastoma, FOXR2-activated. Some tumours show focal ganglion cell formation (ganglioneuroblastoma phenotype).
CNS neuroblastoma, FOXR2-activated. Neurocytic and neuroblastic cells are set in a neuropil-like matrix.
CNS neuroblastoma, FOXR2-activated. Postcontrast T1-weighted image showing thickening and enhancement of overlying meninges as well as inhomogeneous enhancement of solid tumour components.
CNS neuroblastoma, FOXR2-activated. Typically, there is patchy immunoreactivity for synaptophysin, although expression is widespread in this example.
CNS neuroblastoma, FOXR2-activated. Extensive and strong OLIG2 immunolabelling is present in tumour cell nuclei.
CNS neuroblastoma, FOXR2-activated. The Ki-67 proliferation index is high.
CNS neuroblastoma, FOXR2-activated. Widespread and strong immunoreactivity for thyroid transcription factor 1 (TTF1, also called NKX2-1) may be found.
A: FOXR2-activated

Q: The defining diagnostic genetic feature of CNS Tumor with BCOR Internal Tandem Duplication is a heterozygous [...] of the BCOR gene, which typically correlates with strong nuclear immunohistochemical expression.
CNS tumour with BCOR internal tandem duplication. Strong nuclear expression of BCOR is present in all tumour cells.
A: internal tandem duplication (ITD) in exon 15
Back Extra: CNS Tumour with BCOR Internal Tandem Duplication
- Clinical: The clinical presentation of CNS Tumour with BCOR Internal Tandem Duplication includes symptoms of raised intracranial pressure, focal neurological deficits, and seizures.
- Micro: Histological features include uniform oval or spindle-shaped cells, ependymoma-like perivascular pseudorosettes, and a myxoid or microcystic matrix.
- Ancillary: The defining diagnostic feature is a heterozygous internal tandem duplication (ITD) in exon 15 of the BCOR gene.
Reference Gallery:
CNS tumour with BCOR internal tandem duplication. Axial MRI/FLAIR image of a tumour in the basal ganglia.
CNS tumour with BCOR internal tandem duplication. Coronal T2-weighted MRI of a tumour located in the cerebellar hemisphere.
CNS tumour with BCOR internal tandem duplication. This tumour exhibits ependymoma-like pseudorosettes.
CNS tumour with BCOR internal tandem duplication. Strong nuclear expression of BCOR is present in all tumour cells.
CNS tumour with BCOR internal tandem duplication. Areas of necrosis with a palisading pattern can be present.
CNS tumour with BCOR internal tandem duplication. Some tumours demonstrate a glioma-like fibrillarity.
CNS tumour with BCOR internal tandem duplication. This field shows a high cell density and brisk mitotic activity.
CNS tumour with BCOR internal tandem duplication. Marked cytological pleomorphism may occasionally be found.
CNS tumour with BCOR internal tandem duplication. A collagenous stroma and rosette formation are occasionally seen.
CNS tumour with BCOR internal tandem duplication. Expression of OLIG2 is present in a subset of tumour cell nuclei.
CNS tumour with BCOR internal tandem duplication. Expression of NeuN is variable.
CNS tumour with BCOR internal tandem duplication. Weak, granular, cytoplasmic immunoreactivity for EMA is occasionally found.

Q: Histologically, a characteristic finding in CNS Tumor with BCOR Internal Tandem Duplication is the presence of uniform oval or spindle-shaped cells forming [...] within a myxoid or microcystic matrix.
CNS tumour with BCOR internal tandem duplication. This tumour exhibits ependymoma-like pseudorosettes.
A: ependymoma-like perivascular pseudorosettes
Back Extra: CNS Tumour with BCOR Internal Tandem Duplication
- Clinical: The clinical presentation of CNS Tumour with BCOR Internal Tandem Duplication includes symptoms of raised intracranial pressure, focal neurological deficits, and seizures.
- Micro: Histological features include uniform oval or spindle-shaped cells, ependymoma-like perivascular pseudorosettes, and a myxoid or microcystic matrix.
- Ancillary: The defining diagnostic feature is a heterozygous internal tandem duplication (ITD) in exon 15 of the BCOR gene.
Reference Gallery:
CNS tumour with BCOR internal tandem duplication. Axial MRI/FLAIR image of a tumour in the basal ganglia.
CNS tumour with BCOR internal tandem duplication. Coronal T2-weighted MRI of a tumour located in the cerebellar hemisphere.
CNS tumour with BCOR internal tandem duplication. This tumour exhibits ependymoma-like pseudorosettes.
CNS tumour with BCOR internal tandem duplication. Strong nuclear expression of BCOR is present in all tumour cells.
CNS tumour with BCOR internal tandem duplication. Areas of necrosis with a palisading pattern can be present.
CNS tumour with BCOR internal tandem duplication. Some tumours demonstrate a glioma-like fibrillarity.
CNS tumour with BCOR internal tandem duplication. This field shows a high cell density and brisk mitotic activity.
CNS tumour with BCOR internal tandem duplication. Marked cytological pleomorphism may occasionally be found.
CNS tumour with BCOR internal tandem duplication. A collagenous stroma and rosette formation are occasionally seen.
CNS tumour with BCOR internal tandem duplication. Expression of OLIG2 is present in a subset of tumour cell nuclei.
CNS tumour with BCOR internal tandem duplication. Expression of NeuN is variable.
CNS tumour with BCOR internal tandem duplication. Weak, granular, cytoplasmic immunoreactivity for EMA is occasionally found.

Q: A highly cellular pediatric neoplasm characterized by cells arranged in characteristic strands and trabeculae forming well-defined surfaces, an absence of rhabdoid cells, and loss of INI1 expression is known as [...].
Cribriform neuroepithelial tumour. A highly cellular tumour composed of relatively small cells arranged in cribriform strands, and trabeculae of varying thickness, forming well-defined surfaces.
A: Cribriform Neuroepithelial Tumor
Back Extra: Cribriform Neuroepithelial Tumour
- Clinical: Median age of 10 children harbouring CRINET is 20 months (range: 10–129 months) with a M:F ratio of 1.5:1.
- Micro: Highly cellular tumour characterized by cribriform strands and ribbons, absence of rhabdoid cells, and Ki-67/MIB1 proliferation index values between 5% and 35%.
- Ancillary: Loss of nuclear SMARCB1 protein expression, strong EMA expression, frequent tyrosinase expression, and genetic losses on chromosome 22q affecting the SMARCB1 region.
Reference Gallery:
Cribriform neuroepithelial tumour. A highly cellular tumour composed of relatively small cells arranged in cribriform strands, and trabeculae of varying thickness, forming well-defined surfaces.
Cribriform neuroepithelial tumour. Strong EMA expression in the tumour cells.
Cribriform neuroepithelial tumour. Loss of nuclear SMARCB1 (INI1) expression in the tumour cells.

Q: In Cribriform Neuroepithelial Tumor, immunohistochemistry characteristically demonstrates a defining loss of nuclear expression for [...] (INI1), driven by genetic losses on chromosome 22q.
Cribriform neuroepithelial tumour. Loss of nuclear SMARCB1 (INI1) expression in the tumour cells.
A: SMARCB1
Back Extra: Cribriform Neuroepithelial Tumour
- Clinical: Median age of 10 children harbouring CRINET is 20 months (range: 10–129 months) with a M:F ratio of 1.5:1.
- Micro: Highly cellular tumour characterized by cribriform strands and ribbons, absence of rhabdoid cells, and Ki-67/MIB1 proliferation index values between 5% and 35%.
- Ancillary: Loss of nuclear SMARCB1 protein expression, strong EMA expression, frequent tyrosinase expression, and genetic losses on chromosome 22q affecting the SMARCB1 region.
Reference Gallery:
Cribriform neuroepithelial tumour. A highly cellular tumour composed of relatively small cells arranged in cribriform strands, and trabeculae of varying thickness, forming well-defined surfaces.
Cribriform neuroepithelial tumour. Strong EMA expression in the tumour cells.
Cribriform neuroepithelial tumour. Loss of nuclear SMARCB1 (INI1) expression in the tumour cells.

Q: Along with loss of INI1, the neoplastic cells of Cribriform Neuroepithelial Tumor characteristically exhibit strong immunohistochemical expression of [...] (epithelial membrane antigen).
Cribriform neuroepithelial tumour. Strong EMA expression in the tumour cells.
A: EMA
Back Extra: Cribriform Neuroepithelial Tumour
- Clinical: Median age of 10 children harbouring CRINET is 20 months (range: 10–129 months) with a M:F ratio of 1.5:1.
- Micro: Highly cellular tumour characterized by cribriform strands and ribbons, absence of rhabdoid cells, and Ki-67/MIB1 proliferation index values between 5% and 35%.
- Ancillary: Loss of nuclear SMARCB1 protein expression, strong EMA expression, frequent tyrosinase expression, and genetic losses on chromosome 22q affecting the SMARCB1 region.
Reference Gallery:
Cribriform neuroepithelial tumour. A highly cellular tumour composed of relatively small cells arranged in cribriform strands, and trabeculae of varying thickness, forming well-defined surfaces.
Cribriform neuroepithelial tumour. Strong EMA expression in the tumour cells.
Cribriform neuroepithelial tumour. Loss of nuclear SMARCB1 (INI1) expression in the tumour cells.

Q: The defining histologic feature of an Embryonal tumor with multilayered rosettes is the presence of [...], and the tumor can frequently demonstrate ependymoblastoma or medulloepithelioma morphology.
Embryonal tumour with multilayered rosettes (ETMR). Multilayered rosettes are a defining feature of EMTR.
Embryonal tumour with multilayered rosettes (ETMR). ETMR with ependymoblastoma morphology. Multilayered rosettes are abundant.
Embryonal tumour with multilayered rosettes (ETMR). ETMR with medulloepithelioma morphology. Tubular structures resemble embryonic neural tube or elongated multilayered rosettes.
A: multilayered rosettes
Back Extra: Embryonal Tumour with Multilayered Rosettes
- Clinical: ETMRs commonly produce symptoms of raised intracranial pressure, such as headache, nausea, and vomiting, and are often located in the cerebral hemisphere.
- Micro: The presence of multilayered rosettes is a defining feature of ETMRs, which can also show ependymoblastoma or medulloepithelioma morphology.
- Ancillary: Approximately 90% of ETMRs harbour specific structural alterations of the C19MC microRNA cluster on chromosome 19q13.42.
Reference Gallery:
Embryonal tumour with multilayered rosettes. An embryonal tumour with abundant neuropil and true rosettes pattern. Groups of densely packed embryonal cells, some including multilayered rosettes, contrast with neuropil-like areas that typically contain neoplastic neurocytic cells.
Embryonal tumour with multilayered rosettes (ETMR). Multilayered rosettes are a defining feature of EMTR.
Embryonal tumour with multilayered rosettes (ETMR). ETMR with ependymoblastoma morphology. Multilayered rosettes are abundant.
Embryonal tumour with multilayered rosettes (ETMR). ETMR with medulloepithelioma morphology. Tubular structures resemble embryonic neural tube or elongated multilayered rosettes.
Embryonal tumour with multilayered rosettes. Interphase FISH. Amplification (green signals) of the C19MC locus at 19q13.42.
Embryonal tumour with multilayered rosettes. Many cells are immunopositive for vimentin.
Embryonal tumour with multilayered rosettes (ETMR). The neuropil-like matrix of ETMRs with an abundant neuropil and true rosettes pattern is synaptophysin-immunopositive.
Embryonal tumour with multilayered rosettes. Tumour cells are strongly immunopositive for LIN28A.
Embryonal tumour with multilayered rosettes. Panchromosomal copy-number alterations shown by DNA methylation array. Amplification and rearrangement of the C19MC locus on chromosome 19q and gain of chromosome 2 are prominent.

Q: Approximately 90% of Embryonal tumors with multilayered rosettes harbor specific structural alterations (e.g., amplification) of the [...] microRNA cluster on chromosome 19q13.42.
Embryonal tumour with multilayered rosettes. Interphase FISH. Amplification (green signals) of the C19MC locus at 19q13.42.
Embryonal tumour with multilayered rosettes. Panchromosomal copy-number alterations shown by DNA methylation array. Amplification and rearrangement of the C19MC locus on chromosome 19q and gain of chromosome 2 are prominent.
A: C19MC
Back Extra: Embryonal Tumour with Multilayered Rosettes
- Clinical: ETMRs commonly produce symptoms of raised intracranial pressure, such as headache, nausea, and vomiting, and are often located in the cerebral hemisphere.
- Micro: The presence of multilayered rosettes is a defining feature of ETMRs, which can also show ependymoblastoma or medulloepithelioma morphology.
- Ancillary: Approximately 90% of ETMRs harbour specific structural alterations of the C19MC microRNA cluster on chromosome 19q13.42.
Reference Gallery:
Embryonal tumour with multilayered rosettes. An embryonal tumour with abundant neuropil and true rosettes pattern. Groups of densely packed embryonal cells, some including multilayered rosettes, contrast with neuropil-like areas that typically contain neoplastic neurocytic cells.
Embryonal tumour with multilayered rosettes (ETMR). Multilayered rosettes are a defining feature of EMTR.
Embryonal tumour with multilayered rosettes (ETMR). ETMR with ependymoblastoma morphology. Multilayered rosettes are abundant.
Embryonal tumour with multilayered rosettes (ETMR). ETMR with medulloepithelioma morphology. Tubular structures resemble embryonic neural tube or elongated multilayered rosettes.
Embryonal tumour with multilayered rosettes. Interphase FISH. Amplification (green signals) of the C19MC locus at 19q13.42.
Embryonal tumour with multilayered rosettes. Many cells are immunopositive for vimentin.
Embryonal tumour with multilayered rosettes (ETMR). The neuropil-like matrix of ETMRs with an abundant neuropil and true rosettes pattern is synaptophysin-immunopositive.
Embryonal tumour with multilayered rosettes. Tumour cells are strongly immunopositive for LIN28A.
Embryonal tumour with multilayered rosettes. Panchromosomal copy-number alterations shown by DNA methylation array. Amplification and rearrangement of the C19MC locus on chromosome 19q and gain of chromosome 2 are prominent.

Q: By immunohistochemistry, the neoplastic cells in an Embryonal tumor with multilayered rosettes are characteristically and strongly positive for the highly specific marker [...].
Embryonal tumour with multilayered rosettes. Tumour cells are strongly immunopositive for LIN28A.
A: LIN28A
Back Extra: Embryonal Tumour with Multilayered Rosettes
- Clinical: ETMRs commonly produce symptoms of raised intracranial pressure, such as headache, nausea, and vomiting, and are often located in the cerebral hemisphere.
- Micro: The presence of multilayered rosettes is a defining feature of ETMRs, which can also show ependymoblastoma or medulloepithelioma morphology.
- Ancillary: Approximately 90% of ETMRs harbour specific structural alterations of the C19MC microRNA cluster on chromosome 19q13.42.
Reference Gallery:
Embryonal tumour with multilayered rosettes. An embryonal tumour with abundant neuropil and true rosettes pattern. Groups of densely packed embryonal cells, some including multilayered rosettes, contrast with neuropil-like areas that typically contain neoplastic neurocytic cells.
Embryonal tumour with multilayered rosettes (ETMR). Multilayered rosettes are a defining feature of EMTR.
Embryonal tumour with multilayered rosettes (ETMR). ETMR with ependymoblastoma morphology. Multilayered rosettes are abundant.
Embryonal tumour with multilayered rosettes (ETMR). ETMR with medulloepithelioma morphology. Tubular structures resemble embryonic neural tube or elongated multilayered rosettes.
Embryonal tumour with multilayered rosettes. Interphase FISH. Amplification (green signals) of the C19MC locus at 19q13.42.
Embryonal tumour with multilayered rosettes. Many cells are immunopositive for vimentin.
Embryonal tumour with multilayered rosettes (ETMR). The neuropil-like matrix of ETMRs with an abundant neuropil and true rosettes pattern is synaptophysin-immunopositive.
Embryonal tumour with multilayered rosettes. Tumour cells are strongly immunopositive for LIN28A.
Embryonal tumour with multilayered rosettes. Panchromosomal copy-number alterations shown by DNA methylation array. Amplification and rearrangement of the C19MC locus on chromosome 19q and gain of chromosome 2 are prominent.

Q: Myxopapillary Ependymoma typically presents clinically with chronic lower back pain and neuroimaging reveals a well-circumscribed, contrast-enhancing mass classically located in the [...].
Myxopapillary ependymoma. The well-circumscribed, contrast-enhancing primary tumour in the filum is associated with a drop metastasis in the low thecal sac.
A: filum terminale
Q: Myxopapillary Ependymoma
- Clinical: Lower back pain, often chronic, is a common symptom of [...]. Neuroimaging typically reveals a well-circumscribed, contrast-enhancing mass in the filum terminale.
- Micro: [...] is characterized by the radial arrangement of spindled or epithelioid tumour cells around blood vessels, with perivascular myxoid change and microcyst formation.
- Ancillary: [...] shows diffuse immunoreactivity for GFAP, distinguishing it from other spinal cord tumours. Recurrent gains of chromosome 16 and losses of chromosome 10 are also observed.
Reference Gallery:
Myxopapillary ependymoma. The well-circumscribed, contrast-enhancing primary tumour in the filum is associated with a drop metastasis in the low thecal sac.
Myxopapillary ependymoma. Epithelioid tumour cells are arranged around fibrovascular cores and microcysts containing myxoid material.
Myxopapillary ependymoma. Tapering tumour cell processes are oriented towards a fibrovascular core with collaring myxoid matrix.
Myxopapillary ependymoma. Tumour cells are diffusely and strongly GFAP-immunoreactive.
Myxopapillary ependymoma. Papillary structure, perivascular myxoid change, and spindled tumour cells oriented towards fibromyxoid cores are evident in this smear preparation.
A: myxopapillary ependymoma; Myxopapillary ependymoma; Myxopapillary ependymoma

Q: Microscopically, Myxopapillary Ependymoma features spindled or epithelioid tumor cells arranged radially around fibrovascular cores, characteristically accompanied by perivascular [...] change and microcyst formation.
Myxopapillary ependymoma. Epithelioid tumour cells are arranged around fibrovascular cores and microcysts containing myxoid material.
Myxopapillary ependymoma. Tapering tumour cell processes are oriented towards a fibrovascular core with collaring myxoid matrix.
A: myxoid
Q: Myxopapillary Ependymoma
- Clinical: Lower back pain, often chronic, is a common symptom of [...]. Neuroimaging typically reveals a well-circumscribed, contrast-enhancing mass in the filum terminale.
- Micro: [...] is characterized by the radial arrangement of spindled or epithelioid tumour cells around blood vessels, with perivascular myxoid change and microcyst formation.
- Ancillary: [...] shows diffuse immunoreactivity for GFAP, distinguishing it from other spinal cord tumours. Recurrent gains of chromosome 16 and losses of chromosome 10 are also observed.
Reference Gallery:
Myxopapillary ependymoma. The well-circumscribed, contrast-enhancing primary tumour in the filum is associated with a drop metastasis in the low thecal sac.
Myxopapillary ependymoma. Epithelioid tumour cells are arranged around fibrovascular cores and microcysts containing myxoid material.
Myxopapillary ependymoma. Tapering tumour cell processes are oriented towards a fibrovascular core with collaring myxoid matrix.
Myxopapillary ependymoma. Tumour cells are diffusely and strongly GFAP-immunoreactive.
Myxopapillary ependymoma. Papillary structure, perivascular myxoid change, and spindled tumour cells oriented towards fibromyxoid cores are evident in this smear preparation.
A: myxopapillary ependymoma; Myxopapillary ependymoma; Myxopapillary ependymoma

Q: Immunohistochemistry of Myxopapillary Ependymoma typically demonstrates diffuse and strong reactivity for [...], highlighting the tapering tumor cell processes and helping distinguish it from other spinal cord tumors.
Myxopapillary ependymoma. Tumour cells are diffusely and strongly GFAP-immunoreactive.
A: GFAP
Q: Myxopapillary Ependymoma
- Clinical: Lower back pain, often chronic, is a common symptom of [...]. Neuroimaging typically reveals a well-circumscribed, contrast-enhancing mass in the filum terminale.
- Micro: [...] is characterized by the radial arrangement of spindled or epithelioid tumour cells around blood vessels, with perivascular myxoid change and microcyst formation.
- Ancillary: [...] shows diffuse immunoreactivity for GFAP, distinguishing it from other spinal cord tumours. Recurrent gains of chromosome 16 and losses of chromosome 10 are also observed.
Reference Gallery:
Myxopapillary ependymoma. The well-circumscribed, contrast-enhancing primary tumour in the filum is associated with a drop metastasis in the low thecal sac.
Myxopapillary ependymoma. Epithelioid tumour cells are arranged around fibrovascular cores and microcysts containing myxoid material.
Myxopapillary ependymoma. Tapering tumour cell processes are oriented towards a fibrovascular core with collaring myxoid matrix.
Myxopapillary ependymoma. Tumour cells are diffusely and strongly GFAP-immunoreactive.
Myxopapillary ependymoma. Papillary structure, perivascular myxoid change, and spindled tumour cells oriented towards fibromyxoid cores are evident in this smear preparation.
A: myxopapillary ependymoma; Myxopapillary ependymoma; Myxopapillary ependymoma

Q: On histologic examination, a Spinal Ependymoma characteristically exhibits anucleate fibrillary zones around blood vessels, known as [...], which are strongly enriched for GFAP.
Spinal ependymoma. Tumour showing characteristic perivascular anucleate areas (pseudorosettes).
Spinal ependymoma. Tumour showing characteristic GFAP immunoreactivity, enriched in perivascular areas.
A: perivascular pseudorosettes
Back Extra: Spinal Ependymoma
- Clinical: Spinal ependymomas often present with back pain and a myelopathy, and are typically intramedullary tumours on MRI with contrast enhancement.
- Micro: Characterized by isomorphic glial cells with round nuclei, perivascular pseudorosettes, and a moderate to high cell density.
- Ancillary: Immunoreactive for GFAP, S100, and vimentin; dot-like intracytoplasmic EMA immunoreactivity; negative for OLIG2.
Reference Gallery:
Spinal ependymoma, CNS WHO grade 2. Sagittal T1-weighted MRI of a spinal ependymoma showing gadolinium contrast enhancement.
Spinal ependymoma. Tumour showing characteristic perivascular anucleate areas (pseudorosettes).
Spinal ependymoma. Tumour showing characteristic GFAP immunoreactivity, enriched in perivascular areas.
Spinal ependymoma. Tumour showing intracytoplasmic dot-like EMA immunoreactivity corresponding to microlumina.

Q: Immunohistochemical evaluation of a Spinal Ependymoma frequently demonstrates a characteristic intracytoplasmic, dot-like staining pattern for [...], corresponding to microlumina.
Spinal ependymoma. Tumour showing intracytoplasmic dot-like EMA immunoreactivity corresponding to microlumina.
A: EMA
Back Extra: Spinal Ependymoma
- Clinical: Spinal ependymomas often present with back pain and a myelopathy, and are typically intramedullary tumours on MRI with contrast enhancement.
- Micro: Characterized by isomorphic glial cells with round nuclei, perivascular pseudorosettes, and a moderate to high cell density.
- Ancillary: Immunoreactive for GFAP, S100, and vimentin; dot-like intracytoplasmic EMA immunoreactivity; negative for OLIG2.
Reference Gallery:
Spinal ependymoma, CNS WHO grade 2. Sagittal T1-weighted MRI of a spinal ependymoma showing gadolinium contrast enhancement.
Spinal ependymoma. Tumour showing characteristic perivascular anucleate areas (pseudorosettes).
Spinal ependymoma. Tumour showing characteristic GFAP immunoreactivity, enriched in perivascular areas.
Spinal ependymoma. Tumour showing intracytoplasmic dot-like EMA immunoreactivity corresponding to microlumina.

Q: Radiologically, a Spinal Ependymoma typically presents as an [...] spinal cord tumor that demonstrates prominent gadolinium contrast enhancement on MRI.
Spinal ependymoma, CNS WHO grade 2. Sagittal T1-weighted MRI of a spinal ependymoma showing gadolinium contrast enhancement.
A: intramedullary
Back Extra: Spinal Ependymoma
- Clinical: Spinal ependymomas often present with back pain and a myelopathy, and are typically intramedullary tumours on MRI with contrast enhancement.
- Micro: Characterized by isomorphic glial cells with round nuclei, perivascular pseudorosettes, and a moderate to high cell density.
- Ancillary: Immunoreactive for GFAP, S100, and vimentin; dot-like intracytoplasmic EMA immunoreactivity; negative for OLIG2.
Reference Gallery:
Spinal ependymoma, CNS WHO grade 2. Sagittal T1-weighted MRI of a spinal ependymoma showing gadolinium contrast enhancement.
Spinal ependymoma. Tumour showing characteristic perivascular anucleate areas (pseudorosettes).
Spinal ependymoma. Tumour showing characteristic GFAP immunoreactivity, enriched in perivascular areas.
Spinal ependymoma. Tumour showing intracytoplasmic dot-like EMA immunoreactivity corresponding to microlumina.

Q: The ependymoma variant that predominantly occurs in infants and children (median age 3 years) and often presents with high cell density is [...].
Posterior fossa ependymoma. PFA ependymoma (EPN-PFA), sometimes referred to as “infantile posterior fossa ependymoma”, predominantly occurs in infants and children. PFB ependymoma (EPN-PFB) occurs mainly in older children and young adults.
A: Posterior Fossa Group A (PFA) Ependymoma
Back Extra: Posterior Fossa Group A (PFA) Ependymoma
- Clinical: PFA ependymomas predominantly occur in infants and children, with a median age of 3 years and a slightly male predominance (59–62%).
- Micro: PFA ependymomas show high cell density and subtle pseudorosette formation, with a loss of H3 p.K28me3 (K27me3) immunoreactivity in most cases.
- Ancillary: Diagnosis requires demonstration of H3 p.K28me3 (K27me3) loss by immunohistochemistry or DNA methylation profiling, and gain of chromosome 1q is an adverse prognostic indicator.
Reference Gallery:
Posterior fossa group A (PFA) ependymoma. Nodules of high cell density are common in PFA ependymomas.
Posterior fossa group A (PFA) ependymoma. Subtle pseudorosette formation and a high cell density characterize some PFA ependymomas.
Posterior fossa group A (PFA) ependymoma. In most examples of this tumour type, immunoreactivity for H3 p.K28me3 (K27me3) in tumour cells is lost.
Posterior fossa group A (PFA) ependymoma. Immunoreactivity for H3 p.K28me3 (K27me3) can sometimes be retained in a variable proportion of tumour cells.
Posterior fossa ependymoma. PFA ependymoma (EPN-PFA), sometimes referred to as “infantile posterior fossa ependymoma”, predominantly occurs in infants and children. PFB ependymoma (EPN-PFB) occurs mainly in older children and young adults.

Q: The diagnosis of Posterior Fossa Group A (PFA) Ependymoma is highly correlated with a loss of [...] immunoreactivity in most tumor cells.
Posterior fossa group A (PFA) ependymoma. In most examples of this tumour type, immunoreactivity for H3 p.K28me3 (K27me3) in tumour cells is lost.
Posterior fossa group A (PFA) ependymoma. Immunoreactivity for H3 p.K28me3 (K27me3) can sometimes be retained in a variable proportion of tumour cells.
A: H3 p.K28me3 (K27me3)
Back Extra: Posterior Fossa Group A (PFA) Ependymoma
- Clinical: PFA ependymomas predominantly occur in infants and children, with a median age of 3 years and a slightly male predominance (59–62%).
- Micro: PFA ependymomas show high cell density and subtle pseudorosette formation, with a loss of H3 p.K28me3 (K27me3) immunoreactivity in most cases.
- Ancillary: Diagnosis requires demonstration of H3 p.K28me3 (K27me3) loss by immunohistochemistry or DNA methylation profiling, and gain of chromosome 1q is an adverse prognostic indicator.
Reference Gallery:
Posterior fossa group A (PFA) ependymoma. Nodules of high cell density are common in PFA ependymomas.
Posterior fossa group A (PFA) ependymoma. Subtle pseudorosette formation and a high cell density characterize some PFA ependymomas.
Posterior fossa group A (PFA) ependymoma. In most examples of this tumour type, immunoreactivity for H3 p.K28me3 (K27me3) in tumour cells is lost.
Posterior fossa group A (PFA) ependymoma. Immunoreactivity for H3 p.K28me3 (K27me3) can sometimes be retained in a variable proportion of tumour cells.
Posterior fossa ependymoma. PFA ependymoma (EPN-PFA), sometimes referred to as “infantile posterior fossa ependymoma”, predominantly occurs in infants and children. PFB ependymoma (EPN-PFB) occurs mainly in older children and young adults.

Q: Microscopically, Posterior Fossa Group A (PFA) Ependymoma characteristically demonstrates nodules of high cell density and subtle [...] formation.
Posterior fossa group A (PFA) ependymoma. Nodules of high cell density are common in PFA ependymomas.
Posterior fossa group A (PFA) ependymoma. Subtle pseudorosette formation and a high cell density characterize some PFA ependymomas.
A: pseudorosette
Back Extra: Posterior Fossa Group A (PFA) Ependymoma
- Clinical: PFA ependymomas predominantly occur in infants and children, with a median age of 3 years and a slightly male predominance (59–62%).
- Micro: PFA ependymomas show high cell density and subtle pseudorosette formation, with a loss of H3 p.K28me3 (K27me3) immunoreactivity in most cases.
- Ancillary: Diagnosis requires demonstration of H3 p.K28me3 (K27me3) loss by immunohistochemistry or DNA methylation profiling, and gain of chromosome 1q is an adverse prognostic indicator.
Reference Gallery:
Posterior fossa group A (PFA) ependymoma. Nodules of high cell density are common in PFA ependymomas.
Posterior fossa group A (PFA) ependymoma. Subtle pseudorosette formation and a high cell density characterize some PFA ependymomas.
Posterior fossa group A (PFA) ependymoma. In most examples of this tumour type, immunoreactivity for H3 p.K28me3 (K27me3) in tumour cells is lost.
Posterior fossa group A (PFA) ependymoma. Immunoreactivity for H3 p.K28me3 (K27me3) can sometimes be retained in a variable proportion of tumour cells.
Posterior fossa ependymoma. PFA ependymoma (EPN-PFA), sometimes referred to as “infantile posterior fossa ependymoma”, predominantly occurs in infants and children. PFB ependymoma (EPN-PFB) occurs mainly in older children and young adults.

Q: Histologically, a Posterior Fossa Ependymoma is characterized by uniform cells forming true ependymal rosettes and [...], which consist of radially arranged tumor cells around blood vessels with an intervening anucleate zone.
Posterior fossa ependymoma. Perivascular pseudorosettes are characterized by tumour cells radially arranged around blood vessels with an intervening anucleate zone.
Posterior fossa ependymoma. True ependymal rosettes characterized by periluminal cuboidal or columnar cells without a basement membrane.
A: perivascular pseudorosettes
Back Extra: Posterior Fossa Ependymoma
- Clinical: Common clinical presentations of posterior fossa ependymoma include secondary hydrocephalus, headache, vomiting, and lethargy, with babies often presenting with a rapidly growing head circumference.
- Micro: Posterior fossa ependymomas are characterized by uniform small cells with round nuclei, perivascular pseudorosettes, and occasional true ependymal rosettes.
- Ancillary: Immunohistochemistry shows immunoreactivity for S100 and GFAP, with EMA showing a paranuclear dot-like pattern, and ultrastructural features include cilia with a 9 + 2 microtubular pattern.
Reference Gallery:
Posterior fossa ependymoma. MRI shows a tumour in the fourth ventricle (arrows). Note that the aqueduct of Sylvius and the third ventricle are enlarged.
Posterior fossa ependymoma. Perivascular pseudorosettes are characterized by tumour cells radially arranged around blood vessels with an intervening anucleate zone.
Posterior fossa ependymoma. True ependymal rosettes characterized by periluminal cuboidal or columnar cells without a basement membrane.
Posterior fossa ependymoma. Immunoreactivity for EMA typically shows a paranuclear dot-like pattern and occurs along the luminal surface of true ependymal rosettes.
Posterior fossa ependymoma. Immunoreactivity for NFP highlights axons in surrounding brain parenchyma and demonstrates the pushing border of the tumour.
Posterior fossa ependymoma. CNS WHO grade 3 posterior fossa ependymoma showing plentiful mitotic activity but little nuclear pleomorphism.
Posterior fossa ependymoma. Palisading necrosis.
Posterior fossa ependymoma. Microvascular proliferation typically characterized by multilayered endothelial cells.
Posterior fossa ependymoma. At the ultrastructural level, the cells of an ependymoma typically show cilia with a 9 + 2 microtubular pattern and microvilli at luminal surfaces.
Posterior fossa ependymoma. Ependymoma in the fourth ventricle (arrows) displacing adjacent posterior fossa structures.
Posterior fossa ependymoma. A pseudopapillary pattern with finger-like projections lined by a single layer or multiple layers of cuboidal cells.
Posterior fossa ependymoma. Immunoreactivity for GFAP is typically present in many (but not all) tumour cells. Note accentuation of staining in perivascular pseudorosettes.

Q: Immunohistochemical staining for EMA in a Posterior Fossa Ependymoma typically demonstrates a characteristic paranuclear [...] pattern of reactivity.
Posterior fossa ependymoma. Immunoreactivity for EMA typically shows a paranuclear dot-like pattern and occurs along the luminal surface of true ependymal rosettes.
A: dot-like
Back Extra: Posterior Fossa Ependymoma
- Clinical: Common clinical presentations of posterior fossa ependymoma include secondary hydrocephalus, headache, vomiting, and lethargy, with babies often presenting with a rapidly growing head circumference.
- Micro: Posterior fossa ependymomas are characterized by uniform small cells with round nuclei, perivascular pseudorosettes, and occasional true ependymal rosettes.
- Ancillary: Immunohistochemistry shows immunoreactivity for S100 and GFAP, with EMA showing a paranuclear dot-like pattern, and ultrastructural features include cilia with a 9 + 2 microtubular pattern.
Reference Gallery:
Posterior fossa ependymoma. MRI shows a tumour in the fourth ventricle (arrows). Note that the aqueduct of Sylvius and the third ventricle are enlarged.
Posterior fossa ependymoma. Perivascular pseudorosettes are characterized by tumour cells radially arranged around blood vessels with an intervening anucleate zone.
Posterior fossa ependymoma. True ependymal rosettes characterized by periluminal cuboidal or columnar cells without a basement membrane.
Posterior fossa ependymoma. Immunoreactivity for EMA typically shows a paranuclear dot-like pattern and occurs along the luminal surface of true ependymal rosettes.
Posterior fossa ependymoma. Immunoreactivity for NFP highlights axons in surrounding brain parenchyma and demonstrates the pushing border of the tumour.
Posterior fossa ependymoma. CNS WHO grade 3 posterior fossa ependymoma showing plentiful mitotic activity but little nuclear pleomorphism.
Posterior fossa ependymoma. Palisading necrosis.
Posterior fossa ependymoma. Microvascular proliferation typically characterized by multilayered endothelial cells.
Posterior fossa ependymoma. At the ultrastructural level, the cells of an ependymoma typically show cilia with a 9 + 2 microtubular pattern and microvilli at luminal surfaces.
Posterior fossa ependymoma. Ependymoma in the fourth ventricle (arrows) displacing adjacent posterior fossa structures.
Posterior fossa ependymoma. A pseudopapillary pattern with finger-like projections lined by a single layer or multiple layers of cuboidal cells.
Posterior fossa ependymoma. Immunoreactivity for GFAP is typically present in many (but not all) tumour cells. Note accentuation of staining in perivascular pseudorosettes.

Q: At the ultrastructural level, the tumor cells of a Posterior Fossa Ependymoma typically show apical microvilli and cilia containing a characteristic [...] microtubular pattern.
Posterior fossa ependymoma. At the ultrastructural level, the cells of an ependymoma typically show cilia with a 9 + 2 microtubular pattern and microvilli at luminal surfaces.
A: 9 + 2
Back Extra: Posterior Fossa Ependymoma
- Clinical: Common clinical presentations of posterior fossa ependymoma include secondary hydrocephalus, headache, vomiting, and lethargy, with babies often presenting with a rapidly growing head circumference.
- Micro: Posterior fossa ependymomas are characterized by uniform small cells with round nuclei, perivascular pseudorosettes, and occasional true ependymal rosettes.
- Ancillary: Immunohistochemistry shows immunoreactivity for S100 and GFAP, with EMA showing a paranuclear dot-like pattern, and ultrastructural features include cilia with a 9 + 2 microtubular pattern.
Reference Gallery:
Posterior fossa ependymoma. MRI shows a tumour in the fourth ventricle (arrows). Note that the aqueduct of Sylvius and the third ventricle are enlarged.
Posterior fossa ependymoma. Perivascular pseudorosettes are characterized by tumour cells radially arranged around blood vessels with an intervening anucleate zone.
Posterior fossa ependymoma. True ependymal rosettes characterized by periluminal cuboidal or columnar cells without a basement membrane.
Posterior fossa ependymoma. Immunoreactivity for EMA typically shows a paranuclear dot-like pattern and occurs along the luminal surface of true ependymal rosettes.
Posterior fossa ependymoma. Immunoreactivity for NFP highlights axons in surrounding brain parenchyma and demonstrates the pushing border of the tumour.
Posterior fossa ependymoma. CNS WHO grade 3 posterior fossa ependymoma showing plentiful mitotic activity but little nuclear pleomorphism.
Posterior fossa ependymoma. Palisading necrosis.
Posterior fossa ependymoma. Microvascular proliferation typically characterized by multilayered endothelial cells.
Posterior fossa ependymoma. At the ultrastructural level, the cells of an ependymoma typically show cilia with a 9 + 2 microtubular pattern and microvilli at luminal surfaces.
Posterior fossa ependymoma. Ependymoma in the fourth ventricle (arrows) displacing adjacent posterior fossa structures.
Posterior fossa ependymoma. A pseudopapillary pattern with finger-like projections lined by a single layer or multiple layers of cuboidal cells.
Posterior fossa ependymoma. Immunoreactivity for GFAP is typically present in many (but not all) tumour cells. Note accentuation of staining in perivascular pseudorosettes.

Q: Posterior Fossa Group B (PFB) Ependymoma typically presents as a large tumor in the fourth ventricle, most commonly affecting [...] (median age of 30 years).
Posterior fossa group B (PFB) ependymoma. T1-weighted MRI shows a large tumour in the fourth ventricle of a 37-year-old man.
A: adults
Back Extra: Posterior Fossa Group B (PFB) Ependymoma
- Clinical: Posterior Fossa Group B (PFB) ependymomas are more common in adults, with a median age at presentation of 30 years.
- Micro: PFB ependymomas show uniform small cells with round nuclei and prominent perivascular pseudorosettes.
- Ancillary: DNA methylation profiling or immunohistochemistry for H3 p.K28me3 (K27me3) is required for diagnosing PFB ependymomas.
Reference Gallery:
Posterior fossa group B (PFB) ependymoma. T1-weighted MRI shows a large tumour in the fourth ventricle of a 37-year-old man.
Posterior fossa group B (PFB) ependymoma. Pseudopapillary architectural pattern featuring finger-like projections and perivascular pseudorosettes.
Posterior fossa group B (PFB) ependymoma. Expression of H3 p.K28me3 (K27me3) is present in all tumour cells.

Q: Histologically, Posterior Fossa Group B (PFB) Ependymoma can exhibit a pseudopapillary architectural pattern with finger-like projections and characteristic [...].
Posterior fossa group B (PFB) ependymoma. Pseudopapillary architectural pattern featuring finger-like projections and perivascular pseudorosettes.
A: perivascular pseudorosettes
Back Extra: Posterior Fossa Group B (PFB) Ependymoma
- Clinical: Posterior Fossa Group B (PFB) ependymomas are more common in adults, with a median age at presentation of 30 years.
- Micro: PFB ependymomas show uniform small cells with round nuclei and prominent perivascular pseudorosettes.
- Ancillary: DNA methylation profiling or immunohistochemistry for H3 p.K28me3 (K27me3) is required for diagnosing PFB ependymomas.
Reference Gallery:
Posterior fossa group B (PFB) ependymoma. T1-weighted MRI shows a large tumour in the fourth ventricle of a 37-year-old man.
Posterior fossa group B (PFB) ependymoma. Pseudopapillary architectural pattern featuring finger-like projections and perivascular pseudorosettes.
Posterior fossa group B (PFB) ependymoma. Expression of H3 p.K28me3 (K27me3) is present in all tumour cells.

Q: To confirm a diagnosis of Posterior Fossa Group B (PFB) Ependymoma, immunohistochemistry must demonstrate the diffuse expression (retention) of [...].
Posterior fossa group B (PFB) ependymoma. Expression of H3 p.K28me3 (K27me3) is present in all tumour cells.
A: H3 p.K28me3 (K27me3)
Back Extra: Posterior Fossa Group B (PFB) Ependymoma
- Clinical: Posterior Fossa Group B (PFB) ependymomas are more common in adults, with a median age at presentation of 30 years.
- Micro: PFB ependymomas show uniform small cells with round nuclei and prominent perivascular pseudorosettes.
- Ancillary: DNA methylation profiling or immunohistochemistry for H3 p.K28me3 (K27me3) is required for diagnosing PFB ependymomas.
Reference Gallery:
Posterior fossa group B (PFB) ependymoma. T1-weighted MRI shows a large tumour in the fourth ventricle of a 37-year-old man.
Posterior fossa group B (PFB) ependymoma. Pseudopapillary architectural pattern featuring finger-like projections and perivascular pseudorosettes.
Posterior fossa group B (PFB) ependymoma. Expression of H3 p.K28me3 (K27me3) is present in all tumour cells.

Q: In Spinal Ependymoma, MYCN-Amplified, the defining diagnostic feature is extensive nuclear expression of [...] on immunohistochemistry.
Spinal ependymoma, MYCN-amplified. Extensive nuclear expression of MYCN is detected by immunohistochemistry.
A: MYCN
Back Extra: Spinal Ependymoma, MYCN-Amplified
- Clinical: Presenting symptoms include neck or back pain and progressive numbness and weakness in the extremities, with a median age at presentation of 31 years.
- Micro: Tumour cells show high-grade histopathological features, including a high N:C ratio, plentiful mitotic activity, microvascular proliferation, and necrosis.
- Ancillary: MYCN amplification is a defining feature, and immunohistochemistry shows extensive nuclear expression of MYCN and GFAP.
Reference Gallery:
Spinal ependymoma, MYCN-amplified. Tumour with a focal pseudopapillary architecture and densely packed cells.
Spinal ependymoma, MYCN-amplified. High cell density, mitotic activity, and vague pseudorosette formation are present.
Spinal ependymoma, MYCN-amplified. Immunohistochemistry shows many tumour cells expressing GFAP, which is typically present in perivascular radiating processes.
Spinal ependymoma, MYCN-amplified. Nuclear immunoreactivity for H3 p.K28me3 (K27me3) can be completely lost, partially lost (as shown here), or retained.
Spinal ependymoma, MYCN-amplified. Electron microscopy. Intercellular junctions end at a microlumen filled with microvilli, typical of ependymal differentiation. Cilia (black-and-white arrows) and basal bodies (black arrows) are also present.
Spinal ependymoma, MYCN-amplified. Extensive nuclear expression of MYCN is detected by immunohistochemistry.

Q: Microscopically, Spinal Ependymoma, MYCN-Amplified exhibits high cell density, elevated mitotic activity, and vague pseudorosette formation, with tumor cells typically demonstrating robust expression of [...] in perivascular radiating processes.
Spinal ependymoma, MYCN-amplified. High cell density, mitotic activity, and vague pseudorosette formation are present.
Spinal ependymoma, MYCN-amplified. Immunohistochemistry shows many tumour cells expressing GFAP, which is typically present in perivascular radiating processes.
A: GFAP
Back Extra: Spinal Ependymoma, MYCN-Amplified
- Clinical: Presenting symptoms include neck or back pain and progressive numbness and weakness in the extremities, with a median age at presentation of 31 years.
- Micro: Tumour cells show high-grade histopathological features, including a high N:C ratio, plentiful mitotic activity, microvascular proliferation, and necrosis.
- Ancillary: MYCN amplification is a defining feature, and immunohistochemistry shows extensive nuclear expression of MYCN and GFAP.
Reference Gallery:
Spinal ependymoma, MYCN-amplified. Tumour with a focal pseudopapillary architecture and densely packed cells.
Spinal ependymoma, MYCN-amplified. High cell density, mitotic activity, and vague pseudorosette formation are present.
Spinal ependymoma, MYCN-amplified. Immunohistochemistry shows many tumour cells expressing GFAP, which is typically present in perivascular radiating processes.
Spinal ependymoma, MYCN-amplified. Nuclear immunoreactivity for H3 p.K28me3 (K27me3) can be completely lost, partially lost (as shown here), or retained.
Spinal ependymoma, MYCN-amplified. Electron microscopy. Intercellular junctions end at a microlumen filled with microvilli, typical of ependymal differentiation. Cilia (black-and-white arrows) and basal bodies (black arrows) are also present.
Spinal ependymoma, MYCN-amplified. Extensive nuclear expression of MYCN is detected by immunohistochemistry.

Q: Electron microscopy of Spinal Ependymoma, MYCN-Amplified confirms ependymal differentiation by revealing intercellular junctions that terminate at a microlumen filled with cilia and [...].
Spinal ependymoma, MYCN-amplified. Electron microscopy. Intercellular junctions end at a microlumen filled with microvilli, typical of ependymal differentiation. Cilia (black-and-white arrows) and basal bodies (black arrows) are also present.
A: microvilli
Back Extra: Spinal Ependymoma, MYCN-Amplified
- Clinical: Presenting symptoms include neck or back pain and progressive numbness and weakness in the extremities, with a median age at presentation of 31 years.
- Micro: Tumour cells show high-grade histopathological features, including a high N:C ratio, plentiful mitotic activity, microvascular proliferation, and necrosis.
- Ancillary: MYCN amplification is a defining feature, and immunohistochemistry shows extensive nuclear expression of MYCN and GFAP.
Reference Gallery:
Spinal ependymoma, MYCN-amplified. Tumour with a focal pseudopapillary architecture and densely packed cells.
Spinal ependymoma, MYCN-amplified. High cell density, mitotic activity, and vague pseudorosette formation are present.
Spinal ependymoma, MYCN-amplified. Immunohistochemistry shows many tumour cells expressing GFAP, which is typically present in perivascular radiating processes.
Spinal ependymoma, MYCN-amplified. Nuclear immunoreactivity for H3 p.K28me3 (K27me3) can be completely lost, partially lost (as shown here), or retained.
Spinal ependymoma, MYCN-amplified. Electron microscopy. Intercellular junctions end at a microlumen filled with microvilli, typical of ependymal differentiation. Cilia (black-and-white arrows) and basal bodies (black arrows) are also present.
Spinal ependymoma, MYCN-amplified. Extensive nuclear expression of MYCN is detected by immunohistochemistry.

Q: Radiologically, Supratentorial Ependymoma, YAP1 Fusion-Positive typically presents as a large, [...] tumor with solid components, often causing signs of raised intracranial pressure.
Supratentorial ependymoma, YAP1 fusion–positive. T2-weighted coronal MRI showing a large cystic tumour.
Supratentorial ependymoma, YAP1 fusion–positive. Ependymoma with YAP1::MAMLD1 fusion. T1-weighted axial MRI showing a large cystic tumour with contrast enhancement of solid tumour parts.
A: cystic
Back Extra: Supratentorial Ependymoma, YAP1 Fusion-Positive
- Clinical: YAP1 fusion–positive supratentorial ependymomas often present as large, cystic tumours with signs of raised intracranial pressure and focal neurological deficits.
- Micro: These tumours are composed of uniform cells with small to medium-sized round or angulated nuclei, often with ependymal rosettes and a fibrillary matrix.
- Ancillary: Immunohistochemistry shows widespread and strong dot-like EMA immunoreactivity, while L1CAM and p65 (RELA) are negative.
Reference Gallery:
Supratentorial ependymoma, YAP1 fusion–positive. T2-weighted coronal MRI showing a large cystic tumour.
Supratentorial ependymoma, YAP1 fusion–positive. Ependymoma with YAP1::MAMLD1 fusion. T1-weighted axial MRI showing a large cystic tumour with contrast enhancement of solid tumour parts.
Supratentorial ependymoma, YAP1 fusion–positive. Small, slightly angulated nuclei set against a fibrillary matrix.
Supratentorial ependymoma, YAP1 fusion–positive. Typical widespread and strong dot-like EMA immunoreactivity.

Q: Histologically, Supratentorial Ependymoma, YAP1 Fusion-Positive is characterized by uniform cells with small, slightly [...] nuclei set against a prominent fibrillary matrix.
Supratentorial ependymoma, YAP1 fusion–positive. Small, slightly angulated nuclei set against a fibrillary matrix.
A: angulated
Back Extra: Supratentorial Ependymoma, YAP1 Fusion-Positive
- Clinical: YAP1 fusion–positive supratentorial ependymomas often present as large, cystic tumours with signs of raised intracranial pressure and focal neurological deficits.
- Micro: These tumours are composed of uniform cells with small to medium-sized round or angulated nuclei, often with ependymal rosettes and a fibrillary matrix.
- Ancillary: Immunohistochemistry shows widespread and strong dot-like EMA immunoreactivity, while L1CAM and p65 (RELA) are negative.
Reference Gallery:
Supratentorial ependymoma, YAP1 fusion–positive. T2-weighted coronal MRI showing a large cystic tumour.
Supratentorial ependymoma, YAP1 fusion–positive. Ependymoma with YAP1::MAMLD1 fusion. T1-weighted axial MRI showing a large cystic tumour with contrast enhancement of solid tumour parts.
Supratentorial ependymoma, YAP1 fusion–positive. Small, slightly angulated nuclei set against a fibrillary matrix.
Supratentorial ependymoma, YAP1 fusion–positive. Typical widespread and strong dot-like EMA immunoreactivity.

Q: Ancillary immunohistochemistry for Supratentorial Ependymoma, YAP1 Fusion-Positive demonstrates widespread and strong dot-like immunoreactivity for [...], while L1CAM and p65 (RELA) are characteristically negative.
Supratentorial ependymoma, YAP1 fusion–positive. Typical widespread and strong dot-like EMA immunoreactivity.
A: EMA
Back Extra: Supratentorial Ependymoma, YAP1 Fusion-Positive
- Clinical: YAP1 fusion–positive supratentorial ependymomas often present as large, cystic tumours with signs of raised intracranial pressure and focal neurological deficits.
- Micro: These tumours are composed of uniform cells with small to medium-sized round or angulated nuclei, often with ependymal rosettes and a fibrillary matrix.
- Ancillary: Immunohistochemistry shows widespread and strong dot-like EMA immunoreactivity, while L1CAM and p65 (RELA) are negative.
Reference Gallery:
Supratentorial ependymoma, YAP1 fusion–positive. T2-weighted coronal MRI showing a large cystic tumour.
Supratentorial ependymoma, YAP1 fusion–positive. Ependymoma with YAP1::MAMLD1 fusion. T1-weighted axial MRI showing a large cystic tumour with contrast enhancement of solid tumour parts.
Supratentorial ependymoma, YAP1 fusion–positive. Small, slightly angulated nuclei set against a fibrillary matrix.
Supratentorial ependymoma, YAP1 fusion–positive. Typical widespread and strong dot-like EMA immunoreactivity.

Q: Histologically, Supratentorial Ependymoma frequently demonstrates clear cell change, a branching vascular network, and characteristic anucleate zones around blood vessels known as [...].
Supratentorial ependymoma. A branching network of small blood vessels is a frequent architectural feature of supratentorial ependymomas. Perivascular anucleate zones can be subtle.
Supratentorial ependymoma. Clear cell change is a frequent cytological feature of supratentorial ependymomas. Nuclear pleomorphism is mild in most cases, and the number of mitotic figures can be variable.
A: perivascular pseudorosettes
Back Extra: Supratentorial Ependymoma
- Clinical: Supratentorial ependymomas often present with focal neurological deficits or seizures, and can cause headache, nausea, and vomiting due to raised intracranial pressure and hydrocephalus.
- Micro: Histologically, supratentorial ependymomas show a branching network of small blood vessels, perivascular anucleate zones (pseudorosettes), and clear cell change, with mild nuclear pleomorphism.
- Ancillary: Immunohistochemistry typically shows variable expression of GFAP and paranuclear dot-like EMA staining, and molecular analysis is critical to exclude ZFTA (C11orf95) or YAP1 rearrangements.
Reference Gallery:
Supratentorial ependymoma. T2-weighted axial MRI showing a large circumscribed mass in the cerebral hemisphere.
Supratentorial ependymoma. By immunohistochemistry, GFAP is variably expressed in supratentorial ependymomas.
Supratentorial ependymoma. Immunoreactivity for EMA is present in a variable number of tumour cells and usually manifests as paranuclear dots or ring structures.
Supratentorial ependymoma. A branching network of small blood vessels is a frequent architectural feature of supratentorial ependymomas. Perivascular anucleate zones can be subtle.
Supratentorial ependymoma. Ependymal rosettes are present in a minority of cases.
Supratentorial ependymoma. Clear cell change is a frequent cytological feature of supratentorial ependymomas. Nuclear pleomorphism is mild in most cases, and the number of mitotic figures can be variable.
Supratentorial ependymoma. Nuclear pleomorphism is mild in most cases, but it can be marked in some cases.
Supratentorial ependymoma. By immunohistochemistry, GFAP is variably expressed in supratentorial ependymomas.
Supratentorial ependymoma. OLIG2 is usually present in sparse tumour cells.
Supratentorial ependymoma. T1-weighted gadolinium-enhanced axial MRI in an adult, showing an intraventricular nodular lesion with heterogeneous contrast enhancement and solid and cystic components.

Q: By immunohistochemistry, Supratentorial Ependymoma classically shows immunoreactivity for EMA in the form of characteristic [...] or ring structures.
Supratentorial ependymoma. Immunoreactivity for EMA is present in a variable number of tumour cells and usually manifests as paranuclear dots or ring structures.
A: paranuclear dots
Back Extra: Supratentorial Ependymoma
- Clinical: Supratentorial ependymomas often present with focal neurological deficits or seizures, and can cause headache, nausea, and vomiting due to raised intracranial pressure and hydrocephalus.
- Micro: Histologically, supratentorial ependymomas show a branching network of small blood vessels, perivascular anucleate zones (pseudorosettes), and clear cell change, with mild nuclear pleomorphism.
- Ancillary: Immunohistochemistry typically shows variable expression of GFAP and paranuclear dot-like EMA staining, and molecular analysis is critical to exclude ZFTA (C11orf95) or YAP1 rearrangements.
Reference Gallery:
Supratentorial ependymoma. T2-weighted axial MRI showing a large circumscribed mass in the cerebral hemisphere.
Supratentorial ependymoma. By immunohistochemistry, GFAP is variably expressed in supratentorial ependymomas.
Supratentorial ependymoma. Immunoreactivity for EMA is present in a variable number of tumour cells and usually manifests as paranuclear dots or ring structures.
Supratentorial ependymoma. A branching network of small blood vessels is a frequent architectural feature of supratentorial ependymomas. Perivascular anucleate zones can be subtle.
Supratentorial ependymoma. Ependymal rosettes are present in a minority of cases.
Supratentorial ependymoma. Clear cell change is a frequent cytological feature of supratentorial ependymomas. Nuclear pleomorphism is mild in most cases, and the number of mitotic figures can be variable.
Supratentorial ependymoma. Nuclear pleomorphism is mild in most cases, but it can be marked in some cases.
Supratentorial ependymoma. By immunohistochemistry, GFAP is variably expressed in supratentorial ependymomas.
Supratentorial ependymoma. OLIG2 is usually present in sparse tumour cells.
Supratentorial ependymoma. T1-weighted gadolinium-enhanced axial MRI in an adult, showing an intraventricular nodular lesion with heterogeneous contrast enhancement and solid and cystic components.

Q: While perivascular anucleate zones are common, true [...] are only present in a minority of Supratentorial Ependymoma cases.
Supratentorial ependymoma. Ependymal rosettes are present in a minority of cases.
A: ependymal rosettes
Back Extra: Supratentorial Ependymoma
- Clinical: Supratentorial ependymomas often present with focal neurological deficits or seizures, and can cause headache, nausea, and vomiting due to raised intracranial pressure and hydrocephalus.
- Micro: Histologically, supratentorial ependymomas show a branching network of small blood vessels, perivascular anucleate zones (pseudorosettes), and clear cell change, with mild nuclear pleomorphism.
- Ancillary: Immunohistochemistry typically shows variable expression of GFAP and paranuclear dot-like EMA staining, and molecular analysis is critical to exclude ZFTA (C11orf95) or YAP1 rearrangements.
Reference Gallery:
Supratentorial ependymoma. T2-weighted axial MRI showing a large circumscribed mass in the cerebral hemisphere.
Supratentorial ependymoma. By immunohistochemistry, GFAP is variably expressed in supratentorial ependymomas.
Supratentorial ependymoma. Immunoreactivity for EMA is present in a variable number of tumour cells and usually manifests as paranuclear dots or ring structures.
Supratentorial ependymoma. A branching network of small blood vessels is a frequent architectural feature of supratentorial ependymomas. Perivascular anucleate zones can be subtle.
Supratentorial ependymoma. Ependymal rosettes are present in a minority of cases.
Supratentorial ependymoma. Clear cell change is a frequent cytological feature of supratentorial ependymomas. Nuclear pleomorphism is mild in most cases, and the number of mitotic figures can be variable.
Supratentorial ependymoma. Nuclear pleomorphism is mild in most cases, but it can be marked in some cases.
Supratentorial ependymoma. By immunohistochemistry, GFAP is variably expressed in supratentorial ependymomas.
Supratentorial ependymoma. OLIG2 is usually present in sparse tumour cells.
Supratentorial ependymoma. T1-weighted gadolinium-enhanced axial MRI in an adult, showing an intraventricular nodular lesion with heterogeneous contrast enhancement and solid and cystic components.

Q: A highly characteristic immunohistochemical feature of Supratentorial Ependymoma, ZFTA Fusion-Positive is strong, universal cytoplasmic expression of the surrogate marker [...].
Supratentorial ependymoma, ZFTA fusion–positive. Universal cytoplasmic expression of L1CAM.
A: L1CAM
Back Extra: Supratentorial Ependymoma, ZFTA Fusion-Positive
- Clinical: Supratentorial ependymoma, ZFTA fusion–positive presents with focal neurological deficits, seizures, and signs of raised intracranial pressure.
- Micro: Tumour cells are characterized by round uniform nuclei with speckled chromatin and a fibrillary cytoplasm, often with branching capillaries and dystrophic calcification.
- Ancillary: Diagnostic tests include sequencing methods, interphase FISH, and molecular inversion profiling to detect ZFTA fusions.
Reference Gallery:
Supratentorial ependymoma, ZFTA fusion–positive. Universal cytoplasmic expression of L1CAM.
Supratentorial ependymoma, ZFTA fusion–positive. Tumour cells with round nuclei set in a fibrillary matrix. Branching blood vessels and dystrophic calcification can be seen.
Supratentorial ependymoma, ZFTA fusion–positive. Tumour cells with round nuclei set in a fibrillary matrix with branching capillary blood vessels.
Supratentorial ependymoma, ZFTA fusion–positive. Nuclear immunoreactivity for p65 (encoded by RELA).
Supratentorial ependymoma, ZFTA fusion–positive. T1-weighted axial MRI with gadolinium, showing a well-demarcated left frontal lesion with heterogeneous contrast enhancement and areas of necrosis.
Supratentorial ependymoma, ZFTA fusion–positive. Coronal FLAIR MRI showing conspicuous surrounding oedema.
Supratentorial ependymoma, ZFTA fusion–positive. Copy-number profile derived from Illumina 450K array data, showing chromothripsis on chromosome 11.

Q: Histologically, [...] is characterized by tumor cells with round uniform nuclei set in a fibrillary matrix, frequently accompanied by branching capillaries and dystrophic calcification.
Supratentorial ependymoma, ZFTA fusion–positive. Tumour cells with round nuclei set in a fibrillary matrix. Branching blood vessels and dystrophic calcification can be seen.
Supratentorial ependymoma, ZFTA fusion–positive. Tumour cells with round nuclei set in a fibrillary matrix with branching capillary blood vessels.
A: Supratentorial Ependymoma, ZFTA Fusion-Positive
Back Extra: Supratentorial Ependymoma, ZFTA Fusion-Positive
- Clinical: Supratentorial ependymoma, ZFTA fusion–positive presents with focal neurological deficits, seizures, and signs of raised intracranial pressure.
- Micro: Tumour cells are characterized by round uniform nuclei with speckled chromatin and a fibrillary cytoplasm, often with branching capillaries and dystrophic calcification.
- Ancillary: Diagnostic tests include sequencing methods, interphase FISH, and molecular inversion profiling to detect ZFTA fusions.
Reference Gallery:
Supratentorial ependymoma, ZFTA fusion–positive. Universal cytoplasmic expression of L1CAM.
Supratentorial ependymoma, ZFTA fusion–positive. Tumour cells with round nuclei set in a fibrillary matrix. Branching blood vessels and dystrophic calcification can be seen.
Supratentorial ependymoma, ZFTA fusion–positive. Tumour cells with round nuclei set in a fibrillary matrix with branching capillary blood vessels.
Supratentorial ependymoma, ZFTA fusion–positive. Nuclear immunoreactivity for p65 (encoded by RELA).
Supratentorial ependymoma, ZFTA fusion–positive. T1-weighted axial MRI with gadolinium, showing a well-demarcated left frontal lesion with heterogeneous contrast enhancement and areas of necrosis.
Supratentorial ependymoma, ZFTA fusion–positive. Coronal FLAIR MRI showing conspicuous surrounding oedema.
Supratentorial ependymoma, ZFTA fusion–positive. Copy-number profile derived from Illumina 450K array data, showing chromothripsis on chromosome 11.

Q: In Supratentorial Ependymoma, ZFTA Fusion-Positive, strong nuclear immunoreactivity for p65 is frequently seen due to gene fusions involving the [...] gene, which is sometimes associated with chromothripsis on chromosome 11.
Supratentorial ependymoma, ZFTA fusion–positive. Nuclear immunoreactivity for p65 (encoded by RELA).
Supratentorial ependymoma, ZFTA fusion–positive. Copy-number profile derived from Illumina 450K array data, showing chromothripsis on chromosome 11.
A: RELA
Back Extra: Supratentorial Ependymoma, ZFTA Fusion-Positive
- Clinical: Supratentorial ependymoma, ZFTA fusion–positive presents with focal neurological deficits, seizures, and signs of raised intracranial pressure.
- Micro: Tumour cells are characterized by round uniform nuclei with speckled chromatin and a fibrillary cytoplasm, often with branching capillaries and dystrophic calcification.
- Ancillary: Diagnostic tests include sequencing methods, interphase FISH, and molecular inversion profiling to detect ZFTA fusions.
Reference Gallery:
Supratentorial ependymoma, ZFTA fusion–positive. Universal cytoplasmic expression of L1CAM.
Supratentorial ependymoma, ZFTA fusion–positive. Tumour cells with round nuclei set in a fibrillary matrix. Branching blood vessels and dystrophic calcification can be seen.
Supratentorial ependymoma, ZFTA fusion–positive. Tumour cells with round nuclei set in a fibrillary matrix with branching capillary blood vessels.
Supratentorial ependymoma, ZFTA fusion–positive. Nuclear immunoreactivity for p65 (encoded by RELA).
Supratentorial ependymoma, ZFTA fusion–positive. T1-weighted axial MRI with gadolinium, showing a well-demarcated left frontal lesion with heterogeneous contrast enhancement and areas of necrosis.
Supratentorial ependymoma, ZFTA fusion–positive. Coronal FLAIR MRI showing conspicuous surrounding oedema.
Supratentorial ependymoma, ZFTA fusion–positive. Copy-number profile derived from Illumina 450K array data, showing chromothripsis on chromosome 11.

Q: Patients with Angiocentric Glioma typically present clinically with chronic and intractable [...].
Angiocentric glioma. T2-weighted MRI showing a mostly cortical parietal lesion on the right side, with minimal mass effect.
A: partial epilepsy
Q: Angiocentric Glioma
- Clinical: Patients with [...] typically present with chronic and intractable partial epilepsy, headache, and visual impairment.
- Micro: Angiocentric gliomas are characterized by [...] with slender nuclei arranged in a perivascular pattern.
- Ancillary: Immunohistochemistry reveals [...] positivity, with a dot-like or ring-like pattern of EMA staining.
Reference Gallery:
Angiocentric glioma. T2-weighted MRI showing a mostly cortical parietal lesion on the right side, with minimal mass effect.
Angiocentric glioma. Note both the pronounced angiocentric pattern and the entrapped neurons.
Angiocentric glioma. Elongated cells with bipolar cytoplasmic processes are found in most angiocentric gliomas, particularly in solid areas of the tumour.
Angiocentric glioma. Dot-like or ring-like immunoreactivity for EMA is variably present across regions of most angiocentric gliomas.
Angiocentric glioma. Entrapped neurons are present among tumour cells that show a syncytial pattern.
Angiocentric glioma. The perivascular tumour cells are GFAP-immunoreactive.
Angiocentric glioma. Unlike in most low-grade astrocytomas, the tumour cells are predominantly OLIG2-negative, although there are many entrapped immunoreactive oligodendrocytes.
Angiocentric glioma. NFP staining highlights numerous entrapped axons, consistent with an infiltrative growth pattern.
A: angiocentric glioma; bipolar spindle cells; GFAP and EMA

Q: Microscopically, Angiocentric Glioma is characterized by [...] with slender nuclei that tightly aggregate in a characteristic perivascular pattern.
Angiocentric glioma. Note both the pronounced angiocentric pattern and the entrapped neurons.
Angiocentric glioma. Elongated cells with bipolar cytoplasmic processes are found in most angiocentric gliomas, particularly in solid areas of the tumour.
A: bipolar spindle cells
Q: Angiocentric Glioma
- Clinical: Patients with [...] typically present with chronic and intractable partial epilepsy, headache, and visual impairment.
- Micro: Angiocentric gliomas are characterized by [...] with slender nuclei arranged in a perivascular pattern.
- Ancillary: Immunohistochemistry reveals [...] positivity, with a dot-like or ring-like pattern of EMA staining.
Reference Gallery:
Angiocentric glioma. T2-weighted MRI showing a mostly cortical parietal lesion on the right side, with minimal mass effect.
Angiocentric glioma. Note both the pronounced angiocentric pattern and the entrapped neurons.
Angiocentric glioma. Elongated cells with bipolar cytoplasmic processes are found in most angiocentric gliomas, particularly in solid areas of the tumour.
Angiocentric glioma. Dot-like or ring-like immunoreactivity for EMA is variably present across regions of most angiocentric gliomas.
Angiocentric glioma. Entrapped neurons are present among tumour cells that show a syncytial pattern.
Angiocentric glioma. The perivascular tumour cells are GFAP-immunoreactive.
Angiocentric glioma. Unlike in most low-grade astrocytomas, the tumour cells are predominantly OLIG2-negative, although there are many entrapped immunoreactive oligodendrocytes.
Angiocentric glioma. NFP staining highlights numerous entrapped axons, consistent with an infiltrative growth pattern.
A: angiocentric glioma; bipolar spindle cells; GFAP and EMA

Q: Immunohistochemistry in Angiocentric Glioma characteristically reveals a dot-like or ring-like staining pattern for [...].
Angiocentric glioma. Dot-like or ring-like immunoreactivity for EMA is variably present across regions of most angiocentric gliomas.
A: EMA
Q: Angiocentric Glioma
- Clinical: Patients with [...] typically present with chronic and intractable partial epilepsy, headache, and visual impairment.
- Micro: Angiocentric gliomas are characterized by [...] with slender nuclei arranged in a perivascular pattern.
- Ancillary: Immunohistochemistry reveals [...] positivity, with a dot-like or ring-like pattern of EMA staining.
Reference Gallery:
Angiocentric glioma. T2-weighted MRI showing a mostly cortical parietal lesion on the right side, with minimal mass effect.
Angiocentric glioma. Note both the pronounced angiocentric pattern and the entrapped neurons.
Angiocentric glioma. Elongated cells with bipolar cytoplasmic processes are found in most angiocentric gliomas, particularly in solid areas of the tumour.
Angiocentric glioma. Dot-like or ring-like immunoreactivity for EMA is variably present across regions of most angiocentric gliomas.
Angiocentric glioma. Entrapped neurons are present among tumour cells that show a syncytial pattern.
Angiocentric glioma. The perivascular tumour cells are GFAP-immunoreactive.
Angiocentric glioma. Unlike in most low-grade astrocytomas, the tumour cells are predominantly OLIG2-negative, although there are many entrapped immunoreactive oligodendrocytes.
Angiocentric glioma. NFP staining highlights numerous entrapped axons, consistent with an infiltrative growth pattern.
A: angiocentric glioma; bipolar spindle cells; GFAP and EMA

Q: In Astroblastoma, MN1-altered, the histological hallmark is the [...], characterized by radially oriented tumor cells with distally located nuclei and stout processes extending to a central vascular structure.
Astroblastoma, MN1-altered. The histological hallmark is the astroblastic rosette, characterized by radially oriented tumour cells with elongate, stout processes and distally located nuclei extending to a central vascular structure.
Astroblastoma, MN1-altered. A ribbon-like or trabecular pattern is noted when elongated tumour cells oriented to central blood vessels are seen in cross-section.
A: astroblastic rosette
Back Extra: Astroblastoma, MN1-altered
- Clinical: Astroblastoma, MN1-altered typically presents with symptoms such as headache, seizures, paralysis, nausea, and vomiting. MRI shows well-demarcated, solid or cystic masses with heterogeneous contrast enhancement.
- Micro: The histological hallmark of Astroblastoma, MN1-altered is the astroblastic rosette, characterized by radially oriented tumour cells with elongate processes and distally located nuclei extending to a central vascular structure.
- Ancillary: Astroblastoma, MN1-altered is characterized by structural rearrangements of the MN1 gene, detectable by FISH, RT-PCR, RNA sequencing, and next-generation DNA sequencing.
Reference Gallery:
Astroblastoma with primitive cytology. The high cellularity, small round cell cytology, and geographical necrosis in this astroblastoma mimicked an embryonal neoplasm. Molecular testing revealed an MN1::BEND2 fusion.
Astroblastoma, MN1-altered. Postcontrast, T1-weighted MRI shows a large, well-demarcated, contrast-enhancing, solid and cystic right temporoparietal mass.
Astroblastoma, MN1-altered. T2-weighted MRI shows a large, well-demarcated, contrast-enhancing, solid and cystic right temporoparietal mass.
Astroblastoma, MN1-altered. The histological hallmark is the astroblastic rosette, characterized by radially oriented tumour cells with elongate, stout processes and distally located nuclei extending to a central vascular structure.
Astroblastoma, MN1-altered. A ribbon-like or trabecular pattern is noted when elongated tumour cells oriented to central blood vessels are seen in cross-section.
Astroblastoma, MN1-altered. Perivascular and pericellular hyalinization is typical but varies considerably in its severity and extent.
Astroblastoma, MN1-altered. Immunohistochemistry for GFAP often shows strong, diffuse immunoreactivity in astroblastoma, MN1-altered.
Astroblastoma, MN1-altered. Note the sharp demarcation from adjacent brain parenchyma.
Astroblastoma, MN1-altered. This tumour included focal rhabdoid cytological features.
Astroblastoma with primitive cytology. Other areas of this tumour featured perivascular and stromal sclerosis, more typical of astroblastoma.
Astroblastoma, MN1-altered. Patchy membranous and cytoplasmic dot-like immunostaining for EMA.
Astroblastoma, MN1-altered. Membranous and cytoplasmic dot-like D2-40 (podoplanin) staining.

Q: A characteristic histological feature of Astroblastoma, MN1-altered is the presence of extensive perivascular and pericellular [...] (sclerosis), which can vary considerably in severity and extent.
Astroblastoma, MN1-altered. Perivascular and pericellular hyalinization is typical but varies considerably in its severity and extent.
Astroblastoma with primitive cytology. Other areas of this tumour featured perivascular and stromal sclerosis, more typical of astroblastoma.
A: hyalinization
Back Extra: Astroblastoma, MN1-altered
- Clinical: Astroblastoma, MN1-altered typically presents with symptoms such as headache, seizures, paralysis, nausea, and vomiting. MRI shows well-demarcated, solid or cystic masses with heterogeneous contrast enhancement.
- Micro: The histological hallmark of Astroblastoma, MN1-altered is the astroblastic rosette, characterized by radially oriented tumour cells with elongate processes and distally located nuclei extending to a central vascular structure.
- Ancillary: Astroblastoma, MN1-altered is characterized by structural rearrangements of the MN1 gene, detectable by FISH, RT-PCR, RNA sequencing, and next-generation DNA sequencing.
Reference Gallery:
Astroblastoma with primitive cytology. The high cellularity, small round cell cytology, and geographical necrosis in this astroblastoma mimicked an embryonal neoplasm. Molecular testing revealed an MN1::BEND2 fusion.
Astroblastoma, MN1-altered. Postcontrast, T1-weighted MRI shows a large, well-demarcated, contrast-enhancing, solid and cystic right temporoparietal mass.
Astroblastoma, MN1-altered. T2-weighted MRI shows a large, well-demarcated, contrast-enhancing, solid and cystic right temporoparietal mass.
Astroblastoma, MN1-altered. The histological hallmark is the astroblastic rosette, characterized by radially oriented tumour cells with elongate, stout processes and distally located nuclei extending to a central vascular structure.
Astroblastoma, MN1-altered. A ribbon-like or trabecular pattern is noted when elongated tumour cells oriented to central blood vessels are seen in cross-section.
Astroblastoma, MN1-altered. Perivascular and pericellular hyalinization is typical but varies considerably in its severity and extent.
Astroblastoma, MN1-altered. Immunohistochemistry for GFAP often shows strong, diffuse immunoreactivity in astroblastoma, MN1-altered.
Astroblastoma, MN1-altered. Note the sharp demarcation from adjacent brain parenchyma.
Astroblastoma, MN1-altered. This tumour included focal rhabdoid cytological features.
Astroblastoma with primitive cytology. Other areas of this tumour featured perivascular and stromal sclerosis, more typical of astroblastoma.
Astroblastoma, MN1-altered. Patchy membranous and cytoplasmic dot-like immunostaining for EMA.
Astroblastoma, MN1-altered. Membranous and cytoplasmic dot-like D2-40 (podoplanin) staining.

Q: In Astroblastoma, MN1-altered, immunohistochemistry frequently shows strong, diffuse GFAP reactivity alongside characteristic patchy, membranous, and cytoplasmic dot-like staining for [...] and D2-40.
Astroblastoma, MN1-altered. Immunohistochemistry for GFAP often shows strong, diffuse immunoreactivity in astroblastoma, MN1-altered.
Astroblastoma, MN1-altered. Patchy membranous and cytoplasmic dot-like immunostaining for EMA.
Astroblastoma, MN1-altered. Membranous and cytoplasmic dot-like D2-40 (podoplanin) staining.
A: EMA
Back Extra: Astroblastoma, MN1-altered
- Clinical: Astroblastoma, MN1-altered typically presents with symptoms such as headache, seizures, paralysis, nausea, and vomiting. MRI shows well-demarcated, solid or cystic masses with heterogeneous contrast enhancement.
- Micro: The histological hallmark of Astroblastoma, MN1-altered is the astroblastic rosette, characterized by radially oriented tumour cells with elongate processes and distally located nuclei extending to a central vascular structure.
- Ancillary: Astroblastoma, MN1-altered is characterized by structural rearrangements of the MN1 gene, detectable by FISH, RT-PCR, RNA sequencing, and next-generation DNA sequencing.
Reference Gallery:
Astroblastoma with primitive cytology. The high cellularity, small round cell cytology, and geographical necrosis in this astroblastoma mimicked an embryonal neoplasm. Molecular testing revealed an MN1::BEND2 fusion.
Astroblastoma, MN1-altered. Postcontrast, T1-weighted MRI shows a large, well-demarcated, contrast-enhancing, solid and cystic right temporoparietal mass.
Astroblastoma, MN1-altered. T2-weighted MRI shows a large, well-demarcated, contrast-enhancing, solid and cystic right temporoparietal mass.
Astroblastoma, MN1-altered. The histological hallmark is the astroblastic rosette, characterized by radially oriented tumour cells with elongate, stout processes and distally located nuclei extending to a central vascular structure.
Astroblastoma, MN1-altered. A ribbon-like or trabecular pattern is noted when elongated tumour cells oriented to central blood vessels are seen in cross-section.
Astroblastoma, MN1-altered. Perivascular and pericellular hyalinization is typical but varies considerably in its severity and extent.
Astroblastoma, MN1-altered. Immunohistochemistry for GFAP often shows strong, diffuse immunoreactivity in astroblastoma, MN1-altered.
Astroblastoma, MN1-altered. Note the sharp demarcation from adjacent brain parenchyma.
Astroblastoma, MN1-altered. This tumour included focal rhabdoid cytological features.
Astroblastoma with primitive cytology. Other areas of this tumour featured perivascular and stromal sclerosis, more typical of astroblastoma.
Astroblastoma, MN1-altered. Patchy membranous and cytoplasmic dot-like immunostaining for EMA.
Astroblastoma, MN1-altered. Membranous and cytoplasmic dot-like D2-40 (podoplanin) staining.

Q: Patients presenting with long-standing, drug-resistant epileptic seizures since childhood, who demonstrate a diffuse proliferation of bland glial cells on biopsy, may be diagnosed with [...].
Diffuse astrocytoma, MYB- or MYBL1-altered. MRI of a MYBL1-altered diffuse astrocytoma located in the inferior frontal gyrus in a 39-year-old patient with epilepsy since the age of 3 years. The tumour (white arrow) is T1-hypointense (left), T2-hyperintense (middle), and FLAIR-hyperintense (right).
A: Diffuse Astrocytoma, MYB- or MYBL1-altered
Q: Diffuse Astrocytoma, MYB- or MYBL1-altered
- Clinical: Patients typically present with drug-resistant [...], which often have been present since childhood.
- Micro: A proliferation of relatively monomorphic glial cells with bland nuclei and diffuse infiltration into the neuropil is characteristic.
- Ancillary: Sequencing demonstrates a structural variation resulting in a fusion between [...] and a partner gene.
Reference Gallery:
Diffuse astrocytoma, MYB- or MYBL1-altered. MRI of a MYBL1-altered diffuse astrocytoma located in the inferior frontal gyrus in a 39-year-old patient with epilepsy since the age of 3 years. The tumour (white arrow) is T1-hypointense (left), T2-hyperintense (middle), and FLAIR-hyperintense (right).
Diffuse astrocytoma, MYB- or MYBL1-altered. A typical MYB- or MYBL1-altered diffuse astrocytoma showing monomorphic glial cells with bland nuclei and diffusely permeating neuropil.
Diffuse astrocytoma, MYB- or MYBL1-altered. GFAP-immunostained section showing diffuse immunopositivity both of tumour cells and of the background neuropil.
Diffuse astrocytoma, MYBL1-altered. Infiltrative glioma with mild hypercellularity and atypia.
Diffuse astrocytoma, MYBL1-altered. Infiltrative glioma with mild hypercellularity and atypia.
Diffuse astrocytoma, MYBL1-altered. Neurofilament immunostaining highlights numerous entrapped axons.
Diffuse astrocytoma, MYBL1-altered. MAP2 immunostaining highlights entrapped ganglion cells and their processes, but most tumour cells are negative, unlike in most other low-grade astrocytic neoplasms.
Diffuse astrocytoma, MYBL1-altered. In contrast to most other low-grade glioma subtypes, this tumour is mostly negative for OLIG2.
Diffuse astrocytoma, MYBL1-altered. In contrast to most other low-grade astrocytic neoplasms, this tumour is mostly negative for SOX10.
A: epileptic seizures; MYB or MYBL1

Q: Microscopically, [...] is characterized by a proliferation of relatively monomorphic glial cells with bland nuclei and diffuse infiltration into the neuropil.
Diffuse astrocytoma, MYB- or MYBL1-altered. A typical MYB- or MYBL1-altered diffuse astrocytoma showing monomorphic glial cells with bland nuclei and diffusely permeating neuropil.
Diffuse astrocytoma, MYB- or MYBL1-altered. GFAP-immunostained section showing diffuse immunopositivity both of tumour cells and of the background neuropil.
A: Diffuse Astrocytoma, MYB- or MYBL1-altered
Q: Diffuse Astrocytoma, MYB- or MYBL1-altered
- Clinical: Patients typically present with drug-resistant [...], which often have been present since childhood.
- Micro: A proliferation of relatively monomorphic glial cells with bland nuclei and diffuse infiltration into the neuropil is characteristic.
- Ancillary: Sequencing demonstrates a structural variation resulting in a fusion between [...] and a partner gene.
Reference Gallery:
Diffuse astrocytoma, MYB- or MYBL1-altered. MRI of a MYBL1-altered diffuse astrocytoma located in the inferior frontal gyrus in a 39-year-old patient with epilepsy since the age of 3 years. The tumour (white arrow) is T1-hypointense (left), T2-hyperintense (middle), and FLAIR-hyperintense (right).
Diffuse astrocytoma, MYB- or MYBL1-altered. A typical MYB- or MYBL1-altered diffuse astrocytoma showing monomorphic glial cells with bland nuclei and diffusely permeating neuropil.
Diffuse astrocytoma, MYB- or MYBL1-altered. GFAP-immunostained section showing diffuse immunopositivity both of tumour cells and of the background neuropil.
Diffuse astrocytoma, MYBL1-altered. Infiltrative glioma with mild hypercellularity and atypia.
Diffuse astrocytoma, MYBL1-altered. Infiltrative glioma with mild hypercellularity and atypia.
Diffuse astrocytoma, MYBL1-altered. Neurofilament immunostaining highlights numerous entrapped axons.
Diffuse astrocytoma, MYBL1-altered. MAP2 immunostaining highlights entrapped ganglion cells and their processes, but most tumour cells are negative, unlike in most other low-grade astrocytic neoplasms.
Diffuse astrocytoma, MYBL1-altered. In contrast to most other low-grade glioma subtypes, this tumour is mostly negative for OLIG2.
Diffuse astrocytoma, MYBL1-altered. In contrast to most other low-grade astrocytic neoplasms, this tumour is mostly negative for SOX10.
A: epileptic seizures; MYB or MYBL1

Q: In contrast to most other low-grade astrocytic neoplasms, Diffuse Astrocytoma, MYB- or MYBL1-altered is characteristically mostly negative for the glial immunohistochemical markers [...].
Diffuse astrocytoma, MYBL1-altered. In contrast to most other low-grade glioma subtypes, this tumour is mostly negative for OLIG2.
Diffuse astrocytoma, MYBL1-altered. In contrast to most other low-grade astrocytic neoplasms, this tumour is mostly negative for SOX10.
A: OLIG2 and SOX10
Q: Diffuse Astrocytoma, MYB- or MYBL1-altered
- Clinical: Patients typically present with drug-resistant [...], which often have been present since childhood.
- Micro: A proliferation of relatively monomorphic glial cells with bland nuclei and diffuse infiltration into the neuropil is characteristic.
- Ancillary: Sequencing demonstrates a structural variation resulting in a fusion between [...] and a partner gene.
Reference Gallery:
Diffuse astrocytoma, MYB- or MYBL1-altered. MRI of a MYBL1-altered diffuse astrocytoma located in the inferior frontal gyrus in a 39-year-old patient with epilepsy since the age of 3 years. The tumour (white arrow) is T1-hypointense (left), T2-hyperintense (middle), and FLAIR-hyperintense (right).
Diffuse astrocytoma, MYB- or MYBL1-altered. A typical MYB- or MYBL1-altered diffuse astrocytoma showing monomorphic glial cells with bland nuclei and diffusely permeating neuropil.
Diffuse astrocytoma, MYB- or MYBL1-altered. GFAP-immunostained section showing diffuse immunopositivity both of tumour cells and of the background neuropil.
Diffuse astrocytoma, MYBL1-altered. Infiltrative glioma with mild hypercellularity and atypia.
Diffuse astrocytoma, MYBL1-altered. Infiltrative glioma with mild hypercellularity and atypia.
Diffuse astrocytoma, MYBL1-altered. Neurofilament immunostaining highlights numerous entrapped axons.
Diffuse astrocytoma, MYBL1-altered. MAP2 immunostaining highlights entrapped ganglion cells and their processes, but most tumour cells are negative, unlike in most other low-grade astrocytic neoplasms.
Diffuse astrocytoma, MYBL1-altered. In contrast to most other low-grade glioma subtypes, this tumour is mostly negative for OLIG2.
Diffuse astrocytoma, MYBL1-altered. In contrast to most other low-grade astrocytic neoplasms, this tumour is mostly negative for SOX10.
A: epileptic seizures; MYB or MYBL1

Q: Histologically, Diffuse Hemispheric Glioma, H3 G34-Mutant often exhibits a glioblastoma-like pattern characterized by brisk mitotic activity, microvascular proliferation, and palisading [...].
Diffuse hemispheric glioma, H3 G34–mutant. Palisading necrosis.
A: necrosis
Back Extra: Diffuse Hemispheric Glioma, H3 G34-Mutant
- Clinical: Patients with Diffuse Hemispheric Glioma, H3 G34-Mutant often present with seizures and motor or sensory deficits, and MRI typically shows a contrast-enhancing tumour in the cerebral hemispheres, often involving the parietal or temporal lobe.
- Micro: The histology of Diffuse Hemispheric Glioma, H3 G34-Mutant includes a glioblastoma-like pattern with brisk mitotic activity, microvascular proliferation, and necrosis. In some cases, it may resemble CNS embryonal tumours with Homer Wright rosettes.
- Ancillary: Immunohistochemistry for Diffuse Hemispheric Glioma, H3 G34-Mutant typically shows MAP2 positivity, FOXG1 positivity, loss of ATRX expression, and nuclear accumulation of p53. Mutation-specific antibodies for H3.3 p.G35R and p.G35V are available.
Reference Gallery:
Diffuse hemispheric glioma, H3 G34–mutant. Palisading necrosis.
Diffuse hemispheric glioma, H3 G34–mutant. Variable GFAP immunoreactivity.
Diffuse hemispheric glioma, H3 G34–mutant. Tumour cells typically lack nuclear OLIG2 expression.
Diffuse hemispheric glioma, H3 G34–mutant. The tumour cells typically show nuclear accumulation of p53.
Diffuse hemispheric glioma, H3 G34–mutant. Tumour cells usually lack nuclear expression of ATRX.

Q: Immunohistochemistry for Diffuse Hemispheric Glioma, H3 G34-Mutant is characteristically positive for nuclear accumulation of p53 and shows mutation-associated loss of nuclear [...] expression.
Diffuse hemispheric glioma, H3 G34–mutant. The tumour cells typically show nuclear accumulation of p53.
Diffuse hemispheric glioma, H3 G34–mutant. Tumour cells usually lack nuclear expression of ATRX.
A: ATRX
Back Extra: Diffuse Hemispheric Glioma, H3 G34-Mutant
- Clinical: Patients with Diffuse Hemispheric Glioma, H3 G34-Mutant often present with seizures and motor or sensory deficits, and MRI typically shows a contrast-enhancing tumour in the cerebral hemispheres, often involving the parietal or temporal lobe.
- Micro: The histology of Diffuse Hemispheric Glioma, H3 G34-Mutant includes a glioblastoma-like pattern with brisk mitotic activity, microvascular proliferation, and necrosis. In some cases, it may resemble CNS embryonal tumours with Homer Wright rosettes.
- Ancillary: Immunohistochemistry for Diffuse Hemispheric Glioma, H3 G34-Mutant typically shows MAP2 positivity, FOXG1 positivity, loss of ATRX expression, and nuclear accumulation of p53. Mutation-specific antibodies for H3.3 p.G35R and p.G35V are available.
Reference Gallery:
Diffuse hemispheric glioma, H3 G34–mutant. Palisading necrosis.
Diffuse hemispheric glioma, H3 G34–mutant. Variable GFAP immunoreactivity.
Diffuse hemispheric glioma, H3 G34–mutant. Tumour cells typically lack nuclear OLIG2 expression.
Diffuse hemispheric glioma, H3 G34–mutant. The tumour cells typically show nuclear accumulation of p53.
Diffuse hemispheric glioma, H3 G34–mutant. Tumour cells usually lack nuclear expression of ATRX.

Q: A distinct immunohistochemical feature of Diffuse Hemispheric Glioma, H3 G34-Mutant is that the tumor cells typically lack nuclear expression of [...], which contrasts with its variable GFAP immunoreactivity.
Diffuse hemispheric glioma, H3 G34–mutant. Variable GFAP immunoreactivity.
Diffuse hemispheric glioma, H3 G34–mutant. Tumour cells typically lack nuclear OLIG2 expression.
A: OLIG2
Back Extra: Diffuse Hemispheric Glioma, H3 G34-Mutant
- Clinical: Patients with Diffuse Hemispheric Glioma, H3 G34-Mutant often present with seizures and motor or sensory deficits, and MRI typically shows a contrast-enhancing tumour in the cerebral hemispheres, often involving the parietal or temporal lobe.
- Micro: The histology of Diffuse Hemispheric Glioma, H3 G34-Mutant includes a glioblastoma-like pattern with brisk mitotic activity, microvascular proliferation, and necrosis. In some cases, it may resemble CNS embryonal tumours with Homer Wright rosettes.
- Ancillary: Immunohistochemistry for Diffuse Hemispheric Glioma, H3 G34-Mutant typically shows MAP2 positivity, FOXG1 positivity, loss of ATRX expression, and nuclear accumulation of p53. Mutation-specific antibodies for H3.3 p.G35R and p.G35V are available.
Reference Gallery:
Diffuse hemispheric glioma, H3 G34–mutant. Palisading necrosis.
Diffuse hemispheric glioma, H3 G34–mutant. Variable GFAP immunoreactivity.
Diffuse hemispheric glioma, H3 G34–mutant. Tumour cells typically lack nuclear OLIG2 expression.
Diffuse hemispheric glioma, H3 G34–mutant. The tumour cells typically show nuclear accumulation of p53.
Diffuse hemispheric glioma, H3 G34–mutant. Tumour cells usually lack nuclear expression of ATRX.

Q: The definitive diagnosis of Diffuse Low-Grade Glioma, MAPK Pathway-Altered requires the demonstration of a MAPK pathway alteration, such as an FGFR1 duplication or the [...] mutation, alongside the strict absence of IDH or H3 mutations.
Diffuse low-grade glioma, MAPK pathway–altered. Temporal lobe tumour in a 7-year-old patient. Mildly atypical neoplastic glial cells with an astrocytic or oligodendrocytic morphology are diffusely distributed in cerebral cortex and underlying white matter. Nodule formation is rare. An FGFR1 tyrosine kinase domain (TKD) duplication was detected.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells express the mutant protein BRAF p.V600E.
A: BRAF p.V600E
Back Extra: Diffuse Low-Grade Glioma, MAPK Pathway-Altered
- Clinical: Symptoms often include epilepsy and location-specific neurological deficits, with signs of raised intracranial pressure.
- Micro: Tumour cells are mildly atypical, with a bland appearance and rare mitotic activity, showing immunopositivity for OLIG2 and GFAP.
- Ancillary: Diagnosis is confirmed by the presence of MAPK pathway alterations, such as BRAF p.V600E mutation or FGFR1 TKD duplication, in the absence of IDH or H3 p.K28M mutations.
Reference Gallery:
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells show immunopositivity for GFAP.
Diffuse low-grade glioma, MAPK pathway–altered. Temporal lobe tumour in a 7-year-old patient. Mildly atypical neoplastic glial cells with an astrocytic or oligodendrocytic morphology are diffusely distributed in cerebral cortex and underlying white matter. Nodule formation is rare. An FGFR1 tyrosine kinase domain (TKD) duplication was detected.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity entrapping normal neurons. The tumour cells have a bland appearance and are mildly atypical.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells show immunopositivity for OLIG2.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity showing subpial aggregation typical of diffuse gliomas.
Diffuse low-grade glioma, MAPK pathway–altered. Temporal lobe tumour in a 7-year-old patient (same case as in Fig. 21456). A fibrillary matrix is found in some regions.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity. The tumour cells have a bland appearance and are mildly atypical.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells express the mutant protein BRAF p.V600E.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. Postcontrast T1-weighted MRI shows a heterogeneously enhancing mass, with a cystic element, within the medial aspect of the right temporal lobe.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with low T1 signal.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with high T2 signal.

Q: Microscopically, [...] features mildly atypical, bland-appearing cells that diffusely infiltrate the cortex (often entrapping normal neurons) and demonstrate characteristic immunopositivity for both GFAP and OLIG2.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells show immunopositivity for GFAP.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity entrapping normal neurons. The tumour cells have a bland appearance and are mildly atypical.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells show immunopositivity for OLIG2.
A: Diffuse Low-Grade Glioma, MAPK Pathway-Altered
Back Extra: Diffuse Low-Grade Glioma, MAPK Pathway-Altered
- Clinical: Symptoms often include epilepsy and location-specific neurological deficits, with signs of raised intracranial pressure.
- Micro: Tumour cells are mildly atypical, with a bland appearance and rare mitotic activity, showing immunopositivity for OLIG2 and GFAP.
- Ancillary: Diagnosis is confirmed by the presence of MAPK pathway alterations, such as BRAF p.V600E mutation or FGFR1 TKD duplication, in the absence of IDH or H3 p.K28M mutations.
Reference Gallery:
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells show immunopositivity for GFAP.
Diffuse low-grade glioma, MAPK pathway–altered. Temporal lobe tumour in a 7-year-old patient. Mildly atypical neoplastic glial cells with an astrocytic or oligodendrocytic morphology are diffusely distributed in cerebral cortex and underlying white matter. Nodule formation is rare. An FGFR1 tyrosine kinase domain (TKD) duplication was detected.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity entrapping normal neurons. The tumour cells have a bland appearance and are mildly atypical.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells show immunopositivity for OLIG2.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity showing subpial aggregation typical of diffuse gliomas.
Diffuse low-grade glioma, MAPK pathway–altered. Temporal lobe tumour in a 7-year-old patient (same case as in Fig. 21456). A fibrillary matrix is found in some regions.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity. The tumour cells have a bland appearance and are mildly atypical.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells express the mutant protein BRAF p.V600E.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. Postcontrast T1-weighted MRI shows a heterogeneously enhancing mass, with a cystic element, within the medial aspect of the right temporal lobe.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with low T1 signal.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with high T2 signal.

Q: In a pediatric patient presenting with epilepsy, a temporal lobe mass demonstrating high T2 signal and a cystic element on MRI, combined with MAPK pathway alterations and an absence of IDH mutations, is diagnostic of [...].
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. Postcontrast T1-weighted MRI shows a heterogeneously enhancing mass, with a cystic element, within the medial aspect of the right temporal lobe.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with low T1 signal.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with high T2 signal.
A: Diffuse Low-Grade Glioma, MAPK Pathway-Altered
Back Extra: Diffuse Low-Grade Glioma, MAPK Pathway-Altered
- Clinical: Symptoms often include epilepsy and location-specific neurological deficits, with signs of raised intracranial pressure.
- Micro: Tumour cells are mildly atypical, with a bland appearance and rare mitotic activity, showing immunopositivity for OLIG2 and GFAP.
- Ancillary: Diagnosis is confirmed by the presence of MAPK pathway alterations, such as BRAF p.V600E mutation or FGFR1 TKD duplication, in the absence of IDH or H3 p.K28M mutations.
Reference Gallery:
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells show immunopositivity for GFAP.
Diffuse low-grade glioma, MAPK pathway–altered. Temporal lobe tumour in a 7-year-old patient. Mildly atypical neoplastic glial cells with an astrocytic or oligodendrocytic morphology are diffusely distributed in cerebral cortex and underlying white matter. Nodule formation is rare. An FGFR1 tyrosine kinase domain (TKD) duplication was detected.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity entrapping normal neurons. The tumour cells have a bland appearance and are mildly atypical.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells show immunopositivity for OLIG2.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity showing subpial aggregation typical of diffuse gliomas.
Diffuse low-grade glioma, MAPK pathway–altered. Temporal lobe tumour in a 7-year-old patient (same case as in Fig. 21456). A fibrillary matrix is found in some regions.
Diffuse low-grade glioma, MAPK pathway–altered. A low-grade diffuse glioma of moderate cellularity. The tumour cells have a bland appearance and are mildly atypical.
Diffuse low-grade glioma, MAPK pathway–altered. Neoplastic astrocytic glioma cells express the mutant protein BRAF p.V600E.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. Postcontrast T1-weighted MRI shows a heterogeneously enhancing mass, with a cystic element, within the medial aspect of the right temporal lobe.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with low T1 signal.
Diffuse low-grade glioma, MAPK pathway–altered. Diffuse low-grade glioma in a 1-year-old girl. MRI shows a mass within the medial aspect of the right temporal lobe, with high T2 signal.

Q: In Diffuse Midline Glioma, H3 K27-Altered, magnetic resonance imaging typically demonstrates a heterogeneous or T2-bright tumor expanding classic [...] structures such as the pons, thalamus, or spinal cord.
Diffuse midline glioma, H3 K27–altered. Axial MRI shows a T2-bright lesion in a classic midline location, expanding the pons and encasing the basilar artery.
Diffuse midline glioma, H3 K27–altered. MRI showing heterogeneous enhancement of a pontine lesion (a classic midline location) on a postgadolinium T1 sequence.
Diffuse midline glioma, H3 K27–altered. Axial MRI shows a left unithalamic T2-bright lesion with associated obstructive hydrocephalus. There is no peritumoural oedema.
A: midline
Back Extra: Diffuse Midline Glioma, H3 K27-Altered
- Clinical: Most patients with Diffuse Midline Glioma, H3 K27-Altered present with a short medical history and the classic triad: cranial nerve palsy, long tract signs, and ataxia.
- Micro: Tumour cells can show various morphologies, including oligodendroglial, astrocytic, piloid, and giant cell types, often with frequent mitotic figures and occasional palisading necrosis.
- Ancillary: Immunohistochemistry is positive for OLIG2, MAP2, and S100, variable for GFAP, and typically negative for EZHIP, with nuclear p53 accumulation in about 50% of cases.
Reference Gallery:
Diffuse midline glioma, H3 K27–altered. Some cases of H3 K27–altered diffuse midline glioma show an oligodendroglial morphology, with round nuclei and perinuclear haloes.
Diffuse midline glioma, H3 K27–altered. Palisading necrosis can be observed.
Diffuse midline glioma, H3 K27–altered. Occasionally, multinucleated cells are present within H3 K27–altered diffuse midline gliomas.
Diffuse midline glioma, H3 K27–altered. Besides having oligodendroglial morphology, some H3 K27–altered diffuse midline gliomas can mimic glioneuronal tumours with occasional rosette formation. Note the single mitotic figures, which are less common in low-grade glioneuronal tumours.
Diffuse midline glioma, H3 K27–altered. Some tumour cells in H3 K27–altered diffuse midline gliomas demonstrate elongated nuclei.
Diffuse midline glioma, H3 K27–altered. A pontine glioma showing infiltrative neoplastic cells in an oedematous background, with some residual neurons.
Diffuse midline glioma, H3 K27–altered. Immunohistochemical staining for H3 p.K28me3 (K27me3) shows loss of expression in tumour cells, with retention in endothelial cells and residual neurons.
Diffuse midline glioma, H3 K27–altered. Negativity for EZHIP immunostaining.
Diffuse midline glioma, H3 K27–altered. Axial MRI shows a T2-bright lesion in a classic midline location, expanding the pons and encasing the basilar artery.
Diffuse midline glioma, H3 K27–altered. MRI showing heterogeneous enhancement of a pontine lesion (a classic midline location) on a postgadolinium T1 sequence.
Diffuse midline glioma, H3 K27–altered. Axial MRI shows a left unithalamic T2-bright lesion with associated obstructive hydrocephalus. There is no peritumoural oedema.
Diffuse midline glioma, H3 K27–altered. Sagittal postgadolinium T1 sequence reveals an intramedullary tumour (a classic midline location) with heterogeneous annular enhancement.

Q: The defining immunohistochemical finding in Diffuse Midline Glioma, H3 K27-Altered is the selective loss of nuclear [...] (also known as p.K28me3) expression in tumor cells, with retention in background endothelial cells and neurons.
Diffuse midline glioma, H3 K27–altered. Immunohistochemical staining for H3 p.K28me3 (K27me3) shows loss of expression in tumour cells, with retention in endothelial cells and residual neurons.
A: H3 K27me3
Back Extra: Diffuse Midline Glioma, H3 K27-Altered
- Clinical: Most patients with Diffuse Midline Glioma, H3 K27-Altered present with a short medical history and the classic triad: cranial nerve palsy, long tract signs, and ataxia.
- Micro: Tumour cells can show various morphologies, including oligodendroglial, astrocytic, piloid, and giant cell types, often with frequent mitotic figures and occasional palisading necrosis.
- Ancillary: Immunohistochemistry is positive for OLIG2, MAP2, and S100, variable for GFAP, and typically negative for EZHIP, with nuclear p53 accumulation in about 50% of cases.
Reference Gallery:
Diffuse midline glioma, H3 K27–altered. Some cases of H3 K27–altered diffuse midline glioma show an oligodendroglial morphology, with round nuclei and perinuclear haloes.
Diffuse midline glioma, H3 K27–altered. Palisading necrosis can be observed.
Diffuse midline glioma, H3 K27–altered. Occasionally, multinucleated cells are present within H3 K27–altered diffuse midline gliomas.
Diffuse midline glioma, H3 K27–altered. Besides having oligodendroglial morphology, some H3 K27–altered diffuse midline gliomas can mimic glioneuronal tumours with occasional rosette formation. Note the single mitotic figures, which are less common in low-grade glioneuronal tumours.
Diffuse midline glioma, H3 K27–altered. Some tumour cells in H3 K27–altered diffuse midline gliomas demonstrate elongated nuclei.
Diffuse midline glioma, H3 K27–altered. A pontine glioma showing infiltrative neoplastic cells in an oedematous background, with some residual neurons.
Diffuse midline glioma, H3 K27–altered. Immunohistochemical staining for H3 p.K28me3 (K27me3) shows loss of expression in tumour cells, with retention in endothelial cells and residual neurons.
Diffuse midline glioma, H3 K27–altered. Negativity for EZHIP immunostaining.
Diffuse midline glioma, H3 K27–altered. Axial MRI shows a T2-bright lesion in a classic midline location, expanding the pons and encasing the basilar artery.
Diffuse midline glioma, H3 K27–altered. MRI showing heterogeneous enhancement of a pontine lesion (a classic midline location) on a postgadolinium T1 sequence.
Diffuse midline glioma, H3 K27–altered. Axial MRI shows a left unithalamic T2-bright lesion with associated obstructive hydrocephalus. There is no peritumoural oedema.
Diffuse midline glioma, H3 K27–altered. Sagittal postgadolinium T1 sequence reveals an intramedullary tumour (a classic midline location) with heterogeneous annular enhancement.

Q: Microscopically, Diffuse Midline Glioma, H3 K27-Altered can display highly variable morphologies (e.g., oligodendroglial-like cells with perinuclear halos) and frequently demonstrates high-grade histologic features like frequent mitoses and [...].
Diffuse midline glioma, H3 K27–altered. Some cases of H3 K27–altered diffuse midline glioma show an oligodendroglial morphology, with round nuclei and perinuclear haloes.
Diffuse midline glioma, H3 K27–altered. Palisading necrosis can be observed.
A: palisading necrosis
Back Extra: Diffuse Midline Glioma, H3 K27-Altered
- Clinical: Most patients with Diffuse Midline Glioma, H3 K27-Altered present with a short medical history and the classic triad: cranial nerve palsy, long tract signs, and ataxia.
- Micro: Tumour cells can show various morphologies, including oligodendroglial, astrocytic, piloid, and giant cell types, often with frequent mitotic figures and occasional palisading necrosis.
- Ancillary: Immunohistochemistry is positive for OLIG2, MAP2, and S100, variable for GFAP, and typically negative for EZHIP, with nuclear p53 accumulation in about 50% of cases.
Reference Gallery:
Diffuse midline glioma, H3 K27–altered. Some cases of H3 K27–altered diffuse midline glioma show an oligodendroglial morphology, with round nuclei and perinuclear haloes.
Diffuse midline glioma, H3 K27–altered. Palisading necrosis can be observed.
Diffuse midline glioma, H3 K27–altered. Occasionally, multinucleated cells are present within H3 K27–altered diffuse midline gliomas.
Diffuse midline glioma, H3 K27–altered. Besides having oligodendroglial morphology, some H3 K27–altered diffuse midline gliomas can mimic glioneuronal tumours with occasional rosette formation. Note the single mitotic figures, which are less common in low-grade glioneuronal tumours.
Diffuse midline glioma, H3 K27–altered. Some tumour cells in H3 K27–altered diffuse midline gliomas demonstrate elongated nuclei.
Diffuse midline glioma, H3 K27–altered. A pontine glioma showing infiltrative neoplastic cells in an oedematous background, with some residual neurons.
Diffuse midline glioma, H3 K27–altered. Immunohistochemical staining for H3 p.K28me3 (K27me3) shows loss of expression in tumour cells, with retention in endothelial cells and residual neurons.
Diffuse midline glioma, H3 K27–altered. Negativity for EZHIP immunostaining.
Diffuse midline glioma, H3 K27–altered. Axial MRI shows a T2-bright lesion in a classic midline location, expanding the pons and encasing the basilar artery.
Diffuse midline glioma, H3 K27–altered. MRI showing heterogeneous enhancement of a pontine lesion (a classic midline location) on a postgadolinium T1 sequence.
Diffuse midline glioma, H3 K27–altered. Axial MRI shows a left unithalamic T2-bright lesion with associated obstructive hydrocephalus. There is no peritumoural oedema.
Diffuse midline glioma, H3 K27–altered. Sagittal postgadolinium T1 sequence reveals an intramedullary tumour (a classic midline location) with heterogeneous annular enhancement.

Q: Histopathologically, Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype typically presents as either a classic glioblastoma-like malignant tumor or with a highly cellular, primitive [...] morphology.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. The tumour is highly cellular, reminiscent of embryonal morphology, and it shows areas of sharp demarcation from the brain tissue.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. In addition to having glial areas, the tumour may show a prominent embryonal appearance.
A: embryonal
Back Extra: Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
- Clinical: Patients with diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, may develop clinical symptoms such as seizures, motor or sensory deficits, and MRI typically reveals a contrast-enhancing tumour with mass effect.
- Micro: Histopathology of diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, shows features of either a glioblastoma-like malignant tumour or a primitive, undifferentiated morphology, often with areas of glial and primitive differentiation.
- Ancillary: DNA methylation profiling is crucial for identifying molecular subgroups, including pHGG RTK1 (enriched for PDGFRA amplifications), pHGG RTK2 (enriched for EGFR amplifications and TERT promoter mutations), and pHGG MYCN (enriched for MYCN amplifications).
Reference Gallery:
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Axial T1-weighted MRI demonstrating a well-circumscribed lesion in the left insular/temporal region with relatively homogeneous contrast enhancement and central cystic changes.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. The tumour is highly cellular, reminiscent of embryonal morphology, and it shows areas of sharp demarcation from the brain tissue.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. In addition to having glial areas, the tumour may show a prominent embryonal appearance.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. GFAP may be expressed only in scattered cells.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Neuronal markers (here, neurofilament) may also be expressed.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, RTK1 subtype, in Lynch syndrome. This glial tumour of a 10-year-old child shows numerous pleomorphic giant cells. Genetic analysis revealed a germline MSH2 mutation and a high tumour mutation burden. Methylation profiling indicated the RTK1 subtype. Immunohistochemistry showed MSH2/MSH6 loss in tumour cells, and retention in normal cells, compatible with Lynch syndrome.
Radiation-induced diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, RTK1 subtype. In areas, the tumour may show extensive myxoid change.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Copy-number profile calculated from DNA methylation data, showing a MYCN amplification among other changes. Note that the adult-type +7/−10 chromosomal pattern is not present.

Q: DNA methylation profiling is crucial to classify Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype into distinct molecular subgroups, which include the RTK1, RTK2, and [...] subtypes.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Copy-number profile calculated from DNA methylation data, showing a MYCN amplification among other changes. Note that the adult-type +7/−10 chromosomal pattern is not present.
A: MYCN
Back Extra: Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
- Clinical: Patients with diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, may develop clinical symptoms such as seizures, motor or sensory deficits, and MRI typically reveals a contrast-enhancing tumour with mass effect.
- Micro: Histopathology of diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, shows features of either a glioblastoma-like malignant tumour or a primitive, undifferentiated morphology, often with areas of glial and primitive differentiation.
- Ancillary: DNA methylation profiling is crucial for identifying molecular subgroups, including pHGG RTK1 (enriched for PDGFRA amplifications), pHGG RTK2 (enriched for EGFR amplifications and TERT promoter mutations), and pHGG MYCN (enriched for MYCN amplifications).
Reference Gallery:
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Axial T1-weighted MRI demonstrating a well-circumscribed lesion in the left insular/temporal region with relatively homogeneous contrast enhancement and central cystic changes.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. The tumour is highly cellular, reminiscent of embryonal morphology, and it shows areas of sharp demarcation from the brain tissue.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. In addition to having glial areas, the tumour may show a prominent embryonal appearance.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. GFAP may be expressed only in scattered cells.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Neuronal markers (here, neurofilament) may also be expressed.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, RTK1 subtype, in Lynch syndrome. This glial tumour of a 10-year-old child shows numerous pleomorphic giant cells. Genetic analysis revealed a germline MSH2 mutation and a high tumour mutation burden. Methylation profiling indicated the RTK1 subtype. Immunohistochemistry showed MSH2/MSH6 loss in tumour cells, and retention in normal cells, compatible with Lynch syndrome.
Radiation-induced diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, RTK1 subtype. In areas, the tumour may show extensive myxoid change.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Copy-number profile calculated from DNA methylation data, showing a MYCN amplification among other changes. Note that the adult-type +7/−10 chromosomal pattern is not present.

Q: In the highly cellular, primitive components of Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, immunohistochemical staining for the typical glial marker [...] may only be expressed in scattered cells, while neuronal markers like neurofilament can also be positive.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. GFAP may be expressed only in scattered cells.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Neuronal markers (here, neurofilament) may also be expressed.
A: GFAP
Back Extra: Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype
- Clinical: Patients with diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, may develop clinical symptoms such as seizures, motor or sensory deficits, and MRI typically reveals a contrast-enhancing tumour with mass effect.
- Micro: Histopathology of diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, shows features of either a glioblastoma-like malignant tumour or a primitive, undifferentiated morphology, often with areas of glial and primitive differentiation.
- Ancillary: DNA methylation profiling is crucial for identifying molecular subgroups, including pHGG RTK1 (enriched for PDGFRA amplifications), pHGG RTK2 (enriched for EGFR amplifications and TERT promoter mutations), and pHGG MYCN (enriched for MYCN amplifications).
Reference Gallery:
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Axial T1-weighted MRI demonstrating a well-circumscribed lesion in the left insular/temporal region with relatively homogeneous contrast enhancement and central cystic changes.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. The tumour is highly cellular, reminiscent of embryonal morphology, and it shows areas of sharp demarcation from the brain tissue.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. In addition to having glial areas, the tumour may show a prominent embryonal appearance.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. GFAP may be expressed only in scattered cells.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Neuronal markers (here, neurofilament) may also be expressed.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, RTK1 subtype, in Lynch syndrome. This glial tumour of a 10-year-old child shows numerous pleomorphic giant cells. Genetic analysis revealed a germline MSH2 mutation and a high tumour mutation burden. Methylation profiling indicated the RTK1 subtype. Immunohistochemistry showed MSH2/MSH6 loss in tumour cells, and retention in normal cells, compatible with Lynch syndrome.
Radiation-induced diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, RTK1 subtype. In areas, the tumour may show extensive myxoid change.
Diffuse paediatric-type high-grade glioma, H3-wildtype and IDH-wildtype, MYCN subtype. Copy-number profile calculated from DNA methylation data, showing a MYCN amplification among other changes. Note that the adult-type +7/−10 chromosomal pattern is not present.

Q: The definitive diagnosis of High-grade astrocytoma with piloid features relies on [...], which identifies the tumor as a distinct molecular group.
High-grade astrocytoma with piloid features (HGAP) is defined by a specific DNA methylation profile. t-distributed stochastic neighbour embedding (t-SNE) of DNA methylation data of HGAP and several relevant differential diagnoses. HGAP forms a distinct molecular group. Data combined from {29539639} and {29564591}. MES, mesenchymal; PXA, pleomorphic xanthoastrocytoma; RTK, receptor tyrosine kinase.
A: DNA methylation profiling
Back Extra: High-grade astrocytoma with piloid features
- Clinical: High-grade astrocytoma with piloid features (HGAP) is rare, accounting for about 1–3% of brain tumours, with a median age of 40 years and a balanced M:F ratio.
- Micro: HGAP can have a wide range of morphologies, including piloid, glioblastoma-like, and pleomorphic xanthoastrocytoma-like features, with frequent vascular alterations and necrosis.
- Ancillary: Definitive diagnosis of HGAP relies on DNA methylation profiling, which shows a distinct molecular group. Common genetic alterations include homozygous deletion of CDKN2A/B and mutations in ATRX.
Reference Gallery:
High-grade astrocytoma with piloid features. T2-weighted MRI shows a hyperintense lesion without sharp tumour margins in the dorsal pons and right cerebellar peduncle.
High-grade astrocytoma with piloid features. FET PET indicates highly increased amino acid metabolism in the tumour.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 40% of cases have a mainly piloid morphology, sometimes with numerous Rosenthal fibres.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 45% of cases show a mainly glioblastoma-like morphology.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 10% of cases have features reminiscent of pleomorphic xanthoastrocytoma.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. Tumours may rarely resemble epithelioid glioblastoma.
High-grade astrocytoma with piloid features. Sparse infiltration of cerebellar white matter. Note the single pleomorphic cells.
High-grade astrocytoma with piloid features. Diffuse infiltration of the tumour into the pons, with residual pigmented neurons of the locus coeruleus.
Infiltration patterns of HGAP. ATRX immunohistochemistry of same case as in (C) with nuclear ATRX loss in tumour cells but retained staining in preexistent cells.
High-grade astrocytoma with piloid features (HGAP) is defined by a specific DNA methylation profile. t-distributed stochastic neighbour embedding (t-SNE) of DNA methylation data of HGAP and several relevant differential diagnoses. HGAP forms a distinct molecular group. Data combined from {29539639} and {29564591}. MES, mesenchymal; PXA, pleomorphic xanthoastrocytoma; RTK, receptor tyrosine kinase.
High-grade astrocytoma with piloid features. The DNA copy-number profile of this case shows, among other changes, several chromosomal alterations that recurrently occur in this tumour type: homozygous deletion of CDKN2A and/or CDKN2B (observed in close to 80%), partial gain of 12q and 17q (each in ∼30%), and 1p loss (in ∼20%).

Q: Ancillary testing for High-grade astrocytoma with piloid features frequently reveals mutations in ATRX (with corresponding loss of nuclear staining) and a recurrent homozygous deletion of [...].
Infiltration patterns of HGAP. ATRX immunohistochemistry of same case as in (C) with nuclear ATRX loss in tumour cells but retained staining in preexistent cells.
High-grade astrocytoma with piloid features. The DNA copy-number profile of this case shows, among other changes, several chromosomal alterations that recurrently occur in this tumour type: homozygous deletion of CDKN2A and/or CDKN2B (observed in close to 80%), partial gain of 12q and 17q (each in ∼30%), and 1p loss (in ∼20%).
A: CDKN2A/B
Back Extra: High-grade astrocytoma with piloid features
- Clinical: High-grade astrocytoma with piloid features (HGAP) is rare, accounting for about 1–3% of brain tumours, with a median age of 40 years and a balanced M:F ratio.
- Micro: HGAP can have a wide range of morphologies, including piloid, glioblastoma-like, and pleomorphic xanthoastrocytoma-like features, with frequent vascular alterations and necrosis.
- Ancillary: Definitive diagnosis of HGAP relies on DNA methylation profiling, which shows a distinct molecular group. Common genetic alterations include homozygous deletion of CDKN2A/B and mutations in ATRX.
Reference Gallery:
High-grade astrocytoma with piloid features. T2-weighted MRI shows a hyperintense lesion without sharp tumour margins in the dorsal pons and right cerebellar peduncle.
High-grade astrocytoma with piloid features. FET PET indicates highly increased amino acid metabolism in the tumour.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 40% of cases have a mainly piloid morphology, sometimes with numerous Rosenthal fibres.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 45% of cases show a mainly glioblastoma-like morphology.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 10% of cases have features reminiscent of pleomorphic xanthoastrocytoma.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. Tumours may rarely resemble epithelioid glioblastoma.
High-grade astrocytoma with piloid features. Sparse infiltration of cerebellar white matter. Note the single pleomorphic cells.
High-grade astrocytoma with piloid features. Diffuse infiltration of the tumour into the pons, with residual pigmented neurons of the locus coeruleus.
Infiltration patterns of HGAP. ATRX immunohistochemistry of same case as in (C) with nuclear ATRX loss in tumour cells but retained staining in preexistent cells.
High-grade astrocytoma with piloid features (HGAP) is defined by a specific DNA methylation profile. t-distributed stochastic neighbour embedding (t-SNE) of DNA methylation data of HGAP and several relevant differential diagnoses. HGAP forms a distinct molecular group. Data combined from {29539639} and {29564591}. MES, mesenchymal; PXA, pleomorphic xanthoastrocytoma; RTK, receptor tyrosine kinase.
High-grade astrocytoma with piloid features. The DNA copy-number profile of this case shows, among other changes, several chromosomal alterations that recurrently occur in this tumour type: homozygous deletion of CDKN2A and/or CDKN2B (observed in close to 80%), partial gain of 12q and 17q (each in ∼30%), and 1p loss (in ∼20%).

Q: Although High-grade astrocytoma with piloid features can exhibit a wide range of morphologies, approximately 40% of cases show a predominantly piloid pattern that may contain numerous eosinophilic structures known as [...].
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 40% of cases have a mainly piloid morphology, sometimes with numerous Rosenthal fibres.
A: Rosenthal fibers
Back Extra: High-grade astrocytoma with piloid features
- Clinical: High-grade astrocytoma with piloid features (HGAP) is rare, accounting for about 1–3% of brain tumours, with a median age of 40 years and a balanced M:F ratio.
- Micro: HGAP can have a wide range of morphologies, including piloid, glioblastoma-like, and pleomorphic xanthoastrocytoma-like features, with frequent vascular alterations and necrosis.
- Ancillary: Definitive diagnosis of HGAP relies on DNA methylation profiling, which shows a distinct molecular group. Common genetic alterations include homozygous deletion of CDKN2A/B and mutations in ATRX.
Reference Gallery:
High-grade astrocytoma with piloid features. T2-weighted MRI shows a hyperintense lesion without sharp tumour margins in the dorsal pons and right cerebellar peduncle.
High-grade astrocytoma with piloid features. FET PET indicates highly increased amino acid metabolism in the tumour.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 40% of cases have a mainly piloid morphology, sometimes with numerous Rosenthal fibres.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 45% of cases show a mainly glioblastoma-like morphology.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. About 10% of cases have features reminiscent of pleomorphic xanthoastrocytoma.
High-grade astrocytoma with piloid features. This tumour type has a wide range of morphologies. Tumours may rarely resemble epithelioid glioblastoma.
High-grade astrocytoma with piloid features. Sparse infiltration of cerebellar white matter. Note the single pleomorphic cells.
High-grade astrocytoma with piloid features. Diffuse infiltration of the tumour into the pons, with residual pigmented neurons of the locus coeruleus.
Infiltration patterns of HGAP. ATRX immunohistochemistry of same case as in (C) with nuclear ATRX loss in tumour cells but retained staining in preexistent cells.
High-grade astrocytoma with piloid features (HGAP) is defined by a specific DNA methylation profile. t-distributed stochastic neighbour embedding (t-SNE) of DNA methylation data of HGAP and several relevant differential diagnoses. HGAP forms a distinct molecular group. Data combined from {29539639} and {29564591}. MES, mesenchymal; PXA, pleomorphic xanthoastrocytoma; RTK, receptor tyrosine kinase.
High-grade astrocytoma with piloid features. The DNA copy-number profile of this case shows, among other changes, several chromosomal alterations that recurrently occur in this tumour type: homozygous deletion of CDKN2A and/or CDKN2B (observed in close to 80%), partial gain of 12q and 17q (each in ∼30%), and 1p loss (in ∼20%).

Q: A cellular, high-grade appearing brain tumor demonstrating palisading necrosis and microvascular proliferation in a 3-month-old, which often harbors an ALK or MET fusion, is characteristic of an [...].
Infant-type hemispheric glioma. An infant-type hemispheric glioma showing classic features of a high-grade glioma including palisading necrosis and endothelial proliferation.
Infant-type hemispheric glioma. An infant-type hemispheric glioma with a CLIP2::MET fusion showing a cellular glioma with several clusters of more primitive-appearing cells.
A: Infant-Type Hemispheric Glioma
Back Extra: Infant-Type Hemispheric Glioma
- Clinical: Infant-type hemispheric glioma presents acutely in early childhood, often with nonspecific signs like agitation, lethargy, and a large head circumference. Median age at presentation is 2.8 months.
- Micro: The tumor is typically cellular, well-demarcated, and may show palisading necrosis, mitotic activity, and microvascular proliferation. Some cases may have a biphasic appearance with low-grade and high-grade components.
- Ancillary: Immunohistochemistry shows immunoreactivity for GFAP. RTK fusions (NTRK, ALK, ROS1, MET) are present in 60-80% of cases, and methylation array profiling can help establish the diagnosis.
Reference Gallery:
Infant-type hemispheric glioma. An infant-type hemispheric glioma showing classic features of a high-grade glioma including palisading necrosis and endothelial proliferation.
Infant-type hemispheric glioma. An infant-type hemispheric glioma with a CLIP2::MET fusion showing a cellular glioma with several clusters of more primitive-appearing cells.
Infant-type hemispheric glioma. GFAP immunostaining.
Infant-type hemispheric glioma. OLIG2 immunostaining.
Infant-type hemispheric glioma. Immunostaining showing elevated Ki-67 (MIB1) proliferation index.

Q: The pathogenesis of Infant-Type Hemispheric Glioma is most frequently driven by molecular fusions involving [...], such as NTRK, ALK, ROS1, or MET.
Infant-type hemispheric glioma. An infant-type hemispheric glioma with a CLIP2::MET fusion showing a cellular glioma with several clusters of more primitive-appearing cells.
A: receptor tyrosine kinases (RTKs)
Back Extra: Infant-Type Hemispheric Glioma
- Clinical: Infant-type hemispheric glioma presents acutely in early childhood, often with nonspecific signs like agitation, lethargy, and a large head circumference. Median age at presentation is 2.8 months.
- Micro: The tumor is typically cellular, well-demarcated, and may show palisading necrosis, mitotic activity, and microvascular proliferation. Some cases may have a biphasic appearance with low-grade and high-grade components.
- Ancillary: Immunohistochemistry shows immunoreactivity for GFAP. RTK fusions (NTRK, ALK, ROS1, MET) are present in 60-80% of cases, and methylation array profiling can help establish the diagnosis.
Reference Gallery:
Infant-type hemispheric glioma. An infant-type hemispheric glioma showing classic features of a high-grade glioma including palisading necrosis and endothelial proliferation.
Infant-type hemispheric glioma. An infant-type hemispheric glioma with a CLIP2::MET fusion showing a cellular glioma with several clusters of more primitive-appearing cells.
Infant-type hemispheric glioma. GFAP immunostaining.
Infant-type hemispheric glioma. OLIG2 immunostaining.
Infant-type hemispheric glioma. Immunostaining showing elevated Ki-67 (MIB1) proliferation index.

Q: Immunohistochemical evaluation of an Infant-Type Hemispheric Glioma typically demonstrates diffuse positivity for the glial marker [...], often accompanied by an elevated Ki-67 proliferation index.
Infant-type hemispheric glioma. GFAP immunostaining.
Infant-type hemispheric glioma. Immunostaining showing elevated Ki-67 (MIB1) proliferation index.
A: GFAP
Back Extra: Infant-Type Hemispheric Glioma
- Clinical: Infant-type hemispheric glioma presents acutely in early childhood, often with nonspecific signs like agitation, lethargy, and a large head circumference. Median age at presentation is 2.8 months.
- Micro: The tumor is typically cellular, well-demarcated, and may show palisading necrosis, mitotic activity, and microvascular proliferation. Some cases may have a biphasic appearance with low-grade and high-grade components.
- Ancillary: Immunohistochemistry shows immunoreactivity for GFAP. RTK fusions (NTRK, ALK, ROS1, MET) are present in 60-80% of cases, and methylation array profiling can help establish the diagnosis.
Reference Gallery:
Infant-type hemispheric glioma. An infant-type hemispheric glioma showing classic features of a high-grade glioma including palisading necrosis and endothelial proliferation.
Infant-type hemispheric glioma. An infant-type hemispheric glioma with a CLIP2::MET fusion showing a cellular glioma with several clusters of more primitive-appearing cells.
Infant-type hemispheric glioma. GFAP immunostaining.
Infant-type hemispheric glioma. OLIG2 immunostaining.
Infant-type hemispheric glioma. Immunostaining showing elevated Ki-67 (MIB1) proliferation index.

Q: Histologically, Pilocytic Astrocytoma exhibits a biphasic architecture with alternating compact and loose regions, eosinophilic granular bodies, and brightly eosinophilic, corkscrew-shaped [...].
Pilocytic astrocytoma. Typical biphasic appearance of pilocytic astrocytoma. Compact areas that often harbour Rosenthal fibres alternate with loose and somewhat myxoid regions.
Pilocytic astrocytoma. Rosenthal fibres and eosinophilic granular bodies. Typically, Rosenthal fibres are more abundant than eosinophilic granular bodies in pilocytic astrocytomas, but both can be observed, as in this case.
A: Rosenthal fibers
Back Extra: Pilocytic Astrocytoma
- Clinical: Pilocytic astrocytomas often present with symptoms due to mass effect, such as headache, increased intracranial pressure, and visual loss.
- Micro: Histologically, pilocytic astrocytomas show a biphasic pattern with compact and loose regions, Rosenthal fibres, and eosinophilic granular bodies.
- Ancillary: Immunohistochemistry demonstrates strong and diffuse positivity for GFAP, S100, and OLIG2, and most tumours show a KIAA1549::BRAF gene fusion.
Reference Gallery:
Pilocytic astrocytoma. Typical biphasic appearance of pilocytic astrocytoma. Compact areas that often harbour Rosenthal fibres alternate with loose and somewhat myxoid regions.
Pilocytic astrocytoma. Infiltrative edge. In many pilocytic astrocytomas, infiltrative-appearing regions can be recognized. In small biopsies, these areas may evoke the impression of a diffuse astrocytoma.
Pilocytic astrocytoma. Hyaline vessels and Rosenthal fibres. In most pilocytic astrocytomas, vascular structures within the tumour demonstrate brisk hyalinization. Numerous Rosenthal fibres are also observed.
Pilocytic astrocytoma. Rosenthal fibres and eosinophilic granular bodies. Typically, Rosenthal fibres are more abundant than eosinophilic granular bodies in pilocytic astrocytomas, but both can be observed, as in this case.
Pilocytic astrocytoma. Typical MRI appearance of pilocytic astrocytoma in the posterior fossa of a 5-year-old boy, showing a large cystic lesion with an enhancing mural nodule. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion. A T2-weighted image. B Contrast-enhanced T1-weighted image.
Pilocytic astrocytoma. Pilocytic astrocytomas often harbour large cells with multiple nuclei (the pennies-on-a-plate appearance).
Pilocytic astrocytoma. Pilocytic astrocytomas typically show strong and diffusely positive GFAP staining.
Pilocytic astrocytoma with anaplastic features. Region of classic pilocytic astrocytoma with numerous Rosenthal fibres.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features, including increased cellularity and palisading necrosis.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features including increased mitotic activity.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features including increased Ki-67 labelling index.
Pilomyxoid astrocytoma. Pilomyxoid astrocytoma in a 10-month-old boy, located in the hypothalamic region. The typical angiocentric and markedly myxoid pattern is seen throughout the tumour. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion.

Q: On neuroimaging, a classic Pilocytic Astrocytoma in the posterior fossa typically presents as a large cystic lesion containing an intensely enhancing [...].
Pilocytic astrocytoma. Typical MRI appearance of pilocytic astrocytoma in the posterior fossa of a 5-year-old boy, showing a large cystic lesion with an enhancing mural nodule. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion. A T2-weighted image. B Contrast-enhanced T1-weighted image.
A: mural nodule
Back Extra: Pilocytic Astrocytoma
- Clinical: Pilocytic astrocytomas often present with symptoms due to mass effect, such as headache, increased intracranial pressure, and visual loss.
- Micro: Histologically, pilocytic astrocytomas show a biphasic pattern with compact and loose regions, Rosenthal fibres, and eosinophilic granular bodies.
- Ancillary: Immunohistochemistry demonstrates strong and diffuse positivity for GFAP, S100, and OLIG2, and most tumours show a KIAA1549::BRAF gene fusion.
Reference Gallery:
Pilocytic astrocytoma. Typical biphasic appearance of pilocytic astrocytoma. Compact areas that often harbour Rosenthal fibres alternate with loose and somewhat myxoid regions.
Pilocytic astrocytoma. Infiltrative edge. In many pilocytic astrocytomas, infiltrative-appearing regions can be recognized. In small biopsies, these areas may evoke the impression of a diffuse astrocytoma.
Pilocytic astrocytoma. Hyaline vessels and Rosenthal fibres. In most pilocytic astrocytomas, vascular structures within the tumour demonstrate brisk hyalinization. Numerous Rosenthal fibres are also observed.
Pilocytic astrocytoma. Rosenthal fibres and eosinophilic granular bodies. Typically, Rosenthal fibres are more abundant than eosinophilic granular bodies in pilocytic astrocytomas, but both can be observed, as in this case.
Pilocytic astrocytoma. Typical MRI appearance of pilocytic astrocytoma in the posterior fossa of a 5-year-old boy, showing a large cystic lesion with an enhancing mural nodule. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion. A T2-weighted image. B Contrast-enhanced T1-weighted image.
Pilocytic astrocytoma. Pilocytic astrocytomas often harbour large cells with multiple nuclei (the pennies-on-a-plate appearance).
Pilocytic astrocytoma. Pilocytic astrocytomas typically show strong and diffusely positive GFAP staining.
Pilocytic astrocytoma with anaplastic features. Region of classic pilocytic astrocytoma with numerous Rosenthal fibres.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features, including increased cellularity and palisading necrosis.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features including increased mitotic activity.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features including increased Ki-67 labelling index.
Pilomyxoid astrocytoma. Pilomyxoid astrocytoma in a 10-month-old boy, located in the hypothalamic region. The typical angiocentric and markedly myxoid pattern is seen throughout the tumour. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion.

Q: The characteristic molecular driver identified in the vast majority of Pilocytic Astrocytoma cases is the [BRAF] gene fusion.
Pilocytic astrocytoma. Typical MRI appearance of pilocytic astrocytoma in the posterior fossa of a 5-year-old boy, showing a large cystic lesion with an enhancing mural nodule. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion. A T2-weighted image. B Contrast-enhanced T1-weighted image.
Pilomyxoid astrocytoma. Pilomyxoid astrocytoma in a 10-month-old boy, located in the hypothalamic region. The typical angiocentric and markedly myxoid pattern is seen throughout the tumour. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion.
A: KIAA1549
Back Extra: Pilocytic Astrocytoma
- Clinical: Pilocytic astrocytomas often present with symptoms due to mass effect, such as headache, increased intracranial pressure, and visual loss.
- Micro: Histologically, pilocytic astrocytomas show a biphasic pattern with compact and loose regions, Rosenthal fibres, and eosinophilic granular bodies.
- Ancillary: Immunohistochemistry demonstrates strong and diffuse positivity for GFAP, S100, and OLIG2, and most tumours show a KIAA1549::BRAF gene fusion.
Reference Gallery:
Pilocytic astrocytoma. Typical biphasic appearance of pilocytic astrocytoma. Compact areas that often harbour Rosenthal fibres alternate with loose and somewhat myxoid regions.
Pilocytic astrocytoma. Infiltrative edge. In many pilocytic astrocytomas, infiltrative-appearing regions can be recognized. In small biopsies, these areas may evoke the impression of a diffuse astrocytoma.
Pilocytic astrocytoma. Hyaline vessels and Rosenthal fibres. In most pilocytic astrocytomas, vascular structures within the tumour demonstrate brisk hyalinization. Numerous Rosenthal fibres are also observed.
Pilocytic astrocytoma. Rosenthal fibres and eosinophilic granular bodies. Typically, Rosenthal fibres are more abundant than eosinophilic granular bodies in pilocytic astrocytomas, but both can be observed, as in this case.
Pilocytic astrocytoma. Typical MRI appearance of pilocytic astrocytoma in the posterior fossa of a 5-year-old boy, showing a large cystic lesion with an enhancing mural nodule. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion. A T2-weighted image. B Contrast-enhanced T1-weighted image.
Pilocytic astrocytoma. Pilocytic astrocytomas often harbour large cells with multiple nuclei (the pennies-on-a-plate appearance).
Pilocytic astrocytoma. Pilocytic astrocytomas typically show strong and diffusely positive GFAP staining.
Pilocytic astrocytoma with anaplastic features. Region of classic pilocytic astrocytoma with numerous Rosenthal fibres.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features, including increased cellularity and palisading necrosis.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features including increased mitotic activity.
Pilocytic astrocytoma with anaplastic features. Region of tumour with anaplastic features including increased Ki-67 labelling index.
Pilomyxoid astrocytoma. Pilomyxoid astrocytoma in a 10-month-old boy, located in the hypothalamic region. The typical angiocentric and markedly myxoid pattern is seen throughout the tumour. The tumour has BRAF kinase domain duplication with KIAA1549::BRAF gene fusion.

Q: Histologically, Pleomorphic Xanthoastrocytoma is a solid, non-infiltrative tumor characterized by marked cellular pleomorphism, perivascular lymphocytic cuffing, prominent eosinophilic granular bodies, and characteristic lipidized ([...]) cells.
Pleomorphic xanthoastrocytoma, classic histology. Perivascular lymphocytic cuffing is common.
Pleomorphic xanthoastrocytoma, classic histology. Tumour cells show marked cytoplasmic and nuclear pleomorphism with frequent intensely eosinophilic granular bodies (arrow).
Pleomorphic xanthoastrocytoma, classic histology. There are frequent pale granular bodies (arrow) and cytoplasmic vacuolation with xanthomatous cells.
A: xanthomatous
Back Extra: Pleomorphic Xanthoastrocytoma
- Clinical: Many patients with Pleomorphic Xanthoastrocytoma (PXA) present with a long history of seizures. Tumours are usually peripherally located and frequently cystic, often involving the cerebral cortex and overlying leptomeninges.
- Micro: PXA demonstrates a mostly solid, non-infiltrative growth pattern with marked cellular pleomorphism and eosinophilic granular bodies. Tumours often show perivascular lymphocytic cuffing and can have areas of lipidized (xanthomatous) cells.
- Ancillary: PXAs typically express GFAP and S100, and about 60-80% harbour a BRAF p.V600E mutation. Homozygous deletion of CDKN2A and/or CDKN2B is common.
Reference Gallery:
Pleomorphic xanthoastrocytoma. Chromosomal microarray. Typical copy-number profile, demonstrating copy-neutral loss of heterozygosity of chromosome 9 with homozygous deletion of CDKN2A and/or CDKN2B. Additional whole-chromosome gains were present, including gains of chromosomes 4, 14, and 21 (three copies) and chromosome 7 (four copies).
Pleomorphic xanthoastrocytoma. T1-weighted postcontrast MRI of a CNS WHO grade 2 tumour forming a right temporal superficial enhancing nodule with a small cystic component and scalloping of the bone.
Pleomorphic xanthoastrocytoma. T1-weighted postcontrast MRI of a CNS WHO grade 3 tumour forming a large, heterogeneously enhancing tumour with moderate surrounding oedema mass effect.
Pleomorphic xanthoastrocytoma, classic histology. Pleomorphic xanthoastrocytoma is a cellular tumour with marked cellular pleomorphism that is apparent even at low power.
Pleomorphic xanthoastrocytoma, classic histology. Perivascular lymphocytic cuffing is common.
Pleomorphic xanthoastrocytoma, classic histology. Tumour cells show marked cytoplasmic and nuclear pleomorphism with frequent intensely eosinophilic granular bodies (arrow).
Pleomorphic xanthoastrocytoma, classic histology. There are frequent pale granular bodies (arrow) and cytoplasmic vacuolation with xanthomatous cells.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with relative monomorphism.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with only rare eosinophilic granular bodies.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with large pleomorphic cells.
Pleomorphic xanthoastrocytoma. CNS WHO grade 3. This tumour shows classic features, with pleomorphic and xanthomatous cells and brisk mitotic activity (arrows).
Pleomorphic xanthoastrocytoma. CNS WHO grade 3. This tumour shows classic features, with pleomorphic and xanthomatous cells and brisk mitotic activity.

Q: Molecular profiling of Pleomorphic Xanthoastrocytoma frequently reveals a BRAF p.V600E mutation (60-80% of cases) alongside copy-neutral loss of heterozygosity of chromosome 9 with homozygous deletion of [...].
Pleomorphic xanthoastrocytoma. Chromosomal microarray. Typical copy-number profile, demonstrating copy-neutral loss of heterozygosity of chromosome 9 with homozygous deletion of CDKN2A and/or CDKN2B. Additional whole-chromosome gains were present, including gains of chromosomes 4, 14, and 21 (three copies) and chromosome 7 (four copies).
A: CDKN2A and/or CDKN2B
Back Extra: Pleomorphic Xanthoastrocytoma
- Clinical: Many patients with Pleomorphic Xanthoastrocytoma (PXA) present with a long history of seizures. Tumours are usually peripherally located and frequently cystic, often involving the cerebral cortex and overlying leptomeninges.
- Micro: PXA demonstrates a mostly solid, non-infiltrative growth pattern with marked cellular pleomorphism and eosinophilic granular bodies. Tumours often show perivascular lymphocytic cuffing and can have areas of lipidized (xanthomatous) cells.
- Ancillary: PXAs typically express GFAP and S100, and about 60-80% harbour a BRAF p.V600E mutation. Homozygous deletion of CDKN2A and/or CDKN2B is common.
Reference Gallery:
Pleomorphic xanthoastrocytoma. Chromosomal microarray. Typical copy-number profile, demonstrating copy-neutral loss of heterozygosity of chromosome 9 with homozygous deletion of CDKN2A and/or CDKN2B. Additional whole-chromosome gains were present, including gains of chromosomes 4, 14, and 21 (three copies) and chromosome 7 (four copies).
Pleomorphic xanthoastrocytoma. T1-weighted postcontrast MRI of a CNS WHO grade 2 tumour forming a right temporal superficial enhancing nodule with a small cystic component and scalloping of the bone.
Pleomorphic xanthoastrocytoma. T1-weighted postcontrast MRI of a CNS WHO grade 3 tumour forming a large, heterogeneously enhancing tumour with moderate surrounding oedema mass effect.
Pleomorphic xanthoastrocytoma, classic histology. Pleomorphic xanthoastrocytoma is a cellular tumour with marked cellular pleomorphism that is apparent even at low power.
Pleomorphic xanthoastrocytoma, classic histology. Perivascular lymphocytic cuffing is common.
Pleomorphic xanthoastrocytoma, classic histology. Tumour cells show marked cytoplasmic and nuclear pleomorphism with frequent intensely eosinophilic granular bodies (arrow).
Pleomorphic xanthoastrocytoma, classic histology. There are frequent pale granular bodies (arrow) and cytoplasmic vacuolation with xanthomatous cells.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with relative monomorphism.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with only rare eosinophilic granular bodies.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with large pleomorphic cells.
Pleomorphic xanthoastrocytoma. CNS WHO grade 3. This tumour shows classic features, with pleomorphic and xanthomatous cells and brisk mitotic activity (arrows).
Pleomorphic xanthoastrocytoma. CNS WHO grade 3. This tumour shows classic features, with pleomorphic and xanthomatous cells and brisk mitotic activity.

Q: Radiographically, Pleomorphic Xanthoastrocytoma typically presents in patients with a long history of seizures as a superficial, peripherally located cortical tumor that frequently features a [...] component with an enhancing nodule and overlying bone scalloping.
Pleomorphic xanthoastrocytoma. T1-weighted postcontrast MRI of a CNS WHO grade 2 tumour forming a right temporal superficial enhancing nodule with a small cystic component and scalloping of the bone.
A: cystic
Back Extra: Pleomorphic Xanthoastrocytoma
- Clinical: Many patients with Pleomorphic Xanthoastrocytoma (PXA) present with a long history of seizures. Tumours are usually peripherally located and frequently cystic, often involving the cerebral cortex and overlying leptomeninges.
- Micro: PXA demonstrates a mostly solid, non-infiltrative growth pattern with marked cellular pleomorphism and eosinophilic granular bodies. Tumours often show perivascular lymphocytic cuffing and can have areas of lipidized (xanthomatous) cells.
- Ancillary: PXAs typically express GFAP and S100, and about 60-80% harbour a BRAF p.V600E mutation. Homozygous deletion of CDKN2A and/or CDKN2B is common.
Reference Gallery:
Pleomorphic xanthoastrocytoma. Chromosomal microarray. Typical copy-number profile, demonstrating copy-neutral loss of heterozygosity of chromosome 9 with homozygous deletion of CDKN2A and/or CDKN2B. Additional whole-chromosome gains were present, including gains of chromosomes 4, 14, and 21 (three copies) and chromosome 7 (four copies).
Pleomorphic xanthoastrocytoma. T1-weighted postcontrast MRI of a CNS WHO grade 2 tumour forming a right temporal superficial enhancing nodule with a small cystic component and scalloping of the bone.
Pleomorphic xanthoastrocytoma. T1-weighted postcontrast MRI of a CNS WHO grade 3 tumour forming a large, heterogeneously enhancing tumour with moderate surrounding oedema mass effect.
Pleomorphic xanthoastrocytoma, classic histology. Pleomorphic xanthoastrocytoma is a cellular tumour with marked cellular pleomorphism that is apparent even at low power.
Pleomorphic xanthoastrocytoma, classic histology. Perivascular lymphocytic cuffing is common.
Pleomorphic xanthoastrocytoma, classic histology. Tumour cells show marked cytoplasmic and nuclear pleomorphism with frequent intensely eosinophilic granular bodies (arrow).
Pleomorphic xanthoastrocytoma, classic histology. There are frequent pale granular bodies (arrow) and cytoplasmic vacuolation with xanthomatous cells.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with relative monomorphism.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with only rare eosinophilic granular bodies.
Pleomorphic xanthoastrocytoma, spindle cell histology. Some tumours have a predominant cellular and spindle appearance with large pleomorphic cells.
Pleomorphic xanthoastrocytoma. CNS WHO grade 3. This tumour shows classic features, with pleomorphic and xanthomatous cells and brisk mitotic activity (arrows).
Pleomorphic xanthoastrocytoma. CNS WHO grade 3. This tumour shows classic features, with pleomorphic and xanthomatous cells and brisk mitotic activity.

Q: Histologically, Polymorphous Low-Grade Neuroepithelial Tumor of the Young typically exhibits conspicuous calcifications alongside [...]-like features, characterized by small round nuclei with perinuclear halos and delicate branching capillaries.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. A diffuse growth pattern and conspicuous calcification are seen.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Oligodendroglioma-like features include small round nuclei, perinuclear haloes, and delicate branching capillaries.
A: oligodendroglioma
Q: Polymorphous Low-Grade Neuroepithelial Tumor of the Young
- Clinical: Polymorphous low-grade neuroepithelial tumour of the young (PLNTY) typically causes [...] and is associated with [...].
- Micro: PLNTYs exhibit oligodendroglioma-like features with small round nuclei, perinuclear haloes, and delicate branching capillaries, as well as calcifications and astroglial elements.
- Ancillary: PLNTYs are consistently associated with [...], including BRAF p.V600E mutations and FGFR2/3 fusions.
Reference Gallery:
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. FLAIR-hyperintense solid components, cystic changes, and the absence of mass effect are seen in this MRI.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. A diffuse growth pattern and conspicuous calcification are seen.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Oligodendroglioma-like features include small round nuclei, perinuclear haloes, and delicate branching capillaries.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Mild nuclear pleomorphism and membrane irregularities are common.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Astroglial elements here exhibit spindling and more conspicuous atypia without mitotic activity.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Intense regional immunoreactivity of the tumour matrix for CD34 is seen in the lower half of this field.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Ramified, CD34-immunoreactive neural elements are present in associated cerebral cortex.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Coronal FLAIR MRI. The tumour is heterogeneously T2-hyperintense at the subcortical region of the right temporal lobe, without significant vasogenic oedema.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Axial contrast-enhanced T1-weighted MRI. The tumour shows heterogeneous enhancement, which is mainly at the centre of the lesion while the periphery is unenhanced – suggestive of a cystic component.
A: seizures; refractory epilepsy; MAPK pathway-activating abnormalities

Q: A highly characteristic immunohistochemical finding in Polymorphous Low-Grade Neuroepithelial Tumor of the Young is intense, regional expression of [...] within the tumor matrix and ramified cortical neural elements.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Intense regional immunoreactivity of the tumour matrix for CD34 is seen in the lower half of this field.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Ramified, CD34-immunoreactive neural elements are present in associated cerebral cortex.
A: CD34
Q: Polymorphous Low-Grade Neuroepithelial Tumor of the Young
- Clinical: Polymorphous low-grade neuroepithelial tumour of the young (PLNTY) typically causes [...] and is associated with [...].
- Micro: PLNTYs exhibit oligodendroglioma-like features with small round nuclei, perinuclear haloes, and delicate branching capillaries, as well as calcifications and astroglial elements.
- Ancillary: PLNTYs are consistently associated with [...], including BRAF p.V600E mutations and FGFR2/3 fusions.
Reference Gallery:
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. FLAIR-hyperintense solid components, cystic changes, and the absence of mass effect are seen in this MRI.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. A diffuse growth pattern and conspicuous calcification are seen.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Oligodendroglioma-like features include small round nuclei, perinuclear haloes, and delicate branching capillaries.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Mild nuclear pleomorphism and membrane irregularities are common.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Astroglial elements here exhibit spindling and more conspicuous atypia without mitotic activity.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Intense regional immunoreactivity of the tumour matrix for CD34 is seen in the lower half of this field.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Ramified, CD34-immunoreactive neural elements are present in associated cerebral cortex.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Coronal FLAIR MRI. The tumour is heterogeneously T2-hyperintense at the subcortical region of the right temporal lobe, without significant vasogenic oedema.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Axial contrast-enhanced T1-weighted MRI. The tumour shows heterogeneous enhancement, which is mainly at the centre of the lesion while the periphery is unenhanced – suggestive of a cystic component.
A: seizures; refractory epilepsy; MAPK pathway-activating abnormalities

Q: On MRI, Polymorphous Low-Grade Neuroepithelial Tumor of the Young often presents as an epileptogenic, subcortical, FLAIR-hyperintense mass characterized by central [...] changes and an absence of significant vasogenic edema or mass effect.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. FLAIR-hyperintense solid components, cystic changes, and the absence of mass effect are seen in this MRI.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Axial contrast-enhanced T1-weighted MRI. The tumour shows heterogeneous enhancement, which is mainly at the centre of the lesion while the periphery is unenhanced – suggestive of a cystic component.
A: cystic
Q: Polymorphous Low-Grade Neuroepithelial Tumor of the Young
- Clinical: Polymorphous low-grade neuroepithelial tumour of the young (PLNTY) typically causes [...] and is associated with [...].
- Micro: PLNTYs exhibit oligodendroglioma-like features with small round nuclei, perinuclear haloes, and delicate branching capillaries, as well as calcifications and astroglial elements.
- Ancillary: PLNTYs are consistently associated with [...], including BRAF p.V600E mutations and FGFR2/3 fusions.
Reference Gallery:
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. FLAIR-hyperintense solid components, cystic changes, and the absence of mass effect are seen in this MRI.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. A diffuse growth pattern and conspicuous calcification are seen.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Oligodendroglioma-like features include small round nuclei, perinuclear haloes, and delicate branching capillaries.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Mild nuclear pleomorphism and membrane irregularities are common.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Astroglial elements here exhibit spindling and more conspicuous atypia without mitotic activity.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Intense regional immunoreactivity of the tumour matrix for CD34 is seen in the lower half of this field.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Ramified, CD34-immunoreactive neural elements are present in associated cerebral cortex.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Coronal FLAIR MRI. The tumour is heterogeneously T2-hyperintense at the subcortical region of the right temporal lobe, without significant vasogenic oedema.
Diagnosis: Polymorphous low-grade neuroepithelial tumour of the young. Axial contrast-enhanced T1-weighted MRI. The tumour shows heterogeneous enhancement, which is mainly at the centre of the lesion while the periphery is unenhanced – suggestive of a cystic component.
A: seizures; refractory epilepsy; MAPK pathway-activating abnormalities

Q: A Subependymal Giant Cell Astrocytoma classically presents as a mass located near the [...], often leading to obstructive hydrocephalus in patients with tuberous sclerosis.
Subependymal giant cell astrocytoma. Postcontrast axial T1-weighted MRI showing a right subependymal giant cell astrocytoma near the foramen of Monro, with avid enhancement.
Subependymal giant cell astrocytoma. Axial T2-weighted MRI. A large lobulated mass that is T2-isointense to grey matter, arising from the foramen of Monro and causing mild hydrocephalus. Note is also made of the tiny T2-hypointense calcified subependymal nodules along the lining of the right lateral ventricle. There are also T2-hyperintensities in bilateral cerebral hemispheres, representing cortical/subcortical tubers. Overall features are characteristic of tuberous sclerosis.
A: foramen of Monro
Back Extra: Subependymal Giant Cell Astrocytoma
- Clinical: Most patients with Subependymal Giant Cell Astrocytoma (SEGA) present with signs and symptoms of increased intracranial pressure, often due to obstructive hydrocephalus.
- Micro: Histologically, SEGA is characterized by a wide spectrum of glial phenotypes, including large ganglion-like cells, spindle cells, and gemistocyte-like cells.
- Ancillary: Tumour cells in SEGA uniformly express S100 and variably express GFAP. They also show strong phosphorylated S6 immunoreactivity, indicating mTOR pathway activation.
Reference Gallery:
Subependymal giant cell astrocytoma. Postcontrast axial T1-weighted MRI showing a right subependymal giant cell astrocytoma near the foramen of Monro, with avid enhancement.
Subependymal giant cell astrocytoma. Postcontrast axial T1-weighted MRI of the case in Fig. <<#22403>> after 3 months of treatment with an mTOR inhibitor. The tumour shows decreased size and enhancement.
Subependymal giant cell astrocytoma. Class III β-tubulin (as recognized by TUJ1) is the most ubiquitous neuronal marker in these tumours.
Subependymal giant cell astrocytoma. Large cells with voluminous cytoplasm and well-delineated borders may be present.
Subependymal giant cell astrocytoma. Elongated cytoplasmic profiles and a more ganglioid appearance may be a feature.
Subependymal giant cell astrocytoma. Tumours uniformly express S100.
Subependymal giant cell astrocytoma. GFAP expression is more variable than S100, and absent in individual cells, but it is usually present at least focally.
Subependymal giant cell astrocytoma. Markers of neuronal differentiation, including synaptophysin, are frequently positive in these tumours.
Subependymal giant cell astrocytoma. Mitotic activity does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. The rare presence of microvascular proliferation does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. The rare presence of necrosis (even if palisading) does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. Axial T2-weighted MRI. A large lobulated mass that is T2-isointense to grey matter, arising from the foramen of Monro and causing mild hydrocephalus. Note is also made of the tiny T2-hypointense calcified subependymal nodules along the lining of the right lateral ventricle. There are also T2-hyperintensities in bilateral cerebral hemispheres, representing cortical/subcortical tubers. Overall features are characteristic of tuberous sclerosis.

Q: Histologically, a Subependymal Giant Cell Astrocytoma is composed of a wide spectrum of glial phenotypes, most classically including large, [...] cells with voluminous cytoplasm.
Subependymal giant cell astrocytoma. Large cells with voluminous cytoplasm and well-delineated borders may be present.
Subependymal giant cell astrocytoma. Elongated cytoplasmic profiles and a more ganglioid appearance may be a feature.
A: ganglion-like
Back Extra: Subependymal Giant Cell Astrocytoma
- Clinical: Most patients with Subependymal Giant Cell Astrocytoma (SEGA) present with signs and symptoms of increased intracranial pressure, often due to obstructive hydrocephalus.
- Micro: Histologically, SEGA is characterized by a wide spectrum of glial phenotypes, including large ganglion-like cells, spindle cells, and gemistocyte-like cells.
- Ancillary: Tumour cells in SEGA uniformly express S100 and variably express GFAP. They also show strong phosphorylated S6 immunoreactivity, indicating mTOR pathway activation.
Reference Gallery:
Subependymal giant cell astrocytoma. Postcontrast axial T1-weighted MRI showing a right subependymal giant cell astrocytoma near the foramen of Monro, with avid enhancement.
Subependymal giant cell astrocytoma. Postcontrast axial T1-weighted MRI of the case in Fig. <<#22403>> after 3 months of treatment with an mTOR inhibitor. The tumour shows decreased size and enhancement.
Subependymal giant cell astrocytoma. Class III β-tubulin (as recognized by TUJ1) is the most ubiquitous neuronal marker in these tumours.
Subependymal giant cell astrocytoma. Large cells with voluminous cytoplasm and well-delineated borders may be present.
Subependymal giant cell astrocytoma. Elongated cytoplasmic profiles and a more ganglioid appearance may be a feature.
Subependymal giant cell astrocytoma. Tumours uniformly express S100.
Subependymal giant cell astrocytoma. GFAP expression is more variable than S100, and absent in individual cells, but it is usually present at least focally.
Subependymal giant cell astrocytoma. Markers of neuronal differentiation, including synaptophysin, are frequently positive in these tumours.
Subependymal giant cell astrocytoma. Mitotic activity does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. The rare presence of microvascular proliferation does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. The rare presence of necrosis (even if palisading) does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. Axial T2-weighted MRI. A large lobulated mass that is T2-isointense to grey matter, arising from the foramen of Monro and causing mild hydrocephalus. Note is also made of the tiny T2-hypointense calcified subependymal nodules along the lining of the right lateral ventricle. There are also T2-hyperintensities in bilateral cerebral hemispheres, representing cortical/subcortical tubers. Overall features are characteristic of tuberous sclerosis.

Q: Unique among many glial tumors, the presence of necrosis, microvascular proliferation, or elevated mitotic activity in a Subependymal Giant Cell Astrocytoma does not alter its classification as a CNS WHO grade [...] tumor.
Subependymal giant cell astrocytoma. Mitotic activity does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. The rare presence of microvascular proliferation does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. The rare presence of necrosis (even if palisading) does not change the CNS WHO grade 1 designation.
A: 1
Back Extra: Subependymal Giant Cell Astrocytoma
- Clinical: Most patients with Subependymal Giant Cell Astrocytoma (SEGA) present with signs and symptoms of increased intracranial pressure, often due to obstructive hydrocephalus.
- Micro: Histologically, SEGA is characterized by a wide spectrum of glial phenotypes, including large ganglion-like cells, spindle cells, and gemistocyte-like cells.
- Ancillary: Tumour cells in SEGA uniformly express S100 and variably express GFAP. They also show strong phosphorylated S6 immunoreactivity, indicating mTOR pathway activation.
Reference Gallery:
Subependymal giant cell astrocytoma. Postcontrast axial T1-weighted MRI showing a right subependymal giant cell astrocytoma near the foramen of Monro, with avid enhancement.
Subependymal giant cell astrocytoma. Postcontrast axial T1-weighted MRI of the case in Fig. <<#22403>> after 3 months of treatment with an mTOR inhibitor. The tumour shows decreased size and enhancement.
Subependymal giant cell astrocytoma. Class III β-tubulin (as recognized by TUJ1) is the most ubiquitous neuronal marker in these tumours.
Subependymal giant cell astrocytoma. Large cells with voluminous cytoplasm and well-delineated borders may be present.
Subependymal giant cell astrocytoma. Elongated cytoplasmic profiles and a more ganglioid appearance may be a feature.
Subependymal giant cell astrocytoma. Tumours uniformly express S100.
Subependymal giant cell astrocytoma. GFAP expression is more variable than S100, and absent in individual cells, but it is usually present at least focally.
Subependymal giant cell astrocytoma. Markers of neuronal differentiation, including synaptophysin, are frequently positive in these tumours.
Subependymal giant cell astrocytoma. Mitotic activity does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. The rare presence of microvascular proliferation does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. The rare presence of necrosis (even if palisading) does not change the CNS WHO grade 1 designation.
Subependymal giant cell astrocytoma. Axial T2-weighted MRI. A large lobulated mass that is T2-isointense to grey matter, arising from the foramen of Monro and causing mild hydrocephalus. Note is also made of the tiny T2-hypointense calcified subependymal nodules along the lining of the right lateral ventricle. There are also T2-hyperintensities in bilateral cerebral hemispheres, representing cortical/subcortical tubers. Overall features are characteristic of tuberous sclerosis.

Q: Microscopically, Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma is characterized by a prominent [...] leptomeningeal stroma consisting of fibroblast-like, spindle-shaped cells arranged in streams within a collagen matrix.
Desmoplastic infantile ganglioglioma. The tumour shows a marked desmoplastic component, evidenced by reticulin staining, whereas the adjacent cortex is negative.
Desmoplastic infantile ganglioglioma. Neoplastic cells are arranged in streams in the desmoplastic component.
A: desmoplastic
Back Extra: Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma
- Clinical: The most frequent clinical signs of Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma are increased head circumference, bulging of the fontanelles, lethargy, and the sunset sign.
- Micro: The tumour is characterized by a prominent desmoplastic leptomeningeal stroma and a variable proportion of neuroepithelial component. The desmoplastic component consists of fibroblast-like, spindle-shaped cells in a collagen matrix.
- Ancillary: Immunohistochemistry shows strong GFAP expression in the glial component, and synaptophysin expression in neoplastic ganglion cells. The Ki-67 proliferation index is typically very low (<2%) in desmoplastic areas.
Reference Gallery:
Desmoplastic infantile ganglioglioma. The tumour is superficial, with sharp demarcation from the cortex.
Desmoplastic infantile ganglioglioma. The tumour shows a marked desmoplastic component, evidenced by reticulin staining, whereas the adjacent cortex is negative.
Desmoplastic infantile ganglioglioma. Neoplastic cells are arranged in streams in the desmoplastic component.
Desmoplastic infantile ganglioglioma. Some cells express synaptophysin.
Desmoplastic infantile ganglioglioma. The Ki-67 labelling index is very low in desmoplastic areas.
Desmoplastic infantile ganglioglioma. Advanced neuronal differentiation is associated with poorly differentiated cells.
Desmoplastic infantile ganglioglioma. Neuronal cells strongly express synaptophysin.
Desmoplastic infantile ganglioglioma. Cells with advanced neuronal differentiation often express chromogranin.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Axial T2-weighted MRI shows multiple cystic components with cerebrospinal fluid–like signal, and a peripheral solid component that is isointense to grey matter.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Coronal T2-weighted MRI shows multiple cystic components with cerebrospinal fluid–like signal, and a peripheral solid component that is isointense to grey matter.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Susceptibility-weighted MRI shows no blooming effect (pseudoenlargement of the lesion).
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Diffusion-weighted MRI demonstrates a solid hyperintense portion, possibly due to desmoplastic reaction.

Q: In Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma, the neuronal component (when present) strongly expresses [...] on immunohistochemistry, while the dense stroma typically demonstrates a very low (<2%) Ki-67 proliferation index.
Desmoplastic infantile ganglioglioma. Some cells express synaptophysin.
Desmoplastic infantile ganglioglioma. The Ki-67 labelling index is very low in desmoplastic areas.
Desmoplastic infantile ganglioglioma. Neuronal cells strongly express synaptophysin.
A: synaptophysin
Back Extra: Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma
- Clinical: The most frequent clinical signs of Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma are increased head circumference, bulging of the fontanelles, lethargy, and the sunset sign.
- Micro: The tumour is characterized by a prominent desmoplastic leptomeningeal stroma and a variable proportion of neuroepithelial component. The desmoplastic component consists of fibroblast-like, spindle-shaped cells in a collagen matrix.
- Ancillary: Immunohistochemistry shows strong GFAP expression in the glial component, and synaptophysin expression in neoplastic ganglion cells. The Ki-67 proliferation index is typically very low (<2%) in desmoplastic areas.
Reference Gallery:
Desmoplastic infantile ganglioglioma. The tumour is superficial, with sharp demarcation from the cortex.
Desmoplastic infantile ganglioglioma. The tumour shows a marked desmoplastic component, evidenced by reticulin staining, whereas the adjacent cortex is negative.
Desmoplastic infantile ganglioglioma. Neoplastic cells are arranged in streams in the desmoplastic component.
Desmoplastic infantile ganglioglioma. Some cells express synaptophysin.
Desmoplastic infantile ganglioglioma. The Ki-67 labelling index is very low in desmoplastic areas.
Desmoplastic infantile ganglioglioma. Advanced neuronal differentiation is associated with poorly differentiated cells.
Desmoplastic infantile ganglioglioma. Neuronal cells strongly express synaptophysin.
Desmoplastic infantile ganglioglioma. Cells with advanced neuronal differentiation often express chromogranin.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Axial T2-weighted MRI shows multiple cystic components with cerebrospinal fluid–like signal, and a peripheral solid component that is isointense to grey matter.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Coronal T2-weighted MRI shows multiple cystic components with cerebrospinal fluid–like signal, and a peripheral solid component that is isointense to grey matter.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Susceptibility-weighted MRI shows no blooming effect (pseudoenlargement of the lesion).
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Diffusion-weighted MRI demonstrates a solid hyperintense portion, possibly due to desmoplastic reaction.

Q: Radiologically, Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma typically presents in infants as a massive superficial hemispheric tumor featuring multiple [...] components and a peripheral solid region that is isointense to gray matter.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Axial T2-weighted MRI shows multiple cystic components with cerebrospinal fluid–like signal, and a peripheral solid component that is isointense to grey matter.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Coronal T2-weighted MRI shows multiple cystic components with cerebrospinal fluid–like signal, and a peripheral solid component that is isointense to grey matter.
A: cystic
Back Extra: Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma
- Clinical: The most frequent clinical signs of Desmoplastic Infantile Ganglioglioma / Desmoplastic Infantile Astrocytoma are increased head circumference, bulging of the fontanelles, lethargy, and the sunset sign.
- Micro: The tumour is characterized by a prominent desmoplastic leptomeningeal stroma and a variable proportion of neuroepithelial component. The desmoplastic component consists of fibroblast-like, spindle-shaped cells in a collagen matrix.
- Ancillary: Immunohistochemistry shows strong GFAP expression in the glial component, and synaptophysin expression in neoplastic ganglion cells. The Ki-67 proliferation index is typically very low (<2%) in desmoplastic areas.
Reference Gallery:
Desmoplastic infantile ganglioglioma. The tumour is superficial, with sharp demarcation from the cortex.
Desmoplastic infantile ganglioglioma. The tumour shows a marked desmoplastic component, evidenced by reticulin staining, whereas the adjacent cortex is negative.
Desmoplastic infantile ganglioglioma. Neoplastic cells are arranged in streams in the desmoplastic component.
Desmoplastic infantile ganglioglioma. Some cells express synaptophysin.
Desmoplastic infantile ganglioglioma. The Ki-67 labelling index is very low in desmoplastic areas.
Desmoplastic infantile ganglioglioma. Advanced neuronal differentiation is associated with poorly differentiated cells.
Desmoplastic infantile ganglioglioma. Neuronal cells strongly express synaptophysin.
Desmoplastic infantile ganglioglioma. Cells with advanced neuronal differentiation often express chromogranin.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Axial T2-weighted MRI shows multiple cystic components with cerebrospinal fluid–like signal, and a peripheral solid component that is isointense to grey matter.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Coronal T2-weighted MRI shows multiple cystic components with cerebrospinal fluid–like signal, and a peripheral solid component that is isointense to grey matter.
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Susceptibility-weighted MRI shows no blooming effect (pseudoenlargement of the lesion).
Desmoplastic infantile ganglioglioma in the right hemisphere of an 18-month-old girl. Diffusion-weighted MRI demonstrates a solid hyperintense portion, possibly due to desmoplastic reaction.

Q: A defining histologic characteristic of Diffuse Glioneuronal Tumor with Oligodendroglioma-like Features and Nuclear Clusters is the presence of distinctive ring- or C-shaped [...].
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Tumour with clear cell morphology and several ring- or C-shaped nuclear clusters.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Several nuclear clusters (some indicated by arrows).
A: nuclear clusters
Back Extra: Diffuse Glioneuronal Tumour with Oligodendroglioma-like Features and Nuclear Clusters
- Clinical: Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) primarily affects paediatric patients with a median age of 9 years, and is equally distributed between males and females.
- Micro: Histologically, DGONC shows small to medium-sized cells with perinuclear haloes, scattered multinucleated cells, and nuclear clusters, often with microcalcifications.
- Ancillary: DGONC is characterized by a distinct DNA methylation profile and frequent monosomy of chromosome 14, with tumour cells being diffusely OLIG2-positive but GFAP-negative.
Reference Gallery:
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC). DNA methylation profiling. DGONC samples (n = 31) were compared with 160 well-characterized reference samples representing CNS tumours of defined histological and/or molecular subgroups, confirming the distinct nature of the DGONC entity. Reference cohorts: central neurocytoma (CNCYT); CNS high-grade neuroepithelial tumour with BCOR alteration (CNS HGNET-BCOR); CNS Ewing sarcoma family tumour with CIC alteration (CNS EFT-CIC); CNS high-grade neuroepithelial tumour with MN1 alteration (CNS HGNET-MN1); CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2); diffuse leptomeningeal glioneuronal tumour, methylation class 1 and class 2 (DLGNT, MC-1 and MC-2); dysembryoplastic neuroepithelial tumour (DNET); extraventricular neurocytoma (EVNCYT); H3 K27M–mutant glioblastoma (GBM_K27); H3/IDH-wildtype glioblastoma RTK1 group (GBM_PDGFRA); low-grade glioma, MYB- or MYBL1-altered (LGG_MYB); IDH-mutant, 1p/19q-codeleted oligodendroglioma (O_IDH); hemispheric pilocytic astrocytoma (PA_CORT).
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Clear cell histology can resemble oligodendroglioma.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Monomorphic clear cell morphology, resembling oligodendroglioma.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Tumour with clear cell morphology and several ring- or C-shaped nuclear clusters.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Tumour with oligodendroglioma-like perinuclear haloes.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for GFAP is largely confined to reactive astrocytes.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for OLIG2 is positive in the majority of tumour cells.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for synaptophysin shows variable staining.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Several nuclear clusters (some indicated by arrows).

Q: By immunohistochemistry, the neoplastic cells of Diffuse Glioneuronal Tumor with Oligodendroglioma-like Features and Nuclear Clusters are diffusely positive for [...] and typically negative for GFAP.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for GFAP is largely confined to reactive astrocytes.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for OLIG2 is positive in the majority of tumour cells.
A: OLIG2
Back Extra: Diffuse Glioneuronal Tumour with Oligodendroglioma-like Features and Nuclear Clusters
- Clinical: Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) primarily affects paediatric patients with a median age of 9 years, and is equally distributed between males and females.
- Micro: Histologically, DGONC shows small to medium-sized cells with perinuclear haloes, scattered multinucleated cells, and nuclear clusters, often with microcalcifications.
- Ancillary: DGONC is characterized by a distinct DNA methylation profile and frequent monosomy of chromosome 14, with tumour cells being diffusely OLIG2-positive but GFAP-negative.
Reference Gallery:
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC). DNA methylation profiling. DGONC samples (n = 31) were compared with 160 well-characterized reference samples representing CNS tumours of defined histological and/or molecular subgroups, confirming the distinct nature of the DGONC entity. Reference cohorts: central neurocytoma (CNCYT); CNS high-grade neuroepithelial tumour with BCOR alteration (CNS HGNET-BCOR); CNS Ewing sarcoma family tumour with CIC alteration (CNS EFT-CIC); CNS high-grade neuroepithelial tumour with MN1 alteration (CNS HGNET-MN1); CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2); diffuse leptomeningeal glioneuronal tumour, methylation class 1 and class 2 (DLGNT, MC-1 and MC-2); dysembryoplastic neuroepithelial tumour (DNET); extraventricular neurocytoma (EVNCYT); H3 K27M–mutant glioblastoma (GBM_K27); H3/IDH-wildtype glioblastoma RTK1 group (GBM_PDGFRA); low-grade glioma, MYB- or MYBL1-altered (LGG_MYB); IDH-mutant, 1p/19q-codeleted oligodendroglioma (O_IDH); hemispheric pilocytic astrocytoma (PA_CORT).
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Clear cell histology can resemble oligodendroglioma.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Monomorphic clear cell morphology, resembling oligodendroglioma.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Tumour with clear cell morphology and several ring- or C-shaped nuclear clusters.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Tumour with oligodendroglioma-like perinuclear haloes.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for GFAP is largely confined to reactive astrocytes.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for OLIG2 is positive in the majority of tumour cells.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for synaptophysin shows variable staining.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Several nuclear clusters (some indicated by arrows).

Q: In addition to the defining multinucleated groupings, the morphology of Diffuse Glioneuronal Tumor with Oligodendroglioma-like Features and Nuclear Clusters is characterized by monomorphic cells with prominent clear [...].
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Monomorphic clear cell morphology, resembling oligodendroglioma.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Tumour with oligodendroglioma-like perinuclear haloes.
A: perinuclear halos
Back Extra: Diffuse Glioneuronal Tumour with Oligodendroglioma-like Features and Nuclear Clusters
- Clinical: Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC) primarily affects paediatric patients with a median age of 9 years, and is equally distributed between males and females.
- Micro: Histologically, DGONC shows small to medium-sized cells with perinuclear haloes, scattered multinucleated cells, and nuclear clusters, often with microcalcifications.
- Ancillary: DGONC is characterized by a distinct DNA methylation profile and frequent monosomy of chromosome 14, with tumour cells being diffusely OLIG2-positive but GFAP-negative.
Reference Gallery:
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters (DGONC). DNA methylation profiling. DGONC samples (n = 31) were compared with 160 well-characterized reference samples representing CNS tumours of defined histological and/or molecular subgroups, confirming the distinct nature of the DGONC entity. Reference cohorts: central neurocytoma (CNCYT); CNS high-grade neuroepithelial tumour with BCOR alteration (CNS HGNET-BCOR); CNS Ewing sarcoma family tumour with CIC alteration (CNS EFT-CIC); CNS high-grade neuroepithelial tumour with MN1 alteration (CNS HGNET-MN1); CNS neuroblastoma with FOXR2 activation (CNS NB-FOXR2); diffuse leptomeningeal glioneuronal tumour, methylation class 1 and class 2 (DLGNT, MC-1 and MC-2); dysembryoplastic neuroepithelial tumour (DNET); extraventricular neurocytoma (EVNCYT); H3 K27M–mutant glioblastoma (GBM_K27); H3/IDH-wildtype glioblastoma RTK1 group (GBM_PDGFRA); low-grade glioma, MYB- or MYBL1-altered (LGG_MYB); IDH-mutant, 1p/19q-codeleted oligodendroglioma (O_IDH); hemispheric pilocytic astrocytoma (PA_CORT).
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Clear cell histology can resemble oligodendroglioma.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Monomorphic clear cell morphology, resembling oligodendroglioma.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Tumour with clear cell morphology and several ring- or C-shaped nuclear clusters.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Tumour with oligodendroglioma-like perinuclear haloes.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for GFAP is largely confined to reactive astrocytes.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for OLIG2 is positive in the majority of tumour cells.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Immunohistochemistry for synaptophysin shows variable staining.
Diffuse glioneuronal tumour with oligodendroglioma-like features and nuclear clusters. Several nuclear clusters (some indicated by arrows).

Q: The histologic finding of extensive leptomeningeal expansion by uniform, oligodendrocyte-like cells with neuronal differentiation (e.g., neurocytic rosettes and ganglion cells) is characteristic of [...].
Diffuse leptomeningeal glioneuronal tumour. Marked expansion and hypercellularity of the leptomeninges.
Diffuse leptomeningeal glioneuronal tumour. Neuronal differentiation is evident in the form of neurocytic rosettes and perivascular pseudorosettes.
Diffuse leptomeningeal glioneuronal tumour. Neuronal differentiation is evident in the form of ganglion cells.
A: Diffuse Leptomeningeal Glioneuronal Tumor
Back Extra: Diffuse Leptomeningeal Glioneuronal Tumour
- Clinical: Patients often present with acute onset of signs and symptoms of increased intracranial pressure, including headache, nausea, and vomiting, due to obstructive hydrocephalus.
- Micro: The tumour is composed of relatively monomorphic oligodendrocyte-like tumour cells with uniform, medium-sized round nuclei and inconspicuous nucleoli, often showing neuronal differentiation in the form of neurocytic rosettes and ganglion cells.
- Ancillary: Molecular testing confirms the presence of chromosome 1p deletion and KIAA1549::BRAF fusion, with tumour cells showing extensive nuclear immunoreactivity for OLIG2 and often being GFAP-negative.
Reference Gallery:
Diffuse leptomeningeal glioneuronal tumour. Note the extensive intraventricular involvement, as well as the parenchymal cysts.
Diffuse leptomeningeal glioneuronal tumour. Extensive spinal leptomeningeal involvement.
Diffuse leptomeningeal glioneuronal tumour. Marked expansion and hypercellularity of the leptomeninges.
Diffuse leptomeningeal glioneuronal tumour. Extension along the perivascular Virchow–Robin space is evident within the adjacent brain parenchyma of this tumour.
Diffuse leptomeningeal glioneuronal tumour. Neuronal differentiation is evident in the form of neurocytic rosettes and perivascular pseudorosettes.
Diffuse leptomeningeal glioneuronal tumour. Neuronal differentiation is evident in the form of ganglion cells.
Diffuse leptomeningeal glioneuronal tumour. The tumour cells are GFAP-negative.
Diffuse leptomeningeal glioneuronal tumour. Tumour cells show extensive nuclear immunoreactivity for OLIG2.
Diffuse leptomeningeal glioneuronal tumour. FISH studies using BRAF (red) and KIAA1549 (green) probes show increased copy numbers and yellow fusion signals.

Q: In Diffuse Leptomeningeal Glioneuronal Tumor, tumor cells are typically GFAP-negative and strongly OLIG2-positive, and molecular testing frequently confirms a 1p deletion alongside a characteristic [BRAF] fusion.
Diffuse leptomeningeal glioneuronal tumour. The tumour cells are GFAP-negative.
Diffuse leptomeningeal glioneuronal tumour. Tumour cells show extensive nuclear immunoreactivity for OLIG2.
Diffuse leptomeningeal glioneuronal tumour. FISH studies using BRAF (red) and KIAA1549 (green) probes show increased copy numbers and yellow fusion signals.
A: KIAA1549
Back Extra: Diffuse Leptomeningeal Glioneuronal Tumour
- Clinical: Patients often present with acute onset of signs and symptoms of increased intracranial pressure, including headache, nausea, and vomiting, due to obstructive hydrocephalus.
- Micro: The tumour is composed of relatively monomorphic oligodendrocyte-like tumour cells with uniform, medium-sized round nuclei and inconspicuous nucleoli, often showing neuronal differentiation in the form of neurocytic rosettes and ganglion cells.
- Ancillary: Molecular testing confirms the presence of chromosome 1p deletion and KIAA1549::BRAF fusion, with tumour cells showing extensive nuclear immunoreactivity for OLIG2 and often being GFAP-negative.
Reference Gallery:
Diffuse leptomeningeal glioneuronal tumour. Note the extensive intraventricular involvement, as well as the parenchymal cysts.
Diffuse leptomeningeal glioneuronal tumour. Extensive spinal leptomeningeal involvement.
Diffuse leptomeningeal glioneuronal tumour. Marked expansion and hypercellularity of the leptomeninges.
Diffuse leptomeningeal glioneuronal tumour. Extension along the perivascular Virchow–Robin space is evident within the adjacent brain parenchyma of this tumour.
Diffuse leptomeningeal glioneuronal tumour. Neuronal differentiation is evident in the form of neurocytic rosettes and perivascular pseudorosettes.
Diffuse leptomeningeal glioneuronal tumour. Neuronal differentiation is evident in the form of ganglion cells.
Diffuse leptomeningeal glioneuronal tumour. The tumour cells are GFAP-negative.
Diffuse leptomeningeal glioneuronal tumour. Tumour cells show extensive nuclear immunoreactivity for OLIG2.
Diffuse leptomeningeal glioneuronal tumour. FISH studies using BRAF (red) and KIAA1549 (green) probes show increased copy numbers and yellow fusion signals.

Q: Radiographically, [...] classically presents with extensive intraventricular and spinal leptomeningeal involvement, often accompanied by parenchymal cysts and signs of obstructive hydrocephalus.
Diffuse leptomeningeal glioneuronal tumour. Note the extensive intraventricular involvement, as well as the parenchymal cysts.
Diffuse leptomeningeal glioneuronal tumour. Extensive spinal leptomeningeal involvement.
A: Diffuse Leptomeningeal Glioneuronal Tumor
Back Extra: Diffuse Leptomeningeal Glioneuronal Tumour
- Clinical: Patients often present with acute onset of signs and symptoms of increased intracranial pressure, including headache, nausea, and vomiting, due to obstructive hydrocephalus.
- Micro: The tumour is composed of relatively monomorphic oligodendrocyte-like tumour cells with uniform, medium-sized round nuclei and inconspicuous nucleoli, often showing neuronal differentiation in the form of neurocytic rosettes and ganglion cells.
- Ancillary: Molecular testing confirms the presence of chromosome 1p deletion and KIAA1549::BRAF fusion, with tumour cells showing extensive nuclear immunoreactivity for OLIG2 and often being GFAP-negative.
Reference Gallery:
Diffuse leptomeningeal glioneuronal tumour. Note the extensive intraventricular involvement, as well as the parenchymal cysts.
Diffuse leptomeningeal glioneuronal tumour. Extensive spinal leptomeningeal involvement.
Diffuse leptomeningeal glioneuronal tumour. Marked expansion and hypercellularity of the leptomeninges.
Diffuse leptomeningeal glioneuronal tumour. Extension along the perivascular Virchow–Robin space is evident within the adjacent brain parenchyma of this tumour.
Diffuse leptomeningeal glioneuronal tumour. Neuronal differentiation is evident in the form of neurocytic rosettes and perivascular pseudorosettes.
Diffuse leptomeningeal glioneuronal tumour. Neuronal differentiation is evident in the form of ganglion cells.
Diffuse leptomeningeal glioneuronal tumour. The tumour cells are GFAP-negative.
Diffuse leptomeningeal glioneuronal tumour. Tumour cells show extensive nuclear immunoreactivity for OLIG2.
Diffuse leptomeningeal glioneuronal tumour. FISH studies using BRAF (red) and KIAA1549 (green) probes show increased copy numbers and yellow fusion signals.

Q: Histologically, Dysembryoplastic Neuroepithelial Tumor (DNT) is characterized by a specific glioneuronal element and mature, non-dysplastic neurons suspended in a mucoid matrix, classically referred to as [...].
Dysembryoplastic neuroepithelial tumour. Specific glioneuronal element: bundles of axons lined by small oligodendroglia-like cells. Interspersed neurons appear to float in a mucoid matrix (floating neurons).
Dysembryoplastic neuroepithelial tumour. Large floating non-dysplastic neurons in an alcianophilic matrix (Alcian blue staining).
Dysembryoplastic neuroepithelial tumour. Floating neuron (NeuN immunohistochemistry).
A: "floating neurons"
Back Extra: Dysembryoplastic Neuroepithelial Tumor (DNT)
- Clinical: Patients with Dysembryoplastic Neuroepithelial Tumor (DNT) typically present with drug-resistant focal epilepsy with an onset in childhood, adolescence, or early adulthood.
- Micro: The histopathological hallmarks of DNT include the multinodular intracortical growth pattern and the specific glioneuronal element, consisting of columns of axons lined by small oligodendroglia-like cells, and neurons floating in a mucoid matrix.
- Ancillary: FGFR1 alterations (intragenic duplications, missense mutations) are characteristic and considered the main molecular driver in Dysembryoplastic Neuroepithelial Tumors (DNT).
Reference Gallery:
Dysembryoplastic neuroepithelial tumour. Specific glioneuronal element: bundles of axons lined by small oligodendroglia-like cells. Interspersed neurons appear to float in a mucoid matrix (floating neurons).
Dysembryoplastic neuroepithelial tumour. Low-power micrograph illustrating the multinodular intracortical growth pattern.
Dysembryoplastic neuroepithelial tumour. Large floating non-dysplastic neurons in an alcianophilic matrix (Alcian blue staining).
Dysembryoplastic neuroepithelial tumour. Large floating neuron (synaptophysin immunohistochemistry).
Dysembryoplastic neuroepithelial tumour. Floating neuron (NeuN immunohistochemistry).
Dysembryoplastic neuroepithelial tumour. Axial T2-weighted MRI. A cortical-based T2-hyperintense mass extends beyond the normal cortical margin (soap-bubble appearance) and directly remodels the skull. There is no evidence of associated vasogenic oedema.
Dysembryoplastic neuroepithelial tumour. Axial contrast-enhanced T1-weighted MRI shows no evidence of enhancement within the mass. The curvilinear enhancing structures overlaying the mass are normal cortical veins.

Q: On T2-weighted MRI, Dysembryoplastic Neuroepithelial Tumor (DNT) typically presents as a cortical-based, hyperintense mass without vasogenic edema, demonstrating a characteristic [...] appearance.
Dysembryoplastic neuroepithelial tumour. Axial T2-weighted MRI. A cortical-based T2-hyperintense mass extends beyond the normal cortical margin (soap-bubble appearance) and directly remodels the skull. There is no evidence of associated vasogenic oedema.
A: "soap-bubble"
Back Extra: Dysembryoplastic Neuroepithelial Tumor (DNT)
- Clinical: Patients with Dysembryoplastic Neuroepithelial Tumor (DNT) typically present with drug-resistant focal epilepsy with an onset in childhood, adolescence, or early adulthood.
- Micro: The histopathological hallmarks of DNT include the multinodular intracortical growth pattern and the specific glioneuronal element, consisting of columns of axons lined by small oligodendroglia-like cells, and neurons floating in a mucoid matrix.
- Ancillary: FGFR1 alterations (intragenic duplications, missense mutations) are characteristic and considered the main molecular driver in Dysembryoplastic Neuroepithelial Tumors (DNT).
Reference Gallery:
Dysembryoplastic neuroepithelial tumour. Specific glioneuronal element: bundles of axons lined by small oligodendroglia-like cells. Interspersed neurons appear to float in a mucoid matrix (floating neurons).
Dysembryoplastic neuroepithelial tumour. Low-power micrograph illustrating the multinodular intracortical growth pattern.
Dysembryoplastic neuroepithelial tumour. Large floating non-dysplastic neurons in an alcianophilic matrix (Alcian blue staining).
Dysembryoplastic neuroepithelial tumour. Large floating neuron (synaptophysin immunohistochemistry).
Dysembryoplastic neuroepithelial tumour. Floating neuron (NeuN immunohistochemistry).
Dysembryoplastic neuroepithelial tumour. Axial T2-weighted MRI. A cortical-based T2-hyperintense mass extends beyond the normal cortical margin (soap-bubble appearance) and directly remodels the skull. There is no evidence of associated vasogenic oedema.
Dysembryoplastic neuroepithelial tumour. Axial contrast-enhanced T1-weighted MRI shows no evidence of enhancement within the mass. The curvilinear enhancing structures overlaying the mass are normal cortical veins.

Q: At low magnification, Dysembryoplastic Neuroepithelial Tumor (DNT) is classically defined by its highly characteristic [...] intracortical growth pattern.
Dysembryoplastic neuroepithelial tumour. Low-power micrograph illustrating the multinodular intracortical growth pattern.
A: multinodular
Back Extra: Dysembryoplastic Neuroepithelial Tumor (DNT)
- Clinical: Patients with Dysembryoplastic Neuroepithelial Tumor (DNT) typically present with drug-resistant focal epilepsy with an onset in childhood, adolescence, or early adulthood.
- Micro: The histopathological hallmarks of DNT include the multinodular intracortical growth pattern and the specific glioneuronal element, consisting of columns of axons lined by small oligodendroglia-like cells, and neurons floating in a mucoid matrix.
- Ancillary: FGFR1 alterations (intragenic duplications, missense mutations) are characteristic and considered the main molecular driver in Dysembryoplastic Neuroepithelial Tumors (DNT).
Reference Gallery:
Dysembryoplastic neuroepithelial tumour. Specific glioneuronal element: bundles of axons lined by small oligodendroglia-like cells. Interspersed neurons appear to float in a mucoid matrix (floating neurons).
Dysembryoplastic neuroepithelial tumour. Low-power micrograph illustrating the multinodular intracortical growth pattern.
Dysembryoplastic neuroepithelial tumour. Large floating non-dysplastic neurons in an alcianophilic matrix (Alcian blue staining).
Dysembryoplastic neuroepithelial tumour. Large floating neuron (synaptophysin immunohistochemistry).
Dysembryoplastic neuroepithelial tumour. Floating neuron (NeuN immunohistochemistry).
Dysembryoplastic neuroepithelial tumour. Axial T2-weighted MRI. A cortical-based T2-hyperintense mass extends beyond the normal cortical margin (soap-bubble appearance) and directly remodels the skull. There is no evidence of associated vasogenic oedema.
Dysembryoplastic neuroepithelial tumour. Axial contrast-enhanced T1-weighted MRI shows no evidence of enhancement within the mass. The curvilinear enhancing structures overlaying the mass are normal cortical veins.

Q: Histologically characterized by clustered, pale nodules containing monomorphic mature neurons and prominent vacuolar matrix changes, this seizure-associated lesion is known as [...].
Multinodular and vacuolating neuronal tumour. Mature-appearing neurons of intermediate to large size populate this nodule with vacuolar matrix changes.
Multinodular and vacuolating neuronal tumour. Discrete tumour nodules with vacuolar changes are apparent.
A: Multinodular and Vacuolating Neuronal Tumour
Back Extra: Multinodular and Vacuolating Neuronal Tumour
- Clinical: Seizures, particularly of complex partial type, are the most common manifestation of {{Multinodular and Vacuolating Neuronal Tumour}}.
- Micro: {{Multinodular and Vacuolating Neuronal Tumour}} is characterized by pale, hypomyelinated nodules containing monomorphic neuronal elements with vacuolar changes.
- Ancillary: Tumour cells in {{Multinodular and Vacuolating Neuronal Tumour}} consistently express OLIG2, HuC/HuD, and non-phosphorylated 200-kDa NFP.
Reference Gallery:
Multinodular and vacuolating neuronal tumour. Confluent and nodular FLAIR hyperintensity, involvement of cortex and superficial white matter, and absence of mass effect are characteristic on MRI.
Multinodular and vacuolating neuronal tumour. Mature-appearing neurons of intermediate to large size populate this nodule with vacuolar matrix changes.
Multinodular and vacuolating neuronal tumour. The neurons of this example are synaptophysin-immunoreactive (but most only weakly).
Multinodular and vacuolating neuronal tumour. Neoplastic neurons exhibit nuclear and cytoplasmic HuC/HuD immunoreactivity.
Multinodular and vacuolating neuronal tumour. Neoplastic neuronal elements manifest nuclear OLIG2 immunoreactivity.
Multinodular and vacuolating neuronal tumour. Ramified, CD34-immunoreactive neural elements are present in this example.
Multinodular and vacuolating neuronal tumour. Discrete tumour nodules with vacuolar changes are apparent.
Multinodular and vacuolating neuronal tumour. Axial MRI demonstrating clustered, T2-hyperintense nodular lesions in the superficial subcortical white matter.

Q: In Multinodular and Vacuolating Neuronal Tumour, the neoplastic neuronal elements classically exhibit immunoreactivity for neuronal markers (e.g., HuC/HuD) as well as the glial transcription factor [...].
Multinodular and vacuolating neuronal tumour. Neoplastic neurons exhibit nuclear and cytoplasmic HuC/HuD immunoreactivity.
Multinodular and vacuolating neuronal tumour. Neoplastic neuronal elements manifest nuclear OLIG2 immunoreactivity.
A: OLIG2
Back Extra: Multinodular and Vacuolating Neuronal Tumour
- Clinical: Seizures, particularly of complex partial type, are the most common manifestation of {{Multinodular and Vacuolating Neuronal Tumour}}.
- Micro: {{Multinodular and Vacuolating Neuronal Tumour}} is characterized by pale, hypomyelinated nodules containing monomorphic neuronal elements with vacuolar changes.
- Ancillary: Tumour cells in {{Multinodular and Vacuolating Neuronal Tumour}} consistently express OLIG2, HuC/HuD, and non-phosphorylated 200-kDa NFP.
Reference Gallery:
Multinodular and vacuolating neuronal tumour. Confluent and nodular FLAIR hyperintensity, involvement of cortex and superficial white matter, and absence of mass effect are characteristic on MRI.
Multinodular and vacuolating neuronal tumour. Mature-appearing neurons of intermediate to large size populate this nodule with vacuolar matrix changes.
Multinodular and vacuolating neuronal tumour. The neurons of this example are synaptophysin-immunoreactive (but most only weakly).
Multinodular and vacuolating neuronal tumour. Neoplastic neurons exhibit nuclear and cytoplasmic HuC/HuD immunoreactivity.
Multinodular and vacuolating neuronal tumour. Neoplastic neuronal elements manifest nuclear OLIG2 immunoreactivity.
Multinodular and vacuolating neuronal tumour. Ramified, CD34-immunoreactive neural elements are present in this example.
Multinodular and vacuolating neuronal tumour. Discrete tumour nodules with vacuolar changes are apparent.
Multinodular and vacuolating neuronal tumour. Axial MRI demonstrating clustered, T2-hyperintense nodular lesions in the superficial subcortical white matter.

Q: On MRI, Multinodular and Vacuolating Neuronal Tumour characteristically appears as clustered, T2/FLAIR-hyperintense nodules without mass effect, located primarily in the [...].
Multinodular and vacuolating neuronal tumour. Confluent and nodular FLAIR hyperintensity, involvement of cortex and superficial white matter, and absence of mass effect are characteristic on MRI.
Multinodular and vacuolating neuronal tumour. Axial MRI demonstrating clustered, T2-hyperintense nodular lesions in the superficial subcortical white matter.
A: superficial subcortical white matter
Back Extra: Multinodular and Vacuolating Neuronal Tumour
- Clinical: Seizures, particularly of complex partial type, are the most common manifestation of {{Multinodular and Vacuolating Neuronal Tumour}}.
- Micro: {{Multinodular and Vacuolating Neuronal Tumour}} is characterized by pale, hypomyelinated nodules containing monomorphic neuronal elements with vacuolar changes.
- Ancillary: Tumour cells in {{Multinodular and Vacuolating Neuronal Tumour}} consistently express OLIG2, HuC/HuD, and non-phosphorylated 200-kDa NFP.
Reference Gallery:
Multinodular and vacuolating neuronal tumour. Confluent and nodular FLAIR hyperintensity, involvement of cortex and superficial white matter, and absence of mass effect are characteristic on MRI.
Multinodular and vacuolating neuronal tumour. Mature-appearing neurons of intermediate to large size populate this nodule with vacuolar matrix changes.
Multinodular and vacuolating neuronal tumour. The neurons of this example are synaptophysin-immunoreactive (but most only weakly).
Multinodular and vacuolating neuronal tumour. Neoplastic neurons exhibit nuclear and cytoplasmic HuC/HuD immunoreactivity.
Multinodular and vacuolating neuronal tumour. Neoplastic neuronal elements manifest nuclear OLIG2 immunoreactivity.
Multinodular and vacuolating neuronal tumour. Ramified, CD34-immunoreactive neural elements are present in this example.
Multinodular and vacuolating neuronal tumour. Discrete tumour nodules with vacuolar changes are apparent.
Multinodular and vacuolating neuronal tumour. Axial MRI demonstrating clustered, T2-hyperintense nodular lesions in the superficial subcortical white matter.

Q: Histologically, Medulloblastoma, SHH-activated and TP53-mutant often exhibits marked anaplasia and mitotic activity, which is characteristic of the [...] morphologic subtype.
SHH-activated and TP53-mutant medulloblastoma. Marked anaplasia and mitotic activity, consistent with large cell / anaplastic medulloblastoma.
A: large cell / anaplastic
Medulloblastoma, SHH-activated and TP53-mutant
- Clinical: Most patients with Medulloblastoma, SHH-activated and TP53-mutant present with symptoms of raised intracranial pressure due to hydrocephalus, and the tumours often appear as solid, intensely contrast-enhancing masses on imaging.
- Micro: Histologically, Medulloblastoma, SHH-activated and TP53-mutant often shows marked anaplasia and mitotic activity, consistent with the large cell / anaplastic subtype.
- Ancillary: Immunohistochemistry reveals widespread strong nuclear immunoreactivity for p53 in Medulloblastoma, SHH-activated and TP53-mutant, indicating the presence of a TP53 mutation.
Reference Gallery:
SHH-activated and TP53-mutant medulloblastoma. Marked anaplasia and mitotic activity, consistent with large cell / anaplastic medulloblastoma.
SHH-activated and TP53-mutant medulloblastoma. Widespread strong nuclear immunoreactivity for p53, reflecting the presence of a TP53 mutation.

Q: By definition, immunohistochemistry in Medulloblastoma, SHH-activated and TP53-mutant reveals widespread, strong nuclear immunoreactivity for [...].
SHH-activated and TP53-mutant medulloblastoma. Widespread strong nuclear immunoreactivity for p53, reflecting the presence of a TP53 mutation.
A: p53
Medulloblastoma, SHH-activated and TP53-mutant
- Clinical: Most patients with Medulloblastoma, SHH-activated and TP53-mutant present with symptoms of raised intracranial pressure due to hydrocephalus, and the tumours often appear as solid, intensely contrast-enhancing masses on imaging.
- Micro: Histologically, Medulloblastoma, SHH-activated and TP53-mutant often shows marked anaplasia and mitotic activity, consistent with the large cell / anaplastic subtype.
- Ancillary: Immunohistochemistry reveals widespread strong nuclear immunoreactivity for p53 in Medulloblastoma, SHH-activated and TP53-mutant, indicating the presence of a TP53 mutation.
Reference Gallery:
SHH-activated and TP53-mutant medulloblastoma. Marked anaplasia and mitotic activity, consistent with large cell / anaplastic medulloblastoma.
SHH-activated and TP53-mutant medulloblastoma. Widespread strong nuclear immunoreactivity for p53, reflecting the presence of a TP53 mutation.

Q: A characteristic histological finding in the classic variant of Medulloblastoma, histologically defined, is the presence of undifferentiated tumor cells organizing into neuroblastic structures known as [...].
Histopathological features of classic medulloblastoma. Typical syncytial arrangement of undifferentiated tumour cells.
Histopathological features of classic medulloblastoma. Area with Homer Wright (neuroblastic) rosettes.
A: Homer Wright rosettes
Back Extra: Medulloblastoma, histologically defined
- Clinical: Most patients with Medulloblastoma, histologically defined, present with symptoms of raised intracranial pressure due to non-communicating hydrocephalus from occlusion of the fourth ventricle.
- Micro: Classic Medulloblastoma is characterized by densely packed, poorly differentiated cells with hyperchromatic nuclei, increased mitotic activity, and apoptotic bodies.
- Ancillary: Immunohistochemical studies of Medulloblastoma, histologically defined, show expression of CD56, MAP2, NSE, synaptophysin, and NeuN in classic medulloblastomas.
Reference Gallery:
Desmoplastic/nodular medulloblastoma. Reticulin fibre-rich areas of the tumour ensheath fibre-free islands (silver impregnation).
Large cell / anaplastic medulloblastoma. Severe cytological anaplasia with increased nuclear pleomorphism, nuclear moulding, and bizarre mitotic figures.
Large cell / anaplastic medulloblastoma. Large cell cytology with round nuclei and singular large prominent nucleoli.
Medulloblastoma. Axial T2-weighted MRI. The midline tumour is slightly T2-hyperintense as compared with the cerebellar hemispheres. There are markedly hypointense calcifications and hyperintense cystic changes within the tumour.
Histopathological features of classic medulloblastoma. Typical syncytial arrangement of undifferentiated tumour cells.
Histopathological features of classic medulloblastoma. Area with Homer Wright (neuroblastic) rosettes.
Medulloblastoma. Focal expression of synaptophysin.
Medulloblastoma. Focal GFAP staining of tumour cells.
Medulloblastoma. Clusters of medulloblastoma cells expressing retinal S-antigen.
Classic medulloblastoma with nodules but no desmoplasia. These medulloblastomas belong to the non-WNT/non-SHH molecular group and should not be mistaken for desmoplastic/nodular medulloblastomas.
Desmoplastic/nodular medulloblastoma. Reticulin silver impregnation showing the reticulin-free pale islands.
Medulloblastoma with extensive nodularity. Strong immunoreactivity for NeuN in the neurocytic cells of the pale islands.

Q: The desmoplastic/nodular variant of Medulloblastoma, histologically defined, demonstrates a biphasic architecture on silver impregnation characterized by reticulin-rich internodular zones ensheathing reticulin-free [...].
Desmoplastic/nodular medulloblastoma. Reticulin fibre-rich areas of the tumour ensheath fibre-free islands (silver impregnation).
Desmoplastic/nodular medulloblastoma. Reticulin silver impregnation showing the reticulin-free pale islands.
A: pale islands
Back Extra: Medulloblastoma, histologically defined
- Clinical: Most patients with Medulloblastoma, histologically defined, present with symptoms of raised intracranial pressure due to non-communicating hydrocephalus from occlusion of the fourth ventricle.
- Micro: Classic Medulloblastoma is characterized by densely packed, poorly differentiated cells with hyperchromatic nuclei, increased mitotic activity, and apoptotic bodies.
- Ancillary: Immunohistochemical studies of Medulloblastoma, histologically defined, show expression of CD56, MAP2, NSE, synaptophysin, and NeuN in classic medulloblastomas.
Reference Gallery:
Desmoplastic/nodular medulloblastoma. Reticulin fibre-rich areas of the tumour ensheath fibre-free islands (silver impregnation).
Large cell / anaplastic medulloblastoma. Severe cytological anaplasia with increased nuclear pleomorphism, nuclear moulding, and bizarre mitotic figures.
Large cell / anaplastic medulloblastoma. Large cell cytology with round nuclei and singular large prominent nucleoli.
Medulloblastoma. Axial T2-weighted MRI. The midline tumour is slightly T2-hyperintense as compared with the cerebellar hemispheres. There are markedly hypointense calcifications and hyperintense cystic changes within the tumour.
Histopathological features of classic medulloblastoma. Typical syncytial arrangement of undifferentiated tumour cells.
Histopathological features of classic medulloblastoma. Area with Homer Wright (neuroblastic) rosettes.
Medulloblastoma. Focal expression of synaptophysin.
Medulloblastoma. Focal GFAP staining of tumour cells.
Medulloblastoma. Clusters of medulloblastoma cells expressing retinal S-antigen.
Classic medulloblastoma with nodules but no desmoplasia. These medulloblastomas belong to the non-WNT/non-SHH molecular group and should not be mistaken for desmoplastic/nodular medulloblastomas.
Desmoplastic/nodular medulloblastoma. Reticulin silver impregnation showing the reticulin-free pale islands.
Medulloblastoma with extensive nodularity. Strong immunoreactivity for NeuN in the neurocytic cells of the pale islands.

Q: On neuroimaging, Medulloblastoma, histologically defined, typically presents as a midline cerebellar tumor that frequently causes non-communicating hydrocephalus by compressing and occluding the [...].
Medulloblastoma. Axial T2-weighted MRI. The midline tumour is slightly T2-hyperintense as compared with the cerebellar hemispheres. There are markedly hypointense calcifications and hyperintense cystic changes within the tumour.
A: fourth ventricle
Back Extra: Medulloblastoma, histologically defined
- Clinical: Most patients with Medulloblastoma, histologically defined, present with symptoms of raised intracranial pressure due to non-communicating hydrocephalus from occlusion of the fourth ventricle.
- Micro: Classic Medulloblastoma is characterized by densely packed, poorly differentiated cells with hyperchromatic nuclei, increased mitotic activity, and apoptotic bodies.
- Ancillary: Immunohistochemical studies of Medulloblastoma, histologically defined, show expression of CD56, MAP2, NSE, synaptophysin, and NeuN in classic medulloblastomas.
Reference Gallery:
Desmoplastic/nodular medulloblastoma. Reticulin fibre-rich areas of the tumour ensheath fibre-free islands (silver impregnation).
Large cell / anaplastic medulloblastoma. Severe cytological anaplasia with increased nuclear pleomorphism, nuclear moulding, and bizarre mitotic figures.
Large cell / anaplastic medulloblastoma. Large cell cytology with round nuclei and singular large prominent nucleoli.
Medulloblastoma. Axial T2-weighted MRI. The midline tumour is slightly T2-hyperintense as compared with the cerebellar hemispheres. There are markedly hypointense calcifications and hyperintense cystic changes within the tumour.
Histopathological features of classic medulloblastoma. Typical syncytial arrangement of undifferentiated tumour cells.
Histopathological features of classic medulloblastoma. Area with Homer Wright (neuroblastic) rosettes.
Medulloblastoma. Focal expression of synaptophysin.
Medulloblastoma. Focal GFAP staining of tumour cells.
Medulloblastoma. Clusters of medulloblastoma cells expressing retinal S-antigen.
Classic medulloblastoma with nodules but no desmoplasia. These medulloblastomas belong to the non-WNT/non-SHH molecular group and should not be mistaken for desmoplastic/nodular medulloblastomas.
Desmoplastic/nodular medulloblastoma. Reticulin silver impregnation showing the reticulin-free pale islands.
Medulloblastoma with extensive nodularity. Strong immunoreactivity for NeuN in the neurocytic cells of the pale islands.

Q: In Medulloblastoma, WNT-activated, immunohistochemistry characteristically demonstrates patchy or universal nuclear accumulation of [...].
Medulloblastoma, WNT-activated. Diffuse nuclear immunoreactivity for β-catenin.
Medulloblastoma, WNT-activated. Patchy nuclear immunoreactivity for β-catenin.
A: β-catenin
Back Extra: Medulloblastoma, WNT-activated
- Clinical: Most patients present with symptoms of raised intracranial pressure due to obstruction of the fourth ventricle by the primary tumour.
- Micro: Nearly all WNT-activated medulloblastomas have a classic morphology with universal or patchy nuclear immunoreactivity for β-catenin.
- Ancillary: CTNNB1 exon 3 mutations and monosomy 6 are present in > 80% of WNT-activated medulloblastomas.
Reference Gallery:
Medulloblastoma, WNT-activated. MRI of WNT-activated medulloblastoma arising in the cerebellopontine angle.
Medulloblastoma, WNT-activated. Diffuse nuclear immunoreactivity for β-catenin.
Medulloblastoma, WNT-activated. Patchy nuclear immunoreactivity for β-catenin.

Q: While primary tumors often obstruct the fourth ventricle, MRI of Medulloblastoma, WNT-activated may also demonstrate the tumor arising laterally in the [...].
Medulloblastoma, WNT-activated. MRI of WNT-activated medulloblastoma arising in the cerebellopontine angle.
A: cerebellopontine angle
Back Extra: Medulloblastoma, WNT-activated
- Clinical: Most patients present with symptoms of raised intracranial pressure due to obstruction of the fourth ventricle by the primary tumour.
- Micro: Nearly all WNT-activated medulloblastomas have a classic morphology with universal or patchy nuclear immunoreactivity for β-catenin.
- Ancillary: CTNNB1 exon 3 mutations and monosomy 6 are present in > 80% of WNT-activated medulloblastomas.
Reference Gallery:
Medulloblastoma, WNT-activated. MRI of WNT-activated medulloblastoma arising in the cerebellopontine angle.
Medulloblastoma, WNT-activated. Diffuse nuclear immunoreactivity for β-catenin.
Medulloblastoma, WNT-activated. Patchy nuclear immunoreactivity for β-catenin.

Q: In Diffuse Meningeal Melanocytosis and Melanomatosis, the "melanomatosis" component is distinguished histologically by malignant melanocytic cells that diffusely infiltrate the [...], whereas melanocytosis is confined to the subarachnoid and Virchow-Robin spaces.
Meningeal melanocytosis. Melanocytic cells with benign features diffusely proliferate within the meninges between the nerve roots of the lower spinal cord.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
A: CNS parenchyma
Back Extra: Diffuse Meningeal Melanocytosis and Melanomatosis
- Clinical: Patients with diffuse meningeal melanocytosis and melanomatosis often present with neurological symptoms such as neuropsychiatric issues, bowel and bladder dysfunction, and sensory and motor disturbances.
- Micro: Histologically, meningeal melanocytosis is characterized by the proliferation of cytologically bland melanocytic cells within the subarachnoid and Virchow–Robin spaces, while meningeal melanomatosis shows malignant melanocytic cells diffusely infiltrating the CNS parenchyma.
- Ancillary: Immunohistochemistry shows positivity for melanocytic markers (HMB-45, Melan-A, S-100), and molecular testing often reveals NRAS mutations.
Reference Gallery:
Meningeal melanocytosis. Autopsy findings in a child with meningeal melanocytosis. The meninges of the lower spinal cord appear diffusely packed with tumour tissue. The lesion harboured an NRAS p.Q61K mutation.
Meningeal melanomatosis. Macroscopy of meningeal melanomatosis in a child with neurocutaneous melanosis who succumbed at the age of 17 months due to rapid disease progression.
Meningeal melanocytosis. Melanocytic cells with benign features diffusely proliferate within the meninges between the nerve roots of the lower spinal cord.
Meningeal melanomatosis. T1-weighted axial MRI revealing a hyperintense, contrast-enhancing lesion outlining the gyri and sulci in the left fronto-parieto-occipital region in a 5-year-old child.
Meningeal melanomatosis. Macroscopic appearance of the cerebral tissue shows brownish discolouration of the thickened leptomeninges and black discolouration of the underlying cerebral cortex.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
Meningeal melanomatosis. A subpopulation of melanoma cells are heavily pigmented.
Melanoma arising from meningeal melanocytosis. Meningeal melanoma in an adult with neurocutaneous melanosis and melanocytosis. The melanoma cells infiltrate the surrounding brain tissue.
Melanoma arising from meningeal melanocytosis. The areas with meningeal melanocytosis are heavily pigmented.
Melanoma arising from meningeal melanocytosis. The meningeal melanoma infiltrates the brain around the small vessels.

Q: A characteristic gross and radiologic finding in Diffuse Meningeal Melanocytosis and Melanomatosis is diffuse brownish-black discoloration and tumor thickening that predominantly outlines the [...] (following the gyri and sulci).
Meningeal melanomatosis. T1-weighted axial MRI revealing a hyperintense, contrast-enhancing lesion outlining the gyri and sulci in the left fronto-parieto-occipital region in a 5-year-old child.
Meningeal melanomatosis. Macroscopic appearance of the cerebral tissue shows brownish discolouration of the thickened leptomeninges and black discolouration of the underlying cerebral cortex.
A: leptomeninges
Back Extra: Diffuse Meningeal Melanocytosis and Melanomatosis
- Clinical: Patients with diffuse meningeal melanocytosis and melanomatosis often present with neurological symptoms such as neuropsychiatric issues, bowel and bladder dysfunction, and sensory and motor disturbances.
- Micro: Histologically, meningeal melanocytosis is characterized by the proliferation of cytologically bland melanocytic cells within the subarachnoid and Virchow–Robin spaces, while meningeal melanomatosis shows malignant melanocytic cells diffusely infiltrating the CNS parenchyma.
- Ancillary: Immunohistochemistry shows positivity for melanocytic markers (HMB-45, Melan-A, S-100), and molecular testing often reveals NRAS mutations.
Reference Gallery:
Meningeal melanocytosis. Autopsy findings in a child with meningeal melanocytosis. The meninges of the lower spinal cord appear diffusely packed with tumour tissue. The lesion harboured an NRAS p.Q61K mutation.
Meningeal melanomatosis. Macroscopy of meningeal melanomatosis in a child with neurocutaneous melanosis who succumbed at the age of 17 months due to rapid disease progression.
Meningeal melanocytosis. Melanocytic cells with benign features diffusely proliferate within the meninges between the nerve roots of the lower spinal cord.
Meningeal melanomatosis. T1-weighted axial MRI revealing a hyperintense, contrast-enhancing lesion outlining the gyri and sulci in the left fronto-parieto-occipital region in a 5-year-old child.
Meningeal melanomatosis. Macroscopic appearance of the cerebral tissue shows brownish discolouration of the thickened leptomeninges and black discolouration of the underlying cerebral cortex.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
Meningeal melanomatosis. A subpopulation of melanoma cells are heavily pigmented.
Melanoma arising from meningeal melanocytosis. Meningeal melanoma in an adult with neurocutaneous melanosis and melanocytosis. The melanoma cells infiltrate the surrounding brain tissue.
Melanoma arising from meningeal melanocytosis. The areas with meningeal melanocytosis are heavily pigmented.
Melanoma arising from meningeal melanocytosis. The meningeal melanoma infiltrates the brain around the small vessels.

Q: Molecular testing of lesions in Diffuse Meningeal Melanocytosis and Melanomatosis frequently reveals activating mutations in the [...] gene.
Meningeal melanocytosis. Autopsy findings in a child with meningeal melanocytosis. The meninges of the lower spinal cord appear diffusely packed with tumour tissue. The lesion harboured an NRAS p.Q61K mutation.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
A: NRAS
Back Extra: Diffuse Meningeal Melanocytosis and Melanomatosis
- Clinical: Patients with diffuse meningeal melanocytosis and melanomatosis often present with neurological symptoms such as neuropsychiatric issues, bowel and bladder dysfunction, and sensory and motor disturbances.
- Micro: Histologically, meningeal melanocytosis is characterized by the proliferation of cytologically bland melanocytic cells within the subarachnoid and Virchow–Robin spaces, while meningeal melanomatosis shows malignant melanocytic cells diffusely infiltrating the CNS parenchyma.
- Ancillary: Immunohistochemistry shows positivity for melanocytic markers (HMB-45, Melan-A, S-100), and molecular testing often reveals NRAS mutations.
Reference Gallery:
Meningeal melanocytosis. Autopsy findings in a child with meningeal melanocytosis. The meninges of the lower spinal cord appear diffusely packed with tumour tissue. The lesion harboured an NRAS p.Q61K mutation.
Meningeal melanomatosis. Macroscopy of meningeal melanomatosis in a child with neurocutaneous melanosis who succumbed at the age of 17 months due to rapid disease progression.
Meningeal melanocytosis. Melanocytic cells with benign features diffusely proliferate within the meninges between the nerve roots of the lower spinal cord.
Meningeal melanomatosis. T1-weighted axial MRI revealing a hyperintense, contrast-enhancing lesion outlining the gyri and sulci in the left fronto-parieto-occipital region in a 5-year-old child.
Meningeal melanomatosis. Macroscopic appearance of the cerebral tissue shows brownish discolouration of the thickened leptomeninges and black discolouration of the underlying cerebral cortex.
Meningeal melanomatosis. Malignant melanocytic cells diffusely infiltrate the underlying brain parenchyma. The tumour carries an NRAS p.Q61R mutation.
Meningeal melanomatosis. A subpopulation of melanoma cells are heavily pigmented.
Melanoma arising from meningeal melanocytosis. Meningeal melanoma in an adult with neurocutaneous melanosis and melanocytosis. The melanoma cells infiltrate the surrounding brain tissue.
Melanoma arising from meningeal melanocytosis. The areas with meningeal melanocytosis are heavily pigmented.
Melanoma arising from meningeal melanocytosis. The meningeal melanoma infiltrates the brain around the small vessels.

Q: A localized, alopecic, and mildly pigmented scalp mass in a child that microscopically reveals a thinned dermis with scattered, deep syncytial cell clusters is characteristic of [...].
Meningothelial hamartoma. A tumour in the right parieto-occipital paramedian region of the scalp in a 7-year-old child. The lesion is mildly elevated, alopecic, and pigmented.
Meningothelial hamartoma. A low-power view of the scalp lesion shown in Fig. 23743. Note the depressed and atrophic epidermal surface overlying a thinned dermis with decreased adnexal structures.
Meningothelial hamartoma. At higher magnification, the abnormal subcutaneous tissue shows scattered clusters of meningothelial elements.
A: Ectopic Meningioma and Meningothelial Hamartoma
Back Extra: Ectopic Meningioma and Meningothelial Hamartoma
- Clinical: Ectopic meningiomas present as painless, slow-growing masses, while meningothelial hamartomas are typically detected as incidental scalp masses or dimples, sometimes with alopecia and/or tenderness.
- Micro: Both ectopic meningiomas and meningothelial hamartomas can show slit-like spaces resembling lymphatics, with well-formed meningothelial clusters and psammoma bodies in meningiomas.
- Ancillary: Immunohistochemical markers such as EMA and vimentin are crucial for confirming the presence of meningothelial elements in these lesions.
Reference Gallery:
Meningothelial hamartoma. A tumour in the right parieto-occipital paramedian region of the scalp in a 7-year-old child. The lesion is mildly elevated, alopecic, and pigmented.
Meningothelial hamartoma. A low-power view of the scalp lesion shown in Fig. 23743. Note the depressed and atrophic epidermal surface overlying a thinned dermis with decreased adnexal structures.
Meningothelial hamartoma. At higher magnification, the abnormal subcutaneous tissue shows scattered clusters of meningothelial elements.
Meningothelial hamartoma. One of several foci of meningothelial elements from the patient shown in Fig. 23743.
Meningothelial hamartoma. EMA immunohistochemistry highlights the meningothelial elements.

Q: To confirm a diagnosis of Ectopic Meningioma and Meningothelial Hamartoma, immunohistochemistry can be performed to demonstrate that the characteristic subcutaneous cellular clusters are strongly positive for vimentin and [...].
Meningothelial hamartoma. One of several foci of meningothelial elements from the patient shown in Fig. 23743.
Meningothelial hamartoma. EMA immunohistochemistry highlights the meningothelial elements.
A: EMA
Back Extra: Ectopic Meningioma and Meningothelial Hamartoma
- Clinical: Ectopic meningiomas present as painless, slow-growing masses, while meningothelial hamartomas are typically detected as incidental scalp masses or dimples, sometimes with alopecia and/or tenderness.
- Micro: Both ectopic meningiomas and meningothelial hamartomas can show slit-like spaces resembling lymphatics, with well-formed meningothelial clusters and psammoma bodies in meningiomas.
- Ancillary: Immunohistochemical markers such as EMA and vimentin are crucial for confirming the presence of meningothelial elements in these lesions.
Reference Gallery:
Meningothelial hamartoma. A tumour in the right parieto-occipital paramedian region of the scalp in a 7-year-old child. The lesion is mildly elevated, alopecic, and pigmented.
Meningothelial hamartoma. A low-power view of the scalp lesion shown in Fig. 23743. Note the depressed and atrophic epidermal surface overlying a thinned dermis with decreased adnexal structures.
Meningothelial hamartoma. At higher magnification, the abnormal subcutaneous tissue shows scattered clusters of meningothelial elements.
Meningothelial hamartoma. One of several foci of meningothelial elements from the patient shown in Fig. 23743.
Meningothelial hamartoma. EMA immunohistochemistry highlights the meningothelial elements.

Q: Clinically and radiologically, Pineoblastoma often presents as an invasive tumor in the pineal region that frequently causes obstructive [...] due to mass effect.
Pineoblastoma. This patient has obstructive triventricular hydrocephalus (T2-weighted MRI).
Pineoblastoma. A tumour located in the pineal region appears mildly hypointense on T2-weighted MRI.
A: triventricular hydrocephalus
Back Extra: Pineoblastoma
- Clinical: Pineoblastomas often present as large, invasive tumours causing obstructive hydrocephalus and commonly show craniospinal dissemination.
- Micro: Pineoblastomas are highly cellular, composed of small cells with a high N:C ratio, hyperchromatic nuclei, and frequent mitoses and necrosis.
- Ancillary: Pineoblastomas show molecular alterations in miRNA processing genes like DICER1, DROSHA, or DGCR8, and exhibit diffuse nuclear expression of CRX.
Reference Gallery:
Pineoblastoma. This patient has obstructive triventricular hydrocephalus (T2-weighted MRI).
Pineoblastoma. This is a highly cellular tumour composed of small cells with a high N:C ratio; atypical, angular, hyperchromatic nuclei; and frequent mitoses and apoptotic bodies.
Pineoblastoma. These tumours frequently show areas of necrosis.
Pineoblastoma. There is diffuse expression of synaptophysin with paranuclear dot–like reactivity.
Pineoblastoma. A tumour located in the pineal region appears mildly hypointense on T2-weighted MRI.

Q: Microscopically, Pineoblastoma is a highly cellular embryonal tumor composed of small cells with a high N:C ratio, frequent mitoses, apoptotic bodies, and commonly exhibits regions of [...].
Pineoblastoma. This is a highly cellular tumour composed of small cells with a high N:C ratio; atypical, angular, hyperchromatic nuclei; and frequent mitoses and apoptotic bodies.
Pineoblastoma. These tumours frequently show areas of necrosis.
A: necrosis
Back Extra: Pineoblastoma
- Clinical: Pineoblastomas often present as large, invasive tumours causing obstructive hydrocephalus and commonly show craniospinal dissemination.
- Micro: Pineoblastomas are highly cellular, composed of small cells with a high N:C ratio, hyperchromatic nuclei, and frequent mitoses and necrosis.
- Ancillary: Pineoblastomas show molecular alterations in miRNA processing genes like DICER1, DROSHA, or DGCR8, and exhibit diffuse nuclear expression of CRX.
Reference Gallery:
Pineoblastoma. This patient has obstructive triventricular hydrocephalus (T2-weighted MRI).
Pineoblastoma. This is a highly cellular tumour composed of small cells with a high N:C ratio; atypical, angular, hyperchromatic nuclei; and frequent mitoses and apoptotic bodies.
Pineoblastoma. These tumours frequently show areas of necrosis.
Pineoblastoma. There is diffuse expression of synaptophysin with paranuclear dot–like reactivity.
Pineoblastoma. A tumour located in the pineal region appears mildly hypointense on T2-weighted MRI.

Q: Immunohistochemical staining of Pineoblastoma typically demonstrates diffuse expression of [...] with characteristic paranuclear dot-like reactivity.
Pineoblastoma. There is diffuse expression of synaptophysin with paranuclear dot–like reactivity.
A: synaptophysin
Back Extra: Pineoblastoma
- Clinical: Pineoblastomas often present as large, invasive tumours causing obstructive hydrocephalus and commonly show craniospinal dissemination.
- Micro: Pineoblastomas are highly cellular, composed of small cells with a high N:C ratio, hyperchromatic nuclei, and frequent mitoses and necrosis.
- Ancillary: Pineoblastomas show molecular alterations in miRNA processing genes like DICER1, DROSHA, or DGCR8, and exhibit diffuse nuclear expression of CRX.
Reference Gallery:
Pineoblastoma. This patient has obstructive triventricular hydrocephalus (T2-weighted MRI).
Pineoblastoma. This is a highly cellular tumour composed of small cells with a high N:C ratio; atypical, angular, hyperchromatic nuclei; and frequent mitoses and apoptotic bodies.
Pineoblastoma. These tumours frequently show areas of necrosis.
Pineoblastoma. There is diffuse expression of synaptophysin with paranuclear dot–like reactivity.
Pineoblastoma. A tumour located in the pineal region appears mildly hypointense on T2-weighted MRI.

Q: The classic histologic features of Adamantinomatous Craniopharyngioma include basal palisading, a loose stellate reticulum, and nodules of anucleate squamous "ghost" cells known as [...].
Adamantinomatous craniopharyngioma. Basal palisading of tumour cells along the tumour–brain interface, epithelial whorls, stellate reticulum, and wet keratin.
Adamantinomatous craniopharyngioma. A characteristic feature of adamantinomatous craniopharyngioma but not papillary craniopharyngioma is the presence of wet keratin, which is composed of anucleate ghost cells. A second characteristic feature limited to this type is a concentration of cells at the perimeter of the epithelial trabeculae, i.e. tumour palisading.
A: wet keratin
Back Extra: Adamantinomatous Craniopharyngioma
- Clinical: Adamantinomatous craniopharyngioma commonly presents with visual impairment (62–84%) and endocrine deficits (52–87%), affecting growth hormone, LH/FSH, TSH, ACTH, and antidiuretic hormone.
- Micro: The tumour epithelium of adamantinomatous craniopharyngioma is well-differentiated, forming cords, lobules, ribbons, and nodular whorls, with characteristic wet keratin and stellate reticulum.
- Ancillary: Characterized by activating mutations in exon 3 of CTNNB1, with nuclear accumulation of β-catenin observed in only a subset of cells, particularly in epithelial whorls or surrounding wet keratin.
Reference Gallery:
Adamantinomatous craniopharyngioma. Basal palisading of tumour cells along the tumour–brain interface, epithelial whorls, stellate reticulum, and wet keratin.
Adamantinomatous craniopharyngioma. Tumour extending into adjacent brain tissue that has reactive changes including piloid gliosis and Rosenthal fibres. Epithelial whorling is commonly present in protrusions.
Adamantinomatous craniopharyngioma. High-power view of the interface of adamantinomatous craniopharyngioma and brain tissue; Rosenthal fibres are present in the reactive piloid gliosis.
Adamantinomatous craniopharyngioma. Characteristic very high tumour cell proliferation in malignant craniopharyngioma, as indicated by Ki-67 index.
Adamantinomatous craniopharyngioma. Even though mutations in exon 3 of CTNNB1, which encodes β-catenin, are clonal and present across the tumour epithelium, β-catenin protein accumulates in the nucleus of only a subset of cells, such as ones that are scattered individually and present in small clusters.
Adamantinomatous craniopharyngioma. This adamantinomatous craniopharyngioma in an adult is composed of cords and trabeculae of cells punctuated by irregularly distributed clumps of wet keratin with superimposed calcification.
Adamantinomatous craniopharyngioma. A characteristic feature of adamantinomatous craniopharyngioma but not papillary craniopharyngioma is the presence of wet keratin, which is composed of anucleate ghost cells. A second characteristic feature limited to this type is a concentration of cells at the perimeter of the epithelial trabeculae, i.e. tumour palisading.
Adamantinomatous craniopharyngioma. Although cytologically bland, adamantinomatous craniopharyngioma can be clinically aggressive because of its tendency to invade into surrounding eloquent neural tissue, eliciting intense reactive gliosis and Rosenthal fibres. Tumours show oval nuclei with an absence of nuclear pleomorphism and modest amounts of cytoplasm. Note that the calcification occurs within the wet keratin not the epithelium. Note also the mucinous cysts throughout the epithelium; these can coalesce to form larger cysts.
Adamantinomatous craniopharyngioma. In some examples, the tumour architecture forms ribbon-like strands of cells with few (if any) areas of wet keratin.
Adamantinomatous craniopharyngioma. The cytologically bland epithelium is associated with wet keratin, also known as ghost cells – a term that underscores the fact that the faint outline of nuclei may still be visible on H&E in the exfoliated cells from the tumour epithelium.
Adamantinomatous craniopharyngioma. Pankeratin (immunostaining for AE1/AE3 with light haematoxylin counterstain) reveals the few semiviable epithelial cells surrounding the wet keratin in this tumour, with the wet keratin seen as bluish-grey amorphous material on this immunostain (centre and at right).
Adamantinomatous craniopharyngioma. Cholesterol debris, evidenced by cleft formation, can be found in some tumours; this is evidence of prior bleeding into the tumour.

Q: Adamantinomatous Craniopharyngioma is characterized by activating mutations in exon 3 of CTNNB1, which can be identified on immunohistochemistry by the focal nuclear accumulation of [...].
Adamantinomatous craniopharyngioma. Even though mutations in exon 3 of CTNNB1, which encodes β-catenin, are clonal and present across the tumour epithelium, β-catenin protein accumulates in the nucleus of only a subset of cells, such as ones that are scattered individually and present in small clusters.
A: β-catenin
Back Extra: Adamantinomatous Craniopharyngioma
- Clinical: Adamantinomatous craniopharyngioma commonly presents with visual impairment (62–84%) and endocrine deficits (52–87%), affecting growth hormone, LH/FSH, TSH, ACTH, and antidiuretic hormone.
- Micro: The tumour epithelium of adamantinomatous craniopharyngioma is well-differentiated, forming cords, lobules, ribbons, and nodular whorls, with characteristic wet keratin and stellate reticulum.
- Ancillary: Characterized by activating mutations in exon 3 of CTNNB1, with nuclear accumulation of β-catenin observed in only a subset of cells, particularly in epithelial whorls or surrounding wet keratin.
Reference Gallery:
Adamantinomatous craniopharyngioma. Basal palisading of tumour cells along the tumour–brain interface, epithelial whorls, stellate reticulum, and wet keratin.
Adamantinomatous craniopharyngioma. Tumour extending into adjacent brain tissue that has reactive changes including piloid gliosis and Rosenthal fibres. Epithelial whorling is commonly present in protrusions.
Adamantinomatous craniopharyngioma. High-power view of the interface of adamantinomatous craniopharyngioma and brain tissue; Rosenthal fibres are present in the reactive piloid gliosis.
Adamantinomatous craniopharyngioma. Characteristic very high tumour cell proliferation in malignant craniopharyngioma, as indicated by Ki-67 index.
Adamantinomatous craniopharyngioma. Even though mutations in exon 3 of CTNNB1, which encodes β-catenin, are clonal and present across the tumour epithelium, β-catenin protein accumulates in the nucleus of only a subset of cells, such as ones that are scattered individually and present in small clusters.
Adamantinomatous craniopharyngioma. This adamantinomatous craniopharyngioma in an adult is composed of cords and trabeculae of cells punctuated by irregularly distributed clumps of wet keratin with superimposed calcification.
Adamantinomatous craniopharyngioma. A characteristic feature of adamantinomatous craniopharyngioma but not papillary craniopharyngioma is the presence of wet keratin, which is composed of anucleate ghost cells. A second characteristic feature limited to this type is a concentration of cells at the perimeter of the epithelial trabeculae, i.e. tumour palisading.
Adamantinomatous craniopharyngioma. Although cytologically bland, adamantinomatous craniopharyngioma can be clinically aggressive because of its tendency to invade into surrounding eloquent neural tissue, eliciting intense reactive gliosis and Rosenthal fibres. Tumours show oval nuclei with an absence of nuclear pleomorphism and modest amounts of cytoplasm. Note that the calcification occurs within the wet keratin not the epithelium. Note also the mucinous cysts throughout the epithelium; these can coalesce to form larger cysts.
Adamantinomatous craniopharyngioma. In some examples, the tumour architecture forms ribbon-like strands of cells with few (if any) areas of wet keratin.
Adamantinomatous craniopharyngioma. The cytologically bland epithelium is associated with wet keratin, also known as ghost cells – a term that underscores the fact that the faint outline of nuclei may still be visible on H&E in the exfoliated cells from the tumour epithelium.
Adamantinomatous craniopharyngioma. Pankeratin (immunostaining for AE1/AE3 with light haematoxylin counterstain) reveals the few semiviable epithelial cells surrounding the wet keratin in this tumour, with the wet keratin seen as bluish-grey amorphous material on this immunostain (centre and at right).
Adamantinomatous craniopharyngioma. Cholesterol debris, evidenced by cleft formation, can be found in some tumours; this is evidence of prior bleeding into the tumour.

Q: Although cytologically bland, Adamantinomatous Craniopharyngioma often invades adjacent neural tissue, eliciting an intense reactive piloid gliosis that is characteristically rich in [...].
Adamantinomatous craniopharyngioma. High-power view of the interface of adamantinomatous craniopharyngioma and brain tissue; Rosenthal fibres are present in the reactive piloid gliosis.
Adamantinomatous craniopharyngioma. Although cytologically bland, adamantinomatous craniopharyngioma can be clinically aggressive because of its tendency to invade into surrounding eloquent neural tissue, eliciting intense reactive gliosis and Rosenthal fibres. Tumours show oval nuclei with an absence of nuclear pleomorphism and modest amounts of cytoplasm. Note that the calcification occurs within the wet keratin not the epithelium. Note also the mucinous cysts throughout the epithelium; these can coalesce to form larger cysts.
A: Rosenthal fibers
Back Extra: Adamantinomatous Craniopharyngioma
- Clinical: Adamantinomatous craniopharyngioma commonly presents with visual impairment (62–84%) and endocrine deficits (52–87%), affecting growth hormone, LH/FSH, TSH, ACTH, and antidiuretic hormone.
- Micro: The tumour epithelium of adamantinomatous craniopharyngioma is well-differentiated, forming cords, lobules, ribbons, and nodular whorls, with characteristic wet keratin and stellate reticulum.
- Ancillary: Characterized by activating mutations in exon 3 of CTNNB1, with nuclear accumulation of β-catenin observed in only a subset of cells, particularly in epithelial whorls or surrounding wet keratin.
Reference Gallery:
Adamantinomatous craniopharyngioma. Basal palisading of tumour cells along the tumour–brain interface, epithelial whorls, stellate reticulum, and wet keratin.
Adamantinomatous craniopharyngioma. Tumour extending into adjacent brain tissue that has reactive changes including piloid gliosis and Rosenthal fibres. Epithelial whorling is commonly present in protrusions.
Adamantinomatous craniopharyngioma. High-power view of the interface of adamantinomatous craniopharyngioma and brain tissue; Rosenthal fibres are present in the reactive piloid gliosis.
Adamantinomatous craniopharyngioma. Characteristic very high tumour cell proliferation in malignant craniopharyngioma, as indicated by Ki-67 index.
Adamantinomatous craniopharyngioma. Even though mutations in exon 3 of CTNNB1, which encodes β-catenin, are clonal and present across the tumour epithelium, β-catenin protein accumulates in the nucleus of only a subset of cells, such as ones that are scattered individually and present in small clusters.
Adamantinomatous craniopharyngioma. This adamantinomatous craniopharyngioma in an adult is composed of cords and trabeculae of cells punctuated by irregularly distributed clumps of wet keratin with superimposed calcification.
Adamantinomatous craniopharyngioma. A characteristic feature of adamantinomatous craniopharyngioma but not papillary craniopharyngioma is the presence of wet keratin, which is composed of anucleate ghost cells. A second characteristic feature limited to this type is a concentration of cells at the perimeter of the epithelial trabeculae, i.e. tumour palisading.
Adamantinomatous craniopharyngioma. Although cytologically bland, adamantinomatous craniopharyngioma can be clinically aggressive because of its tendency to invade into surrounding eloquent neural tissue, eliciting intense reactive gliosis and Rosenthal fibres. Tumours show oval nuclei with an absence of nuclear pleomorphism and modest amounts of cytoplasm. Note that the calcification occurs within the wet keratin not the epithelium. Note also the mucinous cysts throughout the epithelium; these can coalesce to form larger cysts.
Adamantinomatous craniopharyngioma. In some examples, the tumour architecture forms ribbon-like strands of cells with few (if any) areas of wet keratin.
Adamantinomatous craniopharyngioma. The cytologically bland epithelium is associated with wet keratin, also known as ghost cells – a term that underscores the fact that the faint outline of nuclei may still be visible on H&E in the exfoliated cells from the tumour epithelium.
Adamantinomatous craniopharyngioma. Pankeratin (immunostaining for AE1/AE3 with light haematoxylin counterstain) reveals the few semiviable epithelial cells surrounding the wet keratin in this tumour, with the wet keratin seen as bluish-grey amorphous material on this immunostain (centre and at right).
Adamantinomatous craniopharyngioma. Cholesterol debris, evidenced by cleft formation, can be found in some tumours; this is evidence of prior bleeding into the tumour.

Q: Histologically, Pituitary Adenoma / Pituitary Neuroendocrine Tumor (PitNET) generally consists of a [...] population of cells with bland nuclei and regular chromatin, lacking extensive pleomorphism or brisk mitotic activity.
Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. This image shows a homogeneous population of slightly eosinophilic cells containing a central nucleus with well-dispersed chromatin and a small nucleolus.
A: monomorphic
Back Extra: Pituitary Adenoma / Pituitary Neuroendocrine Tumour (PitNET)
- Clinical: Pituitary Adenoma / PitNETs can present with hormone excess syndromes (e.g., acromegaly, Cushing disease) or as large, symptomatic masses causing headaches, visual disturbances, and hypopituitarism.
- Micro: These tumours are generally monomorphic, with cells arranged in diffuse, papillary, or trabecular patterns. Nuclei are typically bland with regular chromatin, and the presence of extensive cellular pleomorphism, brisk mitotic activity, and necrosis should prompt consideration of other diagnoses.
- Ancillary: Immunohistochemistry (IHC) is crucial for subtyping PitNETs. For example, somatotroph adenomas are strongly positive for GH, while lactotroph adenomas show intense nuclear ER staining and juxtanuclear prolactin positivity.
Reference Gallery:
Pituitary adenoma / pituitary neuroendocrine tumour (PitNET). Proposed cytogenesis. ASC, acidophil stem cell; Crooke, Crooke cell; DG, densely granulated; MS, mammosomatotroph; PD, poorly differentiated; SG, sparsely granulated.
Corticotroph adenoma/tumour and hyperplasia. The patient is a 13-year-old boy with clinical and laboratory findings consistent with Cushing disease. MRI showed a 4 mm lesion in the left lateral wing and cavernous sinus invasion. The surgical specimen showed a corticotroph adenoma/tumour with extensive immunoreaction for ACTH.
Corticotroph adenoma/tumour and hyperplasia. The patient is a 13-year-old boy with clinical and laboratory findings consistent with Cushing disease. MRI showed a 4 mm lesion in the left lateral wing and cavernous sinus invasion. The surgical specimen showed a corticotroph adenoma/tumour with focal areas of incomplete acini disruption suggestive of hyperplasia (reticulin silver).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Here, a dual population of cells can be seen, with large, densely granulated cells (upper right) next to smaller, sparsely granulated cells with slight eosinophilic cytoplasm (lower left).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Immunohistochemical stains characterized a dual population of densely granulated somatotroph cells (see Fig. <<#18157>>) and sparsely granulated lactotroph cells (shown here, prolactin staining).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Ultrastructure confirms the dual population of densely granulated somatotroph cells intermixed with the sparsely granulated lactotroph cells.
Growth hormone–secreting tumour associated with familial isolated pituitary adenoma. Non-identical twin girls presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas requiring emergency neurosurgery. Both patients were found to have silent somatotroph adenomas/tumours on pathological examination (not shown). Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumours of virtually identical characteristics. The adenomas were accompanied by multiple areas of somatotroph hyperplasia (shown here and Fig. <<#18162>>). Genetic analyses revealed a novel E216X mutation of the AIP gene, which was present both in the affected patients and in their unaffected father {21450940}. Here, reticulin silver histochemical stain shows expansion of the acini but maintenance of the regular reticulin network of normal adenohypophysis.
Pituitary adenoma / pituitary neuroendocrine tumour (PitNET). Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. Postcontrast T1-weighted coronal MRI showing a heterogeneously enhancing large pituitary tumour (18.8 × 17.6 mm) occupying the sella and suprasellar extension that abuts the chiasm eccentric to the left, with slight signal abnormality of the chiasm.
Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. This image shows a homogeneous population of slightly eosinophilic cells containing a central nucleus with well-dispersed chromatin and a small nucleolus.
Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. Sparsely granulated lactotroph adenomas have a characteristic prolactin immunoexpression with a dot-like paranuclear location.

Q: Immunohistochemistry is critical for subtyping a Pituitary Adenoma / Pituitary Neuroendocrine Tumor (PitNET); for example, lactotroph adenomas classically show intense nuclear estrogen receptor (ER) staining and a characteristic [...] pattern of prolactin positivity.
Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. Sparsely granulated lactotroph adenomas have a characteristic prolactin immunoexpression with a dot-like paranuclear location.
A: juxtanuclear (dot-like)
Back Extra: Pituitary Adenoma / Pituitary Neuroendocrine Tumour (PitNET)
- Clinical: Pituitary Adenoma / PitNETs can present with hormone excess syndromes (e.g., acromegaly, Cushing disease) or as large, symptomatic masses causing headaches, visual disturbances, and hypopituitarism.
- Micro: These tumours are generally monomorphic, with cells arranged in diffuse, papillary, or trabecular patterns. Nuclei are typically bland with regular chromatin, and the presence of extensive cellular pleomorphism, brisk mitotic activity, and necrosis should prompt consideration of other diagnoses.
- Ancillary: Immunohistochemistry (IHC) is crucial for subtyping PitNETs. For example, somatotroph adenomas are strongly positive for GH, while lactotroph adenomas show intense nuclear ER staining and juxtanuclear prolactin positivity.
Reference Gallery:
Pituitary adenoma / pituitary neuroendocrine tumour (PitNET). Proposed cytogenesis. ASC, acidophil stem cell; Crooke, Crooke cell; DG, densely granulated; MS, mammosomatotroph; PD, poorly differentiated; SG, sparsely granulated.
Corticotroph adenoma/tumour and hyperplasia. The patient is a 13-year-old boy with clinical and laboratory findings consistent with Cushing disease. MRI showed a 4 mm lesion in the left lateral wing and cavernous sinus invasion. The surgical specimen showed a corticotroph adenoma/tumour with extensive immunoreaction for ACTH.
Corticotroph adenoma/tumour and hyperplasia. The patient is a 13-year-old boy with clinical and laboratory findings consistent with Cushing disease. MRI showed a 4 mm lesion in the left lateral wing and cavernous sinus invasion. The surgical specimen showed a corticotroph adenoma/tumour with focal areas of incomplete acini disruption suggestive of hyperplasia (reticulin silver).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Here, a dual population of cells can be seen, with large, densely granulated cells (upper right) next to smaller, sparsely granulated cells with slight eosinophilic cytoplasm (lower left).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Immunohistochemical stains characterized a dual population of densely granulated somatotroph cells (see Fig. <<#18157>>) and sparsely granulated lactotroph cells (shown here, prolactin staining).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Ultrastructure confirms the dual population of densely granulated somatotroph cells intermixed with the sparsely granulated lactotroph cells.
Growth hormone–secreting tumour associated with familial isolated pituitary adenoma. Non-identical twin girls presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas requiring emergency neurosurgery. Both patients were found to have silent somatotroph adenomas/tumours on pathological examination (not shown). Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumours of virtually identical characteristics. The adenomas were accompanied by multiple areas of somatotroph hyperplasia (shown here and Fig. <<#18162>>). Genetic analyses revealed a novel E216X mutation of the AIP gene, which was present both in the affected patients and in their unaffected father {21450940}. Here, reticulin silver histochemical stain shows expansion of the acini but maintenance of the regular reticulin network of normal adenohypophysis.
Pituitary adenoma / pituitary neuroendocrine tumour (PitNET). Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. Postcontrast T1-weighted coronal MRI showing a heterogeneously enhancing large pituitary tumour (18.8 × 17.6 mm) occupying the sella and suprasellar extension that abuts the chiasm eccentric to the left, with slight signal abnormality of the chiasm.
Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. This image shows a homogeneous population of slightly eosinophilic cells containing a central nucleus with well-dispersed chromatin and a small nucleolus.
Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. Sparsely granulated lactotroph adenomas have a characteristic prolactin immunoexpression with a dot-like paranuclear location.

Q: Patients with a large, symptomatic Pituitary Adenoma / Pituitary Neuroendocrine Tumor (PitNET) may present with headaches, hypopituitarism, and [...] due to mass effect and compression of the optic chiasm.
Pituitary adenoma / pituitary neuroendocrine tumour (PitNET). Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. Postcontrast T1-weighted coronal MRI showing a heterogeneously enhancing large pituitary tumour (18.8 × 17.6 mm) occupying the sella and suprasellar extension that abuts the chiasm eccentric to the left, with slight signal abnormality of the chiasm.
A: visual disturbances
Back Extra: Pituitary Adenoma / Pituitary Neuroendocrine Tumour (PitNET)
- Clinical: Pituitary Adenoma / PitNETs can present with hormone excess syndromes (e.g., acromegaly, Cushing disease) or as large, symptomatic masses causing headaches, visual disturbances, and hypopituitarism.
- Micro: These tumours are generally monomorphic, with cells arranged in diffuse, papillary, or trabecular patterns. Nuclei are typically bland with regular chromatin, and the presence of extensive cellular pleomorphism, brisk mitotic activity, and necrosis should prompt consideration of other diagnoses.
- Ancillary: Immunohistochemistry (IHC) is crucial for subtyping PitNETs. For example, somatotroph adenomas are strongly positive for GH, while lactotroph adenomas show intense nuclear ER staining and juxtanuclear prolactin positivity.
Reference Gallery:
Pituitary adenoma / pituitary neuroendocrine tumour (PitNET). Proposed cytogenesis. ASC, acidophil stem cell; Crooke, Crooke cell; DG, densely granulated; MS, mammosomatotroph; PD, poorly differentiated; SG, sparsely granulated.
Corticotroph adenoma/tumour and hyperplasia. The patient is a 13-year-old boy with clinical and laboratory findings consistent with Cushing disease. MRI showed a 4 mm lesion in the left lateral wing and cavernous sinus invasion. The surgical specimen showed a corticotroph adenoma/tumour with extensive immunoreaction for ACTH.
Corticotroph adenoma/tumour and hyperplasia. The patient is a 13-year-old boy with clinical and laboratory findings consistent with Cushing disease. MRI showed a 4 mm lesion in the left lateral wing and cavernous sinus invasion. The surgical specimen showed a corticotroph adenoma/tumour with focal areas of incomplete acini disruption suggestive of hyperplasia (reticulin silver).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Here, a dual population of cells can be seen, with large, densely granulated cells (upper right) next to smaller, sparsely granulated cells with slight eosinophilic cytoplasm (lower left).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Immunohistochemical stains characterized a dual population of densely granulated somatotroph cells (see Fig. <<#18157>>) and sparsely granulated lactotroph cells (shown here, prolactin staining).
Growth hormone–secreting tumour associated with X-linked acrogigantism. A 5-year-old girl referred for treatment of gigantism. The patient’s paediatrician noted consistent elevation of her growth rate after the age of 30 months when she was at the 90th percentile for height. Her weight percentile increased over this time as well, and at the time of surgery at the age of 5 years, she was the height of an average 8-year-old (50th percentile for 8 years). Laboratory tests revealed a growth hormone level of 85.4 ng/mL and an IGF1 level of 806 ng/mL. MRI showed a pituitary macroadenoma with chiasmal compression. Genetic analysis demonstrated a germline GPR101 duplication consistent with X-linked acrogigantism {27245663}. Most patients with X-linked acrogigantism develop growth hormone–secreting tumours, but somatotroph hyperplasia may also be seen. In this patient, a mixed somatotroph and lactotroph adenoma/tumour was present. Ultrastructure confirms the dual population of densely granulated somatotroph cells intermixed with the sparsely granulated lactotroph cells.
Growth hormone–secreting tumour associated with familial isolated pituitary adenoma. Non-identical twin girls presented as adolescents to the emergency department with severe progressive headache caused by large pituitary macroadenomas requiring emergency neurosurgery. Both patients were found to have silent somatotroph adenomas/tumours on pathological examination (not shown). Furthermore, the light microscopic, immunohistochemical, and electron microscopic studies demonstrated tumours of virtually identical characteristics. The adenomas were accompanied by multiple areas of somatotroph hyperplasia (shown here and Fig. <<#18162>>). Genetic analyses revealed a novel E216X mutation of the AIP gene, which was present both in the affected patients and in their unaffected father {21450940}. Here, reticulin silver histochemical stain shows expansion of the acini but maintenance of the regular reticulin network of normal adenohypophysis.
Pituitary adenoma / pituitary neuroendocrine tumour (PitNET). Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. Postcontrast T1-weighted coronal MRI showing a heterogeneously enhancing large pituitary tumour (18.8 × 17.6 mm) occupying the sella and suprasellar extension that abuts the chiasm eccentric to the left, with slight signal abnormality of the chiasm.
Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. This image shows a homogeneous population of slightly eosinophilic cells containing a central nucleus with well-dispersed chromatin and a small nucleolus.
Lactotroph adenoma/tumour. An 11-year-old girl was referred to the pituitary clinic after a pituitary tumour was found incidentally on MRI, which was performed on account of severe persistent headaches. Visual field testing revealed a dense hemianopsia on the right, and inferior temporal loss on the left. Laboratory tests revealed a prolactin level of 433 ng/mL and normal growth hormone, IGF1, free thyroxine (T4), and TSH levels. She was started on cabergoline, with significant reduction in her prolactin level. However, there was little reduction of the tumour size, and the patient continued having persistent headaches and visual deficits. A surgical resection was performed. Sparsely granulated lactotroph adenomas have a characteristic prolactin immunoexpression with a dot-like paranuclear location.

Q: Histologically, Pituitary Blastoma is characterized by a distinctive [...] pattern consisting of large anterior pituitary neuroendocrine cells, primitive Rathke pouch epithelium, and small undifferentiated blastemal cells.
Pituitary blastoma. The cellular components of pituitary blastomas include large anterior pituitary neuroendocrine cells arranged in lobules or diffuse sheets, cuboidal primitive Rathke pouch epithelium with rosette or gland/follicle formation, and scattered small undifferentiated blastemal cells.
A: triphasic
Back Extra: Pituitary Blastoma
- Clinical: Cushing syndrome is a common presenting symptom in patients with pituitary blastoma, with elevated and non-suppressible serum ACTH levels.
- Micro: Pituitary blastomas are characterized by a triphasic pattern of large anterior pituitary neuroendocrine cells, primitive Rathke pouch epithelium, and small undifferentiated blastemal cells.
- Ancillary: Germline and somatic DICER1 variants are frequently identified in pituitary blastomas, making DICER1 sequencing a key diagnostic test.
Reference Gallery:
Pituitary blastoma. The cellular components of pituitary blastomas include large anterior pituitary neuroendocrine cells arranged in lobules or diffuse sheets, cuboidal primitive Rathke pouch epithelium with rosette or gland/follicle formation, and scattered small undifferentiated blastemal cells.
Pituitary blastoma. The anterior pituitary neuroendocrine tumour cells are arranged in diffuse sheets or lobules, and they are variably positive for ACTH. In contrast, rosette- or follicle-forming cuboidal or columnar primitive Rathke pouch epithelium and blastemal undifferentiated cells are negative for ACTH.
Pituitary blastoma. CAM5.2 stains almost all cellular components in pituitary blastomas.
Pituitary blastoma. Strong membranous CD56 expression distinguishes areas of neuroendocrine cells, whereas other cellular elements show less intense staining for CD56.
Pituitary blastoma. EMA shows variable staining in cellular components, with stronger staining in areas with rosette or follicle-forming cuboidal or columnar primitive Rathke pouch epithelium.
Pituitary blastoma. S100 stains scattered folliculostellate cells.
Pituitary blastoma. Proliferative heterogeneity of various cellular components is illustrated in this photomicrograph. The follicle-forming cuboidal or columnar primitive Rathke pouch epithelium shows a higher Ki-67 proliferation index than do the other cellular elements.

Q: Patients with Pituitary Blastoma commonly present clinically with [...], which correlates with the presence of large anterior pituitary neuroendocrine tumor cells that are immunohistochemically positive for ACTH.
Pituitary blastoma. The anterior pituitary neuroendocrine tumour cells are arranged in diffuse sheets or lobules, and they are variably positive for ACTH. In contrast, rosette- or follicle-forming cuboidal or columnar primitive Rathke pouch epithelium and blastemal undifferentiated cells are negative for ACTH.
A: Cushing syndrome
Back Extra: Pituitary Blastoma
- Clinical: Cushing syndrome is a common presenting symptom in patients with pituitary blastoma, with elevated and non-suppressible serum ACTH levels.
- Micro: Pituitary blastomas are characterized by a triphasic pattern of large anterior pituitary neuroendocrine cells, primitive Rathke pouch epithelium, and small undifferentiated blastemal cells.
- Ancillary: Germline and somatic DICER1 variants are frequently identified in pituitary blastomas, making DICER1 sequencing a key diagnostic test.
Reference Gallery:
Pituitary blastoma. The cellular components of pituitary blastomas include large anterior pituitary neuroendocrine cells arranged in lobules or diffuse sheets, cuboidal primitive Rathke pouch epithelium with rosette or gland/follicle formation, and scattered small undifferentiated blastemal cells.
Pituitary blastoma. The anterior pituitary neuroendocrine tumour cells are arranged in diffuse sheets or lobules, and they are variably positive for ACTH. In contrast, rosette- or follicle-forming cuboidal or columnar primitive Rathke pouch epithelium and blastemal undifferentiated cells are negative for ACTH.
Pituitary blastoma. CAM5.2 stains almost all cellular components in pituitary blastomas.
Pituitary blastoma. Strong membranous CD56 expression distinguishes areas of neuroendocrine cells, whereas other cellular elements show less intense staining for CD56.
Pituitary blastoma. EMA shows variable staining in cellular components, with stronger staining in areas with rosette or follicle-forming cuboidal or columnar primitive Rathke pouch epithelium.
Pituitary blastoma. S100 stains scattered folliculostellate cells.
Pituitary blastoma. Proliferative heterogeneity of various cellular components is illustrated in this photomicrograph. The follicle-forming cuboidal or columnar primitive Rathke pouch epithelium shows a higher Ki-67 proliferation index than do the other cellular elements.

Q: Within the cellular components of a Pituitary Blastoma, the cuboidal or columnar cells that frequently form rosettes or follicles represent primitive [...] epithelium.
Pituitary blastoma. The cellular components of pituitary blastomas include large anterior pituitary neuroendocrine cells arranged in lobules or diffuse sheets, cuboidal primitive Rathke pouch epithelium with rosette or gland/follicle formation, and scattered small undifferentiated blastemal cells.
Pituitary blastoma. EMA shows variable staining in cellular components, with stronger staining in areas with rosette or follicle-forming cuboidal or columnar primitive Rathke pouch epithelium.
Pituitary blastoma. Proliferative heterogeneity of various cellular components is illustrated in this photomicrograph. The follicle-forming cuboidal or columnar primitive Rathke pouch epithelium shows a higher Ki-67 proliferation index than do the other cellular elements.
A: Rathke pouch
Back Extra: Pituitary Blastoma
- Clinical: Cushing syndrome is a common presenting symptom in patients with pituitary blastoma, with elevated and non-suppressible serum ACTH levels.
- Micro: Pituitary blastomas are characterized by a triphasic pattern of large anterior pituitary neuroendocrine cells, primitive Rathke pouch epithelium, and small undifferentiated blastemal cells.
- Ancillary: Germline and somatic DICER1 variants are frequently identified in pituitary blastomas, making DICER1 sequencing a key diagnostic test.
Reference Gallery:
Pituitary blastoma. The cellular components of pituitary blastomas include large anterior pituitary neuroendocrine cells arranged in lobules or diffuse sheets, cuboidal primitive Rathke pouch epithelium with rosette or gland/follicle formation, and scattered small undifferentiated blastemal cells.
Pituitary blastoma. The anterior pituitary neuroendocrine tumour cells are arranged in diffuse sheets or lobules, and they are variably positive for ACTH. In contrast, rosette- or follicle-forming cuboidal or columnar primitive Rathke pouch epithelium and blastemal undifferentiated cells are negative for ACTH.
Pituitary blastoma. CAM5.2 stains almost all cellular components in pituitary blastomas.
Pituitary blastoma. Strong membranous CD56 expression distinguishes areas of neuroendocrine cells, whereas other cellular elements show less intense staining for CD56.
Pituitary blastoma. EMA shows variable staining in cellular components, with stronger staining in areas with rosette or follicle-forming cuboidal or columnar primitive Rathke pouch epithelium.
Pituitary blastoma. S100 stains scattered folliculostellate cells.
Pituitary blastoma. Proliferative heterogeneity of various cellular components is illustrated in this photomicrograph. The follicle-forming cuboidal or columnar primitive Rathke pouch epithelium shows a higher Ki-67 proliferation index than do the other cellular elements.

Q: A neural crest tumor demonstrating an intimate blend of classic pheochromocytoma/paraganglioma features (e.g., Zellballen architecture) with another embryologically related tumor type (such as a ganglioneuroma) is diagnosed as a [...].
Adrenal composite tumour. This composite tumour demonstrates a phaeochromocytoma (right) with a well-developed ganglioneuroma, including well-formed ganglion cells.
Adrenal composite tumour. The two elements of this composite tumour show blending, with the phaeochromocytoma Zellballen blending intimately with the ganglioneuroma. The Schwannian cell background is well developed.
A: Composite Phaeochromocytoma/Paraganglioma
Back Extra: Composite Phaeochromocytoma/Paraganglioma
- Clinical: Patients may present with WDHA syndrome (watery diarrhoea, hypokalaemia, and achlorhydria) and paroxysmal high blood pressure.
- Micro: A composite tumour requires the presence of well-developed cytological and architectural features of both a phaeochromocytoma/paraganglioma component and another embryologically related tumour type.
- Ancillary: Genetic testing is indicated for any tumour with a component of phaeochromocytoma/paraganglioma, with MYCN amplification being a poor prognostic factor.
Reference Gallery:
Adrenal composite tumour. This composite tumour demonstrates a phaeochromocytoma (right) with a well-developed ganglioneuroma, including well-formed ganglion cells.
Adrenal composite tumour. The two elements of this composite tumour show blending, with the phaeochromocytoma Zellballen blending intimately with the ganglioneuroma. The Schwannian cell background is well developed.
Adrenal composite tumour. A high-power view shows a nest of phaeochromocytoma adjacent to well-formed ganglion cells in a background of Schwannian cells (ganglioneuroma) in a composite tumour.

Q: In a Composite Phaeochromocytoma/Paraganglioma, the secondary embryologically related tumor component frequently forms a ganglioneuroma, which is histologically characterized by an extensive Schwannian cell stroma containing scattered, well-formed [...].
Adrenal composite tumour. The two elements of this composite tumour show blending, with the phaeochromocytoma Zellballen blending intimately with the ganglioneuroma. The Schwannian cell background is well developed.
Adrenal composite tumour. A high-power view shows a nest of phaeochromocytoma adjacent to well-formed ganglion cells in a background of Schwannian cells (ganglioneuroma) in a composite tumour.
A: ganglion cells
Back Extra: Composite Phaeochromocytoma/Paraganglioma
- Clinical: Patients may present with WDHA syndrome (watery diarrhoea, hypokalaemia, and achlorhydria) and paroxysmal high blood pressure.
- Micro: A composite tumour requires the presence of well-developed cytological and architectural features of both a phaeochromocytoma/paraganglioma component and another embryologically related tumour type.
- Ancillary: Genetic testing is indicated for any tumour with a component of phaeochromocytoma/paraganglioma, with MYCN amplification being a poor prognostic factor.
Reference Gallery:
Adrenal composite tumour. This composite tumour demonstrates a phaeochromocytoma (right) with a well-developed ganglioneuroma, including well-formed ganglion cells.
Adrenal composite tumour. The two elements of this composite tumour show blending, with the phaeochromocytoma Zellballen blending intimately with the ganglioneuroma. The Schwannian cell background is well developed.
Adrenal composite tumour. A high-power view shows a nest of phaeochromocytoma adjacent to well-formed ganglion cells in a background of Schwannian cells (ganglioneuroma) in a composite tumour.

Q: Ganglioneuroblastoma, intermixed is characterized microscopically by well-demarcated foci of neuroblastic cells embedded in [...], randomly distributed within a predominantly ganglioneuromatous background (>50% of the tumor).
Adrenal ganglioneuroblastoma, intermixed. The hallmark feature is the presence of well-demarcated microscopic foci that contain neuroblastic cells embedded in neuropil. The foci are randomly distributed in ganglioneuromatous tissue composed of Schwannian cells and maturing/mature ganglionic cells. The ganglioneuromatous component exceeds 50% of the microscopic tumour section.
Adrenal ganglioneuroblastoma, intermixed. The neuroblastic cells span various stages of differentiation and are dominated by differentiating neuroblasts.
A: neuropil
Ganglioneuroblastoma, intermixed
- Clinical: Patients with Ganglioneuroblastoma, intermixed often present with an asymptomatic mass and lack elevated urine catecholamines seen in neuroblastoma.
- Micro: Ganglioneuroblastoma, intermixed features well-circumscribed lacunar areas of neuroblastic cells embedded in varying amounts of neuropil, randomly distributed in ganglioneuromatous tissue.
- Ancillary: Immunostaining for synaptophysin and S100 aids in distinguishing neuropil and Schwann cells, respectively, in Ganglioneuroblastoma, intermixed.
Reference Gallery:
Adrenal ganglioneuroblastoma, intermixed. The hallmark feature is the presence of well-demarcated microscopic foci that contain neuroblastic cells embedded in neuropil. The foci are randomly distributed in ganglioneuromatous tissue composed of Schwannian cells and maturing/mature ganglionic cells. The ganglioneuromatous component exceeds 50% of the microscopic tumour section.
Adrenal ganglioneuroblastoma, intermixed. The neuroblastic cells span various stages of differentiation and are dominated by differentiating neuroblasts.
Adrenal ganglioneuroblastoma, intermixed. The presence of neuropil in tumour foci is a prerequisite for the diagnosis. Neuropil strongly expresses synaptophysin (shown here) but is negative for S100.
Adrenal ganglioneuroblastoma, intermixed. The presence of neuropil in tumour foci is a prerequisite for the diagnosis of ganglioneuroblastoma, intermixed. Neuropil is negative for S100 (shown here) but strongly expresses synaptophysin.
Adrenal ganglioneuroblastoma, intermixed. In addition to neuropil-containing tumour foci, intermixed ganglioneuroblastoma may show clusters of ganglionic cells that do not include appreciable amounts of synaptophysin-positive neuropil (shown here) but do contain S100-positive Schwann cells. Such clusters are frequently found in maturing and mature ganglioneuromas, thus demonstrating the ongoing differentiation from a stroma-rich to a stroma-dominant tumour. Immunostaining for synaptophysin aids in the identification of neuropil in the differential diagnosis between intermixed ganglioneuroblastoma and ganglioneuroma.
Adrenal ganglioneuroblastoma, intermixed. In addition to neuropil-containing tumour foci, intermixed ganglioneuroblastoma may show clusters of ganglionic cells that contain S100-positive Schwannian cells (shown here) but do not include appreciable amounts of synaptophysin-positive neuropil. Such clusters are frequently found in maturing and mature ganglioneuromas, thus demonstrating the ongoing differentiation from a stroma-rich to a stroma-dominant tumour. Immunostaining for synaptophysin aids in the identification of neuropil in the differential diagnosis between intermixed ganglioneuroblastoma and ganglioneuroma.
Ganglioneuroblastoma. Contrast-enhanced CT shows a solid, well-marginated left paraspinal mass with homogeneous enhancement. The tumour encases the left subclavian artery.
Ganglioneuroblastoma. Contrast-enhanced, fat-suppressed T1-weighted image shows an avidly enhancing mass at the left lung apex encasing the left subclavian artery. The latter remains patent with normal signal void.

Q: For the diagnosis of Ganglioneuroblastoma, intermixed, identifying neuropil in tumor foci is a prerequisite; this fibrillary matrix will stain strongly positive for [...] and negative for S100.
Adrenal ganglioneuroblastoma, intermixed. The presence of neuropil in tumour foci is a prerequisite for the diagnosis. Neuropil strongly expresses synaptophysin (shown here) but is negative for S100.
Adrenal ganglioneuroblastoma, intermixed. The presence of neuropil in tumour foci is a prerequisite for the diagnosis of ganglioneuroblastoma, intermixed. Neuropil is negative for S100 (shown here) but strongly expresses synaptophysin.
A: synaptophysin
Ganglioneuroblastoma, intermixed
- Clinical: Patients with Ganglioneuroblastoma, intermixed often present with an asymptomatic mass and lack elevated urine catecholamines seen in neuroblastoma.
- Micro: Ganglioneuroblastoma, intermixed features well-circumscribed lacunar areas of neuroblastic cells embedded in varying amounts of neuropil, randomly distributed in ganglioneuromatous tissue.
- Ancillary: Immunostaining for synaptophysin and S100 aids in distinguishing neuropil and Schwann cells, respectively, in Ganglioneuroblastoma, intermixed.
Reference Gallery:
Adrenal ganglioneuroblastoma, intermixed. The hallmark feature is the presence of well-demarcated microscopic foci that contain neuroblastic cells embedded in neuropil. The foci are randomly distributed in ganglioneuromatous tissue composed of Schwannian cells and maturing/mature ganglionic cells. The ganglioneuromatous component exceeds 50% of the microscopic tumour section.
Adrenal ganglioneuroblastoma, intermixed. The neuroblastic cells span various stages of differentiation and are dominated by differentiating neuroblasts.
Adrenal ganglioneuroblastoma, intermixed. The presence of neuropil in tumour foci is a prerequisite for the diagnosis. Neuropil strongly expresses synaptophysin (shown here) but is negative for S100.
Adrenal ganglioneuroblastoma, intermixed. The presence of neuropil in tumour foci is a prerequisite for the diagnosis of ganglioneuroblastoma, intermixed. Neuropil is negative for S100 (shown here) but strongly expresses synaptophysin.
Adrenal ganglioneuroblastoma, intermixed. In addition to neuropil-containing tumour foci, intermixed ganglioneuroblastoma may show clusters of ganglionic cells that do not include appreciable amounts of synaptophysin-positive neuropil (shown here) but do contain S100-positive Schwann cells. Such clusters are frequently found in maturing and mature ganglioneuromas, thus demonstrating the ongoing differentiation from a stroma-rich to a stroma-dominant tumour. Immunostaining for synaptophysin aids in the identification of neuropil in the differential diagnosis between intermixed ganglioneuroblastoma and ganglioneuroma.
Adrenal ganglioneuroblastoma, intermixed. In addition to neuropil-containing tumour foci, intermixed ganglioneuroblastoma may show clusters of ganglionic cells that contain S100-positive Schwannian cells (shown here) but do not include appreciable amounts of synaptophysin-positive neuropil. Such clusters are frequently found in maturing and mature ganglioneuromas, thus demonstrating the ongoing differentiation from a stroma-rich to a stroma-dominant tumour. Immunostaining for synaptophysin aids in the identification of neuropil in the differential diagnosis between intermixed ganglioneuroblastoma and ganglioneuroma.
Ganglioneuroblastoma. Contrast-enhanced CT shows a solid, well-marginated left paraspinal mass with homogeneous enhancement. The tumour encases the left subclavian artery.
Ganglioneuroblastoma. Contrast-enhanced, fat-suppressed T1-weighted image shows an avidly enhancing mass at the left lung apex encasing the left subclavian artery. The latter remains patent with normal signal void.

Q: Clinically, Ganglioneuroblastoma, intermixed often presents as an asymptomatic paraspinal mass and typically lacks the elevated [...] seen in classic neuroblastoma.
Ganglioneuroblastoma. Contrast-enhanced CT shows a solid, well-marginated left paraspinal mass with homogeneous enhancement. The tumour encases the left subclavian artery.
A: urine catecholamines
Ganglioneuroblastoma, intermixed
- Clinical: Patients with Ganglioneuroblastoma, intermixed often present with an asymptomatic mass and lack elevated urine catecholamines seen in neuroblastoma.
- Micro: Ganglioneuroblastoma, intermixed features well-circumscribed lacunar areas of neuroblastic cells embedded in varying amounts of neuropil, randomly distributed in ganglioneuromatous tissue.
- Ancillary: Immunostaining for synaptophysin and S100 aids in distinguishing neuropil and Schwann cells, respectively, in Ganglioneuroblastoma, intermixed.
Reference Gallery:
Adrenal ganglioneuroblastoma, intermixed. The hallmark feature is the presence of well-demarcated microscopic foci that contain neuroblastic cells embedded in neuropil. The foci are randomly distributed in ganglioneuromatous tissue composed of Schwannian cells and maturing/mature ganglionic cells. The ganglioneuromatous component exceeds 50% of the microscopic tumour section.
Adrenal ganglioneuroblastoma, intermixed. The neuroblastic cells span various stages of differentiation and are dominated by differentiating neuroblasts.
Adrenal ganglioneuroblastoma, intermixed. The presence of neuropil in tumour foci is a prerequisite for the diagnosis. Neuropil strongly expresses synaptophysin (shown here) but is negative for S100.
Adrenal ganglioneuroblastoma, intermixed. The presence of neuropil in tumour foci is a prerequisite for the diagnosis of ganglioneuroblastoma, intermixed. Neuropil is negative for S100 (shown here) but strongly expresses synaptophysin.
Adrenal ganglioneuroblastoma, intermixed. In addition to neuropil-containing tumour foci, intermixed ganglioneuroblastoma may show clusters of ganglionic cells that do not include appreciable amounts of synaptophysin-positive neuropil (shown here) but do contain S100-positive Schwann cells. Such clusters are frequently found in maturing and mature ganglioneuromas, thus demonstrating the ongoing differentiation from a stroma-rich to a stroma-dominant tumour. Immunostaining for synaptophysin aids in the identification of neuropil in the differential diagnosis between intermixed ganglioneuroblastoma and ganglioneuroma.
Adrenal ganglioneuroblastoma, intermixed. In addition to neuropil-containing tumour foci, intermixed ganglioneuroblastoma may show clusters of ganglionic cells that contain S100-positive Schwannian cells (shown here) but do not include appreciable amounts of synaptophysin-positive neuropil. Such clusters are frequently found in maturing and mature ganglioneuromas, thus demonstrating the ongoing differentiation from a stroma-rich to a stroma-dominant tumour. Immunostaining for synaptophysin aids in the identification of neuropil in the differential diagnosis between intermixed ganglioneuroblastoma and ganglioneuroma.
Ganglioneuroblastoma. Contrast-enhanced CT shows a solid, well-marginated left paraspinal mass with homogeneous enhancement. The tumour encases the left subclavian artery.
Ganglioneuroblastoma. Contrast-enhanced, fat-suppressed T1-weighted image shows an avidly enhancing mass at the left lung apex encasing the left subclavian artery. The latter remains patent with normal signal void.

Q: Macroscopically and microscopically, Ganglioneuroblastoma, nodular is characterized by distinct [...] nodules that demonstrate an abrupt interface with the surrounding Schwannian stroma.
Ganglioneuroblastoma, nodular. Classic appearance, with a single nodule of a neuroblastomatous tumour.
Ganglioneuroblastoma nodular. The interface between the Schwannian component (left) and the nodular neuroblastic component (right) is abrupt.
A: neuroblastic
Back Extra: Ganglioneuroblastoma, nodular
- Clinical: Patients with Ganglioneuroblastoma, nodular typically present with a localized abdominal mass, pain, distention, and fever. They are generally older (83% aged > 18 months).
- Micro: Characterized by one or more macroscopically visible neuroblastic nodules within a ganglioneuromatous background. The interface between the Schwannian component and the nodular neuroblastic component is abrupt.
- Ancillary: Essential diagnostic criteria include grossly distinct nodule(s) with pushing borders, microscopically distinct neuroblastic nodule, and INPC classification of the nodule with the least favourable histology.
Reference Gallery:
Ganglioneuroblastoma, nodular. Classic appearance, with a single nodule of a neuroblastomatous tumour.
Ganglioneuroblastoma, nodular. A less common form, with multiple large nodules.
Ganglioneuroblastoma nodular. The interface between the Schwannian component (left) and the nodular neuroblastic component (right) is abrupt.
Ganglioneuroblastoma, nodular. PHOX2B is specifically expressed by the neuroblasts (right).
Ganglioneuroblastoma, nodular. S100 is specifically expressed by the Schwann cells (left).

Q: In Ganglioneuroblastoma, nodular, immunohistochemistry highlights the distinct components of the tumor: the Schwann cells are positive for S100, whereas the neuroblasts specifically express [...].
Ganglioneuroblastoma, nodular. PHOX2B is specifically expressed by the neuroblasts (right).
Ganglioneuroblastoma, nodular. S100 is specifically expressed by the Schwann cells (left).
A: PHOX2B
Back Extra: Ganglioneuroblastoma, nodular
- Clinical: Patients with Ganglioneuroblastoma, nodular typically present with a localized abdominal mass, pain, distention, and fever. They are generally older (83% aged > 18 months).
- Micro: Characterized by one or more macroscopically visible neuroblastic nodules within a ganglioneuromatous background. The interface between the Schwannian component and the nodular neuroblastic component is abrupt.
- Ancillary: Essential diagnostic criteria include grossly distinct nodule(s) with pushing borders, microscopically distinct neuroblastic nodule, and INPC classification of the nodule with the least favourable histology.
Reference Gallery:
Ganglioneuroblastoma, nodular. Classic appearance, with a single nodule of a neuroblastomatous tumour.
Ganglioneuroblastoma, nodular. A less common form, with multiple large nodules.
Ganglioneuroblastoma nodular. The interface between the Schwannian component (left) and the nodular neuroblastic component (right) is abrupt.
Ganglioneuroblastoma, nodular. PHOX2B is specifically expressed by the neuroblasts (right).
Ganglioneuroblastoma, nodular. S100 is specifically expressed by the Schwann cells (left).

Q: Histologically, a Ganglioneuroma is characterized by an abundant background of bland Schwann cells arranged in fascicles, interspersed with dispersed or clustered mature [...].
Adrenal ganglioneuroma. There is a blending of Schwannian cells with numerous mature ganglion cells noted within the proliferation.
Adrenal ganglioneuroma. There are numerous large mature ganglion cells set within a Schwannian background characteristic of a ganglioneuroma.
Adrenal ganglioneuroma. A core needle biopsy sample demonstrates numerous spindled cells in the background (Schwannian), and isolated mature ganglion cells are present.
A: ganglion cells
Back Extra: Ganglioneuroma
- Clinical: Ganglioneuromas are often incidentally discovered during imaging for unrelated reasons and are typically non-functioning. They mainly affect older children and young adults (median age: 6 years).
- Micro: Histologically, ganglioneuromas contain abundant bland Schwann cells arranged in sheets or fascicles, with maturing and mature ganglion cells dispersed or clustered within the tumor.
- Ancillary: Ancillary studies are generally not clinically relevant for the diagnosis of ganglioneuromas.
Reference Gallery:
Adrenal ganglioneuroma. A gross image of a ganglioneuroma showing a white, fleshy cut surface with compressed adrenal cortex at the periphery.
Adrenal ganglioneuroma. There is a blending of Schwannian cells with numerous mature ganglion cells noted within the proliferation.
Adrenal ganglioneuroma. There are numerous large mature ganglion cells set within a Schwannian background characteristic of a ganglioneuroma.
Adrenal ganglioneuroma. A core needle biopsy sample demonstrates numerous spindled cells in the background (Schwannian), and isolated mature ganglion cells are present.
Ganglioneuroma. Contrast-enhanced CT axial image. There is a well-circumscribed, fairly homogeneous, mildly enhancing mass at the retroperitoneum, which is relatively hypoattenuating relative to muscle. The mass encases the inferior vena cava and aorta. Note the characteristic discrete and punctate calcifications present within the mass.

Q: A benign peripheral nerve sheath tumor featuring a white, fleshy gross cut surface and a microscopic proliferation of mature ganglion cells set within a background of spindled Schwann cells is diagnostic of a [...].
Adrenal ganglioneuroma. A gross image of a ganglioneuroma showing a white, fleshy cut surface with compressed adrenal cortex at the periphery.
Adrenal ganglioneuroma. There are numerous large mature ganglion cells set within a Schwannian background characteristic of a ganglioneuroma.
A: ganglioneuroma
Back Extra: Ganglioneuroma
- Clinical: Ganglioneuromas are often incidentally discovered during imaging for unrelated reasons and are typically non-functioning. They mainly affect older children and young adults (median age: 6 years).
- Micro: Histologically, ganglioneuromas contain abundant bland Schwann cells arranged in sheets or fascicles, with maturing and mature ganglion cells dispersed or clustered within the tumor.
- Ancillary: Ancillary studies are generally not clinically relevant for the diagnosis of ganglioneuromas.
Reference Gallery:
Adrenal ganglioneuroma. A gross image of a ganglioneuroma showing a white, fleshy cut surface with compressed adrenal cortex at the periphery.
Adrenal ganglioneuroma. There is a blending of Schwannian cells with numerous mature ganglion cells noted within the proliferation.
Adrenal ganglioneuroma. There are numerous large mature ganglion cells set within a Schwannian background characteristic of a ganglioneuroma.
Adrenal ganglioneuroma. A core needle biopsy sample demonstrates numerous spindled cells in the background (Schwannian), and isolated mature ganglion cells are present.
Ganglioneuroma. Contrast-enhanced CT axial image. There is a well-circumscribed, fairly homogeneous, mildly enhancing mass at the retroperitoneum, which is relatively hypoattenuating relative to muscle. The mass encases the inferior vena cava and aorta. Note the characteristic discrete and punctate calcifications present within the mass.

Q: On CT imaging, a retroperitoneal Ganglioneuroma typically presents as a well-circumscribed mass that can encase large vessels (like the aorta and IVC) and often contains characteristic discrete and [...].
Ganglioneuroma. Contrast-enhanced CT axial image. There is a well-circumscribed, fairly homogeneous, mildly enhancing mass at the retroperitoneum, which is relatively hypoattenuating relative to muscle. The mass encases the inferior vena cava and aorta. Note the characteristic discrete and punctate calcifications present within the mass.
A: punctate calcifications
Back Extra: Ganglioneuroma
- Clinical: Ganglioneuromas are often incidentally discovered during imaging for unrelated reasons and are typically non-functioning. They mainly affect older children and young adults (median age: 6 years).
- Micro: Histologically, ganglioneuromas contain abundant bland Schwann cells arranged in sheets or fascicles, with maturing and mature ganglion cells dispersed or clustered within the tumor.
- Ancillary: Ancillary studies are generally not clinically relevant for the diagnosis of ganglioneuromas.
Reference Gallery:
Adrenal ganglioneuroma. A gross image of a ganglioneuroma showing a white, fleshy cut surface with compressed adrenal cortex at the periphery.
Adrenal ganglioneuroma. There is a blending of Schwannian cells with numerous mature ganglion cells noted within the proliferation.
Adrenal ganglioneuroma. There are numerous large mature ganglion cells set within a Schwannian background characteristic of a ganglioneuroma.
Adrenal ganglioneuroma. A core needle biopsy sample demonstrates numerous spindled cells in the background (Schwannian), and isolated mature ganglion cells are present.
Ganglioneuroma. Contrast-enhanced CT axial image. There is a well-circumscribed, fairly homogeneous, mildly enhancing mass at the retroperitoneum, which is relatively hypoattenuating relative to muscle. The mass encases the inferior vena cava and aorta. Note the characteristic discrete and punctate calcifications present within the mass.

Q: The poorly differentiated subtype of Neuroblastoma is histologically characterized by the presence of neurites and [...].
Neuroblastoma. Poorly differentiated subtype (inset: higher-magnification view of a Homer Wright rosette).
A: Homer Wright rosettes
Back Extra: Neuroblastoma
- Clinical: Neuroblastoma can present with abdominal distension, constipation, or respiratory distress, depending on the primary tumour location.
- Micro: The poorly differentiated subtype of neuroblastoma is characterized by the presence of neurites and Homer Wright rosettes.
- Ancillary: MYCN amplification in neuroblastoma is a key molecular marker associated with advanced stage and aggressive clinical behaviour.
Reference Gallery:
Neuroblastoma. Left adrenalectomy specimen with a 60 mm haemorrhagic, nodular tumour. Note the central calcification, necrosis, and fibrosis.
Neuroblastoma. Undifferentiated subtype without clearly recognizable neurite formation.
Neuroblastoma. Poorly differentiated subtype (inset: higher-magnification view of a Homer Wright rosette).
Neuroblastoma. Differentiating subtype with active neuritic process production.
MYC-driven neuroblastoma. Comparison of nuclear morphology: MYC-driven neuroblastoma with nucleolar hypertrophy (right) versus non–MYC-driven neuroblastoma with salt-and pepper nuclei (left).
MYC-driven neuroblastoma. Large cell neuroblastoma, a unique pattern of MYCN-driven neuroblastoma.
Neuroblastoma. Dual-colour FISH in a neuroblastoma with heterogeneous MYCN amplification: chromosome 2 a-Satellite D2Z (green signals) and pNB101 cosmid MYCN (red signals). Nuclei are counterstained with DAPI.
MYC-driven neuroblastoma. Typical histology of MYCN-amplified neuroblastoma with a high mitosis-karyorrhexis index.
Neuroblastoma. Plain axial CT image shows a hypodense mass in the left adrenal region. There are internal amorphous/mottled calcifications.
Neuroblastoma. Contrast-enhanced axial CT image shows a heterogeneously enhancing tumour with non-enhancing components suggestive of tumour necrosis. There is compression and anterior displacement of the pancreas.

Q: In Neuroblastoma, [...] gene amplification is a critical molecular marker associated with advanced tumor stage and highly aggressive clinical behavior.
Neuroblastoma. Dual-colour FISH in a neuroblastoma with heterogeneous MYCN amplification: chromosome 2 a-Satellite D2Z (green signals) and pNB101 cosmid MYCN (red signals). Nuclei are counterstained with DAPI.
MYC-driven neuroblastoma. Typical histology of MYCN-amplified neuroblastoma with a high mitosis-karyorrhexis index.
A: MYCN
Back Extra: Neuroblastoma
- Clinical: Neuroblastoma can present with abdominal distension, constipation, or respiratory distress, depending on the primary tumour location.
- Micro: The poorly differentiated subtype of neuroblastoma is characterized by the presence of neurites and Homer Wright rosettes.
- Ancillary: MYCN amplification in neuroblastoma is a key molecular marker associated with advanced stage and aggressive clinical behaviour.
Reference Gallery:
Neuroblastoma. Left adrenalectomy specimen with a 60 mm haemorrhagic, nodular tumour. Note the central calcification, necrosis, and fibrosis.
Neuroblastoma. Undifferentiated subtype without clearly recognizable neurite formation.
Neuroblastoma. Poorly differentiated subtype (inset: higher-magnification view of a Homer Wright rosette).
Neuroblastoma. Differentiating subtype with active neuritic process production.
MYC-driven neuroblastoma. Comparison of nuclear morphology: MYC-driven neuroblastoma with nucleolar hypertrophy (right) versus non–MYC-driven neuroblastoma with salt-and pepper nuclei (left).
MYC-driven neuroblastoma. Large cell neuroblastoma, a unique pattern of MYCN-driven neuroblastoma.
Neuroblastoma. Dual-colour FISH in a neuroblastoma with heterogeneous MYCN amplification: chromosome 2 a-Satellite D2Z (green signals) and pNB101 cosmid MYCN (red signals). Nuclei are counterstained with DAPI.
MYC-driven neuroblastoma. Typical histology of MYCN-amplified neuroblastoma with a high mitosis-karyorrhexis index.
Neuroblastoma. Plain axial CT image shows a hypodense mass in the left adrenal region. There are internal amorphous/mottled calcifications.
Neuroblastoma. Contrast-enhanced axial CT image shows a heterogeneously enhancing tumour with non-enhancing components suggestive of tumour necrosis. There is compression and anterior displacement of the pancreas.

Q: On CT imaging and gross examination, an adrenal Neuroblastoma typically presents as a large, heterogeneously enhancing mass that frequently contains internal areas of necrosis and [...].
Neuroblastoma. Left adrenalectomy specimen with a 60 mm haemorrhagic, nodular tumour. Note the central calcification, necrosis, and fibrosis.
Neuroblastoma. Plain axial CT image shows a hypodense mass in the left adrenal region. There are internal amorphous/mottled calcifications.
Neuroblastoma. Contrast-enhanced axial CT image shows a heterogeneously enhancing tumour with non-enhancing components suggestive of tumour necrosis. There is compression and anterior displacement of the pancreas.
A: calcifications
Back Extra: Neuroblastoma
- Clinical: Neuroblastoma can present with abdominal distension, constipation, or respiratory distress, depending on the primary tumour location.
- Micro: The poorly differentiated subtype of neuroblastoma is characterized by the presence of neurites and Homer Wright rosettes.
- Ancillary: MYCN amplification in neuroblastoma is a key molecular marker associated with advanced stage and aggressive clinical behaviour.
Reference Gallery:
Neuroblastoma. Left adrenalectomy specimen with a 60 mm haemorrhagic, nodular tumour. Note the central calcification, necrosis, and fibrosis.
Neuroblastoma. Undifferentiated subtype without clearly recognizable neurite formation.
Neuroblastoma. Poorly differentiated subtype (inset: higher-magnification view of a Homer Wright rosette).
Neuroblastoma. Differentiating subtype with active neuritic process production.
MYC-driven neuroblastoma. Comparison of nuclear morphology: MYC-driven neuroblastoma with nucleolar hypertrophy (right) versus non–MYC-driven neuroblastoma with salt-and pepper nuclei (left).
MYC-driven neuroblastoma. Large cell neuroblastoma, a unique pattern of MYCN-driven neuroblastoma.
Neuroblastoma. Dual-colour FISH in a neuroblastoma with heterogeneous MYCN amplification: chromosome 2 a-Satellite D2Z (green signals) and pNB101 cosmid MYCN (red signals). Nuclei are counterstained with DAPI.
MYC-driven neuroblastoma. Typical histology of MYCN-amplified neuroblastoma with a high mitosis-karyorrhexis index.
Neuroblastoma. Plain axial CT image shows a hypodense mass in the left adrenal region. There are internal amorphous/mottled calcifications.
Neuroblastoma. Contrast-enhanced axial CT image shows a heterogeneously enhancing tumour with non-enhancing components suggestive of tumour necrosis. There is compression and anterior displacement of the pancreas.

Q: Grossly and histopathologically, Fetus in fetu is distinguished from a mature teratoma by a remarkably high degree of organization, demonstrating recognizable [...] (such as well-formed limbs, a trunk, or a partial face).
Fetus in fetu. Fetus in fetu from the back aspect, showing a combination of anencephaly and craniorachischisis. Note the well-formed limbs and trunk.
Testicular fetus in fetu. A–C This case manifested as an intratesticular mass. It shows fetiform features, with abnormal limb parts. The cut surface reveals advanced organic development.
Fetus in fetu. This example was located in the lumbosacral region of a newborn immediately before excision. The lesion showed a well-developed half of a face, which was able to move the lips and eyebrow.
A: fetal features
Back Extra: Fetus in fetu
- Clinical: Fetus in fetu (FIF) most commonly manifests as an asymptomatic abdominal mass and is usually discovered by prenatal ultrasound.
- Micro: The histopathology of FIF is similar to that of mature teratomas but with a higher degree of organization, including recognizable fetal features like limbs and a face.
- Ancillary: Most genetic analyses reveal genotypic identity between the host and the FIF.
Reference Gallery:
Fetus in fetu. Fetus in fetu from the back aspect, showing a combination of anencephaly and craniorachischisis. Note the well-formed limbs and trunk.
Testicular fetus in fetu. A–C This case manifested as an intratesticular mass. It shows fetiform features, with abnormal limb parts. The cut surface reveals advanced organic development.
Fetus in fetu. This example was located in the lumbosacral region of a newborn immediately before excision. The lesion showed a well-developed half of a face, which was able to move the lips and eyebrow.
Fetus in fetu. Contrast-enhanced sagittal reformatted CT showing a large heterogeneous abdominal mass between the liver and the left kidney, with multiple calcified components favouring fetal parts.
Fetus in fetu. 3D CT with volume-rendering display in bone algorithm showing multiple calcified components within the abdominal mass, resembling the long bones, scapula, and pelvis of a fetus.

Q: On CT imaging, Fetus in fetu often presents as a heterogeneous abdominal mass containing multiple [...] that closely resemble human skeletal structures like long bones, the scapula, and the pelvis.
Fetus in fetu. Contrast-enhanced sagittal reformatted CT showing a large heterogeneous abdominal mass between the liver and the left kidney, with multiple calcified components favouring fetal parts.
Fetus in fetu. 3D CT with volume-rendering display in bone algorithm showing multiple calcified components within the abdominal mass, resembling the long bones, scapula, and pelvis of a fetus.
A: calcified components
Back Extra: Fetus in fetu
- Clinical: Fetus in fetu (FIF) most commonly manifests as an asymptomatic abdominal mass and is usually discovered by prenatal ultrasound.
- Micro: The histopathology of FIF is similar to that of mature teratomas but with a higher degree of organization, including recognizable fetal features like limbs and a face.
- Ancillary: Most genetic analyses reveal genotypic identity between the host and the FIF.
Reference Gallery:
Fetus in fetu. Fetus in fetu from the back aspect, showing a combination of anencephaly and craniorachischisis. Note the well-formed limbs and trunk.
Testicular fetus in fetu. A–C This case manifested as an intratesticular mass. It shows fetiform features, with abnormal limb parts. The cut surface reveals advanced organic development.
Fetus in fetu. This example was located in the lumbosacral region of a newborn immediately before excision. The lesion showed a well-developed half of a face, which was able to move the lips and eyebrow.
Fetus in fetu. Contrast-enhanced sagittal reformatted CT showing a large heterogeneous abdominal mass between the liver and the left kidney, with multiple calcified components favouring fetal parts.
Fetus in fetu. 3D CT with volume-rendering display in bone algorithm showing multiple calcified components within the abdominal mass, resembling the long bones, scapula, and pelvis of a fetus.

Q: [...] is a benign vascular tumor characterized macroscopically by a well-circumscribed, tan-brown mass bulging above the fetal surface, and microscopically by numerous capillaries embedded in a fibroconnective stroma.
Haemangioma of placenta. The cut surface shows a well-circumscribed tan-brown lesion.
Haemangioma of placenta. The lesion is composed of numerous capillaries embedded in a fibroconnective stroma containing fibroblasts and macrophages.
A: Haemangioma of placenta
Back Extra: Haemangioma of placenta
- Clinical: Haemangioma of placenta is most common in patients with multiple gestations, maternal age ≥ 30 years, and conditions such as maternal hypertension, pre-eclampsia, or diabetes mellitus.
- Micro: Placental haemangiomas arise from stem villi and are characterized by numerous capillaries embedded in a fibroconnective stroma with fibroblasts and macrophages.
- Ancillary: The endothelial lining stains for vascular markers like CD31, CD34, GLUT1, and von Willebrand factor, while pericytes stain for MSA.
Reference Gallery:
Haemangioma of placenta. A placental haemangioma (chorangioma) bulging above the fetal surface.
Haemangioma of placenta. The cut surface shows a well-circumscribed tan-brown lesion.
Haemangioma of placenta. Low-power view shows the lesion distinct from surrounding chorionic villi.
Haemangioma of placenta. Trophoblast proliferation can sometimes be seen at the edges of the nodules.
Haemangioma of placenta. The lesion is composed of numerous capillaries embedded in a fibroconnective stroma containing fibroblasts and macrophages.

Q: Haemangioma of placenta, a benign vascular tumor frequently associated with multiple gestations and maternal hypertension, is also known by the specific term [...].
Haemangioma of placenta. A placental haemangioma (chorangioma) bulging above the fetal surface.
A: chorangioma
Back Extra: Haemangioma of placenta
- Clinical: Haemangioma of placenta is most common in patients with multiple gestations, maternal age ≥ 30 years, and conditions such as maternal hypertension, pre-eclampsia, or diabetes mellitus.
- Micro: Placental haemangiomas arise from stem villi and are characterized by numerous capillaries embedded in a fibroconnective stroma with fibroblasts and macrophages.
- Ancillary: The endothelial lining stains for vascular markers like CD31, CD34, GLUT1, and von Willebrand factor, while pericytes stain for MSA.
Reference Gallery:
Haemangioma of placenta. A placental haemangioma (chorangioma) bulging above the fetal surface.
Haemangioma of placenta. The cut surface shows a well-circumscribed tan-brown lesion.
Haemangioma of placenta. Low-power view shows the lesion distinct from surrounding chorionic villi.
Haemangioma of placenta. Trophoblast proliferation can sometimes be seen at the edges of the nodules.
Haemangioma of placenta. The lesion is composed of numerous capillaries embedded in a fibroconnective stroma containing fibroblasts and macrophages.

Q: In the dendritic variant of Blue naevus, histologic examination typically reveals heavily pigmented, spindled, and [...] melanocytes dispersed within a thickened, fibrous dermal background.
Dendritic blue naevus. Dendritic and spindled melanocytes in a fibrous background.
Dendritic blue naevus. At low magnification.
A: dendritic
Back Extra: Blue naevus
- Clinical: Blue naevi are most frequent in children and young adults, with dendritic blue naevi (DBNs) appearing as small, rounded papules and cellular blue naevi (CBNs) as larger, indurated blue nodules.
- Micro: Dendritic blue naevi feature spindled and dendritic melanocytes in a fibrous dermal background, while cellular blue naevi show dense nests and sheets of medium-sized melanocytes extending deeply into the subcutis.
- Ancillary: Blue naevi often contain activating mutations in GNAQ, GNA11, or PLCB4, but lack BRAF, NRAS, and NF1 mutations, distinguishing them from melanoma.
Reference Gallery:
Dendritic blue naevus. Dendritic and spindled melanocytes in a fibrous background.
Dendritic blue naevus. At low magnification.
Cellular blue naevus. Panoramic view of a cellular blue naevus in a 5-year-old.
Cellular blue naevus. Close-up view of a cellular blue naevus in a 5-year-old.
Cellular blue naevus. Higher-magnification view of a cellular blue naevus in a 12-year-old.
Cellular blue naevus. Panoramic view of a cellular blue naevus in a 12-year-old.

Q: In contrast to the dendritic variant, the cellular variant of Blue naevus characteristically forms deep, dense nests and sheets of melanocytes that often extend extensively into the [...].
Cellular blue naevus. Panoramic view of a cellular blue naevus in a 5-year-old.
Cellular blue naevus. Panoramic view of a cellular blue naevus in a 12-year-old.
A: subcutis
Back Extra: Blue naevus
- Clinical: Blue naevi are most frequent in children and young adults, with dendritic blue naevi (DBNs) appearing as small, rounded papules and cellular blue naevi (CBNs) as larger, indurated blue nodules.
- Micro: Dendritic blue naevi feature spindled and dendritic melanocytes in a fibrous dermal background, while cellular blue naevi show dense nests and sheets of medium-sized melanocytes extending deeply into the subcutis.
- Ancillary: Blue naevi often contain activating mutations in GNAQ, GNA11, or PLCB4, but lack BRAF, NRAS, and NF1 mutations, distinguishing them from melanoma.
Reference Gallery:
Dendritic blue naevus. Dendritic and spindled melanocytes in a fibrous background.
Dendritic blue naevus. At low magnification.
Cellular blue naevus. Panoramic view of a cellular blue naevus in a 5-year-old.
Cellular blue naevus. Close-up view of a cellular blue naevus in a 5-year-old.
Cellular blue naevus. Higher-magnification view of a cellular blue naevus in a 12-year-old.
Cellular blue naevus. Panoramic view of a cellular blue naevus in a 12-year-old.

Q: In Congenital Melanocytic Nevus, characteristic histologic features include deep dermal extension wrapping around skin adnexa and [...] infiltration of nevus cells.
Congenital melanocytic naevus. Low-power view of a congenital melanocytic naevus. Note the depth of the dermal component and the skin adnexa surrounded by naevus cells.
Congenital melanocytic naevus. Subendothelial infiltration of naevus cells.
Congenital melanocytic naevus. Another example (at higher magnification) of subendothelial infiltration of naevus cells in a congenital melanocytic naevus.
A: subendothelial
Back Extra: Congenital Melanocytic Nevus
- Clinical: Congenital Melanocytic Nevus (CMN) can present with a wide range of sizes, from small (< 15 mm) to giant (> 400 mm), and may include multiple satellite lesions. Large or giant CMNs can be associated with neurofibroma-like overgrowths and limb atrophy.
- Micro: CMNs are highly cellular at birth and show a characteristic band-like pattern. Neurotization (Wagner–Meissner or Masson bodies) and subendothelial infiltration of naevus cells are common features. Proliferative nodules can occur, raising concerns for atypical behavior.
- Ancillary: Genetic analysis, particularly for NRAS p.Q61 and BRAF p.V600 mutations, may be required for large or atypical CMNs. MAPK pathway activation is a key feature.
Reference Gallery:
Congenital melanocytic naevus. A giant congenital melanocytic naevus (projected adult size of the largest naevus: > 400 mm) and multiple satellite naevi.
Congenital melanocytic naevus. Another example of a giant congenital melanocytic naevus with multiple satellite naevi.
Congenital melanocytic naevus. Multiple benign nodules (some resembling neurofibromas) within a large congenital melanocytic naevus.
Congenital melanocytic naevus. A large congenital melanocytic naevus associated with atrophy of the soft tissues of the arm.
Congenital melanocytic naevus. Low-power view of a congenital melanocytic naevus. Note the depth of the dermal component and the skin adnexa surrounded by naevus cells.
Congenital melanocytic naevus. A giant congenital melanocytic naevus with Wagner–Meissner or Masson bodies, characteristic of neurotization.
Congenital melanocytic naevus. Subendothelial infiltration of naevus cells.
Congenital melanocytic naevus. Another example (at higher magnification) of subendothelial infiltration of naevus cells in a congenital melanocytic naevus.
Congenital melanocytic naevus. A congenital melanocytic naevus with a well-delimited and compact aggregate of naevus cells, characteristic of a proliferative nodule.
Congenital melanocytic naevus. Another example of a proliferative nodule in a congenital melanocytic naevus.

Q: A frequent histologic finding in older lesions of Congenital Melanocytic Nevus is neurotization, characterized by the presence of [...] or Masson bodies.
Congenital melanocytic naevus. A giant congenital melanocytic naevus with Wagner–Meissner or Masson bodies, characteristic of neurotization.
A: Wagner-Meissner
Back Extra: Congenital Melanocytic Nevus
- Clinical: Congenital Melanocytic Nevus (CMN) can present with a wide range of sizes, from small (< 15 mm) to giant (> 400 mm), and may include multiple satellite lesions. Large or giant CMNs can be associated with neurofibroma-like overgrowths and limb atrophy.
- Micro: CMNs are highly cellular at birth and show a characteristic band-like pattern. Neurotization (Wagner–Meissner or Masson bodies) and subendothelial infiltration of naevus cells are common features. Proliferative nodules can occur, raising concerns for atypical behavior.
- Ancillary: Genetic analysis, particularly for NRAS p.Q61 and BRAF p.V600 mutations, may be required for large or atypical CMNs. MAPK pathway activation is a key feature.
Reference Gallery:
Congenital melanocytic naevus. A giant congenital melanocytic naevus (projected adult size of the largest naevus: > 400 mm) and multiple satellite naevi.
Congenital melanocytic naevus. Another example of a giant congenital melanocytic naevus with multiple satellite naevi.
Congenital melanocytic naevus. Multiple benign nodules (some resembling neurofibromas) within a large congenital melanocytic naevus.
Congenital melanocytic naevus. A large congenital melanocytic naevus associated with atrophy of the soft tissues of the arm.
Congenital melanocytic naevus. Low-power view of a congenital melanocytic naevus. Note the depth of the dermal component and the skin adnexa surrounded by naevus cells.
Congenital melanocytic naevus. A giant congenital melanocytic naevus with Wagner–Meissner or Masson bodies, characteristic of neurotization.
Congenital melanocytic naevus. Subendothelial infiltration of naevus cells.
Congenital melanocytic naevus. Another example (at higher magnification) of subendothelial infiltration of naevus cells in a congenital melanocytic naevus.
Congenital melanocytic naevus. A congenital melanocytic naevus with a well-delimited and compact aggregate of naevus cells, characteristic of a proliferative nodule.
Congenital melanocytic naevus. Another example of a proliferative nodule in a congenital melanocytic naevus.

Q: Large or giant variants of Congenital Melanocytic Nevus can develop discrete, compact aggregates of nevus cells called [...] that clinically resemble neurofibromas and may raise concern for atypical behavior.
Congenital melanocytic naevus. Multiple benign nodules (some resembling neurofibromas) within a large congenital melanocytic naevus.
Congenital melanocytic naevus. A congenital melanocytic naevus with a well-delimited and compact aggregate of naevus cells, characteristic of a proliferative nodule.
Congenital melanocytic naevus. Another example of a proliferative nodule in a congenital melanocytic naevus.
A: proliferative nodules
Back Extra: Congenital Melanocytic Nevus
- Clinical: Congenital Melanocytic Nevus (CMN) can present with a wide range of sizes, from small (< 15 mm) to giant (> 400 mm), and may include multiple satellite lesions. Large or giant CMNs can be associated with neurofibroma-like overgrowths and limb atrophy.
- Micro: CMNs are highly cellular at birth and show a characteristic band-like pattern. Neurotization (Wagner–Meissner or Masson bodies) and subendothelial infiltration of naevus cells are common features. Proliferative nodules can occur, raising concerns for atypical behavior.
- Ancillary: Genetic analysis, particularly for NRAS p.Q61 and BRAF p.V600 mutations, may be required for large or atypical CMNs. MAPK pathway activation is a key feature.
Reference Gallery:
Congenital melanocytic naevus. A giant congenital melanocytic naevus (projected adult size of the largest naevus: > 400 mm) and multiple satellite naevi.
Congenital melanocytic naevus. Another example of a giant congenital melanocytic naevus with multiple satellite naevi.
Congenital melanocytic naevus. Multiple benign nodules (some resembling neurofibromas) within a large congenital melanocytic naevus.
Congenital melanocytic naevus. A large congenital melanocytic naevus associated with atrophy of the soft tissues of the arm.
Congenital melanocytic naevus. Low-power view of a congenital melanocytic naevus. Note the depth of the dermal component and the skin adnexa surrounded by naevus cells.
Congenital melanocytic naevus. A giant congenital melanocytic naevus with Wagner–Meissner or Masson bodies, characteristic of neurotization.
Congenital melanocytic naevus. Subendothelial infiltration of naevus cells.
Congenital melanocytic naevus. Another example (at higher magnification) of subendothelial infiltration of naevus cells in a congenital melanocytic naevus.
Congenital melanocytic naevus. A congenital melanocytic naevus with a well-delimited and compact aggregate of naevus cells, characteristic of a proliferative nodule.
Congenital melanocytic naevus. Another example of a proliferative nodule in a congenital melanocytic naevus.

Q: Clinically, Epidermal Naevi typically present as well-circumscribed, hyperkeratotic plaques or papules that characteristically follow the [...].
Common keratinocyte naevus. Hyperkeratotic, brown, velvety papules with a linear arrangement, following the lines of Blaschko.
A: lines of Blaschko
Back Extra: Epidermal Naevi
- Clinical: Epidermal naevi typically present as congenital, well-circumscribed, hyperkeratotic lesions that often follow the lines of Blaschko.
- Micro: Histologically, common keratinocyte naevi show acanthosis, papillomatosis, elongation of the rete ridges, and hyperkeratosis.
- Ancillary: Postzygotic mosaic mutations in genes of the PI3K and RAS/MAPK pathways are often identified in epidermal naevi.
Reference Gallery:
Common keratinocyte naevus. Hyperkeratotic, brown, velvety papules with a linear arrangement, following the lines of Blaschko.
Common keratinocyte naevus. The biopsy shows acanthosis, papillomatosis, elongation of the rete ridges, and hyperkeratosis.
Epidermolytic keratinocyte naevus. Linear arrangement of hyperkeratotic lesions with scaling.
Epidermolytic keratinocyte naevus. The hallmark is epidermolytic hyperkeratosis characterized by hyperkeratosis and vacuolar degeneration with hypergranulosis of the stratum granulosum and stratum spinosum.
Sebaceous naevus. A yellow-orange plaque that has a pebbled surface and is devoid of hairs on the scalp.
Sebaceous naevus. Low-power view showing a complex lesion with abnormal epidermis, sebaceous glands, hair follicles, and sweat glands.
Sebaceous naevus. The epidermis shows features reminiscent of an epidermal naevus. Note the enlarged and abnormally located sebaceous glands.
Sebaceous naevus. Follicles are abnormal and represented by germ-like proliferations of basaloid epithelium.
Porokeratotic eccrine naevus. Linear arrangement of yellowish papules on the sole, with hyperkeratosis on the sweat pores.
Porokeratotic eccrine naevus. Cornoid lamellae overlying acrosyringia and acrotrichia together with marked epidermal acanthosis.
Papular epidermal naevus with skyline basal cell layer. Punch biopsy showing hyperkeratosis and regular acanthosis with broad and rectangular rete ridges.
Papular epidermal naevus with skyline basal cell layer. The basal cell layer shows a striking palisaded arrangement of the nuclei (skyline sign).

Q: The epidermolytic variant of Epidermal Naevi is histologically characterized by [...], showing vacuolar degeneration and prominent hypergranulosis of the upper epidermis.
Epidermolytic keratinocyte naevus. The hallmark is epidermolytic hyperkeratosis characterized by hyperkeratosis and vacuolar degeneration with hypergranulosis of the stratum granulosum and stratum spinosum.
A: epidermolytic hyperkeratosis
Back Extra: Epidermal Naevi
- Clinical: Epidermal naevi typically present as congenital, well-circumscribed, hyperkeratotic lesions that often follow the lines of Blaschko.
- Micro: Histologically, common keratinocyte naevi show acanthosis, papillomatosis, elongation of the rete ridges, and hyperkeratosis.
- Ancillary: Postzygotic mosaic mutations in genes of the PI3K and RAS/MAPK pathways are often identified in epidermal naevi.
Reference Gallery:
Common keratinocyte naevus. Hyperkeratotic, brown, velvety papules with a linear arrangement, following the lines of Blaschko.
Common keratinocyte naevus. The biopsy shows acanthosis, papillomatosis, elongation of the rete ridges, and hyperkeratosis.
Epidermolytic keratinocyte naevus. Linear arrangement of hyperkeratotic lesions with scaling.
Epidermolytic keratinocyte naevus. The hallmark is epidermolytic hyperkeratosis characterized by hyperkeratosis and vacuolar degeneration with hypergranulosis of the stratum granulosum and stratum spinosum.
Sebaceous naevus. A yellow-orange plaque that has a pebbled surface and is devoid of hairs on the scalp.
Sebaceous naevus. Low-power view showing a complex lesion with abnormal epidermis, sebaceous glands, hair follicles, and sweat glands.
Sebaceous naevus. The epidermis shows features reminiscent of an epidermal naevus. Note the enlarged and abnormally located sebaceous glands.
Sebaceous naevus. Follicles are abnormal and represented by germ-like proliferations of basaloid epithelium.
Porokeratotic eccrine naevus. Linear arrangement of yellowish papules on the sole, with hyperkeratosis on the sweat pores.
Porokeratotic eccrine naevus. Cornoid lamellae overlying acrosyringia and acrotrichia together with marked epidermal acanthosis.
Papular epidermal naevus with skyline basal cell layer. Punch biopsy showing hyperkeratosis and regular acanthosis with broad and rectangular rete ridges.
Papular epidermal naevus with skyline basal cell layer. The basal cell layer shows a striking palisaded arrangement of the nuclei (skyline sign).

Q: The papular variant of Epidermal Naevi may demonstrate a pathognomonic palisaded arrangement of nuclei in the basal cell layer, known histologically as the [...].
Papular epidermal naevus with skyline basal cell layer. The basal cell layer shows a striking palisaded arrangement of the nuclei (skyline sign).
A: skyline sign
Back Extra: Epidermal Naevi
- Clinical: Epidermal naevi typically present as congenital, well-circumscribed, hyperkeratotic lesions that often follow the lines of Blaschko.
- Micro: Histologically, common keratinocyte naevi show acanthosis, papillomatosis, elongation of the rete ridges, and hyperkeratosis.
- Ancillary: Postzygotic mosaic mutations in genes of the PI3K and RAS/MAPK pathways are often identified in epidermal naevi.
Reference Gallery:
Common keratinocyte naevus. Hyperkeratotic, brown, velvety papules with a linear arrangement, following the lines of Blaschko.
Common keratinocyte naevus. The biopsy shows acanthosis, papillomatosis, elongation of the rete ridges, and hyperkeratosis.
Epidermolytic keratinocyte naevus. Linear arrangement of hyperkeratotic lesions with scaling.
Epidermolytic keratinocyte naevus. The hallmark is epidermolytic hyperkeratosis characterized by hyperkeratosis and vacuolar degeneration with hypergranulosis of the stratum granulosum and stratum spinosum.
Sebaceous naevus. A yellow-orange plaque that has a pebbled surface and is devoid of hairs on the scalp.
Sebaceous naevus. Low-power view showing a complex lesion with abnormal epidermis, sebaceous glands, hair follicles, and sweat glands.
Sebaceous naevus. The epidermis shows features reminiscent of an epidermal naevus. Note the enlarged and abnormally located sebaceous glands.
Sebaceous naevus. Follicles are abnormal and represented by germ-like proliferations of basaloid epithelium.
Porokeratotic eccrine naevus. Linear arrangement of yellowish papules on the sole, with hyperkeratosis on the sweat pores.
Porokeratotic eccrine naevus. Cornoid lamellae overlying acrosyringia and acrotrichia together with marked epidermal acanthosis.
Papular epidermal naevus with skyline basal cell layer. Punch biopsy showing hyperkeratosis and regular acanthosis with broad and rectangular rete ridges.
Papular epidermal naevus with skyline basal cell layer. The basal cell layer shows a striking palisaded arrangement of the nuclei (skyline sign).

Q: In pediatric patients, Melanoma can present as a rapidly growing nodule arising within a pre-existing [...], often showing atypical epithelioid cells in the dermis and subcutis without connection to the overlying epidermis.
Congenital naevus–associated melanoma occurring at the age of 8 years. A large tumour is located in the dermis and the subcutis, with no connection to the overlying epidermis.
Congenital naevus–associated melanoma occurring at the age of 8 years. Very atypical epithelioid melanocytic cells. The child developed lung metastases at the age of 18 years and was alive without disease at the age of 22 years.
A: congenital nevus
Back Extra: Melanoma
- Clinical: Melanoma in children often presents as rapidly growing nodules within congenital naevi or as unpigmented nodules on normal skin, mimicking other benign conditions.
- Micro: Spitz melanoma is characterized by irregular epidermal hyperplasia, Kamino bodies, and large epithelioid and fusiform melanocytes.
- Ancillary: Genomic analysis can help differentiate Spitz melanoma from atypical Spitz naevus, with Spitz melanomas often showing biallelic loss/inactivation of CDKN2A and TERT promoter mutations.
Reference Gallery:
Congenital melanoma. Cells are positive for HMB45 by immunohistochemistry.
Congenital melanoma. Rounded, irregularly pigmented atypical cells with clear nuclei.
Congenital naevus–associated melanoma occurring at the age of 8 years. A large tumour is located in the dermis and the subcutis, with no connection to the overlying epidermis.
Congenital naevus–associated melanoma occurring at the age of 8 years. At the top left, in the superficial dermis, there is a congenital junctional melanocytic naevus.
Congenital naevus–associated melanoma occurring at the age of 8 years. Very atypical epithelioid melanocytic cells. The child developed lung metastases at the age of 18 years and was alive without disease at the age of 22 years.
Spitz melanoma. Spitz melanoma on the right elbow of an 11-year-old girl. There were no distant metastases or local recurrences after a large excision (5 years of follow-up).
Spitz melanoma. The tumour infiltrates the whole thickness of the dermis and the superficial subcutis. The lesion seems well circumscribed and symmetrical at first glance. There is an ectopic or invasive nodule deep in the subcutis.
Spitz melanoma. High-power view of the deep part of the tumour showing dense cellularity with epithelioid cells and scattered mitotic figures. This tumour showed rearrangement of ALK.
Spitz melanoma. A well-delimited dermal and subcutaneous tumour with replacement of the skin.
Spitz melanoma. Melan-A immunohistochemistry shows heterogeneous staining.
Spitz melanoma. HMB45 immunohistochemistry shows heterogeneous and deep staining, emphasizing the absence of vertical maturation.
Spitz melanoma. p16 immunohistochemistry shows a total loss of expression.

Q: To differentiate a Spitz Melanoma from an atypical Spitz nevus, immunohistochemistry and genomic analysis are highly useful; Spitz Melanoma characteristically shows complete loss of [...] expression due to biallelic inactivation of CDKN2A.
Spitz melanoma. p16 immunohistochemistry shows a total loss of expression.
A: p16
Back Extra: Melanoma
- Clinical: Melanoma in children often presents as rapidly growing nodules within congenital naevi or as unpigmented nodules on normal skin, mimicking other benign conditions.
- Micro: Spitz melanoma is characterized by irregular epidermal hyperplasia, Kamino bodies, and large epithelioid and fusiform melanocytes.
- Ancillary: Genomic analysis can help differentiate Spitz melanoma from atypical Spitz naevus, with Spitz melanomas often showing biallelic loss/inactivation of CDKN2A and TERT promoter mutations.
Reference Gallery:
Congenital melanoma. Cells are positive for HMB45 by immunohistochemistry.
Congenital melanoma. Rounded, irregularly pigmented atypical cells with clear nuclei.
Congenital naevus–associated melanoma occurring at the age of 8 years. A large tumour is located in the dermis and the subcutis, with no connection to the overlying epidermis.
Congenital naevus–associated melanoma occurring at the age of 8 years. At the top left, in the superficial dermis, there is a congenital junctional melanocytic naevus.
Congenital naevus–associated melanoma occurring at the age of 8 years. Very atypical epithelioid melanocytic cells. The child developed lung metastases at the age of 18 years and was alive without disease at the age of 22 years.
Spitz melanoma. Spitz melanoma on the right elbow of an 11-year-old girl. There were no distant metastases or local recurrences after a large excision (5 years of follow-up).
Spitz melanoma. The tumour infiltrates the whole thickness of the dermis and the superficial subcutis. The lesion seems well circumscribed and symmetrical at first glance. There is an ectopic or invasive nodule deep in the subcutis.
Spitz melanoma. High-power view of the deep part of the tumour showing dense cellularity with epithelioid cells and scattered mitotic figures. This tumour showed rearrangement of ALK.
Spitz melanoma. A well-delimited dermal and subcutaneous tumour with replacement of the skin.
Spitz melanoma. Melan-A immunohistochemistry shows heterogeneous staining.
Spitz melanoma. HMB45 immunohistochemistry shows heterogeneous and deep staining, emphasizing the absence of vertical maturation.
Spitz melanoma. p16 immunohistochemistry shows a total loss of expression.

Q: In evaluating a suspected Spitz Melanoma, HMB45 immunohistochemistry typically shows strong, deep staining throughout the tumor, highlighting a diagnostic absence of [...].
Spitz melanoma. HMB45 immunohistochemistry shows heterogeneous and deep staining, emphasizing the absence of vertical maturation.
A: vertical maturation
Back Extra: Melanoma
- Clinical: Melanoma in children often presents as rapidly growing nodules within congenital naevi or as unpigmented nodules on normal skin, mimicking other benign conditions.
- Micro: Spitz melanoma is characterized by irregular epidermal hyperplasia, Kamino bodies, and large epithelioid and fusiform melanocytes.
- Ancillary: Genomic analysis can help differentiate Spitz melanoma from atypical Spitz naevus, with Spitz melanomas often showing biallelic loss/inactivation of CDKN2A and TERT promoter mutations.
Reference Gallery:
Congenital melanoma. Cells are positive for HMB45 by immunohistochemistry.
Congenital melanoma. Rounded, irregularly pigmented atypical cells with clear nuclei.
Congenital naevus–associated melanoma occurring at the age of 8 years. A large tumour is located in the dermis and the subcutis, with no connection to the overlying epidermis.
Congenital naevus–associated melanoma occurring at the age of 8 years. At the top left, in the superficial dermis, there is a congenital junctional melanocytic naevus.
Congenital naevus–associated melanoma occurring at the age of 8 years. Very atypical epithelioid melanocytic cells. The child developed lung metastases at the age of 18 years and was alive without disease at the age of 22 years.
Spitz melanoma. Spitz melanoma on the right elbow of an 11-year-old girl. There were no distant metastases or local recurrences after a large excision (5 years of follow-up).
Spitz melanoma. The tumour infiltrates the whole thickness of the dermis and the superficial subcutis. The lesion seems well circumscribed and symmetrical at first glance. There is an ectopic or invasive nodule deep in the subcutis.
Spitz melanoma. High-power view of the deep part of the tumour showing dense cellularity with epithelioid cells and scattered mitotic figures. This tumour showed rearrangement of ALK.
Spitz melanoma. A well-delimited dermal and subcutaneous tumour with replacement of the skin.
Spitz melanoma. Melan-A immunohistochemistry shows heterogeneous staining.
Spitz melanoma. HMB45 immunohistochemistry shows heterogeneous and deep staining, emphasizing the absence of vertical maturation.
Spitz melanoma. p16 immunohistochemistry shows a total loss of expression.

Q: Microscopically, Naevi are characterized by circumscribed, symmetrical proliferations of cytologically bland [...].
Junctional naevus. Junctional nests of bland melanocytes in a slightly hyperplastic epidermis.
Compound naevus. Nests of bland melanocytes in a slightly hyperplastic epidermis and in the upper dermis (HPS stain).
A: melanocytes
Back Extra: Naevi
- Clinical: Acquired naevi are mostly small (< 5 mm), symmetrical, and uniformly pigmented lesions. They grow slowly during childhood/adolescence and remain stable in size thereafter.
- Micro: Lesions are circumscribed and symmetrical proliferations of cytologically bland melanocytes, often arranged in junctional, dermal, or compound patterns.
- Ancillary: Acquired naevi frequently have BRAF mutations and sometimes NRAS mutations. They do not have chromosomal copy-number changes and have a low Ki-67 proliferation index.
Reference Gallery:
Compound naevus. Predominantly dermal / compound dermal.
Junctional naevus. Junctional nests of bland melanocytes in a slightly hyperplastic epidermis.
Junctional naevus. Junctional nests of bland melanocytes (HPS stain).
Compound naevus. Nests of bland melanocytes in a slightly hyperplastic epidermis and in the upper dermis (HPS stain).
Compound naevus. Nests of bland melanocytes in the junction and upper dermis (HPS stain).

Q: In Naevi, a lesion characterized by nests of bland melanocytes located exclusively along the dermoepidermal junction is classified as having a [...] pattern.
Junctional naevus. Junctional nests of bland melanocytes in a slightly hyperplastic epidermis.
Junctional naevus. Junctional nests of bland melanocytes (HPS stain).
A: junctional
Back Extra: Naevi
- Clinical: Acquired naevi are mostly small (< 5 mm), symmetrical, and uniformly pigmented lesions. They grow slowly during childhood/adolescence and remain stable in size thereafter.
- Micro: Lesions are circumscribed and symmetrical proliferations of cytologically bland melanocytes, often arranged in junctional, dermal, or compound patterns.
- Ancillary: Acquired naevi frequently have BRAF mutations and sometimes NRAS mutations. They do not have chromosomal copy-number changes and have a low Ki-67 proliferation index.
Reference Gallery:
Compound naevus. Predominantly dermal / compound dermal.
Junctional naevus. Junctional nests of bland melanocytes in a slightly hyperplastic epidermis.
Junctional naevus. Junctional nests of bland melanocytes (HPS stain).
Compound naevus. Nests of bland melanocytes in a slightly hyperplastic epidermis and in the upper dermis (HPS stain).
Compound naevus. Nests of bland melanocytes in the junction and upper dermis (HPS stain).

Q: In Naevi, a proliferation of bland melanocytes forming nests in both the dermoepidermal junction and the underlying dermis is classified as having a [...] pattern.
Compound naevus. Predominantly dermal / compound dermal.
Compound naevus. Nests of bland melanocytes in the junction and upper dermis (HPS stain).
A: compound
Back Extra: Naevi
- Clinical: Acquired naevi are mostly small (< 5 mm), symmetrical, and uniformly pigmented lesions. They grow slowly during childhood/adolescence and remain stable in size thereafter.
- Micro: Lesions are circumscribed and symmetrical proliferations of cytologically bland melanocytes, often arranged in junctional, dermal, or compound patterns.
- Ancillary: Acquired naevi frequently have BRAF mutations and sometimes NRAS mutations. They do not have chromosomal copy-number changes and have a low Ki-67 proliferation index.
Reference Gallery:
Compound naevus. Predominantly dermal / compound dermal.
Junctional naevus. Junctional nests of bland melanocytes in a slightly hyperplastic epidermis.
Junctional naevus. Junctional nests of bland melanocytes (HPS stain).
Compound naevus. Nests of bland melanocytes in a slightly hyperplastic epidermis and in the upper dermis (HPS stain).
Compound naevus. Nests of bland melanocytes in the junction and upper dermis (HPS stain).

Q: On dermatoscopy, Pigmented Spindle Cell Naevus (Reed Naevus) frequently presents as a dark macule or papule with a characteristic [...] pattern.
Reed naevus. A well-delimited rounded black papule in the hand of a child.
Reed naevus. On dermatoscopy, a starburst pattern is frequently observed in Reed naevus.
A: starburst
Back Extra: Pigmented Spindle Cell Naevus (Reed Naevus)
- Clinical: Reed naevus usually appears as an asymptomatic, dome-shaped, dark-brown or black macule or papule, commonly affecting the extremities, especially the thigh, in young individuals.
- Micro: Histologically, Reed naevus is characterized by junctional nests of uniform, heavily pigmented spindle cells, often with a symmetrical and well-circumscribed growth pattern.
- Ancillary: NTRK3 rearrangements, detected by break-apart FISH probes, are the most common genetic alteration in Reed naevus, resulting in constitutively activated chimeric fusion proteins.
Reference Gallery:
Reed naevus. A well-delimited rounded black papule in the hand of a child.
Reed naevus. On dermatoscopy, a starburst pattern is frequently observed in Reed naevus.
Reed naevus. A well-circumscribed junctional lesion.
Reed naevus. Large nests of spindle naevomelanocytes with abundant intracytoplasmic melanin.

Q: Histologically, Pigmented Spindle Cell Naevus (Reed Naevus) is a symmetrical, well-circumscribed lesion characterized by large junctional nests of uniform, heavily pigmented [...].
Reed naevus. A well-circumscribed junctional lesion.
Reed naevus. Large nests of spindle naevomelanocytes with abundant intracytoplasmic melanin.
A: spindle cells
Back Extra: Pigmented Spindle Cell Naevus (Reed Naevus)
- Clinical: Reed naevus usually appears as an asymptomatic, dome-shaped, dark-brown or black macule or papule, commonly affecting the extremities, especially the thigh, in young individuals.
- Micro: Histologically, Reed naevus is characterized by junctional nests of uniform, heavily pigmented spindle cells, often with a symmetrical and well-circumscribed growth pattern.
- Ancillary: NTRK3 rearrangements, detected by break-apart FISH probes, are the most common genetic alteration in Reed naevus, resulting in constitutively activated chimeric fusion proteins.
Reference Gallery:
Reed naevus. A well-delimited rounded black papule in the hand of a child.
Reed naevus. On dermatoscopy, a starburst pattern is frequently observed in Reed naevus.
Reed naevus. A well-circumscribed junctional lesion.
Reed naevus. Large nests of spindle naevomelanocytes with abundant intracytoplasmic melanin.

Q: On histopathology, congenital smooth muscle Hamartomas feature disorganized, well-defined bundles of randomly oriented bland [...] with a characteristic cleft between the bundles and surrounding dermis.
Congenital smooth muscle hamartoma. Well-defined bundles of randomly oriented bland smooth muscle cells, with a characteristic cleft between the bundles and the surrounding dermis.
A: smooth muscle cells
Back Extra: Hamartomas
- Clinical: Most hamartomas are congenital and appear as asymptomatic, flesh-coloured dermal plaques or slightly hyperpigmented patches with thick, dark hairs.
- Micro: Histopathology of hamartomas reveals disorganized fascicles of mature smooth muscle in the dermis, increased dermal collagen bundles, or nests of ectopic mature adipose tissue.
- Ancillary: Molecular diagnosis can help classify atypical cases, as the genetic alteration is often present only in the lesion and not in unaffected skin.
Reference Gallery:
Collagen naevus. Skin-coloured papules and nodules on the thigh and buttock.
Collagen naevus. Thickened reticular dermis.
Collagen naevus. Thick and haphazardly oriented collagen bundles.
Congenital smooth muscle hamartoma. A hypertrichotic patch on the back of an infant.
Congenital smooth muscle hamartoma. Well-defined bundles of randomly oriented bland smooth muscle cells, with a characteristic cleft between the bundles and the surrounding dermis.
Becker naevus. Brown hyperpigmentation with irregular serrated borders and coarse dark hairs.
Becker naevus. Increased basal layer pigmentation, mild acanthosis, hyperkeratosis, and regular elongation of rete ridges together with smooth muscle bundles irregularly dispersed within the dermis.
Naevus lipomatosus superficialis. Soft, skin-coloured papules and nodules on a girl’s buttocks.
Naevus lipomatosus superficialis. Nests of ectopic mature adipose tissue within the dermis.

Q: Nevus lipomatosus superficialis, a specific variant among cutaneous Hamartomas, is histologically characterized by nests of ectopic mature [...] within the dermis.
Naevus lipomatosus superficialis. Nests of ectopic mature adipose tissue within the dermis.
A: adipose tissue
Back Extra: Hamartomas
- Clinical: Most hamartomas are congenital and appear as asymptomatic, flesh-coloured dermal plaques or slightly hyperpigmented patches with thick, dark hairs.
- Micro: Histopathology of hamartomas reveals disorganized fascicles of mature smooth muscle in the dermis, increased dermal collagen bundles, or nests of ectopic mature adipose tissue.
- Ancillary: Molecular diagnosis can help classify atypical cases, as the genetic alteration is often present only in the lesion and not in unaffected skin.
Reference Gallery:
Collagen naevus. Skin-coloured papules and nodules on the thigh and buttock.
Collagen naevus. Thickened reticular dermis.
Collagen naevus. Thick and haphazardly oriented collagen bundles.
Congenital smooth muscle hamartoma. A hypertrichotic patch on the back of an infant.
Congenital smooth muscle hamartoma. Well-defined bundles of randomly oriented bland smooth muscle cells, with a characteristic cleft between the bundles and the surrounding dermis.
Becker naevus. Brown hyperpigmentation with irregular serrated borders and coarse dark hairs.
Becker naevus. Increased basal layer pigmentation, mild acanthosis, hyperkeratosis, and regular elongation of rete ridges together with smooth muscle bundles irregularly dispersed within the dermis.
Naevus lipomatosus superficialis. Soft, skin-coloured papules and nodules on a girl’s buttocks.
Naevus lipomatosus superficialis. Nests of ectopic mature adipose tissue within the dermis.

Q: Clinically, congenital smooth muscle Hamartomas often present in infants as asymptomatic, slightly hyperpigmented patches with prominent thick, dark [...] (hypertrichosis).
Congenital smooth muscle hamartoma. A hypertrichotic patch on the back of an infant.
A: hairs
Back Extra: Hamartomas
- Clinical: Most hamartomas are congenital and appear as asymptomatic, flesh-coloured dermal plaques or slightly hyperpigmented patches with thick, dark hairs.
- Micro: Histopathology of hamartomas reveals disorganized fascicles of mature smooth muscle in the dermis, increased dermal collagen bundles, or nests of ectopic mature adipose tissue.
- Ancillary: Molecular diagnosis can help classify atypical cases, as the genetic alteration is often present only in the lesion and not in unaffected skin.
Reference Gallery:
Collagen naevus. Skin-coloured papules and nodules on the thigh and buttock.
Collagen naevus. Thickened reticular dermis.
Collagen naevus. Thick and haphazardly oriented collagen bundles.
Congenital smooth muscle hamartoma. A hypertrichotic patch on the back of an infant.
Congenital smooth muscle hamartoma. Well-defined bundles of randomly oriented bland smooth muscle cells, with a characteristic cleft between the bundles and the surrounding dermis.
Becker naevus. Brown hyperpigmentation with irregular serrated borders and coarse dark hairs.
Becker naevus. Increased basal layer pigmentation, mild acanthosis, hyperkeratosis, and regular elongation of rete ridges together with smooth muscle bundles irregularly dispersed within the dermis.
Naevus lipomatosus superficialis. Soft, skin-coloured papules and nodules on a girl’s buttocks.
Naevus lipomatosus superficialis. Nests of ectopic mature adipose tissue within the dermis.

Q: Histologically, a pilomatricoma typically features a peripheral zone of mitotically active, deeply basophilic cells transitioning into a central zone of pathognomonic, anucleated, eosinophilic [...].
Pilomatricoma. Low-power view of a classic pilomatricoma from the forearm of an 8-year-old child.
Pilomatricoma. Note the small and basophilic basaloid epithelium and the abundant ghost cells, which result from keratinization of the basaloid proliferative component.
A: ghost cells
Back Extra: Pilomatricoma
- Clinical: Pilomatricomas manifest as firm or hard, dermal or hypodermal, slow-growing, usually asymptomatic, solitary nodules measuring 10–30 mm.
- Micro: Pilomatricomas consist of one or several dermal nodules with a peripheral zone of small, deeply basophilic, mitotically active cells and a central zone of eosinophilic ghost cells.
- Ancillary: Most pilomatricomas harbour activating mutations in exon 3 of the CTNNB1 gene, which is involved in the WNT signalling pathway.
Reference Gallery:
Pilomatricoma. Clinical picture of a 3-year-old girl with a pilomatricoma of the face.
Pilomatricoma. Low-power view of a classic pilomatricoma from the forearm of an 8-year-old child.
Pilomatricoma. Note the small and basophilic basaloid epithelium and the abundant ghost cells, which result from keratinization of the basaloid proliferative component.
Pilomatricoma. The ghost cells become calcified, eliciting a vigorous foreign body cell reaction.

Q: A firm, slow-growing dermal nodule that microscopically demonstrates a combination of basophilic basaloid cells, characteristic eosinophilic ghost cells, and frequent calcification with a giant cell reaction is diagnostic of a [...].
Pilomatricoma. Clinical picture of a 3-year-old girl with a pilomatricoma of the face.
Pilomatricoma. Note the small and basophilic basaloid epithelium and the abundant ghost cells, which result from keratinization of the basaloid proliferative component.
Pilomatricoma. The ghost cells become calcified, eliciting a vigorous foreign body cell reaction.
A: pilomatricoma
Back Extra: Pilomatricoma
- Clinical: Pilomatricomas manifest as firm or hard, dermal or hypodermal, slow-growing, usually asymptomatic, solitary nodules measuring 10–30 mm.
- Micro: Pilomatricomas consist of one or several dermal nodules with a peripheral zone of small, deeply basophilic, mitotically active cells and a central zone of eosinophilic ghost cells.
- Ancillary: Most pilomatricomas harbour activating mutations in exon 3 of the CTNNB1 gene, which is involved in the WNT signalling pathway.
Reference Gallery:
Pilomatricoma. Clinical picture of a 3-year-old girl with a pilomatricoma of the face.
Pilomatricoma. Low-power view of a classic pilomatricoma from the forearm of an 8-year-old child.
Pilomatricoma. Note the small and basophilic basaloid epithelium and the abundant ghost cells, which result from keratinization of the basaloid proliferative component.
Pilomatricoma. The ghost cells become calcified, eliciting a vigorous foreign body cell reaction.

Q: Most cases of pilomatricoma harbor an activating mutation in exon 3 of the [...] gene, which is involved in the WNT signaling pathway.
Pilomatricoma. Low-power view of a classic pilomatricoma from the forearm of an 8-year-old child.
A: CTNNB1
Back Extra: Pilomatricoma
- Clinical: Pilomatricomas manifest as firm or hard, dermal or hypodermal, slow-growing, usually asymptomatic, solitary nodules measuring 10–30 mm.
- Micro: Pilomatricomas consist of one or several dermal nodules with a peripheral zone of small, deeply basophilic, mitotically active cells and a central zone of eosinophilic ghost cells.
- Ancillary: Most pilomatricomas harbour activating mutations in exon 3 of the CTNNB1 gene, which is involved in the WNT signalling pathway.
Reference Gallery:
Pilomatricoma. Clinical picture of a 3-year-old girl with a pilomatricoma of the face.
Pilomatricoma. Low-power view of a classic pilomatricoma from the forearm of an 8-year-old child.
Pilomatricoma. Note the small and basophilic basaloid epithelium and the abundant ghost cells, which result from keratinization of the basaloid proliferative component.
Pilomatricoma. The ghost cells become calcified, eliciting a vigorous foreign body cell reaction.

Q: Histologically, a Spitz Naevus is characterized by symmetric nests of plump melanocytes and the frequent presence of extracellular, eosinophilic globules at the dermoepidermal junction known as [...].
Spitz naevus. Kamino bodies and clefting around intraepidermal nests are relatively frequent.
A: Kamino bodies
Back Extra: Spitz Naevus
- Clinical: Spitz naevi often appear as well-defined, pink or flesh-colored papules in children and can grow rapidly before stabilizing.
- Micro: Histologically, Spitz naevi are sharply circumscribed and symmetrical, with nests of large epithelioid and/or spindle melanocytes, often showing pagetoid migration and Kamino bodies.
- Ancillary: Molecular studies, such as FISH and next-generation sequencing, are sometimes necessary to differentiate Spitz naevus from melanoma, especially in cases with atypical features.
Reference Gallery:
Spitz naevus. A well-defined rounded papule in the leg of a child. Note the pink colour and smooth surface.
Spitz naevus. Predominantly epithelioid Spitz naevus with well-circumscribed, mainly intraepidermal nests.
Spitz naevus. Pagetoid migration of naevomelanocytes should not be interpreted as a sign of malignancy in Spitz naevus.
Spitz naevus. Plump epithelioid naevomelanocytes with large nuclei and prominent nucleoli are typically seen.
Spitz naevus. Spitz naevus with predominantly spindle cell morphology, well circumscribed, and with a symmetrical compound pattern.
Spitz naevus. Fascicles of plump spindle naevomelanocytes filling the dermis.
Spitz naevus. Kamino bodies and clefting around intraepidermal nests are relatively frequent.
Chimeric fusions in Spitz naevus. Chimeric fusions of kinase genes involved in Spitz naevi lead to the loss of regulatory and autoinhibitory domains, resulting in constitutive kinase activation.

Q: A characteristic histologic feature of a Spitz Naevus that can mimic melanoma but should not be interpreted as an absolute sign of malignancy is the upward, intraepidermal spread of nevomelanocytes, termed [...].
Spitz naevus. Pagetoid migration of naevomelanocytes should not be interpreted as a sign of malignancy in Spitz naevus.
A: pagetoid migration
Back Extra: Spitz Naevus
- Clinical: Spitz naevi often appear as well-defined, pink or flesh-colored papules in children and can grow rapidly before stabilizing.
- Micro: Histologically, Spitz naevi are sharply circumscribed and symmetrical, with nests of large epithelioid and/or spindle melanocytes, often showing pagetoid migration and Kamino bodies.
- Ancillary: Molecular studies, such as FISH and next-generation sequencing, are sometimes necessary to differentiate Spitz naevus from melanoma, especially in cases with atypical features.
Reference Gallery:
Spitz naevus. A well-defined rounded papule in the leg of a child. Note the pink colour and smooth surface.
Spitz naevus. Predominantly epithelioid Spitz naevus with well-circumscribed, mainly intraepidermal nests.
Spitz naevus. Pagetoid migration of naevomelanocytes should not be interpreted as a sign of malignancy in Spitz naevus.
Spitz naevus. Plump epithelioid naevomelanocytes with large nuclei and prominent nucleoli are typically seen.
Spitz naevus. Spitz naevus with predominantly spindle cell morphology, well circumscribed, and with a symmetrical compound pattern.
Spitz naevus. Fascicles of plump spindle naevomelanocytes filling the dermis.
Spitz naevus. Kamino bodies and clefting around intraepidermal nests are relatively frequent.
Chimeric fusions in Spitz naevus. Chimeric fusions of kinase genes involved in Spitz naevi lead to the loss of regulatory and autoinhibitory domains, resulting in constitutive kinase activation.

Q: Microscopically, the cellular composition of a Spitz Naevus classically consists of well-circumscribed, symmetrical nests composed of large, plump [...] melanocytes.
Spitz naevus. Plump epithelioid naevomelanocytes with large nuclei and prominent nucleoli are typically seen.
Spitz naevus. Spitz naevus with predominantly spindle cell morphology, well circumscribed, and with a symmetrical compound pattern.
A: epithelioid and spindle
Back Extra: Spitz Naevus
- Clinical: Spitz naevi often appear as well-defined, pink or flesh-colored papules in children and can grow rapidly before stabilizing.
- Micro: Histologically, Spitz naevi are sharply circumscribed and symmetrical, with nests of large epithelioid and/or spindle melanocytes, often showing pagetoid migration and Kamino bodies.
- Ancillary: Molecular studies, such as FISH and next-generation sequencing, are sometimes necessary to differentiate Spitz naevus from melanoma, especially in cases with atypical features.
Reference Gallery:
Spitz naevus. A well-defined rounded papule in the leg of a child. Note the pink colour and smooth surface.
Spitz naevus. Predominantly epithelioid Spitz naevus with well-circumscribed, mainly intraepidermal nests.
Spitz naevus. Pagetoid migration of naevomelanocytes should not be interpreted as a sign of malignancy in Spitz naevus.
Spitz naevus. Plump epithelioid naevomelanocytes with large nuclei and prominent nucleoli are typically seen.
Spitz naevus. Spitz naevus with predominantly spindle cell morphology, well circumscribed, and with a symmetrical compound pattern.
Spitz naevus. Fascicles of plump spindle naevomelanocytes filling the dermis.
Spitz naevus. Kamino bodies and clefting around intraepidermal nests are relatively frequent.
Chimeric fusions in Spitz naevus. Chimeric fusions of kinase genes involved in Spitz naevi lead to the loss of regulatory and autoinhibitory domains, resulting in constitutive kinase activation.

Q: Microscopically, cardiac rhabdomyoma is characterized by enlarged, vacuolated myocytes with clear cytoplasm and thin strands of cytoplasm connecting to the peripheral cell membrane, classically known as [...].
Cardiac rhabdomyoma. Panoramic view showing the border between tumour and normal cardiac myocytes.
Cardiac rhabdomyoma. At high magnification, enlarged swollen myocytes with clear cytoplasm are visible. Strands of cytoplasm are connected to the peripheral cell membrane.
A: spider cells
Back Extra: Cardiac Rhabdomyoma
- Clinical: Symptoms vary from asymptomatic to severe, including arrhythmias, outflow obstruction, and valve dysfunction.
- Micro: Characterized by enlarged, vacuolated myocytes with clear cytoplasm and spider-cell morphology.
- Ancillary: Immunohistochemistry shows positive staining for striated muscle cell markers (myoglobin, desmin, actin, and vimentin).
Reference Gallery:
Cardiac rhabdomyoma. Panoramic view showing the border between tumour and normal cardiac myocytes.
Cardiac rhabdomyoma. At high magnification, enlarged swollen myocytes with clear cytoplasm are visible. Strands of cytoplasm are connected to the peripheral cell membrane.
Cardiac rhabdomyoma. 2D echocardiography showing an intracavitary rhabdomyoma of the right ventricular outflow tract.
Cardiac rhabdomyoma. Electrocardiogram-triggered breath-hold proton density (PD)-weighted and T1-weighted fast spin echo MRI in the coronal plane, showing a large homogeneous isointense mass involving the left ventricle wall.
Cardiac rhabdomyoma. The swollen cardiac myocytes are full of glycogen, shown on PAS stain.
Cardiac rhabdomyoma. Autopsy specimen demonstrating multiple cardiac rhabdomyomas involving the left ventricle. The masses can be seen obstructing the ventricular outflow tract.

Q: The characteristic clear cytoplasm of the enlarged myocytes in cardiac rhabdomyoma is due to abundant accumulation of [...], which stains intensely positive on a PAS stain.
Cardiac rhabdomyoma. The swollen cardiac myocytes are full of glycogen, shown on PAS stain.
A: glycogen
Back Extra: Cardiac Rhabdomyoma
- Clinical: Symptoms vary from asymptomatic to severe, including arrhythmias, outflow obstruction, and valve dysfunction.
- Micro: Characterized by enlarged, vacuolated myocytes with clear cytoplasm and spider-cell morphology.
- Ancillary: Immunohistochemistry shows positive staining for striated muscle cell markers (myoglobin, desmin, actin, and vimentin).
Reference Gallery:
Cardiac rhabdomyoma. Panoramic view showing the border between tumour and normal cardiac myocytes.
Cardiac rhabdomyoma. At high magnification, enlarged swollen myocytes with clear cytoplasm are visible. Strands of cytoplasm are connected to the peripheral cell membrane.
Cardiac rhabdomyoma. 2D echocardiography showing an intracavitary rhabdomyoma of the right ventricular outflow tract.
Cardiac rhabdomyoma. Electrocardiogram-triggered breath-hold proton density (PD)-weighted and T1-weighted fast spin echo MRI in the coronal plane, showing a large homogeneous isointense mass involving the left ventricle wall.
Cardiac rhabdomyoma. The swollen cardiac myocytes are full of glycogen, shown on PAS stain.
Cardiac rhabdomyoma. Autopsy specimen demonstrating multiple cardiac rhabdomyomas involving the left ventricle. The masses can be seen obstructing the ventricular outflow tract.

Q: Presenting grossly and radiologically as single or multiple homogeneous masses protruding into the ventricles (often causing outflow tract obstruction), this benign primary heart tumor is diagnosed as [...].
Cardiac rhabdomyoma. 2D echocardiography showing an intracavitary rhabdomyoma of the right ventricular outflow tract.
Cardiac rhabdomyoma. Electrocardiogram-triggered breath-hold proton density (PD)-weighted and T1-weighted fast spin echo MRI in the coronal plane, showing a large homogeneous isointense mass involving the left ventricle wall.
Cardiac rhabdomyoma. Autopsy specimen demonstrating multiple cardiac rhabdomyomas involving the left ventricle. The masses can be seen obstructing the ventricular outflow tract.
A: cardiac rhabdomyoma
Back Extra: Cardiac Rhabdomyoma
- Clinical: Symptoms vary from asymptomatic to severe, including arrhythmias, outflow obstruction, and valve dysfunction.
- Micro: Characterized by enlarged, vacuolated myocytes with clear cytoplasm and spider-cell morphology.
- Ancillary: Immunohistochemistry shows positive staining for striated muscle cell markers (myoglobin, desmin, actin, and vimentin).
Reference Gallery:
Cardiac rhabdomyoma. Panoramic view showing the border between tumour and normal cardiac myocytes.
Cardiac rhabdomyoma. At high magnification, enlarged swollen myocytes with clear cytoplasm are visible. Strands of cytoplasm are connected to the peripheral cell membrane.
Cardiac rhabdomyoma. 2D echocardiography showing an intracavitary rhabdomyoma of the right ventricular outflow tract.
Cardiac rhabdomyoma. Electrocardiogram-triggered breath-hold proton density (PD)-weighted and T1-weighted fast spin echo MRI in the coronal plane, showing a large homogeneous isointense mass involving the left ventricle wall.
Cardiac rhabdomyoma. The swollen cardiac myocytes are full of glycogen, shown on PAS stain.
Cardiac rhabdomyoma. Autopsy specimen demonstrating multiple cardiac rhabdomyomas involving the left ventricle. The masses can be seen obstructing the ventricular outflow tract.

Q: [...] is an infant lung mass characterized microscopically by interlacing fascicles of bland spindle cells that classically infiltrate around bronchial epithelium and large islands of benign cartilage.
Congenital peribronchial myofibroblastic tumour. The lung shows nodular infiltrates of spindle cells around bronchial cartilage and epithelium.
Congenital peribronchial myofibroblastic tumour. The spindle-shaped tumour cells are cytologically bland and infiltrate around the bronchial epithelium and cartilage. There is also extension of tumour cells into the interstitium of surrounding alveolar walls.
A: Congenital Peribronchial Myofibroblastic Tumor
Back Extra: Congenital Peribronchial Myofibroblastic Tumor
- Clinical: The tumour may be evident on antenatal imaging, and it may be associated with hydrops fetalis. Other presentations range from fetal demise or respiratory distress in the newborn period to an incidental radiological mass in an asymptomatic infant.
- Micro: The tumour is composed of interlacing fascicles of uniform spindle cells with eosinophilic cytoplasm and poorly defined cell borders. Large islands of benign cartilage located mainly within peribronchial regions are characteristic.
- Ancillary: Demonstration of ETV6::NTRK3 rearrangement may be helpful in diagnosing this tumour, although no firm molecular diagnostic criteria are available.
Reference Gallery:
Congenital peribronchial myofibroblastic tumour. The lung shows nodular infiltrates of spindle cells around bronchial cartilage and epithelium.
Congenital peribronchial myofibroblastic tumour. The spindle-shaped tumour cells are cytologically bland and infiltrate around the bronchial epithelium and cartilage. There is also extension of tumour cells into the interstitium of surrounding alveolar walls.

Q: A characteristic histologic feature of Fetal Lung Interstitial Tumor is the presence of spongiform, alveolus-like structures resembling the developing lung at [...] weeks' gestation.
Fetal lung interstitial tumour. A localized mass showing spongiform alveolus-like structures resembling lung of 20–24 weeks’ gestation. Note the thick capsule.
A: 20 to 24
Back Extra: Fetal Lung Interstitial Tumour
- Clinical: Fetal Lung Interstitial Tumour (FLIT) manifests in the first 3 months of life as a solid or microcystic lung mass, often presenting with respiratory difficulties.
- Micro: FLIT consists of immature airspaces with widened septa containing uniform, bland mesenchymal cells, and the airway spaces are lined by flattened or cuboidal epithelium.
- Ancillary: Some cases of FLIT have shown ALK fusions, specifically A2M::ALK.
Reference Gallery:
Fetal lung interstitial tumour. A localized mass showing spongiform alveolus-like structures resembling lung of 20–24 weeks’ gestation. Note the thick capsule.
Fetal lung interstitial tumour. Interstitial cells are monotonous and uniformly distributed, with the walls covered by native epithelium.

Q: In a Fetal Lung Interstitial Tumor, the widened septa of the immature airspaces are typically expanded by uniform, monotonous [...] cells and lined by native flattened or cuboidal epithelium.
Fetal lung interstitial tumour. Interstitial cells are monotonous and uniformly distributed, with the walls covered by native epithelium.
A: mesenchymal
Back Extra: Fetal Lung Interstitial Tumour
- Clinical: Fetal Lung Interstitial Tumour (FLIT) manifests in the first 3 months of life as a solid or microcystic lung mass, often presenting with respiratory difficulties.
- Micro: FLIT consists of immature airspaces with widened septa containing uniform, bland mesenchymal cells, and the airway spaces are lined by flattened or cuboidal epithelium.
- Ancillary: Some cases of FLIT have shown ALK fusions, specifically A2M::ALK.
Reference Gallery:
Fetal lung interstitial tumour. A localized mass showing spongiform alveolus-like structures resembling lung of 20–24 weeks’ gestation. Note the thick capsule.
Fetal lung interstitial tumour. Interstitial cells are monotonous and uniformly distributed, with the walls covered by native epithelium.

Q: Mutations in the DICER1 gene are pathognomonic for [...], a pediatric lung tumor whose Type I variant typically exhibits a multilocular cystic architecture with subepithelial primitive mesenchymal cells.
Pleuropulmonary blastoma. A type I pleuropulmonary blastoma showing a typical loculated cystic architecture (left) after removal of purulent fluid from superimposed infection (right).
Type I pleuropulmonary blastoma. Low-power view of the multilocular cystic architecture of a type I pleuropulmonary blastoma. Expanded airspaces are separated by septa of variable thickness.
Type I pleuropulmonary blastoma. High-power view of a cyst wall shows focal subepithelial collections of primitive cells in a pale-blue matrix. This portion of the cyst is lined by cuboidal alveolar type II pneumocytes.
A: Pleuropulmonary Blastoma
Back Extra: Pleuropulmonary Blastoma
- Clinical: Type I PPB presents with shortness of breath, pneumothorax, or asymptomatic cysts on chest X-ray, while Type II and III PPB present with more aggressive symptoms like weight loss and fever.
- Micro: Type I PPB has a multilocular cystic architecture with thin septa and primitive mesenchymal cells beneath the epithelium. Type II and III PPB have solid and sarcomatous components, often with anaplasia and blastemal nodules.
- Ancillary: DICER1 mutations are pathognomonic for PPB, and TP53 mutations are common in Type II and III tumours.
Reference Gallery:
Pleuropulmonary blastoma. A type I pleuropulmonary blastoma showing a typical loculated cystic architecture (left) after removal of purulent fluid from superimposed infection (right).
Type I pleuropulmonary blastoma. Low-power view of the multilocular cystic architecture of a type I pleuropulmonary blastoma. Expanded airspaces are separated by septa of variable thickness.
Solid pleuropulmonary blastoma. High-grade malignant cells with hyperchromatic and enlarged nuclei are common in solid portions of type II and type III pleuropulmonary blastomas. Regions of anaplasia seen here are associated with TP53 mutations.
Solid pleuropulmonary blastoma. Spindle cell sarcoma and malignant cartilage are two other patterns seen in solid portions of type II and type III pleuropulmonary blastomas.
Type I pleuropulmonary blastoma. Medium-power view showing intersecting septa lined by bronchiolar epithelium. Small areas of subepithelial mesenchyme in the cyst wall are seen at the bottom of the image.
Solid pleuropulmonary blastoma. Solid sarcomatous portions of type II and type III pleuropulmonary blastomas commonly have spindled, ovoid, and stellate cells in a pale-blue matrix, resembling embryonal rhabdomyosarcoma. These areas are often associated with more tightly packed blastemal nests of cells with hyperchromatic nuclei and high N:C ratios. A small round blastemal nest is seen in the lower-left portion of this photomicrograph.
Type I pleuropulmonary blastoma. High-power view of a cyst wall shows focal subepithelial collections of primitive cells in a pale-blue matrix. This portion of the cyst is lined by cuboidal alveolar type II pneumocytes.

Q: In solid variants (Type II and III) of Pleuropulmonary Blastoma, the presence of severe cytologic anaplasia (hyperchromatic and enlarged nuclei) is frequently associated with mutations in the [...] gene.
Solid pleuropulmonary blastoma. High-grade malignant cells with hyperchromatic and enlarged nuclei are common in solid portions of type II and type III pleuropulmonary blastomas. Regions of anaplasia seen here are associated with TP53 mutations.
A: TP53
Back Extra: Pleuropulmonary Blastoma
- Clinical: Type I PPB presents with shortness of breath, pneumothorax, or asymptomatic cysts on chest X-ray, while Type II and III PPB present with more aggressive symptoms like weight loss and fever.
- Micro: Type I PPB has a multilocular cystic architecture with thin septa and primitive mesenchymal cells beneath the epithelium. Type II and III PPB have solid and sarcomatous components, often with anaplasia and blastemal nodules.
- Ancillary: DICER1 mutations are pathognomonic for PPB, and TP53 mutations are common in Type II and III tumours.
Reference Gallery:
Pleuropulmonary blastoma. A type I pleuropulmonary blastoma showing a typical loculated cystic architecture (left) after removal of purulent fluid from superimposed infection (right).
Type I pleuropulmonary blastoma. Low-power view of the multilocular cystic architecture of a type I pleuropulmonary blastoma. Expanded airspaces are separated by septa of variable thickness.
Solid pleuropulmonary blastoma. High-grade malignant cells with hyperchromatic and enlarged nuclei are common in solid portions of type II and type III pleuropulmonary blastomas. Regions of anaplasia seen here are associated with TP53 mutations.
Solid pleuropulmonary blastoma. Spindle cell sarcoma and malignant cartilage are two other patterns seen in solid portions of type II and type III pleuropulmonary blastomas.
Type I pleuropulmonary blastoma. Medium-power view showing intersecting septa lined by bronchiolar epithelium. Small areas of subepithelial mesenchyme in the cyst wall are seen at the bottom of the image.
Solid pleuropulmonary blastoma. Solid sarcomatous portions of type II and type III pleuropulmonary blastomas commonly have spindled, ovoid, and stellate cells in a pale-blue matrix, resembling embryonal rhabdomyosarcoma. These areas are often associated with more tightly packed blastemal nests of cells with hyperchromatic nuclei and high N:C ratios. A small round blastemal nest is seen in the lower-left portion of this photomicrograph.
Type I pleuropulmonary blastoma. High-power view of a cyst wall shows focal subepithelial collections of primitive cells in a pale-blue matrix. This portion of the cyst is lined by cuboidal alveolar type II pneumocytes.

Q: Solid, sarcomatous regions of Type II and III Pleuropulmonary Blastoma often resemble embryonal rhabdomyosarcoma and characteristically contain tightly packed nests of primitive cells known as [...] nodules.
Solid pleuropulmonary blastoma. Solid sarcomatous portions of type II and type III pleuropulmonary blastomas commonly have spindled, ovoid, and stellate cells in a pale-blue matrix, resembling embryonal rhabdomyosarcoma. These areas are often associated with more tightly packed blastemal nests of cells with hyperchromatic nuclei and high N:C ratios. A small round blastemal nest is seen in the lower-left portion of this photomicrograph.
A: blastemal
Back Extra: Pleuropulmonary Blastoma
- Clinical: Type I PPB presents with shortness of breath, pneumothorax, or asymptomatic cysts on chest X-ray, while Type II and III PPB present with more aggressive symptoms like weight loss and fever.
- Micro: Type I PPB has a multilocular cystic architecture with thin septa and primitive mesenchymal cells beneath the epithelium. Type II and III PPB have solid and sarcomatous components, often with anaplasia and blastemal nodules.
- Ancillary: DICER1 mutations are pathognomonic for PPB, and TP53 mutations are common in Type II and III tumours.
Reference Gallery:
Pleuropulmonary blastoma. A type I pleuropulmonary blastoma showing a typical loculated cystic architecture (left) after removal of purulent fluid from superimposed infection (right).
Type I pleuropulmonary blastoma. Low-power view of the multilocular cystic architecture of a type I pleuropulmonary blastoma. Expanded airspaces are separated by septa of variable thickness.
Solid pleuropulmonary blastoma. High-grade malignant cells with hyperchromatic and enlarged nuclei are common in solid portions of type II and type III pleuropulmonary blastomas. Regions of anaplasia seen here are associated with TP53 mutations.
Solid pleuropulmonary blastoma. Spindle cell sarcoma and malignant cartilage are two other patterns seen in solid portions of type II and type III pleuropulmonary blastomas.
Type I pleuropulmonary blastoma. Medium-power view showing intersecting septa lined by bronchiolar epithelium. Small areas of subepithelial mesenchyme in the cyst wall are seen at the bottom of the image.
Solid pleuropulmonary blastoma. Solid sarcomatous portions of type II and type III pleuropulmonary blastomas commonly have spindled, ovoid, and stellate cells in a pale-blue matrix, resembling embryonal rhabdomyosarcoma. These areas are often associated with more tightly packed blastemal nests of cells with hyperchromatic nuclei and high N:C ratios. A small round blastemal nest is seen in the lower-left portion of this photomicrograph.
Type I pleuropulmonary blastoma. High-power view of a cyst wall shows focal subepithelial collections of primitive cells in a pale-blue matrix. This portion of the cyst is lined by cuboidal alveolar type II pneumocytes.