Title: WHO / Eye_Orbit
Tags: Eye_Orbit::Eyelid_Adnexal::Benign Eye_Orbit::Hematolymphoid::Lymphoma Eye_Orbit::Lacrimal_Epithelial::Malignant Eye_Orbit::Conjunctiva::Melanocytic_Tumors Eye_Orbit::Eyelid_Adnexal::Malignant Eye_Orbit::Soft_Tissue::Vascular Eye_Orbit::Conjunctiva::Epithelial_Tumors Eye_Orbit::Soft_Tissue::Fibrous_Fibroblastic Eye_Orbit::Hematolymphoid::Histiocytic_Dendritic Eye_Orbit::Soft_Tissue::Peripheral_Nerve_Sheath Eye_Orbit::Eyelid_Epithelial::Benign_Premalignant

Q: The hallmark histologic feature of Mesenchymal Chondrosarcoma is a distinctive [...] morphology, featuring islands of well-differentiated hyaline cartilage abruptly admixed with sheets of undifferentiated small round or spindled cells.
Orbital mesenchymal chondrosarcoma. Tumour shows biphasic component. The cartilage component of the tumour and primitive mesenchymal cells composed of round and spindle cells are seen.
Orbital mesenchymal chondrosarcoma. Cartilage component of the tumour and a mesenchymal component made of undifferentiated small round or spindled cells.
A: biphasic
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Mesenchymal chondrosarcoma of the orbit presents with non-specific symptoms such as proptosis, ptosis, diplopia, loss of vision, and pain. It is more common in adult females in the second and third decades of life.
- Micro: The tumour has a biphasic appearance with foci of well-differentiated hyaline cartilage and a mesenchymal component of undifferentiated small round or spindled cells.
- Ancillary: SOX9 and focal S100 protein are often positive in the round cells. The presence of a HEY1::NCOA2 fusion can be a helpful diagnostic marker.
Reference Gallery:
Orbital mesenchymal chondrosarcoma. Eosinophilic matrix mimicking osteoid and the mesenchymal tumour cells.
Orbital mesenchymal chondrosarcoma. Tumour shows biphasic component. The cartilage component of the tumour and primitive mesenchymal cells composed of round and spindle cells are seen.
Orbital mesenchymal chondrosarcoma. Membrane positivity of CD99 in the tumour cells and negativity in the cartilage component.
Orbital mesenchymal chondrosarcoma. Cartilage component of the tumour and a mesenchymal component made of undifferentiated small round or spindled cells.
Orbital mesenchymal chondrosarcoma. MRI T1 post-contrast fat sat, left orbital conus mass. The two components are subtle with mostly a solid enhancing (round cell component) appearance with subtle flecks of heterogeneous density (cartilage component).
Orbital mesenchymal chondrosarcoma. Two different cases of orbital mesenchymal chondrosarcoma with transition from round cell component to cartilage component, with resting chondrocytes at the interface.
Orbital mesenchymal chondrosarcoma. Two different cases of orbital mesenchymal chondrosarcoma with transition from round cell component to cartilage component, with resting chondrocytes at the interface.
Orbital mesenchymal chondrosarcoma. Round cell to matrix transition with matrix exhibiting a zonal endochondral ossification-like progression of cartilage to bone/mineralization. At the interface between round cells and cartilage on the lower right are resting, then proliferative, then hypertrophic chondrocytes, to ossification/mineralization on the top left.
Orbital mesenchymal chondrosarcoma. This master regulator of chondrogenesis, SOX9, stains both round cells and cartilage, indicating that the primitive round cell component is composed of immature cartilage-phenotype cells.

Q: In Mesenchymal Chondrosarcoma, both the hyaline cartilage and the primitive small round cell component demonstrate nuclear positivity for the master regulator of chondrogenesis, [...].
Orbital mesenchymal chondrosarcoma. This master regulator of chondrogenesis, SOX9, stains both round cells and cartilage, indicating that the primitive round cell component is composed of immature cartilage-phenotype cells.
A: SOX9
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Mesenchymal chondrosarcoma of the orbit presents with non-specific symptoms such as proptosis, ptosis, diplopia, loss of vision, and pain. It is more common in adult females in the second and third decades of life.
- Micro: The tumour has a biphasic appearance with foci of well-differentiated hyaline cartilage and a mesenchymal component of undifferentiated small round or spindled cells.
- Ancillary: SOX9 and focal S100 protein are often positive in the round cells. The presence of a HEY1::NCOA2 fusion can be a helpful diagnostic marker.
Reference Gallery:
Orbital mesenchymal chondrosarcoma. Eosinophilic matrix mimicking osteoid and the mesenchymal tumour cells.
Orbital mesenchymal chondrosarcoma. Tumour shows biphasic component. The cartilage component of the tumour and primitive mesenchymal cells composed of round and spindle cells are seen.
Orbital mesenchymal chondrosarcoma. Membrane positivity of CD99 in the tumour cells and negativity in the cartilage component.
Orbital mesenchymal chondrosarcoma. Cartilage component of the tumour and a mesenchymal component made of undifferentiated small round or spindled cells.
Orbital mesenchymal chondrosarcoma. MRI T1 post-contrast fat sat, left orbital conus mass. The two components are subtle with mostly a solid enhancing (round cell component) appearance with subtle flecks of heterogeneous density (cartilage component).
Orbital mesenchymal chondrosarcoma. Two different cases of orbital mesenchymal chondrosarcoma with transition from round cell component to cartilage component, with resting chondrocytes at the interface.
Orbital mesenchymal chondrosarcoma. Two different cases of orbital mesenchymal chondrosarcoma with transition from round cell component to cartilage component, with resting chondrocytes at the interface.
Orbital mesenchymal chondrosarcoma. Round cell to matrix transition with matrix exhibiting a zonal endochondral ossification-like progression of cartilage to bone/mineralization. At the interface between round cells and cartilage on the lower right are resting, then proliferative, then hypertrophic chondrocytes, to ossification/mineralization on the top left.
Orbital mesenchymal chondrosarcoma. This master regulator of chondrogenesis, SOX9, stains both round cells and cartilage, indicating that the primitive round cell component is composed of immature cartilage-phenotype cells.

Q: At the transition zone between the round cells and the cartilaginous matrix in Mesenchymal Chondrosarcoma, the tissue can display a progression from resting to hypertrophic chondrocytes that mimics [...].
Orbital mesenchymal chondrosarcoma. Round cell to matrix transition with matrix exhibiting a zonal endochondral ossification-like progression of cartilage to bone/mineralization. At the interface between round cells and cartilage on the lower right are resting, then proliferative, then hypertrophic chondrocytes, to ossification/mineralization on the top left.
A: endochondral ossification
Back Extra: Mesenchymal Chondrosarcoma
- Clinical: Mesenchymal chondrosarcoma of the orbit presents with non-specific symptoms such as proptosis, ptosis, diplopia, loss of vision, and pain. It is more common in adult females in the second and third decades of life.
- Micro: The tumour has a biphasic appearance with foci of well-differentiated hyaline cartilage and a mesenchymal component of undifferentiated small round or spindled cells.
- Ancillary: SOX9 and focal S100 protein are often positive in the round cells. The presence of a HEY1::NCOA2 fusion can be a helpful diagnostic marker.
Reference Gallery:
Orbital mesenchymal chondrosarcoma. Eosinophilic matrix mimicking osteoid and the mesenchymal tumour cells.
Orbital mesenchymal chondrosarcoma. Tumour shows biphasic component. The cartilage component of the tumour and primitive mesenchymal cells composed of round and spindle cells are seen.
Orbital mesenchymal chondrosarcoma. Membrane positivity of CD99 in the tumour cells and negativity in the cartilage component.
Orbital mesenchymal chondrosarcoma. Cartilage component of the tumour and a mesenchymal component made of undifferentiated small round or spindled cells.
Orbital mesenchymal chondrosarcoma. MRI T1 post-contrast fat sat, left orbital conus mass. The two components are subtle with mostly a solid enhancing (round cell component) appearance with subtle flecks of heterogeneous density (cartilage component).
Orbital mesenchymal chondrosarcoma. Two different cases of orbital mesenchymal chondrosarcoma with transition from round cell component to cartilage component, with resting chondrocytes at the interface.
Orbital mesenchymal chondrosarcoma. Two different cases of orbital mesenchymal chondrosarcoma with transition from round cell component to cartilage component, with resting chondrocytes at the interface.
Orbital mesenchymal chondrosarcoma. Round cell to matrix transition with matrix exhibiting a zonal endochondral ossification-like progression of cartilage to bone/mineralization. At the interface between round cells and cartilage on the lower right are resting, then proliferative, then hypertrophic chondrocytes, to ossification/mineralization on the top left.
Orbital mesenchymal chondrosarcoma. This master regulator of chondrogenesis, SOX9, stains both round cells and cartilage, indicating that the primitive round cell component is composed of immature cartilage-phenotype cells.

Q: Microscopically, irregular, curvilinear trabeculae of woven bone without peripheral osteoblastic rimming are the classic hallmark of [...].
Diagnosis: Fibrous dysplasia. Trabeculae of woven bone without peripheral osteoblasts.
A: Fibrous Dysplasia
Back Extra: Fibrous Dysplasia
- Clinical: Fibrous dysplasia usually presents with radiolucent images except in cranial and mandibular lesions, which are radiopaque due to more sclerotic bone composition.
- Micro: Microscopically, fibrous dysplasia shows varying extents of fibrous and osseous components with irregular, curvilinear trabeculae of woven bone and rare mitoses.
- Ancillary: GNAS mutation analysis may be helpful to distinguish fibrous dysplasia from low-grade central osteosarcoma, with mutations detected in 50-70% of cases.
Reference Gallery:
Diagnosis: Fibrous dysplasia. Coronal CT. Polyostotic fibrous dysplasia affecting periorbital bones.
Diagnosis: Fibrous dysplasia. CT scan. Polyostotic fibrous dysplasia showing narrowing of the optic canal (arrows).
Diagnosis: Fibrous dysplasia. Trabeculae of woven bone without peripheral osteoblasts.

Q: On imaging, cranial and mandibular lesions of [...] frequently present as expansive, radiopaque (sclerotic) masses that can cause narrowing of adjacent structures (e.g., the optic canal).
Diagnosis: Fibrous dysplasia. Coronal CT. Polyostotic fibrous dysplasia affecting periorbital bones.
Diagnosis: Fibrous dysplasia. CT scan. Polyostotic fibrous dysplasia showing narrowing of the optic canal (arrows).
A: Fibrous Dysplasia
Back Extra: Fibrous Dysplasia
- Clinical: Fibrous dysplasia usually presents with radiolucent images except in cranial and mandibular lesions, which are radiopaque due to more sclerotic bone composition.
- Micro: Microscopically, fibrous dysplasia shows varying extents of fibrous and osseous components with irregular, curvilinear trabeculae of woven bone and rare mitoses.
- Ancillary: GNAS mutation analysis may be helpful to distinguish fibrous dysplasia from low-grade central osteosarcoma, with mutations detected in 50-70% of cases.
Reference Gallery:
Diagnosis: Fibrous dysplasia. Coronal CT. Polyostotic fibrous dysplasia affecting periorbital bones.
Diagnosis: Fibrous dysplasia. CT scan. Polyostotic fibrous dysplasia showing narrowing of the optic canal (arrows).
Diagnosis: Fibrous dysplasia. Trabeculae of woven bone without peripheral osteoblasts.

Q: Radiographically, an Aneurysmal Bone Cyst often appears as a lytic, eccentric, expansile mass that characteristically demonstrates [...] on T2-weighted MRI, corresponding to blood-filled cystic spaces.
Aneurysmal bone cyst. A lesion of the retroorbital bone. Fat suppressed T2-weighted MRI images in the axial (A) and coronal (B) plane showing a multicystic lesion with fluid-fluid levels.
Aneurysmal bone cyst. Gross image of a resected specimen from the retro-orbital bone showing multiple haemorrhagic cystic spaces with intervening septations.
A: fluid-fluid levels
Back Extra: Aneurysmal Bone Cyst
- Clinical: Common signs and symptoms include pain, swelling, proptosis, ophthalmoplegia, and exophthalmos. Radiographically, it appears as a lytic, eccentric, expansile mass with fluid-fluid levels on MRI.
- Micro: Characterized by blood-filled cystic spaces separated by fibrous septa containing spindle cells, osteoclast-like giant cells, and reactive woven bone. ‘Blue bone’ may be present in approximately one-third of cases.
- Ancillary: USP6 gene rearrangement can be detected by FISH using break-apart probes, aiding in the diagnosis of Aneurysmal Bone Cyst.
Reference Gallery:
Aneurysmal bone cyst. A lesion of the retroorbital bone. Fat suppressed T2-weighted MRI images in the axial (A) and coronal (B) plane showing a multicystic lesion with fluid-fluid levels.
Aneurysmal bone cyst. Gross image of a resected specimen from the retro-orbital bone showing multiple haemorrhagic cystic spaces with intervening septations.
Aneurysmal bone cyst. Microscopic images showing cyst wall with multiple septations. Cyst wall showing lack of distinctive cell-lining and composed of spindle cells with scattered osteoclast-like giant cells, haemorrhage, haemosiderin pigment deposition and areas of ‘blue bone’.
Aneurysmal bone cyst. The cyst wall is composed of fibroblast-like spindle cells and osteoclast-like giant cells.

Q: Microscopically, the fibrous septa of an Aneurysmal Bone Cyst contain spindle cells, scattered osteoclast-like giant cells, and reactive woven bone that may present as a distinctive, basophilic matrix known as [...].
Aneurysmal bone cyst. Microscopic images showing cyst wall with multiple septations. Cyst wall showing lack of distinctive cell-lining and composed of spindle cells with scattered osteoclast-like giant cells, haemorrhage, haemosiderin pigment deposition and areas of ‘blue bone’.
Aneurysmal bone cyst. The cyst wall is composed of fibroblast-like spindle cells and osteoclast-like giant cells.
A: "blue bone"
Back Extra: Aneurysmal Bone Cyst
- Clinical: Common signs and symptoms include pain, swelling, proptosis, ophthalmoplegia, and exophthalmos. Radiographically, it appears as a lytic, eccentric, expansile mass with fluid-fluid levels on MRI.
- Micro: Characterized by blood-filled cystic spaces separated by fibrous septa containing spindle cells, osteoclast-like giant cells, and reactive woven bone. ‘Blue bone’ may be present in approximately one-third of cases.
- Ancillary: USP6 gene rearrangement can be detected by FISH using break-apart probes, aiding in the diagnosis of Aneurysmal Bone Cyst.
Reference Gallery:
Aneurysmal bone cyst. A lesion of the retroorbital bone. Fat suppressed T2-weighted MRI images in the axial (A) and coronal (B) plane showing a multicystic lesion with fluid-fluid levels.
Aneurysmal bone cyst. Gross image of a resected specimen from the retro-orbital bone showing multiple haemorrhagic cystic spaces with intervening septations.
Aneurysmal bone cyst. Microscopic images showing cyst wall with multiple septations. Cyst wall showing lack of distinctive cell-lining and composed of spindle cells with scattered osteoclast-like giant cells, haemorrhage, haemosiderin pigment deposition and areas of ‘blue bone’.
Aneurysmal bone cyst. The cyst wall is composed of fibroblast-like spindle cells and osteoclast-like giant cells.

Q: The neoplastic mononuclear stromal cells in Giant Cell Tumor of Bone characteristically harbor a specific histone gene mutation, which can be reliably detected via immunohistochemistry for [...].
Giant cell tumour of bone. H3.3 p.Gly34Trp (G34W) immunoreactivity of atypical stromal cells is present in a large majority of giant cell tumours of bone. It is often absent in patients with a predisposing genetic syndrome such as Paget disease of bone, Gorlin-Goltz syndrome, and Jaffe-Campanacci syndrome.
A: H3.3 p.G34W
Back Extra: Giant Cell Tumor of Bone
- Clinical: Giant Cell Tumor of Bone can present with a visible mass, proptosis, eyelid edema, diplopia, and facial changes due to nerve compression.
- Micro: The tumor is characterized by a predominance of multinucleated osteoclast-like giant cells and mononuclear stromal cells with H3.3 p.G34W mutation.
- Ancillary: H3.3 p.G34W immunoreactivity is a reliable marker for the presence of the mutation in Giant Cell Tumor of Bone.
Reference Gallery:
Giant cell tumour of bone. Lateral view of a recurrent giant cell tumour of the right orbit.
Giant cell tumour of bone. Axial T1 MRI with contrast of a recurrent giant cell tumour of the right orbit.
Giant cell tumour of bone. Coronal T1 MRI with contrast of a recurrent right orbital giant cell tumour.
Giant cell tumour of bone. Typical features of a giant cell tumour showing a predominance of osteoclast-like giant cells with interspersed mononuclear neoplastic cells.
Giant cell tumour of bone. High power view showing nuclear atypia of the neoplastic mononuclear cells with irregular nuclear profiles and moderate- to large-size nucleoli in some cells.
Giant cell tumour of bone. H3.3 p.Gly34Trp (G34W) immunoreactivity of atypical stromal cells is present in a large majority of giant cell tumours of bone. It is often absent in patients with a predisposing genetic syndrome such as Paget disease of bone, Gorlin-Goltz syndrome, and Jaffe-Campanacci syndrome.

Q: The histologic hallmark of Giant Cell Tumor of Bone is a prominent, uniformly distributed population of reactive, multinucleated [...] admixed with the neoplastic mononuclear stromal cells.
Giant cell tumour of bone. Typical features of a giant cell tumour showing a predominance of osteoclast-like giant cells with interspersed mononuclear neoplastic cells.
Giant cell tumour of bone. High power view showing nuclear atypia of the neoplastic mononuclear cells with irregular nuclear profiles and moderate- to large-size nucleoli in some cells.
A: osteoclast-like giant cells
Back Extra: Giant Cell Tumor of Bone
- Clinical: Giant Cell Tumor of Bone can present with a visible mass, proptosis, eyelid edema, diplopia, and facial changes due to nerve compression.
- Micro: The tumor is characterized by a predominance of multinucleated osteoclast-like giant cells and mononuclear stromal cells with H3.3 p.G34W mutation.
- Ancillary: H3.3 p.G34W immunoreactivity is a reliable marker for the presence of the mutation in Giant Cell Tumor of Bone.
Reference Gallery:
Giant cell tumour of bone. Lateral view of a recurrent giant cell tumour of the right orbit.
Giant cell tumour of bone. Axial T1 MRI with contrast of a recurrent giant cell tumour of the right orbit.
Giant cell tumour of bone. Coronal T1 MRI with contrast of a recurrent right orbital giant cell tumour.
Giant cell tumour of bone. Typical features of a giant cell tumour showing a predominance of osteoclast-like giant cells with interspersed mononuclear neoplastic cells.
Giant cell tumour of bone. High power view showing nuclear atypia of the neoplastic mononuclear cells with irregular nuclear profiles and moderate- to large-size nucleoli in some cells.
Giant cell tumour of bone. H3.3 p.Gly34Trp (G34W) immunoreactivity of atypical stromal cells is present in a large majority of giant cell tumours of bone. It is often absent in patients with a predisposing genetic syndrome such as Paget disease of bone, Gorlin-Goltz syndrome, and Jaffe-Campanacci syndrome.

Q: Histologically, Osteoblastoma is characterized by interconnecting, delicate trabeculae of [...] that are conspicuously rimmed by prominent polygonal osteoblasts in a richly vascularized stroma.
Osteoblastoma. Interconnecting trabeculae of woven bone rimmed by osteoblasts in a richly vascularized fibroblastic stroma.
A: woven bone
Back Extra: Osteoblastoma
- Clinical: Osteoblastoma presents frequently with pain and swelling, and in the orbit, it may cause exophthalmos, visual loss, and nasal obstruction.
- Micro: Osteoblastomas are characterized by interconnecting, delicate, woven bone trabeculae rimmed by polygonal osteoblasts, with a richly vascularized stroma.
- Ancillary: FOS gene rearrangement or rarely FOSB gene rearrangement is found in the majority of osteoblastomas, detectable using an antibody against the FOS N-terminus.
Reference Gallery:
Osteoblastoma. Interconnecting trabeculae of woven bone rimmed by osteoblasts in a richly vascularized fibroblastic stroma.
Osteoblastoma. Nuclear expression of FOS (c-FOS) in the laesional cells highlighting the osteoblastic cells.

Q: The majority of Osteoblastoma cases are driven by rearrangements in the [...] gene (or rarely FOSB), which can be demonstrated by diffuse nuclear positivity on immunohistochemistry.
Osteoblastoma. Nuclear expression of FOS (c-FOS) in the laesional cells highlighting the osteoblastic cells.
A: FOS
Back Extra: Osteoblastoma
- Clinical: Osteoblastoma presents frequently with pain and swelling, and in the orbit, it may cause exophthalmos, visual loss, and nasal obstruction.
- Micro: Osteoblastomas are characterized by interconnecting, delicate, woven bone trabeculae rimmed by polygonal osteoblasts, with a richly vascularized stroma.
- Ancillary: FOS gene rearrangement or rarely FOSB gene rearrangement is found in the majority of osteoblastomas, detectable using an antibody against the FOS N-terminus.
Reference Gallery:
Osteoblastoma. Interconnecting trabeculae of woven bone rimmed by osteoblasts in a richly vascularized fibroblastic stroma.
Osteoblastoma. Nuclear expression of FOS (c-FOS) in the laesional cells highlighting the osteoblastic cells.

Q: Histologically, an Osteoma is a benign, slow-growing tumor predominantly composed of compact, mature [...] bone.
Osteoma. Compact mature lamellar/cortical-type bone.
A: lamellar
Back Extra: Osteoma
- Clinical: Osteomas are usually slow-growing and asymptomatic, appearing as round, dense, well-defined ivory-like lesions on radiological imaging.
- Micro: Histologically, osteomas are predominantly composed of mature lamellar/cortical-type bone, with compact mature lamellar/cortical-type bone being the predominant feature.
- Ancillary: In 61.1% of sporadic osteomas, hotspot mutations in the CTNNB1 gene (encoding β-catenin) are found.
Reference Gallery:
Osteoma. Compact mature lamellar/cortical-type bone.

Q: High-grade osteosarcoma is microscopically characterized by severe anaplasia, pleomorphism, and the diagnostic formation of [...].
High-grade osteosarcoma showing neoplastic bone formation and pleomorphic cells.
A: neoplastic bone
Back Extra: Osteosarcoma
- Clinical: Osteosarcoma in the orbit presents as a painful, enlarging mass with restricted eye movement, most common in adolescents and young adults.
- Micro: High-grade osteosarcoma shows severe anaplasia, pleomorphism, and brisk mitotic activity, with neoplastic bone formation.
- Ancillary: MDM2 amplification can help differentiate low-grade osteosarcoma from benign mimics.
Reference Gallery:
High-grade osteosarcoma showing neoplastic bone formation and pleomorphic cells.

Q: Microscopically, Ewing Sarcoma is characterized by a monotonous population of small round cells that often exhibit cleared-out cytoplasm due to the intracellular accumulation of [...].
Ewing sarcoma of bone. Ewing sarcoma. Notice the dark and uniform nuclei and cleared-out cytoplasms, due to glycogen deposits.
A: glycogen
Back Extra: Ewing Sarcoma
- Clinical: Most common presenting complaints are proptosis and upper eyelid swelling, with the disease occurring primarily in children and young adults.
- Micro: Tumours consist of a monotonous population of small round cells with round nuclei, coarse chromatin, and scant eosinophilic or clear cytoplasm.
- Ancillary: Immunohistochemistry shows diffuse, strong, membranous CD99 expression and nuclear FLI1 expression, with a characteristic FET::ETS fusion, most commonly EWSR1::FLI1.
Reference Gallery:
Ewing sarcoma of bone. Ewing sarcoma. Notice the dark and uniform nuclei and cleared-out cytoplasms, due to glycogen deposits.
Ewing Sarcoma. Axial CT, bone window shows bony sclerosis in the left orbit (arrow) and skull base associated with the Ewing sarcoma.
Ewing sarcoma. Sagittal T1 post-contrast MRI shows a heterogeneously enhancing mass arising from the left orbital roof with extension into the orbit and intracranial compartment (arrow).

Q: When presenting in the craniofacial region of children and young adults, Ewing Sarcoma frequently arises from the bony roof of the [...], manifesting on imaging with bony sclerosis and causing clinical proptosis.
Ewing Sarcoma. Axial CT, bone window shows bony sclerosis in the left orbit (arrow) and skull base associated with the Ewing sarcoma.
Ewing sarcoma. Sagittal T1 post-contrast MRI shows a heterogeneously enhancing mass arising from the left orbital roof with extension into the orbit and intracranial compartment (arrow).
A: orbit
Back Extra: Ewing Sarcoma
- Clinical: Most common presenting complaints are proptosis and upper eyelid swelling, with the disease occurring primarily in children and young adults.
- Micro: Tumours consist of a monotonous population of small round cells with round nuclei, coarse chromatin, and scant eosinophilic or clear cytoplasm.
- Ancillary: Immunohistochemistry shows diffuse, strong, membranous CD99 expression and nuclear FLI1 expression, with a characteristic FET::ETS fusion, most commonly EWSR1::FLI1.
Reference Gallery:
Ewing sarcoma of bone. Ewing sarcoma. Notice the dark and uniform nuclei and cleared-out cytoplasms, due to glycogen deposits.
Ewing Sarcoma. Axial CT, bone window shows bony sclerosis in the left orbit (arrow) and skull base associated with the Ewing sarcoma.
Ewing sarcoma. Sagittal T1 post-contrast MRI shows a heterogeneously enhancing mass arising from the left orbital roof with extension into the orbit and intracranial compartment (arrow).

Q: Angiosarcoma of bone is characterized microscopically by sheets of atypical epithelioid cells that form subtle [...].
Angiosarcoma of bone. There are sheets of atypical epithelioid cells forming subtle lumina.
Angiosarcoma of bone. There are sheets of atypical epithelioid cells forming subtle lumina. The tumour cells have enlarged nuclei with prominent nucleoli.
A: lumina
Back Extra: Angiosarcoma of bone
- Clinical: Angiosarcoma of bone typically presents as a rapidly growing mass in the elderly, causing visual disorders, exophthalmia, and pain.
- Micro: The microscopic appearance of Angiosarcoma of bone is characterized by sheets of atypical epithelioid cells forming subtle lumina with enlarged, hyperchromatic nuclei and prominent nucleoli.
- Ancillary: Angiosarcoma of bone expresses CD31, ERG, and FLI1, with variable cytokeratin expression, which can lead to confusion with metastatic carcinoma.
Reference Gallery:
Angiosarcoma of bone. There are sheets of atypical epithelioid cells forming subtle lumina.
Angiosarcoma of bone. There are sheets of atypical epithelioid cells forming subtle lumina. The tumour cells have enlarged nuclei with prominent nucleoli.

Q: Angiosarcoma of bone exhibits tumor cells with enlarged, hyperchromatic nuclei and prominent [...] on high-power histologic examination.
Angiosarcoma of bone. There are sheets of atypical epithelioid cells forming subtle lumina. The tumour cells have enlarged nuclei with prominent nucleoli.
A: nucleoli
Back Extra: Angiosarcoma of bone
- Clinical: Angiosarcoma of bone typically presents as a rapidly growing mass in the elderly, causing visual disorders, exophthalmia, and pain.
- Micro: The microscopic appearance of Angiosarcoma of bone is characterized by sheets of atypical epithelioid cells forming subtle lumina with enlarged, hyperchromatic nuclei and prominent nucleoli.
- Ancillary: Angiosarcoma of bone expresses CD31, ERG, and FLI1, with variable cytokeratin expression, which can lead to confusion with metastatic carcinoma.
Reference Gallery:
Angiosarcoma of bone. There are sheets of atypical epithelioid cells forming subtle lumina.
Angiosarcoma of bone. There are sheets of atypical epithelioid cells forming subtle lumina. The tumour cells have enlarged nuclei with prominent nucleoli.

Q: Microscopically, the tumor cells of Epithelioid Haemangioendothelioma are arranged in short cords or nests within a myxohyaline or collagenous stroma and characteristically form subtle [...].
Epithelioid haemangioenothelioma. The tumour is characterized by in nests or loosely arranged epithelioid endothelial cells forming subtle lumina. The mainly rounded nuclei are slightly pleomorphic. There is a collagenous background.
A: intracytoplasmic lumina
Back Extra: Epithelioid Haemangioendothelioma
- Clinical: Patients present with a slowly growing mass, sometimes painful due to vascular occlusion, with symptoms including proptosis, dystopia, and visual loss.
- Micro: The tumour shows epithelioid-, spindle-, and histiocytoid-appearing endothelial cells with minimal cytological atypia, arranged in short cords and strands in a myxohyaline stroma, often with subtle intracytoplasmic lumina.
- Ancillary: CD31 and ERG are consistently expressed. Identification of fusion genes such as WWTR1::CAMTA1 or YAP1::TFE3 helps distinguish EHE from other tumours.
Reference Gallery:
Epithelioid haemangioenothelioma. The tumour is characterized by in nests or loosely arranged epithelioid endothelial cells forming subtle lumina. The mainly rounded nuclei are slightly pleomorphic. There is a collagenous background.
Epithelioid haemangioendothelioma. CD31 is membranous and cytoplasmic expressed.
Epithelioid haemangioendothelioma. Diffuse expression of ERG.

Q: To confirm the endothelial lineage of an Epithelioid Haemangioendothelioma, the tumor typically demonstrates positive immunohistochemical expression for vascular markers such as CD31 and [...].
Epithelioid haemangioendothelioma. CD31 is membranous and cytoplasmic expressed.
Epithelioid haemangioendothelioma. Diffuse expression of ERG.
A: ERG
Back Extra: Epithelioid Haemangioendothelioma
- Clinical: Patients present with a slowly growing mass, sometimes painful due to vascular occlusion, with symptoms including proptosis, dystopia, and visual loss.
- Micro: The tumour shows epithelioid-, spindle-, and histiocytoid-appearing endothelial cells with minimal cytological atypia, arranged in short cords and strands in a myxohyaline stroma, often with subtle intracytoplasmic lumina.
- Ancillary: CD31 and ERG are consistently expressed. Identification of fusion genes such as WWTR1::CAMTA1 or YAP1::TFE3 helps distinguish EHE from other tumours.
Reference Gallery:
Epithelioid haemangioenothelioma. The tumour is characterized by in nests or loosely arranged epithelioid endothelial cells forming subtle lumina. The mainly rounded nuclei are slightly pleomorphic. There is a collagenous background.
Epithelioid haemangioendothelioma. CD31 is membranous and cytoplasmic expressed.
Epithelioid haemangioendothelioma. Diffuse expression of ERG.

Q: Histologically, Haemangioma of Bone is characterized by irregular, thin- and thick-walled [...] of variable calibers, which are often surrounded by a cellular stroma.
Haemangioma of bone. This is characterized by thin-walled irregular dilated vessels surrounded by a cellular stroma
A: vascular channels
Back Extra: Haemangioma of Bone
- Clinical: Haemangiomas of bone grow slowly and are often asymptomatic, presenting as a swelling/mass and causing symptoms such as pain, proptosis, and diplopia.
- Micro: Histologically, haemangiomas of bone show variable thin and thick-walled vessels of different calibers without remarkable endothelial lining.
- Ancillary: Immunohistochemistry highlights the endothelial cells with CD31, CD34, ERG, and FLI1, and molecular studies reveal fusion genes like EWSR1::NFATC1 or EWSR1::NFATC2.
Reference Gallery:
Haemangioma of bone. This is characterized by thin-walled irregular dilated vessels surrounded by a cellular stroma
Epithelioid haemangioma of bone. The well-formed vascular channels are lined by plump epithelioid endothelial cells

Q: The epithelioid variant of Haemangioma of Bone is distinguished by well-formed vascular spaces lined by plump, [...] endothelial cells, and it may harbor EWSR1 gene fusions.
Epithelioid haemangioma of bone. The well-formed vascular channels are lined by plump epithelioid endothelial cells
A: epithelioid
Back Extra: Haemangioma of Bone
- Clinical: Haemangiomas of bone grow slowly and are often asymptomatic, presenting as a swelling/mass and causing symptoms such as pain, proptosis, and diplopia.
- Micro: Histologically, haemangiomas of bone show variable thin and thick-walled vessels of different calibers without remarkable endothelial lining.
- Ancillary: Immunohistochemistry highlights the endothelial cells with CD31, CD34, ERG, and FLI1, and molecular studies reveal fusion genes like EWSR1::NFATC1 or EWSR1::NFATC2.
Reference Gallery:
Haemangioma of bone. This is characterized by thin-walled irregular dilated vessels surrounded by a cellular stroma
Epithelioid haemangioma of bone. The well-formed vascular channels are lined by plump epithelioid endothelial cells

Q: In an Epibulbar Choristoma (specifically the complex type), histologic examination frequently reveals heterotopic tissues such as cartilage and [...] tissue.
Complex choristoma. A lesion containing cartilage and lacrimal gland tissue.
A: lacrimal gland
Back Extra: Epibulbar Choristoma
- Clinical: Epibulbar dermoids are whitish, firm lesions with hair, while dermolipomas are yellowish, soft, and non-mobile. Complex choristomas can be yellowish or pinkish with gelatinous elevations.
- Micro: Complex choristomas contain various heterotopic tissues, including lacrimal gland and cartilage. Dermolipomas have a large amount of adipose tissue and are less likely to contain skin appendages.
- Ancillary: Malignant transformation is rare, but debulking or excision may be necessary to prevent amblyopia or for cosmetic reasons.
Reference Gallery:
Limbal dermoid. A lesion comprising surface keratinising epithelium and pilosebaceous units embedded within dermal-type stroma.
Dermolipoma. A lesion with surface conjunctival type epithelium, stromal collagen and mature adipose tissue, resembling skin dermis and subcutis. No skin adnexal structures are present.
Complex choristoma. A lesion containing cartilage and lacrimal gland tissue.
Dermoid. A lesion showing skin architecture with dermis, subcutis and pilosebaceous units.

Q: When subtyping an Epibulbar Choristoma, a dermolipoma features prominent mature adipose tissue but distinctly lacks [...] structures (e.g., pilosebaceous units), which are conversely characteristic of a limbal dermoid.
Limbal dermoid. A lesion comprising surface keratinising epithelium and pilosebaceous units embedded within dermal-type stroma.
Dermolipoma. A lesion with surface conjunctival type epithelium, stromal collagen and mature adipose tissue, resembling skin dermis and subcutis. No skin adnexal structures are present.
Dermoid. A lesion showing skin architecture with dermis, subcutis and pilosebaceous units.
A: skin adnexal
Back Extra: Epibulbar Choristoma
- Clinical: Epibulbar dermoids are whitish, firm lesions with hair, while dermolipomas are yellowish, soft, and non-mobile. Complex choristomas can be yellowish or pinkish with gelatinous elevations.
- Micro: Complex choristomas contain various heterotopic tissues, including lacrimal gland and cartilage. Dermolipomas have a large amount of adipose tissue and are less likely to contain skin appendages.
- Ancillary: Malignant transformation is rare, but debulking or excision may be necessary to prevent amblyopia or for cosmetic reasons.
Reference Gallery:
Limbal dermoid. A lesion comprising surface keratinising epithelium and pilosebaceous units embedded within dermal-type stroma.
Dermolipoma. A lesion with surface conjunctival type epithelium, stromal collagen and mature adipose tissue, resembling skin dermis and subcutis. No skin adnexal structures are present.
Complex choristoma. A lesion containing cartilage and lacrimal gland tissue.
Dermoid. A lesion showing skin architecture with dermis, subcutis and pilosebaceous units.

Q: Epibulbar Osseous Choristoma typically presents as a dome-shaped, yellowish subconjunctival mass that is histologically composed of compact [...].
Osseous choristoma. A lesion in the superotemporal conjunctiva, showing a dome-shaped, yellowish mass.
A: lamellar bone
Back Extra: Epibulbar Osseous Choristoma
- Clinical: Epibulbar osseous choristoma presents as a yellow, orange, pink, or white subconjunctival mass, often multinodular and typically found in patients younger than 20 years old.
- Micro: Microscopically, the lesion is composed of compact lamellar bone with normal osteocytes and Haversian canals, surrounded by periosteum and an internal osteogenic layer.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of epibulbar osseous choristoma.
Reference Gallery:
Osseous choristoma. A lesion in the superotemporal conjunctiva, showing a dome-shaped, yellowish mass.

Q: Clinically presenting as a transparent to cloudy, compressible bulbar mass that can cause mechanical irritation or adjacent corneal dellen due to lubrication disturbance, this lesion is known as an [...].
Diagnosis: Bulbar conjunctival cyst. A cyst between the plica semilunaris and nasal limbus with adjacent corneal dellen due to lubrication disturbance.
A: Epithelial Conjunctival Inclusion Cyst
Back Extra: Epithelial Conjunctival Inclusion Cyst
- Clinical: Epithelial conjunctival inclusion cysts are transparent to cloudy, compressible, and mobile or tethered to surrounding structures. They can arise at any age and are asymptomatic unless they cause mechanical irritation or lubrication disturbance.
- Micro: These cysts are lined by non-keratinizing stratified squamous epithelium with or without goblet cells. The cavity may contain proteinaceous material and be surrounded by stromal fibrosis and inflammation.
- Ancillary: Complete excision is curative, and no additional ancillary studies are typically required.
Reference Gallery:
Diagnosis: Bulbar conjunctival cyst. A cyst between the plica semilunaris and nasal limbus with adjacent corneal dellen due to lubrication disturbance.
Diagnosis: Simple conjunctival epithelial cyst. Histopathological appearance of the non-keratinizing epithelium with goblet cells in a simple conjunctival epithelial cyst.
Diagnosis: Conjunctival inclusion cyst. Low power showing a conjunctival inclusion cyst. The normal conjunctival epithelium is on the right.
Diagnosis: Conjunctival inclusion cyst. The cyst epithelium is on the left and is composed of non-keratinising squamous epithelium similar to the appearance of the surface conjunctival epithelium on the right.

Q: Histologically, an [...] is characterized by a cystic cavity lined by non-keratinizing stratified squamous epithelium that may or may not contain admixed goblet cells, closely resembling the adjacent surface mucosa.
Diagnosis: Simple conjunctival epithelial cyst. Histopathological appearance of the non-keratinizing epithelium with goblet cells in a simple conjunctival epithelial cyst.
Diagnosis: Conjunctival inclusion cyst. Low power showing a conjunctival inclusion cyst. The normal conjunctival epithelium is on the right.
Diagnosis: Conjunctival inclusion cyst. The cyst epithelium is on the left and is composed of non-keratinising squamous epithelium similar to the appearance of the surface conjunctival epithelium on the right.
A: Epithelial Conjunctival Inclusion Cyst
Back Extra: Epithelial Conjunctival Inclusion Cyst
- Clinical: Epithelial conjunctival inclusion cysts are transparent to cloudy, compressible, and mobile or tethered to surrounding structures. They can arise at any age and are asymptomatic unless they cause mechanical irritation or lubrication disturbance.
- Micro: These cysts are lined by non-keratinizing stratified squamous epithelium with or without goblet cells. The cavity may contain proteinaceous material and be surrounded by stromal fibrosis and inflammation.
- Ancillary: Complete excision is curative, and no additional ancillary studies are typically required.
Reference Gallery:
Diagnosis: Bulbar conjunctival cyst. A cyst between the plica semilunaris and nasal limbus with adjacent corneal dellen due to lubrication disturbance.
Diagnosis: Simple conjunctival epithelial cyst. Histopathological appearance of the non-keratinizing epithelium with goblet cells in a simple conjunctival epithelial cyst.
Diagnosis: Conjunctival inclusion cyst. Low power showing a conjunctival inclusion cyst. The normal conjunctival epithelium is on the right.
Diagnosis: Conjunctival inclusion cyst. The cyst epithelium is on the left and is composed of non-keratinising squamous epithelium similar to the appearance of the surface conjunctival epithelium on the right.

Q: Histologically, Hereditary Benign Intraepithelial Dyskeratosis is characterized by marked acanthosis and scattered [...] with pyknotic nuclei within an epithelium that lacks dysplasia.
Hereditary benign intraepithelial dyskeratosis. Acanthosis with parakeratosis and intraepithelial dyskeratosis. The epithelium lacks dysplasia. Chronic inflammation is present in the substantia propria.
Hereditary benign intraepithelial dyskeratosis. Dyskeratotic squamous cells are present within the non-dysplastic epithelium.
Hereditary benign intraepithelial dyskeratosis. Dyskeratotic cells with dense eosinophilic cytoplasm and pyknotic nuclei.
A: dyskeratotic cells
Back Extra: Hereditary Benign Intraepithelial Dyskeratosis
- Clinical: Elevated, plaque-like, gray, inflamed, and vascularized lesions at the limbal conjunctiva and cornea, often bilateral and with seasonal variability.
- Micro: Marked acanthosis with multilayered parakeratosis and dyskeratotic cells with pyknotic nuclei within the non-dysplastic epithelium.
- Ancillary: Clinical diagnosis is usually sufficient; genetic analysis is rarely required.
Reference Gallery:
Hereditary benign intraepithelial dyskeratosis. Acanthosis with parakeratosis and intraepithelial dyskeratosis. The epithelium lacks dysplasia. Chronic inflammation is present in the substantia propria.
Hereditary benign intraepithelial dyskeratosis. Dyskeratotic squamous cells are present within the non-dysplastic epithelium.
Hereditary benign intraepithelial dyskeratosis. Dyskeratotic cells with dense eosinophilic cytoplasm and pyknotic nuclei.
Hereditary benign intraepithelial dyskeratosis. Elevated, plaque-like, gray, inflamed and vascularized lesion at the limbal conjunctiva and cornea.

Q: Clinically, Hereditary Benign Intraepithelial Dyskeratosis presents as elevated, gray, inflamed plaque-like lesions that characteristically involve the [...].
Hereditary benign intraepithelial dyskeratosis. Elevated, plaque-like, gray, inflamed and vascularized lesion at the limbal conjunctiva and cornea.
A: limbal conjunctiva and cornea
Back Extra: Hereditary Benign Intraepithelial Dyskeratosis
- Clinical: Elevated, plaque-like, gray, inflamed, and vascularized lesions at the limbal conjunctiva and cornea, often bilateral and with seasonal variability.
- Micro: Marked acanthosis with multilayered parakeratosis and dyskeratotic cells with pyknotic nuclei within the non-dysplastic epithelium.
- Ancillary: Clinical diagnosis is usually sufficient; genetic analysis is rarely required.
Reference Gallery:
Hereditary benign intraepithelial dyskeratosis. Acanthosis with parakeratosis and intraepithelial dyskeratosis. The epithelium lacks dysplasia. Chronic inflammation is present in the substantia propria.
Hereditary benign intraepithelial dyskeratosis. Dyskeratotic squamous cells are present within the non-dysplastic epithelium.
Hereditary benign intraepithelial dyskeratosis. Dyskeratotic cells with dense eosinophilic cytoplasm and pyknotic nuclei.
Hereditary benign intraepithelial dyskeratosis. Elevated, plaque-like, gray, inflamed and vascularized lesion at the limbal conjunctiva and cornea.

Q: Conjunctival Oncocytoma typically presents in elderly patients as a circumscribed, reddish to brownish nodule most commonly located at the [...].
Oncocytoma of the caruncle. Reddish, vascularized nodule at the caruncle in a 83-year-old male.
Oncocytoma of the caruncle. Dark, almost black, ovoid subepithelial caruncular nodule in a 68-year-old male.
A: caruncle
Back Extra: Conjunctival Oncocytoma
- Clinical: Conjunctival oncocytoma appears as a circumscribed, reddish, blueish, or brownish nodule, primarily in elderly patients.
- Micro: Neoplastic cells are arranged in sheets, nests, and microcystic patterns with eosinophilic granular cytoplasm and PAS-positive fluid in luminae.
- Ancillary: The tumour cells stain positively for antimitochondrial MU213-UC antibodies, similar to lacrimal and accessory lacrimal gland duct elements.
Reference Gallery:
Oncocytoma of the caruncle. Reddish, vascularized nodule at the caruncle in a 83-year-old male.
Oncocytoma of the caruncle. Dark, almost black, ovoid subepithelial caruncular nodule in a 68-year-old male.
Oncocytoma of the caruncle. Circumscribed neoplasm composed of eosinophilic oncocytic cells adjacent to goblet cell containing epithelium and sebaceous glands.
Oncocytoma of the caruncle. Higher magnification of the same case showing oncocytes arranged in sheets with luminae containing proteinaceous PAS-positive fluid. Lymphoplasmacytic infiltrate is present between the tumor sheets and beneath the conjunctival epithelium.
Oncocytoma of the caruncle. Circumscribed neoplasm with cystadenomatous architecture and papillary projections of oncocytic epithelium into the lumen. Caruncular epithelium with goblet cells and adnexal units overly the lesion.
Oncocytoma of the caruncle. Papillary projections of columnar oncocytic cells into a lumen filled with eosinophilic granular material.

Q: Conjunctival Oncocytoma is characterized histologically by neoplastic cells arranged in sheets, nests, or papillary projections that feature abundant, granular, [...] cytoplasm.
Oncocytoma of the caruncle. Circumscribed neoplasm composed of eosinophilic oncocytic cells adjacent to goblet cell containing epithelium and sebaceous glands.
Oncocytoma of the caruncle. Papillary projections of columnar oncocytic cells into a lumen filled with eosinophilic granular material.
A: eosinophilic
Back Extra: Conjunctival Oncocytoma
- Clinical: Conjunctival oncocytoma appears as a circumscribed, reddish, blueish, or brownish nodule, primarily in elderly patients.
- Micro: Neoplastic cells are arranged in sheets, nests, and microcystic patterns with eosinophilic granular cytoplasm and PAS-positive fluid in luminae.
- Ancillary: The tumour cells stain positively for antimitochondrial MU213-UC antibodies, similar to lacrimal and accessory lacrimal gland duct elements.
Reference Gallery:
Oncocytoma of the caruncle. Reddish, vascularized nodule at the caruncle in a 83-year-old male.
Oncocytoma of the caruncle. Dark, almost black, ovoid subepithelial caruncular nodule in a 68-year-old male.
Oncocytoma of the caruncle. Circumscribed neoplasm composed of eosinophilic oncocytic cells adjacent to goblet cell containing epithelium and sebaceous glands.
Oncocytoma of the caruncle. Higher magnification of the same case showing oncocytes arranged in sheets with luminae containing proteinaceous PAS-positive fluid. Lymphoplasmacytic infiltrate is present between the tumor sheets and beneath the conjunctival epithelium.
Oncocytoma of the caruncle. Circumscribed neoplasm with cystadenomatous architecture and papillary projections of oncocytic epithelium into the lumen. Caruncular epithelium with goblet cells and adnexal units overly the lesion.
Oncocytoma of the caruncle. Papillary projections of columnar oncocytic cells into a lumen filled with eosinophilic granular material.

Q: Conjunctival Oncocytoma frequently forms microcystic and cystadenomatous spaces with luminae that contain proteinaceous fluid positive for [...] stain.
Oncocytoma of the caruncle. Higher magnification of the same case showing oncocytes arranged in sheets with luminae containing proteinaceous PAS-positive fluid. Lymphoplasmacytic infiltrate is present between the tumor sheets and beneath the conjunctival epithelium.
A: PAS
Back Extra: Conjunctival Oncocytoma
- Clinical: Conjunctival oncocytoma appears as a circumscribed, reddish, blueish, or brownish nodule, primarily in elderly patients.
- Micro: Neoplastic cells are arranged in sheets, nests, and microcystic patterns with eosinophilic granular cytoplasm and PAS-positive fluid in luminae.
- Ancillary: The tumour cells stain positively for antimitochondrial MU213-UC antibodies, similar to lacrimal and accessory lacrimal gland duct elements.
Reference Gallery:
Oncocytoma of the caruncle. Reddish, vascularized nodule at the caruncle in a 83-year-old male.
Oncocytoma of the caruncle. Dark, almost black, ovoid subepithelial caruncular nodule in a 68-year-old male.
Oncocytoma of the caruncle. Circumscribed neoplasm composed of eosinophilic oncocytic cells adjacent to goblet cell containing epithelium and sebaceous glands.
Oncocytoma of the caruncle. Higher magnification of the same case showing oncocytes arranged in sheets with luminae containing proteinaceous PAS-positive fluid. Lymphoplasmacytic infiltrate is present between the tumor sheets and beneath the conjunctival epithelium.
Oncocytoma of the caruncle. Circumscribed neoplasm with cystadenomatous architecture and papillary projections of oncocytic epithelium into the lumen. Caruncular epithelium with goblet cells and adnexal units overly the lesion.
Oncocytoma of the caruncle. Papillary projections of columnar oncocytic cells into a lumen filled with eosinophilic granular material.

Q: Histologically, an exophytic, frond-like, non-keratinizing squamous epithelial proliferation with preserved goblet cells surrounding central fibrovascular cores is characteristic of a [...].
Pedunculated squamous papilloma of the conjunctiva. Fronds of acanthotic epithelium with preserved goblet cells enclose mildly inflamed fibrovascular cores.
Conjunctival squamous papilloma. Pedunculated papilloma composed of epithelial fronds with hairpin-like vascular loops involves the inferior fornix of the conjunctiva. Note an associated secondary melanosis.
A: Conjunctival Squamous Cell Papilloma
Back Extra: Conjunctival Squamous Cell Papilloma
- Clinical: Conjunctival squamous cell papillomas are most common in male adults, typically aged between 21 and 40 years, and can also affect children and adolescents with multiple lesions and extensive forniceal involvement.
- Micro: Exophytic papilloma shows a frond-like non-keratinizing squamous epithelial hyperplasia surrounding central vascular cores, containing varying numbers of goblet cells, and may have small intraepithelial mucous cysts or neutrophilic microabscesses.
- Ancillary: HPV detection methods often reveal a viral etiology, but immunohistochemistry is usually not required for diagnosis; these lesions are positive for cytokeratins (e.g., AE1/AE3, CK10/13, CK14, and CK19).
Reference Gallery:
Pedunculated squamous papilloma of the conjunctiva. Fronds of acanthotic epithelium with preserved goblet cells enclose mildly inflamed fibrovascular cores.
Pedunculated squamous papilloma of the conjunctiva. RNAScope demonstrates presence of low-risk HPV in the lesion.
Conjunctival squamous papilloma. Pedunculated papilloma composed of epithelial fronds with hairpin-like vascular loops involves the inferior fornix of the conjunctiva. Note an associated secondary melanosis.
Inverted conjunctival squamous papilloma. Endophytic squamous proliferation pushing into the substantia propria, without evidence of dysplasia. Secondary melanosis is also present.

Q: The viral etiology of Conjunctival Squamous Cell Papilloma, which can be directly demonstrated via RNAScope, is most commonly attributed to low-risk strains of [...].
Pedunculated squamous papilloma of the conjunctiva. RNAScope demonstrates presence of low-risk HPV in the lesion.
A: human papillomavirus (HPV)
Back Extra: Conjunctival Squamous Cell Papilloma
- Clinical: Conjunctival squamous cell papillomas are most common in male adults, typically aged between 21 and 40 years, and can also affect children and adolescents with multiple lesions and extensive forniceal involvement.
- Micro: Exophytic papilloma shows a frond-like non-keratinizing squamous epithelial hyperplasia surrounding central vascular cores, containing varying numbers of goblet cells, and may have small intraepithelial mucous cysts or neutrophilic microabscesses.
- Ancillary: HPV detection methods often reveal a viral etiology, but immunohistochemistry is usually not required for diagnosis; these lesions are positive for cytokeratins (e.g., AE1/AE3, CK10/13, CK14, and CK19).
Reference Gallery:
Pedunculated squamous papilloma of the conjunctiva. Fronds of acanthotic epithelium with preserved goblet cells enclose mildly inflamed fibrovascular cores.
Pedunculated squamous papilloma of the conjunctiva. RNAScope demonstrates presence of low-risk HPV in the lesion.
Conjunctival squamous papilloma. Pedunculated papilloma composed of epithelial fronds with hairpin-like vascular loops involves the inferior fornix of the conjunctiva. Note an associated secondary melanosis.
Inverted conjunctival squamous papilloma. Endophytic squamous proliferation pushing into the substantia propria, without evidence of dysplasia. Secondary melanosis is also present.

Q: In addition to the classic exophytic presentation, Conjunctival Squamous Cell Papilloma can present as an inverted variant, characterized histologically by an [...] squamous proliferation pushing into the substantia propria without dysplasia.
Inverted conjunctival squamous papilloma. Endophytic squamous proliferation pushing into the substantia propria, without evidence of dysplasia. Secondary melanosis is also present.
A: endophytic
Back Extra: Conjunctival Squamous Cell Papilloma
- Clinical: Conjunctival squamous cell papillomas are most common in male adults, typically aged between 21 and 40 years, and can also affect children and adolescents with multiple lesions and extensive forniceal involvement.
- Micro: Exophytic papilloma shows a frond-like non-keratinizing squamous epithelial hyperplasia surrounding central vascular cores, containing varying numbers of goblet cells, and may have small intraepithelial mucous cysts or neutrophilic microabscesses.
- Ancillary: HPV detection methods often reveal a viral etiology, but immunohistochemistry is usually not required for diagnosis; these lesions are positive for cytokeratins (e.g., AE1/AE3, CK10/13, CK14, and CK19).
Reference Gallery:
Pedunculated squamous papilloma of the conjunctiva. Fronds of acanthotic epithelium with preserved goblet cells enclose mildly inflamed fibrovascular cores.
Pedunculated squamous papilloma of the conjunctiva. RNAScope demonstrates presence of low-risk HPV in the lesion.
Conjunctival squamous papilloma. Pedunculated papilloma composed of epithelial fronds with hairpin-like vascular loops involves the inferior fornix of the conjunctiva. Note an associated secondary melanosis.
Inverted conjunctival squamous papilloma. Endophytic squamous proliferation pushing into the substantia propria, without evidence of dysplasia. Secondary melanosis is also present.

Q: Microscopically, [...] is a biphenotypic tumor defined by the admixed presence of both squamous cell carcinoma and adenocarcinoma components.
Adenosquamous carcinoma. Scanning magnification of conjunctival adenosquamous carcinoma. The adenocarcinoma component is on the left and the invasive squamous cell carcinoma is on the right.
A: Adenosquamous Carcinoma
Back Extra: Adenosquamous Carcinoma
- Clinical: Adenosquamous carcinoma typically presents as a conjunctival mass with a nodular, multinodular, or fleshy pink-red appearance, often associated with mild irritation and a short duration of symptoms (weeks to months).
- Micro: The tumour exhibits bi-phenotypic differentiation, comprising both squamous cell carcinoma (SCC) and adenocarcinoma components. The SCC can be keratinizing or non-keratinizing, while the adenocarcinoma component may show tubulo-glandular or confluent sheets of atypical cells with intracytoplasmic mucin.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with the SCC component positive for p40, CK5/6, and CK17, and the adenocarcinoma component positive for CK7, BerEP4, EMA, MUC-1, and CEA.
Reference Gallery:
Adenosquamous carcinoma. Scanning magnification of conjunctival adenosquamous carcinoma. The adenocarcinoma component is on the left and the invasive squamous cell carcinoma is on the right.
Adenosquamous carcinoma. Invasive non-keratinising squamous carcinoma component of the adenosquamous carcinoma
Adenosquamous carcinoma. Higher magnification of the adenocarcinoma component of the conjunctival adenosquamous carcinoma, with eosinophilic material in the neoplastic gland lumens.
Adenosquamous carcinoma. Combined Alcian Blue-PAS stain of the adenocarcinoma component showing mucin within the adenocarcinoma gland lumens.
Adenosquamous carcinoma. Adenocarcinoma component of adenosquamous carcinoma, comprising confluent sheets of cells with intracytoplasmic mucin, rather than forming glands.
Adenosquamous carcinoma of the conjunctiva. The tumour arises in the tarsal conjunctiva and presents as a tarsal-based mass with involvement of the eyelid margin.
Conjuntival melancytic neoplasia with mucinous differentiation (CIN-muc). Note the intracellular bluish mucin across almost the full-thickness of the dysplastic epithelium. This lesion may be a precursor to invasive adenosquamous carcinoma.

Q: In Adenosquamous Carcinoma, the adenocarcinoma component characteristically contains intracytoplasmic or luminal [...], which can be highlighted using an Alcian Blue-PAS stain.
Adenosquamous carcinoma. Combined Alcian Blue-PAS stain of the adenocarcinoma component showing mucin within the adenocarcinoma gland lumens.
Adenosquamous carcinoma. Adenocarcinoma component of adenosquamous carcinoma, comprising confluent sheets of cells with intracytoplasmic mucin, rather than forming glands.
A: mucin
Back Extra: Adenosquamous Carcinoma
- Clinical: Adenosquamous carcinoma typically presents as a conjunctival mass with a nodular, multinodular, or fleshy pink-red appearance, often associated with mild irritation and a short duration of symptoms (weeks to months).
- Micro: The tumour exhibits bi-phenotypic differentiation, comprising both squamous cell carcinoma (SCC) and adenocarcinoma components. The SCC can be keratinizing or non-keratinizing, while the adenocarcinoma component may show tubulo-glandular or confluent sheets of atypical cells with intracytoplasmic mucin.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with the SCC component positive for p40, CK5/6, and CK17, and the adenocarcinoma component positive for CK7, BerEP4, EMA, MUC-1, and CEA.
Reference Gallery:
Adenosquamous carcinoma. Scanning magnification of conjunctival adenosquamous carcinoma. The adenocarcinoma component is on the left and the invasive squamous cell carcinoma is on the right.
Adenosquamous carcinoma. Invasive non-keratinising squamous carcinoma component of the adenosquamous carcinoma
Adenosquamous carcinoma. Higher magnification of the adenocarcinoma component of the conjunctival adenosquamous carcinoma, with eosinophilic material in the neoplastic gland lumens.
Adenosquamous carcinoma. Combined Alcian Blue-PAS stain of the adenocarcinoma component showing mucin within the adenocarcinoma gland lumens.
Adenosquamous carcinoma. Adenocarcinoma component of adenosquamous carcinoma, comprising confluent sheets of cells with intracytoplasmic mucin, rather than forming glands.
Adenosquamous carcinoma of the conjunctiva. The tumour arises in the tarsal conjunctiva and presents as a tarsal-based mass with involvement of the eyelid margin.
Conjuntival melancytic neoplasia with mucinous differentiation (CIN-muc). Note the intracellular bluish mucin across almost the full-thickness of the dysplastic epithelium. This lesion may be a precursor to invasive adenosquamous carcinoma.

Q: A recognized precursor lesion for invasive Adenosquamous Carcinoma of the conjunctiva is conjunctival intraepithelial neoplasia (CIN) with [...] differentiation.
Conjuntival melancytic neoplasia with mucinous differentiation (CIN-muc). Note the intracellular bluish mucin across almost the full-thickness of the dysplastic epithelium. This lesion may be a precursor to invasive adenosquamous carcinoma.
A: mucinous
Back Extra: Adenosquamous Carcinoma
- Clinical: Adenosquamous carcinoma typically presents as a conjunctival mass with a nodular, multinodular, or fleshy pink-red appearance, often associated with mild irritation and a short duration of symptoms (weeks to months).
- Micro: The tumour exhibits bi-phenotypic differentiation, comprising both squamous cell carcinoma (SCC) and adenocarcinoma components. The SCC can be keratinizing or non-keratinizing, while the adenocarcinoma component may show tubulo-glandular or confluent sheets of atypical cells with intracytoplasmic mucin.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with the SCC component positive for p40, CK5/6, and CK17, and the adenocarcinoma component positive for CK7, BerEP4, EMA, MUC-1, and CEA.
Reference Gallery:
Adenosquamous carcinoma. Scanning magnification of conjunctival adenosquamous carcinoma. The adenocarcinoma component is on the left and the invasive squamous cell carcinoma is on the right.
Adenosquamous carcinoma. Invasive non-keratinising squamous carcinoma component of the adenosquamous carcinoma
Adenosquamous carcinoma. Higher magnification of the adenocarcinoma component of the conjunctival adenosquamous carcinoma, with eosinophilic material in the neoplastic gland lumens.
Adenosquamous carcinoma. Combined Alcian Blue-PAS stain of the adenocarcinoma component showing mucin within the adenocarcinoma gland lumens.
Adenosquamous carcinoma. Adenocarcinoma component of adenosquamous carcinoma, comprising confluent sheets of cells with intracytoplasmic mucin, rather than forming glands.
Adenosquamous carcinoma of the conjunctiva. The tumour arises in the tarsal conjunctiva and presents as a tarsal-based mass with involvement of the eyelid margin.
Conjuntival melancytic neoplasia with mucinous differentiation (CIN-muc). Note the intracellular bluish mucin across almost the full-thickness of the dysplastic epithelium. This lesion may be a precursor to invasive adenosquamous carcinoma.

Q: Microscopically, well-differentiated Conjunctival Squamous Cell Carcinoma is characterized by invasive atypical squamous cells that frequently form squamous eddies and [...].
Conjunctival well-differentiated squamous cell carcinoma. Invasive, keratinizing, well-differentiated squamous cell carcinoma in association with carcinoma in situ. The adjacent substantia propria demonstrates severe actinic elastosis, compatible with a sun-exposed location.
Conjunctival well-differentiated keratinising squamous cell carcinoma. Higher magnification showing atypical squamous cells with squamous eddy and keratin pearl formation.
A: keratin pearls
Back Extra: Conjunctival Squamous Cell Carcinoma
- Clinical: Conjunctival Squamous Cell Carcinoma (SCC) typically presents as a unilateral, elevated, well-demarcated pearly pink-to-grey nodule, often with feeder blood vessels and intrinsic vasculature. It can be leukoplakic, gelatinous, or papilliform.
- Micro: Invasive conjunctival SCC shows squamous differentiation with various degrees of keratinization, hyperchromatic nuclei, and squamous pearls. The tumour cells can show atypia and mitotic figures.
- Ancillary: Immunohistochemistry in poorly differentiated SCC shows positivity for broad spectrum and high molecular weight cytokeratins, EMA, and p63, and negativity for AR. HPV testing can be helpful in some cases.
Reference Gallery:
Conjunctival well-differentiated squamous cell carcinoma. Invasive, keratinizing, well-differentiated squamous cell carcinoma in association with carcinoma in situ. The adjacent substantia propria demonstrates severe actinic elastosis, compatible with a sun-exposed location.
Conjunctival well-differentiated keratinising squamous cell carcinoma. Higher magnification showing atypical squamous cells with squamous eddy and keratin pearl formation.
Conjunctival squamous cell carcinoma with mucinous differentiation. Bands and strands of invasive squamous cell carcinoma with focal keratin pearl formation (top left) and bluish mucin within individual tumour cells (bottom right).
Conjunctival squamous cell carcinoma with mucinous differentiation. Higher magnification of the signet-ring like or goblet cell-like cells containing cytoplasmic mucin.
Conjunctival squamous cell carcinoma with mucinous differentiation. Alcian Blue stain highlights intracytoplasmic mucin in some of the tumour cells.
Conjunctival invasive basaloid squamous carcinoma. A case showing conjunctival in situ squamous carcinoma above and lobules of invasive basaloid pattern of squamous cell carcinoma in the substantia propria.
Conjunctival invasive basaloid squamous carcinoma. Higher power view showing basaloid poorly differentiated invasive squamous cell carcinoma. Note the basaloid cells have a high N:C ratio and do not show keratinization.
Conjunctival squamous cell carcinoma. Sagittal T2-weighted MRI showing a mass in the left lower eyelid, of intermediate signal intensity in T2-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Sagittal T1-weighted MRI showing a mass in the left lower eyelid, of intermediate signal intensity on T1-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Sagittal contrast-enhanced T1-weighted MRI with fat signal suppression showing a mass in the left lower eyelid, of intermediate signal intensity on the T1 and T2-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Axial ADC showing a tumour ADC of 1.2 in the left lower eyelid.
Conjunctival squamous cell carcinoma. Axial DCE with a tumour wash-out perfusion curve in a tumour of the left lower eyelid.

Q: A variant of Conjunctival Squamous Cell Carcinoma can exhibit mucinous differentiation with signet-ring or goblet-like cells containing intracytoplasmic mucin, which is highlighted by an [...] stain.
Conjunctival squamous cell carcinoma with mucinous differentiation. Higher magnification of the signet-ring like or goblet cell-like cells containing cytoplasmic mucin.
Conjunctival squamous cell carcinoma with mucinous differentiation. Alcian Blue stain highlights intracytoplasmic mucin in some of the tumour cells.
A: Alcian Blue
Back Extra: Conjunctival Squamous Cell Carcinoma
- Clinical: Conjunctival Squamous Cell Carcinoma (SCC) typically presents as a unilateral, elevated, well-demarcated pearly pink-to-grey nodule, often with feeder blood vessels and intrinsic vasculature. It can be leukoplakic, gelatinous, or papilliform.
- Micro: Invasive conjunctival SCC shows squamous differentiation with various degrees of keratinization, hyperchromatic nuclei, and squamous pearls. The tumour cells can show atypia and mitotic figures.
- Ancillary: Immunohistochemistry in poorly differentiated SCC shows positivity for broad spectrum and high molecular weight cytokeratins, EMA, and p63, and negativity for AR. HPV testing can be helpful in some cases.
Reference Gallery:
Conjunctival well-differentiated squamous cell carcinoma. Invasive, keratinizing, well-differentiated squamous cell carcinoma in association with carcinoma in situ. The adjacent substantia propria demonstrates severe actinic elastosis, compatible with a sun-exposed location.
Conjunctival well-differentiated keratinising squamous cell carcinoma. Higher magnification showing atypical squamous cells with squamous eddy and keratin pearl formation.
Conjunctival squamous cell carcinoma with mucinous differentiation. Bands and strands of invasive squamous cell carcinoma with focal keratin pearl formation (top left) and bluish mucin within individual tumour cells (bottom right).
Conjunctival squamous cell carcinoma with mucinous differentiation. Higher magnification of the signet-ring like or goblet cell-like cells containing cytoplasmic mucin.
Conjunctival squamous cell carcinoma with mucinous differentiation. Alcian Blue stain highlights intracytoplasmic mucin in some of the tumour cells.
Conjunctival invasive basaloid squamous carcinoma. A case showing conjunctival in situ squamous carcinoma above and lobules of invasive basaloid pattern of squamous cell carcinoma in the substantia propria.
Conjunctival invasive basaloid squamous carcinoma. Higher power view showing basaloid poorly differentiated invasive squamous cell carcinoma. Note the basaloid cells have a high N:C ratio and do not show keratinization.
Conjunctival squamous cell carcinoma. Sagittal T2-weighted MRI showing a mass in the left lower eyelid, of intermediate signal intensity in T2-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Sagittal T1-weighted MRI showing a mass in the left lower eyelid, of intermediate signal intensity on T1-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Sagittal contrast-enhanced T1-weighted MRI with fat signal suppression showing a mass in the left lower eyelid, of intermediate signal intensity on the T1 and T2-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Axial ADC showing a tumour ADC of 1.2 in the left lower eyelid.
Conjunctival squamous cell carcinoma. Axial DCE with a tumour wash-out perfusion curve in a tumour of the left lower eyelid.

Q: The basaloid variant of invasive Conjunctival Squamous Cell Carcinoma is composed of lobules of cells with a high nuclear-to-cytoplasmic ratio that characteristically lack [...].
Conjunctival invasive basaloid squamous carcinoma. A case showing conjunctival in situ squamous carcinoma above and lobules of invasive basaloid pattern of squamous cell carcinoma in the substantia propria.
Conjunctival invasive basaloid squamous carcinoma. Higher power view showing basaloid poorly differentiated invasive squamous cell carcinoma. Note the basaloid cells have a high N:C ratio and do not show keratinization.
A: keratinization
Back Extra: Conjunctival Squamous Cell Carcinoma
- Clinical: Conjunctival Squamous Cell Carcinoma (SCC) typically presents as a unilateral, elevated, well-demarcated pearly pink-to-grey nodule, often with feeder blood vessels and intrinsic vasculature. It can be leukoplakic, gelatinous, or papilliform.
- Micro: Invasive conjunctival SCC shows squamous differentiation with various degrees of keratinization, hyperchromatic nuclei, and squamous pearls. The tumour cells can show atypia and mitotic figures.
- Ancillary: Immunohistochemistry in poorly differentiated SCC shows positivity for broad spectrum and high molecular weight cytokeratins, EMA, and p63, and negativity for AR. HPV testing can be helpful in some cases.
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Conjunctival well-differentiated squamous cell carcinoma. Invasive, keratinizing, well-differentiated squamous cell carcinoma in association with carcinoma in situ. The adjacent substantia propria demonstrates severe actinic elastosis, compatible with a sun-exposed location.
Conjunctival well-differentiated keratinising squamous cell carcinoma. Higher magnification showing atypical squamous cells with squamous eddy and keratin pearl formation.
Conjunctival squamous cell carcinoma with mucinous differentiation. Bands and strands of invasive squamous cell carcinoma with focal keratin pearl formation (top left) and bluish mucin within individual tumour cells (bottom right).
Conjunctival squamous cell carcinoma with mucinous differentiation. Higher magnification of the signet-ring like or goblet cell-like cells containing cytoplasmic mucin.
Conjunctival squamous cell carcinoma with mucinous differentiation. Alcian Blue stain highlights intracytoplasmic mucin in some of the tumour cells.
Conjunctival invasive basaloid squamous carcinoma. A case showing conjunctival in situ squamous carcinoma above and lobules of invasive basaloid pattern of squamous cell carcinoma in the substantia propria.
Conjunctival invasive basaloid squamous carcinoma. Higher power view showing basaloid poorly differentiated invasive squamous cell carcinoma. Note the basaloid cells have a high N:C ratio and do not show keratinization.
Conjunctival squamous cell carcinoma. Sagittal T2-weighted MRI showing a mass in the left lower eyelid, of intermediate signal intensity in T2-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Sagittal T1-weighted MRI showing a mass in the left lower eyelid, of intermediate signal intensity on T1-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Sagittal contrast-enhanced T1-weighted MRI with fat signal suppression showing a mass in the left lower eyelid, of intermediate signal intensity on the T1 and T2-weighted images and enhancing. Anteriorly, it is located both posterior to the inferior tarsus and to the orbicularis oculi muscle. Posteriorly, there is orbital invasion, with the tumor extending until the region of the globe attachment of the inferior rectus muscle.
Conjunctival squamous cell carcinoma. Axial ADC showing a tumour ADC of 1.2 in the left lower eyelid.
Conjunctival squamous cell carcinoma. Axial DCE with a tumour wash-out perfusion curve in a tumour of the left lower eyelid.

Q: A gelatinous, papilliform, or leukoplakic perilimbal lesion with feeder blood vessels on the ocular surface is clinically characteristic of [...].
Clinical photograph showing a left eye with perilimbal, keratinising conjunctival squamous intraepithelial neoplasia (In-situ squamous SCC) from 2 o'clock to 6 o'clock.
A: Conjunctival Squamous Intraepithelial Neoplasia
Back Extra: Conjunctival Squamous Intraepithelial Neoplasia
- Clinical: Conjunctival Squamous Intraepithelial Neoplasia (CSIN) can appear as papilliform, gelatinous, or leukoplakic lesions, often with feeder blood vessels and a pearly appearance.
- Micro: CSIN shows abnormal stratification, loss of polarity, and varying degrees of dysplasia, from mild to severe, with full-thickness dysplasia in in-situ squamous carcinoma.
- Ancillary: High-risk HPV-associated CSIN can be p16+ and shows a basaloid appearance without surface keratinization, while UV-associated cases may have rete-like ridges and keratinization.
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CSIN with severe dysplasia showing almost full thickness squamous epithelial atypia.
HPV16-associated in-situ squamous carcinoma. Basaloid appearance of the dysplastic epithelium without surface keratinization.
Immunohistochemical p16 block positivity of HPV16-associated in-situ squamous carcinoma.
Clinical photograph showing a left eye with perilimbal, keratinising conjunctival squamous intraepithelial neoplasia (In-situ squamous SCC) from 2 o'clock to 6 o'clock.

Q: Microscopically, Conjunctival Squamous Intraepithelial Neoplasia exhibits loss of polarity and abnormal stratification; when severe dysplasia encompasses the full epithelial thickness, it is categorized as [...].
CSIN with severe dysplasia showing almost full thickness squamous epithelial atypia.
HPV16-associated in-situ squamous carcinoma. Basaloid appearance of the dysplastic epithelium without surface keratinization.
A: in-situ squamous carcinoma
Back Extra: Conjunctival Squamous Intraepithelial Neoplasia
- Clinical: Conjunctival Squamous Intraepithelial Neoplasia (CSIN) can appear as papilliform, gelatinous, or leukoplakic lesions, often with feeder blood vessels and a pearly appearance.
- Micro: CSIN shows abnormal stratification, loss of polarity, and varying degrees of dysplasia, from mild to severe, with full-thickness dysplasia in in-situ squamous carcinoma.
- Ancillary: High-risk HPV-associated CSIN can be p16+ and shows a basaloid appearance without surface keratinization, while UV-associated cases may have rete-like ridges and keratinization.
Reference Gallery:
CSIN with severe dysplasia showing almost full thickness squamous epithelial atypia.
HPV16-associated in-situ squamous carcinoma. Basaloid appearance of the dysplastic epithelium without surface keratinization.
Immunohistochemical p16 block positivity of HPV16-associated in-situ squamous carcinoma.
Clinical photograph showing a left eye with perilimbal, keratinising conjunctival squamous intraepithelial neoplasia (In-situ squamous SCC) from 2 o'clock to 6 o'clock.

Q: High-risk HPV-associated Conjunctival Squamous Intraepithelial Neoplasia typically displays a basaloid morphology without surface keratinization and shows strong block positivity for [...] on immunohistochemistry.
HPV16-associated in-situ squamous carcinoma. Basaloid appearance of the dysplastic epithelium without surface keratinization.
Immunohistochemical p16 block positivity of HPV16-associated in-situ squamous carcinoma.
A: p16
Back Extra: Conjunctival Squamous Intraepithelial Neoplasia
- Clinical: Conjunctival Squamous Intraepithelial Neoplasia (CSIN) can appear as papilliform, gelatinous, or leukoplakic lesions, often with feeder blood vessels and a pearly appearance.
- Micro: CSIN shows abnormal stratification, loss of polarity, and varying degrees of dysplasia, from mild to severe, with full-thickness dysplasia in in-situ squamous carcinoma.
- Ancillary: High-risk HPV-associated CSIN can be p16+ and shows a basaloid appearance without surface keratinization, while UV-associated cases may have rete-like ridges and keratinization.
Reference Gallery:
CSIN with severe dysplasia showing almost full thickness squamous epithelial atypia.
HPV16-associated in-situ squamous carcinoma. Basaloid appearance of the dysplastic epithelium without surface keratinization.
Immunohistochemical p16 block positivity of HPV16-associated in-situ squamous carcinoma.
Clinical photograph showing a left eye with perilimbal, keratinising conjunctival squamous intraepithelial neoplasia (In-situ squamous SCC) from 2 o'clock to 6 o'clock.

Q: In Benign Epithelial Melanosis of the Conjunctiva, histopathology characteristically demonstrates increased melanin pigmentation within the basal epithelium but with a normal density of [...].
Benign epithelial melanosis of the conjunctiva. Conjunctival epithelium is pigmented, with some melanophages present in the substantia propria as well. Melanocytes, however, appear normal.
A: melanocytes
Back Extra: Benign Epithelial Melanosis of the Conjunctiva
- Clinical: Benign epithelial melanosis of the conjunctiva is characterized by mottled or patchy intraepithelial pigmented lesions that are not fixed to the sclera, commonly seen in individuals with Fitzpatrick skin types IV - VI.
- Micro: Histopathology shows normal conjunctival melanocytes with increased melanin pigmentation, located within the basal epithelium, and without significant atypia or proliferation.
- Ancillary: Immunohistochemistry demonstrates positive staining for melanocytic markers such as MelanA, MITF, HMB45, and SOX10.
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Benign epithelial melanosis of the conjunctiva. Conjunctival epithelium is pigmented, with some melanophages present in the substantia propria as well. Melanocytes, however, appear normal.
Benign epithelial melanosis of the conjunctiva. A MART-1 immunostain confirms normal density of dendritic-appearing melanocytes.

Q: When evaluating Benign Epithelial Melanosis of the Conjunctiva, immunohistochemical stains such as [...] can be used to confirm a normal density of dendritic-appearing melanocytes without pathologic proliferation.
Benign epithelial melanosis of the conjunctiva. A MART-1 immunostain confirms normal density of dendritic-appearing melanocytes.
A: MART-1
Back Extra: Benign Epithelial Melanosis of the Conjunctiva
- Clinical: Benign epithelial melanosis of the conjunctiva is characterized by mottled or patchy intraepithelial pigmented lesions that are not fixed to the sclera, commonly seen in individuals with Fitzpatrick skin types IV - VI.
- Micro: Histopathology shows normal conjunctival melanocytes with increased melanin pigmentation, located within the basal epithelium, and without significant atypia or proliferation.
- Ancillary: Immunohistochemistry demonstrates positive staining for melanocytic markers such as MelanA, MITF, HMB45, and SOX10.
Reference Gallery:
Benign epithelial melanosis of the conjunctiva. Conjunctival epithelium is pigmented, with some melanophages present in the substantia propria as well. Melanocytes, however, appear normal.
Benign epithelial melanosis of the conjunctiva. A MART-1 immunostain confirms normal density of dendritic-appearing melanocytes.

Q: Microscopically, Blue Naevus of the Conjunctiva is characterized by heavily pigmented, bland, spindle and [...] melanocytic cells with slender, branching networks in the conjunctival substantia propria.
Conjunctival dendritic blue naevus. Conjunctival substantia propria containing pigmented bland spindle / dendritic / stellate melanocytic cells in the conjunctival substantia propria. The melanocytic cells show slender, branching networks of dendritic processes.
A: dendritic
Back Extra: Blue Naevus of the Conjunctiva
- Clinical: Blue naevi present as dark-brown to black, sharply demarcated, unifocal or multifocal, slightly elevated conjunctival masses with a thickness of approximately 2 mm.
- Micro: Dendritic (common) blue naevi are characterized by heavily pigmented bland spindle/dendritic/stellate melanocytic cells in the conjunctival substantia propria, with slender, branching networks of dendritic processes and melanophages.
- Ancillary: Immunohistochemistry shows spindle/dendritic/stellate melanocytic cells positive for S100 protein, melan-A, and SOX10, and G-protein-coupled receptor driver mutations (especially those in GNAQ) can be identified.
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Conjunctival blue naevus. Clinical image showing a peri-limbal conjunctival blue naevus.
Conjunctival dendritic blue naevus. Conjunctival substantia propria containing pigmented bland spindle / dendritic / stellate melanocytic cells in the conjunctival substantia propria. The melanocytic cells show slender, branching networks of dendritic processes.
Conjunctival dendritic blue naevus. A bleach preparation reveals the bland spindle cells of dendritic (common) blue naevus.
Conjunctival cellular blue naevus. This shows a combination of conjunctival conventional blue naevus and cellular blue naevus. The latter is seen as less pigmented nests of plumper spindle / ovoid cells.

Q: When clinically evaluating a dark-brown to black, sharply demarcated mass, the microscopic finding of bland spindle cells that become clearly visible on a bleach preparation is characteristic of [...].
Conjunctival blue naevus. Clinical image showing a peri-limbal conjunctival blue naevus.
Conjunctival dendritic blue naevus. A bleach preparation reveals the bland spindle cells of dendritic (common) blue naevus.
A: Blue Naevus of the Conjunctiva
Back Extra: Blue Naevus of the Conjunctiva
- Clinical: Blue naevi present as dark-brown to black, sharply demarcated, unifocal or multifocal, slightly elevated conjunctival masses with a thickness of approximately 2 mm.
- Micro: Dendritic (common) blue naevi are characterized by heavily pigmented bland spindle/dendritic/stellate melanocytic cells in the conjunctival substantia propria, with slender, branching networks of dendritic processes and melanophages.
- Ancillary: Immunohistochemistry shows spindle/dendritic/stellate melanocytic cells positive for S100 protein, melan-A, and SOX10, and G-protein-coupled receptor driver mutations (especially those in GNAQ) can be identified.
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Conjunctival blue naevus. Clinical image showing a peri-limbal conjunctival blue naevus.
Conjunctival dendritic blue naevus. Conjunctival substantia propria containing pigmented bland spindle / dendritic / stellate melanocytic cells in the conjunctival substantia propria. The melanocytic cells show slender, branching networks of dendritic processes.
Conjunctival dendritic blue naevus. A bleach preparation reveals the bland spindle cells of dendritic (common) blue naevus.
Conjunctival cellular blue naevus. This shows a combination of conjunctival conventional blue naevus and cellular blue naevus. The latter is seen as less pigmented nests of plumper spindle / ovoid cells.

Q: In the cellular variant of Blue Naevus of the Conjunctiva, microscopic evaluation reveals less pigmented nests composed of plumper [...] cells alongside conventional areas.
Conjunctival cellular blue naevus. This shows a combination of conjunctival conventional blue naevus and cellular blue naevus. The latter is seen as less pigmented nests of plumper spindle / ovoid cells.
A: spindle or ovoid
Back Extra: Blue Naevus of the Conjunctiva
- Clinical: Blue naevi present as dark-brown to black, sharply demarcated, unifocal or multifocal, slightly elevated conjunctival masses with a thickness of approximately 2 mm.
- Micro: Dendritic (common) blue naevi are characterized by heavily pigmented bland spindle/dendritic/stellate melanocytic cells in the conjunctival substantia propria, with slender, branching networks of dendritic processes and melanophages.
- Ancillary: Immunohistochemistry shows spindle/dendritic/stellate melanocytic cells positive for S100 protein, melan-A, and SOX10, and G-protein-coupled receptor driver mutations (especially those in GNAQ) can be identified.
Reference Gallery:
Conjunctival blue naevus. Clinical image showing a peri-limbal conjunctival blue naevus.
Conjunctival dendritic blue naevus. Conjunctival substantia propria containing pigmented bland spindle / dendritic / stellate melanocytic cells in the conjunctival substantia propria. The melanocytic cells show slender, branching networks of dendritic processes.
Conjunctival dendritic blue naevus. A bleach preparation reveals the bland spindle cells of dendritic (common) blue naevus.
Conjunctival cellular blue naevus. This shows a combination of conjunctival conventional blue naevus and cellular blue naevus. The latter is seen as less pigmented nests of plumper spindle / ovoid cells.

Q: In Combined Naevus, the microscopic blue nevus component is characteristically composed of moderately to heavily pigmented fusiform and [...] melanocytes.
Combined conventional and blue melanocytic naevus. The blue naevus component is represented by pigmented spindled and dendritic melanocytes.
A: dendritic
Back Extra: Combined Naevus
- Clinical: Combined naevi may show atypical features, including atypical dark coloration, irregular pigmentation, and history of recent growth, prompting surgical excision or even raising the clinical suspicion of a melanoma.
- Micro: The blue naevus component is characterized by moderately to heavily pigmented fusiform and dendritic melanocytes, often located in the deepest part of the naevus but may be superficial.
- Ancillary: Melanocytes in the granular cell component diffusely express HMB-45, while melanocytes in granular cell naevus lack nuclear expression of beta catenin.
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Combined conventional and blue melanocytic naevus. A raised, darkly pigmented lesion on the plica.
Combined conventional and blue melanocytic naevus. The naevus is variably pigmented with entrapped epithelial cysts.
Combined conventional and blue melanocytic naevus. The blue naevus component is represented by pigmented spindled and dendritic melanocytes.
Combined conventional and granular cell melanocytic naevus. The lesion is well circumscribed, raised, and darkly pigmented.
Combined conventional and granular cell melanocytic naevus. A granular cell component predominates (conventional naevus component is on the left).
Combined conventional and granular cell melanocytic naevus. The granular cell component is composed of relatively large melanocytes with lightly pigmented granular cytoplasm.
Combined conventional and granular cell melanocytic naevus. Diffuse positivity for HMB45 in the granular cell component in contrast to the conventional naevus (left).
Combined (tri-phenotypic) melanocytic naevus. Conventional naevus with balloon cell (left) and deep penetrating naevus (right) components.

Q: In a Combined Naevus containing a granular cell component, the melanocytes within the granular portion characteristically show diffuse immunohistochemical expression of [...].
Combined conventional and granular cell melanocytic naevus. The granular cell component is composed of relatively large melanocytes with lightly pigmented granular cytoplasm.
Combined conventional and granular cell melanocytic naevus. Diffuse positivity for HMB45 in the granular cell component in contrast to the conventional naevus (left).
A: HMB-45
Back Extra: Combined Naevus
- Clinical: Combined naevi may show atypical features, including atypical dark coloration, irregular pigmentation, and history of recent growth, prompting surgical excision or even raising the clinical suspicion of a melanoma.
- Micro: The blue naevus component is characterized by moderately to heavily pigmented fusiform and dendritic melanocytes, often located in the deepest part of the naevus but may be superficial.
- Ancillary: Melanocytes in the granular cell component diffusely express HMB-45, while melanocytes in granular cell naevus lack nuclear expression of beta catenin.
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Combined conventional and blue melanocytic naevus. A raised, darkly pigmented lesion on the plica.
Combined conventional and blue melanocytic naevus. The naevus is variably pigmented with entrapped epithelial cysts.
Combined conventional and blue melanocytic naevus. The blue naevus component is represented by pigmented spindled and dendritic melanocytes.
Combined conventional and granular cell melanocytic naevus. The lesion is well circumscribed, raised, and darkly pigmented.
Combined conventional and granular cell melanocytic naevus. A granular cell component predominates (conventional naevus component is on the left).
Combined conventional and granular cell melanocytic naevus. The granular cell component is composed of relatively large melanocytes with lightly pigmented granular cytoplasm.
Combined conventional and granular cell melanocytic naevus. Diffuse positivity for HMB45 in the granular cell component in contrast to the conventional naevus (left).
Combined (tri-phenotypic) melanocytic naevus. Conventional naevus with balloon cell (left) and deep penetrating naevus (right) components.

Q: Histologically, the compound variant of Junctional, Compound and Subepithelial Conjunctival Naevi is characterized by melanocytic nests in both the epithelium and substantia propria, showing maturation with depth and frequently featuring prominent [...].
Conjunctival naevus, compound. An example of a conjunctival compound naevus with prominent cysts.
Conjunctival melanocytic naevus, compound. A lesion associated with epithelial inclusion cysts. The lesion shows maturation with depth.
A: epithelial inclusion cysts
Back Extra: Junctional, Compound and Subepithelial Conjunctival Naevi
- Clinical: Conjunctival naevi are well-defined, variably pigmented (tan-to-brown) or amelanotic, mobile lesions commonly arising on the bulbar conjunctiva.
- Micro: Compound naevi contain naevus cells within the epithelium and the substantia propria, exhibiting maturation with depth and often showing cystic surface epithelial invaginations.
- Ancillary: Conjunctival naevi have mutually exclusive BRAF and NRAS mutations, leading to constitutive activation of the mitogen-activated protein (MAP) kinase pathway.
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Conjunctival naevus, compound. A variably pigmented, well circumscribed lesion.
Conjunctival junctional naevus. Junctional naevus nests of a junctional naevus in a young teenager.
Conjunctival naevus, compound. An example of a conjunctival compound naevus with prominent cysts.
Conjunctival naevus, subepithelial. An example of a subepithelial conjunctival melanocytic naevus with mature naevus cells in the stroma.
Conjunctival naevus, subepithelial. Higher power view of a conjunctival subepithelial melanocytic naevus, showing mature naevus cells.
Conjunctival melanocytic naevus, compound. A lesion associated with epithelial inclusion cysts. The lesion shows maturation with depth.
Conjunctival melanocytic naevus, compound. A case with a nested junctional component. In the context of thin conjunctiva, melanocytic nests appear to be confluent and show consumption of the epidermis. Such pattern is common in conjunctival naevi and does not indicate atypia.

Q: A biopsy of a well-defined, mobile lesion on the bulbar conjunctiva reveals mature melanocytic cells confined entirely to the stroma, confirming the subepithelial variant of [...].
Conjunctival naevus, subepithelial. An example of a subepithelial conjunctival melanocytic naevus with mature naevus cells in the stroma.
Conjunctival naevus, subepithelial. Higher power view of a conjunctival subepithelial melanocytic naevus, showing mature naevus cells.
A: Junctional, Compound and Subepithelial Conjunctival Naevi
Back Extra: Junctional, Compound and Subepithelial Conjunctival Naevi
- Clinical: Conjunctival naevi are well-defined, variably pigmented (tan-to-brown) or amelanotic, mobile lesions commonly arising on the bulbar conjunctiva.
- Micro: Compound naevi contain naevus cells within the epithelium and the substantia propria, exhibiting maturation with depth and often showing cystic surface epithelial invaginations.
- Ancillary: Conjunctival naevi have mutually exclusive BRAF and NRAS mutations, leading to constitutive activation of the mitogen-activated protein (MAP) kinase pathway.
Reference Gallery:
Conjunctival naevus, compound. A variably pigmented, well circumscribed lesion.
Conjunctival junctional naevus. Junctional naevus nests of a junctional naevus in a young teenager.
Conjunctival naevus, compound. An example of a conjunctival compound naevus with prominent cysts.
Conjunctival naevus, subepithelial. An example of a subepithelial conjunctival melanocytic naevus with mature naevus cells in the stroma.
Conjunctival naevus, subepithelial. Higher power view of a conjunctival subepithelial melanocytic naevus, showing mature naevus cells.
Conjunctival melanocytic naevus, compound. A lesion associated with epithelial inclusion cysts. The lesion shows maturation with depth.
Conjunctival melanocytic naevus, compound. A case with a nested junctional component. In the context of thin conjunctiva, melanocytic nests appear to be confluent and show consumption of the epidermis. Such pattern is common in conjunctival naevi and does not indicate atypia.

Q: In the context of the thin mucosa seen in Junctional, Compound and Subepithelial Conjunctival Naevi, the junctional melanocytic nests often appear confluent and exhibit apparent consumption of the epithelium, a common architectural pattern that does not indicate [...].
Conjunctival melanocytic naevus, compound. A case with a nested junctional component. In the context of thin conjunctiva, melanocytic nests appear to be confluent and show consumption of the epidermis. Such pattern is common in conjunctival naevi and does not indicate atypia.
A: atypia
Back Extra: Junctional, Compound and Subepithelial Conjunctival Naevi
- Clinical: Conjunctival naevi are well-defined, variably pigmented (tan-to-brown) or amelanotic, mobile lesions commonly arising on the bulbar conjunctiva.
- Micro: Compound naevi contain naevus cells within the epithelium and the substantia propria, exhibiting maturation with depth and often showing cystic surface epithelial invaginations.
- Ancillary: Conjunctival naevi have mutually exclusive BRAF and NRAS mutations, leading to constitutive activation of the mitogen-activated protein (MAP) kinase pathway.
Reference Gallery:
Conjunctival naevus, compound. A variably pigmented, well circumscribed lesion.
Conjunctival junctional naevus. Junctional naevus nests of a junctional naevus in a young teenager.
Conjunctival naevus, compound. An example of a conjunctival compound naevus with prominent cysts.
Conjunctival naevus, subepithelial. An example of a subepithelial conjunctival melanocytic naevus with mature naevus cells in the stroma.
Conjunctival naevus, subepithelial. Higher power view of a conjunctival subepithelial melanocytic naevus, showing mature naevus cells.
Conjunctival melanocytic naevus, compound. A lesion associated with epithelial inclusion cysts. The lesion shows maturation with depth.
Conjunctival melanocytic naevus, compound. A case with a nested junctional component. In the context of thin conjunctiva, melanocytic nests appear to be confluent and show consumption of the epidermis. Such pattern is common in conjunctival naevi and does not indicate atypia.

Q: A pediatric conjunctival lesion characterized by cystic and solid epithelial nests mixed with prominent lymphocytic inflammation and numerous eosinophils is diagnostic for an [...].
Inflamed juvenile conjunctival naevus. Note the dense inflammatory infiltrate, including numerous eosinophils.
Eosinophils in inflamed juvenile naevus. Notice the eosinophils percolating into the superficial epithelium. In the background there are naevus cells, some with intranuclear inclusions and some plasma cells.
Inflamed juvenile conjunctival naevus. A low power view of the inflamed naevus shows the combination of naevus cells and epithelium with residual cystic component. On the left, there is more inflammatory component with lymphocytes and plasma cells.
A: inflamed juvenile conjunctival naevus
Back Extra: Inflamed Juvenile Conjunctival Naevus
- Clinical: Inflamed juvenile conjunctival naevus (IJCN) typically presents as a well-circumscribed, pale flesh-colored nodule with areas of congested vessels, often seen in boys around the age of 13.
- Micro: IJCN is characterized by the presence of cystic and solid epithelial nests, prominent lymphocytic inflammation, and eosinophils. The junctional component often extends horizontally beyond the subepithelial one.
- Ancillary: IJCN carries mutually exclusive NRAS or BRAF mutations, and immunohistochemistry shows positivity for HMB45 in the superficial layer, Melan A, and S100 protein.
Reference Gallery:
Inflamed juvenile conjunctival naevus. This was removed from a 7 year old boy.
Inflamed juvenile conjunctival naevus. Note the dense inflammatory infiltrate, including numerous eosinophils.
Inflamed juvenile conjunctival naevus. A MITF immunostain highlights the melanocytic elements, including extensive junctional activity as well as naevoid cells surrounding epithelial cysts extending into the substantia propria.
Eosinophils in inflamed juvenile naevus. Notice the eosinophils percolating into the superficial epithelium. In the background there are naevus cells, some with intranuclear inclusions and some plasma cells.
Inflamed juvenile conjunctival naevus. A low power view of the inflamed naevus shows the combination of naevus cells and epithelium with residual cystic component. On the left, there is more inflammatory component with lymphocytes and plasma cells.
Inflamed juvenile compound naevus. Immunohistochemistry using a dual stain with Melan A (cytoplasmic-red) and Ki67 (nuclear-dark brown) shows that the melanocytes have little or no proliferation. Inflammatory cells and epithelium show proliferative activity.
Inflamed juvenile conjunctival naevus. An amelanotic conjunctival lesion adjacent to the temporal limbus with prominent cysts, feeder vessels, and intrinsic vascularity.

Q: In an inflamed juvenile conjunctival naevus, the characteristic dense inflammatory infiltrate contains lymphocytes, plasma cells, and numerous percolating [...].
Inflamed juvenile conjunctival naevus. Note the dense inflammatory infiltrate, including numerous eosinophils.
Eosinophils in inflamed juvenile naevus. Notice the eosinophils percolating into the superficial epithelium. In the background there are naevus cells, some with intranuclear inclusions and some plasma cells.
A: eosinophils
Back Extra: Inflamed Juvenile Conjunctival Naevus
- Clinical: Inflamed juvenile conjunctival naevus (IJCN) typically presents as a well-circumscribed, pale flesh-colored nodule with areas of congested vessels, often seen in boys around the age of 13.
- Micro: IJCN is characterized by the presence of cystic and solid epithelial nests, prominent lymphocytic inflammation, and eosinophils. The junctional component often extends horizontally beyond the subepithelial one.
- Ancillary: IJCN carries mutually exclusive NRAS or BRAF mutations, and immunohistochemistry shows positivity for HMB45 in the superficial layer, Melan A, and S100 protein.
Reference Gallery:
Inflamed juvenile conjunctival naevus. This was removed from a 7 year old boy.
Inflamed juvenile conjunctival naevus. Note the dense inflammatory infiltrate, including numerous eosinophils.
Inflamed juvenile conjunctival naevus. A MITF immunostain highlights the melanocytic elements, including extensive junctional activity as well as naevoid cells surrounding epithelial cysts extending into the substantia propria.
Eosinophils in inflamed juvenile naevus. Notice the eosinophils percolating into the superficial epithelium. In the background there are naevus cells, some with intranuclear inclusions and some plasma cells.
Inflamed juvenile conjunctival naevus. A low power view of the inflamed naevus shows the combination of naevus cells and epithelium with residual cystic component. On the left, there is more inflammatory component with lymphocytes and plasma cells.
Inflamed juvenile compound naevus. Immunohistochemistry using a dual stain with Melan A (cytoplasmic-red) and Ki67 (nuclear-dark brown) shows that the melanocytes have little or no proliferation. Inflammatory cells and epithelium show proliferative activity.
Inflamed juvenile conjunctival naevus. An amelanotic conjunctival lesion adjacent to the temporal limbus with prominent cysts, feeder vessels, and intrinsic vascularity.

Q: Clinically, an inflamed juvenile conjunctival naevus presents as a well-circumscribed, pale, flesh-colored nodule often displaying intrinsic vascularity, congested feeder vessels, and prominent [...].
Inflamed juvenile conjunctival naevus. An amelanotic conjunctival lesion adjacent to the temporal limbus with prominent cysts, feeder vessels, and intrinsic vascularity.
A: cysts
Back Extra: Inflamed Juvenile Conjunctival Naevus
- Clinical: Inflamed juvenile conjunctival naevus (IJCN) typically presents as a well-circumscribed, pale flesh-colored nodule with areas of congested vessels, often seen in boys around the age of 13.
- Micro: IJCN is characterized by the presence of cystic and solid epithelial nests, prominent lymphocytic inflammation, and eosinophils. The junctional component often extends horizontally beyond the subepithelial one.
- Ancillary: IJCN carries mutually exclusive NRAS or BRAF mutations, and immunohistochemistry shows positivity for HMB45 in the superficial layer, Melan A, and S100 protein.
Reference Gallery:
Inflamed juvenile conjunctival naevus. This was removed from a 7 year old boy.
Inflamed juvenile conjunctival naevus. Note the dense inflammatory infiltrate, including numerous eosinophils.
Inflamed juvenile conjunctival naevus. A MITF immunostain highlights the melanocytic elements, including extensive junctional activity as well as naevoid cells surrounding epithelial cysts extending into the substantia propria.
Eosinophils in inflamed juvenile naevus. Notice the eosinophils percolating into the superficial epithelium. In the background there are naevus cells, some with intranuclear inclusions and some plasma cells.
Inflamed juvenile conjunctival naevus. A low power view of the inflamed naevus shows the combination of naevus cells and epithelium with residual cystic component. On the left, there is more inflammatory component with lymphocytes and plasma cells.
Inflamed juvenile compound naevus. Immunohistochemistry using a dual stain with Melan A (cytoplasmic-red) and Ki67 (nuclear-dark brown) shows that the melanocytes have little or no proliferation. Inflammatory cells and epithelium show proliferative activity.
Inflamed juvenile conjunctival naevus. An amelanotic conjunctival lesion adjacent to the temporal limbus with prominent cysts, feeder vessels, and intrinsic vascularity.

Q: Microscopically, WNT-activated deep penetrating/plexiform melanocytoma (naevus) exhibits a nested or plexiform growth of large epithelioid melanocytes with finely pigmented (dusty) cytoplasm, and is practically always accompanied by prominent [...].
Combined deep penetrating naevus. In the deep penetrating naevus, intensely pigmented melanophages predominate over small nests of lightly pigmented epithelioid melanocytes.
Combined deep penetrating naevus. Combined deep penetrating naevus with only a few subepithelial nests of deep penetrating naevus melanocytes accompanied by melanophages.
A: melanophages
Back Extra: WNT-activated deep penetrating/plexiform melanocytoma (naevus)
- Clinical: Most WNT-activated deep penetrating/plexiform melanocytoma (naevus) are darkly pigmented, and changes in size and colour are noted in three quarters of cases.
- Micro: Characterized by nested or plexiform growth of relatively large ovoid or epithelioid melanocytes with finely pigmented (dusty) cytoplasm, and melanophages are practically always present.
- Ancillary: Positive for BRAF p.V600E by immunohistochemistry and nuclear positivity for beta catenin and cyclin D1. Retained p16 and absent or focal PRAME expression help differentiate it from melanoma.
Reference Gallery:
Combined deep penetrating naevus. A variably pigmented combined conventional and deep penetrating naevus involving the bulbar conjunctiva and limbus.
Combined deep penetrating naevus. Pigmented subepithelial deep penetrating naevus beneath a superficially located conventional naevus.
Combined deep penetrating naevus. In the deep penetrating naevus, intensely pigmented melanophages predominate over small nests of lightly pigmented epithelioid melanocytes.
Combined deep penetrating naevus. Subepithelial deep penetrating naevus (left) within a conventional naevus.
Combined deep penetrating naevus. A diffuse nuclear positivity for beta catenin in melanocytes of deep penetrating naevus (lower left) and an absence of nuclear reaction in melanocytes of conventional naevus (right)
Combined deep penetrating naevus. Combined deep penetrating naevus with only a few subepithelial nests of deep penetrating naevus melanocytes accompanied by melanophages.
Combined deep penetrating naevus. Combined deep penetrating naevus with intraepithelial component of deep penetrating naevus within epithelium of inclusion cysts and an adjacent subepithelial component of a conventional naevus.

Q: By immunohistochemistry, WNT-activated deep penetrating/plexiform melanocytoma (naevus) characteristically demonstrates diffuse nuclear positivity for [...], which reflects the underlying pathway activation and helps distinguish it from a conventional nevus.
Combined deep penetrating naevus. A diffuse nuclear positivity for beta catenin in melanocytes of deep penetrating naevus (lower left) and an absence of nuclear reaction in melanocytes of conventional naevus (right)
A: beta-catenin
Back Extra: WNT-activated deep penetrating/plexiform melanocytoma (naevus)
- Clinical: Most WNT-activated deep penetrating/plexiform melanocytoma (naevus) are darkly pigmented, and changes in size and colour are noted in three quarters of cases.
- Micro: Characterized by nested or plexiform growth of relatively large ovoid or epithelioid melanocytes with finely pigmented (dusty) cytoplasm, and melanophages are practically always present.
- Ancillary: Positive for BRAF p.V600E by immunohistochemistry and nuclear positivity for beta catenin and cyclin D1. Retained p16 and absent or focal PRAME expression help differentiate it from melanoma.
Reference Gallery:
Combined deep penetrating naevus. A variably pigmented combined conventional and deep penetrating naevus involving the bulbar conjunctiva and limbus.
Combined deep penetrating naevus. Pigmented subepithelial deep penetrating naevus beneath a superficially located conventional naevus.
Combined deep penetrating naevus. In the deep penetrating naevus, intensely pigmented melanophages predominate over small nests of lightly pigmented epithelioid melanocytes.
Combined deep penetrating naevus. Subepithelial deep penetrating naevus (left) within a conventional naevus.
Combined deep penetrating naevus. A diffuse nuclear positivity for beta catenin in melanocytes of deep penetrating naevus (lower left) and an absence of nuclear reaction in melanocytes of conventional naevus (right)
Combined deep penetrating naevus. Combined deep penetrating naevus with only a few subepithelial nests of deep penetrating naevus melanocytes accompanied by melanophages.
Combined deep penetrating naevus. Combined deep penetrating naevus with intraepithelial component of deep penetrating naevus within epithelium of inclusion cysts and an adjacent subepithelial component of a conventional naevus.

Q: Clinically, Conjunctival Melanocytic Intraepithelial Lesion typically presents in young to middle-aged adults as a [...], flat, irregular brown discoloration of the conjunctiva.
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. An example presenting as a flat, variably pigmented lesion in the bulbar conjunctiva and limbus.
A: unilateral
Back Extra: Conjunctival Melanocytic Intraepithelial Lesion
- Clinical: Conjunctival Melanocytic Intraepithelial Lesion (C-MIL) is typically unilateral, appearing as flat, irregular brown discolourations in young to middle-aged adults.
- Micro: Key microscopic features include increased cellularity of intraepithelial conjunctival melanocytes with cytological atypia, while the basal membrane remains intact.
- Ancillary: Immunohistochemistry shows atypical melanocytes positive for Melan-A, S100, HMB45, MITF, and SOX10.
Reference Gallery:
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. A lentiginous proliferation of melanocytes highlighted by Melan-A immunostaining (inset).
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. An example presenting as a flat, variably pigmented lesion in the bulbar conjunctiva and limbus.

Q: Microscopically, Conjunctival Melanocytic Intraepithelial Lesion demonstrates a [...] proliferation of atypical melanocytes with an intact basal membrane.
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. A lentiginous proliferation of melanocytes highlighted by Melan-A immunostaining (inset).
A: lentiginous
Back Extra: Conjunctival Melanocytic Intraepithelial Lesion
- Clinical: Conjunctival Melanocytic Intraepithelial Lesion (C-MIL) is typically unilateral, appearing as flat, irregular brown discolourations in young to middle-aged adults.
- Micro: Key microscopic features include increased cellularity of intraepithelial conjunctival melanocytes with cytological atypia, while the basal membrane remains intact.
- Ancillary: Immunohistochemistry shows atypical melanocytes positive for Melan-A, S100, HMB45, MITF, and SOX10.
Reference Gallery:
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. A lentiginous proliferation of melanocytes highlighted by Melan-A immunostaining (inset).
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. An example presenting as a flat, variably pigmented lesion in the bulbar conjunctiva and limbus.

Q: A key histologic pitfall in Conjunctival Melanocytic Intraepithelial Lesion is its extension into conjunctival epithelial invaginations known as the [...], which must not be misdiagnosed as invasive melanoma.
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. A lentiginous proliferation of melanocytes highlighted by Melan-A immunostaining (inset).
A: pseudoglands of Henle
Back Extra: Conjunctival Melanocytic Intraepithelial Lesion
- Clinical: Conjunctival Melanocytic Intraepithelial Lesion (C-MIL) is typically unilateral, appearing as flat, irregular brown discolourations in young to middle-aged adults.
- Micro: Key microscopic features include increased cellularity of intraepithelial conjunctival melanocytes with cytological atypia, while the basal membrane remains intact.
- Ancillary: Immunohistochemistry shows atypical melanocytes positive for Melan-A, S100, HMB45, MITF, and SOX10.
Reference Gallery:
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. A lentiginous proliferation of melanocytes highlighted by Melan-A immunostaining (inset).
Potential mimics of CMIL include benign epithelial melanosis of the conjunctiva; oculodermal melanocytosis; conjunctival naevi, particularly those with junctional activity; invasive melanoma; pigmented conjunctival squamous intraepithelial neoplasia; systemic conditions, such as Addison’s disease; postinflammatory hyperpigmentation as well as conjunctival tattooing. Extension of C-MIL into conjunctival epithelial invaginations in the underlying lamina propria (pseudoglands of Henle) should not be misdiagnosed as invasive conjunctival melanoma. Diagnosis: Conjunctival melanocytic intraepithelial lesion. An example presenting as a flat, variably pigmented lesion in the bulbar conjunctiva and limbus.

Q: In Papillary Conjunctivitis, the characteristic flat-topped or dome-shaped papillae are distinguished histologically by the presence of a central [...].
Papillary conjunctivitis. Flat-topped papillae, with fibro-vascular cores, containing inflammatory cells.
Papillary conjunctivitis. Higher power showing the vessel within the core of a papilla and stromal chronic inflammatory cells.
A: fibrovascular core
Back Extra: Papillary Conjunctivitis
- Clinical: Papillary conjunctivitis is characterized by numerous domed-shaped or flat-topped papillae with a vascular core, primarily on the upper tarsal conjunctiva.
- Micro: Histologically, papillae are composed of edematous conjunctival stroma containing capillary-sized vessels and covered by conjunctival epithelium with inflammatory cells in the stroma.
- Ancillary: Ancillary studies are not relevant in the diagnosis of papillary conjunctivitis.
Reference Gallery:
Papillary conjunctivitis. Flat-topped papillae, with fibro-vascular cores, containing inflammatory cells.
Papillary conjunctivitis. Higher power showing the vessel within the core of a papilla and stromal chronic inflammatory cells.

Q: The microscopic finding of flat-topped conjunctival structures with central fibrovascular cores and an edematous stroma infiltrated by chronic inflammatory cells is characteristic of [...].
Papillary conjunctivitis. Flat-topped papillae, with fibro-vascular cores, containing inflammatory cells.
Papillary conjunctivitis. Higher power showing the vessel within the core of a papilla and stromal chronic inflammatory cells.
A: Papillary Conjunctivitis
Back Extra: Papillary Conjunctivitis
- Clinical: Papillary conjunctivitis is characterized by numerous domed-shaped or flat-topped papillae with a vascular core, primarily on the upper tarsal conjunctiva.
- Micro: Histologically, papillae are composed of edematous conjunctival stroma containing capillary-sized vessels and covered by conjunctival epithelium with inflammatory cells in the stroma.
- Ancillary: Ancillary studies are not relevant in the diagnosis of papillary conjunctivitis.
Reference Gallery:
Papillary conjunctivitis. Flat-topped papillae, with fibro-vascular cores, containing inflammatory cells.
Papillary conjunctivitis. Higher power showing the vessel within the core of a papilla and stromal chronic inflammatory cells.

Q: Microscopically, both Pterygium and Pingueculum share the characteristic finding of [...] within the substantia propria, often accompanied by fibrosis and telangiectatic vessels.
Pterygium. There is basophilic elastotic degeneration of the substantia propria. Telengiectatic vessels are seen in the bottom left.
A: basophilic elastotic degeneration
Back Extra: Pterygium and Pingueculum
- Clinical: Pinguecula are often bilateral, located at the interpalpebral para-limbal conjunctiva, and present as a cosmetic complaint or with ocular irritation when inflamed (pingueculitis).
- Micro: Both pterygium and pingueculum show basophilic elastotic degeneration of the substantia propria, fibrosis, and telangiectatic vessels. Pterygium can involve the cornea and may include superficial corneal fibrosis.
- Ancillary: Exfoliative or imprint cytology can be used to detect squamous epithelial dysplasia or malignancy in pterygium and pingueculum.
Reference Gallery:
Pterygium. There is basophilic elastotic degeneration of the substantia propria. Telengiectatic vessels are seen in the bottom left.
Pingueculum. Para-limbal yellow colored, wedge-shaped pingueculum. The incidental corneal lesion is a limbal girdle of Vogt.
Pterygium. Left sided, nasal pterygium encroaching on the visual axis.

Q: When distinguishing between Pterygium and Pingueculum clinically, a pterygium is notable for encroaching onto the [...] (potentially obscuring the visual axis), while a pingueculum typically presents as a yellow, wedge-shaped lesion confined to the para-limbal conjunctiva.
Pingueculum. Para-limbal yellow colored, wedge-shaped pingueculum. The incidental corneal lesion is a limbal girdle of Vogt.
Pterygium. Left sided, nasal pterygium encroaching on the visual axis.
A: cornea
Back Extra: Pterygium and Pingueculum
- Clinical: Pinguecula are often bilateral, located at the interpalpebral para-limbal conjunctiva, and present as a cosmetic complaint or with ocular irritation when inflamed (pingueculitis).
- Micro: Both pterygium and pingueculum show basophilic elastotic degeneration of the substantia propria, fibrosis, and telangiectatic vessels. Pterygium can involve the cornea and may include superficial corneal fibrosis.
- Ancillary: Exfoliative or imprint cytology can be used to detect squamous epithelial dysplasia or malignancy in pterygium and pingueculum.
Reference Gallery:
Pterygium. There is basophilic elastotic degeneration of the substantia propria. Telengiectatic vessels are seen in the bottom left.
Pingueculum. Para-limbal yellow colored, wedge-shaped pingueculum. The incidental corneal lesion is a limbal girdle of Vogt.
Pterygium. Left sided, nasal pterygium encroaching on the visual axis.

Q: The [...] variant of Reactive Epithelial Hyperplasia typically presents as a fleshy limbal mass and histologically features deeply proliferating, acanthotic squamous epithelium with normal keratinocyte maturation.
Pseudoepitheliomatous hyperplasia. A fleshy, gelatinous mass is present from the 8 to 10 o'clock limbus associated with vascular injection.
Pseudoepitheliomatous hyperplasia. Biopsy from a limbal mass displays squamous epithelium proliferating deeply into substantia propria. There is no cellular atypia. A dense lymphocytic infiltrate is present.
A: pseudoepitheliomatous
Back Extra: Reactive Epithelial Hyperplasia
- Clinical: Pseudoepitheliomatous hyperplasia may appear as a fleshy to white-colored mass, minimally raised or thickened, and pseudoglandular hyperplasia appears as a fleshy, ill-defined mass.
- Micro: Pseudoepitheliomatous hyperplasia is characterized by acanthotic epithelium with normal keratinocyte maturation, and pseudoglandular hyperplasia is composed of prominent pseudoglands of Henle, lined with stratified squamous epithelium with goblet cells.
- Ancillary: There are no known genetic abnormalities associated with reactive epithelial hyperplasia.
Reference Gallery:
Pseudoepitheliomatous hyperplasia. A fleshy, gelatinous mass is present from the 8 to 10 o'clock limbus associated with vascular injection.
Pseudoadenomatous hyperplasia. Hyperplastic pseudoglands of Henle, without cytological atypia.
Pseudoepitheliomatous hyperplasia. Biopsy from a limbal mass displays squamous epithelium proliferating deeply into substantia propria. There is no cellular atypia. A dense lymphocytic infiltrate is present.

Q: In the pseudoglandular variant of Reactive Epithelial Hyperplasia, histology reveals prominent, hyperplastic [...] lined by stratified squamous epithelium and goblet cells without cytological atypia.
Pseudoadenomatous hyperplasia. Hyperplastic pseudoglands of Henle, without cytological atypia.
A: pseudoglands of Henle
Back Extra: Reactive Epithelial Hyperplasia
- Clinical: Pseudoepitheliomatous hyperplasia may appear as a fleshy to white-colored mass, minimally raised or thickened, and pseudoglandular hyperplasia appears as a fleshy, ill-defined mass.
- Micro: Pseudoepitheliomatous hyperplasia is characterized by acanthotic epithelium with normal keratinocyte maturation, and pseudoglandular hyperplasia is composed of prominent pseudoglands of Henle, lined with stratified squamous epithelium with goblet cells.
- Ancillary: There are no known genetic abnormalities associated with reactive epithelial hyperplasia.
Reference Gallery:
Pseudoepitheliomatous hyperplasia. A fleshy, gelatinous mass is present from the 8 to 10 o'clock limbus associated with vascular injection.
Pseudoadenomatous hyperplasia. Hyperplastic pseudoglands of Henle, without cytological atypia.
Pseudoepitheliomatous hyperplasia. Biopsy from a limbal mass displays squamous epithelium proliferating deeply into substantia propria. There is no cellular atypia. A dense lymphocytic infiltrate is present.

Q: The characteristic histopathology of Phakomatous Choristoma features islands of cells resembling lens epithelium, which are surrounded by a thick layer of eosinophilic, PAS-positive material analogous to the [...].
Phakomatous choristoma: ovoid, white-gray, firm mass with characteristic histopathology
A: lens capsule
Back Extra: Phakomatous Choristoma
- Clinical: Phakomatous choristoma presents in infancy as a smooth, firm, slowly growing subcutaneous mass in the medial lower eyelid, typically present at birth.
- Micro: Characteristic histopathology includes islands of cuboidal to polygonal cells resembling lens epithelium, surrounded by a thick layer of eosinophilic PAS-positive material analogous to the lens capsule.
- Ancillary: Immunohistochemistry is not required for diagnosis; however, the cells stain positively for vimentin, S100, PAX8, and lens crystalline proteins, and are negative for cytokeratins.
Reference Gallery:
Phakomatous choristoma: ovoid, white-gray, firm mass with characteristic histopathology

Q: Clinically, Phakomatous Choristoma typically presents at birth or in infancy as a smooth, firm subcutaneous mass classically located in the [...].
Phakomatous choristoma: ovoid, white-gray, firm mass with characteristic histopathology
A: medial lower eyelid
Back Extra: Phakomatous Choristoma
- Clinical: Phakomatous choristoma presents in infancy as a smooth, firm, slowly growing subcutaneous mass in the medial lower eyelid, typically present at birth.
- Micro: Characteristic histopathology includes islands of cuboidal to polygonal cells resembling lens epithelium, surrounded by a thick layer of eosinophilic PAS-positive material analogous to the lens capsule.
- Ancillary: Immunohistochemistry is not required for diagnosis; however, the cells stain positively for vimentin, S100, PAX8, and lens crystalline proteins, and are negative for cytokeratins.
Reference Gallery:
Phakomatous choristoma: ovoid, white-gray, firm mass with characteristic histopathology

Q: The provided image shows a proliferation of atypical melanocytes involving the (supra)basal epidermis, which is characteristic of the [...] subtype of In-situ cutaneous melanoma.
Figure 1: Histopathology of lentigo maligna showing atypical melanocytes involving the (supra)basal epidermis.
A: lentigo maligna
Back Extra: In-situ cutaneous melanoma
- Clinical: In-situ cutaneous melanoma, particularly lentigo maligna, typically occurs on the face, scalp, and neck of elderly patients with severe chronic sun damage. Lesions are often large, poorly defined, and may merge with other cutaneous changes.
- Micro: Lentigo maligna shows proliferation of atypical melanocytes involving the (supra)basal epidermis, with possible involvement of hair follicle epithelium or eccrine ducts. Classic lentigo maligna has epidermal atrophy and loss of rete ridges.
- Ancillary: Immunohistochemistry with SOX10 highlights atypical melanocytes, while caution is advised with Melan A or HMB45 staining due to non-specific reactions in keratinocytes of heavy pigmented actinic keratosis.
Reference Gallery:
Figure 1: Histopathology of lentigo maligna showing atypical melanocytes involving the (supra)basal epidermis.

Q: A hallmark histologic feature of dermal Nevi of the Eyelid is [...], which is characterized by nests of melanocytes that progressively decrease in size from the upper superficial dermis to the deeper dermis.
Dermal melanocytic naevus. Larger nests of melanocytes and melanocytes in the upper dermis compared to the depth.
Dermal melanocytic naevus. Smaller nests of melanocytes and melanocytes in the depth compared to the upper dermis (maturation).
A: maturation
Back Extra: Nevi of the Eyelid
- Clinical: Nevi of the eyelid are typically well-circumscribed, light brown to dark lesions, <5 mm in diameter, and do not ulcerate unless traumatized.
- Micro: In a junctional naevus, nests of melanocytes are present at the base of the epidermis, while in a compound naevus, nests are found in both the epidermis and dermis.
- Ancillary: Next-generation sequencing can help differentiate benign naevi from melanoma by identifying driver mutations without additional genetic alterations.
Reference Gallery:
Dermal naevus. Sixty-eight year old man with pigmented lesion upper eyelid edge.
Dermal melanocytic naevus. Larger nests of melanocytes and melanocytes in the upper dermis compared to the depth.
Dermal melanocytic naevus. Smaller nests of melanocytes and melanocytes in the depth compared to the upper dermis (maturation).
Compound naevus. A lesion showing junctional nests and dermal naevus cells as clusters and nests of maturing cells.

Q: In compound Nevi of the Eyelid, melanocytic nests are characteristically located at the epidermodermal junction as well as within the underlying [...].
Compound naevus. A lesion showing junctional nests and dermal naevus cells as clusters and nests of maturing cells.
A: dermis
Back Extra: Nevi of the Eyelid
- Clinical: Nevi of the eyelid are typically well-circumscribed, light brown to dark lesions, <5 mm in diameter, and do not ulcerate unless traumatized.
- Micro: In a junctional naevus, nests of melanocytes are present at the base of the epidermis, while in a compound naevus, nests are found in both the epidermis and dermis.
- Ancillary: Next-generation sequencing can help differentiate benign naevi from melanoma by identifying driver mutations without additional genetic alterations.
Reference Gallery:
Dermal naevus. Sixty-eight year old man with pigmented lesion upper eyelid edge.
Dermal melanocytic naevus. Larger nests of melanocytes and melanocytes in the upper dermis compared to the depth.
Dermal melanocytic naevus. Smaller nests of melanocytes and melanocytes in the depth compared to the upper dermis (maturation).
Compound naevus. A lesion showing junctional nests and dermal naevus cells as clusters and nests of maturing cells.

Q: Well-circumscribed, non-ulcerating, light brown to dark pigmented lesions frequently located on the palpebral margin are clinically characteristic of [...].
Dermal naevus. Sixty-eight year old man with pigmented lesion upper eyelid edge.
A: Nevi of the Eyelid
Back Extra: Nevi of the Eyelid
- Clinical: Nevi of the eyelid are typically well-circumscribed, light brown to dark lesions, <5 mm in diameter, and do not ulcerate unless traumatized.
- Micro: In a junctional naevus, nests of melanocytes are present at the base of the epidermis, while in a compound naevus, nests are found in both the epidermis and dermis.
- Ancillary: Next-generation sequencing can help differentiate benign naevi from melanoma by identifying driver mutations without additional genetic alterations.
Reference Gallery:
Dermal naevus. Sixty-eight year old man with pigmented lesion upper eyelid edge.
Dermal melanocytic naevus. Larger nests of melanocytes and melanocytes in the upper dermis compared to the depth.
Dermal melanocytic naevus. Smaller nests of melanocytes and melanocytes in the depth compared to the upper dermis (maturation).
Compound naevus. A lesion showing junctional nests and dermal naevus cells as clusters and nests of maturing cells.

Q: A symmetrical, well-circumscribed, dome-shaped dermal lesion composed of large spindle and epithelioid cells arranged in fascicles with prominent nucleoli is characteristic of a [...].
Spitz naevus. A symmetrical, well circumscribed, dome shaped dermal lesion with a maximum diameter of 4.9 mm.
Spitz naevus. Large spindle and epithelioid cells with nuclei containing prominent nucleoli arranged in fascicles.
A: Spitz Nevus
Back Extra: Spitz Nevus
- Clinical: Spitz nevi are typically seen in young patients as rapidly growing, pinkish-red, vascularized lesions, most commonly on the head and neck, including occasionally the eyelid.
- Micro: Spitz nevi are well-circumscribed, symmetrical lesions with spindle and/or epithelioid cells arranged in fascicles, often with prominent nucleoli and a uniform cytomorphology.
- Ancillary: Immunohistochemistry shows diffuse expression of S100 and SOX10, with HMB45-positive junctional cells. Ki67 staining is limited to the superficial layers, and p16 is preserved.
Reference Gallery:
Spitz naevus. A symmetrical, well circumscribed, dome shaped dermal lesion with a maximum diameter of 4.9 mm.
Spitz naevus. Large spindle and epithelioid cells with nuclei containing prominent nucleoli arranged in fascicles.
Spitz naevus. There is a diffuse expression of S100.
Spitz naevus. Ki67 highlighting proliferating cells within the lesion. The proliferative activity is limited and only 2 superficial mitoses were present in the sections.

Q: In a Spitz Nevus, immunohistochemistry for Ki67 shows proliferative activity that is characteristically limited to the [...] layers, helping to distinguish it from malignancy.
Spitz naevus. Ki67 highlighting proliferating cells within the lesion. The proliferative activity is limited and only 2 superficial mitoses were present in the sections.
A: superficial
Back Extra: Spitz Nevus
- Clinical: Spitz nevi are typically seen in young patients as rapidly growing, pinkish-red, vascularized lesions, most commonly on the head and neck, including occasionally the eyelid.
- Micro: Spitz nevi are well-circumscribed, symmetrical lesions with spindle and/or epithelioid cells arranged in fascicles, often with prominent nucleoli and a uniform cytomorphology.
- Ancillary: Immunohistochemistry shows diffuse expression of S100 and SOX10, with HMB45-positive junctional cells. Ki67 staining is limited to the superficial layers, and p16 is preserved.
Reference Gallery:
Spitz naevus. A symmetrical, well circumscribed, dome shaped dermal lesion with a maximum diameter of 4.9 mm.
Spitz naevus. Large spindle and epithelioid cells with nuclei containing prominent nucleoli arranged in fascicles.
Spitz naevus. There is a diffuse expression of S100.
Spitz naevus. Ki67 highlighting proliferating cells within the lesion. The proliferative activity is limited and only 2 superficial mitoses were present in the sections.

Q: Immunohistochemistry of a Spitz Nevus typically demonstrates diffuse expression of the neural crest markers SOX10 and [...].
Spitz naevus. There is a diffuse expression of S100.
A: S100
Back Extra: Spitz Nevus
- Clinical: Spitz nevi are typically seen in young patients as rapidly growing, pinkish-red, vascularized lesions, most commonly on the head and neck, including occasionally the eyelid.
- Micro: Spitz nevi are well-circumscribed, symmetrical lesions with spindle and/or epithelioid cells arranged in fascicles, often with prominent nucleoli and a uniform cytomorphology.
- Ancillary: Immunohistochemistry shows diffuse expression of S100 and SOX10, with HMB45-positive junctional cells. Ki67 staining is limited to the superficial layers, and p16 is preserved.
Reference Gallery:
Spitz naevus. A symmetrical, well circumscribed, dome shaped dermal lesion with a maximum diameter of 4.9 mm.
Spitz naevus. Large spindle and epithelioid cells with nuclei containing prominent nucleoli arranged in fascicles.
Spitz naevus. There is a diffuse expression of S100.
Spitz naevus. Ki67 highlighting proliferating cells within the lesion. The proliferative activity is limited and only 2 superficial mitoses were present in the sections.

Q: The defining histologic feature of [...] is the presence of atypical melanocytes breaching the basement membrane to form a dermal proliferation, often seen on a background of chronically sun-damaged skin.
Microinvasive LMM. Atrophic epidermis with highly atypical melanocytes occupying the lower third of the epithelium. Single cells are partly confluent, with pleomorphic and hyperchromatic nuclei, perinuclear halo and pigmentation.
Microinvasive LMM. Higher magnification with single dermal atypical melanocytes and melanophages, corresponding to microinvasive lentigo maligna melanoma with immune reaction.
A: Invasive Cutaneous Melanoma
Back Extra: Invasive Cutaneous Melanoma
- Clinical: Invasive cutaneous melanomas of the eyelid often present with multicolored, asymmetrical lesions with poorly defined borders, commonly found in chronically sun-damaged skin.
- Micro: Histopathologically, invasive cutaneous melanomas show intraepidermal and dermal proliferation of atypical melanocytes, with spindle cell and desmoplastic variants having a lentiginous intraepidermal pattern.
- Ancillary: Immunohistochemical markers such as Melan A and HMB-45 are positive in melanocytic lesions, and molecular testing often reveals BRAF p.V600E or NRAS mutations.
Reference Gallery:
Microinvasive lentigo maligna melanoma. Overview HE: Actinic damaged skin with epidermal atrophy (blue arrow) and elastoid degeneration. Tarsal conjunctiva (black arrow)
Microinvasive LMM. Sun-damaged skin with epidermal atrophy and elastoid degeneration.
Microinvasive LMM. Atrophic epidermis with highly atypical melanocytes occupying the lower third of the epithelium. Single cells are partly confluent, with pleomorphic and hyperchromatic nuclei, perinuclear halo and pigmentation.
Microinvasive LMM. Melan A immunohistochemistry illustrating epidermal location of atypical melanocytes and absence of dermal invasion, corresponding to melanoma in situ component.
Microinvasive LMM. Higher magnification with single dermal atypical melanocytes and melanophages, corresponding to microinvasive lentigo maligna melanoma with immune reaction.
Microinvasive LMM. Higher magnification with single dermal atypical melanocytes and melanophages, corresponding to microinvasive lentigo maligna melanoma with immune reaction (Melan A immunohistochemistry).
Microinvasive LMM. Melan A immunohistochemistry illustrating the increase in epidermal melanocytes, with extension into hair follicles
Lentigo maligna and Primary acquired melanosis of the conjunctiva. LM/LMM involving the face, eyelid, and conjunctiva.

Q: In the evaluation of Invasive Cutaneous Melanoma, immunohistochemical markers such as [...] and HMB-45 are frequently used to highlight atypical melanocytes invading the dermis and extending into hair follicles.
Microinvasive LMM. Higher magnification with single dermal atypical melanocytes and melanophages, corresponding to microinvasive lentigo maligna melanoma with immune reaction (Melan A immunohistochemistry).
Microinvasive LMM. Melan A immunohistochemistry illustrating the increase in epidermal melanocytes, with extension into hair follicles
A: Melan A
Back Extra: Invasive Cutaneous Melanoma
- Clinical: Invasive cutaneous melanomas of the eyelid often present with multicolored, asymmetrical lesions with poorly defined borders, commonly found in chronically sun-damaged skin.
- Micro: Histopathologically, invasive cutaneous melanomas show intraepidermal and dermal proliferation of atypical melanocytes, with spindle cell and desmoplastic variants having a lentiginous intraepidermal pattern.
- Ancillary: Immunohistochemical markers such as Melan A and HMB-45 are positive in melanocytic lesions, and molecular testing often reveals BRAF p.V600E or NRAS mutations.
Reference Gallery:
Microinvasive lentigo maligna melanoma. Overview HE: Actinic damaged skin with epidermal atrophy (blue arrow) and elastoid degeneration. Tarsal conjunctiva (black arrow)
Microinvasive LMM. Sun-damaged skin with epidermal atrophy and elastoid degeneration.
Microinvasive LMM. Atrophic epidermis with highly atypical melanocytes occupying the lower third of the epithelium. Single cells are partly confluent, with pleomorphic and hyperchromatic nuclei, perinuclear halo and pigmentation.
Microinvasive LMM. Melan A immunohistochemistry illustrating epidermal location of atypical melanocytes and absence of dermal invasion, corresponding to melanoma in situ component.
Microinvasive LMM. Higher magnification with single dermal atypical melanocytes and melanophages, corresponding to microinvasive lentigo maligna melanoma with immune reaction.
Microinvasive LMM. Higher magnification with single dermal atypical melanocytes and melanophages, corresponding to microinvasive lentigo maligna melanoma with immune reaction (Melan A immunohistochemistry).
Microinvasive LMM. Melan A immunohistochemistry illustrating the increase in epidermal melanocytes, with extension into hair follicles
Lentigo maligna and Primary acquired melanosis of the conjunctiva. LM/LMM involving the face, eyelid, and conjunctiva.

Q: Clinically, [...] (such as the lentigo maligna subtype) often presents on the chronically sun-damaged skin of the face and eyelids as a multicolored, asymmetrical lesion with poorly defined borders.
Lentigo maligna and Primary acquired melanosis of the conjunctiva. LM/LMM involving the face, eyelid, and conjunctiva.
A: Invasive Cutaneous Melanoma
Back Extra: Invasive Cutaneous Melanoma
- Clinical: Invasive cutaneous melanomas of the eyelid often present with multicolored, asymmetrical lesions with poorly defined borders, commonly found in chronically sun-damaged skin.
- Micro: Histopathologically, invasive cutaneous melanomas show intraepidermal and dermal proliferation of atypical melanocytes, with spindle cell and desmoplastic variants having a lentiginous intraepidermal pattern.
- Ancillary: Immunohistochemical markers such as Melan A and HMB-45 are positive in melanocytic lesions, and molecular testing often reveals BRAF p.V600E or NRAS mutations.
Reference Gallery:
Microinvasive lentigo maligna melanoma. Overview HE: Actinic damaged skin with epidermal atrophy (blue arrow) and elastoid degeneration. Tarsal conjunctiva (black arrow)
Microinvasive LMM. Sun-damaged skin with epidermal atrophy and elastoid degeneration.
Microinvasive LMM. Atrophic epidermis with highly atypical melanocytes occupying the lower third of the epithelium. Single cells are partly confluent, with pleomorphic and hyperchromatic nuclei, perinuclear halo and pigmentation.
Microinvasive LMM. Melan A immunohistochemistry illustrating epidermal location of atypical melanocytes and absence of dermal invasion, corresponding to melanoma in situ component.
Microinvasive LMM. Higher magnification with single dermal atypical melanocytes and melanophages, corresponding to microinvasive lentigo maligna melanoma with immune reaction.
Microinvasive LMM. Higher magnification with single dermal atypical melanocytes and melanophages, corresponding to microinvasive lentigo maligna melanoma with immune reaction (Melan A immunohistochemistry).
Microinvasive LMM. Melan A immunohistochemistry illustrating the increase in epidermal melanocytes, with extension into hair follicles
Lentigo maligna and Primary acquired melanosis of the conjunctiva. LM/LMM involving the face, eyelid, and conjunctiva.

Q: A Ductal Hidrocystoma often presents clinically as a translucent, skin-colored to blue-tinged, soft cyst classically located near the [...] or canthus.
Eccrine hidrocystoma. Translucent cyst at the lateral canthus.
A: eyelid
Back Extra: Ductal Hidrocystoma
- Clinical: Ductal hidrocystomas are skin-colored to blue-tinged, smooth-surfaced, soft, compressible cysts that typically present as less than 5 mm in size on the lower eyelid, lateral canthus, upper eyelid, or medial canthus.
- Micro: Apocrine hidrocystomas are multiloculated cysts with a dual layer of cuboidal to columnar cells and variable decapitation secretions, while eccrine hidrocystomas are unilocular with a low cuboidal epithelial bilayer.
- Ancillary: Immunohistochemistry can help differentiate apocrine hidrocystomas (GCDFP-15 and CK7 positive) from eccrine hidrocystomas (negative for these markers).
Reference Gallery:
Apocrine hidrocystoma. Apocrine hidrocystoma shows a thick fibrous wall and is lined by a dual layer of cuboidal to columnar eosinophilic cells with variable decapitation secretions.
Apocrine hidrocystoma. Multilocular cyst focally filled with eosinophilic proteinaceous material.
Apocrine hidrocystoma. The cyst is composed of an inner layer of cuboidal cells with apical decapitation secretion and an outer layer of flattened myoepithelial cells.
Eccrine hidrocystoma. The epithelial bilayer is composed of low cuboidal cells with pale eosinophilic cytoplasm. Eosinophilic proteinaceous material is present in the lumen.
Eccrine hidrocystoma. Translucent cyst at the lateral canthus.
Apocrine cystadenoma, low-grade cystadenocarcinoma, and endocrine mucin-producing sweat gland carcinoma are main diagnostic considerations and can occur in association with hidrocystoma. Goblet cells/intracytoplasmic mucin, papillae with fibrous cores, and complex cribriform lining should lead to consideration of these entities (See Sections 2.1.1.2 and 2.3.2.5) { 18001413 ; 16160476 }. Essential: Cyst lined by a sweat ductal bilayer containing serous secretion; lack of goblet cells or complex architecture. Desirable: Apocrine secretion in apocrine hidrocystoma. Simple excision is typically curative (recurrence rate of 0-3%).

Q: Microscopically, the apocrine variant of a Ductal Hidrocystoma is often multiloculated and lined by a dual layer of cuboidal to columnar cells exhibiting characteristic apical [...] secretions.
Apocrine hidrocystoma. Apocrine hidrocystoma shows a thick fibrous wall and is lined by a dual layer of cuboidal to columnar eosinophilic cells with variable decapitation secretions.
Apocrine hidrocystoma. The cyst is composed of an inner layer of cuboidal cells with apical decapitation secretion and an outer layer of flattened myoepithelial cells.
A: decapitation
Back Extra: Ductal Hidrocystoma
- Clinical: Ductal hidrocystomas are skin-colored to blue-tinged, smooth-surfaced, soft, compressible cysts that typically present as less than 5 mm in size on the lower eyelid, lateral canthus, upper eyelid, or medial canthus.
- Micro: Apocrine hidrocystomas are multiloculated cysts with a dual layer of cuboidal to columnar cells and variable decapitation secretions, while eccrine hidrocystomas are unilocular with a low cuboidal epithelial bilayer.
- Ancillary: Immunohistochemistry can help differentiate apocrine hidrocystomas (GCDFP-15 and CK7 positive) from eccrine hidrocystomas (negative for these markers).
Reference Gallery:
Apocrine hidrocystoma. Apocrine hidrocystoma shows a thick fibrous wall and is lined by a dual layer of cuboidal to columnar eosinophilic cells with variable decapitation secretions.
Apocrine hidrocystoma. Multilocular cyst focally filled with eosinophilic proteinaceous material.
Apocrine hidrocystoma. The cyst is composed of an inner layer of cuboidal cells with apical decapitation secretion and an outer layer of flattened myoepithelial cells.
Eccrine hidrocystoma. The epithelial bilayer is composed of low cuboidal cells with pale eosinophilic cytoplasm. Eosinophilic proteinaceous material is present in the lumen.
Eccrine hidrocystoma. Translucent cyst at the lateral canthus.
Apocrine cystadenoma, low-grade cystadenocarcinoma, and endocrine mucin-producing sweat gland carcinoma are main diagnostic considerations and can occur in association with hidrocystoma. Goblet cells/intracytoplasmic mucin, papillae with fibrous cores, and complex cribriform lining should lead to consideration of these entities (See Sections 2.1.1.2 and 2.3.2.5) { 18001413 ; 16160476 }. Essential: Cyst lined by a sweat ductal bilayer containing serous secretion; lack of goblet cells or complex architecture. Desirable: Apocrine secretion in apocrine hidrocystoma. Simple excision is typically curative (recurrence rate of 0-3%).

Q: In contrast to the multiloculated apocrine type, the eccrine variant of a Ductal Hidrocystoma is classically a [...] cyst lined by a low cuboidal epithelial bilayer.
Eccrine hidrocystoma. The epithelial bilayer is composed of low cuboidal cells with pale eosinophilic cytoplasm. Eosinophilic proteinaceous material is present in the lumen.
A: unilocular
Back Extra: Ductal Hidrocystoma
- Clinical: Ductal hidrocystomas are skin-colored to blue-tinged, smooth-surfaced, soft, compressible cysts that typically present as less than 5 mm in size on the lower eyelid, lateral canthus, upper eyelid, or medial canthus.
- Micro: Apocrine hidrocystomas are multiloculated cysts with a dual layer of cuboidal to columnar cells and variable decapitation secretions, while eccrine hidrocystomas are unilocular with a low cuboidal epithelial bilayer.
- Ancillary: Immunohistochemistry can help differentiate apocrine hidrocystomas (GCDFP-15 and CK7 positive) from eccrine hidrocystomas (negative for these markers).
Reference Gallery:
Apocrine hidrocystoma. Apocrine hidrocystoma shows a thick fibrous wall and is lined by a dual layer of cuboidal to columnar eosinophilic cells with variable decapitation secretions.
Apocrine hidrocystoma. Multilocular cyst focally filled with eosinophilic proteinaceous material.
Apocrine hidrocystoma. The cyst is composed of an inner layer of cuboidal cells with apical decapitation secretion and an outer layer of flattened myoepithelial cells.
Eccrine hidrocystoma. The epithelial bilayer is composed of low cuboidal cells with pale eosinophilic cytoplasm. Eosinophilic proteinaceous material is present in the lumen.
Eccrine hidrocystoma. Translucent cyst at the lateral canthus.
Apocrine cystadenoma, low-grade cystadenocarcinoma, and endocrine mucin-producing sweat gland carcinoma are main diagnostic considerations and can occur in association with hidrocystoma. Goblet cells/intracytoplasmic mucin, papillae with fibrous cores, and complex cribriform lining should lead to consideration of these entities (See Sections 2.1.1.2 and 2.3.2.5) { 18001413 ; 16160476 }. Essential: Cyst lined by a sweat ductal bilayer containing serous secretion; lack of goblet cells or complex architecture. Desirable: Apocrine secretion in apocrine hidrocystoma. Simple excision is typically curative (recurrence rate of 0-3%).

Q: Histologically, the apocrine subtype of Mixed Tumor is characterized by ducts or tubules lined by an inner epithelial layer and an outer [...] layer, set within a fibromyxoid (mesenchymal) stroma.
Diagnosis: Eyelid mixed tumour (apocrine). Fibromyxoid stroma containing benign ducts / tubules.
Diagnosis: Mixed tumour. Benign ducts / tubules lined by two layers of epithelium: an inner epithelial layer and an outer myoepithelial layer.
A: myoepithelial
Back Extra: Mixed Tumor
- Clinical: Mixed tumours are usually solitary, slowly-growing, asymptomatic, well-circumscribed non-ulcerating nodules with a smooth surface, typically 5-30 mm in size.
- Micro: Mixed tumours have two main subtypes: eccrine and apocrine. Apocrine cases present as a well-circumscribed lesion with three components: epithelial, myoepithelial, and mesenchymal.
- Ancillary: Immunohistochemistry shows that mixed tumours express SOX10, p63, PS100, calponin, SMA, EMA, c-KIT, CEA, various cytokeratins, and PLAG-1.
Reference Gallery:
Diagnosis: Eyelid mixed tumour (apocrine). Scanning power images showing a well-defined, un-encapsulated tumour in the upper medial eyelid, composed of stroma and epithelial ducts.
Diagnosis: Eyelid mixed tumour (apocrine). Fibromyxoid stroma containing benign ducts / tubules.
Diagnosis: Eyelid mixed tumour. A solid myoepithelial rich area within the tumour.
Diagnosis: Mixed tumour. Benign ducts / tubules lined by two layers of epithelium: an inner epithelial layer and an outer myoepithelial layer.
Diagnosis: Mixed tumour. p63 stains the outer myoepithelial cells of the epithelial tubules / ducts, whereas the inner epithelial cells are not stained.
Diagnosis: Mixed tumour. Medial canthus mixed tumour with a smooth surface and bluish coloration.

Q: Immunohistochemistry in Mixed Tumor typically highlights the outer myoepithelial cells of the ducts with the marker [...], whereas the inner epithelial cells are negative.
Diagnosis: Mixed tumour. p63 stains the outer myoepithelial cells of the epithelial tubules / ducts, whereas the inner epithelial cells are not stained.
A: p63
Back Extra: Mixed Tumor
- Clinical: Mixed tumours are usually solitary, slowly-growing, asymptomatic, well-circumscribed non-ulcerating nodules with a smooth surface, typically 5-30 mm in size.
- Micro: Mixed tumours have two main subtypes: eccrine and apocrine. Apocrine cases present as a well-circumscribed lesion with three components: epithelial, myoepithelial, and mesenchymal.
- Ancillary: Immunohistochemistry shows that mixed tumours express SOX10, p63, PS100, calponin, SMA, EMA, c-KIT, CEA, various cytokeratins, and PLAG-1.
Reference Gallery:
Diagnosis: Eyelid mixed tumour (apocrine). Scanning power images showing a well-defined, un-encapsulated tumour in the upper medial eyelid, composed of stroma and epithelial ducts.
Diagnosis: Eyelid mixed tumour (apocrine). Fibromyxoid stroma containing benign ducts / tubules.
Diagnosis: Eyelid mixed tumour. A solid myoepithelial rich area within the tumour.
Diagnosis: Mixed tumour. Benign ducts / tubules lined by two layers of epithelium: an inner epithelial layer and an outer myoepithelial layer.
Diagnosis: Mixed tumour. p63 stains the outer myoepithelial cells of the epithelial tubules / ducts, whereas the inner epithelial cells are not stained.
Diagnosis: Mixed tumour. Medial canthus mixed tumour with a smooth surface and bluish coloration.

Q: A solitary, slow-growing, well-circumscribed, and asymptomatic nodule (often exhibiting a bluish color on the eyelid) that histologically features an admixture of epithelial, myoepithelial, and mesenchymal components is characteristic of a cutaneous [...].
Diagnosis: Eyelid mixed tumour (apocrine). Scanning power images showing a well-defined, un-encapsulated tumour in the upper medial eyelid, composed of stroma and epithelial ducts.
Diagnosis: Mixed tumour. Medial canthus mixed tumour with a smooth surface and bluish coloration.
A: Mixed Tumor
Back Extra: Mixed Tumor
- Clinical: Mixed tumours are usually solitary, slowly-growing, asymptomatic, well-circumscribed non-ulcerating nodules with a smooth surface, typically 5-30 mm in size.
- Micro: Mixed tumours have two main subtypes: eccrine and apocrine. Apocrine cases present as a well-circumscribed lesion with three components: epithelial, myoepithelial, and mesenchymal.
- Ancillary: Immunohistochemistry shows that mixed tumours express SOX10, p63, PS100, calponin, SMA, EMA, c-KIT, CEA, various cytokeratins, and PLAG-1.
Reference Gallery:
Diagnosis: Eyelid mixed tumour (apocrine). Scanning power images showing a well-defined, un-encapsulated tumour in the upper medial eyelid, composed of stroma and epithelial ducts.
Diagnosis: Eyelid mixed tumour (apocrine). Fibromyxoid stroma containing benign ducts / tubules.
Diagnosis: Eyelid mixed tumour. A solid myoepithelial rich area within the tumour.
Diagnosis: Mixed tumour. Benign ducts / tubules lined by two layers of epithelium: an inner epithelial layer and an outer myoepithelial layer.
Diagnosis: Mixed tumour. p63 stains the outer myoepithelial cells of the epithelial tubules / ducts, whereas the inner epithelial cells are not stained.
Diagnosis: Mixed tumour. Medial canthus mixed tumour with a smooth surface and bluish coloration.

Q: Histologically, a pilomatricoma typically comprises dermal nodules with a periphery of mitotically active basaloid cells that transition into a characteristic central area of anucleated [...].
Eyelid pilomatricoma. The three classical components of a pilomatricoma comprising basaloid cells, with scant cytoplasm, an intermediate zone with smaller pyknotic basophilic nuclei with eosinophilic cytoplasm and a central area with shadow cells with eosinophilic cytoplasm and non-staining empty nuclei.
Eyelid pilomatricoma. A deposit of calcium, surrounded by shadow (ghost) cells.
A: shadow (ghost) cells
Q: Pilomatricoma
- Clinical: Pilomatricoma usually presents as a solitary, well-defined, painless, slowly growing, subcutaneous reddish-blue mass, which is firm, freely mobile, and has a gritty sensation due to calcification.
- Micro: The tumour comprises dermal nodules with a periphery of mitotically active basaloid cells, an intermediate zone of smaller pyknotic basophilic nuclei, and a central area of shadow cells with eosinophilic cytoplasm and non-staining empty nuclei.
- Ancillary: Pathogenesis has been linked to a [...].
Reference Gallery:
Pilomatricoma. The clinical appearance of an eyelid pilomatricoma in a child.
Pilomatricoma. Histopathological appearance of pilomatricoma with an area of numerous multi-nucleated foreign body-type giant cells.
Eyelid pilomatricoma. The three classical components of a pilomatricoma comprising basaloid cells, with scant cytoplasm, an intermediate zone with smaller pyknotic basophilic nuclei with eosinophilic cytoplasm and a central area with shadow cells with eosinophilic cytoplasm and non-staining empty nuclei.
Eyelid pilomatricoma. A deposit of calcium, surrounded by shadow (ghost) cells.
Pilomatricoma. Axial T2-weighted MRI showing a mass located superficially in the left upper eyelid, in front of the orbicularis oculi muscle. It is mostly hypointense on T2-WI.
Pilomatricoma. Axial contrast-enhanced T1-weighted MRI with fat signal suppression showing a mass located superficially in the left upper eyelid, in front of the orbicularis oculi muscle. It is heterogeneously enhancing.
Pilomatricoma. Axial DCE with a tumour progressive perfusion curve, showing a mass located superficially in the left upper eyelid, in front of the orbicularis oculi muscle.
A: beta catenin (CTNNB1) gene mutation

Q: A firm, slowly growing, reddish-blue subcutaneous eyelid mass in a child that exhibits anucleate shadow (ghost) cells on biopsy is pathognomonic for a [...].
Pilomatricoma. The clinical appearance of an eyelid pilomatricoma in a child.
Eyelid pilomatricoma. The three classical components of a pilomatricoma comprising basaloid cells, with scant cytoplasm, an intermediate zone with smaller pyknotic basophilic nuclei with eosinophilic cytoplasm and a central area with shadow cells with eosinophilic cytoplasm and non-staining empty nuclei.
A: pilomatricoma
Q: Pilomatricoma
- Clinical: Pilomatricoma usually presents as a solitary, well-defined, painless, slowly growing, subcutaneous reddish-blue mass, which is firm, freely mobile, and has a gritty sensation due to calcification.
- Micro: The tumour comprises dermal nodules with a periphery of mitotically active basaloid cells, an intermediate zone of smaller pyknotic basophilic nuclei, and a central area of shadow cells with eosinophilic cytoplasm and non-staining empty nuclei.
- Ancillary: Pathogenesis has been linked to a [...].
Reference Gallery:
Pilomatricoma. The clinical appearance of an eyelid pilomatricoma in a child.
Pilomatricoma. Histopathological appearance of pilomatricoma with an area of numerous multi-nucleated foreign body-type giant cells.
Eyelid pilomatricoma. The three classical components of a pilomatricoma comprising basaloid cells, with scant cytoplasm, an intermediate zone with smaller pyknotic basophilic nuclei with eosinophilic cytoplasm and a central area with shadow cells with eosinophilic cytoplasm and non-staining empty nuclei.
Eyelid pilomatricoma. A deposit of calcium, surrounded by shadow (ghost) cells.
Pilomatricoma. Axial T2-weighted MRI showing a mass located superficially in the left upper eyelid, in front of the orbicularis oculi muscle. It is mostly hypointense on T2-WI.
Pilomatricoma. Axial contrast-enhanced T1-weighted MRI with fat signal suppression showing a mass located superficially in the left upper eyelid, in front of the orbicularis oculi muscle. It is heterogeneously enhancing.
Pilomatricoma. Axial DCE with a tumour progressive perfusion curve, showing a mass located superficially in the left upper eyelid, in front of the orbicularis oculi muscle.
A: beta catenin (CTNNB1) gene mutation

Q: Clinically, lesions of Sebaceous Hyperplasia, Adenoma, and Sebaceoma typically present on the skin of the head, neck, or ocular adnexa as well-circumscribed, [...] nodules.
Right upper eyelid margin lesion, histologically proven to be sebaceous hyperplasia. The lesion is yellow, dome-shaped, and smooth, with no evidence of eyelash loss.
A right lower eyelid lesion, histologically proven to be sebaceous adenoma. Note the yellow lobulated appearance.
A: yellow-tan
Back Extra: Sebaceous Hyperplasia, Adenoma, and Sebaceoma
- Clinical: Sebaceous hyperplasia, adenoma, and sebaceoma are well-circumscribed, yellow-tan nodules commonly found on the skin of the head and neck, and rarely in the ocular adnexa.
- Micro: Sebaceous hyperplasia consists of multiple enlarged lobules of mature sebaceous glands around a hair follicle, while sebaceous adenoma and sebaceoma are well-circumscribed nodules with sebocytes and basaloid cells in varying proportions.
- Ancillary: Sebaceous adenoma and sebaceoma can be associated with Muir-Torre syndrome, which is characterized by inherited germline abnormalities in DNA mismatch repair protein genes.
Reference Gallery:
Right upper eyelid margin lesion, histologically proven to be sebaceous hyperplasia. The lesion is yellow, dome-shaped, and smooth, with no evidence of eyelash loss.
A right lower eyelid lesion, histologically proven to be sebaceous adenoma. Note the yellow lobulated appearance.
Sebaceous hyperplasia consists of multiple, enlarged lobules of mature sebaceous glands grouped around a central hair follicle.
Higher power view showing well-formed sebocytes predominating over basaloid cells, which are conspicuous in sebaceous adenoma.
A lesion of the eyelid margin showing sebaceous adenoma.
Eyelid sebaceoma with basaloid cells predominating over sebocytes.
Basaloid cells predominate over scattered sebocytes in sebaceoma. Note the conspicuous duct formation.

Q: In the spectrum of Sebaceous Hyperplasia, Adenoma, and Sebaceoma, the hyperplastic variant histologically features multiple enlarged lobules of mature sebaceous glands grouped around a central [...].
Sebaceous hyperplasia consists of multiple, enlarged lobules of mature sebaceous glands grouped around a central hair follicle.
A: hair follicle
Back Extra: Sebaceous Hyperplasia, Adenoma, and Sebaceoma
- Clinical: Sebaceous hyperplasia, adenoma, and sebaceoma are well-circumscribed, yellow-tan nodules commonly found on the skin of the head and neck, and rarely in the ocular adnexa.
- Micro: Sebaceous hyperplasia consists of multiple enlarged lobules of mature sebaceous glands around a hair follicle, while sebaceous adenoma and sebaceoma are well-circumscribed nodules with sebocytes and basaloid cells in varying proportions.
- Ancillary: Sebaceous adenoma and sebaceoma can be associated with Muir-Torre syndrome, which is characterized by inherited germline abnormalities in DNA mismatch repair protein genes.
Reference Gallery:
Right upper eyelid margin lesion, histologically proven to be sebaceous hyperplasia. The lesion is yellow, dome-shaped, and smooth, with no evidence of eyelash loss.
A right lower eyelid lesion, histologically proven to be sebaceous adenoma. Note the yellow lobulated appearance.
Sebaceous hyperplasia consists of multiple, enlarged lobules of mature sebaceous glands grouped around a central hair follicle.
Higher power view showing well-formed sebocytes predominating over basaloid cells, which are conspicuous in sebaceous adenoma.
A lesion of the eyelid margin showing sebaceous adenoma.
Eyelid sebaceoma with basaloid cells predominating over sebocytes.
Basaloid cells predominate over scattered sebocytes in sebaceoma. Note the conspicuous duct formation.

Q: When distinguishing between lesions in the spectrum of Sebaceous Hyperplasia, Adenoma, and Sebaceoma, a sebaceoma is histologically defined by a predominance of [...] over mature sebocytes.
Eyelid sebaceoma with basaloid cells predominating over sebocytes.
Basaloid cells predominate over scattered sebocytes in sebaceoma. Note the conspicuous duct formation.
A: basaloid cells
Back Extra: Sebaceous Hyperplasia, Adenoma, and Sebaceoma
- Clinical: Sebaceous hyperplasia, adenoma, and sebaceoma are well-circumscribed, yellow-tan nodules commonly found on the skin of the head and neck, and rarely in the ocular adnexa.
- Micro: Sebaceous hyperplasia consists of multiple enlarged lobules of mature sebaceous glands around a hair follicle, while sebaceous adenoma and sebaceoma are well-circumscribed nodules with sebocytes and basaloid cells in varying proportions.
- Ancillary: Sebaceous adenoma and sebaceoma can be associated with Muir-Torre syndrome, which is characterized by inherited germline abnormalities in DNA mismatch repair protein genes.
Reference Gallery:
Right upper eyelid margin lesion, histologically proven to be sebaceous hyperplasia. The lesion is yellow, dome-shaped, and smooth, with no evidence of eyelash loss.
A right lower eyelid lesion, histologically proven to be sebaceous adenoma. Note the yellow lobulated appearance.
Sebaceous hyperplasia consists of multiple, enlarged lobules of mature sebaceous glands grouped around a central hair follicle.
Higher power view showing well-formed sebocytes predominating over basaloid cells, which are conspicuous in sebaceous adenoma.
A lesion of the eyelid margin showing sebaceous adenoma.
Eyelid sebaceoma with basaloid cells predominating over sebocytes.
Basaloid cells predominate over scattered sebocytes in sebaceoma. Note the conspicuous duct formation.

Q: At low power, Syringocystadenoma papilliferum characteristically demonstrates an exo-endophytic architecture with cystic invaginations containing papillary projections lined by columnar cells that exhibit [...] secretion.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. Papillary cores draped in epithelial cells showing a papilliform architecture.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. At scanning power the lesion shows an exo-endophytic architecture, with invaginations of epithelium, which is squamous at the surface and papilliform towards the deeper invaginations.
A: decapitation
Back Extra: Syringocystadenoma papilliferum
- Clinical: Syringocystadenoma papilliferum (SCAP) typically presents on the lower lid margin, with symptoms including swelling, pruritus, and bleeding.
- Micro: SCAP is characterized by dilated papillary and cystic structures with an outer myoepithelial layer and inner columnar cells showing decapitation secretion.
- Ancillary: BRAF p.V600E mutation, detected by IHC, is present in 50–64% of SCAPs.
Reference Gallery:
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. Papillary cores draped in epithelial cells showing a papilliform architecture.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. Prominent plasma cells within the cores of the papillary frond.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. At scanning power the lesion shows an exo-endophytic architecture, with invaginations of epithelium, which is squamous at the surface and papilliform towards the deeper invaginations.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Syringocystadenoma papilliferum. Clinical photo of an upper eyelid syringocystadenoma papilliferum (SCAP).

Q: A key histopathological feature that helps distinguish Syringocystadenoma papilliferum from hidradenoma papilliferum is the prominent presence of [...] within the fibrovascular cores of the papillary fronds.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. Prominent plasma cells within the cores of the papillary frond.
A: plasma cells
Back Extra: Syringocystadenoma papilliferum
- Clinical: Syringocystadenoma papilliferum (SCAP) typically presents on the lower lid margin, with symptoms including swelling, pruritus, and bleeding.
- Micro: SCAP is characterized by dilated papillary and cystic structures with an outer myoepithelial layer and inner columnar cells showing decapitation secretion.
- Ancillary: BRAF p.V600E mutation, detected by IHC, is present in 50–64% of SCAPs.
Reference Gallery:
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. Papillary cores draped in epithelial cells showing a papilliform architecture.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. Prominent plasma cells within the cores of the papillary frond.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. At scanning power the lesion shows an exo-endophytic architecture, with invaginations of epithelium, which is squamous at the surface and papilliform towards the deeper invaginations.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Syringocystadenoma papilliferum. Clinical photo of an upper eyelid syringocystadenoma papilliferum (SCAP).

Q: Clinically, Syringocystadenoma papilliferum typically presents as a pruritic, swelling, and sometimes bleeding nodule that frequently arises on the [...] margin.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Syringocystadenoma papilliferum. Clinical photo of an upper eyelid syringocystadenoma papilliferum (SCAP).
A: eyelid
Back Extra: Syringocystadenoma papilliferum
- Clinical: Syringocystadenoma papilliferum (SCAP) typically presents on the lower lid margin, with symptoms including swelling, pruritus, and bleeding.
- Micro: SCAP is characterized by dilated papillary and cystic structures with an outer myoepithelial layer and inner columnar cells showing decapitation secretion.
- Ancillary: BRAF p.V600E mutation, detected by IHC, is present in 50–64% of SCAPs.
Reference Gallery:
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. Papillary cores draped in epithelial cells showing a papilliform architecture.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. Prominent plasma cells within the cores of the papillary frond.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Eyelid syringocystadenoma papilliferum. At scanning power the lesion shows an exo-endophytic architecture, with invaginations of epithelium, which is squamous at the surface and papilliform towards the deeper invaginations.
The histopathological differential diagnosis of SCAP includes hidradenoma papilliferum. Hidradenoma papilliferum has papillary formations similar to those of SCAP, and the epithelial cells lining these structures also show evidence of secretion by decapitation. However, hidradenoma papilliferum is not connected to the epidermis and lacks plasma cells. Diagnosis: Syringocystadenoma papilliferum. Clinical photo of an upper eyelid syringocystadenoma papilliferum (SCAP).

Q: Clinically, a Syringoma classically presents as multiple skin-colored or slightly yellow smooth papules located on the [...].
Clinical photo of the typical appearance of a lower eyelid syringoma
A: lower eyelids
Back Extra: Syringoma
- Clinical: Syringoma presents as skin-coloured or slightly yellow smooth papules, commonly affecting the lower eyelids of middle-aged to older women.
- Micro: Syringomas are well-circumscribed lesions with ductal and tubular structures lined by a double layer of cuboidal cells, often with characteristic 'tail-like' extensions.
- Ancillary: Low-energy radio frequency ablation and CO2 laser are effective treatment options for syringomas.
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Hematoxylin and eosin stained sections showing a neoplasm composed of cystic and tubular structures embedded in a sclerotic stroma
Clinical photo of the typical appearance of a lower eyelid syringoma
Higher power showing the two layers of cuboidal epithelium lining the ductal structures
Some ducts show 'tail-like' structures

Q: Histologically, a Syringoma is composed of a double layer of cuboidal cells forming ductal structures that frequently exhibit characteristic [...] extensions into the stroma.
Hematoxylin and eosin stained sections showing a neoplasm composed of cystic and tubular structures embedded in a sclerotic stroma
Higher power showing the two layers of cuboidal epithelium lining the ductal structures
Some ducts show 'tail-like' structures
A: 'tail-like'
Back Extra: Syringoma
- Clinical: Syringoma presents as skin-coloured or slightly yellow smooth papules, commonly affecting the lower eyelids of middle-aged to older women.
- Micro: Syringomas are well-circumscribed lesions with ductal and tubular structures lined by a double layer of cuboidal cells, often with characteristic 'tail-like' extensions.
- Ancillary: Low-energy radio frequency ablation and CO2 laser are effective treatment options for syringomas.
Reference Gallery:
Hematoxylin and eosin stained sections showing a neoplasm composed of cystic and tubular structures embedded in a sclerotic stroma
Clinical photo of the typical appearance of a lower eyelid syringoma
Higher power showing the two layers of cuboidal epithelium lining the ductal structures
Some ducts show 'tail-like' structures

Q: Microscopically, conventional Trichilemmoma consists of lobules of bland squamoid cells exhibiting characteristic cytoplasmic [...] and surrounded by a prominent eosinophilic basement membrane.
Trichilemmoma. Typical cytoplasmic glycogen vacuolation of trichilemmoma cells, indicative of differentiation towards the hair outer root sheath.
Trichilemomma. A prominent eosinophilic basement membrane can surround the tumour lobules.
A: glycogen vacuolation
Back Extra: Trichilemmoma
- Clinical: Trichilemmoma typically presents as a slow-growing, flesh-colored papule or nodule, usually 1-5 mm in size, and can mimic a verruca vulgaris.
- Micro: Conventional trichilemmomas show lobules of eosinophilic, bland squamoid cells with cytoplasmic glycogen vacuolation and a prominent eosinophilic basement membrane.
- Ancillary: Immunohistochemistry shows expression of CD34 and p16, and negativity for BerEP4. Germline testing for PTEN mutations may be indicated in multiple or pediatric cases.
Reference Gallery:
Trichilemomma. Low power view showing the exophytic 'warty' architectural configuration of a conventional trichilemmoma.
Trichilemmoma. Low power view showing a desmoplastic trichilemmoma of the eyelid.
Trichilemmoma. Typical cytoplasmic glycogen vacuolation of trichilemmoma cells, indicative of differentiation towards the hair outer root sheath.
Trichilemomma. A prominent eosinophilic basement membrane can surround the tumour lobules.
Desmoplastic trichilemmoma. Irregular tongues of more squamoid looking cells, lacking cytoplasmic glycogen vacuolation, embedded within sclerotic stroma. This is the typical appearance of a desmoplastic focus within a desmoplastic trichilemmoma.
Trichilemmoma. Clinical image showing a nodular configuration of trichilemmoma, which in this case, was of desmoplastic histological type.

Q: The desmoplastic variant of Trichilemmoma is characterized by irregular tongues of squamoid cells (which lack typical clear cell changes) embedded within a dense, [...] stroma.
Trichilemmoma. Low power view showing a desmoplastic trichilemmoma of the eyelid.
Desmoplastic trichilemmoma. Irregular tongues of more squamoid looking cells, lacking cytoplasmic glycogen vacuolation, embedded within sclerotic stroma. This is the typical appearance of a desmoplastic focus within a desmoplastic trichilemmoma.
A: sclerotic
Back Extra: Trichilemmoma
- Clinical: Trichilemmoma typically presents as a slow-growing, flesh-colored papule or nodule, usually 1-5 mm in size, and can mimic a verruca vulgaris.
- Micro: Conventional trichilemmomas show lobules of eosinophilic, bland squamoid cells with cytoplasmic glycogen vacuolation and a prominent eosinophilic basement membrane.
- Ancillary: Immunohistochemistry shows expression of CD34 and p16, and negativity for BerEP4. Germline testing for PTEN mutations may be indicated in multiple or pediatric cases.
Reference Gallery:
Trichilemomma. Low power view showing the exophytic 'warty' architectural configuration of a conventional trichilemmoma.
Trichilemmoma. Low power view showing a desmoplastic trichilemmoma of the eyelid.
Trichilemmoma. Typical cytoplasmic glycogen vacuolation of trichilemmoma cells, indicative of differentiation towards the hair outer root sheath.
Trichilemomma. A prominent eosinophilic basement membrane can surround the tumour lobules.
Desmoplastic trichilemmoma. Irregular tongues of more squamoid looking cells, lacking cytoplasmic glycogen vacuolation, embedded within sclerotic stroma. This is the typical appearance of a desmoplastic focus within a desmoplastic trichilemmoma.
Trichilemmoma. Clinical image showing a nodular configuration of trichilemmoma, which in this case, was of desmoplastic histological type.

Q: Clinically and architecturally, a conventional Trichilemmoma typically presents as a slow-growing, flesh-colored papule that often mimics a [...] due to its exophytic, "warty" configuration.
Trichilemomma. Low power view showing the exophytic 'warty' architectural configuration of a conventional trichilemmoma.
Trichilemmoma. Clinical image showing a nodular configuration of trichilemmoma, which in this case, was of desmoplastic histological type.
A: verruca vulgaris
Back Extra: Trichilemmoma
- Clinical: Trichilemmoma typically presents as a slow-growing, flesh-colored papule or nodule, usually 1-5 mm in size, and can mimic a verruca vulgaris.
- Micro: Conventional trichilemmomas show lobules of eosinophilic, bland squamoid cells with cytoplasmic glycogen vacuolation and a prominent eosinophilic basement membrane.
- Ancillary: Immunohistochemistry shows expression of CD34 and p16, and negativity for BerEP4. Germline testing for PTEN mutations may be indicated in multiple or pediatric cases.
Reference Gallery:
Trichilemomma. Low power view showing the exophytic 'warty' architectural configuration of a conventional trichilemmoma.
Trichilemmoma. Low power view showing a desmoplastic trichilemmoma of the eyelid.
Trichilemmoma. Typical cytoplasmic glycogen vacuolation of trichilemmoma cells, indicative of differentiation towards the hair outer root sheath.
Trichilemomma. A prominent eosinophilic basement membrane can surround the tumour lobules.
Desmoplastic trichilemmoma. Irregular tongues of more squamoid looking cells, lacking cytoplasmic glycogen vacuolation, embedded within sclerotic stroma. This is the typical appearance of a desmoplastic focus within a desmoplastic trichilemmoma.
Trichilemmoma. Clinical image showing a nodular configuration of trichilemmoma, which in this case, was of desmoplastic histological type.

Q: Microscopic examination of a Tubular Adenoma typically reveals irregularly shaped tubular structures lined by a characteristic [...] epithelium.
Eyelid tubular adenoma. On the left is an eyelid syringocystadenoma papilliferum and on the right is a tubular adenoma.
Eyelid tubular adenoma. High power view of an eyelid tubular adenoma showing the inner epithelial layer and the outer myoepithelial layer. Note how the inner epithelial layer is papilleroid in some profiles.
A: double-layered
Back Extra: Tubular Adenoma
- Clinical: Tubular adenomas typically present as asymptomatic, well-circumscribed nodules, most often in adults aged 38-63 years with a mean age of 47 years.
- Micro: Histologically, tubular adenomas are characterized by multiple irregularly shaped tubular structures with a double-layered epithelial lining, including an inner columnar layer and an outer myoepithelial layer.
- Ancillary: Immunohistochemistry shows that the luminal cells are positive for CEA and EMA, while the outer myoepithelial cells are positive for SMA, calponin, SOX10, and p63.
Reference Gallery:
Eyelid tubular adenoma. On the left is an eyelid syringocystadenoma papilliferum and on the right is a tubular adenoma.
Eyelid tubular adenoma. High power view of an eyelid tubular adenoma showing the inner epithelial layer and the outer myoepithelial layer. Note how the inner epithelial layer is papilleroid in some profiles.

Q: In a Tubular Adenoma, the characteristic tubular structures possess an inner columnar epithelial layer and an outer [...] layer.
Eyelid tubular adenoma. High power view of an eyelid tubular adenoma showing the inner epithelial layer and the outer myoepithelial layer. Note how the inner epithelial layer is papilleroid in some profiles.
A: myoepithelial
Back Extra: Tubular Adenoma
- Clinical: Tubular adenomas typically present as asymptomatic, well-circumscribed nodules, most often in adults aged 38-63 years with a mean age of 47 years.
- Micro: Histologically, tubular adenomas are characterized by multiple irregularly shaped tubular structures with a double-layered epithelial lining, including an inner columnar layer and an outer myoepithelial layer.
- Ancillary: Immunohistochemistry shows that the luminal cells are positive for CEA and EMA, while the outer myoepithelial cells are positive for SMA, calponin, SOX10, and p63.
Reference Gallery:
Eyelid tubular adenoma. On the left is an eyelid syringocystadenoma papilliferum and on the right is a tubular adenoma.
Eyelid tubular adenoma. High power view of an eyelid tubular adenoma showing the inner epithelial layer and the outer myoepithelial layer. Note how the inner epithelial layer is papilleroid in some profiles.

Q: Microscopically, Adenoid Cystic Carcinoma is classically characterized by a [...] architectural pattern containing basophilic mucinous material and myxoid globules.
Diagnosis: Adenoid cystic carcinoma. The typical cribriform appearance of primary eyelid skin adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. High power view showing the monomorphic myoepithelial cells within cribriform architecture, with myxoid globules.
A: cribriform
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma presents as a slow-growing, non-tender, firm, well-circumscribed nodule with or without distortion or loss of eyelashes.
- Micro: The tumor is characterized by a cribriform pattern with basophilic mucinous material and myxoid globules, along with a solid or tubular growth pattern.
- Ancillary: IHC shows diffuse cytoplasmic positivity for keratins, and molecular studies often reveal MYB gene abnormalities.
Reference Gallery:
Diagnosis: Adenoid cystic carcinoma. A low power view showing a lower lid containing primary adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. The typical cribriform appearance of primary eyelid skin adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. High power view showing the monomorphic myoepithelial cells within cribriform architecture, with myxoid globules.
Diagnosis: Adenoid cystic carcinoma. Perineural invasion is a common feature.
Diagnosis: Adenoid cystic carcinoma. RNA in situ hybridization shows increased Myb expression in a periocular adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. Clinical photograph of primary adenoid cystic carcinoma of lower eyelid in a 43-year-old otherwise healthy woman.

Q: A characteristic histologic feature of Adenoid Cystic Carcinoma is its propensity for frequent and prominent [...] invasion.
Diagnosis: Adenoid cystic carcinoma. Perineural invasion is a common feature.
A: perineural
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma presents as a slow-growing, non-tender, firm, well-circumscribed nodule with or without distortion or loss of eyelashes.
- Micro: The tumor is characterized by a cribriform pattern with basophilic mucinous material and myxoid globules, along with a solid or tubular growth pattern.
- Ancillary: IHC shows diffuse cytoplasmic positivity for keratins, and molecular studies often reveal MYB gene abnormalities.
Reference Gallery:
Diagnosis: Adenoid cystic carcinoma. A low power view showing a lower lid containing primary adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. The typical cribriform appearance of primary eyelid skin adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. High power view showing the monomorphic myoepithelial cells within cribriform architecture, with myxoid globules.
Diagnosis: Adenoid cystic carcinoma. Perineural invasion is a common feature.
Diagnosis: Adenoid cystic carcinoma. RNA in situ hybridization shows increased Myb expression in a periocular adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. Clinical photograph of primary adenoid cystic carcinoma of lower eyelid in a 43-year-old otherwise healthy woman.

Q: The molecular pathogenesis of Adenoid Cystic Carcinoma frequently involves abnormalities or translocations of the [...] gene, leading to its overexpression.
Diagnosis: Adenoid cystic carcinoma. RNA in situ hybridization shows increased Myb expression in a periocular adenoid cystic carcinoma.
A: MYB
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma presents as a slow-growing, non-tender, firm, well-circumscribed nodule with or without distortion or loss of eyelashes.
- Micro: The tumor is characterized by a cribriform pattern with basophilic mucinous material and myxoid globules, along with a solid or tubular growth pattern.
- Ancillary: IHC shows diffuse cytoplasmic positivity for keratins, and molecular studies often reveal MYB gene abnormalities.
Reference Gallery:
Diagnosis: Adenoid cystic carcinoma. A low power view showing a lower lid containing primary adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. The typical cribriform appearance of primary eyelid skin adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. High power view showing the monomorphic myoepithelial cells within cribriform architecture, with myxoid globules.
Diagnosis: Adenoid cystic carcinoma. Perineural invasion is a common feature.
Diagnosis: Adenoid cystic carcinoma. RNA in situ hybridization shows increased Myb expression in a periocular adenoid cystic carcinoma.
Diagnosis: Adenoid cystic carcinoma. Clinical photograph of primary adenoid cystic carcinoma of lower eyelid in a 43-year-old otherwise healthy woman.

Q: The tumor cells in Endocrine Mucin-Producing Sweat Gland Carcinoma exhibit neuroendocrine differentiation and show highly sensitive, diffuse nuclear immunoreactivity for [...].
Endocrine mucin-producing sweat gland carcinoma. Tumour cells show diffuse nuclear staining for insulinoma-associated protein 1 (INSM1), a highly sensitive neuroendocrine marker for EMPSGC.
A: insulinoma-associated protein 1 (INSM1)
Back Extra: Endocrine Mucin-Producing Sweat Gland Carcinoma
- Clinical: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) typically presents as a slow-growing, skin-coloured or bluish nodule, papule, or cyst, often in the sixth and seventh decades, with a higher prevalence in women.
- Micro: EMPSGC is characterized by well-demarcated expansile nodules with cystic, solid, papillary, or cribriform architecture, and tumour cells with amphophilic or bluish cytoplasm, finely stippled chromatin, and small amounts of intracellular and extracellular mucin.
- Ancillary: Immunohistochemistry for insulinoma-associated protein 1 (INSM1) is highly sensitive for EMPSGC, and the tumour cells typically express estrogen and progesterone receptors, cytokeratin 7, and other neuroendocrine markers.
Reference Gallery:
Endocrine mucin-producing sweat gland carcinoma. Architectural patterns of EMPSGC, at low power. A dermal nodule with multinodular, cystic, solid and papillary growth and scattered pools of sparse, light blue stromal mucin. The tumour cells look bland to uniform with bluish, amphophilic cytoplasm.
Endocrine mucin-producing sweat gland carcinoma (EMPSGC). A higher magnification highlights the cyst wall mural thickenings. The tumour cells resemble bland eccrine ductal cells with moderately enlarged ovoid nuclei with stippled chromatin and inconspicuous nucleoli, bluish cytoplasm, and intracellular and extracellular mucin. Note the incomplete myoepithelial rim.
Invasive mucinous carcinoma arising in endocrine mucin-producing sweat gland carcinoma (EMPSGC). EMPSGC with invasive mucinous component, at low power. An expansile EMPSGC nodule with cystic and papillary growth and nests of tumour cells floating in copious, central extracellular mucin, signifying transformation to invasive mucinous carcinoma.
Endocrine Mucin Producing Sweat Gland Carcinoma. Lower eyelid EMPSGC, showing a brown/bluish nodule.
Endocrine mucin-producing sweat gland carcinoma. Tumour cells show diffuse nuclear staining for insulinoma-associated protein 1 (INSM1), a highly sensitive neuroendocrine marker for EMPSGC.

Q: Endocrine Mucin-Producing Sweat Gland Carcinoma is a low-grade adnexal tumor that can undergo transformation into [...], histologically characterized by nests of tumor cells floating in copious pools of extracellular mucin.
Endocrine mucin-producing sweat gland carcinoma. Architectural patterns of EMPSGC, at low power. A dermal nodule with multinodular, cystic, solid and papillary growth and scattered pools of sparse, light blue stromal mucin. The tumour cells look bland to uniform with bluish, amphophilic cytoplasm.
Invasive mucinous carcinoma arising in endocrine mucin-producing sweat gland carcinoma (EMPSGC). EMPSGC with invasive mucinous component, at low power. An expansile EMPSGC nodule with cystic and papillary growth and nests of tumour cells floating in copious, central extracellular mucin, signifying transformation to invasive mucinous carcinoma.
A: invasive mucinous carcinoma
Back Extra: Endocrine Mucin-Producing Sweat Gland Carcinoma
- Clinical: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) typically presents as a slow-growing, skin-coloured or bluish nodule, papule, or cyst, often in the sixth and seventh decades, with a higher prevalence in women.
- Micro: EMPSGC is characterized by well-demarcated expansile nodules with cystic, solid, papillary, or cribriform architecture, and tumour cells with amphophilic or bluish cytoplasm, finely stippled chromatin, and small amounts of intracellular and extracellular mucin.
- Ancillary: Immunohistochemistry for insulinoma-associated protein 1 (INSM1) is highly sensitive for EMPSGC, and the tumour cells typically express estrogen and progesterone receptors, cytokeratin 7, and other neuroendocrine markers.
Reference Gallery:
Endocrine mucin-producing sweat gland carcinoma. Architectural patterns of EMPSGC, at low power. A dermal nodule with multinodular, cystic, solid and papillary growth and scattered pools of sparse, light blue stromal mucin. The tumour cells look bland to uniform with bluish, amphophilic cytoplasm.
Endocrine mucin-producing sweat gland carcinoma (EMPSGC). A higher magnification highlights the cyst wall mural thickenings. The tumour cells resemble bland eccrine ductal cells with moderately enlarged ovoid nuclei with stippled chromatin and inconspicuous nucleoli, bluish cytoplasm, and intracellular and extracellular mucin. Note the incomplete myoepithelial rim.
Invasive mucinous carcinoma arising in endocrine mucin-producing sweat gland carcinoma (EMPSGC). EMPSGC with invasive mucinous component, at low power. An expansile EMPSGC nodule with cystic and papillary growth and nests of tumour cells floating in copious, central extracellular mucin, signifying transformation to invasive mucinous carcinoma.
Endocrine Mucin Producing Sweat Gland Carcinoma. Lower eyelid EMPSGC, showing a brown/bluish nodule.
Endocrine mucin-producing sweat gland carcinoma. Tumour cells show diffuse nuclear staining for insulinoma-associated protein 1 (INSM1), a highly sensitive neuroendocrine marker for EMPSGC.

Q: Clinically, Endocrine Mucin-Producing Sweat Gland Carcinoma typically presents as a slow-growing, skin-colored or bluish nodule on the [...] and microscopically demonstrates expansile, mucin-containing nodules with an incomplete myoepithelial rim.
Endocrine mucin-producing sweat gland carcinoma (EMPSGC). A higher magnification highlights the cyst wall mural thickenings. The tumour cells resemble bland eccrine ductal cells with moderately enlarged ovoid nuclei with stippled chromatin and inconspicuous nucleoli, bluish cytoplasm, and intracellular and extracellular mucin. Note the incomplete myoepithelial rim.
Endocrine Mucin Producing Sweat Gland Carcinoma. Lower eyelid EMPSGC, showing a brown/bluish nodule.
A: eyelid
Back Extra: Endocrine Mucin-Producing Sweat Gland Carcinoma
- Clinical: Endocrine Mucin-Producing Sweat Gland Carcinoma (EMPSGC) typically presents as a slow-growing, skin-coloured or bluish nodule, papule, or cyst, often in the sixth and seventh decades, with a higher prevalence in women.
- Micro: EMPSGC is characterized by well-demarcated expansile nodules with cystic, solid, papillary, or cribriform architecture, and tumour cells with amphophilic or bluish cytoplasm, finely stippled chromatin, and small amounts of intracellular and extracellular mucin.
- Ancillary: Immunohistochemistry for insulinoma-associated protein 1 (INSM1) is highly sensitive for EMPSGC, and the tumour cells typically express estrogen and progesterone receptors, cytokeratin 7, and other neuroendocrine markers.
Reference Gallery:
Endocrine mucin-producing sweat gland carcinoma. Architectural patterns of EMPSGC, at low power. A dermal nodule with multinodular, cystic, solid and papillary growth and scattered pools of sparse, light blue stromal mucin. The tumour cells look bland to uniform with bluish, amphophilic cytoplasm.
Endocrine mucin-producing sweat gland carcinoma (EMPSGC). A higher magnification highlights the cyst wall mural thickenings. The tumour cells resemble bland eccrine ductal cells with moderately enlarged ovoid nuclei with stippled chromatin and inconspicuous nucleoli, bluish cytoplasm, and intracellular and extracellular mucin. Note the incomplete myoepithelial rim.
Invasive mucinous carcinoma arising in endocrine mucin-producing sweat gland carcinoma (EMPSGC). EMPSGC with invasive mucinous component, at low power. An expansile EMPSGC nodule with cystic and papillary growth and nests of tumour cells floating in copious, central extracellular mucin, signifying transformation to invasive mucinous carcinoma.
Endocrine Mucin Producing Sweat Gland Carcinoma. Lower eyelid EMPSGC, showing a brown/bluish nodule.
Endocrine mucin-producing sweat gland carcinoma. Tumour cells show diffuse nuclear staining for insulinoma-associated protein 1 (INSM1), a highly sensitive neuroendocrine marker for EMPSGC.

Q: Histologically, the superficial portion of Microcystic Adnexal Carcinoma typically displays [...], while the deeper component widely infiltrates the subcutaneous tissue.
Microcystic adnexal carcinoma. Low magnification view illustrating infiltrative nature of the tumour with involvement of the subcutaneous tissue.
Microcystic adnexal carcinoma. Superficial portion of the tumour showing trichoepitheliomatous keratocysts, essentially indistinguishable from those expected in trichoeplithelioma.
A: trichoepithelioma-like keratocysts
Back Extra: Microcystic Adnexal Carcinoma
- Clinical: Microcystic adnexal carcinoma presents as a yellow, firm, indurated nodule that can cause eyelid distortion, retraction, and rarely ulceration and madarosis.
- Micro: This carcinoma is characterized by bland cytology, small nests, strands, or columns of epithelial cells, and trichoepithelioma-like keratocysts.
- Ancillary: NGS shows a low mutational burden and mutations in p53 and JAK/STAT signaling pathways, but no UV signature.
Reference Gallery:
Microcystic adnexal carcinoma. Low magnification view illustrating infiltrative nature of the tumour with involvement of the subcutaneous tissue.
Microcystic adnexal carcinoma. Superficial portion of the tumour showing trichoepitheliomatous keratocysts, essentially indistinguishable from those expected in trichoeplithelioma.
Microcystic adnexal carcinoma. Bland cytological features with no mitotic activity.
Eyelid microcystic adnexal carcinoma. Perineural and intraneural invasion by microcystic adnexal carcinoma
Eyelid skin microcystic adnexal carcinoma. Widely infiltrating microcystic adnexal carcinoma, with syringomatous duct-like structures, within the orbicularis muscle and tarsal plate. Note the loose desmoplastic reaction around the tumour nests.
Eyelid microcystic adnexal carcinoma. Strands and nests of invasive microcytic adnexal carcinoma, within the eyelid tarsal plate, surrounded by a loose desmoplastic stromal response.

Q: The deeply infiltrative component of Microcystic Adnexal Carcinoma is composed of syringomatous duct-like structures and strands of cells that induce a characteristic loose, [...] stromal reaction.
Eyelid skin microcystic adnexal carcinoma. Widely infiltrating microcystic adnexal carcinoma, with syringomatous duct-like structures, within the orbicularis muscle and tarsal plate. Note the loose desmoplastic reaction around the tumour nests.
Eyelid microcystic adnexal carcinoma. Strands and nests of invasive microcytic adnexal carcinoma, within the eyelid tarsal plate, surrounded by a loose desmoplastic stromal response.
A: desmoplastic
Back Extra: Microcystic Adnexal Carcinoma
- Clinical: Microcystic adnexal carcinoma presents as a yellow, firm, indurated nodule that can cause eyelid distortion, retraction, and rarely ulceration and madarosis.
- Micro: This carcinoma is characterized by bland cytology, small nests, strands, or columns of epithelial cells, and trichoepithelioma-like keratocysts.
- Ancillary: NGS shows a low mutational burden and mutations in p53 and JAK/STAT signaling pathways, but no UV signature.
Reference Gallery:
Microcystic adnexal carcinoma. Low magnification view illustrating infiltrative nature of the tumour with involvement of the subcutaneous tissue.
Microcystic adnexal carcinoma. Superficial portion of the tumour showing trichoepitheliomatous keratocysts, essentially indistinguishable from those expected in trichoeplithelioma.
Microcystic adnexal carcinoma. Bland cytological features with no mitotic activity.
Eyelid microcystic adnexal carcinoma. Perineural and intraneural invasion by microcystic adnexal carcinoma
Eyelid skin microcystic adnexal carcinoma. Widely infiltrating microcystic adnexal carcinoma, with syringomatous duct-like structures, within the orbicularis muscle and tarsal plate. Note the loose desmoplastic reaction around the tumour nests.
Eyelid microcystic adnexal carcinoma. Strands and nests of invasive microcytic adnexal carcinoma, within the eyelid tarsal plate, surrounded by a loose desmoplastic stromal response.

Q: Despite featuring very bland cytology without mitotic activity, Microcystic Adnexal Carcinoma is aggressive locally and characteristically demonstrates [...] invasion.
Microcystic adnexal carcinoma. Bland cytological features with no mitotic activity.
Eyelid microcystic adnexal carcinoma. Perineural and intraneural invasion by microcystic adnexal carcinoma
A: perineural
Back Extra: Microcystic Adnexal Carcinoma
- Clinical: Microcystic adnexal carcinoma presents as a yellow, firm, indurated nodule that can cause eyelid distortion, retraction, and rarely ulceration and madarosis.
- Micro: This carcinoma is characterized by bland cytology, small nests, strands, or columns of epithelial cells, and trichoepithelioma-like keratocysts.
- Ancillary: NGS shows a low mutational burden and mutations in p53 and JAK/STAT signaling pathways, but no UV signature.
Reference Gallery:
Microcystic adnexal carcinoma. Low magnification view illustrating infiltrative nature of the tumour with involvement of the subcutaneous tissue.
Microcystic adnexal carcinoma. Superficial portion of the tumour showing trichoepitheliomatous keratocysts, essentially indistinguishable from those expected in trichoeplithelioma.
Microcystic adnexal carcinoma. Bland cytological features with no mitotic activity.
Eyelid microcystic adnexal carcinoma. Perineural and intraneural invasion by microcystic adnexal carcinoma
Eyelid skin microcystic adnexal carcinoma. Widely infiltrating microcystic adnexal carcinoma, with syringomatous duct-like structures, within the orbicularis muscle and tarsal plate. Note the loose desmoplastic reaction around the tumour nests.
Eyelid microcystic adnexal carcinoma. Strands and nests of invasive microcytic adnexal carcinoma, within the eyelid tarsal plate, surrounded by a loose desmoplastic stromal response.

Q: The characteristic histologic hallmark of Mucinous Carcinoma is the presence of tumor cell nests, strands, or individual units floating in lakes of [...].
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Nests of tumour cells in pools of mucin.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Tumour nests are composed of relatively bland round to oval cells, and some form glands.
A: extracellular mucin
Back Extra: Mucinous Carcinoma
- Clinical: Mucinous carcinoma is a slowly growing lesion that can present as firm or cystic, tan, blue, red, or grey lesions, often mimicking benign and malignant eyelid tumours.
- Micro: Tumour cells are arranged in nests, strands, or individual units and float in lakes of extracellular mucin, with an in situ component detected in most cases (60-70%).
- Ancillary: Immunohistochemistry shows expression of low-molecular-weight cytokeratins, EMA, CEA, E-cadherin, GATA3, and GCDFP15, with ER and PR expressed in most cases.
Reference Gallery:
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. A tumour extensively involves the eyelid dermis.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Nests of tumour cells in pools of mucin.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Immunohistochemical evidence of progesterone receptor expression supports apocrine differentiation.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Tumour nests are composed of relatively bland round to oval cells, and some form glands.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Eyelid mucinous carcinoma. A lesion of the upper lateral eyelid. Note the bluish-brown raised nodule.

Q: When diagnosing a cutaneous Mucinous Carcinoma, the presence of an [...] confirms the tumor is primary rather than a metastasis from an extra-cutaneous site.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. A tumour extensively involves the eyelid dermis.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Eyelid mucinous carcinoma. A lesion of the upper lateral eyelid. Note the bluish-brown raised nodule.
A: in situ component
Back Extra: Mucinous Carcinoma
- Clinical: Mucinous carcinoma is a slowly growing lesion that can present as firm or cystic, tan, blue, red, or grey lesions, often mimicking benign and malignant eyelid tumours.
- Micro: Tumour cells are arranged in nests, strands, or individual units and float in lakes of extracellular mucin, with an in situ component detected in most cases (60-70%).
- Ancillary: Immunohistochemistry shows expression of low-molecular-weight cytokeratins, EMA, CEA, E-cadherin, GATA3, and GCDFP15, with ER and PR expressed in most cases.
Reference Gallery:
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. A tumour extensively involves the eyelid dermis.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Nests of tumour cells in pools of mucin.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Immunohistochemical evidence of progesterone receptor expression supports apocrine differentiation.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Tumour nests are composed of relatively bland round to oval cells, and some form glands.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Eyelid mucinous carcinoma. A lesion of the upper lateral eyelid. Note the bluish-brown raised nodule.

Q: In primary cutaneous Mucinous Carcinoma, immunohistochemistry often shows expression of estrogen receptor (ER) and [...], which supports apocrine differentiation.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Immunohistochemical evidence of progesterone receptor expression supports apocrine differentiation.
A: progesterone receptor (PR)
Back Extra: Mucinous Carcinoma
- Clinical: Mucinous carcinoma is a slowly growing lesion that can present as firm or cystic, tan, blue, red, or grey lesions, often mimicking benign and malignant eyelid tumours.
- Micro: Tumour cells are arranged in nests, strands, or individual units and float in lakes of extracellular mucin, with an in situ component detected in most cases (60-70%).
- Ancillary: Immunohistochemistry shows expression of low-molecular-weight cytokeratins, EMA, CEA, E-cadherin, GATA3, and GCDFP15, with ER and PR expressed in most cases.
Reference Gallery:
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. A tumour extensively involves the eyelid dermis.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Nests of tumour cells in pools of mucin.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Immunohistochemical evidence of progesterone receptor expression supports apocrine differentiation.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Mucinous carcinoma. Tumour nests are composed of relatively bland round to oval cells, and some form glands.
Primary cutaneous mucinous carcinoma must be differentiated from a metastatic mucinous carcinoma. The presence of an in situ component qualifies the tumour as primary cutaneous; however, its absence does not necessarily imply an extra-cutaneous origin. For such cases, a full clinical work-up is needed to establish the origin. Diagnosis: Eyelid mucinous carcinoma. A lesion of the upper lateral eyelid. Note the bluish-brown raised nodule.

Q: Clinically, Sebaceous Carcinoma frequently presents as an immobile, tan-pink-yellow nodular mass typically involving the [...], which can initially be mistaken for benign inflammatory conditions like chronic blepharoconjunctivitis or a chalazion.
Sebaceous carcinoma. A tumour involving the upper eyelid.
A: eyelid
Back Extra: Sebaceous Carcinoma
- Clinical: Sebaceous carcinoma often presents as a tan-pink-yellow immobile nodular lesion, which may be mistaken for benign conditions like chronic blepharoconjunctivitis.
- Micro: Invasive sebaceous carcinoma shows polygonal tumour cells with atypical nuclei and abundant intracytoplasmic vacuoles, creating a foamy appearance.
- Ancillary: Immunohistochemistry reveals positivity for pan-cytokeratin, adipophilin, and androgen receptor in sebaceous carcinoma.
Reference Gallery:
Sebaceous Carcinoma. CT scan shows periocular sebaceous carcinoma forming a mass lesion in the left eye.
Sebaceous carcinoma. A tumour involving the upper eyelid.
Eyelid skin sebaceous carcinoma. Invasive eyelid skin sebaceous carcinoma showing highly atypical nuclei and multi-vesicular cytoplasmic vacuoles.
Conjunctival intra-epithelial sebaceous carcinoma. Sebaceous tumour cells with multi-vesicualted cytoplasm replacing much of the conjunctival epithelium. Note the intact basal layer of the conjunctival epithelium.
Conjunctival intraepithelial sebaceous carcinoma. Androgen receptor positivity of intraepithelial sebaceous tumour cells. Note the negative staining of the surrounding conjunctival squamous epithelium, including the basal layer beneath the tumour cells.
Conjunctival intraepithelial sebaceous carcinoma. Adipophylin positivity of intraepithelial sebaceous tumour cells. Note the negative staining of the surrounding conjunctival squamous epithelium, including the basal layer beneath the tumour cells.
Sebaceous carcinoma. Cytoplasmic adipophylin staining of invasive sebaceous carcinoma.
Sebaceous carcinoma. Nuclear androgen positivity of invasive sebaceous carcinoma.
Eyelid sebaceous carcinoma. High power image of an invasive eyelid sebaceous carcinoma showing intracytoplasmic lipid vacuoles.

Q: Microscopically, invasive Sebaceous Carcinoma is characterized by polygonal tumor cells with highly atypical nuclei and abundant intracytoplasmic [...], creating a characteristic foamy appearance.
Eyelid skin sebaceous carcinoma. Invasive eyelid skin sebaceous carcinoma showing highly atypical nuclei and multi-vesicular cytoplasmic vacuoles.
Eyelid sebaceous carcinoma. High power image of an invasive eyelid sebaceous carcinoma showing intracytoplasmic lipid vacuoles.
A: lipid vacuoles
Back Extra: Sebaceous Carcinoma
- Clinical: Sebaceous carcinoma often presents as a tan-pink-yellow immobile nodular lesion, which may be mistaken for benign conditions like chronic blepharoconjunctivitis.
- Micro: Invasive sebaceous carcinoma shows polygonal tumour cells with atypical nuclei and abundant intracytoplasmic vacuoles, creating a foamy appearance.
- Ancillary: Immunohistochemistry reveals positivity for pan-cytokeratin, adipophilin, and androgen receptor in sebaceous carcinoma.
Reference Gallery:
Sebaceous Carcinoma. CT scan shows periocular sebaceous carcinoma forming a mass lesion in the left eye.
Sebaceous carcinoma. A tumour involving the upper eyelid.
Eyelid skin sebaceous carcinoma. Invasive eyelid skin sebaceous carcinoma showing highly atypical nuclei and multi-vesicular cytoplasmic vacuoles.
Conjunctival intra-epithelial sebaceous carcinoma. Sebaceous tumour cells with multi-vesicualted cytoplasm replacing much of the conjunctival epithelium. Note the intact basal layer of the conjunctival epithelium.
Conjunctival intraepithelial sebaceous carcinoma. Androgen receptor positivity of intraepithelial sebaceous tumour cells. Note the negative staining of the surrounding conjunctival squamous epithelium, including the basal layer beneath the tumour cells.
Conjunctival intraepithelial sebaceous carcinoma. Adipophylin positivity of intraepithelial sebaceous tumour cells. Note the negative staining of the surrounding conjunctival squamous epithelium, including the basal layer beneath the tumour cells.
Sebaceous carcinoma. Cytoplasmic adipophylin staining of invasive sebaceous carcinoma.
Sebaceous carcinoma. Nuclear androgen positivity of invasive sebaceous carcinoma.
Eyelid sebaceous carcinoma. High power image of an invasive eyelid sebaceous carcinoma showing intracytoplasmic lipid vacuoles.

Q: To confirm sebaceous differentiation, immunohistochemistry for Sebaceous Carcinoma typically demonstrates positivity for pan-cytokeratin, androgen receptor, and [...].
Sebaceous carcinoma. Cytoplasmic adipophylin staining of invasive sebaceous carcinoma.
Sebaceous carcinoma. Nuclear androgen positivity of invasive sebaceous carcinoma.
A: adipophilin
Back Extra: Sebaceous Carcinoma
- Clinical: Sebaceous carcinoma often presents as a tan-pink-yellow immobile nodular lesion, which may be mistaken for benign conditions like chronic blepharoconjunctivitis.
- Micro: Invasive sebaceous carcinoma shows polygonal tumour cells with atypical nuclei and abundant intracytoplasmic vacuoles, creating a foamy appearance.
- Ancillary: Immunohistochemistry reveals positivity for pan-cytokeratin, adipophilin, and androgen receptor in sebaceous carcinoma.
Reference Gallery:
Sebaceous Carcinoma. CT scan shows periocular sebaceous carcinoma forming a mass lesion in the left eye.
Sebaceous carcinoma. A tumour involving the upper eyelid.
Eyelid skin sebaceous carcinoma. Invasive eyelid skin sebaceous carcinoma showing highly atypical nuclei and multi-vesicular cytoplasmic vacuoles.
Conjunctival intra-epithelial sebaceous carcinoma. Sebaceous tumour cells with multi-vesicualted cytoplasm replacing much of the conjunctival epithelium. Note the intact basal layer of the conjunctival epithelium.
Conjunctival intraepithelial sebaceous carcinoma. Androgen receptor positivity of intraepithelial sebaceous tumour cells. Note the negative staining of the surrounding conjunctival squamous epithelium, including the basal layer beneath the tumour cells.
Conjunctival intraepithelial sebaceous carcinoma. Adipophylin positivity of intraepithelial sebaceous tumour cells. Note the negative staining of the surrounding conjunctival squamous epithelium, including the basal layer beneath the tumour cells.
Sebaceous carcinoma. Cytoplasmic adipophylin staining of invasive sebaceous carcinoma.
Sebaceous carcinoma. Nuclear androgen positivity of invasive sebaceous carcinoma.
Eyelid sebaceous carcinoma. High power image of an invasive eyelid sebaceous carcinoma showing intracytoplasmic lipid vacuoles.

Q: Clinically, primary cutaneous Signet Ring Cell/Histiocytoid Carcinoma most commonly presents as an insidious, painless swelling of the [...], demonstrating a diffuse single-cell infiltrative pattern of the tumor on histology.
Eccrine signet ring cell/histiocytoid carcinoma. Low magnification view showing a large tumour infiltrating tissues of the eyelid.
Eccrine signet ring cell/histiocytoid carcinoma. Peripheral edge of the tumor showing single cell infiltration without stromal reaction.
A: eyelids
Back Extra: Signet Ring Cell/Histiocytoid Carcinoma
- Clinical: This tumour is most common in elderly males, presenting insidiously as a painless swelling, often affecting both upper and lower eyelids.
- Micro: The tumour is composed of signet-ring or histiocytoid epithelial cells that diffusely infiltrate the collagen bundles of the dermis with sparing of the epidermis.
- Ancillary: CDH1 mutations, known to confer signet-ring morphology, have been detected in this carcinoma.
Reference Gallery:
Eccrine signet ring/histiocytoid carcinoma. High magnification view illustrating the cytological features of the tumour cells, which show histiocytoid appearance with some signet ring cells showing intracytoplasmic vacuoles and eccentric nuclei.
Eccrine signet ring cell/histiocytoid carcinoma. Low magnification view showing a large tumour infiltrating tissues of the eyelid.
Eccrine signet ring cell/histiocytoid carcinoma. Peripheral edge of the tumor showing single cell infiltration without stromal reaction.
Eccrine signet-ring cell/histiocytoid carcinoma. Combined Alcian Blue/PAS stain showing neutral and acid mucin within the tumour signet ring cytoplasmic vacuoles.
Eccrine signet-ring cell/histiocytoid carcinoma. Pan-cytokeratin (AE1AE3) immunohistochemical positivity of the tumour cells. Note the 'filing' pattern of infiltration.
Eccrine signet-ring cell/histiocytoid carcinoma. GATA3 immunohistochemical nuclear positivity of tumour cells.
Eccrine signet-ring cell/histiocytoid carcinoma. Estrogen receptor positivity.
Histiocytoid carcinoma. Androgen receptor positivity within tumour cells.
Histiocytoid carcinoma. Androgen receptor positivity within tumour cells.
Diagnosis not found. Legend text not found
Diagnosis not found. Legend text not found

Q: In Signet Ring Cell/Histiocytoid Carcinoma, the intracytoplasmic vacuoles contain both neutral and acid mucins, which can be highlighted using a combined [...] stain.
Eccrine signet-ring cell/histiocytoid carcinoma. Combined Alcian Blue/PAS stain showing neutral and acid mucin within the tumour signet ring cytoplasmic vacuoles.
A: Alcian Blue/PAS
Back Extra: Signet Ring Cell/Histiocytoid Carcinoma
- Clinical: This tumour is most common in elderly males, presenting insidiously as a painless swelling, often affecting both upper and lower eyelids.
- Micro: The tumour is composed of signet-ring or histiocytoid epithelial cells that diffusely infiltrate the collagen bundles of the dermis with sparing of the epidermis.
- Ancillary: CDH1 mutations, known to confer signet-ring morphology, have been detected in this carcinoma.
Reference Gallery:
Eccrine signet ring/histiocytoid carcinoma. High magnification view illustrating the cytological features of the tumour cells, which show histiocytoid appearance with some signet ring cells showing intracytoplasmic vacuoles and eccentric nuclei.
Eccrine signet ring cell/histiocytoid carcinoma. Low magnification view showing a large tumour infiltrating tissues of the eyelid.
Eccrine signet ring cell/histiocytoid carcinoma. Peripheral edge of the tumor showing single cell infiltration without stromal reaction.
Eccrine signet-ring cell/histiocytoid carcinoma. Combined Alcian Blue/PAS stain showing neutral and acid mucin within the tumour signet ring cytoplasmic vacuoles.
Eccrine signet-ring cell/histiocytoid carcinoma. Pan-cytokeratin (AE1AE3) immunohistochemical positivity of the tumour cells. Note the 'filing' pattern of infiltration.
Eccrine signet-ring cell/histiocytoid carcinoma. GATA3 immunohistochemical nuclear positivity of tumour cells.
Eccrine signet-ring cell/histiocytoid carcinoma. Estrogen receptor positivity.
Histiocytoid carcinoma. Androgen receptor positivity within tumour cells.
Histiocytoid carcinoma. Androgen receptor positivity within tumour cells.
Diagnosis not found. Legend text not found
Diagnosis not found. Legend text not found

Q: The classic signet-ring morphology and 'Indian file' pattern of single-cell dermal infiltration characteristic of Signet Ring Cell/Histiocytoid Carcinoma are associated with mutations in the [...] gene.
Eccrine signet ring/histiocytoid carcinoma. High magnification view illustrating the cytological features of the tumour cells, which show histiocytoid appearance with some signet ring cells showing intracytoplasmic vacuoles and eccentric nuclei.
Eccrine signet-ring cell/histiocytoid carcinoma. Pan-cytokeratin (AE1AE3) immunohistochemical positivity of the tumour cells. Note the 'filing' pattern of infiltration.
A: CDH1
Back Extra: Signet Ring Cell/Histiocytoid Carcinoma
- Clinical: This tumour is most common in elderly males, presenting insidiously as a painless swelling, often affecting both upper and lower eyelids.
- Micro: The tumour is composed of signet-ring or histiocytoid epithelial cells that diffusely infiltrate the collagen bundles of the dermis with sparing of the epidermis.
- Ancillary: CDH1 mutations, known to confer signet-ring morphology, have been detected in this carcinoma.
Reference Gallery:
Eccrine signet ring/histiocytoid carcinoma. High magnification view illustrating the cytological features of the tumour cells, which show histiocytoid appearance with some signet ring cells showing intracytoplasmic vacuoles and eccentric nuclei.
Eccrine signet ring cell/histiocytoid carcinoma. Low magnification view showing a large tumour infiltrating tissues of the eyelid.
Eccrine signet ring cell/histiocytoid carcinoma. Peripheral edge of the tumor showing single cell infiltration without stromal reaction.
Eccrine signet-ring cell/histiocytoid carcinoma. Combined Alcian Blue/PAS stain showing neutral and acid mucin within the tumour signet ring cytoplasmic vacuoles.
Eccrine signet-ring cell/histiocytoid carcinoma. Pan-cytokeratin (AE1AE3) immunohistochemical positivity of the tumour cells. Note the 'filing' pattern of infiltration.
Eccrine signet-ring cell/histiocytoid carcinoma. GATA3 immunohistochemical nuclear positivity of tumour cells.
Eccrine signet-ring cell/histiocytoid carcinoma. Estrogen receptor positivity.
Histiocytoid carcinoma. Androgen receptor positivity within tumour cells.
Histiocytoid carcinoma. Androgen receptor positivity within tumour cells.
Diagnosis not found. Legend text not found
Diagnosis not found. Legend text not found

Q: Microscopically, the lining of an Epidermal Inclusion Cyst is identical to the surface epidermis, characteristically featuring a well-developed [...].
Epidermal inclusion cyst. The cyst lining recapitulates normal epidermis with a stratum granulosum.
A: stratum granulosum
Back Extra: Epidermal Inclusion Cyst
- Clinical: Epidermal inclusion cysts are typically slow-growing, well-circumscribed, firm, and mobile dermal or subcutaneous masses. A central pore may be visible clinically.
- Micro: The lining of epidermal inclusion cysts is identical to the surface epidermis, with a well-developed stratum granulosum and abundant laminated orthokeratin.
- Ancillary: Fine needle aspiration biopsy is not typically used for diagnosis, as the diagnosis is primarily based on clinical and histological features.
Reference Gallery:
Epidermal inclusion cyst. Dermal based cyst without an epidermal connection containing abundant flaky orthokeratin.
Epidermal inclusion cyst. The cyst lining recapitulates normal epidermis with a stratum granulosum.
Epidermal cyst. Clinical image of a cyst close to the upper lid.

Q: An Epidermal Inclusion Cyst is a well-circumscribed dermal cyst that lacks an epidermal connection and is characteristically filled with abundant, flaky, and laminated [...].
Epidermal inclusion cyst. Dermal based cyst without an epidermal connection containing abundant flaky orthokeratin.
A: orthokeratin
Back Extra: Epidermal Inclusion Cyst
- Clinical: Epidermal inclusion cysts are typically slow-growing, well-circumscribed, firm, and mobile dermal or subcutaneous masses. A central pore may be visible clinically.
- Micro: The lining of epidermal inclusion cysts is identical to the surface epidermis, with a well-developed stratum granulosum and abundant laminated orthokeratin.
- Ancillary: Fine needle aspiration biopsy is not typically used for diagnosis, as the diagnosis is primarily based on clinical and histological features.
Reference Gallery:
Epidermal inclusion cyst. Dermal based cyst without an epidermal connection containing abundant flaky orthokeratin.
Epidermal inclusion cyst. The cyst lining recapitulates normal epidermis with a stratum granulosum.
Epidermal cyst. Clinical image of a cyst close to the upper lid.

Q: Clinically, an Epidermal Inclusion Cyst typically presents as a slow-growing, firm, and mobile dermal mass that may exhibit a visible central [...].
Epidermal cyst. Clinical image of a cyst close to the upper lid.
A: pore
Back Extra: Epidermal Inclusion Cyst
- Clinical: Epidermal inclusion cysts are typically slow-growing, well-circumscribed, firm, and mobile dermal or subcutaneous masses. A central pore may be visible clinically.
- Micro: The lining of epidermal inclusion cysts is identical to the surface epidermis, with a well-developed stratum granulosum and abundant laminated orthokeratin.
- Ancillary: Fine needle aspiration biopsy is not typically used for diagnosis, as the diagnosis is primarily based on clinical and histological features.
Reference Gallery:
Epidermal inclusion cyst. Dermal based cyst without an epidermal connection containing abundant flaky orthokeratin.
Epidermal inclusion cyst. The cyst lining recapitulates normal epidermis with a stratum granulosum.
Epidermal cyst. Clinical image of a cyst close to the upper lid.

Q: Histologically, the epithelial lining of an Intratarsal Cyst is highly characteristic, featuring a stratified squamous epithelium that lacks keratohyalin granules and possesses a distinct [...] facing the lumen.
Intratarsal keratinous cyst. Posterior lamella of eyelid, including tarsus and conjunctiva, with intratarsal cyst. Intratarsal cyst displays characteristic lining with corrugated eosinophilic cuticle and a wispy luminal keratin. Meibomian gland lobules are present in the adjacent tarsus.
Intratarsal keratinous cyst. The cyst lining features palisaded basal layer with hyperchromatic nuclei, corrugated surface without keratohyalin granules, and delicate lamellated luminal keratin (PAS stain).
A: corrugated eosinophilic cuticle
Back Extra: Intratarsal Cyst
- Clinical: Intratarsal cysts present as painless, well-defined firm nodules fixed to the tarsus, typically in the upper eyelids of older individuals.
- Micro: The cysts have a characteristic stratified squamous epithelial lining that is 4-6 cells thick, with a basal layer of hyperchromatic cells and a corrugated eosinophilic cuticle in the lumen.
- Ancillary: Immunohistochemistry shows the lining cells and keratin are strongly positive for CK17, while the luminal portion and contents may be positive for CEA and EMA.
Reference Gallery:
Intratarsal keratinous cyst. Posterior lamella of eyelid, including tarsus and conjunctiva, with intratarsal cyst. Intratarsal cyst displays characteristic lining with corrugated eosinophilic cuticle and a wispy luminal keratin. Meibomian gland lobules are present in the adjacent tarsus.
Intratarsal keratinous cyst. External photograph demonstrates a circumscribed deep-seated lesion in the right upper eyelid.
Intratarsal keratinous cyst. Intraoperatively, the lesion appears as a circumscribed pearly nodule inseparable from the tarsus.
Intratarsal keratinous cyst. The cyst lining features palisaded basal layer with hyperchromatic nuclei, corrugated surface without keratohyalin granules, and delicate lamellated luminal keratin (PAS stain).

Q: A painless, circumscribed pearly nodule that is deeply seated and fixed to the tarsus of the upper eyelid in older individuals is the classic clinical presentation of an [...].
Intratarsal keratinous cyst. External photograph demonstrates a circumscribed deep-seated lesion in the right upper eyelid.
Intratarsal keratinous cyst. Intraoperatively, the lesion appears as a circumscribed pearly nodule inseparable from the tarsus.
A: Intratarsal Cyst
Back Extra: Intratarsal Cyst
- Clinical: Intratarsal cysts present as painless, well-defined firm nodules fixed to the tarsus, typically in the upper eyelids of older individuals.
- Micro: The cysts have a characteristic stratified squamous epithelial lining that is 4-6 cells thick, with a basal layer of hyperchromatic cells and a corrugated eosinophilic cuticle in the lumen.
- Ancillary: Immunohistochemistry shows the lining cells and keratin are strongly positive for CK17, while the luminal portion and contents may be positive for CEA and EMA.
Reference Gallery:
Intratarsal keratinous cyst. Posterior lamella of eyelid, including tarsus and conjunctiva, with intratarsal cyst. Intratarsal cyst displays characteristic lining with corrugated eosinophilic cuticle and a wispy luminal keratin. Meibomian gland lobules are present in the adjacent tarsus.
Intratarsal keratinous cyst. External photograph demonstrates a circumscribed deep-seated lesion in the right upper eyelid.
Intratarsal keratinous cyst. Intraoperatively, the lesion appears as a circumscribed pearly nodule inseparable from the tarsus.
Intratarsal keratinous cyst. The cyst lining features palisaded basal layer with hyperchromatic nuclei, corrugated surface without keratohyalin granules, and delicate lamellated luminal keratin (PAS stain).

Q: Actinic Keratosis is clinically recognized as a common [...] skin lesion, typically presenting as a flat, erythematous, and scaly plaque on chronically sun-damaged skin.
Diagnosis: Actinic keratosis. Erythematous, hyperkeratotic, actinic keratosis at the temporal lower lid
Diagnosis: Actinic keratosis. There is extensive periocular actinic keratosis.
A: precancerous
Back Extra: Actinic Keratosis
- Clinical: Actinic keratosis (AK) is a common precancerous skin lesion, typically presenting as a flat, erythematous, scaly lesion with irregular fuzzy borders in sun-damaged skin.
- Micro: Microscopically, AK shows atrophic or hyperplastic epidermis with hyper-/parakeratosis, dyskeratosis, apoptosis, and dermal elastoid degeneration.
- Ancillary: Actinic keratoses have a high mutational burden and UV signatures, with common alterations in TP53, NOTCH1, NOTCH2, and FAT1 genes.
Reference Gallery:
Diagnosis: Actinic keratosis. Erythematous, hyperkeratotic, actinic keratosis at the temporal lower lid
Diagnosis: Actinic keratosis. Hyperkeratotic actinic keratosis with subepithelial chronic inflammatory infiltration.
Diagnosis: Actinic keratosis. Dysplasia of the epidermis including mitoses of 2 adjacent cells at different levels (arrow) and a superficial cell with an apoptotic nucleus (asterisk).
Diagnosis: Actinic keratosis. There is extensive periocular actinic keratosis.
Diagnosis: Actinic keratosis. Atrophic type, with basaloid downgrowths, and mild dysplasia.

Q: Microscopically, the hallmark feature of Actinic Keratosis is epidermal [...], which may include irregular basaloid downgrowths, scattered mitoses, and superficial apoptotic cells.
Diagnosis: Actinic keratosis. Dysplasia of the epidermis including mitoses of 2 adjacent cells at different levels (arrow) and a superficial cell with an apoptotic nucleus (asterisk).
Diagnosis: Actinic keratosis. Atrophic type, with basaloid downgrowths, and mild dysplasia.
A: dysplasia
Back Extra: Actinic Keratosis
- Clinical: Actinic keratosis (AK) is a common precancerous skin lesion, typically presenting as a flat, erythematous, scaly lesion with irregular fuzzy borders in sun-damaged skin.
- Micro: Microscopically, AK shows atrophic or hyperplastic epidermis with hyper-/parakeratosis, dyskeratosis, apoptosis, and dermal elastoid degeneration.
- Ancillary: Actinic keratoses have a high mutational burden and UV signatures, with common alterations in TP53, NOTCH1, NOTCH2, and FAT1 genes.
Reference Gallery:
Diagnosis: Actinic keratosis. Erythematous, hyperkeratotic, actinic keratosis at the temporal lower lid
Diagnosis: Actinic keratosis. Hyperkeratotic actinic keratosis with subepithelial chronic inflammatory infiltration.
Diagnosis: Actinic keratosis. Dysplasia of the epidermis including mitoses of 2 adjacent cells at different levels (arrow) and a superficial cell with an apoptotic nucleus (asterisk).
Diagnosis: Actinic keratosis. There is extensive periocular actinic keratosis.
Diagnosis: Actinic keratosis. Atrophic type, with basaloid downgrowths, and mild dysplasia.

Q: Histologically, Inverted Follicular Keratosis features a symmetrical, invaginated proliferation of basaloid and squamoid cells with characteristic [...].
Inverted follicular keratosis. Eyelid covered by skin and conjunctiva. There is nodular inverted proliferation of basaloid and squamoid cells deriving from the follicular infundibulum, with a crypt opening to the surface. There is absence of an infiltrative destructive growth pattern. Intermingled basaloid and squamoid cells are present with focal acantholysis and a squamous eddy.
Inverted follicular keratosis. Higher magnification of a squamous eddy with basaloid cells located at the periphery and squamoid cells at the center of the lobule. A single mitotic figure is present.
A: squamous eddies
Back Extra: Inverted Follicular Keratosis
- Clinical: White-tan to pink eyelid asymptomatic papules, which may rarely present as 'cutaneous horns'. Often misdiagnosed as viral warts or basal cell carcinoma.
- Micro: Symmetrical invaginated proliferation of basaloid and squamoid cells forming squamous eddies. Absence of dermal destructive invasion and atypical mitotic figures.
- Ancillary: Multiple IFK can be an indicator of Cowden's syndrome, an autosomal dominant disorder due to a mutation in the PTEN gene.
Reference Gallery:
Inverted follicular keratosis. Eighty-four year old woman with inverted follicular keratosis mimicking a nodular basal cell carcinoma.
Inverted follicular keratosis. Eyelid covered by skin and conjunctiva. There is nodular inverted proliferation of basaloid and squamoid cells deriving from the follicular infundibulum, with a crypt opening to the surface. There is absence of an infiltrative destructive growth pattern. Intermingled basaloid and squamoid cells are present with focal acantholysis and a squamous eddy.
Inverted follicular keratosis. Higher magnification of a squamous eddy with basaloid cells located at the periphery and squamoid cells at the center of the lobule. A single mitotic figure is present.

Q: Clinically, Inverted Follicular Keratosis typically presents as an asymptomatic white-tan to pink papule on the eyelid that can closely mimic a nodular [...].
Inverted follicular keratosis. Eighty-four year old woman with inverted follicular keratosis mimicking a nodular basal cell carcinoma.
A: basal cell carcinoma
Back Extra: Inverted Follicular Keratosis
- Clinical: White-tan to pink eyelid asymptomatic papules, which may rarely present as 'cutaneous horns'. Often misdiagnosed as viral warts or basal cell carcinoma.
- Micro: Symmetrical invaginated proliferation of basaloid and squamoid cells forming squamous eddies. Absence of dermal destructive invasion and atypical mitotic figures.
- Ancillary: Multiple IFK can be an indicator of Cowden's syndrome, an autosomal dominant disorder due to a mutation in the PTEN gene.
Reference Gallery:
Inverted follicular keratosis. Eighty-four year old woman with inverted follicular keratosis mimicking a nodular basal cell carcinoma.
Inverted follicular keratosis. Eyelid covered by skin and conjunctiva. There is nodular inverted proliferation of basaloid and squamoid cells deriving from the follicular infundibulum, with a crypt opening to the surface. There is absence of an infiltrative destructive growth pattern. Intermingled basaloid and squamoid cells are present with focal acantholysis and a squamous eddy.
Inverted follicular keratosis. Higher magnification of a squamous eddy with basaloid cells located at the periphery and squamoid cells at the center of the lobule. A single mitotic figure is present.

Q: Clinically, Molluscum Contagiosum commonly presents as 2-5 mm waxy, flesh-colored papules with a characteristic central depression, classically described as being [...].
Molluscum contagiosum. A child with multiple mollusca contagiosa on the eyelids.
A: umbilicated
Back Extra: Molluscum Contagiosum
- Clinical: Solitary or multiple 2-5 mm umbilicated, waxy, flesh-colored to erythematous papules, often seen on the eyelids.
- Micro: Elevated crateriform lesion with acanthotic epidermis containing large, eosinophilic molluscum bodies.
- Ancillary: Tzanck smear can identify molluscum bodies.
Reference Gallery:
Molluscum contagiosum. A child with multiple mollusca contagiosa on the eyelids.
Molluscum contagiosum. Histopathology showing molluscum bodies
Molluscum contagiosum. Histopathology showing molluscum bodies at high power.

Q: On histology, Molluscum Contagiosum appears as an elevated crateriform lesion with an acanthotic epidermis containing large, eosinophilic cytoplasmic inclusions termed [...].
Molluscum contagiosum. Histopathology showing molluscum bodies
Molluscum contagiosum. Histopathology showing molluscum bodies at high power.
A: molluscum bodies
Back Extra: Molluscum Contagiosum
- Clinical: Solitary or multiple 2-5 mm umbilicated, waxy, flesh-colored to erythematous papules, often seen on the eyelids.
- Micro: Elevated crateriform lesion with acanthotic epidermis containing large, eosinophilic molluscum bodies.
- Ancillary: Tzanck smear can identify molluscum bodies.
Reference Gallery:
Molluscum contagiosum. A child with multiple mollusca contagiosa on the eyelids.
Molluscum contagiosum. Histopathology showing molluscum bodies
Molluscum contagiosum. Histopathology showing molluscum bodies at high power.

Q: Clinically, Seborrheic Keratosis often presents as a papillomatous, tan-to-brown, sessile tumor with a characteristic [...] appearance.
Seborrheic keratosis. Pigmented seborrheic keratosis of the lower lid with papillomatous surface and intact eye lashes
A: stuck-on
Back Extra: Seborrheic Keratosis
- Clinical: Seborrheic keratosis presents as a papillomatous, often sessile tumour with a stuck-on appearance, commonly tan to brown and keratotic.
- Micro: Histologically, it shows a well-demarcated, thickened epidermal layer with increased basaloid keratinocytes, horn cysts, and hyperkeratosis.
- Ancillary: Seborrheic keratoses are UV-associated with typical UV signatures, and somatic mutations in genes like FGFR3, PIK3CA, KRAS, HRAS, EGFR, and AKT1 have been reported.
Reference Gallery:
Seborrheic keratosis. Pigmented seborrheic keratosis of the lower lid with papillomatous surface and intact eye lashes
Seborrheic keratosis. Histology of the same case with acanthotic, reticulated areas, and hyperkeratosis.

Q: Microscopically, Seborrheic Keratosis typically features a well-demarcated, thickened epidermis with increased basaloid keratinocytes, hyperkeratosis, and characteristic [...].
Seborrheic keratosis. Histology of the same case with acanthotic, reticulated areas, and hyperkeratosis.
A: horn cysts
Back Extra: Seborrheic Keratosis
- Clinical: Seborrheic keratosis presents as a papillomatous, often sessile tumour with a stuck-on appearance, commonly tan to brown and keratotic.
- Micro: Histologically, it shows a well-demarcated, thickened epidermal layer with increased basaloid keratinocytes, horn cysts, and hyperkeratosis.
- Ancillary: Seborrheic keratoses are UV-associated with typical UV signatures, and somatic mutations in genes like FGFR3, PIK3CA, KRAS, HRAS, EGFR, and AKT1 have been reported.
Reference Gallery:
Seborrheic keratosis. Pigmented seborrheic keratosis of the lower lid with papillomatous surface and intact eye lashes
Seborrheic keratosis. Histology of the same case with acanthotic, reticulated areas, and hyperkeratosis.

Q: Microscopically, Squamous Cell Papilloma is characterized by an exophytic proliferation of squamous epithelium supported by central [...].
Squamous papilloma. The epidermis is hyperplastic with papillomatous and acanthosis.
A: fibrovascular cores
Back Extra: Squamous Cell Papilloma
- Clinical: Squamous cell papilloma is a sessile or pedunculated soft, smooth lesion, often multiple, with a verrucous or keratin crust and can occur at any age without sex predilection.
- Micro: Microscopically, it is a verrucous, broad-based or finger-like exophytic epithelial neoplasm with a fibrovascular core, hyper-parakeratosis, and absence of dysplasia or dermal invasion.
- Ancillary: HPV cytopathic signs, such as koilocytes or double nuclei, may be present, but ancillary studies are not typically required for diagnosis.
Reference Gallery:
Squamous papilloma. The epidermis is hyperplastic with papillomatous and acanthosis.
Squamous cell papilloma. High magnification shows absence of epidermal dysplasia, mitosis or dermal invasion. This is a highly irritated lesion with hyper-parakeratosis and dermal chronic lichenoid inflammation.
Squamous cell papilloma. Clinical appearance in a 51 year old woman with a papillomatous skin lesion on the upper right eyelid.

Q: Clinically, Squamous Cell Papilloma frequently presents as a sessile or pedunculated, soft skin lesion with a characteristic wart-like or [...] surface.
Squamous cell papilloma. Clinical appearance in a 51 year old woman with a papillomatous skin lesion on the upper right eyelid.
A: verrucous
Back Extra: Squamous Cell Papilloma
- Clinical: Squamous cell papilloma is a sessile or pedunculated soft, smooth lesion, often multiple, with a verrucous or keratin crust and can occur at any age without sex predilection.
- Micro: Microscopically, it is a verrucous, broad-based or finger-like exophytic epithelial neoplasm with a fibrovascular core, hyper-parakeratosis, and absence of dysplasia or dermal invasion.
- Ancillary: HPV cytopathic signs, such as koilocytes or double nuclei, may be present, but ancillary studies are not typically required for diagnosis.
Reference Gallery:
Squamous papilloma. The epidermis is hyperplastic with papillomatous and acanthosis.
Squamous cell papilloma. High magnification shows absence of epidermal dysplasia, mitosis or dermal invasion. This is a highly irritated lesion with hyper-parakeratosis and dermal chronic lichenoid inflammation.
Squamous cell papilloma. Clinical appearance in a 51 year old woman with a papillomatous skin lesion on the upper right eyelid.

Q: A key histologic feature of Squamous Cell Papilloma is the complete absence of epidermal [...] or dermal invasion, distinguishing it from malignant squamous lesions.
Squamous cell papilloma. High magnification shows absence of epidermal dysplasia, mitosis or dermal invasion. This is a highly irritated lesion with hyper-parakeratosis and dermal chronic lichenoid inflammation.
A: dysplasia
Back Extra: Squamous Cell Papilloma
- Clinical: Squamous cell papilloma is a sessile or pedunculated soft, smooth lesion, often multiple, with a verrucous or keratin crust and can occur at any age without sex predilection.
- Micro: Microscopically, it is a verrucous, broad-based or finger-like exophytic epithelial neoplasm with a fibrovascular core, hyper-parakeratosis, and absence of dysplasia or dermal invasion.
- Ancillary: HPV cytopathic signs, such as koilocytes or double nuclei, may be present, but ancillary studies are not typically required for diagnosis.
Reference Gallery:
Squamous papilloma. The epidermis is hyperplastic with papillomatous and acanthosis.
Squamous cell papilloma. High magnification shows absence of epidermal dysplasia, mitosis or dermal invasion. This is a highly irritated lesion with hyper-parakeratosis and dermal chronic lichenoid inflammation.
Squamous cell papilloma. Clinical appearance in a 51 year old woman with a papillomatous skin lesion on the upper right eyelid.

Q: Clinically presenting as single or multiple keratotic papules or plaques, this common cutaneous lesion (seen here on a child's upper eyelid) is known as [...].
Verruca vulgaris. Typical verruca vulgaris on upper eyelid in child
A: Verruca vulgaris
Back Extra: Verruca vulgaris
- Clinical: Verruca vulgaris presents as single or multiple papules, keratotic plaques, and nodules, most ranging between 1 to 20 mm in size.
- Micro: Characterized by papillomatous epidermal projections tipped by columns of parakeratosis, hyperkeratosis, and koilocytes.
- Ancillary: Not relevant; the diagnosis is primarily based on clinical and microscopic features.
Reference Gallery:
Verruca vulgaris. Typical verruca vulgaris on upper eyelid in child
Verruca vulgaris. Epidermal lesion showing hyperkeratosis, acanthosis and papillomatosis.
Verruca vulgaris. There is parakeratosis and koilocytosis, some cells containing coarse keratohyaline granules.

Q: In Verruca vulgaris, the superficial epidermis contains characteristic virally altered squamous cells with perinuclear halos and coarse keratohyaline granules, known as [...].
Verruca vulgaris. There is parakeratosis and koilocytosis, some cells containing coarse keratohyaline granules.
A: koilocytes
Back Extra: Verruca vulgaris
- Clinical: Verruca vulgaris presents as single or multiple papules, keratotic plaques, and nodules, most ranging between 1 to 20 mm in size.
- Micro: Characterized by papillomatous epidermal projections tipped by columns of parakeratosis, hyperkeratosis, and koilocytes.
- Ancillary: Not relevant; the diagnosis is primarily based on clinical and microscopic features.
Reference Gallery:
Verruca vulgaris. Typical verruca vulgaris on upper eyelid in child
Verruca vulgaris. Epidermal lesion showing hyperkeratosis, acanthosis and papillomatosis.
Verruca vulgaris. There is parakeratosis and koilocytosis, some cells containing coarse keratohyaline granules.

Q: Microscopically, [...] is characteristically defined by marked papillomatous epidermal projections tipped by columns of parakeratosis and hyperkeratosis.
Verruca vulgaris. Epidermal lesion showing hyperkeratosis, acanthosis and papillomatosis.
A: Verruca vulgaris
Back Extra: Verruca vulgaris
- Clinical: Verruca vulgaris presents as single or multiple papules, keratotic plaques, and nodules, most ranging between 1 to 20 mm in size.
- Micro: Characterized by papillomatous epidermal projections tipped by columns of parakeratosis, hyperkeratosis, and koilocytes.
- Ancillary: Not relevant; the diagnosis is primarily based on clinical and microscopic features.
Reference Gallery:
Verruca vulgaris. Typical verruca vulgaris on upper eyelid in child
Verruca vulgaris. Epidermal lesion showing hyperkeratosis, acanthosis and papillomatosis.
Verruca vulgaris. There is parakeratosis and koilocytosis, some cells containing coarse keratohyaline granules.

Q: Histopathology of Basal Cell Carcinoma characteristically demonstrates islands of basaloid cells featuring a contraction artifact (clefting) and [...] at the borders of the tumor nests.
Basal cell carcinoma, nodular. There are islands of basaloid cells with peripheral palisading and clefting from the adjacent tumour stroma.
A: peripheral palisading
Back Extra: Basal Cell Carcinoma
- Clinical: Basal Cell Carcinoma (BCC) is the most common eyelid malignancy, predominantly found in sun-exposed areas, with the lower eyelid being the most frequent site (65%).
- Micro: Histopathology of BCC shows islands and nests of basaloid cells with peripheral palisading and contraction artifact to the dermis, often connected to the epidermis.
- Ancillary: Genetic studies may show mutations in the PTCH1 gene and LOH, with P53 mutations also being frequent (44-65%).
Reference Gallery:
Periocular basal cell carcinoma. A 45-year-old male presented with pigmented basal cell carcinoma at the medial canthus of the right eye
Basal cell carcinoma, nodular. Histopathology shows a nodular basaloid epithelial tumour arising from the epidermis and invading the dermis (stroma).
Basal cell carcinoma, nodular. There are islands of basaloid cells with peripheral palisading and clefting from the adjacent tumour stroma.
Basal cell carcinoma. A: Axial T1 post-contrast MRI shows tumor involving the left eyelid, lateral canthus, and periorbital soft tissues (arrow). B: Axial CT with contrast in a different patient shows recurrent tumor in the left upper eyelid (arrow).
Basal cell carcinoma. A, B: Axial and coronal T1 post-contrast MRIs show tumor involving the right premaxillary soft tissues with post-septal extension inferior to the globe (arrows).
Basal cell carcinoma, superficial. Superficial basaloid small nests attached to epidermis on actinic damaged skin with elastoid degeneration.
Basal cell carcinoma, superficial. Small superficial nests of basaloid cells with peripheral palisading and contraction artefact to the dermis.
Recurrent basal cell carcinoma, diffuse infiltrative. Small nest without palisading and single cells infiltrating the subcutaneous tissue.

Q: In Basal Cell Carcinoma, the characteristic histologic appearance consists of basaloid cell nests that demonstrate peripheral palisading and a clear separation from the surrounding dermis known as a [...] (clefting).
Basal cell carcinoma, superficial. Small superficial nests of basaloid cells with peripheral palisading and contraction artefact to the dermis.
A: contraction artifact
Back Extra: Basal Cell Carcinoma
- Clinical: Basal Cell Carcinoma (BCC) is the most common eyelid malignancy, predominantly found in sun-exposed areas, with the lower eyelid being the most frequent site (65%).
- Micro: Histopathology of BCC shows islands and nests of basaloid cells with peripheral palisading and contraction artifact to the dermis, often connected to the epidermis.
- Ancillary: Genetic studies may show mutations in the PTCH1 gene and LOH, with P53 mutations also being frequent (44-65%).
Reference Gallery:
Periocular basal cell carcinoma. A 45-year-old male presented with pigmented basal cell carcinoma at the medial canthus of the right eye
Basal cell carcinoma, nodular. Histopathology shows a nodular basaloid epithelial tumour arising from the epidermis and invading the dermis (stroma).
Basal cell carcinoma, nodular. There are islands of basaloid cells with peripheral palisading and clefting from the adjacent tumour stroma.
Basal cell carcinoma. A: Axial T1 post-contrast MRI shows tumor involving the left eyelid, lateral canthus, and periorbital soft tissues (arrow). B: Axial CT with contrast in a different patient shows recurrent tumor in the left upper eyelid (arrow).
Basal cell carcinoma. A, B: Axial and coronal T1 post-contrast MRIs show tumor involving the right premaxillary soft tissues with post-septal extension inferior to the globe (arrows).
Basal cell carcinoma, superficial. Superficial basaloid small nests attached to epidermis on actinic damaged skin with elastoid degeneration.
Basal cell carcinoma, superficial. Small superficial nests of basaloid cells with peripheral palisading and contraction artefact to the dermis.
Recurrent basal cell carcinoma, diffuse infiltrative. Small nest without palisading and single cells infiltrating the subcutaneous tissue.

Q: A classic microscopic finding in Basal Cell Carcinoma is the presence of nodular or superficial islands composed of [...] cells arising from the epidermis and invading the underlying tumor stroma.
Basal cell carcinoma, nodular. Histopathology shows a nodular basaloid epithelial tumour arising from the epidermis and invading the dermis (stroma).
Basal cell carcinoma, superficial. Superficial basaloid small nests attached to epidermis on actinic damaged skin with elastoid degeneration.
A: basaloid
Back Extra: Basal Cell Carcinoma
- Clinical: Basal Cell Carcinoma (BCC) is the most common eyelid malignancy, predominantly found in sun-exposed areas, with the lower eyelid being the most frequent site (65%).
- Micro: Histopathology of BCC shows islands and nests of basaloid cells with peripheral palisading and contraction artifact to the dermis, often connected to the epidermis.
- Ancillary: Genetic studies may show mutations in the PTCH1 gene and LOH, with P53 mutations also being frequent (44-65%).
Reference Gallery:
Periocular basal cell carcinoma. A 45-year-old male presented with pigmented basal cell carcinoma at the medial canthus of the right eye
Basal cell carcinoma, nodular. Histopathology shows a nodular basaloid epithelial tumour arising from the epidermis and invading the dermis (stroma).
Basal cell carcinoma, nodular. There are islands of basaloid cells with peripheral palisading and clefting from the adjacent tumour stroma.
Basal cell carcinoma. A: Axial T1 post-contrast MRI shows tumor involving the left eyelid, lateral canthus, and periorbital soft tissues (arrow). B: Axial CT with contrast in a different patient shows recurrent tumor in the left upper eyelid (arrow).
Basal cell carcinoma. A, B: Axial and coronal T1 post-contrast MRIs show tumor involving the right premaxillary soft tissues with post-septal extension inferior to the globe (arrows).
Basal cell carcinoma, superficial. Superficial basaloid small nests attached to epidermis on actinic damaged skin with elastoid degeneration.
Basal cell carcinoma, superficial. Small superficial nests of basaloid cells with peripheral palisading and contraction artefact to the dermis.
Recurrent basal cell carcinoma, diffuse infiltrative. Small nest without palisading and single cells infiltrating the subcutaneous tissue.

Q: A rapidly growing, reddish-blue eyelid nodule that histologically shows a high-grade small blue cell tumor with finely granular chromatin, scant cytoplasm, and numerous mitotic figures is highly characteristic of [...].
Clinical photo shows a reddish solitary nodule in the right upper eyelid margin.
Tumour cells are characterized by scant cytoplasm and indistinct cellular membranes. Nuclei have finely dispersed chromatin and nucleoli are inconspicuous. Numerous mitotic figures and pyknotic nuclei are observed.
A: Merkel cell carcinoma
Back Extra: Merkel cell carcinoma
- Clinical: Merkel cell carcinoma presents as a rapidly growing, indurated reddish-blue nodule on sun-exposed skin, often painless and with occasional ulceration. Eyelid tumours can be misdiagnosed as chalazion, delaying diagnosis.
- Micro: High-grade small blue cell neoplasm with uniform cells, round/oval nuclei, scant cytoplasm, and finely granular chromatin. Sheets of tumour cells infiltrate the dermis and subcutaneous tissue, with numerous mitotic figures.
- Ancillary: Immunohistochemistry shows positivity for CK20, chromogranin, and synaptophysin, and negativity for CK7 and TTF1. PCR for Merkel cell polyomavirus (MCV) is positive in most cases.
Reference Gallery:
Clinical photo shows a reddish solitary nodule in the right upper eyelid margin.
Tumour cells are characterized by scant cytoplasm and indistinct cellular membranes. Nuclei have finely dispersed chromatin and nucleoli are inconspicuous. Numerous mitotic figures and pyknotic nuclei are observed.
Perinuclear dot-like pattern observed with CK20 immunohistochemistry.
Diffuse cytoplasmic staining with synaptophysin immunohistochemistry.
Nuclear positivity with Merkel cell polyoma virus immunohistochemistry.
Clinical image of a Merkel cell carcinoma.
A: Axial CT with contrast shows a protuberant mass in the right lower eyelid (arrow). B: 18F-FDG PET/CT shows FDG avidity of the mass (arrow).

Q: In Merkel cell carcinoma, immunohistochemical staining for CK20 characteristically displays a [...] pattern.
Perinuclear dot-like pattern observed with CK20 immunohistochemistry.
A: perinuclear dot-like
Back Extra: Merkel cell carcinoma
- Clinical: Merkel cell carcinoma presents as a rapidly growing, indurated reddish-blue nodule on sun-exposed skin, often painless and with occasional ulceration. Eyelid tumours can be misdiagnosed as chalazion, delaying diagnosis.
- Micro: High-grade small blue cell neoplasm with uniform cells, round/oval nuclei, scant cytoplasm, and finely granular chromatin. Sheets of tumour cells infiltrate the dermis and subcutaneous tissue, with numerous mitotic figures.
- Ancillary: Immunohistochemistry shows positivity for CK20, chromogranin, and synaptophysin, and negativity for CK7 and TTF1. PCR for Merkel cell polyomavirus (MCV) is positive in most cases.
Reference Gallery:
Clinical photo shows a reddish solitary nodule in the right upper eyelid margin.
Tumour cells are characterized by scant cytoplasm and indistinct cellular membranes. Nuclei have finely dispersed chromatin and nucleoli are inconspicuous. Numerous mitotic figures and pyknotic nuclei are observed.
Perinuclear dot-like pattern observed with CK20 immunohistochemistry.
Diffuse cytoplasmic staining with synaptophysin immunohistochemistry.
Nuclear positivity with Merkel cell polyoma virus immunohistochemistry.
Clinical image of a Merkel cell carcinoma.
A: Axial CT with contrast shows a protuberant mass in the right lower eyelid (arrow). B: 18F-FDG PET/CT shows FDG avidity of the mass (arrow).

Q: The pathogenesis of most cases of Merkel cell carcinoma is intimately associated with infection by [...], which can be detected via PCR or demonstrated as distinct nuclear positivity on immunohistochemistry.
Nuclear positivity with Merkel cell polyoma virus immunohistochemistry.
A: Merkel cell polyomavirus
Back Extra: Merkel cell carcinoma
- Clinical: Merkel cell carcinoma presents as a rapidly growing, indurated reddish-blue nodule on sun-exposed skin, often painless and with occasional ulceration. Eyelid tumours can be misdiagnosed as chalazion, delaying diagnosis.
- Micro: High-grade small blue cell neoplasm with uniform cells, round/oval nuclei, scant cytoplasm, and finely granular chromatin. Sheets of tumour cells infiltrate the dermis and subcutaneous tissue, with numerous mitotic figures.
- Ancillary: Immunohistochemistry shows positivity for CK20, chromogranin, and synaptophysin, and negativity for CK7 and TTF1. PCR for Merkel cell polyomavirus (MCV) is positive in most cases.
Reference Gallery:
Clinical photo shows a reddish solitary nodule in the right upper eyelid margin.
Tumour cells are characterized by scant cytoplasm and indistinct cellular membranes. Nuclei have finely dispersed chromatin and nucleoli are inconspicuous. Numerous mitotic figures and pyknotic nuclei are observed.
Perinuclear dot-like pattern observed with CK20 immunohistochemistry.
Diffuse cytoplasmic staining with synaptophysin immunohistochemistry.
Nuclear positivity with Merkel cell polyoma virus immunohistochemistry.
Clinical image of a Merkel cell carcinoma.
A: Axial CT with contrast shows a protuberant mass in the right lower eyelid (arrow). B: 18F-FDG PET/CT shows FDG avidity of the mass (arrow).

Q: Microscopically, well-differentiated Squamous Cell Carcinoma features infiltrating tumor cells with abundant eosinophilic cytoplasm, dyskeratosis, and the pathognomonic presence of [...].
Squamous cell carcinoma. A well-differentiated squamous cell carcinoma arranged in solid areas with pushing borders.
Squamous cell carcinoma. A diffusely infiltrating tumour consisting of cells with abundant eosinophilic cytoplasm and hyperchromatic nuclei, dyskeratosis and preserved intercellular bridges.
A: intercellular bridges
Back Extra: Squamous Cell Carcinoma
- Clinical: SCC of the eyelid is usually painless and presents as an indurated plaque or nodule with keratinization, central ulceration, and rolled out irregular borders.
- Micro: Well-differentiated SCC shows cells with abundant eosinophilic cytoplasm, hyperchromatic nuclei, dyskeratosis, and preserved intercellular bridges.
- Ancillary: Overexpression of EGFR and PD-L1 is often noted in SCC and can be clinically relevant for targeted therapy.
Reference Gallery:
Squamous cell carcinoma. A resection specimen of a large squamous cell carcinoma of the lower eyelid, with histology in << #37954>>.
Squamous cell carcinoma. A well-differentiated squamous cell carcinoma arranged in solid areas with pushing borders.
Squamous cell carcinoma. A diffusely infiltrating tumour consisting of cells with abundant eosinophilic cytoplasm and hyperchromatic nuclei, dyskeratosis and preserved intercellular bridges.
Squamous cell carcinoma. A clinical image of an ulcerated SCC of the lower eyelid.
Squamous cell carcinoma. Clinical appearance of a lower eyelid lesion. Note the rolled edge and central ulceration

Q: Clinically, an eyelid Squamous Cell Carcinoma often presents as an indurated, painless plaque or nodule characterized by irregular rolled-out edges and [...].
Squamous cell carcinoma. A clinical image of an ulcerated SCC of the lower eyelid.
Squamous cell carcinoma. Clinical appearance of a lower eyelid lesion. Note the rolled edge and central ulceration
A: central ulceration
Back Extra: Squamous Cell Carcinoma
- Clinical: SCC of the eyelid is usually painless and presents as an indurated plaque or nodule with keratinization, central ulceration, and rolled out irregular borders.
- Micro: Well-differentiated SCC shows cells with abundant eosinophilic cytoplasm, hyperchromatic nuclei, dyskeratosis, and preserved intercellular bridges.
- Ancillary: Overexpression of EGFR and PD-L1 is often noted in SCC and can be clinically relevant for targeted therapy.
Reference Gallery:
Squamous cell carcinoma. A resection specimen of a large squamous cell carcinoma of the lower eyelid, with histology in << #37954>>.
Squamous cell carcinoma. A well-differentiated squamous cell carcinoma arranged in solid areas with pushing borders.
Squamous cell carcinoma. A diffusely infiltrating tumour consisting of cells with abundant eosinophilic cytoplasm and hyperchromatic nuclei, dyskeratosis and preserved intercellular bridges.
Squamous cell carcinoma. A clinical image of an ulcerated SCC of the lower eyelid.
Squamous cell carcinoma. Clinical appearance of a lower eyelid lesion. Note the rolled edge and central ulceration

Q: Patients with BAP1 Tumor Predisposition Syndrome typically present with characteristic nevi that show dermal clones of large, unpigmented [...] melanocytes with mild atypia.
BAP1 inactiivated naevus. A dermal clone within a common compound naevus (Haematoxylin Eosin Safranin).
BAP1 inactivated naevus. High power view of a dermal clone made of large unpigmented epitheloid melanocytes with mild atypia (Haematoxylin Eosin Safranin).
A: epithelioid
Back Extra: BAP1 Tumor Predisposition Syndrome
- Clinical: BAP1 Tumor Predisposition Syndrome is characterized by an increased risk of uveal melanoma, mesothelioma, cutaneous melanoma, and renal cell carcinoma.
- Micro: Histopathology of BAP1 inactivated naevi shows large unpigmented epitheloid melanocytes with mild atypia and loss of nuclear BAP1 expression.
- Ancillary: Genetic testing for BAP1 mutations and loss of BAP1 immunoreactivity in tumour nuclei are key diagnostic tools for BAP1 Tumor Predisposition Syndrome.
Reference Gallery:
BAP1 inactiivated naevus. A dermal clone within a common compound naevus (Haematoxylin Eosin Safranin).
BAP1 inactivated naevus. High power view of a dermal clone made of large unpigmented epitheloid melanocytes with mild atypia (Haematoxylin Eosin Safranin).
BAP1 inactivated naevus. Loss of nuclear expression of BAP1 in the dermal epithelioid clone. Adjacent naevus retains expression.
BAP1-inactivated naevus. Loss of nuclear expression of BAP1 in the dermal epithelioid clone. Adjacent naevus retains expression.
Uveal melanoma. A uveal melanoma from a patient with the c.1938T>A, p.Tyr646* nonsense germline BAP1 mutation. A highly vascular tumour with heavily pigmented spindle tumour cells. Large areas of necrosis were observed (not shown). The tumour metastasized to liver and other organs.
Uveal melanoma. A uveal melanoma from a patient with the c. 799 C>T, p.G267* nonsense germline BAP1 mutation. Tumour cells were mostly epithelioid. The tumour metastasized to the liver and other organs.

Q: In BAP1 Tumor Predisposition Syndrome, immunohistochemistry of characteristic nevi and tumors demonstrates a diagnostic loss of nuclear expression of [...] within the neoplastic cells.
BAP1 inactivated naevus. Loss of nuclear expression of BAP1 in the dermal epithelioid clone. Adjacent naevus retains expression.
BAP1-inactivated naevus. Loss of nuclear expression of BAP1 in the dermal epithelioid clone. Adjacent naevus retains expression.
A: BAP1
Back Extra: BAP1 Tumor Predisposition Syndrome
- Clinical: BAP1 Tumor Predisposition Syndrome is characterized by an increased risk of uveal melanoma, mesothelioma, cutaneous melanoma, and renal cell carcinoma.
- Micro: Histopathology of BAP1 inactivated naevi shows large unpigmented epitheloid melanocytes with mild atypia and loss of nuclear BAP1 expression.
- Ancillary: Genetic testing for BAP1 mutations and loss of BAP1 immunoreactivity in tumour nuclei are key diagnostic tools for BAP1 Tumor Predisposition Syndrome.
Reference Gallery:
BAP1 inactiivated naevus. A dermal clone within a common compound naevus (Haematoxylin Eosin Safranin).
BAP1 inactivated naevus. High power view of a dermal clone made of large unpigmented epitheloid melanocytes with mild atypia (Haematoxylin Eosin Safranin).
BAP1 inactivated naevus. Loss of nuclear expression of BAP1 in the dermal epithelioid clone. Adjacent naevus retains expression.
BAP1-inactivated naevus. Loss of nuclear expression of BAP1 in the dermal epithelioid clone. Adjacent naevus retains expression.
Uveal melanoma. A uveal melanoma from a patient with the c.1938T>A, p.Tyr646* nonsense germline BAP1 mutation. A highly vascular tumour with heavily pigmented spindle tumour cells. Large areas of necrosis were observed (not shown). The tumour metastasized to liver and other organs.
Uveal melanoma. A uveal melanoma from a patient with the c. 799 C>T, p.G267* nonsense germline BAP1 mutation. Tumour cells were mostly epithelioid. The tumour metastasized to the liver and other organs.

Q: A hallmark malignancy strongly associated with BAP1 Tumor Predisposition Syndrome, occurring alongside an increased risk of mesothelioma and renal cell carcinoma, is [...].
Uveal melanoma. A uveal melanoma from a patient with the c.1938T>A, p.Tyr646* nonsense germline BAP1 mutation. A highly vascular tumour with heavily pigmented spindle tumour cells. Large areas of necrosis were observed (not shown). The tumour metastasized to liver and other organs.
Uveal melanoma. A uveal melanoma from a patient with the c. 799 C>T, p.G267* nonsense germline BAP1 mutation. Tumour cells were mostly epithelioid. The tumour metastasized to the liver and other organs.
A: uveal melanoma
Back Extra: BAP1 Tumor Predisposition Syndrome
- Clinical: BAP1 Tumor Predisposition Syndrome is characterized by an increased risk of uveal melanoma, mesothelioma, cutaneous melanoma, and renal cell carcinoma.
- Micro: Histopathology of BAP1 inactivated naevi shows large unpigmented epitheloid melanocytes with mild atypia and loss of nuclear BAP1 expression.
- Ancillary: Genetic testing for BAP1 mutations and loss of BAP1 immunoreactivity in tumour nuclei are key diagnostic tools for BAP1 Tumor Predisposition Syndrome.
Reference Gallery:
BAP1 inactiivated naevus. A dermal clone within a common compound naevus (Haematoxylin Eosin Safranin).
BAP1 inactivated naevus. High power view of a dermal clone made of large unpigmented epitheloid melanocytes with mild atypia (Haematoxylin Eosin Safranin).
BAP1 inactivated naevus. Loss of nuclear expression of BAP1 in the dermal epithelioid clone. Adjacent naevus retains expression.
BAP1-inactivated naevus. Loss of nuclear expression of BAP1 in the dermal epithelioid clone. Adjacent naevus retains expression.
Uveal melanoma. A uveal melanoma from a patient with the c.1938T>A, p.Tyr646* nonsense germline BAP1 mutation. A highly vascular tumour with heavily pigmented spindle tumour cells. Large areas of necrosis were observed (not shown). The tumour metastasized to liver and other organs.
Uveal melanoma. A uveal melanoma from a patient with the c. 799 C>T, p.G267* nonsense germline BAP1 mutation. Tumour cells were mostly epithelioid. The tumour metastasized to the liver and other organs.

Q: Patients with Goldenhar Syndrome frequently develop ocular malformations such as an [...] (complex choristoma), which presents clinically as a smooth, elevated tan-pink to yellowish ocular mass.
Epibulbar complex choristoma. 6-year-old girl with Goldenhar syndrome and a superotemporal, smooth, elevated tan-pink to yellowish epibulbar mass.
A: epibulbar dermoid
Back Extra: Goldenhar Syndrome
- Clinical: Goldenhar syndrome is characterized by mandibular or hemifacial hypoplasia, ocular and auricular malformations (e.g., limbal dermoids, accessory tragi), and vertebral anomalies.
- Micro: Epibulbar dermoids in Goldenhar syndrome consist of dense subepithelial collagen bundles, dermal appendages, and may contain adipose tissue, cartilage, and lacrimal gland tissue.
- Ancillary: Genetic testing is not necessary for diagnosing Goldenhar syndrome, but heterozygous loss of function variants in SF3B2 have been identified in a subset of patients with a family history.
Reference Gallery:
Epibulbar complex choristoma. 6-year-old girl with Goldenhar syndrome and a superotemporal, smooth, elevated tan-pink to yellowish epibulbar mass.
Epibulbar complex choristoma. Beneath the conjunctival epithelium is a dense collagenous stroma containing mature adipose tissue, hyaline cartilage and lobules of lacrimal gland.

Q: Microscopically, the classic epibulbar mass associated with Goldenhar Syndrome is a complex [...], characterized by normal tissues in an abnormal location such as mature adipose tissue, hyaline cartilage, and lacrimal gland.
Epibulbar complex choristoma. Beneath the conjunctival epithelium is a dense collagenous stroma containing mature adipose tissue, hyaline cartilage and lobules of lacrimal gland.
A: choristoma
Back Extra: Goldenhar Syndrome
- Clinical: Goldenhar syndrome is characterized by mandibular or hemifacial hypoplasia, ocular and auricular malformations (e.g., limbal dermoids, accessory tragi), and vertebral anomalies.
- Micro: Epibulbar dermoids in Goldenhar syndrome consist of dense subepithelial collagen bundles, dermal appendages, and may contain adipose tissue, cartilage, and lacrimal gland tissue.
- Ancillary: Genetic testing is not necessary for diagnosing Goldenhar syndrome, but heterozygous loss of function variants in SF3B2 have been identified in a subset of patients with a family history.
Reference Gallery:
Epibulbar complex choristoma. 6-year-old girl with Goldenhar syndrome and a superotemporal, smooth, elevated tan-pink to yellowish epibulbar mass.
Epibulbar complex choristoma. Beneath the conjunctival epithelium is a dense collagenous stroma containing mature adipose tissue, hyaline cartilage and lobules of lacrimal gland.

Q: Patients with Muir-Torre Syndrome classically present with visceral malignancies (e.g., colorectal or endometrial cancer) concurrent with characteristic cutaneous manifestations, most notably [...] neoplasms and keratoacanthomas.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. A circumscribed lesion protrudes from the Meibomian gland orifice.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Yellow-pink nodule involves the posterior lamella of the eyelid margin adjacent to the lacrimal punctum.
A: sebaceous
Back Extra: Muir-Torre Syndrome
- Clinical: Muir-Torre Syndrome is characterized by the presence of cutaneous manifestations such as sebaceous neoplasms and keratoacanthoma, often before or concurrent with visceral malignancies like colorectal and endometrial cancers.
- Micro: Histopathology of sebaceous neoplasms in Muir-Torre Syndrome can show a lack of normal maturation within the lobules and a predominance of immature sebocytes.
- Ancillary: Immunohistochemistry (IHC) for MMR proteins (MLH1, MSH2, MSH6, PMS2) is crucial in diagnosing Muir-Torre Syndrome, with loss of nuclear expression in the lesional cells being a key finding.
Reference Gallery:
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Papillomatous tarsal conjunctival mass
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. A circumscribed lesion protrudes from the Meibomian gland orifice.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Papillomatous lesion composed of enlarged and haphazardly arranged sebaceous gland lobules with immature sebocytes predominating over mature sebocytes.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Lack of normal maturation within the lobules of sebaceoma.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Intact nuclear expression of PMS2 within the lesional cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Intact nuclear expression of MLH1 within the lesional cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Loss of nuclear MSH6 expression in lesional cells with preservation of staining in the stromal cells and inflammatory cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Wild-type expression of p53.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Yellow-pink nodule involves the posterior lamella of the eyelid margin adjacent to the lacrimal punctum.
Sebaceous adenoma in a patient with Muir-Torre syndrome. A circumscribed neoplasm composed of enlarged, irregular sebaceous gland lobules with prominent central holocrine secretion, contributing to a cystic architecture. Mature sebocytes predominate over the immature sebocytes, when compared to the normal adjacent sebaceous gland lobules.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Loss of nuclear MSH2 in the neoplastic cells with preservation of staining in the tumour-infiltrating lymphocytes, adjacent stroma, normal adjacent sebaceous glands, and the overlying conjunctival epithelium.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Intact nuclear PMS2 in the lesion and the adjacent tissues.

Q: The diagnosis of Muir-Torre Syndrome is heavily supported when immunohistochemistry of the patient's cutaneous neoplasms reveals a loss of nuclear expression for [...] proteins.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Loss of nuclear MSH6 expression in lesional cells with preservation of staining in the stromal cells and inflammatory cells.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Loss of nuclear MSH2 in the neoplastic cells with preservation of staining in the tumour-infiltrating lymphocytes, adjacent stroma, normal adjacent sebaceous glands, and the overlying conjunctival epithelium.
A: mismatch repair (MMR)
Back Extra: Muir-Torre Syndrome
- Clinical: Muir-Torre Syndrome is characterized by the presence of cutaneous manifestations such as sebaceous neoplasms and keratoacanthoma, often before or concurrent with visceral malignancies like colorectal and endometrial cancers.
- Micro: Histopathology of sebaceous neoplasms in Muir-Torre Syndrome can show a lack of normal maturation within the lobules and a predominance of immature sebocytes.
- Ancillary: Immunohistochemistry (IHC) for MMR proteins (MLH1, MSH2, MSH6, PMS2) is crucial in diagnosing Muir-Torre Syndrome, with loss of nuclear expression in the lesional cells being a key finding.
Reference Gallery:
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Papillomatous tarsal conjunctival mass
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. A circumscribed lesion protrudes from the Meibomian gland orifice.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Papillomatous lesion composed of enlarged and haphazardly arranged sebaceous gland lobules with immature sebocytes predominating over mature sebocytes.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Lack of normal maturation within the lobules of sebaceoma.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Intact nuclear expression of PMS2 within the lesional cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Intact nuclear expression of MLH1 within the lesional cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Loss of nuclear MSH6 expression in lesional cells with preservation of staining in the stromal cells and inflammatory cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Wild-type expression of p53.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Yellow-pink nodule involves the posterior lamella of the eyelid margin adjacent to the lacrimal punctum.
Sebaceous adenoma in a patient with Muir-Torre syndrome. A circumscribed neoplasm composed of enlarged, irregular sebaceous gland lobules with prominent central holocrine secretion, contributing to a cystic architecture. Mature sebocytes predominate over the immature sebocytes, when compared to the normal adjacent sebaceous gland lobules.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Loss of nuclear MSH2 in the neoplastic cells with preservation of staining in the tumour-infiltrating lymphocytes, adjacent stroma, normal adjacent sebaceous glands, and the overlying conjunctival epithelium.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Intact nuclear PMS2 in the lesion and the adjacent tissues.

Q: Histologically, sebaceous epitheliomas (sebaceomas) associated with Muir-Torre Syndrome demonstrate a lack of normal maturation within the lobules and a predominance of [...] sebocytes.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Papillomatous lesion composed of enlarged and haphazardly arranged sebaceous gland lobules with immature sebocytes predominating over mature sebocytes.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Lack of normal maturation within the lobules of sebaceoma.
A: immature
Back Extra: Muir-Torre Syndrome
- Clinical: Muir-Torre Syndrome is characterized by the presence of cutaneous manifestations such as sebaceous neoplasms and keratoacanthoma, often before or concurrent with visceral malignancies like colorectal and endometrial cancers.
- Micro: Histopathology of sebaceous neoplasms in Muir-Torre Syndrome can show a lack of normal maturation within the lobules and a predominance of immature sebocytes.
- Ancillary: Immunohistochemistry (IHC) for MMR proteins (MLH1, MSH2, MSH6, PMS2) is crucial in diagnosing Muir-Torre Syndrome, with loss of nuclear expression in the lesional cells being a key finding.
Reference Gallery:
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Papillomatous tarsal conjunctival mass
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. A circumscribed lesion protrudes from the Meibomian gland orifice.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Papillomatous lesion composed of enlarged and haphazardly arranged sebaceous gland lobules with immature sebocytes predominating over mature sebocytes.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Lack of normal maturation within the lobules of sebaceoma.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Intact nuclear expression of PMS2 within the lesional cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Intact nuclear expression of MLH1 within the lesional cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Loss of nuclear MSH6 expression in lesional cells with preservation of staining in the stromal cells and inflammatory cells.
Sebaceous epithelioma (sebaceoma) in a patient with Muir-Torre syndrome. Wild-type expression of p53.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Yellow-pink nodule involves the posterior lamella of the eyelid margin adjacent to the lacrimal punctum.
Sebaceous adenoma in a patient with Muir-Torre syndrome. A circumscribed neoplasm composed of enlarged, irregular sebaceous gland lobules with prominent central holocrine secretion, contributing to a cystic architecture. Mature sebocytes predominate over the immature sebocytes, when compared to the normal adjacent sebaceous gland lobules.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Loss of nuclear MSH2 in the neoplastic cells with preservation of staining in the tumour-infiltrating lymphocytes, adjacent stroma, normal adjacent sebaceous glands, and the overlying conjunctival epithelium.
Sebaceous adenoma in a patient with Muir-Torre syndrome. Intact nuclear PMS2 in the lesion and the adjacent tissues.

Q: Patients with Neurofibromatosis Type 1 frequently develop [...], which are small hamartomas characterized by bland melanocytes on the anterior surface of the iris.
Lisch nodules. Lisch nodules are small hamartomas that involve the anterior surface of the iris and are present in the majority of patients with NF1 at some point.
A: Lisch nodules
Back Extra: Neurofibromatosis Type 1
- Clinical: Multiple café-au-lait macules and Lisch nodules are common in patients with Neurofibromatosis Type 1 (NF1).
- Micro: Lisch nodules in NF1 are characterized by spindle-shaped, cytologically bland melanocytes on the anterior face of the iris.
- Ancillary: Genetic testing for NF1 includes sequencing and deletion/duplication analysis to identify pathogenic variants.
Reference Gallery:
Pilocytic astrocytoma of the optic nerve. Coronal T1-weighted MRI demonstrates an enhancing mass expanding the right optic nerve. The optic nerve is a favored site for glioma development in patients with NF1.
Choroidal abnormalities in NF1. A near-infrared (NIR) image of the posterior pole of a patient affected by neurofibromatosis type 1 (A), showing multiple choroidal abnormalities (CAs), indicated by red arrows. CAs, histologically consisting of variable mixtures of hyperplastic Schwann cells, melanocytes and ganglion cells localized into the choroid, are completely asymptomatic and undetectable by conventional ophthalmoscopy, as shown in the color fundus image in B, representing the same eye of A. Note that several retinal vascular abnormalities (RVAs) are also present.
Lisch nodules. Lisch nodules are small hamartomas that involve the anterior surface of the iris and are present in the majority of patients with NF1 at some point.

Q: In Neurofibromatosis Type 1, the [...] is a favored site for glioma development, which classically manifests as a pilocytic astrocytoma.
Pilocytic astrocytoma of the optic nerve. Coronal T1-weighted MRI demonstrates an enhancing mass expanding the right optic nerve. The optic nerve is a favored site for glioma development in patients with NF1.
A: optic nerve
Back Extra: Neurofibromatosis Type 1
- Clinical: Multiple café-au-lait macules and Lisch nodules are common in patients with Neurofibromatosis Type 1 (NF1).
- Micro: Lisch nodules in NF1 are characterized by spindle-shaped, cytologically bland melanocytes on the anterior face of the iris.
- Ancillary: Genetic testing for NF1 includes sequencing and deletion/duplication analysis to identify pathogenic variants.
Reference Gallery:
Pilocytic astrocytoma of the optic nerve. Coronal T1-weighted MRI demonstrates an enhancing mass expanding the right optic nerve. The optic nerve is a favored site for glioma development in patients with NF1.
Choroidal abnormalities in NF1. A near-infrared (NIR) image of the posterior pole of a patient affected by neurofibromatosis type 1 (A), showing multiple choroidal abnormalities (CAs), indicated by red arrows. CAs, histologically consisting of variable mixtures of hyperplastic Schwann cells, melanocytes and ganglion cells localized into the choroid, are completely asymptomatic and undetectable by conventional ophthalmoscopy, as shown in the color fundus image in B, representing the same eye of A. Note that several retinal vascular abnormalities (RVAs) are also present.
Lisch nodules. Lisch nodules are small hamartomas that involve the anterior surface of the iris and are present in the majority of patients with NF1 at some point.

Q: Patients with Neurofibromatosis Type 1 often have asymptomatic [...] (composed of hyperplastic Schwann cells and melanocytes) that are typically undetectable by conventional ophthalmoscopy but visible on near-infrared imaging.
Choroidal abnormalities in NF1. A near-infrared (NIR) image of the posterior pole of a patient affected by neurofibromatosis type 1 (A), showing multiple choroidal abnormalities (CAs), indicated by red arrows. CAs, histologically consisting of variable mixtures of hyperplastic Schwann cells, melanocytes and ganglion cells localized into the choroid, are completely asymptomatic and undetectable by conventional ophthalmoscopy, as shown in the color fundus image in B, representing the same eye of A. Note that several retinal vascular abnormalities (RVAs) are also present.
A: choroidal abnormalities
Back Extra: Neurofibromatosis Type 1
- Clinical: Multiple café-au-lait macules and Lisch nodules are common in patients with Neurofibromatosis Type 1 (NF1).
- Micro: Lisch nodules in NF1 are characterized by spindle-shaped, cytologically bland melanocytes on the anterior face of the iris.
- Ancillary: Genetic testing for NF1 includes sequencing and deletion/duplication analysis to identify pathogenic variants.
Reference Gallery:
Pilocytic astrocytoma of the optic nerve. Coronal T1-weighted MRI demonstrates an enhancing mass expanding the right optic nerve. The optic nerve is a favored site for glioma development in patients with NF1.
Choroidal abnormalities in NF1. A near-infrared (NIR) image of the posterior pole of a patient affected by neurofibromatosis type 1 (A), showing multiple choroidal abnormalities (CAs), indicated by red arrows. CAs, histologically consisting of variable mixtures of hyperplastic Schwann cells, melanocytes and ganglion cells localized into the choroid, are completely asymptomatic and undetectable by conventional ophthalmoscopy, as shown in the color fundus image in B, representing the same eye of A. Note that several retinal vascular abnormalities (RVAs) are also present.
Lisch nodules. Lisch nodules are small hamartomas that involve the anterior surface of the iris and are present in the majority of patients with NF1 at some point.

Q: In Retinoblastoma Syndrome, the presentation of bilateral intraocular tumors combined with an intracranial midline embryonal tumor is clinically referred to as [...].
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Axial T2 weighted MRI showing an advanced intraocular retinoblastoma in the left eye and a small tumour in the temporal quadrant of the right eye.
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Axial MRI disclosed a pineal tumour.
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Sagittal MRI showing both advanced retinoblastoma of the left eye and the pinealoblastoma.
A: trilateral retinoblastoma
Back Extra: Retinoblastoma Syndrome
- Clinical: MRI of the orbits and brain is performed during the initial diagnosis of intraocular retinoblastoma to exclude extraocular extension and brain involvement with a pineoblastoma.
- Micro: The histological features of the intracranial tumour in trilateral retinoblastoma are identical to those of retinoblastoma. Pineoblastoma is a high-grade embryonal tumour (WHO grade IV).
- Ancillary: Identification of the specific RB1 gene variant and genetic counseling should be considered for any retinoblastoma patient, regardless of laterality or trilateral disease.
Reference Gallery:
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Axial T2 weighted MRI showing an advanced intraocular retinoblastoma in the left eye and a small tumour in the temporal quadrant of the right eye.
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Axial MRI disclosed a pineal tumour.
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Sagittal MRI showing both advanced retinoblastoma of the left eye and the pinealoblastoma.

Q: Initial MRI evaluation in Retinoblastoma Syndrome aims to rule out extraocular extension and the presence of an associated midline intracranial tumor, which is most often a [...].
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Axial MRI disclosed a pineal tumour.
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Sagittal MRI showing both advanced retinoblastoma of the left eye and the pinealoblastoma.
A: pineoblastoma
Back Extra: Retinoblastoma Syndrome
- Clinical: MRI of the orbits and brain is performed during the initial diagnosis of intraocular retinoblastoma to exclude extraocular extension and brain involvement with a pineoblastoma.
- Micro: The histological features of the intracranial tumour in trilateral retinoblastoma are identical to those of retinoblastoma. Pineoblastoma is a high-grade embryonal tumour (WHO grade IV).
- Ancillary: Identification of the specific RB1 gene variant and genetic counseling should be considered for any retinoblastoma patient, regardless of laterality or trilateral disease.
Reference Gallery:
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Axial T2 weighted MRI showing an advanced intraocular retinoblastoma in the left eye and a small tumour in the temporal quadrant of the right eye.
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Axial MRI disclosed a pineal tumour.
Trilateral retinoblastoma. A 6 month-old patient affected by a trilateral retinoblastoma: Sagittal MRI showing both advanced retinoblastoma of the left eye and the pinealoblastoma.

Q: A hallmark clinical finding in Sturge-Weber Syndrome is a facial capillary malformation in the distribution of the ophthalmic branch of the trigeminal nerve (V1), commonly known as a [...].
Sturge-Weber Syndrome. External facial photo of Sturge-Weber Syndrome. The Port-Wine stain is a red discoloration of the skin follows the distribution of the first branch of the trigeminal nerve and the embryonic vasculature in this area.
A: port-wine stain
Back Extra: Sturge-Weber Syndrome
- Clinical: Choroid capillary malformations (CM) in Sturge-Weber Syndrome can cause blurry, distorted, or declined vision due to choroidal thickening and retinal changes.
- Micro: In Sturge-Weber Syndrome, CM in the choroid, episclera, and conjunctiva appear as unencapsulated collections of thin-walled, variably sized vascular channels.
- Ancillary: GNAQ evaluation in affected tissue can identify a somatic heterozygous pathogenic sequence variant consistent with Sturge-Weber Syndrome.
Reference Gallery:
Choroidal haemangioma in Sturge Weber syndrome. This diffuse choroidal haemangioma is associated with extensive changes to the overlying retinal pigment epithelium and retina.
Choroidal haemangioma. Back to back dilated capillary channels in the choroid.
Sturge-Weber Syndrome. External facial photo of Sturge-Weber Syndrome. The Port-Wine stain is a red discoloration of the skin follows the distribution of the first branch of the trigeminal nerve and the embryonic vasculature in this area.
Sturge-Weber Syndrome. Conjunctival photo of Sturge-Weber Syndrome. Conjunctival and episcleral capillary malformations appear as red dilated, tortuous, and elevated vessels.

Q: In Sturge-Weber Syndrome, vascular lesions in the eye are composed of unencapsulated, thin-walled, back-to-back dilated capillary channels, classically representing diffuse choroidal [...].
Choroidal haemangioma in Sturge Weber syndrome. This diffuse choroidal haemangioma is associated with extensive changes to the overlying retinal pigment epithelium and retina.
Choroidal haemangioma. Back to back dilated capillary channels in the choroid.
A: hemangiomas
Back Extra: Sturge-Weber Syndrome
- Clinical: Choroid capillary malformations (CM) in Sturge-Weber Syndrome can cause blurry, distorted, or declined vision due to choroidal thickening and retinal changes.
- Micro: In Sturge-Weber Syndrome, CM in the choroid, episclera, and conjunctiva appear as unencapsulated collections of thin-walled, variably sized vascular channels.
- Ancillary: GNAQ evaluation in affected tissue can identify a somatic heterozygous pathogenic sequence variant consistent with Sturge-Weber Syndrome.
Reference Gallery:
Choroidal haemangioma in Sturge Weber syndrome. This diffuse choroidal haemangioma is associated with extensive changes to the overlying retinal pigment epithelium and retina.
Choroidal haemangioma. Back to back dilated capillary channels in the choroid.
Sturge-Weber Syndrome. External facial photo of Sturge-Weber Syndrome. The Port-Wine stain is a red discoloration of the skin follows the distribution of the first branch of the trigeminal nerve and the embryonic vasculature in this area.
Sturge-Weber Syndrome. Conjunctival photo of Sturge-Weber Syndrome. Conjunctival and episcleral capillary malformations appear as red dilated, tortuous, and elevated vessels.

Q: Ancillary molecular testing of affected capillary malformations (such as those of the skin, conjunctiva, or episclera) in Sturge-Weber Syndrome typically identifies a somatic heterozygous pathogenic sequence variant in the [...] gene.
Sturge-Weber Syndrome. External facial photo of Sturge-Weber Syndrome. The Port-Wine stain is a red discoloration of the skin follows the distribution of the first branch of the trigeminal nerve and the embryonic vasculature in this area.
Sturge-Weber Syndrome. Conjunctival photo of Sturge-Weber Syndrome. Conjunctival and episcleral capillary malformations appear as red dilated, tortuous, and elevated vessels.
A: GNAQ
Back Extra: Sturge-Weber Syndrome
- Clinical: Choroid capillary malformations (CM) in Sturge-Weber Syndrome can cause blurry, distorted, or declined vision due to choroidal thickening and retinal changes.
- Micro: In Sturge-Weber Syndrome, CM in the choroid, episclera, and conjunctiva appear as unencapsulated collections of thin-walled, variably sized vascular channels.
- Ancillary: GNAQ evaluation in affected tissue can identify a somatic heterozygous pathogenic sequence variant consistent with Sturge-Weber Syndrome.
Reference Gallery:
Choroidal haemangioma in Sturge Weber syndrome. This diffuse choroidal haemangioma is associated with extensive changes to the overlying retinal pigment epithelium and retina.
Choroidal haemangioma. Back to back dilated capillary channels in the choroid.
Sturge-Weber Syndrome. External facial photo of Sturge-Weber Syndrome. The Port-Wine stain is a red discoloration of the skin follows the distribution of the first branch of the trigeminal nerve and the embryonic vasculature in this area.
Sturge-Weber Syndrome. Conjunctival photo of Sturge-Weber Syndrome. Conjunctival and episcleral capillary malformations appear as red dilated, tortuous, and elevated vessels.

Q: A hallmark microscopic feature of Adult Orbital Xanthogranulomatous Disease is a mixed inflammatory infiltrate containing [...], which are characterized by a dense central eosinophilic cytoplasm, a wreath-like ring of nuclei, and a peripheral foamy zone.
Adult xanthogranuloma. Small focus of eosinophils and a Touton giant cell in a sclerotic area of orbital xanthogranuloma.
Adult xanthogranuloma. Classic Touton giant cell in orbital xanthogranuloma, with a dense eosinophilic central cytoplasm, a ring of nuclei, surrounded by foamy cytoplasm.
A: Touton giant cells
Back Extra: Adult Orbital Xanthogranulomatous Disease
- Clinical: Adult orbital xanthogranulomatous disease (AOXGD) often presents as a solitary xanthogranulomatous eyelid or orbital lesion, which may be associated with late-onset asthma or systemic findings such as monoclonal gammopathy.
- Micro: Characteristic histopathological features include sheets of mononucleated foamy histiocytes (xanthoma cells) with Touton giant cells and a mixed inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils.
- Ancillary: Immunohistochemically, the foamy histiocytes in AOXGD are typically positive for CD68, CD163, and factor XIIa, but negative for CD1a, S100, and Birbeck granules. Molecular analysis may reveal BRAF mutations in some cases.
Reference Gallery:
Adult xanthogranuloma. Circumscribed nodular xanthogranuloma involving the eyelid in an adult.
Orbital xanthograuloma. A: Axial T2 MRI with fat saturation shows an iso- to hypointense lesion in the right temporal and periorbital soft tissues with involvement of the right upper eyelid and lacrimal gland (arrows). B: Axial T1 post-contrast MRI shows homogenous enhancement of the lesion (arrows).
Orbital xanthogranuloma. A typical mixed inflammatory milieu of xanthomatised histiocytes, plasma cells, some lymphocytes and eosinophils.
Adult xanthogranuloma. Small focus of eosinophils and a Touton giant cell in a sclerotic area of orbital xanthogranuloma.
Adult xanthogranuloma. Xanthomatised histiocytes and a few chronic inflammatory cells.
Adult xanthogranuloma. Reactive lymphoid aggregates, chronic inflammatory cells and clear areas comprising xanthomatised macrophages (top and bottom right especially), surrounding the reactive lymphoid aggregates.
Adult xanthogranuloma. Some perivascular chronic inflammatory cells in orbital xanthogranuloma.
Adult xanthogranuloma. Plasma cells, lymphocytes, and eosinophils in a more sclerotic area of orbital xanthogranuloma.
Adult xanthogranuloma. Xanthomatised histiocytes with foamy cytoplasm and reactive lymphoid aggregate.
Adult xanthogranuloma. Classic Touton giant cell in orbital xanthogranuloma, with a dense eosinophilic central cytoplasm, a ring of nuclei, surrounded by foamy cytoplasm.
Adult xanthogranuloma. Xanthomatised histiocytes between extraocular muscular fibres.
Adult xanthogranuloma. Xanthomatised histiocytes percolating between extraocular muscle fibres.

Q: A patient presenting with an enhancing nodular mass of the eyelid or orbit that histologically reveals an infiltrate of xanthomatized histiocytes and chronic inflammatory cells percolating between extraocular muscle fibers is characteristic of [...].
Orbital xanthograuloma. A: Axial T2 MRI with fat saturation shows an iso- to hypointense lesion in the right temporal and periorbital soft tissues with involvement of the right upper eyelid and lacrimal gland (arrows). B: Axial T1 post-contrast MRI shows homogenous enhancement of the lesion (arrows).
Adult xanthogranuloma. Xanthomatised histiocytes percolating between extraocular muscle fibres.
A: Adult Orbital Xanthogranulomatous Disease
Back Extra: Adult Orbital Xanthogranulomatous Disease
- Clinical: Adult orbital xanthogranulomatous disease (AOXGD) often presents as a solitary xanthogranulomatous eyelid or orbital lesion, which may be associated with late-onset asthma or systemic findings such as monoclonal gammopathy.
- Micro: Characteristic histopathological features include sheets of mononucleated foamy histiocytes (xanthoma cells) with Touton giant cells and a mixed inflammatory infiltrate of lymphocytes, plasma cells, and eosinophils.
- Ancillary: Immunohistochemically, the foamy histiocytes in AOXGD are typically positive for CD68, CD163, and factor XIIa, but negative for CD1a, S100, and Birbeck granules. Molecular analysis may reveal BRAF mutations in some cases.
Reference Gallery:
Adult xanthogranuloma. Circumscribed nodular xanthogranuloma involving the eyelid in an adult.
Orbital xanthograuloma. A: Axial T2 MRI with fat saturation shows an iso- to hypointense lesion in the right temporal and periorbital soft tissues with involvement of the right upper eyelid and lacrimal gland (arrows). B: Axial T1 post-contrast MRI shows homogenous enhancement of the lesion (arrows).
Orbital xanthogranuloma. A typical mixed inflammatory milieu of xanthomatised histiocytes, plasma cells, some lymphocytes and eosinophils.
Adult xanthogranuloma. Small focus of eosinophils and a Touton giant cell in a sclerotic area of orbital xanthogranuloma.
Adult xanthogranuloma. Xanthomatised histiocytes and a few chronic inflammatory cells.
Adult xanthogranuloma. Reactive lymphoid aggregates, chronic inflammatory cells and clear areas comprising xanthomatised macrophages (top and bottom right especially), surrounding the reactive lymphoid aggregates.
Adult xanthogranuloma. Some perivascular chronic inflammatory cells in orbital xanthogranuloma.
Adult xanthogranuloma. Plasma cells, lymphocytes, and eosinophils in a more sclerotic area of orbital xanthogranuloma.
Adult xanthogranuloma. Xanthomatised histiocytes with foamy cytoplasm and reactive lymphoid aggregate.
Adult xanthogranuloma. Classic Touton giant cell in orbital xanthogranuloma, with a dense eosinophilic central cytoplasm, a ring of nuclei, surrounded by foamy cytoplasm.
Adult xanthogranuloma. Xanthomatised histiocytes between extraocular muscular fibres.
Adult xanthogranuloma. Xanthomatised histiocytes percolating between extraocular muscle fibres.

Q: In Erdheim-Chester Disease, the characteristic microscopic finding consists of sheets of xanthomatous (foamy) and lipid-laden [...], often admixed with a lymphoplasmacytic infiltrate and Touton giant cells in a fibrotic background.
Erdheim-Chester Disease. Numerous foamy histiocytes characterized by ample finely vacuolated cytoplasm and small nuclei.
Erdheim-Chester Disease. Sheets of xanthomatous (foamy) and lipid-laden histiocytes admixed with lymphoplasmacytic infiltrate in fibrotic background.
A: histiocytes
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease can present with visual abnormalities, exophthalmos, and retro-orbital pain due to histiocytic infiltration of the retro-orbital soft tissues.
- Micro: Sheets of xanthomatous (foamy) and lipid-laden histiocytes admixed with lymphoplasmacytic infiltrate and Touton giant cells are characteristic findings.
- Ancillary: BRAF p.V600E mutation is common in ECD and can be detected with immunohistochemistry, aiding in diagnosis and guiding targeted therapy.
Reference Gallery:
Erdheim-Chester Disease. Numerous foamy histiocytes characterized by ample finely vacuolated cytoplasm and small nuclei.
Erdheim-Chester Disease. Right eye fundus photograph shows choroidal folds and papilledema secondary to the presence of a posterior orbital mass compressing the globe.
Erdheim-Chester Disease. MRI with contrast shows bilateral, well demarcated, intraconal masses surrounding each optic nerve.
Erdheim-Chester Disease. Sheets of xanthomatous (foamy) and lipid-laden histiocytes admixed with lymphoplasmacytic infiltrate in fibrotic background.
Erdheim-Chester Disease. Left eye fundus photograph shows choroidal folds result of posterior orbital mass compressing the globe.
Erdheim-Chester Disease. Clinical photograph shows bilateral proptosis and lid xanthelasma.
Erdheim-Chester disease. Clinical photograph shows left eye proptosis result of the presence of an orbital mass in a patient with ECD.
Erdheim-Chester disease. Tumour cells are positive for BRAF p.V600E immunohistochemistry, indicating the presence of BRAF mutation.

Q: Patients with Erdheim-Chester Disease may present with visual abnormalities, lid xanthelasma, and bilateral [...] (exophthalmos) secondary to histiocytic infiltration forming retro-orbital intraconal masses.
Erdheim-Chester Disease. MRI with contrast shows bilateral, well demarcated, intraconal masses surrounding each optic nerve.
Erdheim-Chester Disease. Clinical photograph shows bilateral proptosis and lid xanthelasma.
A: proptosis
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease can present with visual abnormalities, exophthalmos, and retro-orbital pain due to histiocytic infiltration of the retro-orbital soft tissues.
- Micro: Sheets of xanthomatous (foamy) and lipid-laden histiocytes admixed with lymphoplasmacytic infiltrate and Touton giant cells are characteristic findings.
- Ancillary: BRAF p.V600E mutation is common in ECD and can be detected with immunohistochemistry, aiding in diagnosis and guiding targeted therapy.
Reference Gallery:
Erdheim-Chester Disease. Numerous foamy histiocytes characterized by ample finely vacuolated cytoplasm and small nuclei.
Erdheim-Chester Disease. Right eye fundus photograph shows choroidal folds and papilledema secondary to the presence of a posterior orbital mass compressing the globe.
Erdheim-Chester Disease. MRI with contrast shows bilateral, well demarcated, intraconal masses surrounding each optic nerve.
Erdheim-Chester Disease. Sheets of xanthomatous (foamy) and lipid-laden histiocytes admixed with lymphoplasmacytic infiltrate in fibrotic background.
Erdheim-Chester Disease. Left eye fundus photograph shows choroidal folds result of posterior orbital mass compressing the globe.
Erdheim-Chester Disease. Clinical photograph shows bilateral proptosis and lid xanthelasma.
Erdheim-Chester disease. Clinical photograph shows left eye proptosis result of the presence of an orbital mass in a patient with ECD.
Erdheim-Chester disease. Tumour cells are positive for BRAF p.V600E immunohistochemistry, indicating the presence of BRAF mutation.

Q: Targeted therapy in Erdheim-Chester Disease is often guided by immunohistochemical detection of the [...] mutation, which is a common genetic driver in these neoplasms.
Erdheim-Chester disease. Tumour cells are positive for BRAF p.V600E immunohistochemistry, indicating the presence of BRAF mutation.
A: BRAF p.V600E
Back Extra: Erdheim-Chester Disease
- Clinical: Erdheim-Chester Disease can present with visual abnormalities, exophthalmos, and retro-orbital pain due to histiocytic infiltration of the retro-orbital soft tissues.
- Micro: Sheets of xanthomatous (foamy) and lipid-laden histiocytes admixed with lymphoplasmacytic infiltrate and Touton giant cells are characteristic findings.
- Ancillary: BRAF p.V600E mutation is common in ECD and can be detected with immunohistochemistry, aiding in diagnosis and guiding targeted therapy.
Reference Gallery:
Erdheim-Chester Disease. Numerous foamy histiocytes characterized by ample finely vacuolated cytoplasm and small nuclei.
Erdheim-Chester Disease. Right eye fundus photograph shows choroidal folds and papilledema secondary to the presence of a posterior orbital mass compressing the globe.
Erdheim-Chester Disease. MRI with contrast shows bilateral, well demarcated, intraconal masses surrounding each optic nerve.
Erdheim-Chester Disease. Sheets of xanthomatous (foamy) and lipid-laden histiocytes admixed with lymphoplasmacytic infiltrate in fibrotic background.
Erdheim-Chester Disease. Left eye fundus photograph shows choroidal folds result of posterior orbital mass compressing the globe.
Erdheim-Chester Disease. Clinical photograph shows bilateral proptosis and lid xanthelasma.
Erdheim-Chester disease. Clinical photograph shows left eye proptosis result of the presence of an orbital mass in a patient with ECD.
Erdheim-Chester disease. Tumour cells are positive for BRAF p.V600E immunohistochemistry, indicating the presence of BRAF mutation.

Q: Histopathologically, Juvenile Xanthogranuloma is characterized by the presence of foamy histiocytes and characteristic [...] giant cells.
Juvenile xanthogranuloma (JXG). Characteristic Touton Giant cell in JXG (PAS stain).
Juvenile xanthogranuloma. Touton giant cells in a case of cutaneous JXG.
Juvenile xanthogranuloma. Typical Touton giant cell.
A: Touton
Back Extra: Juvenile Xanthogranuloma
- Clinical: Juvenile xanthogranuloma (JXG) commonly presents in the first year of life, often as a solitary or multiple yellowish, painless nodules on the eyelid or iris, and may present with spontaneous hyphema.
- Micro: Histopathologically, JXG is characterized by the presence of foamy histiocytes and characteristic Touton giant cells, with a dermal macrophage phenotype.
- Ancillary: JXG histiocytes are positive for CD68, CD163, and CD14 but negative for CD1a and CD207 (langerin), and lack reactivity to S-100 immunohistochemistry.
Reference Gallery:
Juvenile xanthogranuloma (JXG). The histiocytes showing reactivity with CD68 stain in a case of JXG.
Juvenile xanthogranuloma (JXG). Histiocytic infiltration of bone in a case of orbital JXG (PAS stain).
Juvenile xanthogranuloma (JXG). Characteristic Touton Giant cell in JXG (PAS stain).
Juvenile xanthogranuloma (JXG). Ultrasound bio-microscopy (B-scan) of a case of JXG involving the left eye choroid with adjacent vitreous opacities mimicking intraocular malignancy.
Juvenile xanthogranuloma (JXG). Lack of reactivity of the foamy histiocytes in JXG to S-100 immunohistochemistry.
Juvenile xanthogranuloma. The non-Langerhans histiocytes expressing reactivity to CD68.
Juvenile xanthogranuloma. Touton giant cells in a case of cutaneous JXG.
Juvenile xanthogranuloma. Typical Touton giant cell.
Juvenile xanthogranuloma. Juvenile xanthogranuloma involving the iris.
Juvenile xanthogranuloma. Fine needle aspiration showing characteristic Touton cells in a mild inflammatory background.
Juvenile xanthogranuloma. Fine needle aspiration reveals aggregates of histiocytes.

Q: Clinically, ocular Juvenile Xanthogranuloma frequently presents in the first year of life as a yellowish, painless nodule on the [...], which may result in spontaneous hyphema.
Juvenile xanthogranuloma. Juvenile xanthogranuloma involving the iris.
A: iris
Back Extra: Juvenile Xanthogranuloma
- Clinical: Juvenile xanthogranuloma (JXG) commonly presents in the first year of life, often as a solitary or multiple yellowish, painless nodules on the eyelid or iris, and may present with spontaneous hyphema.
- Micro: Histopathologically, JXG is characterized by the presence of foamy histiocytes and characteristic Touton giant cells, with a dermal macrophage phenotype.
- Ancillary: JXG histiocytes are positive for CD68, CD163, and CD14 but negative for CD1a and CD207 (langerin), and lack reactivity to S-100 immunohistochemistry.
Reference Gallery:
Juvenile xanthogranuloma (JXG). The histiocytes showing reactivity with CD68 stain in a case of JXG.
Juvenile xanthogranuloma (JXG). Histiocytic infiltration of bone in a case of orbital JXG (PAS stain).
Juvenile xanthogranuloma (JXG). Characteristic Touton Giant cell in JXG (PAS stain).
Juvenile xanthogranuloma (JXG). Ultrasound bio-microscopy (B-scan) of a case of JXG involving the left eye choroid with adjacent vitreous opacities mimicking intraocular malignancy.
Juvenile xanthogranuloma (JXG). Lack of reactivity of the foamy histiocytes in JXG to S-100 immunohistochemistry.
Juvenile xanthogranuloma. The non-Langerhans histiocytes expressing reactivity to CD68.
Juvenile xanthogranuloma. Touton giant cells in a case of cutaneous JXG.
Juvenile xanthogranuloma. Typical Touton giant cell.
Juvenile xanthogranuloma. Juvenile xanthogranuloma involving the iris.
Juvenile xanthogranuloma. Fine needle aspiration showing characteristic Touton cells in a mild inflammatory background.
Juvenile xanthogranuloma. Fine needle aspiration reveals aggregates of histiocytes.

Q: The foamy histiocytes of Juvenile Xanthogranuloma demonstrate a dermal macrophage phenotype, meaning they are positive for CD68 and CD163, but characteristically lack reactivity to CD1a, langerin, and [...].
Juvenile xanthogranuloma (JXG). The histiocytes showing reactivity with CD68 stain in a case of JXG.
Juvenile xanthogranuloma (JXG). Lack of reactivity of the foamy histiocytes in JXG to S-100 immunohistochemistry.
A: S-100
Back Extra: Juvenile Xanthogranuloma
- Clinical: Juvenile xanthogranuloma (JXG) commonly presents in the first year of life, often as a solitary or multiple yellowish, painless nodules on the eyelid or iris, and may present with spontaneous hyphema.
- Micro: Histopathologically, JXG is characterized by the presence of foamy histiocytes and characteristic Touton giant cells, with a dermal macrophage phenotype.
- Ancillary: JXG histiocytes are positive for CD68, CD163, and CD14 but negative for CD1a and CD207 (langerin), and lack reactivity to S-100 immunohistochemistry.
Reference Gallery:
Juvenile xanthogranuloma (JXG). The histiocytes showing reactivity with CD68 stain in a case of JXG.
Juvenile xanthogranuloma (JXG). Histiocytic infiltration of bone in a case of orbital JXG (PAS stain).
Juvenile xanthogranuloma (JXG). Characteristic Touton Giant cell in JXG (PAS stain).
Juvenile xanthogranuloma (JXG). Ultrasound bio-microscopy (B-scan) of a case of JXG involving the left eye choroid with adjacent vitreous opacities mimicking intraocular malignancy.
Juvenile xanthogranuloma (JXG). Lack of reactivity of the foamy histiocytes in JXG to S-100 immunohistochemistry.
Juvenile xanthogranuloma. The non-Langerhans histiocytes expressing reactivity to CD68.
Juvenile xanthogranuloma. Touton giant cells in a case of cutaneous JXG.
Juvenile xanthogranuloma. Typical Touton giant cell.
Juvenile xanthogranuloma. Juvenile xanthogranuloma involving the iris.
Juvenile xanthogranuloma. Fine needle aspiration showing characteristic Touton cells in a mild inflammatory background.
Juvenile xanthogranuloma. Fine needle aspiration reveals aggregates of histiocytes.

Q: Microscopically, Langerhans Cell Tumors are characterized by an inflammatory infiltrate rich in eosinophils and large neoplastic cells with distinctive [...] nuclei.
Langerhans cell histiocytosis. Typical Langerhans cell histiocytosis with large cells with bean-shaped and grooved nuclei and admixture of leukocytes including neutrophils and eosinophils
Langerhans cell histiocytosis. Orbital involvement of LCH.
A: folded or grooved
Back Extra: Langerhans Cell Tumors
- Clinical: Langerhans cell histiocytosis (LCH) often presents as a unilateral, extraconal orbital mass, affecting the roof and lateral orbital wall, with or without intracranial extension and eyelid involvement.
- Micro: LCH cells are large, with folded or grooved nuclei, abundant eosinophilic cytoplasm, and an inflammatory infiltrate of eosinophils, lymphocytes, and multinucleated giant cells.
- Ancillary: LCH cells are positive for CD1a, CD207 (langerin), and S100 protein, and may show a BRAF p.V600E mutation.
Reference Gallery:
Langerhans cell histiocytosis. CD1a showing strong surface reactivity with a perinuclear dot
Langerhans cell histiocytosis. S100 protein shows cytoplasmic and nuclear staining in the Langerhans cells.
Langerhans cell histiocytosis. Langerin (CD207) shows granular and cytoplasmic staining.
Langerhans cell histiocytosis. Axial T1-weighted MRI with contrast in a young adult with LCH centred on the greater wing of sphenoid.
Langerhans cell sarcoma. Strong diffuse cytoplasmic reactivity for BRAF p.V600E in the neoplastic cells.
Langerhans cell histiocytosis. Axial T1-weighted MRI in an infant presenting with orbital mass with notable soft tissue extension
Langerhans cell histiocytosis. Clinical photograph showing infant presenting with orbital mass with notable soft tissue extension
Langerhans cell histiocytosis. Typical Langerhans cell histiocytosis with large cells with bean-shaped and grooved nuclei and admixture of leukocytes including neutrophils and eosinophils
Langerhans cell histiocytosis. S100 protein immunohistochemistry shows nuclear and cytoplasmic reactivity
Langerhans cell histiocytosis. Orbital involvement of a LCH with a BRAF p.V600E mutation. Immunohistochemistry staining with BRAF antibody.
Langerhans cell histiocytosis. Orbital involvement of a LCH. Tumour cells express CD1a.
Langerhans cell histiocytosis. Orbital involvement of LCH.

Q: By immunohistochemistry, Langerhans Cell Tumors are characteristically positive for S100, CD1a, and the highly specific marker [...] (also known as langerin).
Langerhans cell histiocytosis. CD1a showing strong surface reactivity with a perinuclear dot
Langerhans cell histiocytosis. S100 protein shows cytoplasmic and nuclear staining in the Langerhans cells.
Langerhans cell histiocytosis. Langerin (CD207) shows granular and cytoplasmic staining.
A: CD207
Back Extra: Langerhans Cell Tumors
- Clinical: Langerhans cell histiocytosis (LCH) often presents as a unilateral, extraconal orbital mass, affecting the roof and lateral orbital wall, with or without intracranial extension and eyelid involvement.
- Micro: LCH cells are large, with folded or grooved nuclei, abundant eosinophilic cytoplasm, and an inflammatory infiltrate of eosinophils, lymphocytes, and multinucleated giant cells.
- Ancillary: LCH cells are positive for CD1a, CD207 (langerin), and S100 protein, and may show a BRAF p.V600E mutation.
Reference Gallery:
Langerhans cell histiocytosis. CD1a showing strong surface reactivity with a perinuclear dot
Langerhans cell histiocytosis. S100 protein shows cytoplasmic and nuclear staining in the Langerhans cells.
Langerhans cell histiocytosis. Langerin (CD207) shows granular and cytoplasmic staining.
Langerhans cell histiocytosis. Axial T1-weighted MRI with contrast in a young adult with LCH centred on the greater wing of sphenoid.
Langerhans cell sarcoma. Strong diffuse cytoplasmic reactivity for BRAF p.V600E in the neoplastic cells.
Langerhans cell histiocytosis. Axial T1-weighted MRI in an infant presenting with orbital mass with notable soft tissue extension
Langerhans cell histiocytosis. Clinical photograph showing infant presenting with orbital mass with notable soft tissue extension
Langerhans cell histiocytosis. Typical Langerhans cell histiocytosis with large cells with bean-shaped and grooved nuclei and admixture of leukocytes including neutrophils and eosinophils
Langerhans cell histiocytosis. S100 protein immunohistochemistry shows nuclear and cytoplasmic reactivity
Langerhans cell histiocytosis. Orbital involvement of a LCH with a BRAF p.V600E mutation. Immunohistochemistry staining with BRAF antibody.
Langerhans cell histiocytosis. Orbital involvement of a LCH. Tumour cells express CD1a.
Langerhans cell histiocytosis. Orbital involvement of LCH.

Q: Clinically and radiologically, orbital [...] often present in infants or young adults as a unilateral, extraconal mass typically centered on the roof and lateral orbital wall.
Langerhans cell histiocytosis. Axial T1-weighted MRI with contrast in a young adult with LCH centred on the greater wing of sphenoid.
Langerhans cell histiocytosis. Axial T1-weighted MRI in an infant presenting with orbital mass with notable soft tissue extension
Langerhans cell histiocytosis. Clinical photograph showing infant presenting with orbital mass with notable soft tissue extension
A: Langerhans Cell Tumors
Back Extra: Langerhans Cell Tumors
- Clinical: Langerhans cell histiocytosis (LCH) often presents as a unilateral, extraconal orbital mass, affecting the roof and lateral orbital wall, with or without intracranial extension and eyelid involvement.
- Micro: LCH cells are large, with folded or grooved nuclei, abundant eosinophilic cytoplasm, and an inflammatory infiltrate of eosinophils, lymphocytes, and multinucleated giant cells.
- Ancillary: LCH cells are positive for CD1a, CD207 (langerin), and S100 protein, and may show a BRAF p.V600E mutation.
Reference Gallery:
Langerhans cell histiocytosis. CD1a showing strong surface reactivity with a perinuclear dot
Langerhans cell histiocytosis. S100 protein shows cytoplasmic and nuclear staining in the Langerhans cells.
Langerhans cell histiocytosis. Langerin (CD207) shows granular and cytoplasmic staining.
Langerhans cell histiocytosis. Axial T1-weighted MRI with contrast in a young adult with LCH centred on the greater wing of sphenoid.
Langerhans cell sarcoma. Strong diffuse cytoplasmic reactivity for BRAF p.V600E in the neoplastic cells.
Langerhans cell histiocytosis. Axial T1-weighted MRI in an infant presenting with orbital mass with notable soft tissue extension
Langerhans cell histiocytosis. Clinical photograph showing infant presenting with orbital mass with notable soft tissue extension
Langerhans cell histiocytosis. Typical Langerhans cell histiocytosis with large cells with bean-shaped and grooved nuclei and admixture of leukocytes including neutrophils and eosinophils
Langerhans cell histiocytosis. S100 protein immunohistochemistry shows nuclear and cytoplasmic reactivity
Langerhans cell histiocytosis. Orbital involvement of a LCH with a BRAF p.V600E mutation. Immunohistochemistry staining with BRAF antibody.
Langerhans cell histiocytosis. Orbital involvement of a LCH. Tumour cells express CD1a.
Langerhans cell histiocytosis. Orbital involvement of LCH.

Q: The hallmark histologic finding in Rosai-Dorfman Disease is the engulfment of intact lymphocytes by large histiocytes, a phenomenon termed [...].
Rosai-Dorfman Disease. Biopsy in a case of RDD showing collection of histiocytes, lymphocytes, plasma cells (with Russell body), and typical emperiopolesis.
Rosai-Dorfman disease. RDD infiltrate showing features of emperiopolesis and Russell bodies.
A: emperiopolesis
Back Extra: Rosai-Dorfman Disease
- Clinical: Painless soft tissue mass and/or proptosis are the most common clinical manifestations of orbital Rosai-Dorfman Disease (RDD).
- Micro: RDD typically shows a mixed infiltrate of histiocytes with abundant or vacuolated cytoplasm, lymphocytes, and plasma cells, often displaying emperiopolesis (lymphocytophagocytosis).
- Ancillary: Histiocytes in RDD express markers such as S100, CD14, CD163, CD68, Factor XIIIa, Fascin, and OCT2, but not CD1a or CD207 (Langerin).
Reference Gallery:
Rosai–Dorfman disease. Coronal Computerized Tomography (CT) scan of the orbits in the same patient showing a left infero-medial orbital mass with involvement of the ethmoidal sinuses.
Rosai-Dorfman Disease. Biopsy in a case of RDD showing collection of histiocytes, lymphocytes, plasma cells (with Russell body), and typical emperiopolesis.
Rosai-Dorfman disease. The histiocytes in RDD expressing reaction to S-100 stain. Note the lymphocytes that are engulfed by the macrophage in the center of the photo.
Rosai-Dorfman disease. Mixed infiltrate of histiocytes with abundant vacuolated cytoplasm and lymphocytes are seen.
Rosai-Dorfman disease. RDD infiltrate showing features of emperiopolesis and Russell bodies.
Rosai-Dorfman disease. Axial and coronal T1 post-contrast MRIs show a lesion involving the superotemporal right orbit and right upper eyelid (arrows).
Rosai-Dorfman disease. Axial and coronal T1 post-contrast MRIs show a heterogeneously enhancing lesion in the right lacrimal gland and superotemporal right orbit (arrows).
Rosai-Dorfman disease. A case of RDD in a female presenting at the age of 32 years with left proptosis and superior displacement of the left globe due to an infero-medial orbital mass.

Q: The large, characteristic histiocytes in Rosai-Dorfman Disease demonstrate a distinct immunophenotype, being typically negative for CD1a and positive for [...].
Rosai-Dorfman disease. The histiocytes in RDD expressing reaction to S-100 stain. Note the lymphocytes that are engulfed by the macrophage in the center of the photo.
A: S100
Back Extra: Rosai-Dorfman Disease
- Clinical: Painless soft tissue mass and/or proptosis are the most common clinical manifestations of orbital Rosai-Dorfman Disease (RDD).
- Micro: RDD typically shows a mixed infiltrate of histiocytes with abundant or vacuolated cytoplasm, lymphocytes, and plasma cells, often displaying emperiopolesis (lymphocytophagocytosis).
- Ancillary: Histiocytes in RDD express markers such as S100, CD14, CD163, CD68, Factor XIIIa, Fascin, and OCT2, but not CD1a or CD207 (Langerin).
Reference Gallery:
Rosai–Dorfman disease. Coronal Computerized Tomography (CT) scan of the orbits in the same patient showing a left infero-medial orbital mass with involvement of the ethmoidal sinuses.
Rosai-Dorfman Disease. Biopsy in a case of RDD showing collection of histiocytes, lymphocytes, plasma cells (with Russell body), and typical emperiopolesis.
Rosai-Dorfman disease. The histiocytes in RDD expressing reaction to S-100 stain. Note the lymphocytes that are engulfed by the macrophage in the center of the photo.
Rosai-Dorfman disease. Mixed infiltrate of histiocytes with abundant vacuolated cytoplasm and lymphocytes are seen.
Rosai-Dorfman disease. RDD infiltrate showing features of emperiopolesis and Russell bodies.
Rosai-Dorfman disease. Axial and coronal T1 post-contrast MRIs show a lesion involving the superotemporal right orbit and right upper eyelid (arrows).
Rosai-Dorfman disease. Axial and coronal T1 post-contrast MRIs show a heterogeneously enhancing lesion in the right lacrimal gland and superotemporal right orbit (arrows).
Rosai-Dorfman disease. A case of RDD in a female presenting at the age of 32 years with left proptosis and superior displacement of the left globe due to an infero-medial orbital mass.

Q: Superficial dermal collections of lipid-laden, foamy histiocytes in a biopsy from the medial eyelid are pathognomonic for the diagnosis of [...].
Xanthelasma. Eyelid skin comprising collections of foamy histiocytes in the dermis, associated with some patchy collections of lymphocytes around the vessels. Note how the foamy histiocytes peter out towards the deeper aspect of the biopsy.
Xanthelasma. Higher power image showing the frothy / foamy cytoplasm of the histiocytes and small bland nuclei.
A: Xanthelasma
Back Extra: Xanthelasma
- Clinical: Xanthelasma appears as flat or minimally elevated, yellow lesions commonly in the medial aspect of the eyelids, often bilateral and symmetrical.
- Micro: Xanthelasma shows focal collections of lipid-laden histiocytes distributed mainly around blood vessels and adnexal structures in the eyelid dermis, with chronic inflammatory cells and fibrosis.
- Ancillary: The foamy histiocytes typically express CD68, CD163, and factor XIIa, but lack CD21, CD35, S100, CD1a, and Birbeck granules.
Reference Gallery:
Xanthelasma. Eyelid skin comprising collections of foamy histiocytes in the dermis, associated with some patchy collections of lymphocytes around the vessels. Note how the foamy histiocytes peter out towards the deeper aspect of the biopsy.
Xanthelasma. Higher power image showing the frothy / foamy cytoplasm of the histiocytes and small bland nuclei.

Q: The classic microscopic finding in Xanthelasma is the presence of superficial dermal collections of lipid-laden, [...] with small, bland nuclei.
Xanthelasma. Eyelid skin comprising collections of foamy histiocytes in the dermis, associated with some patchy collections of lymphocytes around the vessels. Note how the foamy histiocytes peter out towards the deeper aspect of the biopsy.
Xanthelasma. Higher power image showing the frothy / foamy cytoplasm of the histiocytes and small bland nuclei.
A: foamy histiocytes
Back Extra: Xanthelasma
- Clinical: Xanthelasma appears as flat or minimally elevated, yellow lesions commonly in the medial aspect of the eyelids, often bilateral and symmetrical.
- Micro: Xanthelasma shows focal collections of lipid-laden histiocytes distributed mainly around blood vessels and adnexal structures in the eyelid dermis, with chronic inflammatory cells and fibrosis.
- Ancillary: The foamy histiocytes typically express CD68, CD163, and factor XIIa, but lack CD21, CD35, S100, CD1a, and Birbeck granules.
Reference Gallery:
Xanthelasma. Eyelid skin comprising collections of foamy histiocytes in the dermis, associated with some patchy collections of lymphocytes around the vessels. Note how the foamy histiocytes peter out towards the deeper aspect of the biopsy.
Xanthelasma. Higher power image showing the frothy / foamy cytoplasm of the histiocytes and small bland nuclei.

Q: Most cases of Primary Choroidal Lymphoma are histologically classified as [...], featuring a diffuse choroidal infiltrate of small centrocyte-like lymphocytes and plasmacytoid cells.
Primary choroid lymphoma. Extranodal marginal zone B-cell lymphoma. Choroidal lymphoma in relation to retina and Bruch's membrane.
Primary choroidal lymphoma. Intraocular biopsy of extranodal marginal zone B-cell lymphoma (Giemsa). Small to medium-size cells resembling centrocytes, with moderate amounts of pale cytoplasm, mild nuclear contour irregularities and inconspicuous nucleoli.
A: extranodal marginal zone B-cell lymphomas
Back Extra: Primary Choroidal Lymphoma
- Clinical: Primary Choroidal Lymphoma (PCL) typically presents with gradual visual loss, painful angle-closure glaucoma, and a visible extraocular salmon-pink tumour nodule.
- Micro: Histologically, PCL shows diffuse infiltration of choroidal tissue by small-to-medium-sized lymphoid cells, often with expansion of small centrocyte-like lymphocytes and plasmacytoid cells.
- Ancillary: Neoplastic cells in PCL express pan B-cell markers (CD20, CD79a, PAX5), BCL2+, IgM+, and show a low Ki67 proliferation index.
Reference Gallery:
Primary choroid lymphoma. Extranodal marginal zone B-cell lymphoma. Choroidal lymphoma in relation to retina and Bruch's membrane.
Extranodal marginal zone B-cell lymphoma. Tumour cells express CD20.
Primary choroidal lymphoma. Extranodal marginal zone B-cell lymphoma. Ki67 showing a low growth fraction.
Primary choroidal lymphoma. Intraocular biopsy of extranodal marginal zone B-cell lymphoma (Giemsa). Small to medium-size cells resembling centrocytes, with moderate amounts of pale cytoplasm, mild nuclear contour irregularities and inconspicuous nucleoli.
Primary choroidal lymphoma. Intraocular biopsy of extranodal marginal zone B-cell lymphoma. Tumour cells are positive for CD79a.

Q: Immunohistochemically, the tumor cells of Primary Choroidal Lymphoma characteristically express [...] markers (e.g., CD20, CD79a) and demonstrate a remarkably low Ki67 proliferation index.
Extranodal marginal zone B-cell lymphoma. Tumour cells express CD20.
Primary choroidal lymphoma. Extranodal marginal zone B-cell lymphoma. Ki67 showing a low growth fraction.
Primary choroidal lymphoma. Intraocular biopsy of extranodal marginal zone B-cell lymphoma. Tumour cells are positive for CD79a.
A: pan B-cell
Back Extra: Primary Choroidal Lymphoma
- Clinical: Primary Choroidal Lymphoma (PCL) typically presents with gradual visual loss, painful angle-closure glaucoma, and a visible extraocular salmon-pink tumour nodule.
- Micro: Histologically, PCL shows diffuse infiltration of choroidal tissue by small-to-medium-sized lymphoid cells, often with expansion of small centrocyte-like lymphocytes and plasmacytoid cells.
- Ancillary: Neoplastic cells in PCL express pan B-cell markers (CD20, CD79a, PAX5), BCL2+, IgM+, and show a low Ki67 proliferation index.
Reference Gallery:
Primary choroid lymphoma. Extranodal marginal zone B-cell lymphoma. Choroidal lymphoma in relation to retina and Bruch's membrane.
Extranodal marginal zone B-cell lymphoma. Tumour cells express CD20.
Primary choroidal lymphoma. Extranodal marginal zone B-cell lymphoma. Ki67 showing a low growth fraction.
Primary choroidal lymphoma. Intraocular biopsy of extranodal marginal zone B-cell lymphoma (Giemsa). Small to medium-size cells resembling centrocytes, with moderate amounts of pale cytoplasm, mild nuclear contour irregularities and inconspicuous nucleoli.
Primary choroidal lymphoma. Intraocular biopsy of extranodal marginal zone B-cell lymphoma. Tumour cells are positive for CD79a.

Q: On fundus examination, Primary Vitreoretinal Large B-Cell Lymphoma typically presents with creamy yellow subretinal deposits, which on optical coherence tomography (OCT) are characteristically located beneath the [...] and above Bruch's membrane.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Colour fundus photography show the creamy yellow subretinal deposits typically seen in vitreoretinal lymphoma.
OCT imaging of a primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Optical coherence tomography (OCT) image through the yellow subretinal deposits show their variable sized deposits located beneath the retinal pigment epithelium (thin red arrow) and above the Bruch’s membrane (thick red arrow).
A: retinal pigment epithelium
Back Extra: Primary Vitreoretinal Large B-Cell Lymphoma
- Clinical: Primary vitreoretinal large B-cell lymphoma (PVR-LBCL) presents with insidious symptoms such as blurred vision, ‘floaters’, and chronic intermediate or posterior uveitis, often mimicking other conditions.
- Micro: Microscopically, PVR-LBCL shows large malignant lymphocytes with pleomorphic, hyperchromatic nuclei and prominent nucleoli, often in the vitreous, neural retina, and beneath the retinal pigment epithelium (RPE).
- Ancillary: Immunophenotyping reveals that neoplastic B cells in PVR-LBCL are positive for CD79a, CD20, PAX5, BCL2, BCL6, MUM1/IRF4, and IgM, with a high Ki67 index.
Reference Gallery:
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Colour fundus photography show the creamy yellow subretinal deposits typically seen in vitreoretinal lymphoma.
OCT imaging of a primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Optical coherence tomography (OCT) image through the yellow subretinal deposits show their variable sized deposits located beneath the retinal pigment epithelium (thin red arrow) and above the Bruch’s membrane (thick red arrow).
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Large malignant lymphocytes with pleomorphic, hyperchromatic nuclei and prominent nucleoli in a background of inflammatory cells.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Immunocytology staining with CD79a, highlighting the dominance of the neoplastic B-cell population within the vitrectomy sample.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Comparative CD3 immunocytochemistry of a vitrectomy sample, showing that only a few reactive T-cells are seen.

Q: Cytologic evaluation of a vitrectomy specimen in Primary Vitreoretinal Large B-Cell Lymphoma typically reveals [...] characterized by pleomorphic, hyperchromatic nuclei and prominent nucleoli within an inflammatory background.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Large malignant lymphocytes with pleomorphic, hyperchromatic nuclei and prominent nucleoli in a background of inflammatory cells.
A: large malignant lymphocytes
Back Extra: Primary Vitreoretinal Large B-Cell Lymphoma
- Clinical: Primary vitreoretinal large B-cell lymphoma (PVR-LBCL) presents with insidious symptoms such as blurred vision, ‘floaters’, and chronic intermediate or posterior uveitis, often mimicking other conditions.
- Micro: Microscopically, PVR-LBCL shows large malignant lymphocytes with pleomorphic, hyperchromatic nuclei and prominent nucleoli, often in the vitreous, neural retina, and beneath the retinal pigment epithelium (RPE).
- Ancillary: Immunophenotyping reveals that neoplastic B cells in PVR-LBCL are positive for CD79a, CD20, PAX5, BCL2, BCL6, MUM1/IRF4, and IgM, with a high Ki67 index.
Reference Gallery:
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Colour fundus photography show the creamy yellow subretinal deposits typically seen in vitreoretinal lymphoma.
OCT imaging of a primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Optical coherence tomography (OCT) image through the yellow subretinal deposits show their variable sized deposits located beneath the retinal pigment epithelium (thin red arrow) and above the Bruch’s membrane (thick red arrow).
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Large malignant lymphocytes with pleomorphic, hyperchromatic nuclei and prominent nucleoli in a background of inflammatory cells.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Immunocytology staining with CD79a, highlighting the dominance of the neoplastic B-cell population within the vitrectomy sample.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Comparative CD3 immunocytochemistry of a vitrectomy sample, showing that only a few reactive T-cells are seen.

Q: In Primary Vitreoretinal Large B-Cell Lymphoma, immunohistochemistry of vitrectomy samples highlights a dominant neoplastic B-cell population that is strongly positive for pan-B-cell markers such as [...] (as well as CD20 and PAX5).
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Immunocytology staining with CD79a, highlighting the dominance of the neoplastic B-cell population within the vitrectomy sample.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Comparative CD3 immunocytochemistry of a vitrectomy sample, showing that only a few reactive T-cells are seen.
A: CD79a
Back Extra: Primary Vitreoretinal Large B-Cell Lymphoma
- Clinical: Primary vitreoretinal large B-cell lymphoma (PVR-LBCL) presents with insidious symptoms such as blurred vision, ‘floaters’, and chronic intermediate or posterior uveitis, often mimicking other conditions.
- Micro: Microscopically, PVR-LBCL shows large malignant lymphocytes with pleomorphic, hyperchromatic nuclei and prominent nucleoli, often in the vitreous, neural retina, and beneath the retinal pigment epithelium (RPE).
- Ancillary: Immunophenotyping reveals that neoplastic B cells in PVR-LBCL are positive for CD79a, CD20, PAX5, BCL2, BCL6, MUM1/IRF4, and IgM, with a high Ki67 index.
Reference Gallery:
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Colour fundus photography show the creamy yellow subretinal deposits typically seen in vitreoretinal lymphoma.
OCT imaging of a primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Optical coherence tomography (OCT) image through the yellow subretinal deposits show their variable sized deposits located beneath the retinal pigment epithelium (thin red arrow) and above the Bruch’s membrane (thick red arrow).
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Large malignant lymphocytes with pleomorphic, hyperchromatic nuclei and prominent nucleoli in a background of inflammatory cells.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Immunocytology staining with CD79a, highlighting the dominance of the neoplastic B-cell population within the vitrectomy sample.
Primary vitreoretinal large cell B-cell lymphoma (PVR-LCBL). Comparative CD3 immunocytochemistry of a vitrectomy sample, showing that only a few reactive T-cells are seen.

Q: In Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL), the neoplastic B-cells (which are positive for CD20) characteristically co-express the markers [...].
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD5 is expressed by the tumour cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD20 is expressed by the small tumoural lymphocytes.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD23 is expressed by the small tumoural lymphocytes.
A: CD5 and CD23
Back Extra: Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL)
- Clinical: Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL) can present with visual acuity disturbance, ocular pain, and ophthalmoplegia.
- Micro: CLL/SLL is characterized by small lymphocytes with clumped chromatin, occasional small nucleoli, and scant cytoplasm.
- Ancillary: CLL/SLL cells express CD19, CD20, CD79a, PAX5, CD5, and CD23, and are negative for CD10 and other germinal center markers.
Reference Gallery:
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). CLL involvement of the ciliary body and iris. Small lymphocytes diffusely infiltrate the stroma of the ciliary body and the root of the iris.
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). SLL in the lacrimal sac with molecularly confirmed monoclonal Ig rearrangement.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD3 is expressed by numerous reactive T-cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD5 is expressed by the tumour cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD10 is not expressed by the tumour cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD20 is expressed by the small tumoural lymphocytes.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD23 is expressed by the small tumoural lymphocytes.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. Cyclin D1 is not expressed by the tumour cells.
SLL/CLL. SLL involving the conjunctiva.

Q: To help differentiate Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL) from follicular lymphoma and mantle cell lymphoma, immunohistochemistry reveals that the tumor cells are typically negative for [...].
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD10 is not expressed by the tumour cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. Cyclin D1 is not expressed by the tumour cells.
A: CD10 and cyclin D1
Back Extra: Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL)
- Clinical: Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL) can present with visual acuity disturbance, ocular pain, and ophthalmoplegia.
- Micro: CLL/SLL is characterized by small lymphocytes with clumped chromatin, occasional small nucleoli, and scant cytoplasm.
- Ancillary: CLL/SLL cells express CD19, CD20, CD79a, PAX5, CD5, and CD23, and are negative for CD10 and other germinal center markers.
Reference Gallery:
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). CLL involvement of the ciliary body and iris. Small lymphocytes diffusely infiltrate the stroma of the ciliary body and the root of the iris.
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). SLL in the lacrimal sac with molecularly confirmed monoclonal Ig rearrangement.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD3 is expressed by numerous reactive T-cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD5 is expressed by the tumour cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD10 is not expressed by the tumour cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD20 is expressed by the small tumoural lymphocytes.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD23 is expressed by the small tumoural lymphocytes.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. Cyclin D1 is not expressed by the tumour cells.
SLL/CLL. SLL involving the conjunctiva.

Q: An ocular adnexal or uveal biopsy demonstrating a diffuse stromal infiltration by small lymphocytes with clumped chromatin, occasional small nucleoli, and scant cytoplasm is highly characteristic of [...].
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). CLL involvement of the ciliary body and iris. Small lymphocytes diffusely infiltrate the stroma of the ciliary body and the root of the iris.
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). SLL in the lacrimal sac with molecularly confirmed monoclonal Ig rearrangement.
A: Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL)
Back Extra: Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL)
- Clinical: Chronic Lymphocytic Leukaemia/Small Lymphocytic Lymphoma (CLL/SLL) can present with visual acuity disturbance, ocular pain, and ophthalmoplegia.
- Micro: CLL/SLL is characterized by small lymphocytes with clumped chromatin, occasional small nucleoli, and scant cytoplasm.
- Ancillary: CLL/SLL cells express CD19, CD20, CD79a, PAX5, CD5, and CD23, and are negative for CD10 and other germinal center markers.
Reference Gallery:
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). CLL involvement of the ciliary body and iris. Small lymphocytes diffusely infiltrate the stroma of the ciliary body and the root of the iris.
Chronic lymphocytic leukaemia/small lymphocytic lymphoma (CLL/SLL). SLL in the lacrimal sac with molecularly confirmed monoclonal Ig rearrangement.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD3 is expressed by numerous reactive T-cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD5 is expressed by the tumour cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD10 is not expressed by the tumour cells.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD20 is expressed by the small tumoural lymphocytes.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. CD23 is expressed by the small tumoural lymphocytes.
Chronic lymphocytic leukaemia/small cell lymphoma (CLL/SLL). SLL involving the lacrimal sac. Cyclin D1 is not expressed by the tumour cells.
SLL/CLL. SLL involving the conjunctiva.

Q: Clinically, Extranodal Marginal Zone Lymphoma involving the eye classically presents as a pink-colored mass in the conjunctiva, often described as a [...].
Extranodal marginal zone lymphoma. A salmon-coloured tumour mass of the upper bulbar conjunctiva.
Extranodal marginal zone lymphoma. A, B: Axial and coronal T1 post-contrast MRIs show an intraconal and extraconal right orbital mass with extraocular muscle involvement (arrows).
A: salmon patch
Back Extra: Extranodal Marginal Zone Lymphoma
- Clinical: Extranodal Marginal Zone Lymphoma often presents as a pink-coloured mass (salmon patch) in the conjunctiva, with orbital masses causing proptosis and displacement of the eyeball.
- Micro: Histologically, the lesion shows a vaguely nodular and diffuse proliferation of small lymphocytes and marginal zone B cells, with abundant plasma cells and occasional Dutcher bodies.
- Ancillary: Immunohistochemistry typically shows CD20+ and CD5- B cells, with monotypic immunoglobulin light chain expression and BCL2 positivity.
Reference Gallery:
Extranodal marginal zone lymphoma. A salmon-coloured tumour mass of the upper bulbar conjunctiva.
Extranodal marginal zone lymphoma involving conjunctiva. Numerous small lymphoid cells obliterate normal stroma and invade overlying conjunctival epithelium.
Extranodal marginal zone lymphoma involving conjunctiva. In this area, there is a broad layer of plasma cells, some with Dutcher bodies.
Extranodal marginal zone lymphoma involving conjunctiva. An immunostain for CD20 shows diffuse staining of most lymphocytes, including many of those invading epithelium.
Extranodal marginal zone lymphoma involving conjunctiva. An immunostain for CD5 shows staining of small numbers of T cells; B cells are CD5-negative.
Extranodal marginal zone lymphoma involving conjunctiva. Multiple subepithelial plasma cells are κ+ (immunostain).
Extranodal marginal zone lymphoma involving conjunctiva. Only rare plasma cells are λ+, consistent with κ+ plasmacytic differentiation of the lymphoma (immunostain).
Extranodal marginal zone lymphoma involving conjunctiva. Numerous supepithelial plasma cells, some with Dutcher bodies, are seen (oil immersion).
Extranodal marginal zone lymphoma. A, B: Axial and coronal T1 post-contrast MRIs show an intraconal and extraconal right orbital mass with extraocular muscle involvement (arrows).

Q: Histologically, Extranodal Marginal Zone Lymphoma exhibits a proliferation of small lymphocytes and plasma cells, which may occasionally contain characteristic intranuclear pseudoinclusions called [...].
Extranodal marginal zone lymphoma involving conjunctiva. In this area, there is a broad layer of plasma cells, some with Dutcher bodies.
Extranodal marginal zone lymphoma involving conjunctiva. Numerous supepithelial plasma cells, some with Dutcher bodies, are seen (oil immersion).
A: Dutcher bodies
Back Extra: Extranodal Marginal Zone Lymphoma
- Clinical: Extranodal Marginal Zone Lymphoma often presents as a pink-coloured mass (salmon patch) in the conjunctiva, with orbital masses causing proptosis and displacement of the eyeball.
- Micro: Histologically, the lesion shows a vaguely nodular and diffuse proliferation of small lymphocytes and marginal zone B cells, with abundant plasma cells and occasional Dutcher bodies.
- Ancillary: Immunohistochemistry typically shows CD20+ and CD5- B cells, with monotypic immunoglobulin light chain expression and BCL2 positivity.
Reference Gallery:
Extranodal marginal zone lymphoma. A salmon-coloured tumour mass of the upper bulbar conjunctiva.
Extranodal marginal zone lymphoma involving conjunctiva. Numerous small lymphoid cells obliterate normal stroma and invade overlying conjunctival epithelium.
Extranodal marginal zone lymphoma involving conjunctiva. In this area, there is a broad layer of plasma cells, some with Dutcher bodies.
Extranodal marginal zone lymphoma involving conjunctiva. An immunostain for CD20 shows diffuse staining of most lymphocytes, including many of those invading epithelium.
Extranodal marginal zone lymphoma involving conjunctiva. An immunostain for CD5 shows staining of small numbers of T cells; B cells are CD5-negative.
Extranodal marginal zone lymphoma involving conjunctiva. Multiple subepithelial plasma cells are κ+ (immunostain).
Extranodal marginal zone lymphoma involving conjunctiva. Only rare plasma cells are λ+, consistent with κ+ plasmacytic differentiation of the lymphoma (immunostain).
Extranodal marginal zone lymphoma involving conjunctiva. Numerous supepithelial plasma cells, some with Dutcher bodies, are seen (oil immersion).
Extranodal marginal zone lymphoma. A, B: Axial and coronal T1 post-contrast MRIs show an intraconal and extraconal right orbital mass with extraocular muscle involvement (arrows).

Q: Immunohistochemical stains in Extranodal Marginal Zone Lymphoma typically show CD20-positive and CD5-negative B cells, and demonstrate [...] immunoglobulin light chain expression in areas of plasmacytic differentiation.
Extranodal marginal zone lymphoma involving conjunctiva. Multiple subepithelial plasma cells are κ+ (immunostain).
Extranodal marginal zone lymphoma involving conjunctiva. Only rare plasma cells are λ+, consistent with κ+ plasmacytic differentiation of the lymphoma (immunostain).
A: monotypic
Back Extra: Extranodal Marginal Zone Lymphoma
- Clinical: Extranodal Marginal Zone Lymphoma often presents as a pink-coloured mass (salmon patch) in the conjunctiva, with orbital masses causing proptosis and displacement of the eyeball.
- Micro: Histologically, the lesion shows a vaguely nodular and diffuse proliferation of small lymphocytes and marginal zone B cells, with abundant plasma cells and occasional Dutcher bodies.
- Ancillary: Immunohistochemistry typically shows CD20+ and CD5- B cells, with monotypic immunoglobulin light chain expression and BCL2 positivity.
Reference Gallery:
Extranodal marginal zone lymphoma. A salmon-coloured tumour mass of the upper bulbar conjunctiva.
Extranodal marginal zone lymphoma involving conjunctiva. Numerous small lymphoid cells obliterate normal stroma and invade overlying conjunctival epithelium.
Extranodal marginal zone lymphoma involving conjunctiva. In this area, there is a broad layer of plasma cells, some with Dutcher bodies.
Extranodal marginal zone lymphoma involving conjunctiva. An immunostain for CD20 shows diffuse staining of most lymphocytes, including many of those invading epithelium.
Extranodal marginal zone lymphoma involving conjunctiva. An immunostain for CD5 shows staining of small numbers of T cells; B cells are CD5-negative.
Extranodal marginal zone lymphoma involving conjunctiva. Multiple subepithelial plasma cells are κ+ (immunostain).
Extranodal marginal zone lymphoma involving conjunctiva. Only rare plasma cells are λ+, consistent with κ+ plasmacytic differentiation of the lymphoma (immunostain).
Extranodal marginal zone lymphoma involving conjunctiva. Numerous supepithelial plasma cells, some with Dutcher bodies, are seen (oil immersion).
Extranodal marginal zone lymphoma. A, B: Axial and coronal T1 post-contrast MRIs show an intraconal and extraconal right orbital mass with extraocular muscle involvement (arrows).

Q: In Mantle Cell Lymphoma, the pathognomonic immunohistochemical marker overexpressed due to the t(11;14) translocation is [...].
Mantle cell lymphoma. Cyclin D1 are expressed by the neoplastic B-cells confirming the diagnosis of mantle cell lymphoma.
A: Cyclin D1
Back Extra: Mantle Cell Lymphoma
- Clinical: Mantle cell lymphoma commonly presents as an ocular adnexal mass, often involving the lacrimal gland, with systemic involvement in most cases.
- Micro: Characterized by a vaguely nodular or diffuse proliferation of small to medium-sized lymphoid cells with irregular nuclei and scant cytoplasm.
- Ancillary: Cyclin D1 positivity and t(11;14) translocation are key diagnostic markers in immunohistochemistry and molecular studies.
Reference Gallery:
Mantle cell lymphoma involving orbital tissue and the lacrimal gland. A highly cellular and diffuse proliferation, sparing the glands, is seen at low power.
Mantle cell lymphoma involving lacrimal gland. The proliferation comprises small to medium-sized lymphoid cells with oval to irregular nuclei, inconspicuous nucleoli and scanty cytoplasm. Occasional pale dendritic histiocytes are observed.
Mantle cell lymphoma. CD20 immunohistochemistry highlighting the density and diffuse spread of the neoplastic mantle cell lymphoma B-cells.
Mantle cell lymphoma. Ki-67 immunohistochemistry highlighting the moderate to high growth fraction of the neoplastic B-cells in this orbital/lacrimal gland mantle cell lymphoma.
Mantle cell lymphoma. Cyclin D1 are expressed by the neoplastic B-cells confirming the diagnosis of mantle cell lymphoma.
Mantle cell lymphoma. A: Axial T2 MRI with fat saturation shows a homogeneously isointense right superotemporal orbital mass (arrow). B, C: Axial and coronal T1 post-contrast MRIs show homogeneous enhancement of the mass (arrows). D: Axial 18F-FDG PET/CT shows FDG avidity of the mass (arrow).

Q: A patient presents with an ocular adnexal mass (often involving the lacrimal gland). Biopsy reveals a diffuse proliferation of small to medium-sized lymphoid cells with irregular nuclei that are positive for CD20 and Cyclin D1. This presentation is characteristic of [...].
Mantle cell lymphoma involving lacrimal gland. The proliferation comprises small to medium-sized lymphoid cells with oval to irregular nuclei, inconspicuous nucleoli and scanty cytoplasm. Occasional pale dendritic histiocytes are observed.
Mantle cell lymphoma. CD20 immunohistochemistry highlighting the density and diffuse spread of the neoplastic mantle cell lymphoma B-cells.
Mantle cell lymphoma. A: Axial T2 MRI with fat saturation shows a homogeneously isointense right superotemporal orbital mass (arrow). B, C: Axial and coronal T1 post-contrast MRIs show homogeneous enhancement of the mass (arrows). D: Axial 18F-FDG PET/CT shows FDG avidity of the mass (arrow).
A: Mantle Cell Lymphoma
Back Extra: Mantle Cell Lymphoma
- Clinical: Mantle cell lymphoma commonly presents as an ocular adnexal mass, often involving the lacrimal gland, with systemic involvement in most cases.
- Micro: Characterized by a vaguely nodular or diffuse proliferation of small to medium-sized lymphoid cells with irregular nuclei and scant cytoplasm.
- Ancillary: Cyclin D1 positivity and t(11;14) translocation are key diagnostic markers in immunohistochemistry and molecular studies.
Reference Gallery:
Mantle cell lymphoma involving orbital tissue and the lacrimal gland. A highly cellular and diffuse proliferation, sparing the glands, is seen at low power.
Mantle cell lymphoma involving lacrimal gland. The proliferation comprises small to medium-sized lymphoid cells with oval to irregular nuclei, inconspicuous nucleoli and scanty cytoplasm. Occasional pale dendritic histiocytes are observed.
Mantle cell lymphoma. CD20 immunohistochemistry highlighting the density and diffuse spread of the neoplastic mantle cell lymphoma B-cells.
Mantle cell lymphoma. Ki-67 immunohistochemistry highlighting the moderate to high growth fraction of the neoplastic B-cells in this orbital/lacrimal gland mantle cell lymphoma.
Mantle cell lymphoma. Cyclin D1 are expressed by the neoplastic B-cells confirming the diagnosis of mantle cell lymphoma.
Mantle cell lymphoma. A: Axial T2 MRI with fat saturation shows a homogeneously isointense right superotemporal orbital mass (arrow). B, C: Axial and coronal T1 post-contrast MRIs show homogeneous enhancement of the mass (arrows). D: Axial 18F-FDG PET/CT shows FDG avidity of the mass (arrow).

Q: Microscopically, a Plasmacytoma is characterized by sheets of neoplastic [...], which typically feature eccentric nuclei with clockwork chromatin.
Secondary plasma cell myeloma / plasma cell neoplasm. Patient with known myeloma and an orbital mass. Sheets of mature appearing plasma cells with eccentric nuclei with clockwork chromatin.
Secondary plasma cell myeloma / plasma cell neoplasm. Patient with known myeloma and an orbital mass. Immature appearing plasma cells with larger nuclear:cytoplasmic ratios and with some prominent nucleoli. Some mature appearing plasma cells are also present.
A: plasma cells
Back Extra: Plasmacytoma
- Clinical: Plasmacytoma usually presents in the elderly age group with symptoms including orbital mass, proptosis, and eyelid swelling.
- Micro: The tumour consists of sheets of plasma cells with varying differentiation, including mature and immature forms.
- Ancillary: Tumour cells are positive for CD138, CD38, and MUM1, with κ or λ light chain restriction.
Reference Gallery:
Secondary plasma cell myeloma / plasma cell neoplasm. Patient with known myeloma and an orbital mass. Sheets of mature appearing plasma cells with eccentric nuclei with clockwork chromatin.
Secondary plasma cell myeloma / plasma cell neoplasm. Patient with known myeloma and an orbital mass. Immature appearing plasma cells with larger nuclear:cytoplasmic ratios and with some prominent nucleoli. Some mature appearing plasma cells are also present.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells are positive for CD138.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells show κ light chain restriction.
Secondary plasma cell myeloma involving orbit. Only a few tumour cells show expression of λ light chain.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells are positive for MUM1.

Q: Immunohistochemical staining of a Plasmacytoma reveals tumor cells that are characteristically positive for MUM1, CD38, and [...].
Secondary plasma cell myeloma involving orbit. The atypical plasma cells are positive for CD138.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells are positive for MUM1.
A: CD138
Back Extra: Plasmacytoma
- Clinical: Plasmacytoma usually presents in the elderly age group with symptoms including orbital mass, proptosis, and eyelid swelling.
- Micro: The tumour consists of sheets of plasma cells with varying differentiation, including mature and immature forms.
- Ancillary: Tumour cells are positive for CD138, CD38, and MUM1, with κ or λ light chain restriction.
Reference Gallery:
Secondary plasma cell myeloma / plasma cell neoplasm. Patient with known myeloma and an orbital mass. Sheets of mature appearing plasma cells with eccentric nuclei with clockwork chromatin.
Secondary plasma cell myeloma / plasma cell neoplasm. Patient with known myeloma and an orbital mass. Immature appearing plasma cells with larger nuclear:cytoplasmic ratios and with some prominent nucleoli. Some mature appearing plasma cells are also present.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells are positive for CD138.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells show κ light chain restriction.
Secondary plasma cell myeloma involving orbit. Only a few tumour cells show expression of λ light chain.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells are positive for MUM1.

Q: To confirm the monoclonal nature of a Plasmacytoma, ancillary studies must demonstrate [...] (either kappa or lambda).
Secondary plasma cell myeloma involving orbit. The atypical plasma cells show κ light chain restriction.
Secondary plasma cell myeloma involving orbit. Only a few tumour cells show expression of λ light chain.
A: light chain restriction
Back Extra: Plasmacytoma
- Clinical: Plasmacytoma usually presents in the elderly age group with symptoms including orbital mass, proptosis, and eyelid swelling.
- Micro: The tumour consists of sheets of plasma cells with varying differentiation, including mature and immature forms.
- Ancillary: Tumour cells are positive for CD138, CD38, and MUM1, with κ or λ light chain restriction.
Reference Gallery:
Secondary plasma cell myeloma / plasma cell neoplasm. Patient with known myeloma and an orbital mass. Sheets of mature appearing plasma cells with eccentric nuclei with clockwork chromatin.
Secondary plasma cell myeloma / plasma cell neoplasm. Patient with known myeloma and an orbital mass. Immature appearing plasma cells with larger nuclear:cytoplasmic ratios and with some prominent nucleoli. Some mature appearing plasma cells are also present.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells are positive for CD138.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells show κ light chain restriction.
Secondary plasma cell myeloma involving orbit. Only a few tumour cells show expression of λ light chain.
Secondary plasma cell myeloma involving orbit. The atypical plasma cells are positive for MUM1.

Q: Microscopically, Extranodal NK/T-cell lymphoma shows a diffuse infiltration of atypical lymphoid cells that classically exhibits uniform immunohistochemical positivity for the NK-cell marker [...].
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. A diffuse infiltration of medium to large-sized atypical lymphoid cells is observed.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. The cells are uniformly positive for CD56.
A: CD56
Back Extra: Extranodal NK/T-cell lymphoma
- Clinical: Extranodal NK/T-cell lymphoma may present with proptosis, diplopia, and limited ocular motility, often associated with nasal blockage and epistaxis.
- Micro: Characterized by diffuse infiltration of atypical lymphoid cells, angiocentric-angiodestructive growth pattern, and coagulative necrosis.
- Ancillary: Neoplastic cells are positive for CD56, CD2, and cytotoxic markers (TIA1, granzyme B, and perforin), and show EBER positivity.
Reference Gallery:
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. A diffuse infiltration of medium to large-sized atypical lymphoid cells is observed.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. The tumour cells show variable expression of the T-cell markers CD2 (shown here) and CD8.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. The tumour cells show variable expression of the T-cell markers CD2 and CD8 (shown here).
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. The cells are uniformly positive for CD56.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. Many tumour cells also stain positive for granzyme B (shown here) and TIA1.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. Many tumour cells also stain positive for granzyme B and TIA1 (shown here).

Q: In Extranodal NK/T-cell lymphoma, the tumor cells characteristically express cytotoxic granule proteins, showing immunohistochemical positivity for markers such as TIA1, perforin, and [...].
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. Many tumour cells also stain positive for granzyme B (shown here) and TIA1.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. Many tumour cells also stain positive for granzyme B and TIA1 (shown here).
A: granzyme B
Back Extra: Extranodal NK/T-cell lymphoma
- Clinical: Extranodal NK/T-cell lymphoma may present with proptosis, diplopia, and limited ocular motility, often associated with nasal blockage and epistaxis.
- Micro: Characterized by diffuse infiltration of atypical lymphoid cells, angiocentric-angiodestructive growth pattern, and coagulative necrosis.
- Ancillary: Neoplastic cells are positive for CD56, CD2, and cytotoxic markers (TIA1, granzyme B, and perforin), and show EBER positivity.
Reference Gallery:
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. A diffuse infiltration of medium to large-sized atypical lymphoid cells is observed.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. The tumour cells show variable expression of the T-cell markers CD2 (shown here) and CD8.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. The tumour cells show variable expression of the T-cell markers CD2 and CD8 (shown here).
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. The cells are uniformly positive for CD56.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. Many tumour cells also stain positive for granzyme B (shown here) and TIA1.
Primary sinonasal extranodal NK/T-cell lymphoma that involved the orbit. Many tumour cells also stain positive for granzyme B and TIA1 (shown here).

Q: A patient presenting with a pink, painless mass involving the eyelid (as seen in the clinical image), with a biopsy showing an atypical CD4+ lymphocytic infiltrate, should be evaluated for [...].
Primary cutaneous T-cell lymphoma involving eyelid. A 35-year-old female, otherwise healthy, with a pink, painless mass at the lateral edge of her right upper lid.
A: Ocular Adnexal T-Cell Lymphoma
Back Extra: Ocular Adnexal T-Cell Lymphoma
- Clinical: Ocular Adnexal T-Cell Lymphoma (OATCL) typically presents with unilateral erythema, ulceration, and swelling of the eyelid, masses with foreign-body sensation, tearing, proptosis, and reduced vision.
- Micro: Histologically, OATCL shows a diffuse infiltration of small-to-medium-sized lymphocytes with atypical nuclei, often with a CD4+ phenotype and monoclonal TCR gene rearrangement.
- Ancillary: IHC is positive for T-cell-associated antigens (CD3, CD4, CD8) and may show positivity for CD30, CD56, and ALK-1 depending on subtype.
Reference Gallery:
Primary cutaneous T-cell lymphoma involving eyelid. A 35-year-old female, otherwise healthy, with a pink, painless mass at the lateral edge of her right upper lid.
Primary cutaneous T-Cell lymphoma. Histology of the upper lid nodule shown above. Small to medium-sized atypical CD4+ T-cells (also CD3+ and CD2+, not shown) with monoclonal rearrangement of the TCR genes.

Q: Histologically, Ocular Adnexal T-Cell Lymphoma often demonstrates a diffuse infiltration of small-to-medium-sized atypical CD4+ lymphocytes that exhibit a monoclonal rearrangement of the [...] genes.
Primary cutaneous T-Cell lymphoma. Histology of the upper lid nodule shown above. Small to medium-sized atypical CD4+ T-cells (also CD3+ and CD2+, not shown) with monoclonal rearrangement of the TCR genes.
A: TCR
Back Extra: Ocular Adnexal T-Cell Lymphoma
- Clinical: Ocular Adnexal T-Cell Lymphoma (OATCL) typically presents with unilateral erythema, ulceration, and swelling of the eyelid, masses with foreign-body sensation, tearing, proptosis, and reduced vision.
- Micro: Histologically, OATCL shows a diffuse infiltration of small-to-medium-sized lymphocytes with atypical nuclei, often with a CD4+ phenotype and monoclonal TCR gene rearrangement.
- Ancillary: IHC is positive for T-cell-associated antigens (CD3, CD4, CD8) and may show positivity for CD30, CD56, and ALK-1 depending on subtype.
Reference Gallery:
Primary cutaneous T-cell lymphoma involving eyelid. A 35-year-old female, otherwise healthy, with a pink, painless mass at the lateral edge of her right upper lid.
Primary cutaneous T-Cell lymphoma. Histology of the upper lid nodule shown above. Small to medium-sized atypical CD4+ T-cells (also CD3+ and CD2+, not shown) with monoclonal rearrangement of the TCR genes.

Q: In Extramedullary Myeloid Sarcoma, the tumor is characterized microscopically by sheets of large neoplastic cells with irregular nuclear contours, conspicuous nucleoli, and fine, [...] chromatin.
Extramedullary myeloid sarcoma. Sheets of large sized neoplastic cells with round nuclei, irregular nuclear contours, fine blastic chromatin and conspicuous nucleoli.
A: blastic
Back Extra: Extramedullary Myeloid Sarcoma
- Clinical: Extramedullary Myeloid Sarcoma (EMS) often presents with unilateral proptosis, diplopia, and eyelid swelling.
- Micro: EMS is characterized by sheets of large neoplastic cells with round nuclei, irregular nuclear contours, fine blastic chromatin, and conspicuous nucleoli.
- Ancillary: Immunohistochemical staining for MPO is strongly positive in EMS, aiding in its diagnosis.
Reference Gallery:
Extramedullary myeloid sarcoma. Sheets of large sized neoplastic cells with round nuclei, irregular nuclear contours, fine blastic chromatin and conspicuous nucleoli.
Extramedullary myeloid sarcoma. The neoplastic cells are strongly positive for MPO, supporting the diagnosis of myeloid sarcoma.

Q: The neoplastic cells of Extramedullary Myeloid Sarcoma are typically strongly positive for [...] on immunohistochemistry, supporting a myeloid lineage.
Extramedullary myeloid sarcoma. The neoplastic cells are strongly positive for MPO, supporting the diagnosis of myeloid sarcoma.
A: myeloperoxidase (MPO)
Back Extra: Extramedullary Myeloid Sarcoma
- Clinical: Extramedullary Myeloid Sarcoma (EMS) often presents with unilateral proptosis, diplopia, and eyelid swelling.
- Micro: EMS is characterized by sheets of large neoplastic cells with round nuclei, irregular nuclear contours, fine blastic chromatin, and conspicuous nucleoli.
- Ancillary: Immunohistochemical staining for MPO is strongly positive in EMS, aiding in its diagnosis.
Reference Gallery:
Extramedullary myeloid sarcoma. Sheets of large sized neoplastic cells with round nuclei, irregular nuclear contours, fine blastic chromatin and conspicuous nucleoli.
Extramedullary myeloid sarcoma. The neoplastic cells are strongly positive for MPO, supporting the diagnosis of myeloid sarcoma.

Q: In Reactive Lymphoid Hyperplasia, histological examination typically shows a diffuse infiltrate of mature lymphocytes with scattered irregular secondary lymphoid follicles containing prominent [...].
Reactive Lymphoid Hyperplasia. Lacrimal gland biopsy shows acinar atrophy and lymphoid hyperplasia with numerous reactive follicles.
Reactive Lymphoid Hyperplasia. Orbital biopsy shows reactive lymphoid follicles with prominent germinal centers.
A: germinal centers
Back Extra: Reactive Lymphoid Hyperplasia
- Clinical: Reactive lymphoid hyperplasia (RLH) presents as a unilateral, red or orange, painless swelling or tumor mass, leading to symptoms such as proptosis, eyelid or conjunctival mass, decreased ocular motility, and visual acuity.
- Micro: RLH shows a diffuse infiltrate of mature lymphocytes within the stroma, along with scattered irregular secondary lymphoid follicles with regular germinal centers and narrow marginal and mantle zones.
- Ancillary: A polyclonal or oligoclonal amplification product is typically obtained on clonality analyses, and flow cytometric analysis can demonstrate the absence of a clonal B-cell population.
Reference Gallery:
Reactive lymphoid hyperplasia. Head CT on a 35-year-old patient, history of left upper eyelid fullness, shows enlargement of the left lacrimal gland.
Reactive Lymphoid Hyperplasia. Lacrimal gland biopsy shows acinar atrophy and lymphoid hyperplasia with numerous reactive follicles.
Reactive Lymphoid Hyperplasia. Lacrimal gland biopsy showing acinar atrophy and reactive lymphoid hyperplasia.
Reactive Lymphoid Hyperplasia. CD3 immunostaining shows positive T-cells around reactive follicles (lacrimal gland biopsy)
Reactive Lymphoid Hyperplasia. CD20 immunostaining shows positivity in the reactive follicles (lacrimal gland biopsy)
Reactive Lymphoid Hyperplasia. Orbital biopsy shows reactive lymphoid follicles with prominent germinal centers.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy demonstrating reactive lymphoid hyperplasia.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy - CD3 immunostaining shows physiologic distribution of T-cells in the perifollicular region.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy - CD20 immunostaining demonstrates physiologic distribution B-cells
Reactive Lymphoid Hyperplasia. Centrocytes and centroblasts in the germinal centers are positive for BCL6 immunostaining
Reactive Lymphoid Hyperplasia. Cells in the germinal centers are positive with CD10 immunostaining.
Reactive Lymphoid Hyperplasia. Centrocytes and centroblasts in the germinal centers are negative with BCL2 immunostaining.

Q: To differentiate Reactive Lymphoid Hyperplasia from follicular lymphoma, immunostaining for [...] is characteristically negative within the centrocytes and centroblasts of the germinal centers.
Reactive Lymphoid Hyperplasia. Centrocytes and centroblasts in the germinal centers are negative with BCL2 immunostaining.
A: BCL2
Back Extra: Reactive Lymphoid Hyperplasia
- Clinical: Reactive lymphoid hyperplasia (RLH) presents as a unilateral, red or orange, painless swelling or tumor mass, leading to symptoms such as proptosis, eyelid or conjunctival mass, decreased ocular motility, and visual acuity.
- Micro: RLH shows a diffuse infiltrate of mature lymphocytes within the stroma, along with scattered irregular secondary lymphoid follicles with regular germinal centers and narrow marginal and mantle zones.
- Ancillary: A polyclonal or oligoclonal amplification product is typically obtained on clonality analyses, and flow cytometric analysis can demonstrate the absence of a clonal B-cell population.
Reference Gallery:
Reactive lymphoid hyperplasia. Head CT on a 35-year-old patient, history of left upper eyelid fullness, shows enlargement of the left lacrimal gland.
Reactive Lymphoid Hyperplasia. Lacrimal gland biopsy shows acinar atrophy and lymphoid hyperplasia with numerous reactive follicles.
Reactive Lymphoid Hyperplasia. Lacrimal gland biopsy showing acinar atrophy and reactive lymphoid hyperplasia.
Reactive Lymphoid Hyperplasia. CD3 immunostaining shows positive T-cells around reactive follicles (lacrimal gland biopsy)
Reactive Lymphoid Hyperplasia. CD20 immunostaining shows positivity in the reactive follicles (lacrimal gland biopsy)
Reactive Lymphoid Hyperplasia. Orbital biopsy shows reactive lymphoid follicles with prominent germinal centers.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy demonstrating reactive lymphoid hyperplasia.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy - CD3 immunostaining shows physiologic distribution of T-cells in the perifollicular region.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy - CD20 immunostaining demonstrates physiologic distribution B-cells
Reactive Lymphoid Hyperplasia. Centrocytes and centroblasts in the germinal centers are positive for BCL6 immunostaining
Reactive Lymphoid Hyperplasia. Cells in the germinal centers are positive with CD10 immunostaining.
Reactive Lymphoid Hyperplasia. Centrocytes and centroblasts in the germinal centers are negative with BCL2 immunostaining.

Q: Immunohistochemistry in Reactive Lymphoid Hyperplasia demonstrates a physiologic distribution of lymphocytes, with B-cells concentrated within the reactive follicles as highlighted by [...] positivity.
Reactive Lymphoid Hyperplasia. CD20 immunostaining shows positivity in the reactive follicles (lacrimal gland biopsy)
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy - CD20 immunostaining demonstrates physiologic distribution B-cells
A: CD20
Back Extra: Reactive Lymphoid Hyperplasia
- Clinical: Reactive lymphoid hyperplasia (RLH) presents as a unilateral, red or orange, painless swelling or tumor mass, leading to symptoms such as proptosis, eyelid or conjunctival mass, decreased ocular motility, and visual acuity.
- Micro: RLH shows a diffuse infiltrate of mature lymphocytes within the stroma, along with scattered irregular secondary lymphoid follicles with regular germinal centers and narrow marginal and mantle zones.
- Ancillary: A polyclonal or oligoclonal amplification product is typically obtained on clonality analyses, and flow cytometric analysis can demonstrate the absence of a clonal B-cell population.
Reference Gallery:
Reactive lymphoid hyperplasia. Head CT on a 35-year-old patient, history of left upper eyelid fullness, shows enlargement of the left lacrimal gland.
Reactive Lymphoid Hyperplasia. Lacrimal gland biopsy shows acinar atrophy and lymphoid hyperplasia with numerous reactive follicles.
Reactive Lymphoid Hyperplasia. Lacrimal gland biopsy showing acinar atrophy and reactive lymphoid hyperplasia.
Reactive Lymphoid Hyperplasia. CD3 immunostaining shows positive T-cells around reactive follicles (lacrimal gland biopsy)
Reactive Lymphoid Hyperplasia. CD20 immunostaining shows positivity in the reactive follicles (lacrimal gland biopsy)
Reactive Lymphoid Hyperplasia. Orbital biopsy shows reactive lymphoid follicles with prominent germinal centers.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy demonstrating reactive lymphoid hyperplasia.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy - CD3 immunostaining shows physiologic distribution of T-cells in the perifollicular region.
Reactive Lymphoid Hyperplasia. Right lateral orbital biopsy - CD20 immunostaining demonstrates physiologic distribution B-cells
Reactive Lymphoid Hyperplasia. Centrocytes and centroblasts in the germinal centers are positive for BCL6 immunostaining
Reactive Lymphoid Hyperplasia. Cells in the germinal centers are positive with CD10 immunostaining.
Reactive Lymphoid Hyperplasia. Centrocytes and centroblasts in the germinal centers are negative with BCL2 immunostaining.

Q: Microscopically, Intraductal Carcinoma of the lacrimal gland is characterized by tumor islands that frequently show a [...] architecture with cystic spaces filled with densely eosinophilic secretions.
Lacrimal intraductal carcinoma. Tumour islands show cribriform architecture with cystic spaced filled with densely eosinophilic secretions.
Lacrimal intraductal carcinoma. Tumour cells show low grade cytology with central nuclei, small single nucleoli, and ample eosinophilic cytoplasm.
A: cribriform
Back Extra: Intraductal Carcinoma
- Clinical: Intraductal carcinoma of the lacrimal gland usually presents with proptosis and inferiomedial globe displacement.
- Micro: The tumour is characterized by round lobules with variable solid, papillary-cystic, cribriform, and micropapillary architecture, surrounded by a single continuous layer of myoepithelial cells.
- Ancillary: Immunohistochemistry shows positivity for S100 and myoepithelial markers such as p63 and SMM-HC.
Reference Gallery:
Lacrimal intraductal carcinoma. The well-circumscribed tumour consists of islands surrounded by lymphoid tissue and focally dense collagenous stroma.
Lacrimal intraductal carcinoma. Tumour islands show cribriform architecture with cystic spaced filled with densely eosinophilic secretions.
Lacrimal intraductal carcinoma. Tumour cells show low grade cytology with central nuclei, small single nucleoli, and ample eosinophilic cytoplasm.
Lacrimal intraductal carcinoma. Smooth muscle myosin heavy chain immunohistochemistry highlights a thin layer of myoepithelial cells surrounding each tumour island.
Lacrimal intraductal carcinoma. The tumour shows diffuse positivity for S100 by immunohistochemistry.

Q: A defining feature of Intraductal Carcinoma is the presence of tumor lobules surrounded by a single continuous layer of [...] cells, which can be highlighted by markers such as smooth muscle myosin heavy chain (SMM-HC).
Lacrimal intraductal carcinoma. Smooth muscle myosin heavy chain immunohistochemistry highlights a thin layer of myoepithelial cells surrounding each tumour island.
A: myoepithelial
Back Extra: Intraductal Carcinoma
- Clinical: Intraductal carcinoma of the lacrimal gland usually presents with proptosis and inferiomedial globe displacement.
- Micro: The tumour is characterized by round lobules with variable solid, papillary-cystic, cribriform, and micropapillary architecture, surrounded by a single continuous layer of myoepithelial cells.
- Ancillary: Immunohistochemistry shows positivity for S100 and myoepithelial markers such as p63 and SMM-HC.
Reference Gallery:
Lacrimal intraductal carcinoma. The well-circumscribed tumour consists of islands surrounded by lymphoid tissue and focally dense collagenous stroma.
Lacrimal intraductal carcinoma. Tumour islands show cribriform architecture with cystic spaced filled with densely eosinophilic secretions.
Lacrimal intraductal carcinoma. Tumour cells show low grade cytology with central nuclei, small single nucleoli, and ample eosinophilic cytoplasm.
Lacrimal intraductal carcinoma. Smooth muscle myosin heavy chain immunohistochemistry highlights a thin layer of myoepithelial cells surrounding each tumour island.
Lacrimal intraductal carcinoma. The tumour shows diffuse positivity for S100 by immunohistochemistry.

Q: Immunohistochemistry in lacrimal Intraductal Carcinoma typically demonstrates diffuse positivity for [...] within the luminal tumor cells.
Lacrimal intraductal carcinoma. The tumour shows diffuse positivity for S100 by immunohistochemistry.
A: S100
Back Extra: Intraductal Carcinoma
- Clinical: Intraductal carcinoma of the lacrimal gland usually presents with proptosis and inferiomedial globe displacement.
- Micro: The tumour is characterized by round lobules with variable solid, papillary-cystic, cribriform, and micropapillary architecture, surrounded by a single continuous layer of myoepithelial cells.
- Ancillary: Immunohistochemistry shows positivity for S100 and myoepithelial markers such as p63 and SMM-HC.
Reference Gallery:
Lacrimal intraductal carcinoma. The well-circumscribed tumour consists of islands surrounded by lymphoid tissue and focally dense collagenous stroma.
Lacrimal intraductal carcinoma. Tumour islands show cribriform architecture with cystic spaced filled with densely eosinophilic secretions.
Lacrimal intraductal carcinoma. Tumour cells show low grade cytology with central nuclei, small single nucleoli, and ample eosinophilic cytoplasm.
Lacrimal intraductal carcinoma. Smooth muscle myosin heavy chain immunohistochemistry highlights a thin layer of myoepithelial cells surrounding each tumour island.
Lacrimal intraductal carcinoma. The tumour shows diffuse positivity for S100 by immunohistochemistry.

Q: A histologic hallmark of Pleomorphic Adenoma is a morphologically diverse stroma that frequently exhibits fibrous, myxoid, and [...] differentiation.
Pleomorphic adenoma. Classic pattern shows a balanced representation of epithelial, myoepithelial, and stromal components.
Pleomorphic adenoma. The stromal component, derived from myoepithelial cells, is often represented by fibrous and myxoid areas.
Pleomorphic adenoma. Chondroid areas are often seen in the stroma.
A: chondroid
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic Adenoma typically presents as a slow-growing, painless mass in the lateral upper eyelid, which can progress to proptosis and globe displacement.
- Micro: The hallmark of Pleomorphic Adenoma is its morphological diversity, showing a balanced representation of epithelial, myoepithelial, and stromal components.
- Ancillary: Immunohistochemistry shows positive staining for PLAG1 (nuclear) in Pleomorphic Adenoma, which is specific for these tumours.
Reference Gallery:
Pleomorphic Adenoma. Well demarcated, encapsulated, nodule with yellowish glistening cut surface.
Pleomorphic adenoma. Low-power microscopic view shows a sharp demarcation between the benign lacrimal gland tissue and the pleomorphic adenoma due to the presence of a pseudocapsule.
Pleomorphic adenoma. Classic pattern shows a balanced representation of epithelial, myoepithelial, and stromal components.
Pleomorphic adenoma. The stromal component, derived from myoepithelial cells, is often represented by fibrous and myxoid areas.
Pleomorphic adenoma. Chondroid areas are often seen in the stroma.
Pleomorphic adenoma. In a few cases, protrusions into and through the pseudocapsule can be seen. These might cause recurrences if the tumour is incompletely excised.
Pleomorphic adenoma. Areas of squamous metaplasia may be observed.
Pleomorphic adenoma. In more cellular pattern tumours, the epithelial component predominates, raising the differential with other epithelial neoplasms.
Pleomorphic adenoma. Note clearing of the myoepithelial cells and a focus of squamous metaplasia in this field.
Pleomorphic adenoma. Axial CT image of a pleomorphic adenoma; note the well-circumscribed round lacrimal gland mass.
Pleomorphic adenoma. Coronal CT image of a pleomorphic adenoma; note the bony expansion of the lacrimal gland fossa and lack of frank bony erosion.
Pleomorphic adenoma. Axial CT image of a “cellular” pleomorphic adenoma of the left lacrimal gland; this lesion was benign but with a higher proliferation rate than the typical pleomorphic adenoma.

Q: A classic microscopic feature of Pleomorphic Adenoma is its sharp demarcation by a [...]; microscopic tumor protrusions through this structure are a common source of recurrence if incompletely excised.
Pleomorphic adenoma. Low-power microscopic view shows a sharp demarcation between the benign lacrimal gland tissue and the pleomorphic adenoma due to the presence of a pseudocapsule.
Pleomorphic adenoma. In a few cases, protrusions into and through the pseudocapsule can be seen. These might cause recurrences if the tumour is incompletely excised.
A: pseudocapsule
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic Adenoma typically presents as a slow-growing, painless mass in the lateral upper eyelid, which can progress to proptosis and globe displacement.
- Micro: The hallmark of Pleomorphic Adenoma is its morphological diversity, showing a balanced representation of epithelial, myoepithelial, and stromal components.
- Ancillary: Immunohistochemistry shows positive staining for PLAG1 (nuclear) in Pleomorphic Adenoma, which is specific for these tumours.
Reference Gallery:
Pleomorphic Adenoma. Well demarcated, encapsulated, nodule with yellowish glistening cut surface.
Pleomorphic adenoma. Low-power microscopic view shows a sharp demarcation between the benign lacrimal gland tissue and the pleomorphic adenoma due to the presence of a pseudocapsule.
Pleomorphic adenoma. Classic pattern shows a balanced representation of epithelial, myoepithelial, and stromal components.
Pleomorphic adenoma. The stromal component, derived from myoepithelial cells, is often represented by fibrous and myxoid areas.
Pleomorphic adenoma. Chondroid areas are often seen in the stroma.
Pleomorphic adenoma. In a few cases, protrusions into and through the pseudocapsule can be seen. These might cause recurrences if the tumour is incompletely excised.
Pleomorphic adenoma. Areas of squamous metaplasia may be observed.
Pleomorphic adenoma. In more cellular pattern tumours, the epithelial component predominates, raising the differential with other epithelial neoplasms.
Pleomorphic adenoma. Note clearing of the myoepithelial cells and a focus of squamous metaplasia in this field.
Pleomorphic adenoma. Axial CT image of a pleomorphic adenoma; note the well-circumscribed round lacrimal gland mass.
Pleomorphic adenoma. Coronal CT image of a pleomorphic adenoma; note the bony expansion of the lacrimal gland fossa and lack of frank bony erosion.
Pleomorphic adenoma. Axial CT image of a “cellular” pleomorphic adenoma of the left lacrimal gland; this lesion was benign but with a higher proliferation rate than the typical pleomorphic adenoma.

Q: On CT imaging, a Pleomorphic Adenoma of the lacrimal gland typically presents as a well-circumscribed mass causing characteristic bony [...] of the lacrimal fossa without frank bone erosion.
Pleomorphic adenoma. Axial CT image of a pleomorphic adenoma; note the well-circumscribed round lacrimal gland mass.
Pleomorphic adenoma. Coronal CT image of a pleomorphic adenoma; note the bony expansion of the lacrimal gland fossa and lack of frank bony erosion.
A: expansion
Back Extra: Pleomorphic Adenoma
- Clinical: Pleomorphic Adenoma typically presents as a slow-growing, painless mass in the lateral upper eyelid, which can progress to proptosis and globe displacement.
- Micro: The hallmark of Pleomorphic Adenoma is its morphological diversity, showing a balanced representation of epithelial, myoepithelial, and stromal components.
- Ancillary: Immunohistochemistry shows positive staining for PLAG1 (nuclear) in Pleomorphic Adenoma, which is specific for these tumours.
Reference Gallery:
Pleomorphic Adenoma. Well demarcated, encapsulated, nodule with yellowish glistening cut surface.
Pleomorphic adenoma. Low-power microscopic view shows a sharp demarcation between the benign lacrimal gland tissue and the pleomorphic adenoma due to the presence of a pseudocapsule.
Pleomorphic adenoma. Classic pattern shows a balanced representation of epithelial, myoepithelial, and stromal components.
Pleomorphic adenoma. The stromal component, derived from myoepithelial cells, is often represented by fibrous and myxoid areas.
Pleomorphic adenoma. Chondroid areas are often seen in the stroma.
Pleomorphic adenoma. In a few cases, protrusions into and through the pseudocapsule can be seen. These might cause recurrences if the tumour is incompletely excised.
Pleomorphic adenoma. Areas of squamous metaplasia may be observed.
Pleomorphic adenoma. In more cellular pattern tumours, the epithelial component predominates, raising the differential with other epithelial neoplasms.
Pleomorphic adenoma. Note clearing of the myoepithelial cells and a focus of squamous metaplasia in this field.
Pleomorphic adenoma. Axial CT image of a pleomorphic adenoma; note the well-circumscribed round lacrimal gland mass.
Pleomorphic adenoma. Coronal CT image of a pleomorphic adenoma; note the bony expansion of the lacrimal gland fossa and lack of frank bony erosion.
Pleomorphic adenoma. Axial CT image of a “cellular” pleomorphic adenoma of the left lacrimal gland; this lesion was benign but with a higher proliferation rate than the typical pleomorphic adenoma.

Q: Radiologically, Adenocarcinoma NOS of the Lacrimal Drainage System typically appears as a heterogeneously enhancing mass in the lacrimal sac, corresponding to a firm, slow-growing clinical mass located at the [...].
Nasolacrimal duct carcinoma. A, B: Axial and coronal T1 post-contrast MRIs show a large, heterogeneously enhancing mass in the region of the right lacrimal sac with involvement of the medial right orbit and the sinonasal cavity (arrows).
A: medial canthus
Back Extra: Adenocarcinoma NOS of the Lacrimal Drainage System
- Clinical: Nearly all patients with Adenocarcinoma NOS of the Lacrimal Drainage System present with epiphora and a firm, slow-growing, immobile mass in the medial canthus.
- Micro: Adenocarcinoma of the lacrimal drainage system often shows sheets, cords, or single cell infiltration of pleomorphic cells forming lumens with variable mucin production.
- Ancillary: Immunohistochemistry typically shows positivity for pancytokeratin (AE1/AE3), CK7, androgen receptor, and GCDFP-15.
Reference Gallery:
Nasolacrimal duct carcinoma. A, B: Axial and coronal T1 post-contrast MRIs show a large, heterogeneously enhancing mass in the region of the right lacrimal sac with involvement of the medial right orbit and the sinonasal cavity (arrows).

Q: Patients with Adenocarcinoma NOS of the Lacrimal Drainage System characteristically present with an obstructive mass in the medial canthus causing excessive tearing, a clinical symptom specifically termed [...].
Nasolacrimal duct carcinoma. A, B: Axial and coronal T1 post-contrast MRIs show a large, heterogeneously enhancing mass in the region of the right lacrimal sac with involvement of the medial right orbit and the sinonasal cavity (arrows).
A: epiphora
Back Extra: Adenocarcinoma NOS of the Lacrimal Drainage System
- Clinical: Nearly all patients with Adenocarcinoma NOS of the Lacrimal Drainage System present with epiphora and a firm, slow-growing, immobile mass in the medial canthus.
- Micro: Adenocarcinoma of the lacrimal drainage system often shows sheets, cords, or single cell infiltration of pleomorphic cells forming lumens with variable mucin production.
- Ancillary: Immunohistochemistry typically shows positivity for pancytokeratin (AE1/AE3), CK7, androgen receptor, and GCDFP-15.
Reference Gallery:
Nasolacrimal duct carcinoma. A, B: Axial and coronal T1 post-contrast MRIs show a large, heterogeneously enhancing mass in the region of the right lacrimal sac with involvement of the medial right orbit and the sinonasal cavity (arrows).

Q: Histopathologically, Adenocarcinoma, NOS of the lacrimal gland is characterized by a solid and glandular growth pattern, with neoplastic cells typically displaying abundant eosinophilic cytoplasm and focal [...].
Adenocarcinoma, NOS. At scanning magnification, the neoplasm arises in the lacrimal gland lobules
Adenocarcinoma, NOS. Higher magnification demonstrates neoplastic cells with abundant eosinophilic cytoplasm with focal intracytoplasmic vacuoles arranged in ductules with eosinophilic secretory material.
A: intracytoplasmic vacuoles
Q: Adenocarcinoma, NOS
- Clinical: Patients with [...] often present with upper eyelid swelling, ptosis, and non-axial proptosis due to the mass effect of the enlarged lacrimal gland.
- Micro: Histopathologically, [...] shows a solid and glandular growth pattern with neoplastic cells having abundant eosinophilic cytoplasm and focal intracytoplasmic vacuoles.
- Ancillary: [...] is non-specific in ancillary studies and lacks the molecular alterations that would categorize it as another specific carcinoma type.
Reference Gallery:
Adenocarcinoma, NOS. At scanning magnification, the neoplasm arises in the lacrimal gland lobules
Adenocarcinoma, NOS. Higher magnification demonstrates neoplastic cells with abundant eosinophilic cytoplasm with focal intracytoplasmic vacuoles arranged in ductules with eosinophilic secretory material.
Adenocarcinoma, NOS. Focal mucin in the neoplastic cells adjacent to the non-neoplastic lacrimal gland acinar cells with PAS-positive zymogen granules.
Adenocarcinoma, NOS. Axial T1 post-contrast MRI shows an enhancing mass in the superior right orbit and periorbital soft tissues (arrow).
Adenocarcinoma, NOS. Axial T2 MRI shows an isointense mass in the superior right orbit (arrow).
A: Adenocarcinoma, NOS; Adenocarcinoma, NOS; Adenocarcinoma, NOS

Q: In Adenocarcinoma, NOS, the neoplastic cells may contain focal [...], which can be seen adjacent to non-neoplastic lacrimal gland acinar cells containing PAS-positive zymogen granules.
Adenocarcinoma, NOS. Focal mucin in the neoplastic cells adjacent to the non-neoplastic lacrimal gland acinar cells with PAS-positive zymogen granules.
A: mucin
Q: Adenocarcinoma, NOS
- Clinical: Patients with [...] often present with upper eyelid swelling, ptosis, and non-axial proptosis due to the mass effect of the enlarged lacrimal gland.
- Micro: Histopathologically, [...] shows a solid and glandular growth pattern with neoplastic cells having abundant eosinophilic cytoplasm and focal intracytoplasmic vacuoles.
- Ancillary: [...] is non-specific in ancillary studies and lacks the molecular alterations that would categorize it as another specific carcinoma type.
Reference Gallery:
Adenocarcinoma, NOS. At scanning magnification, the neoplasm arises in the lacrimal gland lobules
Adenocarcinoma, NOS. Higher magnification demonstrates neoplastic cells with abundant eosinophilic cytoplasm with focal intracytoplasmic vacuoles arranged in ductules with eosinophilic secretory material.
Adenocarcinoma, NOS. Focal mucin in the neoplastic cells adjacent to the non-neoplastic lacrimal gland acinar cells with PAS-positive zymogen granules.
Adenocarcinoma, NOS. Axial T1 post-contrast MRI shows an enhancing mass in the superior right orbit and periorbital soft tissues (arrow).
Adenocarcinoma, NOS. Axial T2 MRI shows an isointense mass in the superior right orbit (arrow).
A: Adenocarcinoma, NOS; Adenocarcinoma, NOS; Adenocarcinoma, NOS

Q: Radiologically, Adenocarcinoma, NOS of the lacrimal gland presents as an enhancing mass in the superior orbit on MRI, which clinically causes upper eyelid swelling, ptosis, and non-axial [...].
Adenocarcinoma, NOS. Axial T1 post-contrast MRI shows an enhancing mass in the superior right orbit and periorbital soft tissues (arrow).
Adenocarcinoma, NOS. Axial T2 MRI shows an isointense mass in the superior right orbit (arrow).
A: proptosis
Q: Adenocarcinoma, NOS
- Clinical: Patients with [...] often present with upper eyelid swelling, ptosis, and non-axial proptosis due to the mass effect of the enlarged lacrimal gland.
- Micro: Histopathologically, [...] shows a solid and glandular growth pattern with neoplastic cells having abundant eosinophilic cytoplasm and focal intracytoplasmic vacuoles.
- Ancillary: [...] is non-specific in ancillary studies and lacks the molecular alterations that would categorize it as another specific carcinoma type.
Reference Gallery:
Adenocarcinoma, NOS. At scanning magnification, the neoplasm arises in the lacrimal gland lobules
Adenocarcinoma, NOS. Higher magnification demonstrates neoplastic cells with abundant eosinophilic cytoplasm with focal intracytoplasmic vacuoles arranged in ductules with eosinophilic secretory material.
Adenocarcinoma, NOS. Focal mucin in the neoplastic cells adjacent to the non-neoplastic lacrimal gland acinar cells with PAS-positive zymogen granules.
Adenocarcinoma, NOS. Axial T1 post-contrast MRI shows an enhancing mass in the superior right orbit and periorbital soft tissues (arrow).
Adenocarcinoma, NOS. Axial T2 MRI shows an isointense mass in the superior right orbit (arrow).
A: Adenocarcinoma, NOS; Adenocarcinoma, NOS; Adenocarcinoma, NOS

Q: Histologically, Adenoid Cystic Carcinoma frequently exhibits a cribriform architectural pattern, classically described as having a [...] appearance due to cystic spaces filled with basophilic glycosaminoglycans and eosinophilic basal lamina.
Adenoid cystic carcinoma. Cribriform pattern with a Swiss-cheese appearance, composed of cystic structures containing basophilic amorphous glycosaminoglycans and eosinophilic hyalinized basal lamina.
A: Swiss-cheese
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma (ACC) commonly presents with lacrimal gland enlargement, inferomedial globe displacement, and non-axial proptosis. Pain and paraesthesia are cardinal signs.
- Micro: ACC is characterized by three main patterns: cribriform (Swiss-cheese appearance), tubular (small glandular structures), and solid/basaloid (compact sheet-like proliferating cells).
- Ancillary: MYB and KIT immunostaining can be used as surrogates for MYB rearrangement molecular studies, with a mean Ki67 index of 30% and p53 expression in 39% of cases.
Reference Gallery:
Adenoid cystic carcinoma. The carcinoma infiltrates the normal lacrimal gland.
Adenoid cystic carcinoma. Cribriform pattern with a Swiss-cheese appearance, composed of cystic structures containing basophilic amorphous glycosaminoglycans and eosinophilic hyalinized basal lamina.
Adenoid cystic carcinoma. The tubular pattern is composed predominantly of small glandular structures.
Adenoid cystic carcinoma. The solid/basaloid pattern is composed of compact sheet-like proliferating basaloid myoepithelial cells that lack the cribriform or tubular architecture.
Adenoid cystic carcinoma. Diffuse CKIT staining is seen in this tumour with a solid/basaloid pattern.
Adenoid cystic carcinoma. Perineural invasion is commonly seen.
Adenoid cystic carcinoma. T1 weighted MRI demonstrates a right lacrimal gland mass; note extension of the lesion along the lateral wall of the orbit posteriorly.
Adenoid cystic carcinoma. Coronal MRI image demonstrates a left lacrimal gland adenoid cystic carcinoma with extradural extension superiorly.
Adenoid cystic carcinoma. Axial MRI demonstrates a recurrent lacrimal gland adenoid cystic carcinoma with intracranial extension; this lesion was treated with inta-arterial chemotherapy and radiation and recurred.
Adenoid cystic carcinoma. Coronal MRI demonstrates a recurrent lacrimal gland adenoid cystic carcinoma after failed treatment with intaarterial chemotherapy and radiation; the lesion extends intracranially.

Q: The cardinal clinical symptoms of pain and paresthesia in patients with Adenoid Cystic Carcinoma of the lacrimal gland strongly correlate with the frequent histologic finding of [...].
Adenoid cystic carcinoma. Perineural invasion is commonly seen.
A: perineural invasion
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma (ACC) commonly presents with lacrimal gland enlargement, inferomedial globe displacement, and non-axial proptosis. Pain and paraesthesia are cardinal signs.
- Micro: ACC is characterized by three main patterns: cribriform (Swiss-cheese appearance), tubular (small glandular structures), and solid/basaloid (compact sheet-like proliferating cells).
- Ancillary: MYB and KIT immunostaining can be used as surrogates for MYB rearrangement molecular studies, with a mean Ki67 index of 30% and p53 expression in 39% of cases.
Reference Gallery:
Adenoid cystic carcinoma. The carcinoma infiltrates the normal lacrimal gland.
Adenoid cystic carcinoma. Cribriform pattern with a Swiss-cheese appearance, composed of cystic structures containing basophilic amorphous glycosaminoglycans and eosinophilic hyalinized basal lamina.
Adenoid cystic carcinoma. The tubular pattern is composed predominantly of small glandular structures.
Adenoid cystic carcinoma. The solid/basaloid pattern is composed of compact sheet-like proliferating basaloid myoepithelial cells that lack the cribriform or tubular architecture.
Adenoid cystic carcinoma. Diffuse CKIT staining is seen in this tumour with a solid/basaloid pattern.
Adenoid cystic carcinoma. Perineural invasion is commonly seen.
Adenoid cystic carcinoma. T1 weighted MRI demonstrates a right lacrimal gland mass; note extension of the lesion along the lateral wall of the orbit posteriorly.
Adenoid cystic carcinoma. Coronal MRI image demonstrates a left lacrimal gland adenoid cystic carcinoma with extradural extension superiorly.
Adenoid cystic carcinoma. Axial MRI demonstrates a recurrent lacrimal gland adenoid cystic carcinoma with intracranial extension; this lesion was treated with inta-arterial chemotherapy and radiation and recurred.
Adenoid cystic carcinoma. Coronal MRI demonstrates a recurrent lacrimal gland adenoid cystic carcinoma after failed treatment with intaarterial chemotherapy and radiation; the lesion extends intracranially.

Q: Molecular alterations involving MYB are a hallmark of Adenoid Cystic Carcinoma, and immunohistochemical staining for MYB and [...] (CD117) can be used as diagnostic surrogates.
Adenoid cystic carcinoma. Diffuse CKIT staining is seen in this tumour with a solid/basaloid pattern.
A: KIT
Back Extra: Adenoid Cystic Carcinoma
- Clinical: Adenoid cystic carcinoma (ACC) commonly presents with lacrimal gland enlargement, inferomedial globe displacement, and non-axial proptosis. Pain and paraesthesia are cardinal signs.
- Micro: ACC is characterized by three main patterns: cribriform (Swiss-cheese appearance), tubular (small glandular structures), and solid/basaloid (compact sheet-like proliferating cells).
- Ancillary: MYB and KIT immunostaining can be used as surrogates for MYB rearrangement molecular studies, with a mean Ki67 index of 30% and p53 expression in 39% of cases.
Reference Gallery:
Adenoid cystic carcinoma. The carcinoma infiltrates the normal lacrimal gland.
Adenoid cystic carcinoma. Cribriform pattern with a Swiss-cheese appearance, composed of cystic structures containing basophilic amorphous glycosaminoglycans and eosinophilic hyalinized basal lamina.
Adenoid cystic carcinoma. The tubular pattern is composed predominantly of small glandular structures.
Adenoid cystic carcinoma. The solid/basaloid pattern is composed of compact sheet-like proliferating basaloid myoepithelial cells that lack the cribriform or tubular architecture.
Adenoid cystic carcinoma. Diffuse CKIT staining is seen in this tumour with a solid/basaloid pattern.
Adenoid cystic carcinoma. Perineural invasion is commonly seen.
Adenoid cystic carcinoma. T1 weighted MRI demonstrates a right lacrimal gland mass; note extension of the lesion along the lateral wall of the orbit posteriorly.
Adenoid cystic carcinoma. Coronal MRI image demonstrates a left lacrimal gland adenoid cystic carcinoma with extradural extension superiorly.
Adenoid cystic carcinoma. Axial MRI demonstrates a recurrent lacrimal gland adenoid cystic carcinoma with intracranial extension; this lesion was treated with inta-arterial chemotherapy and radiation and recurred.
Adenoid cystic carcinoma. Coronal MRI demonstrates a recurrent lacrimal gland adenoid cystic carcinoma after failed treatment with intaarterial chemotherapy and radiation; the lesion extends intracranially.

Q: Microscopically, Carcinoma ex pleomorphic adenoma is characterized by a malignant epithelial component intermixed with or adjacent to residual benign ducts and hyalinized stroma from a pre-existing [...].
Carcinoma ex-pleomorphic adenoma. Hyalinized nodule adjacent to area of adenocarcinoma indicating a pre-existing pleomorphic adenoma.
Carcinoma ex-pleomorphic adenoma. Intracapsular CEPA characterized by the presence of glands lined by atypical cells, and still confined within the pseudo-capsule of a pre-existing pleomorphic adenoma.
Carcinoma ex-pleomorphic adenoma. Higher magnification shows malignant glands intermixed with benign ducts from the pre-existing pleomorphic adenoma.
A: pleomorphic adenoma
Back Extra: Carcinoma ex pleomorphic adenoma
- Clinical: Carcinoma ex pleomorphic adenoma often presents with a previously slow-growing mass in the lacrimal fossa, causing proptosis or inferior globe displacement, and may show rapid growth, pain, or skin ulceration.
- Micro: Microscopically, the lesion shows transition between the malignant component and residual pleomorphic adenoma, with the carcinoma component often resembling adenocarcinoma of salivary duct appearance.
- Ancillary: PLAG1 or HMGA2 rearrangements, detected by FISH, serve as markers of the pre-existing pleomorphic adenoma, aiding in differentiating CEPA from de novo lacrimal gland carcinomas.
Reference Gallery:
Carcinoma ex-pleomorphic adenoma. Hyalinized nodule adjacent to area of adenocarcinoma indicating a pre-existing pleomorphic adenoma.
Carcinoma ex-pleomorphic adenoma. Intracapsular CEPA characterized by the presence of glands lined by atypical cells, and still confined within the pseudo-capsule of a pre-existing pleomorphic adenoma.
Carcinoma ex-pleomorphic adenoma. Higher magnification shows malignant glands intermixed with benign ducts from the pre-existing pleomorphic adenoma.
Carcinoma ex pleomorphic adenoma. A-C: Axial, sagittal, and coronal T1 post-contrast MRIs show a peripherally enhancing mass involving the superotemporal left orbit (arrows) with mass effect upon an inferiorly displaced globe.

Q: The classic clinical history of Carcinoma ex pleomorphic adenoma involves a long-standing, slow-growing lacrimal fossa mass that suddenly undergoes [...], often presenting with pain, ulceration, or globe displacement on MRI.
Carcinoma ex pleomorphic adenoma. A-C: Axial, sagittal, and coronal T1 post-contrast MRIs show a peripherally enhancing mass involving the superotemporal left orbit (arrows) with mass effect upon an inferiorly displaced globe.
A: rapid growth
Back Extra: Carcinoma ex pleomorphic adenoma
- Clinical: Carcinoma ex pleomorphic adenoma often presents with a previously slow-growing mass in the lacrimal fossa, causing proptosis or inferior globe displacement, and may show rapid growth, pain, or skin ulceration.
- Micro: Microscopically, the lesion shows transition between the malignant component and residual pleomorphic adenoma, with the carcinoma component often resembling adenocarcinoma of salivary duct appearance.
- Ancillary: PLAG1 or HMGA2 rearrangements, detected by FISH, serve as markers of the pre-existing pleomorphic adenoma, aiding in differentiating CEPA from de novo lacrimal gland carcinomas.
Reference Gallery:
Carcinoma ex-pleomorphic adenoma. Hyalinized nodule adjacent to area of adenocarcinoma indicating a pre-existing pleomorphic adenoma.
Carcinoma ex-pleomorphic adenoma. Intracapsular CEPA characterized by the presence of glands lined by atypical cells, and still confined within the pseudo-capsule of a pre-existing pleomorphic adenoma.
Carcinoma ex-pleomorphic adenoma. Higher magnification shows malignant glands intermixed with benign ducts from the pre-existing pleomorphic adenoma.
Carcinoma ex pleomorphic adenoma. A-C: Axial, sagittal, and coronal T1 post-contrast MRIs show a peripherally enhancing mass involving the superotemporal left orbit (arrows) with mass effect upon an inferiorly displaced globe.

Q: Histologically, Lymphoepithelial Carcinoma is characterized by islands of poorly differentiated malignant epithelial cells that are heavily infiltrated and obscured by an intense [...] infiltrate.
Lymphoepithelial carcinoma. Histological appearance with islands of poorly differentiated squamous cell carcinoma infiltrated and surrounded by large numbers of lymphocytes.
A: lymphoid
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Lymphoepithelial carcinoma presents with symptoms such as epiphora and swelling over the lacrimal sac, often forming a hard, non-tender, immobile mass.
- Micro: Microscopically, it is characterized by polygonal, undifferentiated malignant epithelial cells mixed with an intense lymphoid infiltrate.
- Ancillary: EBV positivity is essential for diagnosis, with EBER helping establish the presence of EBV infection.
Reference Gallery:
Lymphoepithelial carcinoma. Histological appearance with islands of poorly differentiated squamous cell carcinoma infiltrated and surrounded by large numbers of lymphocytes.

Q: A biopsy of a hard, immobile mass over the lacrimal sac reveals undifferentiated malignant epithelial cells mixed with numerous lymphocytes. Given this histology, a positive test for EBV (e.g., via EBER) is essential to establish the diagnosis of [...].
Lymphoepithelial carcinoma. Histological appearance with islands of poorly differentiated squamous cell carcinoma infiltrated and surrounded by large numbers of lymphocytes.
A: Lymphoepithelial Carcinoma
Back Extra: Lymphoepithelial Carcinoma
- Clinical: Lymphoepithelial carcinoma presents with symptoms such as epiphora and swelling over the lacrimal sac, often forming a hard, non-tender, immobile mass.
- Micro: Microscopically, it is characterized by polygonal, undifferentiated malignant epithelial cells mixed with an intense lymphoid infiltrate.
- Ancillary: EBV positivity is essential for diagnosis, with EBER helping establish the presence of EBV infection.
Reference Gallery:
Lymphoepithelial carcinoma. Histological appearance with islands of poorly differentiated squamous cell carcinoma infiltrated and surrounded by large numbers of lymphocytes.

Q: Clinically and radiographically, Mucoepidermoid Carcinoma typically presents as a slow-growing, enhancing mass in the [...] region, often causing painful proptosis.
Mucoepidermoid carcinoma. Axial T1-weighted post-contrast MRI image showing enhancing mass in the right lacrimal gland
Mucoepidermoid carcinoma. A: Axial T1 post-contrast MRI shows an enhancing mass in the left lower eyelid with post-septal involvement medially (arrows). B: Coronal T1 post-contrast MRI shows an enhancing mass involving the left upper and lower eyelids (arrows).
A: lacrimal gland
Back Extra: Mucoepidermoid Carcinoma
- Clinical: Mucoepidermoid carcinoma (MEC) usually presents as a slow-growing mass in the lacrimal gland region and can cause painful proptosis.
- Micro: MEC of the lacrimal gland is composed of variable proportions of squamous, mucin-secreting, and intermediate cells.
- Ancillary: A CRTC1::MAML2 fusion protein, resulting from a t(11;19)(q21;p13.1) translocation, is present in 80% of salivary gland MECs and may be used as a diagnostic marker.
Reference Gallery:
Mucoepidermoid carcinoma. Axial T1-weighted post-contrast MRI image showing enhancing mass in the right lacrimal gland
Mucoepidermoid carcinoma. A: Axial T1 post-contrast MRI shows an enhancing mass in the left lower eyelid with post-septal involvement medially (arrows). B: Coronal T1 post-contrast MRI shows an enhancing mass involving the left upper and lower eyelids (arrows).

Q: The diagnosis of Mucoepidermoid Carcinoma is supported by identifying a t(11;19) translocation, which results in the characteristic [MAML2] fusion protein.
Mucoepidermoid carcinoma. Axial T1-weighted post-contrast MRI image showing enhancing mass in the right lacrimal gland
A: CRTC1
Back Extra: Mucoepidermoid Carcinoma
- Clinical: Mucoepidermoid carcinoma (MEC) usually presents as a slow-growing mass in the lacrimal gland region and can cause painful proptosis.
- Micro: MEC of the lacrimal gland is composed of variable proportions of squamous, mucin-secreting, and intermediate cells.
- Ancillary: A CRTC1::MAML2 fusion protein, resulting from a t(11;19)(q21;p13.1) translocation, is present in 80% of salivary gland MECs and may be used as a diagnostic marker.
Reference Gallery:
Mucoepidermoid carcinoma. Axial T1-weighted post-contrast MRI image showing enhancing mass in the right lacrimal gland
Mucoepidermoid carcinoma. A: Axial T1 post-contrast MRI shows an enhancing mass in the left lower eyelid with post-septal involvement medially (arrows). B: Coronal T1 post-contrast MRI shows an enhancing mass involving the left upper and lower eyelids (arrows).

Q: Histologically, Primary Ductal Adenocarcinoma of the Lacrimal Gland features polygonal tumor cells with granular eosinophilic cytoplasm and prominent nucleoli, frequently displaying central [...].
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm, prominent nucleoli, mitotic activity, and perineural invasion.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma with abundant geographic and comedo-necrosis.
A: comedo necrosis
Back Extra: Primary Ductal Adenocarcinoma of the Lacrimal Gland
- Clinical: Primary ductal adenocarcinoma of the lacrimal gland presents with painless proptosis, palpable mass, swelling, diplopia, mechanical ptosis, pain, and decreased vision.
- Micro: Tumour cells are polygonal with granular eosinophilic cytoplasm, pleomorphic and vesicular nuclei, prominent nucleoli, and frequent central comedo necrosis.
- Ancillary: Positive immunohistochemical markers include AE1/AE3, CK7, CK19, EMA, AR, GCDFP-15, and HER2, with a Ki67 proliferation index that may reach 70%.
Reference Gallery:
Primary ductal adenocarcinoma of the lacrimal gland. Coronal T1-weighted MRI shows a well-circumscribed isointense mass in the left lateral orbit.
Primary ductal adenocarcinoma of the lacrimal gland. A coronal MRI showing a well-circumscribed mass in the left lateral orbit, with diffuse enhancement on T1-weighted post-contrast imaging.
Primary ductal adenocarcinoma of the lacrimal gland. A coronal T2 weighted MRI showing a well-circumscribed mass in the left lateral orbit, hyperintense on T2-weighted fat-suppression imaging.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm, prominent nucleoli, mitotic activity, and perineural invasion.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm in the background of significant hyalinization.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm forming tubules, simple and cribriform glands invading the adjacent lacrimal gland acini (upper right corner with inflammation).
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma with abundant geographic and comedo-necrosis.

Q: Radiologically, Primary Ductal Adenocarcinoma of the Lacrimal Gland typically presents as a well-circumscribed mass in the [...], often causing painless proptosis and diplopia.
Primary ductal adenocarcinoma of the lacrimal gland. Coronal T1-weighted MRI shows a well-circumscribed isointense mass in the left lateral orbit.
Primary ductal adenocarcinoma of the lacrimal gland. A coronal MRI showing a well-circumscribed mass in the left lateral orbit, with diffuse enhancement on T1-weighted post-contrast imaging.
Primary ductal adenocarcinoma of the lacrimal gland. A coronal T2 weighted MRI showing a well-circumscribed mass in the left lateral orbit, hyperintense on T2-weighted fat-suppression imaging.
A: lateral orbit
Back Extra: Primary Ductal Adenocarcinoma of the Lacrimal Gland
- Clinical: Primary ductal adenocarcinoma of the lacrimal gland presents with painless proptosis, palpable mass, swelling, diplopia, mechanical ptosis, pain, and decreased vision.
- Micro: Tumour cells are polygonal with granular eosinophilic cytoplasm, pleomorphic and vesicular nuclei, prominent nucleoli, and frequent central comedo necrosis.
- Ancillary: Positive immunohistochemical markers include AE1/AE3, CK7, CK19, EMA, AR, GCDFP-15, and HER2, with a Ki67 proliferation index that may reach 70%.
Reference Gallery:
Primary ductal adenocarcinoma of the lacrimal gland. Coronal T1-weighted MRI shows a well-circumscribed isointense mass in the left lateral orbit.
Primary ductal adenocarcinoma of the lacrimal gland. A coronal MRI showing a well-circumscribed mass in the left lateral orbit, with diffuse enhancement on T1-weighted post-contrast imaging.
Primary ductal adenocarcinoma of the lacrimal gland. A coronal T2 weighted MRI showing a well-circumscribed mass in the left lateral orbit, hyperintense on T2-weighted fat-suppression imaging.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm, prominent nucleoli, mitotic activity, and perineural invasion.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm in the background of significant hyalinization.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm forming tubules, simple and cribriform glands invading the adjacent lacrimal gland acini (upper right corner with inflammation).
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma with abundant geographic and comedo-necrosis.

Q: Microscopically, high-grade Primary Ductal Adenocarcinoma of the Lacrimal Gland is characterized by large epithelial cells that form tubules and [...] glands invading adjacent acini.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm forming tubules, simple and cribriform glands invading the adjacent lacrimal gland acini (upper right corner with inflammation).
A: cribriform
Back Extra: Primary Ductal Adenocarcinoma of the Lacrimal Gland
- Clinical: Primary ductal adenocarcinoma of the lacrimal gland presents with painless proptosis, palpable mass, swelling, diplopia, mechanical ptosis, pain, and decreased vision.
- Micro: Tumour cells are polygonal with granular eosinophilic cytoplasm, pleomorphic and vesicular nuclei, prominent nucleoli, and frequent central comedo necrosis.
- Ancillary: Positive immunohistochemical markers include AE1/AE3, CK7, CK19, EMA, AR, GCDFP-15, and HER2, with a Ki67 proliferation index that may reach 70%.
Reference Gallery:
Primary ductal adenocarcinoma of the lacrimal gland. Coronal T1-weighted MRI shows a well-circumscribed isointense mass in the left lateral orbit.
Primary ductal adenocarcinoma of the lacrimal gland. A coronal MRI showing a well-circumscribed mass in the left lateral orbit, with diffuse enhancement on T1-weighted post-contrast imaging.
Primary ductal adenocarcinoma of the lacrimal gland. A coronal T2 weighted MRI showing a well-circumscribed mass in the left lateral orbit, hyperintense on T2-weighted fat-suppression imaging.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm, prominent nucleoli, mitotic activity, and perineural invasion.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm in the background of significant hyalinization.
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma composed of large epithelial cells with abundant eosinophilic cytoplasm forming tubules, simple and cribriform glands invading the adjacent lacrimal gland acini (upper right corner with inflammation).
Primary ductal adenocarcinoma of the lacrimal gland. High-grade carcinoma with abundant geographic and comedo-necrosis.

Q: Secretory Carcinoma is classically characterized by a gene rearrangement involving [...], which can be demonstrated using break-apart fluorescence in situ hybridization (FISH).
Lacrimal secretory carcinoma. ETV6 gene rearrangement can be demonstrated by ETV6 break apart fluorescence in situ hybridization, showing one intact (yellow) probe and a pair of separated red and green probes.
A: ETV6
Back Extra: Secretory Carcinoma
- Clinical: Secretory carcinoma (SC) typically presents as a painless subcutaneous nodule, causing diplopia and proptosis.
- Micro: SC shows papillary-cystic, solid, and microfollicular patterns with cells having round-to-ovoid nuclei and abundant pale eosinophilic cytoplasm.
- Ancillary: IHC for S100, mammaglobin, and NTRK is positive, while p63 and keratin 5 are negative. ETV6 gene rearrangement can be demonstrated by break-apart FISH.
Reference Gallery:
Lacrimal secretory carcinoma. Mammaglobin expression is a hallmark of secretory carcinoma.
Lacrimal secretory carcinoma. S100 shows strong cytoplasmic expression in secretory carcinoma.
Lacrimal secretory carcinoma. Most cases of secretory carcinoma harbour NTRK3 fusion resulting in NTRK protein expression which can be shown with pan-TRK immunohistochemistry.
Lacrimal secretory carcinoma. Mucin stains such as Alcian Blue highlight the extracellular secretions within the microcystic lumina.
Lacrimal secretory carcinoma. ETV6 gene rearrangement can be demonstrated by ETV6 break apart fluorescence in situ hybridization, showing one intact (yellow) probe and a pair of separated red and green probes.

Q: The classic immunohistochemical profile for Secretory Carcinoma is typically positive for S100, mammaglobin, and [...].
Lacrimal secretory carcinoma. Mammaglobin expression is a hallmark of secretory carcinoma.
Lacrimal secretory carcinoma. S100 shows strong cytoplasmic expression in secretory carcinoma.
Lacrimal secretory carcinoma. Most cases of secretory carcinoma harbour NTRK3 fusion resulting in NTRK protein expression which can be shown with pan-TRK immunohistochemistry.
A: NTRK
Back Extra: Secretory Carcinoma
- Clinical: Secretory carcinoma (SC) typically presents as a painless subcutaneous nodule, causing diplopia and proptosis.
- Micro: SC shows papillary-cystic, solid, and microfollicular patterns with cells having round-to-ovoid nuclei and abundant pale eosinophilic cytoplasm.
- Ancillary: IHC for S100, mammaglobin, and NTRK is positive, while p63 and keratin 5 are negative. ETV6 gene rearrangement can be demonstrated by break-apart FISH.
Reference Gallery:
Lacrimal secretory carcinoma. Mammaglobin expression is a hallmark of secretory carcinoma.
Lacrimal secretory carcinoma. S100 shows strong cytoplasmic expression in secretory carcinoma.
Lacrimal secretory carcinoma. Most cases of secretory carcinoma harbour NTRK3 fusion resulting in NTRK protein expression which can be shown with pan-TRK immunohistochemistry.
Lacrimal secretory carcinoma. Mucin stains such as Alcian Blue highlight the extracellular secretions within the microcystic lumina.
Lacrimal secretory carcinoma. ETV6 gene rearrangement can be demonstrated by ETV6 break apart fluorescence in situ hybridization, showing one intact (yellow) probe and a pair of separated red and green probes.

Q: In Secretory Carcinoma, the characteristic extracellular secretions found within the microcystic lumina can be highlighted by mucin stains such as [...].
Lacrimal secretory carcinoma. Mucin stains such as Alcian Blue highlight the extracellular secretions within the microcystic lumina.
A: Alcian blue
Back Extra: Secretory Carcinoma
- Clinical: Secretory carcinoma (SC) typically presents as a painless subcutaneous nodule, causing diplopia and proptosis.
- Micro: SC shows papillary-cystic, solid, and microfollicular patterns with cells having round-to-ovoid nuclei and abundant pale eosinophilic cytoplasm.
- Ancillary: IHC for S100, mammaglobin, and NTRK is positive, while p63 and keratin 5 are negative. ETV6 gene rearrangement can be demonstrated by break-apart FISH.
Reference Gallery:
Lacrimal secretory carcinoma. Mammaglobin expression is a hallmark of secretory carcinoma.
Lacrimal secretory carcinoma. S100 shows strong cytoplasmic expression in secretory carcinoma.
Lacrimal secretory carcinoma. Most cases of secretory carcinoma harbour NTRK3 fusion resulting in NTRK protein expression which can be shown with pan-TRK immunohistochemistry.
Lacrimal secretory carcinoma. Mucin stains such as Alcian Blue highlight the extracellular secretions within the microcystic lumina.
Lacrimal secretory carcinoma. ETV6 gene rearrangement can be demonstrated by ETV6 break apart fluorescence in situ hybridization, showing one intact (yellow) probe and a pair of separated red and green probes.

Q: Histologically, a Dacryops cyst is characteristically lined by non-keratinized, double-layered to pseudostratified columnar epithelium containing dispersed [...].
Diagnosis: Dacryops. Cyst lined by non-keratinized pseudostratified columnar epithelium with dispersed goblet cells. Wall of the cyst shows lacrimal gland acini, variable fibrosis, edema, and patchy mild chronic lymphomononuclear cell infiltration (PAS).
A: goblet cells
Back Extra: Dacryops cyst
- Clinical: Dacryops cyst often presents as an asymptomatic swelling, eyelid fullness, or mild irritation.
- Micro: The cyst is lined by non-keratinized, double-layered columnar to cuboidal epithelium with dispersed goblet cells.
- Ancillary: CK7 and CK18 immunohistochemistry highlight the lining epithelium, with CK18 being more intense superficially.
Reference Gallery:
Diagnosis: Dacryops. Eyelid eversion shows a large cystic lesion in the subconjunctival region.
Diagnosis: Dacryops. Cyst lined by non-keratinized pseudostratified columnar epithelium with dispersed goblet cells. Wall of the cyst shows lacrimal gland acini, variable fibrosis, edema, and patchy mild chronic lymphomononuclear cell infiltration (PAS).
Diagnosis: Dacryops cyst. A, B: Axial and coronal T1 post-contrast MRIs show a non-enhancing cyst in the left lacrimal gland (arrows).

Q: Clinically and radiographically, a [...] presents as an asymptomatic, non-enhancing cystic mass classically located in the lacrimal gland or subconjunctival region.
Diagnosis: Dacryops. Eyelid eversion shows a large cystic lesion in the subconjunctival region.
Diagnosis: Dacryops cyst. A, B: Axial and coronal T1 post-contrast MRIs show a non-enhancing cyst in the left lacrimal gland (arrows).
A: Dacryops cyst
Back Extra: Dacryops cyst
- Clinical: Dacryops cyst often presents as an asymptomatic swelling, eyelid fullness, or mild irritation.
- Micro: The cyst is lined by non-keratinized, double-layered columnar to cuboidal epithelium with dispersed goblet cells.
- Ancillary: CK7 and CK18 immunohistochemistry highlight the lining epithelium, with CK18 being more intense superficially.
Reference Gallery:
Diagnosis: Dacryops. Eyelid eversion shows a large cystic lesion in the subconjunctival region.
Diagnosis: Dacryops. Cyst lined by non-keratinized pseudostratified columnar epithelium with dispersed goblet cells. Wall of the cyst shows lacrimal gland acini, variable fibrosis, edema, and patchy mild chronic lymphomononuclear cell infiltration (PAS).
Diagnosis: Dacryops cyst. A, B: Axial and coronal T1 post-contrast MRIs show a non-enhancing cyst in the left lacrimal gland (arrows).

Q: Optic Nerve Choristoma can present with painless visual decline and a bright T2-weighted MRI signal in the optic nerve; biopsy definitively shows atrophic optic nerve admixed with adipose and [...] tissue.
Optic nerve choristoma. Axial MRI, T2-weighted, bright signal in right optic nerve proximal to optic chiasm.
Optic nerve choristoma. The biopsy exhibits optic nerve glial tissue (left), smooth muscle (centre), and adipose tissue (right).
A: smooth muscle
Back Extra: Optic Nerve Choristoma
- Clinical: Painless, slow, progressive decrease in visual acuity, associated with optic atrophy.
- Micro: Adipose tissue and bundles of smooth muscle in variable amounts within or adjacent to atrophic optic nerve tissue.
- Ancillary: Immunohistochemistry for SMA highlights the smooth muscle component, and GFAP highlights optic nerve tissue.
Reference Gallery:
Optic nerve choristoma. Axial MRI, T2-weighted, bright signal in right optic nerve proximal to optic chiasm.
Optic nerve choristoma. The biopsy exhibits optic nerve glial tissue (left), smooth muscle (centre), and adipose tissue (right).
Optic nerve choristoma. Immunohistochemistry for GFAP highlights glial tissue.
Optic nerve choristoma. Immunohistochemistry for SMA highlights smooth muscle.

Q: Optic Nerve Choristoma evaluation often utilizes immunohistochemistry, where SMA highlights the smooth muscle component and [...] highlights the admixed optic nerve glial tissue.
Optic nerve choristoma. Immunohistochemistry for GFAP highlights glial tissue.
Optic nerve choristoma. Immunohistochemistry for SMA highlights smooth muscle.
A: GFAP
Back Extra: Optic Nerve Choristoma
- Clinical: Painless, slow, progressive decrease in visual acuity, associated with optic atrophy.
- Micro: Adipose tissue and bundles of smooth muscle in variable amounts within or adjacent to atrophic optic nerve tissue.
- Ancillary: Immunohistochemistry for SMA highlights the smooth muscle component, and GFAP highlights optic nerve tissue.
Reference Gallery:
Optic nerve choristoma. Axial MRI, T2-weighted, bright signal in right optic nerve proximal to optic chiasm.
Optic nerve choristoma. The biopsy exhibits optic nerve glial tissue (left), smooth muscle (centre), and adipose tissue (right).
Optic nerve choristoma. Immunohistochemistry for GFAP highlights glial tissue.
Optic nerve choristoma. Immunohistochemistry for SMA highlights smooth muscle.

Q: On histology, the neoplastic cells of a Melanocytoma are so heavily obscured by melanin that clear visualization of their cytological features typically requires [...] (e.g., with potassium permanganate).
Melanocytoma. A heavily pigmented melanocytoma
Melanocytoma. Bland cytological features revealed after potassium permanganate bleaching
A: bleaching
Back Extra: Melanocytoma
- Clinical: Melanocytoma is typically asymptomatic, with visual symptoms occurring in 24% of patients and visual field abnormalities in 90%.
- Micro: Histologically, melanocytoma shows round to oval or polyhedral cells with small nuclei, abundant cytoplasm, and inconspicuous nucleoli, often requiring bleaching for clear visualization.
- Ancillary: Genetic analysis has shown that a mutation in GNAQ is present in some cases, and cases with BAP1 sequence variant plus monosomy 3 are at higher risk of malignant transformation.
Reference Gallery:
Melanocytoma. A heavily pigmented melanocytoma
Melanocytoma. Bland cytological features revealed after potassium permanganate bleaching

Q: After potassium permanganate bleaching, the cytological features of a Melanocytoma are revealed to be characteristically [...], featuring round, oval, or polyhedral cells with small nuclei, abundant cytoplasm, and inconspicuous nucleoli.
Melanocytoma. Bland cytological features revealed after potassium permanganate bleaching
A: bland
Back Extra: Melanocytoma
- Clinical: Melanocytoma is typically asymptomatic, with visual symptoms occurring in 24% of patients and visual field abnormalities in 90%.
- Micro: Histologically, melanocytoma shows round to oval or polyhedral cells with small nuclei, abundant cytoplasm, and inconspicuous nucleoli, often requiring bleaching for clear visualization.
- Ancillary: Genetic analysis has shown that a mutation in GNAQ is present in some cases, and cases with BAP1 sequence variant plus monosomy 3 are at higher risk of malignant transformation.
Reference Gallery:
Melanocytoma. A heavily pigmented melanocytoma
Melanocytoma. Bland cytological features revealed after potassium permanganate bleaching

Q: On T1-weighted postcontrast MRI, Meningioma of the Optic Nerve classically demonstrates a tubular pattern of enhancement along the intraconal optic nerve, known as the [...] appearance.
Meningioma of the optic nerve sheath. T1-weighted postcontrast axial MRI demonstrates a tubular pattern enhancement along the right intraconal optic nerve (tram track appearance)
A: tram track
Back Extra: Meningioma of the Optic Nerve
- Clinical: The classic presentation of meningioma of the optic nerve includes visual loss, optic atrophy, and optociliary shunts.
- Micro: Meningothelial and transitional subtypes predominate, with characteristic whorls and psammoma bodies.
- Ancillary: Meningiomas are EMA and SSTR2A-positive, and fibrous meningiomas may also be positive for S100 protein.
Reference Gallery:
Meningioma of the optic nerve sheath. T1-weighted postcontrast axial MRI demonstrates a tubular pattern enhancement along the right intraconal optic nerve (tram track appearance)
Meningothelial meningioma of the optic nerve sheath. Tumour characterized by syncytial growth, whorls and psammoma bodies.
Meningothelial meningioma of the optic nerve sheath. Optic nerve surrounded by tumour within the optic nerve sheath.
Meningioma. Sphenoid meningioma extending along the optic nerve showing meningiothelial growth pattern.

Q: Histologically, the predominant subtypes of Meningioma of the Optic Nerve feature syncytial growth, concentric whorls, and characteristic calcifications known as [...].
Meningothelial meningioma of the optic nerve sheath. Tumour characterized by syncytial growth, whorls and psammoma bodies.
Meningothelial meningioma of the optic nerve sheath. Optic nerve surrounded by tumour within the optic nerve sheath.
A: psammoma bodies
Back Extra: Meningioma of the Optic Nerve
- Clinical: The classic presentation of meningioma of the optic nerve includes visual loss, optic atrophy, and optociliary shunts.
- Micro: Meningothelial and transitional subtypes predominate, with characteristic whorls and psammoma bodies.
- Ancillary: Meningiomas are EMA and SSTR2A-positive, and fibrous meningiomas may also be positive for S100 protein.
Reference Gallery:
Meningioma of the optic nerve sheath. T1-weighted postcontrast axial MRI demonstrates a tubular pattern enhancement along the right intraconal optic nerve (tram track appearance)
Meningothelial meningioma of the optic nerve sheath. Tumour characterized by syncytial growth, whorls and psammoma bodies.
Meningothelial meningioma of the optic nerve sheath. Optic nerve surrounded by tumour within the optic nerve sheath.
Meningioma. Sphenoid meningioma extending along the optic nerve showing meningiothelial growth pattern.

Q: The most common subtype of Gliomas of the Optic Nerve is the pilocytic astrocytoma, which is characterized histologically by a biphasic growth pattern, bright eosinophilic processes, eosinophilic granular bodies, and characteristic [...].
Pilocytic astrocytoma of the optic nerve. Bright eosinophilic processes characterize these neoplastic astrocytes in a pilocytic astrocytoma of the optic nerve.
A: Rosenthal fibers
Back Extra: Gliomas of the Optic Nerve
- Clinical: Optic nerve gliomas can present with visual impairment, optic atrophy, and proptosis. High-grade gliomas often cause rapid vision loss and bilateral blindness.
- Micro: Pilocytic astrocytomas of the optic nerve exhibit a biphasic growth pattern with delicate bipolar hair-like processes and the presence of Rosenthal fibres and eosinophilic granular bodies.
- Ancillary: The most common genetic alteration in pilocytic astrocytomas is a chromosome 7q34 rearrangement resulting in a KIAA1549::BRAF fusion.
Reference Gallery:
Astrocytoma, IDH mutant. Axial MRI T1-weighted post-contrast demonstrates mild enhancement of the right optic nerve and flattening of the globe posteriorly resulting from optic nerve and intraocular extension from a hemispheric astrocytoma, IDH mutant.
Astrocytoma, IDH mutant. Cell block from a vitreous cytology preparation demonstrating a cellular astrocytic neoplasm with necrosis resulting from optic nerve and intraocular extension of a hemispheric Astrocytoma, IDH mutant.
Astrocytoma, IDH mutant. Immunohistochemistry detected IDH1 p.R132H mutant positive cells in a vitrectomy specimen.
Pilocytic astrocytoma of the optic nerve. Pilocytic astrocytomas involving the optic nerve may extend into the adjacent subarachnoid space.
Pilocytic astrocytoma of the optic nerve. Bright eosinophilic processes characterize these neoplastic astrocytes in a pilocytic astrocytoma of the optic nerve.

Q: While typical pilocytic Gliomas of the Optic Nerve arise within the nerve parenchyma, these neoplasms may also frequently extend outward into the adjacent [...].
Pilocytic astrocytoma of the optic nerve. Pilocytic astrocytomas involving the optic nerve may extend into the adjacent subarachnoid space.
A: subarachnoid space
Back Extra: Gliomas of the Optic Nerve
- Clinical: Optic nerve gliomas can present with visual impairment, optic atrophy, and proptosis. High-grade gliomas often cause rapid vision loss and bilateral blindness.
- Micro: Pilocytic astrocytomas of the optic nerve exhibit a biphasic growth pattern with delicate bipolar hair-like processes and the presence of Rosenthal fibres and eosinophilic granular bodies.
- Ancillary: The most common genetic alteration in pilocytic astrocytomas is a chromosome 7q34 rearrangement resulting in a KIAA1549::BRAF fusion.
Reference Gallery:
Astrocytoma, IDH mutant. Axial MRI T1-weighted post-contrast demonstrates mild enhancement of the right optic nerve and flattening of the globe posteriorly resulting from optic nerve and intraocular extension from a hemispheric astrocytoma, IDH mutant.
Astrocytoma, IDH mutant. Cell block from a vitreous cytology preparation demonstrating a cellular astrocytic neoplasm with necrosis resulting from optic nerve and intraocular extension of a hemispheric Astrocytoma, IDH mutant.
Astrocytoma, IDH mutant. Immunohistochemistry detected IDH1 p.R132H mutant positive cells in a vitrectomy specimen.
Pilocytic astrocytoma of the optic nerve. Pilocytic astrocytomas involving the optic nerve may extend into the adjacent subarachnoid space.
Pilocytic astrocytoma of the optic nerve. Bright eosinophilic processes characterize these neoplastic astrocytes in a pilocytic astrocytoma of the optic nerve.

Q: High-grade Gliomas of the Optic Nerve (or those involving the nerve via direct extension from a hemispheric tumor) often cause rapid vision loss and can demonstrate positivity for the [...] mutation on immunohistochemistry.
Astrocytoma, IDH mutant. Axial MRI T1-weighted post-contrast demonstrates mild enhancement of the right optic nerve and flattening of the globe posteriorly resulting from optic nerve and intraocular extension from a hemispheric astrocytoma, IDH mutant.
Astrocytoma, IDH mutant. Cell block from a vitreous cytology preparation demonstrating a cellular astrocytic neoplasm with necrosis resulting from optic nerve and intraocular extension of a hemispheric Astrocytoma, IDH mutant.
Astrocytoma, IDH mutant. Immunohistochemistry detected IDH1 p.R132H mutant positive cells in a vitrectomy specimen.
A: IDH1 p.R132H
Back Extra: Gliomas of the Optic Nerve
- Clinical: Optic nerve gliomas can present with visual impairment, optic atrophy, and proptosis. High-grade gliomas often cause rapid vision loss and bilateral blindness.
- Micro: Pilocytic astrocytomas of the optic nerve exhibit a biphasic growth pattern with delicate bipolar hair-like processes and the presence of Rosenthal fibres and eosinophilic granular bodies.
- Ancillary: The most common genetic alteration in pilocytic astrocytomas is a chromosome 7q34 rearrangement resulting in a KIAA1549::BRAF fusion.
Reference Gallery:
Astrocytoma, IDH mutant. Axial MRI T1-weighted post-contrast demonstrates mild enhancement of the right optic nerve and flattening of the globe posteriorly resulting from optic nerve and intraocular extension from a hemispheric astrocytoma, IDH mutant.
Astrocytoma, IDH mutant. Cell block from a vitreous cytology preparation demonstrating a cellular astrocytic neoplasm with necrosis resulting from optic nerve and intraocular extension of a hemispheric Astrocytoma, IDH mutant.
Astrocytoma, IDH mutant. Immunohistochemistry detected IDH1 p.R132H mutant positive cells in a vitrectomy specimen.
Pilocytic astrocytoma of the optic nerve. Pilocytic astrocytomas involving the optic nerve may extend into the adjacent subarachnoid space.
Pilocytic astrocytoma of the optic nerve. Bright eosinophilic processes characterize these neoplastic astrocytes in a pilocytic astrocytoma of the optic nerve.

Q: Histologically, the defining feature of an Orbital Dermoid Cyst is a keratinizing, stratified squamous epithelial wall that contains [...] (e.g., hair shafts, sebaceous glands, and sweat glands).
Dermoid cyst. Histopathological appearance of a dermoid cyst wall consisting of keratinizing, stratified squamous epithelium with skin appendages.
Dermoid cyst. The wall of a dermoid cyst with pilosebaceous units and sweat glands.
A: skin appendages
Back Extra: Orbital Dermoid Cyst
- Clinical: Orbital dermoid cysts are typically asymptomatic, slowly progressive, painless masses that are fixed to the underlying bone. Superficial cysts often present in early childhood, while deep cysts are detected later and may cause globe dystopia or bone destruction.
- Micro: Histologically, dermoid cysts have a keratinizing, stratified squamous epithelial wall with skin appendages such as hair shafts, sebaceous glands, and sweat glands. Chronic inflammation and foreign-body giant cells are common findings, especially in ruptured cysts.
- Ancillary: Radiological imaging, such as CT and MRI, is crucial for evaluating the extent and location of orbital dermoid cysts, especially for detecting bony involvement and planning surgical excision.
Reference Gallery:
Dermoid cyst. The clinical appearance of a superficial dermoid cyst in a child.
Dermoid cyst. Intra-operative appearance of the fully excised cyst in the same patient.
Dermoid cyst. Histopathological appearance of a dermoid cyst wall consisting of keratinizing, stratified squamous epithelium with skin appendages.
Dermoid cyst. Higher power of an area of ruptured dermoid cyst wall with numerous foreign body-type giant cells.
Epidermoid cyst. Histopathological appearance of the keratinizing squamous epithelial wall of an epidermoid cyst. Note the absence of skin appendages in contrast to the typical dermoid cyst.
Dermoid cyst. The wall of a dermoid cyst with pilosebaceous units and sweat glands.
Sub-conjunctival component of an orbital dermoid cyst. The histopathological appearance of the sub-conjunctival component of an orbital dermoid cyst with goblet cells stained by PAS and skin appendages.
Dermoid cyst. High power view of an area of ruptured dermoid cyst wall with numerous foreign body-type giant cells on the left and intact epithelium on the right.
Orbital dermoid cyst. Sagittal CT scan without contrast, bone window, shows a dermoid cyst in the lower orbit beneath the conjunctiva.
Dermoid cyst. A: Axial CT without contrast shows a fat density mass in the lateral right orbital (arrow), causing exophthalmos. B: Axial T1 non-contrast MRI without fat saturation shows a hyperintense appearance of the mass (arrow). C. Axial T1 post-contrast MRI with fat saturation shows a hypointense, non-enhancing appearance of the mass due to the fat saturation (arrow).

Q: If an Orbital Dermoid Cyst ruptures, the spillage of its keratinous contents typically incites a prominent chronic inflammatory reaction characterized by numerous [...].
Dermoid cyst. Higher power of an area of ruptured dermoid cyst wall with numerous foreign body-type giant cells.
Dermoid cyst. High power view of an area of ruptured dermoid cyst wall with numerous foreign body-type giant cells on the left and intact epithelium on the right.
A: foreign-body giant cells
Back Extra: Orbital Dermoid Cyst
- Clinical: Orbital dermoid cysts are typically asymptomatic, slowly progressive, painless masses that are fixed to the underlying bone. Superficial cysts often present in early childhood, while deep cysts are detected later and may cause globe dystopia or bone destruction.
- Micro: Histologically, dermoid cysts have a keratinizing, stratified squamous epithelial wall with skin appendages such as hair shafts, sebaceous glands, and sweat glands. Chronic inflammation and foreign-body giant cells are common findings, especially in ruptured cysts.
- Ancillary: Radiological imaging, such as CT and MRI, is crucial for evaluating the extent and location of orbital dermoid cysts, especially for detecting bony involvement and planning surgical excision.
Reference Gallery:
Dermoid cyst. The clinical appearance of a superficial dermoid cyst in a child.
Dermoid cyst. Intra-operative appearance of the fully excised cyst in the same patient.
Dermoid cyst. Histopathological appearance of a dermoid cyst wall consisting of keratinizing, stratified squamous epithelium with skin appendages.
Dermoid cyst. Higher power of an area of ruptured dermoid cyst wall with numerous foreign body-type giant cells.
Epidermoid cyst. Histopathological appearance of the keratinizing squamous epithelial wall of an epidermoid cyst. Note the absence of skin appendages in contrast to the typical dermoid cyst.
Dermoid cyst. The wall of a dermoid cyst with pilosebaceous units and sweat glands.
Sub-conjunctival component of an orbital dermoid cyst. The histopathological appearance of the sub-conjunctival component of an orbital dermoid cyst with goblet cells stained by PAS and skin appendages.
Dermoid cyst. High power view of an area of ruptured dermoid cyst wall with numerous foreign body-type giant cells on the left and intact epithelium on the right.
Orbital dermoid cyst. Sagittal CT scan without contrast, bone window, shows a dermoid cyst in the lower orbit beneath the conjunctiva.
Dermoid cyst. A: Axial CT without contrast shows a fat density mass in the lateral right orbital (arrow), causing exophthalmos. B: Axial T1 non-contrast MRI without fat saturation shows a hyperintense appearance of the mass (arrow). C. Axial T1 post-contrast MRI with fat saturation shows a hypointense, non-enhancing appearance of the mass due to the fat saturation (arrow).

Q: On radiologic imaging, an Orbital Dermoid Cyst characteristically demonstrates a mass with [...] density on CT and hyperintensity on T1 non-contrast MRI that suppresses with saturation sequences.
Dermoid cyst. A: Axial CT without contrast shows a fat density mass in the lateral right orbital (arrow), causing exophthalmos. B: Axial T1 non-contrast MRI without fat saturation shows a hyperintense appearance of the mass (arrow). C. Axial T1 post-contrast MRI with fat saturation shows a hypointense, non-enhancing appearance of the mass due to the fat saturation (arrow).
A: fat
Back Extra: Orbital Dermoid Cyst
- Clinical: Orbital dermoid cysts are typically asymptomatic, slowly progressive, painless masses that are fixed to the underlying bone. Superficial cysts often present in early childhood, while deep cysts are detected later and may cause globe dystopia or bone destruction.
- Micro: Histologically, dermoid cysts have a keratinizing, stratified squamous epithelial wall with skin appendages such as hair shafts, sebaceous glands, and sweat glands. Chronic inflammation and foreign-body giant cells are common findings, especially in ruptured cysts.
- Ancillary: Radiological imaging, such as CT and MRI, is crucial for evaluating the extent and location of orbital dermoid cysts, especially for detecting bony involvement and planning surgical excision.
Reference Gallery:
Dermoid cyst. The clinical appearance of a superficial dermoid cyst in a child.
Dermoid cyst. Intra-operative appearance of the fully excised cyst in the same patient.
Dermoid cyst. Histopathological appearance of a dermoid cyst wall consisting of keratinizing, stratified squamous epithelium with skin appendages.
Dermoid cyst. Higher power of an area of ruptured dermoid cyst wall with numerous foreign body-type giant cells.
Epidermoid cyst. Histopathological appearance of the keratinizing squamous epithelial wall of an epidermoid cyst. Note the absence of skin appendages in contrast to the typical dermoid cyst.
Dermoid cyst. The wall of a dermoid cyst with pilosebaceous units and sweat glands.
Sub-conjunctival component of an orbital dermoid cyst. The histopathological appearance of the sub-conjunctival component of an orbital dermoid cyst with goblet cells stained by PAS and skin appendages.
Dermoid cyst. High power view of an area of ruptured dermoid cyst wall with numerous foreign body-type giant cells on the left and intact epithelium on the right.
Orbital dermoid cyst. Sagittal CT scan without contrast, bone window, shows a dermoid cyst in the lower orbit beneath the conjunctiva.
Dermoid cyst. A: Axial CT without contrast shows a fat density mass in the lateral right orbital (arrow), causing exophthalmos. B: Axial T1 non-contrast MRI without fat saturation shows a hyperintense appearance of the mass (arrow). C. Axial T1 post-contrast MRI with fat saturation shows a hypointense, non-enhancing appearance of the mass due to the fat saturation (arrow).

Q: Microscopically, an Orbital Teratoma contains tissues derived from all three [...], frequently including endodermal derivatives such as intestinal-type epithelium and pancreatic tissue.
Orbital teratoma. Intestinal-type epithelium and glands are frequently observed endodermal derivatives in these tumours.
Orbital teratoma. Pancreatic tissue of endodermal origin may be seen in these tumours.
A: germ layers
Back Extra: Orbital Teratoma
- Clinical: Orbital teratomas in newborns present as rapidly growing, tense masses causing unilateral proptosis, chemosis, and eyelid distension.
- Micro: Microscopically, teratomas contain tissues from all three germ layers: ectoderm (e.g., squamous epithelium), mesoderm (e.g., adipose, bone), and endoderm (e.g., gastrointestinal epithelium).
- Ancillary: MRI imaging shows well-circumscribed cystic areas with hyper-intense T1- and T2-weighted sequences due to sebaceous content.
Reference Gallery:
Orbital teratoma. Intestinal-type epithelium and glands are frequently observed endodermal derivatives in these tumours.
Orbital teratoma. Pancreatic tissue of endodermal origin may be seen in these tumours.
Orbital teratoma. A tumour with solid and cystic areas

Q: Morphologically, an Orbital Teratoma typically presents as a well-circumscribed tumor characterized by a mixture of solid and [...] areas.
Orbital teratoma. A tumour with solid and cystic areas
A: cystic
Back Extra: Orbital Teratoma
- Clinical: Orbital teratomas in newborns present as rapidly growing, tense masses causing unilateral proptosis, chemosis, and eyelid distension.
- Micro: Microscopically, teratomas contain tissues from all three germ layers: ectoderm (e.g., squamous epithelium), mesoderm (e.g., adipose, bone), and endoderm (e.g., gastrointestinal epithelium).
- Ancillary: MRI imaging shows well-circumscribed cystic areas with hyper-intense T1- and T2-weighted sequences due to sebaceous content.
Reference Gallery:
Orbital teratoma. Intestinal-type epithelium and glands are frequently observed endodermal derivatives in these tumours.
Orbital teratoma. Pancreatic tissue of endodermal origin may be seen in these tumours.
Orbital teratoma. A tumour with solid and cystic areas

Q: The hallmark histologic feature of Yolk Sac Tumor, consisting of a central blood vessel surrounded by a layer of tumor cells within a cystic space, is known as a [...].
Yolk sac tumour. Irregular anastomosing channels lined by cuboidal tumour cells with formation of cystic spaces (*). A Schiller-Duval body is near the centre (arrow).
A: Schiller-Duval body
Back Extra: Yolk Sac Tumour
- Clinical: Orbital YST usually presents in early childhood with progressive proptosis, ptosis, ophthalmoplegia, and vision loss.
- Micro: YSTs feature a meshwork of spaces lined by flat to cuboidal epithelium with marked cellular anaplasia and conspicuous mitoses.
- Ancillary: Positive immunohistochemical staining for alpha-fetoprotein (AFP), glypican-3, and nuclear SALL4 is characteristic.
Reference Gallery:
Yolk sac tumour. Irregular anastomosing channels lined by cuboidal tumour cells with formation of cystic spaces (*). A Schiller-Duval body is near the centre (arrow).
Yolk sac tumour. The tumour cells have strong cytoplasmic staining for alpha-fetoprotein.
Yolk sac tumour. Clinical image of a yolk sac tumour in a 3-year-old boy that presented as acute-onset painless progressive protrusion of the left eye.
Yolk sac tumour. Clinical image of a yolk sac tumour in a 3-year-old boy that presented as acute-onset painless progressive protrusion of the left eye.
Yolk sac tumour. Contrast enhanced CT scan shows a well-defined mass with multiple cysts extending from the left pterygopalantine fossa through the inferior orbital fissure
Yolk sac tumour. Contrast enhanced CT scan shows the well-defined mass extending to the left globe inferior to the optic nerve.
Yolk sac tumour. The tumour cells exhibit strong nuclear expression of SALL-4 antibody
Yolk sac tumour. The tumour cells showed high Ki67 index.

Q: In addition to nuclear SALL4 and glypican-3, Yolk Sac Tumor typically shows characteristic strong cytoplasmic immunohistochemical staining for [...].
Yolk sac tumour. The tumour cells have strong cytoplasmic staining for alpha-fetoprotein.
Yolk sac tumour. The tumour cells exhibit strong nuclear expression of SALL-4 antibody
A: alpha-fetoprotein
Back Extra: Yolk Sac Tumour
- Clinical: Orbital YST usually presents in early childhood with progressive proptosis, ptosis, ophthalmoplegia, and vision loss.
- Micro: YSTs feature a meshwork of spaces lined by flat to cuboidal epithelium with marked cellular anaplasia and conspicuous mitoses.
- Ancillary: Positive immunohistochemical staining for alpha-fetoprotein (AFP), glypican-3, and nuclear SALL4 is characteristic.
Reference Gallery:
Yolk sac tumour. Irregular anastomosing channels lined by cuboidal tumour cells with formation of cystic spaces (*). A Schiller-Duval body is near the centre (arrow).
Yolk sac tumour. The tumour cells have strong cytoplasmic staining for alpha-fetoprotein.
Yolk sac tumour. Clinical image of a yolk sac tumour in a 3-year-old boy that presented as acute-onset painless progressive protrusion of the left eye.
Yolk sac tumour. Clinical image of a yolk sac tumour in a 3-year-old boy that presented as acute-onset painless progressive protrusion of the left eye.
Yolk sac tumour. Contrast enhanced CT scan shows a well-defined mass with multiple cysts extending from the left pterygopalantine fossa through the inferior orbital fissure
Yolk sac tumour. Contrast enhanced CT scan shows the well-defined mass extending to the left globe inferior to the optic nerve.
Yolk sac tumour. The tumour cells exhibit strong nuclear expression of SALL-4 antibody
Yolk sac tumour. The tumour cells showed high Ki67 index.

Q: An orbital mass in early childhood presenting with progressive, painless proptosis, characterized microscopically by irregular anastomosing channels and strong expression of alpha-fetoprotein, is diagnostic of a [...].
Yolk sac tumour. Clinical image of a yolk sac tumour in a 3-year-old boy that presented as acute-onset painless progressive protrusion of the left eye.
Yolk sac tumour. Contrast enhanced CT scan shows a well-defined mass with multiple cysts extending from the left pterygopalantine fossa through the inferior orbital fissure
A: Yolk Sac Tumor
Back Extra: Yolk Sac Tumour
- Clinical: Orbital YST usually presents in early childhood with progressive proptosis, ptosis, ophthalmoplegia, and vision loss.
- Micro: YSTs feature a meshwork of spaces lined by flat to cuboidal epithelium with marked cellular anaplasia and conspicuous mitoses.
- Ancillary: Positive immunohistochemical staining for alpha-fetoprotein (AFP), glypican-3, and nuclear SALL4 is characteristic.
Reference Gallery:
Yolk sac tumour. Irregular anastomosing channels lined by cuboidal tumour cells with formation of cystic spaces (*). A Schiller-Duval body is near the centre (arrow).
Yolk sac tumour. The tumour cells have strong cytoplasmic staining for alpha-fetoprotein.
Yolk sac tumour. Clinical image of a yolk sac tumour in a 3-year-old boy that presented as acute-onset painless progressive protrusion of the left eye.
Yolk sac tumour. Clinical image of a yolk sac tumour in a 3-year-old boy that presented as acute-onset painless progressive protrusion of the left eye.
Yolk sac tumour. Contrast enhanced CT scan shows a well-defined mass with multiple cysts extending from the left pterygopalantine fossa through the inferior orbital fissure
Yolk sac tumour. Contrast enhanced CT scan shows the well-defined mass extending to the left globe inferior to the optic nerve.
Yolk sac tumour. The tumour cells exhibit strong nuclear expression of SALL-4 antibody
Yolk sac tumour. The tumour cells showed high Ki67 index.

Q: Microscopically, the [...] variant of Mesenchymal hamartoma of the orbit shows randomly arranged mature striated muscle fibers admixed with adipose tissue, collagen, blood vessels, and peripheral nerves.
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
A: rhabdomyomatous
Back Extra: Mesenchymal hamartoma of the orbit
- Clinical: Mesenchymal hamartoma of the orbit can present as a painless orbital mass causing proptosis, ptosis, and altered ocular motility.
- Micro: Orbital rhabdomyomatous mesenchymal hamartoma shows randomly arranged mature striated muscle fibers with an admixture of adipose tissue, collagen, blood vessels, and peripheral nerves.
- Ancillary: A diagnosis of chondromesenchymal hamartoma should prompt referral for DICER1 genetic testing and lifelong surveillance if positive.
Reference Gallery:
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
Fibrous hamartoma of infancy. Low-power view showing the triphasic morphology with mature adipose tissue, bundles of bland fibroblastic/myofibroblastic cells, and areas of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view of mature adipose tissue, primitive mesenchyme, and bland fibroblastic/myofibroblastic cells.

Q: A diagnosis of the chondromesenchymal variant of Mesenchymal hamartoma of the orbit should prompt referral for _[...]_ genetic testing and lifelong surveillance if positive.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
A: DICER1
Back Extra: Mesenchymal hamartoma of the orbit
- Clinical: Mesenchymal hamartoma of the orbit can present as a painless orbital mass causing proptosis, ptosis, and altered ocular motility.
- Micro: Orbital rhabdomyomatous mesenchymal hamartoma shows randomly arranged mature striated muscle fibers with an admixture of adipose tissue, collagen, blood vessels, and peripheral nerves.
- Ancillary: A diagnosis of chondromesenchymal hamartoma should prompt referral for DICER1 genetic testing and lifelong surveillance if positive.
Reference Gallery:
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
Fibrous hamartoma of infancy. Low-power view showing the triphasic morphology with mature adipose tissue, bundles of bland fibroblastic/myofibroblastic cells, and areas of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view of mature adipose tissue, primitive mesenchyme, and bland fibroblastic/myofibroblastic cells.

Q: The rhabdomyomatous variant of Mesenchymal Hamartoma of the Orbit is histologically characterized by randomly arranged bundles of mature [...] fibers admixed with adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
A: striated muscle
Back Extra: Mesenchymal Hamartoma of the Orbit
- Clinical: Mesenchymal Hamartoma of the Orbit can present as a painless orbital mass, with symptoms including proptosis, ptosis, and altered ocular motility.
- Micro: Rhabdomyomatous mesenchymal hamartoma is characterized by randomly arranged mature striated muscle fibers, adipose tissue, collagen, and blood vessels.
- Ancillary: A diagnosis of chondromesenchymal hamartoma should prompt referral for DICER1 genetic testing and lifelong surveillance if positive.
Reference Gallery:
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
Fibrous hamartoma of infancy. Low-power view showing the triphasic morphology with mature adipose tissue, bundles of bland fibroblastic/myofibroblastic cells, and areas of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view of mature adipose tissue, primitive mesenchyme, and bland fibroblastic/myofibroblastic cells.

Q: A diagnosis of the chondromesenchymal variant of Mesenchymal Hamartoma of the Orbit (which features irregular islands of mature hyaline cartilage) should prompt a referral for [...] genetic testing and lifelong surveillance.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
A: DICER1
Back Extra: Mesenchymal Hamartoma of the Orbit
- Clinical: Mesenchymal Hamartoma of the Orbit can present as a painless orbital mass, with symptoms including proptosis, ptosis, and altered ocular motility.
- Micro: Rhabdomyomatous mesenchymal hamartoma is characterized by randomly arranged mature striated muscle fibers, adipose tissue, collagen, and blood vessels.
- Ancillary: A diagnosis of chondromesenchymal hamartoma should prompt referral for DICER1 genetic testing and lifelong surveillance if positive.
Reference Gallery:
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
Fibrous hamartoma of infancy. Low-power view showing the triphasic morphology with mature adipose tissue, bundles of bland fibroblastic/myofibroblastic cells, and areas of primitive mesenchyme.
Fibrous hamartoma of infancy. Medium-power view of mature adipose tissue, primitive mesenchyme, and bland fibroblastic/myofibroblastic cells.

Q: The rhabdomyomatous variant of Mesenchymal Hamartoma of the Orbit is characterized histologically by randomly arranged bundles of [...] admixed with benign adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
A: mature striated muscle
Back Extra: Mesenchymal Hamartoma of the Orbit
- Clinical: Mesenchymal Hamartoma of the Orbit can present as a painless orbital mass, leading to proptosis, ptosis, and altered ocular motility.
- Micro: Rhabdomyomatous Mesenchymal Hamartoma (RMH) shows mature striated muscle fibres with an admixture of adipose tissue, collagen, blood vessels, and peripheral nerves.
- Ancillary: Chondromesenchymal Hamartoma (CMH) is associated with pathogenic germline DICER1 variants, prompting genetic testing and lifelong surveillance if positive.
Reference Gallery:
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
Fibrous hamartoma of infancy. Low-power view showing the triphasic morphology with mature adipose tissue, bundles of bland fibroblastic/myofibroblastic cells, and areas of primitive mesenchyme.

Q: The chondromesenchymal variant of Mesenchymal Hamartoma of the Orbit (associated with germline DICER1 variants) is characterized histologically by irregular islands of [...] separated by vascularized fibrocollagenous septa.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
A: mature hyaline cartilage
Back Extra: Mesenchymal Hamartoma of the Orbit
- Clinical: Mesenchymal Hamartoma of the Orbit can present as a painless orbital mass, leading to proptosis, ptosis, and altered ocular motility.
- Micro: Rhabdomyomatous Mesenchymal Hamartoma (RMH) shows mature striated muscle fibres with an admixture of adipose tissue, collagen, blood vessels, and peripheral nerves.
- Ancillary: Chondromesenchymal Hamartoma (CMH) is associated with pathogenic germline DICER1 variants, prompting genetic testing and lifelong surveillance if positive.
Reference Gallery:
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
Fibrous hamartoma of infancy. Low-power view showing the triphasic morphology with mature adipose tissue, bundles of bland fibroblastic/myofibroblastic cells, and areas of primitive mesenchyme.

Q: The fibrous hamartoma of infancy variant of Mesenchymal Hamartoma of the Orbit exhibits a characteristic [...] morphology composed of mature adipose tissue, bland fibroblastic bundles, and primitive mesenchyme.
Fibrous hamartoma of infancy. Low-power view showing the triphasic morphology with mature adipose tissue, bundles of bland fibroblastic/myofibroblastic cells, and areas of primitive mesenchyme.
A: triphasic
Back Extra: Mesenchymal Hamartoma of the Orbit
- Clinical: Mesenchymal Hamartoma of the Orbit can present as a painless orbital mass, leading to proptosis, ptosis, and altered ocular motility.
- Micro: Rhabdomyomatous Mesenchymal Hamartoma (RMH) shows mature striated muscle fibres with an admixture of adipose tissue, collagen, blood vessels, and peripheral nerves.
- Ancillary: Chondromesenchymal Hamartoma (CMH) is associated with pathogenic germline DICER1 variants, prompting genetic testing and lifelong surveillance if positive.
Reference Gallery:
Rhabdomyomatous mesenchymal hamartoma. Low-power view showing randomly arranged bundles of mature striated muscle fibres and benign admixed adipose tissue, collagen, and blood vessels.
Rhabdomyomatous mesenchymal hamartoma. Medium-power view showing mature striated muscle, adipose tissue, collagen, blood vessels, and peripheral nerves.
Chondromesenchymal hamartoma. Low-power showing irregular islands of mature hyaline cartilage separated by collagenous septa.
Chondromesenchymal hamartoma. Medium-power view showing vascularized fibrocollagenous tissue merging with mature hyaline cartilage.
Fibrous hamartoma of infancy. Low-power view showing the triphasic morphology with mature adipose tissue, bundles of bland fibroblastic/myofibroblastic cells, and areas of primitive mesenchyme.

Q: The presence of ectopic, mature, and benign neuroglial tissue in the orbit, which may feature microcalcifications, is diagnostic of [...].
Orbital glial heterotopia. Benign neuroglial tissue with microcalcifications.
A: Orbital Glial Heterotopia
Back Extra: Orbital Glial Heterotopia
- Clinical: Orbital glial heterotopia commonly presents with signs such as swelling, strabismus, and proptosis.
- Micro: The lesions are composed of benign and mature brain tissue, including glial and neural components, and may contain microcalcifications and psammoma bodies.
- Ancillary: MRI or CT scans are recommended to localize the lesion and rule out other conditions like encephalocele.
Reference Gallery:
Orbital glial heterotopia. Benign neuroglial tissue with microcalcifications.
Orbital glial heterotopia. The glial tissue is immunoreactive for GFAP
Orbital glial heterotopia. Neurofilament protein shows axons within the tissue
Orbital glial heterotopia. Contrast enhanced T1-weighted magnetic MRI with extraconal enhancing lesion in the right orbit extending posteriorly to the orbital apex.

Q: Immunohistochemistry of Orbital Glial Heterotopia typically demonstrates axons highlighted by neurofilament protein, while the glial components are strongly immunoreactive for [...].
Orbital glial heterotopia. The glial tissue is immunoreactive for GFAP
Orbital glial heterotopia. Neurofilament protein shows axons within the tissue
A: GFAP
Back Extra: Orbital Glial Heterotopia
- Clinical: Orbital glial heterotopia commonly presents with signs such as swelling, strabismus, and proptosis.
- Micro: The lesions are composed of benign and mature brain tissue, including glial and neural components, and may contain microcalcifications and psammoma bodies.
- Ancillary: MRI or CT scans are recommended to localize the lesion and rule out other conditions like encephalocele.
Reference Gallery:
Orbital glial heterotopia. Benign neuroglial tissue with microcalcifications.
Orbital glial heterotopia. The glial tissue is immunoreactive for GFAP
Orbital glial heterotopia. Neurofilament protein shows axons within the tissue
Orbital glial heterotopia. Contrast enhanced T1-weighted magnetic MRI with extraconal enhancing lesion in the right orbit extending posteriorly to the orbital apex.

Q: When evaluating Orbital Glial Heterotopia with MRI or CT, it is critical to confirm the absence of an intracranial connection to rule out an [...].
Orbital glial heterotopia. Contrast enhanced T1-weighted magnetic MRI with extraconal enhancing lesion in the right orbit extending posteriorly to the orbital apex.
A: encephalocele
Back Extra: Orbital Glial Heterotopia
- Clinical: Orbital glial heterotopia commonly presents with signs such as swelling, strabismus, and proptosis.
- Micro: The lesions are composed of benign and mature brain tissue, including glial and neural components, and may contain microcalcifications and psammoma bodies.
- Ancillary: MRI or CT scans are recommended to localize the lesion and rule out other conditions like encephalocele.
Reference Gallery:
Orbital glial heterotopia. Benign neuroglial tissue with microcalcifications.
Orbital glial heterotopia. The glial tissue is immunoreactive for GFAP
Orbital glial heterotopia. Neurofilament protein shows axons within the tissue
Orbital glial heterotopia. Contrast enhanced T1-weighted magnetic MRI with extraconal enhancing lesion in the right orbit extending posteriorly to the orbital apex.

Q: On T1-weighted MRI, Primary Orbital Melanoma classically appears as a [...] well-defined lesion due to the intrinsic properties of melanin.
Diagnosis: MRI orbital melanoma. T1 weighted axial MRI imaging showing a hyperintense well defined lesion of primary orbital melanoma, located in the left medial rectus muscle close to orbital apex.
A: hyperintense
Back Extra: Primary Orbital Melanoma
- Clinical: Primary orbital melanoma commonly presents with unilateral proptosis, decreased visual acuity, periorbital pain, and diplopia.
- Micro: Spindle and epithelioid melanoma cells are identified, with mitotic figures and necrosis seen in some cases.
- Ancillary: Immunohistochemistry shows positivity for S100, MelanA, HMB45, and Sox10, and some cases are nuclear BAP1 negative.
Reference Gallery:
Diagnosis: Primary orbital melanoma. The melanoma is surrounded by melanophages and interfaces with orbital fat and extraocular muscle tissue.
Diagnosis: Primary orbital melanoma. Epithelioid cells within a primary orbital melanoma.
Diagnosis: Primary orbital melanoma. Spindle melanoma cells in a primary orbital melanoma.
Diagnosis: Primary orbital melanoma. Clones in a primary orbital melanoma arranged as back to back ovoid nodules.
Diagnosis: Primary orbital melanoma precursor lesions. Cellular blue naevus in the orbital soft tissue from which primary orbital melanoma can arise.
Diagnosis: Primary orbital melanoma precursor lesions. Benign, pigmented spindle cells of oculodermal melanocytosis, present in the orbital adipose tissue, from which primary orbital melanoma can arise.
Diagnosis: Primary orbital melanoma. Scanning power showing a well defined deposit of primary orbital melanoma, situated between the optic nerve and a dilated orbital blood vessel on the left and extraocular muscle to the right.
Diagnosis: MRI orbital melanoma. T1 weighted axial MRI imaging showing a hyperintense well defined lesion of primary orbital melanoma, located in the left medial rectus muscle close to orbital apex.

Q: Histologically, Primary Orbital Melanoma is typically composed of a mixture of spindle cells and [...] melanoma cells, which may interface directly with orbital fat and extraocular muscle.
Diagnosis: Primary orbital melanoma. The melanoma is surrounded by melanophages and interfaces with orbital fat and extraocular muscle tissue.
Diagnosis: Primary orbital melanoma. Epithelioid cells within a primary orbital melanoma.
Diagnosis: Primary orbital melanoma. Spindle melanoma cells in a primary orbital melanoma.
A: epithelioid
Back Extra: Primary Orbital Melanoma
- Clinical: Primary orbital melanoma commonly presents with unilateral proptosis, decreased visual acuity, periorbital pain, and diplopia.
- Micro: Spindle and epithelioid melanoma cells are identified, with mitotic figures and necrosis seen in some cases.
- Ancillary: Immunohistochemistry shows positivity for S100, MelanA, HMB45, and Sox10, and some cases are nuclear BAP1 negative.
Reference Gallery:
Diagnosis: Primary orbital melanoma. The melanoma is surrounded by melanophages and interfaces with orbital fat and extraocular muscle tissue.
Diagnosis: Primary orbital melanoma. Epithelioid cells within a primary orbital melanoma.
Diagnosis: Primary orbital melanoma. Spindle melanoma cells in a primary orbital melanoma.
Diagnosis: Primary orbital melanoma. Clones in a primary orbital melanoma arranged as back to back ovoid nodules.
Diagnosis: Primary orbital melanoma precursor lesions. Cellular blue naevus in the orbital soft tissue from which primary orbital melanoma can arise.
Diagnosis: Primary orbital melanoma precursor lesions. Benign, pigmented spindle cells of oculodermal melanocytosis, present in the orbital adipose tissue, from which primary orbital melanoma can arise.
Diagnosis: Primary orbital melanoma. Scanning power showing a well defined deposit of primary orbital melanoma, situated between the optic nerve and a dilated orbital blood vessel on the left and extraocular muscle to the right.
Diagnosis: MRI orbital melanoma. T1 weighted axial MRI imaging showing a hyperintense well defined lesion of primary orbital melanoma, located in the left medial rectus muscle close to orbital apex.

Q: Primary Orbital Melanoma can arise from benign orbital soft tissue precursor lesions, such as a cellular blue nevus or oculodermal [...].
Diagnosis: Primary orbital melanoma precursor lesions. Cellular blue naevus in the orbital soft tissue from which primary orbital melanoma can arise.
Diagnosis: Primary orbital melanoma precursor lesions. Benign, pigmented spindle cells of oculodermal melanocytosis, present in the orbital adipose tissue, from which primary orbital melanoma can arise.
A: melanocytosis
Back Extra: Primary Orbital Melanoma
- Clinical: Primary orbital melanoma commonly presents with unilateral proptosis, decreased visual acuity, periorbital pain, and diplopia.
- Micro: Spindle and epithelioid melanoma cells are identified, with mitotic figures and necrosis seen in some cases.
- Ancillary: Immunohistochemistry shows positivity for S100, MelanA, HMB45, and Sox10, and some cases are nuclear BAP1 negative.
Reference Gallery:
Diagnosis: Primary orbital melanoma. The melanoma is surrounded by melanophages and interfaces with orbital fat and extraocular muscle tissue.
Diagnosis: Primary orbital melanoma. Epithelioid cells within a primary orbital melanoma.
Diagnosis: Primary orbital melanoma. Spindle melanoma cells in a primary orbital melanoma.
Diagnosis: Primary orbital melanoma. Clones in a primary orbital melanoma arranged as back to back ovoid nodules.
Diagnosis: Primary orbital melanoma precursor lesions. Cellular blue naevus in the orbital soft tissue from which primary orbital melanoma can arise.
Diagnosis: Primary orbital melanoma precursor lesions. Benign, pigmented spindle cells of oculodermal melanocytosis, present in the orbital adipose tissue, from which primary orbital melanoma can arise.
Diagnosis: Primary orbital melanoma. Scanning power showing a well defined deposit of primary orbital melanoma, situated between the optic nerve and a dilated orbital blood vessel on the left and extraocular muscle to the right.
Diagnosis: MRI orbital melanoma. T1 weighted axial MRI imaging showing a hyperintense well defined lesion of primary orbital melanoma, located in the left medial rectus muscle close to orbital apex.

Q: Histologically, an arteriovenous malformation features clusters of tortuous arterioles and thick-walled veins that are directly connected without an intervening [...].
Arteriovenous malformation. Clusters of arterioles and small veins are directly connected without a capillary bed.
A: capillary bed
Back Extra: Arteriovenous Malformation
- Clinical: Arteriovenous malformations (AVMs) are usually present at birth and show significant arteriovenous shunting with raised skin temperature and pulsation if superficial.
- Micro: Histologically, AVMs are characterized by numerous large-caliber arteries and thick-walled veins, with arteries often being tortuous and veins showing intimal and adventitial fibrosis.
- Ancillary: Members of the MAPK signaling pathway, including hyperactivating changes in RAS genes and MAP2K1, have been implicated in sporadic AVMs.
Reference Gallery:
Arteriovenous malformation. Clusters of arterioles and small veins are directly connected without a capillary bed.
Orbital arteriovenous malformation. Clinical image demonstrating AVM of the left upper eyelid, medial brow, glabella and medial orbit.
Orbital arteriovenous malformation. CT with contrast demonstrating tangle of arterialized vessels in the medial orbit, with frontal sinus floor defect from previous surgery.
Orbital arteriovenous malformation. MRI with contrast demonstrating arterialized mass in the medial orbit, glabella and lateral radix.
Orbital arteriovenous malformation. Subtraction angiogram demonstrating arterialized veins in the orbit, with feeders from the supraorbital, infraorbital and superficial temporal arteries.

Q: Superficial presentations of an arteriovenous malformation often exhibit raised skin temperature and palpable [...] due to significant high-flow shunting between arteries and arterialized veins.
Orbital arteriovenous malformation. Clinical image demonstrating AVM of the left upper eyelid, medial brow, glabella and medial orbit.
Orbital arteriovenous malformation. Subtraction angiogram demonstrating arterialized veins in the orbit, with feeders from the supraorbital, infraorbital and superficial temporal arteries.
A: pulsation
Back Extra: Arteriovenous Malformation
- Clinical: Arteriovenous malformations (AVMs) are usually present at birth and show significant arteriovenous shunting with raised skin temperature and pulsation if superficial.
- Micro: Histologically, AVMs are characterized by numerous large-caliber arteries and thick-walled veins, with arteries often being tortuous and veins showing intimal and adventitial fibrosis.
- Ancillary: Members of the MAPK signaling pathway, including hyperactivating changes in RAS genes and MAP2K1, have been implicated in sporadic AVMs.
Reference Gallery:
Arteriovenous malformation. Clusters of arterioles and small veins are directly connected without a capillary bed.
Orbital arteriovenous malformation. Clinical image demonstrating AVM of the left upper eyelid, medial brow, glabella and medial orbit.
Orbital arteriovenous malformation. CT with contrast demonstrating tangle of arterialized vessels in the medial orbit, with frontal sinus floor defect from previous surgery.
Orbital arteriovenous malformation. MRI with contrast demonstrating arterialized mass in the medial orbit, glabella and lateral radix.
Orbital arteriovenous malformation. Subtraction angiogram demonstrating arterialized veins in the orbit, with feeders from the supraorbital, infraorbital and superficial temporal arteries.

Q: A patient presenting with an orbital mass and progressive axial [...] may undergo excision revealing a well-defined reddish-purple lesion, characteristic of a Cavernous Vascular Malformation.
Cavernous vascular malformation. A 53-year-old male presented with a history of proptosis in the left eye for 2 years.
Cavernous vascular malformation. Complete excisional biopsy was performed by transcutaneous orbitotomy. Gross examination revealed a well-defined reddish-purple lesion.
A: proptosis
Back Extra: Cavernous Vascular Malformation
- Clinical: Cavernous vascular malformation presents as an orbital mass with progressive axial proptosis. Pain can be noted in up to a third of patients, and visual impairment is typically due to optic neuropathy or hyperopic shift.
- Micro: Cavernous vascular malformation is a circumscribed encapsulated lesion characterized by clustered cavernous dilated veins lined by normal-appearing endothelial cells.
- Ancillary: GJA4 mutation is found in a high proportion of cavernous vascular malformations, encoding a transmembrane protein involved in gap junctions and hemichannels in vessels.
Reference Gallery:
Cavernous vascular malformation. A 53-year-old male presented with a history of proptosis in the left eye for 2 years.
Cavernous vascular malformation. Magnetic resonance imaging of the orbit revealed a well-defined hyperintense lesion in the mid-orbit.
Cavernous vascular malformation. The lesion is superolateral to the optic nerve.
Cavernous vascular malformation. Complete excisional biopsy was performed by transcutaneous orbitotomy. Gross examination revealed a well-defined reddish-purple lesion.
Cavernous vascular malformation. Higher magnification shows the flattened vessel walls with normal endothelial cells.
Cavernous vascular malformation. Circumscribed lesion consisting of dilated/cavernous veins.
Cavernous vascular malformation. aSMA highlights the walls of the veins

Q: Microscopically, a Cavernous Vascular Malformation presents as a circumscribed, encapsulated lesion characterized by clustered, cavernous dilated [...] lined by normal-appearing endothelial cells.
Cavernous vascular malformation. Higher magnification shows the flattened vessel walls with normal endothelial cells.
Cavernous vascular malformation. Circumscribed lesion consisting of dilated/cavernous veins.
A: veins
Back Extra: Cavernous Vascular Malformation
- Clinical: Cavernous vascular malformation presents as an orbital mass with progressive axial proptosis. Pain can be noted in up to a third of patients, and visual impairment is typically due to optic neuropathy or hyperopic shift.
- Micro: Cavernous vascular malformation is a circumscribed encapsulated lesion characterized by clustered cavernous dilated veins lined by normal-appearing endothelial cells.
- Ancillary: GJA4 mutation is found in a high proportion of cavernous vascular malformations, encoding a transmembrane protein involved in gap junctions and hemichannels in vessels.
Reference Gallery:
Cavernous vascular malformation. A 53-year-old male presented with a history of proptosis in the left eye for 2 years.
Cavernous vascular malformation. Magnetic resonance imaging of the orbit revealed a well-defined hyperintense lesion in the mid-orbit.
Cavernous vascular malformation. The lesion is superolateral to the optic nerve.
Cavernous vascular malformation. Complete excisional biopsy was performed by transcutaneous orbitotomy. Gross examination revealed a well-defined reddish-purple lesion.
Cavernous vascular malformation. Higher magnification shows the flattened vessel walls with normal endothelial cells.
Cavernous vascular malformation. Circumscribed lesion consisting of dilated/cavernous veins.
Cavernous vascular malformation. aSMA highlights the walls of the veins

Q: In Cavernous Vascular Malformation, the walls of the dilated vessels can be highlighted using an immunohistochemical stain for [...] (smooth muscle actin).
Cavernous vascular malformation. aSMA highlights the walls of the veins
A: SMA
Back Extra: Cavernous Vascular Malformation
- Clinical: Cavernous vascular malformation presents as an orbital mass with progressive axial proptosis. Pain can be noted in up to a third of patients, and visual impairment is typically due to optic neuropathy or hyperopic shift.
- Micro: Cavernous vascular malformation is a circumscribed encapsulated lesion characterized by clustered cavernous dilated veins lined by normal-appearing endothelial cells.
- Ancillary: GJA4 mutation is found in a high proportion of cavernous vascular malformations, encoding a transmembrane protein involved in gap junctions and hemichannels in vessels.
Reference Gallery:
Cavernous vascular malformation. A 53-year-old male presented with a history of proptosis in the left eye for 2 years.
Cavernous vascular malformation. Magnetic resonance imaging of the orbit revealed a well-defined hyperintense lesion in the mid-orbit.
Cavernous vascular malformation. The lesion is superolateral to the optic nerve.
Cavernous vascular malformation. Complete excisional biopsy was performed by transcutaneous orbitotomy. Gross examination revealed a well-defined reddish-purple lesion.
Cavernous vascular malformation. Higher magnification shows the flattened vessel walls with normal endothelial cells.
Cavernous vascular malformation. Circumscribed lesion consisting of dilated/cavernous veins.
Cavernous vascular malformation. aSMA highlights the walls of the veins

Q: Patients with Combined Lymphatic-Venous Malformation of the Orbit frequently present with unilateral proptosis that can undergo rapid clinical expansion secondary to a viral illness or intralesional [...].
Combined lymphatic-venous malformation of the orbit. A 10-year-old girl presented with sudden proptosis of the left eye.
Combined lymphatic-venous malformation of the orbit. Computed tomography of the orbit revealed an ill-defined heterogenous lesion in the pre-septal tissues and intraconal space of the left orbit.
A: hemorrhage
Back Extra: Combined Lymphatic-Venous Malformation of the Orbit
- Clinical: Combined lymphatic-venous malformation (LVM) can present with unilateral proptosis, extraocular motility disturbance, ptosis, and visual loss. It can expand during viral illness or intralesional haemorrhage.
- Micro: LVM forms an unencapsulated mass of malformed endothelial-lined channels, often containing lymphoid follicles and haemosiderin-laden macrophages.
- Ancillary: Detection of somatic mutations (e.g., MTOR or PI3K inhibitors) can guide targeted treatments.
Reference Gallery:
Combined lymphatic-venous malformation of the orbit. Endothelial cells lining the dilated channels of an orbital LVM. Note lymphocytes at a sub-endothelial location.
Combined lymphatic-venous malformation of the orbit. Abnormally formed intermingled veins and lymphatic channels are present.
Combined lymphatic-venous malformation of the orbit. A 10-year-old girl presented with sudden proptosis of the left eye.
Combined lymphatic-venous malformation of the orbit. Computed tomography of the orbit revealed an ill-defined heterogenous lesion in the pre-septal tissues and intraconal space of the left orbit.
Combined lymphatic-venous malformation of the orbit. The lesion regressed after treatment with two sessions of sclerotherapy with intralesional bleomycin.
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA

Q: Histologically, Combined Lymphatic-Venous Malformation of the Orbit features an unencapsulated mass of malformed, intermingled venous and lymphatic channels that often contain hemosiderin-laden macrophages and sub-endothelial [...].
Combined lymphatic-venous malformation of the orbit. Endothelial cells lining the dilated channels of an orbital LVM. Note lymphocytes at a sub-endothelial location.
Combined lymphatic-venous malformation of the orbit. Abnormally formed intermingled veins and lymphatic channels are present.
A: lymphocytes
Back Extra: Combined Lymphatic-Venous Malformation of the Orbit
- Clinical: Combined lymphatic-venous malformation (LVM) can present with unilateral proptosis, extraocular motility disturbance, ptosis, and visual loss. It can expand during viral illness or intralesional haemorrhage.
- Micro: LVM forms an unencapsulated mass of malformed endothelial-lined channels, often containing lymphoid follicles and haemosiderin-laden macrophages.
- Ancillary: Detection of somatic mutations (e.g., MTOR or PI3K inhibitors) can guide targeted treatments.
Reference Gallery:
Combined lymphatic-venous malformation of the orbit. Endothelial cells lining the dilated channels of an orbital LVM. Note lymphocytes at a sub-endothelial location.
Combined lymphatic-venous malformation of the orbit. Abnormally formed intermingled veins and lymphatic channels are present.
Combined lymphatic-venous malformation of the orbit. A 10-year-old girl presented with sudden proptosis of the left eye.
Combined lymphatic-venous malformation of the orbit. Computed tomography of the orbit revealed an ill-defined heterogenous lesion in the pre-septal tissues and intraconal space of the left orbit.
Combined lymphatic-venous malformation of the orbit. The lesion regressed after treatment with two sessions of sclerotherapy with intralesional bleomycin.
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA
Combined lymphatic-venous malformation of the orbit. TBA

Q: On magnetic resonance imaging, an Orbital Venous Malformation characteristically exhibits heterogeneous early enhancement followed by delayed, complete [...] with contrast over time.
Orbital venous malformation. A: Axial T2 MRI shows an iso- to hyperintense right orbital mass (arrow). B: Axial T1 post-contrast MRI obtained immediately after contrast administration shows heterogeneous enhancement of the mass (arrow). C: Sagittal T1 post-contrast MRI (delayed image) shows complete filling-in of the mass with contrast over time.
A: filling-in
Back Extra: Orbital Venous Malformation
- Clinical: Orbital venous malformations (VM) can present as bluish subdermal lesions when superficial and typically present later in life. Deeper lesions can cause proptosis, strabismus, and globe dystopia, especially during Valsalva maneuvers.
- Micro: The lesions consist of an abnormal collection of enlarged veins with a variable diameter and thickness of the smooth muscle layer. Thrombi and phleboliths with signs of recanalization are common.
- Ancillary: Molecular studies are not typically required for diagnosis, but in GVMs, mutations in genes like TEK and PIK3CA are relevant. Orbital lesions have not been studied molecularly.
Reference Gallery:
Orbital venous malformation. A 48-year-old woman presented with progressively increasing violet-red lesion in her right eye extending anteriorly from the orbit.
Orbital venous malformation. Magnetic resonance imaging of the orbits revealed an ill-defined lesion on the ocular surface with a diffuse lesion in the right orbit and ipsilateral ethmoidal sinus mucosa, with intense contrast enhancement suggestive of right-sided orbito-conjunctivo-sinus venous malformation.
Venous malformation. Abnormal veins are arranged in clusters.
Venous malformation. Higher magnification shows the abnormal texture of the malformed vessel wall.
Orbital venous malformation. A: Axial T2 MRI shows an iso- to hyperintense right orbital mass (arrow). B: Axial T1 post-contrast MRI obtained immediately after contrast administration shows heterogeneous enhancement of the mass (arrow). C: Sagittal T1 post-contrast MRI (delayed image) shows complete filling-in of the mass with contrast over time.

Q: Histologically, an Orbital Venous Malformation consists of an abnormal collection of enlarged veins arranged in clusters, characterized by variable diameters and irregularly thickened [...] layers within the vessel walls.
Venous malformation. Abnormal veins are arranged in clusters.
Venous malformation. Higher magnification shows the abnormal texture of the malformed vessel wall.
A: smooth muscle
Back Extra: Orbital Venous Malformation
- Clinical: Orbital venous malformations (VM) can present as bluish subdermal lesions when superficial and typically present later in life. Deeper lesions can cause proptosis, strabismus, and globe dystopia, especially during Valsalva maneuvers.
- Micro: The lesions consist of an abnormal collection of enlarged veins with a variable diameter and thickness of the smooth muscle layer. Thrombi and phleboliths with signs of recanalization are common.
- Ancillary: Molecular studies are not typically required for diagnosis, but in GVMs, mutations in genes like TEK and PIK3CA are relevant. Orbital lesions have not been studied molecularly.
Reference Gallery:
Orbital venous malformation. A 48-year-old woman presented with progressively increasing violet-red lesion in her right eye extending anteriorly from the orbit.
Orbital venous malformation. Magnetic resonance imaging of the orbits revealed an ill-defined lesion on the ocular surface with a diffuse lesion in the right orbit and ipsilateral ethmoidal sinus mucosa, with intense contrast enhancement suggestive of right-sided orbito-conjunctivo-sinus venous malformation.
Venous malformation. Abnormal veins are arranged in clusters.
Venous malformation. Higher magnification shows the abnormal texture of the malformed vessel wall.
Orbital venous malformation. A: Axial T2 MRI shows an iso- to hyperintense right orbital mass (arrow). B: Axial T1 post-contrast MRI obtained immediately after contrast administration shows heterogeneous enhancement of the mass (arrow). C: Sagittal T1 post-contrast MRI (delayed image) shows complete filling-in of the mass with contrast over time.

Q: Clinically, a superficial Orbital Venous Malformation often presents later in life as a progressively enlarging, [...] subdermal lesion extending from the orbit.
Orbital venous malformation. A 48-year-old woman presented with progressively increasing violet-red lesion in her right eye extending anteriorly from the orbit.
A: bluish-violet
Back Extra: Orbital Venous Malformation
- Clinical: Orbital venous malformations (VM) can present as bluish subdermal lesions when superficial and typically present later in life. Deeper lesions can cause proptosis, strabismus, and globe dystopia, especially during Valsalva maneuvers.
- Micro: The lesions consist of an abnormal collection of enlarged veins with a variable diameter and thickness of the smooth muscle layer. Thrombi and phleboliths with signs of recanalization are common.
- Ancillary: Molecular studies are not typically required for diagnosis, but in GVMs, mutations in genes like TEK and PIK3CA are relevant. Orbital lesions have not been studied molecularly.
Reference Gallery:
Orbital venous malformation. A 48-year-old woman presented with progressively increasing violet-red lesion in her right eye extending anteriorly from the orbit.
Orbital venous malformation. Magnetic resonance imaging of the orbits revealed an ill-defined lesion on the ocular surface with a diffuse lesion in the right orbit and ipsilateral ethmoidal sinus mucosa, with intense contrast enhancement suggestive of right-sided orbito-conjunctivo-sinus venous malformation.
Venous malformation. Abnormal veins are arranged in clusters.
Venous malformation. Higher magnification shows the abnormal texture of the malformed vessel wall.
Orbital venous malformation. A: Axial T2 MRI shows an iso- to hyperintense right orbital mass (arrow). B: Axial T1 post-contrast MRI obtained immediately after contrast administration shows heterogeneous enhancement of the mass (arrow). C: Sagittal T1 post-contrast MRI (delayed image) shows complete filling-in of the mass with contrast over time.

Q: Microscopically, Adenocarcinoma of the Ciliary Body typically forms strands, cords, and duct-like structures of atypical cuboidal to epithelioid cells surrounded by prominent [...] material.
Non-pigmented ciliary body adenocarcinoma. Prominent basement membrane elaboration.
Ciliary body adenocarcinoma. A fine needle aspiration biopsy shows a cohesive cluster of atypical cuboidal epithelial cells with larger hyperchromatic nuclei, vacuolated cytoplasm, and associated basement membrane material (arrow). Pigment is absent (Giemsa).
A: basement membrane
Back Extra: Adenocarcinoma of the Ciliary Body
- Clinical: Adenocarcinomas of the ciliary body can present as asymptomatic or cause visual disturbances, including secondary glaucoma and sectoral cataract.
- Micro: Non-pigmented and pigmented adenocarcinomas show strands, cords, and duct-like structures of atypical cuboidal to epithelioid cells surrounded by basement membrane material.
- Ancillary: PAX8 nuclear immunopositivity is useful in differentiating adenocarcinoma from melanocytic lesions.
Reference Gallery:
Non-pigmented ciliary body adenocarcinoma. Prominent basement membrane elaboration.
Non-pigmented ciliary body adenocarcinoma. Tumour (bottom of field) invading beyond the sclera (eosinophilic collagenous band) to an extraocular location (top of field).
Ciliary body adenocarcinoma. A fine needle aspiration biopsy shows a cohesive cluster of atypical cuboidal epithelial cells with larger hyperchromatic nuclei, vacuolated cytoplasm, and associated basement membrane material (arrow). Pigment is absent (Giemsa).
Ciliary body adenocarcinoma. (Left) A partially pigmented ciliary body mass extending to the iris surface. (Right) B-scan ultrasonography shows a mass with abrupt borders.
Non-pigmented ciliary body adenoma. Trabecular pattern with hyalinised stroma.
Non-pigmented ciliary body adenoma. Extracellular mucopolysaccharide elaboration.
Non-pigmented ciliary body adenoma. High power showing the bland cytolological features.
Non-pigmented ciliary body adenoma. Tubuloglandular pattern with extracellular mucopolysaccharide elaboration.
Pigmented ciliary body adenoma. Cords and nests of pigmented epithelial cells separated by fibrous septa.
Non-pigmented ciliary body adenoma. PAX8 nuclear immunopositivity; a pigmented adenoma would show an identical pattern.
Ciliary body adenoma. A fine needle aspiration biopsy shows nests of polygonal epithelial cells with round to oval nuclei, small nucleoli, and focal pigmentation. Note prominent basement membrane material (arrow) (Giemsa).
Ciliary body epithelial adenoma. A dark brown, well-defined, solid mass (arrow) located behind the iris.

Q: A key feature highlighting the malignant nature of Adenocarcinoma of the Ciliary Body is its capacity for destructive local growth, such as the ability to [...] into an extraocular location.
Non-pigmented ciliary body adenocarcinoma. Tumour (bottom of field) invading beyond the sclera (eosinophilic collagenous band) to an extraocular location (top of field).
A: invade beyond the sclera
Back Extra: Adenocarcinoma of the Ciliary Body
- Clinical: Adenocarcinomas of the ciliary body can present as asymptomatic or cause visual disturbances, including secondary glaucoma and sectoral cataract.
- Micro: Non-pigmented and pigmented adenocarcinomas show strands, cords, and duct-like structures of atypical cuboidal to epithelioid cells surrounded by basement membrane material.
- Ancillary: PAX8 nuclear immunopositivity is useful in differentiating adenocarcinoma from melanocytic lesions.
Reference Gallery:
Non-pigmented ciliary body adenocarcinoma. Prominent basement membrane elaboration.
Non-pigmented ciliary body adenocarcinoma. Tumour (bottom of field) invading beyond the sclera (eosinophilic collagenous band) to an extraocular location (top of field).
Ciliary body adenocarcinoma. A fine needle aspiration biopsy shows a cohesive cluster of atypical cuboidal epithelial cells with larger hyperchromatic nuclei, vacuolated cytoplasm, and associated basement membrane material (arrow). Pigment is absent (Giemsa).
Ciliary body adenocarcinoma. (Left) A partially pigmented ciliary body mass extending to the iris surface. (Right) B-scan ultrasonography shows a mass with abrupt borders.
Non-pigmented ciliary body adenoma. Trabecular pattern with hyalinised stroma.
Non-pigmented ciliary body adenoma. Extracellular mucopolysaccharide elaboration.
Non-pigmented ciliary body adenoma. High power showing the bland cytolological features.
Non-pigmented ciliary body adenoma. Tubuloglandular pattern with extracellular mucopolysaccharide elaboration.
Pigmented ciliary body adenoma. Cords and nests of pigmented epithelial cells separated by fibrous septa.
Non-pigmented ciliary body adenoma. PAX8 nuclear immunopositivity; a pigmented adenoma would show an identical pattern.
Ciliary body adenoma. A fine needle aspiration biopsy shows nests of polygonal epithelial cells with round to oval nuclei, small nucleoli, and focal pigmentation. Note prominent basement membrane material (arrow) (Giemsa).
Ciliary body epithelial adenoma. A dark brown, well-defined, solid mass (arrow) located behind the iris.

Q: Microscopically, Medulloepithelioma of the Ciliary Body is characterized by anastomosing cords and bands of polarized neuroepithelial cells surrounding a myxoid stroma that is particularly rich in [...] (hyaluronidase-sensitive mucopolysaccharide).
Medulloepithelioma of the ciliary body. Thick bands of polarized neuroepithelium, which resembles medullary epithelium, and a diktyomatous meshwork pattern consisting of thinner strands are present. Pools of hyaluronic acid surround the neuroepithelial elements. PAS stain.
Medulloepithelioma of the ciliary body. Myxoid stroma of hyaluronidase-sensitive mucopolysaccharide surrounds the neuroepitheloid elements. Colloidal iron stain.
A: hyaluronic acid
Back Extra: Medulloepithelioma of the Ciliary Body
- Clinical: Medulloepithelioma of the ciliary body commonly presents with poor vision, leukokoria, strabismus, or a red, painful eye. Neovascularization of the iris and secondary glaucoma occur in about 45% of cases.
- Micro: Characterized by anastomosing cords, bands, and ribbons of polarized neuroepithelial cells resembling embryonic medullary epithelium. A myxoid stroma rich in hyaluronidase-sensitive mucopolysaccharide is a key feature.
- Ancillary: Immunohistochemistry shows diffuse immunoreactivity for vimentin and neuron-specific enolase. LIN28A is highly expressed, which may correlate with aggressive behavior.
Reference Gallery:
Teratoid medulloepithelioma of the ciliary body. A tumour is seen behind the iris. Intratumoural cysts and whitish foci of heteroplastic cartilage are evident.
Malignant teratoid medulloepithelioma of the ciliary body. A tumour on the inner surface of the ciliary body with cystoid spaces and foci of heteroplastic hyaline cartilage abuts the posterior surface of the lens.
Medulloepithelioma of the ciliary body. Thick bands of polarized neuroepithelium, which resembles medullary epithelium, and a diktyomatous meshwork pattern consisting of thinner strands are present. Pools of hyaluronic acid surround the neuroepithelial elements. PAS stain.
Medulloepithelioma of the ciliary body. Myxoid stroma of hyaluronidase-sensitive mucopolysaccharide surrounds the neuroepitheloid elements. Colloidal iron stain.
Malignant medulloepithelioma of the ciliary body. A poorly differentiated area in that resembles retinoblastoma. Several Flexner-Wintersteiner rosettes are present.
Malignant teratoid medulloepithelioma of the ciliary body. A teratoid tumour with a prominent island of heteroplastic hyaline cartilage. Retinoblastoma-like tissue also is present between foci of cartilage.
teratoid medulloepithelioma. Coronal CT of teratoid medulloepithelioma, malignant of the ciliary body in an 11-year-old girl

Q: The teratoid variant of Medulloepithelioma of the Ciliary Body is classically defined by the presence of heteroplastic elements, most commonly islands of [...].
Malignant teratoid medulloepithelioma of the ciliary body. A tumour on the inner surface of the ciliary body with cystoid spaces and foci of heteroplastic hyaline cartilage abuts the posterior surface of the lens.
Malignant teratoid medulloepithelioma of the ciliary body. A teratoid tumour with a prominent island of heteroplastic hyaline cartilage. Retinoblastoma-like tissue also is present between foci of cartilage.
A: hyaline cartilage
Back Extra: Medulloepithelioma of the Ciliary Body
- Clinical: Medulloepithelioma of the ciliary body commonly presents with poor vision, leukokoria, strabismus, or a red, painful eye. Neovascularization of the iris and secondary glaucoma occur in about 45% of cases.
- Micro: Characterized by anastomosing cords, bands, and ribbons of polarized neuroepithelial cells resembling embryonic medullary epithelium. A myxoid stroma rich in hyaluronidase-sensitive mucopolysaccharide is a key feature.
- Ancillary: Immunohistochemistry shows diffuse immunoreactivity for vimentin and neuron-specific enolase. LIN28A is highly expressed, which may correlate with aggressive behavior.
Reference Gallery:
Teratoid medulloepithelioma of the ciliary body. A tumour is seen behind the iris. Intratumoural cysts and whitish foci of heteroplastic cartilage are evident.
Malignant teratoid medulloepithelioma of the ciliary body. A tumour on the inner surface of the ciliary body with cystoid spaces and foci of heteroplastic hyaline cartilage abuts the posterior surface of the lens.
Medulloepithelioma of the ciliary body. Thick bands of polarized neuroepithelium, which resembles medullary epithelium, and a diktyomatous meshwork pattern consisting of thinner strands are present. Pools of hyaluronic acid surround the neuroepithelial elements. PAS stain.
Medulloepithelioma of the ciliary body. Myxoid stroma of hyaluronidase-sensitive mucopolysaccharide surrounds the neuroepitheloid elements. Colloidal iron stain.
Malignant medulloepithelioma of the ciliary body. A poorly differentiated area in that resembles retinoblastoma. Several Flexner-Wintersteiner rosettes are present.
Malignant teratoid medulloepithelioma of the ciliary body. A teratoid tumour with a prominent island of heteroplastic hyaline cartilage. Retinoblastoma-like tissue also is present between foci of cartilage.
teratoid medulloepithelioma. Coronal CT of teratoid medulloepithelioma, malignant of the ciliary body in an 11-year-old girl

Q: Poorly differentiated, malignant areas of Medulloepithelioma of the Ciliary Body can closely resemble retinoblastoma and may occasionally demonstrate characteristic [...].
Malignant medulloepithelioma of the ciliary body. A poorly differentiated area in that resembles retinoblastoma. Several Flexner-Wintersteiner rosettes are present.
A: Flexner-Wintersteiner rosettes
Back Extra: Medulloepithelioma of the Ciliary Body
- Clinical: Medulloepithelioma of the ciliary body commonly presents with poor vision, leukokoria, strabismus, or a red, painful eye. Neovascularization of the iris and secondary glaucoma occur in about 45% of cases.
- Micro: Characterized by anastomosing cords, bands, and ribbons of polarized neuroepithelial cells resembling embryonic medullary epithelium. A myxoid stroma rich in hyaluronidase-sensitive mucopolysaccharide is a key feature.
- Ancillary: Immunohistochemistry shows diffuse immunoreactivity for vimentin and neuron-specific enolase. LIN28A is highly expressed, which may correlate with aggressive behavior.
Reference Gallery:
Teratoid medulloepithelioma of the ciliary body. A tumour is seen behind the iris. Intratumoural cysts and whitish foci of heteroplastic cartilage are evident.
Malignant teratoid medulloepithelioma of the ciliary body. A tumour on the inner surface of the ciliary body with cystoid spaces and foci of heteroplastic hyaline cartilage abuts the posterior surface of the lens.
Medulloepithelioma of the ciliary body. Thick bands of polarized neuroepithelium, which resembles medullary epithelium, and a diktyomatous meshwork pattern consisting of thinner strands are present. Pools of hyaluronic acid surround the neuroepithelial elements. PAS stain.
Medulloepithelioma of the ciliary body. Myxoid stroma of hyaluronidase-sensitive mucopolysaccharide surrounds the neuroepitheloid elements. Colloidal iron stain.
Malignant medulloepithelioma of the ciliary body. A poorly differentiated area in that resembles retinoblastoma. Several Flexner-Wintersteiner rosettes are present.
Malignant teratoid medulloepithelioma of the ciliary body. A teratoid tumour with a prominent island of heteroplastic hyaline cartilage. Retinoblastoma-like tissue also is present between foci of cartilage.
teratoid medulloepithelioma. Coronal CT of teratoid medulloepithelioma, malignant of the ciliary body in an 11-year-old girl

Q: A [...] is a characteristic intraocular lesion frequently located between the posterior iris and ciliary body, microscopically lined by a monolayer of cuboidal cells with densely packed melanosomes.
Pigmented epithelial cyst. An iris pigment epithelial cyst located between the posterior iris (to the left) and ciliary body (to the right).
Pigmented epithelial cyst. A higher magnification showing a monolayer of cuboidal cells containing densely packed melanosomes, obscuring the nuclei.
A: Pigmented Epithelial Cyst
Back Extra: Pigmented Epithelial Cyst
- Clinical: Single or multiple dark brown lesions that bulge the iris stroma anteriorly, often detected via ultrasound biomicroscopy or anterior segment OCT.
- Micro: Pigmented cysts are lined by a monolayer of iris pigmented epithelial cells, which can be columnar or cuboidal, with densely packed melanosomes.
- Ancillary: Complete excision is curative and necessary for enlarging cysts that may cause visual deterioration and precipitate angle closure glaucoma.
Reference Gallery:
Pigmented epithelial cyst. An iris pigment epithelial cyst located between the posterior iris (to the left) and ciliary body (to the right).
Pigmented epithelial cyst. A higher magnification showing a monolayer of cuboidal cells containing densely packed melanosomes, obscuring the nuclei.

Q: In a Pigmented Epithelial Cyst, the lining characteristically consists of a [...] of cuboidal or columnar cells containing melanosomes so densely packed that they obscure the nuclei.
Pigmented epithelial cyst. A higher magnification showing a monolayer of cuboidal cells containing densely packed melanosomes, obscuring the nuclei.
A: monolayer
Back Extra: Pigmented Epithelial Cyst
- Clinical: Single or multiple dark brown lesions that bulge the iris stroma anteriorly, often detected via ultrasound biomicroscopy or anterior segment OCT.
- Micro: Pigmented cysts are lined by a monolayer of iris pigmented epithelial cells, which can be columnar or cuboidal, with densely packed melanosomes.
- Ancillary: Complete excision is curative and necessary for enlarging cysts that may cause visual deterioration and precipitate angle closure glaucoma.
Reference Gallery:
Pigmented epithelial cyst. An iris pigment epithelial cyst located between the posterior iris (to the left) and ciliary body (to the right).
Pigmented epithelial cyst. A higher magnification showing a monolayer of cuboidal cells containing densely packed melanosomes, obscuring the nuclei.

Q: In Reactive Epithelial Hyperplasia of the Ciliary Epithelium, gross examination of an eye with longstanding retinal detachment often reveals a fibrous sheet extending from the ciliary body, termed a [...].
Cyclitic membrane showing reactive epithelial hyperplasia. A macroscopic photo of an aphakic eye with longstanding retinal detachment and formation of a cyclitic membrane forming a fibrous sheet extending from the ciliary body.
A: cyclitic membrane
Back Extra: Reactive Epithelial Hyperplasia of the Ciliary Epithelium
- Clinical: Reactive epithelial hyperplasia is typically an incidental finding in eyes enucleated because of other substantial pathology, often seen in eyes with significant injury, surgery, inflammation, or longstanding retinal detachment.
- Micro: The hyperplastic ciliary epithelium forms cords and strands or pseudoacinar structures, primarily derived from the inner, non-pigmented layer of the ciliary epithelium, entrapped within fibrous stroma.
- Ancillary: No specific ancillary studies are available for the diagnosis of reactive epithelial hyperplasia.
Reference Gallery:
Cyclitic membrane showing reactive epithelial hyperplasia. A macroscopic photo of an aphakic eye with longstanding retinal detachment and formation of a cyclitic membrane forming a fibrous sheet extending from the ciliary body.
Reactive epithelial hyperplasia. A reactive proliferation of the non-pigmented ciliary epithelium forming cords and glandular structures within the fibrous tissue of a cyclitic membrane in an enucleation specimen after failed treatment of retinal detachment.
Reactive epithelial hyperplasia. A multilayered proliferation of cells of the non-pigmented inner layer of the ciliary epithelium flanked by its non-proliferating pigmented outer layer, in an enucleated eye from a 3-year-old child with persistent fetal vasculature (previously called persistent hyperplastic primary vitreous).

Q: Microscopically, Reactive Epithelial Hyperplasia of the Ciliary Epithelium is characterized by cords and pseudoacinar structures that are primarily derived from the [...] layer of the ciliary epithelium.
Reactive epithelial hyperplasia. A reactive proliferation of the non-pigmented ciliary epithelium forming cords and glandular structures within the fibrous tissue of a cyclitic membrane in an enucleation specimen after failed treatment of retinal detachment.
Reactive epithelial hyperplasia. A multilayered proliferation of cells of the non-pigmented inner layer of the ciliary epithelium flanked by its non-proliferating pigmented outer layer, in an enucleated eye from a 3-year-old child with persistent fetal vasculature (previously called persistent hyperplastic primary vitreous).
A: inner, non-pigmented
Back Extra: Reactive Epithelial Hyperplasia of the Ciliary Epithelium
- Clinical: Reactive epithelial hyperplasia is typically an incidental finding in eyes enucleated because of other substantial pathology, often seen in eyes with significant injury, surgery, inflammation, or longstanding retinal detachment.
- Micro: The hyperplastic ciliary epithelium forms cords and strands or pseudoacinar structures, primarily derived from the inner, non-pigmented layer of the ciliary epithelium, entrapped within fibrous stroma.
- Ancillary: No specific ancillary studies are available for the diagnosis of reactive epithelial hyperplasia.
Reference Gallery:
Cyclitic membrane showing reactive epithelial hyperplasia. A macroscopic photo of an aphakic eye with longstanding retinal detachment and formation of a cyclitic membrane forming a fibrous sheet extending from the ciliary body.
Reactive epithelial hyperplasia. A reactive proliferation of the non-pigmented ciliary epithelium forming cords and glandular structures within the fibrous tissue of a cyclitic membrane in an enucleation specimen after failed treatment of retinal detachment.
Reactive epithelial hyperplasia. A multilayered proliferation of cells of the non-pigmented inner layer of the ciliary epithelium flanked by its non-proliferating pigmented outer layer, in an enucleated eye from a 3-year-old child with persistent fetal vasculature (previously called persistent hyperplastic primary vitreous).

Q: In Retinal Astrocytic Tumours, the giant cell variant is characterized by [...] cells with abundant, billowing, eosinophilic cytoplasm and eccentric nuclei.
Acquired retinal astrocytoma. This giant cell astrocytoma extends into the subretinal space from the retina.
Acquired retinal astrocytoma. Giant cell astrocytoma of the retina containing gemistocytic cells with billowing, eosinophilic cytoplasm and eccentric nuclei.
A: gemistocytic
Back Extra: Retinal Astrocytic Tumours
- Clinical: Astrocytic tumours of the retina are usually asymptomatic and are detected incidentally or on screening of patients with suspected phakomatoses.
- Micro: Two main histopathological patterns: 1) Fascicular pattern with spindle-shaped cells, 2) Giant cell astrocytoma with gemistocytic cells and abundant eosinophilic cytoplasm.
- Ancillary: Immunohistochemistry shows diffuse positivity for GFAP and S100, and these tumours are usually negative for neuronal markers.
Reference Gallery:
Acquired retinal astrocytoma. This giant cell astrocytoma extends into the subretinal space from the retina.
Acquired retinal astrocytoma. A focal astrocytoma arises in the ganglion cell layer of the retina.
Acquired retinal astrocytoma. Giant cell astrocytoma of the retina containing gemistocytic cells with billowing, eosinophilic cytoplasm and eccentric nuclei.
Acquired retinal astrocytoma. Giant cell astrocytoma of the retina may also contain spindle shaped cells with fibrillary cytoplasm and fusiform nuclei.

Q: Histologically, focal Retinal Astrocytic Tumours characteristically arise within the [...] layer of the retina.
Acquired retinal astrocytoma. A focal astrocytoma arises in the ganglion cell layer of the retina.
A: ganglion cell
Back Extra: Retinal Astrocytic Tumours
- Clinical: Astrocytic tumours of the retina are usually asymptomatic and are detected incidentally or on screening of patients with suspected phakomatoses.
- Micro: Two main histopathological patterns: 1) Fascicular pattern with spindle-shaped cells, 2) Giant cell astrocytoma with gemistocytic cells and abundant eosinophilic cytoplasm.
- Ancillary: Immunohistochemistry shows diffuse positivity for GFAP and S100, and these tumours are usually negative for neuronal markers.
Reference Gallery:
Acquired retinal astrocytoma. This giant cell astrocytoma extends into the subretinal space from the retina.
Acquired retinal astrocytoma. A focal astrocytoma arises in the ganglion cell layer of the retina.
Acquired retinal astrocytoma. Giant cell astrocytoma of the retina containing gemistocytic cells with billowing, eosinophilic cytoplasm and eccentric nuclei.
Acquired retinal astrocytoma. Giant cell astrocytoma of the retina may also contain spindle shaped cells with fibrillary cytoplasm and fusiform nuclei.

Q: In addition to giant cells, Retinal Astrocytic Tumours may exhibit a fascicular pattern composed of [...]-shaped cells with fibrillary cytoplasm.
Acquired retinal astrocytoma. Giant cell astrocytoma of the retina may also contain spindle shaped cells with fibrillary cytoplasm and fusiform nuclei.
A: spindle
Back Extra: Retinal Astrocytic Tumours
- Clinical: Astrocytic tumours of the retina are usually asymptomatic and are detected incidentally or on screening of patients with suspected phakomatoses.
- Micro: Two main histopathological patterns: 1) Fascicular pattern with spindle-shaped cells, 2) Giant cell astrocytoma with gemistocytic cells and abundant eosinophilic cytoplasm.
- Ancillary: Immunohistochemistry shows diffuse positivity for GFAP and S100, and these tumours are usually negative for neuronal markers.
Reference Gallery:
Acquired retinal astrocytoma. This giant cell astrocytoma extends into the subretinal space from the retina.
Acquired retinal astrocytoma. A focal astrocytoma arises in the ganglion cell layer of the retina.
Acquired retinal astrocytoma. Giant cell astrocytoma of the retina containing gemistocytic cells with billowing, eosinophilic cytoplasm and eccentric nuclei.
Acquired retinal astrocytoma. Giant cell astrocytoma of the retina may also contain spindle shaped cells with fibrillary cytoplasm and fusiform nuclei.

Q: Microscopically, Nodular and Massive Retinal Gliosis is characterized by a proliferation of elongated, spindle-shaped [...] with filamentous eosinophilic cytoplasm and hyalinized vessels.
Massive retinal gliosis. Microscopic examination shows a proliferation of glial cells.
Nodular retinal gliosis. The lesion is composed of spindle-shaped fibrous astrocytes with filamentous cytoplasm and hyalinized vessels.
A: fibrous astrocytes
Back Extra: Nodular and Massive Retinal Gliosis
- Clinical: Nodular and massive retinal gliosis often present as yellow-orange to pink-red masses with a vascular appearance, causing blurring of vision due to macular exudation or exudative retinal detachment.
- Micro: Microscopically, nodular and massive retinal gliosis is characterized by elongated spindle-shaped fibrous astrocytes with filamentous eosinophilic cytoplasm, positive for GFAP and S100.
- Ancillary: Immunohistochemistry shows positivity for GFAP and S100, and there are no clinically relevant molecular findings.
Reference Gallery:
Massive retinal gliosis. Macroscopic view of a mass filling the vitreous cavity
Massive retinal gliosis. Microscopic examination shows a proliferation of glial cells.
Nodular retinal gliosis. Macroscopic view of a discrete yellow-white retinal mass with scattered vessels.
Nodular retinal gliosis. The lesion is composed of spindle-shaped fibrous astrocytes with filamentous cytoplasm and hyalinized vessels.

Q: Macroscopically, Nodular and Massive Retinal Gliosis can present as a discrete, vascularized retinal mass or as a large lesion expanding to fill the [...].
Massive retinal gliosis. Macroscopic view of a mass filling the vitreous cavity
Nodular retinal gliosis. Macroscopic view of a discrete yellow-white retinal mass with scattered vessels.
A: vitreous cavity
Back Extra: Nodular and Massive Retinal Gliosis
- Clinical: Nodular and massive retinal gliosis often present as yellow-orange to pink-red masses with a vascular appearance, causing blurring of vision due to macular exudation or exudative retinal detachment.
- Micro: Microscopically, nodular and massive retinal gliosis is characterized by elongated spindle-shaped fibrous astrocytes with filamentous eosinophilic cytoplasm, positive for GFAP and S100.
- Ancillary: Immunohistochemistry shows positivity for GFAP and S100, and there are no clinically relevant molecular findings.
Reference Gallery:
Massive retinal gliosis. Macroscopic view of a mass filling the vitreous cavity
Massive retinal gliosis. Microscopic examination shows a proliferation of glial cells.
Nodular retinal gliosis. Macroscopic view of a discrete yellow-white retinal mass with scattered vessels.
Nodular retinal gliosis. The lesion is composed of spindle-shaped fibrous astrocytes with filamentous cytoplasm and hyalinized vessels.

Q: Microscopically, Retinocytoma is characterized by a uniform population of bland cells showing photoreceptor differentiation that form bouquet-like aggregates known as [...].
Retinocytoma. The retinal tumour is composed largely of cells showing photoreceptor differentiation. Foci of calcification are present within viable part of tumour.
Retinocytoma. Photoreceptor differentiation (fleurettes). Inner segments of neoplastic photoreceptors form bouquet-like aggregates called fleurettes. Cells have bland round nuclei and mitoses and apoptosis are not present.
A: fleurettes
Back Extra: Retinocytoma
- Clinical: Retinocytomas are often asymptomatic but can present with blurred vision and strabismus. They can be found in the same or fellow eye with retinoblastoma and in phthisical eyes.
- Micro: Retinocytoma is characterized by a uniform population of bland cells with round or oval nuclei and photoreceptor differentiation, forming fleurettes. Flexner-Wintersteiner rosettes are generally absent.
- Ancillary: Retinocytoma is initiated by biallelic RB1 sequence alterations. High expression of senescence-associated proteins such as p16INK4A and p130 is common.
Reference Gallery:
Retinocytoma. Retinal tumour is composed of translucent cytoplasm. It contains cartilage and is bordered by a zone of atrophic RPE.
Retinocytoma. The retinal tumour is composed largely of cells showing photoreceptor differentiation. Foci of calcification are present within viable part of tumour.
Retinocytoma. Photoreceptor differentiation (fleurettes). Inner segments of neoplastic photoreceptors form bouquet-like aggregates called fleurettes. Cells have bland round nuclei and mitoses and apoptosis are not present.
Malignant transformation of retinocytoma. The base of the lesion is relatively eosinophilic and paucicellular compared to overlying retinoblastoma which is seeding into the vitreous. A portion of the retinocytoma contains fractured foci of calcification. Malignant transformation was observed clinically.

Q: A Retinocytoma can undergo malignant transformation into a [...], which is typically characterized microscopically by a hypercellular, seeding proliferation overlying the more paucicellular, eosinophilic base of the original benign tumor.
Malignant transformation of retinocytoma. The base of the lesion is relatively eosinophilic and paucicellular compared to overlying retinoblastoma which is seeding into the vitreous. A portion of the retinocytoma contains fractured foci of calcification. Malignant transformation was observed clinically.
A: retinoblastoma
Back Extra: Retinocytoma
- Clinical: Retinocytomas are often asymptomatic but can present with blurred vision and strabismus. They can be found in the same or fellow eye with retinoblastoma and in phthisical eyes.
- Micro: Retinocytoma is characterized by a uniform population of bland cells with round or oval nuclei and photoreceptor differentiation, forming fleurettes. Flexner-Wintersteiner rosettes are generally absent.
- Ancillary: Retinocytoma is initiated by biallelic RB1 sequence alterations. High expression of senescence-associated proteins such as p16INK4A and p130 is common.
Reference Gallery:
Retinocytoma. Retinal tumour is composed of translucent cytoplasm. It contains cartilage and is bordered by a zone of atrophic RPE.
Retinocytoma. The retinal tumour is composed largely of cells showing photoreceptor differentiation. Foci of calcification are present within viable part of tumour.
Retinocytoma. Photoreceptor differentiation (fleurettes). Inner segments of neoplastic photoreceptors form bouquet-like aggregates called fleurettes. Cells have bland round nuclei and mitoses and apoptosis are not present.
Malignant transformation of retinocytoma. The base of the lesion is relatively eosinophilic and paucicellular compared to overlying retinoblastoma which is seeding into the vitreous. A portion of the retinocytoma contains fractured foci of calcification. Malignant transformation was observed clinically.

Q: Histopathologically, adenoma and adenocarcinoma of the retinal pigment epithelium are typically characterized by tumor cells arranged in characteristic [...] that rest on PAS-positive septa.
Adenocarcinoma of the RPE. Linear bands of tumour cells rest on PAS-positive septa. The tumour cells have prominent nucleoli (Periodic-Acid Schiff).
Adenoma of the RPE. The cells forming characteristic linear bands and have bland nuclei.
A: linear bands
Back Extra: Adenoma and Adenocarcinoma of the Retinal Pigment Epithelium
- Clinical: Adenoma and Adenocarcinoma of the Retinal Pigment Epithelium (RPE) typically present as darkly pigmented lesions with abrupt margins and may cause blurred vision or retinal detachment.
- Micro: Histopathologically, these tumours are characterized by the presence of linear bands of tumour cells on PAS-positive septa, with nuclear atypia and prominent nucleoli in adenocarcinomas.
- Ancillary: Immunohistochemistry shows variable immunoreactivity for epithelial markers (CK7, AE1/AE3, CAM 5.2, EMA) and melanocytic markers (S100, Melan A, HMB-45) in RPE neoplasms.
Reference Gallery:
Adenocarcinoma of the RPE. Clinical ophthalmoscopy image showing a darkly pigmented tumour with abrupt margins. The tumour has perforated the retina and is surrounded by exudates.
Cystic adenoma of the RPE. This heavily pigmented tumour is located on the inner surface of the choroid as a cytologically bland neoplasm containing cyst-like spaces.
Adenocarcinoma of the RPE. A heavily pigmented tumour resting on the inner surface of choroid and invading overlying retina.
Adenocarcinoma of the RPE. A largely non-pigmented RPE adenocarcinoma with abrupt margins. The tumour rests on inner surface of choroid and invades overlying retina. This tumour was observed clinically to arise from a CHRPE.
Adenocarcinoma of the RPE. Linear bands of tumour cells rest on PAS-positive septa. The tumour cells have prominent nucleoli (Periodic-Acid Schiff).
Adenocarcinoma of the RPE. Nuclei of pleomorphic RPE tumours have prominent nucleoli and peripheral chromatin margination.
Adenoma of the RPE. The cells forming characteristic linear bands and have bland nuclei.
Adenoma of the RPE. A mass lies below the retina in this clinical image.

Q: On clinical ophthalmoscopy, adenoma and adenocarcinoma of the retinal pigment epithelium frequently present as darkly pigmented intraocular lesions that are distinguished by their highly characteristic [...].
Adenocarcinoma of the RPE. Clinical ophthalmoscopy image showing a darkly pigmented tumour with abrupt margins. The tumour has perforated the retina and is surrounded by exudates.
Adenocarcinoma of the RPE. A largely non-pigmented RPE adenocarcinoma with abrupt margins. The tumour rests on inner surface of choroid and invades overlying retina. This tumour was observed clinically to arise from a CHRPE.
A: abrupt margins
Back Extra: Adenoma and Adenocarcinoma of the Retinal Pigment Epithelium
- Clinical: Adenoma and Adenocarcinoma of the Retinal Pigment Epithelium (RPE) typically present as darkly pigmented lesions with abrupt margins and may cause blurred vision or retinal detachment.
- Micro: Histopathologically, these tumours are characterized by the presence of linear bands of tumour cells on PAS-positive septa, with nuclear atypia and prominent nucleoli in adenocarcinomas.
- Ancillary: Immunohistochemistry shows variable immunoreactivity for epithelial markers (CK7, AE1/AE3, CAM 5.2, EMA) and melanocytic markers (S100, Melan A, HMB-45) in RPE neoplasms.
Reference Gallery:
Adenocarcinoma of the RPE. Clinical ophthalmoscopy image showing a darkly pigmented tumour with abrupt margins. The tumour has perforated the retina and is surrounded by exudates.
Cystic adenoma of the RPE. This heavily pigmented tumour is located on the inner surface of the choroid as a cytologically bland neoplasm containing cyst-like spaces.
Adenocarcinoma of the RPE. A heavily pigmented tumour resting on the inner surface of choroid and invading overlying retina.
Adenocarcinoma of the RPE. A largely non-pigmented RPE adenocarcinoma with abrupt margins. The tumour rests on inner surface of choroid and invades overlying retina. This tumour was observed clinically to arise from a CHRPE.
Adenocarcinoma of the RPE. Linear bands of tumour cells rest on PAS-positive septa. The tumour cells have prominent nucleoli (Periodic-Acid Schiff).
Adenocarcinoma of the RPE. Nuclei of pleomorphic RPE tumours have prominent nucleoli and peripheral chromatin margination.
Adenoma of the RPE. The cells forming characteristic linear bands and have bland nuclei.
Adenoma of the RPE. A mass lies below the retina in this clinical image.

Q: On ophthalmoscopy, Congenital Hypertrophy of the Retinal Pigment Epithelium typically appears as a sharply demarcated, deeply pigmented flat plaque, which may develop multiple depigmented [...].
Congenital hypertrophy of the retinal pigment epithelium. Ophthalmoscopy discloses a round, deeply pigmented lesion with no lacunae.
Congenital hypertrophy of the retinal pigment epithelium. A larger lesion has smooth, scalloped margins and multiple depigmented lacunae.
A: lacunae
Back Extra: Congenital Hypertrophy of the Retinal Pigment Epithelium
- Clinical: Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) is typically unilateral, sharply demarcated, and appears as a dark, flat or minimally elevated plaque.
- Micro: Histologically, CHRPE shows a monolayer of thickened RPE cells with large, round melanosomes that often obscure the nucleus.
- Ancillary: Optical coherence tomography (OCT) reveals thinning and photoreceptor loss in the overlying retina of CHRPE lesions.
Reference Gallery:
Congenital hypertrophy of the retinal pigment epithelium. Ophthalmoscopy discloses a round, deeply pigmented lesion with no lacunae.
Congenital hypertrophy of the retinal pigment epithelium. A larger lesion has smooth, scalloped margins and multiple depigmented lacunae.
Congenital hypertrophy of the retinal pigment epithelium. The cytoplasm of tall retinal pigment epithelial cells is packed with large round melanosomes (including macromelanosomes).

Q: Histologically, the affected monolayer of cells in Congenital Hypertrophy of the Retinal Pigment Epithelium is packed with large, round pigment granules known as [...].
Congenital hypertrophy of the retinal pigment epithelium. The cytoplasm of tall retinal pigment epithelial cells is packed with large round melanosomes (including macromelanosomes).
A: macromelanosomes
Back Extra: Congenital Hypertrophy of the Retinal Pigment Epithelium
- Clinical: Congenital Hypertrophy of the Retinal Pigment Epithelium (CHRPE) is typically unilateral, sharply demarcated, and appears as a dark, flat or minimally elevated plaque.
- Micro: Histologically, CHRPE shows a monolayer of thickened RPE cells with large, round melanosomes that often obscure the nucleus.
- Ancillary: Optical coherence tomography (OCT) reveals thinning and photoreceptor loss in the overlying retina of CHRPE lesions.
Reference Gallery:
Congenital hypertrophy of the retinal pigment epithelium. Ophthalmoscopy discloses a round, deeply pigmented lesion with no lacunae.
Congenital hypertrophy of the retinal pigment epithelium. A larger lesion has smooth, scalloped margins and multiple depigmented lacunae.
Congenital hypertrophy of the retinal pigment epithelium. The cytoplasm of tall retinal pigment epithelial cells is packed with large round melanosomes (including macromelanosomes).

Q: In the combined variant of Hamartoma of the retinal pigment epithelium, the epiretinal glial component typically exerts prominent [...] on the retinal blood vessels, leading to folds and progressive visual loss.
Combined hamartoma of the retina and RPE. The epiretinal glial component of this gray subfoveal combined hamartoma exerts vitreoretinal traction on retinal vessels.
Combined hamartoma of retina and RPE. OCT of this combined hamartoma discloses focal area of thickened disorganized retina with an epiretinal membrane and retinal folds.
A: vitreoretinal traction
Back Extra: Hamartoma of the retinal pigment epithelium
- Clinical: Combined hamartoma of the retina and RPE (CHR-RPE) can appear as an ill-defined gray retinal mass with tortuous or straightened blood vessels, often causing retinal traction and progressive visual loss.
- Micro: Simple hamartomas of the RPE show a nodular proliferation of hyperplastic RPE with fibrous metaplasia, while combined hamartomas have disorganized glial tissue and numerous blood vessels.
- Ancillary: Fluorescein angiography of hamartoma of the retinal pigment epithelium shows early hypofluorescent areas due to hyperpigmentation, followed by abnormal dilated capillaries and leakage in later phases.
Reference Gallery:
Congenital simple RPE hamartoma. This discrete heavily pigmented simple RPE hamartoma is located near the fovea.
Congenital simple RPE hamartoma. OCT of this simple RPE hamartoma shows discrete full-thickness lesion with surface hyperreflectivity and deep optical shadowing.
Combined hamartoma of the retina and RPE. The epiretinal glial component of this gray subfoveal combined hamartoma exerts vitreoretinal traction on retinal vessels.
Combined hamartoma of retina and RPE. OCT of this combined hamartoma discloses focal area of thickened disorganized retina with an epiretinal membrane and retinal folds.

Q: Optical coherence tomography (OCT) of a simple Hamartoma of the retinal pigment epithelium characteristically demonstrates a discrete, heavily pigmented full-thickness lesion with surface hyperreflectivity and deep [...].
Congenital simple RPE hamartoma. This discrete heavily pigmented simple RPE hamartoma is located near the fovea.
Congenital simple RPE hamartoma. OCT of this simple RPE hamartoma shows discrete full-thickness lesion with surface hyperreflectivity and deep optical shadowing.
A: optical shadowing
Back Extra: Hamartoma of the retinal pigment epithelium
- Clinical: Combined hamartoma of the retina and RPE (CHR-RPE) can appear as an ill-defined gray retinal mass with tortuous or straightened blood vessels, often causing retinal traction and progressive visual loss.
- Micro: Simple hamartomas of the RPE show a nodular proliferation of hyperplastic RPE with fibrous metaplasia, while combined hamartomas have disorganized glial tissue and numerous blood vessels.
- Ancillary: Fluorescein angiography of hamartoma of the retinal pigment epithelium shows early hypofluorescent areas due to hyperpigmentation, followed by abnormal dilated capillaries and leakage in later phases.
Reference Gallery:
Congenital simple RPE hamartoma. This discrete heavily pigmented simple RPE hamartoma is located near the fovea.
Congenital simple RPE hamartoma. OCT of this simple RPE hamartoma shows discrete full-thickness lesion with surface hyperreflectivity and deep optical shadowing.
Combined hamartoma of the retina and RPE. The epiretinal glial component of this gray subfoveal combined hamartoma exerts vitreoretinal traction on retinal vessels.
Combined hamartoma of retina and RPE. OCT of this combined hamartoma discloses focal area of thickened disorganized retina with an epiretinal membrane and retinal folds.

Q: Microscopically, Reactive Hyperplasia of the Retinal Pigment Epithelium is characterized by layers of proliferating pigmented cells that alternate with extracellular [...] material.
Reactive hyperplasia of the retinal pigment epithelium. Layers of proliferating pigmented retinal pigment epithelial cells over the choroid (lower field) alternate with extracellular basement membrane material.
A: basement membrane
Back Extra: Reactive Hyperplasia of the Retinal Pigment Epithelium
- Clinical: Reactive hyperplasia of the retinal pigment epithelium (RPE) is classified as localized, multifocal, or diffuse, and presents as darkly pigmented deposits.
- Micro: Reactive RPE hyperplasia can range from simple duplication of cells to massive proliferations with intervening basement membrane material.
- Ancillary: On fluorescein angiography, reactive RPE hyperplasia shows early hypofluorescence, with areas of hyperfluorescence in the late phase.
Reference Gallery:
Reactive hyperplasia of the retinal pigment epithelium. Layers of proliferating pigmented retinal pigment epithelial cells over the choroid (lower field) alternate with extracellular basement membrane material.
Reactive hyperplasia of the peripheral retinal pigment epithelium. The Ringschwiele, shows lymphocytic infiltration close by, possible source of growth factors.
Reactive hyperplasia of the retinal pigment epithelium. A darkly pigmented nodule is present in the retina.

Q: Peripheral cases of Reactive Hyperplasia of the Retinal Pigment Epithelium can present with a proliferation known as a [...], which is frequently accompanied by a localized lymphocytic infiltration.
Reactive hyperplasia of the peripheral retinal pigment epithelium. The Ringschwiele, shows lymphocytic infiltration close by, possible source of growth factors.
A: Ringschwiele
Back Extra: Reactive Hyperplasia of the Retinal Pigment Epithelium
- Clinical: Reactive hyperplasia of the retinal pigment epithelium (RPE) is classified as localized, multifocal, or diffuse, and presents as darkly pigmented deposits.
- Micro: Reactive RPE hyperplasia can range from simple duplication of cells to massive proliferations with intervening basement membrane material.
- Ancillary: On fluorescein angiography, reactive RPE hyperplasia shows early hypofluorescence, with areas of hyperfluorescence in the late phase.
Reference Gallery:
Reactive hyperplasia of the retinal pigment epithelium. Layers of proliferating pigmented retinal pigment epithelial cells over the choroid (lower field) alternate with extracellular basement membrane material.
Reactive hyperplasia of the peripheral retinal pigment epithelium. The Ringschwiele, shows lymphocytic infiltration close by, possible source of growth factors.
Reactive hyperplasia of the retinal pigment epithelium. A darkly pigmented nodule is present in the retina.

Q: Clinically, Reactive Hyperplasia of the Retinal Pigment Epithelium typically presents as localized, multifocal, or diffuse nodules that are characteristically [...].
Reactive hyperplasia of the retinal pigment epithelium. A darkly pigmented nodule is present in the retina.
A: darkly pigmented
Back Extra: Reactive Hyperplasia of the Retinal Pigment Epithelium
- Clinical: Reactive hyperplasia of the retinal pigment epithelium (RPE) is classified as localized, multifocal, or diffuse, and presents as darkly pigmented deposits.
- Micro: Reactive RPE hyperplasia can range from simple duplication of cells to massive proliferations with intervening basement membrane material.
- Ancillary: On fluorescein angiography, reactive RPE hyperplasia shows early hypofluorescence, with areas of hyperfluorescence in the late phase.
Reference Gallery:
Reactive hyperplasia of the retinal pigment epithelium. Layers of proliferating pigmented retinal pigment epithelial cells over the choroid (lower field) alternate with extracellular basement membrane material.
Reactive hyperplasia of the peripheral retinal pigment epithelium. The Ringschwiele, shows lymphocytic infiltration close by, possible source of growth factors.
Reactive hyperplasia of the retinal pigment epithelium. A darkly pigmented nodule is present in the retina.

Q: The spindle cell/pleomorphic variant of Benign Lipomatous Tumours is characterized by a histologic triad of mature adipocytes, bland spindle cells, and [...].
Spindle cell/pleomorphic lipoma of the orbit. The tumour is composed of a triad of mature adipocytes, bland spindle cells, and rope-like collagen fibrils.
A: rope-like collagen fibrils
Back Extra: Benign Lipomatous Tumours
- Clinical: Benign lipomatous tumours are often asymptomatic but can cause proptosis, globe displacement, or diplopia if they grow large enough.
- Micro: Spindle cell/pleomorphic lipoma (SCL/PL) is characterized by a triad of mature adipocytes, bland spindle cells, and rope-like collagen fibrils, with possible multinucleated cells.
- Ancillary: Lesional adipocytes in benign lipomatous tumours are positive for HMGA2, and SCL/PL spindle cells express CD34 with loss of nuclear RB1 protein.
Reference Gallery:
Spindle cell/pleomorphic lipoma of the orbit. Mature adipocytes within a spindle cell tumour are seen.
Spindle cell/pleomorphic lipoma of the orbit. The tumour is composed of a triad of mature adipocytes, bland spindle cells, and rope-like collagen fibrils.
Spindle cell/pleomorphic lipoma of the orbit. This tumour stains strongly for CD34.
Spindle cell/pleomorphic lipoma of the orbit. The lesion contains a proliferation of spindle shaped cells with bland nuclei.
Spindle cell/pleomorphic lipoma of the orbit. The lesion may contain multinucleated cells.

Q: In the spindle cell/pleomorphic variant of Benign Lipomatous Tumours, the bland spindle cells characteristically demonstrate strong immunohistochemical expression of [...] alongside the loss of nuclear RB1 protein.
Spindle cell/pleomorphic lipoma of the orbit. This tumour stains strongly for CD34.
Spindle cell/pleomorphic lipoma of the orbit. The lesion contains a proliferation of spindle shaped cells with bland nuclei.
A: CD34
Back Extra: Benign Lipomatous Tumours
- Clinical: Benign lipomatous tumours are often asymptomatic but can cause proptosis, globe displacement, or diplopia if they grow large enough.
- Micro: Spindle cell/pleomorphic lipoma (SCL/PL) is characterized by a triad of mature adipocytes, bland spindle cells, and rope-like collagen fibrils, with possible multinucleated cells.
- Ancillary: Lesional adipocytes in benign lipomatous tumours are positive for HMGA2, and SCL/PL spindle cells express CD34 with loss of nuclear RB1 protein.
Reference Gallery:
Spindle cell/pleomorphic lipoma of the orbit. Mature adipocytes within a spindle cell tumour are seen.
Spindle cell/pleomorphic lipoma of the orbit. The tumour is composed of a triad of mature adipocytes, bland spindle cells, and rope-like collagen fibrils.
Spindle cell/pleomorphic lipoma of the orbit. This tumour stains strongly for CD34.
Spindle cell/pleomorphic lipoma of the orbit. The lesion contains a proliferation of spindle shaped cells with bland nuclei.
Spindle cell/pleomorphic lipoma of the orbit. The lesion may contain multinucleated cells.

Q: A key ancillary finding in diagnosing atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDLS) and dedifferentiated subtypes of Malignant Adipocytic Tumors is the amplification of [...], which can be detected by fluorescence in situ hybridization (FISH) or immunohistochemistry.
Atypical lipomatous tumour/well-differentiated liposarcoma, fluorescence in situ hybridization for MDM2 amplification status. The 2 green CEP12 signals are located on the centromere of chromosome 12 and the red MDM2 signals are located on the long arm of the same chromosome. There is amplification of MDM2 relative to CEP12.
A: MDM2 and/or CDK4
Back Extra: Malignant Adipocytic Tumours
- Clinical: Primary orbital liposarcoma is rare, accounting for < 1% of orbital tumours, and typically presents in the 5th to 6th decade with symptoms such as eye displacement, diplopia, and optic nerve compression.
- Micro: Atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLS) can present with sclerosing or inflammatory patterns, characterized by fibrous background and varying adipocyte sizes with atypical nuclei.
- Ancillary: MDM2 and/or CDK4 amplification detected by FISH or IHC is a key feature in diagnosing ALT/WDLS and dedifferentiated liposarcoma (DDLPS).
Reference Gallery:
Sclerosing pattern of atypical lipomatous tumour/well-differentiated liposarcoma. Fibrous background with adipocytes of varying sizes. Within the fibrous tissue there are scattered cells with atypical nuclei.
Inflammatory pattern of atypical lipomatous tumour/well-differentiated liposarcoma. Fibrous background with adipocytes of varying sizes. Inflammatory infiltrate partially obscures atypical cells within the fibrous tissue.
Atypical lipomatous tumour/well-differentiated liposarcoma, fluorescence in situ hybridization for MDM2 amplification status. The 2 green CEP12 signals are located on the centromere of chromosome 12 and the red MDM2 signals are located on the long arm of the same chromosome. There is amplification of MDM2 relative to CEP12.
Dedifferentiated liposarcoma. A high grade spindle cell sarcoma has arisen within an atypical lipomatous tumour/well differentiated liposarcoma.
Pleomorphic liposarcoma. There is a background of pleomorphic sarcoma with scattered pleomorphic lipoblasts.
Atypical lipomatous tumour/well-differentiated liposarcoma. Coronal MRI demonstrates a heterogeneous mass in the left orbit.
Atypical lipomatous tumour/well differentiated liposarcoma of the orbit. MRI shows right anterior medial orbital mass.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.

Q: In Malignant Adipocytic Tumors, the [...] subtype frequently presents with either a sclerosing or inflammatory histologic pattern, characterized by a fibrous background containing varying adipocyte sizes and scattered atypical nuclei.
Sclerosing pattern of atypical lipomatous tumour/well-differentiated liposarcoma. Fibrous background with adipocytes of varying sizes. Within the fibrous tissue there are scattered cells with atypical nuclei.
Inflammatory pattern of atypical lipomatous tumour/well-differentiated liposarcoma. Fibrous background with adipocytes of varying sizes. Inflammatory infiltrate partially obscures atypical cells within the fibrous tissue.
A: atypical lipomatous tumor/well-differentiated liposarcoma
Back Extra: Malignant Adipocytic Tumours
- Clinical: Primary orbital liposarcoma is rare, accounting for < 1% of orbital tumours, and typically presents in the 5th to 6th decade with symptoms such as eye displacement, diplopia, and optic nerve compression.
- Micro: Atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLS) can present with sclerosing or inflammatory patterns, characterized by fibrous background and varying adipocyte sizes with atypical nuclei.
- Ancillary: MDM2 and/or CDK4 amplification detected by FISH or IHC is a key feature in diagnosing ALT/WDLS and dedifferentiated liposarcoma (DDLPS).
Reference Gallery:
Sclerosing pattern of atypical lipomatous tumour/well-differentiated liposarcoma. Fibrous background with adipocytes of varying sizes. Within the fibrous tissue there are scattered cells with atypical nuclei.
Inflammatory pattern of atypical lipomatous tumour/well-differentiated liposarcoma. Fibrous background with adipocytes of varying sizes. Inflammatory infiltrate partially obscures atypical cells within the fibrous tissue.
Atypical lipomatous tumour/well-differentiated liposarcoma, fluorescence in situ hybridization for MDM2 amplification status. The 2 green CEP12 signals are located on the centromere of chromosome 12 and the red MDM2 signals are located on the long arm of the same chromosome. There is amplification of MDM2 relative to CEP12.
Dedifferentiated liposarcoma. A high grade spindle cell sarcoma has arisen within an atypical lipomatous tumour/well differentiated liposarcoma.
Pleomorphic liposarcoma. There is a background of pleomorphic sarcoma with scattered pleomorphic lipoblasts.
Atypical lipomatous tumour/well-differentiated liposarcoma. Coronal MRI demonstrates a heterogeneous mass in the left orbit.
Atypical lipomatous tumour/well differentiated liposarcoma of the orbit. MRI shows right anterior medial orbital mass.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.

Q: Primary orbital [...], a rare category of Malignant Adipocytic Tumors (<1% of orbital tumors), typically presents in the 5th to 6th decade as a heterogeneous mass that can cause clinical symptoms such as eye displacement, diplopia, and optic nerve compression.
Atypical lipomatous tumour/well-differentiated liposarcoma. Coronal MRI demonstrates a heterogeneous mass in the left orbit.
Atypical lipomatous tumour/well differentiated liposarcoma of the orbit. MRI shows right anterior medial orbital mass.
A: liposarcoma
Back Extra: Malignant Adipocytic Tumours
- Clinical: Primary orbital liposarcoma is rare, accounting for < 1% of orbital tumours, and typically presents in the 5th to 6th decade with symptoms such as eye displacement, diplopia, and optic nerve compression.
- Micro: Atypical lipomatous tumour/well-differentiated liposarcoma (ALT/WDLS) can present with sclerosing or inflammatory patterns, characterized by fibrous background and varying adipocyte sizes with atypical nuclei.
- Ancillary: MDM2 and/or CDK4 amplification detected by FISH or IHC is a key feature in diagnosing ALT/WDLS and dedifferentiated liposarcoma (DDLPS).
Reference Gallery:
Sclerosing pattern of atypical lipomatous tumour/well-differentiated liposarcoma. Fibrous background with adipocytes of varying sizes. Within the fibrous tissue there are scattered cells with atypical nuclei.
Inflammatory pattern of atypical lipomatous tumour/well-differentiated liposarcoma. Fibrous background with adipocytes of varying sizes. Inflammatory infiltrate partially obscures atypical cells within the fibrous tissue.
Atypical lipomatous tumour/well-differentiated liposarcoma, fluorescence in situ hybridization for MDM2 amplification status. The 2 green CEP12 signals are located on the centromere of chromosome 12 and the red MDM2 signals are located on the long arm of the same chromosome. There is amplification of MDM2 relative to CEP12.
Dedifferentiated liposarcoma. A high grade spindle cell sarcoma has arisen within an atypical lipomatous tumour/well differentiated liposarcoma.
Pleomorphic liposarcoma. There is a background of pleomorphic sarcoma with scattered pleomorphic lipoblasts.
Atypical lipomatous tumour/well-differentiated liposarcoma. Coronal MRI demonstrates a heterogeneous mass in the left orbit.
Atypical lipomatous tumour/well differentiated liposarcoma of the orbit. MRI shows right anterior medial orbital mass.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.
Atypical lipomatous tumour/well differentiated liposarcoma involving orbit. This lesion was initially interpreted as spindle cell lipoma, recurred a decade later, and showed MDM2 and CDK4 amplification by FISH in both original and recurrent tumour.

Q: Histologically, a superficial Angiomyxoma is a poorly circumscribed tumor composed of spindle to stellate-shaped cells in a myxoid stroma with prominent [...].
Superficial angiomyxoma. The tumour is composed of spindle to stellate shaped cells in a myxoid background with thin walled capillaries.
A: thin-walled capillaries
Back Extra: Angiomyxoma
- Clinical: Angiomyxomas present as multinodular, polypoid, or pedunculated slow-growing dermal/subcutaneous masses involving the eyelid margin, or as well-circumscribed, fleshy masses in the conjunctiva.
- Micro: Superficial angiomyxomas are poorly circumscribed, with spindle to stellate-shaped cells in a myxoid stroma and thin-walled vessels. Deep angiomyxomas have increased cellularity and thick-walled vessels with perivascular hyalinization.
- Ancillary: Tumour cells express vimentin and CD34, and are negative for S100, desmin, smooth muscle actin, and cytokeratins. PRKAR1A expression is lost in Carney complex-associated lesions.
Reference Gallery:
Angiomyxoma. Inferior displacement of the globe in a young boy.
Superficial angiomyxoma. The tumour is composed of spindle to stellate shaped cells in a myxoid background with thin walled capillaries.
Deep angiomyxoma. An example of a deep angiomyxoma showing thick walled blood vessels.
Angiomyxoma. Alcian blue PAS staining of the lesion demonstrates abundant myxoid material.

Q: Compared to the superficial variant, a deep Angiomyxoma displays increased cellularity and characteristic [...] with perivascular hyalinization.
Deep angiomyxoma. An example of a deep angiomyxoma showing thick walled blood vessels.
A: thick-walled blood vessels
Back Extra: Angiomyxoma
- Clinical: Angiomyxomas present as multinodular, polypoid, or pedunculated slow-growing dermal/subcutaneous masses involving the eyelid margin, or as well-circumscribed, fleshy masses in the conjunctiva.
- Micro: Superficial angiomyxomas are poorly circumscribed, with spindle to stellate-shaped cells in a myxoid stroma and thin-walled vessels. Deep angiomyxomas have increased cellularity and thick-walled vessels with perivascular hyalinization.
- Ancillary: Tumour cells express vimentin and CD34, and are negative for S100, desmin, smooth muscle actin, and cytokeratins. PRKAR1A expression is lost in Carney complex-associated lesions.
Reference Gallery:
Angiomyxoma. Inferior displacement of the globe in a young boy.
Superficial angiomyxoma. The tumour is composed of spindle to stellate shaped cells in a myxoid background with thin walled capillaries.
Deep angiomyxoma. An example of a deep angiomyxoma showing thick walled blood vessels.
Angiomyxoma. Alcian blue PAS staining of the lesion demonstrates abundant myxoid material.

Q: The abundant myxoid stroma characteristic of an Angiomyxoma can be highlighted using an [...] stain.
Angiomyxoma. Alcian blue PAS staining of the lesion demonstrates abundant myxoid material.
A: Alcian blue PAS
Back Extra: Angiomyxoma
- Clinical: Angiomyxomas present as multinodular, polypoid, or pedunculated slow-growing dermal/subcutaneous masses involving the eyelid margin, or as well-circumscribed, fleshy masses in the conjunctiva.
- Micro: Superficial angiomyxomas are poorly circumscribed, with spindle to stellate-shaped cells in a myxoid stroma and thin-walled vessels. Deep angiomyxomas have increased cellularity and thick-walled vessels with perivascular hyalinization.
- Ancillary: Tumour cells express vimentin and CD34, and are negative for S100, desmin, smooth muscle actin, and cytokeratins. PRKAR1A expression is lost in Carney complex-associated lesions.
Reference Gallery:
Angiomyxoma. Inferior displacement of the globe in a young boy.
Superficial angiomyxoma. The tumour is composed of spindle to stellate shaped cells in a myxoid background with thin walled capillaries.
Deep angiomyxoma. An example of a deep angiomyxoma showing thick walled blood vessels.
Angiomyxoma. Alcian blue PAS staining of the lesion demonstrates abundant myxoid material.

Q: Microscopically, the two variants of Conjunctival Stromal Tumour and Ocular Surface Fibroma are distinct: the former features a myxoid matrix with characteristic [...], whereas the latter displays a dense, collagen-rich stroma.
Ocular surface fibroma. A collagen-rich lesion in the conjunctival substantia propria is observed.
Conjunctival stromal tumour (COST). A loose myxoid matrix, wiry collagen and cells with nuclear pseudoinclusions.
A: nuclear pseudoinclusions
Back Extra: Conjunctival Stromal Tumour and Ocular Surface Fibroma
- Clinical: Patients with Conjunctival Stromal Tumour (COST) and Ocular Surface Fibroma (OSF) often report a foreign body sensation and mild ocular injection.
- Micro: COST is characterized by a variably myxoid stroma with spindle-shaped cells and pseudonuclear inclusions, while OSF has a collagen-rich stroma with bland spindle cells.
- Ancillary: Both COST and OSF show positive staining for CD34 and Factor XIIIa.
Reference Gallery:
Ocular surface fibroma. A collagen-rich lesion in the conjunctival substantia propria is observed.
Ocular surface fibroma. Non-atypical spindle and stellate cells, with inconspicuous nucleoli and delicate basophilic cytoplasm, embedded in the collagen-rich stroma are seen.
Ocular surface fibroma. Ovoid, rounded cells in the collagen-rich stroma.
Ocular surface fibroma. The spindle and oval cells are positive for CD34.
Ocular surface fibroma. Fewer scattered stromal cells are positive for Factor13a.
Ocular surface fibroma. Toluidine Blue stain showing scattered mast cells.
Ocular surface fibroma. External photograph of the left eye showing a circumscribed, pink, translucent temporal bulbar mass beneath conjunctival epithelium.
Conjunctival stromal tumour (COST). A loose myxoid matrix, wiry collagen and cells with nuclear pseudoinclusions.

Q: Immunohistochemical staining of Conjunctival Stromal Tumour and Ocular Surface Fibroma typically demonstrates positive expression for Factor XIIIa and [...].
Ocular surface fibroma. The spindle and oval cells are positive for CD34.
Ocular surface fibroma. Fewer scattered stromal cells are positive for Factor13a.
A: CD34
Back Extra: Conjunctival Stromal Tumour and Ocular Surface Fibroma
- Clinical: Patients with Conjunctival Stromal Tumour (COST) and Ocular Surface Fibroma (OSF) often report a foreign body sensation and mild ocular injection.
- Micro: COST is characterized by a variably myxoid stroma with spindle-shaped cells and pseudonuclear inclusions, while OSF has a collagen-rich stroma with bland spindle cells.
- Ancillary: Both COST and OSF show positive staining for CD34 and Factor XIIIa.
Reference Gallery:
Ocular surface fibroma. A collagen-rich lesion in the conjunctival substantia propria is observed.
Ocular surface fibroma. Non-atypical spindle and stellate cells, with inconspicuous nucleoli and delicate basophilic cytoplasm, embedded in the collagen-rich stroma are seen.
Ocular surface fibroma. Ovoid, rounded cells in the collagen-rich stroma.
Ocular surface fibroma. The spindle and oval cells are positive for CD34.
Ocular surface fibroma. Fewer scattered stromal cells are positive for Factor13a.
Ocular surface fibroma. Toluidine Blue stain showing scattered mast cells.
Ocular surface fibroma. External photograph of the left eye showing a circumscribed, pink, translucent temporal bulbar mass beneath conjunctival epithelium.
Conjunctival stromal tumour (COST). A loose myxoid matrix, wiry collagen and cells with nuclear pseudoinclusions.

Q: A painless, yellowish, dome-shaped nodular tumor on the limbal conjunctiva or upper eyelid is a characteristic clinical presentation of [...].
Fibrous histiocytoma of the limbal conjunctiva. A nodular yellowish tumour.
A: Fibrous Histiocytoma
Back Extra: Fibrous Histiocytoma
- Clinical: Fibrous histiocytoma typically presents as a painless, nodular lesion on the upper eyelid or a yellowish, dome-shaped mass in the conjunctiva.
- Micro: Histologically, it is characterized by a polymorphous population of spindled to rounded cells with collagen bundles and characteristic 'collagen balls'.
- Ancillary: Immunohistochemistry shows CD68 and CD163 positivity in histiocytes, and Factor XIIIa positivity in reactive dendrocytes.
Reference Gallery:
Fibrous histiocytoma of the limbal conjunctiva. A nodular yellowish tumour.
Fibrous histiocytoma of the limbal conjunctiva. Expansion of the stroma is seen.
Fibrous histiocytoma of the limbal conjunctiva. The stroma is expanded by plump spindle cells.
Fibrous histiocytoma of the limbal conjunctiva. Reactive dendrocytes are positive for factor XIII.
Fibrous histiocytoma involving eyelid. A fibrocollagenous lesion in the dermis without epidermal hyperplasia is observed.
Fibrous histiocytoma involving eyelid. The tumour comprises bland spindle, ovoid, and triangular fibroblast-like cells between coarse collagen.
Fibroma histiocytoma involving eyelid. Factor XIIIa positive reactive dendrocytes are seen within the tumour.

Q: Microscopically, a conjunctival or eyelid tumor comprising a polymorphous population of bland spindled, ovoid, and triangular fibroblast-like cells interspersed between thick, coarse bundles of collagen is characteristic of [...].
Fibrous histiocytoma of the limbal conjunctiva. The stroma is expanded by plump spindle cells.
Fibrous histiocytoma involving eyelid. The tumour comprises bland spindle, ovoid, and triangular fibroblast-like cells between coarse collagen.
A: Fibrous Histiocytoma
Back Extra: Fibrous Histiocytoma
- Clinical: Fibrous histiocytoma typically presents as a painless, nodular lesion on the upper eyelid or a yellowish, dome-shaped mass in the conjunctiva.
- Micro: Histologically, it is characterized by a polymorphous population of spindled to rounded cells with collagen bundles and characteristic 'collagen balls'.
- Ancillary: Immunohistochemistry shows CD68 and CD163 positivity in histiocytes, and Factor XIIIa positivity in reactive dendrocytes.
Reference Gallery:
Fibrous histiocytoma of the limbal conjunctiva. A nodular yellowish tumour.
Fibrous histiocytoma of the limbal conjunctiva. Expansion of the stroma is seen.
Fibrous histiocytoma of the limbal conjunctiva. The stroma is expanded by plump spindle cells.
Fibrous histiocytoma of the limbal conjunctiva. Reactive dendrocytes are positive for factor XIII.
Fibrous histiocytoma involving eyelid. A fibrocollagenous lesion in the dermis without epidermal hyperplasia is observed.
Fibrous histiocytoma involving eyelid. The tumour comprises bland spindle, ovoid, and triangular fibroblast-like cells between coarse collagen.
Fibroma histiocytoma involving eyelid. Factor XIIIa positive reactive dendrocytes are seen within the tumour.

Q: In Fibrous Histiocytoma, immunohistochemistry typically reveals scattered interspersed reactive dendrocytes that are strongly positive for [...].
Fibrous histiocytoma of the limbal conjunctiva. Reactive dendrocytes are positive for factor XIII.
Fibroma histiocytoma involving eyelid. Factor XIIIa positive reactive dendrocytes are seen within the tumour.
A: Factor XIIIa
Back Extra: Fibrous Histiocytoma
- Clinical: Fibrous histiocytoma typically presents as a painless, nodular lesion on the upper eyelid or a yellowish, dome-shaped mass in the conjunctiva.
- Micro: Histologically, it is characterized by a polymorphous population of spindled to rounded cells with collagen bundles and characteristic 'collagen balls'.
- Ancillary: Immunohistochemistry shows CD68 and CD163 positivity in histiocytes, and Factor XIIIa positivity in reactive dendrocytes.
Reference Gallery:
Fibrous histiocytoma of the limbal conjunctiva. A nodular yellowish tumour.
Fibrous histiocytoma of the limbal conjunctiva. Expansion of the stroma is seen.
Fibrous histiocytoma of the limbal conjunctiva. The stroma is expanded by plump spindle cells.
Fibrous histiocytoma of the limbal conjunctiva. Reactive dendrocytes are positive for factor XIII.
Fibrous histiocytoma involving eyelid. A fibrocollagenous lesion in the dermis without epidermal hyperplasia is observed.
Fibrous histiocytoma involving eyelid. The tumour comprises bland spindle, ovoid, and triangular fibroblast-like cells between coarse collagen.
Fibroma histiocytoma involving eyelid. Factor XIIIa positive reactive dendrocytes are seen within the tumour.

Q: Histologically, Inflammatory Myofibroblastic Tumor features a proliferation of spindle cells in a collagenous to fibromyxoid stroma, characteristically admixed with an inflammatory infiltrate rich in lymphocytes and [...].
Inflammatory myofibroblastic tumour. Spindle tumour cells proliferate in a background of collagenous and myxoid stroma.
Inflammatory myofibroblastic tumour. Spindle tumour cells are admixed with lymphocytes and plasma cells.
A: plasma cells
Back Extra: Inflammatory Myofibroblastic Tumour
- Clinical: Symptoms of orbital IMT include proptosis, ptosis, diplopia, visual loss, swelling, and pain.
- Micro: Histologically, IMT shows a mix of spindle cells, lymphocytes, and plasma cells in a fibromyxoid stroma.
- Ancillary: Most IMTs in patients under 40 years express ALK, correlating with ALK gene rearrangements.
Reference Gallery:
Inflammatory myofibroblastic tumour. Gd-enhanced T1-weighted MR image.
Inflammatory myofibroblastic tumour. Spindle tumour cells proliferate in a background of collagenous and myxoid stroma.
Inflammatory myofibroblastic tumour. Spindle tumour cells are admixed with lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour. ALK immunohistochemistry. Spindle tumour cells show diffuse cytoplasmic positivity.

Q: A substantial subset of cases of Inflammatory Myofibroblastic Tumor, particularly in patients under 40 years of age, demonstrates diffuse cytoplasmic positivity for [...] by immunohistochemistry due to underlying gene rearrangements.
Inflammatory myofibroblastic tumour. ALK immunohistochemistry. Spindle tumour cells show diffuse cytoplasmic positivity.
A: ALK
Back Extra: Inflammatory Myofibroblastic Tumour
- Clinical: Symptoms of orbital IMT include proptosis, ptosis, diplopia, visual loss, swelling, and pain.
- Micro: Histologically, IMT shows a mix of spindle cells, lymphocytes, and plasma cells in a fibromyxoid stroma.
- Ancillary: Most IMTs in patients under 40 years express ALK, correlating with ALK gene rearrangements.
Reference Gallery:
Inflammatory myofibroblastic tumour. Gd-enhanced T1-weighted MR image.
Inflammatory myofibroblastic tumour. Spindle tumour cells proliferate in a background of collagenous and myxoid stroma.
Inflammatory myofibroblastic tumour. Spindle tumour cells are admixed with lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour. ALK immunohistochemistry. Spindle tumour cells show diffuse cytoplasmic positivity.

Q: A patient presenting with orbital pain, proptosis, diplopia, and a gadolinium-enhancing mass on T1-weighted MRI (as seen in the image) should be evaluated for an orbital presentation of [...].
Inflammatory myofibroblastic tumour. Gd-enhanced T1-weighted MR image.
A: Inflammatory Myofibroblastic Tumor
Back Extra: Inflammatory Myofibroblastic Tumour
- Clinical: Symptoms of orbital IMT include proptosis, ptosis, diplopia, visual loss, swelling, and pain.
- Micro: Histologically, IMT shows a mix of spindle cells, lymphocytes, and plasma cells in a fibromyxoid stroma.
- Ancillary: Most IMTs in patients under 40 years express ALK, correlating with ALK gene rearrangements.
Reference Gallery:
Inflammatory myofibroblastic tumour. Gd-enhanced T1-weighted MR image.
Inflammatory myofibroblastic tumour. Spindle tumour cells proliferate in a background of collagenous and myxoid stroma.
Inflammatory myofibroblastic tumour. Spindle tumour cells are admixed with lymphocytes and plasma cells.
Inflammatory myofibroblastic tumour. ALK immunohistochemistry. Spindle tumour cells show diffuse cytoplasmic positivity.

Q: In Nodular and Proliferative Fasciitis, histopathology characteristically shows plump spindle and stellate cells with frequent mitoses set in a myxoid stroma with a [...] arrangement.
Nodular fasciitis. Feathery, plump spindled cells with conspicuous mitotic activity in a tissue culture-like arrangement.
Nodular fasciitis. A hypocellular area with myxoid stroma.
Nodular fasciitis. Discohesive spindle cells in a tissue culture-like arrangement and myxoid stroma with extravasated erythrocytes.
A: tissue culture-like
Back Extra: Nodular and Proliferative Fasciitis
- Clinical: Nodular fasciitis of the ocular adnexa is a rapidly growing (over weeks to months) epibulbar, anterior periorbital, or orbital mass that is typically well circumscribed.
- Micro: Characterized by plump spindle and stellate cells in a tissue culture-like arrangement, with frequent mitotic activity and myxoid stroma.
- Ancillary: Immunohistochemistry shows SMA and MSA expression in a 'tram-track' pattern, and USP6 rearrangement can be confirmatory in uncommon sites like the ocular adnexa.
Reference Gallery:
Nodular fasciitis. Feathery, plump spindled cells with conspicuous mitotic activity in a tissue culture-like arrangement.
Nodular fasciitis. A hypocellular area with myxoid stroma.
Nodular fasciitis of the orbit. Axial CT-scan demonstrates a circumscribed mass in the region of left lacrimal sac.
Nodular fasciitis. Discohesive spindle cells in a tissue culture-like arrangement and myxoid stroma with extravasated erythrocytes.
Nodular fasciitis. Spindle cells express SMA in at the periphery of a cytoplasm ('tram-track' pattern), compatible with myofibroblastic proliferation.

Q: Immunohistochemistry in Nodular and Proliferative Fasciitis highlights myofibroblastic differentiation, showing SMA expression at the periphery of the cytoplasm in a characteristic [...] pattern.
Nodular fasciitis. Spindle cells express SMA in at the periphery of a cytoplasm ('tram-track' pattern), compatible with myofibroblastic proliferation.
A: 'tram-track'
Back Extra: Nodular and Proliferative Fasciitis
- Clinical: Nodular fasciitis of the ocular adnexa is a rapidly growing (over weeks to months) epibulbar, anterior periorbital, or orbital mass that is typically well circumscribed.
- Micro: Characterized by plump spindle and stellate cells in a tissue culture-like arrangement, with frequent mitotic activity and myxoid stroma.
- Ancillary: Immunohistochemistry shows SMA and MSA expression in a 'tram-track' pattern, and USP6 rearrangement can be confirmatory in uncommon sites like the ocular adnexa.
Reference Gallery:
Nodular fasciitis. Feathery, plump spindled cells with conspicuous mitotic activity in a tissue culture-like arrangement.
Nodular fasciitis. A hypocellular area with myxoid stroma.
Nodular fasciitis of the orbit. Axial CT-scan demonstrates a circumscribed mass in the region of left lacrimal sac.
Nodular fasciitis. Discohesive spindle cells in a tissue culture-like arrangement and myxoid stroma with extravasated erythrocytes.
Nodular fasciitis. Spindle cells express SMA in at the periphery of a cytoplasm ('tram-track' pattern), compatible with myofibroblastic proliferation.

Q: Clinically, Nodular and Proliferative Fasciitis of the ocular adnexa typically presents as a well-circumscribed mass that is characteristically [...] over a period of weeks to months, often clinically mimicking a malignancy.
Nodular fasciitis of the orbit. Axial CT-scan demonstrates a circumscribed mass in the region of left lacrimal sac.
A: rapidly growing
Back Extra: Nodular and Proliferative Fasciitis
- Clinical: Nodular fasciitis of the ocular adnexa is a rapidly growing (over weeks to months) epibulbar, anterior periorbital, or orbital mass that is typically well circumscribed.
- Micro: Characterized by plump spindle and stellate cells in a tissue culture-like arrangement, with frequent mitotic activity and myxoid stroma.
- Ancillary: Immunohistochemistry shows SMA and MSA expression in a 'tram-track' pattern, and USP6 rearrangement can be confirmatory in uncommon sites like the ocular adnexa.
Reference Gallery:
Nodular fasciitis. Feathery, plump spindled cells with conspicuous mitotic activity in a tissue culture-like arrangement.
Nodular fasciitis. A hypocellular area with myxoid stroma.
Nodular fasciitis of the orbit. Axial CT-scan demonstrates a circumscribed mass in the region of left lacrimal sac.
Nodular fasciitis. Discohesive spindle cells in a tissue culture-like arrangement and myxoid stroma with extravasated erythrocytes.
Nodular fasciitis. Spindle cells express SMA in at the periphery of a cytoplasm ('tram-track' pattern), compatible with myofibroblastic proliferation.

Q: Histologically, a solitary fibrous tumor is characterized by a "patternless" arrangement of spindle cells and characteristic branching, [...]-like vascular channels within a collagenous stroma.
Solitary fibrous tumour. Pattern-less arrangement of spindle cells in a collagenous stroma with a branching, staghorn-like vascular channel.
Solitary fibrous tumour. The tumour is comprised of ovoid to spindle cells and elongated thin-walled vascular channels in a variably collagenous stroma, surrounded by a fibrous capsule.
A: staghorn
Back Extra: Solitary Fibrous Tumour
- Clinical: Solitary fibrous tumour commonly presents with periorbital fullness, orbital mass, globe displacement, and limitation of extraocular motility.
- Micro: Histologically, the tumour is characterized by a pattern-less arrangement of spindle cells in a collagenous stroma with a branching, staghorn-like vascular network.
- Ancillary: STAT6 immunohistochemistry is the most sensitive and specific marker for diagnosing solitary fibrous tumour.
Reference Gallery:
Solitary fibrous tumour. The clinical appearance of an anterior orbital solitary fibrous tumour in a patient presenting with right upper lid mass and downward/inward globe displacement.
Solitary fibrous tumour. Computed tomography axial scan showing well-defined contrast-enhancing right orbital soft tissue mass without bone involvement in the same patient.
Solitary fibrous tumour. Pattern-less arrangement of spindle cells in a collagenous stroma with a branching, staghorn-like vascular channel.
Solitary fibrous tumour. Low magnification histopathological appearance of a giant cell-rich solitary fibrous tumour.
Solitary fibrous tumour. Higher magnification appearance of the same giant cell-rich tumour.
Solitary fibrous tumour. Diffuse and strong nuclear expression of STAT6 by the tumour cells.
Solitary fibrous tumour. The tumour is comprised of ovoid to spindle cells and elongated thin-walled vascular channels in a variably collagenous stroma, surrounded by a fibrous capsule.
Solitary fibrous tumour. Axial T1 post-contrast MRI shows an enhancing mass in the superior left orbit (arrow). Punctate and linear hypointense areas in the mass suggest the presence of vessels.
Solitary fibrous tumour. Axial T2 MRI shows a hypointense appearance of the mass (arrow).

Q: The most sensitive and specific immunohistochemical marker for diagnosing a solitary fibrous tumor is [...], which demonstrates diffuse and strong nuclear expression.
Solitary fibrous tumour. Diffuse and strong nuclear expression of STAT6 by the tumour cells.
A: STAT6
Back Extra: Solitary Fibrous Tumour
- Clinical: Solitary fibrous tumour commonly presents with periorbital fullness, orbital mass, globe displacement, and limitation of extraocular motility.
- Micro: Histologically, the tumour is characterized by a pattern-less arrangement of spindle cells in a collagenous stroma with a branching, staghorn-like vascular network.
- Ancillary: STAT6 immunohistochemistry is the most sensitive and specific marker for diagnosing solitary fibrous tumour.
Reference Gallery:
Solitary fibrous tumour. The clinical appearance of an anterior orbital solitary fibrous tumour in a patient presenting with right upper lid mass and downward/inward globe displacement.
Solitary fibrous tumour. Computed tomography axial scan showing well-defined contrast-enhancing right orbital soft tissue mass without bone involvement in the same patient.
Solitary fibrous tumour. Pattern-less arrangement of spindle cells in a collagenous stroma with a branching, staghorn-like vascular channel.
Solitary fibrous tumour. Low magnification histopathological appearance of a giant cell-rich solitary fibrous tumour.
Solitary fibrous tumour. Higher magnification appearance of the same giant cell-rich tumour.
Solitary fibrous tumour. Diffuse and strong nuclear expression of STAT6 by the tumour cells.
Solitary fibrous tumour. The tumour is comprised of ovoid to spindle cells and elongated thin-walled vascular channels in a variably collagenous stroma, surrounded by a fibrous capsule.
Solitary fibrous tumour. Axial T1 post-contrast MRI shows an enhancing mass in the superior left orbit (arrow). Punctate and linear hypointense areas in the mass suggest the presence of vessels.
Solitary fibrous tumour. Axial T2 MRI shows a hypointense appearance of the mass (arrow).

Q: On MRI, a solitary fibrous tumor classically presents as a well-defined enhancing mass that appears characteristically [...] on T2-weighted imaging due to its dense collagenous stroma.
Solitary fibrous tumour. Axial T1 post-contrast MRI shows an enhancing mass in the superior left orbit (arrow). Punctate and linear hypointense areas in the mass suggest the presence of vessels.
Solitary fibrous tumour. Axial T2 MRI shows a hypointense appearance of the mass (arrow).
A: hypointense
Back Extra: Solitary Fibrous Tumour
- Clinical: Solitary fibrous tumour commonly presents with periorbital fullness, orbital mass, globe displacement, and limitation of extraocular motility.
- Micro: Histologically, the tumour is characterized by a pattern-less arrangement of spindle cells in a collagenous stroma with a branching, staghorn-like vascular network.
- Ancillary: STAT6 immunohistochemistry is the most sensitive and specific marker for diagnosing solitary fibrous tumour.
Reference Gallery:
Solitary fibrous tumour. The clinical appearance of an anterior orbital solitary fibrous tumour in a patient presenting with right upper lid mass and downward/inward globe displacement.
Solitary fibrous tumour. Computed tomography axial scan showing well-defined contrast-enhancing right orbital soft tissue mass without bone involvement in the same patient.
Solitary fibrous tumour. Pattern-less arrangement of spindle cells in a collagenous stroma with a branching, staghorn-like vascular channel.
Solitary fibrous tumour. Low magnification histopathological appearance of a giant cell-rich solitary fibrous tumour.
Solitary fibrous tumour. Higher magnification appearance of the same giant cell-rich tumour.
Solitary fibrous tumour. Diffuse and strong nuclear expression of STAT6 by the tumour cells.
Solitary fibrous tumour. The tumour is comprised of ovoid to spindle cells and elongated thin-walled vascular channels in a variably collagenous stroma, surrounded by a fibrous capsule.
Solitary fibrous tumour. Axial T1 post-contrast MRI shows an enhancing mass in the superior left orbit (arrow). Punctate and linear hypointense areas in the mass suggest the presence of vessels.
Solitary fibrous tumour. Axial T2 MRI shows a hypointense appearance of the mass (arrow).

Q: Histologically, a Granular Cell Tumor is composed of sheets and nests of cells characterized by abundant [...] cytoplasm.
Granular cell tumour. An example from the eyelid showing granular eosinophilic cytoplasm.
Granular cell tumour. An example from the eyelid showing granular cytoplasm at high magnification.
A: eosinophilic granular
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours typically present as slow-growing, painless lesions, often causing proptosis, diplopia, and restricted eye movement.
- Micro: These tumours are characterized by sheets, nests, and trabeculae of epithelioid to polygonal cells with abundant eosinophilic granular cytoplasm and PAS-positive/diastase-resistant cytoplasmic granules.
- Ancillary: Immunohistochemistry shows strong and diffuse expression of S100 protein, SOX10, and inhibin, with consistent negativity for HMB45.
Reference Gallery:
Granular cell tumour. An example infiltrating the extraocular muscle.
Granular cell tumour. PAS staining showing diastase resistant positivity in granular cell tumour.
Granular cell tumour. S100 positive staining in granular cell tumour.
Granular cell tumour. A localized tumour on the eyelid margin.
Granular cell tumour. A Masson trichrome showing the cellular detail with small regular nuclei and granular cytoplasm.
Granular cell tumour. An example from the eyelid showing granular eosinophilic cytoplasm.
Granular cell tumour. An example from the eyelid showing granular cytoplasm at high magnification.

Q: The characteristic cytoplasmic granules of a Granular Cell Tumor highlight strongly with a [...] stain and are uniquely resistant to diastase.
Granular cell tumour. PAS staining showing diastase resistant positivity in granular cell tumour.
A: PAS (periodic acid-Schiff)
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours typically present as slow-growing, painless lesions, often causing proptosis, diplopia, and restricted eye movement.
- Micro: These tumours are characterized by sheets, nests, and trabeculae of epithelioid to polygonal cells with abundant eosinophilic granular cytoplasm and PAS-positive/diastase-resistant cytoplasmic granules.
- Ancillary: Immunohistochemistry shows strong and diffuse expression of S100 protein, SOX10, and inhibin, with consistent negativity for HMB45.
Reference Gallery:
Granular cell tumour. An example infiltrating the extraocular muscle.
Granular cell tumour. PAS staining showing diastase resistant positivity in granular cell tumour.
Granular cell tumour. S100 positive staining in granular cell tumour.
Granular cell tumour. A localized tumour on the eyelid margin.
Granular cell tumour. A Masson trichrome showing the cellular detail with small regular nuclei and granular cytoplasm.
Granular cell tumour. An example from the eyelid showing granular eosinophilic cytoplasm.
Granular cell tumour. An example from the eyelid showing granular cytoplasm at high magnification.

Q: On immunohistochemistry, a Granular Cell Tumor typically shows strong and diffuse positivity for SOX10 and [...], reflecting its neural/Schwannian derivation.
Granular cell tumour. S100 positive staining in granular cell tumour.
A: S100
Back Extra: Granular Cell Tumour
- Clinical: Granular cell tumours typically present as slow-growing, painless lesions, often causing proptosis, diplopia, and restricted eye movement.
- Micro: These tumours are characterized by sheets, nests, and trabeculae of epithelioid to polygonal cells with abundant eosinophilic granular cytoplasm and PAS-positive/diastase-resistant cytoplasmic granules.
- Ancillary: Immunohistochemistry shows strong and diffuse expression of S100 protein, SOX10, and inhibin, with consistent negativity for HMB45.
Reference Gallery:
Granular cell tumour. An example infiltrating the extraocular muscle.
Granular cell tumour. PAS staining showing diastase resistant positivity in granular cell tumour.
Granular cell tumour. S100 positive staining in granular cell tumour.
Granular cell tumour. A localized tumour on the eyelid margin.
Granular cell tumour. A Masson trichrome showing the cellular detail with small regular nuclei and granular cytoplasm.
Granular cell tumour. An example from the eyelid showing granular eosinophilic cytoplasm.
Granular cell tumour. An example from the eyelid showing granular cytoplasm at high magnification.

Q: At low magnification, Malignant Peripheral Nerve Sheath Tumor characteristically exhibits a marbled appearance due to alternating hypercellular and [...] areas.
Malignant peripheral nerve sheath tumour. A marbled appearance (alternating pale and dark zones) is common at low magnification.
A: hypocellular
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumours (MPNSTs) typically present between 20-50 years of age, with younger ages for NF1-associated tumours, often causing proptosis and displacement of the globe.
- Micro: MPNSTs show interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas, frequent mitotic figures, and areas of geographical necrosis.
- Ancillary: MPNSTs often show complete loss of staining for H3K27me3, and DNA methylation profiling can help identify the specific tumour signature.
Reference Gallery:
Malignant peripheral nerve sheath tumour. A marbled appearance (alternating pale and dark zones) is common at low magnification.
Malignant peripheral nerve sheath tumor. Spindle cell neoplasm with frequent mitotic figures.
Malignant peripheral nerve sheath tumour. Loss of H3K27me3 expression in tumour nuclei, with retained expression in entrapped non-neoplastic elements.

Q: Histologically, Malignant Peripheral Nerve Sheath Tumor typically presents as interlacing fascicles of spindle-shaped cells featuring frequent [...] and areas of geographical necrosis.
Malignant peripheral nerve sheath tumor. Spindle cell neoplasm with frequent mitotic figures.
A: mitotic figures
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumours (MPNSTs) typically present between 20-50 years of age, with younger ages for NF1-associated tumours, often causing proptosis and displacement of the globe.
- Micro: MPNSTs show interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas, frequent mitotic figures, and areas of geographical necrosis.
- Ancillary: MPNSTs often show complete loss of staining for H3K27me3, and DNA methylation profiling can help identify the specific tumour signature.
Reference Gallery:
Malignant peripheral nerve sheath tumour. A marbled appearance (alternating pale and dark zones) is common at low magnification.
Malignant peripheral nerve sheath tumor. Spindle cell neoplasm with frequent mitotic figures.
Malignant peripheral nerve sheath tumour. Loss of H3K27me3 expression in tumour nuclei, with retained expression in entrapped non-neoplastic elements.

Q: A highly specific immunohistochemical finding in Malignant Peripheral Nerve Sheath Tumor is the complete loss of nuclear staining for [...].
Malignant peripheral nerve sheath tumour. Loss of H3K27me3 expression in tumour nuclei, with retained expression in entrapped non-neoplastic elements.
A: H3K27me3
Back Extra: Malignant Peripheral Nerve Sheath Tumour
- Clinical: Malignant Peripheral Nerve Sheath Tumours (MPNSTs) typically present between 20-50 years of age, with younger ages for NF1-associated tumours, often causing proptosis and displacement of the globe.
- Micro: MPNSTs show interlacing fascicles of spindle-shaped cells with alternating hypercellular and hypocellular areas, frequent mitotic figures, and areas of geographical necrosis.
- Ancillary: MPNSTs often show complete loss of staining for H3K27me3, and DNA methylation profiling can help identify the specific tumour signature.
Reference Gallery:
Malignant peripheral nerve sheath tumour. A marbled appearance (alternating pale and dark zones) is common at low magnification.
Malignant peripheral nerve sheath tumor. Spindle cell neoplasm with frequent mitotic figures.
Malignant peripheral nerve sheath tumour. Loss of H3K27me3 expression in tumour nuclei, with retained expression in entrapped non-neoplastic elements.

Q: Microscopically, Neurofibroma features a haphazard proliferation of [...], fibroblasts, and mast cells set within a mucinous or myxomatous extracellular matrix.
Neurofibroma of the choroid. Diffuse expansion of the choroid by a proliferation of Schwann cells.
A: Schwann cells
Back Extra: Neurofibroma
- Clinical: Orbital neurofibroma can manifest as proptosis and optic nerve compression, and is often associated with neurofibromatosis type 1 (NF1).
- Micro: Neurofibroma is characterized by a haphazard proliferation of Schwann cells, fibroblasts, and mast cells, with a mucinous or myxomatous extracellular matrix.
- Ancillary: Chromosomal copy-number profiling may be helpful for differentiating atypical neurofibroma from malignant peripheral nerve sheath tumour (MPNST).
Reference Gallery:
Neurofibroma of the choroid. Diffuse expansion of the choroid by a proliferation of Schwann cells.
Neurofibroma of the choroid. Ovoid bodies resembling Meissner (tactile) corpuscles are composed of concentric Schwann cell processes.
Plexiform neurofibroma. Macroscopic impression of plexiform neurofibroma of the orbit at grossing.
Plexiform neurofibroma. Plexiform neurofibroma infiltrating the lacrimal gland.

Q: Grossly and microscopically, the [...] variant of Neurofibroma often features a multi-nodular, infiltrative growth pattern (e.g., involving the orbit or lacrimal gland) and is highly associated with neurofibromatosis type 1 (NF1).
Plexiform neurofibroma. Macroscopic impression of plexiform neurofibroma of the orbit at grossing.
Plexiform neurofibroma. Plexiform neurofibroma infiltrating the lacrimal gland.
A: plexiform
Back Extra: Neurofibroma
- Clinical: Orbital neurofibroma can manifest as proptosis and optic nerve compression, and is often associated with neurofibromatosis type 1 (NF1).
- Micro: Neurofibroma is characterized by a haphazard proliferation of Schwann cells, fibroblasts, and mast cells, with a mucinous or myxomatous extracellular matrix.
- Ancillary: Chromosomal copy-number profiling may be helpful for differentiating atypical neurofibroma from malignant peripheral nerve sheath tumour (MPNST).
Reference Gallery:
Neurofibroma of the choroid. Diffuse expansion of the choroid by a proliferation of Schwann cells.
Neurofibroma of the choroid. Ovoid bodies resembling Meissner (tactile) corpuscles are composed of concentric Schwann cell processes.
Plexiform neurofibroma. Macroscopic impression of plexiform neurofibroma of the orbit at grossing.
Plexiform neurofibroma. Plexiform neurofibroma infiltrating the lacrimal gland.

Q: A characteristic histologic finding in some variants of Neurofibroma is the presence of distinct ovoid bodies composed of concentric cellular processes that morphologically resemble tactile [...] corpuscles.
Neurofibroma of the choroid. Ovoid bodies resembling Meissner (tactile) corpuscles are composed of concentric Schwann cell processes.
A: Meissner
Back Extra: Neurofibroma
- Clinical: Orbital neurofibroma can manifest as proptosis and optic nerve compression, and is often associated with neurofibromatosis type 1 (NF1).
- Micro: Neurofibroma is characterized by a haphazard proliferation of Schwann cells, fibroblasts, and mast cells, with a mucinous or myxomatous extracellular matrix.
- Ancillary: Chromosomal copy-number profiling may be helpful for differentiating atypical neurofibroma from malignant peripheral nerve sheath tumour (MPNST).
Reference Gallery:
Neurofibroma of the choroid. Diffuse expansion of the choroid by a proliferation of Schwann cells.
Neurofibroma of the choroid. Ovoid bodies resembling Meissner (tactile) corpuscles are composed of concentric Schwann cell processes.
Plexiform neurofibroma. Macroscopic impression of plexiform neurofibroma of the orbit at grossing.
Plexiform neurofibroma. Plexiform neurofibroma infiltrating the lacrimal gland.

Q: Microscopically, Schwannoma is an encapsulated spindle cell tumor featuring compact hypercellular areas (Antoni A tissue) that classically contain [...], characterized by palisades of nuclei around anucleate zones.
Orbital Schwannoma. Verocay bodies are important diagnostic features of schwannoma, identifiable as palisades of neoplastic schwann cells around anucleate zones.
A: Verocay bodies
Back Extra: Schwannoma
- Clinical: Schwannomas are slow-growing, often asymptomatic masses or incidental findings on imaging. They can cause pain if associated with schwannomatosis.
- Micro: Schwannomas are encapsulated spindle cell tumours with biphasic areas: Antoni A (compact with Verocay bodies) and Antoni B (loosely arranged with degenerative changes).
- Ancillary: Strong S100 and SOX10 immunoreactivity are consistent findings in schwannomas, with EMA limited to the periphery/capsular area.
Reference Gallery:
Orbital Schwannoma. Axial T2 image demonstrating a well circumscribed left orbital mass with a histologic diagnosis of schwannoma.
Orbital Schwannoma. Verocay bodies are important diagnostic features of schwannoma, identifiable as palisades of neoplastic schwann cells around anucleate zones.
Orbital Schwannoma. Frequent degenerative changes in schwannomas include hyalinized vessels, hemosiderin deposition and foamy macrophages.
Orbital Schannoma. Strong S100 expression is a consistent finding in schwannomas of all sites, including those involvign the orbit.
Orbital Schwannoma. As S100, SOX10 expression is also consistently presented in Schwannomas of all sites, but it is a pure nuclear stain.
Orbital Schwannoma. EMA immunoreactivity is limited to the periphery/capsular area in Schwannomas at all sites, including orbital examples.
Orbital Plexiform Schwannoma. Schwann cell morphology is present at intermediate power in this plexiform schwannoma arising in the orbit.

Q: Immunohistochemistry for Schwannoma demonstrates strong, diffuse positivity for S100 and [...], while EMA expression is typically limited to the tumor's peripheral capsule.
Orbital Schannoma. Strong S100 expression is a consistent finding in schwannomas of all sites, including those involvign the orbit.
Orbital Schwannoma. As S100, SOX10 expression is also consistently presented in Schwannomas of all sites, but it is a pure nuclear stain.
Orbital Schwannoma. EMA immunoreactivity is limited to the periphery/capsular area in Schwannomas at all sites, including orbital examples.
A: SOX10
Back Extra: Schwannoma
- Clinical: Schwannomas are slow-growing, often asymptomatic masses or incidental findings on imaging. They can cause pain if associated with schwannomatosis.
- Micro: Schwannomas are encapsulated spindle cell tumours with biphasic areas: Antoni A (compact with Verocay bodies) and Antoni B (loosely arranged with degenerative changes).
- Ancillary: Strong S100 and SOX10 immunoreactivity are consistent findings in schwannomas, with EMA limited to the periphery/capsular area.
Reference Gallery:
Orbital Schwannoma. Axial T2 image demonstrating a well circumscribed left orbital mass with a histologic diagnosis of schwannoma.
Orbital Schwannoma. Verocay bodies are important diagnostic features of schwannoma, identifiable as palisades of neoplastic schwann cells around anucleate zones.
Orbital Schwannoma. Frequent degenerative changes in schwannomas include hyalinized vessels, hemosiderin deposition and foamy macrophages.
Orbital Schannoma. Strong S100 expression is a consistent finding in schwannomas of all sites, including those involvign the orbit.
Orbital Schwannoma. As S100, SOX10 expression is also consistently presented in Schwannomas of all sites, but it is a pure nuclear stain.
Orbital Schwannoma. EMA immunoreactivity is limited to the periphery/capsular area in Schwannomas at all sites, including orbital examples.
Orbital Plexiform Schwannoma. Schwann cell morphology is present at intermediate power in this plexiform schwannoma arising in the orbit.

Q: A Schwannoma exhibits a biphasic architecture with dense Antoni A tissue and loosely arranged [...] areas, which frequently show degenerative changes such as hyalinized vessels, hemosiderin, and foamy macrophages.
Orbital Schwannoma. Frequent degenerative changes in schwannomas include hyalinized vessels, hemosiderin deposition and foamy macrophages.
A: Antoni B
Back Extra: Schwannoma
- Clinical: Schwannomas are slow-growing, often asymptomatic masses or incidental findings on imaging. They can cause pain if associated with schwannomatosis.
- Micro: Schwannomas are encapsulated spindle cell tumours with biphasic areas: Antoni A (compact with Verocay bodies) and Antoni B (loosely arranged with degenerative changes).
- Ancillary: Strong S100 and SOX10 immunoreactivity are consistent findings in schwannomas, with EMA limited to the periphery/capsular area.
Reference Gallery:
Orbital Schwannoma. Axial T2 image demonstrating a well circumscribed left orbital mass with a histologic diagnosis of schwannoma.
Orbital Schwannoma. Verocay bodies are important diagnostic features of schwannoma, identifiable as palisades of neoplastic schwann cells around anucleate zones.
Orbital Schwannoma. Frequent degenerative changes in schwannomas include hyalinized vessels, hemosiderin deposition and foamy macrophages.
Orbital Schannoma. Strong S100 expression is a consistent finding in schwannomas of all sites, including those involvign the orbit.
Orbital Schwannoma. As S100, SOX10 expression is also consistently presented in Schwannomas of all sites, but it is a pure nuclear stain.
Orbital Schwannoma. EMA immunoreactivity is limited to the periphery/capsular area in Schwannomas at all sites, including orbital examples.
Orbital Plexiform Schwannoma. Schwann cell morphology is present at intermediate power in this plexiform schwannoma arising in the orbit.

Q: To distinguish Solitary Circumscribed Neuroma from a schwannoma, immunohistochemistry for neurofilament protein (NFP) will reveal a characteristic [...].
Solitary circumscribed neuroma. Neurofilament protein highlights a high axonal density in solitary circumscribed neuroma, a usual feature that distinguishes it from schwannoma.
A: high axonal density
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma (SCN) usually presents as a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly in the fifth to seventh decades of life.
- Micro: SCN is characterized by bland spindle-shaped cells with wavy nuclei, often forming well-developed fascicles and showing characteristic palisading of nuclei.
- Ancillary: The spindle cells in SCN are strongly and diffusely positive for S100, and neurofilament protein staining highlights a high axonal density, distinguishing it from schwannoma.
Reference Gallery:
Solitary circumscribed neuroma. Solitary circumscribed neuroma involving the eyelid.
Solitary circumscribed neuroma. Solitary circumscribed neuromas form well circumscribed nodules evident at low magnification.
Solitary circumscribed neuroma. Solitary circumscribed neuromas are characterized by a predominant content of Schwann cells.
Solitary circumscribed neuroma. Neurofilament protein highlights a high axonal density in solitary circumscribed neuroma, a usual feature that distinguishes it from schwannoma.
Solitary circumscribed neuroma. Perineurial cells at the periphery are typically highlighted with EMA.

Q: In a Solitary Circumscribed Neuroma, an EMA immunostain characteristically highlights a peripheral pseudo-capsule predominantly composed of [...].
Solitary circumscribed neuroma. Perineurial cells at the periphery are typically highlighted with EMA.
A: perineurial cells
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma (SCN) usually presents as a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly in the fifth to seventh decades of life.
- Micro: SCN is characterized by bland spindle-shaped cells with wavy nuclei, often forming well-developed fascicles and showing characteristic palisading of nuclei.
- Ancillary: The spindle cells in SCN are strongly and diffusely positive for S100, and neurofilament protein staining highlights a high axonal density, distinguishing it from schwannoma.
Reference Gallery:
Solitary circumscribed neuroma. Solitary circumscribed neuroma involving the eyelid.
Solitary circumscribed neuroma. Solitary circumscribed neuromas form well circumscribed nodules evident at low magnification.
Solitary circumscribed neuroma. Solitary circumscribed neuromas are characterized by a predominant content of Schwann cells.
Solitary circumscribed neuroma. Neurofilament protein highlights a high axonal density in solitary circumscribed neuroma, a usual feature that distinguishes it from schwannoma.
Solitary circumscribed neuroma. Perineurial cells at the periphery are typically highlighted with EMA.

Q: Microscopically, Solitary Circumscribed Neuroma forms a well-circumscribed dermal nodule predominantly composed of S100-positive [...] with bland, wavy nuclei.
Solitary circumscribed neuroma. Solitary circumscribed neuroma involving the eyelid.
Solitary circumscribed neuroma. Solitary circumscribed neuromas form well circumscribed nodules evident at low magnification.
Solitary circumscribed neuroma. Solitary circumscribed neuromas are characterized by a predominant content of Schwann cells.
A: Schwann cells
Back Extra: Solitary Circumscribed Neuroma
- Clinical: Solitary circumscribed neuroma (SCN) usually presents as a slow-growing, firm, painless, circumscribed dermal-based nodule, most commonly in the fifth to seventh decades of life.
- Micro: SCN is characterized by bland spindle-shaped cells with wavy nuclei, often forming well-developed fascicles and showing characteristic palisading of nuclei.
- Ancillary: The spindle cells in SCN are strongly and diffusely positive for S100, and neurofilament protein staining highlights a high axonal density, distinguishing it from schwannoma.
Reference Gallery:
Solitary circumscribed neuroma. Solitary circumscribed neuroma involving the eyelid.
Solitary circumscribed neuroma. Solitary circumscribed neuromas form well circumscribed nodules evident at low magnification.
Solitary circumscribed neuroma. Solitary circumscribed neuromas are characterized by a predominant content of Schwann cells.
Solitary circumscribed neuroma. Neurofilament protein highlights a high axonal density in solitary circumscribed neuroma, a usual feature that distinguishes it from schwannoma.
Solitary circumscribed neuroma. Perineurial cells at the periphery are typically highlighted with EMA.

Q: Microscopically, [...] typically presents with sheets of round to polygonal cells with eosinophilic to amphophilic cytoplasm and monomorphic central nuclei arranged around a delicate capillary-sized vasculature.
Glomus tumour. Conventional glomus tumour with sheets of polygonal cells with monomorphic central nuclei.
A: Glomus Tumor
Back Extra: Glomus Tumor
- Clinical: Pain is a common manifestation, and eye tumors may present with blindness and/or proptosis.
- Micro: Sheets of round to polygonal cells with eosinophilic to amphophilic cytoplasm and monomorphic nuclei; delicate capillary-sized vasculature.
- Ancillary: Immunohistochemistry is typically positive for smooth muscle actin and h-caldesmon, with variable staining for desmin and CD34.
Reference Gallery:
Glomus tumour. Conventional glomus tumour with sheets of polygonal cells with monomorphic central nuclei.
Glomangioma. Glomangioma with ectatic vascular spaces lined by multiple layers of glomus cells.
Symplastic glomus tumour. This example shows marked nuclear atypia but absent mitotic activity.
Malignant glomus tumour. This tumour was MIR143::NOTCH1 fusion positive.

Q: The glomangioma variant of Glomus Tumor is morphologically characterized by prominent [...] lined by multiple layers of monomorphic glomus cells.
Glomangioma. Glomangioma with ectatic vascular spaces lined by multiple layers of glomus cells.
A: ectatic vascular spaces
Back Extra: Glomus Tumor
- Clinical: Pain is a common manifestation, and eye tumors may present with blindness and/or proptosis.
- Micro: Sheets of round to polygonal cells with eosinophilic to amphophilic cytoplasm and monomorphic nuclei; delicate capillary-sized vasculature.
- Ancillary: Immunohistochemistry is typically positive for smooth muscle actin and h-caldesmon, with variable staining for desmin and CD34.
Reference Gallery:
Glomus tumour. Conventional glomus tumour with sheets of polygonal cells with monomorphic central nuclei.
Glomangioma. Glomangioma with ectatic vascular spaces lined by multiple layers of glomus cells.
Symplastic glomus tumour. This example shows marked nuclear atypia but absent mitotic activity.
Malignant glomus tumour. This tumour was MIR143::NOTCH1 fusion positive.

Q: The symplastic variant of Glomus Tumor displays marked nuclear atypia, but it typically lacks [...], helping distinguish it from a true malignant tumor.
Symplastic glomus tumour. This example shows marked nuclear atypia but absent mitotic activity.
A: mitotic activity
Back Extra: Glomus Tumor
- Clinical: Pain is a common manifestation, and eye tumors may present with blindness and/or proptosis.
- Micro: Sheets of round to polygonal cells with eosinophilic to amphophilic cytoplasm and monomorphic nuclei; delicate capillary-sized vasculature.
- Ancillary: Immunohistochemistry is typically positive for smooth muscle actin and h-caldesmon, with variable staining for desmin and CD34.
Reference Gallery:
Glomus tumour. Conventional glomus tumour with sheets of polygonal cells with monomorphic central nuclei.
Glomangioma. Glomangioma with ectatic vascular spaces lined by multiple layers of glomus cells.
Symplastic glomus tumour. This example shows marked nuclear atypia but absent mitotic activity.
Malignant glomus tumour. This tumour was MIR143::NOTCH1 fusion positive.

Q: Histologically, [...] is characterized by cytologically bland myoid spindle cells that exhibit a characteristic concentric perivascular arrangement.
Myopericytoma. Scanning power of this well-circumscribed cutaneous lesion of the eyelid shows the characteristic concentric perivascular arrangement of tumour cells.
Myopericytoma. High power view showing cytologically-bland myoid spindle cells.
A: Myopericytoma, including myofibroma
Back Extra: Myopericytoma, including myofibroma
- Clinical: Myopericytomas often present as painless masses, sometimes with ptosis or eye displacement, and are more common in adult males.
- Micro: Myopericytomas are characterized by myoid spindle cells arranged concentrically around vasculature, while myofibromas may show a biphasic pattern with central hypercellularity and peripheral hyalinization.
- Ancillary: Diagnostic studies include the expression of smooth muscle actin and the presence of PDGFRB mutations or SRF rearrangements.
Reference Gallery:
Myopericytoma. Scanning power of this well-circumscribed cutaneous lesion of the eyelid shows the characteristic concentric perivascular arrangement of tumour cells.
Myopericytoma. High power view showing cytologically-bland myoid spindle cells.

Q: A defining microscopic feature of Myopericytoma, including myofibroma is the arrangement of cytologically bland [...] concentrically around the tumor vasculature.
Myopericytoma. Scanning power of this well-circumscribed cutaneous lesion of the eyelid shows the characteristic concentric perivascular arrangement of tumour cells.
Myopericytoma. High power view showing cytologically-bland myoid spindle cells.
A: myoid spindle cells
Back Extra: Myopericytoma, including myofibroma
- Clinical: Myopericytomas often present as painless masses, sometimes with ptosis or eye displacement, and are more common in adult males.
- Micro: Myopericytomas are characterized by myoid spindle cells arranged concentrically around vasculature, while myofibromas may show a biphasic pattern with central hypercellularity and peripheral hyalinization.
- Ancillary: Diagnostic studies include the expression of smooth muscle actin and the presence of PDGFRB mutations or SRF rearrangements.
Reference Gallery:
Myopericytoma. Scanning power of this well-circumscribed cutaneous lesion of the eyelid shows the characteristic concentric perivascular arrangement of tumour cells.
Myopericytoma. High power view showing cytologically-bland myoid spindle cells.

Q: Tumors in the Rhabdomyosarcoma Family characteristically demonstrate immunohistochemical expression of skeletal muscle markers, including desmin, MYOD1, and nuclear [...].
Orbital alveolar rhabdomyosarcoma. Diffuse nuclear expression of myogenin in neoplastic cells.
Orbital embryonal rhabdomyosarcoma. Neoplastic cells diffusely express desmin.
A: myogenin
Back Extra: Rhabdomyosarcoma Family
- Clinical: Ocular rhabdomyosarcoma most commonly presents in the orbit with proptosis, eyelid swelling, and blepharoptosis.
- Micro: Embryonal rhabdomyosarcoma (ERMS) is characterized by atypical primitive round and spindle-shaped cells in a variably myxoid background, with possible large differentiated rhabdomyoblasts.
- Ancillary: All types of rhabdomyosarcoma express desmin, myogenin, and MYOD1, with diffuse myogenin expression more common in alveolar rhabdomyosarcoma (ARMS) than in ERMS.
Reference Gallery:
Eyelid embryonal rhabdomyosarcoma. A cellular malignant neoplasm composed of mitotically active undifferentiated spindle cells which infiltrate skeletal muscle.
Orbital alveolar rhabdomyosarcoma. A malignant small round cell neoplasm with a prominent alveolar growth pattern characterized by nests of tumour cells with central dyscohesion.
Anaplastic embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma with anaplastic features characterized by pronounced nuclear pleomorphism and large atypical mitotic figures.
Orbital embryonal rhabdomyosarcoma. The tumour consists of primitive round and spindle cells set in a variably myxoid stroma.
Embryonal Rhabdomyosarcoma MRI. Saggital MRI demonstrates a homogeneously enhancing extraconal mass in the inferior orbit.
Orbital alveolar rhabdomyosarcoma. Diffuse nuclear expression of myogenin in neoplastic cells.
Orbital embryonal rhabdomyosarcoma. Neoplastic cells diffusely express desmin.
Rhabdomyosarcoma. Axial T1 post-contrast MRI shows a heterogeneously enhancing mass in the superior left orbit (arrow).

Q: An orbital mass presenting with rapid proptosis, eyelid swelling, and demonstrating an enhancing extraconal mass on MRI is highly suspicious for a tumor in the [...].
Embryonal Rhabdomyosarcoma MRI. Saggital MRI demonstrates a homogeneously enhancing extraconal mass in the inferior orbit.
Rhabdomyosarcoma. Axial T1 post-contrast MRI shows a heterogeneously enhancing mass in the superior left orbit (arrow).
A: Rhabdomyosarcoma Family
Back Extra: Rhabdomyosarcoma Family
- Clinical: Ocular rhabdomyosarcoma most commonly presents in the orbit with proptosis, eyelid swelling, and blepharoptosis.
- Micro: Embryonal rhabdomyosarcoma (ERMS) is characterized by atypical primitive round and spindle-shaped cells in a variably myxoid background, with possible large differentiated rhabdomyoblasts.
- Ancillary: All types of rhabdomyosarcoma express desmin, myogenin, and MYOD1, with diffuse myogenin expression more common in alveolar rhabdomyosarcoma (ARMS) than in ERMS.
Reference Gallery:
Eyelid embryonal rhabdomyosarcoma. A cellular malignant neoplasm composed of mitotically active undifferentiated spindle cells which infiltrate skeletal muscle.
Orbital alveolar rhabdomyosarcoma. A malignant small round cell neoplasm with a prominent alveolar growth pattern characterized by nests of tumour cells with central dyscohesion.
Anaplastic embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma with anaplastic features characterized by pronounced nuclear pleomorphism and large atypical mitotic figures.
Orbital embryonal rhabdomyosarcoma. The tumour consists of primitive round and spindle cells set in a variably myxoid stroma.
Embryonal Rhabdomyosarcoma MRI. Saggital MRI demonstrates a homogeneously enhancing extraconal mass in the inferior orbit.
Orbital alveolar rhabdomyosarcoma. Diffuse nuclear expression of myogenin in neoplastic cells.
Orbital embryonal rhabdomyosarcoma. Neoplastic cells diffusely express desmin.
Rhabdomyosarcoma. Axial T1 post-contrast MRI shows a heterogeneously enhancing mass in the superior left orbit (arrow).

Q: In the Rhabdomyosarcoma Family, the embryonal subtype is microscopically characterized by primitive round and spindle-shaped cells in a variably myxoid background, sometimes containing large, differentiated [...].
Eyelid embryonal rhabdomyosarcoma. A cellular malignant neoplasm composed of mitotically active undifferentiated spindle cells which infiltrate skeletal muscle.
Orbital embryonal rhabdomyosarcoma. The tumour consists of primitive round and spindle cells set in a variably myxoid stroma.
A: rhabdomyoblasts
Back Extra: Rhabdomyosarcoma Family
- Clinical: Ocular rhabdomyosarcoma most commonly presents in the orbit with proptosis, eyelid swelling, and blepharoptosis.
- Micro: Embryonal rhabdomyosarcoma (ERMS) is characterized by atypical primitive round and spindle-shaped cells in a variably myxoid background, with possible large differentiated rhabdomyoblasts.
- Ancillary: All types of rhabdomyosarcoma express desmin, myogenin, and MYOD1, with diffuse myogenin expression more common in alveolar rhabdomyosarcoma (ARMS) than in ERMS.
Reference Gallery:
Eyelid embryonal rhabdomyosarcoma. A cellular malignant neoplasm composed of mitotically active undifferentiated spindle cells which infiltrate skeletal muscle.
Orbital alveolar rhabdomyosarcoma. A malignant small round cell neoplasm with a prominent alveolar growth pattern characterized by nests of tumour cells with central dyscohesion.
Anaplastic embryonal rhabdomyosarcoma. Embryonal rhabdomyosarcoma with anaplastic features characterized by pronounced nuclear pleomorphism and large atypical mitotic figures.
Orbital embryonal rhabdomyosarcoma. The tumour consists of primitive round and spindle cells set in a variably myxoid stroma.
Embryonal Rhabdomyosarcoma MRI. Saggital MRI demonstrates a homogeneously enhancing extraconal mass in the inferior orbit.
Orbital alveolar rhabdomyosarcoma. Diffuse nuclear expression of myogenin in neoplastic cells.
Orbital embryonal rhabdomyosarcoma. Neoplastic cells diffusely express desmin.
Rhabdomyosarcoma. Axial T1 post-contrast MRI shows a heterogeneously enhancing mass in the superior left orbit (arrow).

Q: Leiomyoma is histologically composed of intersecting fascicles of spindled cells with eosinophilic cytoplasm and characteristic blunt-ended, [...] nuclei.
Leiomyoma. Leiomyoma intersecting fascicles of spindled cells with blunt end cigar-shaped nuclei and eosinophilic cytoplasm.
Leiomyoma. Intersecting fascicles of spindled cells with blunt end cigar-shaped nuclei and eosinophilic cytoplasm.
A: cigar-shaped
Q: Leiomyoma
- Clinical: Orbital [...] may cause proptosis, diplopia, deviation of the globe, and pain.
- Micro: Ocular [...] are composed of intersecting fascicles of spindled cells with blunt ended cigar-shaped nuclei and eosinophilic cytoplasm.
- Ancillary: Spindle cells in [...] are positive for SMA, desmin, and h-caldesmon.
Reference Gallery:
Leiomyoma. Leiomyoma intersecting fascicles of spindled cells with blunt end cigar-shaped nuclei and eosinophilic cytoplasm.
Leiomyoma. Intersecting fascicles of spindled cells with blunt end cigar-shaped nuclei and eosinophilic cytoplasm.
Leiomyoma. Expression of desmin is a characteristic feature.
Leiomyoma. Expression of SMA is a characteristic feature.
A: leiomyomas; leiomyomas; leiomyomas

Q: Leiomyoma characteristically exhibits immunohistochemical positivity for h-caldesmon, as well as the smooth muscle markers [...].
Leiomyoma. Expression of desmin is a characteristic feature.
Leiomyoma. Expression of SMA is a characteristic feature.
A: SMA and desmin
Q: Leiomyoma
- Clinical: Orbital [...] may cause proptosis, diplopia, deviation of the globe, and pain.
- Micro: Ocular [...] are composed of intersecting fascicles of spindled cells with blunt ended cigar-shaped nuclei and eosinophilic cytoplasm.
- Ancillary: Spindle cells in [...] are positive for SMA, desmin, and h-caldesmon.
Reference Gallery:
Leiomyoma. Leiomyoma intersecting fascicles of spindled cells with blunt end cigar-shaped nuclei and eosinophilic cytoplasm.
Leiomyoma. Intersecting fascicles of spindled cells with blunt end cigar-shaped nuclei and eosinophilic cytoplasm.
Leiomyoma. Expression of desmin is a characteristic feature.
Leiomyoma. Expression of SMA is a characteristic feature.
A: leiomyomas; leiomyomas; leiomyomas

Q: Histologically, Leiomyosarcoma is characterized by spindle to [...]-shaped cells with moderate eosinophilic cytoplasm arranged in fascicles and bundles, often with abundant mitotic activity.
Conjunctival leiomyosarcoma. The tumour is composed of spindle cells arranged in bundle and fascicles with scattered mitotic activity.
A: cigar
Back Extra: Leiomyosarcoma
- Clinical: Conjunctival Leiomyosarcoma presents as a raised, fleshy, pale to hyperaemic growth, often extending from the fornix to the limbus. Orbital lesions are usually painless mass lesions with occasional proptosis.
- Micro: Leiomyosarcoma is characterized by spindle to cigar-shaped cells with moderate eosinophilic cytoplasm arranged in fascicles, sheets, and bundles. Mitotic figures are generally abundant, and areas of necrosis may be present.
- Ancillary: Leiomyosarcoma cells are positive for smooth muscle markers (SMA, MSA, desmin, caldesmon) and may be positive for cytokeratins, EMA, and CD34. They are negative for S-100 protein and MyoD1.
Reference Gallery:
Conjunctival Leiomyosarcoma. Spindle neoplastic cells exhibiting strong immunoreactivity with SMA antibodies.
Conjunctival Leiomyosarcoma. Spindle neoplastic cells display a high Ki-67 index.
Conjunctival leiomyosarcoma. Clinical image showing a nodular pink growth in the caruncle.
Conjunctival leiomyosarcoma. The tumour is composed of spindle cells arranged in bundle and fascicles with scattered mitotic activity.

Q: Immunohistochemically, the neoplastic spindle cells of a Leiomyosarcoma classically exhibit strong reactivity for smooth muscle markers, such as [...] (shown in image).
Conjunctival Leiomyosarcoma. Spindle neoplastic cells exhibiting strong immunoreactivity with SMA antibodies.
A: SMA
Back Extra: Leiomyosarcoma
- Clinical: Conjunctival Leiomyosarcoma presents as a raised, fleshy, pale to hyperaemic growth, often extending from the fornix to the limbus. Orbital lesions are usually painless mass lesions with occasional proptosis.
- Micro: Leiomyosarcoma is characterized by spindle to cigar-shaped cells with moderate eosinophilic cytoplasm arranged in fascicles, sheets, and bundles. Mitotic figures are generally abundant, and areas of necrosis may be present.
- Ancillary: Leiomyosarcoma cells are positive for smooth muscle markers (SMA, MSA, desmin, caldesmon) and may be positive for cytokeratins, EMA, and CD34. They are negative for S-100 protein and MyoD1.
Reference Gallery:
Conjunctival Leiomyosarcoma. Spindle neoplastic cells exhibiting strong immunoreactivity with SMA antibodies.
Conjunctival Leiomyosarcoma. Spindle neoplastic cells display a high Ki-67 index.
Conjunctival leiomyosarcoma. Clinical image showing a nodular pink growth in the caruncle.
Conjunctival leiomyosarcoma. The tumour is composed of spindle cells arranged in bundle and fascicles with scattered mitotic activity.

Q: A raised, fleshy, pink conjunctival growth that microscopically demonstrates malignant spindle cells with a high Ki-67 proliferation index is characteristic of conjunctival [...].
Conjunctival Leiomyosarcoma. Spindle neoplastic cells display a high Ki-67 index.
Conjunctival leiomyosarcoma. Clinical image showing a nodular pink growth in the caruncle.
A: Leiomyosarcoma
Back Extra: Leiomyosarcoma
- Clinical: Conjunctival Leiomyosarcoma presents as a raised, fleshy, pale to hyperaemic growth, often extending from the fornix to the limbus. Orbital lesions are usually painless mass lesions with occasional proptosis.
- Micro: Leiomyosarcoma is characterized by spindle to cigar-shaped cells with moderate eosinophilic cytoplasm arranged in fascicles, sheets, and bundles. Mitotic figures are generally abundant, and areas of necrosis may be present.
- Ancillary: Leiomyosarcoma cells are positive for smooth muscle markers (SMA, MSA, desmin, caldesmon) and may be positive for cytokeratins, EMA, and CD34. They are negative for S-100 protein and MyoD1.
Reference Gallery:
Conjunctival Leiomyosarcoma. Spindle neoplastic cells exhibiting strong immunoreactivity with SMA antibodies.
Conjunctival Leiomyosarcoma. Spindle neoplastic cells display a high Ki-67 index.
Conjunctival leiomyosarcoma. Clinical image showing a nodular pink growth in the caruncle.
Conjunctival leiomyosarcoma. The tumour is composed of spindle cells arranged in bundle and fascicles with scattered mitotic activity.

Q: Histologically, Mesectodermal Leiomyoma is composed of spindle to epithelioid cells with fibrillary eosinophilic cytoplasm and granular nuclei that are frequently indented by [...].
Mesectodermal Leiomyoma. H&E showing spindle cells with fibrillary eosinophilic cytoplasm contain oval, granular nuclei, some of which are indented by cytoplasmic paranuclear vacuoles
A: perinuclear cytoplasmic vacuoles
Back Extra: Mesectodermal Leiomyoma
- Clinical: Mesectodermal leiomyoma typically affects females in their reproductive age (second to fourth decades) and can present as a dome-shaped, yellow to orange mass with intrinsic vascularity or darkly pigmented mass causing anterior staphyloma or acute symptoms such as loss of vision and glaucoma.
- Micro: Histologically, mesectodermal leiomyoma is characterized by spindle to epithelioid-shaped cells with fibrillary eosinophilic cytoplasm, round to oval nuclei, and perinuclear cytoplasmic vacuoles. Scattered melanocytes can also be present.
- Ancillary: Immunohistochemically, mesectodermal leiomyoma is positive for smooth muscle actin (SMA), myosin smooth muscle actin (MSA), caldesmon, calponin, and desmin. Some cases may express nuclear progesterone receptors.
Reference Gallery:
Mesectodermal Leiomyoma. A macroscopic image of an enucleation specimen showing a ciliary body mesectodermal leiomyoma. It has a solid whorled cut surface and is present in a supra-uveal location, with its base against the sclera.
Mesectodermal Leiomyoma. H&E showing spindle cells with fibrillary eosinophilic cytoplasm contain oval, granular nuclei, some of which are indented by cytoplasmic paranuclear vacuoles
Mesectodermal Leiomyoma. Transmission electron microscopy showing smooth muscle densities.
Mesectodermal Leiomyoma. Transmission electron microscopy revealing skeinoid fibres in the cytoplasm.
Mesectodermal leiomyoma. Immunohistochemical demonstration of nuclear progesterone receptor positivity in some of the lesional cells.
Mesectodermal leiomyoma. Higher power image of the macroscopic appearance of a mesectodermal leiomyoma. Note the suprauveal location, with the solid white leiomyoma abutting the sclera on the left and lifting off the pigmented choroid superiorly.
Mesectodermal leiomyoma. Clinical photograph of left eye showing a ciliary body mesectodermal leiomyoma. A pink mass is seen laterally with displacement of the iris.
Mesectodermal leiomyoma. Cytoplasmic smooth muscle actin positivity of the tumour.

Q: Immunohistochemically, Mesectodermal Leiomyoma is characteristically positive for smooth muscle markers (such as SMA and desmin) and frequently expresses nuclear [...], which correlates with its typical presentation in reproductive-age females.
Mesectodermal leiomyoma. Immunohistochemical demonstration of nuclear progesterone receptor positivity in some of the lesional cells.
Mesectodermal leiomyoma. Cytoplasmic smooth muscle actin positivity of the tumour.
A: progesterone receptors
Back Extra: Mesectodermal Leiomyoma
- Clinical: Mesectodermal leiomyoma typically affects females in their reproductive age (second to fourth decades) and can present as a dome-shaped, yellow to orange mass with intrinsic vascularity or darkly pigmented mass causing anterior staphyloma or acute symptoms such as loss of vision and glaucoma.
- Micro: Histologically, mesectodermal leiomyoma is characterized by spindle to epithelioid-shaped cells with fibrillary eosinophilic cytoplasm, round to oval nuclei, and perinuclear cytoplasmic vacuoles. Scattered melanocytes can also be present.
- Ancillary: Immunohistochemically, mesectodermal leiomyoma is positive for smooth muscle actin (SMA), myosin smooth muscle actin (MSA), caldesmon, calponin, and desmin. Some cases may express nuclear progesterone receptors.
Reference Gallery:
Mesectodermal Leiomyoma. A macroscopic image of an enucleation specimen showing a ciliary body mesectodermal leiomyoma. It has a solid whorled cut surface and is present in a supra-uveal location, with its base against the sclera.
Mesectodermal Leiomyoma. H&E showing spindle cells with fibrillary eosinophilic cytoplasm contain oval, granular nuclei, some of which are indented by cytoplasmic paranuclear vacuoles
Mesectodermal Leiomyoma. Transmission electron microscopy showing smooth muscle densities.
Mesectodermal Leiomyoma. Transmission electron microscopy revealing skeinoid fibres in the cytoplasm.
Mesectodermal leiomyoma. Immunohistochemical demonstration of nuclear progesterone receptor positivity in some of the lesional cells.
Mesectodermal leiomyoma. Higher power image of the macroscopic appearance of a mesectodermal leiomyoma. Note the suprauveal location, with the solid white leiomyoma abutting the sclera on the left and lifting off the pigmented choroid superiorly.
Mesectodermal leiomyoma. Clinical photograph of left eye showing a ciliary body mesectodermal leiomyoma. A pink mass is seen laterally with displacement of the iris.
Mesectodermal leiomyoma. Cytoplasmic smooth muscle actin positivity of the tumour.

Q: Macroscopically, a Mesectodermal Leiomyoma of the ciliary body typically presents as a solid, whorled mass in a [...] location, where its base rests against the sclera, lifting the pigmented choroid.
Mesectodermal Leiomyoma. A macroscopic image of an enucleation specimen showing a ciliary body mesectodermal leiomyoma. It has a solid whorled cut surface and is present in a supra-uveal location, with its base against the sclera.
Mesectodermal leiomyoma. Higher power image of the macroscopic appearance of a mesectodermal leiomyoma. Note the suprauveal location, with the solid white leiomyoma abutting the sclera on the left and lifting off the pigmented choroid superiorly.
Mesectodermal leiomyoma. Clinical photograph of left eye showing a ciliary body mesectodermal leiomyoma. A pink mass is seen laterally with displacement of the iris.
A: supra-uveal
Back Extra: Mesectodermal Leiomyoma
- Clinical: Mesectodermal leiomyoma typically affects females in their reproductive age (second to fourth decades) and can present as a dome-shaped, yellow to orange mass with intrinsic vascularity or darkly pigmented mass causing anterior staphyloma or acute symptoms such as loss of vision and glaucoma.
- Micro: Histologically, mesectodermal leiomyoma is characterized by spindle to epithelioid-shaped cells with fibrillary eosinophilic cytoplasm, round to oval nuclei, and perinuclear cytoplasmic vacuoles. Scattered melanocytes can also be present.
- Ancillary: Immunohistochemically, mesectodermal leiomyoma is positive for smooth muscle actin (SMA), myosin smooth muscle actin (MSA), caldesmon, calponin, and desmin. Some cases may express nuclear progesterone receptors.
Reference Gallery:
Mesectodermal Leiomyoma. A macroscopic image of an enucleation specimen showing a ciliary body mesectodermal leiomyoma. It has a solid whorled cut surface and is present in a supra-uveal location, with its base against the sclera.
Mesectodermal Leiomyoma. H&E showing spindle cells with fibrillary eosinophilic cytoplasm contain oval, granular nuclei, some of which are indented by cytoplasmic paranuclear vacuoles
Mesectodermal Leiomyoma. Transmission electron microscopy showing smooth muscle densities.
Mesectodermal Leiomyoma. Transmission electron microscopy revealing skeinoid fibres in the cytoplasm.
Mesectodermal leiomyoma. Immunohistochemical demonstration of nuclear progesterone receptor positivity in some of the lesional cells.
Mesectodermal leiomyoma. Higher power image of the macroscopic appearance of a mesectodermal leiomyoma. Note the suprauveal location, with the solid white leiomyoma abutting the sclera on the left and lifting off the pigmented choroid superiorly.
Mesectodermal leiomyoma. Clinical photograph of left eye showing a ciliary body mesectodermal leiomyoma. A pink mass is seen laterally with displacement of the iris.
Mesectodermal leiomyoma. Cytoplasmic smooth muscle actin positivity of the tumour.

Q: Microscopically, Alveolar Soft Part Sarcoma is characterized by large, polygonal cells with abundant, granular eosinophilic cytoplasm arranged in nests with central discohesion, resulting in a distinct [...] pattern.
Alveolar soft part sarcoma (ASPS). Large, polygonal cells of ASPS with distinct cell borders, eosinophilic granular cytoplasm and central vesicular nucleus having a prominent nucleolus admixed with rhabdoid cells having eccentric nuclei.
A: alveolar
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) typically presents as a slowly progressive, painless proptosis with eyelid swelling and dilatation of conjunctival vessels.
- Micro: The characteristic microscopic pattern includes an organoid or nest-like arrangement with a central discohesion, resulting in the alveolar pattern and a rich sinusoidal vascular network.
- Ancillary: The presence of intracytoplasmic rod-like/crystalline structures, which are PAS-positive and diastase-resistant, and strong nuclear TFE3 staining are key diagnostic features.
Reference Gallery:
Alveolar soft part sarcoma. Numerous intracytoplasmic PAS positive diastase resistant granules are seen.
Alveolar soft part sarcoma. Tumour cells show strong nuclear staining for TFE3.
Alveolar soft part sarcoma (ASPS). Large, polygonal cells of ASPS with distinct cell borders, eosinophilic granular cytoplasm and central vesicular nucleus having a prominent nucleolus admixed with rhabdoid cells having eccentric nuclei.
Orbital alveolar soft part sarcoma. Computed tomography showed a hyperdense, orbital mass extending to the apex and indenting the globe.

Q: A highly sensitive and characteristic immunohistochemical marker for Alveolar Soft Part Sarcoma is strong nuclear expression of [...].
Alveolar soft part sarcoma. Tumour cells show strong nuclear staining for TFE3.
A: TFE3
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) typically presents as a slowly progressive, painless proptosis with eyelid swelling and dilatation of conjunctival vessels.
- Micro: The characteristic microscopic pattern includes an organoid or nest-like arrangement with a central discohesion, resulting in the alveolar pattern and a rich sinusoidal vascular network.
- Ancillary: The presence of intracytoplasmic rod-like/crystalline structures, which are PAS-positive and diastase-resistant, and strong nuclear TFE3 staining are key diagnostic features.
Reference Gallery:
Alveolar soft part sarcoma. Numerous intracytoplasmic PAS positive diastase resistant granules are seen.
Alveolar soft part sarcoma. Tumour cells show strong nuclear staining for TFE3.
Alveolar soft part sarcoma (ASPS). Large, polygonal cells of ASPS with distinct cell borders, eosinophilic granular cytoplasm and central vesicular nucleus having a prominent nucleolus admixed with rhabdoid cells having eccentric nuclei.
Orbital alveolar soft part sarcoma. Computed tomography showed a hyperdense, orbital mass extending to the apex and indenting the globe.

Q: A classic histologic finding in Alveolar Soft Part Sarcoma is the presence of intracytoplasmic rod-like crystalline structures that are characteristically [...].
Alveolar soft part sarcoma. Numerous intracytoplasmic PAS positive diastase resistant granules are seen.
A: PAS-positive and diastase-resistant
Back Extra: Alveolar Soft Part Sarcoma
- Clinical: Alveolar Soft Part Sarcoma (ASPS) typically presents as a slowly progressive, painless proptosis with eyelid swelling and dilatation of conjunctival vessels.
- Micro: The characteristic microscopic pattern includes an organoid or nest-like arrangement with a central discohesion, resulting in the alveolar pattern and a rich sinusoidal vascular network.
- Ancillary: The presence of intracytoplasmic rod-like/crystalline structures, which are PAS-positive and diastase-resistant, and strong nuclear TFE3 staining are key diagnostic features.
Reference Gallery:
Alveolar soft part sarcoma. Numerous intracytoplasmic PAS positive diastase resistant granules are seen.
Alveolar soft part sarcoma. Tumour cells show strong nuclear staining for TFE3.
Alveolar soft part sarcoma (ASPS). Large, polygonal cells of ASPS with distinct cell borders, eosinophilic granular cytoplasm and central vesicular nucleus having a prominent nucleolus admixed with rhabdoid cells having eccentric nuclei.
Orbital alveolar soft part sarcoma. Computed tomography showed a hyperdense, orbital mass extending to the apex and indenting the globe.

Q: In conventional Epithelioid Sarcoma, plump spindle cells blend into larger polygonal epithelioid cells to form infiltrative granuloma-like nodules around areas of central [...].
Classic/conventional epithelioid sarcoma. Granulomatous nodule composed of polygonal epithelioid cells, accompanied by central necrosis.
A: necrosis
Back Extra: Epithelioid Sarcoma
- Clinical: Patients typically present with a mass which may cause globe displacement, and the disease is aggressive with a significant risk of local recurrence and metastasis.
- Micro: Conventional epithelioid sarcoma shows plump spindle cells blending into larger polygonal epithelioid cells, forming infiltrative sheets around necrosis. The proximal variant has more purely epithelioid carcinoma-like cells.
- Ancillary: Loss of SMARCB1 (INI1) expression is a key diagnostic marker for epithelioid sarcoma, and panel sequencing may detect inactivating mutations in SMARCB1.
Reference Gallery:
Classic/conventional epithelioid sarcoma. Granulomatous nodule composed of polygonal epithelioid cells, accompanied by central necrosis.
Proximal epithelioid sarcoma. Sheet-like arrangement of poorly differentiated carcinoma-like epithelioid cells with enlarged nuclei and prominent nucleoli.
Proximal epithelioid sarcoma. There is loss of expression of SMARCB1/INI1 in the nuclei of neoplastic tumour cells with retention in stromal and vascular nuclei.

Q: The proximal variant of Epithelioid Sarcoma is characterized by sheet-like arrangements of poorly differentiated, [...] cells with enlarged nuclei and prominent nucleoli.
Proximal epithelioid sarcoma. Sheet-like arrangement of poorly differentiated carcinoma-like epithelioid cells with enlarged nuclei and prominent nucleoli.
A: carcinoma-like
Back Extra: Epithelioid Sarcoma
- Clinical: Patients typically present with a mass which may cause globe displacement, and the disease is aggressive with a significant risk of local recurrence and metastasis.
- Micro: Conventional epithelioid sarcoma shows plump spindle cells blending into larger polygonal epithelioid cells, forming infiltrative sheets around necrosis. The proximal variant has more purely epithelioid carcinoma-like cells.
- Ancillary: Loss of SMARCB1 (INI1) expression is a key diagnostic marker for epithelioid sarcoma, and panel sequencing may detect inactivating mutations in SMARCB1.
Reference Gallery:
Classic/conventional epithelioid sarcoma. Granulomatous nodule composed of polygonal epithelioid cells, accompanied by central necrosis.
Proximal epithelioid sarcoma. Sheet-like arrangement of poorly differentiated carcinoma-like epithelioid cells with enlarged nuclei and prominent nucleoli.
Proximal epithelioid sarcoma. There is loss of expression of SMARCB1/INI1 in the nuclei of neoplastic tumour cells with retention in stromal and vascular nuclei.

Q: A key diagnostic feature of Epithelioid Sarcoma is the characteristic loss of nuclear expression of [...] in neoplastic cells.
Proximal epithelioid sarcoma. There is loss of expression of SMARCB1/INI1 in the nuclei of neoplastic tumour cells with retention in stromal and vascular nuclei.
A: SMARCB1 (INI1)
Back Extra: Epithelioid Sarcoma
- Clinical: Patients typically present with a mass which may cause globe displacement, and the disease is aggressive with a significant risk of local recurrence and metastasis.
- Micro: Conventional epithelioid sarcoma shows plump spindle cells blending into larger polygonal epithelioid cells, forming infiltrative sheets around necrosis. The proximal variant has more purely epithelioid carcinoma-like cells.
- Ancillary: Loss of SMARCB1 (INI1) expression is a key diagnostic marker for epithelioid sarcoma, and panel sequencing may detect inactivating mutations in SMARCB1.
Reference Gallery:
Classic/conventional epithelioid sarcoma. Granulomatous nodule composed of polygonal epithelioid cells, accompanied by central necrosis.
Proximal epithelioid sarcoma. Sheet-like arrangement of poorly differentiated carcinoma-like epithelioid cells with enlarged nuclei and prominent nucleoli.
Proximal epithelioid sarcoma. There is loss of expression of SMARCB1/INI1 in the nuclei of neoplastic tumour cells with retention in stromal and vascular nuclei.

Q: Immunohistochemically, PEComa characteristically demonstrates co-expression of muscle markers (e.g., SMA, desmin) and [...] markers (e.g., HMB45, Melan-A).
PEComa. HMB45 immunohistochemical expression in the cytoplasm of tumour cells.
PEComa. SMA immunohistochemistry focally expressed in perivascular epithelioid cells.
A: melanocytic
Back Extra: PEComa
- Clinical: PEComas in and around the eye usually present as slow-growing masses, with less frequent symptoms including proptosis, lid swelling, and loss of vision.
- Micro: PEComas typically show a nested growth pattern with epithelioid or spindled cells, or a mix thereof, surrounded by thin-walled capillaries.
- Ancillary: PEComas characteristically express both melanocytic markers (e.g., HMB45, melan-A, MITF) and muscle markers (e.g., SMA, desmin, caldesmon).
Reference Gallery:
PEComa. Nested and solid alveolar growth patterns are observed.
PEComa. Nested growth pattern of polygonal and epithelioid cells. The cells have a large oval nuclei with a prominent nucleoli. The cytoplasm is abundant, eosinophilic and granular.
PEComa. HMB45 immunohistochemical expression in the cytoplasm of tumour cells.
PEComa. SMA immunohistochemistry focally expressed in perivascular epithelioid cells.
PEComa. Diffuse and strong nuclear expression of TFE3 in tumour cells.

Q: Histologically, PEComa classically features a [...] growth pattern of epithelioid to spindled cells with prominent nucleoli and abundant, eosinophilic, granular cytoplasm.
PEComa. Nested and solid alveolar growth patterns are observed.
PEComa. Nested growth pattern of polygonal and epithelioid cells. The cells have a large oval nuclei with a prominent nucleoli. The cytoplasm is abundant, eosinophilic and granular.
A: nested
Back Extra: PEComa
- Clinical: PEComas in and around the eye usually present as slow-growing masses, with less frequent symptoms including proptosis, lid swelling, and loss of vision.
- Micro: PEComas typically show a nested growth pattern with epithelioid or spindled cells, or a mix thereof, surrounded by thin-walled capillaries.
- Ancillary: PEComas characteristically express both melanocytic markers (e.g., HMB45, melan-A, MITF) and muscle markers (e.g., SMA, desmin, caldesmon).
Reference Gallery:
PEComa. Nested and solid alveolar growth patterns are observed.
PEComa. Nested growth pattern of polygonal and epithelioid cells. The cells have a large oval nuclei with a prominent nucleoli. The cytoplasm is abundant, eosinophilic and granular.
PEComa. HMB45 immunohistochemical expression in the cytoplasm of tumour cells.
PEComa. SMA immunohistochemistry focally expressed in perivascular epithelioid cells.
PEComa. Diffuse and strong nuclear expression of TFE3 in tumour cells.

Q: A subset of PEComa tumors harbors gene fusions that result in diffuse and strong nuclear immunohistochemical expression of [...].
PEComa. Diffuse and strong nuclear expression of TFE3 in tumour cells.
A: TFE3
Back Extra: PEComa
- Clinical: PEComas in and around the eye usually present as slow-growing masses, with less frequent symptoms including proptosis, lid swelling, and loss of vision.
- Micro: PEComas typically show a nested growth pattern with epithelioid or spindled cells, or a mix thereof, surrounded by thin-walled capillaries.
- Ancillary: PEComas characteristically express both melanocytic markers (e.g., HMB45, melan-A, MITF) and muscle markers (e.g., SMA, desmin, caldesmon).
Reference Gallery:
PEComa. Nested and solid alveolar growth patterns are observed.
PEComa. Nested growth pattern of polygonal and epithelioid cells. The cells have a large oval nuclei with a prominent nucleoli. The cytoplasm is abundant, eosinophilic and granular.
PEComa. HMB45 immunohistochemical expression in the cytoplasm of tumour cells.
PEComa. SMA immunohistochemistry focally expressed in perivascular epithelioid cells.
PEComa. Diffuse and strong nuclear expression of TFE3 in tumour cells.

Q: Definitive diagnosis of Synovial Sarcoma requires identification of the pathognomonic [...] fusion gene, which can be demonstrated via FISH break-apart probes or diffuse nuclear immunohistochemical staining.
Synovial sarcoma, monophasic. Strong diffuse nuclear staining with SS18-SSX antibody.
Synovial sarcoma. FISH with SS18 break-apart probes shows a yellow signal corresponding to the closely apposed red and green signals (arrowhead) indicative of the absence of SS18 rearrangement (wild-type allele). The widely separated red and green signals (arrows) correspond to separation of SS18 gene loci, indicative of SS18 gene rearrangement.
A: SS18-SSX
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma can present insidiously with pain, proptosis, periorbital swelling, and diplopia, and is more common in adolescents and young adults.
- Micro: Monophasic synovial sarcoma is characterized by uniform spindle cells arranged in fascicles, with dense fibrosis and myxoid change in up to one-third of cases.
- Ancillary: The diagnosis of synovial sarcoma is confirmed by the presence of the SS18-SSX fusion gene, detected by FISH or immunohistochemistry.
Reference Gallery:
Synovial sarcoma. Axial CT-scan demonstrates a circumscribed weakly enhancing mass in superomedial orbit (arrow).
Synovial sarcoma, monophasic. Cellular fascicles of monotonous spindle cells with nuclear overlapping and scant collagenous matrix.
Synovial sarcoma, monophasic. Spindle cells in a coarsely collagenous, hyalinized stroma.
Synovial sarcoma, monophasic. Strong diffuse nuclear staining with SS18-SSX antibody.
Synovial sarcoma. FISH with SS18 break-apart probes shows a yellow signal corresponding to the closely apposed red and green signals (arrowhead) indicative of the absence of SS18 rearrangement (wild-type allele). The widely separated red and green signals (arrows) correspond to separation of SS18 gene loci, indicative of SS18 gene rearrangement.
Synovial sarcoma, monophasic. This SS shows myxoid stromal change.
Synovial sarcoma, macroscopic findings. White-tan cut surface with poorly defined margins.
Synovial sarcoma. Cellular arrangement of spindle cells with overlapping hyperchromatic nuclei and mitotic figures.
Synovial sarcoma, biphasic. Cuboidal epithelial cells arranged in glands and nests set in a background of a spindle cell sarcoma.
Synovial sarcoma, poorly differentiated. Small round hyperchromatic cells with brisk mitotic activity.

Q: Monophasic [...] is characterized by uniform spindle cells arranged in cellular fascicles with overlapping nuclei, and it can frequently exhibit prominent hyalinized collagen or myxoid stromal change.
Synovial sarcoma, monophasic. Cellular fascicles of monotonous spindle cells with nuclear overlapping and scant collagenous matrix.
Synovial sarcoma, monophasic. Spindle cells in a coarsely collagenous, hyalinized stroma.
Synovial sarcoma, monophasic. This SS shows myxoid stromal change.
A: Synovial Sarcoma
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma can present insidiously with pain, proptosis, periorbital swelling, and diplopia, and is more common in adolescents and young adults.
- Micro: Monophasic synovial sarcoma is characterized by uniform spindle cells arranged in fascicles, with dense fibrosis and myxoid change in up to one-third of cases.
- Ancillary: The diagnosis of synovial sarcoma is confirmed by the presence of the SS18-SSX fusion gene, detected by FISH or immunohistochemistry.
Reference Gallery:
Synovial sarcoma. Axial CT-scan demonstrates a circumscribed weakly enhancing mass in superomedial orbit (arrow).
Synovial sarcoma, monophasic. Cellular fascicles of monotonous spindle cells with nuclear overlapping and scant collagenous matrix.
Synovial sarcoma, monophasic. Spindle cells in a coarsely collagenous, hyalinized stroma.
Synovial sarcoma, monophasic. Strong diffuse nuclear staining with SS18-SSX antibody.
Synovial sarcoma. FISH with SS18 break-apart probes shows a yellow signal corresponding to the closely apposed red and green signals (arrowhead) indicative of the absence of SS18 rearrangement (wild-type allele). The widely separated red and green signals (arrows) correspond to separation of SS18 gene loci, indicative of SS18 gene rearrangement.
Synovial sarcoma, monophasic. This SS shows myxoid stromal change.
Synovial sarcoma, macroscopic findings. White-tan cut surface with poorly defined margins.
Synovial sarcoma. Cellular arrangement of spindle cells with overlapping hyperchromatic nuclei and mitotic figures.
Synovial sarcoma, biphasic. Cuboidal epithelial cells arranged in glands and nests set in a background of a spindle cell sarcoma.
Synovial sarcoma, poorly differentiated. Small round hyperchromatic cells with brisk mitotic activity.

Q: The biphasic variant of [...] is a distinct morphological subtype defined by a background of malignant spindle cells admixed with cuboidal epithelial cells forming discrete glands and nests.
Synovial sarcoma, biphasic. Cuboidal epithelial cells arranged in glands and nests set in a background of a spindle cell sarcoma.
A: Synovial Sarcoma
Back Extra: Synovial Sarcoma
- Clinical: Synovial sarcoma can present insidiously with pain, proptosis, periorbital swelling, and diplopia, and is more common in adolescents and young adults.
- Micro: Monophasic synovial sarcoma is characterized by uniform spindle cells arranged in fascicles, with dense fibrosis and myxoid change in up to one-third of cases.
- Ancillary: The diagnosis of synovial sarcoma is confirmed by the presence of the SS18-SSX fusion gene, detected by FISH or immunohistochemistry.
Reference Gallery:
Synovial sarcoma. Axial CT-scan demonstrates a circumscribed weakly enhancing mass in superomedial orbit (arrow).
Synovial sarcoma, monophasic. Cellular fascicles of monotonous spindle cells with nuclear overlapping and scant collagenous matrix.
Synovial sarcoma, monophasic. Spindle cells in a coarsely collagenous, hyalinized stroma.
Synovial sarcoma, monophasic. Strong diffuse nuclear staining with SS18-SSX antibody.
Synovial sarcoma. FISH with SS18 break-apart probes shows a yellow signal corresponding to the closely apposed red and green signals (arrowhead) indicative of the absence of SS18 rearrangement (wild-type allele). The widely separated red and green signals (arrows) correspond to separation of SS18 gene loci, indicative of SS18 gene rearrangement.
Synovial sarcoma, monophasic. This SS shows myxoid stromal change.
Synovial sarcoma, macroscopic findings. White-tan cut surface with poorly defined margins.
Synovial sarcoma. Cellular arrangement of spindle cells with overlapping hyperchromatic nuclei and mitotic figures.
Synovial sarcoma, biphasic. Cuboidal epithelial cells arranged in glands and nests set in a background of a spindle cell sarcoma.
Synovial sarcoma, poorly differentiated. Small round hyperchromatic cells with brisk mitotic activity.

Q: Morphologically, Angiosarcoma is characterized by focal vasoformative growth with multilayering of atypical endothelial cells that are reliably positive for ERG and [...].
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
A: CD31
Back Extra: Angiosarcoma
- Clinical: Angiosarcoma (AS) usually presents as a rapidly growing haemorrhagic mass or plaque, causing visual loss and ptosis.
- Micro: The spectrum of AS ranges from well to poorly differentiated lesions with atypical spindle or epithelioid endothelial cells and frequent mitotic figures.
- Ancillary: The most reliable immunohistochemical markers for AS are CD31 and ERG, with variable CD34 and frequent D2-40 co-expression.
Reference Gallery:
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.

Q: A characteristic molecular finding that strongly supports the diagnosis of irradiation-induced Angiosarcoma is the amplification of the [...] gene.
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
A: MYC
Back Extra: Angiosarcoma
- Clinical: Angiosarcoma (AS) usually presents as a rapidly growing haemorrhagic mass or plaque, causing visual loss and ptosis.
- Micro: The spectrum of AS ranges from well to poorly differentiated lesions with atypical spindle or epithelioid endothelial cells and frequent mitotic figures.
- Ancillary: The most reliable immunohistochemical markers for AS are CD31 and ERG, with variable CD34 and frequent D2-40 co-expression.
Reference Gallery:
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.

Q: When distinguishing Angiosarcoma from benign vascular lesions, immunohistochemistry demonstrates a loss of pericytic layers typically highlighted by [...].
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
A: alpha-SMA
Back Extra: Angiosarcoma
- Clinical: Angiosarcoma (AS) usually presents as a rapidly growing haemorrhagic mass or plaque, causing visual loss and ptosis.
- Micro: The spectrum of AS ranges from well to poorly differentiated lesions with atypical spindle or epithelioid endothelial cells and frequent mitotic figures.
- Ancillary: The most reliable immunohistochemical markers for AS are CD31 and ERG, with variable CD34 and frequent D2-40 co-expression.
Reference Gallery:
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.
Loss of pericytic layers by αSMA discriminates AS from benign vascular lesions. AS with keratin expression can mimic carcinomas. Cytology demonstrates loosely cohesive clusters and dispersed atypical often oval to spindled cells with pleomorphic variably hyperchromatic nuclei, nucleoli, mitotic and apoptotic figures. Sometimes cytoplasmic vacuoles are seen. MYC amplification may support the diagnosis of irradiation-induced AS and to a lesser extent (40%) UV-associated AS. Methylation profiling can be helpful in discriminating AS from other (vascular) lesions. Essential and desirable diagnostic criteria: At least focal vasoformative growth, Multilayering of endothelial cells in morphologically well-differentiated neoplasm, Nuclear atypia, increased mitoses, CD31 and ERG positivity. Staging is not recommended as the aggressive nature of AS does not align with soft tissue staging systems. AS of soft tissue is highly aggressive. 5-year overall survival is ~25-50%.

Q: In Epithelioid Haemangioma, the plump epithelioid endothelial cells often contain large cytoplasmic vacuoles referred to as [...], and they may protrude into vessel lumens creating a characteristic "tombstone" pattern.
Epithelioid haemangioma. Endothelial cells may have large cytoplasmic vacuoles (arrow), so-called “blister cells.” This orbital tumour has numerous stromal eosinophils.
Epithelioid haemangioma. Endothelial cells lining larger caliber vessels may protrude into the lumen with a “tombstone” pattern, as in this lacrimal gland tumour.
A: "blister cells"
Back Extra: Epithelioid Haemangioma
- Clinical: Clinical signs include eyelid fullness, ptosis, globe displacement/proptosis, and ocular motility restriction.
- Micro: Histologically, EH shows a lobular or multinodular proliferation of small vessels with plump epithelioid endothelial cells and a chronic inflammatory infiltrate.
- Ancillary: Endothelial cells express CD31, FLI1, and ERG, and may show focal CK and EMA expression.
Reference Gallery:
Epithelioid haemangioma. Prominent lymphoid follicles and intervening vascular proliferation are observed.
Epithelioid haemangioma. High power view showing proliferating vessels with epithelioid endothelial cells with abundant eosinophilic cytoplasm, round or oval nuclei, small nucleoli in some cells, and lack of vascular lumens. The stroma has a mixture of mononuclear leukocytes and eosinophils.
Epithelioid haemangioma. Endothelial cells may have large cytoplasmic vacuoles (arrow), so-called “blister cells.” This orbital tumour has numerous stromal eosinophils.
Epithelioid haemangioma. Endothelial cells lining larger caliber vessels may protrude into the lumen with a “tombstone” pattern, as in this lacrimal gland tumour.
Epithelioid haemangioma. Coronal T1 MRI of the right superior orbital epithelioid haemangioma.
Epithelioid haemangioma. Coronal T1 MRI with contrast of the right superior orbital epithelioid haemangioma.

Q: The stroma of an Epithelioid Haemangioma characteristically contains prominent lymphoid follicles and a dense inflammatory infiltrate that is distinctively rich in [...].
Epithelioid haemangioma. Prominent lymphoid follicles and intervening vascular proliferation are observed.
Epithelioid haemangioma. High power view showing proliferating vessels with epithelioid endothelial cells with abundant eosinophilic cytoplasm, round or oval nuclei, small nucleoli in some cells, and lack of vascular lumens. The stroma has a mixture of mononuclear leukocytes and eosinophils.
A: eosinophils
Back Extra: Epithelioid Haemangioma
- Clinical: Clinical signs include eyelid fullness, ptosis, globe displacement/proptosis, and ocular motility restriction.
- Micro: Histologically, EH shows a lobular or multinodular proliferation of small vessels with plump epithelioid endothelial cells and a chronic inflammatory infiltrate.
- Ancillary: Endothelial cells express CD31, FLI1, and ERG, and may show focal CK and EMA expression.
Reference Gallery:
Epithelioid haemangioma. Prominent lymphoid follicles and intervening vascular proliferation are observed.
Epithelioid haemangioma. High power view showing proliferating vessels with epithelioid endothelial cells with abundant eosinophilic cytoplasm, round or oval nuclei, small nucleoli in some cells, and lack of vascular lumens. The stroma has a mixture of mononuclear leukocytes and eosinophils.
Epithelioid haemangioma. Endothelial cells may have large cytoplasmic vacuoles (arrow), so-called “blister cells.” This orbital tumour has numerous stromal eosinophils.
Epithelioid haemangioma. Endothelial cells lining larger caliber vessels may protrude into the lumen with a “tombstone” pattern, as in this lacrimal gland tumour.
Epithelioid haemangioma. Coronal T1 MRI of the right superior orbital epithelioid haemangioma.
Epithelioid haemangioma. Coronal T1 MRI with contrast of the right superior orbital epithelioid haemangioma.

Q: A retinal [...] is a vascular tumor characterized histologically by numerous capillary-sized channels interspersed with distinctive stromal cells that possess foamy or clear cytoplasm.
Haemangioblastoma of the retina. A low-magnification photomicrograph of a retinal haemangioblastoma; there are numerous stromal cells and capillary-sized vessels.
Haemangioblastoma of the retina. A high magnification of a retinal haemangioblastoma shows the foamy/clear cytoplasm of stromal cells and numerous small vascular channels.
A: Haemangioblastoma
Back Extra: Haemangioblastoma
- Clinical: Haemangioblastomas can appear as flat or slightly raised clumps of capillary-sized vessels, with larger lesions often associated with serous retinal detachment and exudative changes.
- Micro: Haemangioblastomas are characterized by stromal cells with hyperchromatic nuclei and foamy cytoplasm, along with capillary-sized vascular channels.
- Ancillary: Immunohistochemistry shows stromal cells positive for inhibin, CD133, aquaporin, D2-40, and cytoplasmic brachyury, and negative for PAX2, PAX8, RCC, and EMA.
Reference Gallery:
Haemangioblastoma of the retina. A low-magnification photomicrograph of a retinal haemangioblastoma; there are numerous stromal cells and capillary-sized vessels.
Haemangioblastoma of the retina. A high magnification of a retinal haemangioblastoma shows the foamy/clear cytoplasm of stromal cells and numerous small vascular channels.

Q: In Haemangioblastoma, the characteristic interstitial [...] typically possess hyperchromatic nuclei and distinctive foamy or clear cytoplasm.
Haemangioblastoma of the retina. A high magnification of a retinal haemangioblastoma shows the foamy/clear cytoplasm of stromal cells and numerous small vascular channels.
A: stromal cells
Back Extra: Haemangioblastoma
- Clinical: Haemangioblastomas can appear as flat or slightly raised clumps of capillary-sized vessels, with larger lesions often associated with serous retinal detachment and exudative changes.
- Micro: Haemangioblastomas are characterized by stromal cells with hyperchromatic nuclei and foamy cytoplasm, along with capillary-sized vascular channels.
- Ancillary: Immunohistochemistry shows stromal cells positive for inhibin, CD133, aquaporin, D2-40, and cytoplasmic brachyury, and negative for PAX2, PAX8, RCC, and EMA.
Reference Gallery:
Haemangioblastoma of the retina. A low-magnification photomicrograph of a retinal haemangioblastoma; there are numerous stromal cells and capillary-sized vessels.
Haemangioblastoma of the retina. A high magnification of a retinal haemangioblastoma shows the foamy/clear cytoplasm of stromal cells and numerous small vascular channels.

Q: In Infantile Hemangioma, the endothelial cells characteristically show diffuse and strong immunohistochemical expression of [...].
Diagnosis: Infantile haemangioma. Vascular endothelium strongly and diffusely expresses GLUT1. Note GLUT1 expression in the red blood cells, an internal positive control.
A: GLUT1
Back Extra: Infantile Hemangioma
- Clinical: Infantile Hemangiomas appear as red masses soon after birth, undergo rapid growth up to 2 years, and involute by 48 months.
- Micro: Proliferative stage shows capillary-sized vascular channels lined by plump endothelial cells in a lobular arrangement.
- Ancillary: Endothelial cells are GLUT1 positive, which is a key marker for diagnosis.
Reference Gallery:
Diagnosis: Infantile haemangioma. Unencapsulated lesion, composed of lobular proliferation of capillary-sized vascular channels arranged around larger vessels.
Diagnosis: Infantile haemangioma. Higher magnification highlights plump endothelial cells lining the small caliber vascular channels.
Diagnosis: Involuting infantile haemangioma. Partially involuted infantile haemangioma following propranolol therapy demonstrates sclerosing vascular channels and apoptotic debris.
Diagnosis: Infantile haemangioma. Vascular endothelium strongly and diffusely expresses GLUT1. Note GLUT1 expression in the red blood cells, an internal positive control.
Diagnosis: Choroidal haemangioma. Fundus photograph showing a circumscribed choroidal haemangioma.

Q: During the proliferative stage, the characteristic histologic pattern of an Infantile Hemangioma is an unencapsulated, [...] proliferation of capillary-sized vascular channels lined by plump endothelial cells.
Diagnosis: Infantile haemangioma. Unencapsulated lesion, composed of lobular proliferation of capillary-sized vascular channels arranged around larger vessels.
Diagnosis: Infantile haemangioma. Higher magnification highlights plump endothelial cells lining the small caliber vascular channels.
A: lobular
Back Extra: Infantile Hemangioma
- Clinical: Infantile Hemangiomas appear as red masses soon after birth, undergo rapid growth up to 2 years, and involute by 48 months.
- Micro: Proliferative stage shows capillary-sized vascular channels lined by plump endothelial cells in a lobular arrangement.
- Ancillary: Endothelial cells are GLUT1 positive, which is a key marker for diagnosis.
Reference Gallery:
Diagnosis: Infantile haemangioma. Unencapsulated lesion, composed of lobular proliferation of capillary-sized vascular channels arranged around larger vessels.
Diagnosis: Infantile haemangioma. Higher magnification highlights plump endothelial cells lining the small caliber vascular channels.
Diagnosis: Involuting infantile haemangioma. Partially involuted infantile haemangioma following propranolol therapy demonstrates sclerosing vascular channels and apoptotic debris.
Diagnosis: Infantile haemangioma. Vascular endothelium strongly and diffusely expresses GLUT1. Note GLUT1 expression in the red blood cells, an internal positive control.
Diagnosis: Choroidal haemangioma. Fundus photograph showing a circumscribed choroidal haemangioma.

Q: The natural clinical course of an Infantile Hemangioma involves early rapid growth followed by spontaneous [...], a regressive phase that can be accelerated by propranolol therapy to reveal sclerosing vascular channels and apoptotic debris.
Diagnosis: Involuting infantile haemangioma. Partially involuted infantile haemangioma following propranolol therapy demonstrates sclerosing vascular channels and apoptotic debris.
A: involution
Back Extra: Infantile Hemangioma
- Clinical: Infantile Hemangiomas appear as red masses soon after birth, undergo rapid growth up to 2 years, and involute by 48 months.
- Micro: Proliferative stage shows capillary-sized vascular channels lined by plump endothelial cells in a lobular arrangement.
- Ancillary: Endothelial cells are GLUT1 positive, which is a key marker for diagnosis.
Reference Gallery:
Diagnosis: Infantile haemangioma. Unencapsulated lesion, composed of lobular proliferation of capillary-sized vascular channels arranged around larger vessels.
Diagnosis: Infantile haemangioma. Higher magnification highlights plump endothelial cells lining the small caliber vascular channels.
Diagnosis: Involuting infantile haemangioma. Partially involuted infantile haemangioma following propranolol therapy demonstrates sclerosing vascular channels and apoptotic debris.
Diagnosis: Infantile haemangioma. Vascular endothelium strongly and diffusely expresses GLUT1. Note GLUT1 expression in the red blood cells, an internal positive control.
Diagnosis: Choroidal haemangioma. Fundus photograph showing a circumscribed choroidal haemangioma.

Q: A rapidly growing, dome-shaped, red vascular mass on the eyelid or conjunctiva that frequently undergoes surface ulceration is a classic clinical presentation for [...].
Lobular capillary haemangioma of the eyelid skin. A dome-shaped ulcerated nodule in the upper eyelid in a 35-year-old man.
A: Lobular Capillary Haemangioma
Back Extra: Lobular Capillary Haemangioma
- Clinical: Lobular Capillary Haemangioma (LCH) typically presents as a rapidly growing, circumscribed, lobular, red, and occasionally ulcerated vascular mass, commonly found in the eyelid and conjunctiva.
- Micro: Histologically, LCH shows a lobular arrangement of numerous capillary-sized vessels lined by proliferating endothelial cells, often with a surrounding layer of pericytes and thinned, ulcerated overlying epithelium.
- Ancillary: Immunohistochemistry reveals that endothelial cells are positive for CD31, ERG, and CD34, and negative for D2-40 and GLUT1.
Reference Gallery:
Lobular capillary haemangioma of the conjunctiva. Lobules of capillary-sized vessels of varying canalization in the conjunctival substantia propria.
Lobular capillary haemangioma of the conjunctiva. A solid area of vascular endothelial proliferation with minimal canalization.
Lobular capillary haemangioma of the conjunctiva. A more mature area showing canalized capillary vessels.
Lobular capillary haemangioma of the conjunctiva. Sclerotic focus in lobular capillary haemangioma.
Lobular capillary haemangioma of the eyelid skin. A dome-shaped ulcerated nodule in the upper eyelid in a 35-year-old man.
Lobular capillary haemangioma of the eyelid skin. Lobular proliferation of small vascular channels.
Lobular capillary haemangioma of the eyelid skin. D2-40 highlights entrapped lymphatic channels and is negative in the lesional cells.
Lobular capillary haemangioma of the eyelid skin. CD31 is diffusely positive in vascular endothelial cells.
Lobular capillary haemangioma of the eyelid skin. GLUT1 decorates red blood cells in the vascular lumina and is negative in lesional cells.

Q: Microscopically, [...] is characterized by a circumscribed, lobular arrangement of numerous capillary-sized vessels lined by proliferating endothelial cells.
Lobular capillary haemangioma of the conjunctiva. Lobules of capillary-sized vessels of varying canalization in the conjunctival substantia propria.
Lobular capillary haemangioma of the eyelid skin. Lobular proliferation of small vascular channels.
A: Lobular Capillary Haemangioma
Back Extra: Lobular Capillary Haemangioma
- Clinical: Lobular Capillary Haemangioma (LCH) typically presents as a rapidly growing, circumscribed, lobular, red, and occasionally ulcerated vascular mass, commonly found in the eyelid and conjunctiva.
- Micro: Histologically, LCH shows a lobular arrangement of numerous capillary-sized vessels lined by proliferating endothelial cells, often with a surrounding layer of pericytes and thinned, ulcerated overlying epithelium.
- Ancillary: Immunohistochemistry reveals that endothelial cells are positive for CD31, ERG, and CD34, and negative for D2-40 and GLUT1.
Reference Gallery:
Lobular capillary haemangioma of the conjunctiva. Lobules of capillary-sized vessels of varying canalization in the conjunctival substantia propria.
Lobular capillary haemangioma of the conjunctiva. A solid area of vascular endothelial proliferation with minimal canalization.
Lobular capillary haemangioma of the conjunctiva. A more mature area showing canalized capillary vessels.
Lobular capillary haemangioma of the conjunctiva. Sclerotic focus in lobular capillary haemangioma.
Lobular capillary haemangioma of the eyelid skin. A dome-shaped ulcerated nodule in the upper eyelid in a 35-year-old man.
Lobular capillary haemangioma of the eyelid skin. Lobular proliferation of small vascular channels.
Lobular capillary haemangioma of the eyelid skin. D2-40 highlights entrapped lymphatic channels and is negative in the lesional cells.
Lobular capillary haemangioma of the eyelid skin. CD31 is diffusely positive in vascular endothelial cells.
Lobular capillary haemangioma of the eyelid skin. GLUT1 decorates red blood cells in the vascular lumina and is negative in lesional cells.

Q: Immunohistochemically, the lesional endothelial cells in Lobular Capillary Haemangioma can be distinguished from those in infantile hemangiomas because they are characteristically negative for [...].
Lobular capillary haemangioma of the eyelid skin. GLUT1 decorates red blood cells in the vascular lumina and is negative in lesional cells.
A: GLUT1
Back Extra: Lobular Capillary Haemangioma
- Clinical: Lobular Capillary Haemangioma (LCH) typically presents as a rapidly growing, circumscribed, lobular, red, and occasionally ulcerated vascular mass, commonly found in the eyelid and conjunctiva.
- Micro: Histologically, LCH shows a lobular arrangement of numerous capillary-sized vessels lined by proliferating endothelial cells, often with a surrounding layer of pericytes and thinned, ulcerated overlying epithelium.
- Ancillary: Immunohistochemistry reveals that endothelial cells are positive for CD31, ERG, and CD34, and negative for D2-40 and GLUT1.
Reference Gallery:
Lobular capillary haemangioma of the conjunctiva. Lobules of capillary-sized vessels of varying canalization in the conjunctival substantia propria.
Lobular capillary haemangioma of the conjunctiva. A solid area of vascular endothelial proliferation with minimal canalization.
Lobular capillary haemangioma of the conjunctiva. A more mature area showing canalized capillary vessels.
Lobular capillary haemangioma of the conjunctiva. Sclerotic focus in lobular capillary haemangioma.
Lobular capillary haemangioma of the eyelid skin. A dome-shaped ulcerated nodule in the upper eyelid in a 35-year-old man.
Lobular capillary haemangioma of the eyelid skin. Lobular proliferation of small vascular channels.
Lobular capillary haemangioma of the eyelid skin. D2-40 highlights entrapped lymphatic channels and is negative in the lesional cells.
Lobular capillary haemangioma of the eyelid skin. CD31 is diffusely positive in vascular endothelial cells.
Lobular capillary haemangioma of the eyelid skin. GLUT1 decorates red blood cells in the vascular lumina and is negative in lesional cells.

Q: A multi-loculated, clear cystic lesion on the conjunctiva causing ocular surface irritation is the typical clinical presentation of [...].
Conjunctival lymphangiectasia. Lymphangiectasis of the medial conjunctiva showing a multi-loculated, clear cystic lesion.
A: Lymphangiectasia
Back Extra: Lymphangiectasia
- Clinical: Lymphangiectasia presents with ocular surface irritation and often involves the temporal bulbar conjunctiva.
- Micro: Microscopy reveals dilated lymphatic channels lined by flattened endothelial cells, with proteinaceous material and lymphocyte clusters in the lumen.
- Ancillary: Immunohistochemistry shows CD31, CD34, and D2-40 positivity in the endothelial cells.
Reference Gallery:
Conjunctival lymphangiectasia. Dilation of a conjunctival lymphatic channel with luminal eosinophilic proteinaceous material and the surrounding oedematous and chronically inflamed substantia propria.
Conjunctival lymphangiectasia. Higher magnification showing flattened endothelial cells lining the fibrous wall of an ectatic lymphatic channel.
Conjunctival lymphangiectasia. Lymphangiectasis of the medial conjunctiva showing a multi-loculated, clear cystic lesion.

Q: Microscopically, Lymphangiectasia is characterized by markedly dilated lymphatic channels lined by flattened endothelial cells and often containing luminal eosinophilic [...].
Conjunctival lymphangiectasia. Dilation of a conjunctival lymphatic channel with luminal eosinophilic proteinaceous material and the surrounding oedematous and chronically inflamed substantia propria.
Conjunctival lymphangiectasia. Higher magnification showing flattened endothelial cells lining the fibrous wall of an ectatic lymphatic channel.
A: proteinaceous material
Back Extra: Lymphangiectasia
- Clinical: Lymphangiectasia presents with ocular surface irritation and often involves the temporal bulbar conjunctiva.
- Micro: Microscopy reveals dilated lymphatic channels lined by flattened endothelial cells, with proteinaceous material and lymphocyte clusters in the lumen.
- Ancillary: Immunohistochemistry shows CD31, CD34, and D2-40 positivity in the endothelial cells.
Reference Gallery:
Conjunctival lymphangiectasia. Dilation of a conjunctival lymphatic channel with luminal eosinophilic proteinaceous material and the surrounding oedematous and chronically inflamed substantia propria.
Conjunctival lymphangiectasia. Higher magnification showing flattened endothelial cells lining the fibrous wall of an ectatic lymphatic channel.
Conjunctival lymphangiectasia. Lymphangiectasis of the medial conjunctiva showing a multi-loculated, clear cystic lesion.

Q: Histologically, a Masson tumor features papillary and interconnecting fibrous trabeculae lined by a single layer of endothelial cells, which characteristically form within organizing [...].
Diagnosis: Masson tumour. Higher magnification demonstrates a thrombus with partial recanalization and vascular proliferation.
Diagnosis: Masson tumour. The lesion is composed of papillary and interconnecting fibrous trabeculae lined by a single layer of endothelial cells.
A: fibrin thrombi
Back Extra: Masson Tumour
- Clinical: Masson tumours present as painless, slow-growing, solid or cystic, red-purple vascular masses, often in the eyelids, orbit, or conjunctiva.
- Micro: The lesion is a circumscribed mass with papillary and interconnecting fibrous trabeculae lined by a single layer of endothelial cells, often within fibrin thrombi.
- Ancillary: Immunohistochemistry shows positivity for CD31, CD34, ERG, and SMA, which is generally not required for diagnosis.
Reference Gallery:
Diagnosis: Masson tumour. Vascular proliferation in a background of organizing haemorrhage within a dilated varix.
Diagnosis: Masson tumour. Higher magnification demonstrates a thrombus with partial recanalization and vascular proliferation.
Diagnosis: Masson tumour. The lesion is composed of papillary and interconnecting fibrous trabeculae lined by a single layer of endothelial cells.
Diagnosis: Masson tumour. The flattened endothelial cells express CD31.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Endothelial proliferation within a thrombus associated with lymphatic-venous malformation.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Higher magnification of endothelial proliferation.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Endothelial proliferation, arranged in a monolayer, is highlighted with CD34.

Q: A benign intravascular lesion characterized by papillary endothelial proliferation associated with an organizing, recanalizing thrombus is diagnosed as a [...].
Diagnosis: Masson tumour. Vascular proliferation in a background of organizing haemorrhage within a dilated varix.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Endothelial proliferation within a thrombus associated with lymphatic-venous malformation.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Higher magnification of endothelial proliferation.
A: Masson tumor
Back Extra: Masson Tumour
- Clinical: Masson tumours present as painless, slow-growing, solid or cystic, red-purple vascular masses, often in the eyelids, orbit, or conjunctiva.
- Micro: The lesion is a circumscribed mass with papillary and interconnecting fibrous trabeculae lined by a single layer of endothelial cells, often within fibrin thrombi.
- Ancillary: Immunohistochemistry shows positivity for CD31, CD34, ERG, and SMA, which is generally not required for diagnosis.
Reference Gallery:
Diagnosis: Masson tumour. Vascular proliferation in a background of organizing haemorrhage within a dilated varix.
Diagnosis: Masson tumour. Higher magnification demonstrates a thrombus with partial recanalization and vascular proliferation.
Diagnosis: Masson tumour. The lesion is composed of papillary and interconnecting fibrous trabeculae lined by a single layer of endothelial cells.
Diagnosis: Masson tumour. The flattened endothelial cells express CD31.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Endothelial proliferation within a thrombus associated with lymphatic-venous malformation.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Higher magnification of endothelial proliferation.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Endothelial proliferation, arranged in a monolayer, is highlighted with CD34.

Q: In a Masson tumor, the monolayer of proliferating cells lining the interconnecting fibrous trabeculae represents an endothelial process, which can be highlighted by immunohistochemical stains for CD34, ERG, and [...].
Diagnosis: Masson tumour. The flattened endothelial cells express CD31.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Endothelial proliferation, arranged in a monolayer, is highlighted with CD34.
A: CD31
Back Extra: Masson Tumour
- Clinical: Masson tumours present as painless, slow-growing, solid or cystic, red-purple vascular masses, often in the eyelids, orbit, or conjunctiva.
- Micro: The lesion is a circumscribed mass with papillary and interconnecting fibrous trabeculae lined by a single layer of endothelial cells, often within fibrin thrombi.
- Ancillary: Immunohistochemistry shows positivity for CD31, CD34, ERG, and SMA, which is generally not required for diagnosis.
Reference Gallery:
Diagnosis: Masson tumour. Vascular proliferation in a background of organizing haemorrhage within a dilated varix.
Diagnosis: Masson tumour. Higher magnification demonstrates a thrombus with partial recanalization and vascular proliferation.
Diagnosis: Masson tumour. The lesion is composed of papillary and interconnecting fibrous trabeculae lined by a single layer of endothelial cells.
Diagnosis: Masson tumour. The flattened endothelial cells express CD31.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Endothelial proliferation within a thrombus associated with lymphatic-venous malformation.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Higher magnification of endothelial proliferation.
Diagnosis: Masson tumour in association with lymphatic-venous malformation. Endothelial proliferation, arranged in a monolayer, is highlighted with CD34.

Q: Patients with [...] characteristically present with rapidly progressive vision loss, exudative retinal detachment, rapidly progressive cataracts, and multiple red-black spots at the level of the choroid.
Bilateral diffuse uveal melanocytic proliferation. A macroscopic image of involvement of the entire uveal tract (arrows) in an enucleated eye. Most of the lesion is lightly pigmented to amelanotic but some pigmented areas are present posteriorly (left in the image). The other eye was similarly affected.
Bilateral diffuse uveal melanocytic proliferation. Optomap false colour clinical images of both fundi that show multiple bilateral red-black spots at the level of the choroid.
A: bilateral diffuse uveal melanocytic proliferation
Q: Bilateral Diffuse Uveal Melanocytic Proliferation
- Clinical: Patients with [...] often experience rapidly progressive bilateral vision loss, exudative retinal detachment, and rapidly progressive cataracts.
- Micro: The uvea is thickened by a proliferation of spindle-shaped melanocytic cells that spare the choriocapillaris in [...].
- Ancillary: Melanocytes in [...] stain positively for Melan-A, HMB45, and SOX10 but do not overexpress p53 and show a low proliferation rate with Ki67 and Cyclin D1.
Reference Gallery:
Bilateral diffuse uveal melanocytic proliferation. A macroscopic image of involvement of the entire uveal tract (arrows) in an enucleated eye. Most of the lesion is lightly pigmented to amelanotic but some pigmented areas are present posteriorly (left in the image). The other eye was similarly affected.
Bilateral diffuse uveal melanocytic proliferation. Bilateral diffuse uveal melanocytic proliferation. Low power histology from the same macroscopic specimen <<#32376>>, showing the thickening of the entire uveal tract (arrows). Note the nodular thickening of the ciliary body anteriorly and the rather flatter thickening of the choroid posteriorly.
Bilateral diffuse uveal melanocytic proliferation. Higher power macroscopic image showing the diffuse tan-coloured expansion of the choroid.
Bilateral diffuse uveal melanocytic proliferation. Pigmented epithelioid cell area of the lesion.
Bilateral diffuse uveal melanocytic proliferation. The choroid shows a syncytical arrangement of bland proliferating amelanotic spindle cells that spare the choriocapillaris.
Bilateral diffuse uveal melanocytic proliferation. The choroid shows abundant, very sparsely pigmented, spindle-shaped proliferating melanocytes.
Bilateral diffuse uveal melanocytic proliferation. Optomap false colour clinical images of both fundi that show multiple bilateral red-black spots at the level of the choroid.
Bilateral diffuse uveal melanocytic proliferation. Optical computed tomography showing destruction of the RPE.
Bilateral diffuse uveal melanocytic proliferation. Optical computed tomography following intravitreal steroids showing resolution of the exudative detachment.
A: bilateral diffuse uveal melanocytic proliferation; bilateral diffuse uveal melanocytic proliferation; bilateral diffuse uveal melanocytic proliferation

Q: In bilateral diffuse uveal melanocytic proliferation, the uvea is characteristically thickened by a proliferation of bland, spindle-shaped melanocytic cells that spare the [...].
Bilateral diffuse uveal melanocytic proliferation. Bilateral diffuse uveal melanocytic proliferation. Low power histology from the same macroscopic specimen <<#32376>>, showing the thickening of the entire uveal tract (arrows). Note the nodular thickening of the ciliary body anteriorly and the rather flatter thickening of the choroid posteriorly.
Bilateral diffuse uveal melanocytic proliferation. The choroid shows a syncytical arrangement of bland proliferating amelanotic spindle cells that spare the choriocapillaris.
Bilateral diffuse uveal melanocytic proliferation. The choroid shows abundant, very sparsely pigmented, spindle-shaped proliferating melanocytes.
A: choriocapillaris
Q: Bilateral Diffuse Uveal Melanocytic Proliferation
- Clinical: Patients with [...] often experience rapidly progressive bilateral vision loss, exudative retinal detachment, and rapidly progressive cataracts.
- Micro: The uvea is thickened by a proliferation of spindle-shaped melanocytic cells that spare the choriocapillaris in [...].
- Ancillary: Melanocytes in [...] stain positively for Melan-A, HMB45, and SOX10 but do not overexpress p53 and show a low proliferation rate with Ki67 and Cyclin D1.
Reference Gallery:
Bilateral diffuse uveal melanocytic proliferation. A macroscopic image of involvement of the entire uveal tract (arrows) in an enucleated eye. Most of the lesion is lightly pigmented to amelanotic but some pigmented areas are present posteriorly (left in the image). The other eye was similarly affected.
Bilateral diffuse uveal melanocytic proliferation. Bilateral diffuse uveal melanocytic proliferation. Low power histology from the same macroscopic specimen <<#32376>>, showing the thickening of the entire uveal tract (arrows). Note the nodular thickening of the ciliary body anteriorly and the rather flatter thickening of the choroid posteriorly.
Bilateral diffuse uveal melanocytic proliferation. Higher power macroscopic image showing the diffuse tan-coloured expansion of the choroid.
Bilateral diffuse uveal melanocytic proliferation. Pigmented epithelioid cell area of the lesion.
Bilateral diffuse uveal melanocytic proliferation. The choroid shows a syncytical arrangement of bland proliferating amelanotic spindle cells that spare the choriocapillaris.
Bilateral diffuse uveal melanocytic proliferation. The choroid shows abundant, very sparsely pigmented, spindle-shaped proliferating melanocytes.
Bilateral diffuse uveal melanocytic proliferation. Optomap false colour clinical images of both fundi that show multiple bilateral red-black spots at the level of the choroid.
Bilateral diffuse uveal melanocytic proliferation. Optical computed tomography showing destruction of the RPE.
Bilateral diffuse uveal melanocytic proliferation. Optical computed tomography following intravitreal steroids showing resolution of the exudative detachment.
A: bilateral diffuse uveal melanocytic proliferation; bilateral diffuse uveal melanocytic proliferation; bilateral diffuse uveal melanocytic proliferation

Q: Clinically and microscopically, [...] present as typically asymptomatic, small, flat, pigmented lesions that often show associated drusen and retinal pigment epithelium atrophy.
Common choroidal naevus. Small choroidal naevus infero-temporal to the left optic disc.
Choroidal naevus. An incidental naevus in a postmortem donor eye; the retina was detached and the retinal pigment epithelium disrupted. A pigmented spindle cell naevus in the outer choroid. A PAS-positive drusen is also observed. PAS stain.
A: Choroidal and Ciliary Body Naevi
Back Extra: Choroidal and Ciliary Body Naevi
- Clinical: Choroidal and ciliary body naevi are usually asymptomatic and appear as small, flat, pigmented lesions with a greyish surface, often showing drusen and retinal pigment epithelium atrophy.
- Micro: Histologically, choroidal and ciliary body naevi are composed of variably pigmented polygonal and spindle cells with bland nuclei, with possible stromal thickening and sparing of the choriocapillaris.
- Ancillary: Choroidal and ciliary body naevi can be distinguished from melanomas by the absence of genetic aberrations such as mutations in GNAQ, GNA11, and CYSTLR2, and the lack of loss of nuclear BAP1 immunostaining.
Reference Gallery:
Common choroidal naevus. Small choroidal naevus infero-temporal to the left optic disc.
Common choroidal naevus. Fundus autofluorescence image showing no retinal pigment epithelial abnormalities over a flat naevus.
Common choroidal naevus. Optical coherence imaging showing a flat choroidal naevus with no abnormalities in the overlying retinal pigment epithelium and sensory retina.
Melanocytic choroidal tumour of indeterminate malignancy. Colour photograph showing a superotemporal melanocytic choroidal tumour of uncertain malignancy.
Melanocytic choroidal tumour of indeterminate malignancy. Fundus autofluorescence image showing the tumour to be hypo-autofluorescent with adjacent hyper-autofluorescence caused by serous retinal detachment.
Melanocytic choroidal tumour of indeterminate malignancy. Optical coherence tomography showing disorganisation of the retinal pigment epithelium and outer sensory retina with subretinal fluid over the tumour.
Melanocytic choroidal tumour of indeterminate malignancy. B-scan ultrasound showing the tumour to be dome shaped, with a basal diameter of 5.5 mm, a thickness of 1.6 mm, and high internal acoustic reflectivity.
Melanocytic choroidal naevus. Melanocytic choroidal naevus. Pigmented naevus cells are densely packed and thicken the choroid, with sparing of the choriocapillaris and inconspicuous tumour vasculature. Haematoxylin-eosin stain.
Choroidal naevus. Sagittal-oblique 3 Tesla MR-image showing enhancement of the naevus after contrast administration.
Choroidal naevus. An incidental naevus in a postmortem donor eye; the retina was detached and the retinal pigment epithelium disrupted. A pigmented spindle cell naevus in the outer choroid. A PAS-positive drusen is also observed. PAS stain.

Q: Histologically, Choroidal and Ciliary Body Naevi are composed of bland, variably pigmented polygonal and spindle cells that thicken the stroma but characteristically demonstrate sparing of the [...].
Melanocytic choroidal naevus. Melanocytic choroidal naevus. Pigmented naevus cells are densely packed and thicken the choroid, with sparing of the choriocapillaris and inconspicuous tumour vasculature. Haematoxylin-eosin stain.
A: choriocapillaris
Back Extra: Choroidal and Ciliary Body Naevi
- Clinical: Choroidal and ciliary body naevi are usually asymptomatic and appear as small, flat, pigmented lesions with a greyish surface, often showing drusen and retinal pigment epithelium atrophy.
- Micro: Histologically, choroidal and ciliary body naevi are composed of variably pigmented polygonal and spindle cells with bland nuclei, with possible stromal thickening and sparing of the choriocapillaris.
- Ancillary: Choroidal and ciliary body naevi can be distinguished from melanomas by the absence of genetic aberrations such as mutations in GNAQ, GNA11, and CYSTLR2, and the lack of loss of nuclear BAP1 immunostaining.
Reference Gallery:
Common choroidal naevus. Small choroidal naevus infero-temporal to the left optic disc.
Common choroidal naevus. Fundus autofluorescence image showing no retinal pigment epithelial abnormalities over a flat naevus.
Common choroidal naevus. Optical coherence imaging showing a flat choroidal naevus with no abnormalities in the overlying retinal pigment epithelium and sensory retina.
Melanocytic choroidal tumour of indeterminate malignancy. Colour photograph showing a superotemporal melanocytic choroidal tumour of uncertain malignancy.
Melanocytic choroidal tumour of indeterminate malignancy. Fundus autofluorescence image showing the tumour to be hypo-autofluorescent with adjacent hyper-autofluorescence caused by serous retinal detachment.
Melanocytic choroidal tumour of indeterminate malignancy. Optical coherence tomography showing disorganisation of the retinal pigment epithelium and outer sensory retina with subretinal fluid over the tumour.
Melanocytic choroidal tumour of indeterminate malignancy. B-scan ultrasound showing the tumour to be dome shaped, with a basal diameter of 5.5 mm, a thickness of 1.6 mm, and high internal acoustic reflectivity.
Melanocytic choroidal naevus. Melanocytic choroidal naevus. Pigmented naevus cells are densely packed and thicken the choroid, with sparing of the choriocapillaris and inconspicuous tumour vasculature. Haematoxylin-eosin stain.
Choroidal naevus. Sagittal-oblique 3 Tesla MR-image showing enhancement of the naevus after contrast administration.
Choroidal naevus. An incidental naevus in a postmortem donor eye; the retina was detached and the retinal pigment epithelium disrupted. A pigmented spindle cell naevus in the outer choroid. A PAS-positive drusen is also observed. PAS stain.

Q: Grossly, Uveal Melanocytoma typically presents as a dark-gray to black, heavily pigmented [...] mass that can elevate the retina.
Ciliary body melanocytoma. A resection specimen shows a heavily pigmented dome-shaped mass.
A: dome-shaped
Back Extra: Uveal Melanocytoma
- Clinical: Uveal melanocytoma may clinically be similar to an ordinary iris, ciliary body, or choroidal naevus or a small to medium-sized melanoma. Most choroidal melanocytomas form a discoid or dome-shaped dark-gray to black mass that elevates the retina.
- Micro: Uveal melanocytomas are composed of large, polygonal cells with abundant intracytoplasmic melanin pigment that obscures cellular and nuclear details. Bleaching of melanin is required to adequately evaluate the tumour cells.
- Ancillary: Diagnostic fine needle aspiration biopsies of melanocytomas show large, ovoid cells with small centrally located nuclei and heavily pigmented cytoplasm. The cells are immunoreactive for melanocytic markers and show rare or no cells in cycle with Ki67 immunostaining.
Reference Gallery:
Ciliary body melanocytoma. An unbleached section shows heavily melanised, polygonal melanocytic cells that are artefactually separated. Their nuclei are central to peripheral.
Ciliary body melanocytoma. A resection specimen shows a heavily pigmented dome-shaped mass.
Uveal melanocytoma. Polyhedral tumour cells with abundant cytoplasmic pigmentation that obscures nuclear features.
Uveal melanocytoma. Bleaching allows for removal of cytoplasmic melanin pigment granules, revealing tumour cells with low nuclear-to-cytoplasmic ratio and small round nuclei with inconspicuous nucleoli.

Q: Histologically, Uveal Melanocytoma consists of large, polygonal cells packed with abundant intracytoplasmic [...] pigment that characteristically obscures cellular and nuclear details.
Ciliary body melanocytoma. An unbleached section shows heavily melanised, polygonal melanocytic cells that are artefactually separated. Their nuclei are central to peripheral.
Uveal melanocytoma. Polyhedral tumour cells with abundant cytoplasmic pigmentation that obscures nuclear features.
A: melanin
Back Extra: Uveal Melanocytoma
- Clinical: Uveal melanocytoma may clinically be similar to an ordinary iris, ciliary body, or choroidal naevus or a small to medium-sized melanoma. Most choroidal melanocytomas form a discoid or dome-shaped dark-gray to black mass that elevates the retina.
- Micro: Uveal melanocytomas are composed of large, polygonal cells with abundant intracytoplasmic melanin pigment that obscures cellular and nuclear details. Bleaching of melanin is required to adequately evaluate the tumour cells.
- Ancillary: Diagnostic fine needle aspiration biopsies of melanocytomas show large, ovoid cells with small centrally located nuclei and heavily pigmented cytoplasm. The cells are immunoreactive for melanocytic markers and show rare or no cells in cycle with Ki67 immunostaining.
Reference Gallery:
Ciliary body melanocytoma. An unbleached section shows heavily melanised, polygonal melanocytic cells that are artefactually separated. Their nuclei are central to peripheral.
Ciliary body melanocytoma. A resection specimen shows a heavily pigmented dome-shaped mass.
Uveal melanocytoma. Polyhedral tumour cells with abundant cytoplasmic pigmentation that obscures nuclear features.
Uveal melanocytoma. Bleaching allows for removal of cytoplasmic melanin pigment granules, revealing tumour cells with low nuclear-to-cytoplasmic ratio and small round nuclei with inconspicuous nucleoli.

Q: Because of heavy pigmentation in Uveal Melanocytoma, microscopic evaluation requires [...] to adequately evaluate the tumor cells, revealing a low nuclear-to-cytoplasmic ratio and small, bland nuclei.
Uveal melanocytoma. Polyhedral tumour cells with abundant cytoplasmic pigmentation that obscures nuclear features.
Uveal melanocytoma. Bleaching allows for removal of cytoplasmic melanin pigment granules, revealing tumour cells with low nuclear-to-cytoplasmic ratio and small round nuclei with inconspicuous nucleoli.
A: bleaching
Back Extra: Uveal Melanocytoma
- Clinical: Uveal melanocytoma may clinically be similar to an ordinary iris, ciliary body, or choroidal naevus or a small to medium-sized melanoma. Most choroidal melanocytomas form a discoid or dome-shaped dark-gray to black mass that elevates the retina.
- Micro: Uveal melanocytomas are composed of large, polygonal cells with abundant intracytoplasmic melanin pigment that obscures cellular and nuclear details. Bleaching of melanin is required to adequately evaluate the tumour cells.
- Ancillary: Diagnostic fine needle aspiration biopsies of melanocytomas show large, ovoid cells with small centrally located nuclei and heavily pigmented cytoplasm. The cells are immunoreactive for melanocytic markers and show rare or no cells in cycle with Ki67 immunostaining.
Reference Gallery:
Ciliary body melanocytoma. An unbleached section shows heavily melanised, polygonal melanocytic cells that are artefactually separated. Their nuclei are central to peripheral.
Ciliary body melanocytoma. A resection specimen shows a heavily pigmented dome-shaped mass.
Uveal melanocytoma. Polyhedral tumour cells with abundant cytoplasmic pigmentation that obscures nuclear features.
Uveal melanocytoma. Bleaching allows for removal of cytoplasmic melanin pigment granules, revealing tumour cells with low nuclear-to-cytoplasmic ratio and small round nuclei with inconspicuous nucleoli.

Q: In Choroidal and Ciliary Body Melanoma, loss of [...] protein expression by immunohistochemistry is strongly associated with a high risk of metastasis.
Choroidal melanoma. Immunohistiochemistry for BAP1 labels the nuclei in this BAP1-preserved case.
Choroidal melanoma. BAP1 loss. Immunohistochemistry for BAP1 shows no expression in the nuclei.
A: BAP1
Back Extra: Choroidal and Ciliary Body Melanoma
- Clinical: Approximately 25% of patients with Choroidal and Ciliary Body Melanoma have no symptoms and are diagnosed during a routine eye examination. Symptoms include photopsia, floaters, and loss of vision.
- Micro: Choroidal and Ciliary Body Melanomas can be classified into four morphological subtypes: spindle A, spindle B, epithelioid, and mixed. Epithelioid cells are non-cohesive with large, round nuclei and abundant, eosinophilic cytoplasm.
- Ancillary: Loss of BAP1 protein by immunohistochemistry is strongly associated with a high risk of metastasis in Choroidal and Ciliary Body Melanomas.
Reference Gallery:
Choroidal melanoma. Immunohistiochemistry for BAP1 labels the nuclei in this BAP1-preserved case.
Choroidal melanoma. BAP1 loss. Immunohistochemistry for BAP1 shows no expression in the nuclei.
Choroidal melanoma. Fundus photograph showing a mushroom shaped choroidal tumour.
Choroidal melanoma. Ultrasound A-scan showing low internal reflectivity in a choroid mass.
Choroidal melanoma. Ultrasound scan showing a mushroom-shaped mass arising from the choroid.
Choroidal melanoma. Typical presentation of a choroidal melanoma on Magnetic Resonance Imaging. The mass appears iso-intense to the choroid on T1-weighted images and enhances after contrast administration (CE T1). On T2-weighted images it is slightly hyperintense compared to the extra-ocular muscles. Posterior and anterior of the mass small retinal detachments can be seen, which do not enhance on CE T1 and are slightly hypointense compared to the melanoma on T2. On perfusion weighted imaging the choroidal melanoma shows a typical wash-out curve.
Choroidal melanoma. MRI showing an intraocular mass in the right eye.
Choroidal melanoma. US echography and Doppler showing an intense circulation of blood in intratumoral neovessels suggestive of an uveal melanoma.
Choroidal melanoma. US echography of showing an anterior intraocular tumour.

Q: A classic clinical and radiologic finding in Choroidal and Ciliary Body Melanoma is a [...]-shaped intraocular mass, which is often classically visualized on ultrasound or fundus photography.
Choroidal melanoma. Fundus photograph showing a mushroom shaped choroidal tumour.
Choroidal melanoma. Ultrasound scan showing a mushroom-shaped mass arising from the choroid.
A: mushroom
Back Extra: Choroidal and Ciliary Body Melanoma
- Clinical: Approximately 25% of patients with Choroidal and Ciliary Body Melanoma have no symptoms and are diagnosed during a routine eye examination. Symptoms include photopsia, floaters, and loss of vision.
- Micro: Choroidal and Ciliary Body Melanomas can be classified into four morphological subtypes: spindle A, spindle B, epithelioid, and mixed. Epithelioid cells are non-cohesive with large, round nuclei and abundant, eosinophilic cytoplasm.
- Ancillary: Loss of BAP1 protein by immunohistochemistry is strongly associated with a high risk of metastasis in Choroidal and Ciliary Body Melanomas.
Reference Gallery:
Choroidal melanoma. Immunohistiochemistry for BAP1 labels the nuclei in this BAP1-preserved case.
Choroidal melanoma. BAP1 loss. Immunohistochemistry for BAP1 shows no expression in the nuclei.
Choroidal melanoma. Fundus photograph showing a mushroom shaped choroidal tumour.
Choroidal melanoma. Ultrasound A-scan showing low internal reflectivity in a choroid mass.
Choroidal melanoma. Ultrasound scan showing a mushroom-shaped mass arising from the choroid.
Choroidal melanoma. Typical presentation of a choroidal melanoma on Magnetic Resonance Imaging. The mass appears iso-intense to the choroid on T1-weighted images and enhances after contrast administration (CE T1). On T2-weighted images it is slightly hyperintense compared to the extra-ocular muscles. Posterior and anterior of the mass small retinal detachments can be seen, which do not enhance on CE T1 and are slightly hypointense compared to the melanoma on T2. On perfusion weighted imaging the choroidal melanoma shows a typical wash-out curve.
Choroidal melanoma. MRI showing an intraocular mass in the right eye.
Choroidal melanoma. US echography and Doppler showing an intense circulation of blood in intratumoral neovessels suggestive of an uveal melanoma.
Choroidal melanoma. US echography of showing an anterior intraocular tumour.

Q: An implantation cyst of the iris is a translucent cyst in the iris stroma that classically develops following a [...] or surgery, and is often associated with secondary glaucoma and corneal edema.
Implantation cyst of the iris. Implantation cyst of the iris. A cyst is located at the upper temporal periphery following perforating injury 30 years earlier.
A: perforating injury
Back Extra: Implantation cyst of the iris
- Clinical: Implantation cysts of the iris are translucent cysts in the iris stroma, containing clear or slightly opaque fluid, often associated with secondary glaucoma, corneal oedema, and amblyopia.
- Micro: These cysts are lined by concentric layers of stratified squamous epithelium, with or without goblet cells and keratinisation.
- Ancillary: Ancillary studies are not typically relevant for the diagnosis of implantation cysts of the iris.
Reference Gallery:
Implantation cyst of the iris. Implantation cyst of the iris. A cyst is located at the upper temporal periphery following perforating injury 30 years earlier.

Q: Microscopic examination of a Lisch Nodule reveals a proliferation of bland, spindle-shaped [...] arranged haphazardly on the anterior face and stroma of the iris.
Lisch nodule. Lisch nodule. Anterior border of the iris shows a nodule composed of bland spindle-shaped melanocytes within the superficial iris stroma. Haematoxylin-eosin stain.
A: melanocytes
Back Extra: Lisch Nodule
- Clinical: Two or more Lisch nodules constitute one of the seven NIH diagnostic criteria for neurofibromatosis type 1 (NF1).
- Micro: Lisch nodules are composed of bland spindle-shaped melanocytes arranged haphazardly on the anterior face and stroma of the iris.
- Ancillary: Immunohistochemistry shows S100 positivity in the melanocytic cells of Lisch nodules.
Reference Gallery:
Lisch nodule. Lisch nodule. Anterior border of the iris shows a nodule composed of bland spindle-shaped melanocytes within the superficial iris stroma. Haematoxylin-eosin stain.
Lisch nodule. Lisch nodule. Immunohistochemistry shows S100 positivity of the melanocytic cells.

Q: In a Lisch Nodule, immunohistochemistry typically shows strong positivity for [...] within the constituent spindle-shaped cells.
Lisch nodule. Lisch nodule. Immunohistochemistry shows S100 positivity of the melanocytic cells.
A: S100
Back Extra: Lisch Nodule
- Clinical: Two or more Lisch nodules constitute one of the seven NIH diagnostic criteria for neurofibromatosis type 1 (NF1).
- Micro: Lisch nodules are composed of bland spindle-shaped melanocytes arranged haphazardly on the anterior face and stroma of the iris.
- Ancillary: Immunohistochemistry shows S100 positivity in the melanocytic cells of Lisch nodules.
Reference Gallery:
Lisch nodule. Lisch nodule. Anterior border of the iris shows a nodule composed of bland spindle-shaped melanocytes within the superficial iris stroma. Haematoxylin-eosin stain.
Lisch nodule. Lisch nodule. Immunohistochemistry shows S100 positivity of the melanocytic cells.

Q: Microscopically, an Iris Melanoma is composed of variably pigmented malignant melanocytes that typically exhibit either an epithelioid or a [...] cell morphology.
Iris melanoma. High power view of sparsely pigmented spindle-shaped tumour cells.
Iris melanoma. Epithelioid cell rich iris melanoma.
A: spindle
Back Extra: Iris Melanoma
- Clinical: Iris melanoma is often asymptomatic, but it can present as a variably brown enlarging spot or nodule on the iris. Common clinical features include a displaced pupil, ectropion uveae, and secondary glaucoma.
- Micro: Iris melanoma cells can be spindle-shaped or epithelioid, with spindle B and epithelioid cells showing more atypia and mitotic figures. The tumour can be nodular, multinodular, diffuse, or plaquelike.
- Ancillary: Iris melanomas are positive for S100, MelanA, HMB45, and SOX10. Loss of BAP1 nuclear immunoreactivity and chromosomal aberrations (e.g., monosomy 3) can be seen, similar to other uveal melanomas.
Reference Gallery:
Iris melanoma. Low power image of an iris melanoma. The posterior iris pigment epithelium is at the bottom of the image.
Iris melanoma. High power view of sparsely pigmented spindle-shaped tumour cells.
Iris melanoma. Epithelioid cell rich iris melanoma.
Iris melanoma. A spindle cell rich iris melanoma with tumour vessels.
Iris melanoma. Abundant epithelioid cells with variable pigmentation.
Iris melanoma. Triangular darkly pigmented tumour in the inferolateral quadrant of the right eye.
Iris melanoma. A more diffuse tumour within the inferior half of the right eye.

Q: The clinical presentation of an [...] typically involves an asymptomatic but visibly enlarging, darkly pigmented (triangular or diffuse) mass directly on the iris.
Iris melanoma. Triangular darkly pigmented tumour in the inferolateral quadrant of the right eye.
Iris melanoma. A more diffuse tumour within the inferior half of the right eye.
A: Iris Melanoma
Back Extra: Iris Melanoma
- Clinical: Iris melanoma is often asymptomatic, but it can present as a variably brown enlarging spot or nodule on the iris. Common clinical features include a displaced pupil, ectropion uveae, and secondary glaucoma.
- Micro: Iris melanoma cells can be spindle-shaped or epithelioid, with spindle B and epithelioid cells showing more atypia and mitotic figures. The tumour can be nodular, multinodular, diffuse, or plaquelike.
- Ancillary: Iris melanomas are positive for S100, MelanA, HMB45, and SOX10. Loss of BAP1 nuclear immunoreactivity and chromosomal aberrations (e.g., monosomy 3) can be seen, similar to other uveal melanomas.
Reference Gallery:
Iris melanoma. Low power image of an iris melanoma. The posterior iris pigment epithelium is at the bottom of the image.
Iris melanoma. High power view of sparsely pigmented spindle-shaped tumour cells.
Iris melanoma. Epithelioid cell rich iris melanoma.
Iris melanoma. A spindle cell rich iris melanoma with tumour vessels.
Iris melanoma. Abundant epithelioid cells with variable pigmentation.
Iris melanoma. Triangular darkly pigmented tumour in the inferolateral quadrant of the right eye.
Iris melanoma. A more diffuse tumour within the inferior half of the right eye.

Q: Histologically, an Iris Nevus is composed of regular spindle to polygonal cells lacking atypia, and may characteristically demonstrate [...] differentiation.
Diagnosis: Iris nevus. Neuroid differentiation within a well-circumscribed iris nevus.
Diagnosis: Iris nevus. Neuroid differentiation, at high power within a well-circumscribed iris nevus, showing a lack of nuclear atypia.
A: neuroid
Back Extra: Iris Nevus
- Clinical: Iris nevi are benign, pigmented or non-pigmented spots or nodules that can cause uveal ectropion (dragging of the pigmented iris epithelium toward the anterior iris surface).
- Micro: Iris nevus cells are spindle to rounded polygonal with regular elongated nuclei, fine chromatin, and inconspicuous nucleoli. Neuroid differentiation may be present.
- Ancillary: Immunohistochemistry shows positive SOX10 and focal HMB45 expression, with retained BAP1. Genetic studies may reveal mutations in GNAQ, GNA11, NRAS, PTEN, KIT, and TP53.
Reference Gallery:
Diagnosis: Iris nevus. Macroscopic examination of an iris nevus (arrow) showing a light beige colour and located in the iris stroma (x1)
Diagnosis: Iris nevus. Iris nevus. Immunohistochemistry for SOX10 highlights the unusually numerous melanocytes within the iris stroma and on the anterior iris surface.
Diagnosis: Iris nevus. Iris nevus. Immunohistochemistry for HMB45 shows only focal positivity in the nevus.
Diagnosis: Iris nevus. Low power view of an iris nevus on the anterior surface of the iris.
Diagnosis: Iris nevus. High power view of an iris nevus showing mature nevus cells.
Diagnosis: Iris nevus. Neuroid differentiation within a well-circumscribed iris nevus.
Diagnosis: Iris nevus. Neuroid differentiation, at high power within a well-circumscribed iris nevus, showing a lack of nuclear atypia.
Diagnosis: Iris nevus. Pigmented iris nevi.
Diagnosis: Iris nevus. Cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.
Diagnosis: Iris nevus. Cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli. BAP1 expression is retained in iris nevi.
Diagnosis: Iris nevus. A cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.
Diagnosis: Iris nevus. A cellular lesion, at high power, composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.

Q: Unlike many malignant uveal melanomas, an Iris Nevus characteristically demonstrates retained nuclear expression of [...] on immunohistochemistry.
Diagnosis: Iris nevus. Cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli. BAP1 expression is retained in iris nevi.
A: BAP1
Back Extra: Iris Nevus
- Clinical: Iris nevi are benign, pigmented or non-pigmented spots or nodules that can cause uveal ectropion (dragging of the pigmented iris epithelium toward the anterior iris surface).
- Micro: Iris nevus cells are spindle to rounded polygonal with regular elongated nuclei, fine chromatin, and inconspicuous nucleoli. Neuroid differentiation may be present.
- Ancillary: Immunohistochemistry shows positive SOX10 and focal HMB45 expression, with retained BAP1. Genetic studies may reveal mutations in GNAQ, GNA11, NRAS, PTEN, KIT, and TP53.
Reference Gallery:
Diagnosis: Iris nevus. Macroscopic examination of an iris nevus (arrow) showing a light beige colour and located in the iris stroma (x1)
Diagnosis: Iris nevus. Iris nevus. Immunohistochemistry for SOX10 highlights the unusually numerous melanocytes within the iris stroma and on the anterior iris surface.
Diagnosis: Iris nevus. Iris nevus. Immunohistochemistry for HMB45 shows only focal positivity in the nevus.
Diagnosis: Iris nevus. Low power view of an iris nevus on the anterior surface of the iris.
Diagnosis: Iris nevus. High power view of an iris nevus showing mature nevus cells.
Diagnosis: Iris nevus. Neuroid differentiation within a well-circumscribed iris nevus.
Diagnosis: Iris nevus. Neuroid differentiation, at high power within a well-circumscribed iris nevus, showing a lack of nuclear atypia.
Diagnosis: Iris nevus. Pigmented iris nevi.
Diagnosis: Iris nevus. Cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.
Diagnosis: Iris nevus. Cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli. BAP1 expression is retained in iris nevi.
Diagnosis: Iris nevus. A cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.
Diagnosis: Iris nevus. A cellular lesion, at high power, composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.

Q: Immunohistochemical staining of an Iris Nevus highlights numerous melanocytes with diffuse SOX10, but typically shows only focal positivity for [...].
Diagnosis: Iris nevus. Iris nevus. Immunohistochemistry for SOX10 highlights the unusually numerous melanocytes within the iris stroma and on the anterior iris surface.
Diagnosis: Iris nevus. Iris nevus. Immunohistochemistry for HMB45 shows only focal positivity in the nevus.
A: HMB45
Back Extra: Iris Nevus
- Clinical: Iris nevi are benign, pigmented or non-pigmented spots or nodules that can cause uveal ectropion (dragging of the pigmented iris epithelium toward the anterior iris surface).
- Micro: Iris nevus cells are spindle to rounded polygonal with regular elongated nuclei, fine chromatin, and inconspicuous nucleoli. Neuroid differentiation may be present.
- Ancillary: Immunohistochemistry shows positive SOX10 and focal HMB45 expression, with retained BAP1. Genetic studies may reveal mutations in GNAQ, GNA11, NRAS, PTEN, KIT, and TP53.
Reference Gallery:
Diagnosis: Iris nevus. Macroscopic examination of an iris nevus (arrow) showing a light beige colour and located in the iris stroma (x1)
Diagnosis: Iris nevus. Iris nevus. Immunohistochemistry for SOX10 highlights the unusually numerous melanocytes within the iris stroma and on the anterior iris surface.
Diagnosis: Iris nevus. Iris nevus. Immunohistochemistry for HMB45 shows only focal positivity in the nevus.
Diagnosis: Iris nevus. Low power view of an iris nevus on the anterior surface of the iris.
Diagnosis: Iris nevus. High power view of an iris nevus showing mature nevus cells.
Diagnosis: Iris nevus. Neuroid differentiation within a well-circumscribed iris nevus.
Diagnosis: Iris nevus. Neuroid differentiation, at high power within a well-circumscribed iris nevus, showing a lack of nuclear atypia.
Diagnosis: Iris nevus. Pigmented iris nevi.
Diagnosis: Iris nevus. Cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.
Diagnosis: Iris nevus. Cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli. BAP1 expression is retained in iris nevi.
Diagnosis: Iris nevus. A cellular lesion composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.
Diagnosis: Iris nevus. A cellular lesion, at high power, composed of spindle cells showing regular elongated nuclei with a fine chromatin and inconspicuous nucleoli.

Q: In Ocular Melanocytosis, the clinical presentation includes patchy hyperpigmentation of the sclera, iris heterochromia, and distinct iris nodules referred to as [...].
Ocular melanocytosis. Left eye: Class 4D+ Naevus of Ota showing loss of Iris crypts and the presence of iris mammilations.
A: iris mammillations
Back Extra: Ocular Melanocytosis
- Clinical: Ocular melanocytosis is characterized by iris heterochromia, iris nodules (‘iris mammillations’), and patchy hyperpigmentation of the sclera.
- Micro: The histopathology shows overpopulation with spindle-shaped, bipolar, or dendritic melanocytes in the uvea, sclera, and orbit.
- Ancillary: Somatic activating mutations of GNA11 or GNAQ have been found in some patients with ocular melanocytosis.
Reference Gallery:
Ocular melanocytosis. Left eye: Class 4D+ Naevus of Ota showing loss of Iris crypts and the presence of iris mammilations.
Bilateral naevus of Ota. Bilateral calcaneus hyperpigmentation. Conjunctival melanosis, scleral melanoctyosis and iris hyperpigmentation. Ocular class 4D+
Ocular surface melanosis. Ocular surface 4 quadrant involvement (scleral melanocytosis and conjunctival melanosis) class 4D+.
Ocular melanocytosis. Heavily pigmented spindled melanocytic cells of ocular melanocytosis in the choroid, sparing the choriocapillaris.
Ocular melanocytosis. Heavily pigmented spindled melanocytic cells of ocular melanocytosis within the episclera.

Q: An overpopulation of heavily pigmented, spindle-shaped, bipolar, or dendritic melanocytes within the uvea, sclera, and orbit is the histologic hallmark of [...].
Ocular melanocytosis. Heavily pigmented spindled melanocytic cells of ocular melanocytosis in the choroid, sparing the choriocapillaris.
Ocular melanocytosis. Heavily pigmented spindled melanocytic cells of ocular melanocytosis within the episclera.
A: Ocular Melanocytosis
Back Extra: Ocular Melanocytosis
- Clinical: Ocular melanocytosis is characterized by iris heterochromia, iris nodules (‘iris mammillations’), and patchy hyperpigmentation of the sclera.
- Micro: The histopathology shows overpopulation with spindle-shaped, bipolar, or dendritic melanocytes in the uvea, sclera, and orbit.
- Ancillary: Somatic activating mutations of GNA11 or GNAQ have been found in some patients with ocular melanocytosis.
Reference Gallery:
Ocular melanocytosis. Left eye: Class 4D+ Naevus of Ota showing loss of Iris crypts and the presence of iris mammilations.
Bilateral naevus of Ota. Bilateral calcaneus hyperpigmentation. Conjunctival melanosis, scleral melanoctyosis and iris hyperpigmentation. Ocular class 4D+
Ocular surface melanosis. Ocular surface 4 quadrant involvement (scleral melanocytosis and conjunctival melanosis) class 4D+.
Ocular melanocytosis. Heavily pigmented spindled melanocytic cells of ocular melanocytosis in the choroid, sparing the choriocapillaris.
Ocular melanocytosis. Heavily pigmented spindled melanocytic cells of ocular melanocytosis within the episclera.