Title: WHO / GU
Tags: GU::Kidney::Renal_cell GU::Testis::Germ_Cell_Tumors GU::Testis::Paratesticular GU::Testis::Sex_Cord_Stromal_Tumors GU::Kidney::Mesenchymal GU::Bladder::Urothelial GU::Bladder::Mesenchymal GU::Kidney::Metanephric GU::Prostate::Glandular_neoplasms GU::Bladder::Neuroendocrine GU::Testis::Heme GU::Kidney::Other GU::Penis::Squamous_Neoplasms GU::Urothelial::Other GU::Kidney::Nephroblastic_Nephrogenic GU::Prostate::Squamous_Neoplasms GU::Bladder::Squamous_Neoplasms GU::Bladder::Other

Q: On imaging and gross examination, Urachal Carcinoma typically presents as a mass arising at the [...] and frequently demonstrates calcifications, especially in mucinous subtypes.
Urachal carcinoma. CT showing a calcified mucinous urachal adenocarcinoma (arrow) growing into the urinary bladder.
Urachal carcinoma. Resection specimen of a mucinous urachal adenocarcinoma with partial cystectomy of the bladder dome (arrow), tumour (asterisk), median umbilical ligament (+) and umbilicus (>).
Urachal carcinoma. Cut surface of a mucinous urachal adenocarcinoma (asterisk) with ulceration of the bladder dome (arrow) and sharp/cystic demarcation as well as calcifications.
A: bladder dome
Back Extra: Urachal Carcinoma
- Clinical: Common symptoms include haematuria, abdominal pain, dysuria, and mucusuria. CT often shows calcifications, especially in mucinous urachal cancer.
- Micro: Morphologically indistinguishable from colorectal adenocarcinoma, with glandular and cribriform architecture, nuclear pseudostratification, and necrosis. The mucinous subtype shows a predominance of extracellular mucin pools.
- Ancillary: Positive for CDX2 and CK20; 50% positive for CK7; and usually positive for CD15 and CEA. Enriched in TP53 mutations and often shows activation of the MAPK and PI3K pathways.
Reference Gallery:
Urachal carcinoma. Genomic alterations in bladder tumours with the glandular phenotype. BAC, bladder adenocarcinoma; UCg, urothelial carcinoma with glandular differentiation; UAC, urachal adenocarcinoma; *Only hotspots analysed {32198650}.
Urachal carcinoma. CT showing a calcified mucinous urachal adenocarcinoma (arrow) growing into the urinary bladder.
Urachal carcinoma. Resection specimen of a mucinous urachal adenocarcinoma with partial cystectomy of the bladder dome (arrow), tumour (asterisk), median umbilical ligament (+) and umbilicus (>).
Urachal carcinoma. Cut surface of a mucinous urachal adenocarcinoma (asterisk) with ulceration of the bladder dome (arrow) and sharp/cystic demarcation as well as calcifications.
Urachal carcinoma. Mucinous urachal adenocarcinoma showing abundant extracellular mucin, a malignant mucinous epithelial lining, and some free-floating tumour cell formations.
Urachal carcinoma. Signet-ring cell subtype of urachal adenocarcinoma.
Urachal carcinoma. Intestinal-type urachal adenocarcinoma showing glandular architecture, pseudostratified malignant epithelia, and cellular debris.
Urachal carcinoma. Urachal adenocarcinoma NOS showing an indistinct malignant glandular architecture.

Q: Histologically, the intestinal type of Urachal Carcinoma is nearly indistinguishable from colorectal adenocarcinoma, while its most common mucinous subtype is characteristically defined by abundant pools of [...].
Urachal carcinoma. Mucinous urachal adenocarcinoma showing abundant extracellular mucin, a malignant mucinous epithelial lining, and some free-floating tumour cell formations.
Urachal carcinoma. Intestinal-type urachal adenocarcinoma showing glandular architecture, pseudostratified malignant epithelia, and cellular debris.
A: extracellular mucin
Back Extra: Urachal Carcinoma
- Clinical: Common symptoms include haematuria, abdominal pain, dysuria, and mucusuria. CT often shows calcifications, especially in mucinous urachal cancer.
- Micro: Morphologically indistinguishable from colorectal adenocarcinoma, with glandular and cribriform architecture, nuclear pseudostratification, and necrosis. The mucinous subtype shows a predominance of extracellular mucin pools.
- Ancillary: Positive for CDX2 and CK20; 50% positive for CK7; and usually positive for CD15 and CEA. Enriched in TP53 mutations and often shows activation of the MAPK and PI3K pathways.
Reference Gallery:
Urachal carcinoma. Genomic alterations in bladder tumours with the glandular phenotype. BAC, bladder adenocarcinoma; UCg, urothelial carcinoma with glandular differentiation; UAC, urachal adenocarcinoma; *Only hotspots analysed {32198650}.
Urachal carcinoma. CT showing a calcified mucinous urachal adenocarcinoma (arrow) growing into the urinary bladder.
Urachal carcinoma. Resection specimen of a mucinous urachal adenocarcinoma with partial cystectomy of the bladder dome (arrow), tumour (asterisk), median umbilical ligament (+) and umbilicus (>).
Urachal carcinoma. Cut surface of a mucinous urachal adenocarcinoma (asterisk) with ulceration of the bladder dome (arrow) and sharp/cystic demarcation as well as calcifications.
Urachal carcinoma. Mucinous urachal adenocarcinoma showing abundant extracellular mucin, a malignant mucinous epithelial lining, and some free-floating tumour cell formations.
Urachal carcinoma. Signet-ring cell subtype of urachal adenocarcinoma.
Urachal carcinoma. Intestinal-type urachal adenocarcinoma showing glandular architecture, pseudostratified malignant epithelia, and cellular debris.
Urachal carcinoma. Urachal adenocarcinoma NOS showing an indistinct malignant glandular architecture.

Q: Microscopically, [...] of the bladder is histologically identical to its colorectal counterpart, featuring elongated villoglandular fronds lined by a pseudostratified columnar epithelium, often with focal intestinal metaplasia.
Villous adenoma of the bladder. Villous adenoma is characterized by elongated villous structures lined by epithelium with focal intestinal metaplasia, nuclear pleomorphism, and hyperchromasia. Tubular areas are also present focally.
A: Villous Adenoma
Back Extra: Villous Adenoma
- Clinical: Patients with villous adenoma often present with haematuria and/or irritative symptoms.
- Micro: Villous adenoma is histologically identical to its colorectal counterpart, with villoglandular fronds lined by a pseudostratified columnar epithelial layer.
- Ancillary: Mutations associated with APC, PRKDC, ROS1, ATM, and KMT2D have been described in a subset of cases of villous adenoma.
Reference Gallery:
Villous adenoma of the bladder. Villous adenoma is characterized by elongated villous structures lined by epithelium with focal intestinal metaplasia, nuclear pleomorphism, and hyperchromasia. Tubular areas are also present focally.

Q: Microscopically, [...] typically demonstrates well-formed, anastomosing vascular channels lined by atypical cells with notable endothelial multilayering and hobnailing.
Angiosarcoma. This lesion shows well-formed (although frequently angulated and irregular) vascular spaces lined by moderately atypical endothelial cells with areas of stratification and hobnailing. The surrounding stroma shows chronic inflammation with haemosiderin-laden macrophages.
A: Angiosarcoma
Back Extra: Angiosarcoma
- Clinical: Angiosarcoma can present with haematuria and flank pain, and is most commonly found in the sixth or seventh decade of life, with a male predominance.
- Micro: Angiosarcomas show well-formed anastomosing vascular channels to solid sheets of large atypical cells, with features like endothelial multilayering and hobnailing.
- Ancillary: Angiosarcomas are positive for CD31 and ERG, with variable expression of CD34, Factor VIII, and FLI1.
Reference Gallery:
Angiosarcoma. This lesion shows well-formed (although frequently angulated and irregular) vascular spaces lined by moderately atypical endothelial cells with areas of stratification and hobnailing. The surrounding stroma shows chronic inflammation with haemosiderin-laden macrophages.
Angiosarcoma. Although the neoplastic endothelial cells here show relatively minimal atypia, vasoformation is rudimentary, with small, poorly defined vascular channels containing erythrocytes.
Epithelioid angiosarcoma. Poorly defined vascular channels are lined by large, moderately pleomorphic cells with ovoid nuclei, with areas of stratification. There is prominent surrounding blood, with mixed inflammation and haemosiderin deposition.
Epithelioid angiosarcoma. This neoplasm has a predominantly solid architecture, with sparse vasoformation. The cells are large with moderately atypical vesicular nuclei and prominent nucleoli. Foci of rudimentary vasoformation with intracytoplasmic lumina are present.
Angiosarcoma. This poorly differentiated angiosarcoma shows strong diffuse nuclear expression of ERG, the most sensitive and specific endothelial marker. Immunohistochemical confirmation of endothelial differentiation is critical for the diagnosis of tumours without discernible vasoformation.
Angiosarcoma of the bladder. Transurethral resection of bladder tumour (TURBT) specimen.
Angiosarcoma of the bladder. Strong nuclear positivity for FLI1.
Angiosarcoma of the bladder. Pleomorphic hyperchromatic nuclei.
Angiosarcoma of the bladder. Strong nuclear positivity for ERG.

Q: The epithelioid variant of Angiosarcoma frequently displays a solid architecture composed of large, pleomorphic cells with prominent nucleoli, often showing rudimentary vasoformation characterized by the presence of [...].
Epithelioid angiosarcoma. This neoplasm has a predominantly solid architecture, with sparse vasoformation. The cells are large with moderately atypical vesicular nuclei and prominent nucleoli. Foci of rudimentary vasoformation with intracytoplasmic lumina are present.
A: intracytoplasmic lumina
Back Extra: Angiosarcoma
- Clinical: Angiosarcoma can present with haematuria and flank pain, and is most commonly found in the sixth or seventh decade of life, with a male predominance.
- Micro: Angiosarcomas show well-formed anastomosing vascular channels to solid sheets of large atypical cells, with features like endothelial multilayering and hobnailing.
- Ancillary: Angiosarcomas are positive for CD31 and ERG, with variable expression of CD34, Factor VIII, and FLI1.
Reference Gallery:
Angiosarcoma. This lesion shows well-formed (although frequently angulated and irregular) vascular spaces lined by moderately atypical endothelial cells with areas of stratification and hobnailing. The surrounding stroma shows chronic inflammation with haemosiderin-laden macrophages.
Angiosarcoma. Although the neoplastic endothelial cells here show relatively minimal atypia, vasoformation is rudimentary, with small, poorly defined vascular channels containing erythrocytes.
Epithelioid angiosarcoma. Poorly defined vascular channels are lined by large, moderately pleomorphic cells with ovoid nuclei, with areas of stratification. There is prominent surrounding blood, with mixed inflammation and haemosiderin deposition.
Epithelioid angiosarcoma. This neoplasm has a predominantly solid architecture, with sparse vasoformation. The cells are large with moderately atypical vesicular nuclei and prominent nucleoli. Foci of rudimentary vasoformation with intracytoplasmic lumina are present.
Angiosarcoma. This poorly differentiated angiosarcoma shows strong diffuse nuclear expression of ERG, the most sensitive and specific endothelial marker. Immunohistochemical confirmation of endothelial differentiation is critical for the diagnosis of tumours without discernible vasoformation.
Angiosarcoma of the bladder. Transurethral resection of bladder tumour (TURBT) specimen.
Angiosarcoma of the bladder. Strong nuclear positivity for FLI1.
Angiosarcoma of the bladder. Pleomorphic hyperchromatic nuclei.
Angiosarcoma of the bladder. Strong nuclear positivity for ERG.

Q: Immunohistochemical confirmation is critical for poorly differentiated Angiosarcomas lacking discernible vasoformation; these tumors characteristically show strong, diffuse nuclear expression of [...], which is the most sensitive and specific endothelial marker.
Angiosarcoma. This poorly differentiated angiosarcoma shows strong diffuse nuclear expression of ERG, the most sensitive and specific endothelial marker. Immunohistochemical confirmation of endothelial differentiation is critical for the diagnosis of tumours without discernible vasoformation.
Angiosarcoma of the bladder. Strong nuclear positivity for ERG.
A: ERG
Back Extra: Angiosarcoma
- Clinical: Angiosarcoma can present with haematuria and flank pain, and is most commonly found in the sixth or seventh decade of life, with a male predominance.
- Micro: Angiosarcomas show well-formed anastomosing vascular channels to solid sheets of large atypical cells, with features like endothelial multilayering and hobnailing.
- Ancillary: Angiosarcomas are positive for CD31 and ERG, with variable expression of CD34, Factor VIII, and FLI1.
Reference Gallery:
Angiosarcoma. This lesion shows well-formed (although frequently angulated and irregular) vascular spaces lined by moderately atypical endothelial cells with areas of stratification and hobnailing. The surrounding stroma shows chronic inflammation with haemosiderin-laden macrophages.
Angiosarcoma. Although the neoplastic endothelial cells here show relatively minimal atypia, vasoformation is rudimentary, with small, poorly defined vascular channels containing erythrocytes.
Epithelioid angiosarcoma. Poorly defined vascular channels are lined by large, moderately pleomorphic cells with ovoid nuclei, with areas of stratification. There is prominent surrounding blood, with mixed inflammation and haemosiderin deposition.
Epithelioid angiosarcoma. This neoplasm has a predominantly solid architecture, with sparse vasoformation. The cells are large with moderately atypical vesicular nuclei and prominent nucleoli. Foci of rudimentary vasoformation with intracytoplasmic lumina are present.
Angiosarcoma. This poorly differentiated angiosarcoma shows strong diffuse nuclear expression of ERG, the most sensitive and specific endothelial marker. Immunohistochemical confirmation of endothelial differentiation is critical for the diagnosis of tumours without discernible vasoformation.
Angiosarcoma of the bladder. Transurethral resection of bladder tumour (TURBT) specimen.
Angiosarcoma of the bladder. Strong nuclear positivity for FLI1.
Angiosarcoma of the bladder. Pleomorphic hyperchromatic nuclei.
Angiosarcoma of the bladder. Strong nuclear positivity for ERG.

Q: Histologically, the lesion characterized by cytologically bland spindle-shaped cells with a myofibroblastic phenotype (diffuse SMA expression), interspersed with a variable inflammatory infiltrate of lymphocytes and plasma cells, is known as [...].
Inflammatory myofibroblastic tumour. Cytologically bland spindle-shaped cells are interspersed with rare lymphocytes.
Inflammatory myofibroblastic tumour. Immunohistochemistry for SMA shows diffuse labelling, supporting a myofibroblastic phenotype.
A: inflammatory myofibroblastic tumor
Back Extra: Inflammatory Myofibroblastic Tumour
- Clinical: Inflammatory myofibroblastic tumour often presents with haematuria, dysuria, or abdominal pain, and can occur after a previous procedure.
- Micro: The tumour is composed of spindle-shaped cells with a myofibroblastic appearance, interspersed with an inflammatory infiltrate of lymphocytes and plasma cells.
- Ancillary: Molecular studies, such as FISH or sequencing, can confirm the presence of an ALK gene rearrangement, which is present in a variable proportion of cases (35-89%).
Reference Gallery:
Inflammatory myofibroblastic tumour. Cytologically bland spindle-shaped cells are interspersed with rare lymphocytes.
Inflammatory myofibroblastic tumour. Immunohistochemistry for SMA shows diffuse labelling, supporting a myofibroblastic phenotype.
Inflammatory myofibroblastic tumour. Immunohistochemistry for ALK protein shows positive labelling. This tumour was molecularly confirmed to have FN1::ALK fusion.
Pseudosarcomatous myofibroblastic proliferation. This urinary bladder myofibroblastic proliferation resembles inflammatory myofibroblastic tumour but demonstrated no detectable gene fusions by next-generation sequencing, and immunohistochemistry for ALK was negative.

Q: Ancillary testing in inflammatory myofibroblastic tumor frequently (35-89% of cases) reveals a characteristic gene rearrangement involving the [...] gene, which can be detected via molecular sequencing, FISH, or immunohistochemistry.
Inflammatory myofibroblastic tumour. Immunohistochemistry for ALK protein shows positive labelling. This tumour was molecularly confirmed to have FN1::ALK fusion.
A: ALK
Back Extra: Inflammatory Myofibroblastic Tumour
- Clinical: Inflammatory myofibroblastic tumour often presents with haematuria, dysuria, or abdominal pain, and can occur after a previous procedure.
- Micro: The tumour is composed of spindle-shaped cells with a myofibroblastic appearance, interspersed with an inflammatory infiltrate of lymphocytes and plasma cells.
- Ancillary: Molecular studies, such as FISH or sequencing, can confirm the presence of an ALK gene rearrangement, which is present in a variable proportion of cases (35-89%).
Reference Gallery:
Inflammatory myofibroblastic tumour. Cytologically bland spindle-shaped cells are interspersed with rare lymphocytes.
Inflammatory myofibroblastic tumour. Immunohistochemistry for SMA shows diffuse labelling, supporting a myofibroblastic phenotype.
Inflammatory myofibroblastic tumour. Immunohistochemistry for ALK protein shows positive labelling. This tumour was molecularly confirmed to have FN1::ALK fusion.
Pseudosarcomatous myofibroblastic proliferation. This urinary bladder myofibroblastic proliferation resembles inflammatory myofibroblastic tumour but demonstrated no detectable gene fusions by next-generation sequencing, and immunohistochemistry for ALK was negative.

Q: Histologically, a Leiomyoma is characterized by spindle cells with eosinophilic cytoplasm and uniform, blunt-ended, [...] nuclei arranged in orderly intersecting fascicles.
Bladder leiomyoma. There are eosinophilic spindle cells showing uniform nuclei and fascicular growth.
Renal leiomyoma. A renal tumour with eosinophilic spindle cells arranged in intersecting fascicles.
Renal leiomyoma. The cells have uniform blunt-ended, cigar-shaped nuclei.
A: cigar-shaped
Back Extra: Leiomyoma
- Clinical: Most bladder and urethral leiomyomas are detected incidentally during cystoscopy or imaging, but some may present with obstruction, irritative voiding symptoms, and/or haemorrhage.
- Micro: Leiomyoma cells have eosinophilic cytoplasm and uniform blunt-ended, cigar-shaped nuclei, arranged in orderly intersecting fascicles.
- Ancillary: Tumour cells are positive for SMA, desmin, and h-caldesmon, and negative for S100. Cathepsin K negativity in the kidney helps distinguish leiomyoma from angiomyolipoma.
Reference Gallery:
Bladder leiomyoma. There are eosinophilic spindle cells showing uniform nuclei and fascicular growth.
Renal leiomyoma. A renal tumour with eosinophilic spindle cells arranged in intersecting fascicles.
Renal leiomyoma. The cells have uniform blunt-ended, cigar-shaped nuclei.
Renal leiomyoma. The tumour cells are positive for SMA.

Q: By immunohistochemistry, the tumor cells of a Leiomyoma characteristically show strong positivity for [...], desmin, and h-caldesmon.
Renal leiomyoma. The tumour cells are positive for SMA.
A: SMA
Back Extra: Leiomyoma
- Clinical: Most bladder and urethral leiomyomas are detected incidentally during cystoscopy or imaging, but some may present with obstruction, irritative voiding symptoms, and/or haemorrhage.
- Micro: Leiomyoma cells have eosinophilic cytoplasm and uniform blunt-ended, cigar-shaped nuclei, arranged in orderly intersecting fascicles.
- Ancillary: Tumour cells are positive for SMA, desmin, and h-caldesmon, and negative for S100. Cathepsin K negativity in the kidney helps distinguish leiomyoma from angiomyolipoma.
Reference Gallery:
Bladder leiomyoma. There are eosinophilic spindle cells showing uniform nuclei and fascicular growth.
Renal leiomyoma. A renal tumour with eosinophilic spindle cells arranged in intersecting fascicles.
Renal leiomyoma. The cells have uniform blunt-ended, cigar-shaped nuclei.
Renal leiomyoma. The tumour cells are positive for SMA.

Q: Histologically, myopericytoma is characterized by a concentric, [...] proliferation of bland, oval to spindle-shaped cells surrounding numerous thin-walled vessels.
Myopericytoma. Myopericytoma is characterized by a perivascular concentric proliferation of bland, oval to spindle-shaped cells with round to spindled nuclei.
A: perivascular
Back Extra: Myopericytoma
- Clinical: Renal myopericytomas are usually asymptomatic and discovered incidentally. Bladder myopericytomas present with gross hematuria, dysuria, and urinary frequency.
- Micro: Myopericytoma features a perivascular concentric proliferation of bland, oval to spindle-shaped cells with numerous thin-walled vessels. The stroma may be edematous, hyalinized, or myxoid.
- Ancillary: Immunohistochemistry shows positivity for SMA and h-caldesmon, with focal positivity for desmin and/or CD34. PDGFRB gene abnormalities are common.
Reference Gallery:
Myopericytoma. Myopericytoma is characterized by a perivascular concentric proliferation of bland, oval to spindle-shaped cells with round to spindled nuclei.

Q: [...] is a neoplasm that typically presents on H&E with a characteristic perivascular concentric proliferation of bland, oval to spindle-shaped cells.
Myopericytoma. Myopericytoma is characterized by a perivascular concentric proliferation of bland, oval to spindle-shaped cells with round to spindled nuclei.
A: Myopericytoma
Back Extra: Myopericytoma
- Clinical: Renal myopericytomas are usually asymptomatic and discovered incidentally. Bladder myopericytomas present with gross hematuria, dysuria, and urinary frequency.
- Micro: Myopericytoma features a perivascular concentric proliferation of bland, oval to spindle-shaped cells with numerous thin-walled vessels. The stroma may be edematous, hyalinized, or myxoid.
- Ancillary: Immunohistochemistry shows positivity for SMA and h-caldesmon, with focal positivity for desmin and/or CD34. PDGFRB gene abnormalities are common.
Reference Gallery:
Myopericytoma. Myopericytoma is characterized by a perivascular concentric proliferation of bland, oval to spindle-shaped cells with round to spindled nuclei.

Q: Characterized by a nested or alveolar proliferation of epithelioid cells with clear to granular cytoplasm, spindle cells, and co-expression of melanocytic and smooth muscle markers, the diagnosis shown is an [...].
Extrarenal PEComa. This tumour is composed of epithelioid cells with clear and/or granular cytoplasm combined with eosinophilic spindle cells.
Extrarenal PEComa. Low-power view of a PEComa arranged in a nested and alveolar architecture in the bladder wall, with normal overlying urothelium.
Extrarenal PEComa. The neoplasm is characterized by epithelioid cells that have a large amount of eosinophilic to clear, slightly granular cytoplasm and round nuclei with inconspicuous nucleoli. Occasional cells show readily visible melanin.
A: Extrarenal PEComa
Back Extra: Extrarenal PEComa
- Clinical: Extrarenal PEComas can cause organ enlargement and are typically found incidentally; age range is 15-67 years with no sex predilection.
- Micro: PEComas are composed of epithelioid cells with clear/granular cytoplasm and spindle cells, often arranged in a nested/alveolar pattern around hyalinized blood vessels.
- Ancillary: Positive staining for both melanocytic (HMB45, Melan-A) and muscle (Actin, Desmin) markers, and TFE3 rearrangements.
Reference Gallery:
Extrarenal PEComa. This tumour is composed of epithelioid cells with clear and/or granular cytoplasm combined with eosinophilic spindle cells.
Extrarenal PEComa. PEComas are positive for melanocytic markers, such as HMB45 in this tumour.
Extrarenal PEComa. Low-power view of a PEComa arranged in a nested and alveolar architecture in the bladder wall, with normal overlying urothelium.
Extrarenal PEComa. The neoplasm is characterized by epithelioid cells that have a large amount of eosinophilic to clear, slightly granular cytoplasm and round nuclei with inconspicuous nucleoli. Occasional cells show readily visible melanin.
Extrarenal PEComa. There is nuclear positivity for TFE3 in the neoplastic cells.
Extrarenal PEComa. There is weak staining for tyrosinase in this example.

Q: In an Extrarenal PEComa, the neoplastic cells characteristically show positive immunohistochemical staining for smooth muscle markers alongside melanocytic markers, most notably [...] and Melan-A.
Extrarenal PEComa. PEComas are positive for melanocytic markers, such as HMB45 in this tumour.
A: HMB45
Back Extra: Extrarenal PEComa
- Clinical: Extrarenal PEComas can cause organ enlargement and are typically found incidentally; age range is 15-67 years with no sex predilection.
- Micro: PEComas are composed of epithelioid cells with clear/granular cytoplasm and spindle cells, often arranged in a nested/alveolar pattern around hyalinized blood vessels.
- Ancillary: Positive staining for both melanocytic (HMB45, Melan-A) and muscle (Actin, Desmin) markers, and TFE3 rearrangements.
Reference Gallery:
Extrarenal PEComa. This tumour is composed of epithelioid cells with clear and/or granular cytoplasm combined with eosinophilic spindle cells.
Extrarenal PEComa. PEComas are positive for melanocytic markers, such as HMB45 in this tumour.
Extrarenal PEComa. Low-power view of a PEComa arranged in a nested and alveolar architecture in the bladder wall, with normal overlying urothelium.
Extrarenal PEComa. The neoplasm is characterized by epithelioid cells that have a large amount of eosinophilic to clear, slightly granular cytoplasm and round nuclei with inconspicuous nucleoli. Occasional cells show readily visible melanin.
Extrarenal PEComa. There is nuclear positivity for TFE3 in the neoplastic cells.
Extrarenal PEComa. There is weak staining for tyrosinase in this example.

Q: A distinct subset of Extrarenal PEComa tumors harbor specific gene rearrangements that result in characteristic, strong nuclear immunohistochemical staining for [...].
Extrarenal PEComa. There is nuclear positivity for TFE3 in the neoplastic cells.
A: TFE3
Back Extra: Extrarenal PEComa
- Clinical: Extrarenal PEComas can cause organ enlargement and are typically found incidentally; age range is 15-67 years with no sex predilection.
- Micro: PEComas are composed of epithelioid cells with clear/granular cytoplasm and spindle cells, often arranged in a nested/alveolar pattern around hyalinized blood vessels.
- Ancillary: Positive staining for both melanocytic (HMB45, Melan-A) and muscle (Actin, Desmin) markers, and TFE3 rearrangements.
Reference Gallery:
Extrarenal PEComa. This tumour is composed of epithelioid cells with clear and/or granular cytoplasm combined with eosinophilic spindle cells.
Extrarenal PEComa. PEComas are positive for melanocytic markers, such as HMB45 in this tumour.
Extrarenal PEComa. Low-power view of a PEComa arranged in a nested and alveolar architecture in the bladder wall, with normal overlying urothelium.
Extrarenal PEComa. The neoplasm is characterized by epithelioid cells that have a large amount of eosinophilic to clear, slightly granular cytoplasm and round nuclei with inconspicuous nucleoli. Occasional cells show readily visible melanin.
Extrarenal PEComa. There is nuclear positivity for TFE3 in the neoplastic cells.
Extrarenal PEComa. There is weak staining for tyrosinase in this example.

Q: The [...] variant of embryonal Rhabdomyosarcoma (often seen in the urinary bladder) is characterized microscopically by a characteristic subepithelial cellular condensation of neoplastic cells (cambium layer).
Embryonal rhabdomyosarcoma. The botryoid type of embryonal rhabdomyosarcoma, such as this tumour in the urinary bladder, is characterized by a cellular condensation of neoplastic cells abutting the epithelium-lined surface.
A: botryoid
Back Extra: Rhabdomyosarcoma
- Clinical: Patients with rhabdomyosarcoma of the genitourinary tract may present with a scrotal mass, haematuria, or urinary retention.
- Micro: Embryonal rhabdomyosarcoma (ERMS) is characterized by a primitive spindle cell component, often with a myxoid stroma and scattered differentiating rhabdomyoblasts.
- Ancillary: Myogenin and MYOD1 are typically positive in rhabdomyosarcoma, and a PAX3::FOXO1 or PAX7::FOXO1 fusion is common in alveolar rhabdomyosarcoma (ARMS).
Reference Gallery:
Embryonal rhabdomyosarcoma. The botryoid type of embryonal rhabdomyosarcoma, such as this tumour in the urinary bladder, is characterized by a cellular condensation of neoplastic cells abutting the epithelium-lined surface.
Spindle cell rhabdomyosarcoma of the paratestis. The monomorphic spindle cell morphology and fascicular architecture are characteristic.
Embryonal rhabdomyosarcoma. There is usually strong staining for desmin.
Embryonal rhabdomyosarcoma. Nuclear staining for myogenin.

Q: The spindle cell variant of Rhabdomyosarcoma, which commonly presents as a paratesticular mass, is characterized by a monomorphic spindle cell morphology arranged in a [...] architecture.
Spindle cell rhabdomyosarcoma of the paratestis. The monomorphic spindle cell morphology and fascicular architecture are characteristic.
A: fascicular
Back Extra: Rhabdomyosarcoma
- Clinical: Patients with rhabdomyosarcoma of the genitourinary tract may present with a scrotal mass, haematuria, or urinary retention.
- Micro: Embryonal rhabdomyosarcoma (ERMS) is characterized by a primitive spindle cell component, often with a myxoid stroma and scattered differentiating rhabdomyoblasts.
- Ancillary: Myogenin and MYOD1 are typically positive in rhabdomyosarcoma, and a PAX3::FOXO1 or PAX7::FOXO1 fusion is common in alveolar rhabdomyosarcoma (ARMS).
Reference Gallery:
Embryonal rhabdomyosarcoma. The botryoid type of embryonal rhabdomyosarcoma, such as this tumour in the urinary bladder, is characterized by a cellular condensation of neoplastic cells abutting the epithelium-lined surface.
Spindle cell rhabdomyosarcoma of the paratestis. The monomorphic spindle cell morphology and fascicular architecture are characteristic.
Embryonal rhabdomyosarcoma. There is usually strong staining for desmin.
Embryonal rhabdomyosarcoma. Nuclear staining for myogenin.

Q: Immunohistochemistry for Rhabdomyosarcoma typically demonstrates strong staining for desmin, alongside specific nuclear positivity for MYOD1 and [...].
Embryonal rhabdomyosarcoma. There is usually strong staining for desmin.
Embryonal rhabdomyosarcoma. Nuclear staining for myogenin.
A: myogenin
Back Extra: Rhabdomyosarcoma
- Clinical: Patients with rhabdomyosarcoma of the genitourinary tract may present with a scrotal mass, haematuria, or urinary retention.
- Micro: Embryonal rhabdomyosarcoma (ERMS) is characterized by a primitive spindle cell component, often with a myxoid stroma and scattered differentiating rhabdomyoblasts.
- Ancillary: Myogenin and MYOD1 are typically positive in rhabdomyosarcoma, and a PAX3::FOXO1 or PAX7::FOXO1 fusion is common in alveolar rhabdomyosarcoma (ARMS).
Reference Gallery:
Embryonal rhabdomyosarcoma. The botryoid type of embryonal rhabdomyosarcoma, such as this tumour in the urinary bladder, is characterized by a cellular condensation of neoplastic cells abutting the epithelium-lined surface.
Spindle cell rhabdomyosarcoma of the paratestis. The monomorphic spindle cell morphology and fascicular architecture are characteristic.
Embryonal rhabdomyosarcoma. There is usually strong staining for desmin.
Embryonal rhabdomyosarcoma. Nuclear staining for myogenin.

Q: A solitary fibrous tumor is histologically composed of haphazardly arranged bland spindle cells, variable stromal collagenization, and a characteristic branching [...] vasculature.
Solitary fibrous tumour. Typical solitary fibrous tumour consisting of haphazardly arranged uniform spindle cells with scant cytoplasm.
Solitary fibrous tumour. Some tumours may have a predominantly collagenous appearance with low cellularity.
A: hemangiopericytomatous
Back Extra: Solitary Fibrous Tumour
- Clinical: Solitary Fibrous Tumours (SFTs) are often found incidentally or may cause mass effect symptoms. They can also lead to paraneoplastic syndromes like Doege–Potter syndrome, characterized by severe hypoglycaemia.
- Micro: SFTs typically consist of bland ovoid to spindled cells arranged haphazardly, with a haemangiopericytomatous vasculature and variable stromal collagenization.
- Ancillary: The NAB2::STAT6 gene fusion is the molecular hallmark of SFT, and nuclear expression of STAT6 by immunohistochemistry is a reliable surrogate marker.
Reference Gallery:
Solitary fibrous tumour. Typical solitary fibrous tumour consisting of haphazardly arranged uniform spindle cells with scant cytoplasm.
Solitary fibrous tumour. Some tumours may have a predominantly collagenous appearance with low cellularity.
Solitary fibrous tumour. Dedifferentiated solitary fibrous tumour exhibiting increased cellularity with marked nuclear pleomorphism.
Solitary fibrous tumour. Strong and diffuse nuclear expression of STAT6 is characteristic.

Q: The NAB2::STAT6 gene fusion is the molecular hallmark of a solitary fibrous tumor, reliably manifesting as strong and diffuse nuclear expression of [...] on immunohistochemistry.
Solitary fibrous tumour. Strong and diffuse nuclear expression of STAT6 is characteristic.
A: STAT6
Back Extra: Solitary Fibrous Tumour
- Clinical: Solitary Fibrous Tumours (SFTs) are often found incidentally or may cause mass effect symptoms. They can also lead to paraneoplastic syndromes like Doege–Potter syndrome, characterized by severe hypoglycaemia.
- Micro: SFTs typically consist of bland ovoid to spindled cells arranged haphazardly, with a haemangiopericytomatous vasculature and variable stromal collagenization.
- Ancillary: The NAB2::STAT6 gene fusion is the molecular hallmark of SFT, and nuclear expression of STAT6 by immunohistochemistry is a reliable surrogate marker.
Reference Gallery:
Solitary fibrous tumour. Typical solitary fibrous tumour consisting of haphazardly arranged uniform spindle cells with scant cytoplasm.
Solitary fibrous tumour. Some tumours may have a predominantly collagenous appearance with low cellularity.
Solitary fibrous tumour. Dedifferentiated solitary fibrous tumour exhibiting increased cellularity with marked nuclear pleomorphism.
Solitary fibrous tumour. Strong and diffuse nuclear expression of STAT6 is characteristic.

Q: An abrupt histologic transition from a bland spindle cell proliferation to a high-grade sarcoma with increased cellularity and marked nuclear pleomorphism is characteristic of a dedifferentiated [...].
Solitary fibrous tumour. Dedifferentiated solitary fibrous tumour exhibiting increased cellularity with marked nuclear pleomorphism.
A: solitary fibrous tumor
Back Extra: Solitary Fibrous Tumour
- Clinical: Solitary Fibrous Tumours (SFTs) are often found incidentally or may cause mass effect symptoms. They can also lead to paraneoplastic syndromes like Doege–Potter syndrome, characterized by severe hypoglycaemia.
- Micro: SFTs typically consist of bland ovoid to spindled cells arranged haphazardly, with a haemangiopericytomatous vasculature and variable stromal collagenization.
- Ancillary: The NAB2::STAT6 gene fusion is the molecular hallmark of SFT, and nuclear expression of STAT6 by immunohistochemistry is a reliable surrogate marker.
Reference Gallery:
Solitary fibrous tumour. Typical solitary fibrous tumour consisting of haphazardly arranged uniform spindle cells with scant cytoplasm.
Solitary fibrous tumour. Some tumours may have a predominantly collagenous appearance with low cellularity.
Solitary fibrous tumour. Dedifferentiated solitary fibrous tumour exhibiting increased cellularity with marked nuclear pleomorphism.
Solitary fibrous tumour. Strong and diffuse nuclear expression of STAT6 is characteristic.

Q: The characteristic microscopic appearance of a Paraganglioma features nests of tumor cells separated by a delicate fibrovascular network, known as a [...] pattern.
Paraganglioma. Malignant pelvic extra-adrenal paraganglioma in a 9-year-old girl with a germline SDHB mutation. She presented with two lesions that were shown to be clonally related, for which reason the smaller lesion was considered a metastasis. H&E image of the primary tumour showing typical nested tumour cells (Zellballen).
A: Zellballen
Back Extra: Paraganglioma
- Clinical: Paragangliomas can cause symptoms due to catecholamine excess, including sweating, palpitation, and anxiety, with paroxysmal hypertension and tachycardia.
- Micro: Paragangliomas have a characteristic Zellballen pattern, with nests of tumour cells separated by a delicate fibrovascular network.
- Ancillary: Immunohistochemistry shows strong positive staining for neuroendocrine markers such as chromogranin A, synaptophysin, and tyrosine hydroxylase.
Reference Gallery:
Paraganglioma. Malignant pelvic extra-adrenal paraganglioma in a 9-year-old girl with a germline SDHB mutation. She presented with two lesions that were shown to be clonally related, for which reason the smaller lesion was considered a metastasis. H&E image of the primary tumour showing typical nested tumour cells (Zellballen).
Paraganglioma. Immunostaining for chromogranin A showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for synaptophysin showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for tyrosine hydroxylase showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for SSTR2A showing diffuse membranous and cytoplasmic labelling.
Paraganglioma. Immunostaining for GATA3 showing diffuse nuclear labelling, which may be seen in paragangliomas and cannot be used for discrimination from urothelial carcinoma.
Paraganglioma. Immunostaining for SDHA showing strong diffuse granular cytoplasmic labelling, which is the normal pattern in all cells and indicates that an SDHA mutation is unlikely to be present.
Paraganglioma. Immunostaining for SDHB showing absent cytoplasmic labelling but retained granular cytoplasmic labelling in normal endothelial cells (internal positive control). This pattern strongly suggests the presence of a mutation in any of the SDH subunit genes (with the exception of SDHA, because the pattern was normal). Upon further genetic counselling and testing, a germline SDHB mutation was found.
Paraganglioma. Maximum-intensity projection of 68Ga-DOTATOC PET-CT in a patient with extra-adrenal sympathetic paraganglioma.
Paraganglioma. Intense SSTR uptake is observed in soft tissue located centrally in the pelvis, cranial to the bladder (coronal fused PET-CT reconstruction).
Paraganglioma. Intense SSTR uptake is observed in soft tissue located centrally in the pelvis, cranial to the bladder (axial fused PET-CT reconstruction).

Q: Immunohistochemistry of Paraganglioma demonstrates diffuse positivity for neuroendocrine markers like chromogranin A and synaptophysin, along with strong staining for [...], reflecting its catecholamine-producing nature.
Paraganglioma. Immunostaining for chromogranin A showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for synaptophysin showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for tyrosine hydroxylase showing strong diffuse cytoplasmic labelling.
A: tyrosine hydroxylase
Back Extra: Paraganglioma
- Clinical: Paragangliomas can cause symptoms due to catecholamine excess, including sweating, palpitation, and anxiety, with paroxysmal hypertension and tachycardia.
- Micro: Paragangliomas have a characteristic Zellballen pattern, with nests of tumour cells separated by a delicate fibrovascular network.
- Ancillary: Immunohistochemistry shows strong positive staining for neuroendocrine markers such as chromogranin A, synaptophysin, and tyrosine hydroxylase.
Reference Gallery:
Paraganglioma. Malignant pelvic extra-adrenal paraganglioma in a 9-year-old girl with a germline SDHB mutation. She presented with two lesions that were shown to be clonally related, for which reason the smaller lesion was considered a metastasis. H&E image of the primary tumour showing typical nested tumour cells (Zellballen).
Paraganglioma. Immunostaining for chromogranin A showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for synaptophysin showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for tyrosine hydroxylase showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for SSTR2A showing diffuse membranous and cytoplasmic labelling.
Paraganglioma. Immunostaining for GATA3 showing diffuse nuclear labelling, which may be seen in paragangliomas and cannot be used for discrimination from urothelial carcinoma.
Paraganglioma. Immunostaining for SDHA showing strong diffuse granular cytoplasmic labelling, which is the normal pattern in all cells and indicates that an SDHA mutation is unlikely to be present.
Paraganglioma. Immunostaining for SDHB showing absent cytoplasmic labelling but retained granular cytoplasmic labelling in normal endothelial cells (internal positive control). This pattern strongly suggests the presence of a mutation in any of the SDH subunit genes (with the exception of SDHA, because the pattern was normal). Upon further genetic counselling and testing, a germline SDHB mutation was found.
Paraganglioma. Maximum-intensity projection of 68Ga-DOTATOC PET-CT in a patient with extra-adrenal sympathetic paraganglioma.
Paraganglioma. Intense SSTR uptake is observed in soft tissue located centrally in the pelvis, cranial to the bladder (coronal fused PET-CT reconstruction).
Paraganglioma. Intense SSTR uptake is observed in soft tissue located centrally in the pelvis, cranial to the bladder (axial fused PET-CT reconstruction).

Q: In Paraganglioma, absent immunohistochemical staining for [...] in tumor cells, with retained granular staining in normal endothelial cells, is highly suggestive of an underlying germline mutation in the succinate dehydrogenase complex.
Paraganglioma. Immunostaining for SDHB showing absent cytoplasmic labelling but retained granular cytoplasmic labelling in normal endothelial cells (internal positive control). This pattern strongly suggests the presence of a mutation in any of the SDH subunit genes (with the exception of SDHA, because the pattern was normal). Upon further genetic counselling and testing, a germline SDHB mutation was found.
A: SDHB
Back Extra: Paraganglioma
- Clinical: Paragangliomas can cause symptoms due to catecholamine excess, including sweating, palpitation, and anxiety, with paroxysmal hypertension and tachycardia.
- Micro: Paragangliomas have a characteristic Zellballen pattern, with nests of tumour cells separated by a delicate fibrovascular network.
- Ancillary: Immunohistochemistry shows strong positive staining for neuroendocrine markers such as chromogranin A, synaptophysin, and tyrosine hydroxylase.
Reference Gallery:
Paraganglioma. Malignant pelvic extra-adrenal paraganglioma in a 9-year-old girl with a germline SDHB mutation. She presented with two lesions that were shown to be clonally related, for which reason the smaller lesion was considered a metastasis. H&E image of the primary tumour showing typical nested tumour cells (Zellballen).
Paraganglioma. Immunostaining for chromogranin A showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for synaptophysin showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for tyrosine hydroxylase showing strong diffuse cytoplasmic labelling.
Paraganglioma. Immunostaining for SSTR2A showing diffuse membranous and cytoplasmic labelling.
Paraganglioma. Immunostaining for GATA3 showing diffuse nuclear labelling, which may be seen in paragangliomas and cannot be used for discrimination from urothelial carcinoma.
Paraganglioma. Immunostaining for SDHA showing strong diffuse granular cytoplasmic labelling, which is the normal pattern in all cells and indicates that an SDHA mutation is unlikely to be present.
Paraganglioma. Immunostaining for SDHB showing absent cytoplasmic labelling but retained granular cytoplasmic labelling in normal endothelial cells (internal positive control). This pattern strongly suggests the presence of a mutation in any of the SDH subunit genes (with the exception of SDHA, because the pattern was normal). Upon further genetic counselling and testing, a germline SDHB mutation was found.
Paraganglioma. Maximum-intensity projection of 68Ga-DOTATOC PET-CT in a patient with extra-adrenal sympathetic paraganglioma.
Paraganglioma. Intense SSTR uptake is observed in soft tissue located centrally in the pelvis, cranial to the bladder (coronal fused PET-CT reconstruction).
Paraganglioma. Intense SSTR uptake is observed in soft tissue located centrally in the pelvis, cranial to the bladder (axial fused PET-CT reconstruction).

Q: A high-grade malignancy characterized microscopically by nests and trabeculae of large pleomorphic cells with prominent nucleoli, ample eosinophilic cytoplasm, and areas of tumor necrosis is diagnostic of [...].
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. LCNEC with an admixture of necrotic and viable tumour areas.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. High-power view highlighting nuclear pleomorphism with prominent nucleoli and ample eosinophilic cytoplasm.
A: Large Cell Neuroendocrine Carcinoma
Q: Large Cell Neuroendocrine Carcinoma
- Clinical: Patients with bladder [...] often present with haematuria and may have a dismal prognosis with a median survival time of < 1 year.
- Micro: LCNEC is characterized by large cells with prominent nucleoli, arranged in nests, acini, and trabeculae, and often mixed with urothelial carcinoma.
- Ancillary: Immunohistochemistry shows positivity for [...] and [...] with a high Ki-67 labelling index, and typically negative for androgen receptor (AR) in prostatic LCNEC.
Reference Gallery:
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. LCNEC with an admixture of necrotic and viable tumour areas.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. High-power view highlighting nuclear pleomorphism with prominent nucleoli and ample eosinophilic cytoplasm.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. There is diffuse cytoplasmic labelling for chromogranin A.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. Synaptophysin immunoreactivity.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. Immunostaining shows a high Ki-67 labelling index, which may be as high as 90%.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. These tumours are typically negative for AR.
A: Large Cell Neuroendocrine Carcinoma (LCNEC); chromogranin A; synaptophysin

Q: By immunohistochemistry, Large Cell Neuroendocrine Carcinoma typically exhibits a very high Ki-67 proliferation index and diffuse positivity for the neuroendocrine markers [...].
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. There is diffuse cytoplasmic labelling for chromogranin A.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. Synaptophysin immunoreactivity.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. Immunostaining shows a high Ki-67 labelling index, which may be as high as 90%.
A: chromogranin A and synaptophysin
Q: Large Cell Neuroendocrine Carcinoma
- Clinical: Patients with bladder [...] often present with haematuria and may have a dismal prognosis with a median survival time of < 1 year.
- Micro: LCNEC is characterized by large cells with prominent nucleoli, arranged in nests, acini, and trabeculae, and often mixed with urothelial carcinoma.
- Ancillary: Immunohistochemistry shows positivity for [...] and [...] with a high Ki-67 labelling index, and typically negative for androgen receptor (AR) in prostatic LCNEC.
Reference Gallery:
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. LCNEC with an admixture of necrotic and viable tumour areas.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. High-power view highlighting nuclear pleomorphism with prominent nucleoli and ample eosinophilic cytoplasm.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. There is diffuse cytoplasmic labelling for chromogranin A.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. Synaptophysin immunoreactivity.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. Immunostaining shows a high Ki-67 labelling index, which may be as high as 90%.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. These tumours are typically negative for AR.
A: Large Cell Neuroendocrine Carcinoma (LCNEC); chromogranin A; synaptophysin

Q: When arising in the prostate, Large Cell Neuroendocrine Carcinoma is characteristically immunohistochemically negative for the [...], which helps differentiate it from conventional high-grade acinar adenocarcinoma.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. These tumours are typically negative for AR.
A: androgen receptor (AR)
Q: Large Cell Neuroendocrine Carcinoma
- Clinical: Patients with bladder [...] often present with haematuria and may have a dismal prognosis with a median survival time of < 1 year.
- Micro: LCNEC is characterized by large cells with prominent nucleoli, arranged in nests, acini, and trabeculae, and often mixed with urothelial carcinoma.
- Ancillary: Immunohistochemistry shows positivity for [...] and [...] with a high Ki-67 labelling index, and typically negative for androgen receptor (AR) in prostatic LCNEC.
Reference Gallery:
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. LCNEC with an admixture of necrotic and viable tumour areas.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. High-power view highlighting nuclear pleomorphism with prominent nucleoli and ample eosinophilic cytoplasm.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. There is diffuse cytoplasmic labelling for chromogranin A.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. Synaptophysin immunoreactivity.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. Immunostaining shows a high Ki-67 labelling index, which may be as high as 90%.
Large cell neuroendocrine carcinoma (LCNEC) of the prostate. These tumours are typically negative for AR.
A: Large Cell Neuroendocrine Carcinoma (LCNEC); chromogranin A; synaptophysin

Q: Histologically, Mixed Neuroendocrine Neoplasms typically display an [...] transition between the neuroendocrine and non-neuroendocrine tumor components.
Mixed neuroendocrine neoplasm (NEN). A tumour composed of large cell neuroendocrine carcinoma (LCNEC) (right) and prostatic acinar carcinoma (Gleason score: 5 + 4) (left).
A: abrupt
Back Extra: Mixed Neuroendocrine Neoplasms
- Clinical: Mixed Neuroendocrine Neoplasms (NENs) have clinical features similar to small cell neuroendocrine carcinomas (SCNECs) and large cell neuroendocrine carcinomas (LCNECs). They are often associated with a poor prognosis.
- Micro: The small cell neuroendocrine carcinoma (SCNEC) component shows nuclear p53 staining and thyroid transcription factor 1 (TTF1) in about half of the cases. The transition between the neuroendocrine and non-neuroendocrine components is usually abrupt.
- Ancillary: Diagnosis of Mixed Neuroendocrine Neoplasms requires immunostaining for neuroendocrine markers (synaptophysin, chromogranin A) and non-neuroendocrine markers (CK20, p40, TTF1, AR).
Reference Gallery:
Mixed neuroendocrine neoplasm (NEN). Small cell carcinoma component at high magnification showing nuclei with salt-and-pepper chromatin, as well as a high mitotic count and tumour necrosis.
Mixed neuroendocrine neoplasm (NEN). High Ki-67 proliferation index in the small cell carcinoma component (left) and low Ki-67 proliferation index in the urothelial carcinoma component (right).
Mixed neuroendocrine neoplasm (NEN). Small cell neuroendocrine carcinoma (SCNEC) component in a mixed NEN of the prostate.
Mixed neuroendocrine neoplasm (NEN). Prostatic acinar adenocarcinoma component (Gleason score: 5 + 4; grade group: 5) in a mixed NEN.
Mixed neuroendocrine neoplasm (NEN). A tumour composed of large cell neuroendocrine carcinoma (LCNEC) (right) and prostatic acinar carcinoma (Gleason score: 5 + 4) (left).
Mixed neuroendocrine neoplasm (NEN). Positive chromogranin A stain in the neuroendocrine carcinoma component (right) and negative chromogranin A stain in the prostatic acinar carcinoma component (Gleason score: 5 + 4) (left).

Q: To confirm the diagnosis of Mixed Neuroendocrine Neoplasms, immunohistochemical stains such as [...] and synaptophysin are used, which specifically highlight the neuroendocrine component while remaining negative in the adjacent non-neuroendocrine areas.
Mixed neuroendocrine neoplasm (NEN). Positive chromogranin A stain in the neuroendocrine carcinoma component (right) and negative chromogranin A stain in the prostatic acinar carcinoma component (Gleason score: 5 + 4) (left).
A: chromogranin A
Back Extra: Mixed Neuroendocrine Neoplasms
- Clinical: Mixed Neuroendocrine Neoplasms (NENs) have clinical features similar to small cell neuroendocrine carcinomas (SCNECs) and large cell neuroendocrine carcinomas (LCNECs). They are often associated with a poor prognosis.
- Micro: The small cell neuroendocrine carcinoma (SCNEC) component shows nuclear p53 staining and thyroid transcription factor 1 (TTF1) in about half of the cases. The transition between the neuroendocrine and non-neuroendocrine components is usually abrupt.
- Ancillary: Diagnosis of Mixed Neuroendocrine Neoplasms requires immunostaining for neuroendocrine markers (synaptophysin, chromogranin A) and non-neuroendocrine markers (CK20, p40, TTF1, AR).
Reference Gallery:
Mixed neuroendocrine neoplasm (NEN). Small cell carcinoma component at high magnification showing nuclei with salt-and-pepper chromatin, as well as a high mitotic count and tumour necrosis.
Mixed neuroendocrine neoplasm (NEN). High Ki-67 proliferation index in the small cell carcinoma component (left) and low Ki-67 proliferation index in the urothelial carcinoma component (right).
Mixed neuroendocrine neoplasm (NEN). Small cell neuroendocrine carcinoma (SCNEC) component in a mixed NEN of the prostate.
Mixed neuroendocrine neoplasm (NEN). Prostatic acinar adenocarcinoma component (Gleason score: 5 + 4; grade group: 5) in a mixed NEN.
Mixed neuroendocrine neoplasm (NEN). A tumour composed of large cell neuroendocrine carcinoma (LCNEC) (right) and prostatic acinar carcinoma (Gleason score: 5 + 4) (left).
Mixed neuroendocrine neoplasm (NEN). Positive chromogranin A stain in the neuroendocrine carcinoma component (right) and negative chromogranin A stain in the prostatic acinar carcinoma component (Gleason score: 5 + 4) (left).

Q: In Mixed Neuroendocrine Neoplasms, immunostaining reveals a stark contrast in cellular proliferation, with the small cell carcinoma component demonstrating a remarkably high [...] index compared to the non-neuroendocrine component.
Mixed neuroendocrine neoplasm (NEN). High Ki-67 proliferation index in the small cell carcinoma component (left) and low Ki-67 proliferation index in the urothelial carcinoma component (right).
A: Ki-67
Back Extra: Mixed Neuroendocrine Neoplasms
- Clinical: Mixed Neuroendocrine Neoplasms (NENs) have clinical features similar to small cell neuroendocrine carcinomas (SCNECs) and large cell neuroendocrine carcinomas (LCNECs). They are often associated with a poor prognosis.
- Micro: The small cell neuroendocrine carcinoma (SCNEC) component shows nuclear p53 staining and thyroid transcription factor 1 (TTF1) in about half of the cases. The transition between the neuroendocrine and non-neuroendocrine components is usually abrupt.
- Ancillary: Diagnosis of Mixed Neuroendocrine Neoplasms requires immunostaining for neuroendocrine markers (synaptophysin, chromogranin A) and non-neuroendocrine markers (CK20, p40, TTF1, AR).
Reference Gallery:
Mixed neuroendocrine neoplasm (NEN). Small cell carcinoma component at high magnification showing nuclei with salt-and-pepper chromatin, as well as a high mitotic count and tumour necrosis.
Mixed neuroendocrine neoplasm (NEN). High Ki-67 proliferation index in the small cell carcinoma component (left) and low Ki-67 proliferation index in the urothelial carcinoma component (right).
Mixed neuroendocrine neoplasm (NEN). Small cell neuroendocrine carcinoma (SCNEC) component in a mixed NEN of the prostate.
Mixed neuroendocrine neoplasm (NEN). Prostatic acinar adenocarcinoma component (Gleason score: 5 + 4; grade group: 5) in a mixed NEN.
Mixed neuroendocrine neoplasm (NEN). A tumour composed of large cell neuroendocrine carcinoma (LCNEC) (right) and prostatic acinar carcinoma (Gleason score: 5 + 4) (left).
Mixed neuroendocrine neoplasm (NEN). Positive chromogranin A stain in the neuroendocrine carcinoma component (right) and negative chromogranin A stain in the prostatic acinar carcinoma component (Gleason score: 5 + 4) (left).

Q: Microscopically, Small Cell Neuroendocrine Carcinoma is composed of high-grade cells with a high N:C ratio, scant cytoplasm, prominent apoptosis, crush artifact, and characteristic [...].
Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder. Note the malignant SCNEC cells (with a high N:C ratio, nuclear moulding, and crush artefact) in the lamina propria. Urothelial carcinoma in situ is evident in the surface epithelium.
Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder. The malignant SCNEC cells show prominent apoptosis and nuclear moulding.
A: nuclear molding
Back Extra: Small Cell Neuroendocrine Carcinoma
- Clinical: Small cell neuroendocrine carcinoma (SCNEC) can present with paraneoplastic syndromes such as hypercalcaemia, Cushing syndrome, and SIADH.
- Micro: SCNEC shows small cells with a high N:C ratio, nuclear moulding, and prominent apoptosis.
- Ancillary: Immunohistochemistry shows positivity for synaptophysin, chromogranin A, and CD56, with CD56 being the most sensitive but least specific marker.
Reference Gallery:
Small cell neuroendocrine carcinoma (SCNEC). SCNEC showing high-grade nuclei without nucleoli and with scant cytoplasm. Apoptosis is prominent.
Small cell neuroendocrine carcinoma (SCNEC). Cells are strongly positive for synaptophysin.
Small cell neuroendocrine carcinoma (SCNEC). CD56 positivity, although not specific for SCNEC, is the most sensitive marker for neuroendocrine differentiation.
Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder. Note the malignant SCNEC cells (with a high N:C ratio, nuclear moulding, and crush artefact) in the lamina propria. Urothelial carcinoma in situ is evident in the surface epithelium.
Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder. The malignant SCNEC cells show prominent apoptosis and nuclear moulding.

Q: By immunohistochemistry, Small Cell Neuroendocrine Carcinoma demonstrates positivity for neuroendocrine markers such as synaptophysin, chromogranin A, and [...], which is the most sensitive but least specific marker.
Small cell neuroendocrine carcinoma (SCNEC). Cells are strongly positive for synaptophysin.
Small cell neuroendocrine carcinoma (SCNEC). CD56 positivity, although not specific for SCNEC, is the most sensitive marker for neuroendocrine differentiation.
A: CD56
Back Extra: Small Cell Neuroendocrine Carcinoma
- Clinical: Small cell neuroendocrine carcinoma (SCNEC) can present with paraneoplastic syndromes such as hypercalcaemia, Cushing syndrome, and SIADH.
- Micro: SCNEC shows small cells with a high N:C ratio, nuclear moulding, and prominent apoptosis.
- Ancillary: Immunohistochemistry shows positivity for synaptophysin, chromogranin A, and CD56, with CD56 being the most sensitive but least specific marker.
Reference Gallery:
Small cell neuroendocrine carcinoma (SCNEC). SCNEC showing high-grade nuclei without nucleoli and with scant cytoplasm. Apoptosis is prominent.
Small cell neuroendocrine carcinoma (SCNEC). Cells are strongly positive for synaptophysin.
Small cell neuroendocrine carcinoma (SCNEC). CD56 positivity, although not specific for SCNEC, is the most sensitive marker for neuroendocrine differentiation.
Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder. Note the malignant SCNEC cells (with a high N:C ratio, nuclear moulding, and crush artefact) in the lamina propria. Urothelial carcinoma in situ is evident in the surface epithelium.
Small cell neuroendocrine carcinoma (SCNEC) of the urinary bladder. The malignant SCNEC cells show prominent apoptosis and nuclear moulding.

Q: A key histologic feature distinguishing the involved outpouching in Diverticular Carcinoma from the normal urinary bladder wall is the complete absence of a true [...] layer.
Diverticular carcinoma. Urothelial tumour with glandular differentiation in the diverticulum, with a hypertrophic muscularis mucosae layer (asterisk) directly under the diverticular urothelium.
Diverticular carcinoma. Urothelial tumour with glandular differentiation in the diverticulum without detrusor muscle invasion (+) and in the neighbouring bladder with detrusor muscle invasion (asterisk).
A: detrusor muscle
Back Extra: Diverticular Carcinoma
- Clinical: Most patients with Diverticular Carcinoma present in the sixth decade of life, and the condition is more common in men. Diagnosis is often established via cystoscopy, urine cytology, ultrasonography, and cross-sectional imaging studies.
- Micro: The histopathology of Diverticular Carcinoma resembles that of other urinary tract carcinomas, with the most common type being urothelial carcinoma. Diverticula often have a hypertrophic layer of muscularis mucosae but lack a detrusor muscle layer.
- Ancillary: Ancillary studies for Diverticular Carcinoma are generally not clinically relevant.
Reference Gallery:
Diverticular carcinoma. Urothelial tumour with glandular differentiation in the diverticulum, with a hypertrophic muscularis mucosae layer (asterisk) directly under the diverticular urothelium.
Diverticular carcinoma. A urinary bladder diverticulum with carcinoma.
Diverticular carcinoma. Cross-sections of urinary bladder diverticulum with carcinoma with perivesical fat involvement.
Diverticular carcinoma. Urothelial tumour with glandular differentiation in the diverticulum without detrusor muscle invasion (+) and in the neighbouring bladder with detrusor muscle invasion (asterisk).

Q: Because a urinary bladder diverticulum lacks a thick muscular wall, Diverticular Carcinoma often undergoes rapid, direct invasion into the surrounding [...].
Diverticular carcinoma. A urinary bladder diverticulum with carcinoma.
Diverticular carcinoma. Cross-sections of urinary bladder diverticulum with carcinoma with perivesical fat involvement.
A: perivesical fat
Back Extra: Diverticular Carcinoma
- Clinical: Most patients with Diverticular Carcinoma present in the sixth decade of life, and the condition is more common in men. Diagnosis is often established via cystoscopy, urine cytology, ultrasonography, and cross-sectional imaging studies.
- Micro: The histopathology of Diverticular Carcinoma resembles that of other urinary tract carcinomas, with the most common type being urothelial carcinoma. Diverticula often have a hypertrophic layer of muscularis mucosae but lack a detrusor muscle layer.
- Ancillary: Ancillary studies for Diverticular Carcinoma are generally not clinically relevant.
Reference Gallery:
Diverticular carcinoma. Urothelial tumour with glandular differentiation in the diverticulum, with a hypertrophic muscularis mucosae layer (asterisk) directly under the diverticular urothelium.
Diverticular carcinoma. A urinary bladder diverticulum with carcinoma.
Diverticular carcinoma. Cross-sections of urinary bladder diverticulum with carcinoma with perivesical fat involvement.
Diverticular carcinoma. Urothelial tumour with glandular differentiation in the diverticulum without detrusor muscle invasion (+) and in the neighbouring bladder with detrusor muscle invasion (asterisk).

Q: The vast majority of tumors comprising Metastasis to the Urinary Tract are histologically classified as [...], which can pose a significant diagnostic challenge by mimicking primary bladder lesions.
Metastasis to bladder from ovarian carcinoma. This tumour resembles an endometrioid carcinoma.
Metastasis to bladder from prostatic adenocarcinoma. The lesion has produced a polypoid mass.
A: adenocarcinomas
Back Extra: Metastasis to the Urinary Tract
- Clinical: Patients with metastasis to the urinary tract often present with haematuria and obstructive uropathy.
- Micro: Most metastatic tumours in the urinary tract are adenocarcinomas, which can pose a diagnostic challenge due to their similarity to primary bladder adenocarcinomas.
- Ancillary: NKX3-1 and PSA expression are helpful in identifying prostatic adenocarcinoma, while mammaglobin and GCDFP-15 can help confirm breast carcinoma.
Reference Gallery:
Metastasis to bladder from ovarian carcinoma. This tumour resembles an endometrioid carcinoma.
Metastasis to bladder from ovarian carcinoma. The nuclei of the ovarian carcinoma stain positively for ER, which helps to confirm the origin of the metastasis.
Metastasis to bladder from lobular breast carcinoma. Note the single cells with eccentric nuclei in the submucosa.
Metastasis to bladder from lobular breast carcinoma. The nuclei stain positively for ER.
Metastasis to bladder from prostatic adenocarcinoma. The lesion has produced a polypoid mass.
Metastasis to bladder from prostatic adenocarcinoma. The tumour cells stain for NKX3-1.
Metastasis to bladder from prostatic adenocarcinoma. The urothelium stains for CK7 whereas the metastatic tumour cells are negative.

Q: A distinct morphological pattern of Metastasis to the Urinary Tract features single, infiltrating neoplastic cells with eccentric nuclei within the submucosa, characteristic of a primary [...].
Metastasis to bladder from lobular breast carcinoma. Note the single cells with eccentric nuclei in the submucosa.
Metastasis to bladder from lobular breast carcinoma. The nuclei stain positively for ER.
A: lobular breast carcinoma
Back Extra: Metastasis to the Urinary Tract
- Clinical: Patients with metastasis to the urinary tract often present with haematuria and obstructive uropathy.
- Micro: Most metastatic tumours in the urinary tract are adenocarcinomas, which can pose a diagnostic challenge due to their similarity to primary bladder adenocarcinomas.
- Ancillary: NKX3-1 and PSA expression are helpful in identifying prostatic adenocarcinoma, while mammaglobin and GCDFP-15 can help confirm breast carcinoma.
Reference Gallery:
Metastasis to bladder from ovarian carcinoma. This tumour resembles an endometrioid carcinoma.
Metastasis to bladder from ovarian carcinoma. The nuclei of the ovarian carcinoma stain positively for ER, which helps to confirm the origin of the metastasis.
Metastasis to bladder from lobular breast carcinoma. Note the single cells with eccentric nuclei in the submucosa.
Metastasis to bladder from lobular breast carcinoma. The nuclei stain positively for ER.
Metastasis to bladder from prostatic adenocarcinoma. The lesion has produced a polypoid mass.
Metastasis to bladder from prostatic adenocarcinoma. The tumour cells stain for NKX3-1.
Metastasis to bladder from prostatic adenocarcinoma. The urothelium stains for CK7 whereas the metastatic tumour cells are negative.

Q: When distinguishing primary bladder tumors from a prostatic Metastasis to the Urinary Tract, the metastatic cells will typically demonstrate strong nuclear expression of [...].
Metastasis to bladder from prostatic adenocarcinoma. The tumour cells stain for NKX3-1.
Metastasis to bladder from prostatic adenocarcinoma. The urothelium stains for CK7 whereas the metastatic tumour cells are negative.
A: NKX3.1
Back Extra: Metastasis to the Urinary Tract
- Clinical: Patients with metastasis to the urinary tract often present with haematuria and obstructive uropathy.
- Micro: Most metastatic tumours in the urinary tract are adenocarcinomas, which can pose a diagnostic challenge due to their similarity to primary bladder adenocarcinomas.
- Ancillary: NKX3-1 and PSA expression are helpful in identifying prostatic adenocarcinoma, while mammaglobin and GCDFP-15 can help confirm breast carcinoma.
Reference Gallery:
Metastasis to bladder from ovarian carcinoma. This tumour resembles an endometrioid carcinoma.
Metastasis to bladder from ovarian carcinoma. The nuclei of the ovarian carcinoma stain positively for ER, which helps to confirm the origin of the metastasis.
Metastasis to bladder from lobular breast carcinoma. Note the single cells with eccentric nuclei in the submucosa.
Metastasis to bladder from lobular breast carcinoma. The nuclei stain positively for ER.
Metastasis to bladder from prostatic adenocarcinoma. The lesion has produced a polypoid mass.
Metastasis to bladder from prostatic adenocarcinoma. The tumour cells stain for NKX3-1.
Metastasis to bladder from prostatic adenocarcinoma. The urothelium stains for CK7 whereas the metastatic tumour cells are negative.

Q: In certain endemic regions, Pure Squamous Carcinoma of the Urothelial Tract is classically associated with [...] infection, and the characteristic parasite eggs can sometimes be observed within the tumor stroma.
Squamous carcinoma of the bladder. A moderately differentiated tumour associated with Schistosoma infection. Note the Schistosoma egg in the centre.
A: Schistosoma
Back Extra: Pure Squamous Carcinoma of the Urothelial Tract
- Clinical: Patients with pure squamous carcinoma of the urothelial tract often present with gross haematuria, urinary frequency, urgency, urinary obstruction, or dysuria.
- Micro: Squamous carcinoma of the bladder shows invasive carcinoma nests with squamous differentiation, which can range from well-differentiated cells with keratin formation to poorly differentiated cells with marked atypia.
- Ancillary: Immunohistochemistry can show positivity for CK5, CK6, CK14, desmocollin-2, desmoglein-3, and MAC387, while negativity for GATA3, FOXA1, uroplakin-2, and uroplakin-3 is common.
Reference Gallery:
Squamous carcinoma of the bladder. A moderately differentiated tumour associated with Schistosoma infection. Note the Schistosoma egg in the centre.
Squamous carcinoma of the bladder. Malignant squamous cell clusters invading the lamina propria of the bladder.

Q: Microscopically, Pure Squamous Carcinoma of the Urothelial Tract displays invasive malignant nests showing overt squamous differentiation, frequently accompanied by the formation of [...].
Squamous carcinoma of the bladder. Malignant squamous cell clusters invading the lamina propria of the bladder.
A: keratin
Back Extra: Pure Squamous Carcinoma of the Urothelial Tract
- Clinical: Patients with pure squamous carcinoma of the urothelial tract often present with gross haematuria, urinary frequency, urgency, urinary obstruction, or dysuria.
- Micro: Squamous carcinoma of the bladder shows invasive carcinoma nests with squamous differentiation, which can range from well-differentiated cells with keratin formation to poorly differentiated cells with marked atypia.
- Ancillary: Immunohistochemistry can show positivity for CK5, CK6, CK14, desmocollin-2, desmoglein-3, and MAC387, while negativity for GATA3, FOXA1, uroplakin-2, and uroplakin-3 is common.
Reference Gallery:
Squamous carcinoma of the bladder. A moderately differentiated tumour associated with Schistosoma infection. Note the Schistosoma egg in the centre.
Squamous carcinoma of the bladder. Malignant squamous cell clusters invading the lamina propria of the bladder.

Q: Microscopically, Squamous Papilloma of the Urothelial Tract is characterized by papillary projections with a fibrovascular core that are covered by benign, [...] epithelium.
Squamous papilloma. A pedunculated squamous papilloma with a fibrovascular core covered by keratinizing epithelium.
A: keratinizing squamous
Back Extra: Squamous Papilloma of the Urothelial Tract
- Clinical: Squamous papillomas generally occur in elderly people and can present with gross hematuria, urinary frequency, urgency, or dysuria.
- Micro: Squamous papilloma consists of papillary projections with a fibrovascular core covered by benign, keratinizing squamous epithelium.
- Ancillary: Squamous papilloma typically shows a diploid pattern with minimal nuclear p53 accumulation.
Reference Gallery:
Squamous papilloma. A pedunculated squamous papilloma with a fibrovascular core covered by keratinizing epithelium.

Q: Morphologically, Squamous Papilloma of the Urothelial Tract typically presents as a [...] mass featuring a prominent fibrovascular core.
Squamous papilloma. A pedunculated squamous papilloma with a fibrovascular core covered by keratinizing epithelium.
A: pedunculated
Back Extra: Squamous Papilloma of the Urothelial Tract
- Clinical: Squamous papillomas generally occur in elderly people and can present with gross hematuria, urinary frequency, urgency, or dysuria.
- Micro: Squamous papilloma consists of papillary projections with a fibrovascular core covered by benign, keratinizing squamous epithelium.
- Ancillary: Squamous papilloma typically shows a diploid pattern with minimal nuclear p53 accumulation.
Reference Gallery:
Squamous papilloma. A pedunculated squamous papilloma with a fibrovascular core covered by keratinizing epithelium.

Q: Microscopically, Verrucous Carcinoma of the Bladder is characterized by well-differentiated squamous epithelium that classically displays a [...] along with minimal cytological atypia.
Verrucous carcinoma. Papillary proliferation of squamous epithelium composed of well-differentiated cells with a pushing tumour border.
A: broad, pushing invasive front
Back Extra: Verrucous Carcinoma of the Bladder
- Clinical: Patients often present with haematuria, dysuria, urinary frequency, or obstructive symptoms. Verrucous carcinoma is more common in men and is often seen in the fifth decade of life.
- Micro: Verrucous carcinoma is characterized by well-differentiated squamous epithelium with a broad, pushing invasive front and minimal cytological atypia. Large hyperkeratotic papillae and acanthosis are common features.
- Ancillary: Focal cytoplasmic and membranous positivity for EGFR and TGF-α, as well as increased p53 expression, have been reported.
Reference Gallery:
Verrucous carcinoma. A well-differentiated verrucous carcinoma with exophytic growth.
Verrucous carcinoma. Papillary proliferation of squamous epithelium composed of well-differentiated cells with a pushing tumour border.

Q: Histologically, Verrucous Carcinoma of the Bladder typically exhibits an exophytic growth pattern featuring marked acanthosis and large, hyperkeratotic [...].
Verrucous carcinoma. A well-differentiated verrucous carcinoma with exophytic growth.
Verrucous carcinoma. Papillary proliferation of squamous epithelium composed of well-differentiated cells with a pushing tumour border.
A: papillae
Back Extra: Verrucous Carcinoma of the Bladder
- Clinical: Patients often present with haematuria, dysuria, urinary frequency, or obstructive symptoms. Verrucous carcinoma is more common in men and is often seen in the fifth decade of life.
- Micro: Verrucous carcinoma is characterized by well-differentiated squamous epithelium with a broad, pushing invasive front and minimal cytological atypia. Large hyperkeratotic papillae and acanthosis are common features.
- Ancillary: Focal cytoplasmic and membranous positivity for EGFR and TGF-α, as well as increased p53 expression, have been reported.
Reference Gallery:
Verrucous carcinoma. A well-differentiated verrucous carcinoma with exophytic growth.
Verrucous carcinoma. Papillary proliferation of squamous epithelium composed of well-differentiated cells with a pushing tumour border.

Q: The provided image demonstrates a non-descriptive glandular growth pattern with atypical glandular proliferation and high-grade nuclear atypia, which is characteristic of primary [...] of the urinary bladder.
Primary adenocarcinoma of the urinary bladder NOS. Note the atypical glandular proliferation with high-grade nuclear atypia.
A: Adenocarcinoma NOS
Back Extra: Adenocarcinoma NOS
- Clinical: Haematuria is the most common symptom in patients with Adenocarcinoma NOS, occurring in approximately 90% of cases.
- Micro: Adenocarcinoma NOS shows a non-descriptive glandular growth pattern with atypical glandular proliferation and high-grade nuclear atypia.
- Ancillary: Immunohistochemistry in Adenocarcinoma NOS is positive for CK20, villin, and CDX2, and invariable positivity for CK7.
Reference Gallery:
Primary adenocarcinoma of the urinary bladder NOS. Note the atypical glandular proliferation with high-grade nuclear atypia.
Primary adenocarcinoma of the urinary bladder, signet-ring cell subtype. The tumour is characterized by infiltrative tumour cells with a large intracellular mucin vacuole and an indented nucleus.
Primary adenocarcinoma of the urinary bladder, mucinous subtype. Note the tumour cells floating in a pool of extracellular mucin.
Adenocarcinoma in situ of the urinary bladder. Enteric-type malignant glands growing on the bladder mucosal surface.
Adenocarcinoma of the urethra. The tumour is composed of atypical glandular structures with nuclear pleomorphism and loss of nuclear polarity.
Adenocarcinoma of the urethra. Adenocarcinoma of the prostatic urethra. Tumour glands (upper part of image) and benign prostate glands (lower part of image).
Mucinous (columnar) carcinoma of the urethra. Note the signet-ring cell–like morphology.
Mucinous (columnar) carcinoma of the urethra. A superficial glandular lesion is visible and mucin lakes dissect the stroma.
Mucinous (columnar) carcinoma of the urethra. Note the tumour cell clusters floating in mucinous lakes.
Mucinous (columnar) carcinoma of the urethra. Signet-ring cell–like morphology is present.
Mucinous (columnar) carcinoma of the urethra. Signet-ring cell–like morphology is present.

Q: Microscopic evaluation of Invasive Urothelial Carcinoma can reveal diverse morphologic variants; the subtype characterized by dispersed, dyscohesive cells with eccentrically placed high-grade nuclei and intracytoplasmic vacuoles is the [...] variant.
Plasmacytoid urothelial carcinoma. Invasive carcinoma comprising dispersed, dyscohesive cells with eccentrically placed high-grade nuclei imparting a plasmacytoid appearance. Intracytoplasmic vacuoles can be seen.
A: plasmacytoid
Back Extra: Invasive Urothelial Carcinoma
- Clinical: Invasive urothelial carcinoma presents with symptoms such as microscopic or macroscopic haematuria, urinary urgency, urinary frequency, and dysuria. Advanced disease may manifest as weight loss or bone pain.
- Micro: Invasive urothelial carcinoma shows diverse morphological appearances, including micropapillary, plasmacytoid, sarcomatoid, and nested subtypes. Conventional forms present as nests, sheets, and cords of cells with high-grade features.
- Ancillary: TERT promoter mutations are common and can help distinguish malignant processes from benign conditions. FGFR3 alterations can determine eligibility for targeted therapies, and PDL1 expression can predict response to immune checkpoint inhibitors.
Reference Gallery:
Plasmacytoid urothelial carcinoma. Invasive carcinoma comprising dispersed, dyscohesive cells with eccentrically placed high-grade nuclei imparting a plasmacytoid appearance. Intracytoplasmic vacuoles can be seen.
Sarcomatoid urothelial carcinoma. Spindle-shaped tumour cells with occasional epithelioid appearance and marked nuclear atypia.
Lymphoepithelioma-like urothelial carcinoma. Invasive carcinoma composed of sheets of pleomorphic cells with a syncytial arrangement admixed with a rich lymphocytic infiltrate.
Microcystic urothelial carcinoma. Relatively bland cystic structures infiltrate a non-reactive stroma.
Micropapillary urothelial carcinoma. Invasive tumour clusters with a micropapillary architecture are set in cleft-like spaces.
Clear cell (glycogen-rich) urothelial carcinoma. Sheets of clear cells have well-defined cell membranes and abundant optically clear cytoplasm.
Lymphoepithelioma-like urothelial carcinoma. Sheets of CK7-positive pleomorphic cells with a syncytial arrangement.
Lymphoepithelioma-like urothelial carcinoma. Rich lymphocytic infiltrate (CD45-positive) highlighted in lymphoepithelioma-like urothelial carcinoma.
Bladder specimen with sarcomatoid urothelial carcinoma. Macroscopic appearance of sarcomatoid urothelial carcinoma infiltrating and expanding the bladder wall.
Lipid-rich urothelial carcinoma. An invasive carcinoma composed of lipid-containing vacuolated cells imparting a lipoblast-like appearance.
Lipid-rich urothelial carcinoma. An invasive carcinoma composed of lipid-containing vacuolated cells imparting a lipoblast-like appearance.
Mutation, copy-number alteration, and mutation signature landscape of invasive urothelial carcinoma. A Genomic landscape for 412 primary, muscle-invasive urothelial carcinomas. Top to bottom: synonymous and non-synonymous somatic mutation rates, mutation signature (Msig) cluster, APOBEC mutation load, and neoantigen load by quartile; significantly mutated genes (≥ 7% of tumours); copy-number alterations and fusions for selected genes. B Kaplan–Meier plots for overall survival. Left to right: overall mutation burden (single-nucleotide variants); mutation signature clusters (Msig1–4); APOBEC-mediated mutation load; neoantigen load {28988769}.

Q: The [...] variant of Invasive Urothelial Carcinoma is a high-grade subtype characterized microscopically by spindle-shaped tumor cells with occasional epithelioid appearances and marked nuclear atypia.
Sarcomatoid urothelial carcinoma. Spindle-shaped tumour cells with occasional epithelioid appearance and marked nuclear atypia.
Bladder specimen with sarcomatoid urothelial carcinoma. Macroscopic appearance of sarcomatoid urothelial carcinoma infiltrating and expanding the bladder wall.
A: sarcomatoid
Back Extra: Invasive Urothelial Carcinoma
- Clinical: Invasive urothelial carcinoma presents with symptoms such as microscopic or macroscopic haematuria, urinary urgency, urinary frequency, and dysuria. Advanced disease may manifest as weight loss or bone pain.
- Micro: Invasive urothelial carcinoma shows diverse morphological appearances, including micropapillary, plasmacytoid, sarcomatoid, and nested subtypes. Conventional forms present as nests, sheets, and cords of cells with high-grade features.
- Ancillary: TERT promoter mutations are common and can help distinguish malignant processes from benign conditions. FGFR3 alterations can determine eligibility for targeted therapies, and PDL1 expression can predict response to immune checkpoint inhibitors.
Reference Gallery:
Plasmacytoid urothelial carcinoma. Invasive carcinoma comprising dispersed, dyscohesive cells with eccentrically placed high-grade nuclei imparting a plasmacytoid appearance. Intracytoplasmic vacuoles can be seen.
Sarcomatoid urothelial carcinoma. Spindle-shaped tumour cells with occasional epithelioid appearance and marked nuclear atypia.
Lymphoepithelioma-like urothelial carcinoma. Invasive carcinoma composed of sheets of pleomorphic cells with a syncytial arrangement admixed with a rich lymphocytic infiltrate.
Microcystic urothelial carcinoma. Relatively bland cystic structures infiltrate a non-reactive stroma.
Micropapillary urothelial carcinoma. Invasive tumour clusters with a micropapillary architecture are set in cleft-like spaces.
Clear cell (glycogen-rich) urothelial carcinoma. Sheets of clear cells have well-defined cell membranes and abundant optically clear cytoplasm.
Lymphoepithelioma-like urothelial carcinoma. Sheets of CK7-positive pleomorphic cells with a syncytial arrangement.
Lymphoepithelioma-like urothelial carcinoma. Rich lymphocytic infiltrate (CD45-positive) highlighted in lymphoepithelioma-like urothelial carcinoma.
Bladder specimen with sarcomatoid urothelial carcinoma. Macroscopic appearance of sarcomatoid urothelial carcinoma infiltrating and expanding the bladder wall.
Lipid-rich urothelial carcinoma. An invasive carcinoma composed of lipid-containing vacuolated cells imparting a lipoblast-like appearance.
Lipid-rich urothelial carcinoma. An invasive carcinoma composed of lipid-containing vacuolated cells imparting a lipoblast-like appearance.
Mutation, copy-number alteration, and mutation signature landscape of invasive urothelial carcinoma. A Genomic landscape for 412 primary, muscle-invasive urothelial carcinomas. Top to bottom: synonymous and non-synonymous somatic mutation rates, mutation signature (Msig) cluster, APOBEC mutation load, and neoantigen load by quartile; significantly mutated genes (≥ 7% of tumours); copy-number alterations and fusions for selected genes. B Kaplan–Meier plots for overall survival. Left to right: overall mutation burden (single-nucleotide variants); mutation signature clusters (Msig1–4); APOBEC-mediated mutation load; neoantigen load {28988769}.

Q: The [...] variant of Invasive Urothelial Carcinoma is characterized microscopically by tight tumor clusters that lack fibrovascular cores and reside within empty, cleft-like spaces.
Micropapillary urothelial carcinoma. Invasive tumour clusters with a micropapillary architecture are set in cleft-like spaces.
A: micropapillary
Back Extra: Invasive Urothelial Carcinoma
- Clinical: Invasive urothelial carcinoma presents with symptoms such as microscopic or macroscopic haematuria, urinary urgency, urinary frequency, and dysuria. Advanced disease may manifest as weight loss or bone pain.
- Micro: Invasive urothelial carcinoma shows diverse morphological appearances, including micropapillary, plasmacytoid, sarcomatoid, and nested subtypes. Conventional forms present as nests, sheets, and cords of cells with high-grade features.
- Ancillary: TERT promoter mutations are common and can help distinguish malignant processes from benign conditions. FGFR3 alterations can determine eligibility for targeted therapies, and PDL1 expression can predict response to immune checkpoint inhibitors.
Reference Gallery:
Plasmacytoid urothelial carcinoma. Invasive carcinoma comprising dispersed, dyscohesive cells with eccentrically placed high-grade nuclei imparting a plasmacytoid appearance. Intracytoplasmic vacuoles can be seen.
Sarcomatoid urothelial carcinoma. Spindle-shaped tumour cells with occasional epithelioid appearance and marked nuclear atypia.
Lymphoepithelioma-like urothelial carcinoma. Invasive carcinoma composed of sheets of pleomorphic cells with a syncytial arrangement admixed with a rich lymphocytic infiltrate.
Microcystic urothelial carcinoma. Relatively bland cystic structures infiltrate a non-reactive stroma.
Micropapillary urothelial carcinoma. Invasive tumour clusters with a micropapillary architecture are set in cleft-like spaces.
Clear cell (glycogen-rich) urothelial carcinoma. Sheets of clear cells have well-defined cell membranes and abundant optically clear cytoplasm.
Lymphoepithelioma-like urothelial carcinoma. Sheets of CK7-positive pleomorphic cells with a syncytial arrangement.
Lymphoepithelioma-like urothelial carcinoma. Rich lymphocytic infiltrate (CD45-positive) highlighted in lymphoepithelioma-like urothelial carcinoma.
Bladder specimen with sarcomatoid urothelial carcinoma. Macroscopic appearance of sarcomatoid urothelial carcinoma infiltrating and expanding the bladder wall.
Lipid-rich urothelial carcinoma. An invasive carcinoma composed of lipid-containing vacuolated cells imparting a lipoblast-like appearance.
Lipid-rich urothelial carcinoma. An invasive carcinoma composed of lipid-containing vacuolated cells imparting a lipoblast-like appearance.
Mutation, copy-number alteration, and mutation signature landscape of invasive urothelial carcinoma. A Genomic landscape for 412 primary, muscle-invasive urothelial carcinomas. Top to bottom: synonymous and non-synonymous somatic mutation rates, mutation signature (Msig) cluster, APOBEC mutation load, and neoantigen load by quartile; significantly mutated genes (≥ 7% of tumours); copy-number alterations and fusions for selected genes. B Kaplan–Meier plots for overall survival. Left to right: overall mutation burden (single-nucleotide variants); mutation signature clusters (Msig1–4); APOBEC-mediated mutation load; neoantigen load {28988769}.

Q: Microscopically, an inverted urothelial papilloma is classically characterized by an [...] growth pattern of anastomosing urothelial cords extending into the lamina propria.
Inverted urothelial papilloma. Endophytic urothelial growth from the overlying urothelium.
Inverted urothelial papilloma. Endophytic urothelial growth covered with normal urothelium.
A: endophytic
Back Extra: Inverted Urothelial Papilloma
- Clinical: Inverted urothelial papilloma presents with haematuria, dysuria, and irritative voiding symptoms, with a male predominance (M:F ratio: 5.8–7.3:1).
- Micro: Characterized by anastomosing urothelial cords of normal thickness (5–10 cells) with preserved polarity, growing in an endophytic pattern into the lamina propria.
- Ancillary: Inverted papillomas are CK20-negative and show low p53 expression and a low Ki-67 proliferation index.
Reference Gallery:
Inverted urothelial papilloma. Endophytic urothelial growth from the overlying urothelium.
Inverted urothelial papilloma. Thin, anastomosing, uniform trabeculae with peripheral palisading.
Inverted urothelial papilloma. Focal degenerative cytological atypia without associated mitotic activity.
Inverted urothelial papilloma. Cystoscopy showing a sessile polypoid mass with a smooth surface.
Inverted urothelial papilloma. Endophytic urothelial growth covered with normal urothelium.
Inverted urothelial papilloma. Anastomosing uniform sheets with focal microcyst formation.

Q: Histologically, the thin, anastomosing urothelial trabeculae of an inverted urothelial papilloma characteristically exhibit [...].
Inverted urothelial papilloma. Thin, anastomosing, uniform trabeculae with peripheral palisading.
A: peripheral palisading
Back Extra: Inverted Urothelial Papilloma
- Clinical: Inverted urothelial papilloma presents with haematuria, dysuria, and irritative voiding symptoms, with a male predominance (M:F ratio: 5.8–7.3:1).
- Micro: Characterized by anastomosing urothelial cords of normal thickness (5–10 cells) with preserved polarity, growing in an endophytic pattern into the lamina propria.
- Ancillary: Inverted papillomas are CK20-negative and show low p53 expression and a low Ki-67 proliferation index.
Reference Gallery:
Inverted urothelial papilloma. Endophytic urothelial growth from the overlying urothelium.
Inverted urothelial papilloma. Thin, anastomosing, uniform trabeculae with peripheral palisading.
Inverted urothelial papilloma. Focal degenerative cytological atypia without associated mitotic activity.
Inverted urothelial papilloma. Cystoscopy showing a sessile polypoid mass with a smooth surface.
Inverted urothelial papilloma. Endophytic urothelial growth covered with normal urothelium.
Inverted urothelial papilloma. Anastomosing uniform sheets with focal microcyst formation.

Q: On cystoscopy, an inverted urothelial papilloma typically presents as a sessile polypoid mass with a [...] surface, contrasting with the frond-like appearance of exophytic lesions.
Inverted urothelial papilloma. Cystoscopy showing a sessile polypoid mass with a smooth surface.
A: smooth
Back Extra: Inverted Urothelial Papilloma
- Clinical: Inverted urothelial papilloma presents with haematuria, dysuria, and irritative voiding symptoms, with a male predominance (M:F ratio: 5.8–7.3:1).
- Micro: Characterized by anastomosing urothelial cords of normal thickness (5–10 cells) with preserved polarity, growing in an endophytic pattern into the lamina propria.
- Ancillary: Inverted papillomas are CK20-negative and show low p53 expression and a low Ki-67 proliferation index.
Reference Gallery:
Inverted urothelial papilloma. Endophytic urothelial growth from the overlying urothelium.
Inverted urothelial papilloma. Thin, anastomosing, uniform trabeculae with peripheral palisading.
Inverted urothelial papilloma. Focal degenerative cytological atypia without associated mitotic activity.
Inverted urothelial papilloma. Cystoscopy showing a sessile polypoid mass with a smooth surface.
Inverted urothelial papilloma. Endophytic urothelial growth covered with normal urothelium.
Inverted urothelial papilloma. Anastomosing uniform sheets with focal microcyst formation.

Q: Characterized histologically by papillae with thin fibrovascular cores lined by thickened urothelium demonstrating mild cytological atypia and minimal architectural disorder, the diagnosis is [...].
Non-invasive papillary urothelial carcinoma, low-grade. Papillae are lined by thickened urothelium with mild cytological atypia and minimal architectural disorder.
Non-invasive papillary urothelial carcinoma, low-grade. Papillae are lined by urothelium with minor cytological and architectural disorder.
Non-invasive papillary urothelial carcinoma, low-grade. High-magnification view shows papillary cores lined by thickened urothelium with mild cytological atypia and no marked pleomorphism.
A: Non-invasive Papillary Urothelial Carcinoma, Low-Grade
Back Extra: Non-invasive Papillary Urothelial Carcinoma, Low-Grade
- Clinical: Non-invasive papillary urothelial carcinoma, low-grade typically presents with haematuria and lower urinary tract symptoms; it has a male predominance and tends to occur in patients over 60 years old.
- Micro: Low-grade, non-invasive papillary urothelial carcinoma is characterized by thin fibrovascular cores lined by urothelial cells with mild nuclear atypia and architectural disorder. Papillary structures may branch or fuse, and occasional mitotic figures can be present.
- Ancillary: Molecular studies often reveal mutations in FGFR3 and TERT promoter, and frequent mutations in HRAS, PIK3CA, PTEN, STAG2, and TSC1. CDKN2A deletion or TP53/RB1 loss can indicate progression to high-grade invasive carcinoma.
Reference Gallery:
Non-invasive papillary urothelial carcinoma, low-grade. Papillae are lined by thickened urothelium with mild cytological atypia and minimal architectural disorder.
Non-invasive papillary urothelial carcinoma, low-grade. Papillae are lined by urothelium with minor cytological and architectural disorder.
Non-invasive papillary urothelial carcinoma, low-grade. Thickened and fused papillary structures are lined by mildly atypical urothelial cells.
Non-invasive papillary urothelial carcinoma, low-grade. High-magnification view shows papillary cores lined by thickened urothelium with mild cytological atypia and no marked pleomorphism.
Non-invasive papillary urothelial carcinoma, low-grade, with inverted growth pattern. Complex interconnecting inverted growth of thick cords and nodules of urothelial cells into the lamina propria with only mild nuclear atypia.

Q: A distinct histologic presentation of Non-invasive Papillary Urothelial Carcinoma, Low-Grade features an [...] growth pattern, demonstrating complex interconnecting thick cords and nodules of mildly atypical urothelial cells extending down into the lamina propria.
Non-invasive papillary urothelial carcinoma, low-grade, with inverted growth pattern. Complex interconnecting inverted growth of thick cords and nodules of urothelial cells into the lamina propria with only mild nuclear atypia.
A: inverted
Back Extra: Non-invasive Papillary Urothelial Carcinoma, Low-Grade
- Clinical: Non-invasive papillary urothelial carcinoma, low-grade typically presents with haematuria and lower urinary tract symptoms; it has a male predominance and tends to occur in patients over 60 years old.
- Micro: Low-grade, non-invasive papillary urothelial carcinoma is characterized by thin fibrovascular cores lined by urothelial cells with mild nuclear atypia and architectural disorder. Papillary structures may branch or fuse, and occasional mitotic figures can be present.
- Ancillary: Molecular studies often reveal mutations in FGFR3 and TERT promoter, and frequent mutations in HRAS, PIK3CA, PTEN, STAG2, and TSC1. CDKN2A deletion or TP53/RB1 loss can indicate progression to high-grade invasive carcinoma.
Reference Gallery:
Non-invasive papillary urothelial carcinoma, low-grade. Papillae are lined by thickened urothelium with mild cytological atypia and minimal architectural disorder.
Non-invasive papillary urothelial carcinoma, low-grade. Papillae are lined by urothelium with minor cytological and architectural disorder.
Non-invasive papillary urothelial carcinoma, low-grade. Thickened and fused papillary structures are lined by mildly atypical urothelial cells.
Non-invasive papillary urothelial carcinoma, low-grade. High-magnification view shows papillary cores lined by thickened urothelium with mild cytological atypia and no marked pleomorphism.
Non-invasive papillary urothelial carcinoma, low-grade, with inverted growth pattern. Complex interconnecting inverted growth of thick cords and nodules of urothelial cells into the lamina propria with only mild nuclear atypia.

Q: Alongside typical branching, the fibrovascular papillae in Non-invasive Papillary Urothelial Carcinoma, Low-Grade can frequently undergo architectural [...], appearing as thickened, interconnected structures lined by mildly atypical urothelium.
Non-invasive papillary urothelial carcinoma, low-grade. Thickened and fused papillary structures are lined by mildly atypical urothelial cells.
A: fusion
Back Extra: Non-invasive Papillary Urothelial Carcinoma, Low-Grade
- Clinical: Non-invasive papillary urothelial carcinoma, low-grade typically presents with haematuria and lower urinary tract symptoms; it has a male predominance and tends to occur in patients over 60 years old.
- Micro: Low-grade, non-invasive papillary urothelial carcinoma is characterized by thin fibrovascular cores lined by urothelial cells with mild nuclear atypia and architectural disorder. Papillary structures may branch or fuse, and occasional mitotic figures can be present.
- Ancillary: Molecular studies often reveal mutations in FGFR3 and TERT promoter, and frequent mutations in HRAS, PIK3CA, PTEN, STAG2, and TSC1. CDKN2A deletion or TP53/RB1 loss can indicate progression to high-grade invasive carcinoma.
Reference Gallery:
Non-invasive papillary urothelial carcinoma, low-grade. Papillae are lined by thickened urothelium with mild cytological atypia and minimal architectural disorder.
Non-invasive papillary urothelial carcinoma, low-grade. Papillae are lined by urothelium with minor cytological and architectural disorder.
Non-invasive papillary urothelial carcinoma, low-grade. Thickened and fused papillary structures are lined by mildly atypical urothelial cells.
Non-invasive papillary urothelial carcinoma, low-grade. High-magnification view shows papillary cores lined by thickened urothelium with mild cytological atypia and no marked pleomorphism.
Non-invasive papillary urothelial carcinoma, low-grade, with inverted growth pattern. Complex interconnecting inverted growth of thick cords and nodules of urothelial cells into the lamina propria with only mild nuclear atypia.

Q: Microscopically, Non-invasive Papillary Urothelial Carcinoma, High-Grade displays complex papillae with fusion and branching, as well as marked architectural disorder and cytological [...] with a high N:C ratio and loss of polarity.
Non-invasive papillary urothelial carcinoma, high-grade. Note the disordered architecture and nuclear pleomorphism with nuclear hyperchromasia.
Non-invasive papillary urothelial carcinoma, high-grade. High-magnification view illustrating the marked nuclear pleomorphism, high N:C ratio, and loss of polarity.
A: pleomorphism
Q: Non-invasive Papillary Urothelial Carcinoma, High-Grade
- Clinical: The most frequent presenting symptom of [...] is microscopic or macroscopic haematuria, with other common symptoms including urinary frequency, urgency, and irritative voiding symptoms.
- Micro: [...] displays marked architectural and cytological disorder, with papillae that are more complex than in low-grade tumours, showing fusion and frequent branching, and cells with irregular and pleomorphic nuclei.
- Ancillary: In [...], immunohistochemistry often shows positivity for GATA3, p63, CK20, or CK5/6, and a high Ki-67 index, with common somatic TERT promoter mutations and allelic loss of chromosome 9.
Reference Gallery:
Non-invasive papillary urothelial carcinoma, high-grade. Note the disordered architecture and nuclear pleomorphism with nuclear hyperchromasia.
Non-invasive papillary urothelial carcinoma, high-grade. High-magnification view illustrating the marked nuclear pleomorphism, high N:C ratio, and loss of polarity.
Non-invasive papillary urothelial carcinoma, high-grade. Nuclear pleomorphism is evident.
Non-invasive papillary urothelial carcinoma, high-grade. Micropapillary pattern. Note the secondary structures; micropapillary tufts.
Non-invasive papillary urothelial carcinoma, high-grade. Villoglandular pattern. The papillary structures have acquired a villous morphology with focal columnar cell lining.
Non-invasive papillary urothelial carcinoma, high-grade, with inverted growth pattern. The inverted growth pattern is characterized by the endophytic growth of sheets and nodules into the lamina propria. The smooth stromal epithelial interface is the key to establishing the non-invasive nature of the tumour.
Non-invasive papillary urothelial carcinoma, high-grade, with inverted growth pattern. High-magnification view of the endophytic growth of urothelial nodules into the lamina propria. Note the smooth stromal epithelial interface and absence of stromal desmoplasia or retraction artefact.
Non-invasive papillary urothelial carcinoma, high-grade. Urine cytology. Smear showing urothelial cells with a high N:C ratio, hyperchromatic nuclei, and an irregular nuclear membrane.
Non-invasive papillary urothelial carcinoma, high-grade. Urine cytology. Urothelial cells with a high N:C ratio, enlarged hyperchromatic nuclei, and an irregular nuclear membrane.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology of a stage Ta tumour.
A: Non-invasive Papillary Urothelial Carcinoma, High-Grade; Non-invasive Papillary Urothelial Carcinoma, High-Grade; Non-invasive Papillary Urothelial Carcinoma, High-Grade

Q: Urine cytology of Non-invasive Papillary Urothelial Carcinoma, High-Grade typically reveals shedding of abnormal urothelial cells with a high N:C ratio, enlarged hyperchromatic nuclei, and an irregular [...].
Non-invasive papillary urothelial carcinoma, high-grade. Urine cytology. Smear showing urothelial cells with a high N:C ratio, hyperchromatic nuclei, and an irregular nuclear membrane.
Non-invasive papillary urothelial carcinoma, high-grade. Urine cytology. Urothelial cells with a high N:C ratio, enlarged hyperchromatic nuclei, and an irregular nuclear membrane.
A: nuclear membrane
Q: Non-invasive Papillary Urothelial Carcinoma, High-Grade
- Clinical: The most frequent presenting symptom of [...] is microscopic or macroscopic haematuria, with other common symptoms including urinary frequency, urgency, and irritative voiding symptoms.
- Micro: [...] displays marked architectural and cytological disorder, with papillae that are more complex than in low-grade tumours, showing fusion and frequent branching, and cells with irregular and pleomorphic nuclei.
- Ancillary: In [...], immunohistochemistry often shows positivity for GATA3, p63, CK20, or CK5/6, and a high Ki-67 index, with common somatic TERT promoter mutations and allelic loss of chromosome 9.
Reference Gallery:
Non-invasive papillary urothelial carcinoma, high-grade. Note the disordered architecture and nuclear pleomorphism with nuclear hyperchromasia.
Non-invasive papillary urothelial carcinoma, high-grade. High-magnification view illustrating the marked nuclear pleomorphism, high N:C ratio, and loss of polarity.
Non-invasive papillary urothelial carcinoma, high-grade. Nuclear pleomorphism is evident.
Non-invasive papillary urothelial carcinoma, high-grade. Micropapillary pattern. Note the secondary structures; micropapillary tufts.
Non-invasive papillary urothelial carcinoma, high-grade. Villoglandular pattern. The papillary structures have acquired a villous morphology with focal columnar cell lining.
Non-invasive papillary urothelial carcinoma, high-grade, with inverted growth pattern. The inverted growth pattern is characterized by the endophytic growth of sheets and nodules into the lamina propria. The smooth stromal epithelial interface is the key to establishing the non-invasive nature of the tumour.
Non-invasive papillary urothelial carcinoma, high-grade, with inverted growth pattern. High-magnification view of the endophytic growth of urothelial nodules into the lamina propria. Note the smooth stromal epithelial interface and absence of stromal desmoplasia or retraction artefact.
Non-invasive papillary urothelial carcinoma, high-grade. Urine cytology. Smear showing urothelial cells with a high N:C ratio, hyperchromatic nuclei, and an irregular nuclear membrane.
Non-invasive papillary urothelial carcinoma, high-grade. Urine cytology. Urothelial cells with a high N:C ratio, enlarged hyperchromatic nuclei, and an irregular nuclear membrane.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology of a stage Ta tumour.
A: Non-invasive Papillary Urothelial Carcinoma, High-Grade; Non-invasive Papillary Urothelial Carcinoma, High-Grade; Non-invasive Papillary Urothelial Carcinoma, High-Grade

Q: In cases of Non-invasive Papillary Urothelial Carcinoma, High-Grade with an inverted growth pattern, the non-invasive nature of the tumor is established by the presence of a smooth [...] and the absence of desmoplasia or retraction artifact.
Non-invasive papillary urothelial carcinoma, high-grade, with inverted growth pattern. The inverted growth pattern is characterized by the endophytic growth of sheets and nodules into the lamina propria. The smooth stromal epithelial interface is the key to establishing the non-invasive nature of the tumour.
Non-invasive papillary urothelial carcinoma, high-grade, with inverted growth pattern. High-magnification view of the endophytic growth of urothelial nodules into the lamina propria. Note the smooth stromal epithelial interface and absence of stromal desmoplasia or retraction artefact.
A: stromal-epithelial interface
Q: Non-invasive Papillary Urothelial Carcinoma, High-Grade
- Clinical: The most frequent presenting symptom of [...] is microscopic or macroscopic haematuria, with other common symptoms including urinary frequency, urgency, and irritative voiding symptoms.
- Micro: [...] displays marked architectural and cytological disorder, with papillae that are more complex than in low-grade tumours, showing fusion and frequent branching, and cells with irregular and pleomorphic nuclei.
- Ancillary: In [...], immunohistochemistry often shows positivity for GATA3, p63, CK20, or CK5/6, and a high Ki-67 index, with common somatic TERT promoter mutations and allelic loss of chromosome 9.
Reference Gallery:
Non-invasive papillary urothelial carcinoma, high-grade. Note the disordered architecture and nuclear pleomorphism with nuclear hyperchromasia.
Non-invasive papillary urothelial carcinoma, high-grade. High-magnification view illustrating the marked nuclear pleomorphism, high N:C ratio, and loss of polarity.
Non-invasive papillary urothelial carcinoma, high-grade. Nuclear pleomorphism is evident.
Non-invasive papillary urothelial carcinoma, high-grade. Micropapillary pattern. Note the secondary structures; micropapillary tufts.
Non-invasive papillary urothelial carcinoma, high-grade. Villoglandular pattern. The papillary structures have acquired a villous morphology with focal columnar cell lining.
Non-invasive papillary urothelial carcinoma, high-grade, with inverted growth pattern. The inverted growth pattern is characterized by the endophytic growth of sheets and nodules into the lamina propria. The smooth stromal epithelial interface is the key to establishing the non-invasive nature of the tumour.
Non-invasive papillary urothelial carcinoma, high-grade, with inverted growth pattern. High-magnification view of the endophytic growth of urothelial nodules into the lamina propria. Note the smooth stromal epithelial interface and absence of stromal desmoplasia or retraction artefact.
Non-invasive papillary urothelial carcinoma, high-grade. Urine cytology. Smear showing urothelial cells with a high N:C ratio, hyperchromatic nuclei, and an irregular nuclear membrane.
Non-invasive papillary urothelial carcinoma, high-grade. Urine cytology. Urothelial cells with a high N:C ratio, enlarged hyperchromatic nuclei, and an irregular nuclear membrane.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology.
Non-invasive papillary urothelial carcinoma, high-grade. Cytology of a stage Ta tumour.
A: Non-invasive Papillary Urothelial Carcinoma, High-Grade; Non-invasive Papillary Urothelial Carcinoma, High-Grade; Non-invasive Papillary Urothelial Carcinoma, High-Grade

Q: Microscopically, Papillary Urothelial Neoplasm of Low Malignant Potential features branching papillary structures lined by a thickened urothelium that characteristically lacks significant [...].
Papillary urothelial neoplasm of low malignant potential. Papillary cores are lined by urothelial cells without overt cytological atypia.
Papillary urothelial neoplasm of low malignant potential. High-magnification view shows thickened urothelium without cytological atypia lining papillary structures.
A: cytological atypia
Back Extra: Papillary Urothelial Neoplasm of Low Malignant Potential
- Clinical: Patients typically present with haematuria or other lower urinary tract symptoms, and PUNLMP has a strong male predominance.
- Micro: PUNLMP features branching papillary structures lined by thickened urothelium with mild cellular and nuclear enlargement but without significant cytological atypia.
- Ancillary: Immunohistochemistry for CK20 or p53 is not clinically relevant in the diagnosis of PUNLMP.
Reference Gallery:
Papillary urothelial neoplasm of low malignant potential. Papillary cores are lined by urothelial cells without overt cytological atypia.
Papillary urothelial neoplasm of low malignant potential. High-magnification view shows thickened urothelium without cytological atypia lining papillary structures.

Q: In Urothelial Carcinoma in Situ, the microscopic appearance is characterized by high-grade cytological atypia, hyperchromasia, large pleomorphic nuclei, and a complete loss of [...].
Urothelial carcinoma in situ. Most of the urothelium has been replaced by high-grade malignant cells; however, a layer of benign cells is preserved at the base of the epithelium.
Urothelial carcinoma in situ. High-magnification view shows urothelial cells with high-grade cytological atypia.
A: nuclear polarity
Back Extra: Urothelial Carcinoma in Situ
- Clinical: Patients with Urothelial Carcinoma in Situ (CIS) can present with microscopic or macroscopic haematuria, dysuria, urinary frequency, and urgency. It is often asymptomatic and detected during surveillance for prior urothelial carcinoma.
- Micro: Urothelial Carcinoma in Situ is characterized by large pleomorphic nuclei with hyperchromasia, irregular chromatin, and loss of nuclear polarity. Pagetoid spread and cells undermining benign urothelium are diagnostic features.
- Ancillary: Immunohistochemistry in Urothelial Carcinoma in Situ often shows full-thickness CK20 positivity, abnormal p53 expression, and decreased CD44 staining.
Reference Gallery:
Urothelial carcinoma in situ. Most of the urothelium has been replaced by high-grade malignant cells; however, a layer of benign cells is preserved at the base of the epithelium.
Urothelial carcinoma in situ. This example is predominantly denuded; however, the residual epithelial cells have hyperchromatic nuclei with a high N:C ratio and a plasmacytoid appearance.
Urothelial carcinoma in situ. The large cell pattern of carcinoma in situ contains large cells with voluminous cytoplasm, usually eosinophilic.
Urothelial carcinoma in situ. This example spreads in a pagetoid fashion through metaplastic keratinized squamous epithelium of the lateral bladder wall.
Urothelial carcinoma in situ. High-magnification view shows urothelial cells with high-grade cytological atypia.
Urothelial carcinoma in situ. Dysplasia of the urothelium.
Carcinoma in situ. Carcinoma in situ with numerous mitoses.
Carcinoma in situ. This example shows multiple glandular lumina and apically polarized cytoplasm, consistent with adenocarcinoma in situ or carcinoma in situ with glandular differentiation.

Q: A classic diagnostic pattern of Urothelial Carcinoma in Situ occurs when large malignant cells spread through the epithelium in a [...] fashion or selectively undermine the residual benign urothelium.
Urothelial carcinoma in situ. This example spreads in a pagetoid fashion through metaplastic keratinized squamous epithelium of the lateral bladder wall.
Urothelial carcinoma in situ. Most of the urothelium has been replaced by high-grade malignant cells; however, a layer of benign cells is preserved at the base of the epithelium.
A: pagetoid
Back Extra: Urothelial Carcinoma in Situ
- Clinical: Patients with Urothelial Carcinoma in Situ (CIS) can present with microscopic or macroscopic haematuria, dysuria, urinary frequency, and urgency. It is often asymptomatic and detected during surveillance for prior urothelial carcinoma.
- Micro: Urothelial Carcinoma in Situ is characterized by large pleomorphic nuclei with hyperchromasia, irregular chromatin, and loss of nuclear polarity. Pagetoid spread and cells undermining benign urothelium are diagnostic features.
- Ancillary: Immunohistochemistry in Urothelial Carcinoma in Situ often shows full-thickness CK20 positivity, abnormal p53 expression, and decreased CD44 staining.
Reference Gallery:
Urothelial carcinoma in situ. Most of the urothelium has been replaced by high-grade malignant cells; however, a layer of benign cells is preserved at the base of the epithelium.
Urothelial carcinoma in situ. This example is predominantly denuded; however, the residual epithelial cells have hyperchromatic nuclei with a high N:C ratio and a plasmacytoid appearance.
Urothelial carcinoma in situ. The large cell pattern of carcinoma in situ contains large cells with voluminous cytoplasm, usually eosinophilic.
Urothelial carcinoma in situ. This example spreads in a pagetoid fashion through metaplastic keratinized squamous epithelium of the lateral bladder wall.
Urothelial carcinoma in situ. High-magnification view shows urothelial cells with high-grade cytological atypia.
Urothelial carcinoma in situ. Dysplasia of the urothelium.
Carcinoma in situ. Carcinoma in situ with numerous mitoses.
Carcinoma in situ. This example shows multiple glandular lumina and apically polarized cytoplasm, consistent with adenocarcinoma in situ or carcinoma in situ with glandular differentiation.

Q: Because the high-grade malignant cells lack normal cohesiveness, Urothelial Carcinoma in Situ frequently presents histologically as a predominantly [...] urothelium, leaving only sparse residual cells with high N:C ratios.
Urothelial carcinoma in situ. This example is predominantly denuded; however, the residual epithelial cells have hyperchromatic nuclei with a high N:C ratio and a plasmacytoid appearance.
A: denuded
Back Extra: Urothelial Carcinoma in Situ
- Clinical: Patients with Urothelial Carcinoma in Situ (CIS) can present with microscopic or macroscopic haematuria, dysuria, urinary frequency, and urgency. It is often asymptomatic and detected during surveillance for prior urothelial carcinoma.
- Micro: Urothelial Carcinoma in Situ is characterized by large pleomorphic nuclei with hyperchromasia, irregular chromatin, and loss of nuclear polarity. Pagetoid spread and cells undermining benign urothelium are diagnostic features.
- Ancillary: Immunohistochemistry in Urothelial Carcinoma in Situ often shows full-thickness CK20 positivity, abnormal p53 expression, and decreased CD44 staining.
Reference Gallery:
Urothelial carcinoma in situ. Most of the urothelium has been replaced by high-grade malignant cells; however, a layer of benign cells is preserved at the base of the epithelium.
Urothelial carcinoma in situ. This example is predominantly denuded; however, the residual epithelial cells have hyperchromatic nuclei with a high N:C ratio and a plasmacytoid appearance.
Urothelial carcinoma in situ. The large cell pattern of carcinoma in situ contains large cells with voluminous cytoplasm, usually eosinophilic.
Urothelial carcinoma in situ. This example spreads in a pagetoid fashion through metaplastic keratinized squamous epithelium of the lateral bladder wall.
Urothelial carcinoma in situ. High-magnification view shows urothelial cells with high-grade cytological atypia.
Urothelial carcinoma in situ. Dysplasia of the urothelium.
Carcinoma in situ. Carcinoma in situ with numerous mitoses.
Carcinoma in situ. This example shows multiple glandular lumina and apically polarized cytoplasm, consistent with adenocarcinoma in situ or carcinoma in situ with glandular differentiation.

Q: Microscopically, [...] is characterized by delicate, exophytic papillae with minimal branching, lined by normal-appearing urothelium of normal thickness (≤ 7 cell layers).
Urothelial papilloma. Exophytic slender papillary structures with minimal branching and urothelial lining of normal thickness.
Urothelial papilloma. Exophytic slender papillary structures with minimal branching and urothelial lining of normal thickness.
A: Urothelial Papilloma
Q: Urothelial Papilloma
- Clinical: Symptoms of [...] include microscopic or gross hematuria, and it is more common in males in their fifth decade of life.
- Micro: [...] is characterized by delicate papillae lined by normal-appearing urothelium of normal thickness (≤ 7 cell layers) with minimal branching.
- Ancillary: [...] are not required for the diagnosis of urothelial papilloma, but may be useful in patients with a history of prior non–muscle-invasive bladder cancer.
Reference Gallery:
Urothelial papilloma. Note the vacuolated umbrella cells.
Urothelial papilloma. Exophytic slender papillary structures with minimal branching and urothelial lining of normal thickness.
Urothelial papilloma. Exophytic slender papillary structures with minimal branching. The urothelial lining is of normal thickness, with cuboidal umbrella cells with slightly enlarged nuclei and occasional vacuoles.
Urothelial papilloma. Exophytic slender papillary structures with minimal branching and urothelial lining of normal thickness.
A: Urothelial papilloma; Urothelial papilloma; Molecular diagnostics

Q: In Urothelial Papilloma, the delicate papillae are lined by normal urothelium whose surface frequently features prominent, occasionally vacuolated [...].
Urothelial papilloma. Note the vacuolated umbrella cells.
Urothelial papilloma. Exophytic slender papillary structures with minimal branching. The urothelial lining is of normal thickness, with cuboidal umbrella cells with slightly enlarged nuclei and occasional vacuoles.
A: umbrella cells
Q: Urothelial Papilloma
- Clinical: Symptoms of [...] include microscopic or gross hematuria, and it is more common in males in their fifth decade of life.
- Micro: [...] is characterized by delicate papillae lined by normal-appearing urothelium of normal thickness (≤ 7 cell layers) with minimal branching.
- Ancillary: [...] are not required for the diagnosis of urothelial papilloma, but may be useful in patients with a history of prior non–muscle-invasive bladder cancer.
Reference Gallery:
Urothelial papilloma. Note the vacuolated umbrella cells.
Urothelial papilloma. Exophytic slender papillary structures with minimal branching and urothelial lining of normal thickness.
Urothelial papilloma. Exophytic slender papillary structures with minimal branching. The urothelial lining is of normal thickness, with cuboidal umbrella cells with slightly enlarged nuclei and occasional vacuoles.
Urothelial papilloma. Exophytic slender papillary structures with minimal branching and urothelial lining of normal thickness.
A: Urothelial papilloma; Urothelial papilloma; Molecular diagnostics

Q: The characteristic appearance of [...] consists of a triphasic mixture of mature adipose tissue, thick-walled blood vessels, and smooth muscle cells.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma composed of adipose tissue, smooth muscle cells, and thick-walled blood vessels.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. Gross section with all three components: lipomatous, vascular, and smooth muscle tissue.
A: Classic Angiomyolipoma / PEComa of the Kidney
Back Extra: Classic Angiomyolipoma / PEComa of the Kidney
- Clinical: Most cases of Classic Angiomyolipoma / PEComa of the Kidney are asymptomatic and diagnosed incidentally during imaging. They are more likely to require intervention if larger, due to the risk of life-threatening haemorrhage (Wunderlich syndrome).
- Micro: Microscopic features include a variable mixture of adipose tissue, thick-walled blood vessels, and smooth muscle cells. The smooth muscle cells often form sunburst-like structures around vessels.
- Ancillary: Immunohistochemistry shows coexpression of melanocytic markers (HMB45, melan-A, and MITF) and smooth muscle markers (SMA and calponin). Epithelial markers are always negative.
Reference Gallery:
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma composed of adipose tissue, smooth muscle cells, and thick-walled blood vessels.
Classic angiomyolipoma. Patchy HMB45 staining, in particular around the blood vessels.
Classic angiomyolipoma / PEComa of the kidney. Angiomyolipoma with epithelial cysts. High-magnification view. Note the hobnail cells lining the cysts, and the compact cambium-like layer of stromal cells underneath.
Microhamartoma. A small nodule with some features of angiomyolipoma is called a microhamartoma.
Classic angiomyolipoma / PEComa of the kidney. An enlarged kidney with multiple cysts and angiomyolipomas in a patient with TSC2/PKD1 contiguous gene syndrome.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. Gross section with all three components: lipomatous, vascular, and smooth muscle tissue.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma, gross view. Predominantly lipomatous angiomyolipoma resembling normal fatty retroperitoneal tissue.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. Predominantly smooth muscle with an abortive thick-walled vessel in the upper-left corner.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. This example is smooth muscle–rich, without a lipomatous component.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. This tumour is composed of smooth muscle tissue with numerous thick-walled vessels and a sharp expansive border with the surrounding lipomatous tissue.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. Low-power view showing well-demarcated, smooth muscle–rich classic angiomyolipoma within the renal cortex.
Classic angiomyolipoma. Melan-A immunohistochemistry (red substrate detection).

Q: Immunohistochemistry for Classic Angiomyolipoma / PEComa of the Kidney is diagnostically unique due to the coexpression of smooth muscle markers (e.g., SMA, calponin) and melanocytic markers, particularly Melan-A and [...].
Classic angiomyolipoma. Patchy HMB45 staining, in particular around the blood vessels.
Classic angiomyolipoma. Melan-A immunohistochemistry (red substrate detection).
A: HMB45
Back Extra: Classic Angiomyolipoma / PEComa of the Kidney
- Clinical: Most cases of Classic Angiomyolipoma / PEComa of the Kidney are asymptomatic and diagnosed incidentally during imaging. They are more likely to require intervention if larger, due to the risk of life-threatening haemorrhage (Wunderlich syndrome).
- Micro: Microscopic features include a variable mixture of adipose tissue, thick-walled blood vessels, and smooth muscle cells. The smooth muscle cells often form sunburst-like structures around vessels.
- Ancillary: Immunohistochemistry shows coexpression of melanocytic markers (HMB45, melan-A, and MITF) and smooth muscle markers (SMA and calponin). Epithelial markers are always negative.
Reference Gallery:
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma composed of adipose tissue, smooth muscle cells, and thick-walled blood vessels.
Classic angiomyolipoma. Patchy HMB45 staining, in particular around the blood vessels.
Classic angiomyolipoma / PEComa of the kidney. Angiomyolipoma with epithelial cysts. High-magnification view. Note the hobnail cells lining the cysts, and the compact cambium-like layer of stromal cells underneath.
Microhamartoma. A small nodule with some features of angiomyolipoma is called a microhamartoma.
Classic angiomyolipoma / PEComa of the kidney. An enlarged kidney with multiple cysts and angiomyolipomas in a patient with TSC2/PKD1 contiguous gene syndrome.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. Gross section with all three components: lipomatous, vascular, and smooth muscle tissue.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma, gross view. Predominantly lipomatous angiomyolipoma resembling normal fatty retroperitoneal tissue.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. Predominantly smooth muscle with an abortive thick-walled vessel in the upper-left corner.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. This example is smooth muscle–rich, without a lipomatous component.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. This tumour is composed of smooth muscle tissue with numerous thick-walled vessels and a sharp expansive border with the surrounding lipomatous tissue.
Classic angiomyolipoma / PEComa of the kidney. Classic angiomyolipoma. Low-power view showing well-demarcated, smooth muscle–rich classic angiomyolipoma within the renal cortex.
Classic angiomyolipoma. Melan-A immunohistochemistry (red substrate detection).

Q: A pediatric renal tumor displaying plump ovoid cells with variably clear nuclei, an arborizing delicate branching vasculature, and diffuse nuclear positivity for cyclin D1 is characteristic of [...].
Clear cell sarcoma of the kidney. Classic areas feature ovoid tumour cells with variably clear nuclei and cytoplasm. Note the delicate branching vasculature.
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for cyclin D1. Note that vascular endothelial cells are negative.
A: Clear Cell Sarcoma of the Kidney
Back Extra: Clear Cell Sarcoma of the Kidney
- Clinical: Clear cell sarcoma of the kidney (CCSK) typically presents in children with nonspecific symptoms such as abdominal distension, pain, or a palpable mass. It constitutes 3–5% of malignant renal tumours in childhood, with a mean age at diagnosis of 3 years and a male-to-female ratio of 2:1.
- Micro: Histologically, CCSK shows various patterns including classic, cellular, myxoid, sclerosing, epithelioid, palisading, and spindled. The classic pattern features plump ovoid tumour cells with clear nuclei and cytoplasm, arranged in broad trabeculae or nests with arborizing fibrovascular septa.
- Ancillary: Immunohistochemistry shows strong and diffuse nuclear staining for cyclin D1 and BCOR, supporting the diagnosis of CCSK. Molecularly, CCSK is characterized by BCOR mutations or YWHAE::NUTM2 gene fusion.
Reference Gallery:
Clear cell sarcoma of the kidney. Grossly, this tumour is a well-circumscribed fleshy mass.
Clear cell sarcoma of the kidney. Classic areas feature ovoid tumour cells with variably clear nuclei and cytoplasm. Note the delicate branching vasculature.
Clear cell sarcoma of the kidney. Cellular areas feature overlapping of the nuclei.
Clear cell sarcoma of the kidney. Myxoid areas show increased extracellular matrix. Cyst formation is possible.
Clear cell sarcoma of the kidney. Epithelioid areas feature tumour cells arranged as tubules or trabeculae.
Clear cell sarcoma of the kidney. Palisading areas resemble Verocay bodies of schwannomas.
Clear cell sarcoma of the kidney. Spindled areas feature fascicular groups of elongated tumour cells, resembling a spindle cell sarcoma.
Clear cell sarcoma of the kidney. Anaplasia may rarely occur in clear cell sarcoma of the kidney. It is defined as for nephroblastoma.
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for cyclin D1. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for BCOR. Note that vascular endothelial cells are negative.

Q: In cases of Clear Cell Sarcoma of the Kidney, immunohistochemistry characteristically demonstrates strong and diffuse nuclear staining for cyclin D1 and [...].
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for cyclin D1. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for BCOR. Note that vascular endothelial cells are negative.
A: BCOR
Back Extra: Clear Cell Sarcoma of the Kidney
- Clinical: Clear cell sarcoma of the kidney (CCSK) typically presents in children with nonspecific symptoms such as abdominal distension, pain, or a palpable mass. It constitutes 3–5% of malignant renal tumours in childhood, with a mean age at diagnosis of 3 years and a male-to-female ratio of 2:1.
- Micro: Histologically, CCSK shows various patterns including classic, cellular, myxoid, sclerosing, epithelioid, palisading, and spindled. The classic pattern features plump ovoid tumour cells with clear nuclei and cytoplasm, arranged in broad trabeculae or nests with arborizing fibrovascular septa.
- Ancillary: Immunohistochemistry shows strong and diffuse nuclear staining for cyclin D1 and BCOR, supporting the diagnosis of CCSK. Molecularly, CCSK is characterized by BCOR mutations or YWHAE::NUTM2 gene fusion.
Reference Gallery:
Clear cell sarcoma of the kidney. Grossly, this tumour is a well-circumscribed fleshy mass.
Clear cell sarcoma of the kidney. Classic areas feature ovoid tumour cells with variably clear nuclei and cytoplasm. Note the delicate branching vasculature.
Clear cell sarcoma of the kidney. Cellular areas feature overlapping of the nuclei.
Clear cell sarcoma of the kidney. Myxoid areas show increased extracellular matrix. Cyst formation is possible.
Clear cell sarcoma of the kidney. Epithelioid areas feature tumour cells arranged as tubules or trabeculae.
Clear cell sarcoma of the kidney. Palisading areas resemble Verocay bodies of schwannomas.
Clear cell sarcoma of the kidney. Spindled areas feature fascicular groups of elongated tumour cells, resembling a spindle cell sarcoma.
Clear cell sarcoma of the kidney. Anaplasia may rarely occur in clear cell sarcoma of the kidney. It is defined as for nephroblastoma.
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for cyclin D1. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for BCOR. Note that vascular endothelial cells are negative.

Q: Among its diverse morphologic patterns, Clear Cell Sarcoma of the Kidney can exhibit a palisading arrangement of tumor cells that closely resembles the [...] characteristically seen in schwannomas.
Clear cell sarcoma of the kidney. Palisading areas resemble Verocay bodies of schwannomas.
A: Verocay bodies
Back Extra: Clear Cell Sarcoma of the Kidney
- Clinical: Clear cell sarcoma of the kidney (CCSK) typically presents in children with nonspecific symptoms such as abdominal distension, pain, or a palpable mass. It constitutes 3–5% of malignant renal tumours in childhood, with a mean age at diagnosis of 3 years and a male-to-female ratio of 2:1.
- Micro: Histologically, CCSK shows various patterns including classic, cellular, myxoid, sclerosing, epithelioid, palisading, and spindled. The classic pattern features plump ovoid tumour cells with clear nuclei and cytoplasm, arranged in broad trabeculae or nests with arborizing fibrovascular septa.
- Ancillary: Immunohistochemistry shows strong and diffuse nuclear staining for cyclin D1 and BCOR, supporting the diagnosis of CCSK. Molecularly, CCSK is characterized by BCOR mutations or YWHAE::NUTM2 gene fusion.
Reference Gallery:
Clear cell sarcoma of the kidney. Grossly, this tumour is a well-circumscribed fleshy mass.
Clear cell sarcoma of the kidney. Classic areas feature ovoid tumour cells with variably clear nuclei and cytoplasm. Note the delicate branching vasculature.
Clear cell sarcoma of the kidney. Cellular areas feature overlapping of the nuclei.
Clear cell sarcoma of the kidney. Myxoid areas show increased extracellular matrix. Cyst formation is possible.
Clear cell sarcoma of the kidney. Epithelioid areas feature tumour cells arranged as tubules or trabeculae.
Clear cell sarcoma of the kidney. Palisading areas resemble Verocay bodies of schwannomas.
Clear cell sarcoma of the kidney. Spindled areas feature fascicular groups of elongated tumour cells, resembling a spindle cell sarcoma.
Clear cell sarcoma of the kidney. Anaplasia may rarely occur in clear cell sarcoma of the kidney. It is defined as for nephroblastoma.
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for cyclin D1. Note that vascular endothelial cells are negative.
Clear cell sarcoma of the kidney. Tumour cell nuclei are strongly and diffusely positive for BCOR. Note that vascular endothelial cells are negative.

Q: By immunohistochemistry, Epithelioid Angiomyolipoma characteristically exhibits strong expression of melanocytic markers (e.g., HMB45, melan-A) as well as [...].
Epithelioid angiomyolipoma. Granular cytoplasmic expression of HMB45.
Epithelioid angiomyolipoma. Strong and diffuse expression of cathepsin K.
A: cathepsin K
Back Extra: Epithelioid Angiomyolipoma
- Clinical: Epithelioid angiomyolipoma is radiologically and clinically similar to renal cell carcinoma, with a mean patient age of 50 years and no sex predilection.
- Micro: Epithelioid angiomyolipoma displays two patterns: a carcinoma-like pattern with nests of atypical large eosinophilic cells and a diffuse growth pattern with sheets of epithelioid and plump spindle cells.
- Ancillary: Immunohistochemistry shows strong positivity for melanocytic markers (HMB45, melan-A, and MITF), cathepsin K, and CD68 (PGM1).
Reference Gallery:
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma with epithelioid and plump spindle cells in diffuse growth. Note the multinucleated cells.
Epithelioid angiomyolipoma. High-magnification view of epithelioid and plump spindle cells in diffuse growth. Note the relatively uniform epithelioid cells with clear to granular, feathery eosinophilic cytoplasm.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma with a carcinoma-like pattern characterized by large eosinophilic cells with atypical nuclei and prominent nucleoli arranged as nests.
Epithelioid angiomyolipoma. Granular cytoplasmic expression of HMB45.
Epithelioid angiomyolipoma. Strong and diffuse expression of cathepsin K.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma on gross section shows a solid structure and beige colour.
Epithelioid angiomyolipoma. Core biopsy can be helpful in establishing a preoperative diagnosis.

Q: Microscopically, Epithelioid Angiomyolipoma commonly displays a carcinoma-like pattern with nests of atypical large eosinophilic cells, alongside a diffuse growth pattern composed of epithelioid and plump [...] cells.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma with epithelioid and plump spindle cells in diffuse growth. Note the multinucleated cells.
Epithelioid angiomyolipoma. High-magnification view of epithelioid and plump spindle cells in diffuse growth. Note the relatively uniform epithelioid cells with clear to granular, feathery eosinophilic cytoplasm.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma with a carcinoma-like pattern characterized by large eosinophilic cells with atypical nuclei and prominent nucleoli arranged as nests.
A: spindle
Back Extra: Epithelioid Angiomyolipoma
- Clinical: Epithelioid angiomyolipoma is radiologically and clinically similar to renal cell carcinoma, with a mean patient age of 50 years and no sex predilection.
- Micro: Epithelioid angiomyolipoma displays two patterns: a carcinoma-like pattern with nests of atypical large eosinophilic cells and a diffuse growth pattern with sheets of epithelioid and plump spindle cells.
- Ancillary: Immunohistochemistry shows strong positivity for melanocytic markers (HMB45, melan-A, and MITF), cathepsin K, and CD68 (PGM1).
Reference Gallery:
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma with epithelioid and plump spindle cells in diffuse growth. Note the multinucleated cells.
Epithelioid angiomyolipoma. High-magnification view of epithelioid and plump spindle cells in diffuse growth. Note the relatively uniform epithelioid cells with clear to granular, feathery eosinophilic cytoplasm.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma with a carcinoma-like pattern characterized by large eosinophilic cells with atypical nuclei and prominent nucleoli arranged as nests.
Epithelioid angiomyolipoma. Granular cytoplasmic expression of HMB45.
Epithelioid angiomyolipoma. Strong and diffuse expression of cathepsin K.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma on gross section shows a solid structure and beige colour.
Epithelioid angiomyolipoma. Core biopsy can be helpful in establishing a preoperative diagnosis.

Q: On gross examination, Epithelioid Angiomyolipoma frequently presents as a solid tumor with a characteristic [...] color, which can clinically mimic renal cell carcinoma.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma on gross section shows a solid structure and beige colour.
A: beige
Back Extra: Epithelioid Angiomyolipoma
- Clinical: Epithelioid angiomyolipoma is radiologically and clinically similar to renal cell carcinoma, with a mean patient age of 50 years and no sex predilection.
- Micro: Epithelioid angiomyolipoma displays two patterns: a carcinoma-like pattern with nests of atypical large eosinophilic cells and a diffuse growth pattern with sheets of epithelioid and plump spindle cells.
- Ancillary: Immunohistochemistry shows strong positivity for melanocytic markers (HMB45, melan-A, and MITF), cathepsin K, and CD68 (PGM1).
Reference Gallery:
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma with epithelioid and plump spindle cells in diffuse growth. Note the multinucleated cells.
Epithelioid angiomyolipoma. High-magnification view of epithelioid and plump spindle cells in diffuse growth. Note the relatively uniform epithelioid cells with clear to granular, feathery eosinophilic cytoplasm.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma with a carcinoma-like pattern characterized by large eosinophilic cells with atypical nuclei and prominent nucleoli arranged as nests.
Epithelioid angiomyolipoma. Granular cytoplasmic expression of HMB45.
Epithelioid angiomyolipoma. Strong and diffuse expression of cathepsin K.
Epithelioid angiomyolipoma. Epithelioid angiomyolipoma on gross section shows a solid structure and beige colour.
Epithelioid angiomyolipoma. Core biopsy can be helpful in establishing a preoperative diagnosis.

Q: Microscopically, a Glomus Tumor is classically composed of monotonous small round cells with well-defined cell borders that are characteristically arranged around [...].
Glomus tumor. Solid glomus tumor with bland, small, round to oval monomorphic cells arranged around small-calibre blood vessels.
A: small blood vessels
Back Extra: Glomus Tumor
- Clinical: Most renal glomus tumors are discovered incidentally. Common presentations include flank pain, hematuria, or a mass lesion.
- Micro: Glomus tumors are composed of monotonous small round cells with central round nuclei and well-defined cell borders, arranged around small vessels.
- Ancillary: Immunohistochemistry shows positivity for SMA, MSA, h-caldesmon, pericellular collagen IV, and calponin, while keratins and melanoma-associated markers are negative.
Reference Gallery:
Glomus tumor. Solid glomus tumor with bland, small, round to oval monomorphic cells arranged around small-calibre blood vessels.
Glomus tumor. Glomangiomyoma. Glomus cells are arranged around blood vessels with areas of smooth muscle differentiation.
Glomus tumor. Glomangioma. A cavernous hemangioma–like architecture with vascular spaces lined by glomus cells is present.
Glomus tumor. Glomus tumor with symplastic change. This tumor demonstrates cytological atypia in the absence of mitotic activity.
Glomus tumor. Diffuse immunoreactivity for SMA is present in glomus tumors.
Glomus tumor. Ultrastructural studies demonstrate cytoplasmic filaments consistent with the myoid origin of glomus tumors.

Q: A specific histologic variant of a Glomus Tumor that exhibits a cavernous hemangioma–like architecture with dilated vascular spaces lined by glomus cells is termed a [...].
Glomus tumor. Glomangioma. A cavernous hemangioma–like architecture with vascular spaces lined by glomus cells is present.
A: glomangioma
Back Extra: Glomus Tumor
- Clinical: Most renal glomus tumors are discovered incidentally. Common presentations include flank pain, hematuria, or a mass lesion.
- Micro: Glomus tumors are composed of monotonous small round cells with central round nuclei and well-defined cell borders, arranged around small vessels.
- Ancillary: Immunohistochemistry shows positivity for SMA, MSA, h-caldesmon, pericellular collagen IV, and calponin, while keratins and melanoma-associated markers are negative.
Reference Gallery:
Glomus tumor. Solid glomus tumor with bland, small, round to oval monomorphic cells arranged around small-calibre blood vessels.
Glomus tumor. Glomangiomyoma. Glomus cells are arranged around blood vessels with areas of smooth muscle differentiation.
Glomus tumor. Glomangioma. A cavernous hemangioma–like architecture with vascular spaces lined by glomus cells is present.
Glomus tumor. Glomus tumor with symplastic change. This tumor demonstrates cytological atypia in the absence of mitotic activity.
Glomus tumor. Diffuse immunoreactivity for SMA is present in glomus tumors.
Glomus tumor. Ultrastructural studies demonstrate cytoplasmic filaments consistent with the myoid origin of glomus tumors.

Q: By immunohistochemistry, the neoplastic cells of a Glomus Tumor consistently demonstrate diffuse positivity for [...] along with h-caldesmon and pericellular collagen IV, reflecting their myoid differentiation.
Glomus tumor. Diffuse immunoreactivity for SMA is present in glomus tumors.
Glomus tumor. Ultrastructural studies demonstrate cytoplasmic filaments consistent with the myoid origin of glomus tumors.
A: SMA
Back Extra: Glomus Tumor
- Clinical: Most renal glomus tumors are discovered incidentally. Common presentations include flank pain, hematuria, or a mass lesion.
- Micro: Glomus tumors are composed of monotonous small round cells with central round nuclei and well-defined cell borders, arranged around small vessels.
- Ancillary: Immunohistochemistry shows positivity for SMA, MSA, h-caldesmon, pericellular collagen IV, and calponin, while keratins and melanoma-associated markers are negative.
Reference Gallery:
Glomus tumor. Solid glomus tumor with bland, small, round to oval monomorphic cells arranged around small-calibre blood vessels.
Glomus tumor. Glomangiomyoma. Glomus cells are arranged around blood vessels with areas of smooth muscle differentiation.
Glomus tumor. Glomangioma. A cavernous hemangioma–like architecture with vascular spaces lined by glomus cells is present.
Glomus tumor. Glomus tumor with symplastic change. This tumor demonstrates cytological atypia in the absence of mitotic activity.
Glomus tumor. Diffuse immunoreactivity for SMA is present in glomus tumors.
Glomus tumor. Ultrastructural studies demonstrate cytoplasmic filaments consistent with the myoid origin of glomus tumors.

Q: Ultrastructural analysis of a Juxtaglomerular Cell Tumor classically reveals the presence of pathognomonic [...].
Juxtaglomerular cell tumour. Rhomboid shaped renin crystals are characteristic of juxtaglomerular cell tumours on ultrastructural analysis.
A: rhomboid-shaped renin crystals
Back Extra: Juxtaglomerular Cell Tumour
- Clinical: Patients present with severe hypertension, hyperaldosteronism, and hypokalaemia due to tumour renin secretion.
- Micro: Tumours are composed of round to polygonal cells with indistinct cell borders, arranged in solid sheets or lobules with prominent vasculature.
- Ancillary: Immunohistochemistry shows diffuse granular cytoplasmic renin positivity, and ultrastructural analysis reveals rhomboid-shaped renin crystals.
Reference Gallery:
Juxtaglomerular cell tumour. The tumour is composed of small bland round to polygonal cells arranged around blood vessels.
Juxtaglomerular cell tumour. Renin immunohistochemistry shows diffuse positivity.
Juxtaglomerular cell tumour. Rhomboid shaped renin crystals are characteristic of juxtaglomerular cell tumours on ultrastructural analysis.

Q: Patients with a Juxtaglomerular Cell Tumor typically present with severe hypertension and hypokalemia due to the secretion of [...], which also exhibits diffuse granular positivity on immunohistochemistry.
Juxtaglomerular cell tumour. Renin immunohistochemistry shows diffuse positivity.
A: renin
Back Extra: Juxtaglomerular Cell Tumour
- Clinical: Patients present with severe hypertension, hyperaldosteronism, and hypokalaemia due to tumour renin secretion.
- Micro: Tumours are composed of round to polygonal cells with indistinct cell borders, arranged in solid sheets or lobules with prominent vasculature.
- Ancillary: Immunohistochemistry shows diffuse granular cytoplasmic renin positivity, and ultrastructural analysis reveals rhomboid-shaped renin crystals.
Reference Gallery:
Juxtaglomerular cell tumour. The tumour is composed of small bland round to polygonal cells arranged around blood vessels.
Juxtaglomerular cell tumour. Renin immunohistochemistry shows diffuse positivity.
Juxtaglomerular cell tumour. Rhomboid shaped renin crystals are characteristic of juxtaglomerular cell tumours on ultrastructural analysis.

Q: A renal neoplasm causing severe hypertension shows bland, round to polygonal cells arranged around prominent vasculature on H&E. This histologic appearance in this clinical context is characteristic of a [...].
Juxtaglomerular cell tumour. The tumour is composed of small bland round to polygonal cells arranged around blood vessels.
A: Juxtaglomerular Cell Tumor
Back Extra: Juxtaglomerular Cell Tumour
- Clinical: Patients present with severe hypertension, hyperaldosteronism, and hypokalaemia due to tumour renin secretion.
- Micro: Tumours are composed of round to polygonal cells with indistinct cell borders, arranged in solid sheets or lobules with prominent vasculature.
- Ancillary: Immunohistochemistry shows diffuse granular cytoplasmic renin positivity, and ultrastructural analysis reveals rhomboid-shaped renin crystals.
Reference Gallery:
Juxtaglomerular cell tumour. The tumour is composed of small bland round to polygonal cells arranged around blood vessels.
Juxtaglomerular cell tumour. Renin immunohistochemistry shows diffuse positivity.
Juxtaglomerular cell tumour. Rhomboid shaped renin crystals are characteristic of juxtaglomerular cell tumours on ultrastructural analysis.

Q: Histologically, leiomyosarcoma is composed of intersecting fascicles of pleomorphic spindle cells that characteristically feature [...] nuclei, accompanied by increased mitoses.
Kidney leiomyosarcoma. This leiomyosarcoma shows fascicles of pleomorphic spindle cells.
Kidney leiomyosarcoma. This leiomyosarcoma shows significant nuclear pleomorphism.
A: blunt-ended
Back Extra: Leiomyosarcoma
- Clinical: Patients with leiomyosarcoma commonly present with abdominal fullness, pain, or symptoms related to organ involvement, such as back pain, urinary frequency, and dysuria.
- Micro: Leiomyosarcomas are characterized by elongated spindle cells with blunt-ended nuclei arranged in intersecting fascicles, often with nuclear pleomorphism and increased mitotic activity.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with leiomyosarcoma cells typically positive for α-SMA, desmin, h-caldesmon, and calponin.
Reference Gallery:
Kidney leiomyosarcoma. This leiomyosarcoma shows fascicles of pleomorphic spindle cells.
Kidney leiomyosarcoma. This leiomyosarcoma shows significant nuclear pleomorphism.
Bladder leiomyosarcoma. A leiomyosarcoma of the bladder with necrosis and nuclear atypia.
Bladder leiomyosarcoma. A leiomyosarcoma of the bladder with nuclear atypia and high mitotic activity.

Q: To differentiate a leiomyosarcoma from a benign leiomyoma, pathologists look for malignant features such as marked nuclear atypia, high mitotic activity, and tumor cell [...].
Bladder leiomyosarcoma. A leiomyosarcoma of the bladder with necrosis and nuclear atypia.
Bladder leiomyosarcoma. A leiomyosarcoma of the bladder with nuclear atypia and high mitotic activity.
A: necrosis
Back Extra: Leiomyosarcoma
- Clinical: Patients with leiomyosarcoma commonly present with abdominal fullness, pain, or symptoms related to organ involvement, such as back pain, urinary frequency, and dysuria.
- Micro: Leiomyosarcomas are characterized by elongated spindle cells with blunt-ended nuclei arranged in intersecting fascicles, often with nuclear pleomorphism and increased mitotic activity.
- Ancillary: Immunohistochemistry is crucial for diagnosis, with leiomyosarcoma cells typically positive for α-SMA, desmin, h-caldesmon, and calponin.
Reference Gallery:
Kidney leiomyosarcoma. This leiomyosarcoma shows fascicles of pleomorphic spindle cells.
Kidney leiomyosarcoma. This leiomyosarcoma shows significant nuclear pleomorphism.
Bladder leiomyosarcoma. A leiomyosarcoma of the bladder with necrosis and nuclear atypia.
Bladder leiomyosarcoma. A leiomyosarcoma of the bladder with nuclear atypia and high mitotic activity.

Q: The anastomosing variant of Haemangioma is characterized histologically by irregular, sinusoidal capillary-sized spaces lined by a single layer of endothelial cells displaying a characteristic [...] morphology.
Anastomosing haemangioma. Interconnecting vascular channels are present, and there is focal extramedullary haematopoiesis manifesting as megakaryocytes and erythrocyte precursors.
Anastomosing haemangioma. This haemangioma intermingles with renal sinus fat.
A: hobnail
Back Extra: Haemangioma
- Clinical: Haemangiomas in the genitourinary system can present with macroscopic haematuria, irritative urinary symptoms, or be asymptomatic and discovered incidentally.
- Micro: Anastomosing haemangiomas are characterized by irregular, anastomosing, sinusoidal, capillary-sized spaces lined by a single layer of endothelial cells with hobnail morphology.
- Ancillary: Activating point mutations of GNAQ, GNA11, or GNA14, resulting in upregulation of the MAPK signalling pathway, are common in anastomosing haemangiomas.
Reference Gallery:
Anastomosing haemangioma. Macroscopic examination shows an unencapsulated red-brown lesion in the renal hilum.
Anastomosing haemangioma. Interconnecting vascular channels are present, and there is focal extramedullary haematopoiesis manifesting as megakaryocytes and erythrocyte precursors.
Anastomosing haemangioma. This haemangioma intermingles with renal sinus fat.
Haemangioma. This urinary bladder haemangioma shows denuded surface epithelium with complex capillary proliferation in the lamina propria.
Haemangioma. This cavernous-type haemangioma of the urinary bladder demonstrates large vascular channels containing focal fibrin.
Epithelioid haemangioma. This epithelioid haemangioma of the testis surrounds a benign seminiferous tubule and is composed of plump endothelial cells with eosinophilic cytoplasm.

Q: Activating point mutations in GNAQ, GNA11, or GNA14 are commonly identified in the anastomosing variant of [...], leading to the upregulation of the MAPK signaling pathway.
Anastomosing haemangioma. Macroscopic examination shows an unencapsulated red-brown lesion in the renal hilum.
Anastomosing haemangioma. Interconnecting vascular channels are present, and there is focal extramedullary haematopoiesis manifesting as megakaryocytes and erythrocyte precursors.
A: Haemangioma
Back Extra: Haemangioma
- Clinical: Haemangiomas in the genitourinary system can present with macroscopic haematuria, irritative urinary symptoms, or be asymptomatic and discovered incidentally.
- Micro: Anastomosing haemangiomas are characterized by irregular, anastomosing, sinusoidal, capillary-sized spaces lined by a single layer of endothelial cells with hobnail morphology.
- Ancillary: Activating point mutations of GNAQ, GNA11, or GNA14, resulting in upregulation of the MAPK signalling pathway, are common in anastomosing haemangiomas.
Reference Gallery:
Anastomosing haemangioma. Macroscopic examination shows an unencapsulated red-brown lesion in the renal hilum.
Anastomosing haemangioma. Interconnecting vascular channels are present, and there is focal extramedullary haematopoiesis manifesting as megakaryocytes and erythrocyte precursors.
Anastomosing haemangioma. This haemangioma intermingles with renal sinus fat.
Haemangioma. This urinary bladder haemangioma shows denuded surface epithelium with complex capillary proliferation in the lamina propria.
Haemangioma. This cavernous-type haemangioma of the urinary bladder demonstrates large vascular channels containing focal fibrin.
Epithelioid haemangioma. This epithelioid haemangioma of the testis surrounds a benign seminiferous tubule and is composed of plump endothelial cells with eosinophilic cytoplasm.

Q: Microscopically, a Renal Haemangioblastoma is composed of sheets of cells with clear to slightly eosinophilic cytoplasm that are characteristically traversed by an [...] network of thin-walled capillaries.
Renal haemangioblastoma. The tumour comprises sheets of ovoid cells that are traversed by an arborizing network of delicate vessels, many of which are ectatic.
Renal haemangioblastoma. The tumour cells have pale to eosinophilic cytoplasm and small pale vacuoles. Occasional pleomorphic nuclei are present.
A: arborizing
Back Extra: Renal Haemangioblastoma
- Clinical: Renal haemangioblastomas have been reported only in adults, with most patients being asymptomatic, but some presenting with haematuria and abdominal/back pain.
- Micro: The tumours are well circumscribed and composed of sheets of cells with round to oval nuclei, clear to slightly eosinophilic cytoplasm, and a network of arborizing thin-walled capillaries.
- Ancillary: Immunohistochemical findings show staining for PAX8, α-inhibin, NSE, S100, and vimentin.
Reference Gallery:
Renal haemangioblastoma. The tumour comprises sheets of ovoid cells that are traversed by an arborizing network of delicate vessels, many of which are ectatic.
Renal haemangioblastoma. The tumour cells have pale to eosinophilic cytoplasm and small pale vacuoles. Occasional pleomorphic nuclei are present.
Renal haemangioblastoma. The tumour cells are positive for α-inhibin.
Renal haemangioblastoma. The tumour cells are positive for PAX8.

Q: A key immunohistochemical feature of Renal Haemangioblastoma is co-expression of $\alpha$-inhibin, S100, vimentin, and [...].
Renal haemangioblastoma. The tumour cells are positive for α-inhibin.
Renal haemangioblastoma. The tumour cells are positive for PAX8.
A: PAX8
Back Extra: Renal Haemangioblastoma
- Clinical: Renal haemangioblastomas have been reported only in adults, with most patients being asymptomatic, but some presenting with haematuria and abdominal/back pain.
- Micro: The tumours are well circumscribed and composed of sheets of cells with round to oval nuclei, clear to slightly eosinophilic cytoplasm, and a network of arborizing thin-walled capillaries.
- Ancillary: Immunohistochemical findings show staining for PAX8, α-inhibin, NSE, S100, and vimentin.
Reference Gallery:
Renal haemangioblastoma. The tumour comprises sheets of ovoid cells that are traversed by an arborizing network of delicate vessels, many of which are ectatic.
Renal haemangioblastoma. The tumour cells have pale to eosinophilic cytoplasm and small pale vacuoles. Occasional pleomorphic nuclei are present.
Renal haemangioblastoma. The tumour cells are positive for α-inhibin.
Renal haemangioblastoma. The tumour cells are positive for PAX8.

Q: Grossly, a Renomedullary Interstitial Cell Tumor typically presents as an incidental white-tan nodule in the renal medulla that is classically [...] in size.
Renomedullary interstitial cell tumour. The characteristic gross appearance is a small, white-tan nodule (arrow) in the renal medulla, usually < 6 mm.
A: ≤ 6 mm
Back Extra: Renomedullary Interstitial Cell Tumour
- Clinical: Renomedullary interstitial cell tumours are usually ≤ 6 mm and found incidentally during pathological examination or autopsy.
- Micro: The tumour is composed of elongated spindle-shaped to stellate cells with bland nuclei and scant cytoplasm, often with entrapped renal tubules.
- Ancillary: Immunohistochemistry shows weak to moderate positivity for SMA and calponin, and is usually negative or weak for CD34.
Reference Gallery:
Renomedullary interstitial cell tumour. A small, circumscribed nodule of spindle-shaped cells is present within the renal medulla.
Renomedullary interstitial cell tumour. This lesion is relatively cellular and contains entrapped cystic tubules.
Renomedullary interstitial cell tumour. The characteristic gross appearance is a small, white-tan nodule (arrow) in the renal medulla, usually < 6 mm.

Q: Microscopically, a Renomedullary Interstitial Cell Tumor consists of a circumscribed nodule of bland spindle-shaped to stellate cells and characteristically features [...].
Renomedullary interstitial cell tumour. A small, circumscribed nodule of spindle-shaped cells is present within the renal medulla.
Renomedullary interstitial cell tumour. This lesion is relatively cellular and contains entrapped cystic tubules.
A: entrapped renal tubules
Back Extra: Renomedullary Interstitial Cell Tumour
- Clinical: Renomedullary interstitial cell tumours are usually ≤ 6 mm and found incidentally during pathological examination or autopsy.
- Micro: The tumour is composed of elongated spindle-shaped to stellate cells with bland nuclei and scant cytoplasm, often with entrapped renal tubules.
- Ancillary: Immunohistochemistry shows weak to moderate positivity for SMA and calponin, and is usually negative or weak for CD34.
Reference Gallery:
Renomedullary interstitial cell tumour. A small, circumscribed nodule of spindle-shaped cells is present within the renal medulla.
Renomedullary interstitial cell tumour. This lesion is relatively cellular and contains entrapped cystic tubules.
Renomedullary interstitial cell tumour. The characteristic gross appearance is a small, white-tan nodule (arrow) in the renal medulla, usually < 6 mm.

Q: Microscopic examination of monophasic Synovial Sarcoma characteristically shows fascicles of monomorphic blue [...] cells, often with associated wiry collagen.
Uniform spindle proliferation with wiry collagen.
A: spindle
Back Extra: Synovial Sarcoma
- Clinical: Renal Synovial Sarcoma is associated with abdominal pain, followed by hematuria; intraprostatic SS is associated with dysuria, increased urinary frequency, and nocturia.
- Micro: Monophasic SS shows fascicles of monomorphic blue spindle cells with a high N:C ratio; poorly differentiated SS exhibits greater cellularity and nuclear atypia.
- Ancillary: IHC with SS18::SSX fusion–specific antibody and diffuse nuclear TLE1 staining are critical for diagnosing Synovial Sarcoma.
Reference Gallery:
Strong nuclear staining with the SS18::SSX fusion–specific antibody.
Uniform spindle proliferation with wiry collagen.
Poorly differentiated synovial sarcoma.
Diffuse and strong TLE1 nuclear staining.

Q: The [...] variant of Synovial Sarcoma microscopically exhibits greater cellularity and prominent nuclear atypia compared to the classic monophasic type.
Poorly differentiated synovial sarcoma.
A: poorly differentiated
Back Extra: Synovial Sarcoma
- Clinical: Renal Synovial Sarcoma is associated with abdominal pain, followed by hematuria; intraprostatic SS is associated with dysuria, increased urinary frequency, and nocturia.
- Micro: Monophasic SS shows fascicles of monomorphic blue spindle cells with a high N:C ratio; poorly differentiated SS exhibits greater cellularity and nuclear atypia.
- Ancillary: IHC with SS18::SSX fusion–specific antibody and diffuse nuclear TLE1 staining are critical for diagnosing Synovial Sarcoma.
Reference Gallery:
Strong nuclear staining with the SS18::SSX fusion–specific antibody.
Uniform spindle proliferation with wiry collagen.
Poorly differentiated synovial sarcoma.
Diffuse and strong TLE1 nuclear staining.

Q: Immunohistochemistry for Synovial Sarcoma classically demonstrates diffuse nuclear staining for TLE1 and positivity for the highly specific [SSX] fusion antibody.
Strong nuclear staining with the SS18::SSX fusion–specific antibody.
Diffuse and strong TLE1 nuclear staining.
A: SS18
Back Extra: Synovial Sarcoma
- Clinical: Renal Synovial Sarcoma is associated with abdominal pain, followed by hematuria; intraprostatic SS is associated with dysuria, increased urinary frequency, and nocturia.
- Micro: Monophasic SS shows fascicles of monomorphic blue spindle cells with a high N:C ratio; poorly differentiated SS exhibits greater cellularity and nuclear atypia.
- Ancillary: IHC with SS18::SSX fusion–specific antibody and diffuse nuclear TLE1 staining are critical for diagnosing Synovial Sarcoma.
Reference Gallery:
Strong nuclear staining with the SS18::SSX fusion–specific antibody.
Uniform spindle proliferation with wiry collagen.
Poorly differentiated synovial sarcoma.
Diffuse and strong TLE1 nuclear staining.

Q: Paediatric Cystic Nephroma is distinguished from other pediatric kidney tumors by the microscopic appearance of its septa, which completely lack [...].
Cystic nephroma. Although mature tubules and chronic inflammation may be present, no primitive nephroblastic elements are present within the septa.
A: primitive nephroblastic elements
Back Extra: Paediatric Cystic Nephroma
- Clinical: Paediatric cystic nephroma typically presents as an abdominal mass in children aged < 24 months, more commonly in boys.
- Micro: The lesion is entirely cystic, with septa containing bland fibrous tissue and well-differentiated tubules.
- Ancillary: Demonstration of DICER1 mutation is helpful in confirming the diagnosis.
Reference Gallery:
Cystic nephroma. The lesion is entirely cystic, and the cysts mould the septa.
Cystic nephroma. The septa are typically thin and composed of bland fibrous tissue.
Cystic nephroma. Although mature tubules and chronic inflammation may be present, no primitive nephroblastic elements are present within the septa.

Q: Paediatric Cystic Nephroma forms an entirely cystic lesion in which the cysts characteristically [...] the intervening septa.
Cystic nephroma. The lesion is entirely cystic, and the cysts mould the septa.
A: mold
Back Extra: Paediatric Cystic Nephroma
- Clinical: Paediatric cystic nephroma typically presents as an abdominal mass in children aged < 24 months, more commonly in boys.
- Micro: The lesion is entirely cystic, with septa containing bland fibrous tissue and well-differentiated tubules.
- Ancillary: Demonstration of DICER1 mutation is helpful in confirming the diagnosis.
Reference Gallery:
Cystic nephroma. The lesion is entirely cystic, and the cysts mould the septa.
Cystic nephroma. The septa are typically thin and composed of bland fibrous tissue.
Cystic nephroma. Although mature tubules and chronic inflammation may be present, no primitive nephroblastic elements are present within the septa.

Q: Paediatric Cystic Nephroma is characterized by thin septa composed of bland fibrous tissue that often contain mature, well-differentiated [...].
Cystic nephroma. The septa are typically thin and composed of bland fibrous tissue.
Cystic nephroma. Although mature tubules and chronic inflammation may be present, no primitive nephroblastic elements are present within the septa.
A: tubules
Back Extra: Paediatric Cystic Nephroma
- Clinical: Paediatric cystic nephroma typically presents as an abdominal mass in children aged < 24 months, more commonly in boys.
- Micro: The lesion is entirely cystic, with septa containing bland fibrous tissue and well-differentiated tubules.
- Ancillary: Demonstration of DICER1 mutation is helpful in confirming the diagnosis.
Reference Gallery:
Cystic nephroma. The lesion is entirely cystic, and the cysts mould the septa.
Cystic nephroma. The septa are typically thin and composed of bland fibrous tissue.
Cystic nephroma. Although mature tubules and chronic inflammation may be present, no primitive nephroblastic elements are present within the septa.

Q: Metanephric Adenofibroma is a pediatric renal tumor defined by its characteristic [...] morphology, which consists of both a bland spindle cell stroma and primitive epithelial tubules.
Metanephric adenofibroma. The metanephric stromal tumour component (right) is composed of bland spindle cells, and the metanephric adenoma component (left) is composed of primitive but mitotically inactive tubules.
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, but an epithelial nodule that is identical to metanephric adenoma is present at the top. Note the unencapsulated border with the native kidney at the top of the image.
A: biphasic
Back Extra: Metanephric Adenofibroma
- Clinical: Patients with metanephric adenofibroma often present with polycythaemia (4/14 cases) or haematuria (3/14 cases), with a median age of 6.8 years.
- Micro: The tumour is characterized by a biphasic pattern with a spindle cell stromal component and an epithelial component, both morphologically identical to metanephric stromal tumour and metanephric adenoma, respectively.
- Ancillary: Metanephric adenofibromas uniformly harbour BRAF p.V600E mutations, similar to other metanephric neoplasms.
Reference Gallery:
Metanephric adenofibroma. The metanephric stromal tumour component (right) is composed of bland spindle cells, and the metanephric adenoma component (left) is composed of primitive but mitotically inactive tubules.
Metanephric adenofibroma. The bland spindle cell stromal component is on the left, and the primitive but mitotically inactive epithelial component is on the right.
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, but an epithelial nodule that is identical to metanephric adenoma is present at the top. Note the unencapsulated border with the native kidney at the top of the image.
Metanephric adenofibroma. The metanephric stromal tumour component (left) is composed of bland spindle cells, and the metanephric adenoma component (right) is composed of primitive but mitotically inactive tubules.
Metanephric adenofibroma. The bland spindle cell stromal component is at the bottom, and the primitive but mitotically inactive epithelial component is at the top right. Note the unencapsulated border with the native kidney at the top of the image.

Q: Metanephric Adenofibroma features an epithelial component composed of primitive but mitotically inactive tubules that are morphologically identical to a(n) [...].
Metanephric adenofibroma. The bland spindle cell stromal component is on the left, and the primitive but mitotically inactive epithelial component is on the right.
Metanephric adenofibroma. The metanephric stromal tumour component (left) is composed of bland spindle cells, and the metanephric adenoma component (right) is composed of primitive but mitotically inactive tubules.
A: metanephric adenoma
Back Extra: Metanephric Adenofibroma
- Clinical: Patients with metanephric adenofibroma often present with polycythaemia (4/14 cases) or haematuria (3/14 cases), with a median age of 6.8 years.
- Micro: The tumour is characterized by a biphasic pattern with a spindle cell stromal component and an epithelial component, both morphologically identical to metanephric stromal tumour and metanephric adenoma, respectively.
- Ancillary: Metanephric adenofibromas uniformly harbour BRAF p.V600E mutations, similar to other metanephric neoplasms.
Reference Gallery:
Metanephric adenofibroma. The metanephric stromal tumour component (right) is composed of bland spindle cells, and the metanephric adenoma component (left) is composed of primitive but mitotically inactive tubules.
Metanephric adenofibroma. The bland spindle cell stromal component is on the left, and the primitive but mitotically inactive epithelial component is on the right.
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, but an epithelial nodule that is identical to metanephric adenoma is present at the top. Note the unencapsulated border with the native kidney at the top of the image.
Metanephric adenofibroma. The metanephric stromal tumour component (left) is composed of bland spindle cells, and the metanephric adenoma component (right) is composed of primitive but mitotically inactive tubules.
Metanephric adenofibroma. The bland spindle cell stromal component is at the bottom, and the primitive but mitotically inactive epithelial component is at the top right. Note the unencapsulated border with the native kidney at the top of the image.

Q: Metanephric Adenofibroma contains a bland, unencapsulated spindle cell stroma that is morphologically indistinguishable from a(n) [...].
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, but an epithelial nodule that is identical to metanephric adenoma is present at the top. Note the unencapsulated border with the native kidney at the top of the image.
Metanephric adenofibroma. The bland spindle cell stromal component is at the bottom, and the primitive but mitotically inactive epithelial component is at the top right. Note the unencapsulated border with the native kidney at the top of the image.
A: metanephric stromal tumor
Back Extra: Metanephric Adenofibroma
- Clinical: Patients with metanephric adenofibroma often present with polycythaemia (4/14 cases) or haematuria (3/14 cases), with a median age of 6.8 years.
- Micro: The tumour is characterized by a biphasic pattern with a spindle cell stromal component and an epithelial component, both morphologically identical to metanephric stromal tumour and metanephric adenoma, respectively.
- Ancillary: Metanephric adenofibromas uniformly harbour BRAF p.V600E mutations, similar to other metanephric neoplasms.
Reference Gallery:
Metanephric adenofibroma. The metanephric stromal tumour component (right) is composed of bland spindle cells, and the metanephric adenoma component (left) is composed of primitive but mitotically inactive tubules.
Metanephric adenofibroma. The bland spindle cell stromal component is on the left, and the primitive but mitotically inactive epithelial component is on the right.
Metanephric adenofibroma. The majority of this biphasic neoplasm is a stromal neoplasm identical to metanephric stromal tumour, but an epithelial nodule that is identical to metanephric adenoma is present at the top. Note the unencapsulated border with the native kidney at the top of the image.
Metanephric adenofibroma. The metanephric stromal tumour component (left) is composed of bland spindle cells, and the metanephric adenoma component (right) is composed of primitive but mitotically inactive tubules.
Metanephric adenofibroma. The bland spindle cell stromal component is at the bottom, and the primitive but mitotically inactive epithelial component is at the top right. Note the unencapsulated border with the native kidney at the top of the image.

Q: Microscopically, Metanephric Adenoma is characterized by small, crowded acini and branching tubules in an edematous stroma that create a characteristic [...] appearance.
Metanephric adenoma. The stroma is oedematous and contains branching tubules and tubulopapillary structures that create a fingerprint-like appearance.
A: fingerprint-like
Back Extra: Metanephric Adenoma
- Clinical: Approximately 50% of metanephric adenomas are identified incidentally, with abdominal pain and haematuria being the most common presenting symptoms.
- Micro: Microscopically, metanephric adenomas are composed of small, crowded acini in a hyalinized, oedematous stroma, often with a fingerprint-like appearance due to branching tubules.
- Ancillary: Metanephric adenomas typically show diffuse nuclear immunoreactivity for WT1 and cytoplasmic/membranous labelling for CD57.
Reference Gallery:
Metanephric adenoma. The neoplasm is unencapsulated and directly abuts the native kidney to the right. The neoplasm is composed of cuboidal cells with primitive basophilic nuclei and minimal cytoplasm, forming small tubules. Mitotic activity is not evident.
Metanephric adenoma. The stroma is oedematous and contains branching tubules and tubulopapillary structures that create a fingerprint-like appearance.
Metanephric adenoma. Metanephric adenomas with more prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and lack of stromal foam cells are clues to the diagnosis of metanephric adenoma.
Metanephric adenoma. Tumours typically demonstrate diffuse nuclear immunoreactivity for WT1.
Metanephric adenoma. Small acini with cells characterized by scant cytoplasm, delicate chromatin, and absent mitoses.
Metanephric adenoma. Metanephric adenoma with dystrophic calcification.
Metanephric adenoma. WT1 immunohistochemistry.
Metanephric adenoma. CD57 immunohistochemistry.
Metanephric adenoma. Smear shows dyscohesive clusters and a papillary pattern of atypical cells. The cells are ovoid, with scant cytoplasm and hyperchromatic nuclei.
Metanephric adenoma. Smear shows clusters of small, oval to round cells arranged in a microfollicular pattern. The tumour cells have scant cytoplasm, fine chromatin, and absent nucleoli.
Metanephric adenoma. A well-circumscribed grey-white tumour.
Metanephric adenoma. Small acini with cells characterized by scant cytoplasm, delicate chromatin, and absent mitoses.

Q: Immunohistochemically, Metanephric Adenoma typically demonstrates diffuse nuclear positivity for [...] along with cytoplasmic or membranous labeling for CD57.
Metanephric adenoma. WT1 immunohistochemistry.
Metanephric adenoma. CD57 immunohistochemistry.
A: WT1
Back Extra: Metanephric Adenoma
- Clinical: Approximately 50% of metanephric adenomas are identified incidentally, with abdominal pain and haematuria being the most common presenting symptoms.
- Micro: Microscopically, metanephric adenomas are composed of small, crowded acini in a hyalinized, oedematous stroma, often with a fingerprint-like appearance due to branching tubules.
- Ancillary: Metanephric adenomas typically show diffuse nuclear immunoreactivity for WT1 and cytoplasmic/membranous labelling for CD57.
Reference Gallery:
Metanephric adenoma. The neoplasm is unencapsulated and directly abuts the native kidney to the right. The neoplasm is composed of cuboidal cells with primitive basophilic nuclei and minimal cytoplasm, forming small tubules. Mitotic activity is not evident.
Metanephric adenoma. The stroma is oedematous and contains branching tubules and tubulopapillary structures that create a fingerprint-like appearance.
Metanephric adenoma. Metanephric adenomas with more prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and lack of stromal foam cells are clues to the diagnosis of metanephric adenoma.
Metanephric adenoma. Tumours typically demonstrate diffuse nuclear immunoreactivity for WT1.
Metanephric adenoma. Small acini with cells characterized by scant cytoplasm, delicate chromatin, and absent mitoses.
Metanephric adenoma. Metanephric adenoma with dystrophic calcification.
Metanephric adenoma. WT1 immunohistochemistry.
Metanephric adenoma. CD57 immunohistochemistry.
Metanephric adenoma. Smear shows dyscohesive clusters and a papillary pattern of atypical cells. The cells are ovoid, with scant cytoplasm and hyperchromatic nuclei.
Metanephric adenoma. Smear shows clusters of small, oval to round cells arranged in a microfollicular pattern. The tumour cells have scant cytoplasm, fine chromatin, and absent nucleoli.
Metanephric adenoma. A well-circumscribed grey-white tumour.
Metanephric adenoma. Small acini with cells characterized by scant cytoplasm, delicate chromatin, and absent mitoses.

Q: While prominent papillary areas in Metanephric Adenoma can closely mimic low-grade papillary renal cell carcinoma, it lacks the characteristic stromal [...] typically seen in the latter.
Metanephric adenoma. Metanephric adenomas with more prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and lack of stromal foam cells are clues to the diagnosis of metanephric adenoma.
A: foam cells
Back Extra: Metanephric Adenoma
- Clinical: Approximately 50% of metanephric adenomas are identified incidentally, with abdominal pain and haematuria being the most common presenting symptoms.
- Micro: Microscopically, metanephric adenomas are composed of small, crowded acini in a hyalinized, oedematous stroma, often with a fingerprint-like appearance due to branching tubules.
- Ancillary: Metanephric adenomas typically show diffuse nuclear immunoreactivity for WT1 and cytoplasmic/membranous labelling for CD57.
Reference Gallery:
Metanephric adenoma. The neoplasm is unencapsulated and directly abuts the native kidney to the right. The neoplasm is composed of cuboidal cells with primitive basophilic nuclei and minimal cytoplasm, forming small tubules. Mitotic activity is not evident.
Metanephric adenoma. The stroma is oedematous and contains branching tubules and tubulopapillary structures that create a fingerprint-like appearance.
Metanephric adenoma. Metanephric adenomas with more prominent papillary areas can be confused with low-grade papillary renal cell carcinoma. The more hyperchromatic nuclei and lack of stromal foam cells are clues to the diagnosis of metanephric adenoma.
Metanephric adenoma. Tumours typically demonstrate diffuse nuclear immunoreactivity for WT1.
Metanephric adenoma. Small acini with cells characterized by scant cytoplasm, delicate chromatin, and absent mitoses.
Metanephric adenoma. Metanephric adenoma with dystrophic calcification.
Metanephric adenoma. WT1 immunohistochemistry.
Metanephric adenoma. CD57 immunohistochemistry.
Metanephric adenoma. Smear shows dyscohesive clusters and a papillary pattern of atypical cells. The cells are ovoid, with scant cytoplasm and hyperchromatic nuclei.
Metanephric adenoma. Smear shows clusters of small, oval to round cells arranged in a microfollicular pattern. The tumour cells have scant cytoplasm, fine chromatin, and absent nucleoli.
Metanephric adenoma. A well-circumscribed grey-white tumour.
Metanephric adenoma. Small acini with cells characterized by scant cytoplasm, delicate chromatin, and absent mitoses.

Q: Microscopically, a Metanephric Stromal Tumor features neoplastic spindle cells encircling entrapped native tubules in a concentric fashion, yielding a characteristic [...] pattern.
Metanephric stromal tumour. Neoplastic spindle cells encircle entrapped native tubules in a concentric fashion, yielding an onion-skin pattern.
A: onion-skin
Back Extra: Metanephric Stromal Tumour
- Clinical: Metanephric stromal tumour presents as an abdominal mass, with some patients showing hypertension or haemorrhage due to extrarenal vasculopathy.
- Micro: Characterized by spindle-shaped to stellate cells forming concentric (onion-skin) rings around entrapped tubules and vessels in a myxoid background.
- Ancillary: Immunohistochemistry shows positivity for CD34 and frequent presence of BRAF p.V600E mutations, distinguishing it from other renal neoplasms.
Reference Gallery:
Metanephric stromal tumour. This is a fibrous neoplasm centred in the medulla of this bivalved kidney. Note the scalloped border with the native kidney.
Metanephric stromal tumour. Neoplastic spindle cells encircle entrapped native tubules in a concentric fashion, yielding an onion-skin pattern.
Metanephric stromal tumour. Glomeruli entrapped within a metanephric stromal tumour frequently demonstrate florid juxtaglomerular cell hyperplasia. This may result in hyperreninism.
Metanephric stromal tumour. Arterioles within and occasionally outside a metanephric stromal tumour frequently demonstrate angiodysplasia. The majority of this arterial wall is markedly thickened, having undergone myxoid degeneration. The normally spindled smooth muscle cells have become epithelioid. These vessels can rupture, leading to haemorrhage.

Q: Glomeruli entrapped within a Metanephric Stromal Tumor frequently demonstrate florid [...], which may result in hyperreninism and clinical hypertension.
Metanephric stromal tumour. Glomeruli entrapped within a metanephric stromal tumour frequently demonstrate florid juxtaglomerular cell hyperplasia. This may result in hyperreninism.
A: juxtaglomerular cell hyperplasia
Back Extra: Metanephric Stromal Tumour
- Clinical: Metanephric stromal tumour presents as an abdominal mass, with some patients showing hypertension or haemorrhage due to extrarenal vasculopathy.
- Micro: Characterized by spindle-shaped to stellate cells forming concentric (onion-skin) rings around entrapped tubules and vessels in a myxoid background.
- Ancillary: Immunohistochemistry shows positivity for CD34 and frequent presence of BRAF p.V600E mutations, distinguishing it from other renal neoplasms.
Reference Gallery:
Metanephric stromal tumour. This is a fibrous neoplasm centred in the medulla of this bivalved kidney. Note the scalloped border with the native kidney.
Metanephric stromal tumour. Neoplastic spindle cells encircle entrapped native tubules in a concentric fashion, yielding an onion-skin pattern.
Metanephric stromal tumour. Glomeruli entrapped within a metanephric stromal tumour frequently demonstrate florid juxtaglomerular cell hyperplasia. This may result in hyperreninism.
Metanephric stromal tumour. Arterioles within and occasionally outside a metanephric stromal tumour frequently demonstrate angiodysplasia. The majority of this arterial wall is markedly thickened, having undergone myxoid degeneration. The normally spindled smooth muscle cells have become epithelioid. These vessels can rupture, leading to haemorrhage.

Q: Grossly, a Metanephric Stromal Tumor presents as a fibrous neoplasm with a scalloped border that is characteristically centered in the renal [...].
Metanephric stromal tumour. This is a fibrous neoplasm centred in the medulla of this bivalved kidney. Note the scalloped border with the native kidney.
A: medulla
Back Extra: Metanephric Stromal Tumour
- Clinical: Metanephric stromal tumour presents as an abdominal mass, with some patients showing hypertension or haemorrhage due to extrarenal vasculopathy.
- Micro: Characterized by spindle-shaped to stellate cells forming concentric (onion-skin) rings around entrapped tubules and vessels in a myxoid background.
- Ancillary: Immunohistochemistry shows positivity for CD34 and frequent presence of BRAF p.V600E mutations, distinguishing it from other renal neoplasms.
Reference Gallery:
Metanephric stromal tumour. This is a fibrous neoplasm centred in the medulla of this bivalved kidney. Note the scalloped border with the native kidney.
Metanephric stromal tumour. Neoplastic spindle cells encircle entrapped native tubules in a concentric fashion, yielding an onion-skin pattern.
Metanephric stromal tumour. Glomeruli entrapped within a metanephric stromal tumour frequently demonstrate florid juxtaglomerular cell hyperplasia. This may result in hyperreninism.
Metanephric stromal tumour. Arterioles within and occasionally outside a metanephric stromal tumour frequently demonstrate angiodysplasia. The majority of this arterial wall is markedly thickened, having undergone myxoid degeneration. The normally spindled smooth muscle cells have become epithelioid. These vessels can rupture, leading to haemorrhage.

Q: A classic histologic feature of Mixed Epithelial and Stromal Tumor is a biphasic pattern consisting of benign-appearing epithelium separated by a cellular spindle cell stroma that characteristically resembles [...].
Mixed epithelial and stromal tumour. A cyst (left) is lined by flattened epithelial cells and surrounded by spindle cell stroma (centre) resembling ovarian stroma.
Mixed epithelial and stromal tumour. A solid area demonstrates ovarian-like stroma containing numerous tubules with flattened lining, resembling thyroid tubules.
A: ovarian stroma
Back Extra: Mixed Epithelial and Stromal Tumour
- Clinical: Mixed Epithelial and Stromal Tumour (MEST) is more common in middle-aged women (M:F ratio 1:7) and is often asymptomatic. Symptoms, if present, include haematuria and abdominal pain.
- Micro: MESTs are characterized by a biphasic pattern with variably sized cysts and glands lined by benign-appearing epithelium, separated by a stroma that resembles ovarian stroma and can show myxoid changes.
- Ancillary: The stromal component is typically positive for actin, desmin, CD10, ER, and PR. The epithelial component is PAX2/8-positive. Molecular studies, such as the absence of SS18 rearrangement, can help differentiate MEST from renal synovial sarcoma.
Reference Gallery:
Mixed epithelial and stromal tumour. A gross specimen containing mixed epithelial and stromal tumour shows a white-tan fibrous mass with scattered cysts that involves the renal medulla and renal pelvis.
Mixed epithelial and stromal tumour. A cyst (left) is lined by flattened epithelial cells and surrounded by spindle cell stroma (centre) resembling ovarian stroma.
Mixed epithelial and stromal tumour. A solid area demonstrates ovarian-like stroma containing numerous tubules with flattened lining, resembling thyroid tubules.
Mixed epithelial and stromal tumour. Spindle-shaped cells within glandular structures create a phyllodes tumour–like appearance.

Q: In some areas of a Mixed Epithelial and Stromal Tumor, the spindle-shaped stromal cells can project into glandular structures, creating an architecture with a characteristic [...]-like appearance.
Mixed epithelial and stromal tumour. Spindle-shaped cells within glandular structures create a phyllodes tumour–like appearance.
A: phyllodes tumor
Back Extra: Mixed Epithelial and Stromal Tumour
- Clinical: Mixed Epithelial and Stromal Tumour (MEST) is more common in middle-aged women (M:F ratio 1:7) and is often asymptomatic. Symptoms, if present, include haematuria and abdominal pain.
- Micro: MESTs are characterized by a biphasic pattern with variably sized cysts and glands lined by benign-appearing epithelium, separated by a stroma that resembles ovarian stroma and can show myxoid changes.
- Ancillary: The stromal component is typically positive for actin, desmin, CD10, ER, and PR. The epithelial component is PAX2/8-positive. Molecular studies, such as the absence of SS18 rearrangement, can help differentiate MEST from renal synovial sarcoma.
Reference Gallery:
Mixed epithelial and stromal tumour. A gross specimen containing mixed epithelial and stromal tumour shows a white-tan fibrous mass with scattered cysts that involves the renal medulla and renal pelvis.
Mixed epithelial and stromal tumour. A cyst (left) is lined by flattened epithelial cells and surrounded by spindle cell stroma (centre) resembling ovarian stroma.
Mixed epithelial and stromal tumour. A solid area demonstrates ovarian-like stroma containing numerous tubules with flattened lining, resembling thyroid tubules.
Mixed epithelial and stromal tumour. Spindle-shaped cells within glandular structures create a phyllodes tumour–like appearance.

Q: The cellular type of Congenital Mesoblastic Nephroma (shown) features high cellularity and poorly defined fascicles, and frequently demonstrates the characteristic [NTRK3] gene fusion.
Congenital mesoblastic nephroma. Cellular type. The neoplasm features poorly defined fascicles, high cellularity, and abundant mitotic activity.
A: ETV6
Back Extra: Congenital Mesoblastic Nephroma
- Clinical: Congenital Mesoblastic Nephroma (CMN) typically presents as an abdominal mass in infants, with hypertension and hematuria being less common.
- Micro: The cellular type of CMN is characterized by poorly defined fascicles, high cellularity, and abundant mitotic activity.
- Ancillary: Cellular CMN often demonstrates the characteristic ETV6::NTRK3 gene fusion, while classic CMN shows EGFR internal tandem duplications (ITD).
Reference Gallery:
Congenital mesoblastic nephroma. Cellular type. The neoplasm features poorly defined fascicles, high cellularity, and abundant mitotic activity.
Congenital mesoblastic nephroma. Mixed type. The left half is identical to the cellular type and the right half is identical to the classic type.

Q: The mixed type of Congenital Mesoblastic Nephroma contains both cellular and classic components; the classic component typically harbors characteristic [...] internal tandem duplications (ITD).
Congenital mesoblastic nephroma. Mixed type. The left half is identical to the cellular type and the right half is identical to the classic type.
A: EGFR
Back Extra: Congenital Mesoblastic Nephroma
- Clinical: Congenital Mesoblastic Nephroma (CMN) typically presents as an abdominal mass in infants, with hypertension and hematuria being less common.
- Micro: The cellular type of CMN is characterized by poorly defined fascicles, high cellularity, and abundant mitotic activity.
- Ancillary: Cellular CMN often demonstrates the characteristic ETV6::NTRK3 gene fusion, while classic CMN shows EGFR internal tandem duplications (ITD).
Reference Gallery:
Congenital mesoblastic nephroma. Cellular type. The neoplasm features poorly defined fascicles, high cellularity, and abundant mitotic activity.
Congenital mesoblastic nephroma. Mixed type. The left half is identical to the cellular type and the right half is identical to the classic type.

Q: Cystic partially differentiated nephroblastoma is a multicystic pediatric renal tumor in which the fibrous septa characteristically contain primitive [...] elements.
Cystic partially differentiated nephroblastoma. Primitive nephroblastic elements are focally present within the septa.
A: nephroblastic
Back Extra: Cystic Partially Differentiated Nephroblastoma
- Clinical: Cystic Partially Differentiated Nephroblastoma typically presents as an abdominal mass in very young children, usually before the age of 2 years, with a male predominance.
- Micro: The tumor is composed entirely of septated cysts, lined with flattened, cuboidal, or hobnail epithelium, with septa containing undifferentiated and differentiated mesenchyme and nephroblastomatous elements.
- Ancillary: No specific molecular abnormalities have been reported for Cystic Partially Differentiated Nephroblastoma.
Reference Gallery:
Cystic partially differentiated nephroblastoma. The lesion is entirely cystic, and the cysts mould the septa.
Cystic partially differentiated nephroblastoma. Primitive nephroblastic elements are focally present within the septa.

Q: A pediatric renal mass composed entirely of septated cysts with primitive nephroblastomatous elements restricted to the intervening septa is diagnostic of [...].
Cystic partially differentiated nephroblastoma. The lesion is entirely cystic, and the cysts mould the septa.
Cystic partially differentiated nephroblastoma. Primitive nephroblastic elements are focally present within the septa.
A: cystic partially differentiated nephroblastoma
Back Extra: Cystic Partially Differentiated Nephroblastoma
- Clinical: Cystic Partially Differentiated Nephroblastoma typically presents as an abdominal mass in very young children, usually before the age of 2 years, with a male predominance.
- Micro: The tumor is composed entirely of septated cysts, lined with flattened, cuboidal, or hobnail epithelium, with septa containing undifferentiated and differentiated mesenchyme and nephroblastomatous elements.
- Ancillary: No specific molecular abnormalities have been reported for Cystic Partially Differentiated Nephroblastoma.
Reference Gallery:
Cystic partially differentiated nephroblastoma. The lesion is entirely cystic, and the cysts mould the septa.
Cystic partially differentiated nephroblastoma. Primitive nephroblastic elements are focally present within the septa.

Q: Histologically, Nephroblastoma (Wilms Tumor) is classically characterized by a [...] pattern consisting of blastemal, stromal, and epithelial components.
Nephroblastoma. Classic triphasic growth pattern, of blastemal cells, stromal cells, and epithelial differentiation including tubules and primitive glomeruli.
A: triphasic
Back Extra: Nephroblastoma (Wilms Tumor)
- Clinical: Nephroblastomas most commonly present as an abdominal mass, with 20-30% of patients also experiencing abdominal pain, haematuria, hypertension, and anaemia.
- Micro: Nephroblastomas are characterized by a triphasic pattern of blastemal, stromal, and epithelial components, though monophasic and biphasic patterns are also observed.
- Ancillary: Immunohistochemistry shows blastemal cells and epithelial components typically positive for WT1, while the stroma is negative.
Reference Gallery:
Nephroblastoma. Classic triphasic growth pattern, of blastemal cells, stromal cells, and epithelial differentiation including tubules and primitive glomeruli.
Nephroblastoma. The stromal component commonly shows rhabdomyoblastic differentiation.
Nephroblastoma. Diffuse blastemal pattern demonstrating undifferentiated small blue round cell tumour pattern.
Nephroblastoma. Diffuse blastemal pattern demonstrating intrarenal vascular invasion.
Nephroblastoma. Anaplastic nephroblastoma. Blastemal and stromal neoplasm with enlarged, hyperchromatic nuclei and multipolar mitotic figures.
Anaplastic nephroblastoma. Blastemal and stromal neoplasm with enlarged, hyperchromatic nuclei (best evident in the stroma) and multipolar mitotic figures.
Focally anaplastic nephroblastoma. p53 immunohistochemistry highlights the focally anaplastic area.
Nephroblastoma. WT1 immunohistochemistry labels blastemal cells and primitive tubules, but not stromal cells or better-formed tubules.
Nephroblastoma. The neoplasm is well delineated and fleshy, with small yellow areas of necrosis. A multinodular internal structure is typical.

Q: In Nephroblastoma (Wilms Tumor), immunohistochemistry typically shows that the blastemal cells and primitive epithelial components are positive for [...], whereas the stroma is negative.
Nephroblastoma. WT1 immunohistochemistry labels blastemal cells and primitive tubules, but not stromal cells or better-formed tubules.
A: WT1
Back Extra: Nephroblastoma (Wilms Tumor)
- Clinical: Nephroblastomas most commonly present as an abdominal mass, with 20-30% of patients also experiencing abdominal pain, haematuria, hypertension, and anaemia.
- Micro: Nephroblastomas are characterized by a triphasic pattern of blastemal, stromal, and epithelial components, though monophasic and biphasic patterns are also observed.
- Ancillary: Immunohistochemistry shows blastemal cells and epithelial components typically positive for WT1, while the stroma is negative.
Reference Gallery:
Nephroblastoma. Classic triphasic growth pattern, of blastemal cells, stromal cells, and epithelial differentiation including tubules and primitive glomeruli.
Nephroblastoma. The stromal component commonly shows rhabdomyoblastic differentiation.
Nephroblastoma. Diffuse blastemal pattern demonstrating undifferentiated small blue round cell tumour pattern.
Nephroblastoma. Diffuse blastemal pattern demonstrating intrarenal vascular invasion.
Nephroblastoma. Anaplastic nephroblastoma. Blastemal and stromal neoplasm with enlarged, hyperchromatic nuclei and multipolar mitotic figures.
Anaplastic nephroblastoma. Blastemal and stromal neoplasm with enlarged, hyperchromatic nuclei (best evident in the stroma) and multipolar mitotic figures.
Focally anaplastic nephroblastoma. p53 immunohistochemistry highlights the focally anaplastic area.
Nephroblastoma. WT1 immunohistochemistry labels blastemal cells and primitive tubules, but not stromal cells or better-formed tubules.
Nephroblastoma. The neoplasm is well delineated and fleshy, with small yellow areas of necrosis. A multinodular internal structure is typical.

Q: The anaplastic variant of Nephroblastoma (Wilms Tumor) presents with markedly enlarged, hyperchromatic nuclei and multipolar mitotic figures, which typically correlates with positive immunohistochemical staining for [...].
Nephroblastoma. Anaplastic nephroblastoma. Blastemal and stromal neoplasm with enlarged, hyperchromatic nuclei and multipolar mitotic figures.
Focally anaplastic nephroblastoma. p53 immunohistochemistry highlights the focally anaplastic area.
A: p53
Back Extra: Nephroblastoma (Wilms Tumor)
- Clinical: Nephroblastomas most commonly present as an abdominal mass, with 20-30% of patients also experiencing abdominal pain, haematuria, hypertension, and anaemia.
- Micro: Nephroblastomas are characterized by a triphasic pattern of blastemal, stromal, and epithelial components, though monophasic and biphasic patterns are also observed.
- Ancillary: Immunohistochemistry shows blastemal cells and epithelial components typically positive for WT1, while the stroma is negative.
Reference Gallery:
Nephroblastoma. Classic triphasic growth pattern, of blastemal cells, stromal cells, and epithelial differentiation including tubules and primitive glomeruli.
Nephroblastoma. The stromal component commonly shows rhabdomyoblastic differentiation.
Nephroblastoma. Diffuse blastemal pattern demonstrating undifferentiated small blue round cell tumour pattern.
Nephroblastoma. Diffuse blastemal pattern demonstrating intrarenal vascular invasion.
Nephroblastoma. Anaplastic nephroblastoma. Blastemal and stromal neoplasm with enlarged, hyperchromatic nuclei and multipolar mitotic figures.
Anaplastic nephroblastoma. Blastemal and stromal neoplasm with enlarged, hyperchromatic nuclei (best evident in the stroma) and multipolar mitotic figures.
Focally anaplastic nephroblastoma. p53 immunohistochemistry highlights the focally anaplastic area.
Nephroblastoma. WT1 immunohistochemistry labels blastemal cells and primitive tubules, but not stromal cells or better-formed tubules.
Nephroblastoma. The neoplasm is well delineated and fleshy, with small yellow areas of necrosis. A multinodular internal structure is typical.

Q: In Nephrogenic Rests, the perilobar subtype is typically well-demarcated and subcapsular, whereas the [...] subtype is poorly defined and intermingles with the native kidney.
Nephrogenic rest. Perilobar rest. Well-demarcated, lens-shaped subcapsular collections of primitive blastemal and tubular cells.
Nephrogenic rest. Intralobar rest. Poorly defined proliferation of embryonal cells that intermingles with the native kidney.
A: intralobar
Back Extra: Nephrogenic Rests
- Clinical: Nephrogenic rests are usually asymptomatic, but diffuse hyperplastic perilobar nephroblastomatosis can present with an abdominal mass.
- Micro: Perilobar nephrogenic rests (PLNRs) are well-demarcated and subcapsular, while intralobar nephrogenic rests (ILNRs) are poorly defined and intermingle with the native kidney.
- Ancillary: The presence of adipose tissue is more common in intralobar nephrogenic rests compared to nephroblastomas.
Reference Gallery:
Nephrogenic rest. Perilobar rest. Well-demarcated, lens-shaped subcapsular collections of primitive blastemal and tubular cells.
Nephrogenic rest. Perilobar rest. Hyperplastic areas commonly show mitotic activity.
Nephrogenic rest. Intralobar rest. Poorly defined proliferation of embryonal cells that intermingles with the native kidney.
Nephrogenic rest. Intralobar rest. Adipose tissue is a common component in intralobar rests, along with primitive nephroblastic epithelial tissue.

Q: In Nephrogenic Rests, the presence of [...] tissue is a common component specifically in the intralobar subtype, helping distinguish it from nephroblastoma.
Nephrogenic rest. Intralobar rest. Adipose tissue is a common component in intralobar rests, along with primitive nephroblastic epithelial tissue.
A: adipose
Back Extra: Nephrogenic Rests
- Clinical: Nephrogenic rests are usually asymptomatic, but diffuse hyperplastic perilobar nephroblastomatosis can present with an abdominal mass.
- Micro: Perilobar nephrogenic rests (PLNRs) are well-demarcated and subcapsular, while intralobar nephrogenic rests (ILNRs) are poorly defined and intermingle with the native kidney.
- Ancillary: The presence of adipose tissue is more common in intralobar nephrogenic rests compared to nephroblastomas.
Reference Gallery:
Nephrogenic rest. Perilobar rest. Well-demarcated, lens-shaped subcapsular collections of primitive blastemal and tubular cells.
Nephrogenic rest. Perilobar rest. Hyperplastic areas commonly show mitotic activity.
Nephrogenic rest. Intralobar rest. Poorly defined proliferation of embryonal cells that intermingles with the native kidney.
Nephrogenic rest. Intralobar rest. Adipose tissue is a common component in intralobar rests, along with primitive nephroblastic epithelial tissue.

Q: A hallmark histologic feature of Well-Differentiated Neuroendocrine Tumor (NET) is the prominent cellular [...], with cells often displaying typical speckled chromatin and growing in acini, cords, nests, and trabeculae.
Well-differentiated neuroendocrine tumour (NET) of the kidney. H&E staining at the renal parenchyma–tumour interface, with the typical trabecular and acinar growth pattern of the tumour and a sharp non-infiltrative tumour border. Even at this magnification, the cellular monotony is prominent.
Well-differentiated renal neuroendocrine tumour (NET). Islands, trabeculae, and cords of well-differentiated neuroendocrine cells separated by thick and thin fibrovascular septa.
A: monotony
Back Extra: Well-Differentiated Neuroendocrine Tumor (NET)
- Clinical: Patients with renal NET most frequently present with abdominal (flank or back) pain and haematuria, which are also the most frequent symptoms of bladder NET.
- Micro: The tumours are composed of bland, monotonous cells with mild nuclear pleomorphism and typical speckled chromatin, arranged in acini, cords, nests, and trabeculae.
- Ancillary: Immunohistochemically, the tumour cells are reactive for chromogranin A, synaptophysin, and CD56.
Reference Gallery:
Well-differentiated neuroendocrine tumour (NET) of the kidney. H&E staining at the renal parenchyma–tumour interface, with the typical trabecular and acinar growth pattern of the tumour and a sharp non-infiltrative tumour border. Even at this magnification, the cellular monotony is prominent.
Well-differentiated neuroendocrine tumour (NET). NET of the urinary bladder showing the bland monotonous tumour cells in nests separated by thin capillaries as a network within the lamina propria beneath the native urothelium.
Well-differentiated renal neuroendocrine tumour (NET). Gross image of a well-circumscribed and well-defined tumour with haemorrhagic areas, seen in the lower pole of the kidney.
Well-differentiated neuroendocrine tumour (NET). NET of the prostate showing well-differentiated neuroendocrine cells in a trabecular pattern. Note the monomorphic appearance of the cells.
Well-differentiated renal neuroendocrine tumour (NET). Islands, trabeculae, and cords of well-differentiated neuroendocrine cells separated by thick and thin fibrovascular septa.
Well-differentiated renal neuroendocrine tumour (NET). Higher-power view of trabeculae and small groups of NET cells.
Well-differentiated renal neuroendocrine tumour (NET). Immunohistochemistry. Tumour cells within this NET strongly express chromogranin.

Q: Immunohistochemically, a Well-Differentiated Neuroendocrine Tumor (NET) is characteristically reactive for neuroendocrine markers such as synaptophysin, CD56, and [...].
Well-differentiated renal neuroendocrine tumour (NET). Immunohistochemistry. Tumour cells within this NET strongly express chromogranin.
A: chromogranin A
Back Extra: Well-Differentiated Neuroendocrine Tumor (NET)
- Clinical: Patients with renal NET most frequently present with abdominal (flank or back) pain and haematuria, which are also the most frequent symptoms of bladder NET.
- Micro: The tumours are composed of bland, monotonous cells with mild nuclear pleomorphism and typical speckled chromatin, arranged in acini, cords, nests, and trabeculae.
- Ancillary: Immunohistochemically, the tumour cells are reactive for chromogranin A, synaptophysin, and CD56.
Reference Gallery:
Well-differentiated neuroendocrine tumour (NET) of the kidney. H&E staining at the renal parenchyma–tumour interface, with the typical trabecular and acinar growth pattern of the tumour and a sharp non-infiltrative tumour border. Even at this magnification, the cellular monotony is prominent.
Well-differentiated neuroendocrine tumour (NET). NET of the urinary bladder showing the bland monotonous tumour cells in nests separated by thin capillaries as a network within the lamina propria beneath the native urothelium.
Well-differentiated renal neuroendocrine tumour (NET). Gross image of a well-circumscribed and well-defined tumour with haemorrhagic areas, seen in the lower pole of the kidney.
Well-differentiated neuroendocrine tumour (NET). NET of the prostate showing well-differentiated neuroendocrine cells in a trabecular pattern. Note the monomorphic appearance of the cells.
Well-differentiated renal neuroendocrine tumour (NET). Islands, trabeculae, and cords of well-differentiated neuroendocrine cells separated by thick and thin fibrovascular septa.
Well-differentiated renal neuroendocrine tumour (NET). Higher-power view of trabeculae and small groups of NET cells.
Well-differentiated renal neuroendocrine tumour (NET). Immunohistochemistry. Tumour cells within this NET strongly express chromogranin.

Q: Macroscopically, a renal Well-Differentiated Neuroendocrine Tumor (NET) typically presents as a well-circumscribed mass with focal [...] areas, which can clinically manifest with flank pain and hematuria.
Well-differentiated renal neuroendocrine tumour (NET). Gross image of a well-circumscribed and well-defined tumour with haemorrhagic areas, seen in the lower pole of the kidney.
A: hemorrhagic
Back Extra: Well-Differentiated Neuroendocrine Tumor (NET)
- Clinical: Patients with renal NET most frequently present with abdominal (flank or back) pain and haematuria, which are also the most frequent symptoms of bladder NET.
- Micro: The tumours are composed of bland, monotonous cells with mild nuclear pleomorphism and typical speckled chromatin, arranged in acini, cords, nests, and trabeculae.
- Ancillary: Immunohistochemically, the tumour cells are reactive for chromogranin A, synaptophysin, and CD56.
Reference Gallery:
Well-differentiated neuroendocrine tumour (NET) of the kidney. H&E staining at the renal parenchyma–tumour interface, with the typical trabecular and acinar growth pattern of the tumour and a sharp non-infiltrative tumour border. Even at this magnification, the cellular monotony is prominent.
Well-differentiated neuroendocrine tumour (NET). NET of the urinary bladder showing the bland monotonous tumour cells in nests separated by thin capillaries as a network within the lamina propria beneath the native urothelium.
Well-differentiated renal neuroendocrine tumour (NET). Gross image of a well-circumscribed and well-defined tumour with haemorrhagic areas, seen in the lower pole of the kidney.
Well-differentiated neuroendocrine tumour (NET). NET of the prostate showing well-differentiated neuroendocrine cells in a trabecular pattern. Note the monomorphic appearance of the cells.
Well-differentiated renal neuroendocrine tumour (NET). Islands, trabeculae, and cords of well-differentiated neuroendocrine cells separated by thick and thin fibrovascular septa.
Well-differentiated renal neuroendocrine tumour (NET). Higher-power view of trabeculae and small groups of NET cells.
Well-differentiated renal neuroendocrine tumour (NET). Immunohistochemistry. Tumour cells within this NET strongly express chromogranin.

Q: In Germ Cell Tumors of the Kidney, teratomas display multi-lineage differentiation and may be uniquely associated with well-differentiated [...] (carcinoid).
Renal germ cell tumour. A renal teratoma with an associated well-differentiated neuroendocrine tumour (carcinoid).
A: neuroendocrine tumors
Back Extra: Germ Cell Tumors of the Kidney
- Clinical: Patients may present with abdominal pain or a palpable mass, or be asymptomatic on imaging. Primary germ cell tumours of the kidney are rare, with fewer than 25 cases reported.
- Micro: Teratomas display a wide range of patterns reflecting ectodermal, endodermal, and mesenchymal differentiation. These tumours may be associated with well-differentiated neuroendocrine tumours (carcinoid).
- Ancillary: Germ cell tumours of the kidney lack chromosome 12p abnormalities, which distinguishes them from some other germ cell tumours.
Reference Gallery:
Renal germ cell tumour. A renal teratoma with an associated well-differentiated neuroendocrine tumour (carcinoid).

Q: In cases of Metastasis to the Kidney originating from a lung adenocarcinoma, the metastatic tumor cells are characteristically positive for the immunohistochemical marker [...].
Kidney metastasis from lung adenocarcinoma. Malignant glands extend between the renal glomeruli.
Kidney metastasis from lung adenocarcinoma. Tumour cells are positive for thyroid transcription factor 1 (TTF1).
A: TTF1
Back Extra: Metastasis to the Kidney
- Clinical: Metastatic tumours manifesting as renal masses are rare and often mimic primary renal tumours, especially in patients with a history of a non-renal malignancy.
- Micro: The histopathological features reflect the primary origin of the tumour, with locoregional spread and involvement of the renal sinus fat or perinephric fat.
- Ancillary: Confirmatory immunohistochemistry is essential for distinguishing metastatic tumours from primary renal tumours, particularly using markers like TTF1, CDX2, and thyroglobulin.
Reference Gallery:
Kidney metastasis from lung adenocarcinoma. Malignant glands extend between the renal glomeruli.
Kidney metastasis from lung adenocarcinoma. Tumour cells are positive for thyroid transcription factor 1 (TTF1).
Kidney metastasis from colonic adenocarcinoma. There is a desmoplastic and inflammatory response around the metastatic glands, and the kidney parenchyma is atrophic.
Kidney metastasis from colonic adenocarcinoma. The surrounding renal parenchyma is compressed and atrophic.
Kidney metastasis from colonic adenocarcinoma. CDX2 stain is positive.

Q: When Metastasis to the Kidney arises from a colonic adenocarcinoma, the neoplastic glands often elicit a desmoplastic response and are typically positive for the immunohistochemical marker [...].
Kidney metastasis from colonic adenocarcinoma. There is a desmoplastic and inflammatory response around the metastatic glands, and the kidney parenchyma is atrophic.
Kidney metastasis from colonic adenocarcinoma. CDX2 stain is positive.
A: CDX2
Back Extra: Metastasis to the Kidney
- Clinical: Metastatic tumours manifesting as renal masses are rare and often mimic primary renal tumours, especially in patients with a history of a non-renal malignancy.
- Micro: The histopathological features reflect the primary origin of the tumour, with locoregional spread and involvement of the renal sinus fat or perinephric fat.
- Ancillary: Confirmatory immunohistochemistry is essential for distinguishing metastatic tumours from primary renal tumours, particularly using markers like TTF1, CDX2, and thyroglobulin.
Reference Gallery:
Kidney metastasis from lung adenocarcinoma. Malignant glands extend between the renal glomeruli.
Kidney metastasis from lung adenocarcinoma. Tumour cells are positive for thyroid transcription factor 1 (TTF1).
Kidney metastasis from colonic adenocarcinoma. There is a desmoplastic and inflammatory response around the metastatic glands, and the kidney parenchyma is atrophic.
Kidney metastasis from colonic adenocarcinoma. The surrounding renal parenchyma is compressed and atrophic.
Kidney metastasis from colonic adenocarcinoma. CDX2 stain is positive.

Q: An infant presenting with gross hematuria and a calcified mass protruding into the renal pelvis or calyces on imaging is highly suggestive of [...].
Ossifying renal tumour of infancy. Tumour within the renal calyx.
A: ossifying renal tumor of infancy
Back Extra: Ossifying Renal Tumour of Infancy
- Clinical: Ossifying renal tumour of infancy (ORTI) typically presents with gross haematuria and a calcified mass protruding into the renal pelvis on imaging.
- Micro: ORTI is characterized by the presence of osteoblast-like cells and spindle cells, with the osteoblast-like cells often positive for EMA and vimentin.
- Ancillary: Clonal trisomy 4 is a recurrent molecular abnormality found in ORTI cases.
Reference Gallery:
Ossifying renal tumour of infancy. Calcified part with osteoblastic cells.
Ossifying renal tumour of infancy. Spindle cell component.
Ossifying renal tumour of infancy. Tumour within the renal calyx.

Q: Histologically, ossifying renal tumor of infancy is uniquely characterized by a cellular spindle cell proliferation and a centrally calcified core lined by [...] cells.
Ossifying renal tumour of infancy. Calcified part with osteoblastic cells.
Ossifying renal tumour of infancy. Spindle cell component.
A: osteoblast-like
Back Extra: Ossifying Renal Tumour of Infancy
- Clinical: Ossifying renal tumour of infancy (ORTI) typically presents with gross haematuria and a calcified mass protruding into the renal pelvis on imaging.
- Micro: ORTI is characterized by the presence of osteoblast-like cells and spindle cells, with the osteoblast-like cells often positive for EMA and vimentin.
- Ancillary: Clonal trisomy 4 is a recurrent molecular abnormality found in ORTI cases.
Reference Gallery:
Ossifying renal tumour of infancy. Calcified part with osteoblastic cells.
Ossifying renal tumour of infancy. Spindle cell component.
Ossifying renal tumour of infancy. Tumour within the renal calyx.

Q: The defining immunohistochemical feature of Extrarenal Rhabdoid Tumor is the complete loss of nuclear [...] expression within the tumor cells, with retained staining in normal endothelial cells.
Rhabdoid tumour. SMARCB1 (INI1) immunostaining showing a complete loss of staining in the tumour cells, with the retained labelling of endothelial cells lining small vessels serving as an internal positive control.
A: SMARCB1 (INI1)
Back Extra: Extrarenal Rhabdoid Tumour
- Clinical: Extrarenal Rhabdoid Tumours often present as an abdominal mass in infants and young children, with a mean/median patient age of 1 year.
- Micro: The tumour is characterized by large, vesicular nuclei with prominent nucleoli and frequent mitoses and necrosis. sheets of large, non-cohesive cells with characteristic eosinophilic intracytoplasmic inclusions are commonly seen.
- Ancillary: The diagnosis is supported by the absence of nuclear SMARCB1 (INI1) staining in tumour cells, with retained staining in normal cells serving as an internal positive control.
Reference Gallery:
Rhabdoid tumour. Microscopic image of a tumour composed of sheets of cells without differentiation.
Rhabdoid tumour. Higher magnification of tumour cells with prominent nuclear pleomorphism and occasional prominent nucleoli. The typical feature of rhabdoid cells with eosinophilic cytoplasmic inclusions is lacking in most of the tumour cells. Compare with Fig. <<#21212>> in <<3.4.2.3>>Rhabdoid tumour of the kidney.
Rhabdoid tumour. SMARCB1 (INI1) immunostaining showing a complete loss of staining in the tumour cells, with the retained labelling of endothelial cells lining small vessels serving as an internal positive control.

Q: A highly aggressive neoplasm typically presenting as an abdominal mass in infants, characterized microscopically by sheets of undifferentiated cells with prominent nucleoli and an absolute loss of nuclear SMARCB1 (INI1) staining, is most consistent with an [...].
Rhabdoid tumour. Microscopic image of a tumour composed of sheets of cells without differentiation.
Rhabdoid tumour. Higher magnification of tumour cells with prominent nuclear pleomorphism and occasional prominent nucleoli. The typical feature of rhabdoid cells with eosinophilic cytoplasmic inclusions is lacking in most of the tumour cells. Compare with Fig. <<#21212>> in <<3.4.2.3>>Rhabdoid tumour of the kidney.
Rhabdoid tumour. SMARCB1 (INI1) immunostaining showing a complete loss of staining in the tumour cells, with the retained labelling of endothelial cells lining small vessels serving as an internal positive control.
A: Extrarenal Rhabdoid Tumor
Back Extra: Extrarenal Rhabdoid Tumour
- Clinical: Extrarenal Rhabdoid Tumours often present as an abdominal mass in infants and young children, with a mean/median patient age of 1 year.
- Micro: The tumour is characterized by large, vesicular nuclei with prominent nucleoli and frequent mitoses and necrosis. sheets of large, non-cohesive cells with characteristic eosinophilic intracytoplasmic inclusions are commonly seen.
- Ancillary: The diagnosis is supported by the absence of nuclear SMARCB1 (INI1) staining in tumour cells, with retained staining in normal cells serving as an internal positive control.
Reference Gallery:
Rhabdoid tumour. Microscopic image of a tumour composed of sheets of cells without differentiation.
Rhabdoid tumour. Higher magnification of tumour cells with prominent nuclear pleomorphism and occasional prominent nucleoli. The typical feature of rhabdoid cells with eosinophilic cytoplasmic inclusions is lacking in most of the tumour cells. Compare with Fig. <<#21212>> in <<3.4.2.3>>Rhabdoid tumour of the kidney.
Rhabdoid tumour. SMARCB1 (INI1) immunostaining showing a complete loss of staining in the tumour cells, with the retained labelling of endothelial cells lining small vessels serving as an internal positive control.

Q: In Rhabdoid Tumor of the Kidney, the classic microscopic appearance consists of large, non-cohesive cells with prominent nucleoli and distinct [...].
Rhabdoid tumour of the kidney. Section highlighting the diffuse growth and the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions.
Rhabdoid tumour of the kidney. High-power view showing the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions in some cells.
A: cytoplasmic inclusions
Back Extra: Rhabdoid Tumor of the Kidney
- Clinical: Rhabdoid Tumor of the Kidney often presents with hypercalcaemia, fever, haematuria, and an abdominal mass, with 80% of cases diagnosed before the age of 2 years.
- Micro: The tumour is characterized by large, non-cohesive cells with prominent nucleoli and cytoplasmic inclusions, growing in a diffuse infiltrative pattern.
- Ancillary: Immunohistochemistry shows a loss of SMARCB1 (INI1) staining in tumour cells, which serves as a key diagnostic marker.
Reference Gallery:
Rhabdoid tumour of the kidney. Section highlighting the diffuse growth and the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions.
Rhabdoid tumour of the kidney. Tumour cells lack SMARCB1 (INI1) immunostaining, whereas it is retained in normal cells.
Rhabdoid tumour of the kidney. Diffuse growth pattern of tumour cells.
Rhabdoid tumour of the kidney. High-power view showing the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions in some cells.
Rhabdoid tumour of the kidney. Lack of SMARCB1 (INI1) immunostaining in tumour cells. SMARCB1 staining is retained in normal cells and serves as an internal positive control.
Rhabdoid tumour of the kidney. T1-weighted MRI of a 6-month-old boy with a renal tumour.

Q: The defining immunohistochemical feature of Rhabdoid Tumor of the Kidney is the complete loss of [...] staining in the neoplastic cells.
Rhabdoid tumour of the kidney. Tumour cells lack SMARCB1 (INI1) immunostaining, whereas it is retained in normal cells.
Rhabdoid tumour of the kidney. Lack of SMARCB1 (INI1) immunostaining in tumour cells. SMARCB1 staining is retained in normal cells and serves as an internal positive control.
A: SMARCB1 (INI1)
Back Extra: Rhabdoid Tumor of the Kidney
- Clinical: Rhabdoid Tumor of the Kidney often presents with hypercalcaemia, fever, haematuria, and an abdominal mass, with 80% of cases diagnosed before the age of 2 years.
- Micro: The tumour is characterized by large, non-cohesive cells with prominent nucleoli and cytoplasmic inclusions, growing in a diffuse infiltrative pattern.
- Ancillary: Immunohistochemistry shows a loss of SMARCB1 (INI1) staining in tumour cells, which serves as a key diagnostic marker.
Reference Gallery:
Rhabdoid tumour of the kidney. Section highlighting the diffuse growth and the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions.
Rhabdoid tumour of the kidney. Tumour cells lack SMARCB1 (INI1) immunostaining, whereas it is retained in normal cells.
Rhabdoid tumour of the kidney. Diffuse growth pattern of tumour cells.
Rhabdoid tumour of the kidney. High-power view showing the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions in some cells.
Rhabdoid tumour of the kidney. Lack of SMARCB1 (INI1) immunostaining in tumour cells. SMARCB1 staining is retained in normal cells and serves as an internal positive control.
Rhabdoid tumour of the kidney. T1-weighted MRI of a 6-month-old boy with a renal tumour.

Q: A highly aggressive pediatric renal neoplasm that typically presents with an abdominal mass, hematuria, and hypercalcemia in children under 2 years of age is the [...].
Rhabdoid tumour of the kidney. T1-weighted MRI of a 6-month-old boy with a renal tumour.
A: Rhabdoid Tumor of the Kidney
Back Extra: Rhabdoid Tumor of the Kidney
- Clinical: Rhabdoid Tumor of the Kidney often presents with hypercalcaemia, fever, haematuria, and an abdominal mass, with 80% of cases diagnosed before the age of 2 years.
- Micro: The tumour is characterized by large, non-cohesive cells with prominent nucleoli and cytoplasmic inclusions, growing in a diffuse infiltrative pattern.
- Ancillary: Immunohistochemistry shows a loss of SMARCB1 (INI1) staining in tumour cells, which serves as a key diagnostic marker.
Reference Gallery:
Rhabdoid tumour of the kidney. Section highlighting the diffuse growth and the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions.
Rhabdoid tumour of the kidney. Tumour cells lack SMARCB1 (INI1) immunostaining, whereas it is retained in normal cells.
Rhabdoid tumour of the kidney. Diffuse growth pattern of tumour cells.
Rhabdoid tumour of the kidney. High-power view showing the typical cellular aspect with prominent nucleoli and cytoplasmic inclusions in some cells.
Rhabdoid tumour of the kidney. Lack of SMARCB1 (INI1) immunostaining in tumour cells. SMARCB1 staining is retained in normal cells and serves as an internal positive control.
Rhabdoid tumour of the kidney. T1-weighted MRI of a 6-month-old boy with a renal tumour.

Q: Grossly, Acquired Cystic Disease-Associated Renal Cell Carcinoma often presents as a hemorrhagic mass within a cyst, occurring almost exclusively in patients with acquired cystic disease who have a history of long-term [...].
Acquired cystic disease–associated renal cell carcinoma. The tumour forms a haemorrhagic mass in a cyst. There are numerous cysts in the background.
A: dialysis
Back Extra: Acquired Cystic Disease-Associated Renal Cell Carcinoma
- Clinical: Acquired cystic disease–associated renal cell carcinoma (ACD-RCC) occurs exclusively in patients with acquired cystic disease, usually after long-term dialysis, and is mostly asymptomatic, found incidentally by imaging.
- Micro: ACD-RCC shows tubulopapillary, tubular, and microcystic patterns with eosinophilic cells, prominent nucleoli, and characteristic sieve-like growth due to intracytoplasmic or intercytoplasmic lumina.
- Ancillary: Immunohistochemically, ACD-RCC is positive for PAX8, CD10, RCCm, and AMACR, and negative for GATA3, CK7, and KIT. Recurrent KMT2C or TSC2 gene mutations are reported.
Reference Gallery:
Acquired cystic disease–associated renal cell carcinoma. The tumour forms a haemorrhagic mass in a cyst. There are numerous cysts in the background.
Acquired cystic disease–associated renal cell carcinoma. The tumour shows tubulopapillary growth composed of abundant eosinophilic cells with a prominent nucleolus, some of which have intracytoplasmic or intercytoplasmic holes imparting sieve-like growth and calcium oxalate crystal deposition.

Q: Histologically, Acquired Cystic Disease-Associated Renal Cell Carcinoma frequently features abundant eosinophilic cells with prominent nucleoli, a sieve-like growth pattern, and the characteristic deposition of [...] crystals.
Acquired cystic disease–associated renal cell carcinoma. The tumour shows tubulopapillary growth composed of abundant eosinophilic cells with a prominent nucleolus, some of which have intracytoplasmic or intercytoplasmic holes imparting sieve-like growth and calcium oxalate crystal deposition.
A: calcium oxalate
Back Extra: Acquired Cystic Disease-Associated Renal Cell Carcinoma
- Clinical: Acquired cystic disease–associated renal cell carcinoma (ACD-RCC) occurs exclusively in patients with acquired cystic disease, usually after long-term dialysis, and is mostly asymptomatic, found incidentally by imaging.
- Micro: ACD-RCC shows tubulopapillary, tubular, and microcystic patterns with eosinophilic cells, prominent nucleoli, and characteristic sieve-like growth due to intracytoplasmic or intercytoplasmic lumina.
- Ancillary: Immunohistochemically, ACD-RCC is positive for PAX8, CD10, RCCm, and AMACR, and negative for GATA3, CK7, and KIT. Recurrent KMT2C or TSC2 gene mutations are reported.
Reference Gallery:
Acquired cystic disease–associated renal cell carcinoma. The tumour forms a haemorrhagic mass in a cyst. There are numerous cysts in the background.
Acquired cystic disease–associated renal cell carcinoma. The tumour shows tubulopapillary growth composed of abundant eosinophilic cells with a prominent nucleolus, some of which have intracytoplasmic or intercytoplasmic holes imparting sieve-like growth and calcium oxalate crystal deposition.

Q: The VCL::ALK fusion variant of ALK-Rearranged Renal Cell Carcinoma classically demonstrates polygonal neoplastic cells with abundant eosinophilic cytoplasm and striking [...].
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate striking cytoplasmic vacuolization.
Renal cell carcinoma with VCL::ALK gene fusion. There are numerous sickled erythrocytes scattered among the vacuolated neoplastic cells.
A: cytoplasmic vacuolization
Back Extra: ALK-Rearranged Renal Cell Carcinoma
- Clinical: ALK-rearranged renal cell carcinomas are rare, with about 50 reported cases, and they are generally small and organ-confined at presentation (pT1).
- Micro: The morphology of ALK-rearranged RCCs with VCL::ALK fusions is distinctive, with polygonal neoplastic cells showing abundant eosinophilic cytoplasm and striking cytoplasmic vacuolization.
- Ancillary: Immunohistochemistry for ALK protein is a useful screening test, and ALK rearrangement can be confirmed by break-apart FISH or sequencing.
Reference Gallery:
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate striking cytoplasmic vacuolization.
Renal cell carcinoma with VCL::ALK gene fusion. There are numerous sickled erythrocytes scattered among the vacuolated neoplastic cells.
Renal cell carcinoma with EML4::ALK gene fusion. The tumour has a striking desmoplastic reaction, and it infiltrates the native kidney.
Renal cell carcinoma with EML4::ALK gene fusion. The neoplastic cells form irregular glands and cribriform structures within an oedematous and desmoplastic stroma.
ALK translocation renal cell carcinoma. Break-apart FISH for the ALK gene shows most nuclei with one split signal (separate red and green probes) per nucleus and the second copy with a fused (normal) pattern for the ALK gene.

Q: The EML4::ALK fusion variant of ALK-Rearranged Renal Cell Carcinoma is characterized by the formation of irregular glands and cribriform structures within a prominent [...] and edematous stroma.
Renal cell carcinoma with EML4::ALK gene fusion. The tumour has a striking desmoplastic reaction, and it infiltrates the native kidney.
Renal cell carcinoma with EML4::ALK gene fusion. The neoplastic cells form irregular glands and cribriform structures within an oedematous and desmoplastic stroma.
A: desmoplastic
Back Extra: ALK-Rearranged Renal Cell Carcinoma
- Clinical: ALK-rearranged renal cell carcinomas are rare, with about 50 reported cases, and they are generally small and organ-confined at presentation (pT1).
- Micro: The morphology of ALK-rearranged RCCs with VCL::ALK fusions is distinctive, with polygonal neoplastic cells showing abundant eosinophilic cytoplasm and striking cytoplasmic vacuolization.
- Ancillary: Immunohistochemistry for ALK protein is a useful screening test, and ALK rearrangement can be confirmed by break-apart FISH or sequencing.
Reference Gallery:
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate striking cytoplasmic vacuolization.
Renal cell carcinoma with VCL::ALK gene fusion. There are numerous sickled erythrocytes scattered among the vacuolated neoplastic cells.
Renal cell carcinoma with EML4::ALK gene fusion. The tumour has a striking desmoplastic reaction, and it infiltrates the native kidney.
Renal cell carcinoma with EML4::ALK gene fusion. The neoplastic cells form irregular glands and cribriform structures within an oedematous and desmoplastic stroma.
ALK translocation renal cell carcinoma. Break-apart FISH for the ALK gene shows most nuclei with one split signal (separate red and green probes) per nucleus and the second copy with a fused (normal) pattern for the ALK gene.

Q: Diagnosis of ALK-Rearranged Renal Cell Carcinoma can be confirmed via break-apart FISH, which typically demonstrates one [...] signal (separated red and green probes) per nucleus.
ALK translocation renal cell carcinoma. Break-apart FISH for the ALK gene shows most nuclei with one split signal (separate red and green probes) per nucleus and the second copy with a fused (normal) pattern for the ALK gene.
A: split
Back Extra: ALK-Rearranged Renal Cell Carcinoma
- Clinical: ALK-rearranged renal cell carcinomas are rare, with about 50 reported cases, and they are generally small and organ-confined at presentation (pT1).
- Micro: The morphology of ALK-rearranged RCCs with VCL::ALK fusions is distinctive, with polygonal neoplastic cells showing abundant eosinophilic cytoplasm and striking cytoplasmic vacuolization.
- Ancillary: Immunohistochemistry for ALK protein is a useful screening test, and ALK rearrangement can be confirmed by break-apart FISH or sequencing.
Reference Gallery:
Renal cell carcinoma with VCL::ALK gene fusion. The neoplastic cells demonstrate striking cytoplasmic vacuolization.
Renal cell carcinoma with VCL::ALK gene fusion. There are numerous sickled erythrocytes scattered among the vacuolated neoplastic cells.
Renal cell carcinoma with EML4::ALK gene fusion. The tumour has a striking desmoplastic reaction, and it infiltrates the native kidney.
Renal cell carcinoma with EML4::ALK gene fusion. The neoplastic cells form irregular glands and cribriform structures within an oedematous and desmoplastic stroma.
ALK translocation renal cell carcinoma. Break-apart FISH for the ALK gene shows most nuclei with one split signal (separate red and green probes) per nucleus and the second copy with a fused (normal) pattern for the ALK gene.

Q: Microscopically, classic Chromophobe Renal Cell Carcinoma is characterized by pale cells with reticulated cytoplasm and highly distinct, [...] (often resembling plant cells), while the eosinophilic variant typically displays distinctive perinuclear halos.
Chromophobe renal cell carcinoma. Classic pattern. The pale cells show reticulated cytoplasm and prominent cell borders.
Chromophobe renal cell carcinoma. Eosinophilic pattern. The tumour is composed of eosinophilic cells with irregular nuclei and perinuclear haloes.
A: prominent cell borders
Q: Chromophobe Renal Cell Carcinoma
- Clinical: Most [...] are discovered incidentally in asymptomatic patients, with some association with Birt–Hogg–Dubé syndrome.
- Micro: [...] show a predominance of pale cells with clear to foamy cytoplasm and prominent cell borders.
- Ancillary: [...] are frequently positive for CK7 and KIT (CD117) on immunohistochemistry.
Reference Gallery:
Chromophobe renal cell carcinoma. Classic pattern. The tumour cells are arranged in a sheet-like pattern, separated by incomplete vascular septa.
Chromophobe renal cell carcinoma. Classic pattern. The pale cells show reticulated cytoplasm and prominent cell borders.
Chromophobe renal cell carcinoma. Eosinophilic pattern. The tumour is composed of eosinophilic cells with irregular nuclei and perinuclear haloes.
Chromophobe renal cell carcinoma. This example shows coagulative necrosis.
Chromophobe renal cell carcinoma. This example shows sarcomatoid differentiation.
Chromophobe renal cell carcinoma. CK7 immunohistochemistry shows membrane positivity.
Chromophobe renal cell carcinoma. A well-circumscribed and unencapsulated mass.
Chromophobe renal cell carcinoma. KIT (CD117) immunohistochemistry shows membrane positivity.
Chromophobe renal cell carcinoma. Hale colloidal iron reveals acid mucopolysaccharides stained blue within the cytoplasm (nuclei are stained red).
Chromophobe renal cell carcinoma. A well-circumscribed mass with a tan-yellow cut surface.
A: Chromophobe Renal Cell Carcinomas; Chromophobe Renal Cell Carcinomas; Chromophobe Renal Cell Carcinomas

Q: For ancillary diagnostic confirmation, Chromophobe Renal Cell Carcinoma characteristically shows membranous immunohistochemical positivity for CK7 and KIT (CD117), and demonstrates acid mucopolysaccharides as blue cytoplasmic staining using the [...] stain.
Chromophobe renal cell carcinoma. CK7 immunohistochemistry shows membrane positivity.
Chromophobe renal cell carcinoma. KIT (CD117) immunohistochemistry shows membrane positivity.
Chromophobe renal cell carcinoma. Hale colloidal iron reveals acid mucopolysaccharides stained blue within the cytoplasm (nuclei are stained red).
A: Hale colloidal iron
Q: Chromophobe Renal Cell Carcinoma
- Clinical: Most [...] are discovered incidentally in asymptomatic patients, with some association with Birt–Hogg–Dubé syndrome.
- Micro: [...] show a predominance of pale cells with clear to foamy cytoplasm and prominent cell borders.
- Ancillary: [...] are frequently positive for CK7 and KIT (CD117) on immunohistochemistry.
Reference Gallery:
Chromophobe renal cell carcinoma. Classic pattern. The tumour cells are arranged in a sheet-like pattern, separated by incomplete vascular septa.
Chromophobe renal cell carcinoma. Classic pattern. The pale cells show reticulated cytoplasm and prominent cell borders.
Chromophobe renal cell carcinoma. Eosinophilic pattern. The tumour is composed of eosinophilic cells with irregular nuclei and perinuclear haloes.
Chromophobe renal cell carcinoma. This example shows coagulative necrosis.
Chromophobe renal cell carcinoma. This example shows sarcomatoid differentiation.
Chromophobe renal cell carcinoma. CK7 immunohistochemistry shows membrane positivity.
Chromophobe renal cell carcinoma. A well-circumscribed and unencapsulated mass.
Chromophobe renal cell carcinoma. KIT (CD117) immunohistochemistry shows membrane positivity.
Chromophobe renal cell carcinoma. Hale colloidal iron reveals acid mucopolysaccharides stained blue within the cytoplasm (nuclei are stained red).
Chromophobe renal cell carcinoma. A well-circumscribed mass with a tan-yellow cut surface.
A: Chromophobe Renal Cell Carcinomas; Chromophobe Renal Cell Carcinomas; Chromophobe Renal Cell Carcinomas

Q: Patients with Birt-Hogg-Dubé syndrome are at an increased risk of developing [...], which frequently presents grossly as a well-circumscribed, unencapsulated mass with a tan-yellow cut surface.
Chromophobe renal cell carcinoma. A well-circumscribed and unencapsulated mass.
Chromophobe renal cell carcinoma. A well-circumscribed mass with a tan-yellow cut surface.
A: Chromophobe Renal Cell Carcinoma
Q: Chromophobe Renal Cell Carcinoma
- Clinical: Most [...] are discovered incidentally in asymptomatic patients, with some association with Birt–Hogg–Dubé syndrome.
- Micro: [...] show a predominance of pale cells with clear to foamy cytoplasm and prominent cell borders.
- Ancillary: [...] are frequently positive for CK7 and KIT (CD117) on immunohistochemistry.
Reference Gallery:
Chromophobe renal cell carcinoma. Classic pattern. The tumour cells are arranged in a sheet-like pattern, separated by incomplete vascular septa.
Chromophobe renal cell carcinoma. Classic pattern. The pale cells show reticulated cytoplasm and prominent cell borders.
Chromophobe renal cell carcinoma. Eosinophilic pattern. The tumour is composed of eosinophilic cells with irregular nuclei and perinuclear haloes.
Chromophobe renal cell carcinoma. This example shows coagulative necrosis.
Chromophobe renal cell carcinoma. This example shows sarcomatoid differentiation.
Chromophobe renal cell carcinoma. CK7 immunohistochemistry shows membrane positivity.
Chromophobe renal cell carcinoma. A well-circumscribed and unencapsulated mass.
Chromophobe renal cell carcinoma. KIT (CD117) immunohistochemistry shows membrane positivity.
Chromophobe renal cell carcinoma. Hale colloidal iron reveals acid mucopolysaccharides stained blue within the cytoplasm (nuclei are stained red).
Chromophobe renal cell carcinoma. A well-circumscribed mass with a tan-yellow cut surface.
A: Chromophobe Renal Cell Carcinomas; Chromophobe Renal Cell Carcinomas; Chromophobe Renal Cell Carcinomas

Q: Immunohistochemistry for CAIX in Clear Cell Papillary Renal Cell Tumor characteristically demonstrates a [...] staining pattern.
Clear cell papillary tumour. CAIX-positive immunohistochemistry (cup-like stain).
A: cup-like
Back Extra: Clear Cell Papillary Renal Cell Tumor
- Clinical: Clear cell papillary renal cell tumors are typically incidental findings, accounting for about 3% of renal cell carcinomas in adults.
- Micro: These tumors are composed of tubules, papillae, nests, and cysts, with cuboidal to low columnar cells and small nucleoli.
- Ancillary: Distinguished by diffuse CK7 positivity and cup-like CAIX staining, lacking chromosome 3p loss and VHL alterations seen in clear cell RCC.
Reference Gallery:
Clear cell papillary tumour. CK7-positive immunohistochemistry.
Clear cell papillary tumour. CAIX-positive immunohistochemistry (cup-like stain).
Clear cell papillary tumour. Cuboidal tumour cells with uniform nuclei and inconspicuous nucleoli.
Clear cell papillary tumour. Large cystic tumour.

Q: Unlike conventional clear cell RCC, Clear Cell Papillary Renal Cell Tumor typically demonstrates strong, diffuse immunohistochemical expression of [...].
Clear cell papillary tumour. CK7-positive immunohistochemistry.
A: CK7
Back Extra: Clear Cell Papillary Renal Cell Tumor
- Clinical: Clear cell papillary renal cell tumors are typically incidental findings, accounting for about 3% of renal cell carcinomas in adults.
- Micro: These tumors are composed of tubules, papillae, nests, and cysts, with cuboidal to low columnar cells and small nucleoli.
- Ancillary: Distinguished by diffuse CK7 positivity and cup-like CAIX staining, lacking chromosome 3p loss and VHL alterations seen in clear cell RCC.
Reference Gallery:
Clear cell papillary tumour. CK7-positive immunohistochemistry.
Clear cell papillary tumour. CAIX-positive immunohistochemistry (cup-like stain).
Clear cell papillary tumour. Cuboidal tumour cells with uniform nuclei and inconspicuous nucleoli.
Clear cell papillary tumour. Large cystic tumour.

Q: A cystic kidney mass showing tubules, papillae, and nests lined by cuboidal clear cells with uniform nuclei and inconspicuous nucleoli is most characteristic of a [...].
Clear cell papillary tumour. Cuboidal tumour cells with uniform nuclei and inconspicuous nucleoli.
Clear cell papillary tumour. Large cystic tumour.
A: Clear Cell Papillary Renal Cell Tumor
Back Extra: Clear Cell Papillary Renal Cell Tumor
- Clinical: Clear cell papillary renal cell tumors are typically incidental findings, accounting for about 3% of renal cell carcinomas in adults.
- Micro: These tumors are composed of tubules, papillae, nests, and cysts, with cuboidal to low columnar cells and small nucleoli.
- Ancillary: Distinguished by diffuse CK7 positivity and cup-like CAIX staining, lacking chromosome 3p loss and VHL alterations seen in clear cell RCC.
Reference Gallery:
Clear cell papillary tumour. CK7-positive immunohistochemistry.
Clear cell papillary tumour. CAIX-positive immunohistochemistry (cup-like stain).
Clear cell papillary tumour. Cuboidal tumour cells with uniform nuclei and inconspicuous nucleoli.
Clear cell papillary tumour. Large cystic tumour.

Q: The classic histological appearance of Clear Cell Renal Cell Carcinoma features a nested or alveolar growth pattern separated by a complex, arborizing vascular network, with cells typically exhibiting [...] cytoplasm.
Clear cell renal cell carcinoma. Grade 1 nuclei with nucleoli that are absent to inconspicuous and basophilic at ×400 magnification.
Clear cell renal cell carcinoma. Grade 2 nuclei, where nucleoli are visible although not prominent at ×100 magnification (left) but conspicuous and eosinophilic at ×400 magnification (right).
A: optically clear
Back Extra: Clear Cell Renal Cell Carcinoma
- Clinical: Clear cell renal cell carcinomas (CCRCC) often present with haematuria, flank pain, and weight loss in advanced stages. They can metastasize haematogenously, leading to pulmonary and bone metastases.
- Micro: The classic histological appearance of CCRCC is a nested, tubular, or alveolar growth pattern with cells having optically clear cytoplasm and a complex vascular network.
- Ancillary: Inactivation of the VHL complex is the defining event in CCRCC, with most sporadic cases showing loss of chromosome arm 3p and inactivating mutations or promoter methylation of the VHL gene.
Reference Gallery:
Clear cell renal cell carcinoma, cytology. An imprint smear of the core needle biopsy shows an aggregate of cells with ample delicate, vacuolated cytoplasm, and vesicular to hyperchromatic nuclei.
Clear cell renal cell carcinoma, cytology. Dissociated tumour cells show enlarged hyperchromatic nuclei and abundant cytoplasm with fine lipid vacuoles (Diff-Quik stain).
Clear cell renal cell carcinoma. Macroscopic appearance showing a haemorrhagic variegated cut surface with tumour extension into the renal sinus.
Clear cell renal cell carcinoma. The tumour extends into a large vessel in the kidney hilum.
Clear cell renal cell carcinoma. This example shows rhabdoid cells with ample pink cytoplasm and eccentrically placed abnormal nuclei, indicating grade 4.
Clear cell renal cell carcinoma. Necrosis within a tumour.
Clear cell renal cell carcinoma. This example includes necrosis, rhabdoid cells, and multinucleated cells.
Clear cell renal cell carcinoma. Grade 1 nuclei with nucleoli that are absent to inconspicuous and basophilic at ×400 magnification.
Clear cell renal cell carcinoma. Grade 2 nuclei, where nucleoli are visible although not prominent at ×100 magnification (left) but conspicuous and eosinophilic at ×400 magnification (right).
Clear cell renal cell carcinoma. Grade 3 histology shows nucleoli that are conspicuous and eosinophilic at ×100 magnification.
Clear cell renal cell carcinoma. Survival outcomes of patients stratified according to stage. Data from the Mayo Clinic Nephrectomy Registry.
Clear cell renal cell carcinoma. Survival outcomes of patients stratified according to WHO Classification of Tumours / International Society of Urological Pathology (WHO/ISUP) grade. Data from the Mayo Clinic Nephrectomy Registry.

Q: On cytology, Clear Cell Renal Cell Carcinoma characteristically presents with dissociated tumor cells or aggregates that possess vesicular to hyperchromatic nuclei and abundant cytoplasm filled with fine [...].
Clear cell renal cell carcinoma, cytology. An imprint smear of the core needle biopsy shows an aggregate of cells with ample delicate, vacuolated cytoplasm, and vesicular to hyperchromatic nuclei.
Clear cell renal cell carcinoma, cytology. Dissociated tumour cells show enlarged hyperchromatic nuclei and abundant cytoplasm with fine lipid vacuoles (Diff-Quik stain).
A: lipid vacuoles
Back Extra: Clear Cell Renal Cell Carcinoma
- Clinical: Clear cell renal cell carcinomas (CCRCC) often present with haematuria, flank pain, and weight loss in advanced stages. They can metastasize haematogenously, leading to pulmonary and bone metastases.
- Micro: The classic histological appearance of CCRCC is a nested, tubular, or alveolar growth pattern with cells having optically clear cytoplasm and a complex vascular network.
- Ancillary: Inactivation of the VHL complex is the defining event in CCRCC, with most sporadic cases showing loss of chromosome arm 3p and inactivating mutations or promoter methylation of the VHL gene.
Reference Gallery:
Clear cell renal cell carcinoma, cytology. An imprint smear of the core needle biopsy shows an aggregate of cells with ample delicate, vacuolated cytoplasm, and vesicular to hyperchromatic nuclei.
Clear cell renal cell carcinoma, cytology. Dissociated tumour cells show enlarged hyperchromatic nuclei and abundant cytoplasm with fine lipid vacuoles (Diff-Quik stain).
Clear cell renal cell carcinoma. Macroscopic appearance showing a haemorrhagic variegated cut surface with tumour extension into the renal sinus.
Clear cell renal cell carcinoma. The tumour extends into a large vessel in the kidney hilum.
Clear cell renal cell carcinoma. This example shows rhabdoid cells with ample pink cytoplasm and eccentrically placed abnormal nuclei, indicating grade 4.
Clear cell renal cell carcinoma. Necrosis within a tumour.
Clear cell renal cell carcinoma. This example includes necrosis, rhabdoid cells, and multinucleated cells.
Clear cell renal cell carcinoma. Grade 1 nuclei with nucleoli that are absent to inconspicuous and basophilic at ×400 magnification.
Clear cell renal cell carcinoma. Grade 2 nuclei, where nucleoli are visible although not prominent at ×100 magnification (left) but conspicuous and eosinophilic at ×400 magnification (right).
Clear cell renal cell carcinoma. Grade 3 histology shows nucleoli that are conspicuous and eosinophilic at ×100 magnification.
Clear cell renal cell carcinoma. Survival outcomes of patients stratified according to stage. Data from the Mayo Clinic Nephrectomy Registry.
Clear cell renal cell carcinoma. Survival outcomes of patients stratified according to WHO Classification of Tumours / International Society of Urological Pathology (WHO/ISUP) grade. Data from the Mayo Clinic Nephrectomy Registry.

Q: Macroscopically, Clear Cell Renal Cell Carcinoma frequently displays a hemorrhagic, variegated cut surface and is notable for its tendency to aggressively invade large blood vessels, often extending directly into the [...] or hilar structures.
Clear cell renal cell carcinoma. Macroscopic appearance showing a haemorrhagic variegated cut surface with tumour extension into the renal sinus.
Clear cell renal cell carcinoma. The tumour extends into a large vessel in the kidney hilum.
A: renal sinus
Back Extra: Clear Cell Renal Cell Carcinoma
- Clinical: Clear cell renal cell carcinomas (CCRCC) often present with haematuria, flank pain, and weight loss in advanced stages. They can metastasize haematogenously, leading to pulmonary and bone metastases.
- Micro: The classic histological appearance of CCRCC is a nested, tubular, or alveolar growth pattern with cells having optically clear cytoplasm and a complex vascular network.
- Ancillary: Inactivation of the VHL complex is the defining event in CCRCC, with most sporadic cases showing loss of chromosome arm 3p and inactivating mutations or promoter methylation of the VHL gene.
Reference Gallery:
Clear cell renal cell carcinoma, cytology. An imprint smear of the core needle biopsy shows an aggregate of cells with ample delicate, vacuolated cytoplasm, and vesicular to hyperchromatic nuclei.
Clear cell renal cell carcinoma, cytology. Dissociated tumour cells show enlarged hyperchromatic nuclei and abundant cytoplasm with fine lipid vacuoles (Diff-Quik stain).
Clear cell renal cell carcinoma. Macroscopic appearance showing a haemorrhagic variegated cut surface with tumour extension into the renal sinus.
Clear cell renal cell carcinoma. The tumour extends into a large vessel in the kidney hilum.
Clear cell renal cell carcinoma. This example shows rhabdoid cells with ample pink cytoplasm and eccentrically placed abnormal nuclei, indicating grade 4.
Clear cell renal cell carcinoma. Necrosis within a tumour.
Clear cell renal cell carcinoma. This example includes necrosis, rhabdoid cells, and multinucleated cells.
Clear cell renal cell carcinoma. Grade 1 nuclei with nucleoli that are absent to inconspicuous and basophilic at ×400 magnification.
Clear cell renal cell carcinoma. Grade 2 nuclei, where nucleoli are visible although not prominent at ×100 magnification (left) but conspicuous and eosinophilic at ×400 magnification (right).
Clear cell renal cell carcinoma. Grade 3 histology shows nucleoli that are conspicuous and eosinophilic at ×100 magnification.
Clear cell renal cell carcinoma. Survival outcomes of patients stratified according to stage. Data from the Mayo Clinic Nephrectomy Registry.
Clear cell renal cell carcinoma. Survival outcomes of patients stratified according to WHO Classification of Tumours / International Society of Urological Pathology (WHO/ISUP) grade. Data from the Mayo Clinic Nephrectomy Registry.

Q: Histologically, Collecting Duct Carcinoma is characterized by infiltrative tubular or tubulopapillary glands set within a prominent [...] stroma.
Collecting duct carcinoma. This tumour involves the renal medulla and shows infiltrative tubular/tubulopapillary growth with stromal desmoplasia.
A: desmoplastic
Back Extra: Collecting Duct Carcinoma
- Clinical: Two thirds of patients present with haematuria, back pain, fatigue, or weight loss. Approximately 40% present with metastasis, including to the lungs, liver, bone, adrenal glands, and brain.
- Micro: CDC typically shows tubular and tubulopapillary architectural patterns with irregular, infiltrating glands and associated desmoplastic stroma. Solid nested or sheet-like, trabecular, cord-like individual cells, as well as microcystic patterns, may also be present.
- Ancillary: CDCs are typically positive for high-molecular-weight cytokeratins (34βE12), low-molecular-weight cytokeratins (e.g. CK19, CK7), and PAX8, and they have retained expression of SMARCB1 (also known as INI1 or BAF47) and fumarate hydratase.
Reference Gallery:
Collecting duct carcinoma. This tumour involves the renal medulla and shows infiltrative tubular/tubulopapillary growth with stromal desmoplasia.
Collecting duct carcinoma. This tumour has a tubulopapillary pattern and high-grade nuclear features, with cuboidal and hobnail cells.
Collecting duct carcinoma. Tubules and cords of tumour cells infiltrating between non-neoplastic tubules. There is a prominent neutrophil-rich inflammatory infiltrate.
Collecting duct carcinoma. Gross aspect. A grey-white and firm tumour with areas of haemorrhage and an irregular, poorly defined contour.

Q: In Collecting Duct Carcinoma, the high-grade tumor cells often exhibit cuboidal to [...] morphology, and the background often features a prominent neutrophil-rich inflammatory infiltrate.
Collecting duct carcinoma. This tumour has a tubulopapillary pattern and high-grade nuclear features, with cuboidal and hobnail cells.
Collecting duct carcinoma. Tubules and cords of tumour cells infiltrating between non-neoplastic tubules. There is a prominent neutrophil-rich inflammatory infiltrate.
A: hobnail
Back Extra: Collecting Duct Carcinoma
- Clinical: Two thirds of patients present with haematuria, back pain, fatigue, or weight loss. Approximately 40% present with metastasis, including to the lungs, liver, bone, adrenal glands, and brain.
- Micro: CDC typically shows tubular and tubulopapillary architectural patterns with irregular, infiltrating glands and associated desmoplastic stroma. Solid nested or sheet-like, trabecular, cord-like individual cells, as well as microcystic patterns, may also be present.
- Ancillary: CDCs are typically positive for high-molecular-weight cytokeratins (34βE12), low-molecular-weight cytokeratins (e.g. CK19, CK7), and PAX8, and they have retained expression of SMARCB1 (also known as INI1 or BAF47) and fumarate hydratase.
Reference Gallery:
Collecting duct carcinoma. This tumour involves the renal medulla and shows infiltrative tubular/tubulopapillary growth with stromal desmoplasia.
Collecting duct carcinoma. This tumour has a tubulopapillary pattern and high-grade nuclear features, with cuboidal and hobnail cells.
Collecting duct carcinoma. Tubules and cords of tumour cells infiltrating between non-neoplastic tubules. There is a prominent neutrophil-rich inflammatory infiltrate.
Collecting duct carcinoma. Gross aspect. A grey-white and firm tumour with areas of haemorrhage and an irregular, poorly defined contour.

Q: Grossly, Collecting Duct Carcinoma typically arises in the renal [...] and presents as a firm, gray-white tumor with poorly defined, irregular borders.
Collecting duct carcinoma. This tumour involves the renal medulla and shows infiltrative tubular/tubulopapillary growth with stromal desmoplasia.
Collecting duct carcinoma. Gross aspect. A grey-white and firm tumour with areas of haemorrhage and an irregular, poorly defined contour.
A: medulla
Back Extra: Collecting Duct Carcinoma
- Clinical: Two thirds of patients present with haematuria, back pain, fatigue, or weight loss. Approximately 40% present with metastasis, including to the lungs, liver, bone, adrenal glands, and brain.
- Micro: CDC typically shows tubular and tubulopapillary architectural patterns with irregular, infiltrating glands and associated desmoplastic stroma. Solid nested or sheet-like, trabecular, cord-like individual cells, as well as microcystic patterns, may also be present.
- Ancillary: CDCs are typically positive for high-molecular-weight cytokeratins (34βE12), low-molecular-weight cytokeratins (e.g. CK19, CK7), and PAX8, and they have retained expression of SMARCB1 (also known as INI1 or BAF47) and fumarate hydratase.
Reference Gallery:
Collecting duct carcinoma. This tumour involves the renal medulla and shows infiltrative tubular/tubulopapillary growth with stromal desmoplasia.
Collecting duct carcinoma. This tumour has a tubulopapillary pattern and high-grade nuclear features, with cuboidal and hobnail cells.
Collecting duct carcinoma. Tubules and cords of tumour cells infiltrating between non-neoplastic tubules. There is a prominent neutrophil-rich inflammatory infiltrate.
Collecting duct carcinoma. Gross aspect. A grey-white and firm tumour with areas of haemorrhage and an irregular, poorly defined contour.

Q: Microscopically, ELOC (TCEB1)-mutated renal cell carcinoma features a branching tubulopapillary architecture and neoplastic cells that characteristically intermingle with prominent, thick transecting [...].
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplasm demonstrates a branching tubulopapillary architecture and prominent smooth muscle stroma.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplastic clear cells intermingle with smooth muscle bundles.
A: fibromuscular bands
Back Extra: ELOC (TCEB1)-mutated renal cell carcinoma
- Clinical: ELOC (TCEB1)-mutated renal cell carcinomas are often detected incidentally in imaging studies for conditions like haematuria, with a median age of 60 years and a male predominance.
- Micro: These neoplasms have a nodular appearance with thick transecting fibromuscular bands, branching infolding tubules, and well-formed papillae with voluminous clear cytoplasm and prominent cell borders.
- Ancillary: Characterized by mutations in the ELOC (TCEB1) gene, leading to the inactivation of elongin C and accumulation of HIF1α.
Reference Gallery:
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplasm demonstrates a branching tubulopapillary architecture and prominent smooth muscle stroma.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplastic clear cells intermingle with smooth muscle bundles.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplasm has a tubulopapillary architecture and clear cells.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplastic cells have voluminous cytoplasm.
ELOC (TCEB1)-mutated renal cell carcinoma. Small and well-delineated renal tumour with fibrous-appearing bands separating the nodules.

Q: On gross examination, ELOC (TCEB1)-mutated renal cell carcinoma typically presents as a small, well-delineated tumor characterized by a nodular appearance with distinct nodules separated by [...].
ELOC (TCEB1)-mutated renal cell carcinoma. Small and well-delineated renal tumour with fibrous-appearing bands separating the nodules.
A: fibrous-appearing bands
Back Extra: ELOC (TCEB1)-mutated renal cell carcinoma
- Clinical: ELOC (TCEB1)-mutated renal cell carcinomas are often detected incidentally in imaging studies for conditions like haematuria, with a median age of 60 years and a male predominance.
- Micro: These neoplasms have a nodular appearance with thick transecting fibromuscular bands, branching infolding tubules, and well-formed papillae with voluminous clear cytoplasm and prominent cell borders.
- Ancillary: Characterized by mutations in the ELOC (TCEB1) gene, leading to the inactivation of elongin C and accumulation of HIF1α.
Reference Gallery:
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplasm demonstrates a branching tubulopapillary architecture and prominent smooth muscle stroma.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplastic clear cells intermingle with smooth muscle bundles.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplasm has a tubulopapillary architecture and clear cells.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplastic cells have voluminous cytoplasm.
ELOC (TCEB1)-mutated renal cell carcinoma. Small and well-delineated renal tumour with fibrous-appearing bands separating the nodules.

Q: At high magnification, the neoplastic cells of ELOC (TCEB1)-mutated renal cell carcinoma are characterized by prominent cell borders and voluminous [...].
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplasm has a tubulopapillary architecture and clear cells.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplastic cells have voluminous cytoplasm.
A: clear cytoplasm
Back Extra: ELOC (TCEB1)-mutated renal cell carcinoma
- Clinical: ELOC (TCEB1)-mutated renal cell carcinomas are often detected incidentally in imaging studies for conditions like haematuria, with a median age of 60 years and a male predominance.
- Micro: These neoplasms have a nodular appearance with thick transecting fibromuscular bands, branching infolding tubules, and well-formed papillae with voluminous clear cytoplasm and prominent cell borders.
- Ancillary: Characterized by mutations in the ELOC (TCEB1) gene, leading to the inactivation of elongin C and accumulation of HIF1α.
Reference Gallery:
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplasm demonstrates a branching tubulopapillary architecture and prominent smooth muscle stroma.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplastic clear cells intermingle with smooth muscle bundles.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplasm has a tubulopapillary architecture and clear cells.
ELOC (TCEB1)-mutated renal cell carcinoma. The neoplastic cells have voluminous cytoplasm.
ELOC (TCEB1)-mutated renal cell carcinoma. Small and well-delineated renal tumour with fibrous-appearing bands separating the nodules.

Q: Microscopically, the neoplastic cells of Eosinophilic Solid and Cystic Renal Cell Carcinoma have a solid architecture and characteristically demonstrate coarse [...].
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells have a solid architecture and characteristically demonstrate basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells characteristically demonstrate coarse basophilic cytoplasmic stippling.
A: basophilic cytoplasmic stippling
Back Extra: Eosinophilic Solid and Cystic Renal Cell Carcinoma
- Clinical: Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC-RCC) often presents as an asymptomatic, solid and cystic renal mass identified incidentally on imaging.
- Micro: The neoplastic cells of ESC-RCC have a solid and cystic architecture, with prominent eosinophilic cytoplasm and basophilic cytoplasmic stippling.
- Ancillary: ESC-RCC typically shows focal to diffuse CK20 expression and is usually positive for PAX8. Cathepsin K is often positive in a patchy pattern.
Reference Gallery:
Eosinophilic solid and cystic renal cell carcinoma. This neoplasm demonstrates solid and cystic areas. The solid areas are tan-grey.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasm has predominantly solid architecture and cysts with thin septa.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated, and they have particularly voluminous eosinophilic cytoplasm. The cells in the solid areas are focally vacuolated.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells have a solid architecture and characteristically demonstrate basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells characteristically demonstrate coarse basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. Some tumours are more diffusely positive for CK20.
Eosinophilic solid and cystic renal cell carcinoma. There is typically focal CK20 expression on immunohistochemistry.

Q: On immunohistochemistry, Eosinophilic Solid and Cystic Renal Cell Carcinoma is typically positive for PAX8, patchy Cathepsin K, and shows characteristic focal to diffuse expression of [...].
Eosinophilic solid and cystic renal cell carcinoma. Some tumours are more diffusely positive for CK20.
Eosinophilic solid and cystic renal cell carcinoma. There is typically focal CK20 expression on immunohistochemistry.
A: CK20
Back Extra: Eosinophilic Solid and Cystic Renal Cell Carcinoma
- Clinical: Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC-RCC) often presents as an asymptomatic, solid and cystic renal mass identified incidentally on imaging.
- Micro: The neoplastic cells of ESC-RCC have a solid and cystic architecture, with prominent eosinophilic cytoplasm and basophilic cytoplasmic stippling.
- Ancillary: ESC-RCC typically shows focal to diffuse CK20 expression and is usually positive for PAX8. Cathepsin K is often positive in a patchy pattern.
Reference Gallery:
Eosinophilic solid and cystic renal cell carcinoma. This neoplasm demonstrates solid and cystic areas. The solid areas are tan-grey.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasm has predominantly solid architecture and cysts with thin septa.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated, and they have particularly voluminous eosinophilic cytoplasm. The cells in the solid areas are focally vacuolated.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells have a solid architecture and characteristically demonstrate basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells characteristically demonstrate coarse basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. Some tumours are more diffusely positive for CK20.
Eosinophilic solid and cystic renal cell carcinoma. There is typically focal CK20 expression on immunohistochemistry.

Q: Morphologically, Eosinophilic Solid and Cystic Renal Cell Carcinoma features a solid and cystic architecture, where the cysts are frequently lined by [...] cells with voluminous eosinophilic cytoplasm.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated, and they have particularly voluminous eosinophilic cytoplasm. The cells in the solid areas are focally vacuolated.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated.
A: multinucleated
Back Extra: Eosinophilic Solid and Cystic Renal Cell Carcinoma
- Clinical: Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC-RCC) often presents as an asymptomatic, solid and cystic renal mass identified incidentally on imaging.
- Micro: The neoplastic cells of ESC-RCC have a solid and cystic architecture, with prominent eosinophilic cytoplasm and basophilic cytoplasmic stippling.
- Ancillary: ESC-RCC typically shows focal to diffuse CK20 expression and is usually positive for PAX8. Cathepsin K is often positive in a patchy pattern.
Reference Gallery:
Eosinophilic solid and cystic renal cell carcinoma. This neoplasm demonstrates solid and cystic areas. The solid areas are tan-grey.
Eosinophilic solid and cystic renal cell carcinoma. The neoplasm has predominantly solid architecture and cysts with thin septa.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated, and they have particularly voluminous eosinophilic cytoplasm. The cells in the solid areas are focally vacuolated.
Eosinophilic solid and cystic renal cell carcinoma. The cells lining the cysts are frequently multinucleated.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells have a solid architecture and characteristically demonstrate basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. The neoplastic cells characteristically demonstrate coarse basophilic cytoplasmic stippling.
Eosinophilic solid and cystic renal cell carcinoma. Some tumours are more diffusely positive for CK20.
Eosinophilic solid and cystic renal cell carcinoma. There is typically focal CK20 expression on immunohistochemistry.

Q: Microscopically, Fumarate Hydratase-Deficient Renal Cell Carcinoma typically displays a multiplicity of admixed architectural patterns (e.g., papillary, solid, tubulocystic) and cells with characteristic prominent eosinophilic [...], often featuring perinucleolar halos.
Fumarate hydratase–deficient renal cell carcinoma. A multiplicity (typically ≥ 2) of admixed morphological patterns is typical. The most common is the papillary pattern; the papillae are often hyalinized and lack foamy cells.
Fumarate hydratase–deficient renal cell carcinoma. The cells show at least focal eosinophilic macronucleoli, often with perinucleolar haloes.
A: macronucleoli
Back Extra: Fumarate Hydratase-Deficient Renal Cell Carcinoma
- Clinical: Patients often present with flank pain and haematuria, and frequently have large unilateral solitary tumours, often at an advanced stage.
- Micro: Characterized by a multiplicity of admixed morphological patterns, commonly including papillary, solid, tubulocystic, cribriform/sieve-like, and cystic patterns, with prominent eosinophilic macronucleoli.
- Ancillary: Genetic testing for biallelic FH mutation/inactivation is essential, and immunohistochemical evidence of FH deficiency (FH loss and/or 2SC expression) is highly specific.
Reference Gallery:
Fumarate hydratase–deficient renal cell carcinoma. A multiplicity (typically ≥ 2) of admixed morphological patterns is typical. The most common is the papillary pattern; the papillae are often hyalinized and lack foamy cells.
Fumarate hydratase–deficient renal cell carcinoma. The cells show at least focal eosinophilic macronucleoli, often with perinucleolar haloes.
Fumarate hydratase–deficient renal cell carcinoma. Tumours with oncocytic morphology are immunohistochemically negative for fumarate hydratase. The retained positivity in non-tumour cells serves as an internal positive control.
Fumarate hydratase–deficient renal cell carcinoma. This example resembles succinate dehydrogenase–deficient renal cell carcinoma, but prominent nucleoli are not identified and the intracytoplasmic vacuoles that are typical for succinate dehydrogenase–deficient renal cell carcinoma are not seen.
Fumarate hydratase–deficient renal cell carcinoma. This example has a sieve-like architectural pattern.
Fumarate hydratase–deficient renal cell carcinoma. Fumarate hydratase immunohistochemistry in an example with a sieve-like architectural pattern.
Fumarate hydratase–deficient renal cell carcinoma. This example shows solid and papillary architectural patterns.
Fumarate hydratase–deficient renal cell carcinoma. Immunohistochemistry for 2-succinocysteine in an example with solid and papillary architectural patterns. Note the presence of nuclear and cytoplasmic staining.

Q: The diagnosis of Fumarate Hydratase-Deficient Renal Cell Carcinoma is confirmed immunohistochemically by the loss of fumarate hydratase (FH) expression and the diffuse, aberrant nuclear and cytoplasmic accumulation of [...].
Fumarate hydratase–deficient renal cell carcinoma. Tumours with oncocytic morphology are immunohistochemically negative for fumarate hydratase. The retained positivity in non-tumour cells serves as an internal positive control.
Fumarate hydratase–deficient renal cell carcinoma. Immunohistochemistry for 2-succinocysteine in an example with solid and papillary architectural patterns. Note the presence of nuclear and cytoplasmic staining.
A: 2-succinocysteine
Back Extra: Fumarate Hydratase-Deficient Renal Cell Carcinoma
- Clinical: Patients often present with flank pain and haematuria, and frequently have large unilateral solitary tumours, often at an advanced stage.
- Micro: Characterized by a multiplicity of admixed morphological patterns, commonly including papillary, solid, tubulocystic, cribriform/sieve-like, and cystic patterns, with prominent eosinophilic macronucleoli.
- Ancillary: Genetic testing for biallelic FH mutation/inactivation is essential, and immunohistochemical evidence of FH deficiency (FH loss and/or 2SC expression) is highly specific.
Reference Gallery:
Fumarate hydratase–deficient renal cell carcinoma. A multiplicity (typically ≥ 2) of admixed morphological patterns is typical. The most common is the papillary pattern; the papillae are often hyalinized and lack foamy cells.
Fumarate hydratase–deficient renal cell carcinoma. The cells show at least focal eosinophilic macronucleoli, often with perinucleolar haloes.
Fumarate hydratase–deficient renal cell carcinoma. Tumours with oncocytic morphology are immunohistochemically negative for fumarate hydratase. The retained positivity in non-tumour cells serves as an internal positive control.
Fumarate hydratase–deficient renal cell carcinoma. This example resembles succinate dehydrogenase–deficient renal cell carcinoma, but prominent nucleoli are not identified and the intracytoplasmic vacuoles that are typical for succinate dehydrogenase–deficient renal cell carcinoma are not seen.
Fumarate hydratase–deficient renal cell carcinoma. This example has a sieve-like architectural pattern.
Fumarate hydratase–deficient renal cell carcinoma. Fumarate hydratase immunohistochemistry in an example with a sieve-like architectural pattern.
Fumarate hydratase–deficient renal cell carcinoma. This example shows solid and papillary architectural patterns.
Fumarate hydratase–deficient renal cell carcinoma. Immunohistochemistry for 2-succinocysteine in an example with solid and papillary architectural patterns. Note the presence of nuclear and cytoplasmic staining.

Q: In patients with [...], SMARCB1-deficient renal medullary carcinoma classically presents with hematuria, flank or abdominal pain, and an abdominal mass.
Renal medullary carcinoma. Extravasated red blood cells within the neoplasm demonstrate sickling.
A: sickle cell trait
Back Extra: SMARCB1-deficient renal medullary carcinoma
- Clinical: SMARCB1-deficient renal medullary carcinoma typically presents with hematuria, flank or abdominal pain, and an abdominal mass in patients with sickle cell trait.
- Micro: The neoplastic cells form cords, nests, microcysts, sheets, and tubules, often with a cribriform or adenoid cystic carcinoma-like appearance and a prominent myxoid desmoplastic stroma.
- Ancillary: Immunohistochemistry shows loss of SMARCB1 (INI1) and diffuse labeling for PAX8, broad-spectrum cytokeratins, EMA, and vimentin.
Reference Gallery:
Renal medullary carcinoma. The fleshy neoplasm has an irregular border with the native kidney.
Renal medullary carcinoma. The neoplastic cells form cribriform, adenoid cystic–like structures within an oedematous desmoplastic stroma. A native renal tubule is present to the lower left.
Renal medullary carcinoma. The neoplasm invades into the renal pelvic urothelium, which leads to haematuria.
Renal medullary carcinoma. The neoplastic cells form cords in a desmoplastic stroma. They frequently undergo necrosis.
Renal medullary carcinoma. Extravasated red blood cells within the neoplasm demonstrate sickling.
Undifferentiated SMARCB1-deficient renal cell carcinoma NOS. The neoplastic cells demonstrate loss of SMARCB1 (INI1). The surrounding non-neoplastic stromal cells and entrapped native renal tubules demonstrate appropriate nuclear immunoreactivity.

Q: Microscopically, SMARCB1-deficient renal medullary carcinoma often features a prominent myxoid desmoplastic stroma with neoplastic cells forming a characteristic [...] appearance.
Renal medullary carcinoma. The neoplastic cells form cribriform, adenoid cystic–like structures within an oedematous desmoplastic stroma. A native renal tubule is present to the lower left.
A: cribriform or adenoid cystic-like
Back Extra: SMARCB1-deficient renal medullary carcinoma
- Clinical: SMARCB1-deficient renal medullary carcinoma typically presents with hematuria, flank or abdominal pain, and an abdominal mass in patients with sickle cell trait.
- Micro: The neoplastic cells form cords, nests, microcysts, sheets, and tubules, often with a cribriform or adenoid cystic carcinoma-like appearance and a prominent myxoid desmoplastic stroma.
- Ancillary: Immunohistochemistry shows loss of SMARCB1 (INI1) and diffuse labeling for PAX8, broad-spectrum cytokeratins, EMA, and vimentin.
Reference Gallery:
Renal medullary carcinoma. The fleshy neoplasm has an irregular border with the native kidney.
Renal medullary carcinoma. The neoplastic cells form cribriform, adenoid cystic–like structures within an oedematous desmoplastic stroma. A native renal tubule is present to the lower left.
Renal medullary carcinoma. The neoplasm invades into the renal pelvic urothelium, which leads to haematuria.
Renal medullary carcinoma. The neoplastic cells form cords in a desmoplastic stroma. They frequently undergo necrosis.
Renal medullary carcinoma. Extravasated red blood cells within the neoplasm demonstrate sickling.
Undifferentiated SMARCB1-deficient renal cell carcinoma NOS. The neoplastic cells demonstrate loss of SMARCB1 (INI1). The surrounding non-neoplastic stromal cells and entrapped native renal tubules demonstrate appropriate nuclear immunoreactivity.

Q: Microscopically, Mucinous Tubular and Spindle Cell Carcinoma classically consists of tightly packed, elongated tubules lined by low-grade cuboidal cells that merge with bland spindle cells in a [...] (or myxoid) stroma.
Mucinous tubular and spindle cell carcinoma. The tumour is composed of admixed tubular formations and spindle cells in a mucinous stroma.
Mucinous tubular and spindle cell carcinoma. The spindle cell–dominant area within a mucinous tubular and spindle cell carcinoma.
A: mucinous
Back Extra: Mucinous Tubular and Spindle Cell Carcinoma
- Clinical: Most patients with Mucinous Tubular and Spindle Cell Carcinoma are asymptomatic, with the tumour often discovered incidentally.
- Micro: The tumour classically consists of tightly packed, elongated tubules lined by low-grade cuboidal cells merging with bland spindle cells in a myxoid stroma.
- Ancillary: Recurrent copy-number alterations and multiple chromosomal losses, often involving chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, are common in Mucinous Tubular and Spindle Cell Carcinoma.
Reference Gallery:
Mucinous tubular and spindle cell carcinoma. The tumour is composed of admixed tubular formations and spindle cells in a mucinous stroma.
Mucinous tubular and spindle cell carcinoma. Whorled tubules with tufting form micronodules. Mast cells are frequently present.
Mucinous tubular and spindle cell carcinoma. The spindle cell–dominant area within a mucinous tubular and spindle cell carcinoma.
Mucinous tubular and spindle cell carcinoma. High-grade epithelial transformation. The tumour cells exhibit high-grade, pleomorphic nuclei. Tubules with low-grade nuclei (upper right) are focally present.
Mucinous tubular and spindle cell carcinoma. A well-circumscribed mass with a solid, grey-white, tan, or yellow cut surface.
Mucinous tubular and spindle cell carcinoma. A well-circumscribed mass with a solid, grey-white, tan, or yellow cut surface.

Q: On gross examination, Mucinous Tubular and Spindle Cell Carcinoma typically presents as a [...] tumor with a solid, gray-white, tan, or yellow cut surface.
Mucinous tubular and spindle cell carcinoma. A well-circumscribed mass with a solid, grey-white, tan, or yellow cut surface.
Mucinous tubular and spindle cell carcinoma. A well-circumscribed mass with a solid, grey-white, tan, or yellow cut surface.
A: well-circumscribed
Back Extra: Mucinous Tubular and Spindle Cell Carcinoma
- Clinical: Most patients with Mucinous Tubular and Spindle Cell Carcinoma are asymptomatic, with the tumour often discovered incidentally.
- Micro: The tumour classically consists of tightly packed, elongated tubules lined by low-grade cuboidal cells merging with bland spindle cells in a myxoid stroma.
- Ancillary: Recurrent copy-number alterations and multiple chromosomal losses, often involving chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, are common in Mucinous Tubular and Spindle Cell Carcinoma.
Reference Gallery:
Mucinous tubular and spindle cell carcinoma. The tumour is composed of admixed tubular formations and spindle cells in a mucinous stroma.
Mucinous tubular and spindle cell carcinoma. Whorled tubules with tufting form micronodules. Mast cells are frequently present.
Mucinous tubular and spindle cell carcinoma. The spindle cell–dominant area within a mucinous tubular and spindle cell carcinoma.
Mucinous tubular and spindle cell carcinoma. High-grade epithelial transformation. The tumour cells exhibit high-grade, pleomorphic nuclei. Tubules with low-grade nuclei (upper right) are focally present.
Mucinous tubular and spindle cell carcinoma. A well-circumscribed mass with a solid, grey-white, tan, or yellow cut surface.
Mucinous tubular and spindle cell carcinoma. A well-circumscribed mass with a solid, grey-white, tan, or yellow cut surface.

Q: Although typically a low-grade tumor, Mucinous Tubular and Spindle Cell Carcinoma can occasionally undergo high-grade epithelial transformation characterized by markedly [...] nuclei.
Mucinous tubular and spindle cell carcinoma. High-grade epithelial transformation. The tumour cells exhibit high-grade, pleomorphic nuclei. Tubules with low-grade nuclei (upper right) are focally present.
A: pleomorphic
Back Extra: Mucinous Tubular and Spindle Cell Carcinoma
- Clinical: Most patients with Mucinous Tubular and Spindle Cell Carcinoma are asymptomatic, with the tumour often discovered incidentally.
- Micro: The tumour classically consists of tightly packed, elongated tubules lined by low-grade cuboidal cells merging with bland spindle cells in a myxoid stroma.
- Ancillary: Recurrent copy-number alterations and multiple chromosomal losses, often involving chromosomes 1, 4, 6, 8, 9, 13, 14, 15, and 22, are common in Mucinous Tubular and Spindle Cell Carcinoma.
Reference Gallery:
Mucinous tubular and spindle cell carcinoma. The tumour is composed of admixed tubular formations and spindle cells in a mucinous stroma.
Mucinous tubular and spindle cell carcinoma. Whorled tubules with tufting form micronodules. Mast cells are frequently present.
Mucinous tubular and spindle cell carcinoma. The spindle cell–dominant area within a mucinous tubular and spindle cell carcinoma.
Mucinous tubular and spindle cell carcinoma. High-grade epithelial transformation. The tumour cells exhibit high-grade, pleomorphic nuclei. Tubules with low-grade nuclei (upper right) are focally present.
Mucinous tubular and spindle cell carcinoma. A well-circumscribed mass with a solid, grey-white, tan, or yellow cut surface.
Mucinous tubular and spindle cell carcinoma. A well-circumscribed mass with a solid, grey-white, tan, or yellow cut surface.

Q: [...] is defined histologically as a purely cystic tumor with thin septations devoid of expansile solid growth, lined by one or a few layers of bland, optically clear cells with randomly distributed WHO grade 1 or 2 nuclei.
Multilocular cystic renal neoplasm of low malignant potential. Whole-mount section of a pure cystic cortical tumour with thin septations devoid of solid growth.
Multilocular cystic renal neoplasm of low malignant potential. The clear cell lining shows one or two layers of clear cells with randomly distributed WHO grade 1 nuclei.
A: Multilocular Cystic Renal Neoplasm of Low Malignant Potential
Back Extra: Multilocular Cystic Renal Neoplasm of Low Malignant Potential
- Clinical: Multilocular cystic renal neoplasm of low malignant potential (MCNLMP) is often detected incidentally on radiological imaging, with 90% of cases being asymptomatic.
- Micro: The cyst lining consists of one or a few layers of optically clear, bland-looking cells with randomly distributed WHO grade 1 or 2 nuclei.
- Ancillary: Loss of chromosome 3 or its short arm (3p) is detected in 77% of MCNLMP cases, and inactivating VHL mutations are found in 25–40% of cases.
Reference Gallery:
Multilocular cystic renal neoplasm of low malignant potential. Whole-mount section of a pure cystic cortical tumour with thin septations devoid of solid growth.
Multilocular cystic renal neoplasm of low malignant potential. The clear cell lining shows one or two layers of clear cells with randomly distributed WHO grade 1 nuclei.
Multilocular cystic renal neoplasm of low malignant potential. Tumour cells are CAIX-positive.
Multilocular cystic renal neoplasm of low malignant potential. A well-circumscribed multiloculated mass with gelatinous, serous, and haemorrhagic cystic content.
Multilocular cystic renal neoplasm of low malignant potential. A well-circumscribed multiloculated mass with gelatinous, serous, and haemorrhagic cystic content.

Q: [...] presents grossly as a well-circumscribed multiloculated mass containing cysts filled with gelatinous, serous, or hemorrhagic fluid.
Multilocular cystic renal neoplasm of low malignant potential. A well-circumscribed multiloculated mass with gelatinous, serous, and haemorrhagic cystic content.
Multilocular cystic renal neoplasm of low malignant potential. A well-circumscribed multiloculated mass with gelatinous, serous, and haemorrhagic cystic content.
A: Multilocular Cystic Renal Neoplasm of Low Malignant Potential
Back Extra: Multilocular Cystic Renal Neoplasm of Low Malignant Potential
- Clinical: Multilocular cystic renal neoplasm of low malignant potential (MCNLMP) is often detected incidentally on radiological imaging, with 90% of cases being asymptomatic.
- Micro: The cyst lining consists of one or a few layers of optically clear, bland-looking cells with randomly distributed WHO grade 1 or 2 nuclei.
- Ancillary: Loss of chromosome 3 or its short arm (3p) is detected in 77% of MCNLMP cases, and inactivating VHL mutations are found in 25–40% of cases.
Reference Gallery:
Multilocular cystic renal neoplasm of low malignant potential. Whole-mount section of a pure cystic cortical tumour with thin septations devoid of solid growth.
Multilocular cystic renal neoplasm of low malignant potential. The clear cell lining shows one or two layers of clear cells with randomly distributed WHO grade 1 nuclei.
Multilocular cystic renal neoplasm of low malignant potential. Tumour cells are CAIX-positive.
Multilocular cystic renal neoplasm of low malignant potential. A well-circumscribed multiloculated mass with gelatinous, serous, and haemorrhagic cystic content.
Multilocular cystic renal neoplasm of low malignant potential. A well-circumscribed multiloculated mass with gelatinous, serous, and haemorrhagic cystic content.

Q: [...] typically demonstrates diffuse CAIX positivity in the cyst lining cells, and molecular testing frequently reveals loss of chromosome 3p or inactivating VHL mutations.
Multilocular cystic renal neoplasm of low malignant potential. Tumour cells are CAIX-positive.
A: Multilocular Cystic Renal Neoplasm of Low Malignant Potential
Back Extra: Multilocular Cystic Renal Neoplasm of Low Malignant Potential
- Clinical: Multilocular cystic renal neoplasm of low malignant potential (MCNLMP) is often detected incidentally on radiological imaging, with 90% of cases being asymptomatic.
- Micro: The cyst lining consists of one or a few layers of optically clear, bland-looking cells with randomly distributed WHO grade 1 or 2 nuclei.
- Ancillary: Loss of chromosome 3 or its short arm (3p) is detected in 77% of MCNLMP cases, and inactivating VHL mutations are found in 25–40% of cases.
Reference Gallery:
Multilocular cystic renal neoplasm of low malignant potential. Whole-mount section of a pure cystic cortical tumour with thin septations devoid of solid growth.
Multilocular cystic renal neoplasm of low malignant potential. The clear cell lining shows one or two layers of clear cells with randomly distributed WHO grade 1 nuclei.
Multilocular cystic renal neoplasm of low malignant potential. Tumour cells are CAIX-positive.
Multilocular cystic renal neoplasm of low malignant potential. A well-circumscribed multiloculated mass with gelatinous, serous, and haemorrhagic cystic content.
Multilocular cystic renal neoplasm of low malignant potential. A well-circumscribed multiloculated mass with gelatinous, serous, and haemorrhagic cystic content.

Q: Grossly, Oncocytoma of the Kidney typically presents as a well-circumscribed, mahogany-brown tumor with a characteristic [...].
Oncocytoma. Well-circumscribed mahogany-brown tumour with a big central stellate scar and slight haemorrhage.
A: central stellate scar
Back Extra: Oncocytoma of the Kidney
- Clinical: The majority of oncocytomas are asymptomatic and detected incidentally on radiological investigations.
- Micro: Oncocytomas are composed of eosinophilic cells with densely granular cytoplasm and round uniform nuclei, arranged in solid nests, microcysts, or tubules.
- Ancillary: Immunohistochemistry shows positivity for KIT (CD117) and occasional CK7 positivity.
Reference Gallery:
Oncocytoma. Tumours are epithelial, typically with solid or solid nested architecture and embedded in a hypocellular hyalinized or myxoid stroma.
Oncocytoma. Classic archipelago-like and nested architecture of uniform oncocytic cells with round nuclei and abundant eosinophilic cytoplasm.
Oncocytoma. Predominantly macrocystic and microcystic growth pattern with entrapped benign kidney tubules.
Oncocytoma. Focal areas of discohesive cells with degenerative hyperchromasia, multinucleation, and pleomorphism may occur.
Oncocytoma. Pseudorosette formation of small oncoblasts packed around hyaline material.
Oncocytoma. Tumour composed of compact acini and tubules with minimal intervening stroma.
Oncocytoma. Invasion of perinephric or hilar fat without desmoplastic response is common and does not influence tumour behaviour.
Oncocytoma. Rare finding of a typical mitotic figure in otherwise classic oncocytoma.
Oncocytoma. KIT (CD117) immunohistochemistry is positive.
Oncocytoma. CK7 immunohistochemistry. Occasional cells are positive.
Oncocytoma. Well-circumscribed mahogany-brown tumour with a big central stellate scar and slight haemorrhage.

Q: Histologically, a nested or archipelago-like architecture composed of uniform cells with abundant, densely granular eosinophilic cytoplasm is classically seen in [...].
Oncocytoma. Tumours are epithelial, typically with solid or solid nested architecture and embedded in a hypocellular hyalinized or myxoid stroma.
Oncocytoma. Classic archipelago-like and nested architecture of uniform oncocytic cells with round nuclei and abundant eosinophilic cytoplasm.
A: Oncocytoma of the Kidney
Back Extra: Oncocytoma of the Kidney
- Clinical: The majority of oncocytomas are asymptomatic and detected incidentally on radiological investigations.
- Micro: Oncocytomas are composed of eosinophilic cells with densely granular cytoplasm and round uniform nuclei, arranged in solid nests, microcysts, or tubules.
- Ancillary: Immunohistochemistry shows positivity for KIT (CD117) and occasional CK7 positivity.
Reference Gallery:
Oncocytoma. Tumours are epithelial, typically with solid or solid nested architecture and embedded in a hypocellular hyalinized or myxoid stroma.
Oncocytoma. Classic archipelago-like and nested architecture of uniform oncocytic cells with round nuclei and abundant eosinophilic cytoplasm.
Oncocytoma. Predominantly macrocystic and microcystic growth pattern with entrapped benign kidney tubules.
Oncocytoma. Focal areas of discohesive cells with degenerative hyperchromasia, multinucleation, and pleomorphism may occur.
Oncocytoma. Pseudorosette formation of small oncoblasts packed around hyaline material.
Oncocytoma. Tumour composed of compact acini and tubules with minimal intervening stroma.
Oncocytoma. Invasion of perinephric or hilar fat without desmoplastic response is common and does not influence tumour behaviour.
Oncocytoma. Rare finding of a typical mitotic figure in otherwise classic oncocytoma.
Oncocytoma. KIT (CD117) immunohistochemistry is positive.
Oncocytoma. CK7 immunohistochemistry. Occasional cells are positive.
Oncocytoma. Well-circumscribed mahogany-brown tumour with a big central stellate scar and slight haemorrhage.

Q: The characteristic immunohistochemical profile of Oncocytoma of the Kidney shows diffuse positivity for [...] and only scattered, occasional positivity for CK7.
Oncocytoma. KIT (CD117) immunohistochemistry is positive.
Oncocytoma. CK7 immunohistochemistry. Occasional cells are positive.
A: KIT (CD117)
Back Extra: Oncocytoma of the Kidney
- Clinical: The majority of oncocytomas are asymptomatic and detected incidentally on radiological investigations.
- Micro: Oncocytomas are composed of eosinophilic cells with densely granular cytoplasm and round uniform nuclei, arranged in solid nests, microcysts, or tubules.
- Ancillary: Immunohistochemistry shows positivity for KIT (CD117) and occasional CK7 positivity.
Reference Gallery:
Oncocytoma. Tumours are epithelial, typically with solid or solid nested architecture and embedded in a hypocellular hyalinized or myxoid stroma.
Oncocytoma. Classic archipelago-like and nested architecture of uniform oncocytic cells with round nuclei and abundant eosinophilic cytoplasm.
Oncocytoma. Predominantly macrocystic and microcystic growth pattern with entrapped benign kidney tubules.
Oncocytoma. Focal areas of discohesive cells with degenerative hyperchromasia, multinucleation, and pleomorphism may occur.
Oncocytoma. Pseudorosette formation of small oncoblasts packed around hyaline material.
Oncocytoma. Tumour composed of compact acini and tubules with minimal intervening stroma.
Oncocytoma. Invasion of perinephric or hilar fat without desmoplastic response is common and does not influence tumour behaviour.
Oncocytoma. Rare finding of a typical mitotic figure in otherwise classic oncocytoma.
Oncocytoma. KIT (CD117) immunohistochemistry is positive.
Oncocytoma. CK7 immunohistochemistry. Occasional cells are positive.
Oncocytoma. Well-circumscribed mahogany-brown tumour with a big central stellate scar and slight haemorrhage.

Q: Microscopically, Other Oncocytic Tumours of the Kidney are characterized by a solid architecture of eosinophilic (oncocytic) cells, frequently demonstrating overlapping features between an oncocytoma and a [...].
Oncocytic tumour NOS. Tumours resemble oncocytomas with a solid architecture and are composed of eosinophilic cells.
Oncocytic tumour NOS. This example shows overlapping morphology of low-grade oncocytic tumour and chromophobe renal cell carcinoma composed of eosinophilic granular cells with perinuclear haloes.
A: chromophobe renal cell carcinoma
Back Extra: Other Oncocytic Tumours of the Kidney
- Clinical: Other oncocytic tumours of the kidney are often discovered incidentally on imaging and are generally low-grade, with limited data suggesting rare recurrence or progression.
- Micro: These tumours are characterized by a solid architecture of eosinophilic/oncocytic cells, often showing overlapping features between oncocytoma and chromophobe renal cell carcinoma.
- Ancillary: Detection of mutations in the mTOR pathway genes (TSC1, TSC2, MTOR) and FLCN (in Birt–Hogg–Dubé syndrome) can aid in confirming the diagnosis.
Reference Gallery:
Oncocytic tumour NOS. Tumours resemble oncocytomas with a solid architecture and are composed of eosinophilic cells.
Oncocytic tumour NOS. This example shows overlapping morphology of low-grade oncocytic tumour and chromophobe renal cell carcinoma composed of eosinophilic granular cells with perinuclear haloes.
Oncocytic tumour. This shows a well-circumscribed brown solid tumour.
Eosinophilic vacuolated tumour. At low magnification, solid growth of eosinophilic cells with cytoplasmic vacuolation and prominent nucleoli can be seen.
Birt–Hogg–Dubé syndrome–related tumour. Characterized by clusters and individual cells with clear cytoplasm, often exhibiting a checkerboard mosaic pattern.
Eosinophilic vacuolated tumour. High-magnification view shows solid growth of eosinophilic cells with cytoplasmic vacuolation and prominent nucleoli.
Low-grade oncocytic tumour. High-magnification view shows solid growth of eosinophilic (oncocytic) cells with bland (low-grade) nuclei lacking prominent nucleoli or nuclear irregularity.
Low-grade oncocytic tumour. Strong and diffuse CK7 positivity in tumour cells.
Eosinophilic vacuolated tumour. Cathepsin K–positive tumour cells.
Eosinophilic vacuolated tumour. CD10-positive tumour cells.
Eosinophilic vacuolated tumour. CD117-positive tumour cells.

Q: Some cases of Other Oncocytic Tumours of the Kidney are associated with FLCN mutations and arise in patients with [...] syndrome, often exhibiting a checkerboard mosaic pattern of cells with clear cytoplasm.
Birt–Hogg–Dubé syndrome–related tumour. Characterized by clusters and individual cells with clear cytoplasm, often exhibiting a checkerboard mosaic pattern.
A: Birt-Hogg-Dubé
Back Extra: Other Oncocytic Tumours of the Kidney
- Clinical: Other oncocytic tumours of the kidney are often discovered incidentally on imaging and are generally low-grade, with limited data suggesting rare recurrence or progression.
- Micro: These tumours are characterized by a solid architecture of eosinophilic/oncocytic cells, often showing overlapping features between oncocytoma and chromophobe renal cell carcinoma.
- Ancillary: Detection of mutations in the mTOR pathway genes (TSC1, TSC2, MTOR) and FLCN (in Birt–Hogg–Dubé syndrome) can aid in confirming the diagnosis.
Reference Gallery:
Oncocytic tumour NOS. Tumours resemble oncocytomas with a solid architecture and are composed of eosinophilic cells.
Oncocytic tumour NOS. This example shows overlapping morphology of low-grade oncocytic tumour and chromophobe renal cell carcinoma composed of eosinophilic granular cells with perinuclear haloes.
Oncocytic tumour. This shows a well-circumscribed brown solid tumour.
Eosinophilic vacuolated tumour. At low magnification, solid growth of eosinophilic cells with cytoplasmic vacuolation and prominent nucleoli can be seen.
Birt–Hogg–Dubé syndrome–related tumour. Characterized by clusters and individual cells with clear cytoplasm, often exhibiting a checkerboard mosaic pattern.
Eosinophilic vacuolated tumour. High-magnification view shows solid growth of eosinophilic cells with cytoplasmic vacuolation and prominent nucleoli.
Low-grade oncocytic tumour. High-magnification view shows solid growth of eosinophilic (oncocytic) cells with bland (low-grade) nuclei lacking prominent nucleoli or nuclear irregularity.
Low-grade oncocytic tumour. Strong and diffuse CK7 positivity in tumour cells.
Eosinophilic vacuolated tumour. Cathepsin K–positive tumour cells.
Eosinophilic vacuolated tumour. CD10-positive tumour cells.
Eosinophilic vacuolated tumour. CD117-positive tumour cells.

Q: Ancillary testing in Other Oncocytic Tumours of the Kidney may reveal mutations in the FLCN gene or in genes of the [...] pathway (e.g., TSC1, TSC2), which can present microscopically as solid growths of cells with cytoplasmic vacuolation and prominent nucleoli.
Eosinophilic vacuolated tumour. At low magnification, solid growth of eosinophilic cells with cytoplasmic vacuolation and prominent nucleoli can be seen.
Eosinophilic vacuolated tumour. High-magnification view shows solid growth of eosinophilic cells with cytoplasmic vacuolation and prominent nucleoli.
A: mTOR
Back Extra: Other Oncocytic Tumours of the Kidney
- Clinical: Other oncocytic tumours of the kidney are often discovered incidentally on imaging and are generally low-grade, with limited data suggesting rare recurrence or progression.
- Micro: These tumours are characterized by a solid architecture of eosinophilic/oncocytic cells, often showing overlapping features between oncocytoma and chromophobe renal cell carcinoma.
- Ancillary: Detection of mutations in the mTOR pathway genes (TSC1, TSC2, MTOR) and FLCN (in Birt–Hogg–Dubé syndrome) can aid in confirming the diagnosis.
Reference Gallery:
Oncocytic tumour NOS. Tumours resemble oncocytomas with a solid architecture and are composed of eosinophilic cells.
Oncocytic tumour NOS. This example shows overlapping morphology of low-grade oncocytic tumour and chromophobe renal cell carcinoma composed of eosinophilic granular cells with perinuclear haloes.
Oncocytic tumour. This shows a well-circumscribed brown solid tumour.
Eosinophilic vacuolated tumour. At low magnification, solid growth of eosinophilic cells with cytoplasmic vacuolation and prominent nucleoli can be seen.
Birt–Hogg–Dubé syndrome–related tumour. Characterized by clusters and individual cells with clear cytoplasm, often exhibiting a checkerboard mosaic pattern.
Eosinophilic vacuolated tumour. High-magnification view shows solid growth of eosinophilic cells with cytoplasmic vacuolation and prominent nucleoli.
Low-grade oncocytic tumour. High-magnification view shows solid growth of eosinophilic (oncocytic) cells with bland (low-grade) nuclei lacking prominent nucleoli or nuclear irregularity.
Low-grade oncocytic tumour. Strong and diffuse CK7 positivity in tumour cells.
Eosinophilic vacuolated tumour. Cathepsin K–positive tumour cells.
Eosinophilic vacuolated tumour. CD10-positive tumour cells.
Eosinophilic vacuolated tumour. CD117-positive tumour cells.

Q: Microscopically, Hereditary Papillary Renal Carcinoma is characterized by papillae covered by cells with nuclei arranged in a [...] on the papillary cores, often with hemosiderin deposition and foamy macrophages.
Hereditary papillary renal carcinoma. This type of papillary renal cell carcinoma has papillae covered by cells with nuclei arranged in a single layer on the papillary cores.
Hereditary papillary renal carcinoma. This type of papillary renal cell carcinoma has papillae covered by cells with nuclei arranged in a single layer on the papillary cores, mostly with scant pale cytoplasm. Frequent haemosiderin deposition is seen.
Hereditary papillary renal carcinoma. Papillae covered by cells with nuclei arranged in a single layer on the papillary cores with many foamy macrophages.
A: single layer
Back Extra: Hereditary Papillary Renal Carcinoma
- Clinical: Multiple and bilateral renal tumours are seen on imaging, often with a family history of renal cancer.
- Micro: Papillary renal cell carcinomas in HPRC have papillae covered by cells with nuclei arranged in a single layer on the papillary cores, with frequent haemosiderin deposition.
- Ancillary: Germline mutations in the MET proto-oncogene are causative in Hereditary Papillary Renal Carcinoma.
Reference Gallery:
Hereditary papillary renal carcinoma. Shows features of typical low-grade papillary carcinoma (formerly known as type 1 papillary carcinoma).
Hereditary papillary renal carcinoma. This type of papillary renal cell carcinoma has papillae covered by cells with nuclei arranged in a single layer on the papillary cores.
Hereditary papillary renal carcinoma. This type of papillary renal cell carcinoma has papillae covered by cells with nuclei arranged in a single layer on the papillary cores, mostly with scant pale cytoplasm. Frequent haemosiderin deposition is seen.
Hereditary papillary renal carcinoma. Papillae covered by cells with nuclei arranged in a single layer on the papillary cores with many foamy macrophages.

Q: Patients with Hereditary Papillary Renal Carcinoma characteristically present with multiple, bilateral tumors caused by a germline mutation in the [...] proto-oncogene.
Hereditary papillary renal carcinoma. Shows features of typical low-grade papillary carcinoma (formerly known as type 1 papillary carcinoma).
A: MET
Back Extra: Hereditary Papillary Renal Carcinoma
- Clinical: Multiple and bilateral renal tumours are seen on imaging, often with a family history of renal cancer.
- Micro: Papillary renal cell carcinomas in HPRC have papillae covered by cells with nuclei arranged in a single layer on the papillary cores, with frequent haemosiderin deposition.
- Ancillary: Germline mutations in the MET proto-oncogene are causative in Hereditary Papillary Renal Carcinoma.
Reference Gallery:
Hereditary papillary renal carcinoma. Shows features of typical low-grade papillary carcinoma (formerly known as type 1 papillary carcinoma).
Hereditary papillary renal carcinoma. This type of papillary renal cell carcinoma has papillae covered by cells with nuclei arranged in a single layer on the papillary cores.
Hereditary papillary renal carcinoma. This type of papillary renal cell carcinoma has papillae covered by cells with nuclei arranged in a single layer on the papillary cores, mostly with scant pale cytoplasm. Frequent haemosiderin deposition is seen.
Hereditary papillary renal carcinoma. Papillae covered by cells with nuclei arranged in a single layer on the papillary cores with many foamy macrophages.

Q: The tumors seen in Hereditary Papillary Renal Carcinoma typically exhibit features of low-grade papillary carcinoma, which was formerly classified as [...] papillary renal cell carcinoma.
Hereditary papillary renal carcinoma. Shows features of typical low-grade papillary carcinoma (formerly known as type 1 papillary carcinoma).
A: type 1
Back Extra: Hereditary Papillary Renal Carcinoma
- Clinical: Multiple and bilateral renal tumours are seen on imaging, often with a family history of renal cancer.
- Micro: Papillary renal cell carcinomas in HPRC have papillae covered by cells with nuclei arranged in a single layer on the papillary cores, with frequent haemosiderin deposition.
- Ancillary: Germline mutations in the MET proto-oncogene are causative in Hereditary Papillary Renal Carcinoma.
Reference Gallery:
Hereditary papillary renal carcinoma. Shows features of typical low-grade papillary carcinoma (formerly known as type 1 papillary carcinoma).
Hereditary papillary renal carcinoma. This type of papillary renal cell carcinoma has papillae covered by cells with nuclei arranged in a single layer on the papillary cores.
Hereditary papillary renal carcinoma. This type of papillary renal cell carcinoma has papillae covered by cells with nuclei arranged in a single layer on the papillary cores, mostly with scant pale cytoplasm. Frequent haemosiderin deposition is seen.
Hereditary papillary renal carcinoma. Papillae covered by cells with nuclei arranged in a single layer on the papillary cores with many foamy macrophages.

Q: The classic microscopic pattern of Papillary Renal Cell Carcinoma features papillary structures lined by cells with a basophilic appearance and a characteristic accumulation of [...] in the fibrovascular cores.
Papillary renal cell carcinoma. The classic pattern has a basophilic appearance, with cells that have scant cytoplasm and variable foamy macrophages.
Papillary renal cell carcinoma. This example has abundant foamy macrophages, and tumour cells are also vacuolated, yielding a clear cell appearance.
A: foamy macrophages
Back Extra: Papillary Renal Cell Carcinoma
- Clinical: Papillary Renal Cell Carcinoma (PRCC) is often asymptomatic and commonly discovered incidentally on imaging.
- Micro: The classic pattern of PRCC features papillary and tubular structures with cuboidal cells and a basophilic cytoplasm, often accompanied by foamy macrophages.
- Ancillary: PRCC typically shows diffuse strong immunohistochemical labelling for AMACR and CK7, with trisomy and tetrasomy of chromosomes 7 and 17.
Reference Gallery:
Papillary renal cell carcinoma. Grossly, this partial nephrectomy specimen is highly granular, suggesting the underlying papillary architecture.
Papillary renal cell carcinoma. The classic pattern has a basophilic appearance, with cells that have scant cytoplasm and variable foamy macrophages.
Papillary renal cell carcinoma. This example has abundant foamy macrophages, and tumour cells are also vacuolated, yielding a clear cell appearance.
Papillary renal cell carcinoma. The recently described biphasic pattern contains cells with abundant eosinophilic cytoplasm in the lumina of glands.
Papillary renal neoplasm with reverse polarity. Papillary structures are lined by eosinophilic cells with nuclei aligned at the apex.
Papillary renal neoplasm with reverse polarity. Nuclear labelling for GATA3 immunohistochemistry is typical in this tumour subtype.
Papillary renal cell carcinoma. Large tumour with necrosis involving the renal sinus and the perirenal tissue.

Q: On macroscopic evaluation, the cut surface of a Papillary Renal Cell Carcinoma often exhibits a highly [...] texture, reflecting its underlying architecture.
Papillary renal cell carcinoma. Grossly, this partial nephrectomy specimen is highly granular, suggesting the underlying papillary architecture.
A: granular
Back Extra: Papillary Renal Cell Carcinoma
- Clinical: Papillary Renal Cell Carcinoma (PRCC) is often asymptomatic and commonly discovered incidentally on imaging.
- Micro: The classic pattern of PRCC features papillary and tubular structures with cuboidal cells and a basophilic cytoplasm, often accompanied by foamy macrophages.
- Ancillary: PRCC typically shows diffuse strong immunohistochemical labelling for AMACR and CK7, with trisomy and tetrasomy of chromosomes 7 and 17.
Reference Gallery:
Papillary renal cell carcinoma. Grossly, this partial nephrectomy specimen is highly granular, suggesting the underlying papillary architecture.
Papillary renal cell carcinoma. The classic pattern has a basophilic appearance, with cells that have scant cytoplasm and variable foamy macrophages.
Papillary renal cell carcinoma. This example has abundant foamy macrophages, and tumour cells are also vacuolated, yielding a clear cell appearance.
Papillary renal cell carcinoma. The recently described biphasic pattern contains cells with abundant eosinophilic cytoplasm in the lumina of glands.
Papillary renal neoplasm with reverse polarity. Papillary structures are lined by eosinophilic cells with nuclei aligned at the apex.
Papillary renal neoplasm with reverse polarity. Nuclear labelling for GATA3 immunohistochemistry is typical in this tumour subtype.
Papillary renal cell carcinoma. Large tumour with necrosis involving the renal sinus and the perirenal tissue.

Q: Papillary Renal Cell Carcinoma is classically characterized by specific cytogenetic abnormalities, most notably trisomy and tetrasomy of chromosomes [...].
Papillary renal cell carcinoma. The classic pattern has a basophilic appearance, with cells that have scant cytoplasm and variable foamy macrophages.
A: 7 and 17
Back Extra: Papillary Renal Cell Carcinoma
- Clinical: Papillary Renal Cell Carcinoma (PRCC) is often asymptomatic and commonly discovered incidentally on imaging.
- Micro: The classic pattern of PRCC features papillary and tubular structures with cuboidal cells and a basophilic cytoplasm, often accompanied by foamy macrophages.
- Ancillary: PRCC typically shows diffuse strong immunohistochemical labelling for AMACR and CK7, with trisomy and tetrasomy of chromosomes 7 and 17.
Reference Gallery:
Papillary renal cell carcinoma. Grossly, this partial nephrectomy specimen is highly granular, suggesting the underlying papillary architecture.
Papillary renal cell carcinoma. The classic pattern has a basophilic appearance, with cells that have scant cytoplasm and variable foamy macrophages.
Papillary renal cell carcinoma. This example has abundant foamy macrophages, and tumour cells are also vacuolated, yielding a clear cell appearance.
Papillary renal cell carcinoma. The recently described biphasic pattern contains cells with abundant eosinophilic cytoplasm in the lumina of glands.
Papillary renal neoplasm with reverse polarity. Papillary structures are lined by eosinophilic cells with nuclei aligned at the apex.
Papillary renal neoplasm with reverse polarity. Nuclear labelling for GATA3 immunohistochemistry is typical in this tumour subtype.
Papillary renal cell carcinoma. Large tumour with necrosis involving the renal sinus and the perirenal tissue.

Q: Microscopically, Renal Papillary Adenoma exhibits low-grade cells with minimal nuclear pleomorphism organized in a [...] architecture.
Renal papillary adenoma. This example shows low-grade morphology.
Renal papillary adenoma. This example shows low-grade morphology.
A: papillary, tubular, or tubulopapillary
Renal Papillary Adenoma
- Clinical: Virtually all Renal Papillary Adenomas are clinically silent and discovered as incidental findings.
- Micro: Renal Papillary Adenomas show papillary, tubular, or tubulopapillary architecture with round to oval nuclei and minimal nuclear pleomorphism.
- Ancillary: Whole-exome sequencing has demonstrated that KMT2C mutations may be an important early event in the evolution of Renal Papillary Adenomas.
Reference Gallery:
Renal papillary adenoma. Two adjacent papillary adenomas without capsules.
Renal papillary adenoma. This example shows low-grade morphology.
Renal papillary adenoma. Two adjacent papillary adenomas without capsules.
Renal papillary adenoma. This example shows low-grade morphology.
Renal papillary adenoma. Macroscopic image.

Q: A characteristic microscopic finding of Renal Papillary Adenoma is that it frequently lacks a [...], often presenting as multiple adjacent nodules merging with the surrounding parenchyma.
Renal papillary adenoma. Two adjacent papillary adenomas without capsules.
Renal papillary adenoma. Two adjacent papillary adenomas without capsules.
A: capsule
Renal Papillary Adenoma
- Clinical: Virtually all Renal Papillary Adenomas are clinically silent and discovered as incidental findings.
- Micro: Renal Papillary Adenomas show papillary, tubular, or tubulopapillary architecture with round to oval nuclei and minimal nuclear pleomorphism.
- Ancillary: Whole-exome sequencing has demonstrated that KMT2C mutations may be an important early event in the evolution of Renal Papillary Adenomas.
Reference Gallery:
Renal papillary adenoma. Two adjacent papillary adenomas without capsules.
Renal papillary adenoma. This example shows low-grade morphology.
Renal papillary adenoma. Two adjacent papillary adenomas without capsules.
Renal papillary adenoma. This example shows low-grade morphology.
Renal papillary adenoma. Macroscopic image.

Q: Virtually all cases of Renal Papillary Adenoma are clinically silent and typically discovered as macroscopic, [...] findings.
Renal papillary adenoma. Macroscopic image.
A: incidental
Renal Papillary Adenoma
- Clinical: Virtually all Renal Papillary Adenomas are clinically silent and discovered as incidental findings.
- Micro: Renal Papillary Adenomas show papillary, tubular, or tubulopapillary architecture with round to oval nuclei and minimal nuclear pleomorphism.
- Ancillary: Whole-exome sequencing has demonstrated that KMT2C mutations may be an important early event in the evolution of Renal Papillary Adenomas.
Reference Gallery:
Renal papillary adenoma. Two adjacent papillary adenomas without capsules.
Renal papillary adenoma. This example shows low-grade morphology.
Renal papillary adenoma. Two adjacent papillary adenomas without capsules.
Renal papillary adenoma. This example shows low-grade morphology.
Renal papillary adenoma. Macroscopic image.

Q: A characteristic microscopic finding in Succinate Dehydrogenase-Deficient Renal Cell Carcinoma is the presence of distinctive [...] containing eosinophilic or pale flocculent material.
Succinate dehydrogenase–deficient renal cell carcinoma. The neoplastic cells are cuboidal with eosinophilic to bubbly pale cytoplasm.
Succinate dehydrogenase–deficient renal cell carcinoma. Distinctive cytoplasmic inclusions containing eosinophilic or pale flocculent material.
A: cytoplasmic inclusions
Back Extra: Succinate Dehydrogenase-Deficient Renal Cell Carcinoma
- Clinical: Patients with Succinate Dehydrogenase-Deficient Renal Cell Carcinoma may present with vague flank pain or metastasis, but it is more commonly asymptomatic and identified incidentally on imaging.
- Micro: The majority of Succinate Dehydrogenase-Deficient Renal Cell Carcinomas are well-circumscribed or lobulated, with bland cells and eosinophilic cytoplasm, often containing cytoplasmic inclusions of eosinophilic or pale flocculent material.
- Ancillary: Loss of immunohistochemical expression of SDHB is a prerequisite for the diagnosis of Succinate Dehydrogenase-Deficient Renal Cell Carcinoma.
Reference Gallery:
Succinate dehydrogenase–deficient renal cell carcinoma. The neoplastic cells are cuboidal with eosinophilic to bubbly pale cytoplasm.
Succinate dehydrogenase–deficient renal cell carcinoma. In this example, the neoplastic cells demonstrate weak diffuse cytoplasmic expression of SDHB. Because this lacks a mitochondrial (i.e. granular) pattern of cytoplasmic expression and contrasts markedly with the expression in the internal positive controls, this pattern is considered negative.
Succinate dehydrogenase–deficient renal cell carcinoma. Distinctive cytoplasmic inclusions containing eosinophilic or pale flocculent material.
Succinate dehydrogenase–deficient renal cell carcinoma. High-grade transformation in direct continuity with more typical areas.

Q: A prerequisite for the diagnosis of Succinate Dehydrogenase-Deficient Renal Cell Carcinoma is the loss of immunohistochemical expression of [...], which normally displays a granular mitochondrial staining pattern.
Succinate dehydrogenase–deficient renal cell carcinoma. In this example, the neoplastic cells demonstrate weak diffuse cytoplasmic expression of SDHB. Because this lacks a mitochondrial (i.e. granular) pattern of cytoplasmic expression and contrasts markedly with the expression in the internal positive controls, this pattern is considered negative.
A: SDHB
Back Extra: Succinate Dehydrogenase-Deficient Renal Cell Carcinoma
- Clinical: Patients with Succinate Dehydrogenase-Deficient Renal Cell Carcinoma may present with vague flank pain or metastasis, but it is more commonly asymptomatic and identified incidentally on imaging.
- Micro: The majority of Succinate Dehydrogenase-Deficient Renal Cell Carcinomas are well-circumscribed or lobulated, with bland cells and eosinophilic cytoplasm, often containing cytoplasmic inclusions of eosinophilic or pale flocculent material.
- Ancillary: Loss of immunohistochemical expression of SDHB is a prerequisite for the diagnosis of Succinate Dehydrogenase-Deficient Renal Cell Carcinoma.
Reference Gallery:
Succinate dehydrogenase–deficient renal cell carcinoma. The neoplastic cells are cuboidal with eosinophilic to bubbly pale cytoplasm.
Succinate dehydrogenase–deficient renal cell carcinoma. In this example, the neoplastic cells demonstrate weak diffuse cytoplasmic expression of SDHB. Because this lacks a mitochondrial (i.e. granular) pattern of cytoplasmic expression and contrasts markedly with the expression in the internal positive controls, this pattern is considered negative.
Succinate dehydrogenase–deficient renal cell carcinoma. Distinctive cytoplasmic inclusions containing eosinophilic or pale flocculent material.
Succinate dehydrogenase–deficient renal cell carcinoma. High-grade transformation in direct continuity with more typical areas.

Q: In TFEB-altered renal cell carcinomas (specifically the rearranged subtype), the distinctive microscopic pattern is a biphasic neoplasm comprising larger epithelioid cells and smaller cells clustered around central [...] material.
t(6;11) renal cell carcinoma. Note the biphasic appearance of the neoplasm, with larger epithelioid cells at the periphery of the nests and smaller cells clustered around hyaline basement membrane material in the centre.
t(6;11) renal cell carcinoma. Larger epithelioid cells are at the periphery of the nests and smaller cells are clustered around hyaline basement membrane material in the centre.
A: hyaline basement membrane
Back Extra: TFEB-altered renal cell carcinomas
- Clinical: TFEB-altered renal cell carcinomas typically present as a renal mass, with a mean patient age of 31 years for TFEB-rearranged RCC and 65 years for TFEB-amplified RCC.
- Micro: The most distinctive pattern of TFEB-rearranged RCC is a biphasic neoplasm comprising larger epithelioid cells and smaller cells around basement membrane material.
- Ancillary: Nuclear immunoreactivity for TFEB protein is highly specific for TFEB-rearranged RCC, and a TFEB break-apart FISH assay is the preferred diagnostic test.
Reference Gallery:
t(6;11) renal cell carcinoma. Note the biphasic appearance of the neoplasm, with larger epithelioid cells at the periphery of the nests and smaller cells clustered around hyaline basement membrane material in the centre.
t(6;11) renal cell carcinoma. Larger epithelioid cells are at the periphery of the nests and smaller cells are clustered around hyaline basement membrane material in the centre.
t(6;11) renal cell carcinoma. Strong nuclear labelling for TFEB protein by immunohistochemistry. Note the absence of labelling in lymphocytes, native endothelial cells, and native renal tubules.
Renal cell carcinoma with TFEB amplification. The tumour has a solid nested appearance, and nuclei show prominent nucleoli.
Renal cell carcinoma with TFEB amplification. This tumour has tubulopapillary architecture and is high-grade.

Q: The highly specific diagnostic immunohistochemical finding for the rearranged subtype of TFEB-altered renal cell carcinomas is strong nuclear immunoreactivity for [...] protein.
t(6;11) renal cell carcinoma. Strong nuclear labelling for TFEB protein by immunohistochemistry. Note the absence of labelling in lymphocytes, native endothelial cells, and native renal tubules.
A: TFEB
Back Extra: TFEB-altered renal cell carcinomas
- Clinical: TFEB-altered renal cell carcinomas typically present as a renal mass, with a mean patient age of 31 years for TFEB-rearranged RCC and 65 years for TFEB-amplified RCC.
- Micro: The most distinctive pattern of TFEB-rearranged RCC is a biphasic neoplasm comprising larger epithelioid cells and smaller cells around basement membrane material.
- Ancillary: Nuclear immunoreactivity for TFEB protein is highly specific for TFEB-rearranged RCC, and a TFEB break-apart FISH assay is the preferred diagnostic test.
Reference Gallery:
t(6;11) renal cell carcinoma. Note the biphasic appearance of the neoplasm, with larger epithelioid cells at the periphery of the nests and smaller cells clustered around hyaline basement membrane material in the centre.
t(6;11) renal cell carcinoma. Larger epithelioid cells are at the periphery of the nests and smaller cells are clustered around hyaline basement membrane material in the centre.
t(6;11) renal cell carcinoma. Strong nuclear labelling for TFEB protein by immunohistochemistry. Note the absence of labelling in lymphocytes, native endothelial cells, and native renal tubules.
Renal cell carcinoma with TFEB amplification. The tumour has a solid nested appearance, and nuclei show prominent nucleoli.
Renal cell carcinoma with TFEB amplification. This tumour has tubulopapillary architecture and is high-grade.

Q: Microscopically, Tubulocystic Renal Cell Carcinoma comprises small to intermediate-sized tubules and larger cysts lined by a single layer of flattened, cuboidal/columnar, and characteristic [...] epithelium.
Tubulocystic renal cell carcinoma. Small and intermediate-sized tubules and cysts.
Tubulocystic renal cell carcinoma. Cysts are lined by a single layer of hobnail epithelium.
A: hobnail
Q: Tubulocystic Renal Cell Carcinoma
- Clinical: Most cases of [...] are incidental findings, often presenting with haematuria, abdominal pain, and (rarely) end-stage renal disease.
- Micro: [...] comprises small to intermediate-sized tubules and larger cysts lined by a single layer of flattened, cuboidal/columnar, and hobnail epithelium.
- Ancillary: [...] often shows a gain of chromosome 17 and losses of chromosomes 9 and Y, along with mutations in ABL1, PDGFRA, KMT2C, and KDM5C.
Reference Gallery:
Tubulocystic renal cell carcinoma. The cut surface consists of small white cysts that contain clear fluid.
Tubulocystic renal cell carcinoma. The tumour has many cystic spaces at low magnification.
Tubulocystic renal cell carcinoma. Small and intermediate-sized tubules and cysts.
Tubulocystic renal cell carcinoma. Cysts are lined by a single layer of hobnail epithelium.
A: Tubulocystic Renal Cell Carcinoma; Tubulocystic Renal Cell Carcinoma; Tubulocystic Renal Cell Carcinoma

Q: Grossly and microscopically, [...] is a renal tumor characterized by a spongy appearance of small white fluid-filled cysts, intermediate-sized tubules, and a single layer of hobnail epithelium.
Tubulocystic renal cell carcinoma. The cut surface consists of small white cysts that contain clear fluid.
Tubulocystic renal cell carcinoma. The tumour has many cystic spaces at low magnification.
A: Tubulocystic Renal Cell Carcinoma
Q: Tubulocystic Renal Cell Carcinoma
- Clinical: Most cases of [...] are incidental findings, often presenting with haematuria, abdominal pain, and (rarely) end-stage renal disease.
- Micro: [...] comprises small to intermediate-sized tubules and larger cysts lined by a single layer of flattened, cuboidal/columnar, and hobnail epithelium.
- Ancillary: [...] often shows a gain of chromosome 17 and losses of chromosomes 9 and Y, along with mutations in ABL1, PDGFRA, KMT2C, and KDM5C.
Reference Gallery:
Tubulocystic renal cell carcinoma. The cut surface consists of small white cysts that contain clear fluid.
Tubulocystic renal cell carcinoma. The tumour has many cystic spaces at low magnification.
Tubulocystic renal cell carcinoma. Small and intermediate-sized tubules and cysts.
Tubulocystic renal cell carcinoma. Cysts are lined by a single layer of hobnail epithelium.
A: Tubulocystic Renal Cell Carcinoma; Tubulocystic Renal Cell Carcinoma; Tubulocystic Renal Cell Carcinoma

Q: Histologically, TFE3-rearranged Renal Cell Carcinoma typically features a mixed solid and papillary architecture composed of epithelioid clear cells with frequent, concentrically laminated calcifications known as [...].
TFE3-rearranged renal cell carcinoma. Note the solid to papillary architecture and the psammoma bodies.
TFE3-rearranged renal cell carcinoma. This tumour with ASPSCR1::TFE3 fusion demonstrates voluminous cytoplasm and psammoma bodies.
A: psammoma bodies
Back Extra: TFE3-rearranged Renal Cell Carcinoma
- Clinical: TFE3-rearranged renal cell carcinoma (RCC) often presents as a renal mass and can be heavily calcified on imaging, mimicking renal lithiasis. It accounts for approximately 40% of paediatric RCCs and 1.6–4% of adult RCCs.
- Micro: Histologically, TFE3-rearranged RCCs typically exhibit a papillary architecture with epithelioid clear cells and abundant psammoma bodies. They can also mimic other renal neoplasms such as clear cell RCC and papillary RCC.
- Ancillary: Strong nuclear TFE3 immunoreactivity is highly sensitive and specific for TFE3-rearranged RCCs. TFE3 break-apart FISH assays are generally more useful for confirming the diagnosis.
Reference Gallery:
TFE3-rearranged renal cell carcinoma. Note the solid to papillary architecture and the psammoma bodies.
TFE3-rearranged renal cell carcinoma. Note the solid nested areas resembling clear cell renal cell carcinoma at the bottom and papillary architecture at the top.
TFE3-rearranged renal cell carcinoma. This tumour with ASPSCR1::TFE3 fusion demonstrates voluminous cytoplasm and psammoma bodies.
TFE3-rearranged renal cell carcinoma. Strong nuclear labelling for TFE3 protein by immunohistochemistry. Note the absence of labelling in native endothelial cells.

Q: The diagnosis of TFE3-rearranged Renal Cell Carcinoma is typically supported by strong nuclear immunohistochemical expression of [...], though break-apart FISH assays are often used for definitive confirmation.
TFE3-rearranged renal cell carcinoma. Strong nuclear labelling for TFE3 protein by immunohistochemistry. Note the absence of labelling in native endothelial cells.
A: TFE3
Back Extra: TFE3-rearranged Renal Cell Carcinoma
- Clinical: TFE3-rearranged renal cell carcinoma (RCC) often presents as a renal mass and can be heavily calcified on imaging, mimicking renal lithiasis. It accounts for approximately 40% of paediatric RCCs and 1.6–4% of adult RCCs.
- Micro: Histologically, TFE3-rearranged RCCs typically exhibit a papillary architecture with epithelioid clear cells and abundant psammoma bodies. They can also mimic other renal neoplasms such as clear cell RCC and papillary RCC.
- Ancillary: Strong nuclear TFE3 immunoreactivity is highly sensitive and specific for TFE3-rearranged RCCs. TFE3 break-apart FISH assays are generally more useful for confirming the diagnosis.
Reference Gallery:
TFE3-rearranged renal cell carcinoma. Note the solid to papillary architecture and the psammoma bodies.
TFE3-rearranged renal cell carcinoma. Note the solid nested areas resembling clear cell renal cell carcinoma at the bottom and papillary architecture at the top.
TFE3-rearranged renal cell carcinoma. This tumour with ASPSCR1::TFE3 fusion demonstrates voluminous cytoplasm and psammoma bodies.
TFE3-rearranged renal cell carcinoma. Strong nuclear labelling for TFE3 protein by immunohistochemistry. Note the absence of labelling in native endothelial cells.

Q: Histologically, Cellular Angiofibroma is characterized by a uniform proliferation of short spindle cells accompanied by numerous small- to medium-sized vessels with thick, [...] walls.
Cellular angiofibroma. The tumour is composed of short spindle cells in a rich fibrovascular stroma.
Cellular angiofibroma. Numerous small to medium-sized vessels are present, with thick hyalinized walls.
A: hyalinized
Back Extra: Cellular Angiofibroma
- Clinical: Cellular angiofibroma typically presents as a slow-growing, painless mass, more common in women in their fifth decade and men in their seventh decade.
- Micro: The tumour is characterized by a moderately to highly cellular proliferation of uniform short spindle cells, a prominent fibrovascular stroma, and small to medium-sized vessels with thick hyalinized walls.
- Ancillary: Immunohistochemistry often shows positivity for CD34 and SMA, with frequent loss of RB1 protein expression.
Reference Gallery:
Cellular angiofibroma. The tumour is composed of short spindle cells in a rich fibrovascular stroma.
Cellular angiofibroma. The cellularity is variable and the tumour is highly vascular.
Cellular angiofibroma. Numerous small to medium-sized vessels are present, with thick hyalinized walls.

Q: A highly vascular soft tissue tumor composed of uniform short spindle cells arranged in a rich fibrovascular stroma with thick-walled vessels is characteristic of [...].
Cellular angiofibroma. The tumour is composed of short spindle cells in a rich fibrovascular stroma.
Cellular angiofibroma. The cellularity is variable and the tumour is highly vascular.
Cellular angiofibroma. Numerous small to medium-sized vessels are present, with thick hyalinized walls.
A: Cellular Angiofibroma
Back Extra: Cellular Angiofibroma
- Clinical: Cellular angiofibroma typically presents as a slow-growing, painless mass, more common in women in their fifth decade and men in their seventh decade.
- Micro: The tumour is characterized by a moderately to highly cellular proliferation of uniform short spindle cells, a prominent fibrovascular stroma, and small to medium-sized vessels with thick hyalinized walls.
- Ancillary: Immunohistochemistry often shows positivity for CD34 and SMA, with frequent loss of RB1 protein expression.
Reference Gallery:
Cellular angiofibroma. The tumour is composed of short spindle cells in a rich fibrovascular stroma.
Cellular angiofibroma. The cellularity is variable and the tumour is highly vascular.
Cellular angiofibroma. Numerous small to medium-sized vessels are present, with thick hyalinized walls.

Q: Histopathologic evaluation of primary Mucosal Melanoma typically demonstrates expansive nodules of pleomorphic epithelioid or spindled tumor cells, often accompanied by atypical melanocytes in the basal layer of the overlying squamous epithelium representing an [...] component.
Mucosal melanoma involving the glans penis around the external urethral meatus. The invasive tumour cells are large, pleomorphic, and ovoid to spindled in shape; many include fine intracytoplasmic pigmentation. There are scattered pigment-laden macrophages and lymphocytes in the background. A few scattered single atypical melanocytes are present in the basal portion of the overlying squamous epithelium.
Mucosal melanoma involving the glans penis around the external urethral meatus. In situ mucosal melanoma involving the fossa navicularis of the distal urethra. Numerous moderately atypical melanocytes are present involving the basal half of the squamous epithelium.
A: in situ
Back Extra: Mucosal Melanoma
- Clinical: The median patient age at diagnosis is approximately 65 years, about a decade older than for cutaneous melanoma. Symptoms and signs depend on the anatomical location. Patients with penile melanomas usually present with a…
- Micro: The tumour is usually formed by sheets or expansive nodules of large pleomorphic epithelioid or (less commonly) spindle-shaped malignant melanocytic cells. Necrosis is uncommon. The nuclei often have vesicular chromatin …
- Cyto: Urethral or bladder melanoma may be detected by urinary cytology. FNA specimens are usually obtained from metastases. The typical cytological appearance includes a dissociated population of large epithelioid (or sometime…
- Ancillary: The characteristic mutations include several with clinical significance for treatment. Mucosal melanomas should be tested for BRAF and KIT mutations, in particular when systemic treatment with targeted therapy is being c…
Reference Gallery:
Mucosal melanoma. Clinical photograph of mucosal melanoma involving the glans penis around the external urethral meatus.
Mucosal melanoma involving the glans penis around the external urethral meatus. The invasive tumour cells are large, pleomorphic, and ovoid to spindled in shape; many include fine intracytoplasmic pigmentation. There are scattered pigment-laden macrophages and lymphocytes in the background. A few scattered single atypical melanocytes are present in the basal portion of the overlying squamous epithelium.
Mucosal melanoma involving the glans penis around the external urethral meatus. SOX10 immunostain highlighting both the invasive pigmented melanoma and the overlying in situ melanoma.
Mucosal melanoma involving the glans penis around the external urethral meatus. In situ mucosal melanoma involving the fossa navicularis of the distal urethra. Numerous moderately atypical melanocytes are present involving the basal half of the squamous epithelium.
Mucosal melanoma involving the glans penis around the external urethral meatus. SOX10 immunostain highlights the in situ mucosal melanoma involving the fossa navicularis.

Q: In the evaluation of Mucosal Melanoma, both the invasive tumor cells and the overlying in situ component are characteristically highlighted by the melanocytic nuclear immunostain [...].
Mucosal melanoma involving the glans penis around the external urethral meatus. SOX10 immunostain highlighting both the invasive pigmented melanoma and the overlying in situ melanoma.
Mucosal melanoma involving the glans penis around the external urethral meatus. SOX10 immunostain highlights the in situ mucosal melanoma involving the fossa navicularis.
A: SOX10
Back Extra: Mucosal Melanoma
- Clinical: The median patient age at diagnosis is approximately 65 years, about a decade older than for cutaneous melanoma. Symptoms and signs depend on the anatomical location. Patients with penile melanomas usually present with a…
- Micro: The tumour is usually formed by sheets or expansive nodules of large pleomorphic epithelioid or (less commonly) spindle-shaped malignant melanocytic cells. Necrosis is uncommon. The nuclei often have vesicular chromatin …
- Cyto: Urethral or bladder melanoma may be detected by urinary cytology. FNA specimens are usually obtained from metastases. The typical cytological appearance includes a dissociated population of large epithelioid (or sometime…
- Ancillary: The characteristic mutations include several with clinical significance for treatment. Mucosal melanomas should be tested for BRAF and KIT mutations, in particular when systemic treatment with targeted therapy is being c…
Reference Gallery:
Mucosal melanoma. Clinical photograph of mucosal melanoma involving the glans penis around the external urethral meatus.
Mucosal melanoma involving the glans penis around the external urethral meatus. The invasive tumour cells are large, pleomorphic, and ovoid to spindled in shape; many include fine intracytoplasmic pigmentation. There are scattered pigment-laden macrophages and lymphocytes in the background. A few scattered single atypical melanocytes are present in the basal portion of the overlying squamous epithelium.
Mucosal melanoma involving the glans penis around the external urethral meatus. SOX10 immunostain highlighting both the invasive pigmented melanoma and the overlying in situ melanoma.
Mucosal melanoma involving the glans penis around the external urethral meatus. In situ mucosal melanoma involving the fossa navicularis of the distal urethra. Numerous moderately atypical melanocytes are present involving the basal half of the squamous epithelium.
Mucosal melanoma involving the glans penis around the external urethral meatus. SOX10 immunostain highlights the in situ mucosal melanoma involving the fossa navicularis.

Q: Microscopically, Littre Gland Adenocarcinoma of the Urethra typically displays a characteristic [...] architecture composed of atypical glands lined by columnar mucinous cells.
Littré gland adenocarcinoma. Adenocarcinoma with tubulopapillary architecture, with atypical glands composed of columnar mucinous cells.
Littré gland adenocarcinoma. High-power view showing carcinoma (right) and normal Littré gland (left).
A: tubulopapillary
Back Extra: Littre Gland Adenocarcinoma of the Urethra
- Clinical: Main symptoms include bloody or mucous urethral discharge, haematospermia, haematuria, and a palpable mass.
- Micro: Adenocarcinoma with papillary or tubulopapillary architecture, columnar cells with mucinous vacuoles, and large, oval nuclei without marked pleomorphism.
- Ancillary: Neoplastic cells are positive for CK7 and negative for PSA.
Reference Gallery:
Littré gland adenocarcinoma. Adenocarcinoma with tubulopapillary architecture, with atypical glands composed of columnar mucinous cells.
Littré gland adenocarcinoma. High-power view showing carcinoma (right) and normal Littré gland (left).

Q: A patient presenting with hematospermia, hematuria, and mucous urethral discharge undergoes biopsy of a palpable mass. Histology showing a tubulopapillary proliferation of columnar mucinous cells confirms the diagnosis of [...].
Littré gland adenocarcinoma. Adenocarcinoma with tubulopapillary architecture, with atypical glands composed of columnar mucinous cells.
A: Littre Gland Adenocarcinoma of the Urethra
Back Extra: Littre Gland Adenocarcinoma of the Urethra
- Clinical: Main symptoms include bloody or mucous urethral discharge, haematospermia, haematuria, and a palpable mass.
- Micro: Adenocarcinoma with papillary or tubulopapillary architecture, columnar cells with mucinous vacuoles, and large, oval nuclei without marked pleomorphism.
- Ancillary: Neoplastic cells are positive for CK7 and negative for PSA.
Reference Gallery:
Littré gland adenocarcinoma. Adenocarcinoma with tubulopapillary architecture, with atypical glands composed of columnar mucinous cells.
Littré gland adenocarcinoma. High-power view showing carcinoma (right) and normal Littré gland (left).

Q: In Condyloma Acuminatum, the pathognomonic histologic feature of HPV infection is [...], characterized by enlarged, wrinkled nuclei and perinuclear halos.
Condyloma acuminatum. Prominent koilocytic atypia (viral cytopathic change) in the upper levels of the epithelium close to the surface. The koilocytes have enlarged, wrinkled nuclei surrounded by a perinuclear halo.
A: koilocytic atypia
Back Extra: Condyloma Acuminatum
- Clinical: Condyloma acuminatum presents as nodular warts, often multifocal, and most commonly affects young men in their twenties and thirties.
- Micro: Characterized by papillomatosis, acanthosis, hyperkeratosis, and the presence of koilocytic atypia, with koilocytes showing enlarged, wrinkled nuclei and perinuclear halos.
- Ancillary: HPV types 6 and 11 are most commonly associated, though high-risk HPVs like 16 and 18 can also be present in up to 15% of cases.
Reference Gallery:
Condyloma acuminatum. Prominent koilocytic atypia (viral cytopathic change) in the upper levels of the epithelium close to the surface. The koilocytes have enlarged, wrinkled nuclei surrounded by a perinuclear halo.

Q: The characteristic viral cytopathic changes (seen on histology) and multifocal nodular warts of Condyloma Acuminatum are most commonly associated with human papillomavirus (HPV) types [...].
Condyloma acuminatum. Prominent koilocytic atypia (viral cytopathic change) in the upper levels of the epithelium close to the surface. The koilocytes have enlarged, wrinkled nuclei surrounded by a perinuclear halo.
A: 6 and 11
Back Extra: Condyloma Acuminatum
- Clinical: Condyloma acuminatum presents as nodular warts, often multifocal, and most commonly affects young men in their twenties and thirties.
- Micro: Characterized by papillomatosis, acanthosis, hyperkeratosis, and the presence of koilocytic atypia, with koilocytes showing enlarged, wrinkled nuclei and perinuclear halos.
- Ancillary: HPV types 6 and 11 are most commonly associated, though high-risk HPVs like 16 and 18 can also be present in up to 15% of cases.
Reference Gallery:
Condyloma acuminatum. Prominent koilocytic atypia (viral cytopathic change) in the upper levels of the epithelium close to the surface. The koilocytes have enlarged, wrinkled nuclei surrounded by a perinuclear halo.

Q: A painless nodule on the glans penis characterized histologically by growth within the pre-existing vascular spaces of the corpus spongiosum is diagnostic of [...].
Myointimoma. The tumour grows within the pre-existing vascular spaces of the corpus spongiosum of the glans penis.
A: myointimoma
Back Extra: Myointimoma
- Clinical: Patients with myointimoma usually present with a painless and asymptomatic nodule within the glans penis, primarily in boys and less frequently in men.
- Micro: Myointimoma is characterized by neoplastic cells with eosinophilic cytoplasm and small nuclei, arranged in a plexiform pattern within the pre-existing vascular spaces of the corpus spongiosum.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of myointimoma.
Reference Gallery:
Myointimoma. The tumour grows within the pre-existing vascular spaces of the corpus spongiosum of the glans penis.
Myointimoma. The cytoplasm of the neoplastic cells is mostly eosinophilic. Nuclei are small and lack any mitotic activity.

Q: Histologically, myointimoma is characterized by neoplastic cells with small nuclei and predominantly eosinophilic cytoplasm that specifically grow within the pre-existing [...] of the corpus spongiosum.
Myointimoma. The tumour grows within the pre-existing vascular spaces of the corpus spongiosum of the glans penis.
Myointimoma. The cytoplasm of the neoplastic cells is mostly eosinophilic. Nuclei are small and lack any mitotic activity.
A: vascular spaces
Back Extra: Myointimoma
- Clinical: Patients with myointimoma usually present with a painless and asymptomatic nodule within the glans penis, primarily in boys and less frequently in men.
- Micro: Myointimoma is characterized by neoplastic cells with eosinophilic cytoplasm and small nuclei, arranged in a plexiform pattern within the pre-existing vascular spaces of the corpus spongiosum.
- Ancillary: Ancillary studies are not clinically relevant for the diagnosis of myointimoma.
Reference Gallery:
Myointimoma. The tumour grows within the pre-existing vascular spaces of the corpus spongiosum of the glans penis.
Myointimoma. The cytoplasm of the neoplastic cells is mostly eosinophilic. Nuclei are small and lack any mitotic activity.

Q: Microscopically, Extramammary Paget Disease is characterized by the presence of large cells with prominent nucleoli that infiltrate the epidermis and adnexal structures singly or in small clusters, known as [...].
Paget disease of the scrotum associated with invasive carcinoma. Nests and single tumour cells involve the epidermis. Single cells and cords of tumour cells are present within the dermis. A hair follicle (right) is also involved.
A: Paget cells
Back Extra: Extramammary Paget Disease
- Clinical: Extramammary Paget Disease typically presents in older men with symptoms such as pruritus, erythema, pain, and exudation, often leading to a delayed diagnosis.
- Micro: Paget cells in Extramammary Paget Disease are characterized by their presence singly or in small clusters in the epidermis, with large nuclei and prominent nucleoli, and frequent involvement of sweat glands and hair follicles.
- Ancillary: Immunohistochemistry in Extramammary Paget Disease shows positive staining for CK7 and CEA, with variable expression of ERBB2 and GCDFP-15, while HMB45, S100, CK20, vimentin, and CDX2 are usually negative.
Reference Gallery:
Paget disease of the scrotum associated with invasive carcinoma. Nests and single tumour cells involve the epidermis. Single cells and cords of tumour cells are present within the dermis. A hair follicle (right) is also involved.
Paget disease of the scrotum associated with invasive carcinoma. CK7 immunohistochemical stain highlights tumour cells in the epithelium, dermis, and hair follicle.

Q: A key immunohistochemical marker used in the diagnosis of Extramammary Paget Disease is [...], which strongly highlights the tumor cells within the epithelium and adnexa.
Paget disease of the scrotum associated with invasive carcinoma. CK7 immunohistochemical stain highlights tumour cells in the epithelium, dermis, and hair follicle.
A: CK7
Back Extra: Extramammary Paget Disease
- Clinical: Extramammary Paget Disease typically presents in older men with symptoms such as pruritus, erythema, pain, and exudation, often leading to a delayed diagnosis.
- Micro: Paget cells in Extramammary Paget Disease are characterized by their presence singly or in small clusters in the epidermis, with large nuclei and prominent nucleoli, and frequent involvement of sweat glands and hair follicles.
- Ancillary: Immunohistochemistry in Extramammary Paget Disease shows positive staining for CK7 and CEA, with variable expression of ERBB2 and GCDFP-15, while HMB45, S100, CK20, vimentin, and CDX2 are usually negative.
Reference Gallery:
Paget disease of the scrotum associated with invasive carcinoma. Nests and single tumour cells involve the epidermis. Single cells and cords of tumour cells are present within the dermis. A hair follicle (right) is also involved.
Paget disease of the scrotum associated with invasive carcinoma. CK7 immunohistochemical stain highlights tumour cells in the epithelium, dermis, and hair follicle.

Q: In Differentiated Penile Intraepithelial Neoplasia, HPV-independent, the atypical, hyperchromatic cells with prominent nucleoli are characteristically confined to the [...] layers, with normal maturation towards the surface.
Differentiated penile intraepithelial neoplasia, HPV-independent. The basal and parabasal nuclei of the squamous epithelium are atypical, with many showing prominent nucleoli. Cells with abundant eosinophilic cytoplasm are seen, along with prominent intercellular bridges.
Differentiated penile intraepithelial neoplasia, HPV-independent. Characteristic epithelial hyperplasia with surface maturation and hypergranulosis with hyperchromatic, atypical cells confined to the basal and parabasal layers.
A: basal and parabasal
Back Extra: Differentiated Penile Intraepithelial Neoplasia, HPV-independent
- Clinical: Differentiated Penile Intraepithelial Neoplasia, HPV-independent tends to develop in older men, often uncircumcised, with a history of lichen sclerosus.
- Micro: Characterized by epithelial hyperplasia, hyperkeratosis, parakeratosis, and atypical cells with prominent nucleoli in the basal and parabasal layers.
- Ancillary: Lacks p16 overexpression but commonly shows nuclear p53 expression and strong COX-2 expression.
Reference Gallery:
Differentiated penile intraepithelial neoplasia, HPV-independent. The hyperplastic squamous epithelium shows the presence of some enlarged keratinocytes with eosinophilic cytoplasm. The basal layer shows nuclear abnormalities.
Differentiated penile intraepithelial neoplasia, HPV-independent. The basal layers show abnormal nuclear changes that are more pronounced in some of the elongated rete. The eosinophilic cytoplasm of scattered keratinocytes may be a prominent feature.
Differentiated penile intraepithelial neoplasia, HPV-independent. Hyperplastic squamous epithelium of the foreskin showing parakeratosis and hyperkeratosis.
Differentiated penile intraepithelial neoplasia, HPV-independent. The basal and parabasal nuclei of the squamous epithelium are atypical, with many showing prominent nucleoli. Cells with abundant eosinophilic cytoplasm are seen, along with prominent intercellular bridges.
Differentiated penile intraepithelial neoplasia, HPV-independent. Characteristic epithelial hyperplasia with surface maturation and hypergranulosis with hyperchromatic, atypical cells confined to the basal and parabasal layers.

Q: The hyperplastic squamous epithelium in Differentiated Penile Intraepithelial Neoplasia, HPV-independent often features scattered enlarged keratinocytes with abundant [...] cytoplasm and prominent intercellular bridges.
Differentiated penile intraepithelial neoplasia, HPV-independent. The hyperplastic squamous epithelium shows the presence of some enlarged keratinocytes with eosinophilic cytoplasm. The basal layer shows nuclear abnormalities.
Differentiated penile intraepithelial neoplasia, HPV-independent. The basal layers show abnormal nuclear changes that are more pronounced in some of the elongated rete. The eosinophilic cytoplasm of scattered keratinocytes may be a prominent feature.
A: eosinophilic
Back Extra: Differentiated Penile Intraepithelial Neoplasia, HPV-independent
- Clinical: Differentiated Penile Intraepithelial Neoplasia, HPV-independent tends to develop in older men, often uncircumcised, with a history of lichen sclerosus.
- Micro: Characterized by epithelial hyperplasia, hyperkeratosis, parakeratosis, and atypical cells with prominent nucleoli in the basal and parabasal layers.
- Ancillary: Lacks p16 overexpression but commonly shows nuclear p53 expression and strong COX-2 expression.
Reference Gallery:
Differentiated penile intraepithelial neoplasia, HPV-independent. The hyperplastic squamous epithelium shows the presence of some enlarged keratinocytes with eosinophilic cytoplasm. The basal layer shows nuclear abnormalities.
Differentiated penile intraepithelial neoplasia, HPV-independent. The basal layers show abnormal nuclear changes that are more pronounced in some of the elongated rete. The eosinophilic cytoplasm of scattered keratinocytes may be a prominent feature.
Differentiated penile intraepithelial neoplasia, HPV-independent. Hyperplastic squamous epithelium of the foreskin showing parakeratosis and hyperkeratosis.
Differentiated penile intraepithelial neoplasia, HPV-independent. The basal and parabasal nuclei of the squamous epithelium are atypical, with many showing prominent nucleoli. Cells with abundant eosinophilic cytoplasm are seen, along with prominent intercellular bridges.
Differentiated penile intraepithelial neoplasia, HPV-independent. Characteristic epithelial hyperplasia with surface maturation and hypergranulosis with hyperchromatic, atypical cells confined to the basal and parabasal layers.

Q: Architecturally, Differentiated Penile Intraepithelial Neoplasia, HPV-independent is characterized by squamous epithelial hyperplasia accompanied by surface hyperkeratosis and [...].
Differentiated penile intraepithelial neoplasia, HPV-independent. Hyperplastic squamous epithelium of the foreskin showing parakeratosis and hyperkeratosis.
A: parakeratosis
Back Extra: Differentiated Penile Intraepithelial Neoplasia, HPV-independent
- Clinical: Differentiated Penile Intraepithelial Neoplasia, HPV-independent tends to develop in older men, often uncircumcised, with a history of lichen sclerosus.
- Micro: Characterized by epithelial hyperplasia, hyperkeratosis, parakeratosis, and atypical cells with prominent nucleoli in the basal and parabasal layers.
- Ancillary: Lacks p16 overexpression but commonly shows nuclear p53 expression and strong COX-2 expression.
Reference Gallery:
Differentiated penile intraepithelial neoplasia, HPV-independent. The hyperplastic squamous epithelium shows the presence of some enlarged keratinocytes with eosinophilic cytoplasm. The basal layer shows nuclear abnormalities.
Differentiated penile intraepithelial neoplasia, HPV-independent. The basal layers show abnormal nuclear changes that are more pronounced in some of the elongated rete. The eosinophilic cytoplasm of scattered keratinocytes may be a prominent feature.
Differentiated penile intraepithelial neoplasia, HPV-independent. Hyperplastic squamous epithelium of the foreskin showing parakeratosis and hyperkeratosis.
Differentiated penile intraepithelial neoplasia, HPV-independent. The basal and parabasal nuclei of the squamous epithelium are atypical, with many showing prominent nucleoli. Cells with abundant eosinophilic cytoplasm are seen, along with prominent intercellular bridges.
Differentiated penile intraepithelial neoplasia, HPV-independent. Characteristic epithelial hyperplasia with surface maturation and hypergranulosis with hyperchromatic, atypical cells confined to the basal and parabasal layers.

Q: Histologically, Penile Intraepithelial Neoplasia, HPV-associated frequently exhibits basaloid, warty, or mixed patterns, with characteristic viral cytopathic features towards the surface known as [...].
Penile intraepithelial neoplasia, HPV-associated. Warty (condylomatous) penile intraepithelial neoplasia.
Penile intraepithelial neoplasia, HPV-associated. At higher power, there is mixed (warty/basaloid) penile intraepithelial neoplasia showing basaloid features (small immature cells) at the base and more differentiated cells with warty features (koilocytic atypia) towards the surface.
A: koilocytic atypia
Back Extra: Penile Intraepithelial Neoplasia, HPV-associated
- Clinical: HPV-associated penile intraepithelial neoplasia (PeIN) often presents as sharply defined plaques with a velvety erythematous appearance on the glans, and may be associated with erosions and bleeding.
- Micro: Histologically, HPV-associated PeIN can show basaloid, warty, or mixed patterns, with characteristic features such as koilocytic atypia and increased mitotic activity.
- Ancillary: In situ hybridization for high-risk HPV and immunohistochemical staining for p16 (p16INK4a) are useful in confirming the diagnosis of HPV-associated PeIN.
Reference Gallery:
Undifferentiated penile intraepithelial neoplasia. Monotonous replacement of the entire epithelium by small immature cells with a high N:C ratio.
Undifferentiated penile intraepithelial neoplasia. Monotonous replacement of the entire epithelium by small immature cells with a high N:C ratio, numerous mitoses, and prominent apoptosis.
Penile intraepithelial neoplasia, HPV-associated. Warty (condylomatous) penile intraepithelial neoplasia.
Penile intraepithelial neoplasia, HPV-associated. At higher power, there is mixed (warty/basaloid) penile intraepithelial neoplasia showing basaloid features (small immature cells) at the base and more differentiated cells with warty features (koilocytic atypia) towards the surface.

Q: Monotonous replacement of the entire epithelium by small immature cells with a high N:C ratio, numerous mitoses, and prominent apoptosis is characteristic of the undifferentiated (basaloid) variant of [...].
Undifferentiated penile intraepithelial neoplasia. Monotonous replacement of the entire epithelium by small immature cells with a high N:C ratio.
Undifferentiated penile intraepithelial neoplasia. Monotonous replacement of the entire epithelium by small immature cells with a high N:C ratio, numerous mitoses, and prominent apoptosis.
A: Penile Intraepithelial Neoplasia, HPV-associated
Back Extra: Penile Intraepithelial Neoplasia, HPV-associated
- Clinical: HPV-associated penile intraepithelial neoplasia (PeIN) often presents as sharply defined plaques with a velvety erythematous appearance on the glans, and may be associated with erosions and bleeding.
- Micro: Histologically, HPV-associated PeIN can show basaloid, warty, or mixed patterns, with characteristic features such as koilocytic atypia and increased mitotic activity.
- Ancillary: In situ hybridization for high-risk HPV and immunohistochemical staining for p16 (p16INK4a) are useful in confirming the diagnosis of HPV-associated PeIN.
Reference Gallery:
Undifferentiated penile intraepithelial neoplasia. Monotonous replacement of the entire epithelium by small immature cells with a high N:C ratio.
Undifferentiated penile intraepithelial neoplasia. Monotonous replacement of the entire epithelium by small immature cells with a high N:C ratio, numerous mitoses, and prominent apoptosis.
Penile intraepithelial neoplasia, HPV-associated. Warty (condylomatous) penile intraepithelial neoplasia.
Penile intraepithelial neoplasia, HPV-associated. At higher power, there is mixed (warty/basaloid) penile intraepithelial neoplasia showing basaloid features (small immature cells) at the base and more differentiated cells with warty features (koilocytic atypia) towards the surface.

Q: Histologic examination showing proliferating nests of basaloid cells with characteristic peripheral palisading, microcyst formation, and retraction spaces in a scrotal lesion is diagnostic of [...].
Basal cell carcinoma of the scrotum. The proliferating nests and cords of basaloid cells show characteristic peripheral palisading with occasional central squamous differentiation, microcyst formation, and retraction spaces.
A: Basal Cell Carcinoma of the Scrotum
Back Extra: Basal Cell Carcinoma of the Scrotum
- Clinical: Basal cell carcinoma of the scrotum (BCC-S) typically appears as red papules, plaques, or nodules on the scrotum, with local invasion being common and no specific symptoms.
- Micro: Histologically, BCC-S shows proliferating nests and cords of basaloid cells with characteristic peripheral palisading, occasional central squamous differentiation, microcyst formation, and retraction spaces.
- Ancillary: Mutations in TP53 and PTCH1, associated with UV exposure, are linked to BCC-S, though no specific molecular studies have been conducted.
Reference Gallery:
Basal cell carcinoma of the scrotum. The proliferating nests and cords of basaloid cells show characteristic peripheral palisading with occasional central squamous differentiation, microcyst formation, and retraction spaces.

Q: In Basal Cell Carcinoma of the Scrotum, the proliferating nests of tumor cells typically exhibit a characteristic parallel alignment of their outermost cells, a feature known as [...].
Basal cell carcinoma of the scrotum. The proliferating nests and cords of basaloid cells show characteristic peripheral palisading with occasional central squamous differentiation, microcyst formation, and retraction spaces.
A: peripheral palisading
Back Extra: Basal Cell Carcinoma of the Scrotum
- Clinical: Basal cell carcinoma of the scrotum (BCC-S) typically appears as red papules, plaques, or nodules on the scrotum, with local invasion being common and no specific symptoms.
- Micro: Histologically, BCC-S shows proliferating nests and cords of basaloid cells with characteristic peripheral palisading, occasional central squamous differentiation, microcyst formation, and retraction spaces.
- Ancillary: Mutations in TP53 and PTCH1, associated with UV exposure, are linked to BCC-S, though no specific molecular studies have been conducted.
Reference Gallery:
Basal cell carcinoma of the scrotum. The proliferating nests and cords of basaloid cells show characteristic peripheral palisading with occasional central squamous differentiation, microcyst formation, and retraction spaces.

Q: In HPV-associated squamous cell carcinoma, the basaloid variant is characterized by solid nests of small, uniform [...] cells with inconspicuous nucleoli and numerous mitotic figures.
HPV-associated squamous cell carcinoma. Basaloid squamous cell carcinoma, characterized by solid nests of small uniform basaloid cells, inconspicuous nucleoli, and numerous mitotic figures.
HPV-associated squamous cell carcinoma. Basaloid squamous cell carcinoma showing surface ulceration and deep invasion of the stroma by islands of basaloid cells.
A: basaloid
Back Extra: HPV-associated squamous cell carcinoma
- Clinical: HPV-associated squamous cell carcinoma is more common in low- and middle-income countries, with high-risk HPV, especially HPV16, found in about 33% of cases.
- Micro: Basaloid squamous cell carcinoma is characterized by solid nests of small uniform basaloid cells with numerous mitotic figures and frequent vascular and perineural invasion.
- Ancillary: Immunohistochemistry shows strong positivity for p16 in HPV-associated squamous cell carcinoma.
Reference Gallery:
HPV-associated squamous cell carcinoma. Basaloid squamous cell carcinoma, characterized by solid nests of small uniform basaloid cells, inconspicuous nucleoli, and numerous mitotic figures.
HPV-associated squamous cell carcinoma. Basaloid squamous cell carcinoma showing surface ulceration and deep invasion of the stroma by islands of basaloid cells.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Definitive cytological atypia and malignant infiltrative architecture. Tumours have a combined exophytic/endophytic growth pattern and a parakeratotic papillomatous surface with conspicuous frankly atypical koilocytosis throughout the tumour.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Endophytic growth with a malignant infiltrative pattern.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Immunohistochemistry positive for p16.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Immunohistochemistry positive for p16.

Q: The warty variant of HPV-associated squamous cell carcinoma typically exhibits a combined exophytic and endophytic growth pattern with conspicuous, atypical [...] throughout the tumor.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Definitive cytological atypia and malignant infiltrative architecture. Tumours have a combined exophytic/endophytic growth pattern and a parakeratotic papillomatous surface with conspicuous frankly atypical koilocytosis throughout the tumour.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Endophytic growth with a malignant infiltrative pattern.
A: koilocytosis
Back Extra: HPV-associated squamous cell carcinoma
- Clinical: HPV-associated squamous cell carcinoma is more common in low- and middle-income countries, with high-risk HPV, especially HPV16, found in about 33% of cases.
- Micro: Basaloid squamous cell carcinoma is characterized by solid nests of small uniform basaloid cells with numerous mitotic figures and frequent vascular and perineural invasion.
- Ancillary: Immunohistochemistry shows strong positivity for p16 in HPV-associated squamous cell carcinoma.
Reference Gallery:
HPV-associated squamous cell carcinoma. Basaloid squamous cell carcinoma, characterized by solid nests of small uniform basaloid cells, inconspicuous nucleoli, and numerous mitotic figures.
HPV-associated squamous cell carcinoma. Basaloid squamous cell carcinoma showing surface ulceration and deep invasion of the stroma by islands of basaloid cells.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Definitive cytological atypia and malignant infiltrative architecture. Tumours have a combined exophytic/endophytic growth pattern and a parakeratotic papillomatous surface with conspicuous frankly atypical koilocytosis throughout the tumour.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Endophytic growth with a malignant infiltrative pattern.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Immunohistochemistry positive for p16.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Immunohistochemistry positive for p16.

Q: A key diagnostic ancillary feature of HPV-associated squamous cell carcinoma is strong immunohistochemical positivity for [...].
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Immunohistochemistry positive for p16.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Immunohistochemistry positive for p16.
A: p16
Back Extra: HPV-associated squamous cell carcinoma
- Clinical: HPV-associated squamous cell carcinoma is more common in low- and middle-income countries, with high-risk HPV, especially HPV16, found in about 33% of cases.
- Micro: Basaloid squamous cell carcinoma is characterized by solid nests of small uniform basaloid cells with numerous mitotic figures and frequent vascular and perineural invasion.
- Ancillary: Immunohistochemistry shows strong positivity for p16 in HPV-associated squamous cell carcinoma.
Reference Gallery:
HPV-associated squamous cell carcinoma. Basaloid squamous cell carcinoma, characterized by solid nests of small uniform basaloid cells, inconspicuous nucleoli, and numerous mitotic figures.
HPV-associated squamous cell carcinoma. Basaloid squamous cell carcinoma showing surface ulceration and deep invasion of the stroma by islands of basaloid cells.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Definitive cytological atypia and malignant infiltrative architecture. Tumours have a combined exophytic/endophytic growth pattern and a parakeratotic papillomatous surface with conspicuous frankly atypical koilocytosis throughout the tumour.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Endophytic growth with a malignant infiltrative pattern.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Immunohistochemistry positive for p16.
HPV-associated squamous cell carcinoma. Warty squamous cell carcinoma. Immunohistochemistry positive for p16.

Q: Microscopically, HPV-independent Squamous Cell Carcinoma is typically characterized as an invasive [...] carcinoma arising from the penile mucosal or cutaneous compartments.
HPV-independent squamous cell carcinoma. Invasive keratinizing carcinoma arising from penile mucosal or cutaneous compartments.
HPV-independent squamous cell carcinoma. Invasive keratinizing carcinoma arising from penile mucosal or cutaneous compartments.
A: keratinizing
Back Extra: HPV-independent Squamous Cell Carcinoma
- Clinical: HPV-independent squamous cell carcinoma is most frequently diagnosed in the sixth and seventh decades of life, with an average patient age of 58 years. It commonly presents as a slow-growing tumour with rapid enlargement and ulceration.
- Micro: Microscopically, HPV-independent squamous cell carcinoma is characterized by invasive keratinizing carcinoma arising from penile mucosal or cutaneous compartments, with a variable spectrum of well- to poorly differentiated squamous cell carcinoma.
- Ancillary: Immunohistochemical markers such as 34βE12 and p63 are useful for demonstrating epithelial histogenesis. Molecular studies often reveal oncogenic activation of TP53 and mutations in PIK3CA, KRAS, and HRAS.
Reference Gallery:
Squamous cell carcinoma, usual type. Cut surface of a penectomy specimen showing a predominantly superficially spreading carcinoma.
HPV-independent squamous cell carcinoma. Invasive keratinizing carcinoma arising from penile mucosal or cutaneous compartments.
HPV-independent squamous cell carcinoma. Invasive keratinizing carcinoma arising from penile mucosal or cutaneous compartments.
Sarcomatoid squamous cell carcinoma. There is a heterogeneous spectrum of features simulating various sarcomas along with confluent squamous cell carcinoma of the usual type.

Q: Grossly, the usual type of [...] can present as a slow-growing penile tumor that may demonstrate a predominantly superficially spreading pattern on the cut surface, as well as potential ulceration.
Squamous cell carcinoma, usual type. Cut surface of a penectomy specimen showing a predominantly superficially spreading carcinoma.
A: HPV-independent Squamous Cell Carcinoma
Back Extra: HPV-independent Squamous Cell Carcinoma
- Clinical: HPV-independent squamous cell carcinoma is most frequently diagnosed in the sixth and seventh decades of life, with an average patient age of 58 years. It commonly presents as a slow-growing tumour with rapid enlargement and ulceration.
- Micro: Microscopically, HPV-independent squamous cell carcinoma is characterized by invasive keratinizing carcinoma arising from penile mucosal or cutaneous compartments, with a variable spectrum of well- to poorly differentiated squamous cell carcinoma.
- Ancillary: Immunohistochemical markers such as 34βE12 and p63 are useful for demonstrating epithelial histogenesis. Molecular studies often reveal oncogenic activation of TP53 and mutations in PIK3CA, KRAS, and HRAS.
Reference Gallery:
Squamous cell carcinoma, usual type. Cut surface of a penectomy specimen showing a predominantly superficially spreading carcinoma.
HPV-independent squamous cell carcinoma. Invasive keratinizing carcinoma arising from penile mucosal or cutaneous compartments.
HPV-independent squamous cell carcinoma. Invasive keratinizing carcinoma arising from penile mucosal or cutaneous compartments.
Sarcomatoid squamous cell carcinoma. There is a heterogeneous spectrum of features simulating various sarcomas along with confluent squamous cell carcinoma of the usual type.

Q: Histologically, the adenosquamous variant of Penile Adenosquamous and Mucoepidermoid Carcinomas is characterized by an admixture of squamous cell carcinoma and overt [...] differentiation.
Penile adenosquamous carcinoma. A tumour with both glandular and squamous features.
A: glandular
Back Extra: Penile Adenosquamous and Mucoepidermoid Carcinomas
- Clinical: Patients are usually in their sixth decade of life and present with a penile mass. Fewer than 15 cases have been reported.
- Micro: ASCs have gland-forming SCCs, while MECs are solid tumours without overt gland formation. The glandular component is often in the perimeatal region, with columnar or cuboidal cells, intracellular mucin, and sometimes intraluminal mucin.
- Ancillary: SCC with gland formation and/or mucin-producing cells positive for CK7, CEA, and mucin stains and negative for p16.
Reference Gallery:
Penile adenosquamous carcinoma. A tumour with both glandular and squamous features.

Q: Microscopically, Squamous Cell Carcinoma NOS is characterized by nests and sheets of [...].
Squamous cell carcinoma NOS. Nests of invasive keratinizing squamous cells.
Squamous cell carcinoma NOS. Nests of invasive squamous cells.
Squamous cell carcinoma NOS. Sheets and nests of invasive keratinizing squamous cells.
A: invasive keratinizing squamous cells
Back Extra: Squamous Cell Carcinoma NOS
- Clinical: Squamous cell carcinoma NOS (SCC-NOS) typically presents as a mass on the glans or coronal sulcus, with the foreskin rarely being the primary site of involvement.
- Micro: Histologically, SCC-NOS is characterized by nests and sheets of invasive keratinizing squamous cells, often with a variable degree of keratinization.
- Ancillary: HPV testing and p16 immunohistochemistry are not available or not performed in SCC-NOS, making it distinct from HPV-related SCC.
Reference Gallery:
Squamous cell carcinoma NOS. Nests of invasive keratinizing squamous cells.
Squamous cell carcinoma NOS. Nests of invasive squamous cells.
Squamous cell carcinoma NOS. Sheets and nests of invasive keratinizing squamous cells.

Q: In Squamous Cell Carcinoma NOS, the malignant nests of squamous cells typically exhibit a variable degree of [...].
Squamous cell carcinoma NOS. Nests of invasive keratinizing squamous cells.
Squamous cell carcinoma NOS. Sheets and nests of invasive keratinizing squamous cells.
A: keratinization
Back Extra: Squamous Cell Carcinoma NOS
- Clinical: Squamous cell carcinoma NOS (SCC-NOS) typically presents as a mass on the glans or coronal sulcus, with the foreskin rarely being the primary site of involvement.
- Micro: Histologically, SCC-NOS is characterized by nests and sheets of invasive keratinizing squamous cells, often with a variable degree of keratinization.
- Ancillary: HPV testing and p16 immunohistochemistry are not available or not performed in SCC-NOS, making it distinct from HPV-related SCC.
Reference Gallery:
Squamous cell carcinoma NOS. Nests of invasive keratinizing squamous cells.
Squamous cell carcinoma NOS. Nests of invasive squamous cells.
Squamous cell carcinoma NOS. Sheets and nests of invasive keratinizing squamous cells.

Q: Microscopic examination of High-grade prostatic intraepithelial neoplasia reveals atypical secretory epithelial cells with prominent nucleoli, but unlike invasive adenocarcinoma, the glands uniquely retain a(n) [...].
High-grade prostatic intraepithelial neoplasia with adjacent normal glands. Tufted and micropapillary patterns. Secretory cells show nuclear stratification and prominent nucleoli; basal cells are retained.
A: basal cell layer
Back Extra: High-grade prostatic intraepithelial neoplasia
- Clinical: High-grade prostatic intraepithelial neoplasia (HGPIN) is incidentally detected in histological samples and does not lead to clinical manifestations. It is more common in African-American men and less common in Asian men.
- Micro: HGPIN is characterized by atypical proliferation of secretory epithelial cells with enlarged, hyperchromatic nuclei and prominent nucleoli. The basal cell layer is retained but may be reduced in number.
- Ancillary: Immunostaining for high-molecular-weight cytokeratin and/or p63 can help distinguish HGPIN from adenocarcinoma by confirming the presence of basal cells.
Reference Gallery:
Prostatic intraepithelial neoplasia with small-cell changes. A lesion with centrally located solid sheets of dark small-cell populations punctuated by rosette formations.
Inverted high-grade prostatic intraepithelial neoplasia. This example demonstrates nuclei that are polarized towards the lumen.
High-grade prostatic intraepithelial neoplasia with adjacent normal glands. Tufted and micropapillary patterns. Secretory cells show nuclear stratification and prominent nucleoli; basal cells are retained.

Q: An unusual morphologic variant of High-grade prostatic intraepithelial neoplasia is the inverted pattern, in which the atypical nuclei are characteristically polarized toward the [...].
Inverted high-grade prostatic intraepithelial neoplasia. This example demonstrates nuclei that are polarized towards the lumen.
A: lumen
Back Extra: High-grade prostatic intraepithelial neoplasia
- Clinical: High-grade prostatic intraepithelial neoplasia (HGPIN) is incidentally detected in histological samples and does not lead to clinical manifestations. It is more common in African-American men and less common in Asian men.
- Micro: HGPIN is characterized by atypical proliferation of secretory epithelial cells with enlarged, hyperchromatic nuclei and prominent nucleoli. The basal cell layer is retained but may be reduced in number.
- Ancillary: Immunostaining for high-molecular-weight cytokeratin and/or p63 can help distinguish HGPIN from adenocarcinoma by confirming the presence of basal cells.
Reference Gallery:
Prostatic intraepithelial neoplasia with small-cell changes. A lesion with centrally located solid sheets of dark small-cell populations punctuated by rosette formations.
Inverted high-grade prostatic intraepithelial neoplasia. This example demonstrates nuclei that are polarized towards the lumen.
High-grade prostatic intraepithelial neoplasia with adjacent normal glands. Tufted and micropapillary patterns. Secretory cells show nuclear stratification and prominent nucleoli; basal cells are retained.

Q: High-grade prostatic intraepithelial neoplasia can rarely exhibit small-cell changes, demonstrating solid sheets of dark cells that are often punctuated by the formation of [...].
Prostatic intraepithelial neoplasia with small-cell changes. A lesion with centrally located solid sheets of dark small-cell populations punctuated by rosette formations.
A: rosettes
Back Extra: High-grade prostatic intraepithelial neoplasia
- Clinical: High-grade prostatic intraepithelial neoplasia (HGPIN) is incidentally detected in histological samples and does not lead to clinical manifestations. It is more common in African-American men and less common in Asian men.
- Micro: HGPIN is characterized by atypical proliferation of secretory epithelial cells with enlarged, hyperchromatic nuclei and prominent nucleoli. The basal cell layer is retained but may be reduced in number.
- Ancillary: Immunostaining for high-molecular-weight cytokeratin and/or p63 can help distinguish HGPIN from adenocarcinoma by confirming the presence of basal cells.
Reference Gallery:
Prostatic intraepithelial neoplasia with small-cell changes. A lesion with centrally located solid sheets of dark small-cell populations punctuated by rosette formations.
Inverted high-grade prostatic intraepithelial neoplasia. This example demonstrates nuclei that are polarized towards the lumen.
High-grade prostatic intraepithelial neoplasia with adjacent normal glands. Tufted and micropapillary patterns. Secretory cells show nuclear stratification and prominent nucleoli; basal cells are retained.

Q: Histologically, Intraductal Carcinoma of the Prostate is characterized by solid or dense cribriform growth and frequent comedonecrosis, crucially with preservation of the [...].
Intraductal carcinoma of the prostate. Core biopsy showing solid cribriform glands.
Intraductal carcinoma of the prostate. There is partial involvement of a benign gland.
A: basal cell layer
Back Extra: Intraductal Carcinoma of the Prostate
- Clinical: Intraductal Carcinoma of the Prostate (IDC-P) is often associated with high-grade and high-volume invasive prostate cancer, with a prevalence of 15.4–31.1% in radical prostatectomies and 2.8% in biopsies.
- Micro: Histopathologically, IDC-P is characterized by solid or dense cribriform growth patterns, cytological atypia, and frequent comedonecrosis, often with preservation of the basal cell layer.
- Ancillary: Immunohistochemistry with basal cell markers (e.g., high-molecular-weight cytokeratin, p63) is crucial for distinguishing IDC-P from invasive prostate cancer, especially in cases without concomitant invasive cancer.
Reference Gallery:
Intraductal carcinoma of the prostate. Core biopsy showing solid cribriform glands.
Intraductal carcinoma of the prostate. Surrounding basal cells are highlighted by high-molecular-weight cytokeratin and p63 immunostaining. AMACR is positive in cancer cells.
Intraductal carcinoma of the prostate. Comedonecrosis in dense cribriform glands. Corpora amylacea are present in several glands, suggestive of involvement of pre-existing benign glands.
Intraductal carcinoma of the prostate. There is partial involvement of a benign gland.
Intraductal carcinoma of the prostate. An example with markedly pleomorphic nuclei.
Intraductal carcinoma of the prostate. High-power view of Fig. #20864.
Intraductal carcinoma of the prostate. High-power view of Fig. #20864.

Q: To distinguish Intraductal Carcinoma of the Prostate from invasive prostate cancer, immunohistochemistry highlighting preserved basal cells typically utilizes high-molecular-weight cytokeratin and [...].
Intraductal carcinoma of the prostate. Surrounding basal cells are highlighted by high-molecular-weight cytokeratin and p63 immunostaining. AMACR is positive in cancer cells.
A: p63
Back Extra: Intraductal Carcinoma of the Prostate
- Clinical: Intraductal Carcinoma of the Prostate (IDC-P) is often associated with high-grade and high-volume invasive prostate cancer, with a prevalence of 15.4–31.1% in radical prostatectomies and 2.8% in biopsies.
- Micro: Histopathologically, IDC-P is characterized by solid or dense cribriform growth patterns, cytological atypia, and frequent comedonecrosis, often with preservation of the basal cell layer.
- Ancillary: Immunohistochemistry with basal cell markers (e.g., high-molecular-weight cytokeratin, p63) is crucial for distinguishing IDC-P from invasive prostate cancer, especially in cases without concomitant invasive cancer.
Reference Gallery:
Intraductal carcinoma of the prostate. Core biopsy showing solid cribriform glands.
Intraductal carcinoma of the prostate. Surrounding basal cells are highlighted by high-molecular-weight cytokeratin and p63 immunostaining. AMACR is positive in cancer cells.
Intraductal carcinoma of the prostate. Comedonecrosis in dense cribriform glands. Corpora amylacea are present in several glands, suggestive of involvement of pre-existing benign glands.
Intraductal carcinoma of the prostate. There is partial involvement of a benign gland.
Intraductal carcinoma of the prostate. An example with markedly pleomorphic nuclei.
Intraductal carcinoma of the prostate. High-power view of Fig. #20864.
Intraductal carcinoma of the prostate. High-power view of Fig. #20864.

Q: A characteristic histopathologic finding within the dense cribriform glands of Intraductal Carcinoma of the Prostate is the frequent presence of central [...].
Intraductal carcinoma of the prostate. Comedonecrosis in dense cribriform glands. Corpora amylacea are present in several glands, suggestive of involvement of pre-existing benign glands.
A: comedonecrosis
Back Extra: Intraductal Carcinoma of the Prostate
- Clinical: Intraductal Carcinoma of the Prostate (IDC-P) is often associated with high-grade and high-volume invasive prostate cancer, with a prevalence of 15.4–31.1% in radical prostatectomies and 2.8% in biopsies.
- Micro: Histopathologically, IDC-P is characterized by solid or dense cribriform growth patterns, cytological atypia, and frequent comedonecrosis, often with preservation of the basal cell layer.
- Ancillary: Immunohistochemistry with basal cell markers (e.g., high-molecular-weight cytokeratin, p63) is crucial for distinguishing IDC-P from invasive prostate cancer, especially in cases without concomitant invasive cancer.
Reference Gallery:
Intraductal carcinoma of the prostate. Core biopsy showing solid cribriform glands.
Intraductal carcinoma of the prostate. Surrounding basal cells are highlighted by high-molecular-weight cytokeratin and p63 immunostaining. AMACR is positive in cancer cells.
Intraductal carcinoma of the prostate. Comedonecrosis in dense cribriform glands. Corpora amylacea are present in several glands, suggestive of involvement of pre-existing benign glands.
Intraductal carcinoma of the prostate. There is partial involvement of a benign gland.
Intraductal carcinoma of the prostate. An example with markedly pleomorphic nuclei.
Intraductal carcinoma of the prostate. High-power view of Fig. #20864.
Intraductal carcinoma of the prostate. High-power view of Fig. #20864.

Q: Histologically, a prostatic cystadenoma features large multilocular cysts lined by a characteristic dual layer consisting of inner, PSA-positive secretory cells and an intact outer layer of flattened [...].
Whole Slide Image of Prostatic Cystadenoma
Whole Slide Image of Prostatic Cystadenoma
A: basal cells
Back Extra: Prostatic Cystadenoma
- Clinical: Patients may present with obstructive urinary symptoms, constipation, abdominal distention, and pain. Imaging often shows large multiseptate masses involving the prostate gland and/or retrovesical space.
- Micro: Cysts are lined by a dual layer consisting of low columnar or atrophic secretory cells and flattened outer basal cells. Focal bland papillae may be seen. Squamous metaplasia may be present.
- Ancillary: Immunohistochemistry shows the lining epithelium stains for PSA, PAP, and other prostate lineage–specific markers. Basal cells are positive for high-molecular-weight cytokeratin and p63.
Reference Gallery:
Whole Slide Image of Prostatic Cystadenoma
Whole Slide Image of Prostatic Cystadenoma

Q: The defining microscopic appearance of a prostatic cystadenoma includes multiseptate cysts that frequently demonstrate areas of squamous metaplasia and focal bland [...] projecting into the lumens.
Whole Slide Image of Prostatic Cystadenoma
Whole Slide Image of Prostatic Cystadenoma
A: papillae
Back Extra: Prostatic Cystadenoma
- Clinical: Patients may present with obstructive urinary symptoms, constipation, abdominal distention, and pain. Imaging often shows large multiseptate masses involving the prostate gland and/or retrovesical space.
- Micro: Cysts are lined by a dual layer consisting of low columnar or atrophic secretory cells and flattened outer basal cells. Focal bland papillae may be seen. Squamous metaplasia may be present.
- Ancillary: Immunohistochemistry shows the lining epithelium stains for PSA, PAP, and other prostate lineage–specific markers. Basal cells are positive for high-molecular-weight cytokeratin and p63.
Reference Gallery:
Whole Slide Image of Prostatic Cystadenoma
Whole Slide Image of Prostatic Cystadenoma

Q: Microscopically, Prostatic Ductal Adenocarcinoma is classically characterized by [...] architectural patterns lined by pseudostratified tall columnar cells.
Ductal adenocarcinoma. Ductal adenocarcinoma with cribriform and papillary architecture (left). A minor component of typical acinar adenocarcinoma is also present (upper right).
A: papillary and large cribriform
Q: Prostatic Ductal Adenocarcinoma
- Clinical: Patients with [...] may present with symptoms of bladder outflow obstruction and gross haematuria due to periurethral tumour involvement.
- Micro: [...] is characterized by papillary and large cribriform patterns with pseudostratified tall columnar cells and a desmoplastic stroma.
- Ancillary: [...] is positive for prostatic markers such as PSA, PAP, PSMA, NKX3-1, and AMACR. Genomic studies show clonal relations with acinar adenocarcinoma and frequent WNT pathway mutations.
Reference Gallery:
Ductal adenocarcinoma. Ductal adenocarcinoma with cribriform and papillary architecture (left). A minor component of typical acinar adenocarcinoma is also present (upper right).
Ductal adenocarcinoma. Ductal adenocarcinoma showing tall pseudostratified columnar epithelium. This case is the same as that shown in Fig. 21026.
Ductal adenocarcinoma. Ductal adenocarcinoma with stratified high-grade nuclei.
Lung metastasis of prostatic ductal adenocarcinoma. Ductal features are preserved, including papillary formations lined by tall columnar carcinoma cells and conventional acinar adenocarcinoma glands located within the pulmonary parenchyma.
A: Prostatic Ductal Adenocarcinoma; Prostatic Ductal Adenocarcinoma; Prostatic Ductal Adenocarcinoma

Q: The characteristic epithelial lining of Prostatic Ductal Adenocarcinoma consists of [...] cells, frequently demonstrating stratified high-grade nuclei.
Ductal adenocarcinoma. Ductal adenocarcinoma showing tall pseudostratified columnar epithelium. This case is the same as that shown in Fig. 21026.
Ductal adenocarcinoma. Ductal adenocarcinoma with stratified high-grade nuclei.
A: pseudostratified tall columnar
Q: Prostatic Ductal Adenocarcinoma
- Clinical: Patients with [...] may present with symptoms of bladder outflow obstruction and gross haematuria due to periurethral tumour involvement.
- Micro: [...] is characterized by papillary and large cribriform patterns with pseudostratified tall columnar cells and a desmoplastic stroma.
- Ancillary: [...] is positive for prostatic markers such as PSA, PAP, PSMA, NKX3-1, and AMACR. Genomic studies show clonal relations with acinar adenocarcinoma and frequent WNT pathway mutations.
Reference Gallery:
Ductal adenocarcinoma. Ductal adenocarcinoma with cribriform and papillary architecture (left). A minor component of typical acinar adenocarcinoma is also present (upper right).
Ductal adenocarcinoma. Ductal adenocarcinoma showing tall pseudostratified columnar epithelium. This case is the same as that shown in Fig. 21026.
Ductal adenocarcinoma. Ductal adenocarcinoma with stratified high-grade nuclei.
Lung metastasis of prostatic ductal adenocarcinoma. Ductal features are preserved, including papillary formations lined by tall columnar carcinoma cells and conventional acinar adenocarcinoma glands located within the pulmonary parenchyma.
A: Prostatic Ductal Adenocarcinoma; Prostatic Ductal Adenocarcinoma; Prostatic Ductal Adenocarcinoma

Q: Even in distant pulmonary metastases, Prostatic Ductal Adenocarcinoma often preserves its distinct morphology, including papillary formations lined by [...] carcinoma cells.
Lung metastasis of prostatic ductal adenocarcinoma. Ductal features are preserved, including papillary formations lined by tall columnar carcinoma cells and conventional acinar adenocarcinoma glands located within the pulmonary parenchyma.
A: tall columnar
Q: Prostatic Ductal Adenocarcinoma
- Clinical: Patients with [...] may present with symptoms of bladder outflow obstruction and gross haematuria due to periurethral tumour involvement.
- Micro: [...] is characterized by papillary and large cribriform patterns with pseudostratified tall columnar cells and a desmoplastic stroma.
- Ancillary: [...] is positive for prostatic markers such as PSA, PAP, PSMA, NKX3-1, and AMACR. Genomic studies show clonal relations with acinar adenocarcinoma and frequent WNT pathway mutations.
Reference Gallery:
Ductal adenocarcinoma. Ductal adenocarcinoma with cribriform and papillary architecture (left). A minor component of typical acinar adenocarcinoma is also present (upper right).
Ductal adenocarcinoma. Ductal adenocarcinoma showing tall pseudostratified columnar epithelium. This case is the same as that shown in Fig. 21026.
Ductal adenocarcinoma. Ductal adenocarcinoma with stratified high-grade nuclei.
Lung metastasis of prostatic ductal adenocarcinoma. Ductal features are preserved, including papillary formations lined by tall columnar carcinoma cells and conventional acinar adenocarcinoma glands located within the pulmonary parenchyma.
A: Prostatic Ductal Adenocarcinoma; Prostatic Ductal Adenocarcinoma; Prostatic Ductal Adenocarcinoma

Q: Microscopically, Treatment-Related Neuroendocrine Prostatic Carcinoma is characterized by scant cytoplasm, a high N:C ratio, nuclear molding, and fine or [...] chromatin.
Treatment-related neuroendocrine prostatic carcinoma. These tumours display scant cytoplasm, a high N:C ratio, nuclear moulding, fine or salt-and-pepper chromatin, and inconspicuous nucleoli.
A: salt-and-pepper
Back Extra: Treatment-Related Neuroendocrine Prostatic Carcinoma
- Clinical: Treatment-related neuroendocrine prostatic carcinoma (t-NEPC) represents 10-15% of castration-resistant prostate adenocarcinomas and is associated with a poor prognosis, with a median survival of only 7 months post-transdifferentiation.
- Micro: t-NEPC displays scant cytoplasm, a high N:C ratio, nuclear moulding, and salt-and-pepper chromatin, which are characteristic of small cell neuroendocrine carcinoma.
- Ancillary: t-NEPC typically shows loss of AR expression and is positive for neuroendocrine markers such as synaptophysin and chromogranin.
Reference Gallery:
Treatment-related neuroendocrine prostatic carcinoma. These tumours display scant cytoplasm, a high N:C ratio, nuclear moulding, fine or salt-and-pepper chromatin, and inconspicuous nucleoli.
Treatment-related neuroendocrine prostatic carcinoma. Most examples show a loss of AR expression, consistent with AR-signalling indifference.
Treatment-related neuroendocrine prostatic carcinoma. The tumours are positive for neuroendocrine markers such as synaptophysin.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. This tumour type is characterized by abundant cytoplasm, round nuclei, and prominent nucleoli; it may also show gland formation.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. By immunohistochemistry, this tumour type shows strong AR expression.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. Tumours usually lack expression of neuroendocrine markers such as synaptophysin.

Q: In Treatment-Related Neuroendocrine Prostatic Carcinoma, immunohistochemistry typically demonstrates a loss of [...] expression, distinguishing it from usual castration-resistant prostatic adenocarcinoma.
Treatment-related neuroendocrine prostatic carcinoma. Most examples show a loss of AR expression, consistent with AR-signalling indifference.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. By immunohistochemistry, this tumour type shows strong AR expression.
A: androgen receptor (AR)
Back Extra: Treatment-Related Neuroendocrine Prostatic Carcinoma
- Clinical: Treatment-related neuroendocrine prostatic carcinoma (t-NEPC) represents 10-15% of castration-resistant prostate adenocarcinomas and is associated with a poor prognosis, with a median survival of only 7 months post-transdifferentiation.
- Micro: t-NEPC displays scant cytoplasm, a high N:C ratio, nuclear moulding, and salt-and-pepper chromatin, which are characteristic of small cell neuroendocrine carcinoma.
- Ancillary: t-NEPC typically shows loss of AR expression and is positive for neuroendocrine markers such as synaptophysin and chromogranin.
Reference Gallery:
Treatment-related neuroendocrine prostatic carcinoma. These tumours display scant cytoplasm, a high N:C ratio, nuclear moulding, fine or salt-and-pepper chromatin, and inconspicuous nucleoli.
Treatment-related neuroendocrine prostatic carcinoma. Most examples show a loss of AR expression, consistent with AR-signalling indifference.
Treatment-related neuroendocrine prostatic carcinoma. The tumours are positive for neuroendocrine markers such as synaptophysin.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. This tumour type is characterized by abundant cytoplasm, round nuclei, and prominent nucleoli; it may also show gland formation.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. By immunohistochemistry, this tumour type shows strong AR expression.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. Tumours usually lack expression of neuroendocrine markers such as synaptophysin.

Q: Treatment-Related Neuroendocrine Prostatic Carcinoma characteristically shows positive immunohistochemical staining for neuroendocrine markers such as chromogranin and [...].
Treatment-related neuroendocrine prostatic carcinoma. The tumours are positive for neuroendocrine markers such as synaptophysin.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. Tumours usually lack expression of neuroendocrine markers such as synaptophysin.
A: synaptophysin
Back Extra: Treatment-Related Neuroendocrine Prostatic Carcinoma
- Clinical: Treatment-related neuroendocrine prostatic carcinoma (t-NEPC) represents 10-15% of castration-resistant prostate adenocarcinomas and is associated with a poor prognosis, with a median survival of only 7 months post-transdifferentiation.
- Micro: t-NEPC displays scant cytoplasm, a high N:C ratio, nuclear moulding, and salt-and-pepper chromatin, which are characteristic of small cell neuroendocrine carcinoma.
- Ancillary: t-NEPC typically shows loss of AR expression and is positive for neuroendocrine markers such as synaptophysin and chromogranin.
Reference Gallery:
Treatment-related neuroendocrine prostatic carcinoma. These tumours display scant cytoplasm, a high N:C ratio, nuclear moulding, fine or salt-and-pepper chromatin, and inconspicuous nucleoli.
Treatment-related neuroendocrine prostatic carcinoma. Most examples show a loss of AR expression, consistent with AR-signalling indifference.
Treatment-related neuroendocrine prostatic carcinoma. The tumours are positive for neuroendocrine markers such as synaptophysin.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. This tumour type is characterized by abundant cytoplasm, round nuclei, and prominent nucleoli; it may also show gland formation.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. By immunohistochemistry, this tumour type shows strong AR expression.
Castration-resistant prostate cancer: usual prostatic adenocarcinoma. Tumours usually lack expression of neuroendocrine markers such as synaptophysin.

Q: In Adenoid Cystic (Basal Cell) Carcinoma of the Prostate, immunohistochemistry characteristically demonstrates strong nuclear immunoreactivity for [...], while PSA is commonly negative.
Basal cell carcinoma. Strong nuclear p63 immunoreactivity is characteristic. PSA is commonly negative.
A: p63
Back Extra: Adenoid Cystic (Basal Cell) Carcinoma of the Prostate
- Clinical: Patients often have urinary obstruction; diagnosis is most commonly made on transurethral resection specimens.
- Micro: Most cases show varying proportions of the adenoid cystic / cribriform pattern and the basaloid pattern with small solid nests of basal cells.
- Ancillary: By FISH, 17–47% of adenoid cystic (basal cell) carcinomas of the prostate harbour the MYB::NFIB fusion.
Reference Gallery:
Basal cell carcinoma. Strong nuclear p63 immunoreactivity is characteristic. PSA is commonly negative.
Basal cell carcinoma. This non-adenoid cystic-like pattern has irregular anastomosing sheets of basaloid neoplastic cells.

Q: Microscopically, Adenoid Cystic (Basal Cell) Carcinoma of the Prostate frequently exhibits a mixed architecture that includes an adenoid cystic/cribriform pattern as well as irregular anastomosing sheets and solid nests of [...] neoplastic cells.
Basal cell carcinoma. This non-adenoid cystic-like pattern has irregular anastomosing sheets of basaloid neoplastic cells.
A: basaloid
Back Extra: Adenoid Cystic (Basal Cell) Carcinoma of the Prostate
- Clinical: Patients often have urinary obstruction; diagnosis is most commonly made on transurethral resection specimens.
- Micro: Most cases show varying proportions of the adenoid cystic / cribriform pattern and the basaloid pattern with small solid nests of basal cells.
- Ancillary: By FISH, 17–47% of adenoid cystic (basal cell) carcinomas of the prostate harbour the MYB::NFIB fusion.
Reference Gallery:
Basal cell carcinoma. Strong nuclear p63 immunoreactivity is characteristic. PSA is commonly negative.
Basal cell carcinoma. This non-adenoid cystic-like pattern has irregular anastomosing sheets of basaloid neoplastic cells.

Q: In Adenosquamous Carcinoma of the Prostate, microscopic examination classically demonstrates a distinct transition between typical glandular (acinar) elements and a [...] component.
Adenosquamous cell carcinoma of the prostate. This example shows a distinct squamous component with a transition to the glandular component.
A: squamous
Back Extra: Adenosquamous Carcinoma of the Prostate
- Clinical: Most patients present with urinary obstructive symptoms and increased urinary frequency. Serum PSA levels can be elevated or normal.
- Micro: Adenosquamous carcinoma is composed of both glandular (acinar) and squamous components. The squamous component can range from 5% to 95% and can show a wide range of differentiation.
- Ancillary: Molecular investigation (for TMPRSS2::ERG fusions, PTEN deletions, and SPOP mutations) may be helpful in selected cases.
Reference Gallery:
Adenosquamous cell carcinoma of the prostate. This example shows a distinct squamous component with a transition to the glandular component.

Q: Microscopically, Prostatic Stromal Sarcoma is characterized by a diffuse growth of malignant [...] exhibiting hypercellularity, marked pleomorphism, and atypical mitoses, which often surround benign prostatic acini.
Prostatic stromal sarcoma. Pleomorphic nuclei and increased mitoses.
Prostatic stromal sarcoma. Prostatic acini surrounded by malignant spindle cells. A few cells with bizarre nuclei are seen.
Prostatic stromal sarcoma. Malignant spindle cells in diffuse sheets and interlacing fascicles.
A: spindle cells
Q: Prostatic Stromal Sarcoma
- Clinical: Patients present with lower urinary tract obstruction, with a mean age of [...] years.
- Micro: Tumour cells exhibit hypercellularity, cytological atypia, increased mitoses, and atypical mitosis.
- Ancillary: Essential features include diffuse stromal growth with hypercellularity, cytological atypia, increased or atypical mitosis, and necrosis.
Reference Gallery:
Prostatic stromal sarcoma. Vague storiform growth.
Prostatic stromal sarcoma. Pleomorphic nuclei and increased mitoses.
Prostatic stromal sarcoma. Cystoprostatectomy specimen showing unremarkable bladder mucosa along with a large globular prostatic mass. Cut surface shows a well-circumscribed, grey-white, firm tumour with a whorled and lobulated appearance.
Prostatic stromal sarcoma. Prostatic acini surrounded by malignant spindle cells. A few cells with bizarre nuclei are seen.
Prostatic stromal sarcoma. Malignant spindle cells in diffuse sheets and interlacing fascicles.
Prostatic stromal sarcoma. Diffuse and strong immunohistochemical positivity for CD34.
Prostatic stromal sarcoma. Diffuse and strong immunohistochemical positivity for desmin.
Prostatic stromal sarcoma. Tumour cells are positive for PR by immunohistochemistry.
A: 51.5

Q: The malignant cells in Prostatic Stromal Sarcoma characteristically demonstrate diffuse and strong immunohistochemical positivity for [...], as well as frequent expression of progesterone receptors (PR).
Prostatic stromal sarcoma. Diffuse and strong immunohistochemical positivity for CD34.
Prostatic stromal sarcoma. Diffuse and strong immunohistochemical positivity for desmin.
Prostatic stromal sarcoma. Tumour cells are positive for PR by immunohistochemistry.
A: CD34 and desmin
Q: Prostatic Stromal Sarcoma
- Clinical: Patients present with lower urinary tract obstruction, with a mean age of [...] years.
- Micro: Tumour cells exhibit hypercellularity, cytological atypia, increased mitoses, and atypical mitosis.
- Ancillary: Essential features include diffuse stromal growth with hypercellularity, cytological atypia, increased or atypical mitosis, and necrosis.
Reference Gallery:
Prostatic stromal sarcoma. Vague storiform growth.
Prostatic stromal sarcoma. Pleomorphic nuclei and increased mitoses.
Prostatic stromal sarcoma. Cystoprostatectomy specimen showing unremarkable bladder mucosa along with a large globular prostatic mass. Cut surface shows a well-circumscribed, grey-white, firm tumour with a whorled and lobulated appearance.
Prostatic stromal sarcoma. Prostatic acini surrounded by malignant spindle cells. A few cells with bizarre nuclei are seen.
Prostatic stromal sarcoma. Malignant spindle cells in diffuse sheets and interlacing fascicles.
Prostatic stromal sarcoma. Diffuse and strong immunohistochemical positivity for CD34.
Prostatic stromal sarcoma. Diffuse and strong immunohistochemical positivity for desmin.
Prostatic stromal sarcoma. Tumour cells are positive for PR by immunohistochemistry.
A: 51.5

Q: Grossly, Prostatic Stromal Sarcoma frequently presents in middle-aged men with lower urinary tract obstruction as a large, circumscribed, firm prostatic mass with a characteristic [...] gray-white cut surface.
Prostatic stromal sarcoma. Cystoprostatectomy specimen showing unremarkable bladder mucosa along with a large globular prostatic mass. Cut surface shows a well-circumscribed, grey-white, firm tumour with a whorled and lobulated appearance.
A: whorled and lobulated
Q: Prostatic Stromal Sarcoma
- Clinical: Patients present with lower urinary tract obstruction, with a mean age of [...] years.
- Micro: Tumour cells exhibit hypercellularity, cytological atypia, increased mitoses, and atypical mitosis.
- Ancillary: Essential features include diffuse stromal growth with hypercellularity, cytological atypia, increased or atypical mitosis, and necrosis.
Reference Gallery:
Prostatic stromal sarcoma. Vague storiform growth.
Prostatic stromal sarcoma. Pleomorphic nuclei and increased mitoses.
Prostatic stromal sarcoma. Cystoprostatectomy specimen showing unremarkable bladder mucosa along with a large globular prostatic mass. Cut surface shows a well-circumscribed, grey-white, firm tumour with a whorled and lobulated appearance.
Prostatic stromal sarcoma. Prostatic acini surrounded by malignant spindle cells. A few cells with bizarre nuclei are seen.
Prostatic stromal sarcoma. Malignant spindle cells in diffuse sheets and interlacing fascicles.
Prostatic stromal sarcoma. Diffuse and strong immunohistochemical positivity for CD34.
Prostatic stromal sarcoma. Diffuse and strong immunohistochemical positivity for desmin.
Prostatic stromal sarcoma. Tumour cells are positive for PR by immunohistochemistry.
A: 51.5

Q: Microscopic examination of Squamous Cell Carcinoma of the Prostate reveals infiltrating nests of squamous epithelium with characteristic intercellular bridges and [...] (as demonstrated in the image).
Squamous cell carcinoma of the prostate. Infiltration of the stroma by a nest of squamous epithelium, with some cells showing keratinization.
A: keratinization
Back Extra: Squamous Cell Carcinoma of the Prostate
- Clinical: Squamous Cell Carcinoma of the Prostate typically presents in elderly patients with a history of hormone or radiation therapy for prostatic adenocarcinoma. Common symptoms include urinary obstruction, dysuria, haematuria, and bone pain from metastatic disease.
- Micro: Microscopically, Squamous Cell Carcinoma of the Prostate shows squamous architecture with keratinization and intercellular bridges, with no glandular elements present. Gleason grading is not applicable.
- Ancillary: Ancillary studies for Squamous Cell Carcinoma of the Prostate include the presence of squamous architecture, keratinization, and intercellular bridges, and the absence of glandular differentiation. TMPRSS2::ERG fusion and PTEN loss are common findings.
Reference Gallery:
Squamous cell carcinoma of the prostate. Infiltration of the stroma by a nest of squamous epithelium, with some cells showing keratinization.

Q: In Squamous Cell Carcinoma of the Prostate, the tumor consists exclusively of squamous elements. Because it completely lacks [...] differentiation, the standard Gleason grading system is not applicable.
Squamous cell carcinoma of the prostate. Infiltration of the stroma by a nest of squamous epithelium, with some cells showing keratinization.
A: glandular
Back Extra: Squamous Cell Carcinoma of the Prostate
- Clinical: Squamous Cell Carcinoma of the Prostate typically presents in elderly patients with a history of hormone or radiation therapy for prostatic adenocarcinoma. Common symptoms include urinary obstruction, dysuria, haematuria, and bone pain from metastatic disease.
- Micro: Microscopically, Squamous Cell Carcinoma of the Prostate shows squamous architecture with keratinization and intercellular bridges, with no glandular elements present. Gleason grading is not applicable.
- Ancillary: Ancillary studies for Squamous Cell Carcinoma of the Prostate include the presence of squamous architecture, keratinization, and intercellular bridges, and the absence of glandular differentiation. TMPRSS2::ERG fusion and PTEN loss are common findings.
Reference Gallery:
Squamous cell carcinoma of the prostate. Infiltration of the stroma by a nest of squamous epithelium, with some cells showing keratinization.

Q: Microscopically, Adenocarcinoma of the Seminal Vesicle often demonstrates a characteristic [...] growth pattern, alongside glandular and trabecular differentiation.
Primary adenocarcinoma of the seminal vesicle. The tumour displays a papillary growth pattern.
A: papillary
Back Extra: Adenocarcinoma of the Seminal Vesicle
- Clinical: Approximately 60 cases of primary adenocarcinoma of the seminal vesicles have been reported, with patients often presenting with urinary obstruction and haematuria.
- Micro: The tumour has a glandular differentiation, often with trabecular and papillary growth patterns. Goblet cells and mucin secretion are frequently observed.
- Ancillary: Serum CA125 level may be a useful biomarker for disease recurrence.
Reference Gallery:
Primary adenocarcinoma of the seminal vesicle. The tumour displays a papillary growth pattern.
Primary adenocarcinoma of the seminal vesicle. Goblet cells and mucin depositions can be seen. Prominent retraction artefacts are also present (lower-right corner).

Q: A frequent microscopic feature in Adenocarcinoma of the Seminal Vesicle is the presence of mucin secretion and [...], which can often be seen alongside prominent retraction artifacts.
Primary adenocarcinoma of the seminal vesicle. Goblet cells and mucin depositions can be seen. Prominent retraction artefacts are also present (lower-right corner).
A: goblet cells
Back Extra: Adenocarcinoma of the Seminal Vesicle
- Clinical: Approximately 60 cases of primary adenocarcinoma of the seminal vesicles have been reported, with patients often presenting with urinary obstruction and haematuria.
- Micro: The tumour has a glandular differentiation, often with trabecular and papillary growth patterns. Goblet cells and mucin secretion are frequently observed.
- Ancillary: Serum CA125 level may be a useful biomarker for disease recurrence.
Reference Gallery:
Primary adenocarcinoma of the seminal vesicle. The tumour displays a papillary growth pattern.
Primary adenocarcinoma of the seminal vesicle. Goblet cells and mucin depositions can be seen. Prominent retraction artefacts are also present (lower-right corner).

Q: A patient presents with urinary obstruction and hematuria. Histologic examination reveals a tumor with a papillary growth pattern, glandular differentiation, and numerous goblet cells with mucin deposition. This presentation is characteristic of [...].
Primary adenocarcinoma of the seminal vesicle. The tumour displays a papillary growth pattern.
Primary adenocarcinoma of the seminal vesicle. Goblet cells and mucin depositions can be seen. Prominent retraction artefacts are also present (lower-right corner).
A: Adenocarcinoma of the Seminal Vesicle
Back Extra: Adenocarcinoma of the Seminal Vesicle
- Clinical: Approximately 60 cases of primary adenocarcinoma of the seminal vesicles have been reported, with patients often presenting with urinary obstruction and haematuria.
- Micro: The tumour has a glandular differentiation, often with trabecular and papillary growth patterns. Goblet cells and mucin secretion are frequently observed.
- Ancillary: Serum CA125 level may be a useful biomarker for disease recurrence.
Reference Gallery:
Primary adenocarcinoma of the seminal vesicle. The tumour displays a papillary growth pattern.
Primary adenocarcinoma of the seminal vesicle. Goblet cells and mucin depositions can be seen. Prominent retraction artefacts are also present (lower-right corner).

Q: Histologically, Cystadenoma of the Seminal Vesicle is characterized by large cysts lined by a single layer of bland [...] cells without atypia.
Cystadenoma of the seminal vesicle. Large cyst lined by cuboidal cells without atypia.
A: cuboidal
Back Extra: Cystadenoma of the Seminal Vesicle
- Clinical: Cystadenoma of the seminal vesicle typically presents with obstructive urinary symptoms or as an asymptomatic mass, with patient age ranging from 23 to 66 years.
- Micro: Cystadenoma of the seminal vesicle is characterized by glandular spaces of varying sizes lined by bland cuboidal cells without atypia, arranged in a lobular pattern forming branching lumina and cysts in a scant stroma.
- Ancillary: Epithelial cells in cystadenoma of the seminal vesicle are positive for cytokeratin and negative for PSA, PAP, and calretinin. Focal luminal AMACR positivity can be seen.
Reference Gallery:
Cystadenoma of the seminal vesicle. The single layer of epithelium lining this cyst is folded and forms papillary structures.
Cystadenoma of the seminal vesicle. Large cyst lined by cuboidal cells without atypia.

Q: In Cystadenoma of the Seminal Vesicle, the single layer of epithelium lining the cysts can become folded, forming benign [...] structures.
Cystadenoma of the seminal vesicle. The single layer of epithelium lining this cyst is folded and forms papillary structures.
A: papillary
Back Extra: Cystadenoma of the Seminal Vesicle
- Clinical: Cystadenoma of the seminal vesicle typically presents with obstructive urinary symptoms or as an asymptomatic mass, with patient age ranging from 23 to 66 years.
- Micro: Cystadenoma of the seminal vesicle is characterized by glandular spaces of varying sizes lined by bland cuboidal cells without atypia, arranged in a lobular pattern forming branching lumina and cysts in a scant stroma.
- Ancillary: Epithelial cells in cystadenoma of the seminal vesicle are positive for cytokeratin and negative for PSA, PAP, and calretinin. Focal luminal AMACR positivity can be seen.
Reference Gallery:
Cystadenoma of the seminal vesicle. The single layer of epithelium lining this cyst is folded and forms papillary structures.
Cystadenoma of the seminal vesicle. Large cyst lined by cuboidal cells without atypia.

Q: Histologic examination of a well-circumscribed mass reveals a biphasic neoplasm composed of abundant stromal elements and variably sized cysts containing eosinophilic secretions (as shown). This morphology is characteristic of a [...].
Mixed epithelial and stromal tumour of the seminal vesicle. The tumour is well circumscribed with variably sized cysts. The cysts contain eosinophilic secretions. There are abundant stromal elements. Inset: gross appearance.
A: Mixed Epithelial and Stromal Tumor of the Seminal Vesicle
Back Extra: Mixed Epithelial and Stromal Tumour of the Seminal Vesicle
- Clinical: Patients often present with obstructive lower urinary tract symptoms, haematospermia, fever, or abdominal pain.
- Micro: The tumour is composed of both stromal and benign epithelial components, with variably sized cysts lined by columnar or cuboidal epithelial cells.
- Ancillary: Stromal cells stain positively for ER, PR, vimentin, desmin, SMA, h-caldesmon, and CD34, while epithelial cells are positive for CK7.
Reference Gallery:
Mixed epithelial and stromal tumour of the seminal vesicle. The tumour is well circumscribed with variably sized cysts. The cysts contain eosinophilic secretions. There are abundant stromal elements. Inset: gross appearance.

Q: Histologically, Squamous Cell Carcinoma of the Seminal Vesicle is characterized by larger nests of tumor cells that frequently demonstrate [...] and the formation of cystic spaces.
Primary squamous cell carcinoma of the seminal vesicle. Typical appearances with central keratinization within larger nests of tumour cells.
A: central keratinization
Back Extra: Squamous Cell Carcinoma of the Seminal Vesicle
- Clinical: The most frequent presenting symptom of Squamous Cell Carcinoma of the Seminal Vesicle is gross haematuria. Other common symptoms include haematospermia, dysuria, and bladder outlet obstruction.
- Micro: Squamous Cell Carcinoma of the Seminal Vesicle often presents with keratinizing squamous cell carcinoma with cystic spaces and central keratinization within larger nests of tumour cells.
- Ancillary: In Squamous Cell Carcinoma of the Seminal Vesicle, ancillary studies are not relevant, but the tumour cells are positive for p63 and CK5/6, and negative for CK7, CK20, PSA, and CEA.
Reference Gallery:
Primary squamous cell carcinoma of the seminal vesicle. Typical appearances with central keratinization within larger nests of tumour cells.

Q: In BAP1 Tumor Predisposition Syndrome, associated clear cell renal cell carcinomas characteristically demonstrate a complete loss of BAP1 immunoreactivity in the [...] of tumor cells, reflecting a two-hit inactivation.
Clear cell renal cell carcinoma in BAP1 tumour predisposition syndrome. This tumour demonstrates typical morphological features.
Clear cell renal cell carcinoma in BAP1 tumour predisposition syndrome. Immunohistochemistry shows a complete loss of expression of BAP1 in all neoplastic cells. The non-neoplastic cells demonstrate retained nuclear expression and serve as an internal positive control.
A: nuclei
Back Extra: BAP1 Tumor Predisposition Syndrome
- Clinical: BAP1 tumor predisposition syndrome is associated with increased risks of uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other malignancies. Up to 85% of patients develop malignancy by age 65.
- Micro: Clear cell renal cell carcinomas (CCRCCs) in BAP1 tumor predisposition syndrome show typical morphological features and a complete loss of BAP1 immunoreactivity in the tumor nuclei, confirming a two-hit inactivation of BAP1.
- Ancillary: Diagnosis of BAP1 tumor predisposition syndrome is confirmed by identifying a germline heterozygous pathogenic variant in the BAP1 gene through molecular genetic testing.
Reference Gallery:
Clear cell renal cell carcinoma in BAP1 tumour predisposition syndrome. This tumour demonstrates typical morphological features.
Clear cell renal cell carcinoma in BAP1 tumour predisposition syndrome. Immunohistochemistry shows a complete loss of expression of BAP1 in all neoplastic cells. The non-neoplastic cells demonstrate retained nuclear expression and serve as an internal positive control.
Skin lesion in BAP1 tumour predisposition syndrome. Representative section of a 7 mm irregular papule in a patient with germline heterozygous BAP1 pathogenic mutation (NM_004656.3 BAP1 c.102_109del; p.D34Efs*32). The section shows an intradermal proliferation composed largely of epithelioid melanocytes with round to oval nuclei, abundant glassy cytoplasm, and haphazard maturation. There is nuclear pleomorphism and an occasional nuclear pseudoinclusion. Mitotic figures are not readily identified.
Skin lesion in BAP1 tumour predisposition syndrome. BAP1 immunohistochemistry in this skin papule reveals that the lesional melanocytes lack nuclear expression of BAP1.

Q: Cutaneous lesions in BAP1 Tumor Predisposition Syndrome often present as papules composed of an intradermal proliferation of [...] melanocytes that show a complete loss of nuclear BAP1 expression on immunohistochemistry.
Skin lesion in BAP1 tumour predisposition syndrome. Representative section of a 7 mm irregular papule in a patient with germline heterozygous BAP1 pathogenic mutation (NM_004656.3 BAP1 c.102_109del; p.D34Efs*32). The section shows an intradermal proliferation composed largely of epithelioid melanocytes with round to oval nuclei, abundant glassy cytoplasm, and haphazard maturation. There is nuclear pleomorphism and an occasional nuclear pseudoinclusion. Mitotic figures are not readily identified.
Skin lesion in BAP1 tumour predisposition syndrome. BAP1 immunohistochemistry in this skin papule reveals that the lesional melanocytes lack nuclear expression of BAP1.
A: epithelioid
Back Extra: BAP1 Tumor Predisposition Syndrome
- Clinical: BAP1 tumor predisposition syndrome is associated with increased risks of uveal melanoma, mesothelioma, cutaneous melanoma, renal cell carcinoma, and other malignancies. Up to 85% of patients develop malignancy by age 65.
- Micro: Clear cell renal cell carcinomas (CCRCCs) in BAP1 tumor predisposition syndrome show typical morphological features and a complete loss of BAP1 immunoreactivity in the tumor nuclei, confirming a two-hit inactivation of BAP1.
- Ancillary: Diagnosis of BAP1 tumor predisposition syndrome is confirmed by identifying a germline heterozygous pathogenic variant in the BAP1 gene through molecular genetic testing.
Reference Gallery:
Clear cell renal cell carcinoma in BAP1 tumour predisposition syndrome. This tumour demonstrates typical morphological features.
Clear cell renal cell carcinoma in BAP1 tumour predisposition syndrome. Immunohistochemistry shows a complete loss of expression of BAP1 in all neoplastic cells. The non-neoplastic cells demonstrate retained nuclear expression and serve as an internal positive control.
Skin lesion in BAP1 tumour predisposition syndrome. Representative section of a 7 mm irregular papule in a patient with germline heterozygous BAP1 pathogenic mutation (NM_004656.3 BAP1 c.102_109del; p.D34Efs*32). The section shows an intradermal proliferation composed largely of epithelioid melanocytes with round to oval nuclei, abundant glassy cytoplasm, and haphazard maturation. There is nuclear pleomorphism and an occasional nuclear pseudoinclusion. Mitotic figures are not readily identified.
Skin lesion in BAP1 tumour predisposition syndrome. BAP1 immunohistochemistry in this skin papule reveals that the lesional melanocytes lack nuclear expression of BAP1.

Q: In Birt-Hogg-Dube Syndrome, renal tumors characteristically exhibit mixed oncocytic and clear cell differentiation, frequently arranged in a [...].
Birt–Hogg–Dubé syndrome. Many tumours associated with Birt–Hogg–Dubé syndrome show mixed oncocytic and clear cell differentiation, sometimes in a checkerboard pattern.
A: checkerboard pattern
Back Extra: Birt-Hogg-Dube Syndrome
- Clinical: Birt-Hogg-Dube Syndrome is characterized by skin lesions (fibrofolliculomas, trichodiscomas, and acrochordons), lung cysts, and renal tumours, with a 15–30% increased risk of developing renal tumours.
- Micro: BHD-related renal tumours show a range of morphologies but commonly exhibit oncocytic and clear cell differentiation, with a potential for mixed patterns.
- Ancillary: Immunohistochemistry for PAX8 is positive in all tumours, while CK7 highlights clear cells and is negative in oncocytic cells. Genetic testing for FLCN mutations is essential for diagnosis.
Reference Gallery:
Birt–Hogg–Dubé syndrome. The renal tumours are usually well circumscribed, with a pale to tan colour.
Birt–Hogg–Dubé syndrome. Oncocytosis indicated by small groups of oncocytic or clear cells in the otherwise non-neoplastic kidney.
Birt–Hogg–Dubé syndrome. Cells resembling chromophobes may be positive for MOC31.
Birt–Hogg–Dubé syndrome. Many tumours associated with Birt–Hogg–Dubé syndrome show mixed oncocytic and clear cell differentiation, sometimes in a checkerboard pattern.
Birt–Hogg–Dubé syndrome. Hale colloidal iron usually only stains individual cells resembling those of chromophobe renal cell carcinoma.
Birt–Hogg–Dubé syndrome. Immunohistochemistry for CK7 highlights the clear cells but is commonly negative in the oncocytic cells.
Birt–Hogg–Dubé syndrome. BerEP4 immunohistochemistry.

Q: When evaluating renal tumors in Birt-Hogg-Dube Syndrome, CK7 immunohistochemistry characteristically highlights the [...], while remaining negative in the oncocytic cells.
Birt–Hogg–Dubé syndrome. Immunohistochemistry for CK7 highlights the clear cells but is commonly negative in the oncocytic cells.
A: clear cells
Back Extra: Birt-Hogg-Dube Syndrome
- Clinical: Birt-Hogg-Dube Syndrome is characterized by skin lesions (fibrofolliculomas, trichodiscomas, and acrochordons), lung cysts, and renal tumours, with a 15–30% increased risk of developing renal tumours.
- Micro: BHD-related renal tumours show a range of morphologies but commonly exhibit oncocytic and clear cell differentiation, with a potential for mixed patterns.
- Ancillary: Immunohistochemistry for PAX8 is positive in all tumours, while CK7 highlights clear cells and is negative in oncocytic cells. Genetic testing for FLCN mutations is essential for diagnosis.
Reference Gallery:
Birt–Hogg–Dubé syndrome. The renal tumours are usually well circumscribed, with a pale to tan colour.
Birt–Hogg–Dubé syndrome. Oncocytosis indicated by small groups of oncocytic or clear cells in the otherwise non-neoplastic kidney.
Birt–Hogg–Dubé syndrome. Cells resembling chromophobes may be positive for MOC31.
Birt–Hogg–Dubé syndrome. Many tumours associated with Birt–Hogg–Dubé syndrome show mixed oncocytic and clear cell differentiation, sometimes in a checkerboard pattern.
Birt–Hogg–Dubé syndrome. Hale colloidal iron usually only stains individual cells resembling those of chromophobe renal cell carcinoma.
Birt–Hogg–Dubé syndrome. Immunohistochemistry for CK7 highlights the clear cells but is commonly negative in the oncocytic cells.
Birt–Hogg–Dubé syndrome. BerEP4 immunohistochemistry.

Q: A characteristic background histologic finding in the non-neoplastic kidney of patients with Birt-Hogg-Dube Syndrome is the presence of [...], which presents as small nests of oncocytic or clear cells.
Birt–Hogg–Dubé syndrome. Oncocytosis indicated by small groups of oncocytic or clear cells in the otherwise non-neoplastic kidney.
A: oncocytosis
Back Extra: Birt-Hogg-Dube Syndrome
- Clinical: Birt-Hogg-Dube Syndrome is characterized by skin lesions (fibrofolliculomas, trichodiscomas, and acrochordons), lung cysts, and renal tumours, with a 15–30% increased risk of developing renal tumours.
- Micro: BHD-related renal tumours show a range of morphologies but commonly exhibit oncocytic and clear cell differentiation, with a potential for mixed patterns.
- Ancillary: Immunohistochemistry for PAX8 is positive in all tumours, while CK7 highlights clear cells and is negative in oncocytic cells. Genetic testing for FLCN mutations is essential for diagnosis.
Reference Gallery:
Birt–Hogg–Dubé syndrome. The renal tumours are usually well circumscribed, with a pale to tan colour.
Birt–Hogg–Dubé syndrome. Oncocytosis indicated by small groups of oncocytic or clear cells in the otherwise non-neoplastic kidney.
Birt–Hogg–Dubé syndrome. Cells resembling chromophobes may be positive for MOC31.
Birt–Hogg–Dubé syndrome. Many tumours associated with Birt–Hogg–Dubé syndrome show mixed oncocytic and clear cell differentiation, sometimes in a checkerboard pattern.
Birt–Hogg–Dubé syndrome. Hale colloidal iron usually only stains individual cells resembling those of chromophobe renal cell carcinoma.
Birt–Hogg–Dubé syndrome. Immunohistochemistry for CK7 highlights the clear cells but is commonly negative in the oncocytic cells.
Birt–Hogg–Dubé syndrome. BerEP4 immunohistochemistry.

Q: In Carney Complex, a characteristic testicular neoplasm is the [...].
Large cell calcifying Sertoli cell tumour. A tumour of the testis from a 32-year-old man with Carney complex.
A: large cell calcifying Sertoli cell tumor
Back Extra: Carney Complex
- Clinical: Carney Complex (CNC) is characterized by multifocal benign neoplasms, particularly affecting the endocrine system, gonads, heart, and skin.
- Micro: Histopathology of large cell calcifying Sertoli cell tumours (LCCSCTs) and other tumours is detailed in the relevant volumes of the WHO Classification of Tumours series.
- Ancillary: PRKAR1A gene mutations, located at 17q24.2, are the primary genetic defect in CNC, leading to constitutive activation of protein kinase A.
Reference Gallery:
Large cell calcifying Sertoli cell tumour. A tumour of the testis from a 32-year-old man with Carney complex.
PRKAR1A mutation pathway. The G protein–coupled intracellular pathways and the defect in Carney complex patients: PRKAR1A mutations result in deficient/inefficient regulatory subunits, leading to constitutional activation of C subunits (https://prkar1a.nichd.nih.gov).

Q: The primary genetic defect in Carney Complex is a mutation in the [...] gene, leading to the constitutive activation of protein kinase A.
PRKAR1A mutation pathway. The G protein–coupled intracellular pathways and the defect in Carney complex patients: PRKAR1A mutations result in deficient/inefficient regulatory subunits, leading to constitutional activation of C subunits (https://prkar1a.nichd.nih.gov).
A: PRKAR1A
Back Extra: Carney Complex
- Clinical: Carney Complex (CNC) is characterized by multifocal benign neoplasms, particularly affecting the endocrine system, gonads, heart, and skin.
- Micro: Histopathology of large cell calcifying Sertoli cell tumours (LCCSCTs) and other tumours is detailed in the relevant volumes of the WHO Classification of Tumours series.
- Ancillary: PRKAR1A gene mutations, located at 17q24.2, are the primary genetic defect in CNC, leading to constitutive activation of protein kinase A.
Reference Gallery:
Large cell calcifying Sertoli cell tumour. A tumour of the testis from a 32-year-old man with Carney complex.
PRKAR1A mutation pathway. The G protein–coupled intracellular pathways and the defect in Carney complex patients: PRKAR1A mutations result in deficient/inefficient regulatory subunits, leading to constitutional activation of C subunits (https://prkar1a.nichd.nih.gov).

Q: In Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome, patients frequently develop multiple cutaneous [...], which typically present on the trunk and are notably sensitive to cold or light touch.
Multiple cutaneous leiomyomas arising in hereditary leiomyomatosis and renal cell carcinoma syndrome. The cutaneous leiomyomas arising in this syndrome are more common on the trunk and may be clustered in a segmental distribution.
Multiple cutaneous leiomyomas arising in hereditary leiomyomatosis and renal cell carcinoma syndrome. The cutaneous leiomyomas arising in this syndrome are more common on the trunk and may be clustered in a segmental distribution.
A: leiomyomas
Back Extra: Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome
- Clinical: Cutaneous leiomyomas, which are sensitive to cold or light touch, are found in at least 75% of individuals with Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.
- Micro: Most FH-deficient uterine leiomyomas show symplastic-type nuclear atypia, multinucleation, and prominent eosinophilic nucleoli.
- Ancillary: Aberrant positive staining for 2-succinocysteine (2SC) is highly sensitive for all FH-deficient neoplasms.
Reference Gallery:
Multiple cutaneous leiomyomas arising in hereditary leiomyomatosis and renal cell carcinoma syndrome. The cutaneous leiomyomas arising in this syndrome are more common on the trunk and may be clustered in a segmental distribution.
Multiple cutaneous leiomyomas arising in hereditary leiomyomatosis and renal cell carcinoma syndrome. The cutaneous leiomyomas arising in this syndrome are more common on the trunk and may be clustered in a segmental distribution.
Hereditary leiomyomatosis and renal cell carcinoma syndrome. Fumarate hydratase–deficient phaeochromocytoma arising in the setting of hereditary leiomyomatosis and renal cell carcinoma syndrome is morphologically indistinguishable from sporadic cases.
Fumarate hydratase–deficient cutaneous leiomyoma. These leiomyomas are morphologically indistinguishable from sporadic leiomyomas.
Fumarate hydratase–deficient cutaneous leiomyoma. Negative staining for fumarate hydratase in a fumarate hydratase–deficient cutaneous leiomyoma. Positive staining in non-neoplastic cells, which acts as an internal positive control, is noted.
Fumarate hydratase–deficient cutaneous leiomyoma. Aberrant positive staining for 2-succinocysteine (2SC).
Fumarate hydratase–deficient cutaneous leiomyoma. These leiomyomas are morphologically indistinguishable from sporadic leiomyomas.
Fumarate hydratase–deficient cutaneous leiomyoma. Fumarate hydratase–deficient cutaneous leiomyoma demonstrating a loss of expression of fumarate hydratase. Fumarate hydratase immunohistochemistry may be difficult to interpret in cutaneous tumours because of admixed neural and other non-neoplastic elements.
Hereditary leiomyomatosis and renal cell carcinoma syndrome. Fumarate hydratase–deficient cutaneous leiomyoma. Aberrant expression of 2-succinocysteine (2SC).
Hereditary leiomyomatosis and renal cell carcinoma syndrome. This fumarate hydratase–deficient uterine leiomyoma shows marked stromal oedema (alveolar oedema).
Fumarate hydratase–deficient uterine leiomyoma. Symplastic-type nuclear atypia with some multinucleation.
Fumarate hydratase–deficient uterine leiomyoma. Symplastic-type nuclear atypia, multinucleation, and eosinophilic cytoplasmic inclusions.

Q: Uterine tumors associated with Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome frequently exhibit [...]-type nuclear atypia, multinucleation, and prominent eosinophilic nucleoli.
Fumarate hydratase–deficient uterine leiomyoma. Symplastic-type nuclear atypia with some multinucleation.
Fumarate hydratase–deficient uterine leiomyoma. Symplastic-type nuclear atypia, multinucleation, and eosinophilic cytoplasmic inclusions.
A: symplastic
Back Extra: Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome
- Clinical: Cutaneous leiomyomas, which are sensitive to cold or light touch, are found in at least 75% of individuals with Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.
- Micro: Most FH-deficient uterine leiomyomas show symplastic-type nuclear atypia, multinucleation, and prominent eosinophilic nucleoli.
- Ancillary: Aberrant positive staining for 2-succinocysteine (2SC) is highly sensitive for all FH-deficient neoplasms.
Reference Gallery:
Multiple cutaneous leiomyomas arising in hereditary leiomyomatosis and renal cell carcinoma syndrome. The cutaneous leiomyomas arising in this syndrome are more common on the trunk and may be clustered in a segmental distribution.
Multiple cutaneous leiomyomas arising in hereditary leiomyomatosis and renal cell carcinoma syndrome. The cutaneous leiomyomas arising in this syndrome are more common on the trunk and may be clustered in a segmental distribution.
Hereditary leiomyomatosis and renal cell carcinoma syndrome. Fumarate hydratase–deficient phaeochromocytoma arising in the setting of hereditary leiomyomatosis and renal cell carcinoma syndrome is morphologically indistinguishable from sporadic cases.
Fumarate hydratase–deficient cutaneous leiomyoma. These leiomyomas are morphologically indistinguishable from sporadic leiomyomas.
Fumarate hydratase–deficient cutaneous leiomyoma. Negative staining for fumarate hydratase in a fumarate hydratase–deficient cutaneous leiomyoma. Positive staining in non-neoplastic cells, which acts as an internal positive control, is noted.
Fumarate hydratase–deficient cutaneous leiomyoma. Aberrant positive staining for 2-succinocysteine (2SC).
Fumarate hydratase–deficient cutaneous leiomyoma. These leiomyomas are morphologically indistinguishable from sporadic leiomyomas.
Fumarate hydratase–deficient cutaneous leiomyoma. Fumarate hydratase–deficient cutaneous leiomyoma demonstrating a loss of expression of fumarate hydratase. Fumarate hydratase immunohistochemistry may be difficult to interpret in cutaneous tumours because of admixed neural and other non-neoplastic elements.
Hereditary leiomyomatosis and renal cell carcinoma syndrome. Fumarate hydratase–deficient cutaneous leiomyoma. Aberrant expression of 2-succinocysteine (2SC).
Hereditary leiomyomatosis and renal cell carcinoma syndrome. This fumarate hydratase–deficient uterine leiomyoma shows marked stromal oedema (alveolar oedema).
Fumarate hydratase–deficient uterine leiomyoma. Symplastic-type nuclear atypia with some multinucleation.
Fumarate hydratase–deficient uterine leiomyoma. Symplastic-type nuclear atypia, multinucleation, and eosinophilic cytoplasmic inclusions.

Q: In Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome, immunohistochemistry demonstrates a loss of fumarate hydratase (FH) and highly sensitive, aberrant positive staining for [...].
Fumarate hydratase–deficient cutaneous leiomyoma. Aberrant positive staining for 2-succinocysteine (2SC).
Hereditary leiomyomatosis and renal cell carcinoma syndrome. Fumarate hydratase–deficient cutaneous leiomyoma. Aberrant expression of 2-succinocysteine (2SC).
A: 2-succinocysteine (2SC)
Back Extra: Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome
- Clinical: Cutaneous leiomyomas, which are sensitive to cold or light touch, are found in at least 75% of individuals with Hereditary Leiomyomatosis and Renal Cell Carcinoma Syndrome.
- Micro: Most FH-deficient uterine leiomyomas show symplastic-type nuclear atypia, multinucleation, and prominent eosinophilic nucleoli.
- Ancillary: Aberrant positive staining for 2-succinocysteine (2SC) is highly sensitive for all FH-deficient neoplasms.
Reference Gallery:
Multiple cutaneous leiomyomas arising in hereditary leiomyomatosis and renal cell carcinoma syndrome. The cutaneous leiomyomas arising in this syndrome are more common on the trunk and may be clustered in a segmental distribution.
Multiple cutaneous leiomyomas arising in hereditary leiomyomatosis and renal cell carcinoma syndrome. The cutaneous leiomyomas arising in this syndrome are more common on the trunk and may be clustered in a segmental distribution.
Hereditary leiomyomatosis and renal cell carcinoma syndrome. Fumarate hydratase–deficient phaeochromocytoma arising in the setting of hereditary leiomyomatosis and renal cell carcinoma syndrome is morphologically indistinguishable from sporadic cases.
Fumarate hydratase–deficient cutaneous leiomyoma. These leiomyomas are morphologically indistinguishable from sporadic leiomyomas.
Fumarate hydratase–deficient cutaneous leiomyoma. Negative staining for fumarate hydratase in a fumarate hydratase–deficient cutaneous leiomyoma. Positive staining in non-neoplastic cells, which acts as an internal positive control, is noted.
Fumarate hydratase–deficient cutaneous leiomyoma. Aberrant positive staining for 2-succinocysteine (2SC).
Fumarate hydratase–deficient cutaneous leiomyoma. These leiomyomas are morphologically indistinguishable from sporadic leiomyomas.
Fumarate hydratase–deficient cutaneous leiomyoma. Fumarate hydratase–deficient cutaneous leiomyoma demonstrating a loss of expression of fumarate hydratase. Fumarate hydratase immunohistochemistry may be difficult to interpret in cutaneous tumours because of admixed neural and other non-neoplastic elements.
Hereditary leiomyomatosis and renal cell carcinoma syndrome. Fumarate hydratase–deficient cutaneous leiomyoma. Aberrant expression of 2-succinocysteine (2SC).
Hereditary leiomyomatosis and renal cell carcinoma syndrome. This fumarate hydratase–deficient uterine leiomyoma shows marked stromal oedema (alveolar oedema).
Fumarate hydratase–deficient uterine leiomyoma. Symplastic-type nuclear atypia with some multinucleation.
Fumarate hydratase–deficient uterine leiomyoma. Symplastic-type nuclear atypia, multinucleation, and eosinophilic cytoplasmic inclusions.

Q: The classic histologic architecture of tumors in Hereditary Phaeochromocytoma-Paraganglioma Syndromes consists of well-defined nests of cells surrounded by a fibrovascular network, known as a [...] pattern.
Phaeochromocytoma. A nested (Zellballen) growth pattern is seen in this phaeochromocytoma in multiple endocrine neoplasia type 2.
A: Zellballen
Back Extra: Hereditary Phaeochromocytoma-Paraganglioma Syndromes
- Clinical: Patients with Hereditary Phaeochromocytoma-Paraganglioma Syndromes may present with hypertension, tachycardia, sweating, and anxiety.
- Micro: Phaeochromocytomas in these syndromes can have a nested (Zellballen) growth pattern and may be associated with hyaline globules or oedematous stroma.
- Ancillary: Loss of SDHB immunoreactivity in tumour cells can indicate a mutation in any SDH subunit, which is a key diagnostic feature.
Reference Gallery:
Phaeochromocytoma. A nested (Zellballen) growth pattern is seen in this phaeochromocytoma in multiple endocrine neoplasia type 2.
Phaeochromocytoma. Hyaline globules in a phaeochromocytoma in the setting of multiple endocrine neoplasia type 2.
Phaeochromocytoma. Oedematous stroma in a phaeochromocytoma in the setting of von Hippel–Lindau syndrome.
Phaeochromocytoma. This phaeochromocytoma occurred in the setting of neurofibromatosis type 1. This is a typical phaeochromocytoma, but composite tumours can also occur, particularly in the setting of neurofibromatosis type 1.

Q: Microscopically, tumors in Hereditary Phaeochromocytoma-Paraganglioma Syndromes (particularly in the setting of multiple endocrine neoplasia type 2) frequently exhibit distinct intracytoplasmic [...].
Phaeochromocytoma. Hyaline globules in a phaeochromocytoma in the setting of multiple endocrine neoplasia type 2.
A: hyaline globules
Back Extra: Hereditary Phaeochromocytoma-Paraganglioma Syndromes
- Clinical: Patients with Hereditary Phaeochromocytoma-Paraganglioma Syndromes may present with hypertension, tachycardia, sweating, and anxiety.
- Micro: Phaeochromocytomas in these syndromes can have a nested (Zellballen) growth pattern and may be associated with hyaline globules or oedematous stroma.
- Ancillary: Loss of SDHB immunoreactivity in tumour cells can indicate a mutation in any SDH subunit, which is a key diagnostic feature.
Reference Gallery:
Phaeochromocytoma. A nested (Zellballen) growth pattern is seen in this phaeochromocytoma in multiple endocrine neoplasia type 2.
Phaeochromocytoma. Hyaline globules in a phaeochromocytoma in the setting of multiple endocrine neoplasia type 2.
Phaeochromocytoma. Oedematous stroma in a phaeochromocytoma in the setting of von Hippel–Lindau syndrome.
Phaeochromocytoma. This phaeochromocytoma occurred in the setting of neurofibromatosis type 1. This is a typical phaeochromocytoma, but composite tumours can also occur, particularly in the setting of neurofibromatosis type 1.

Q: Tumors occurring in the setting of Hereditary Phaeochromocytoma-Paraganglioma Syndromes (such as von Hippel-Lindau syndrome) may classically demonstrate a distinctly [...] stroma.
Phaeochromocytoma. Oedematous stroma in a phaeochromocytoma in the setting of von Hippel–Lindau syndrome.
A: edematous
Back Extra: Hereditary Phaeochromocytoma-Paraganglioma Syndromes
- Clinical: Patients with Hereditary Phaeochromocytoma-Paraganglioma Syndromes may present with hypertension, tachycardia, sweating, and anxiety.
- Micro: Phaeochromocytomas in these syndromes can have a nested (Zellballen) growth pattern and may be associated with hyaline globules or oedematous stroma.
- Ancillary: Loss of SDHB immunoreactivity in tumour cells can indicate a mutation in any SDH subunit, which is a key diagnostic feature.
Reference Gallery:
Phaeochromocytoma. A nested (Zellballen) growth pattern is seen in this phaeochromocytoma in multiple endocrine neoplasia type 2.
Phaeochromocytoma. Hyaline globules in a phaeochromocytoma in the setting of multiple endocrine neoplasia type 2.
Phaeochromocytoma. Oedematous stroma in a phaeochromocytoma in the setting of von Hippel–Lindau syndrome.
Phaeochromocytoma. This phaeochromocytoma occurred in the setting of neurofibromatosis type 1. This is a typical phaeochromocytoma, but composite tumours can also occur, particularly in the setting of neurofibromatosis type 1.

Q: In Hereditary Tumor Syndromes Associated with Homologous Recombination Pathway Mutations, patients frequently present with aggressive, advanced-stage or metastatic [...] (often demonstrating Gleason scores ≥ 8).
Tc-99m bone scan in a patient with BRCA2 mutation and prostate cancer. Homologous recombination repair–deficient tumours are overrepresented in patients presenting with advanced prostate cancer.
Prostate carcinoma. Lumbar spine metastasis from homologous recombination repair–deficient prostate carcinoma.
A: prostate cancer
Back Extra: Hereditary Tumor Syndromes Associated with Homologous Recombination Pathway Mutations
- Clinical: Tumours associated with hereditary homologous recombination pathway mutations often present more aggressively and are enriched in advanced or metastatic prostate cancer and high-risk urothelial carcinoma.
- Micro: Prostate cancer cases associated with BRCA1 and BRCA2 alterations more often have higher Gleason scores (≥ 8), higher stages, and a greater incidence of lymph node metastases.
- Ancillary: Germline mutations in BRCA1, BRCA2, ATM, and CHEK2 are identified using next-generation sequencing on patient blood samples, and tumour tissue sequencing can indicate either germline or somatic origin.
Reference Gallery:
Tc-99m bone scan in a patient with BRCA2 mutation and prostate cancer. Homologous recombination repair–deficient tumours are overrepresented in patients presenting with advanced prostate cancer.
Prostate carcinoma. Lumbar spine metastasis from homologous recombination repair–deficient prostate carcinoma.
Cell response to DNA damage with and without BRCA mutation. A Normal cell. If a normal cell incurs DNA damage, PARP binds to the site (left) and recruits DNA repair proteins. If PARP is inhibited (right), BRCA will be activated and the cell will still survive. B Cancer cell with BRCA mutation. A cell with BRCA mutation does not activate the downstream effectors, but if PARP is still functional (left), it can assist in the repair process. If a cell has BRCA mutation and PARP is inhibited (right), a synthetic lethality occurs. The cell cannot survive, and it dies. DSB, double-strand break; HR, homologous recombination; PARP, poly (ADP-ribose) polymerase; PARPi, PARP inhibitor; SSB, single-strand break.

Q: For tumors arising in Hereditary Tumor Syndromes Associated with Homologous Recombination Pathway Mutations (such as those with BRCA1 or BRCA2 alterations), therapeutic blockade of single-strand DNA repair using [...] leads to cancer cell death via synthetic lethality.
Cell response to DNA damage with and without BRCA mutation. A Normal cell. If a normal cell incurs DNA damage, PARP binds to the site (left) and recruits DNA repair proteins. If PARP is inhibited (right), BRCA will be activated and the cell will still survive. B Cancer cell with BRCA mutation. A cell with BRCA mutation does not activate the downstream effectors, but if PARP is still functional (left), it can assist in the repair process. If a cell has BRCA mutation and PARP is inhibited (right), a synthetic lethality occurs. The cell cannot survive, and it dies. DSB, double-strand break; HR, homologous recombination; PARP, poly (ADP-ribose) polymerase; PARPi, PARP inhibitor; SSB, single-strand break.
A: PARP inhibitors
Back Extra: Hereditary Tumor Syndromes Associated with Homologous Recombination Pathway Mutations
- Clinical: Tumours associated with hereditary homologous recombination pathway mutations often present more aggressively and are enriched in advanced or metastatic prostate cancer and high-risk urothelial carcinoma.
- Micro: Prostate cancer cases associated with BRCA1 and BRCA2 alterations more often have higher Gleason scores (≥ 8), higher stages, and a greater incidence of lymph node metastases.
- Ancillary: Germline mutations in BRCA1, BRCA2, ATM, and CHEK2 are identified using next-generation sequencing on patient blood samples, and tumour tissue sequencing can indicate either germline or somatic origin.
Reference Gallery:
Tc-99m bone scan in a patient with BRCA2 mutation and prostate cancer. Homologous recombination repair–deficient tumours are overrepresented in patients presenting with advanced prostate cancer.
Prostate carcinoma. Lumbar spine metastasis from homologous recombination repair–deficient prostate carcinoma.
Cell response to DNA damage with and without BRCA mutation. A Normal cell. If a normal cell incurs DNA damage, PARP binds to the site (left) and recruits DNA repair proteins. If PARP is inhibited (right), BRCA will be activated and the cell will still survive. B Cancer cell with BRCA mutation. A cell with BRCA mutation does not activate the downstream effectors, but if PARP is still functional (left), it can assist in the repair process. If a cell has BRCA mutation and PARP is inhibited (right), a synthetic lethality occurs. The cell cannot survive, and it dies. DSB, double-strand break; HR, homologous recombination; PARP, poly (ADP-ribose) polymerase; PARPi, PARP inhibitor; SSB, single-strand break.

Q: In Succinate Dehydrogenase-Deficient Tumor Syndromes, gastrointestinal stromal tumors (GISTs) classically exhibit an epithelioid cytomorphology and a characteristic [...] or plexiform growth pattern.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumours commonly demonstrate a multilobulated or plexiform growth pattern.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. These tumours are usually epithelioid-predominant.
A: multilobulated
Back Extra: Succinate Dehydrogenase-Deficient Tumor Syndromes
- Clinical: SDH-deficient tumour syndromes are characterized by SDH-deficient phaeochromocytoma–paraganglioma, gastrointestinal stromal tumours (GIST), renal carcinoma, pituitary adenoma/PitNET, and pulmonary chondroma.
- Micro: SDH-deficient GISTs are commonly multilobulated or plexiform and more frequently show lymph node metastases.
- Ancillary: Immunohistochemistry for SDHA and SDHB can be useful to assess the pathogenicity of genetic variants of uncertain significance.
Reference Gallery:
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumours commonly demonstrate a multilobulated or plexiform growth pattern.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. These tumours are usually epithelioid-predominant.
Succinate dehydrogenase–deficient paraganglioma. Morphological clues to these tumours are inconsistent but include well-developed, almost circular nests of epithelioid cells, sometimes with pale or vacuolated cytoplasm.
Succinate dehydrogenase–deficient pituitary adenoma / PitNET. This tumour is indistinguishable morphologically from other pituitary adenomas / PitNETs.
Pulmonary chondroma. In contrast to pulmonary hamartoma, the pulmonary chondromas associated with Carney triad do not show entrapped respiratory epithelium between the lobules of cartilage and do not contain other mesenchymal elements such as fat, smooth muscle, or myxoid spindle cells.
Pulmonary chondroma. In contrast to pulmonary hamartoma, the pulmonary chondromas associated with Carney triad show a smooth contour, lacking invaginations of entrapped respiratory epithelium between cartilage.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Despite being wildtype for both KIT and PDGFRA, succinate dehydrogenase–deficient gastrointestinal stromal tumours show diffuse strong expression of DOG1 by immunohistochemistry.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Despite being wildtype for both KIT and PDGFRA, succinate dehydrogenase–deficient gastrointestinal stromal tumours show diffuse strong expression of KIT by immunohistochemistry.

Q: In Succinate Dehydrogenase-Deficient Tumor Syndromes, patients may develop pulmonary chondromas (e.g., as part of Carney triad), which can be distinguished from pulmonary hamartomas because they lack entrapped [...] between the lobules of cartilage.
Pulmonary chondroma. In contrast to pulmonary hamartoma, the pulmonary chondromas associated with Carney triad do not show entrapped respiratory epithelium between the lobules of cartilage and do not contain other mesenchymal elements such as fat, smooth muscle, or myxoid spindle cells.
Pulmonary chondroma. In contrast to pulmonary hamartoma, the pulmonary chondromas associated with Carney triad show a smooth contour, lacking invaginations of entrapped respiratory epithelium between cartilage.
A: respiratory epithelium
Back Extra: Succinate Dehydrogenase-Deficient Tumor Syndromes
- Clinical: SDH-deficient tumour syndromes are characterized by SDH-deficient phaeochromocytoma–paraganglioma, gastrointestinal stromal tumours (GIST), renal carcinoma, pituitary adenoma/PitNET, and pulmonary chondroma.
- Micro: SDH-deficient GISTs are commonly multilobulated or plexiform and more frequently show lymph node metastases.
- Ancillary: Immunohistochemistry for SDHA and SDHB can be useful to assess the pathogenicity of genetic variants of uncertain significance.
Reference Gallery:
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumours commonly demonstrate a multilobulated or plexiform growth pattern.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. These tumours are usually epithelioid-predominant.
Succinate dehydrogenase–deficient paraganglioma. Morphological clues to these tumours are inconsistent but include well-developed, almost circular nests of epithelioid cells, sometimes with pale or vacuolated cytoplasm.
Succinate dehydrogenase–deficient pituitary adenoma / PitNET. This tumour is indistinguishable morphologically from other pituitary adenomas / PitNETs.
Pulmonary chondroma. In contrast to pulmonary hamartoma, the pulmonary chondromas associated with Carney triad do not show entrapped respiratory epithelium between the lobules of cartilage and do not contain other mesenchymal elements such as fat, smooth muscle, or myxoid spindle cells.
Pulmonary chondroma. In contrast to pulmonary hamartoma, the pulmonary chondromas associated with Carney triad show a smooth contour, lacking invaginations of entrapped respiratory epithelium between cartilage.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Despite being wildtype for both KIT and PDGFRA, succinate dehydrogenase–deficient gastrointestinal stromal tumours show diffuse strong expression of DOG1 by immunohistochemistry.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Despite being wildtype for both KIT and PDGFRA, succinate dehydrogenase–deficient gastrointestinal stromal tumours show diffuse strong expression of KIT by immunohistochemistry.

Q: In Succinate Dehydrogenase-Deficient Tumor Syndromes, the associated gastrointestinal stromal tumors (GISTs) typically lack KIT and PDGFRA mutations, but surprisingly still show diffuse strong expression of [...] on immunohistochemistry.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Despite being wildtype for both KIT and PDGFRA, succinate dehydrogenase–deficient gastrointestinal stromal tumours show diffuse strong expression of DOG1 by immunohistochemistry.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Despite being wildtype for both KIT and PDGFRA, succinate dehydrogenase–deficient gastrointestinal stromal tumours show diffuse strong expression of KIT by immunohistochemistry.
A: KIT and DOG1
Back Extra: Succinate Dehydrogenase-Deficient Tumor Syndromes
- Clinical: SDH-deficient tumour syndromes are characterized by SDH-deficient phaeochromocytoma–paraganglioma, gastrointestinal stromal tumours (GIST), renal carcinoma, pituitary adenoma/PitNET, and pulmonary chondroma.
- Micro: SDH-deficient GISTs are commonly multilobulated or plexiform and more frequently show lymph node metastases.
- Ancillary: Immunohistochemistry for SDHA and SDHB can be useful to assess the pathogenicity of genetic variants of uncertain significance.
Reference Gallery:
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. The tumours commonly demonstrate a multilobulated or plexiform growth pattern.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. These tumours are usually epithelioid-predominant.
Succinate dehydrogenase–deficient paraganglioma. Morphological clues to these tumours are inconsistent but include well-developed, almost circular nests of epithelioid cells, sometimes with pale or vacuolated cytoplasm.
Succinate dehydrogenase–deficient pituitary adenoma / PitNET. This tumour is indistinguishable morphologically from other pituitary adenomas / PitNETs.
Pulmonary chondroma. In contrast to pulmonary hamartoma, the pulmonary chondromas associated with Carney triad do not show entrapped respiratory epithelium between the lobules of cartilage and do not contain other mesenchymal elements such as fat, smooth muscle, or myxoid spindle cells.
Pulmonary chondroma. In contrast to pulmonary hamartoma, the pulmonary chondromas associated with Carney triad show a smooth contour, lacking invaginations of entrapped respiratory epithelium between cartilage.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Despite being wildtype for both KIT and PDGFRA, succinate dehydrogenase–deficient gastrointestinal stromal tumours show diffuse strong expression of DOG1 by immunohistochemistry.
Succinate dehydrogenase–deficient gastrointestinal stromal tumour. Despite being wildtype for both KIT and PDGFRA, succinate dehydrogenase–deficient gastrointestinal stromal tumours show diffuse strong expression of KIT by immunohistochemistry.

Q: In Tuberous Sclerosis, patients frequently develop a characteristic triphasic renal tumor known as an [...] (a type of PEComa), which is composed of abnormal blood vessels, smooth muscle, and adipose tissue.
PEComa (angiomyolipoma). PEComa arising in the soft tissue adjacent to the kidney in a patient with confirmed tuberous sclerosis.
A: angiomyolipoma
Back Extra: Tuberous Sclerosis
- Clinical: Tuberous sclerosis is a multisystem disorder that can affect any organ, leading to neurological disorders, developmental delay, epilepsy, and renal lesions.
- Micro: Angiomyolipomas in tuberous sclerosis are characterized by abnormal vessels, smooth muscle cells, and adipose tissue.
- Ancillary: Most patients with tuberous sclerosis have demonstrable germline mutations in either TSC1 or TSC2, and mTOR pathway upregulation is a key therapeutic target.
Reference Gallery:
PEComa (angiomyolipoma). PEComa arising in the soft tissue adjacent to the kidney in a patient with confirmed tuberous sclerosis.
Oncocytoma. A renal oncocytoma-like tumour 15 mm in diameter arising in a patient with confirmed tuberous sclerosis.
Oncocytoma. A renal oncocytoma-like tumour arising in a patient with confirmed tuberous sclerosis.

Q: Patients with [...] (a syndrome caused by germline mutations in TSC1 or TSC2) may develop renal oncocytoma-like tumors in addition to more classic angiomyolipomas.
Oncocytoma. A renal oncocytoma-like tumour 15 mm in diameter arising in a patient with confirmed tuberous sclerosis.
Oncocytoma. A renal oncocytoma-like tumour arising in a patient with confirmed tuberous sclerosis.
A: Tuberous Sclerosis
Back Extra: Tuberous Sclerosis
- Clinical: Tuberous sclerosis is a multisystem disorder that can affect any organ, leading to neurological disorders, developmental delay, epilepsy, and renal lesions.
- Micro: Angiomyolipomas in tuberous sclerosis are characterized by abnormal vessels, smooth muscle cells, and adipose tissue.
- Ancillary: Most patients with tuberous sclerosis have demonstrable germline mutations in either TSC1 or TSC2, and mTOR pathway upregulation is a key therapeutic target.
Reference Gallery:
PEComa (angiomyolipoma). PEComa arising in the soft tissue adjacent to the kidney in a patient with confirmed tuberous sclerosis.
Oncocytoma. A renal oncocytoma-like tumour 15 mm in diameter arising in a patient with confirmed tuberous sclerosis.
Oncocytoma. A renal oncocytoma-like tumour arising in a patient with confirmed tuberous sclerosis.

Q: The gross finding of multiple bilateral renal cysts alongside multicentric, early-onset clear cell renal cell carcinomas is the classic renal presentation of [...].
Von Hippel–Lindau syndrome. Gross image of a kidney from a patient with known von Hippel–Lindau syndrome. There are multiple cystic lesions as well as solid areas of clear cell renal cell carcinoma.
A: Von Hippel-Lindau Syndrome
Back Extra: Von Hippel-Lindau Syndrome
- Clinical: Patients with Von Hippel-Lindau Syndrome often develop multiple bilateral renal cysts and clear cell renal cell carcinoma (CCRCC), with RCCs manifesting at a younger age compared to sporadic cases.
- Micro: Renal cysts in VHL are lined by clear cells with low-grade nuclei, and RCCs are typically of the clear cell type, morphologically indistinguishable from sporadic CCRCC.
- Ancillary: The VHL gene is located on chromosome 3p25.3, and loss of the p arm of chromosome 3 in CCRCC serves as a potential diagnostic marker.
Reference Gallery:
Von Hippel–Lindau syndrome. Gross image of a kidney from a patient with known von Hippel–Lindau syndrome. There are multiple cystic lesions as well as solid areas of clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. A cystic lesion in the kidney in a patient with von Hippel–Lindau syndrome. Although this bears a superficial resemblance to clear cell papillary renal cell tumour, this is best considered a precursor lesion to clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. Clear cell renal cell carcinoma arising in von Hippel–Lindau syndrome. This tumour is morphologically indistinguishable from sporadic clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. Clear cell renal cell carcinoma in von Hippel–Lindau syndrome showing areas that resemble clear cell papillary renal cell tumour. These areas may show a tubulopapillary growth pattern, papillary tufting, and apically located nuclei.

Q: In Von Hippel-Lindau Syndrome, the characteristic multiple renal cysts are typically lined by low-grade clear cells and act as precursor lesions to [...].
Von Hippel–Lindau syndrome. A cystic lesion in the kidney in a patient with von Hippel–Lindau syndrome. Although this bears a superficial resemblance to clear cell papillary renal cell tumour, this is best considered a precursor lesion to clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. Clear cell renal cell carcinoma arising in von Hippel–Lindau syndrome. This tumour is morphologically indistinguishable from sporadic clear cell renal cell carcinoma.
A: clear cell renal cell carcinoma
Back Extra: Von Hippel-Lindau Syndrome
- Clinical: Patients with Von Hippel-Lindau Syndrome often develop multiple bilateral renal cysts and clear cell renal cell carcinoma (CCRCC), with RCCs manifesting at a younger age compared to sporadic cases.
- Micro: Renal cysts in VHL are lined by clear cells with low-grade nuclei, and RCCs are typically of the clear cell type, morphologically indistinguishable from sporadic CCRCC.
- Ancillary: The VHL gene is located on chromosome 3p25.3, and loss of the p arm of chromosome 3 in CCRCC serves as a potential diagnostic marker.
Reference Gallery:
Von Hippel–Lindau syndrome. Gross image of a kidney from a patient with known von Hippel–Lindau syndrome. There are multiple cystic lesions as well as solid areas of clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. A cystic lesion in the kidney in a patient with von Hippel–Lindau syndrome. Although this bears a superficial resemblance to clear cell papillary renal cell tumour, this is best considered a precursor lesion to clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. Clear cell renal cell carcinoma arising in von Hippel–Lindau syndrome. This tumour is morphologically indistinguishable from sporadic clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. Clear cell renal cell carcinoma in von Hippel–Lindau syndrome showing areas that resemble clear cell papillary renal cell tumour. These areas may show a tubulopapillary growth pattern, papillary tufting, and apically located nuclei.

Q: In Von Hippel-Lindau Syndrome, some areas of the associated carcinomas may exhibit a tubulopapillary growth pattern and apically located nuclei, histologically mimicking a sporadic [...].
Von Hippel–Lindau syndrome. Clear cell renal cell carcinoma in von Hippel–Lindau syndrome showing areas that resemble clear cell papillary renal cell tumour. These areas may show a tubulopapillary growth pattern, papillary tufting, and apically located nuclei.
A: clear cell papillary renal cell tumor
Back Extra: Von Hippel-Lindau Syndrome
- Clinical: Patients with Von Hippel-Lindau Syndrome often develop multiple bilateral renal cysts and clear cell renal cell carcinoma (CCRCC), with RCCs manifesting at a younger age compared to sporadic cases.
- Micro: Renal cysts in VHL are lined by clear cells with low-grade nuclei, and RCCs are typically of the clear cell type, morphologically indistinguishable from sporadic CCRCC.
- Ancillary: The VHL gene is located on chromosome 3p25.3, and loss of the p arm of chromosome 3 in CCRCC serves as a potential diagnostic marker.
Reference Gallery:
Von Hippel–Lindau syndrome. Gross image of a kidney from a patient with known von Hippel–Lindau syndrome. There are multiple cystic lesions as well as solid areas of clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. A cystic lesion in the kidney in a patient with von Hippel–Lindau syndrome. Although this bears a superficial resemblance to clear cell papillary renal cell tumour, this is best considered a precursor lesion to clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. Clear cell renal cell carcinoma arising in von Hippel–Lindau syndrome. This tumour is morphologically indistinguishable from sporadic clear cell renal cell carcinoma.
Von Hippel–Lindau syndrome. Clear cell renal cell carcinoma in von Hippel–Lindau syndrome showing areas that resemble clear cell papillary renal cell tumour. These areas may show a tubulopapillary growth pattern, papillary tufting, and apically located nuclei.

Q: Microscopically, Choriocarcinoma characteristically shows a biphasic appearance consisting of mononucleated cytotrophoblasts and multinucleated [...] set in a markedly hemorrhagic and necrotic background.
Choriocarcinoma. Haemorrhagic tumour with a biphasic population of cells composed of mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts.
Choriocarcinoma. Haemorrhage and cyst formation with viable tumour showing capping of cytotrophoblasts with syncytiotrophoblasts.
A: syncytiotrophoblasts
Back Extra: Choriocarcinoma
- Clinical: Choriocarcinoma is often diagnosed with disseminated metastasis, commonly involving the lungs, brain, and liver, and is associated with high serum hCG levels (> 50,000 IU/L).
- Micro: Microscopically, choriocarcinoma shows a biphasic appearance with mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts in a necrotic and haemorrhagic background.
- Ancillary: Immunohistochemistry shows strong positivity for hCG, GATA3, and inhibin in syncytiotrophoblasts, and SALL4 and p63 in cytotrophoblasts.
Reference Gallery:
Choriocarcinoma. Pleomorphic tumour cells with clear cytoplasm.
Choriocarcinoma. Haemorrhagic tumour with a biphasic population of cells composed of mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts.
Choriocarcinoma. Haemorrhage and cyst formation with viable tumour showing capping of cytotrophoblasts with syncytiotrophoblasts.
Choriocarcinoma. Clusters of syncytiotrophoblasts lying within vascular spaces. Prominent cytoplasmic vacuolation and lacunae with red blood cells are present.
Choriocarcinoma. Monophasic appearance with an abundance of cytotrophoblasts and only rare syncytiotrophoblasts.
Choriocarcinoma. GATA3 nuclear positivity in trophoblastic cells.
Mixed germ cell tumour with choriocarcinoma. Well-circumscribed tumour with prominent haemorrhagic areas.

Q: A markedly hemorrhagic and necrotic tumor composed of pleomorphic trophoblastic cells that is often associated with widely disseminated metastasis and serum hCG levels > 50,000 IU/L is classic for [...].
Mixed germ cell tumour with choriocarcinoma. Well-circumscribed tumour with prominent haemorrhagic areas.
Choriocarcinoma. Haemorrhagic tumour with a biphasic population of cells composed of mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts.
A: Choriocarcinoma
Back Extra: Choriocarcinoma
- Clinical: Choriocarcinoma is often diagnosed with disseminated metastasis, commonly involving the lungs, brain, and liver, and is associated with high serum hCG levels (> 50,000 IU/L).
- Micro: Microscopically, choriocarcinoma shows a biphasic appearance with mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts in a necrotic and haemorrhagic background.
- Ancillary: Immunohistochemistry shows strong positivity for hCG, GATA3, and inhibin in syncytiotrophoblasts, and SALL4 and p63 in cytotrophoblasts.
Reference Gallery:
Choriocarcinoma. Pleomorphic tumour cells with clear cytoplasm.
Choriocarcinoma. Haemorrhagic tumour with a biphasic population of cells composed of mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts.
Choriocarcinoma. Haemorrhage and cyst formation with viable tumour showing capping of cytotrophoblasts with syncytiotrophoblasts.
Choriocarcinoma. Clusters of syncytiotrophoblasts lying within vascular spaces. Prominent cytoplasmic vacuolation and lacunae with red blood cells are present.
Choriocarcinoma. Monophasic appearance with an abundance of cytotrophoblasts and only rare syncytiotrophoblasts.
Choriocarcinoma. GATA3 nuclear positivity in trophoblastic cells.
Mixed germ cell tumour with choriocarcinoma. Well-circumscribed tumour with prominent haemorrhagic areas.

Q: In Choriocarcinoma, immunohistochemistry of the trophoblastic tumor cells typically demonstrates strong nuclear positivity for the transcription factor [...].
Choriocarcinoma. GATA3 nuclear positivity in trophoblastic cells.
A: GATA3
Back Extra: Choriocarcinoma
- Clinical: Choriocarcinoma is often diagnosed with disseminated metastasis, commonly involving the lungs, brain, and liver, and is associated with high serum hCG levels (> 50,000 IU/L).
- Micro: Microscopically, choriocarcinoma shows a biphasic appearance with mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts in a necrotic and haemorrhagic background.
- Ancillary: Immunohistochemistry shows strong positivity for hCG, GATA3, and inhibin in syncytiotrophoblasts, and SALL4 and p63 in cytotrophoblasts.
Reference Gallery:
Choriocarcinoma. Pleomorphic tumour cells with clear cytoplasm.
Choriocarcinoma. Haemorrhagic tumour with a biphasic population of cells composed of mononucleated cytotrophoblasts and multinucleated syncytiotrophoblasts.
Choriocarcinoma. Haemorrhage and cyst formation with viable tumour showing capping of cytotrophoblasts with syncytiotrophoblasts.
Choriocarcinoma. Clusters of syncytiotrophoblasts lying within vascular spaces. Prominent cytoplasmic vacuolation and lacunae with red blood cells are present.
Choriocarcinoma. Monophasic appearance with an abundance of cytotrophoblasts and only rare syncytiotrophoblasts.
Choriocarcinoma. GATA3 nuclear positivity in trophoblastic cells.
Mixed germ cell tumour with choriocarcinoma. Well-circumscribed tumour with prominent haemorrhagic areas.

Q: A [...] is characterized by interconnected cysts filled with eosinophilic material or blood, lined by trophoblastic cells with smudged nuclei and extensive cytoplasmic vacuolization forming lacunae.
Cystic trophoblastic tumour. Multiple interconnected cysts lined by trophoblastic cells. The cysts are often filled with eosinophilic material or blood.
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
A: cystic trophoblastic tumor
Back Extra: Cystic Trophoblastic Tumour
- Clinical: Cystic Trophoblastic Tumour (CTT) is often identified in retroperitoneal lymph node dissections after chemotherapy and can occur as part of primary testicular mixed germ cell tumours.
- Micro: CTT is characterized by cystic structures lined by trophoblastic cells with smudged nuclei and abundant eosinophilic cytoplasm, often showing cytoplasmic lacunae.
- Ancillary: CTTs are diffusely positive for GATA3 and variably positive for Inhibin, p63, and hCG.
Reference Gallery:
Cystic trophoblastic tumour. Cystic structure lined by trophoblastic cells with extensive vacuolization (lacunae).
Cystic trophoblastic tumour. Multiple interconnected cysts lined by trophoblastic cells. The cysts are often filled with eosinophilic material or blood.
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
Cystic trophoblastic tumour. The cysts are often compressed and surrounded by fibrinoid material. The cells have large vacuoles that coalesce to form lacunae. Hyaline material is usually present within and outside the cells. Often, a cord-like arrangement of trophoblastic cells is seen within the fibrinoid material.
Cystic trophoblastic tumour. Multinucleation, hyperchromasia, and nuclear atypia are common findings.

Q: In a cystic trophoblastic tumor, the trophoblast cells lining the cysts typically display abundant eosinophilic cytoplasm, clear vacuoles, and characteristic degenerating or [...] nuclei.
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
Cystic trophoblastic tumour. Multinucleation, hyperchromasia, and nuclear atypia are common findings.
A: smudged
Back Extra: Cystic Trophoblastic Tumour
- Clinical: Cystic Trophoblastic Tumour (CTT) is often identified in retroperitoneal lymph node dissections after chemotherapy and can occur as part of primary testicular mixed germ cell tumours.
- Micro: CTT is characterized by cystic structures lined by trophoblastic cells with smudged nuclei and abundant eosinophilic cytoplasm, often showing cytoplasmic lacunae.
- Ancillary: CTTs are diffusely positive for GATA3 and variably positive for Inhibin, p63, and hCG.
Reference Gallery:
Cystic trophoblastic tumour. Cystic structure lined by trophoblastic cells with extensive vacuolization (lacunae).
Cystic trophoblastic tumour. Multiple interconnected cysts lined by trophoblastic cells. The cysts are often filled with eosinophilic material or blood.
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
Cystic trophoblastic tumour. The cysts are often compressed and surrounded by fibrinoid material. The cells have large vacuoles that coalesce to form lacunae. Hyaline material is usually present within and outside the cells. Often, a cord-like arrangement of trophoblastic cells is seen within the fibrinoid material.
Cystic trophoblastic tumour. Multinucleation, hyperchromasia, and nuclear atypia are common findings.

Q: The trophoblastic cells in a cystic trophoblastic tumor frequently contain large, clear cytoplasmic vacuoles that coalesce to form extensive [...].
Cystic trophoblastic tumour. Cystic structure lined by trophoblastic cells with extensive vacuolization (lacunae).
Cystic trophoblastic tumour. The cysts are often compressed and surrounded by fibrinoid material. The cells have large vacuoles that coalesce to form lacunae. Hyaline material is usually present within and outside the cells. Often, a cord-like arrangement of trophoblastic cells is seen within the fibrinoid material.
A: lacunae
Back Extra: Cystic Trophoblastic Tumour
- Clinical: Cystic Trophoblastic Tumour (CTT) is often identified in retroperitoneal lymph node dissections after chemotherapy and can occur as part of primary testicular mixed germ cell tumours.
- Micro: CTT is characterized by cystic structures lined by trophoblastic cells with smudged nuclei and abundant eosinophilic cytoplasm, often showing cytoplasmic lacunae.
- Ancillary: CTTs are diffusely positive for GATA3 and variably positive for Inhibin, p63, and hCG.
Reference Gallery:
Cystic trophoblastic tumour. Cystic structure lined by trophoblastic cells with extensive vacuolization (lacunae).
Cystic trophoblastic tumour. Multiple interconnected cysts lined by trophoblastic cells. The cysts are often filled with eosinophilic material or blood.
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
Cystic trophoblastic tumour. The cysts are often compressed and surrounded by fibrinoid material. The cells have large vacuoles that coalesce to form lacunae. Hyaline material is usually present within and outside the cells. Often, a cord-like arrangement of trophoblastic cells is seen within the fibrinoid material.
Cystic trophoblastic tumour. Multinucleation, hyperchromasia, and nuclear atypia are common findings.

Q: Histologically, Cystic Trophoblastic Tumor is characterized by cystic structures lined by trophoblastic cells that exhibit abundant eosinophilic cytoplasm and prominent large [...] (forming lacunae).
Cystic trophoblastic tumour. Cystic structure lined by trophoblastic cells with extensive vacuolization (lacunae).
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
Cystic trophoblastic tumour. The cysts are often compressed and surrounded by fibrinoid material. The cells have large vacuoles that coalesce to form lacunae. Hyaline material is usually present within and outside the cells. Often, a cord-like arrangement of trophoblastic cells is seen within the fibrinoid material.
A: vacuoles
Back Extra: Cystic Trophoblastic Tumour
- Clinical: Cystic trophoblastic tumour (CTT) is often seen in metastatic sites after chemotherapy for germ cell tumours and can occur as part of primary testicular mixed germ cell tumours.
- Micro: CTT is characterized by cystic structures lined by trophoblastic cells with abundant eosinophilic cytoplasm and large vacuoles. The cysts often contain eosinophilic material or blood.
- Ancillary: CTTs are diffusely positive for GATA3, and variably positive for Inhibin, p63, and hCG.
Reference Gallery:
Cystic trophoblastic tumour. Cystic structure lined by trophoblastic cells with extensive vacuolization (lacunae).
Cystic trophoblastic tumour. Multiple interconnected cysts lined by trophoblastic cells. The cysts are often filled with eosinophilic material or blood.
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
Cystic trophoblastic tumour. The cysts are often compressed and surrounded by fibrinoid material. The cells have large vacuoles that coalesce to form lacunae. Hyaline material is usually present within and outside the cells. Often, a cord-like arrangement of trophoblastic cells is seen within the fibrinoid material.
Cystic trophoblastic tumour. Multinucleation, hyperchromasia, and nuclear atypia are common findings.

Q: A characteristic microscopic finding in Cystic Trophoblastic Tumor is the presence of interconnected cysts that are typically filled with blood or amorphous [...].
Cystic trophoblastic tumour. Multiple interconnected cysts lined by trophoblastic cells. The cysts are often filled with eosinophilic material or blood.
A: eosinophilic material
Back Extra: Cystic Trophoblastic Tumour
- Clinical: Cystic trophoblastic tumour (CTT) is often seen in metastatic sites after chemotherapy for germ cell tumours and can occur as part of primary testicular mixed germ cell tumours.
- Micro: CTT is characterized by cystic structures lined by trophoblastic cells with abundant eosinophilic cytoplasm and large vacuoles. The cysts often contain eosinophilic material or blood.
- Ancillary: CTTs are diffusely positive for GATA3, and variably positive for Inhibin, p63, and hCG.
Reference Gallery:
Cystic trophoblastic tumour. Cystic structure lined by trophoblastic cells with extensive vacuolization (lacunae).
Cystic trophoblastic tumour. Multiple interconnected cysts lined by trophoblastic cells. The cysts are often filled with eosinophilic material or blood.
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
Cystic trophoblastic tumour. The cysts are often compressed and surrounded by fibrinoid material. The cells have large vacuoles that coalesce to form lacunae. Hyaline material is usually present within and outside the cells. Often, a cord-like arrangement of trophoblastic cells is seen within the fibrinoid material.
Cystic trophoblastic tumour. Multinucleation, hyperchromasia, and nuclear atypia are common findings.

Q: The trophoblastic cells in Cystic Trophoblastic Tumor frequently exhibit nuclear atypia, hyperchromasia, and prominent [...] despite often having smudged or degenerating nuclei.
Cystic trophoblastic tumour. Multinucleation, hyperchromasia, and nuclear atypia are common findings.
A: multinucleation
Back Extra: Cystic Trophoblastic Tumour
- Clinical: Cystic trophoblastic tumour (CTT) is often seen in metastatic sites after chemotherapy for germ cell tumours and can occur as part of primary testicular mixed germ cell tumours.
- Micro: CTT is characterized by cystic structures lined by trophoblastic cells with abundant eosinophilic cytoplasm and large vacuoles. The cysts often contain eosinophilic material or blood.
- Ancillary: CTTs are diffusely positive for GATA3, and variably positive for Inhibin, p63, and hCG.
Reference Gallery:
Cystic trophoblastic tumour. Cystic structure lined by trophoblastic cells with extensive vacuolization (lacunae).
Cystic trophoblastic tumour. Multiple interconnected cysts lined by trophoblastic cells. The cysts are often filled with eosinophilic material or blood.
Cystic trophoblastic tumour. The trophoblast cells lining the cysts have abundant eosinophilic cytoplasm with large clear vacuoles. The nuclei appear smudged and degenerating. The cell boundaries are well demarcated.
Cystic trophoblastic tumour. The cysts are often compressed and surrounded by fibrinoid material. The cells have large vacuoles that coalesce to form lacunae. Hyaline material is usually present within and outside the cells. Often, a cord-like arrangement of trophoblastic cells is seen within the fibrinoid material.
Cystic trophoblastic tumour. Multinucleation, hyperchromasia, and nuclear atypia are common findings.

Q: The key diagnostic microscopic features of [...] include large, highly pleomorphic epithelioid cells with vesicular nuclei, macronucleoli, and dense amphophilic cytoplasm arranged in solid, glandular, or papillary patterns.
Embryonal carcinoma. Glandular pattern.
Embryonal carcinoma. Papillary pattern with thick and thin papillae. Some areas resemble yolk sac tumour, but the larger cell size supports this being embryonal carcinoma; immunohistochemistry can be performed for confirmation.
Embryonal carcinoma. High-power view showing highly pleomorphic cells with mitoses and necrosis.
A: embryonal carcinoma
Back Extra: Embryonal Carcinoma
- Clinical: Embryonal carcinoma is the second most prevalent germ cell tumour of the testis, accounting for 4–16% of cases in pure form, and is most common in people aged 15–34 years.
- Micro: Key diagnostic features include large pleomorphic epithelioid cells with vesicular nuclei, macronucleoli, and dense amphophilic cytoplasm, often in solid, glandular, or papillary patterns.
- Ancillary: Embryonal carcinomas consistently express CD30 (membrane), OCT3/4 (nuclear), SALL4, and AE1/AE3, and may show i(12p) or overrepresentation of chromosome 12p.
Reference Gallery:
Embryonal carcinoma. Glandular pattern.
Embryonal carcinoma. Papillary pattern with thick and thin papillae. Some areas resemble yolk sac tumour, but the larger cell size supports this being embryonal carcinoma; immunohistochemistry can be performed for confirmation.
Embryonal carcinoma. Solid pattern showing neoplastic stroma with atypia and mitoses (left) and non-neoplastic stroma (upper right).
Embryonal carcinoma. Small nests of embryonal carcinoma among widespread necrosis. Syncytiotrophoblastic giant cells are seen (right).
Embryonal carcinoma. High-power view showing highly pleomorphic cells with mitoses and necrosis.
Embryonal carcinoma. Solid pattern with packed highly pleomorphic cells.
Embryonal carcinoma. Immunohistochemistry for CD30 showing strong membranous staining in embryonal carcinoma.
Embryonal carcinoma. Vascular invasion.
Embryonal carcinoma. Solid tumour with cysts and haemorrhage.

Q: A hallmark immunohistochemical feature of embryonal carcinoma is strong membranous expression of [...], which helps distinguish it from other germ cell tumors alongside nuclear OCT3/4 and SALL4 positivity.
Embryonal carcinoma. Immunohistochemistry for CD30 showing strong membranous staining in embryonal carcinoma.
A: CD30
Back Extra: Embryonal Carcinoma
- Clinical: Embryonal carcinoma is the second most prevalent germ cell tumour of the testis, accounting for 4–16% of cases in pure form, and is most common in people aged 15–34 years.
- Micro: Key diagnostic features include large pleomorphic epithelioid cells with vesicular nuclei, macronucleoli, and dense amphophilic cytoplasm, often in solid, glandular, or papillary patterns.
- Ancillary: Embryonal carcinomas consistently express CD30 (membrane), OCT3/4 (nuclear), SALL4, and AE1/AE3, and may show i(12p) or overrepresentation of chromosome 12p.
Reference Gallery:
Embryonal carcinoma. Glandular pattern.
Embryonal carcinoma. Papillary pattern with thick and thin papillae. Some areas resemble yolk sac tumour, but the larger cell size supports this being embryonal carcinoma; immunohistochemistry can be performed for confirmation.
Embryonal carcinoma. Solid pattern showing neoplastic stroma with atypia and mitoses (left) and non-neoplastic stroma (upper right).
Embryonal carcinoma. Small nests of embryonal carcinoma among widespread necrosis. Syncytiotrophoblastic giant cells are seen (right).
Embryonal carcinoma. High-power view showing highly pleomorphic cells with mitoses and necrosis.
Embryonal carcinoma. Solid pattern with packed highly pleomorphic cells.
Embryonal carcinoma. Immunohistochemistry for CD30 showing strong membranous staining in embryonal carcinoma.
Embryonal carcinoma. Vascular invasion.
Embryonal carcinoma. Solid tumour with cysts and haemorrhage.

Q: Frequent vascular invasion and a gross appearance showing a solid tumor with cysts, widespread necrosis, and prominent hemorrhage are characteristic features of [...].
Embryonal carcinoma. Small nests of embryonal carcinoma among widespread necrosis. Syncytiotrophoblastic giant cells are seen (right).
Embryonal carcinoma. Vascular invasion.
Embryonal carcinoma. Solid tumour with cysts and haemorrhage.
A: embryonal carcinoma
Back Extra: Embryonal Carcinoma
- Clinical: Embryonal carcinoma is the second most prevalent germ cell tumour of the testis, accounting for 4–16% of cases in pure form, and is most common in people aged 15–34 years.
- Micro: Key diagnostic features include large pleomorphic epithelioid cells with vesicular nuclei, macronucleoli, and dense amphophilic cytoplasm, often in solid, glandular, or papillary patterns.
- Ancillary: Embryonal carcinomas consistently express CD30 (membrane), OCT3/4 (nuclear), SALL4, and AE1/AE3, and may show i(12p) or overrepresentation of chromosome 12p.
Reference Gallery:
Embryonal carcinoma. Glandular pattern.
Embryonal carcinoma. Papillary pattern with thick and thin papillae. Some areas resemble yolk sac tumour, but the larger cell size supports this being embryonal carcinoma; immunohistochemistry can be performed for confirmation.
Embryonal carcinoma. Solid pattern showing neoplastic stroma with atypia and mitoses (left) and non-neoplastic stroma (upper right).
Embryonal carcinoma. Small nests of embryonal carcinoma among widespread necrosis. Syncytiotrophoblastic giant cells are seen (right).
Embryonal carcinoma. High-power view showing highly pleomorphic cells with mitoses and necrosis.
Embryonal carcinoma. Solid pattern with packed highly pleomorphic cells.
Embryonal carcinoma. Immunohistochemistry for CD30 showing strong membranous staining in embryonal carcinoma.
Embryonal carcinoma. Vascular invasion.
Embryonal carcinoma. Solid tumour with cysts and haemorrhage.

Q: Microscopically, epithelioid trophoblastic tumor is characteristically composed of cohesive nests of [...]-appearing cells exhibiting prominent apoptosis and necrosis.
Epithelioid trophoblastic tumour. Cohesive groups of squamoid cells with areas of necrosis and apoptosis.
Epithelioid trophoblastic tumour. The squamoid tumour cells are pleomorphic and often multinucleated; the nuclei contain prominent nucleoli. The cells contain hyaline globules and show prominent apoptosis and necrosis. Mitotic figures are easily identified.
A: squamoid
Back Extra: Epithelioid Trophoblastic Tumour
- Clinical: Epithelioid Trophoblastic Tumour (ETT) is a rare malignant neoplasm, with only 5 cases reported in men, often presenting as metastases or in mixed germ cell tumours.
- Micro: ETTs show cohesive nests of squamoid-appearing cells with pleomorphic, hyperchromatic nuclei, prominent nucleoli, and abundant pink cytoplasm.
- Ancillary: ETTs are positive for inhibin, GATA3, p63, and PLAP, and may express hCG. hPL staining is typically focal.
Reference Gallery:
Epithelioid trophoblastic tumour. Cohesive groups of squamoid cells with areas of necrosis and apoptosis.
Epithelioid trophoblastic tumour. The squamoid tumour cells are pleomorphic and often multinucleated; the nuclei contain prominent nucleoli. The cells contain hyaline globules and show prominent apoptosis and necrosis. Mitotic figures are easily identified.
Epithelioid trophoblastic tumour. p63 expression in trophoblastic tumour cells suggests chorion laeve–type intermediate trophoblastic cells.

Q: In epithelioid trophoblastic tumor, the neoplastic cells typically show strong nuclear expression for the immunohistochemical marker [...], suggesting a chorion laeve–type intermediate trophoblastic origin.
Epithelioid trophoblastic tumour. p63 expression in trophoblastic tumour cells suggests chorion laeve–type intermediate trophoblastic cells.
A: p63
Back Extra: Epithelioid Trophoblastic Tumour
- Clinical: Epithelioid Trophoblastic Tumour (ETT) is a rare malignant neoplasm, with only 5 cases reported in men, often presenting as metastases or in mixed germ cell tumours.
- Micro: ETTs show cohesive nests of squamoid-appearing cells with pleomorphic, hyperchromatic nuclei, prominent nucleoli, and abundant pink cytoplasm.
- Ancillary: ETTs are positive for inhibin, GATA3, p63, and PLAP, and may express hCG. hPL staining is typically focal.
Reference Gallery:
Epithelioid trophoblastic tumour. Cohesive groups of squamoid cells with areas of necrosis and apoptosis.
Epithelioid trophoblastic tumour. The squamoid tumour cells are pleomorphic and often multinucleated; the nuclei contain prominent nucleoli. The cells contain hyaline globules and show prominent apoptosis and necrosis. Mitotic figures are easily identified.
Epithelioid trophoblastic tumour. p63 expression in trophoblastic tumour cells suggests chorion laeve–type intermediate trophoblastic cells.

Q: In Germ Cell Neoplasia in Situ, atypical cells resembling gonocytes with ample clear cytoplasm and large angulated nuclei are characteristically located along the basement membrane in the [...].
Germ cell neoplasia in situ. Seminiferous tubules, most showing germ cell neoplasia in situ arranged as atypical gonocytes in the spermatogonial niche.
A: spermatogonial niche
Back Extra: Germ Cell Neoplasia in Situ
- Clinical: Adults with isolated Germ Cell Neoplasia in Situ (GCNIS) are usually symptomless or present with mild testicular pain and relatively small testes (6–12 mL).
- Micro: GCNIS consists of atypical cells resembling gonocytes with ample clear cytoplasm and large angulated nuclei, typically located in the spermatogonial niche.
- Ancillary: The immunoprofiles of gonocytes, GCNIS, and seminoma are similar, with key markers including PLAP, OCT4, and KIT (CD117).
Reference Gallery:
Germ cell neoplasia in situ. Seminiferous tubules, most showing germ cell neoplasia in situ arranged as atypical gonocytes in the spermatogonial niche.
Germ cell neoplasia in situ. Immunochemistry for PLAP. Germ cell neoplasia in situ cells are seen largely in the spermatogonial niche. Note the PLAP-positive smooth muscle.
Germ cell neoplasia in situ. Immunochemistry for KIT (CD117) showing membranous positivity in germ cell neoplasia in situ cells.
Germ cell neoplasia in situ. Immunochemistry for OCT4 showing strong nuclear positivity of germ cell neoplasia in situ cells.

Q: The atypical cells of Germ Cell Neoplasia in Situ share an immunoprofile with classic seminoma, demonstrating positivity for PLAP, membranous KIT (CD117), and strong nuclear expression of [...].
Germ cell neoplasia in situ. Immunochemistry for PLAP. Germ cell neoplasia in situ cells are seen largely in the spermatogonial niche. Note the PLAP-positive smooth muscle.
Germ cell neoplasia in situ. Immunochemistry for KIT (CD117) showing membranous positivity in germ cell neoplasia in situ cells.
Germ cell neoplasia in situ. Immunochemistry for OCT4 showing strong nuclear positivity of germ cell neoplasia in situ cells.
A: OCT4
Back Extra: Germ Cell Neoplasia in Situ
- Clinical: Adults with isolated Germ Cell Neoplasia in Situ (GCNIS) are usually symptomless or present with mild testicular pain and relatively small testes (6–12 mL).
- Micro: GCNIS consists of atypical cells resembling gonocytes with ample clear cytoplasm and large angulated nuclei, typically located in the spermatogonial niche.
- Ancillary: The immunoprofiles of gonocytes, GCNIS, and seminoma are similar, with key markers including PLAP, OCT4, and KIT (CD117).
Reference Gallery:
Germ cell neoplasia in situ. Seminiferous tubules, most showing germ cell neoplasia in situ arranged as atypical gonocytes in the spermatogonial niche.
Germ cell neoplasia in situ. Immunochemistry for PLAP. Germ cell neoplasia in situ cells are seen largely in the spermatogonial niche. Note the PLAP-positive smooth muscle.
Germ cell neoplasia in situ. Immunochemistry for KIT (CD117) showing membranous positivity in germ cell neoplasia in situ cells.
Germ cell neoplasia in situ. Immunochemistry for OCT4 showing strong nuclear positivity of germ cell neoplasia in situ cells.

Q: [...] is a pre-invasive lesion consisting of atypical, clear-cytoplasm gonocytes located in the spermatogonial niche that typically express OCT4, PLAP, and KIT (CD117).
Germ cell neoplasia in situ. Seminiferous tubules, most showing germ cell neoplasia in situ arranged as atypical gonocytes in the spermatogonial niche.
Germ cell neoplasia in situ. Immunochemistry for OCT4 showing strong nuclear positivity of germ cell neoplasia in situ cells.
A: Germ Cell Neoplasia in Situ
Back Extra: Germ Cell Neoplasia in Situ
- Clinical: Adults with isolated Germ Cell Neoplasia in Situ (GCNIS) are usually symptomless or present with mild testicular pain and relatively small testes (6–12 mL).
- Micro: GCNIS consists of atypical cells resembling gonocytes with ample clear cytoplasm and large angulated nuclei, typically located in the spermatogonial niche.
- Ancillary: The immunoprofiles of gonocytes, GCNIS, and seminoma are similar, with key markers including PLAP, OCT4, and KIT (CD117).
Reference Gallery:
Germ cell neoplasia in situ. Seminiferous tubules, most showing germ cell neoplasia in situ arranged as atypical gonocytes in the spermatogonial niche.
Germ cell neoplasia in situ. Immunochemistry for PLAP. Germ cell neoplasia in situ cells are seen largely in the spermatogonial niche. Note the PLAP-positive smooth muscle.
Germ cell neoplasia in situ. Immunochemistry for KIT (CD117) showing membranous positivity in germ cell neoplasia in situ cells.
Germ cell neoplasia in situ. Immunochemistry for OCT4 showing strong nuclear positivity of germ cell neoplasia in situ cells.

Q: Regarding Specific Forms of Intratubular Germ Cell Neoplasia, [...] is microscopically characterized by enlarged seminiferous tubules filled with neoplastic cells that entirely displace normal Sertoli cells.
Intratubular seminoma. Seminiferous tubules are enlarged and filled with cells identical to invasive seminoma. Sertoli cells are not seen. This area was adjacent to an invasive seminoma.
A: intratubular seminoma
Q: Specific Forms of Intratubular Germ Cell Neoplasia
- Clinical: Because [...] only exceptionally occurs without invasive tumours, there are no specific clinical features.
- Micro: Intratubular seminoma is characterized by seminiferous tubules filled with cells identical to invasive seminoma, displacing Sertoli cells and often surrounded by lymphocytic infiltrates.
- Ancillary: Intratubular embryonal carcinoma is positive for [...], although immature Sertoli cells may also be falsely positive.
Reference Gallery:
Embryonal carcinoma. Intratubular spread of embryonal carcinoma with central comedonecrosis.
Intratubular seminoma. Seminiferous tubules are enlarged and filled with cells identical to invasive seminoma. Sertoli cells are not seen. This area was adjacent to an invasive seminoma.
Intratubular embryonal carcinoma and germ cell neoplasia in situ. KIT (CD117) staining in germ cell neoplasia in situ (left) and pleomorphic intratubular cells of intratubular embryonal carcinoma (right).
Intratubular germ cell neoplasia. Seminiferous tubule with a syncytiotrophoblastic cell.
A: intratubular germ cell neoplasia; CD30

Q: Among the Specific Forms of Intratubular Germ Cell Neoplasia, the intratubular spread of embryonal carcinoma may uniquely exhibit central [...] within the tubules.
Embryonal carcinoma. Intratubular spread of embryonal carcinoma with central comedonecrosis.
A: comedonecrosis
Q: Specific Forms of Intratubular Germ Cell Neoplasia
- Clinical: Because [...] only exceptionally occurs without invasive tumours, there are no specific clinical features.
- Micro: Intratubular seminoma is characterized by seminiferous tubules filled with cells identical to invasive seminoma, displacing Sertoli cells and often surrounded by lymphocytic infiltrates.
- Ancillary: Intratubular embryonal carcinoma is positive for [...], although immature Sertoli cells may also be falsely positive.
Reference Gallery:
Embryonal carcinoma. Intratubular spread of embryonal carcinoma with central comedonecrosis.
Intratubular seminoma. Seminiferous tubules are enlarged and filled with cells identical to invasive seminoma. Sertoli cells are not seen. This area was adjacent to an invasive seminoma.
Intratubular embryonal carcinoma and germ cell neoplasia in situ. KIT (CD117) staining in germ cell neoplasia in situ (left) and pleomorphic intratubular cells of intratubular embryonal carcinoma (right).
Intratubular germ cell neoplasia. Seminiferous tubule with a syncytiotrophoblastic cell.
A: intratubular germ cell neoplasia; CD30

Q: In Specific Forms of Intratubular Germ Cell Neoplasia, rare morphologic variants can be identified within the seminiferous tubules, such as the presence of a multinucleated [...].
Intratubular germ cell neoplasia. Seminiferous tubule with a syncytiotrophoblastic cell.
A: syncytiotrophoblastic cell
Q: Specific Forms of Intratubular Germ Cell Neoplasia
- Clinical: Because [...] only exceptionally occurs without invasive tumours, there are no specific clinical features.
- Micro: Intratubular seminoma is characterized by seminiferous tubules filled with cells identical to invasive seminoma, displacing Sertoli cells and often surrounded by lymphocytic infiltrates.
- Ancillary: Intratubular embryonal carcinoma is positive for [...], although immature Sertoli cells may also be falsely positive.
Reference Gallery:
Embryonal carcinoma. Intratubular spread of embryonal carcinoma with central comedonecrosis.
Intratubular seminoma. Seminiferous tubules are enlarged and filled with cells identical to invasive seminoma. Sertoli cells are not seen. This area was adjacent to an invasive seminoma.
Intratubular embryonal carcinoma and germ cell neoplasia in situ. KIT (CD117) staining in germ cell neoplasia in situ (left) and pleomorphic intratubular cells of intratubular embryonal carcinoma (right).
Intratubular germ cell neoplasia. Seminiferous tubule with a syncytiotrophoblastic cell.
A: intratubular germ cell neoplasia; CD30

Q: In Mixed Teratoma and Yolk Sac Tumor, Prepubertal-Type, the typical microscopic appearance features mucinous glands representing the teratoma set within a [...] yolk sac tumor background.
Mixed teratoma and yolk sac tumour, prepubertal-type. Mucinous glands representing teratoma in a reticular and microcytic yolk sac tumour background.
Mixed teratoma and yolk sac tumour, prepubertal-type. A mucinous gland set in a background of yolk sac tumour.
A: reticular and microcystic
Back Extra: Mixed Teratoma and Yolk Sac Tumour, Prepubertal-Type
- Clinical: Mixed Teratoma and Yolk Sac Tumour, Prepubertal-Type predominantly occurs in children aged < 6 years and is extremely rare in adults.
- Micro: YST foci in teratomas are usually small and associated with immature elements, making them easy to overlook on microscopic examination.
- Ancillary: Immunohistochemical staining for AFP (alpha-fetoprotein) and SALL4 can help identify YST components in these tumours.
Reference Gallery:
Mixed teratoma and yolk sac tumour, prepubertal-type. The prepubertal testis is replaced by a solid, pale tumour.
Mixed teratoma and yolk sac tumour, prepubertal-type. Mucinous glands representing teratoma in a reticular and microcytic yolk sac tumour background.
Mixed teratoma and yolk sac tumour, prepubertal-type. A mucinous gland set in a background of yolk sac tumour.

Q: Clinically, Mixed Teratoma and Yolk Sac Tumor, Prepubertal-Type typically presents as a solid, pale mass replacing the testis and predominantly occurs in children aged [...].
Mixed teratoma and yolk sac tumour, prepubertal-type. The prepubertal testis is replaced by a solid, pale tumour.
A: < 6 years
Back Extra: Mixed Teratoma and Yolk Sac Tumour, Prepubertal-Type
- Clinical: Mixed Teratoma and Yolk Sac Tumour, Prepubertal-Type predominantly occurs in children aged < 6 years and is extremely rare in adults.
- Micro: YST foci in teratomas are usually small and associated with immature elements, making them easy to overlook on microscopic examination.
- Ancillary: Immunohistochemical staining for AFP (alpha-fetoprotein) and SALL4 can help identify YST components in these tumours.
Reference Gallery:
Mixed teratoma and yolk sac tumour, prepubertal-type. The prepubertal testis is replaced by a solid, pale tumour.
Mixed teratoma and yolk sac tumour, prepubertal-type. Mucinous glands representing teratoma in a reticular and microcytic yolk sac tumour background.
Mixed teratoma and yolk sac tumour, prepubertal-type. A mucinous gland set in a background of yolk sac tumour.

Q: A hallmark microscopic feature of Placental Site Trophoblastic Tumor is the presence of pleomorphic trophoblastic cells exhibiting prominent [...], often leading to the near-complete destruction of the vessel wall within a fibrinoid background.
Placental site trophoblastic tumour. Pleomorphic trophoblastic cells in a fibrinoid background with prominent vascular invasion. The tumour shows a cohesive growth pattern with areas of cells growing in small clusters and singly.
Placental site trophoblastic tumour. Hyperchromatic, pleomorphic, often multinucleated tumour cells invading the vessels, with the almost complete destruction of the vessel wall.
A: vascular invasion
Back Extra: Placental Site Trophoblastic Tumour
- Clinical: Only 7 cases of testicular Placental Site Trophoblastic Tumour have been described, with a median age of 33 years.
- Micro: PSTT consists of mononucleated implantation-type intermediate trophoblastic cells with abundant eosinophilic or focally vacuolated cytoplasm, and irregular nuclei.
- Ancillary: PSTT expresses HSD3B1, inhibin, GATA3, and CK18, and is specifically positive for hPL.
Reference Gallery:
Placental site trophoblastic tumour. Pleomorphic trophoblastic cells in a fibrinoid background with prominent vascular invasion. The tumour shows a cohesive growth pattern with areas of cells growing in small clusters and singly.
Placental site trophoblastic tumour. Hyperchromatic, pleomorphic, often multinucleated tumour cells invading the vessels, with the almost complete destruction of the vessel wall.

Q: The neoplastic population in Placental Site Trophoblastic Tumor consists predominantly of mononucleated, implantation-type [...] cells characterized by abundant eosinophilic cytoplasm and irregular nuclei.
Placental site trophoblastic tumour. Pleomorphic trophoblastic cells in a fibrinoid background with prominent vascular invasion. The tumour shows a cohesive growth pattern with areas of cells growing in small clusters and singly.
A: intermediate trophoblastic
Back Extra: Placental Site Trophoblastic Tumour
- Clinical: Only 7 cases of testicular Placental Site Trophoblastic Tumour have been described, with a median age of 33 years.
- Micro: PSTT consists of mononucleated implantation-type intermediate trophoblastic cells with abundant eosinophilic or focally vacuolated cytoplasm, and irregular nuclei.
- Ancillary: PSTT expresses HSD3B1, inhibin, GATA3, and CK18, and is specifically positive for hPL.
Reference Gallery:
Placental site trophoblastic tumour. Pleomorphic trophoblastic cells in a fibrinoid background with prominent vascular invasion. The tumour shows a cohesive growth pattern with areas of cells growing in small clusters and singly.
Placental site trophoblastic tumour. Hyperchromatic, pleomorphic, often multinucleated tumour cells invading the vessels, with the almost complete destruction of the vessel wall.

Q: Grossly, a Regressed Germ Cell Tumor typically appears as a focal, well-delineated white [...] (sometimes with central hemorrhage), and these patients often paradoxically present with symptomatic metastatic disease in the retroperitoneum.
Regressed germ cell tumour. There is a well-delineated white fibrotic area with central haemorrhage. Many patients with completely regressed germ cell tumour present with retroperitoneal metastatic disease.
Regressed germ cell tumour. An irregular area of discolouration is noted. There is no definite mass lesion. Microscopy showed typical areas of regression.
A: fibrotic scar
Back Extra: Regressed Germ Cell Tumor
- Clinical: Fewer than 5% of germ cell tumours show spontaneous regression, often presenting with retroperitoneal metastatic disease and symptoms like back pain.
- Micro: The hallmark of regressed germ cell tumour is a vascularized hyaline scar with possible necrosis, lymphoplasmacytic inflammation, and tubular calcifications.
- Ancillary: Immunohistochemistry is usually not required, but it can confirm the presence of germ cell tumour in necrotic areas.
Reference Gallery:
Regressed germ cell tumour. There is a well-delineated white fibrotic area with central haemorrhage. Many patients with completely regressed germ cell tumour present with retroperitoneal metastatic disease.
Regressed germ cell tumour. Vascularized scar with lymphocytic infiltration. A few entrapped seminiferous tubules are present.
Regressed germ cell tumour. Partial regression with a small component of mature teratoma (smooth muscle and enteric-type gland) amid chronic inflammation.
Regressed germ cell tumour. An irregular area of discolouration is noted. There is no definite mass lesion. Microscopy showed typical areas of regression.
Germ cell neoplasia in situ adjacent to a regressed germ cell tumour. Area adjacent to a regressed germ cell tumour with a very focal area of germ cell neoplasia in situ (OCT4 immunohistochemistry).
Regressed germ cell tumour. A large, completely regressed germ cell tumour showing an area of necrosis with surrounding fibrous tissue.

Q: The histologic hallmark of a Regressed Germ Cell Tumor is a [...] that is often accompanied by a lymphoplasmacytic infiltrate, necrosis, and tubular calcifications.
Regressed germ cell tumour. Vascularized scar with lymphocytic infiltration. A few entrapped seminiferous tubules are present.
Regressed germ cell tumour. A large, completely regressed germ cell tumour showing an area of necrosis with surrounding fibrous tissue.
A: vascularized scar
Back Extra: Regressed Germ Cell Tumor
- Clinical: Fewer than 5% of germ cell tumours show spontaneous regression, often presenting with retroperitoneal metastatic disease and symptoms like back pain.
- Micro: The hallmark of regressed germ cell tumour is a vascularized hyaline scar with possible necrosis, lymphoplasmacytic inflammation, and tubular calcifications.
- Ancillary: Immunohistochemistry is usually not required, but it can confirm the presence of germ cell tumour in necrotic areas.
Reference Gallery:
Regressed germ cell tumour. There is a well-delineated white fibrotic area with central haemorrhage. Many patients with completely regressed germ cell tumour present with retroperitoneal metastatic disease.
Regressed germ cell tumour. Vascularized scar with lymphocytic infiltration. A few entrapped seminiferous tubules are present.
Regressed germ cell tumour. Partial regression with a small component of mature teratoma (smooth muscle and enteric-type gland) amid chronic inflammation.
Regressed germ cell tumour. An irregular area of discolouration is noted. There is no definite mass lesion. Microscopy showed typical areas of regression.
Germ cell neoplasia in situ adjacent to a regressed germ cell tumour. Area adjacent to a regressed germ cell tumour with a very focal area of germ cell neoplasia in situ (OCT4 immunohistochemistry).
Regressed germ cell tumour. A large, completely regressed germ cell tumour showing an area of necrosis with surrounding fibrous tissue.

Q: When evaluating a testis for a Regressed Germ Cell Tumor, an OCT4 immunostain can be utilized to highlight adjacent, unregressed focal areas of [...] (GCNIS).
Germ cell neoplasia in situ adjacent to a regressed germ cell tumour. Area adjacent to a regressed germ cell tumour with a very focal area of germ cell neoplasia in situ (OCT4 immunohistochemistry).
A: germ cell neoplasia in situ
Back Extra: Regressed Germ Cell Tumor
- Clinical: Fewer than 5% of germ cell tumours show spontaneous regression, often presenting with retroperitoneal metastatic disease and symptoms like back pain.
- Micro: The hallmark of regressed germ cell tumour is a vascularized hyaline scar with possible necrosis, lymphoplasmacytic inflammation, and tubular calcifications.
- Ancillary: Immunohistochemistry is usually not required, but it can confirm the presence of germ cell tumour in necrotic areas.
Reference Gallery:
Regressed germ cell tumour. There is a well-delineated white fibrotic area with central haemorrhage. Many patients with completely regressed germ cell tumour present with retroperitoneal metastatic disease.
Regressed germ cell tumour. Vascularized scar with lymphocytic infiltration. A few entrapped seminiferous tubules are present.
Regressed germ cell tumour. Partial regression with a small component of mature teratoma (smooth muscle and enteric-type gland) amid chronic inflammation.
Regressed germ cell tumour. An irregular area of discolouration is noted. There is no definite mass lesion. Microscopy showed typical areas of regression.
Germ cell neoplasia in situ adjacent to a regressed germ cell tumour. Area adjacent to a regressed germ cell tumour with a very focal area of germ cell neoplasia in situ (OCT4 immunohistochemistry).
Regressed germ cell tumour. A large, completely regressed germ cell tumour showing an area of necrosis with surrounding fibrous tissue.

Q: The classic histologic appearance of [...] consists of large uniform tumor cells with clear cytoplasm and prominent nucleoli arranged in sheets divided by fibrous septa that contain a prominent lymphocytic infiltrate.
Seminoma. Tumour cells with cytological features of distinct cytoplasmic membranes, clear cytoplasm, and nuclei with prominent nucleoli. Lymphoid infiltrate is present.
Seminoma. Classic seminoma. Sheets of tumour cells with lymphocytic infiltrates and fibrous septa.
A: Seminoma
Back Extra: Seminoma
- Clinical: Seminoma is the most common testicular germ cell tumour, typically presenting as a self-identified mass in postpubertal men with an average age of 37–41 years.
- Micro: The most prevalent growth pattern is a diffuse sheet-like arrangement with interspersed fibrous septa, large, clear, or lightly eosinophilic cytoplasm, and prominent nucleoli.
- Ancillary: Seminomas express OCT3/4, SALL4, PLAP, KIT, and SOX17, but are negative for CD30, AFP, and EMA.
Reference Gallery:
Seminoma. Tumour cells with cytological features of distinct cytoplasmic membranes, clear cytoplasm, and nuclei with prominent nucleoli. Lymphoid infiltrate is present.
Seminoma and germ cell neoplasia in situ. Germ cell neoplasia in situ adjacent to invasive seminoma.
Seminoma. Seminoma infiltrating the rete testis in a pagetoid pattern. The seminoma cells are positive for OCT4.
Seminoma. Classic seminoma. Sheets of tumour cells with lymphocytic infiltrates and fibrous septa.
Seminoma. Exuberant lymphocytic infiltrate predominates over the seminoma cells.
Seminoma. A prominent granulomatous reaction is often observed.
Seminoma. Occasional syncytiotrophoblasts are usually seen dispersed among seminoma cells.
Seminoma. hCG immunostaining highlights the syncytiotrophoblasts.
Seminoma. Seminoma, pseudoglandular. Central cellular degeneration creates spaces imparting a pseudoglandular appearance.
Seminoma. Seminoma, signet-ring cells. Many cells show vacuolation of the cytoplasm, with nuclei pushed to the side, creating a signet-ring cell appearance.
Seminoma. Seminoma, peritubular. Groups of invasive seminoma cells closely embracing the tubules (a very rare pattern).
Seminoma. Sheets of seminoma cells showing the nuclear detail. Angulated cells and prominent, often smudged, nucleoli are seen.

Q: On immunohistochemistry, the tumor cells of Seminoma classically express SALL4, PLAP, KIT, and [...], while remaining negative for CD30 and AFP.
Seminoma. Seminoma infiltrating the rete testis in a pagetoid pattern. The seminoma cells are positive for OCT4.
A: OCT3/4
Back Extra: Seminoma
- Clinical: Seminoma is the most common testicular germ cell tumour, typically presenting as a self-identified mass in postpubertal men with an average age of 37–41 years.
- Micro: The most prevalent growth pattern is a diffuse sheet-like arrangement with interspersed fibrous septa, large, clear, or lightly eosinophilic cytoplasm, and prominent nucleoli.
- Ancillary: Seminomas express OCT3/4, SALL4, PLAP, KIT, and SOX17, but are negative for CD30, AFP, and EMA.
Reference Gallery:
Seminoma. Tumour cells with cytological features of distinct cytoplasmic membranes, clear cytoplasm, and nuclei with prominent nucleoli. Lymphoid infiltrate is present.
Seminoma and germ cell neoplasia in situ. Germ cell neoplasia in situ adjacent to invasive seminoma.
Seminoma. Seminoma infiltrating the rete testis in a pagetoid pattern. The seminoma cells are positive for OCT4.
Seminoma. Classic seminoma. Sheets of tumour cells with lymphocytic infiltrates and fibrous septa.
Seminoma. Exuberant lymphocytic infiltrate predominates over the seminoma cells.
Seminoma. A prominent granulomatous reaction is often observed.
Seminoma. Occasional syncytiotrophoblasts are usually seen dispersed among seminoma cells.
Seminoma. hCG immunostaining highlights the syncytiotrophoblasts.
Seminoma. Seminoma, pseudoglandular. Central cellular degeneration creates spaces imparting a pseudoglandular appearance.
Seminoma. Seminoma, signet-ring cells. Many cells show vacuolation of the cytoplasm, with nuclei pushed to the side, creating a signet-ring cell appearance.
Seminoma. Seminoma, peritubular. Groups of invasive seminoma cells closely embracing the tubules (a very rare pattern).
Seminoma. Sheets of seminoma cells showing the nuclear detail. Angulated cells and prominent, often smudged, nucleoli are seen.

Q: While Seminoma is typically negative for most serum markers, occasional scattered [...] may be observed interspersed among the tumor cells, which highlight positively for hCG on immunostaining.
Seminoma. Occasional syncytiotrophoblasts are usually seen dispersed among seminoma cells.
Seminoma. hCG immunostaining highlights the syncytiotrophoblasts.
A: syncytiotrophoblasts
Back Extra: Seminoma
- Clinical: Seminoma is the most common testicular germ cell tumour, typically presenting as a self-identified mass in postpubertal men with an average age of 37–41 years.
- Micro: The most prevalent growth pattern is a diffuse sheet-like arrangement with interspersed fibrous septa, large, clear, or lightly eosinophilic cytoplasm, and prominent nucleoli.
- Ancillary: Seminomas express OCT3/4, SALL4, PLAP, KIT, and SOX17, but are negative for CD30, AFP, and EMA.
Reference Gallery:
Seminoma. Tumour cells with cytological features of distinct cytoplasmic membranes, clear cytoplasm, and nuclei with prominent nucleoli. Lymphoid infiltrate is present.
Seminoma and germ cell neoplasia in situ. Germ cell neoplasia in situ adjacent to invasive seminoma.
Seminoma. Seminoma infiltrating the rete testis in a pagetoid pattern. The seminoma cells are positive for OCT4.
Seminoma. Classic seminoma. Sheets of tumour cells with lymphocytic infiltrates and fibrous septa.
Seminoma. Exuberant lymphocytic infiltrate predominates over the seminoma cells.
Seminoma. A prominent granulomatous reaction is often observed.
Seminoma. Occasional syncytiotrophoblasts are usually seen dispersed among seminoma cells.
Seminoma. hCG immunostaining highlights the syncytiotrophoblasts.
Seminoma. Seminoma, pseudoglandular. Central cellular degeneration creates spaces imparting a pseudoglandular appearance.
Seminoma. Seminoma, signet-ring cells. Many cells show vacuolation of the cytoplasm, with nuclei pushed to the side, creating a signet-ring cell appearance.
Seminoma. Seminoma, peritubular. Groups of invasive seminoma cells closely embracing the tubules (a very rare pattern).
Seminoma. Sheets of seminoma cells showing the nuclear detail. Angulated cells and prominent, often smudged, nucleoli are seen.

Q: The pathognomonic microscopic feature of Spermatocytic Tumor is a polymorphous population comprised of [...] cells.
Spermatocytic tumour. High-magnification photomicrograph showing three different cell types. The giant cell has a huge nucleus showing finely granular chromatin, and cytoplasm is abundant, showing vacuolation.
Spermatocytic tumour. Typical features of spermatocytic tumour with variable cytological/nuclear features in the tumour cells.
A: small, intermediate, and giant
Back Extra: Spermatocytic Tumor
- Clinical: Most patients with Spermatocytic Tumor present with a painless, incidentally found testicular mass. Serum markers are typically not elevated.
- Micro: The tumour cells are arranged in diffuse to multinodular patterns, often with stromal oedema. A characteristic feature is a polymorphous cell population consisting of three distinct cell types: small, intermediate, and giant cells.
- Ancillary: Spermatocytic tumours are non-reactive to many germ cell tumour markers (OCT3/4, PLAP, AFP, β-hCG, CD30, and AP-2γ) but express proteins found in spermatogonia and early spermatocytes (MAGEA4, KIT, SSX2, SYCP1, XPA, SAGE1, DMRT1, SALL4, and OCT2).
Reference Gallery:
Spermatocytic tumour. Intratubular growth of tumour cells; the seminiferous tubules are expanded by variably sized tumour cells.
Spermatocytic tumour. High-magnification photomicrograph showing three different cell types. The giant cell has a huge nucleus showing finely granular chromatin, and cytoplasm is abundant, showing vacuolation.
Spermatocytic tumour. Three different types of cells. The giant cell has a large nucleus pushed to the cytoplasmic membrane by a cytoplasmic vacuole. The chromatin is dense and filamentous (spireme).
Spermatocytic tumour. Sheet-like arrangement of variably sized tumour cells. Stroma is minimal. Single cells or cell groups with apoptosis create a pseudoglandular appearance.
Spermatocytic tumour. The predominance of larger intermediate cells with exuberant mitotic activity gives the impression of an aggressive malignant neoplasm. Some authors refer to this type of tumour as anaplastic spermatocytic tumour.
Spermatocytic tumour. Intratubular spread.
Spermatocytic tumour. Typical features of spermatocytic tumour with variable cytological/nuclear features in the tumour cells.

Q: The giant cells in Spermatocytic Tumor frequently exhibit a large nucleus with dense, filamentous chromatin, a feature classically described as [...] chromatin.
Spermatocytic tumour. Three different types of cells. The giant cell has a large nucleus pushed to the cytoplasmic membrane by a cytoplasmic vacuole. The chromatin is dense and filamentous (spireme).
A: spireme
Back Extra: Spermatocytic Tumor
- Clinical: Most patients with Spermatocytic Tumor present with a painless, incidentally found testicular mass. Serum markers are typically not elevated.
- Micro: The tumour cells are arranged in diffuse to multinodular patterns, often with stromal oedema. A characteristic feature is a polymorphous cell population consisting of three distinct cell types: small, intermediate, and giant cells.
- Ancillary: Spermatocytic tumours are non-reactive to many germ cell tumour markers (OCT3/4, PLAP, AFP, β-hCG, CD30, and AP-2γ) but express proteins found in spermatogonia and early spermatocytes (MAGEA4, KIT, SSX2, SYCP1, XPA, SAGE1, DMRT1, SALL4, and OCT2).
Reference Gallery:
Spermatocytic tumour. Intratubular growth of tumour cells; the seminiferous tubules are expanded by variably sized tumour cells.
Spermatocytic tumour. High-magnification photomicrograph showing three different cell types. The giant cell has a huge nucleus showing finely granular chromatin, and cytoplasm is abundant, showing vacuolation.
Spermatocytic tumour. Three different types of cells. The giant cell has a large nucleus pushed to the cytoplasmic membrane by a cytoplasmic vacuole. The chromatin is dense and filamentous (spireme).
Spermatocytic tumour. Sheet-like arrangement of variably sized tumour cells. Stroma is minimal. Single cells or cell groups with apoptosis create a pseudoglandular appearance.
Spermatocytic tumour. The predominance of larger intermediate cells with exuberant mitotic activity gives the impression of an aggressive malignant neoplasm. Some authors refer to this type of tumour as anaplastic spermatocytic tumour.
Spermatocytic tumour. Intratubular spread.
Spermatocytic tumour. Typical features of spermatocytic tumour with variable cytological/nuclear features in the tumour cells.

Q: A testicular germ cell tumor in a young adult showing mixed tissues from all three germ layers (e.g., hypercellular cartilage with cytologic atypia and glandular epithelium) is characteristic of [...].
Teratoma, postpubertal-type. This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
Teratoma, postpubertal-type. Cartilage and glandular tissue are seen in this teratoma. The cartilage appears hypercellular and shows prominent cellular atypia.
A: Teratoma, Postpubertal-Type
Back Extra: Teratoma, Postpubertal-Type
- Clinical: Postpubertal teratoma typically presents as a firm, irregular scrotal mass in young men and can occur in disorders of sex development in children.
- Micro: Typical features include mixed tissues from all three germ layers, such as glandular, cartilage, and neuroectodermal elements, with varying degrees of cytological atypia.
- Ancillary: Postpubertal teratoma is hypotriploid and often shows isochromosome 12p and 12p overrepresentation. Immunohistochemistry can show markers such as EMA, AFP, and hCG.
Reference Gallery:
Teratoma, postpubertal-type. Mixed teratomatous elements with embryonic-type neuroectodermal components.
Teratoma, postpubertal-type. This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
Teratoma, postpubertal-type. Cartilage and glandular tissue are seen in this teratoma. The cartilage appears hypercellular and shows prominent cellular atypia.
Teratoma, postpubertal-type. Glandular epithelium showing goblet cells. The surrounding spindle cell stroma is predominantly aggregating around the glands.
Teratoma, postpubertal-type. This example shows mature cartilage and an embryonal-type neuroectodermal component.
Teratoma, postpubertal-type. A single gland is surrounded by highly cellular spindle cell stroma in a myxoid matrix.
Teratoma, postpubertal-type. Mature glandular elements with mild nuclear atypia and pleomorphism. Note the syncytiotrophoblast with intracytoplasmic red blood cells and the spindle cell stroma displaying variable cellularity.
Teratoma, postpubertal-type. Periglandular stromal cuffing. Both mesenchymal and epithelial components show nuclear atypia.
Teratoma, postpubertal-type. Rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular and mesenchymal component with prominent rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (high-power view).
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (low-power view).

Q: In Teratoma, Postpubertal-Type, a distinctive histologic feature is the condensation of highly cellular spindle cell stroma around glandular structures, a morphological pattern referred to as [...].
Teratoma, postpubertal-type. Glandular epithelium showing goblet cells. The surrounding spindle cell stroma is predominantly aggregating around the glands.
Teratoma, postpubertal-type. Periglandular stromal cuffing. Both mesenchymal and epithelial components show nuclear atypia.
A: periglandular stromal cuffing
Back Extra: Teratoma, Postpubertal-Type
- Clinical: Postpubertal teratoma typically presents as a firm, irregular scrotal mass in young men and can occur in disorders of sex development in children.
- Micro: Typical features include mixed tissues from all three germ layers, such as glandular, cartilage, and neuroectodermal elements, with varying degrees of cytological atypia.
- Ancillary: Postpubertal teratoma is hypotriploid and often shows isochromosome 12p and 12p overrepresentation. Immunohistochemistry can show markers such as EMA, AFP, and hCG.
Reference Gallery:
Teratoma, postpubertal-type. Mixed teratomatous elements with embryonic-type neuroectodermal components.
Teratoma, postpubertal-type. This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
Teratoma, postpubertal-type. Cartilage and glandular tissue are seen in this teratoma. The cartilage appears hypercellular and shows prominent cellular atypia.
Teratoma, postpubertal-type. Glandular epithelium showing goblet cells. The surrounding spindle cell stroma is predominantly aggregating around the glands.
Teratoma, postpubertal-type. This example shows mature cartilage and an embryonal-type neuroectodermal component.
Teratoma, postpubertal-type. A single gland is surrounded by highly cellular spindle cell stroma in a myxoid matrix.
Teratoma, postpubertal-type. Mature glandular elements with mild nuclear atypia and pleomorphism. Note the syncytiotrophoblast with intracytoplasmic red blood cells and the spindle cell stroma displaying variable cellularity.
Teratoma, postpubertal-type. Periglandular stromal cuffing. Both mesenchymal and epithelial components show nuclear atypia.
Teratoma, postpubertal-type. Rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular and mesenchymal component with prominent rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (high-power view).
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (low-power view).

Q: In addition to mature tissues like squamous epithelium or cartilage, Teratoma, Postpubertal-Type frequently exhibits primitive tissue elements, notably embryonic-type [...] components.
Teratoma, postpubertal-type. Mixed teratomatous elements with embryonic-type neuroectodermal components.
Teratoma, postpubertal-type. This example shows mature cartilage and an embryonal-type neuroectodermal component.
A: neuroectodermal
Back Extra: Teratoma, Postpubertal-Type
- Clinical: Postpubertal teratoma typically presents as a firm, irregular scrotal mass in young men and can occur in disorders of sex development in children.
- Micro: Typical features include mixed tissues from all three germ layers, such as glandular, cartilage, and neuroectodermal elements, with varying degrees of cytological atypia.
- Ancillary: Postpubertal teratoma is hypotriploid and often shows isochromosome 12p and 12p overrepresentation. Immunohistochemistry can show markers such as EMA, AFP, and hCG.
Reference Gallery:
Teratoma, postpubertal-type. Mixed teratomatous elements with embryonic-type neuroectodermal components.
Teratoma, postpubertal-type. This example shows several mature tissue types, including squamous epithelium, mature cartilage, glandular epithelium, adipose tissue, and myofibroblastic stroma.
Teratoma, postpubertal-type. Cartilage and glandular tissue are seen in this teratoma. The cartilage appears hypercellular and shows prominent cellular atypia.
Teratoma, postpubertal-type. Glandular epithelium showing goblet cells. The surrounding spindle cell stroma is predominantly aggregating around the glands.
Teratoma, postpubertal-type. This example shows mature cartilage and an embryonal-type neuroectodermal component.
Teratoma, postpubertal-type. A single gland is surrounded by highly cellular spindle cell stroma in a myxoid matrix.
Teratoma, postpubertal-type. Mature glandular elements with mild nuclear atypia and pleomorphism. Note the syncytiotrophoblast with intracytoplasmic red blood cells and the spindle cell stroma displaying variable cellularity.
Teratoma, postpubertal-type. Periglandular stromal cuffing. Both mesenchymal and epithelial components show nuclear atypia.
Teratoma, postpubertal-type. Rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular and mesenchymal component with prominent rhabdomyomatous differentiation.
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (high-power view).
Teratoma, postpubertal-type. Glandular tissue, fibrous stroma, and adipose tissue (low-power view).

Q: Histologically, Prepubertal-Type Teratoma displays a variety of mature somatic tissues (e.g., bone, muscle, and glands) in an organoid pattern and characteristically lacks associated [...].
Teratoma, prepubertal-type. This example shows bone, muscle, and glandular cystic areas.
A: germ cell neoplasia in situ (GCNIS)
Back Extra: Prepubertal-Type Teratoma
- Clinical: Most prepubertal-type teratomas present as lumps in prepubertal boys, often discovered by patients or parents, and may be partially cystic on ultrasound.
- Micro: The tumor shows a variety of somatic tissues in an organoid pattern, with no marked cytological atypia or germ cell neoplasia in situ (GCNIS).
- Ancillary: Prepubertal-type teratomas are diploid and lack the genetic abnormalities typically seen in postpubertal-type teratomas, such as chromosome 12p gain.
Reference Gallery:
Epidermoid cyst. Enucleated epidermoid cyst of the testis.
Teratoma, prepubertal-type. This example shows bone, muscle, and glandular cystic areas.
Teratoma, prepubertal-type, with neuroendocrine tumour (NET). Prepubertal-type teratomas are often associated with small, low-grade NETs.
Epidermoid cyst. The wall of an epidermoid cyst of the testis. No other teratomatous elements are seen.

Q: In addition to mature somatic elements, Prepubertal-Type Teratoma is often associated with small, low-grade [...].
Teratoma, prepubertal-type, with neuroendocrine tumour (NET). Prepubertal-type teratomas are often associated with small, low-grade NETs.
A: neuroendocrine tumors
Back Extra: Prepubertal-Type Teratoma
- Clinical: Most prepubertal-type teratomas present as lumps in prepubertal boys, often discovered by patients or parents, and may be partially cystic on ultrasound.
- Micro: The tumor shows a variety of somatic tissues in an organoid pattern, with no marked cytological atypia or germ cell neoplasia in situ (GCNIS).
- Ancillary: Prepubertal-type teratomas are diploid and lack the genetic abnormalities typically seen in postpubertal-type teratomas, such as chromosome 12p gain.
Reference Gallery:
Epidermoid cyst. Enucleated epidermoid cyst of the testis.
Teratoma, prepubertal-type. This example shows bone, muscle, and glandular cystic areas.
Teratoma, prepubertal-type, with neuroendocrine tumour (NET). Prepubertal-type teratomas are often associated with small, low-grade NETs.
Epidermoid cyst. The wall of an epidermoid cyst of the testis. No other teratomatous elements are seen.

Q: In Teratoma with Somatic-Type Malignancy, sarcomas are more common than carcinomas, with the most frequently identified sarcoma being [...], which histologically displays pleomorphic spindle cells and differentiated rhabdomyoblasts.
Rhabdomyosarcoma. Embryonal-type rhabdomyosarcoma showing pleomorphic spindle cells and differentiated rhabdomyoblasts.
Rhabdomyosarcoma. High-power view showing rhabdomyoblasts and pleomorphic spindle cells.
A: rhabdomyosarcoma
Back Extra: Teratoma with Somatic-Type Malignancy
- Clinical: Somatic-type malignancies occur in 2.5–8.0% of testicular germ cell tumours, primarily in postpubertal patients, and are often found in metastatic sites after chemotherapy.
- Micro: Sarcomas are more common than carcinomas and often appear early in the course of the disease, with rhabdomyosarcoma being the most frequently identified sarcoma.
- Ancillary: Isochromosome 12p and overrepresentation of 12p are commonly found in somatic-type malignancies, and these tumours often show loss of immunoreactivity for PLAP, OCT3/4, and AFP.
Reference Gallery:
Somatic-type malignancy. Embryonic-type neuroectodermal tumour arising within a testis, exhibiting involvement of hilar and adnexal structures.
Rhabdomyosarcoma. Embryonal-type rhabdomyosarcoma showing pleomorphic spindle cells and differentiated rhabdomyoblasts.
Rhabdomyosarcoma. High-power view showing rhabdomyoblasts and pleomorphic spindle cells.
Embryonic-type neuroectodermal tumour. Embryonic-type neuroectodermal tumour showing hyperchromatic cells in rosettes.
Nephroblastoma. Immature, blastema-like, dark blue rounded cells and prominent tubule formation. Stroma appears fibrocollagenous.
Nephroblastoma. Tubules and clusters of immature-appearing dark blue cells.
Squamous cell carcinoma. Well-differentiated squamous cell carcinoma arising from a metastatic teratoma.
Undifferentiated pleomorphic sarcoma. Markedly pleomorphic spindled cells in a collagenous background.

Q: When Teratoma with Somatic-Type Malignancy presents as an embryonic-type neuroectodermal tumor, the histology frequently features hyperchromatic cells arranged in characteristic [...].
Embryonic-type neuroectodermal tumour. Embryonic-type neuroectodermal tumour showing hyperchromatic cells in rosettes.
A: rosettes
Back Extra: Teratoma with Somatic-Type Malignancy
- Clinical: Somatic-type malignancies occur in 2.5–8.0% of testicular germ cell tumours, primarily in postpubertal patients, and are often found in metastatic sites after chemotherapy.
- Micro: Sarcomas are more common than carcinomas and often appear early in the course of the disease, with rhabdomyosarcoma being the most frequently identified sarcoma.
- Ancillary: Isochromosome 12p and overrepresentation of 12p are commonly found in somatic-type malignancies, and these tumours often show loss of immunoreactivity for PLAP, OCT3/4, and AFP.
Reference Gallery:
Somatic-type malignancy. Embryonic-type neuroectodermal tumour arising within a testis, exhibiting involvement of hilar and adnexal structures.
Rhabdomyosarcoma. Embryonal-type rhabdomyosarcoma showing pleomorphic spindle cells and differentiated rhabdomyoblasts.
Rhabdomyosarcoma. High-power view showing rhabdomyoblasts and pleomorphic spindle cells.
Embryonic-type neuroectodermal tumour. Embryonic-type neuroectodermal tumour showing hyperchromatic cells in rosettes.
Nephroblastoma. Immature, blastema-like, dark blue rounded cells and prominent tubule formation. Stroma appears fibrocollagenous.
Nephroblastoma. Tubules and clusters of immature-appearing dark blue cells.
Squamous cell carcinoma. Well-differentiated squamous cell carcinoma arising from a metastatic teratoma.
Undifferentiated pleomorphic sarcoma. Markedly pleomorphic spindled cells in a collagenous background.

Q: While sarcomas are the most frequent form of Teratoma with Somatic-Type Malignancy, malignant epithelial tumors such as well-differentiated [...] can often be found arising in metastatic sites following chemotherapy.
Squamous cell carcinoma. Well-differentiated squamous cell carcinoma arising from a metastatic teratoma.
A: squamous cell carcinoma
Back Extra: Teratoma with Somatic-Type Malignancy
- Clinical: Somatic-type malignancies occur in 2.5–8.0% of testicular germ cell tumours, primarily in postpubertal patients, and are often found in metastatic sites after chemotherapy.
- Micro: Sarcomas are more common than carcinomas and often appear early in the course of the disease, with rhabdomyosarcoma being the most frequently identified sarcoma.
- Ancillary: Isochromosome 12p and overrepresentation of 12p are commonly found in somatic-type malignancies, and these tumours often show loss of immunoreactivity for PLAP, OCT3/4, and AFP.
Reference Gallery:
Somatic-type malignancy. Embryonic-type neuroectodermal tumour arising within a testis, exhibiting involvement of hilar and adnexal structures.
Rhabdomyosarcoma. Embryonal-type rhabdomyosarcoma showing pleomorphic spindle cells and differentiated rhabdomyoblasts.
Rhabdomyosarcoma. High-power view showing rhabdomyoblasts and pleomorphic spindle cells.
Embryonic-type neuroectodermal tumour. Embryonic-type neuroectodermal tumour showing hyperchromatic cells in rosettes.
Nephroblastoma. Immature, blastema-like, dark blue rounded cells and prominent tubule formation. Stroma appears fibrocollagenous.
Nephroblastoma. Tubules and clusters of immature-appearing dark blue cells.
Squamous cell carcinoma. Well-differentiated squamous cell carcinoma arising from a metastatic teratoma.
Undifferentiated pleomorphic sarcoma. Markedly pleomorphic spindled cells in a collagenous background.

Q: In Yolk Sac Tumour, Postpubertal-Type, common histologic patterns include solid and papillary growth, often accompanied by characteristic intracytoplasmic and extracellular [...].
Yolk sac tumour, postpubertal-type. Solid pattern with sheets of tumour cells that have clear cytoplasm and scattered hyaline globules. Note the lack of lymphocytes and fibrous septa compared with seminoma.
A: hyaline globules
Back Extra: Yolk Sac Tumour, Postpubertal-Type
- Clinical: Postpubertal-type YST is most often found as a component of mixed germ cell tumour and is associated with elevated serum levels of AFP (typically hundreds to thousands of ng/mL).
- Micro: Common patterns include solid, papillary, and polyvesicular vitelline patterns, often with intracytoplasmic and extracellular hyaline globules and parietal differentiation.
- Ancillary: Immunohistochemical markers such as AFP, GPC3, and SALL4 are frequently positive, with GPC3 being more sensitive than AFP.
Reference Gallery:
Yolk sac tumour, postpubertal-type. Solid pattern with sheets of tumour cells that have clear cytoplasm and scattered hyaline globules. Note the lack of lymphocytes and fibrous septa compared with seminoma.
Yolk sac tumour, postpubertal-type. Solid pattern with a blastematous appearance.
Yolk sac tumour, postpubertal-type. Papillary pattern with basement membrane deposits (parietal differentiation) within the papillae.
Yolk sac tumour, postpubertal-type. Sarcomatoid pattern showing stellate and spindled tumour cells in a myxoid stroma. The tumour cells are focally arranged in ringlets within the stroma.
Yolk sac tumour, postpubertal-type. Sarcomatoid pattern of postpubertal yolk sac tumour containing epithelioid cells with round, plump nuclei in a fibrous background.
Yolk sac tumour, postpubertal-type. Parietal pattern of postpubertal yolk sac tumour with large amounts of basement membrane material (parietal differentiation).
Yolk sac tumour, postpubertal-type. Polyvesicular vitelline pattern showing vesicles with eccentric constrictions (figure-of-eight appearance) and lined by flat tumour cells in a loose fibrous stroma.
Yolk sac tumour, postpubertal-type. Glandular yolk sac tumour. The glandular pattern is more common in late recurrences.
Yolk sac tumour, postpubertal-type. Solid yolk sac tumour with intense staining for glypican-3 (GPC3).
Yolk sac tumour, postpubertal-type. Microcystic/reticular yolk sac tumour (upper-left corner) adjacent to solid yolk sac tumour (right), illustrating how the intensity of glypican-3 (GPC3) staining is typically weaker in the solid pattern.
Yolk sac tumour, postpubertal-type. AFP can be completely negative in solid yolk sac tumour.
Yolk sac tumour. Vascular invasion.

Q: A highly characteristic architectural arrangement in Yolk Sac Tumour, Postpubertal-Type is the [...] pattern, which features vesicles with eccentric constrictions that create a "figure-of-eight" appearance.
Yolk sac tumour, postpubertal-type. Polyvesicular vitelline pattern showing vesicles with eccentric constrictions (figure-of-eight appearance) and lined by flat tumour cells in a loose fibrous stroma.
A: polyvesicular vitelline
Back Extra: Yolk Sac Tumour, Postpubertal-Type
- Clinical: Postpubertal-type YST is most often found as a component of mixed germ cell tumour and is associated with elevated serum levels of AFP (typically hundreds to thousands of ng/mL).
- Micro: Common patterns include solid, papillary, and polyvesicular vitelline patterns, often with intracytoplasmic and extracellular hyaline globules and parietal differentiation.
- Ancillary: Immunohistochemical markers such as AFP, GPC3, and SALL4 are frequently positive, with GPC3 being more sensitive than AFP.
Reference Gallery:
Yolk sac tumour, postpubertal-type. Solid pattern with sheets of tumour cells that have clear cytoplasm and scattered hyaline globules. Note the lack of lymphocytes and fibrous septa compared with seminoma.
Yolk sac tumour, postpubertal-type. Solid pattern with a blastematous appearance.
Yolk sac tumour, postpubertal-type. Papillary pattern with basement membrane deposits (parietal differentiation) within the papillae.
Yolk sac tumour, postpubertal-type. Sarcomatoid pattern showing stellate and spindled tumour cells in a myxoid stroma. The tumour cells are focally arranged in ringlets within the stroma.
Yolk sac tumour, postpubertal-type. Sarcomatoid pattern of postpubertal yolk sac tumour containing epithelioid cells with round, plump nuclei in a fibrous background.
Yolk sac tumour, postpubertal-type. Parietal pattern of postpubertal yolk sac tumour with large amounts of basement membrane material (parietal differentiation).
Yolk sac tumour, postpubertal-type. Polyvesicular vitelline pattern showing vesicles with eccentric constrictions (figure-of-eight appearance) and lined by flat tumour cells in a loose fibrous stroma.
Yolk sac tumour, postpubertal-type. Glandular yolk sac tumour. The glandular pattern is more common in late recurrences.
Yolk sac tumour, postpubertal-type. Solid yolk sac tumour with intense staining for glypican-3 (GPC3).
Yolk sac tumour, postpubertal-type. Microcystic/reticular yolk sac tumour (upper-left corner) adjacent to solid yolk sac tumour (right), illustrating how the intensity of glypican-3 (GPC3) staining is typically weaker in the solid pattern.
Yolk sac tumour, postpubertal-type. AFP can be completely negative in solid yolk sac tumour.
Yolk sac tumour. Vascular invasion.

Q: In Yolk Sac Tumour, Postpubertal-Type, immunohistochemical staining for [...] is considered more sensitive than AFP, particularly because AFP can be completely negative in solid tumor areas.
Yolk sac tumour, postpubertal-type. Solid yolk sac tumour with intense staining for glypican-3 (GPC3).
Yolk sac tumour, postpubertal-type. AFP can be completely negative in solid yolk sac tumour.
A: glypican-3 (GPC3)
Back Extra: Yolk Sac Tumour, Postpubertal-Type
- Clinical: Postpubertal-type YST is most often found as a component of mixed germ cell tumour and is associated with elevated serum levels of AFP (typically hundreds to thousands of ng/mL).
- Micro: Common patterns include solid, papillary, and polyvesicular vitelline patterns, often with intracytoplasmic and extracellular hyaline globules and parietal differentiation.
- Ancillary: Immunohistochemical markers such as AFP, GPC3, and SALL4 are frequently positive, with GPC3 being more sensitive than AFP.
Reference Gallery:
Yolk sac tumour, postpubertal-type. Solid pattern with sheets of tumour cells that have clear cytoplasm and scattered hyaline globules. Note the lack of lymphocytes and fibrous septa compared with seminoma.
Yolk sac tumour, postpubertal-type. Solid pattern with a blastematous appearance.
Yolk sac tumour, postpubertal-type. Papillary pattern with basement membrane deposits (parietal differentiation) within the papillae.
Yolk sac tumour, postpubertal-type. Sarcomatoid pattern showing stellate and spindled tumour cells in a myxoid stroma. The tumour cells are focally arranged in ringlets within the stroma.
Yolk sac tumour, postpubertal-type. Sarcomatoid pattern of postpubertal yolk sac tumour containing epithelioid cells with round, plump nuclei in a fibrous background.
Yolk sac tumour, postpubertal-type. Parietal pattern of postpubertal yolk sac tumour with large amounts of basement membrane material (parietal differentiation).
Yolk sac tumour, postpubertal-type. Polyvesicular vitelline pattern showing vesicles with eccentric constrictions (figure-of-eight appearance) and lined by flat tumour cells in a loose fibrous stroma.
Yolk sac tumour, postpubertal-type. Glandular yolk sac tumour. The glandular pattern is more common in late recurrences.
Yolk sac tumour, postpubertal-type. Solid yolk sac tumour with intense staining for glypican-3 (GPC3).
Yolk sac tumour, postpubertal-type. Microcystic/reticular yolk sac tumour (upper-left corner) adjacent to solid yolk sac tumour (right), illustrating how the intensity of glypican-3 (GPC3) staining is typically weaker in the solid pattern.
Yolk sac tumour, postpubertal-type. AFP can be completely negative in solid yolk sac tumour.
Yolk sac tumour. Vascular invasion.

Q: A key clinical marker for a Yolk Sac Tumor, Prepubertal-Type is a markedly elevated serum level of [...], which is seen in over 90% of cases.
Yolk sac tumour, prepubertal-type. Solid yellow cut surface with very few cysts.
A: alpha-fetoprotein (AFP)
Back Extra: Yolk Sac Tumour, Prepubertal-Type
- Clinical: Prepubertal-type YSTs typically present as painless testicular swellings, often with elevated serum AFP levels (over 90% of cases) and a low incidence of metastasis at diagnosis.
- Micro: Characterized by a broad spectrum of growth patterns including reticular/microcystic, glandular, solid, macrocystic, papillary, and myxomatous, with intracytoplasmic hyaline globules and Schiller–Duval bodies.
- Ancillary: IHC shows positivity for SALL4, glypican-3 (GPC3), and HNF1β, and negativity for OCT3/4 and markers of sex cord stromal tumours. Molecular studies reveal aneuploidy and occasional amplification of 12p13.
Reference Gallery:
Yolk sac tumour, prepubertal-type. Solid yellow cut surface with very few cysts.
Yolk sac tumour, prepubertal-type. Note the prepubertal seminiferous tubules.
Yolk sac tumour, prepubertal-type. This example has adjacent prepubertal testicular tubules.

Q: Microscopically, a Yolk Sac Tumor, Prepubertal-Type is typically found adjacent to background [...], helping to confirm the age-related context of the tumor.
Yolk sac tumour, prepubertal-type. Note the prepubertal seminiferous tubules.
Yolk sac tumour, prepubertal-type. This example has adjacent prepubertal testicular tubules.
A: prepubertal seminiferous tubules
Back Extra: Yolk Sac Tumour, Prepubertal-Type
- Clinical: Prepubertal-type YSTs typically present as painless testicular swellings, often with elevated serum AFP levels (over 90% of cases) and a low incidence of metastasis at diagnosis.
- Micro: Characterized by a broad spectrum of growth patterns including reticular/microcystic, glandular, solid, macrocystic, papillary, and myxomatous, with intracytoplasmic hyaline globules and Schiller–Duval bodies.
- Ancillary: IHC shows positivity for SALL4, glypican-3 (GPC3), and HNF1β, and negativity for OCT3/4 and markers of sex cord stromal tumours. Molecular studies reveal aneuploidy and occasional amplification of 12p13.
Reference Gallery:
Yolk sac tumour, prepubertal-type. Solid yellow cut surface with very few cysts.
Yolk sac tumour, prepubertal-type. Note the prepubertal seminiferous tubules.
Yolk sac tumour, prepubertal-type. This example has adjacent prepubertal testicular tubules.

Q: Grossly, a painless testicular mass presenting with a solid yellow cut surface and very few cysts in a child is highly characteristic of a [...].
Yolk sac tumour, prepubertal-type. Solid yellow cut surface with very few cysts.
A: Yolk Sac Tumor, Prepubertal-Type
Back Extra: Yolk Sac Tumour, Prepubertal-Type
- Clinical: Prepubertal-type YSTs typically present as painless testicular swellings, often with elevated serum AFP levels (over 90% of cases) and a low incidence of metastasis at diagnosis.
- Micro: Characterized by a broad spectrum of growth patterns including reticular/microcystic, glandular, solid, macrocystic, papillary, and myxomatous, with intracytoplasmic hyaline globules and Schiller–Duval bodies.
- Ancillary: IHC shows positivity for SALL4, glypican-3 (GPC3), and HNF1β, and negativity for OCT3/4 and markers of sex cord stromal tumours. Molecular studies reveal aneuploidy and occasional amplification of 12p13.
Reference Gallery:
Yolk sac tumour, prepubertal-type. Solid yellow cut surface with very few cysts.
Yolk sac tumour, prepubertal-type. Note the prepubertal seminiferous tubules.
Yolk sac tumour, prepubertal-type. This example has adjacent prepubertal testicular tubules.

Q: Microscopically, Diffuse large B-cell lymphoma typically replaces normal tissue architecture with solid sheets of [...] featuring scant cytoplasm, irregular nuclear contours, and prominent nucleoli.
Diffuse large B-cell lymphoma. Sheets of large neoplastic lymphoid cells replace most of the renal parenchyma. An engulfed glomerulus is appreciated among the malignant lymphoid cells.
Diffuse large B-cell lymphoma. Neoplastic cells from the specimen shown in Fig. 20929 are large and have scant cytoplasm, irregular nuclear contours, and prominent nucleoli. A few small reactive lymphocytes are also seen accompanying the neoplastic infiltrate.
A: large neoplastic lymphoid cells
Q: Diffuse large B-cell lymphoma
- Clinical: Signs and symptoms of [...] are location-dependent and include haematuria, urinary obstruction, dysuria, back pain, abdominal pain, and scrotal swelling. Some patients are asymptomatic.
- Micro: In [...], sheets of large neoplastic lymphoid cells replace most of the renal parenchyma, with an increased N:C ratio, prominent nucleoli, and scant cytoplasm.
- Ancillary: Diagnosis of [...] requires expression of CD20 and/or other B-cell antigens. Desirable markers include CD10, BCL2, BCL6, MYC, and Ki-67 for subtyping and prognosticating.
Reference Gallery:
Diffuse large B-cell lymphoma. Macroscopic image of a testicular tumour. Note the pale/tan and fleshy appearance of the neoplasm. It extends to involve epididymis and base of the cord.
Diffuse large B-cell lymphoma. The neoplastic B cells diffusely and strongly express CD20.
Diffuse large B-cell lymphoma. Malignant lymphoid cells from the specimen shown in Fig. 20927 show strong IRF4 (MUM1) expression.
Diffuse large B-cell lymphoma. Sheets of large neoplastic lymphoid cells replace most of the renal parenchyma. An engulfed glomerulus is appreciated among the malignant lymphoid cells.
Diffuse large B-cell lymphoma. Neoplastic cells from the specimen shown in Fig. 20929 are large and have scant cytoplasm, irregular nuclear contours, and prominent nucleoli. A few small reactive lymphocytes are also seen accompanying the neoplastic infiltrate.
A: Diffuse large B-cell lymphoma; Diffuse large B-cell lymphoma; Diffuse large B-cell lymphoma

Q: The malignant cells in Diffuse large B-cell lymphoma require confirmation of B-cell lineage, which is classically demonstrated by strong, diffuse membranous expression of the immunohistochemical marker [...].
Diffuse large B-cell lymphoma. The neoplastic B cells diffusely and strongly express CD20.
A: CD20
Q: Diffuse large B-cell lymphoma
- Clinical: Signs and symptoms of [...] are location-dependent and include haematuria, urinary obstruction, dysuria, back pain, abdominal pain, and scrotal swelling. Some patients are asymptomatic.
- Micro: In [...], sheets of large neoplastic lymphoid cells replace most of the renal parenchyma, with an increased N:C ratio, prominent nucleoli, and scant cytoplasm.
- Ancillary: Diagnosis of [...] requires expression of CD20 and/or other B-cell antigens. Desirable markers include CD10, BCL2, BCL6, MYC, and Ki-67 for subtyping and prognosticating.
Reference Gallery:
Diffuse large B-cell lymphoma. Macroscopic image of a testicular tumour. Note the pale/tan and fleshy appearance of the neoplasm. It extends to involve epididymis and base of the cord.
Diffuse large B-cell lymphoma. The neoplastic B cells diffusely and strongly express CD20.
Diffuse large B-cell lymphoma. Malignant lymphoid cells from the specimen shown in Fig. 20927 show strong IRF4 (MUM1) expression.
Diffuse large B-cell lymphoma. Sheets of large neoplastic lymphoid cells replace most of the renal parenchyma. An engulfed glomerulus is appreciated among the malignant lymphoid cells.
Diffuse large B-cell lymphoma. Neoplastic cells from the specimen shown in Fig. 20929 are large and have scant cytoplasm, irregular nuclear contours, and prominent nucleoli. A few small reactive lymphocytes are also seen accompanying the neoplastic infiltrate.
A: Diffuse large B-cell lymphoma; Diffuse large B-cell lymphoma; Diffuse large B-cell lymphoma

Q: Grossly, extranodal presentations of Diffuse large B-cell lymphoma (such as in the testis) characteristically form a pale, tan, and [...] solid tumor.
Diffuse large B-cell lymphoma. Macroscopic image of a testicular tumour. Note the pale/tan and fleshy appearance of the neoplasm. It extends to involve epididymis and base of the cord.
A: fleshy
Q: Diffuse large B-cell lymphoma
- Clinical: Signs and symptoms of [...] are location-dependent and include haematuria, urinary obstruction, dysuria, back pain, abdominal pain, and scrotal swelling. Some patients are asymptomatic.
- Micro: In [...], sheets of large neoplastic lymphoid cells replace most of the renal parenchyma, with an increased N:C ratio, prominent nucleoli, and scant cytoplasm.
- Ancillary: Diagnosis of [...] requires expression of CD20 and/or other B-cell antigens. Desirable markers include CD10, BCL2, BCL6, MYC, and Ki-67 for subtyping and prognosticating.
Reference Gallery:
Diffuse large B-cell lymphoma. Macroscopic image of a testicular tumour. Note the pale/tan and fleshy appearance of the neoplasm. It extends to involve epididymis and base of the cord.
Diffuse large B-cell lymphoma. The neoplastic B cells diffusely and strongly express CD20.
Diffuse large B-cell lymphoma. Malignant lymphoid cells from the specimen shown in Fig. 20927 show strong IRF4 (MUM1) expression.
Diffuse large B-cell lymphoma. Sheets of large neoplastic lymphoid cells replace most of the renal parenchyma. An engulfed glomerulus is appreciated among the malignant lymphoid cells.
Diffuse large B-cell lymphoma. Neoplastic cells from the specimen shown in Fig. 20929 are large and have scant cytoplasm, irregular nuclear contours, and prominent nucleoli. A few small reactive lymphocytes are also seen accompanying the neoplastic infiltrate.
A: Diffuse large B-cell lymphoma; Diffuse large B-cell lymphoma; Diffuse large B-cell lymphoma

Q: Histologically, Extranodal Marginal Zone Lymphoma of MALT is classically characterized by a diffuse monomorphic infiltrate of [...] cells, which possess cleaved nuclei and pale to clear cytoplasm.
MALT lymphoma. The infiltrate is monomorphic small lymphoid cells with cleaved nuclei and a moderate amount of pale eosinophilic cytoplasm (characteristic centrocyte-like cells).
MALT lymphoma. Most of the infiltrate is monomorphic small lymphoid cells with cleaved nuclei and a moderate amount of pale/clear cytoplasm (characteristic centrocyte-like cells). These cells do not have a prominent nucleolus. These cells expressed CD20 and BCL2, and they were negative for CD5, CD10, BCL6, cyclin D1, and SOX11. Ki-67 expression was < 10%.
A: centrocyte-like
Back Extra: Extranodal Marginal Zone Lymphoma of MALT
- Clinical: Extranodal Marginal Zone Lymphoma of MALT often presents with symptoms such as haematuria, frequency, urinary obstruction, dysuria, and lower abdominal pain, and can be asymptomatic.
- Micro: Characterized by a diffuse infiltrate of centrocyte-like cells, scattered larger nucleolated cells, and cells showing plasmacytic features. Ki-67 expression is typically < 10%.
- Ancillary: Lymphoid cells express CD20 and are negative for CD5, CD10, BCL6, cyclin D1, and SOX11.
Reference Gallery:
MALT lymphoma. CD21 immunostaining identifies collapsed follicular dendritic cell meshworks in the lymphoid infiltrate.
MALT lymphoma. The infiltrate is monomorphic small lymphoid cells with cleaved nuclei and a moderate amount of pale eosinophilic cytoplasm (characteristic centrocyte-like cells).
MALT lymphoma. Lymphoid cells express CD20. These were negative for CD5, CD10, and cyclin D1.
MALT lymphoma. Urinary bladder biopsy shows a urothelium-covered lymphoid lesion with a poorly defined large-nodular pattern.
MALT lymphoma. The centre of the nodule shows clusters of larger cells representing remnants of a reactive germinal centre.
MALT lymphoma. Most of the infiltrate is monomorphic small lymphoid cells with cleaved nuclei and a moderate amount of pale/clear cytoplasm (characteristic centrocyte-like cells). These cells do not have a prominent nucleolus. These cells expressed CD20 and BCL2, and they were negative for CD5, CD10, BCL6, cyclin D1, and SOX11. Ki-67 expression was < 10%.
MALT lymphoma. In parts of the lesion, lymphoid cells show plasmacytic differentiation.
MALT lymphoma of the urinary bladder. The lamina propria is expanded by sheets of small monomorphic lymphocytes beneath the native urothelium.
MALT lymphoma of the urinary bladder. Transurethral resection of bladder tumour (TURBT) specimen showing aggregates of small lymphoid cells with interspersed hyalinized blood vessels.

Q: Immunohistochemically, the neoplastic cells in Extranodal Marginal Zone Lymphoma of MALT characteristically express [...], while remaining typically negative for CD5, CD10, BCL6, and cyclin D1.
MALT lymphoma. Lymphoid cells express CD20. These were negative for CD5, CD10, and cyclin D1.
A: CD20
Back Extra: Extranodal Marginal Zone Lymphoma of MALT
- Clinical: Extranodal Marginal Zone Lymphoma of MALT often presents with symptoms such as haematuria, frequency, urinary obstruction, dysuria, and lower abdominal pain, and can be asymptomatic.
- Micro: Characterized by a diffuse infiltrate of centrocyte-like cells, scattered larger nucleolated cells, and cells showing plasmacytic features. Ki-67 expression is typically < 10%.
- Ancillary: Lymphoid cells express CD20 and are negative for CD5, CD10, BCL6, cyclin D1, and SOX11.
Reference Gallery:
MALT lymphoma. CD21 immunostaining identifies collapsed follicular dendritic cell meshworks in the lymphoid infiltrate.
MALT lymphoma. The infiltrate is monomorphic small lymphoid cells with cleaved nuclei and a moderate amount of pale eosinophilic cytoplasm (characteristic centrocyte-like cells).
MALT lymphoma. Lymphoid cells express CD20. These were negative for CD5, CD10, and cyclin D1.
MALT lymphoma. Urinary bladder biopsy shows a urothelium-covered lymphoid lesion with a poorly defined large-nodular pattern.
MALT lymphoma. The centre of the nodule shows clusters of larger cells representing remnants of a reactive germinal centre.
MALT lymphoma. Most of the infiltrate is monomorphic small lymphoid cells with cleaved nuclei and a moderate amount of pale/clear cytoplasm (characteristic centrocyte-like cells). These cells do not have a prominent nucleolus. These cells expressed CD20 and BCL2, and they were negative for CD5, CD10, BCL6, cyclin D1, and SOX11. Ki-67 expression was < 10%.
MALT lymphoma. In parts of the lesion, lymphoid cells show plasmacytic differentiation.
MALT lymphoma of the urinary bladder. The lamina propria is expanded by sheets of small monomorphic lymphocytes beneath the native urothelium.
MALT lymphoma of the urinary bladder. Transurethral resection of bladder tumour (TURBT) specimen showing aggregates of small lymphoid cells with interspersed hyalinized blood vessels.

Q: A notable morphologic feature often observed in Extranodal Marginal Zone Lymphoma of MALT is that a portion of the lymphoid infiltrate can exhibit [...] differentiation.
MALT lymphoma. In parts of the lesion, lymphoid cells show plasmacytic differentiation.
A: plasmacytic
Back Extra: Extranodal Marginal Zone Lymphoma of MALT
- Clinical: Extranodal Marginal Zone Lymphoma of MALT often presents with symptoms such as haematuria, frequency, urinary obstruction, dysuria, and lower abdominal pain, and can be asymptomatic.
- Micro: Characterized by a diffuse infiltrate of centrocyte-like cells, scattered larger nucleolated cells, and cells showing plasmacytic features. Ki-67 expression is typically < 10%.
- Ancillary: Lymphoid cells express CD20 and are negative for CD5, CD10, BCL6, cyclin D1, and SOX11.
Reference Gallery:
MALT lymphoma. CD21 immunostaining identifies collapsed follicular dendritic cell meshworks in the lymphoid infiltrate.
MALT lymphoma. The infiltrate is monomorphic small lymphoid cells with cleaved nuclei and a moderate amount of pale eosinophilic cytoplasm (characteristic centrocyte-like cells).
MALT lymphoma. Lymphoid cells express CD20. These were negative for CD5, CD10, and cyclin D1.
MALT lymphoma. Urinary bladder biopsy shows a urothelium-covered lymphoid lesion with a poorly defined large-nodular pattern.
MALT lymphoma. The centre of the nodule shows clusters of larger cells representing remnants of a reactive germinal centre.
MALT lymphoma. Most of the infiltrate is monomorphic small lymphoid cells with cleaved nuclei and a moderate amount of pale/clear cytoplasm (characteristic centrocyte-like cells). These cells do not have a prominent nucleolus. These cells expressed CD20 and BCL2, and they were negative for CD5, CD10, BCL6, cyclin D1, and SOX11. Ki-67 expression was < 10%.
MALT lymphoma. In parts of the lesion, lymphoid cells show plasmacytic differentiation.
MALT lymphoma of the urinary bladder. The lamina propria is expanded by sheets of small monomorphic lymphocytes beneath the native urothelium.
MALT lymphoma of the urinary bladder. Transurethral resection of bladder tumour (TURBT) specimen showing aggregates of small lymphoid cells with interspersed hyalinized blood vessels.

Q: Microscopically, Juvenile Xanthogranuloma typically shows an unencapsulated proliferation predominantly composed of [...], which are often interspersed with capillaries and a sprinkling of eosinophils.
Juvenile xanthogranuloma of testis. There are sheets of foamy histiocytes with interspersed capillaries and a sprinkling of eosinophils. A primitive/immature seminiferous tubule can be appreciated (upper left).
A: foamy histiocytes
Back Extra: Juvenile Xanthogranuloma
- Clinical: Testicular Juvenile Xanthogranuloma (JXG) typically presents as a painless mass in infants aged 2.5–13 months.
- Micro: JXG shows an unencapsulated, well-demarcated histiocytic proliferation with foamy histiocytes, lymphocytes, eosinophils, and multinucleated Touton giant cells.
- Ancillary: JXG is positive for CD68, CD163, factor XIIIa, CD4, and fascin, and negative for CD1a, CD207 (langerin), and S100.
Reference Gallery:
Juvenile xanthogranuloma of testis. There are sheets of foamy histiocytes with interspersed capillaries and a sprinkling of eosinophils. A primitive/immature seminiferous tubule can be appreciated (upper left).

Q: Testicular Juvenile Xanthogranuloma classically presents as a painless mass and microscopically shows a histiocytic infiltrate intermixed with primitive or immature seminiferous tubules, reflecting its typical presentation in [...].
Juvenile xanthogranuloma of testis. There are sheets of foamy histiocytes with interspersed capillaries and a sprinkling of eosinophils. A primitive/immature seminiferous tubule can be appreciated (upper left).
A: infants
Back Extra: Juvenile Xanthogranuloma
- Clinical: Testicular Juvenile Xanthogranuloma (JXG) typically presents as a painless mass in infants aged 2.5–13 months.
- Micro: JXG shows an unencapsulated, well-demarcated histiocytic proliferation with foamy histiocytes, lymphocytes, eosinophils, and multinucleated Touton giant cells.
- Ancillary: JXG is positive for CD68, CD163, factor XIIIa, CD4, and fascin, and negative for CD1a, CD207 (langerin), and S100.
Reference Gallery:
Juvenile xanthogranuloma of testis. There are sheets of foamy histiocytes with interspersed capillaries and a sprinkling of eosinophils. A primitive/immature seminiferous tubule can be appreciated (upper left).

Q: Microscopically, a testicular plasmacytoma features an intertubular proliferation of atypical cells that often exhibit characteristic nuclear chromatin and a prominent [...].
Testicular plasmacytoma. The plasmacytoma involves the testis in an intertubular pattern.
Testicular plasmacytoma. Plasma cells range from small and mature to large and atypical. Note the characteristic nuclear chromatin and the paranuclear halo in some of the cells.
A: paranuclear halo
Back Extra: Plasmacytoma
- Clinical: Patients with genitourinary plasmacytoma may present with a mass lesion or haematuria, or they may be asymptomatic.
- Micro: Sheets of mature or atypical plasma cells are seen in testicular plasmacytomas, often ranging from small and mature to large and atypical cells.
- Ancillary: Neoplastic plasma cells in plasmacytoma express monotypic kappa or lambda light chain, and there is a clonal IGH gene rearrangement.
Reference Gallery:
Testicular plasmacytoma. A fleshy tan tumour bulges from the cut surface of the testis. The patient had a history of plasma cell myeloma.
Testicular plasmacytoma. Low-power view shows a diffuse proliferation of plasma cells almost completely obliterating the seminiferous tubules.
Testicular plasmacytoma. The plasmacytoma involves the testis in an intertubular pattern.
Testicular plasmacytoma. Sheets of atypical plasma cells adjacent to an atrophic seminiferous tubule.
Testicular plasmacytoma. Plasma cells range from small and mature to large and atypical. Note the characteristic nuclear chromatin and the paranuclear halo in some of the cells.
Testicular plasmacytoma. Neoplastic plasma cells express monotypic kappa light chain.
Testicular plasmacytoma. Neoplastic plasma cells are negative for lambda light chain.

Q: To differentiate a plasmacytoma from a reactive infiltrate, ancillary studies are used to demonstrate [...], showing monotypic expression of either kappa or lambda.
Testicular plasmacytoma. Neoplastic plasma cells express monotypic kappa light chain.
Testicular plasmacytoma. Neoplastic plasma cells are negative for lambda light chain.
A: light chain restriction
Back Extra: Plasmacytoma
- Clinical: Patients with genitourinary plasmacytoma may present with a mass lesion or haematuria, or they may be asymptomatic.
- Micro: Sheets of mature or atypical plasma cells are seen in testicular plasmacytomas, often ranging from small and mature to large and atypical cells.
- Ancillary: Neoplastic plasma cells in plasmacytoma express monotypic kappa or lambda light chain, and there is a clonal IGH gene rearrangement.
Reference Gallery:
Testicular plasmacytoma. A fleshy tan tumour bulges from the cut surface of the testis. The patient had a history of plasma cell myeloma.
Testicular plasmacytoma. Low-power view shows a diffuse proliferation of plasma cells almost completely obliterating the seminiferous tubules.
Testicular plasmacytoma. The plasmacytoma involves the testis in an intertubular pattern.
Testicular plasmacytoma. Sheets of atypical plasma cells adjacent to an atrophic seminiferous tubule.
Testicular plasmacytoma. Plasma cells range from small and mature to large and atypical. Note the characteristic nuclear chromatin and the paranuclear halo in some of the cells.
Testicular plasmacytoma. Neoplastic plasma cells express monotypic kappa light chain.
Testicular plasmacytoma. Neoplastic plasma cells are negative for lambda light chain.

Q: Grossly, a genitourinary plasmacytoma may present as a fleshy, tan tumor bulging from the cut surface; patients often present with a mass, hematuria, or a known history of systemic [...].
Testicular plasmacytoma. A fleshy tan tumour bulges from the cut surface of the testis. The patient had a history of plasma cell myeloma.
A: plasma cell myeloma
Back Extra: Plasmacytoma
- Clinical: Patients with genitourinary plasmacytoma may present with a mass lesion or haematuria, or they may be asymptomatic.
- Micro: Sheets of mature or atypical plasma cells are seen in testicular plasmacytomas, often ranging from small and mature to large and atypical cells.
- Ancillary: Neoplastic plasma cells in plasmacytoma express monotypic kappa or lambda light chain, and there is a clonal IGH gene rearrangement.
Reference Gallery:
Testicular plasmacytoma. A fleshy tan tumour bulges from the cut surface of the testis. The patient had a history of plasma cell myeloma.
Testicular plasmacytoma. Low-power view shows a diffuse proliferation of plasma cells almost completely obliterating the seminiferous tubules.
Testicular plasmacytoma. The plasmacytoma involves the testis in an intertubular pattern.
Testicular plasmacytoma. Sheets of atypical plasma cells adjacent to an atrophic seminiferous tubule.
Testicular plasmacytoma. Plasma cells range from small and mature to large and atypical. Note the characteristic nuclear chromatin and the paranuclear halo in some of the cells.
Testicular plasmacytoma. Neoplastic plasma cells express monotypic kappa light chain.
Testicular plasmacytoma. Neoplastic plasma cells are negative for lambda light chain.

Q: In Metastasis to the Testis and Paratestis, the most common microscopic growth pattern (seen in approximately 40% of cases), which classically spreads between but spares the seminiferous tubules, is the [...] pattern.
Prostate cancer metastatic to the testis. An interstitial growth pattern is present in this field.
A: interstitial
Back Extra: Metastasis to the Testis and Paratestis
- Clinical: Metastases to the testis and paratestis usually occur in patients with a history of cancer and may present as testicular enlargement, a palpable testicular mass, or hydrocoele.
- Micro: Common growth patterns include interstitial (40%), destructive (26%), and nodular (21%). Intratubular growth can be observed in lymphomas and carcinomas from the prostate, kidney, and bladder.
- Ancillary: Appropriate immunohistochemical studies are necessary for identifying the origin of metastatic tumours, with markers like PSA being helpful but requiring cautious interpretation.
Reference Gallery:
Colon adenocarcinoma metastatic to the paratestis. This colonic adenocarcinoma (colloid/mucinous type) has produced a mass adjacent to the testis.
Prostate cancer metastatic to the testis. The metastasis has produced a solitary nodule, as seen in a whole mount.
Prostate cancer metastatic to the testis. An interstitial growth pattern is present in this field.
Prostate cancer metastatic to the testis. The neoplasm is intensely positive for PSMA.

Q: Immunohistochemistry is essential for confirming the primary origin of a Metastasis to the Testis and Paratestis; for example, metastatic prostate cancer will be intensely positive for markers like PSA and [...].
Prostate cancer metastatic to the testis. The neoplasm is intensely positive for PSMA.
A: PSMA
Back Extra: Metastasis to the Testis and Paratestis
- Clinical: Metastases to the testis and paratestis usually occur in patients with a history of cancer and may present as testicular enlargement, a palpable testicular mass, or hydrocoele.
- Micro: Common growth patterns include interstitial (40%), destructive (26%), and nodular (21%). Intratubular growth can be observed in lymphomas and carcinomas from the prostate, kidney, and bladder.
- Ancillary: Appropriate immunohistochemical studies are necessary for identifying the origin of metastatic tumours, with markers like PSA being helpful but requiring cautious interpretation.
Reference Gallery:
Colon adenocarcinoma metastatic to the paratestis. This colonic adenocarcinoma (colloid/mucinous type) has produced a mass adjacent to the testis.
Prostate cancer metastatic to the testis. The metastasis has produced a solitary nodule, as seen in a whole mount.
Prostate cancer metastatic to the testis. An interstitial growth pattern is present in this field.
Prostate cancer metastatic to the testis. The neoplasm is intensely positive for PSMA.

Q: Grossly, Metastasis to the Testis and Paratestis from a colonic adenocarcinoma primary often presents as a mass adjacent to the testis and may exhibit a mucinous or [...] appearance.
Colon adenocarcinoma metastatic to the paratestis. This colonic adenocarcinoma (colloid/mucinous type) has produced a mass adjacent to the testis.
A: colloid
Back Extra: Metastasis to the Testis and Paratestis
- Clinical: Metastases to the testis and paratestis usually occur in patients with a history of cancer and may present as testicular enlargement, a palpable testicular mass, or hydrocoele.
- Micro: Common growth patterns include interstitial (40%), destructive (26%), and nodular (21%). Intratubular growth can be observed in lymphomas and carcinomas from the prostate, kidney, and bladder.
- Ancillary: Appropriate immunohistochemical studies are necessary for identifying the origin of metastatic tumours, with markers like PSA being helpful but requiring cautious interpretation.
Reference Gallery:
Colon adenocarcinoma metastatic to the paratestis. This colonic adenocarcinoma (colloid/mucinous type) has produced a mass adjacent to the testis.
Prostate cancer metastatic to the testis. The metastasis has produced a solitary nodule, as seen in a whole mount.
Prostate cancer metastatic to the testis. An interstitial growth pattern is present in this field.
Prostate cancer metastatic to the testis. The neoplasm is intensely positive for PSMA.

Q: A well-circumscribed testicular mass that presents histologically with an insular or glandular architecture, uniform cells with punctate chromatin, and strong synaptophysin expression is characteristic of [...].
Testicular neuroendocrine tumour (NET), prepubertal-type. The tumour is well circumscribed and demarcated from the surrounding testicular parenchyma.
Testicular neuroendocrine tumour (NET), prepubertal-type. Insular and glandular patterns. Note the punctate chromatin and mucin in the glandular lumen.
Testicular neuroendocrine tumour (NET), prepubertal-type. Immunostaining for synaptophysin is strongly positive.
A: Testicular Neuroendocrine Tumor, Prepubertal-Type
Back Extra: Testicular Neuroendocrine Tumour, Prepubertal-Type
- Clinical: A testicular mass or swelling is the most common presenting symptom, with a minority of patients experiencing carcinoid syndrome symptoms such as hot flashes and diarrhoea.
- Micro: The tumour typically exhibits an insular or trabecular architecture with eosinophilic cytoplasm and uniform round nuclei with fine chromatin.
- Ancillary: The tumour cells express chromogranin A, synaptophysin, and serotonin, while being negative for thyroid transcription factor 1 (TTF1), KIT, CDX2, and OCT3/4.
Reference Gallery:
Testicular neuroendocrine tumour (NET), prepubertal-type. The tumour is well circumscribed and demarcated from the surrounding testicular parenchyma.
Testicular neuroendocrine tumour (NET), prepubertal-type. Insular and glandular patterns. Note the punctate chromatin and mucin in the glandular lumen.
Testicular neuroendocrine tumour (NET), prepubertal-type. Immunostaining for synaptophysin is strongly positive.

Q: In Testicular Neuroendocrine Tumor, Prepubertal-Type, the tumor cells typically exhibit an insular or trabecular architecture and feature uniform round nuclei with distinctive [...].
Testicular neuroendocrine tumour (NET), prepubertal-type. Insular and glandular patterns. Note the punctate chromatin and mucin in the glandular lumen.
A: fine, punctate chromatin
Back Extra: Testicular Neuroendocrine Tumour, Prepubertal-Type
- Clinical: A testicular mass or swelling is the most common presenting symptom, with a minority of patients experiencing carcinoid syndrome symptoms such as hot flashes and diarrhoea.
- Micro: The tumour typically exhibits an insular or trabecular architecture with eosinophilic cytoplasm and uniform round nuclei with fine chromatin.
- Ancillary: The tumour cells express chromogranin A, synaptophysin, and serotonin, while being negative for thyroid transcription factor 1 (TTF1), KIT, CDX2, and OCT3/4.
Reference Gallery:
Testicular neuroendocrine tumour (NET), prepubertal-type. The tumour is well circumscribed and demarcated from the surrounding testicular parenchyma.
Testicular neuroendocrine tumour (NET), prepubertal-type. Insular and glandular patterns. Note the punctate chromatin and mucin in the glandular lumen.
Testicular neuroendocrine tumour (NET), prepubertal-type. Immunostaining for synaptophysin is strongly positive.

Q: Immunohistochemically, the cells of Testicular Neuroendocrine Tumor, Prepubertal-Type are characteristically negative for germ cell markers (like OCT3/4) but strongly express neuroendocrine markers such as chromogranin A and [...].
Testicular neuroendocrine tumour (NET), prepubertal-type. Immunostaining for synaptophysin is strongly positive.
A: synaptophysin
Back Extra: Testicular Neuroendocrine Tumour, Prepubertal-Type
- Clinical: A testicular mass or swelling is the most common presenting symptom, with a minority of patients experiencing carcinoid syndrome symptoms such as hot flashes and diarrhoea.
- Micro: The tumour typically exhibits an insular or trabecular architecture with eosinophilic cytoplasm and uniform round nuclei with fine chromatin.
- Ancillary: The tumour cells express chromogranin A, synaptophysin, and serotonin, while being negative for thyroid transcription factor 1 (TTF1), KIT, CDX2, and OCT3/4.
Reference Gallery:
Testicular neuroendocrine tumour (NET), prepubertal-type. The tumour is well circumscribed and demarcated from the surrounding testicular parenchyma.
Testicular neuroendocrine tumour (NET), prepubertal-type. Insular and glandular patterns. Note the punctate chromatin and mucin in the glandular lumen.
Testicular neuroendocrine tumour (NET), prepubertal-type. Immunostaining for synaptophysin is strongly positive.

Q: Microscopic evaluation of a testicular mass revealing neoplastic rete epithelium with intra-rete and invasive growth, characteristically composed of eosinophilic and clear cells with noticeable cytological atypia, is diagnostic for [...].
Adenocarcinoma of the rete testis. The tumour is composed of eosinophilic and clear cells.
Adenocarcinoma of the rete testis. Neoplastic rete epithelium.
A: Adenocarcinoma of the Collecting Ducts and Rete Testis
Back Extra: Adenocarcinoma of the Collecting Ducts and Rete Testis
- Clinical: Most patients present with a mass and/or pain. The tumour can be associated with hydrocoele. Local spread and metastasis to para-aortic and iliac lymph nodes are common.
- Micro: Histologically, the tumours show intrarete and invasive growth, with a range of patterns such as papillary, solid, glandular, cribriform, and glomeruloid. Tumour cells are cuboidal to columnar with nuclear pseudostratification and noticeable cytological atypia.
- Ancillary: Immunohistochemistry is positive for CK7, AE1/AE3, EMA, vimentin, PAX8, and BerEP4. Diagnostic molecular pathology is not relevant.
Reference Gallery:
Adenocarcinoma of the rete testis. The tumour is composed of eosinophilic and clear cells.
Adenocarcinoma of the rete testis. Neoplastic rete epithelium.

Q: Histologic sections of Adenocarcinoma of the Epididymis typically demonstrate malignant glands and tubules lined by tall cuboidal to columnar cells with hyperchromatic nuclei and characteristic [...] (or eosinophilic) cytoplasm.
Adenocarcinoma of the epididymis. Malignant glands and tubules.
Adenocarcinoma of the epididymis. Tubules are lined by tall cuboidal to columnar cells with hyperchromatic nuclei and clear to eosinophilic cytoplasm.
A: clear to amphophilic
Back Extra: Adenocarcinoma of the Epididymis
- Clinical: Adenocarcinoma of the epididymis presents as a scrotal mass, hydrocoele, and pain, with symptoms lasting from 1 month to 5 years.
- Micro: The morphological patterns include tubular, papillary, tubulopapillary, papillary cystic, and undifferentiated sheet-like growth. Tubules are lined by cuboidal to columnar cells with clear to amphophilic cytoplasm.
- Ancillary: Immunohistochemistry is positive for EMA, CEA, PAX8, PAX2, and villin, and negative for WT1, CDX2, AMACR, PSA, and RCCm.
Reference Gallery:
Adenocarcinoma of the epididymis. Malignant glands and tubules.
Adenocarcinoma of the epididymis. Area of necrosis along with malignant glands and tubules.
Adenocarcinoma of the epididymis. Tubules are lined by tall cuboidal to columnar cells with hyperchromatic nuclei and clear to eosinophilic cytoplasm.
Adenocarcinoma of the epididymis. Tumour cells are immunoreactive for EMA.

Q: Immunohistochemical analysis of Adenocarcinoma of the Epididymis characteristically demonstrates positivity for PAX8, CEA, and the epithelial marker [...].
Adenocarcinoma of the epididymis. Tumour cells are immunoreactive for EMA.
A: EMA
Back Extra: Adenocarcinoma of the Epididymis
- Clinical: Adenocarcinoma of the epididymis presents as a scrotal mass, hydrocoele, and pain, with symptoms lasting from 1 month to 5 years.
- Micro: The morphological patterns include tubular, papillary, tubulopapillary, papillary cystic, and undifferentiated sheet-like growth. Tubules are lined by cuboidal to columnar cells with clear to amphophilic cytoplasm.
- Ancillary: Immunohistochemistry is positive for EMA, CEA, PAX8, PAX2, and villin, and negative for WT1, CDX2, AMACR, PSA, and RCCm.
Reference Gallery:
Adenocarcinoma of the epididymis. Malignant glands and tubules.
Adenocarcinoma of the epididymis. Area of necrosis along with malignant glands and tubules.
Adenocarcinoma of the epididymis. Tubules are lined by tall cuboidal to columnar cells with hyperchromatic nuclei and clear to eosinophilic cytoplasm.
Adenocarcinoma of the epididymis. Tumour cells are immunoreactive for EMA.

Q: In Adenoma of the collecting ducts and rete testis, the characteristic microscopic appearance features variably sized, dilated [...] lined by a single layer of cytologically bland cuboidal to low columnar cells.
Adenoma of the rete testis. Cystadenoma of the rete testis characterized by dilated cystic spaces with papillae lined by a single layer of cytologically bland columnar cells.
A: cystic spaces
Back Extra: Adenoma of the collecting ducts and rete testis
- Clinical: Patients generally present with a unilateral painless mass, or the tumour is found incidentally in an orchiectomy specimen.
- Micro: The tumour is composed of variably sized dilated cystic spaces lined by cuboidal to low columnar cells, sometimes ciliated, with bland nuclear features.
- Ancillary: No specific ancillary studies are typically required for diagnosis.
Reference Gallery:
Adenoma of the rete testis. Cystadenoma of the rete testis characterized by dilated cystic spaces with papillae lined by a single layer of cytologically bland columnar cells.

Q: An ovarian epithelial-type tumor of the testis or paratestis that exhibits a solid, tubulocystic, or papillary architecture lined by hobnail or polygonal cells with prominent clear to eosinophilic cytoplasm is diagnostic of [...].
Clear cell adenocarcinoma. Tumour abuts the paratesticular tissue. It consists of clear and eosinophilic cells.
Clear cell adenocarcinoma. Ovarian epithelial–type tumour showing polygonal cells with clear cytoplasm and papillary architecture.
Clear cell adenocarcinoma. This ovarian epithelial–type tumour is characterized by clear and eosinophilic cells.
A: Clear Cell Adenocarcinoma
Back Extra: Clear Cell Adenocarcinoma
- Clinical: Patients present with an intratesticular or paratesticular mass, often with or without local or abdominal pain.
- Micro: The tumour consists of polygonal, columnar, or hobnail cells with clear cytoplasm and shows a solid, tubulocystic, or papillary architecture.
- Ancillary: Immunohistochemistry shows positivity for CK7, EMA, PAX8, and AR, and negativity for WT1, CA19-9, CK20, calretinin, D2-40, ER, and PR.
Reference Gallery:
Clear cell adenocarcinoma. Tumour abuts the paratesticular tissue. It consists of clear and eosinophilic cells.
Clear cell adenocarcinoma. Ovarian epithelial–type tumour showing polygonal cells with clear cytoplasm and papillary architecture.
Clear cell adenocarcinoma. This ovarian epithelial–type tumour is characterized by clear and eosinophilic cells.

Q: Microscopically, Clear Cell Adenocarcinoma often displays a solid, tubulocystic, or [...] architecture lined by characteristic hobnail or polygonal cells with distinct clear cytoplasm.
Clear cell adenocarcinoma. Ovarian epithelial–type tumour showing polygonal cells with clear cytoplasm and papillary architecture.
A: papillary
Back Extra: Clear Cell Adenocarcinoma
- Clinical: Patients present with an intratesticular or paratesticular mass, often with or without local or abdominal pain.
- Micro: The tumour consists of polygonal, columnar, or hobnail cells with clear cytoplasm and shows a solid, tubulocystic, or papillary architecture.
- Ancillary: Immunohistochemistry shows positivity for CK7, EMA, PAX8, and AR, and negativity for WT1, CA19-9, CK20, calretinin, D2-40, ER, and PR.
Reference Gallery:
Clear cell adenocarcinoma. Tumour abuts the paratesticular tissue. It consists of clear and eosinophilic cells.
Clear cell adenocarcinoma. Ovarian epithelial–type tumour showing polygonal cells with clear cytoplasm and papillary architecture.
Clear cell adenocarcinoma. This ovarian epithelial–type tumour is characterized by clear and eosinophilic cells.

Q: [...] of the paratestis are surface epithelial neoplasms that characteristically feature confluent glands, a cribriform growth pattern, and squamous differentiation.
Endometrioid adenocarcinoma. A paratesticular endometrioid adenocarcinoma of the ovarian surface epithelial type showing confluent glands and cribriform pattern (right) and hyalinized and atrophic seminiferous tubules (left).
Endometrioid adenocarcinoma. A paratesticular endometrioid adenocarcinoma of the ovarian surface epithelial type showing malignant endometrioid glands with squamous/squamoid morules.
A: Endometrioid tumors
Back Extra: Endometrioid Tumours
- Clinical: Patients with endometrioid tumours typically present with scrotal swelling, and the mean age at diagnosis is 68 years.
- Micro: The histological features of endometrioid adenocarcinomas include glandular, papillary, cribriform, or solid growth patterns, often with squamous differentiation.
- Ancillary: Immunohistochemically, endometrioid tumours are positive for CK7, PAX8, ER, and PR, and negative for CK20, CDX2, and GPC3.
Reference Gallery:
Endometrioid adenocarcinoma. A paratesticular endometrioid adenocarcinoma of the ovarian surface epithelial type showing confluent glands and cribriform pattern (right) and hyalinized and atrophic seminiferous tubules (left).
Endometrioid adenocarcinoma. A paratesticular endometrioid adenocarcinoma of the ovarian surface epithelial type showing malignant endometrioid glands with squamous/squamoid morules.

Q: A characteristic histologic finding in paratesticular endometrioid tumors is the presence of malignant glands forming squamoid morules, which represents [...].
Endometrioid adenocarcinoma. A paratesticular endometrioid adenocarcinoma of the ovarian surface epithelial type showing malignant endometrioid glands with squamous/squamoid morules.
A: squamous differentiation
Back Extra: Endometrioid Tumours
- Clinical: Patients with endometrioid tumours typically present with scrotal swelling, and the mean age at diagnosis is 68 years.
- Micro: The histological features of endometrioid adenocarcinomas include glandular, papillary, cribriform, or solid growth patterns, often with squamous differentiation.
- Ancillary: Immunohistochemically, endometrioid tumours are positive for CK7, PAX8, ER, and PR, and negative for CK20, CDX2, and GPC3.
Reference Gallery:
Endometrioid adenocarcinoma. A paratesticular endometrioid adenocarcinoma of the ovarian surface epithelial type showing confluent glands and cribriform pattern (right) and hyalinized and atrophic seminiferous tubules (left).
Endometrioid adenocarcinoma. A paratesticular endometrioid adenocarcinoma of the ovarian surface epithelial type showing malignant endometrioid glands with squamous/squamoid morules.

Q: On gross examination, the cut surface of a mucinous borderline tumor typically reveals a combination of solid and cystic components containing fibrotic and [...] material.
Mucinous borderline tumour. The cut surface shows a cystic and solid tumour with mucoid and fibrotic areas.
A: mucoid
Back Extra: Mucinous Borderline Tumour
- Clinical: Patients usually present with a painless or occasionally painful swelling of the testis, most commonly in middle-aged and elderly men.
- Micro: The tumour is characterized by cystic areas with papillary projections lined by intestinal-type epithelium, showing mild to moderate cytological atypia and complex architecture.
- Ancillary: CK20 positivity with variable expression of CK7 and CDX2 is typically observed, but no specific diagnostic molecular pathology is relevant.
Reference Gallery:
Mucinous borderline tumour. The cut surface shows a cystic and solid tumour with mucoid and fibrotic areas.
Mucinous borderline tumour. The cystic areas are lined by intestinal-type epithelium, showing usually mild to moderate cellular atypia and stratification of the nuclei.
Mucinous borderline tumour. The tumour comprises predominantly cystic areas, containing papillary projections with a complex architecture. There is a surrounding fibrotic wall with inflammation.

Q: Microscopically, the cystic areas and complex papillary projections of a mucinous borderline tumor are characteristically lined by [...] epithelium exhibiting mild to moderate nuclear stratification and atypia.
Mucinous borderline tumour. The cystic areas are lined by intestinal-type epithelium, showing usually mild to moderate cellular atypia and stratification of the nuclei.
Mucinous borderline tumour. The tumour comprises predominantly cystic areas, containing papillary projections with a complex architecture. There is a surrounding fibrotic wall with inflammation.
A: intestinal-type
Back Extra: Mucinous Borderline Tumour
- Clinical: Patients usually present with a painless or occasionally painful swelling of the testis, most commonly in middle-aged and elderly men.
- Micro: The tumour is characterized by cystic areas with papillary projections lined by intestinal-type epithelium, showing mild to moderate cytological atypia and complex architecture.
- Ancillary: CK20 positivity with variable expression of CK7 and CDX2 is typically observed, but no specific diagnostic molecular pathology is relevant.
Reference Gallery:
Mucinous borderline tumour. The cut surface shows a cystic and solid tumour with mucoid and fibrotic areas.
Mucinous borderline tumour. The cystic areas are lined by intestinal-type epithelium, showing usually mild to moderate cellular atypia and stratification of the nuclei.
Mucinous borderline tumour. The tumour comprises predominantly cystic areas, containing papillary projections with a complex architecture. There is a surrounding fibrotic wall with inflammation.

Q: Microscopically, an invasive testicular tumor composed of severely atypical epithelial cells forming back-to-back cribriform glands and floating in extracellular mucin pools is characteristic of [...].
Mucinous cystadenocarcinoma. The neoplastic cells show severe cytological atypia and form cribriform glandular structures. The tumour infiltrates into and between seminiferous tubules.
Mucinous cystadenocarcinoma. Pools of mucin containing severely atypical columnar to cuboidal epithelial cells.
A: mucinous cystadenocarcinoma
Back Extra: Mucinous Cystadenocarcinoma
- Clinical: Patients usually present with a painful or painless enlargement of the testis, occasionally with erectile dysfunction or ulceration.
- Micro: Mucinous cystadenocarcinoma is an invasive tumour composed of cuboidal to columnar cells with severe cytological atypia, forming back-to-back cribriform glands and papillary structures.
- Ancillary: Mucinous cystadenocarcinomas are typically positive for CK20, CDX2, and MUC2, and they show various degrees of CK7 positivity, indicating an intestinal phenotype.
Reference Gallery:
Mucinous cystadenocarcinoma. The neoplastic cells show severe cytological atypia and form cribriform glandular structures. The tumour infiltrates into and between seminiferous tubules.
Mucinous cystadenocarcinoma. Pools of mucin containing severely atypical columnar to cuboidal epithelial cells.
Mucinous cystadenocarcinoma. Paratesticular tumour mixed with background benign component.

Q: Mucinous cystadenocarcinoma of the testis typically demonstrates immunohistochemical positivity for CK20, CDX2, and MUC2, which is indicative of an [...] phenotype.
Mucinous cystadenocarcinoma. Pools of mucin containing severely atypical columnar to cuboidal epithelial cells.
A: intestinal
Back Extra: Mucinous Cystadenocarcinoma
- Clinical: Patients usually present with a painful or painless enlargement of the testis, occasionally with erectile dysfunction or ulceration.
- Micro: Mucinous cystadenocarcinoma is an invasive tumour composed of cuboidal to columnar cells with severe cytological atypia, forming back-to-back cribriform glands and papillary structures.
- Ancillary: Mucinous cystadenocarcinomas are typically positive for CK20, CDX2, and MUC2, and they show various degrees of CK7 positivity, indicating an intestinal phenotype.
Reference Gallery:
Mucinous cystadenocarcinoma. The neoplastic cells show severe cytological atypia and form cribriform glandular structures. The tumour infiltrates into and between seminiferous tubules.
Mucinous cystadenocarcinoma. Pools of mucin containing severely atypical columnar to cuboidal epithelial cells.
Mucinous cystadenocarcinoma. Paratesticular tumour mixed with background benign component.

Q: A paratesticular mass exhibiting well-formed papillary structures lined by serous-type epithelium with low-grade atypia is characteristic of [...].
Serous cystadenocarcinoma. Well-formed papillary structures are lined by serous-type epithelium with low-grade atypia.
A: serous cystadenocarcinoma
Back Extra: Serous Cystadenocarcinoma
- Clinical: Serous cystadenocarcinoma presents as testicular enlargement due to a paratesticular mass or a deeper lesion in the testicular parenchyma.
- Micro: The tumor shows well-formed papillary, tubular, or cribriform structures lined by serous-type epithelium, often with desmoplastic stroma and psammoma bodies.
- Ancillary: Immunohistochemistry is positive for PAX8, AE1/AE3, CK8/18, CK7, ER, EMA, WT1, BerEP4, CA125, and CK5/6, and negative for CK20, inhibin, calretinin, PLAP, CD30, OCT4, and AFP.
Reference Gallery:
Serous cystadenocarcinoma. Well-formed papillary structures are lined by serous-type epithelium with low-grade atypia.
Serous cystadenocarcinoma. Tumour cells lie within desmoplastic stroma with associated psammoma bodies.
Serous cystadenocarcinoma. Surrounding areas contain remnants of a serous tumour of borderline malignancy.

Q: A characteristic histologic finding in serous cystadenocarcinoma is the presence of tumor cells within a desmoplastic stroma accompanied by concentric calcifications known as [...].
Serous cystadenocarcinoma. Tumour cells lie within desmoplastic stroma with associated psammoma bodies.
A: psammoma bodies
Back Extra: Serous Cystadenocarcinoma
- Clinical: Serous cystadenocarcinoma presents as testicular enlargement due to a paratesticular mass or a deeper lesion in the testicular parenchyma.
- Micro: The tumor shows well-formed papillary, tubular, or cribriform structures lined by serous-type epithelium, often with desmoplastic stroma and psammoma bodies.
- Ancillary: Immunohistochemistry is positive for PAX8, AE1/AE3, CK8/18, CK7, ER, EMA, WT1, BerEP4, CA125, and CK5/6, and negative for CK20, inhibin, calretinin, PLAP, CD30, OCT4, and AFP.
Reference Gallery:
Serous cystadenocarcinoma. Well-formed papillary structures are lined by serous-type epithelium with low-grade atypia.
Serous cystadenocarcinoma. Tumour cells lie within desmoplastic stroma with associated psammoma bodies.
Serous cystadenocarcinoma. Surrounding areas contain remnants of a serous tumour of borderline malignancy.

Q: Histologic sections of serous cystadenocarcinoma may reveal surrounding remnants of a precursor lesion known as a [...].
Serous cystadenocarcinoma. Surrounding areas contain remnants of a serous tumour of borderline malignancy.
A: serous tumor of borderline malignancy
Back Extra: Serous Cystadenocarcinoma
- Clinical: Serous cystadenocarcinoma presents as testicular enlargement due to a paratesticular mass or a deeper lesion in the testicular parenchyma.
- Micro: The tumor shows well-formed papillary, tubular, or cribriform structures lined by serous-type epithelium, often with desmoplastic stroma and psammoma bodies.
- Ancillary: Immunohistochemistry is positive for PAX8, AE1/AE3, CK8/18, CK7, ER, EMA, WT1, BerEP4, CA125, and CK5/6, and negative for CK20, inhibin, calretinin, PLAP, CD30, OCT4, and AFP.
Reference Gallery:
Serous cystadenocarcinoma. Well-formed papillary structures are lined by serous-type epithelium with low-grade atypia.
Serous cystadenocarcinoma. Tumour cells lie within desmoplastic stroma with associated psammoma bodies.
Serous cystadenocarcinoma. Surrounding areas contain remnants of a serous tumour of borderline malignancy.

Q: A cystic tumor lined by a single layer of bland, ciliated columnar to cuboidal epithelium without atypia or mitotic figures is the histologic hallmark of a [...].
Serous cystadenoma. Cystic tumour lined by a single layer of columnar ciliated cells.
A: Serous Cystadenoma
Back Extra: Serous Cystadenoma
- Clinical: Serous cystadenomas are usually cystic tumours that may cause symptoms related to mass effects or be incidental findings, with patient ages ranging from 35 to 73 years.
- Micro: Tumours are cystic and contain serous fluid. The cysts are lined by a non-stratified cuboidal to ciliated columnar epithelium with bland nuclei and abundant pale cytoplasm.
- Ancillary: Essential for diagnosis are cystic tumours lined by a single layer of ciliated columnar or cuboidal epithelium without atypia or mitotic figures, and positive immunohistochemistry for ER, PR, WT1, and PAX8.
Reference Gallery:
Serous cystadenoma. Cystic tumour lined by a single layer of columnar ciliated cells.

Q: Microscopically, the cysts of a Serous Cystadenoma are classically lined by a single layer of bland, non-stratified [...] columnar to cuboidal cells containing pale cytoplasm.
Serous cystadenoma. Cystic tumour lined by a single layer of columnar ciliated cells.
A: ciliated
Back Extra: Serous Cystadenoma
- Clinical: Serous cystadenomas are usually cystic tumours that may cause symptoms related to mass effects or be incidental findings, with patient ages ranging from 35 to 73 years.
- Micro: Tumours are cystic and contain serous fluid. The cysts are lined by a non-stratified cuboidal to ciliated columnar epithelium with bland nuclei and abundant pale cytoplasm.
- Ancillary: Essential for diagnosis are cystic tumours lined by a single layer of ciliated columnar or cuboidal epithelium without atypia or mitotic figures, and positive immunohistochemistry for ER, PR, WT1, and PAX8.
Reference Gallery:
Serous cystadenoma. Cystic tumour lined by a single layer of columnar ciliated cells.

Q: Clinically, an adenomatoid tumor in males most commonly presents as a painless mass in the [...] region, often arising from the epididymis.
Adenomatoid tumour. Paratesticular adenomatoid tumour arising from the epididymis and pushing into the testicular parenchyma. The cut surface is homogeneous and greyish to whitish tan.
Adenomatoid tumour. Low magnification of a paratesticular adenomatoid tumour adjacent to the tunica vaginalis of the testis.
A: paratesticular
Back Extra: Adenomatoid Tumour
- Clinical: Adenomatoid tumours are most commonly discovered as a painless paratesticular mass, often found incidentally on routine examination or imaging.
- Micro: Microscopically, adenomatoid tumours show tubules and cystic spaces lined by flattened to plump mesothelial cells, with thin, thread-like cytoplasmic bridges and a fibrous stroma.
- Ancillary: Immunohistochemical studies show positivity for calretinin, WT1, and BAP1, which helps in confirming the diagnosis of an adenomatoid tumour.
Reference Gallery:
Adenomatoid tumour. Paratesticular adenomatoid tumour arising from the epididymis and pushing into the testicular parenchyma. The cut surface is homogeneous and greyish to whitish tan.
Adenomatoid tumour. Low magnification of a paratesticular adenomatoid tumour adjacent to the tunica vaginalis of the testis.
Adenomatoid tumour. The tumour shows tubules and cystic spaces lined by flattened to plump mesothelial cells. Thin, thread-like cytoplasmic bridges are present. Basophilic material may be seen within the tubular or cystic structures. The stroma is fibrous to collagenous.
Adenomatoid tumour. Tubules lined by plump mesothelial cells with cribriform architecture. The mesothelial cells are rounded and show prominent nuclei. The stroma is collagenous to fibrous.
Adenomatoid tumour. A cellular adenomatoid tumour with tubules and cord-like structures. The cells are plump and round to oval with prominent nuclei.
Adenomatoid tumour. Prominent lymphocytic sprinkling and aggregates are present in many tumours.
Adenomatoid tumour. Intratesticular adenomatoid tumour extending between the seminiferous tubules.
Adenomatoid tumour. Necrosis in an adenomatoid tumour may be confusing and lead to its erroneous interpretation as a malignant neoplasm.
Adenomatoid tumour. Tubules and cord-like structures lined by mesothelial cells are diffusely positive for calretinin.
Adenomatoid tumour. BAP1 nuclear expression is retained, favouring the diagnosis of an adenomatoid tumour.
Adenomatoid tumour. The cells are plump with abundant eosinophilic cytoplasm and rounded nuclei with conspicuous nucleoli. Prominent nuclear inclusions are present.

Q: Microscopically, an adenomatoid tumor is characterized by tubules and cystic spaces lined by mesothelial cells that frequently display characteristic thin, [...].
Adenomatoid tumour. The tumour shows tubules and cystic spaces lined by flattened to plump mesothelial cells. Thin, thread-like cytoplasmic bridges are present. Basophilic material may be seen within the tubular or cystic structures. The stroma is fibrous to collagenous.
A: thread-like cytoplasmic bridges
Back Extra: Adenomatoid Tumour
- Clinical: Adenomatoid tumours are most commonly discovered as a painless paratesticular mass, often found incidentally on routine examination or imaging.
- Micro: Microscopically, adenomatoid tumours show tubules and cystic spaces lined by flattened to plump mesothelial cells, with thin, thread-like cytoplasmic bridges and a fibrous stroma.
- Ancillary: Immunohistochemical studies show positivity for calretinin, WT1, and BAP1, which helps in confirming the diagnosis of an adenomatoid tumour.
Reference Gallery:
Adenomatoid tumour. Paratesticular adenomatoid tumour arising from the epididymis and pushing into the testicular parenchyma. The cut surface is homogeneous and greyish to whitish tan.
Adenomatoid tumour. Low magnification of a paratesticular adenomatoid tumour adjacent to the tunica vaginalis of the testis.
Adenomatoid tumour. The tumour shows tubules and cystic spaces lined by flattened to plump mesothelial cells. Thin, thread-like cytoplasmic bridges are present. Basophilic material may be seen within the tubular or cystic structures. The stroma is fibrous to collagenous.
Adenomatoid tumour. Tubules lined by plump mesothelial cells with cribriform architecture. The mesothelial cells are rounded and show prominent nuclei. The stroma is collagenous to fibrous.
Adenomatoid tumour. A cellular adenomatoid tumour with tubules and cord-like structures. The cells are plump and round to oval with prominent nuclei.
Adenomatoid tumour. Prominent lymphocytic sprinkling and aggregates are present in many tumours.
Adenomatoid tumour. Intratesticular adenomatoid tumour extending between the seminiferous tubules.
Adenomatoid tumour. Necrosis in an adenomatoid tumour may be confusing and lead to its erroneous interpretation as a malignant neoplasm.
Adenomatoid tumour. Tubules and cord-like structures lined by mesothelial cells are diffusely positive for calretinin.
Adenomatoid tumour. BAP1 nuclear expression is retained, favouring the diagnosis of an adenomatoid tumour.
Adenomatoid tumour. The cells are plump with abundant eosinophilic cytoplasm and rounded nuclei with conspicuous nucleoli. Prominent nuclear inclusions are present.

Q: Immunohistochemical studies of an adenomatoid tumor confirm its mesothelial origin with diffuse positivity for WT1 and [...], alongside retained nuclear expression of BAP1.
Adenomatoid tumour. Tubules and cord-like structures lined by mesothelial cells are diffusely positive for calretinin.
Adenomatoid tumour. BAP1 nuclear expression is retained, favouring the diagnosis of an adenomatoid tumour.
A: calretinin
Back Extra: Adenomatoid Tumour
- Clinical: Adenomatoid tumours are most commonly discovered as a painless paratesticular mass, often found incidentally on routine examination or imaging.
- Micro: Microscopically, adenomatoid tumours show tubules and cystic spaces lined by flattened to plump mesothelial cells, with thin, thread-like cytoplasmic bridges and a fibrous stroma.
- Ancillary: Immunohistochemical studies show positivity for calretinin, WT1, and BAP1, which helps in confirming the diagnosis of an adenomatoid tumour.
Reference Gallery:
Adenomatoid tumour. Paratesticular adenomatoid tumour arising from the epididymis and pushing into the testicular parenchyma. The cut surface is homogeneous and greyish to whitish tan.
Adenomatoid tumour. Low magnification of a paratesticular adenomatoid tumour adjacent to the tunica vaginalis of the testis.
Adenomatoid tumour. The tumour shows tubules and cystic spaces lined by flattened to plump mesothelial cells. Thin, thread-like cytoplasmic bridges are present. Basophilic material may be seen within the tubular or cystic structures. The stroma is fibrous to collagenous.
Adenomatoid tumour. Tubules lined by plump mesothelial cells with cribriform architecture. The mesothelial cells are rounded and show prominent nuclei. The stroma is collagenous to fibrous.
Adenomatoid tumour. A cellular adenomatoid tumour with tubules and cord-like structures. The cells are plump and round to oval with prominent nuclei.
Adenomatoid tumour. Prominent lymphocytic sprinkling and aggregates are present in many tumours.
Adenomatoid tumour. Intratesticular adenomatoid tumour extending between the seminiferous tubules.
Adenomatoid tumour. Necrosis in an adenomatoid tumour may be confusing and lead to its erroneous interpretation as a malignant neoplasm.
Adenomatoid tumour. Tubules and cord-like structures lined by mesothelial cells are diffusely positive for calretinin.
Adenomatoid tumour. BAP1 nuclear expression is retained, favouring the diagnosis of an adenomatoid tumour.
Adenomatoid tumour. The cells are plump with abundant eosinophilic cytoplasm and rounded nuclei with conspicuous nucleoli. Prominent nuclear inclusions are present.

Q: Microscopically, Cystadenoma of the epididymis is characterized by fibrovascular cores and cystic structures lined by bland, tall columnar cells with apical [...].
Cystadenoma of the epididymis. Fibrovascular cores lined by columnar epithelium with apical cilia.
A: cilia
Back Extra: Cystadenoma of the epididymis
- Clinical: Cystadenoma of the epididymis presents as a scrotal mass, sometimes associated with infertility, and 10% of patients may have pain.
- Micro: The tumor is characterized by tubular and cystic structures lined by bland tall columnar cells with eosinophilic cytoplasm and apical cilia.
- Ancillary: Cystadenoma cells are negative for PSA and PAP, which helps in differentiating it from metastatic prostatic carcinoma.
Reference Gallery:
Cystadenoma of the epididymis. Fibrovascular cores lined by columnar epithelium with apical cilia.

Q: A benign scrotal mass demonstrating fibrovascular cores lined by bland columnar epithelium with prominent apical cilia is the hallmark microscopic presentation of [...].
Cystadenoma of the epididymis. Fibrovascular cores lined by columnar epithelium with apical cilia.
A: Cystadenoma of the epididymis
Back Extra: Cystadenoma of the epididymis
- Clinical: Cystadenoma of the epididymis presents as a scrotal mass, sometimes associated with infertility, and 10% of patients may have pain.
- Micro: The tumor is characterized by tubular and cystic structures lined by bland tall columnar cells with eosinophilic cytoplasm and apical cilia.
- Ancillary: Cystadenoma cells are negative for PSA and PAP, which helps in differentiating it from metastatic prostatic carcinoma.
Reference Gallery:
Cystadenoma of the epididymis. Fibrovascular cores lined by columnar epithelium with apical cilia.

Q: Microscopically, Papillary cystadenoma of the epididymis is characterized by tubules and papillae lined by epithelial cells with bland apical nuclei and characteristic [...].
Papillary cystadenoma. Tubules and papillae with slender fibrovascular cores. The cells have bland apical nuclei and clear basal cytoplasm.
Papillary cystadenoma. Tumour cells with bland nuclei and clear cytoplasm.
A: clear basal cytoplasm
Back Extra: Papillary cystadenoma of the epididymis
- Clinical: Most patients present in their third decade of life with a painless, slowly growing scrotal swelling.
- Micro: Tubules and papillae lined by cuboidal to columnar epithelial cells with bland apical nuclei and clear basal cytoplasm.
- Ancillary: Immunoreactive for CK7, PAX8, and CAIX with cup-like basolateral positivity; negative for CD10, calretinin, and WT1.
Reference Gallery:
Papillary cystadenoma. Tubules and papillae projecting into the lumen.
Papillary cystadenoma. The cyst contains an eosinophilic, colloid-like secretion.
Papillary cystadenoma. Tubules and papillae with slender fibrovascular cores. The cells have bland apical nuclei and clear basal cytoplasm.
Papillary cystadenoma. Tumour cells with bland nuclei and clear cytoplasm.

Q: Histologically, the cystic spaces in Papillary cystadenoma of the epididymis frequently contain an eosinophilic, [...] secretion.
Papillary cystadenoma. The cyst contains an eosinophilic, colloid-like secretion.
A: colloid-like
Back Extra: Papillary cystadenoma of the epididymis
- Clinical: Most patients present in their third decade of life with a painless, slowly growing scrotal swelling.
- Micro: Tubules and papillae lined by cuboidal to columnar epithelial cells with bland apical nuclei and clear basal cytoplasm.
- Ancillary: Immunoreactive for CK7, PAX8, and CAIX with cup-like basolateral positivity; negative for CD10, calretinin, and WT1.
Reference Gallery:
Papillary cystadenoma. Tubules and papillae projecting into the lumen.
Papillary cystadenoma. The cyst contains an eosinophilic, colloid-like secretion.
Papillary cystadenoma. Tubules and papillae with slender fibrovascular cores. The cells have bland apical nuclei and clear basal cytoplasm.
Papillary cystadenoma. Tumour cells with bland nuclei and clear cytoplasm.

Q: The defining architectural feature of Papillary cystadenoma of the epididymis involves [...] with slender fibrovascular cores projecting into the cystic lumen.
Papillary cystadenoma. Tubules and papillae projecting into the lumen.
Papillary cystadenoma. Tubules and papillae with slender fibrovascular cores. The cells have bland apical nuclei and clear basal cytoplasm.
A: tubules and papillae
Back Extra: Papillary cystadenoma of the epididymis
- Clinical: Most patients present in their third decade of life with a painless, slowly growing scrotal swelling.
- Micro: Tubules and papillae lined by cuboidal to columnar epithelial cells with bland apical nuclei and clear basal cytoplasm.
- Ancillary: Immunoreactive for CK7, PAX8, and CAIX with cup-like basolateral positivity; negative for CD10, calretinin, and WT1.
Reference Gallery:
Papillary cystadenoma. Tubules and papillae projecting into the lumen.
Papillary cystadenoma. The cyst contains an eosinophilic, colloid-like secretion.
Papillary cystadenoma. Tubules and papillae with slender fibrovascular cores. The cells have bland apical nuclei and clear basal cytoplasm.
Papillary cystadenoma. Tumour cells with bland nuclei and clear cytoplasm.

Q: Microscopically, Mesothelioma often features epithelioid cells with tubulopapillary architecture, but it can also present with a [...] pattern, demonstrating a mixture of both plump epithelioid and spindle cell components.
Mesothelioma. Invasive tubular and tubulopapillary mesothelioma with a prominent desmoplastic reaction. The cells are moderately pleomorphic.
Mesothelioma. There is a mixture of plump epithelioid cells, with some spindle cell components (right), consistent with a biphasic mesothelioma.
A: biphasic
Back Extra: Mesothelioma
- Clinical: Mesothelioma often presents with a hydrocoele or a palpable mass, and is typically diagnosed after surgical resection. It is rare, occurring in patients in their sixth to seventh decade of life.
- Micro: Tumours are predominantly epithelioid with papillary, tubular, and tubulopapillary architecture. High-grade mesotheliomas show necrosis and marked pleomorphism.
- Ancillary: Mesothelioma cells are positive for calretinin, podoplanin, and WT1. CDKN2A homozygous deletion and BAP1 loss are characteristic molecular findings.
Reference Gallery:
Mesothelioma. Low-magnification photomicrograph showing a nodular invasive tumour with tubulopapillary and solid architecture and a surrounding desmoplastic reaction. Prominent necrosis is present in high-grade mesothelioma.
Mesothelioma. Invasive tubular and tubulopapillary mesothelioma with a prominent desmoplastic reaction. The cells are moderately pleomorphic.
Mesothelioma. Invasive mesothelioma in continuity with the normal mesothelium lining of the tunica vaginalis.
Mesothelioma. High magnification of a solid epithelioid mesothelioma with variably pleomorphic tumour cells that have prominent nucleoli, prominent mitoses, single-cell apoptosis, and multinucleation, in a collagenous background.
Mesothelioma. There is a mixture of plump epithelioid cells, with some spindle cell components (right), consistent with a biphasic mesothelioma.
Mesothelioma. Testicular parenchyma and mesothelioma of the tunica vaginalis.
Mesothelioma. Infiltration of the epididymis.

Q: Paratesticular Mesothelioma can be diagnosed histologically when an invasive tumor is seen arising in direct continuity with the normal mesothelial lining of the [...].
Mesothelioma. Invasive mesothelioma in continuity with the normal mesothelium lining of the tunica vaginalis.
Mesothelioma. Testicular parenchyma and mesothelioma of the tunica vaginalis.
A: tunica vaginalis
Back Extra: Mesothelioma
- Clinical: Mesothelioma often presents with a hydrocoele or a palpable mass, and is typically diagnosed after surgical resection. It is rare, occurring in patients in their sixth to seventh decade of life.
- Micro: Tumours are predominantly epithelioid with papillary, tubular, and tubulopapillary architecture. High-grade mesotheliomas show necrosis and marked pleomorphism.
- Ancillary: Mesothelioma cells are positive for calretinin, podoplanin, and WT1. CDKN2A homozygous deletion and BAP1 loss are characteristic molecular findings.
Reference Gallery:
Mesothelioma. Low-magnification photomicrograph showing a nodular invasive tumour with tubulopapillary and solid architecture and a surrounding desmoplastic reaction. Prominent necrosis is present in high-grade mesothelioma.
Mesothelioma. Invasive tubular and tubulopapillary mesothelioma with a prominent desmoplastic reaction. The cells are moderately pleomorphic.
Mesothelioma. Invasive mesothelioma in continuity with the normal mesothelium lining of the tunica vaginalis.
Mesothelioma. High magnification of a solid epithelioid mesothelioma with variably pleomorphic tumour cells that have prominent nucleoli, prominent mitoses, single-cell apoptosis, and multinucleation, in a collagenous background.
Mesothelioma. There is a mixture of plump epithelioid cells, with some spindle cell components (right), consistent with a biphasic mesothelioma.
Mesothelioma. Testicular parenchyma and mesothelioma of the tunica vaginalis.
Mesothelioma. Infiltration of the epididymis.

Q: A firm, painless scrotal mass demonstrating a classic biphasic population of small neuroblast-like cells and large pigment-laden cells in a tubular pattern is characteristic of [...].
Melanotic neuroectodermal tumour of the epididymis. Dual populations of tumour cells comprising small neuroblast-like cells and large pigment-laden cells arranged in a tubular pattern.
A: Melanotic Neuroectodermal Tumor of the Epididymis
Back Extra: Melanotic Neuroectodermal Tumour of the Epididymis
- Clinical: Patients present with a firm, painless, rapidly growing, well-circumscribed scrotal mass, often accompanied by hydrocoele.
- Micro: MNT is characterized by nests, cords, and gland-like structures of large epithelioid cells and small neuroblast-like cells in a fibrocollagenous stroma.
- Ancillary: The tumour cells are immunoreactive for synaptophysin, CD57, NSE, and other markers, with large cells being positive for pancytokeratins and HMB45.
Reference Gallery:
Melanotic neuroectodermal tumour of the epididymis. Epididymis involved by melanotic neuroectodermal tumour.
Melanotic neuroectodermal tumour of the epididymis. Biphasic tumour cells are interspersed among epididymal tubules.
Melanotic neuroectodermal tumour of the epididymis. Biphasic tumour cells are present between the muscle layers.
Melanotic neuroectodermal tumour of the epididymis. Dual populations of tumour cells comprising small neuroblast-like cells and large pigment-laden cells arranged in a tubular pattern.
Melanotic neuroectodermal tumour of the epididymis. Small tumour cells immunoreactive for synaptophysin.

Q: In Melanotic Neuroectodermal Tumor of the Epididymis, the smaller population of neuroblast-like cells characteristically shows strong immunoreactivity for neuroendocrine markers such as [...].
Melanotic neuroectodermal tumour of the epididymis. Small tumour cells immunoreactive for synaptophysin.
A: synaptophysin
Back Extra: Melanotic Neuroectodermal Tumour of the Epididymis
- Clinical: Patients present with a firm, painless, rapidly growing, well-circumscribed scrotal mass, often accompanied by hydrocoele.
- Micro: MNT is characterized by nests, cords, and gland-like structures of large epithelioid cells and small neuroblast-like cells in a fibrocollagenous stroma.
- Ancillary: The tumour cells are immunoreactive for synaptophysin, CD57, NSE, and other markers, with large cells being positive for pancytokeratins and HMB45.
Reference Gallery:
Melanotic neuroectodermal tumour of the epididymis. Epididymis involved by melanotic neuroectodermal tumour.
Melanotic neuroectodermal tumour of the epididymis. Biphasic tumour cells are interspersed among epididymal tubules.
Melanotic neuroectodermal tumour of the epididymis. Biphasic tumour cells are present between the muscle layers.
Melanotic neuroectodermal tumour of the epididymis. Dual populations of tumour cells comprising small neuroblast-like cells and large pigment-laden cells arranged in a tubular pattern.
Melanotic neuroectodermal tumour of the epididymis. Small tumour cells immunoreactive for synaptophysin.

Q: In Desmoplastic Small Round Cell Tumor, the characteristic histologic appearance consists of sharply outlined nests of uniform small cells set in a prominent [...].
Desmoplastic small round cell tumour. Sharply outlined nests of neoplastic cells set in a desmoplastic stroma.
Desmoplastic small round cell tumour. The individual neoplastic cells are commonly uniform small cells with scant cytoplasm.
A: desmoplastic stroma
Back Extra: Desmoplastic Small Round Cell Tumour
- Clinical: Patients with paratesticular tumours present with a palpable mass, and spread to the intra-abdominal cavity is common. DSRCT primarily affects children and young adults, with a peak incidence in the third decade of life.
- Micro: DSRCT is characterized by sharply outlined nests of uniform small cells with scant cytoplasm set in a prominent desmoplastic stroma. Mitoses are frequent, and individual cell necrosis is common.
- Ancillary: Immunohistochemically, DSRCT shows multiphenotypic expression with reactivity for markers of epithelial, muscle, and neural differentiation. The presence of EWSR1::WT1 gene rearrangements is characteristic.
Reference Gallery:
Desmoplastic small round cell tumour. Sharply outlined nests of neoplastic cells set in a desmoplastic stroma.
Desmoplastic small round cell tumour. The individual neoplastic cells are commonly uniform small cells with scant cytoplasm.

Q: Biopsy of an intra-abdominal mass in a young adult reveals sharply outlined nests of uniform small cells with scant cytoplasm within a prominent desmoplastic stroma, a histologic appearance highly characteristic of [...].
Desmoplastic small round cell tumour. Sharply outlined nests of neoplastic cells set in a desmoplastic stroma.
Desmoplastic small round cell tumour. The individual neoplastic cells are commonly uniform small cells with scant cytoplasm.
A: Desmoplastic Small Round Cell Tumor
Back Extra: Desmoplastic Small Round Cell Tumour
- Clinical: Patients with paratesticular tumours present with a palpable mass, and spread to the intra-abdominal cavity is common. DSRCT primarily affects children and young adults, with a peak incidence in the third decade of life.
- Micro: DSRCT is characterized by sharply outlined nests of uniform small cells with scant cytoplasm set in a prominent desmoplastic stroma. Mitoses are frequent, and individual cell necrosis is common.
- Ancillary: Immunohistochemically, DSRCT shows multiphenotypic expression with reactivity for markers of epithelial, muscle, and neural differentiation. The presence of EWSR1::WT1 gene rearrangements is characteristic.
Reference Gallery:
Desmoplastic small round cell tumour. Sharply outlined nests of neoplastic cells set in a desmoplastic stroma.
Desmoplastic small round cell tumour. The individual neoplastic cells are commonly uniform small cells with scant cytoplasm.

Q: A patient presents with a hard scrotal mass and an associated hydrocele. Microscopic examination reveals cords and nests of pleomorphic cells with keratinization, nuclear hyperchromasia, and eosinophilic to clear cytoplasm, establishing the diagnosis of [...].
Squamous cell carcinoma arising from the tunica vaginalis. Low-power view showing cords and nests of cells with eosinophilic to clear cytoplasm and necrosis.
Squamous cell carcinoma arising from the tunica vaginalis. Low-power view of the carcinoma and benign testis.
A: Squamous Cell Carcinoma of the Epididymis
Back Extra: Squamous Cell Carcinoma of the Epididymis
- Clinical: Patients present with a hard scrotal mass, often associated with a hydrocoele.
- Micro: The tumor displays variably pleomorphic squamous cells, keratinization, nuclear hyperchromasia, and eosinophilic to amphophilic to clear cytoplasm.
- Ancillary: No specific ancillary studies are relevant for the diagnosis.
Reference Gallery:
Squamous cell carcinoma arising from the tunica vaginalis. Low-power view showing cords and nests of cells with eosinophilic to clear cytoplasm and necrosis.
Squamous cell carcinoma arising from the tunica vaginalis. Low-power view of the carcinoma and benign testis.
Squamous cell carcinoma arising from the tunica vaginalis. Foci of nests of cells with eosinophilic cytoplasm.
Squamous cell carcinoma arising from the tunica vaginalis. Foci of nests of cells with eosinophilic cytoplasm.

Q: Histologically, Squamous Cell Carcinoma of the Epididymis is characterized by cords and nests of variably pleomorphic cells that display nuclear hyperchromasia, eosinophilic to clear cytoplasm, and characteristic [...].
Squamous cell carcinoma arising from the tunica vaginalis. Foci of nests of cells with eosinophilic cytoplasm.
Squamous cell carcinoma arising from the tunica vaginalis. Foci of nests of cells with eosinophilic cytoplasm.
A: keratinization
Back Extra: Squamous Cell Carcinoma of the Epididymis
- Clinical: Patients present with a hard scrotal mass, often associated with a hydrocoele.
- Micro: The tumor displays variably pleomorphic squamous cells, keratinization, nuclear hyperchromasia, and eosinophilic to amphophilic to clear cytoplasm.
- Ancillary: No specific ancillary studies are relevant for the diagnosis.
Reference Gallery:
Squamous cell carcinoma arising from the tunica vaginalis. Low-power view showing cords and nests of cells with eosinophilic to clear cytoplasm and necrosis.
Squamous cell carcinoma arising from the tunica vaginalis. Low-power view of the carcinoma and benign testis.
Squamous cell carcinoma arising from the tunica vaginalis. Foci of nests of cells with eosinophilic cytoplasm.
Squamous cell carcinoma arising from the tunica vaginalis. Foci of nests of cells with eosinophilic cytoplasm.

Q: Histologically, a well-demarcated testicular tumor containing cystic cavities lined by a single layer of mucinous columnar epithelium without marked atypia or architectural complexity is highly characteristic of a [...].
Mucinous cystadenoma. The tumour is well demarcated with a fibrotic wall.
Mucinous cystadenoma. The cystic cavities are lined by a single layer of mucinous columnar epithelium without marked cellular atypia or architectural complexity.
A: mucinous cystadenoma
Q: Mucinous Cystadenoma
- Clinical: Patients with [...] usually present with a painless enlargement of the testis. Occasionally, pain or heaviness is reported.
- Micro: The cystic cavities in [...] are lined by a single layer of columnar epithelium that resembles intestinal, gastric, or cervical mucosa, without cellular atypia or architectural complexity.
- Ancillary: Immunohistochemistry shows [...] cells positive for CK20 and CDX2, with variable expression of CK7.
Reference Gallery:
Mucinous cystadenoma. The tumour is well demarcated with a fibrotic wall.
Mucinous cystadenoma. The cystic cavities are lined by a single layer of mucinous columnar epithelium without marked cellular atypia or architectural complexity.
Mucinous cystadenoma. The tumour cells show positive immunohistochemical staining for CK20.
Mucinous cystadenoma. The tumour cells show positive immunohistochemical nuclear staining for CDX2.
A: mucinous cystadenoma; mucinous cystadenoma; mucinous cystadenoma

Q: Immunohistochemistry in a mucinous cystadenoma reveals that the tumor cells are classically positive for CK20 and the intestinal nuclear marker [...].
Mucinous cystadenoma. The tumour cells show positive immunohistochemical staining for CK20.
Mucinous cystadenoma. The tumour cells show positive immunohistochemical nuclear staining for CDX2.
A: CDX2
Q: Mucinous Cystadenoma
- Clinical: Patients with [...] usually present with a painless enlargement of the testis. Occasionally, pain or heaviness is reported.
- Micro: The cystic cavities in [...] are lined by a single layer of columnar epithelium that resembles intestinal, gastric, or cervical mucosa, without cellular atypia or architectural complexity.
- Ancillary: Immunohistochemistry shows [...] cells positive for CK20 and CDX2, with variable expression of CK7.
Reference Gallery:
Mucinous cystadenoma. The tumour is well demarcated with a fibrotic wall.
Mucinous cystadenoma. The cystic cavities are lined by a single layer of mucinous columnar epithelium without marked cellular atypia or architectural complexity.
Mucinous cystadenoma. The tumour cells show positive immunohistochemical staining for CK20.
Mucinous cystadenoma. The tumour cells show positive immunohistochemical nuclear staining for CDX2.
A: mucinous cystadenoma; mucinous cystadenoma; mucinous cystadenoma

Q: A paratesticular or intratesticular mass demonstrating irregular papillary formations lined by stratified ciliated columnar cells with mild to moderate cytological atypia is characteristic of [...].
Serous tumour of borderline malignancy. The tumour consists of papillary structures lined by partially stratified columnar cells with mild to moderate cytological atypia.
Serous tumour of borderline malignancy. Irregular papillary formations with irregular hierarchical branching.
A: serous tumor of borderline malignancy
Q: Serous Tumour of Borderline Malignancy
- Clinical: Symptoms of [...] are related to a paratesticular or intratesticular mass, commonly presenting in a wide age range, including children.
- Micro: Microscopic findings of [...] include irregular papillary formations with stratified ciliated columnar cells and mild to moderate cytological atypia.
- Ancillary: Ancillary studies show that tumour cells in [...] are positive for pancytokeratin, WT1, PAX8, ER, PR, CA125, CEA, CK5/6, and CK7, and about 50% show mutations in the BRAF gene.
Reference Gallery:
Serous tumour of borderline malignancy. The cystic tumour is separated by a fibrous wall. The cyst contains serous fluid.
Serous tumour of borderline malignancy. The tumour consists of papillary structures lined by partially stratified columnar cells with mild to moderate cytological atypia.
Serous tumour of borderline malignancy. The tumour has a low Ki-67 index.
Serous tumour of borderline malignancy. The tumour is positive for PAX8.
Serous tumour of borderline malignancy. Irregular papillary formations with irregular hierarchical branching.
A: Serous Tumour of Borderline Malignancy; Serous Tumour of Borderline Malignancy; Serous Tumour of Borderline Malignancy

Q: Immunohistochemical analysis of serous tumor of borderline malignancy typically demonstrates strong nuclear positivity for the Müllerian marker [...].
Serous tumour of borderline malignancy. The tumour is positive for PAX8.
A: PAX8
Q: Serous Tumour of Borderline Malignancy
- Clinical: Symptoms of [...] are related to a paratesticular or intratesticular mass, commonly presenting in a wide age range, including children.
- Micro: Microscopic findings of [...] include irregular papillary formations with stratified ciliated columnar cells and mild to moderate cytological atypia.
- Ancillary: Ancillary studies show that tumour cells in [...] are positive for pancytokeratin, WT1, PAX8, ER, PR, CA125, CEA, CK5/6, and CK7, and about 50% show mutations in the BRAF gene.
Reference Gallery:
Serous tumour of borderline malignancy. The cystic tumour is separated by a fibrous wall. The cyst contains serous fluid.
Serous tumour of borderline malignancy. The tumour consists of papillary structures lined by partially stratified columnar cells with mild to moderate cytological atypia.
Serous tumour of borderline malignancy. The tumour has a low Ki-67 index.
Serous tumour of borderline malignancy. The tumour is positive for PAX8.
Serous tumour of borderline malignancy. Irregular papillary formations with irregular hierarchical branching.
A: Serous Tumour of Borderline Malignancy; Serous Tumour of Borderline Malignancy; Serous Tumour of Borderline Malignancy

Q: Macroscopically, a serous tumor of borderline malignancy typically presents as a [...] mass that is separated by a fibrous wall and filled with serous fluid.
Serous tumour of borderline malignancy. The cystic tumour is separated by a fibrous wall. The cyst contains serous fluid.
A: cystic
Q: Serous Tumour of Borderline Malignancy
- Clinical: Symptoms of [...] are related to a paratesticular or intratesticular mass, commonly presenting in a wide age range, including children.
- Micro: Microscopic findings of [...] include irregular papillary formations with stratified ciliated columnar cells and mild to moderate cytological atypia.
- Ancillary: Ancillary studies show that tumour cells in [...] are positive for pancytokeratin, WT1, PAX8, ER, PR, CA125, CEA, CK5/6, and CK7, and about 50% show mutations in the BRAF gene.
Reference Gallery:
Serous tumour of borderline malignancy. The cystic tumour is separated by a fibrous wall. The cyst contains serous fluid.
Serous tumour of borderline malignancy. The tumour consists of papillary structures lined by partially stratified columnar cells with mild to moderate cytological atypia.
Serous tumour of borderline malignancy. The tumour has a low Ki-67 index.
Serous tumour of borderline malignancy. The tumour is positive for PAX8.
Serous tumour of borderline malignancy. Irregular papillary formations with irregular hierarchical branching.
A: Serous Tumour of Borderline Malignancy; Serous Tumour of Borderline Malignancy; Serous Tumour of Borderline Malignancy

Q: Often associated with a hydrocele clinically, a [...] is microscopically characterized by papillary structures with a stromal core, lined by a single row of bland cuboidal cells.
Well-differentiated papillary mesothelial tumour. Papillary structures with stromal formation, lined by a single row of cuboidal cells with bland nuclear features and exceptional to absent mitosis.
Well-differentiated papillary mesothelial tumour. Papillary structures with stromal formation, lined by a single row of cuboidal cells with bland nuclear features.
A: Well-Differentiated Papillary Mesothelial Tumor
Back Extra: Well-Differentiated Papillary Mesothelial Tumour
- Clinical: Most cases are associated with a hydrocoele; tumours rarely occur as a scrotal mass. The patient age range is 18–70 years.
- Micro: WDPMTs display papillary structures with a stromal formation, lined by a single row of cuboidal cells that have bland nuclear features and minimal to absent mitosis.
- Ancillary: WDPMT is positive for mesothelial markers including calretinin, WT1, HBME1, and D2-40. It is negative for B72.3, CEA, and CD15.
Reference Gallery:
Well-differentiated papillary mesothelial tumour. Papillary structures with stromal formation, lined by a single row of cuboidal cells with bland nuclear features and exceptional to absent mitosis.
Well-differentiated papillary mesothelial tumour. Papillary structures with stromal formation, lined by a single row of cuboidal cells with bland nuclear features.

Q: In a Well-Differentiated Papillary Mesothelial Tumor, the papillary structures are classically lined by a [...] that possess bland nuclear features and minimal to absent mitoses.
Well-differentiated papillary mesothelial tumour. Papillary structures with stromal formation, lined by a single row of cuboidal cells with bland nuclear features and exceptional to absent mitosis.
Well-differentiated papillary mesothelial tumour. Papillary structures with stromal formation, lined by a single row of cuboidal cells with bland nuclear features.
A: single row of cuboidal cells
Back Extra: Well-Differentiated Papillary Mesothelial Tumour
- Clinical: Most cases are associated with a hydrocoele; tumours rarely occur as a scrotal mass. The patient age range is 18–70 years.
- Micro: WDPMTs display papillary structures with a stromal formation, lined by a single row of cuboidal cells that have bland nuclear features and minimal to absent mitosis.
- Ancillary: WDPMT is positive for mesothelial markers including calretinin, WT1, HBME1, and D2-40. It is negative for B72.3, CEA, and CD15.
Reference Gallery:
Well-differentiated papillary mesothelial tumour. Papillary structures with stromal formation, lined by a single row of cuboidal cells with bland nuclear features and exceptional to absent mitosis.
Well-differentiated papillary mesothelial tumour. Papillary structures with stromal formation, lined by a single row of cuboidal cells with bland nuclear features.

Q: At high power, the neoplastic cells of an Adult Granulosa Cell Tumor are classically characterized by scant cytoplasm and elongated nuclei containing distinct [...].
Adult granulosa cell tumour. Adult granulosa cell tumour of the testis. Tumour cells with scant cytoplasm and nuclear grooves.
A: nuclear grooves
Back Extra: Adult Granulosa Cell Tumor
- Clinical: Patients typically present with a testicular mass, which may be associated with gynaecomastia.
- Micro: The tumour cells have scant cytoplasm and elongated nuclei with nuclear grooves, often forming nests or cords.
- Ancillary: Immunohistochemistry shows positivity for SF1, vimentin, inhibin, calretinin, and FOXL2.
Reference Gallery:
Adult granulosa cell tumour. Tumour nodules growing diffusely with cystic areas.
Adult granulosa cell tumour. Adult granulosa cell tumour in corded and nested patterns with luteinization of granulosa cells (left).
Adult granulosa cell tumour. Unencapsulated tumour with nodular growth.
Adult granulosa cell tumour. Adult granulosa cell tumour of the testis. The neoplastic cells form nests.
Adult granulosa cell tumour. Adult granulosa cell tumour of the testis. Tumour cells with scant cytoplasm and nuclear grooves.

Q: Architecturally, an Adult Granulosa Cell Tumor frequently displays unencapsulated growth with cells forming corded and [...] patterns.
Adult granulosa cell tumour. Adult granulosa cell tumour in corded and nested patterns with luteinization of granulosa cells (left).
Adult granulosa cell tumour. Adult granulosa cell tumour of the testis. The neoplastic cells form nests.
A: nested
Back Extra: Adult Granulosa Cell Tumor
- Clinical: Patients typically present with a testicular mass, which may be associated with gynaecomastia.
- Micro: The tumour cells have scant cytoplasm and elongated nuclei with nuclear grooves, often forming nests or cords.
- Ancillary: Immunohistochemistry shows positivity for SF1, vimentin, inhibin, calretinin, and FOXL2.
Reference Gallery:
Adult granulosa cell tumour. Tumour nodules growing diffusely with cystic areas.
Adult granulosa cell tumour. Adult granulosa cell tumour in corded and nested patterns with luteinization of granulosa cells (left).
Adult granulosa cell tumour. Unencapsulated tumour with nodular growth.
Adult granulosa cell tumour. Adult granulosa cell tumour of the testis. The neoplastic cells form nests.
Adult granulosa cell tumour. Adult granulosa cell tumour of the testis. Tumour cells with scant cytoplasm and nuclear grooves.

Q: A mixed germ cell-sex cord tumor that most commonly arises in dysgenetic gonads in patients with a disorder of sex development (DSD) is known as [...].
Gonadoblastoma in a dysgenetic gonad. Dysgenetic testis from a 4-year-old girl with a disorder of sex development and 45,X/46,XY mosaicism in which a gonadoblastoma is starting to develop. Note the dysplastic testicular cords/tubules and an early focus of gonadoblastoma in the centre left.
Gonadoblastoma. Low-power view. A gonadoblastoma in a streak gonad shows the characteristic small nests in a cellular stroma. This case shows extensive calcifications, some with a mulberry-like configuration.
A: Gonadoblastoma
Gonadoblastoma
- Clinical: Most patients with gonadoblastoma present as neonates with ambiguous genitalia in the setting of a disorder of sex development (DSD).
- Micro: Gonadoblastoma features round nests and cords composed of germ cells, small sex cord cells, and globoid deposits of hyaline basement membrane material.
- Ancillary: Immunohistochemistry for PLAP, KIT (CD117), and podoplanin in the germ cells, and inhibin, nuclear SOX9, and FOXL2 in the sex cord cells, helps in diagnosing gonadoblastoma.
Reference Gallery:
Gonadoblastoma in a dysgenetic gonad. Dysgenetic testis from a 4-year-old girl with a disorder of sex development and 45,X/46,XY mosaicism in which a gonadoblastoma is starting to develop. Note the dysplastic testicular cords/tubules and an early focus of gonadoblastoma in the centre left.
Gonadoblastoma in dysgenetic gonad. Dysgenetic testis from a 4-year-old girl with a disorder of sex development and 45,X/46,XY mosaicism in which a gonadoblastoma is starting to develop. Closer view of the developing gonadoblastoma in the same case as is shown in Fig. 20225. Note the basement membrane hyaline deposits and nests of two cellular populations (germ cells and sex cord cells).
Gonadoblastoma. Germ cells of gonadoblastoma showing nuclei positive for OCT3/4.
Gonadoblastoma. Germ cells of gonadoblastoma showing membranous staining of PLAP.
Gonadoblastoma. Sex cord cells of gonadoblastoma showing positive staining of inhibin.
Gonadoblastoma. Sex cord cells of gonadoblastoma showing positive nuclear staining of SOX9.
Gonadoblastoma. Gonadoblastoma nest with germ cells of variable appearance, from spermatogonia-like cells to cells resembling those of germ cell neoplasia in situ / seminoma / dysgerminoma, as well as incompletely differentiated sex cord cells and round hyaline material. The surrounding spindle cell gonadal stroma contains Leydig-like or lutein-like cells.
Gonadoblastoma. An immunostain for PLAP strongly highlights germ cells.
Gonadoblastoma. Low-power view. A gonadoblastoma in a streak gonad shows the characteristic small nests in a cellular stroma. This case shows extensive calcifications, some with a mulberry-like configuration.
Gonadoblastoma. High-power view. The three components can be seen: germ cells, most resembling those of germ cell neoplasia in situ; sex cord cells; and round deposits of basement membrane matrix. A dissecting pattern is at the top, mimicking a focus of invasive germinoma.

Q: Histologically, Gonadoblastoma is characterized by round nests composed of germ cells and small sex cord cells, often arranged around globoid deposits of [...] material (which frequently undergo calcification).
Gonadoblastoma in dysgenetic gonad. Dysgenetic testis from a 4-year-old girl with a disorder of sex development and 45,X/46,XY mosaicism in which a gonadoblastoma is starting to develop. Closer view of the developing gonadoblastoma in the same case as is shown in Fig. 20225. Note the basement membrane hyaline deposits and nests of two cellular populations (germ cells and sex cord cells).
Gonadoblastoma. High-power view. The three components can be seen: germ cells, most resembling those of germ cell neoplasia in situ; sex cord cells; and round deposits of basement membrane matrix. A dissecting pattern is at the top, mimicking a focus of invasive germinoma.
A: hyaline basement membrane
Gonadoblastoma
- Clinical: Most patients with gonadoblastoma present as neonates with ambiguous genitalia in the setting of a disorder of sex development (DSD).
- Micro: Gonadoblastoma features round nests and cords composed of germ cells, small sex cord cells, and globoid deposits of hyaline basement membrane material.
- Ancillary: Immunohistochemistry for PLAP, KIT (CD117), and podoplanin in the germ cells, and inhibin, nuclear SOX9, and FOXL2 in the sex cord cells, helps in diagnosing gonadoblastoma.
Reference Gallery:
Gonadoblastoma in a dysgenetic gonad. Dysgenetic testis from a 4-year-old girl with a disorder of sex development and 45,X/46,XY mosaicism in which a gonadoblastoma is starting to develop. Note the dysplastic testicular cords/tubules and an early focus of gonadoblastoma in the centre left.
Gonadoblastoma in dysgenetic gonad. Dysgenetic testis from a 4-year-old girl with a disorder of sex development and 45,X/46,XY mosaicism in which a gonadoblastoma is starting to develop. Closer view of the developing gonadoblastoma in the same case as is shown in Fig. 20225. Note the basement membrane hyaline deposits and nests of two cellular populations (germ cells and sex cord cells).
Gonadoblastoma. Germ cells of gonadoblastoma showing nuclei positive for OCT3/4.
Gonadoblastoma. Germ cells of gonadoblastoma showing membranous staining of PLAP.
Gonadoblastoma. Sex cord cells of gonadoblastoma showing positive staining of inhibin.
Gonadoblastoma. Sex cord cells of gonadoblastoma showing positive nuclear staining of SOX9.
Gonadoblastoma. Gonadoblastoma nest with germ cells of variable appearance, from spermatogonia-like cells to cells resembling those of germ cell neoplasia in situ / seminoma / dysgerminoma, as well as incompletely differentiated sex cord cells and round hyaline material. The surrounding spindle cell gonadal stroma contains Leydig-like or lutein-like cells.
Gonadoblastoma. An immunostain for PLAP strongly highlights germ cells.
Gonadoblastoma. Low-power view. A gonadoblastoma in a streak gonad shows the characteristic small nests in a cellular stroma. This case shows extensive calcifications, some with a mulberry-like configuration.
Gonadoblastoma. High-power view. The three components can be seen: germ cells, most resembling those of germ cell neoplasia in situ; sex cord cells; and round deposits of basement membrane matrix. A dissecting pattern is at the top, mimicking a focus of invasive germinoma.

Q: In Gonadoblastoma, immunohistochemistry confirms the biphasic cellular populations: the germ cells are typically positive for OCT3/4 and PLAP, while the sex cord cells are characteristically positive for [...] and SOX9.
Gonadoblastoma. Germ cells of gonadoblastoma showing nuclei positive for OCT3/4.
Gonadoblastoma. Germ cells of gonadoblastoma showing membranous staining of PLAP.
Gonadoblastoma. Sex cord cells of gonadoblastoma showing positive staining of inhibin.
A: inhibin
Gonadoblastoma
- Clinical: Most patients with gonadoblastoma present as neonates with ambiguous genitalia in the setting of a disorder of sex development (DSD).
- Micro: Gonadoblastoma features round nests and cords composed of germ cells, small sex cord cells, and globoid deposits of hyaline basement membrane material.
- Ancillary: Immunohistochemistry for PLAP, KIT (CD117), and podoplanin in the germ cells, and inhibin, nuclear SOX9, and FOXL2 in the sex cord cells, helps in diagnosing gonadoblastoma.
Reference Gallery:
Gonadoblastoma in a dysgenetic gonad. Dysgenetic testis from a 4-year-old girl with a disorder of sex development and 45,X/46,XY mosaicism in which a gonadoblastoma is starting to develop. Note the dysplastic testicular cords/tubules and an early focus of gonadoblastoma in the centre left.
Gonadoblastoma in dysgenetic gonad. Dysgenetic testis from a 4-year-old girl with a disorder of sex development and 45,X/46,XY mosaicism in which a gonadoblastoma is starting to develop. Closer view of the developing gonadoblastoma in the same case as is shown in Fig. 20225. Note the basement membrane hyaline deposits and nests of two cellular populations (germ cells and sex cord cells).
Gonadoblastoma. Germ cells of gonadoblastoma showing nuclei positive for OCT3/4.
Gonadoblastoma. Germ cells of gonadoblastoma showing membranous staining of PLAP.
Gonadoblastoma. Sex cord cells of gonadoblastoma showing positive staining of inhibin.
Gonadoblastoma. Sex cord cells of gonadoblastoma showing positive nuclear staining of SOX9.
Gonadoblastoma. Gonadoblastoma nest with germ cells of variable appearance, from spermatogonia-like cells to cells resembling those of germ cell neoplasia in situ / seminoma / dysgerminoma, as well as incompletely differentiated sex cord cells and round hyaline material. The surrounding spindle cell gonadal stroma contains Leydig-like or lutein-like cells.
Gonadoblastoma. An immunostain for PLAP strongly highlights germ cells.
Gonadoblastoma. Low-power view. A gonadoblastoma in a streak gonad shows the characteristic small nests in a cellular stroma. This case shows extensive calcifications, some with a mulberry-like configuration.
Gonadoblastoma. High-power view. The three components can be seen: germ cells, most resembling those of germ cell neoplasia in situ; sex cord cells; and round deposits of basement membrane matrix. A dissecting pattern is at the top, mimicking a focus of invasive germinoma.

Q: Histologically, Intratubular Large Cell Hyalinizing Sertoli Cell Neoplasia is characterized by expanded seminiferous tubules filled with large, pale eosinophilic cells and a prominently [...].
Intratubular large cell hyalinizing Sertoli cell tumour. Expanded seminiferous tubules with prominent thick basement membrane and globular basement membrane deposits.
Intratubular large cell hyalinizing Sertoli cell tumour. Seminiferous tubules with thickened basement membrane material projecting into tubular lumina filled with large pale eosinophilic Sertoli cells.
A: thickened basement membrane
Back Extra: Intratubular Large Cell Hyalinizing Sertoli Cell Neoplasia
- Clinical: Intratubular large cell hyalinizing Sertoli cell neoplasia primarily manifests in prepubertal children with bilateral gynaecomastia, elevated serum estrogen levels, and advanced bone age.
- Micro: Characterized by intratubular proliferation of large, pale eosinophilic Sertoli cells within seminiferous tubules with a prominent thickened basement membrane.
- Ancillary: Positive for inhibin, aromatase, and cytokeratin (AE1/AE3).
Reference Gallery:
Intratubular large cell hyalinizing Sertoli cell tumour. Expanded seminiferous tubules with prominent thick basement membrane and globular basement membrane deposits.
Intratubular large cell hyalinizing Sertoli cell tumour. Seminiferous tubules with thickened basement membrane material projecting into tubular lumina filled with large pale eosinophilic Sertoli cells.
Intratubular large cell hyalinizing Sertoli cell tumour. Patchy distribution of expanded seminiferous tubules.

Q: The diagnosis of [...] is classically suspected in a prepubertal child presenting with bilateral gynecomastia whose testicular biopsy reveals an intratubular proliferation of large, pale eosinophilic cells with prominent globular basement membrane deposits.
Intratubular large cell hyalinizing Sertoli cell tumour. Expanded seminiferous tubules with prominent thick basement membrane and globular basement membrane deposits.
Intratubular large cell hyalinizing Sertoli cell tumour. Patchy distribution of expanded seminiferous tubules.
A: Intratubular Large Cell Hyalinizing Sertoli Cell Neoplasia
Back Extra: Intratubular Large Cell Hyalinizing Sertoli Cell Neoplasia
- Clinical: Intratubular large cell hyalinizing Sertoli cell neoplasia primarily manifests in prepubertal children with bilateral gynaecomastia, elevated serum estrogen levels, and advanced bone age.
- Micro: Characterized by intratubular proliferation of large, pale eosinophilic Sertoli cells within seminiferous tubules with a prominent thickened basement membrane.
- Ancillary: Positive for inhibin, aromatase, and cytokeratin (AE1/AE3).
Reference Gallery:
Intratubular large cell hyalinizing Sertoli cell tumour. Expanded seminiferous tubules with prominent thick basement membrane and globular basement membrane deposits.
Intratubular large cell hyalinizing Sertoli cell tumour. Seminiferous tubules with thickened basement membrane material projecting into tubular lumina filled with large pale eosinophilic Sertoli cells.
Intratubular large cell hyalinizing Sertoli cell tumour. Patchy distribution of expanded seminiferous tubules.

Q: A testicular mass typically presenting in the first 6 months of life, featuring a cut surface with a mix of cystic and solid areas and microscopic follicle-like structures, is characteristic of [...].
Juvenile granulosa cell tumour. Cut surface showing cystic and solid areas.
Juvenile granulosa cell tumour. Overview showing follicle-like structures.
A: Juvenile Granulosa Cell Tumor
Back Extra: Juvenile Granulosa Cell Tumour
- Clinical: Juvenile granulosa cell tumour (JGCT) usually presents as a testicular mass, rarely with gynaecomastia or premature puberty, and predominantly occurs in the first 6 months of life.
- Micro: JGCT shows a lobulated growth pattern with cystic and solid areas, follicle-like structures, and primitive-appearing granulosa cells without nuclear atypia.
- Ancillary: JGCTs commonly express SF1, calretinin, inhibin, SOX9, WT1, and FOXL2, and are usually negative for SALL4, AFP, and GPC3.
Reference Gallery:
Juvenile granulosa cell tumour. Cut surface showing cystic and solid areas.
Juvenile granulosa cell tumour. Overview showing follicle-like structures.
Juvenile granulosa cell tumour. Solid area composed of primitive-appearing granulosa cells without nuclear atypia.

Q: Microscopically, a Juvenile Granulosa Cell Tumor features primitive-appearing granulosa cells without nuclear atypia that frequently arrange into distinctive [...] structures.
Juvenile granulosa cell tumour. Overview showing follicle-like structures.
Juvenile granulosa cell tumour. Solid area composed of primitive-appearing granulosa cells without nuclear atypia.
A: follicle-like
Back Extra: Juvenile Granulosa Cell Tumour
- Clinical: Juvenile granulosa cell tumour (JGCT) usually presents as a testicular mass, rarely with gynaecomastia or premature puberty, and predominantly occurs in the first 6 months of life.
- Micro: JGCT shows a lobulated growth pattern with cystic and solid areas, follicle-like structures, and primitive-appearing granulosa cells without nuclear atypia.
- Ancillary: JGCTs commonly express SF1, calretinin, inhibin, SOX9, WT1, and FOXL2, and are usually negative for SALL4, AFP, and GPC3.
Reference Gallery:
Juvenile granulosa cell tumour. Cut surface showing cystic and solid areas.
Juvenile granulosa cell tumour. Overview showing follicle-like structures.
Juvenile granulosa cell tumour. Solid area composed of primitive-appearing granulosa cells without nuclear atypia.

Q: Microscopically, Large Cell Calcifying Sertoli Cell Tumor features nests and cords of cells with abundant eosinophilic cytoplasm and a myxoid to fibrous stroma that frequently contains prominent [...].
Large cell calcifying Sertoli cell tumour. Tumoural area replaced by collagenous stroma containing large numbers of calcific bodies of various sizes and shapes.
Large cell calcifying Sertoli cell tumour. The tumour cells contain abundant eosinophilic cytoplasm; several laminated foci of calcification are present.
A: calcifications
Back Extra: Large Cell Calcifying Sertoli Cell Tumour
- Clinical: Large cell calcifying Sertoli cell tumours (LCCSCTs) often present as painless testicular masses, and in teenagers, they may present with gynaecomastia and isosexual pseudoprecocity, especially if associated with Carney complex.
- Micro: LCCSCTs are characterized by nests and cords of cells with abundant eosinophilic cytoplasm, embedded in a myxoid to fibrous stroma, and often containing calcifications or ossification.
- Ancillary: LCCSCTs show reactivity for vimentin, inhibin, calretinin, SF1, S100, NSE, desmin, EMA, and focal cytokeratin, and are negative for nuclear β-catenin. Many cases have germline mutations in the PRKAR1A gene.
Reference Gallery:
Large cell calcifying Sertoli cell tumour. Tumoural area replaced by collagenous stroma containing large numbers of calcific bodies of various sizes and shapes.
Large cell calcifying Sertoli cell tumour. The tumour cells contain abundant eosinophilic cytoplasm; several laminated foci of calcification are present.
Large cell calcifying Sertoli cell tumour. Intratubular tumour shows strong immunohistochemical positivity for inhibin adjacent to the invasive tumour.
Large cell calcifying Sertoli cell tumour. The tumour cells with abundant eosinophilic cytoplasm are arranged in cords and nests in a myxoid stroma.

Q: Immunohistochemical evaluation of a Large Cell Calcifying Sertoli Cell Tumor typically demonstrates strong positivity for sex cord-stromal markers, such as [...].
Large cell calcifying Sertoli cell tumour. Intratubular tumour shows strong immunohistochemical positivity for inhibin adjacent to the invasive tumour.
A: inhibin
Back Extra: Large Cell Calcifying Sertoli Cell Tumour
- Clinical: Large cell calcifying Sertoli cell tumours (LCCSCTs) often present as painless testicular masses, and in teenagers, they may present with gynaecomastia and isosexual pseudoprecocity, especially if associated with Carney complex.
- Micro: LCCSCTs are characterized by nests and cords of cells with abundant eosinophilic cytoplasm, embedded in a myxoid to fibrous stroma, and often containing calcifications or ossification.
- Ancillary: LCCSCTs show reactivity for vimentin, inhibin, calretinin, SF1, S100, NSE, desmin, EMA, and focal cytokeratin, and are negative for nuclear β-catenin. Many cases have germline mutations in the PRKAR1A gene.
Reference Gallery:
Large cell calcifying Sertoli cell tumour. Tumoural area replaced by collagenous stroma containing large numbers of calcific bodies of various sizes and shapes.
Large cell calcifying Sertoli cell tumour. The tumour cells contain abundant eosinophilic cytoplasm; several laminated foci of calcification are present.
Large cell calcifying Sertoli cell tumour. Intratubular tumour shows strong immunohistochemical positivity for inhibin adjacent to the invasive tumour.
Large cell calcifying Sertoli cell tumour. The tumour cells with abundant eosinophilic cytoplasm are arranged in cords and nests in a myxoid stroma.

Q: A well-circumscribed, solid testicular mass with a characteristically yellow cut surface that may cause precocious puberty in children or feminization in adults is most likely a [...].
Leydig cell tumour. Gross aspect of a well-delineated Leydig cell tumour.
Leydig cell tumour. Nodule with a yellow cut surface.
A: Leydig cell tumor
Back Extra: Leydig Cell Tumor
- Clinical: Leydig cell tumours can cause precocious puberty in children and feminization in adults due to estrogen secretion.
- Micro: Tumour cells are large, with abundant eosinophilic cytoplasm and prominent nucleoli. Reinke crystals are present in one third of cases.
- Ancillary: Immunohistochemistry shows positivity for calretinin, α-inhibin, and MDM2 amplification in malignant cases.
Reference Gallery:
Leydig cell tumour. Tumour cells with typical nuclei and prominent nucleoli.
Leydig cell tumour. Gross aspect of a well-delineated Leydig cell tumour.
Leydig cell tumour. Clarified cells but typical nuclei with prominent nucleoli.
Leydig cell tumour. Malignant tumour with plentiful mitoses and some atypia.
Leydig cell tumour. Nodule with a yellow cut surface.
Leydig cell tumour. Tumour with lipid-rich cells.
Leydig cell tumour. This malignant tumour infiltrates the soft tissue near the epididymis.
Leydig cell tumour. Positive immunostaining for MDM2 in malignant Leydig cells in the testis.
Leydig cell tumour. There is a huge area of necrosis in this malignant neoplasm.
Spermatic cord sampling in mixed stromal tumour. The presence of extraparenchymal Leydig cells in perineural spaces is a normal incidental finding and can be observed in the spermatic cord. It should not be misinterpreted as tumour dissemination.

Q: While most cases are benign, malignant variants of a Leydig cell tumor often demonstrate nuclear atypia, necrosis, and immunohistochemical positivity for [...] amplification.
Leydig cell tumour. Positive immunostaining for MDM2 in malignant Leydig cells in the testis.
Leydig cell tumour. There is a huge area of necrosis in this malignant neoplasm.
A: MDM2
Back Extra: Leydig Cell Tumor
- Clinical: Leydig cell tumours can cause precocious puberty in children and feminization in adults due to estrogen secretion.
- Micro: Tumour cells are large, with abundant eosinophilic cytoplasm and prominent nucleoli. Reinke crystals are present in one third of cases.
- Ancillary: Immunohistochemistry shows positivity for calretinin, α-inhibin, and MDM2 amplification in malignant cases.
Reference Gallery:
Leydig cell tumour. Tumour cells with typical nuclei and prominent nucleoli.
Leydig cell tumour. Gross aspect of a well-delineated Leydig cell tumour.
Leydig cell tumour. Clarified cells but typical nuclei with prominent nucleoli.
Leydig cell tumour. Malignant tumour with plentiful mitoses and some atypia.
Leydig cell tumour. Nodule with a yellow cut surface.
Leydig cell tumour. Tumour with lipid-rich cells.
Leydig cell tumour. This malignant tumour infiltrates the soft tissue near the epididymis.
Leydig cell tumour. Positive immunostaining for MDM2 in malignant Leydig cells in the testis.
Leydig cell tumour. There is a huge area of necrosis in this malignant neoplasm.
Spermatic cord sampling in mixed stromal tumour. The presence of extraparenchymal Leydig cells in perineural spaces is a normal incidental finding and can be observed in the spermatic cord. It should not be misinterpreted as tumour dissemination.

Q: At the microscopic level, the neoplastic cells of a [...] are typically large and polygonal with abundant eosinophilic or lipid-rich cytoplasm and characteristically prominent nucleoli.
Leydig cell tumour. Tumour cells with typical nuclei and prominent nucleoli.
Leydig cell tumour. Tumour with lipid-rich cells.
A: Leydig cell tumor
Back Extra: Leydig Cell Tumor
- Clinical: Leydig cell tumours can cause precocious puberty in children and feminization in adults due to estrogen secretion.
- Micro: Tumour cells are large, with abundant eosinophilic cytoplasm and prominent nucleoli. Reinke crystals are present in one third of cases.
- Ancillary: Immunohistochemistry shows positivity for calretinin, α-inhibin, and MDM2 amplification in malignant cases.
Reference Gallery:
Leydig cell tumour. Tumour cells with typical nuclei and prominent nucleoli.
Leydig cell tumour. Gross aspect of a well-delineated Leydig cell tumour.
Leydig cell tumour. Clarified cells but typical nuclei with prominent nucleoli.
Leydig cell tumour. Malignant tumour with plentiful mitoses and some atypia.
Leydig cell tumour. Nodule with a yellow cut surface.
Leydig cell tumour. Tumour with lipid-rich cells.
Leydig cell tumour. This malignant tumour infiltrates the soft tissue near the epididymis.
Leydig cell tumour. Positive immunostaining for MDM2 in malignant Leydig cells in the testis.
Leydig cell tumour. There is a huge area of necrosis in this malignant neoplasm.
Spermatic cord sampling in mixed stromal tumour. The presence of extraparenchymal Leydig cells in perineural spaces is a normal incidental finding and can be observed in the spermatic cord. It should not be misinterpreted as tumour dissemination.

Q: Microscopically, a Mixed Sex Cord Stromal Tumour is composed of Leydig, Sertoli, and granulosa cells intermixed with a stromal component that exhibits a [...] morphology.
Mixed sex cord stromal tumour. Sex cord cells intermixed with a stromal component with spindled morphology.
Mixed sex cord stromal tumour. Well-circumscribed tumour with sex cord cells and a stromal component with spindled morphology.
Mixed sex cord stromal tumour. Sex cord cells and spindled stromal cells are intimately admixed.
A: spindled
Back Extra: Mixed Sex Cord Stromal Tumour
- Clinical: Painless testicular enlargement is the most common presenting symptom, with gynaecomastia reported in 10% of cases.
- Micro: Mixed sex cord stromal tumour contains Leydig, Sertoli, and granulosa cells intermixed with a stromal component with spindled morphology.
- Ancillary: Immunohistochemistry shows positivity for inhibin, S100, and SMA in the tumour cells.
Reference Gallery:
Mixed sex cord stromal tumour. Well-circumscribed grey-white to yellow tumour.
Mixed sex cord stromal tumour. Sex cord cells intermixed with a stromal component with spindled morphology.
Mixed sex cord stromal tumour. Well-circumscribed tumour with sex cord cells and a stromal component with spindled morphology.
Mixed sex cord stromal tumour. Sex cord cells and spindled stromal cells are intimately admixed.
Mixed sex cord stromal tumour. Inhibin immunohistochemistry.
Mixed sex cord stromal tumour. Focal positivity for SF1 can be seen.

Q: Immunohistochemistry of a Mixed Sex Cord Stromal Tumour typically shows tumor cells that are positive for S100, SMA, and the characteristic sex cord-stromal marker [...].
Mixed sex cord stromal tumour. Inhibin immunohistochemistry.
A: inhibin
Back Extra: Mixed Sex Cord Stromal Tumour
- Clinical: Painless testicular enlargement is the most common presenting symptom, with gynaecomastia reported in 10% of cases.
- Micro: Mixed sex cord stromal tumour contains Leydig, Sertoli, and granulosa cells intermixed with a stromal component with spindled morphology.
- Ancillary: Immunohistochemistry shows positivity for inhibin, S100, and SMA in the tumour cells.
Reference Gallery:
Mixed sex cord stromal tumour. Well-circumscribed grey-white to yellow tumour.
Mixed sex cord stromal tumour. Sex cord cells intermixed with a stromal component with spindled morphology.
Mixed sex cord stromal tumour. Well-circumscribed tumour with sex cord cells and a stromal component with spindled morphology.
Mixed sex cord stromal tumour. Sex cord cells and spindled stromal cells are intimately admixed.
Mixed sex cord stromal tumour. Inhibin immunohistochemistry.
Mixed sex cord stromal tumour. Focal positivity for SF1 can be seen.

Q: On gross examination, a Mixed Sex Cord Stromal Tumour typically presents as a well-circumscribed, solid tumor that ranges in color from gray-white to [...].
Mixed sex cord stromal tumour. Well-circumscribed grey-white to yellow tumour.
A: yellow
Back Extra: Mixed Sex Cord Stromal Tumour
- Clinical: Painless testicular enlargement is the most common presenting symptom, with gynaecomastia reported in 10% of cases.
- Micro: Mixed sex cord stromal tumour contains Leydig, Sertoli, and granulosa cells intermixed with a stromal component with spindled morphology.
- Ancillary: Immunohistochemistry shows positivity for inhibin, S100, and SMA in the tumour cells.
Reference Gallery:
Mixed sex cord stromal tumour. Well-circumscribed grey-white to yellow tumour.
Mixed sex cord stromal tumour. Sex cord cells intermixed with a stromal component with spindled morphology.
Mixed sex cord stromal tumour. Well-circumscribed tumour with sex cord cells and a stromal component with spindled morphology.
Mixed sex cord stromal tumour. Sex cord cells and spindled stromal cells are intimately admixed.
Mixed sex cord stromal tumour. Inhibin immunohistochemistry.
Mixed sex cord stromal tumour. Focal positivity for SF1 can be seen.

Q: The intratesticular mass shown here, characterized by short fascicles of spindled cells with eosinophilic cytoplasm that typically surround and entrap residual seminiferous tubules, is a [...].
Myoid gonadal stromal tumour. Fascicles of fusiform to elongated spindled cells with relatively scant to eosinophilic cytoplasm.
Myoid gonadal stromal tumour. Well-circumscribed intratesticular unencapsulated lesion with entrapped atrophic tubules.
A: myoid gonadal stromal tumor
Back Extra: Myoid Gonadal Stromal Tumour
- Clinical: Myoid gonadal stromal tumours are intratesticular masses found mainly in adults (mean age: ~40 years), with one reported case in a 4-year-old boy.
- Micro: The tumour consists of short fascicles of spindled cells with fusiform nuclei and scant to moderate eosinophilic cytoplasm, often surrounding residual seminiferous tubules.
- Ancillary: Tumour cells are positive for actin, S100, FOXL2, SF1, vimentin, inhibin (focal), and desmin, with ultrastructural evidence of myofilaments and nuclear grooves.
Reference Gallery:
Myoid gonadal stromal tumour. Fascicles of fusiform to elongated spindled cells with relatively scant to eosinophilic cytoplasm.
Myoid gonadal stromal tumour. Well-circumscribed intratesticular unencapsulated lesion with entrapped atrophic tubules.
Myoid gonadal stromal tumour. Tumour cells are positive for S100.
Myoid gonadal stromal tumour. Electron micrograph showing thin myofilaments (arrow) in the cytoplasm of a cell with a nuclear groove (57 000× magnification).

Q: In a myoid gonadal stromal tumor, the spindled cells characteristically show co-expression of sex cord-stromal markers (e.g., SF1, FOXL2), muscle markers (actin), and [...], as shown in the provided immunostain.
Myoid gonadal stromal tumour. Tumour cells are positive for S100.
A: S100
Back Extra: Myoid Gonadal Stromal Tumour
- Clinical: Myoid gonadal stromal tumours are intratesticular masses found mainly in adults (mean age: ~40 years), with one reported case in a 4-year-old boy.
- Micro: The tumour consists of short fascicles of spindled cells with fusiform nuclei and scant to moderate eosinophilic cytoplasm, often surrounding residual seminiferous tubules.
- Ancillary: Tumour cells are positive for actin, S100, FOXL2, SF1, vimentin, inhibin (focal), and desmin, with ultrastructural evidence of myofilaments and nuclear grooves.
Reference Gallery:
Myoid gonadal stromal tumour. Fascicles of fusiform to elongated spindled cells with relatively scant to eosinophilic cytoplasm.
Myoid gonadal stromal tumour. Well-circumscribed intratesticular unencapsulated lesion with entrapped atrophic tubules.
Myoid gonadal stromal tumour. Tumour cells are positive for S100.
Myoid gonadal stromal tumour. Electron micrograph showing thin myofilaments (arrow) in the cytoplasm of a cell with a nuclear groove (57 000× magnification).

Q: Electron microscopy of a myoid gonadal stromal tumor typically reveals nuclear grooves and cytoplasmic [...] (arrow), which reflects its partial smooth muscle differentiation.
Myoid gonadal stromal tumour. Electron micrograph showing thin myofilaments (arrow) in the cytoplasm of a cell with a nuclear groove (57 000× magnification).
A: myofilaments
Back Extra: Myoid Gonadal Stromal Tumour
- Clinical: Myoid gonadal stromal tumours are intratesticular masses found mainly in adults (mean age: ~40 years), with one reported case in a 4-year-old boy.
- Micro: The tumour consists of short fascicles of spindled cells with fusiform nuclei and scant to moderate eosinophilic cytoplasm, often surrounding residual seminiferous tubules.
- Ancillary: Tumour cells are positive for actin, S100, FOXL2, SF1, vimentin, inhibin (focal), and desmin, with ultrastructural evidence of myofilaments and nuclear grooves.
Reference Gallery:
Myoid gonadal stromal tumour. Fascicles of fusiform to elongated spindled cells with relatively scant to eosinophilic cytoplasm.
Myoid gonadal stromal tumour. Well-circumscribed intratesticular unencapsulated lesion with entrapped atrophic tubules.
Myoid gonadal stromal tumour. Tumour cells are positive for S100.
Myoid gonadal stromal tumour. Electron micrograph showing thin myofilaments (arrow) in the cytoplasm of a cell with a nuclear groove (57 000× magnification).

Q: Microscopically, a Sertoli Cell Tumor is characterized by solid or hollow [...], frequently set within intersecting bands of fibrous tissue with varying degrees of stromal sclerosis.
Sertoli cell tumour. This tumour shows prominent stromal sclerosis. Many Sertoli cell tumours show variable sclerosing features.
Sertoli cell tumour. The characteristic solid or hollow tubular architecture is present, at least focally, in most cases.
Sertoli cell tumour. Sertoli cells lining hollow tubules.
A: tubules
Back Extra: Sertoli Cell Tumour
- Clinical: Sertoli cell tumours typically present as incidental findings on ultrasound or as a testicular mass, and can cause gynaecomastia.
- Micro: Characterized by tubular structures with intersecting bands of fibrous tissue and varying degrees of stromal sclerosis.
- Ancillary: Positive for nuclear β-catenin and diffuse nuclear staining for SF1 in a majority of cases.
Reference Gallery:
Sertoli cell tumour. Tubules and cords with interanastomosing growth.
Sertoli cell tumour. Tumour with typical trabecular aspects.
Sertoli cell tumour. Prominent nuclear immunohistochemical positivity for β-catenin.
Sertoli cell tumour. This tumour shows prominent stromal sclerosis. Many Sertoli cell tumours show variable sclerosing features.
Sertoli cell tumour. The characteristic solid or hollow tubular architecture is present, at least focally, in most cases.
Sertoli cell tumour. Tumour with the typical trabecular pattern.
Sertoli cell tumour. Sertoli cells lining hollow tubules.
Sertoli cell tumour. Well-circumscribed tumour composed of tubules of variable shape and size.
Sertoli cell tumour. Diffuse nuclear staining for SF1.
Sertoli cell tumour. Diffuse nuclear staining for SF1.

Q: Immunohistochemically, a Sertoli Cell Tumor characteristically reveals diffuse nuclear staining for SF1 and prominent nuclear positivity for [...].
Sertoli cell tumour. Prominent nuclear immunohistochemical positivity for β-catenin.
Sertoli cell tumour. Diffuse nuclear staining for SF1.
A: β-catenin
Back Extra: Sertoli Cell Tumour
- Clinical: Sertoli cell tumours typically present as incidental findings on ultrasound or as a testicular mass, and can cause gynaecomastia.
- Micro: Characterized by tubular structures with intersecting bands of fibrous tissue and varying degrees of stromal sclerosis.
- Ancillary: Positive for nuclear β-catenin and diffuse nuclear staining for SF1 in a majority of cases.
Reference Gallery:
Sertoli cell tumour. Tubules and cords with interanastomosing growth.
Sertoli cell tumour. Tumour with typical trabecular aspects.
Sertoli cell tumour. Prominent nuclear immunohistochemical positivity for β-catenin.
Sertoli cell tumour. This tumour shows prominent stromal sclerosis. Many Sertoli cell tumours show variable sclerosing features.
Sertoli cell tumour. The characteristic solid or hollow tubular architecture is present, at least focally, in most cases.
Sertoli cell tumour. Tumour with the typical trabecular pattern.
Sertoli cell tumour. Sertoli cells lining hollow tubules.
Sertoli cell tumour. Well-circumscribed tumour composed of tubules of variable shape and size.
Sertoli cell tumour. Diffuse nuclear staining for SF1.
Sertoli cell tumour. Diffuse nuclear staining for SF1.

Q: Histologically, sex cord stromal tumor NOS typically consists of undifferentiated stromal elements that frequently demonstrate a prominent [...] component.
Sex cord stromal tumour NOS. The tumour shows undifferentiated stromal elements consisting of a spindle cell component.
Sex cord stromal tumour NOS. Prominent spindle cell growth.
A: spindle cell
Back Extra: Sex Cord Stromal Tumour NOS
- Clinical: Patients with Sex Cord Stromal Tumour NOS often present with a painless intratesticular mass. About 50% of cases occur in children, while the rest occur in men of any age.
- Micro: Histologically, Sex Cord Stromal Tumour NOS consists of tumour cells with undifferentiated stromal elements, often showing a spindle cell component. Reticulin fibres surround aggregates of cells rather than individual cells.
- Ancillary: Immunohistochemistry shows positive staining for SF1, desmin, vimentin, actin, S100, CD99, FOXL2, inhibin (focal), and calretinin. Epithelial markers (cytokeratins) are not expressed by neoplastic cells.
Reference Gallery:
Sex cord stromal tumour NOS. The tumour shows undifferentiated stromal elements consisting of a spindle cell component.
Sex cord stromal tumour NOS. Small, well-circumscribed tumour with low-grade spindle cell component.
Sex cord stromal tumour NOS. Prominent spindle cell growth.

Q: An intratesticular mass exhibiting undifferentiated stromal elements and a low-grade spindle cell component without a more specific line of differentiation is best classified as [...].
Sex cord stromal tumour NOS. Small, well-circumscribed tumour with low-grade spindle cell component.
A: sex cord stromal tumor NOS
Back Extra: Sex Cord Stromal Tumour NOS
- Clinical: Patients with Sex Cord Stromal Tumour NOS often present with a painless intratesticular mass. About 50% of cases occur in children, while the rest occur in men of any age.
- Micro: Histologically, Sex Cord Stromal Tumour NOS consists of tumour cells with undifferentiated stromal elements, often showing a spindle cell component. Reticulin fibres surround aggregates of cells rather than individual cells.
- Ancillary: Immunohistochemistry shows positive staining for SF1, desmin, vimentin, actin, S100, CD99, FOXL2, inhibin (focal), and calretinin. Epithelial markers (cytokeratins) are not expressed by neoplastic cells.
Reference Gallery:
Sex cord stromal tumour NOS. The tumour shows undifferentiated stromal elements consisting of a spindle cell component.
Sex cord stromal tumour NOS. Small, well-circumscribed tumour with low-grade spindle cell component.
Sex cord stromal tumour NOS. Prominent spindle cell growth.

Q: Histologically, Signet Ring Stromal Tumor is composed of characteristic signet ring–like cells with large cytoplasmic vacuoles that are distinctly negative for PAS and [...].
Signet ring stromal tumour. The tumour shows signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles, and it may contain eosinophilic cells or sclerotic areas.
Signet ring stromal tumour. Most parts of the tumour consist of PAS- and mucin-negative signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles.
A: mucin
Back Extra: Signet Ring Stromal Tumour
- Clinical: Signet Ring Stromal Tumours are typically asymptomatic intratesticular masses found in patients aged 29–69 years.
- Micro: The tumour is surrounded by a thick fibrous capsule and contains PAS- and mucin-negative signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles.
- Ancillary: IHC is positive for vimentin, nuclear β-catenin, cyclin D1, S100, CD10, NSE, and synaptophysin, and negative for inhibin, calretinin, actin, desmin, and melan-A.
Reference Gallery:
Signet ring stromal tumour. The tumour cells are arranged in solid nests of cells with a signet-ring cell appearance.
Signet ring stromal tumour. The tumour shows signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles, and it may contain eosinophilic cells or sclerotic areas.
Signet ring stromal tumour. Most parts of the tumour consist of PAS- and mucin-negative signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles.

Q: The characteristic cells in a Signet Ring Stromal Tumor form solid nests and feature large cytoplasmic vacuoles that push the nuclei into an [...] position.
Signet ring stromal tumour. The tumour cells are arranged in solid nests of cells with a signet-ring cell appearance.
Signet ring stromal tumour. The tumour shows signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles, and it may contain eosinophilic cells or sclerotic areas.
A: eccentric
Back Extra: Signet Ring Stromal Tumour
- Clinical: Signet Ring Stromal Tumours are typically asymptomatic intratesticular masses found in patients aged 29–69 years.
- Micro: The tumour is surrounded by a thick fibrous capsule and contains PAS- and mucin-negative signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles.
- Ancillary: IHC is positive for vimentin, nuclear β-catenin, cyclin D1, S100, CD10, NSE, and synaptophysin, and negative for inhibin, calretinin, actin, desmin, and melan-A.
Reference Gallery:
Signet ring stromal tumour. The tumour cells are arranged in solid nests of cells with a signet-ring cell appearance.
Signet ring stromal tumour. The tumour shows signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles, and it may contain eosinophilic cells or sclerotic areas.
Signet ring stromal tumour. Most parts of the tumour consist of PAS- and mucin-negative signet ring–like cells with eccentric nuclei and large cytoplasmic vacuoles.

Q: Microscopically, a Fibrothecoma typically presents as a well-circumscribed tumor composed of short fascicles arranged in a [...] growth pattern.
Fibrothecoma. The tumour is well circumscribed.
Fibrothecoma. The tumour shows a storiform growth pattern with short fascicles.
A: storiform
Q: Fibrothecoma
- Clinical: Patients with [...] present with a testicular mass or are identified incidentally on ultrasound.
- Micro: [...] shows a well-circumscribed tumour with a storiform growth pattern and can surround seminiferous tubules.
- Ancillary: Immunohistochemistry for [...] is not helpful for differential diagnosis; most are positive for inhibin.
Reference Gallery:
Fibrothecoma. The tumour is well circumscribed.
Fibrothecoma. Seminiferous tubules are surrounded by the tumour, mostly in its periphery.
Fibrothecoma. The tumour shows a storiform growth pattern with short fascicles.
Fibrothecoma. Edge of a fibrothecoma showing seminiferous tubules at the top.
Fibrothecoma. Testicular fibrothecoma invading the rete testis.
A: Fibrothecoma; Fibrothecoma; Fibrothecoma

Q: A characteristic microscopic feature of a testicular Fibrothecoma is its tendency to entrap and surround normal [...], particularly at the periphery of the tumor.
Fibrothecoma. Seminiferous tubules are surrounded by the tumour, mostly in its periphery.
Fibrothecoma. Edge of a fibrothecoma showing seminiferous tubules at the top.
A: seminiferous tubules
Q: Fibrothecoma
- Clinical: Patients with [...] present with a testicular mass or are identified incidentally on ultrasound.
- Micro: [...] shows a well-circumscribed tumour with a storiform growth pattern and can surround seminiferous tubules.
- Ancillary: Immunohistochemistry for [...] is not helpful for differential diagnosis; most are positive for inhibin.
Reference Gallery:
Fibrothecoma. The tumour is well circumscribed.
Fibrothecoma. Seminiferous tubules are surrounded by the tumour, mostly in its periphery.
Fibrothecoma. The tumour shows a storiform growth pattern with short fascicles.
Fibrothecoma. Edge of a fibrothecoma showing seminiferous tubules at the top.
Fibrothecoma. Testicular fibrothecoma invading the rete testis.
A: Fibrothecoma; Fibrothecoma; Fibrothecoma

Q: Microscopically, [...] frequently displays an admixture of papillary, tubulocystic, and solid growth patterns, with the tumor cells exhibiting clear to eosinophilic cytoplasm and moderate to severe atypia.
Clear cell adenocarcinoma of the bladder. Tubules and microcysts lined by cells with scant to abundant clear cytoplasm and moderately atypical nuclei.
Clear cell adenocarcinoma of the bladder. Tubules and papillae lined by mostly clear cells with large pleomorphic nuclei, irregular nuclear membranes, and prominent nucleoli.
A: Clear Cell Adenocarcinoma of the Urinary Tract
Back Extra: Clear Cell Adenocarcinoma of the Urinary Tract
- Clinical: Clear cell adenocarcinoma of the urinary tract shows a female predominance (M:F ratio: 1:4.6) and typically presents with hematuria or urinary symptoms. The tumour is often advanced at diagnosis.
- Micro: The tumour displays papillary, tubulocystic, and solid growth patterns, with cells showing clear to eosinophilic cytoplasm and prominent nucleoli. Cytological atypia is moderate to severe.
- Ancillary: Immunohistochemically, the tumour is positive for CK7, CA125, PAX8, AMACR, HNF1β, p53, and napsin A, and negative for GATA3, p63, 34βE12, PSA, ER, PR, and WT1.
Reference Gallery:
Clear cell adenocarcinoma of the bladder. Sheets of neoplastic cells with abundant eosinophilic to clear cytoplasm, large pleomorphic nuclei, and prominent nucleoli. Numerous mitotic figures are present.
Clear cell adenocarcinoma of the bladder. Tubules arranged back to back and solid areas lined by cells showing abundant eosinophilic cytoplasm, large pleomorphic nuclei, and prominent nucleoli. Background myxoid stroma is common.
Clear cell adenocarcinoma of the bladder. Tubules and microcysts lined by cells with scant to abundant clear cytoplasm and moderately atypical nuclei.
Clear cell adenocarcinoma of the bladder. Tubules and papillae lined by mostly clear cells with large pleomorphic nuclei, irregular nuclear membranes, and prominent nucleoli.
Clear cell adenocarcinoma of the bladder. Solid areas (left) of highly atypical cells merging with tubules (right) showing a nephrogenic adenoma-like growth pattern with a low degree of atypia. Superficial biopsies of similar cases may raise the differential diagnosis of nephrogenic adenoma.

Q: Because of its tubular architecture and areas of low-grade atypia, superficial biopsies of Clear Cell Adenocarcinoma of the Urinary Tract can closely mimic the benign entity [...].
Clear cell adenocarcinoma of the bladder. Solid areas (left) of highly atypical cells merging with tubules (right) showing a nephrogenic adenoma-like growth pattern with a low degree of atypia. Superficial biopsies of similar cases may raise the differential diagnosis of nephrogenic adenoma.
A: nephrogenic adenoma
Back Extra: Clear Cell Adenocarcinoma of the Urinary Tract
- Clinical: Clear cell adenocarcinoma of the urinary tract shows a female predominance (M:F ratio: 1:4.6) and typically presents with hematuria or urinary symptoms. The tumour is often advanced at diagnosis.
- Micro: The tumour displays papillary, tubulocystic, and solid growth patterns, with cells showing clear to eosinophilic cytoplasm and prominent nucleoli. Cytological atypia is moderate to severe.
- Ancillary: Immunohistochemically, the tumour is positive for CK7, CA125, PAX8, AMACR, HNF1β, p53, and napsin A, and negative for GATA3, p63, 34βE12, PSA, ER, PR, and WT1.
Reference Gallery:
Clear cell adenocarcinoma of the bladder. Sheets of neoplastic cells with abundant eosinophilic to clear cytoplasm, large pleomorphic nuclei, and prominent nucleoli. Numerous mitotic figures are present.
Clear cell adenocarcinoma of the bladder. Tubules arranged back to back and solid areas lined by cells showing abundant eosinophilic cytoplasm, large pleomorphic nuclei, and prominent nucleoli. Background myxoid stroma is common.
Clear cell adenocarcinoma of the bladder. Tubules and microcysts lined by cells with scant to abundant clear cytoplasm and moderately atypical nuclei.
Clear cell adenocarcinoma of the bladder. Tubules and papillae lined by mostly clear cells with large pleomorphic nuclei, irregular nuclear membranes, and prominent nucleoli.
Clear cell adenocarcinoma of the bladder. Solid areas (left) of highly atypical cells merging with tubules (right) showing a nephrogenic adenoma-like growth pattern with a low degree of atypia. Superficial biopsies of similar cases may raise the differential diagnosis of nephrogenic adenoma.

Q: Histological examination of Cowper Gland Adenocarcinoma of the Urethra typically reveals tubular, solid, and cribriform growth patterns, alongside frequent [...] spread.
Cowper gland adenocarcinoma. Tumour with tubular and cribriform patterns growing around a thick-walled vessel.
Cowper gland adenocarcinoma. Perineural and intraneural spread is common in Cowper gland adenocarcinoma.
A: perineural
Back Extra: Cowper Gland Adenocarcinoma of the Urethra
- Clinical: Cowper gland adenocarcinoma usually presents as perianal or perirectal pain/discomfort, and/or urinary retention. It affects men in the fifth to seventh decades of life.
- Micro: Tumours exhibit cribriform, trabecular, and solid patterns. Perineural spread is frequent, and glandular structures often contain mucoid material.
- Ancillary: Confirmation of the MYB::NFIB fusion is desirable for diagnosis. Immunohistochemistry shows positivity for CK7 and high-molecular-weight cytokeratin.
Reference Gallery:
Cowper gland adenocarcinoma. Invasion of Cowper gland adenocarcinoma into fatty tissue around the urethra.
Cowper gland adenocarcinoma. Tumour with tubular and cribriform patterns growing around a thick-walled vessel.
Cowper gland adenocarcinoma. Perineural and intraneural spread is common in Cowper gland adenocarcinoma.

Q: An older male patient presenting with perianal pain and urinary retention is found to have a periurethral tumor invading surrounding fatty tissue, displaying cribriform architecture, and exhibiting prominent perineural spread. These features are highly characteristic of [...].
Cowper gland adenocarcinoma. Invasion of Cowper gland adenocarcinoma into fatty tissue around the urethra.
Cowper gland adenocarcinoma. Tumour with tubular and cribriform patterns growing around a thick-walled vessel.
Cowper gland adenocarcinoma. Perineural and intraneural spread is common in Cowper gland adenocarcinoma.
A: Cowper Gland Adenocarcinoma of the Urethra
Back Extra: Cowper Gland Adenocarcinoma of the Urethra
- Clinical: Cowper gland adenocarcinoma usually presents as perianal or perirectal pain/discomfort, and/or urinary retention. It affects men in the fifth to seventh decades of life.
- Micro: Tumours exhibit cribriform, trabecular, and solid patterns. Perineural spread is frequent, and glandular structures often contain mucoid material.
- Ancillary: Confirmation of the MYB::NFIB fusion is desirable for diagnosis. Immunohistochemistry shows positivity for CK7 and high-molecular-weight cytokeratin.
Reference Gallery:
Cowper gland adenocarcinoma. Invasion of Cowper gland adenocarcinoma into fatty tissue around the urethra.
Cowper gland adenocarcinoma. Tumour with tubular and cribriform patterns growing around a thick-walled vessel.
Cowper gland adenocarcinoma. Perineural and intraneural spread is common in Cowper gland adenocarcinoma.

Q: Morphologically, Skene Gland Adenocarcinoma exhibits a tubular or cribriform pattern that closely resembles acinar [...] adenocarcinoma.
Skene gland adenocarcinoma. Skene gland adenocarcinoma resembles acinar prostatic adenocarcinoma in its morphology and in its immunohistochemical profile.
A: prostatic
Back Extra: Skene Gland Adenocarcinoma
- Clinical: Patients may present with gross haematuria or urinary urgency. Serum PSA level may be elevated, and the disease primarily affects postmenopausal women.
- Micro: Tumors exhibit a tubular or cribriform pattern, often with pseudostratification, and neoplastic cells are positive for prostatic markers like PSA, PAP, and NKX3-1.
- Ancillary: Mutation and loss of heterozygosity of the PTEN gene have been detected in one case, but no further information is available.
Reference Gallery:
Skene gland adenocarcinoma. Skene gland adenocarcinoma resembles acinar prostatic adenocarcinoma in its morphology and in its immunohistochemical profile.
Skene gland adenocarcinoma. Strong diffuse positivity with PSA.

Q: Due to its embryologic homology, Skene Gland Adenocarcinoma uniquely demonstrates strong diffuse immunohistochemical positivity for male-associated markers such as [...] (along with PAP and NKX3.1).
Skene gland adenocarcinoma. Strong diffuse positivity with PSA.
A: PSA
Back Extra: Skene Gland Adenocarcinoma
- Clinical: Patients may present with gross haematuria or urinary urgency. Serum PSA level may be elevated, and the disease primarily affects postmenopausal women.
- Micro: Tumors exhibit a tubular or cribriform pattern, often with pseudostratification, and neoplastic cells are positive for prostatic markers like PSA, PAP, and NKX3-1.
- Ancillary: Mutation and loss of heterozygosity of the PTEN gene have been detected in one case, but no further information is available.
Reference Gallery:
Skene gland adenocarcinoma. Skene gland adenocarcinoma resembles acinar prostatic adenocarcinoma in its morphology and in its immunohistochemical profile.
Skene gland adenocarcinoma. Strong diffuse positivity with PSA.

Q: Histologically, Endometrioid Carcinoma of the Urinary Tract is typically characterized by a crowded glandular pattern with characteristic [...] glands.
Endometrioid carcinoma of the ureter. The tumour is relatively well differentiated, with a crowded glandular pattern and back-to-back glands, showing basal nuclei.
Endometrioid carcinoma. This example is moderately differentiated, with greater glandular architectural atypia and loss of nuclear polarity.
A: back-to-back
Back Extra: Endometrioid Carcinoma of the Urinary Tract
- Clinical: Intermittent or painless haematuria, frequent urination, and micturition pain during the menstrual period.
- Micro: Characterized by a glandular pattern with back-to-back glands, nuclear pleomorphism, and coexistence of malignant and benign glands.
- Ancillary: Strong immunoreactivity for estrogen and progesterone; positive for CAM5.2, CK7, and EMA.
Reference Gallery:
Endometrioid carcinoma of the ureter. The tumour is relatively well differentiated, with a crowded glandular pattern and back-to-back glands, showing basal nuclei.
Endometrioid carcinoma. ER positivity in endometrioid carcinoma of the bladder.
Endometrioid carcinoma. This example is moderately differentiated, with greater glandular architectural atypia and loss of nuclear polarity.

Q: To support the diagnosis of Endometrioid Carcinoma of the Urinary Tract, immunohistochemistry is characteristically strongly positive for [...] and progesterone receptors.
Endometrioid carcinoma. ER positivity in endometrioid carcinoma of the bladder.
A: estrogen
Back Extra: Endometrioid Carcinoma of the Urinary Tract
- Clinical: Intermittent or painless haematuria, frequent urination, and micturition pain during the menstrual period.
- Micro: Characterized by a glandular pattern with back-to-back glands, nuclear pleomorphism, and coexistence of malignant and benign glands.
- Ancillary: Strong immunoreactivity for estrogen and progesterone; positive for CAM5.2, CK7, and EMA.
Reference Gallery:
Endometrioid carcinoma of the ureter. The tumour is relatively well differentiated, with a crowded glandular pattern and back-to-back glands, showing basal nuclei.
Endometrioid carcinoma. ER positivity in endometrioid carcinoma of the bladder.
Endometrioid carcinoma. This example is moderately differentiated, with greater glandular architectural atypia and loss of nuclear polarity.

Q: Increased intratumoral lymphocytes, an inverted growth pattern, and a pushing, non-infiltrative stromal interface in a patient with an upper urinary tract malignancy are morphologic clues that should raise suspicion for [...].
Lynch syndrome–associated upper tract urothelial carcinoma. Although features such as prominence of tumour-infiltrating lymphocytes (as apparent by H&E stain here) have been described for Lynch syndrome–associated urothelial carcinoma, such features are insufficiently specific to recognize cases prospectively. Instead, increasingly universal screening for Lynch syndrome by mismatch repair protein immunohistochemistry is recommended.
Lynch syndrome–associated upper tract urothelial carcinoma. These tumours often show at least a focal inverted growth pattern, and overall they lack pleomorphism and subtype differentiation. A pushing, non-infiltrative stromal interface is often apparent, although such features are insufficient to facilitate prospective recognition.
A: Lynch Syndrome-Associated Upper Tract Urothelial Carcinoma
Back Extra: Lynch Syndrome-Associated Upper Tract Urothelial Carcinoma
- Clinical: Patients with Lynch Syndrome-Associated Upper Tract Urothelial Carcinoma (LS-UTUC) are often younger and more frequently female compared to the general population with UTUC.
- Micro: Increased intratumoural lymphocytes, an inverted growth pattern, and a non-infiltrative stromal interface are associated with LS-UTUC, though these features are not specific.
- Ancillary: Reflex screening of UTUCs by mismatch repair immunohistochemistry is recommended to identify candidates for genetic testing for Lynch syndrome.
Reference Gallery:
Lynch syndrome–associated upper tract urothelial carcinoma. Although features such as prominence of tumour-infiltrating lymphocytes (as apparent by H&E stain here) have been described for Lynch syndrome–associated urothelial carcinoma, such features are insufficiently specific to recognize cases prospectively. Instead, increasingly universal screening for Lynch syndrome by mismatch repair protein immunohistochemistry is recommended.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear MLH1 expression is normal/retained, as expected for this case, in which MSH2 germline mutation was eventually proved by sequencing.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear MSH2 expression is absent/lost in tumour cells but retained in inflammatory cells (internal control). This abnormal pattern was expected for this case, in which MSH2 germline mutation was eventually proved by sequencing.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear MSH6 expression is absent/lost in tumour cells but retained in inflammatory cells (internal control). This abnormal pattern was expected in this case, in which MSH2 germline mutation was eventually proved by sequencing. If MSH2 is mutated, MSH6 expression is often lost as well, because of its dimerization with MSH2.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear PMS2 expression is present in tumour cells, as expected for this case, in which MSH2 germline mutation was eventually proved by sequencing.
Lynch syndrome–associated upper tract urothelial carcinoma. These tumours often show at least a focal inverted growth pattern, and overall they lack pleomorphism and subtype differentiation. A pushing, non-infiltrative stromal interface is often apparent, although such features are insufficient to facilitate prospective recognition.

Q: Because morphologic features alone are insufficiently specific for prospective recognition, universal reflex screening by [...] immunohistochemistry is highly recommended to identify Lynch Syndrome-Associated Upper Tract Urothelial Carcinoma.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear MSH2 expression is absent/lost in tumour cells but retained in inflammatory cells (internal control). This abnormal pattern was expected for this case, in which MSH2 germline mutation was eventually proved by sequencing.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear MSH6 expression is absent/lost in tumour cells but retained in inflammatory cells (internal control). This abnormal pattern was expected in this case, in which MSH2 germline mutation was eventually proved by sequencing. If MSH2 is mutated, MSH6 expression is often lost as well, because of its dimerization with MSH2.
A: mismatch repair
Back Extra: Lynch Syndrome-Associated Upper Tract Urothelial Carcinoma
- Clinical: Patients with Lynch Syndrome-Associated Upper Tract Urothelial Carcinoma (LS-UTUC) are often younger and more frequently female compared to the general population with UTUC.
- Micro: Increased intratumoural lymphocytes, an inverted growth pattern, and a non-infiltrative stromal interface are associated with LS-UTUC, though these features are not specific.
- Ancillary: Reflex screening of UTUCs by mismatch repair immunohistochemistry is recommended to identify candidates for genetic testing for Lynch syndrome.
Reference Gallery:
Lynch syndrome–associated upper tract urothelial carcinoma. Although features such as prominence of tumour-infiltrating lymphocytes (as apparent by H&E stain here) have been described for Lynch syndrome–associated urothelial carcinoma, such features are insufficiently specific to recognize cases prospectively. Instead, increasingly universal screening for Lynch syndrome by mismatch repair protein immunohistochemistry is recommended.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear MLH1 expression is normal/retained, as expected for this case, in which MSH2 germline mutation was eventually proved by sequencing.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear MSH2 expression is absent/lost in tumour cells but retained in inflammatory cells (internal control). This abnormal pattern was expected for this case, in which MSH2 germline mutation was eventually proved by sequencing.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear MSH6 expression is absent/lost in tumour cells but retained in inflammatory cells (internal control). This abnormal pattern was expected in this case, in which MSH2 germline mutation was eventually proved by sequencing. If MSH2 is mutated, MSH6 expression is often lost as well, because of its dimerization with MSH2.
Lynch syndrome–associated upper tract urothelial carcinoma. Mismatch repair immunostains were performed in this tumour for Lynch syndrome screening. Here, nuclear PMS2 expression is present in tumour cells, as expected for this case, in which MSH2 germline mutation was eventually proved by sequencing.
Lynch syndrome–associated upper tract urothelial carcinoma. These tumours often show at least a focal inverted growth pattern, and overall they lack pleomorphism and subtype differentiation. A pushing, non-infiltrative stromal interface is often apparent, although such features are insufficient to facilitate prospective recognition.