Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Yembur Ahmad
This case talks about a 50-year-old male with a breast mass.
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Clinical history: A 50 year-old male with a breast mass
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Diagnosis: A. Angiolipoma
Histology: Histologic sections reveal abundant mature adipose tissue with no appreciable atypia (i.e., no nuclear enlargement or hyperchromasia). The adipose tissue contains small, thin-walled vessels with prominent pericytes, some of which are clustered or nested together but do not appear to be anastomosing. Some of the vessels contain bright red erythrocytes inside their lumens, but some of the vessels contain acellular, pink glassy material within their lumens. These are fibrin thrombi.
Discussion: Angiolipomas are characterized by the presence of mature adipose tissue with small, often clustered thin-walled vessels and fibrin thrombi. They are considered a lipoma variant, not a vascular neoplasm. They are typically subcutaneous nodules that can occur throughout the body, most commonly on the trunk or upper extremities. Angiolipomas are part of the group of painful subcutaneous nodules, which can be remembered with the acronym “ANGEL”: angiolipoma, neuroma, glomus tumor, eccrine spiradenoma, and leiomyoma. Angiolipomas can occur on the breast, in both males and females, and do not require surgical excision unless painful or bothersome to the patient. It is important to recognize an angiolipoma and not mistake it for a vascular neoplasm, which may have different management implications, particularly in the breast.
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Diagnosis: A. Angiolipoma
Histology: Histologic sections reveal abundant mature adipose tissue with no appreciable atypia (i.e., no nuclear enlargement or hyperchromasia). The adipose tissue contains small, thin-walled vessels with prominent pericytes, some of which are clustered or nested together but do not appear to be anastomosing. Some of the vessels contain bright red erythrocytes inside their lumens, but some of the vessels contain acellular, pink glassy material within their lumens. These are fibrin thrombi.
Discussion: Angiolipomas are characterized by the presence of mature adipose tissue with small, often clustered thin-walled vessels and fibrin thrombi. They are considered a lipoma variant, not a vascular neoplasm. They are typically subcutaneous nodules that can occur throughout the body, most commonly on the trunk or upper extremities. Angiolipomas are part of the group of painful subcutaneous nodules, which can be remembered with the acronym “ANGEL”: angiolipoma, neuroma, glomus tumor, eccrine spiradenoma, and leiomyoma. Angiolipomas can occur on the breast, in both males and females, and do not require surgical excision unless painful or bothersome to the patient. It is important to recognize an angiolipoma and not mistake it for a vascular neoplasm, which may have different management implications, particularly in the breast.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Yembur Ahmad
This case talks about a 60-year-old female with an anal mass.
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Clinical history: A 60 year-old female with an anal mass
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Diagnosis: D. Hemorrhoid
Histology: The polypoid fragment of tissue is lined by benign squamous epithelium with normal maturation and foci of underlying anorectal glands without significant atypia. Within the center of the polypoid fragment are large, dilated vascular spaces lined by flattened endothelium with no appreciable atypia. The vascular spaces are not anastomosing.
Discussion: The resection specimen shows classic histologic features of a hemorrhoid, which are the presence of dilated veins (perianal venous plexuses). Internal hemorrhoids occur above (proximal to) the dentate line and are lined by anorectal glandular mucosa. External hemorrhoids occur below (distal to) the dentate line and are lined by squamous mucosa. Why on earth am I showing you a hemorrhoid? It is important to remember to evaluate the hemorrhoids for the presence of any low or high grade squamous intraepithelial lesions (LSIL or HSIL), also known as anal intraepithelial neoplasia 1 (AIN 1) or anal intraepithelial neoplasia 2-3 (AIN 2-3), respectively. In addition, in situ or invasive squamous cell carcinoma can involve hemorrhoids. These features are not present in this case, but you should always remember to look for atypia. For this reason, it is prudent to ink the resection margin of the hemorrhoids, just in case there is any atypia seen microscopically. Ink, don’t think. It only takes 2 seconds.
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Diagnosis: D. Hemorrhoid
Histology: The polypoid fragment of tissue is lined by benign squamous epithelium with normal maturation and foci of underlying anorectal glands without significant atypia. Within the center of the polypoid fragment are large, dilated vascular spaces lined by flattened endothelium with no appreciable atypia. The vascular spaces are not anastomosing.
Discussion: The resection specimen shows classic histologic features of a hemorrhoid, which are the presence of dilated veins (perianal venous plexuses). Internal hemorrhoids occur above (proximal to) the dentate line and are lined by anorectal glandular mucosa. External hemorrhoids occur below (distal to) the dentate line and are lined by squamous mucosa. Why on earth am I showing you a hemorrhoid? It is important to remember to evaluate the hemorrhoids for the presence of any low or high grade squamous intraepithelial lesions (LSIL or HSIL), also known as anal intraepithelial neoplasia 1 (AIN 1) or anal intraepithelial neoplasia 2-3 (AIN 2-3), respectively. In addition, in situ or invasive squamous cell carcinoma can involve hemorrhoids. These features are not present in this case, but you should always remember to look for atypia. For this reason, it is prudent to ink the resection margin of the hemorrhoids, just in case there is any atypia seen microscopically. Ink, don’t think. It only takes 2 seconds.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Yembur Ahmad
This case talks about an 80-year-old female with a retroperitoneal mass.
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Clinical history: An 80 year-old female with a retroperitoneal mass
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Diagnosis: D. Leiomyosarcoma
Histology: Sections reveal intersecting fascicles of spindle cells with blunt-ended (cigar shaped) nuclei, scattered enlarged and hyperchromatic nuclei, indistinct cell borders, pink cytoplasm, and brisk mitotic activity. The neoplasm closely approximates a large vein and appears to either arise from it or invade into it.
Discussion: This tumor is a retroperitoneal leiomyosarcoma arising from the renal vein. Retroperitoneal leiomyosarcomas in females are usually gynecologic in origin (e.g., uterine), but leiomyosarcomas can arise from the smooth muscle wall of blood vessels. Leiomyosarcomas label for markers of smooth muscle differentiation, including smooth muscle actin and desmin. The differential diagnosis of a spindle cell neoplasm of the retroperitoneum should always include dedifferentiated liposarcoma, as liposarcomas are the most common retroperitoneal sarcoma. It may not be possible to definitively classify a spindle cell neoplasm on core biopsy if the diagnostic features are not present due to partial sampling. Features that would favor a dedifferentiated liposarcoma include the presence of a well-differentiated component (which may be very focal) and MDM2 amplification (although this can be seen in other sarcomas). Features that would favor a leiomyosarcoma include absence of a well-differentiated liposarcoma, well developed histology of fascicular architecture and uniform blunt-ended nuclei, and association with a specific site of origin such as a large vessel or the uterus.
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Diagnosis: D. Leiomyosarcoma
Histology: Sections reveal intersecting fascicles of spindle cells with blunt-ended (cigar shaped) nuclei, scattered enlarged and hyperchromatic nuclei, indistinct cell borders, pink cytoplasm, and brisk mitotic activity. The neoplasm closely approximates a large vein and appears to either arise from it or invade into it.
Discussion: This tumor is a retroperitoneal leiomyosarcoma arising from the renal vein. Retroperitoneal leiomyosarcomas in females are usually gynecologic in origin (e.g., uterine), but leiomyosarcomas can arise from the smooth muscle wall of blood vessels. Leiomyosarcomas label for markers of smooth muscle differentiation, including smooth muscle actin and desmin. The differential diagnosis of a spindle cell neoplasm of the retroperitoneum should always include dedifferentiated liposarcoma, as liposarcomas are the most common retroperitoneal sarcoma. It may not be possible to definitively classify a spindle cell neoplasm on core biopsy if the diagnostic features are not present due to partial sampling. Features that would favor a dedifferentiated liposarcoma include the presence of a well-differentiated component (which may be very focal) and MDM2 amplification (although this can be seen in other sarcomas). Features that would favor a leiomyosarcoma include absence of a well-differentiated liposarcoma, well developed histology of fascicular architecture and uniform blunt-ended nuclei, and association with a specific site of origin such as a large vessel or the uterus.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Yembur Ahmad
This case talks about a 30-year-old female with an abdominal mass.
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Clinical history: A 30 year-old female with an abdominal mass
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Diagnosis: D. Endometriosis
Histology: The resection specimen shows areas of scarring with scattered infiltrative-appearing glands. The glands are composed of cuboidal cells with occasional admixed small cells with clear cytoplasm. There is no cytologic atypia or mitotic activity. The glands are surrounded by a stroma of small, round to oval blue cells with minimal cytoplasm. In areas, the stroma cells are associated with extravasated red blood cells and hemosiderin-laden macrophages.
Discussion: Endometriosis is the presence of ectopic endometrial tissue, including the glands and stroma. There are three characteristic features: benign endometrial glands, associated endometrial stroma, and the presence of hemorrhage or hemosiderin-laden macrophages. At least two of these three features are required to definitively classify a lesion as endometriosis. Endometriosis can involve essentially any site in the pelvic and abdominal cavity, but can occasionally be seen in supradiaphragmatic locations such as lymph nodes. The most common site of endometriosis is the ovary, which can form a dominant cystic nodule termed an endometrioma. Endometriosis can give rise to endometrioid carcinoma or clear cell carcinoma, and the risk of malignancy is highest in the ovary. The glands of endometriosis can irregularly “infiltrate” through benign tissues, and the most important point is to not mistake endometriosis for invasive carcinoma.
Histology: The resection specimen shows areas of scarring with scattered infiltrative-appearing glands. The glands are composed of cuboidal cells with occasional admixed small cells with clear cytoplasm. There is no cytologic atypia or mitotic activity. The glands are surrounded by a stroma of small, round to oval blue cells with minimal cytoplasm. In areas, the stroma cells are associated with extravasated red blood cells and hemosiderin-laden macrophages.
Discussion: Endometriosis is the presence of ectopic endometrial tissue, including the glands and stroma. There are three characteristic features: benign endometrial glands, associated endometrial stroma, and the presence of hemorrhage or hemosiderin-laden macrophages. At least two of these three features are required to definitively classify a lesion as endometriosis. Endometriosis can involve essentially any site in the pelvic and abdominal cavity, but can occasionally be seen in supradiaphragmatic locations such as lymph nodes. The most common site of endometriosis is the ovary, which can form a dominant cystic nodule termed an endometrioma. Endometriosis can give rise to endometrioid carcinoma or clear cell carcinoma, and the risk of malignancy is highest in the ovary. The glands of endometriosis can irregularly “infiltrate” through benign tissues, and the most important point is to not mistake endometriosis for invasive carcinoma.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Yembur Ahmad
This case talks about a 60-year-old female undergoing heart valve replacement.
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Clinical history: A 60 year-old female undergoing heart valve replacement
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Diagnosis: D. Papillary fibroelastoma
Histology: The lesion has a papillary architecture characterized by delicate, arborizing fronds. The papillary fronds are hyalinized and acellular; stromal fibroblasts or capillaries are not apparent. The papillary fronds are lined by a single layer of bland spindle cells. There is no acute or chronic inflammation.
Discussion: This is a beautiful example of a papillary fibroelastoma, a benign lesion that arises on the cardiac valves. They are characterized by avascular, fibroelastic papillary fronds with delicate branching. The fronds are lined by bland endocardium. A subset of papillary fibroelastomas have mutations in KRAS, suggesting at least a subset are neoplastic. The differential diagnosis includes Lambl’s excrescences, which have the histologic similarity of avascular hyalinized-appearing fronds lined by endocardium; however, Lambl’s excrescences are not papillary and do not arborize. The primary clinical risk with papillary fibroelastoma is the risk of tumor emboli and stroke.
Reference:
Bois MC, Milosevic D, Kipp BR, Maleszewski JJ. KRAS Mutations in Papillary Fibroelastomas: A Study of 50 Cases With Etiologic and Diagnostic Implications. Am J Surg Pathol. 2020 May;44(5):626-632.
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Diagnosis: D. Papillary fibroelastoma
Histology: The lesion has a papillary architecture characterized by delicate, arborizing fronds. The papillary fronds are hyalinized and acellular; stromal fibroblasts or capillaries are not apparent. The papillary fronds are lined by a single layer of bland spindle cells. There is no acute or chronic inflammation.
Discussion: This is a beautiful example of a papillary fibroelastoma, a benign lesion that arises on the cardiac valves. They are characterized by avascular, fibroelastic papillary fronds with delicate branching. The fronds are lined by bland endocardium. A subset of papillary fibroelastomas have mutations in KRAS, suggesting at least a subset are neoplastic. The differential diagnosis includes Lambl’s excrescences, which have the histologic similarity of avascular hyalinized-appearing fronds lined by endocardium; however, Lambl’s excrescences are not papillary and do not arborize. The primary clinical risk with papillary fibroelastoma is the risk of tumor emboli and stroke.
Reference:
Bois MC, Milosevic D, Kipp BR, Maleszewski JJ. KRAS Mutations in Papillary Fibroelastomas: A Study of 50 Cases With Etiologic and Diagnostic Implications. Am J Surg Pathol. 2020 May;44(5):626-632.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Yembur Ahmad
This case talks about a 60-year-old female with an arm mass.
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Clinical history: A 60 year-old female with an arm mass
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Diagnosis: E. Tumoral calcinosis
Histology: The dermis and subcutaneous tissues are involved by variably sized, acellular nodules of pink to purple, amorphous material. The darker purple nodules display tissue cracking, suggesting calcification. Foreign body giant cells are identified at the periphery of some of the nodules.
Discussion: This is an example of tumoral calcinosis, in which calcium deposits develop in the dermis and soft tissues primarily in periarticular areas (e.g., elbow, knee) but also elsewhere. These nodules can present as hard but painless subcutaneous or soft tissue nodules. They develop under conditions of hypercalcemia, such as renal failure or hyperparathyroidism. The presence of foreign body giant cells around the calcific nodules should not be mistaken for the epithelioid histiocytes of a granuloma.
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Diagnosis: E. Tumoral calcinosis
Histology: The dermis and subcutaneous tissues are involved by variably sized, acellular nodules of pink to purple, amorphous material. The darker purple nodules display tissue cracking, suggesting calcification. Foreign body giant cells are identified at the periphery of some of the nodules.
Discussion: This is an example of tumoral calcinosis, in which calcium deposits develop in the dermis and soft tissues primarily in periarticular areas (e.g., elbow, knee) but also elsewhere. These nodules can present as hard but painless subcutaneous or soft tissue nodules. They develop under conditions of hypercalcemia, such as renal failure or hyperparathyroidism. The presence of foreign body giant cells around the calcific nodules should not be mistaken for the epithelioid histiocytes of a granuloma.
Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about a 40-year-old man with a prostatic mass.
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History: A 40 year old man underwent a radical prostatectomy for a prostatic mass.
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Correct Diagnosis: D
Histological Description: Part of this tumor contains a nodule with the most common pattern of STUMP consisting of slightly hypercellular or normocellular stroma with scattered atypical, but degenerative appearing cells. The STUMP atypical cells contain hyperchromatic multinucleated nuclei with degenerative appearing smudgy chromatin lacking mitotic activity. Intervening benign prostate glands between the STUMP cells are crowded with basal cell hyperplasia. In addition, there are spindled areas with marked hypercellularity and increased mitotic activity including atypical mitotic figures with an infiltrative pattern extending between benign prostate glands.
Discussion: STUMPs are well-circumscribed nodules. They may recur within a few months or years after TURP resulting in urinary obstruction. Uncommonly, STUMPs can be associated with stromal sarcoma on concurrent material (as in this case) or on repeat biopsy, suggesting a malignant progression. If entirely resected and no sarcomatous component, then STUMPs are entirely cured. Stromal sarcomas can extend out of the prostate and metastasize to distant sites, such as bone, lung, abdomen and retroperitoneum. Both STUMPs and stromal sarcomas are often positive for CD34, smooth muscle actin, desmin, and progesterone receptor, such that immunohistochemistry is not helpful in the differential diagnosis. Leiomyomas and leiomyosarcomas of the prostate present as well-circumscribed nodules with intersecting fascicles and even leiomyosarcomas lack a very infiltrative growth pattern.
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Correct Diagnosis: D
Histological Description: Part of this tumor contains a nodule with the most common pattern of STUMP consisting of slightly hypercellular or normocellular stroma with scattered atypical, but degenerative appearing cells. The STUMP atypical cells contain hyperchromatic multinucleated nuclei with degenerative appearing smudgy chromatin lacking mitotic activity. Intervening benign prostate glands between the STUMP cells are crowded with basal cell hyperplasia. In addition, there are spindled areas with marked hypercellularity and increased mitotic activity including atypical mitotic figures with an infiltrative pattern extending between benign prostate glands.
Discussion: STUMPs are well-circumscribed nodules. They may recur within a few months or years after TURP resulting in urinary obstruction. Uncommonly, STUMPs can be associated with stromal sarcoma on concurrent material (as in this case) or on repeat biopsy, suggesting a malignant progression. If entirely resected and no sarcomatous component, then STUMPs are entirely cured. Stromal sarcomas can extend out of the prostate and metastasize to distant sites, such as bone, lung, abdomen and retroperitoneum. Both STUMPs and stromal sarcomas are often positive for CD34, smooth muscle actin, desmin, and progesterone receptor, such that immunohistochemistry is not helpful in the differential diagnosis. Leiomyomas and leiomyosarcomas of the prostate present as well-circumscribed nodules with intersecting fascicles and even leiomyosarcomas lack a very infiltrative growth pattern.
Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about a 40-year-old man with a testicular mass.
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History: A 28 year old man presented with a large testicular mass and an orchiectomy was performed. In addition to small foci of embryonal carcinoma, there is:
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Answer: C
Histological Description: The tumor consists of nodules of atypical cartilage, some with necrosis. In areas, the cartilage nodules occupy areas of a 4x field without intervening other germ cell components. In addition to the embryonal carcinoma, there is a single cluster of acellular keratin.
Discussion: This is an example of a teratoma with associated non-germ cell malignancy, also known as a somatic malignancy arising in a teratoma. It is seen in 3%-6% of germ cell tumors with a teratomatous component, more frequently in metastatic sites following chemotherapy for a germ cell tumor. Most common somatic malignancies arising in teratomas are: Wilms tumor; primitive neuroectodermal tumor (PNET); and rhabdomyosarcoma, where these elements sheet out occupying <4x field without intervening other germ cell elements. Also can see sheets of various patterns of carcinoma or sarcoma where the glands sheet out greater than a 4x field. Atypia in epithelium or mesenchymal elements that do not sheet out >4x field have no significance and are not even noted in the pathology report and are just part of post-pubertal type teratoma. Non germ cell malignancies arising in teratomas retain chromosomal gains in 12p seen in usual germ cell tumors. Somatic malignancy in a teratoma does not alter the prognosis if confined to the testis. When a non-germ cell malignancy arises in a metastatic teratoma the prognosis is markedly worsened. Chemotherapy protocol specific to its somatic lineage is often used, although it is controversial whether it is superior to germ cell therapy. Best chance for cure is if the metastases are surgically resectable.
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Answer: C
Histological Description: The tumor consists of nodules of atypical cartilage, some with necrosis. In areas, the cartilage nodules occupy areas of a 4x field without intervening other germ cell components. In addition to the embryonal carcinoma, there is a single cluster of acellular keratin.
Discussion: This is an example of a teratoma with associated non-germ cell malignancy, also known as a somatic malignancy arising in a teratoma. It is seen in 3%-6% of germ cell tumors with a teratomatous component, more frequently in metastatic sites following chemotherapy for a germ cell tumor. Most common somatic malignancies arising in teratomas are: Wilms tumor; primitive neuroectodermal tumor (PNET); and rhabdomyosarcoma, where these elements sheet out occupying <4x field without intervening other germ cell elements. Also can see sheets of various patterns of carcinoma or sarcoma where the glands sheet out greater than a 4x field. Atypia in epithelium or mesenchymal elements that do not sheet out >4x field have no significance and are not even noted in the pathology report and are just part of post-pubertal type teratoma. Non germ cell malignancies arising in teratomas retain chromosomal gains in 12p seen in usual germ cell tumors. Somatic malignancy in a teratoma does not alter the prognosis if confined to the testis. When a non-germ cell malignancy arises in a metastatic teratoma the prognosis is markedly worsened. Chemotherapy protocol specific to its somatic lineage is often used, although it is controversial whether it is superior to germ cell therapy. Best chance for cure is if the metastases are surgically resectable.
Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about a 23 year-old man who undergoes orchiectomy.
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History: A 23 year old man underwent an orchiectomy for testicular pain and induration. The epididymis was uninvolved.
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Answer: D
Histological Description: Affecting part of the testis there are non-necrotizing granulomas filling seminiferous tubules. Granulomas are composed of epithelioid histiocytes, giant cells admixed with lymphocytes and plasma cells. Chronic inflammatory cells including eosinophils and plasma cells infiltrate interstitium. The surrounding seminiferous tubules show active spermatogenesis.
Discussion: Idiopathic granulomatous orchitis is of unknown etiology. It is a benign inflammatory condition that can be bilateral and lead to loss of spermatogenesis in involved testes even if orchiectomy avoided. In infectious processes, necrotizing and/or non-necrotizing granulomatous inflammation composed of epithelioid histiocytes and multinucleated giant cells mainly involving the testicular interstitium. Infectious processes involving the testis also always start in the epididymis. The same interstitial distribution is also seen in sarcoidosis, yet non-necrotizing granulomas are seen. Germ cell neoplasia in situ (GCNIS) can also be associated with a granulomatous reaction. Intratubular epithelioid histiocytes, fewer giant cells are associated with GCNIS. GCNIS cells are enlarged, atypical germ cells residing within seminiferous tubules as isolated cells or a single row along a usually thickened basement membrane. GCNIS cells have clear cytoplasm, irregular nuclear contours, coarse chromatin, and enlarged single or multiple nucleoli. Some GCNIS cells have mummified pyknotic enlarged hyperchromatic nuclei. Seminiferous tubules containing GCNIS usually lack active spermatogenesis and contain mostly Sertoli cells. GCNIS cells can be highlighted by immunohistochemistry for PLAP and OCT4. Typically GCNIS with a granulomatous reaction is accompanied by invasive seminoma with a granulomatous reaction.
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Answer: D
Histological Description: Affecting part of the testis there are non-necrotizing granulomas filling seminiferous tubules. Granulomas are composed of epithelioid histiocytes, giant cells admixed with lymphocytes and plasma cells. Chronic inflammatory cells including eosinophils and plasma cells infiltrate interstitium. The surrounding seminiferous tubules show active spermatogenesis.
Discussion: Idiopathic granulomatous orchitis is of unknown etiology. It is a benign inflammatory condition that can be bilateral and lead to loss of spermatogenesis in involved testes even if orchiectomy avoided. In infectious processes, necrotizing and/or non-necrotizing granulomatous inflammation composed of epithelioid histiocytes and multinucleated giant cells mainly involving the testicular interstitium. Infectious processes involving the testis also always start in the epididymis. The same interstitial distribution is also seen in sarcoidosis, yet non-necrotizing granulomas are seen. Germ cell neoplasia in situ (GCNIS) can also be associated with a granulomatous reaction. Intratubular epithelioid histiocytes, fewer giant cells are associated with GCNIS. GCNIS cells are enlarged, atypical germ cells residing within seminiferous tubules as isolated cells or a single row along a usually thickened basement membrane. GCNIS cells have clear cytoplasm, irregular nuclear contours, coarse chromatin, and enlarged single or multiple nucleoli. Some GCNIS cells have mummified pyknotic enlarged hyperchromatic nuclei. Seminiferous tubules containing GCNIS usually lack active spermatogenesis and contain mostly Sertoli cells. GCNIS cells can be highlighted by immunohistochemistry for PLAP and OCT4. Typically GCNIS with a granulomatous reaction is accompanied by invasive seminoma with a granulomatous reaction.
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about an adult male with a bladder tumor.
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An adult male presents with a bladder tumor.
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Correct: B
Histology: The tissue shows hyperplastic prostatic glands surrounded by hypercellular stroma with scattered pleomorphic cells with degenerative nuclear atypia.
Discussion: Stromal tumors of the specialized prostatic stroma are classified as STUMP and prostatic stromal sarcoma. STUMPS present at any age with a median age of 58 years. STUMP can be detected as an incidental finding in prostate needle biopsy performed for elevated PSA or due to obstructive urinary symptoms or rectal fullness in cases of large tumors (up to 19 cm in size). There are five histological patterns of STUMPs. The most common is the hypercellular stroma with scattered large pleomorphic stromal cells with degenerative nuclear atypia growing in between benign glands. The glands entrapped within the lesion frequently show hyperplasia and other changes including clear basal cell hyperplasia, clear cell cribriform hyperplasia, urothelial metaplasia, or PIN. The glandular complexity may mask the underlying stromal neoplasm, and in these cases STUMP may be undiagnosed. A second histologic pattern that is much less frequent than the previous is the phyllodes subtype, characterized by leaf-like stromal projections lined by benign prostatic epithelium. A third pattern is with sheets of myxoid stroma containing bland stromal cells usually without glands. The fourth pattern is hypercellular stroma with eosinophilic cytoplasm but without the classic degenerative nuclear atypia. The last pattern is very subtle and characterized by a cellular stroma with epithelioid or round stromal cells. Similar to the myxoid and the hypercellular types, the nuclei are bland and lack significant atypia, making the diagnosis more challenging. Mitotic figures or necrosis are typically absent and when these features are present, prostatic stromal sarcoma should be considered.
While the name of this tumor suggests that the malignant potential is “uncertain,” once completely excised and if the specimen does not show a prostatic stromal sarcoma, the tumor will have a benign behavior. However, low-grade or high-grade prostatic stromal sarcomas are identified in approximately 10% of the cases or may develop over time if unresected, where the term the uncertain malignant potential applies on needle biopsy. Tumors that compress the rectum often show a peritumoral fibrous reaction that should not be interpreted as rectal invasion. STUMPs are positive for CD34, and for progesterone receptor, and variable expression of smooth muscle markers including SMA or desmin. The differential diagnoses of STUMPs include stromal nodule of BPH, stromal sarcoma, solitary fibrous tumor, inflammatory myofibroblastic tumor, gastrointestinal stromal tumor (GIST), leiomyosarcoma, and synovial sarcoma. The myxoid pattern of STUMP is the subtype that more closely resembles a stromal nodule of BPH given the lack of associated glands or significant nuclear atypia. The presence of thick-walled blood vessels is a feature of stromal nodule of BPH and not of STUMP. Immunohistochemistry is usually not helpful in the differential diagnosis of STUMP and stromal nodule of BPH or prostatic stromal sarcoma. The other differential diagnoses are discussed below.
Reference:
1. Leong JY, Chandrasekar T, Sebastiano C, Rshaidat H, Steward JE, Trabulsi EJ. Prostatic Stromal Tumors of Uncertain Malignant Potential. Urology. 2019.
2. Nagar M, Epstein JI. Epithelial proliferations in prostatic stromal tumors of uncertain malignant potential (STUMP). Am J Surg Pathol. 2011;35(6):898-903.
3. Sadimin ET, Epstein JI. Round cell pattern of prostatic stromal tumor of uncertain malignant potential: a subtle newly recognized variant. Hum Pathol. 2016;52:68-73.
4. Herawi M, Epstein JI. Specialized stromal tumors of the prostate: a clinicopathologic study of 50 cases. Am J Surg Pathol. 2006;30(6):694-704.
Incorrect
Correct: B
Histology: The tissue shows hyperplastic prostatic glands surrounded by hypercellular stroma with scattered pleomorphic cells with degenerative nuclear atypia.
Discussion: Stromal tumors of the specialized prostatic stroma are classified as STUMP and prostatic stromal sarcoma. STUMPS present at any age with a median age of 58 years. STUMP can be detected as an incidental finding in prostate needle biopsy performed for elevated PSA or due to obstructive urinary symptoms or rectal fullness in cases of large tumors (up to 19 cm in size). There are five histological patterns of STUMPs. The most common is the hypercellular stroma with scattered large pleomorphic stromal cells with degenerative nuclear atypia growing in between benign glands. The glands entrapped within the lesion frequently show hyperplasia and other changes including clear basal cell hyperplasia, clear cell cribriform hyperplasia, urothelial metaplasia, or PIN. The glandular complexity may mask the underlying stromal neoplasm, and in these cases STUMP may be undiagnosed. A second histologic pattern that is much less frequent than the previous is the phyllodes subtype, characterized by leaf-like stromal projections lined by benign prostatic epithelium. A third pattern is with sheets of myxoid stroma containing bland stromal cells usually without glands. The fourth pattern is hypercellular stroma with eosinophilic cytoplasm but without the classic degenerative nuclear atypia. The last pattern is very subtle and characterized by a cellular stroma with epithelioid or round stromal cells. Similar to the myxoid and the hypercellular types, the nuclei are bland and lack significant atypia, making the diagnosis more challenging. Mitotic figures or necrosis are typically absent and when these features are present, prostatic stromal sarcoma should be considered.
While the name of this tumor suggests that the malignant potential is “uncertain,” once completely excised and if the specimen does not show a prostatic stromal sarcoma, the tumor will have a benign behavior. However, low-grade or high-grade prostatic stromal sarcomas are identified in approximately 10% of the cases or may develop over time if unresected, where the term the uncertain malignant potential applies on needle biopsy. Tumors that compress the rectum often show a peritumoral fibrous reaction that should not be interpreted as rectal invasion. STUMPs are positive for CD34, and for progesterone receptor, and variable expression of smooth muscle markers including SMA or desmin. The differential diagnoses of STUMPs include stromal nodule of BPH, stromal sarcoma, solitary fibrous tumor, inflammatory myofibroblastic tumor, gastrointestinal stromal tumor (GIST), leiomyosarcoma, and synovial sarcoma. The myxoid pattern of STUMP is the subtype that more closely resembles a stromal nodule of BPH given the lack of associated glands or significant nuclear atypia. The presence of thick-walled blood vessels is a feature of stromal nodule of BPH and not of STUMP. Immunohistochemistry is usually not helpful in the differential diagnosis of STUMP and stromal nodule of BPH or prostatic stromal sarcoma. The other differential diagnoses are discussed below.
Reference:
1. Leong JY, Chandrasekar T, Sebastiano C, Rshaidat H, Steward JE, Trabulsi EJ. Prostatic Stromal Tumors of Uncertain Malignant Potential. Urology. 2019.
2. Nagar M, Epstein JI. Epithelial proliferations in prostatic stromal tumors of uncertain malignant potential (STUMP). Am J Surg Pathol. 2011;35(6):898-903.
3. Sadimin ET, Epstein JI. Round cell pattern of prostatic stromal tumor of uncertain malignant potential: a subtle newly recognized variant. Hum Pathol. 2016;52:68-73.
4. Herawi M, Epstein JI. Specialized stromal tumors of the prostate: a clinicopathologic study of 50 cases. Am J Surg Pathol. 2006;30(6):694-704.
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about a 50 year old male with a testicular tumor.
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A 50 year old male presents with a testicular tumor.
Correct
Correct: D
Histology: This tumor is centered in the hilum of the testis and invades the epididymis and testicular parenchyma and is composed of large solid nests of tumor cells with central necrosis.
Discussion: Colon cancer usually metastasizes to regional lymph nodes, liver, lung, bone, and brain. Metastatic colorectal carcinoma to the testis is rare. In general, secondary malignancies of the testis are rare and the most common sites of origin include prostate, stomach, lung, malignant melanoma, pancreas and renal cell carcinoma. The key to arrive at the diagnosis is to recognize the absence of intratubular germ cell neoplasia in-situ in the surrounding testis and knowing the clinical history of previous malignancy. Most commonly, metastatic tumors are centered in the hilum of the testis in the junction of the testicular parenchyma and the epididymis.
References:
1. Hatoum HA, Abi Saad, GS, Otrock ZK, Barada KA, Shamseddine AI. Int J Clin Oncol (2011) 16:203-209
Incorrect
Correct: D
Histology: This tumor is centered in the hilum of the testis and invades the epididymis and testicular parenchyma and is composed of large solid nests of tumor cells with central necrosis.
Discussion: Colon cancer usually metastasizes to regional lymph nodes, liver, lung, bone, and brain. Metastatic colorectal carcinoma to the testis is rare. In general, secondary malignancies of the testis are rare and the most common sites of origin include prostate, stomach, lung, malignant melanoma, pancreas and renal cell carcinoma. The key to arrive at the diagnosis is to recognize the absence of intratubular germ cell neoplasia in-situ in the surrounding testis and knowing the clinical history of previous malignancy. Most commonly, metastatic tumors are centered in the hilum of the testis in the junction of the testicular parenchyma and the epididymis.
References:
1. Hatoum HA, Abi Saad, GS, Otrock ZK, Barada KA, Shamseddine AI. Int J Clin Oncol (2011) 16:203-209
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about an adult man who has undergone TURP.
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An adult male presents with lower urinary tract symptoms and undergoes transurethral resection of the prostate (TURP).
Correct
Correct: C
Histology: Prostate tissue with nodules of cribriform glands with clear cytoplasm, bland nuclei and foci of dark basal cell layer.
Discussion: Clear cell cribriform hyperplasia (CCCH) is a rare form of benign prostatic hyperplasia. When detected, it is most often on TURPs as it is located in the central and transition zone. It comprises of nodules of cribriform glands with clear cytoplasm, bland nuclei, and a prominent dark basal layer. It can be misconstrued as a Gleason score 4+4=8 (Grade Group 4) due to its cribriform morphology. The key to differentiating clear cell cribriform hyperplasia from high-grade PIN/Intraductal carcinoma is the lack of cytologic atypia (no prominent nucleoli). HMWK or p63 stains basal cells, although not every gland will be positive, differentiating it from a high-grade adenocarcinoma.
References
1. Frauenhoffer EE, Ro JY, el-Naggar AK, Ordonez NG, Ayala AG. Clear cell cribriform hyperplasia of the prostate. Immunohistochemical and DNA flow cytometric study. Am J Clin Pathol. 1991;95(4):446-453.
2. Ayala AG, Srigley JR, Ro JY, Abdul-Karim FW, Johnson DE. Clear cell cribriform hyperplasia of prostate. Report of 10 cases. Am J Surg Pathol. 1986;10(10):665-671.
Incorrect
Correct: C
Histology: Prostate tissue with nodules of cribriform glands with clear cytoplasm, bland nuclei and foci of dark basal cell layer.
Discussion: Clear cell cribriform hyperplasia (CCCH) is a rare form of benign prostatic hyperplasia. When detected, it is most often on TURPs as it is located in the central and transition zone. It comprises of nodules of cribriform glands with clear cytoplasm, bland nuclei, and a prominent dark basal layer. It can be misconstrued as a Gleason score 4+4=8 (Grade Group 4) due to its cribriform morphology. The key to differentiating clear cell cribriform hyperplasia from high-grade PIN/Intraductal carcinoma is the lack of cytologic atypia (no prominent nucleoli). HMWK or p63 stains basal cells, although not every gland will be positive, differentiating it from a high-grade adenocarcinoma.
References
1. Frauenhoffer EE, Ro JY, el-Naggar AK, Ordonez NG, Ayala AG. Clear cell cribriform hyperplasia of the prostate. Immunohistochemical and DNA flow cytometric study. Am J Clin Pathol. 1991;95(4):446-453.
2. Ayala AG, Srigley JR, Ro JY, Abdul-Karim FW, Johnson DE. Clear cell cribriform hyperplasia of prostate. Report of 10 cases. Am J Surg Pathol. 1986;10(10):665-671.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case talks about a 80-year-old man with a scalp tumor.
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This is an 80 year old male with a scalp tumor. The neoplastic cells were negative for S100, HMB45, cytokeratins Cam5.2, AE1/3, and 34BE12, as well as CD34.
Diagnoses:
Correct
Answer: D
Histologic Description: This is a pleomorphic spindle cell neoplasm that involves the dermis but also extends into the subcutaneous tissue and skeletal muscle. In some sections, perineural and vascular invasion were identified. The lesion is arising in chronically sun damaged skin; however, there is no evidence of in situ or invasive melanoma or squamous cell carcinoma. These are the typical features of pleomorphic dermal sarcoma.
Differential Diagnosis: Atypical fibroxanthoma (AFX) is on the spectrum of pleomorphic dermal sarcoma; however, by definition it does not involve subcutaneous tissues, does not show lymphovascular invasion or perineural invasion, and does not show necrosis. AFX generally has a benign outcome, reflecting its extremely superficial nature. Squamous cell carcinomas should demonstrate in situ component or labeling for cytokeratins, while melanoma would demonstrate either in situ or invasive component, and should demonstrate some labeling for S100 or HMB45. Unlike AFX, pleomorphic dermal sarcoma has significant potential for metastatic spread. Patients who do develop metastases have poor outcome.
Incorrect
Answer: D
Histologic Description: This is a pleomorphic spindle cell neoplasm that involves the dermis but also extends into the subcutaneous tissue and skeletal muscle. In some sections, perineural and vascular invasion were identified. The lesion is arising in chronically sun damaged skin; however, there is no evidence of in situ or invasive melanoma or squamous cell carcinoma. These are the typical features of pleomorphic dermal sarcoma.
Differential Diagnosis: Atypical fibroxanthoma (AFX) is on the spectrum of pleomorphic dermal sarcoma; however, by definition it does not involve subcutaneous tissues, does not show lymphovascular invasion or perineural invasion, and does not show necrosis. AFX generally has a benign outcome, reflecting its extremely superficial nature. Squamous cell carcinomas should demonstrate in situ component or labeling for cytokeratins, while melanoma would demonstrate either in situ or invasive component, and should demonstrate some labeling for S100 or HMB45. Unlike AFX, pleomorphic dermal sarcoma has significant potential for metastatic spread. Patients who do develop metastases have poor outcome.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case talks about a 50-year-old woman who has undergone lung transplantation.
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This is a 50 year old female who has undergone lung transplantation. This is the native explant.
Diagnoses:
Correct
Answer: B
Histologic Description: This clearly is a process that is centered on the airways, which should be paired with small arterioles in the lung. What is striking about the specimen is that the many of the small airways have been completely obliterated, such they appear as small fibrous nodules adjacent to medium sized arterioles. This is best demonstrated using the Movat stain, which demonstrates either obliteration or concentric narrowing of the airways by new fibrous tissue. These are the typical findings of constrictive bronchiolitis.
Differential Diagnosis: Respiratory bronchiolitis is typically associated with smoking, and would feature pigmented macrophages centered upon airways with extension into the adjacent alveolar spaces, frequently associated with interstitial fibrosis. Follicular bronchiolitis would demonstrate more prominent lymphoid follicles centered on the airways, without the narrowing seen in this case. Bronchiolitis obliterans organizing pneumonia would feature fibrous plugs which extend out of the bronchioles into the adjacent alveolar spaces. The concentric narrowing seen in constrictive bronchiolitis differs from the polypoid fibrosis seen in bronchiolitis obliterans organizing pneumonia.
Constrictive bronchiolitis is frequently idiopathic, but may be secondary to viral infections or other etiologies. In a lung transplant, constrictive bronchiolitis usually represents chronic rejection.
Incorrect
Answer: B
Histologic Description: This clearly is a process that is centered on the airways, which should be paired with small arterioles in the lung. What is striking about the specimen is that the many of the small airways have been completely obliterated, such they appear as small fibrous nodules adjacent to medium sized arterioles. This is best demonstrated using the Movat stain, which demonstrates either obliteration or concentric narrowing of the airways by new fibrous tissue. These are the typical findings of constrictive bronchiolitis.
Differential Diagnosis: Respiratory bronchiolitis is typically associated with smoking, and would feature pigmented macrophages centered upon airways with extension into the adjacent alveolar spaces, frequently associated with interstitial fibrosis. Follicular bronchiolitis would demonstrate more prominent lymphoid follicles centered on the airways, without the narrowing seen in this case. Bronchiolitis obliterans organizing pneumonia would feature fibrous plugs which extend out of the bronchioles into the adjacent alveolar spaces. The concentric narrowing seen in constrictive bronchiolitis differs from the polypoid fibrosis seen in bronchiolitis obliterans organizing pneumonia.
Constrictive bronchiolitis is frequently idiopathic, but may be secondary to viral infections or other etiologies. In a lung transplant, constrictive bronchiolitis usually represents chronic rejection.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case talks about a 82 year old man with colon polyps.
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This is an 82 year old male with diverticulosis and associated mucosal polyps.
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Answer: D
Histologic Description: This polypoid lesion is characterized by a lamina propria which has abundant fresh hemorrhage and hemosiderin, and has been replaced by bundles of smooth muscle. The crypts within tend to have a “diamond shaped appearance.” Superficially, the lesion is ulcerated, and the glands have a more hyperplastic appearance. These are the typical features of mucosal prolapse. Adjacent to diverticula, this constellation of findings has been referred to as “polypoid prolapsing mucosal fold.” The late Johns Hopkins pathologist Dr. Belur Bhagavan was one of the first to recognize this lesion.
Differential Diagnosis: Sessile serrated adenomas would typically demonstrate boat-shaped crypts at their base, and demonstrate greater serrations superficially. Adenomatous polyps would demonstrate nuclear stratification and hyperchromasia, typically at the top of the lesion. Neither a sessile serrated polyp nor adenomatous polyp would typically have the prominent smooth muscle replacement of lamina propria and hemosiderin seen in the current case. Peutz-Jeghers polyps typically have bands of smooth muscle which are well-formed and have a branching pattern, which is dissimilar to that seen in the current case.
Incorrect
Answer: D
Histologic Description: This polypoid lesion is characterized by a lamina propria which has abundant fresh hemorrhage and hemosiderin, and has been replaced by bundles of smooth muscle. The crypts within tend to have a “diamond shaped appearance.” Superficially, the lesion is ulcerated, and the glands have a more hyperplastic appearance. These are the typical features of mucosal prolapse. Adjacent to diverticula, this constellation of findings has been referred to as “polypoid prolapsing mucosal fold.” The late Johns Hopkins pathologist Dr. Belur Bhagavan was one of the first to recognize this lesion.
Differential Diagnosis: Sessile serrated adenomas would typically demonstrate boat-shaped crypts at their base, and demonstrate greater serrations superficially. Adenomatous polyps would demonstrate nuclear stratification and hyperchromasia, typically at the top of the lesion. Neither a sessile serrated polyp nor adenomatous polyp would typically have the prominent smooth muscle replacement of lamina propria and hemosiderin seen in the current case. Peutz-Jeghers polyps typically have bands of smooth muscle which are well-formed and have a branching pattern, which is dissimilar to that seen in the current case.
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about an adult man with a kidney mass.
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An adult male presents with a kidney mass.
What is the diagnosis?
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Correct: D
Histology: The tumor is well circumscribed and surrounded by a thick fibrous capsule. Tumor cells have a primitive appearance and are columnar in areas of tubule formation. Mitoses are frequent.
Discussion: Wilms tumor, also known as nephroblastoma, is the most common kidney malignancy in children, occurring mainly in the first 5 years of life. Wilms tumor is very rare in adults with an incidence of about 0.2 per million per year. Histologically, the Wilms tumors are comprised of blastemal, stromal and epithelial elements, but cases can be monophasic or biphasic. The blastemal elements can be present in nodular fashion or have a syncytial pattern. Spindle cells are the most common form of stromal component but some tumors can show heterologous elements including skeletal muscle, smooth muscle, adipose tissue, cartilage, osteoid/bone, glial tissue, and squamous, ciliated, and glandular epithelium (teratoid Wilms tumors). Classical triphasic WT rarely presents diagnostic difficulty for pathologists, but when only one component is present, especially in a small biopsy specimen, the differential diagnosis may include renal cell carcinoma, metanephric adenoma and hyperplastic nephrogenic rest for epithelial elements, and clear cell sarcoma of the kidney, mesoblastic nephroma and synovial sarcoma for stromal elements. Pure blastemal-type WT may be difficult to distinguish from other embryonal small round blue cell tumors, including neuroblastoma, Ewing sarcoma, desmoplastic small round cell tumor and lymphoma. The presence of anaplasia defined as nuclear sized 3× tumor cells and tripolar mitosis is associated with high risk. All the three components, though usually blastema, can become anaplastic, leading to the diagnosis of either focal or diffuse anaplasia. WT with diffuse anaplasia and WT with blastemal predominance (after preoperative chemotherapy) are regarded as high-risk tumors and require more aggressive treatment. By immunohistochemistry, tumor cells are positive for WT1, PAX8 and CD56 and negative for CK7.
Histology: The tumor is well circumscribed and surrounded by a thick fibrous capsule. Tumor cells have a primitive appearance and are columnar in areas of tubule formation. Mitoses are frequent.
Discussion: Wilms tumor, also known as nephroblastoma, is the most common kidney malignancy in children, occurring mainly in the first 5 years of life. Wilms tumor is very rare in adults with an incidence of about 0.2 per million per year. Histologically, the Wilms tumors are comprised of blastemal, stromal and epithelial elements, but cases can be monophasic or biphasic. The blastemal elements can be present in nodular fashion or have a syncytial pattern. Spindle cells are the most common form of stromal component but some tumors can show heterologous elements including skeletal muscle, smooth muscle, adipose tissue, cartilage, osteoid/bone, glial tissue, and squamous, ciliated, and glandular epithelium (teratoid Wilms tumors). Classical triphasic WT rarely presents diagnostic difficulty for pathologists, but when only one component is present, especially in a small biopsy specimen, the differential diagnosis may include renal cell carcinoma, metanephric adenoma and hyperplastic nephrogenic rest for epithelial elements, and clear cell sarcoma of the kidney, mesoblastic nephroma and synovial sarcoma for stromal elements. Pure blastemal-type WT may be difficult to distinguish from other embryonal small round blue cell tumors, including neuroblastoma, Ewing sarcoma, desmoplastic small round cell tumor and lymphoma. The presence of anaplasia defined as nuclear sized 3× tumor cells and tripolar mitosis is associated with high risk. All the three components, though usually blastema, can become anaplastic, leading to the diagnosis of either focal or diffuse anaplasia. WT with diffuse anaplasia and WT with blastemal predominance (after preoperative chemotherapy) are regarded as high-risk tumors and require more aggressive treatment. By immunohistochemistry, tumor cells are positive for WT1, PAX8 and CD56 and negative for CK7.
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about a 30 year old female with a kidney mass.
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A 30 year old female presents with a kidney mass.
What is the diagnosis?
Correct
Correct: B
Histology: This tumor is composed of large nests with papillary structures lines by clear cells with large nuclei. There are stromal septa composed of smooth muscle separating the tumor nests.
Discussion: This is translocation RCC involving region Xp11.2, resulting in fusion of the TFE3 gene. While they represent approximately 40% of pediatric RCCs, they can also develop in adults. Microscopically, the overall features are typically those of an RCC but are very heterogeneous. Papillary structures may be prominent, and the tumor cells can be either clear or have a markedly granular eosinophilic cytoplasm; however, some cases are more solid and clear cell predominant, closely mimicking clear cell RCC. Admixed psammoma bodies may be abundant (not present in the current case). The presence of large nests with prominent papillary structures lined by clear cells and separated by thick stromal septa could be a morphologic clue to the diagnosis. By immunohistochemistry, a proportion of these tumors express PAX8 and Cathepsin-K, and can be negative or weakly positive for cytokeratins.
References:
Am J Surg Pathol. 40:723-737 2016
Am J Clin Pathol. 126 (3):332-334 2006
Incorrect
Correct: B
Histology: This tumor is composed of large nests with papillary structures lines by clear cells with large nuclei. There are stromal septa composed of smooth muscle separating the tumor nests.
Discussion: This is translocation RCC involving region Xp11.2, resulting in fusion of the TFE3 gene. While they represent approximately 40% of pediatric RCCs, they can also develop in adults. Microscopically, the overall features are typically those of an RCC but are very heterogeneous. Papillary structures may be prominent, and the tumor cells can be either clear or have a markedly granular eosinophilic cytoplasm; however, some cases are more solid and clear cell predominant, closely mimicking clear cell RCC. Admixed psammoma bodies may be abundant (not present in the current case). The presence of large nests with prominent papillary structures lined by clear cells and separated by thick stromal septa could be a morphologic clue to the diagnosis. By immunohistochemistry, a proportion of these tumors express PAX8 and Cathepsin-K, and can be negative or weakly positive for cytokeratins.
References:
Am J Surg Pathol. 40:723-737 2016
Am J Clin Pathol. 126 (3):332-334 2006
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about an adult male with a bladder tumor.
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An adult male presents with a bladder tumor.
What is the diagnosis?
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Correct: C
Histology: Proliferation of nests and cords of urothelium with an endophytic growth and covered by normal or flattened urothelium.
Discussion: Inverted urothelial papillomas (IUP) are rare and account for approximately 1% of bladder tumors and can occur at any age (average age at presentation is 60). The most common location is the bladder neck and trigone. Painless gross hematuria is the most common presenting symptom. The majority of the tumors are smaller than 5 cm. Histologically, the tumor is composed of anastomosing nest and thin cords of urothelium growing endophytically from the superficial urothelium. An exophytic component should be absent. Tumor cells are bland and often streaming towards the center of the cords and with peripheral palisading. Some cases show focal squamous metaplasia. The main differential diagnosis is with low grade papillary urothelial carcinoma with inverted growth pattern, which is characterized by the presence of larger nests and/or cytologic atypia. Any stromal reaction/desmoplasia or involvement of the muscularis propria are not features of IUP and are suggestive of invasive carcinoma. Mitotic activity is usually low. The recurrence rate is ~5%.
References:
Can Urol Assoc J. 2017 Jan-Feb; 11(1-2): 66–69.
Incorrect
Correct: C
Histology: Proliferation of nests and cords of urothelium with an endophytic growth and covered by normal or flattened urothelium.
Discussion: Inverted urothelial papillomas (IUP) are rare and account for approximately 1% of bladder tumors and can occur at any age (average age at presentation is 60). The most common location is the bladder neck and trigone. Painless gross hematuria is the most common presenting symptom. The majority of the tumors are smaller than 5 cm. Histologically, the tumor is composed of anastomosing nest and thin cords of urothelium growing endophytically from the superficial urothelium. An exophytic component should be absent. Tumor cells are bland and often streaming towards the center of the cords and with peripheral palisading. Some cases show focal squamous metaplasia. The main differential diagnosis is with low grade papillary urothelial carcinoma with inverted growth pattern, which is characterized by the presence of larger nests and/or cytologic atypia. Any stromal reaction/desmoplasia or involvement of the muscularis propria are not features of IUP and are suggestive of invasive carcinoma. Mitotic activity is usually low. The recurrence rate is ~5%.
References:
Can Urol Assoc J. 2017 Jan-Feb; 11(1-2): 66–69.
Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about a 63 year old female with a renal mass.
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Clinical History: A 63 year old female underwent a partial nephrectomy for a peripherally located renal mass.
Choose the correct diagnosis:
Correct
Answer: B
Histological description: Grossly, the tumor was well-circumscribed with minimally infiltrative borders. The tumor has a uniform appearance of bland epithelioid to slightly spindled cells with nuclei having delicate chromatin. The cytoplasm was lightly eosinophilic and in areas had a filamentous appearance. Focally, the stroma had thicker eosinophilic collagen bundles. The lesion lacked necrosis, increased mitoses, and atypical mitoses. In areas, epithelioid and spindle cells radiated off of vessel walls. The tumor lacked an adipose component.
Discussion: Angiomylipoma (AML) in the kidney are more often sporadic but can be seen in the setting of Tuberous Sclerosis where presentation is in younger individuals and the lesions are multifocal and bilateral. In contrast to leiomyomas that arise from vessels in the renal hilum, AMLs typically arise from the cortex and can extend out of the kidney or even be predominantly or exclusively in the perirenal fat. AMLs are most often spindled with smooth muscle cells having identical nuclei to low grade leiomyosarcomas, yet AMLs have cytoplasm that is looser and filamentous. The smooth muscle component in AML can be fascicular and indistinguishable from a smooth muscle tumor, and in other areas more haphazard. AMLs, including epithelioid cases that lack atypical features, are benign although they can involve lymph nodes. Some AMLs are associated with significant morbidity and even mortality due to massive retroperitoneal hemorrhage. There do exist atypical epithelioid AMLs where epithelioid cells have overall high N/C ratios with variable amount of pale clear to eosinophilic cytoplasm. There are populations of pleomorphic cells with multinucleation and abundant cytoplasm termed “amoeboid cells”. In these cases, malignant behavior correlates with the presence of 3 of the 4 following features: 1) >70% atypical epithelioid areas; 2) >2 mitoses per 10 HPF; 3) atypical mitotic figures; or 4) necrosis. AMLs are typically positive for HMB45, Melan A, and Cathepsin K. Cytokeratins and PAX8 are negative. The key features to recognize in the current case were the characteristic bland epithelioid to slightly spindled cells with lightly eosinophilic filamentous cytoplasm and the radiating cells coming off of some of the vessels. Also, for the diagnosis of AML, it is not necessary for the lesion to have an adipose tissue component, and typically lesions that come to resection are fat-poor AMLs as AMLs with a prominent fatty component can be recognized on imaging and unless symptomatic and not resected.
Incorrect
Answer: B
Histological description: Grossly, the tumor was well-circumscribed with minimally infiltrative borders. The tumor has a uniform appearance of bland epithelioid to slightly spindled cells with nuclei having delicate chromatin. The cytoplasm was lightly eosinophilic and in areas had a filamentous appearance. Focally, the stroma had thicker eosinophilic collagen bundles. The lesion lacked necrosis, increased mitoses, and atypical mitoses. In areas, epithelioid and spindle cells radiated off of vessel walls. The tumor lacked an adipose component.
Discussion: Angiomylipoma (AML) in the kidney are more often sporadic but can be seen in the setting of Tuberous Sclerosis where presentation is in younger individuals and the lesions are multifocal and bilateral. In contrast to leiomyomas that arise from vessels in the renal hilum, AMLs typically arise from the cortex and can extend out of the kidney or even be predominantly or exclusively in the perirenal fat. AMLs are most often spindled with smooth muscle cells having identical nuclei to low grade leiomyosarcomas, yet AMLs have cytoplasm that is looser and filamentous. The smooth muscle component in AML can be fascicular and indistinguishable from a smooth muscle tumor, and in other areas more haphazard. AMLs, including epithelioid cases that lack atypical features, are benign although they can involve lymph nodes. Some AMLs are associated with significant morbidity and even mortality due to massive retroperitoneal hemorrhage. There do exist atypical epithelioid AMLs where epithelioid cells have overall high N/C ratios with variable amount of pale clear to eosinophilic cytoplasm. There are populations of pleomorphic cells with multinucleation and abundant cytoplasm termed “amoeboid cells”. In these cases, malignant behavior correlates with the presence of 3 of the 4 following features: 1) >70% atypical epithelioid areas; 2) >2 mitoses per 10 HPF; 3) atypical mitotic figures; or 4) necrosis. AMLs are typically positive for HMB45, Melan A, and Cathepsin K. Cytokeratins and PAX8 are negative. The key features to recognize in the current case were the characteristic bland epithelioid to slightly spindled cells with lightly eosinophilic filamentous cytoplasm and the radiating cells coming off of some of the vessels. Also, for the diagnosis of AML, it is not necessary for the lesion to have an adipose tissue component, and typically lesions that come to resection are fat-poor AMLs as AMLs with a prominent fatty component can be recognized on imaging and unless symptomatic and not resected.
Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about a 45-year-old man with a bladder tumor.
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Clinical History: A 45 year-old man underwent a TUR for a bladder tumor.
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Answer: D
Histological Description: Within the lamina propria there is a proliferation of cells with amphophilic cytoplasm and overt pleomorphism. Although at a casual glance, the cells appear to grow in a diffuse sheet, upon closer inspection the cells are arranged in nests with a network of thin capillaries separating the nests. The tumor does not have prominent mitotic activity. The tumor invades muscularis propria.
Discussion: The mean age of paragangliomas in the bladder is 41 years with a broad range from 10-88 years. Although they often present with hematuria, patients may also have more specific symptoms of micturition attacks consisting of syncope, headache, hypertension, palpitation, blurred vision and/or sweating following straining when urinating. Two thirds of patients have hypertension. Most are exophytic with an intact smooth mucosa unless ulcerated. Tumors vary in size from several millimeters to 10 cm. Most are solitary. Usually, there are uniform sized and shaped nests delineated by delicate fibrovascular septae. Uncommonly, as in this case, paragangliomas can have foci of more diffuse growth where the nesting pattern is not as evident. The key to the correct diagnosis is recognizing the abundant amphophilic granular cytoplasm and also not having tunnel vision to only consider urothelial carcinoma when confronted with a nested tumor in the bladder. Another aspect of the current case that is diagnostically difficult is that in the typical case of paraganglioma involving the bladder, nuclei are typically uniform small and round with uniform chromatin. However, cases like our can have occasional scattered pleomorphic enlarged nuclei, most with a degenerative appearance consisting of smudgy indistinct chromatin. In contrast to a high grade pleomorphic urothelial carcinoma, mitotic figures are uncommon. In contrast to urothelial carcinoma, paragangliomas are cytokeratin negative and synaptophysin and chromogranin positive. In some cases, S100 highlights sustentacular cells surrounding tumor nests. An immunohistochemical pitfall is that both invasive urothelial carcinoma and paraganglioma are positive for GATA3. All paragangliomas should also be evaluated immunohistochemically for SDHB which can be lost as a result of a sporadic mutation but could also represent a germline mutation associated with the hereditary paraganglioma syndrome. Paragangliomas which show loss of SDHB have a higher risk of malignant behavior. Depending on the location and size of the tumor, final treatment could be only the initial TUR, repeat TUR, or partial or radical cystectomy. Paragangliomas can invade the muscularis propria, as seen in the current case. 10% of bladder paragangliomas are malignant, which cannot be predicted based on the morphology.
Incorrect
Answer: D
Histological Description: Within the lamina propria there is a proliferation of cells with amphophilic cytoplasm and overt pleomorphism. Although at a casual glance, the cells appear to grow in a diffuse sheet, upon closer inspection the cells are arranged in nests with a network of thin capillaries separating the nests. The tumor does not have prominent mitotic activity. The tumor invades muscularis propria.
Discussion: The mean age of paragangliomas in the bladder is 41 years with a broad range from 10-88 years. Although they often present with hematuria, patients may also have more specific symptoms of micturition attacks consisting of syncope, headache, hypertension, palpitation, blurred vision and/or sweating following straining when urinating. Two thirds of patients have hypertension. Most are exophytic with an intact smooth mucosa unless ulcerated. Tumors vary in size from several millimeters to 10 cm. Most are solitary. Usually, there are uniform sized and shaped nests delineated by delicate fibrovascular septae. Uncommonly, as in this case, paragangliomas can have foci of more diffuse growth where the nesting pattern is not as evident. The key to the correct diagnosis is recognizing the abundant amphophilic granular cytoplasm and also not having tunnel vision to only consider urothelial carcinoma when confronted with a nested tumor in the bladder. Another aspect of the current case that is diagnostically difficult is that in the typical case of paraganglioma involving the bladder, nuclei are typically uniform small and round with uniform chromatin. However, cases like our can have occasional scattered pleomorphic enlarged nuclei, most with a degenerative appearance consisting of smudgy indistinct chromatin. In contrast to a high grade pleomorphic urothelial carcinoma, mitotic figures are uncommon. In contrast to urothelial carcinoma, paragangliomas are cytokeratin negative and synaptophysin and chromogranin positive. In some cases, S100 highlights sustentacular cells surrounding tumor nests. An immunohistochemical pitfall is that both invasive urothelial carcinoma and paraganglioma are positive for GATA3. All paragangliomas should also be evaluated immunohistochemically for SDHB which can be lost as a result of a sporadic mutation but could also represent a germline mutation associated with the hereditary paraganglioma syndrome. Paragangliomas which show loss of SDHB have a higher risk of malignant behavior. Depending on the location and size of the tumor, final treatment could be only the initial TUR, repeat TUR, or partial or radical cystectomy. Paragangliomas can invade the muscularis propria, as seen in the current case. 10% of bladder paragangliomas are malignant, which cannot be predicted based on the morphology.
Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about a 55 year old male with a hydrocele.
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Clinical History: A 55 year old man presented with a hydrocele, upon which the hydrocele sac was resected.
Choose the correct diagnosis:
Correct
Answer: A
Histological Description: At the interface of more dense fibrous and more reactive inflammatory fibrous tissue there is a linear proliferation of tubules with focal papillary formation. Cytologically, the tubules are lined by bland cuboidal epithelium.
Discussion. Hydroceles which are fluid-filled mesothelial-lined sacs surrounding the testis that in adults usually does not communicate with the peritoneal cavity. The fluid accumulates as a reaction to injury, most often as a reaction to infection (i.e. epididymitis). In this setting, the hydrocele sac may have an associated florid reactive mesothelial proliferation, mimicking malignant mesothelioma. Further compounding the diagnostic difficulty, is that hydroceles can also arise as a reaction to malignancy in this site, such as malignant mesothelioma. The key to recognizing that the process is not malignant is that the reactive proliferation remains confined to a sharply demarcated zone immediately underlying the luminal surface. Proliferating mesothelial cells typically form lines that parallel the surface of hydrocele and fail to penetrate beyond the associated superficial zone of inflammation and fibrosis. Tubules do not invade adipose tissue. Architecturally, simple papillary structures, tubules and nests can be present, but solid areas and broad arborizing complex papillary structures with hyalinized fibrous cores are not identified. Reactive cells maintain abundant cytoplasm and may contain enlarged vesicular nuclei and brisk mitotic activity in inflamed areas. Cytologically, malignant mesothelioma in this region can also have relatively uniform bland cuboidal cells with only modest amount of eosinophilic cytoplasm, although occasionally, frank anaplasia may be demonstrated. Architecturally, malignant mesothelioma has broad arborizing complex papillary and tubular structures and nests with occasional solid areas. Although at times predominantly involving surface as exophytic papillary growth, at least focally, a haphazard infiltrative tubular or nested component exists. Malignant mesotheliomas often invades adipose tissue. In general, immunohistochemistry is often not helpful in the differential diagnosis, although malignant mesothelioma can show loss of MTAP and BAP1 in 50% of malignant mesotheliomas and not reactive mesothelial proliferations.
Incorrect
Answer: A
Histological Description: At the interface of more dense fibrous and more reactive inflammatory fibrous tissue there is a linear proliferation of tubules with focal papillary formation. Cytologically, the tubules are lined by bland cuboidal epithelium.
Discussion. Hydroceles which are fluid-filled mesothelial-lined sacs surrounding the testis that in adults usually does not communicate with the peritoneal cavity. The fluid accumulates as a reaction to injury, most often as a reaction to infection (i.e. epididymitis). In this setting, the hydrocele sac may have an associated florid reactive mesothelial proliferation, mimicking malignant mesothelioma. Further compounding the diagnostic difficulty, is that hydroceles can also arise as a reaction to malignancy in this site, such as malignant mesothelioma. The key to recognizing that the process is not malignant is that the reactive proliferation remains confined to a sharply demarcated zone immediately underlying the luminal surface. Proliferating mesothelial cells typically form lines that parallel the surface of hydrocele and fail to penetrate beyond the associated superficial zone of inflammation and fibrosis. Tubules do not invade adipose tissue. Architecturally, simple papillary structures, tubules and nests can be present, but solid areas and broad arborizing complex papillary structures with hyalinized fibrous cores are not identified. Reactive cells maintain abundant cytoplasm and may contain enlarged vesicular nuclei and brisk mitotic activity in inflamed areas. Cytologically, malignant mesothelioma in this region can also have relatively uniform bland cuboidal cells with only modest amount of eosinophilic cytoplasm, although occasionally, frank anaplasia may be demonstrated. Architecturally, malignant mesothelioma has broad arborizing complex papillary and tubular structures and nests with occasional solid areas. Although at times predominantly involving surface as exophytic papillary growth, at least focally, a haphazard infiltrative tubular or nested component exists. Malignant mesotheliomas often invades adipose tissue. In general, immunohistochemistry is often not helpful in the differential diagnosis, although malignant mesothelioma can show loss of MTAP and BAP1 in 50% of malignant mesotheliomas and not reactive mesothelial proliferations.
Presented by Dr. John Gross and prepared by Dr. Yembur Ahmad
This case talks about a 62 year-old female with a bony lesion.
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This is a 62-year-old female with a bony lesion.
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The lesion is predominantly lytic with a ring and arc pattern of radiodensity on x-ray which is typical of chondroid differentiation. The border is sclerotic, indicating a low grade lesion. Histologically, the nuclei are lymphocyte-like or low grade, and there is no evidence of permeative growth. These are the typical features of an enchondroma.
Chrondrosarcoma would demonstrate greater atypia and more permeative growth in the marrow. Chrondoblastoma has neoplastic cells with grooved nuclei and a grungy chicken-wire calcified matrix. Chrondoblastic osteosarcoma would demonstrate greater cytologic atypia in the neoplastic cells which, at least focally, produce neoplastic bone justifying the diagnosis of osteosarcoma.
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The lesion is predominantly lytic with a ring and arc pattern of radiodensity on x-ray which is typical of chondroid differentiation. The border is sclerotic, indicating a low grade lesion. Histologically, the nuclei are lymphocyte-like or low grade, and there is no evidence of permeative growth. These are the typical features of an enchondroma.
Chrondrosarcoma would demonstrate greater atypia and more permeative growth in the marrow. Chrondoblastoma has neoplastic cells with grooved nuclei and a grungy chicken-wire calcified matrix. Chrondoblastic osteosarcoma would demonstrate greater cytologic atypia in the neoplastic cells which, at least focally, produce neoplastic bone justifying the diagnosis of osteosarcoma.
Presented by Dr. John Gross and prepared by Dr. Yembur Ahmad
This case talks about a 13-year-old male with knee pain.
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This is a 13-year-old male with knee pain.
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Chondromyxoid fibroma is a rare benign cartilage tumor typically affecting young adults and presenting as a metaphyseal, eccentric, and well-defined lesion on radiographs. Chondromyxoid fibroma is composed of bland spindle to stellate cells growing in a background chondromyxoid matrix. The tumor tends to condense into macro- or microlobular pattern and may grow in cords and trabeculae. This low power diagnosis showing a peripheral condensation with central hypocellularity is important two recognize for this diagnosis. Fibrous dysplasia is benign bone tumor which often shows a ground glass radiographic appearance which may expand or deform the bone and shows well defined margins. Histologically, fibrous dysplasia shows randomly arranged trabeculae of woven bone with inconspicuous osteoblastic rimming. The fibrous stroma is bland without cytologic atypia and may grow in a storiform pattern. Non-ossifying fibroma often shows a similar radiographic appearance as chondromyxoid fibroma with a well-defined lesion in metaphysis at an eccentric location. Histologically, non-ossifying fibroma shows bland spindle cells, osteoclast-type giant cells, hemosiderin laden macrophages, and variable amounts of hemorrhage and reactive woven bone. Finally, myofibroma may rarely occur as a primary intraosseous neoplasm and has a predilection for craniofacial sites. If a myofibroma were to occur as a lytic, eccentric mass with sclerotic borders in the metaphysis of a young patient, the radiographic appearance could mimic a chondromyxoid fibroma; however, histologically, myofibromas do not show the same lobulated pattern and instead grow in a more sheet-like or fascicular architecture and have cells with eosinophilic “myoid” cytoplasm with plump oval to spindled nuclei with fine chromatin and tiny, dot-like nucleoli.
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Chondromyxoid fibroma is a rare benign cartilage tumor typically affecting young adults and presenting as a metaphyseal, eccentric, and well-defined lesion on radiographs. Chondromyxoid fibroma is composed of bland spindle to stellate cells growing in a background chondromyxoid matrix. The tumor tends to condense into macro- or microlobular pattern and may grow in cords and trabeculae. This low power diagnosis showing a peripheral condensation with central hypocellularity is important two recognize for this diagnosis. Fibrous dysplasia is benign bone tumor which often shows a ground glass radiographic appearance which may expand or deform the bone and shows well defined margins. Histologically, fibrous dysplasia shows randomly arranged trabeculae of woven bone with inconspicuous osteoblastic rimming. The fibrous stroma is bland without cytologic atypia and may grow in a storiform pattern. Non-ossifying fibroma often shows a similar radiographic appearance as chondromyxoid fibroma with a well-defined lesion in metaphysis at an eccentric location. Histologically, non-ossifying fibroma shows bland spindle cells, osteoclast-type giant cells, hemosiderin laden macrophages, and variable amounts of hemorrhage and reactive woven bone. Finally, myofibroma may rarely occur as a primary intraosseous neoplasm and has a predilection for craniofacial sites. If a myofibroma were to occur as a lytic, eccentric mass with sclerotic borders in the metaphysis of a young patient, the radiographic appearance could mimic a chondromyxoid fibroma; however, histologically, myofibromas do not show the same lobulated pattern and instead grow in a more sheet-like or fascicular architecture and have cells with eosinophilic “myoid” cytoplasm with plump oval to spindled nuclei with fine chromatin and tiny, dot-like nucleoli.
Presented by Dr. John Gross and prepared by Dr. Yembur Ahmad
This case talks about a 15-year-old male with a lytic tibial lesion.
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This is a 15-year-old male with a lytic tibial lesion.
Diagnosis:
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The lesion is lytic with a rim of new bone walling it off. The lesion consists of bland storiform and spindle cells with admixed foamy macrophages and hemosiderin. One may see reactive woven bone in this lesion, which should not dissuade one from the diagnosis of non-ossifying fibroma.
Differential Diagnosis: Giant cell tumor of bone should involve skeletally mature patients, and is a lytic lesion which extends to the epiphysis and has a non-sclerotic border. Histologically it would consist of evenly-admixed neoplastic mononuclear cells and osteoclasts which frequently have over 50 nuclei per cell. Chondroblastoma would also be centered in the epiphysis, and is characterized by nuclei with grooves and grungy, chicken-wire type calcification. A primary bone sarcoma would demonstrate greater cytologic atypia and a more aggressive radiologic appearance.
Incorrect
The lesion is lytic with a rim of new bone walling it off. The lesion consists of bland storiform and spindle cells with admixed foamy macrophages and hemosiderin. One may see reactive woven bone in this lesion, which should not dissuade one from the diagnosis of non-ossifying fibroma.
Differential Diagnosis: Giant cell tumor of bone should involve skeletally mature patients, and is a lytic lesion which extends to the epiphysis and has a non-sclerotic border. Histologically it would consist of evenly-admixed neoplastic mononuclear cells and osteoclasts which frequently have over 50 nuclei per cell. Chondroblastoma would also be centered in the epiphysis, and is characterized by nuclei with grooves and grungy, chicken-wire type calcification. A primary bone sarcoma would demonstrate greater cytologic atypia and a more aggressive radiologic appearance.
Presented by Dr. John Gross and prepared by Dr. Yembur Ahmad
This case talks about a 29-year-old female with a rib lesion.
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This is a 29-year-old female with a rib lesion.
Diagnosis:
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The neoplasm contains bland spindle cell stroma which directly gives rise to woven bone. Notably, there is a lack of osteoblastic riming. The woven bone fragments are in variable shapes, resembling letters. These are the typical features of fibrous dysplasia. The diffuse expansion of bone is seen on imaging is quite characteristic of this entity.
Differential Diagnosis: Osteochondroma would present as a polypoid growth of bone away from the growth plate, and would demonstrate endochondral ossification histologically. Osteosarcoma, even if low grade, would demonstrate greater cytologic atypia and would show MDM2 amplification if of the low grade central type which is the main differential diagnosis here. Osteoid osteoma would have a distinct radiographic appearance, more vascularized stroma, and would have well-developed riming of new bone.
Incorrect
The neoplasm contains bland spindle cell stroma which directly gives rise to woven bone. Notably, there is a lack of osteoblastic riming. The woven bone fragments are in variable shapes, resembling letters. These are the typical features of fibrous dysplasia. The diffuse expansion of bone is seen on imaging is quite characteristic of this entity.
Differential Diagnosis: Osteochondroma would present as a polypoid growth of bone away from the growth plate, and would demonstrate endochondral ossification histologically. Osteosarcoma, even if low grade, would demonstrate greater cytologic atypia and would show MDM2 amplification if of the low grade central type which is the main differential diagnosis here. Osteoid osteoma would have a distinct radiographic appearance, more vascularized stroma, and would have well-developed riming of new bone.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case talks about an 84 year old male who undergoes a transurethral resection of the prostate.
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This is an 84 year old male who undergoes a transurethral resection of the prostate.
Diagnosis:
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Answer: C
Histologic Description: This is an unusual and worrisome lesion, since the glandular component is irregular and forms cords, which suggests the diagnosis of a prostatic adenocarcinoma with Gleason pattern 4. However, the key to the diagnosis is that the lesion is relatively circumscribed, and associated with altered stroma. Altered stroma is not commonly seen in prostatic adenocarcinoma, in contrast to most other invasive carcinomas. The lesional cells are surrounded modified basal cells with myoepithelial differentiation, as evidenced by S100 and actin staining. This supports the diagnosis of prostatic sclerosing adenosis.
Prostatic sclerosing adenosis is rare, and is one condition in which the basal cells of the prostate differentiate towards myoepithelial cells of the breast in that they label for actin and S100 protein. The presence of basal/myoepithelial cells precludes the possibility of prostatic adenocarcinoma in this case, as does the relatively circumscribed nature of the lesion. Prostatic infarct would be associated with stromal necrosis and frequently is associated with squamous metaplasia, which are not seen in the current case.
Incorrect
Answer: C
Histologic Description: This is an unusual and worrisome lesion, since the glandular component is irregular and forms cords, which suggests the diagnosis of a prostatic adenocarcinoma with Gleason pattern 4. However, the key to the diagnosis is that the lesion is relatively circumscribed, and associated with altered stroma. Altered stroma is not commonly seen in prostatic adenocarcinoma, in contrast to most other invasive carcinomas. The lesional cells are surrounded modified basal cells with myoepithelial differentiation, as evidenced by S100 and actin staining. This supports the diagnosis of prostatic sclerosing adenosis.
Prostatic sclerosing adenosis is rare, and is one condition in which the basal cells of the prostate differentiate towards myoepithelial cells of the breast in that they label for actin and S100 protein. The presence of basal/myoepithelial cells precludes the possibility of prostatic adenocarcinoma in this case, as does the relatively circumscribed nature of the lesion. Prostatic infarct would be associated with stromal necrosis and frequently is associated with squamous metaplasia, which are not seen in the current case.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case talks about a 64 year old female with a peripancreatic nodule.
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This is a 64 year old female with a peripancreatic nodule.
Diagnosis:
Correct
Answer: C
Histologic Description: This is a highly sclerotic lesion, containing nests and cords of epithelioid cells. These cells have fine nuclear chromatin that is dispersed in a neuroendocrine type pattern, and the cytoplasm is finely granular. While the cording pattern suggests an epithelial lesion, the lesion is negative for cytokeratins, demonstrates diffuse labeling for chromogranin and synaptophysin, and demonstrates nuclear labeling for GATA3. These features support the diagnosis of a sclerosing paraganglioma.
Differential Diagnosis: Metastatic lobular carcinoma is a significant concern when one encounters a cord like lesion is the abdominal cavity of a women. However, the lesion is cytokeratin negative, and was negative for estrogen receptors which excludes a low grade lobular carcinoma. The absence of labeling for cytokeratin excludes a well differentiated pancreatic endocrine neoplasm. The diffuse labeling for chromogranin and synaptophysin would argue against a gastrointestinal stromal tumor, as would the negativity for CD117.
Incorrect
Answer: C
Histologic Description: This is a highly sclerotic lesion, containing nests and cords of epithelioid cells. These cells have fine nuclear chromatin that is dispersed in a neuroendocrine type pattern, and the cytoplasm is finely granular. While the cording pattern suggests an epithelial lesion, the lesion is negative for cytokeratins, demonstrates diffuse labeling for chromogranin and synaptophysin, and demonstrates nuclear labeling for GATA3. These features support the diagnosis of a sclerosing paraganglioma.
Differential Diagnosis: Metastatic lobular carcinoma is a significant concern when one encounters a cord like lesion is the abdominal cavity of a women. However, the lesion is cytokeratin negative, and was negative for estrogen receptors which excludes a low grade lobular carcinoma. The absence of labeling for cytokeratin excludes a well differentiated pancreatic endocrine neoplasm. The diffuse labeling for chromogranin and synaptophysin would argue against a gastrointestinal stromal tumor, as would the negativity for CD117.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case talks about a 50 year old female with a renal mass.
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Case 1: This is a 50 year old female with a renal mass.
Diagnosis:
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Answer: B
Histologic Description: This is a cystic renal neoplasm which contains a cellular spindle cell stroma and cysts which are lined by bland renal tubular epithelial cells. The stroma has a fascicular pattern, lacks significant mitotic activity, and is associated with hyalinized collagen, and thus is reminiscent of ovarian stroma. The cellular stroma entraps native renal tubules at its periphery. The stroma labeled diffusely for estrogen receptor and in a patchy fashion for inhibin, supporting the diagnosis of mixed epithelial stromal tumor.
Differential Diagnosis: Angiomyolipoma with epithelial cysts also might label with hormone receptors and contains entrapped native renal tubular epithelium forming cysts; however, the stroma is that of a stromal predominant angiomyolipoma, and thus would label for HMB45 and muscle markers. Cystic partially differentiated nephroblastoma would be exclusively cystic and lack solid areas. The stroma would contain primitive nephroblastic elements similar to those seen in Wilms tumor, though limited to the thin septa of the lesion. Primary renal synovial sarcoma would feature greater mitotic activity, typically would not label for estrogen receptor, and would demonstrate the characteristic SS18-SSX1/2 gene fusions of that entity.
Incorrect
Answer: B
Histologic Description: This is a cystic renal neoplasm which contains a cellular spindle cell stroma and cysts which are lined by bland renal tubular epithelial cells. The stroma has a fascicular pattern, lacks significant mitotic activity, and is associated with hyalinized collagen, and thus is reminiscent of ovarian stroma. The cellular stroma entraps native renal tubules at its periphery. The stroma labeled diffusely for estrogen receptor and in a patchy fashion for inhibin, supporting the diagnosis of mixed epithelial stromal tumor.
Differential Diagnosis: Angiomyolipoma with epithelial cysts also might label with hormone receptors and contains entrapped native renal tubular epithelium forming cysts; however, the stroma is that of a stromal predominant angiomyolipoma, and thus would label for HMB45 and muscle markers. Cystic partially differentiated nephroblastoma would be exclusively cystic and lack solid areas. The stroma would contain primitive nephroblastic elements similar to those seen in Wilms tumor, though limited to the thin septa of the lesion. Primary renal synovial sarcoma would feature greater mitotic activity, typically would not label for estrogen receptor, and would demonstrate the characteristic SS18-SSX1/2 gene fusions of that entity.
Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about an adult male with a testicular tumor.
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Clinical History: A 40 year old man underwent an orchiectomy for a testicular tumor.
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Correct Diagnosis: A
Histological Description: The tumor consisted of sheets of neoplastic cells, Cytologically, there were three basic cell types. The predominant cell type was round-intermediate size with eosinophilic cytoplasm and round nuclei with characteristic lacy filamentous chromatin (spiremic pattern). The second type is smaller cells with dark nuclei and scant eosinophilic cytoplasm, while the third type is large mononucleated or multinucleated giant cells. Mitotic activity was brisk. A lymphoplasmacytic and granulomatous infiltrate was absent.
Discussion: Spermatocytic tumor was formerly called spermatocytic seminoma with the term classic seminoma used for the typical seminoma. Given that the former has virtually no similarities to usual seminoma, spermatocytic seminoma was renamed spermatocytic tumor. As there is no longer a spermatocytic variant of seminoma, there is no need to use the term “classic seminoma” and currently usual seminoma is just classified as “seminoma”. Spermatocytic tumors usually occur in older males, typically 5th -6th decades, yet uncommonly can be seen in younger men in the 2nd to 4th decades with overlap with seminoma. In contrast to seminoma, spermatocytic tumors: 1) have no primary extra-testicular counterpart; 2) usually lack a lymphoplasmacytic infiltrate; 3) have no associated granulomatous response; 4) have no associated syncitiotrophoblastic giant cells; 5 ) lack germ cell neoplasia in situ yet may have intratubular spermatocytic tumor; 6) OCT4 is negative; 7) no gain of isochromosome 12p; 8) are never admixed with other germ cell tumors; and 9) with the exception of extremely rare cases associated with sarcoma at presentation, have a benign behavior regardless of the presence of vascular or tunical invasion.
Incorrect
Correct Diagnosis: A
Histological Description: The tumor consisted of sheets of neoplastic cells, Cytologically, there were three basic cell types. The predominant cell type was round-intermediate size with eosinophilic cytoplasm and round nuclei with characteristic lacy filamentous chromatin (spiremic pattern). The second type is smaller cells with dark nuclei and scant eosinophilic cytoplasm, while the third type is large mononucleated or multinucleated giant cells. Mitotic activity was brisk. A lymphoplasmacytic and granulomatous infiltrate was absent.
Discussion: Spermatocytic tumor was formerly called spermatocytic seminoma with the term classic seminoma used for the typical seminoma. Given that the former has virtually no similarities to usual seminoma, spermatocytic seminoma was renamed spermatocytic tumor. As there is no longer a spermatocytic variant of seminoma, there is no need to use the term “classic seminoma” and currently usual seminoma is just classified as “seminoma”. Spermatocytic tumors usually occur in older males, typically 5th -6th decades, yet uncommonly can be seen in younger men in the 2nd to 4th decades with overlap with seminoma. In contrast to seminoma, spermatocytic tumors: 1) have no primary extra-testicular counterpart; 2) usually lack a lymphoplasmacytic infiltrate; 3) have no associated granulomatous response; 4) have no associated syncitiotrophoblastic giant cells; 5 ) lack germ cell neoplasia in situ yet may have intratubular spermatocytic tumor; 6) OCT4 is negative; 7) no gain of isochromosome 12p; 8) are never admixed with other germ cell tumors; and 9) with the exception of extremely rare cases associated with sarcoma at presentation, have a benign behavior regardless of the presence of vascular or tunical invasion.
Presented by Dr. Jonathan Epstein and prepared by Dr. Yembur Ahmad
This case talks about an adult male with a bladder neck mass.
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A 65 year old man presented with a large bladder neck mass and a transurethral resection (TUR) was performed.
Choose the correct diagnosis:
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Answer: D
Histological Description: The tumor consists of sheets of cells. The tumor has a pseudopapillary appearance due to tumor necrosis away from the blood vessels. In contrast to true papillary formation, at the edges of the papillary appearing structures, there are necrotic cells and karryorrhectic debris. The tumor also has subtle rudimentary cribriform formation. Nuclei are relatively uniform with centrally located prominent eosinophilic nucleoli. Mitotic figures are fairly frequent.
Discussion: A common and critical differential diagnosis is between poorly differentiated urothelial carcinoma and prostate adenocarcinoma involving the bladder neck and even the trigone. Clinically, the two entities can be indistinguishable even to expert urologists. Some poorly differentiated prostate carcinomas lack significant PSA production further confounding the issue. Typically, prostate adenocarcinoma has more uniform nuclei with prominent nucleoli and relatively few mitotic figures. However, the key for pathologists is to recognize that poorly differentiated prostate adenocarcinoma can have pseudopapillary formation, increased mitotic figures, as well as in some cases pleomorphic giant cell features that overlap with the degree of cytological atypia seen in urothelial carcinoma. In uncommon cases, prostate adenocarcinoma can even colonize the urothelial surface further mimicking a bladder primary. The finding of cribriform glands strongly favors prostate adenocarcinoma, as urothelial carcinoma with glandular differentiation typically lacks cribriform glands. In the setting of a poorly differentiated tumor in the bladder neck and trigone, pathologists should have a low threshold to performing stains to differentiate between the two primaries.
Poorly differentiated prostate adenocarcinoma is variably and focally positive for prostate markers (PSA, PSMA, P501S, NKX3.1). The most sensitive and specific prostate marker is NKX3.1 A small percent of prostate adenocarcinomas are negative for PSA such that other prostate markers should be done before assuming PSA negative cancer is urothelial carcinoma. It is critical to have strong staining in the positive control of benign prostate tissue since prostate carcinoma shows lower expression. A pitfall is that occasional prostate adenocarcinomas can aberrantly express high molecular weight cytokeratin (HMWCK) in a non-basal cell distribution, less commonly seen with p63. GATA-3 with exceedingly rare exception is negative. AMACR (racemase) does not differentiate between prostate and urothelial carcinoma. The most sensitive and specific marker for urothelial carcinoma is GATA3 with fewer cases positive for thrombomodulin. Approximately 2/3rds of urothelial carcinoma are positive for HMWCK or p63, such that negative staining for these markers do not rule out urothelial carcinoma. Uroplakin II, although negative in prostate adenocarcinoma, is not that sensitive in high grade urothelial carcinomas. It is critical to recognize the difference between prostate adenocarcinoma and urothelial carcinoma since advanced high grade prostatic adenocarcinoma are treated with anti-androgen therapy, while advance urothelial carcinoma would be treated with chemotherapy +/- radical cystectomy.
Incorrect
Answer: D
Histological Description: The tumor consists of sheets of cells. The tumor has a pseudopapillary appearance due to tumor necrosis away from the blood vessels. In contrast to true papillary formation, at the edges of the papillary appearing structures, there are necrotic cells and karryorrhectic debris. The tumor also has subtle rudimentary cribriform formation. Nuclei are relatively uniform with centrally located prominent eosinophilic nucleoli. Mitotic figures are fairly frequent.
Discussion: A common and critical differential diagnosis is between poorly differentiated urothelial carcinoma and prostate adenocarcinoma involving the bladder neck and even the trigone. Clinically, the two entities can be indistinguishable even to expert urologists. Some poorly differentiated prostate carcinomas lack significant PSA production further confounding the issue. Typically, prostate adenocarcinoma has more uniform nuclei with prominent nucleoli and relatively few mitotic figures. However, the key for pathologists is to recognize that poorly differentiated prostate adenocarcinoma can have pseudopapillary formation, increased mitotic figures, as well as in some cases pleomorphic giant cell features that overlap with the degree of cytological atypia seen in urothelial carcinoma. In uncommon cases, prostate adenocarcinoma can even colonize the urothelial surface further mimicking a bladder primary. The finding of cribriform glands strongly favors prostate adenocarcinoma, as urothelial carcinoma with glandular differentiation typically lacks cribriform glands. In the setting of a poorly differentiated tumor in the bladder neck and trigone, pathologists should have a low threshold to performing stains to differentiate between the two primaries.
Poorly differentiated prostate adenocarcinoma is variably and focally positive for prostate markers (PSA, PSMA, P501S, NKX3.1). The most sensitive and specific prostate marker is NKX3.1 A small percent of prostate adenocarcinomas are negative for PSA such that other prostate markers should be done before assuming PSA negative cancer is urothelial carcinoma. It is critical to have strong staining in the positive control of benign prostate tissue since prostate carcinoma shows lower expression. A pitfall is that occasional prostate adenocarcinomas can aberrantly express high molecular weight cytokeratin (HMWCK) in a non-basal cell distribution, less commonly seen with p63. GATA-3 with exceedingly rare exception is negative. AMACR (racemase) does not differentiate between prostate and urothelial carcinoma. The most sensitive and specific marker for urothelial carcinoma is GATA3 with fewer cases positive for thrombomodulin. Approximately 2/3rds of urothelial carcinoma are positive for HMWCK or p63, such that negative staining for these markers do not rule out urothelial carcinoma. Uroplakin II, although negative in prostate adenocarcinoma, is not that sensitive in high grade urothelial carcinomas. It is critical to recognize the difference between prostate adenocarcinoma and urothelial carcinoma since advanced high grade prostatic adenocarcinoma are treated with anti-androgen therapy, while advance urothelial carcinoma would be treated with chemotherapy +/- radical cystectomy.
Presented by Dr. Jonathan Epstein and prepared by Dr Yembur Ahmad
This case talks about an adult male with a renal mass.
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History: A 55 year old man underwent a nephrectomy for a mass in the renal pelvis. A low grade noninvasive papillary urothelial carcinoma was noted. In addition, there was a proliferation of urothelial nests which requires a diagnosis.
Choose the correct diagnosis:
Correct
Answer: B
Histological Description: Arising from the renal pelvis is a low grade papillary urothelial carcinoma with minimal cytological atypia. In addition, there is a proliferation of irregular nests in the hilar peri-pelvic adipose tissue. The nests are associated with a desmoplastic stromal reaction. Cytologically, the tumor within the nests are very bland with virtually no atypia and no mitotic figures.
Discussion: Florid von Brunn nest (VBN) proliferations are very common in the ureter and renal pelvis. At cystoscopy, VBN proliferations can be tumor-like presenting as a polypoid mass with a smooth surface. These are usually < 3 cm., but can have a wide range in size. At low magnification, the surface is smooth without exophytic papillary fronds. The lamina propria is filled with evenly small rounded uniform nests. In resection specimens, one can appreciate that the nests are linear or lobular without an infiltrative lower border (i.e. can mentally draw a straight line at the base of the lesion). There is no associated stromal reaction. Most cases have a low ki67 rate.
With an inverted component of noninvasive low grade papillary urothelial carcinoma, the vast majority of papillary urothelial neoplasms have some exophytic component, although uncommonly the entire lesion is inverted. The lamina propria filled with large rounded nests of urothelium which lack an infiltrative border at the base of the lesion and would not extend into renal hilar adipose tissue. The nests are crowded with a more uniform spacing than nested carcinoma. There is lack of desmoplastic stroma. Ki67 can be low although typically higher than proliferation of VBN.
Nested urothelial carcinoma typically occur in the bladder, with only rare cases in the renal pelvis or ureter. At cystoscopy, there is a nodular surface typically without an exophytic papillary component with a wide range in size. At low magnification, the surface is typically smooth without exophytic papillary fronds, although uncommonly, as in the current case, the surface shows CIS or papillary urothelial carcinoma. The lamina propria is filled with small crowded nests of urothelium in the classic variant and large irregular nests in the large nested variant. As in the current case, there is an irregular base with infiltrative nests extending to different depths. In the current example, the nests are in adipose tissue in the renal hilum that is diagnostic of invasive carcinoma. Typically, there is no stromal reaction in the usual nested variant but a variable desmoplastic stroma with variable inflammatory response can be seen in the large nested variant. The diagnosis of nested urothelial carcinoma should not be made on biopsy of the ureter or renal pelvis in the absence of muscularis propria invasion, since on biopsy one cannot appreciate an infiltrative border and given the overlapping morphological features with von Brunn nests in these sites. Most cases have a low ki67 rate, with only a few cases with a rate >20%. Nested carcinoma has an aggressive behavior comparable to invasive high grade urothelial carcinoma.
Incorrect
Answer: B
Histological Description: Arising from the renal pelvis is a low grade papillary urothelial carcinoma with minimal cytological atypia. In addition, there is a proliferation of irregular nests in the hilar peri-pelvic adipose tissue. The nests are associated with a desmoplastic stromal reaction. Cytologically, the tumor within the nests are very bland with virtually no atypia and no mitotic figures.
Discussion: Florid von Brunn nest (VBN) proliferations are very common in the ureter and renal pelvis. At cystoscopy, VBN proliferations can be tumor-like presenting as a polypoid mass with a smooth surface. These are usually < 3 cm., but can have a wide range in size. At low magnification, the surface is smooth without exophytic papillary fronds. The lamina propria is filled with evenly small rounded uniform nests. In resection specimens, one can appreciate that the nests are linear or lobular without an infiltrative lower border (i.e. can mentally draw a straight line at the base of the lesion). There is no associated stromal reaction. Most cases have a low ki67 rate.
With an inverted component of noninvasive low grade papillary urothelial carcinoma, the vast majority of papillary urothelial neoplasms have some exophytic component, although uncommonly the entire lesion is inverted. The lamina propria filled with large rounded nests of urothelium which lack an infiltrative border at the base of the lesion and would not extend into renal hilar adipose tissue. The nests are crowded with a more uniform spacing than nested carcinoma. There is lack of desmoplastic stroma. Ki67 can be low although typically higher than proliferation of VBN.
Nested urothelial carcinoma typically occur in the bladder, with only rare cases in the renal pelvis or ureter. At cystoscopy, there is a nodular surface typically without an exophytic papillary component with a wide range in size. At low magnification, the surface is typically smooth without exophytic papillary fronds, although uncommonly, as in the current case, the surface shows CIS or papillary urothelial carcinoma. The lamina propria is filled with small crowded nests of urothelium in the classic variant and large irregular nests in the large nested variant. As in the current case, there is an irregular base with infiltrative nests extending to different depths. In the current example, the nests are in adipose tissue in the renal hilum that is diagnostic of invasive carcinoma. Typically, there is no stromal reaction in the usual nested variant but a variable desmoplastic stroma with variable inflammatory response can be seen in the large nested variant. The diagnosis of nested urothelial carcinoma should not be made on biopsy of the ureter or renal pelvis in the absence of muscularis propria invasion, since on biopsy one cannot appreciate an infiltrative border and given the overlapping morphological features with von Brunn nests in these sites. Most cases have a low ki67 rate, with only a few cases with a rate >20%. Nested carcinoma has an aggressive behavior comparable to invasive high grade urothelial carcinoma.
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about an adult female with a kidney mass.
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Correct: D
Histology: The tumor is composed of compressed and elongated tubules, spindle cells and extracellular mucin. There are areas of hemorrhage and foci of necrosis. Tumor cells have nuclei with large nucleoli, visible at 10X.
Discussion: MTSC is most commonly a low-grade carcinoma presenting in older individuals as a well circumscribed small mass and patients have a favorable prognosis. A small proportion of cases can show more aggressive histologic features including high nuclear grade, necrosis, and sarcomatoid transformation. The main differential diagnosis is papillary RCC, and the distinction is often difficult in cases with not very well-developed morphology. The immunohistochemistry profile is similar to papillary RCC including positive staining for CK7 and AMACR.
Expression of VSTM2A, detected by mRNA in situ hybridization, has been recently proposed as a diagnostic marker of MTSC.
Reference:
Hatayama T, et al. IJU Case Rep. 2019. PMID: 32743410
Bulimbasic S, et al. Hum Pathol. 2009. PMID: 19442792
Miura K, et al. J Surg Case Rep. 2020. PMID: 32104563
Kwon R, et al. Am J Surg Pathol. 2021. PMID: 33239504
Incorrect
Correct: D
Histology: The tumor is composed of compressed and elongated tubules, spindle cells and extracellular mucin. There are areas of hemorrhage and foci of necrosis. Tumor cells have nuclei with large nucleoli, visible at 10X.
Discussion: MTSC is most commonly a low-grade carcinoma presenting in older individuals as a well circumscribed small mass and patients have a favorable prognosis. A small proportion of cases can show more aggressive histologic features including high nuclear grade, necrosis, and sarcomatoid transformation. The main differential diagnosis is papillary RCC, and the distinction is often difficult in cases with not very well-developed morphology. The immunohistochemistry profile is similar to papillary RCC including positive staining for CK7 and AMACR.
Expression of VSTM2A, detected by mRNA in situ hybridization, has been recently proposed as a diagnostic marker of MTSC.
Reference:
Hatayama T, et al. IJU Case Rep. 2019. PMID: 32743410
Bulimbasic S, et al. Hum Pathol. 2009. PMID: 19442792
Miura K, et al. J Surg Case Rep. 2020. PMID: 32104563
Kwon R, et al. Am J Surg Pathol. 2021. PMID: 33239504
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about an adult female with a brain mass.
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Histology: The tumor is composed of solid sheets of medium-sized tumor cells with oval nuclei with delicate chromatin and eosinophilic cytoplasm. There are scattered vacuolar spaces with eosinophilic globules.
Discussion: Secretory meningioma is a variant characterized by the presence of intracellular lumina containing PAS-positive eosinophilic secretions called pseudopsammoma bodies. The pseudopsammoma bodies show immunoreactivity for carcinoembryonic antigen (CEA) which can be used as a serologic biomarker of recurrence. The epithelial cells with vacuoles containing pseudopsammoma bodies are also positive for cytokeratin stain.
References:
Louis DN, et al. J Neurosurg. 1991. PMID:1984492
Incorrect
Correct: B
Histology: The tumor is composed of solid sheets of medium-sized tumor cells with oval nuclei with delicate chromatin and eosinophilic cytoplasm. There are scattered vacuolar spaces with eosinophilic globules.
Discussion: Secretory meningioma is a variant characterized by the presence of intracellular lumina containing PAS-positive eosinophilic secretions called pseudopsammoma bodies. The pseudopsammoma bodies show immunoreactivity for carcinoembryonic antigen (CEA) which can be used as a serologic biomarker of recurrence. The epithelial cells with vacuoles containing pseudopsammoma bodies are also positive for cytokeratin stain.
References:
Louis DN, et al. J Neurosurg. 1991. PMID:1984492
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
This case talks about an adult male with a paratesticular mass.
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Histology: Proliferation of tubules, lined with cells with clear cytoplasm and small uniform nuclei.
Discussion: Papillary cystadenoma of the epididymis is a benign neoplasm of the epididymis. The most common clinical presentation is a paratesticular mass or an incidental finding detected during fertility workup. The tumor is composed of cysts and papillae lined with cuboidal or low columnar cells with glycogen-rich clear or vacuolated cytoplasm. There is colloid-like secretion in the cysts. By immunohistochemistry, tumor cells are diffusely positive for CK7 and CAIX shows a cup shape distribution, the same immunophenotype as clear cell papillary renal cell tumor. Papillary cystadenomas of the epididymis are more frequently sporadic and bilateral cases have been associated with vHL disease.
References
Mayo Clin Proc. 2021 Mar;96(3):828-829.
Urology. 2018 Aug;118:189-191.
Am J Surg Pathol. 2014 May;38(5):713-8.
Incorrect
Correct: B
Histology: Proliferation of tubules, lined with cells with clear cytoplasm and small uniform nuclei.
Discussion: Papillary cystadenoma of the epididymis is a benign neoplasm of the epididymis. The most common clinical presentation is a paratesticular mass or an incidental finding detected during fertility workup. The tumor is composed of cysts and papillae lined with cuboidal or low columnar cells with glycogen-rich clear or vacuolated cytoplasm. There is colloid-like secretion in the cysts. By immunohistochemistry, tumor cells are diffusely positive for CK7 and CAIX shows a cup shape distribution, the same immunophenotype as clear cell papillary renal cell tumor. Papillary cystadenomas of the epididymis are more frequently sporadic and bilateral cases have been associated with vHL disease.
References
Mayo Clin Proc. 2021 Mar;96(3):828-829.
Urology. 2018 Aug;118:189-191.
Am J Surg Pathol. 2014 May;38(5):713-8.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case talks about an adult patient with a renal mass.
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This is an adult patient with a 6 cm renal mass. What is the diagnosis?
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Answer: A
Histologic Description: This is a cellular neoplasm composed of spindle and epithelioid cells. There are strands of collagen throughout the lesion that have a ropy quality. The neoplasm was diffusely immunoreactive for CD34 and demonstrated STAT6 nuclear labeling, supporting the diagnosis of cellular solitary fibrous tumor.
Differential Diagnosis: Synovial sarcoma will not label for CD34 and STAT6, and typically demonstrates focal cytokeratin immunoreactivity. Like the current lesion, clear cell sarcoma of the kidney could label for BCOR, but would have much more open chromatin and would be extremely uncommon in a patient of this age. Sarcomatoid renal cell carcinoma would be defined by seeing a well-defined epithelioid renal cell carcinoma component in addition to malignant spindle cells.
Incorrect
Answer: A
Histologic Description: This is a cellular neoplasm composed of spindle and epithelioid cells. There are strands of collagen throughout the lesion that have a ropy quality. The neoplasm was diffusely immunoreactive for CD34 and demonstrated STAT6 nuclear labeling, supporting the diagnosis of cellular solitary fibrous tumor.
Differential Diagnosis: Synovial sarcoma will not label for CD34 and STAT6, and typically demonstrates focal cytokeratin immunoreactivity. Like the current lesion, clear cell sarcoma of the kidney could label for BCOR, but would have much more open chromatin and would be extremely uncommon in a patient of this age. Sarcomatoid renal cell carcinoma would be defined by seeing a well-defined epithelioid renal cell carcinoma component in addition to malignant spindle cells.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case talks about bilateral renal tumors in a pediatric patient.
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A young child presents with bilateral renal tumors after therapy. The tumor illustrated is the largest one. What is the diagnosis?
Correct
Answer: C
Histologic Description: This is a post-therapy specimen, so there are large areas of regression consisting of macrophages and scarring. There are also areas of differentiated epithelium at the periphery of the tumor. Other areas show the usual proliferating blastemal elements that are non-anaplastic. However, there is well-defined nodule of blastemal cells with markedly enlarged nuclei showing hyperchromasia, along with atypical mitotic figures. This focus was well delineated and confined to the kidney, which justifies the diagnosis of focal anaplasia.
Differential Diagnosis: The presence of enlarged hyperchromatic nuclei demonstrating atypical mitotic figures supports the diagnosis of anaplasia (unfavorable histology). Focal anaplasia must be well delineated and confined to the kidney, as seen in the current case. If not, anaplasia is considered diffuse by default. Desmoplastic small round cell tumor is immunoreactive for WT1, desmin and keratin like the current Wilms tumor; however, it typically demonstrates desmoplastic stroma and nuclei that have coarser chromatin than the delicate chromatin of a blastemal Wilms tumor nucleus.
Incorrect
Answer: C
Histologic Description: This is a post-therapy specimen, so there are large areas of regression consisting of macrophages and scarring. There are also areas of differentiated epithelium at the periphery of the tumor. Other areas show the usual proliferating blastemal elements that are non-anaplastic. However, there is well-defined nodule of blastemal cells with markedly enlarged nuclei showing hyperchromasia, along with atypical mitotic figures. This focus was well delineated and confined to the kidney, which justifies the diagnosis of focal anaplasia.
Differential Diagnosis: The presence of enlarged hyperchromatic nuclei demonstrating atypical mitotic figures supports the diagnosis of anaplasia (unfavorable histology). Focal anaplasia must be well delineated and confined to the kidney, as seen in the current case. If not, anaplasia is considered diffuse by default. Desmoplastic small round cell tumor is immunoreactive for WT1, desmin and keratin like the current Wilms tumor; however, it typically demonstrates desmoplastic stroma and nuclei that have coarser chromatin than the delicate chromatin of a blastemal Wilms tumor nucleus.
Presented by Dr. Pedram Argani and prepared by Dr. Yembur Ahmad
This case is about a young adult patient with a renal tumor.
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A young adult patient presents with a renal tumor showing sinus vascular invasion. What is the diagnosis?
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Answer: B
Histologic Description: The neoplasm is separated by fibrous septa which have a hyalinized appearance. The neoplastic cells have well defined cell borders and irregular nuclei with perinuclear halos. There is abundant psammomatous calcification present. The latter suggests the possibility of Xp11 translocation RCC, but can be seen in chromophobe RCC. The neoplasm demonstrated diffuse membranous labeling for CD117, supporting the diagnosis of chromophobe RCC.
Differential Diagnosis: Xp11 translocation RCC does not usually show diffuse membranous labeling for CD117, and would label for TFE3. Clear cell RCC would have more vascularized septa, and lack the prominent perinuclear halos and nuclear irregularities of this case. t(6;11) renal cell carcinomas typically have a biphasic large cell /small cell morphology, and label for melanocytic markers like Melan A.
Incorrect
Answer: B
Histologic Description: The neoplasm is separated by fibrous septa which have a hyalinized appearance. The neoplastic cells have well defined cell borders and irregular nuclei with perinuclear halos. There is abundant psammomatous calcification present. The latter suggests the possibility of Xp11 translocation RCC, but can be seen in chromophobe RCC. The neoplasm demonstrated diffuse membranous labeling for CD117, supporting the diagnosis of chromophobe RCC.
Differential Diagnosis: Xp11 translocation RCC does not usually show diffuse membranous labeling for CD117, and would label for TFE3. Clear cell RCC would have more vascularized septa, and lack the prominent perinuclear halos and nuclear irregularities of this case. t(6;11) renal cell carcinomas typically have a biphasic large cell /small cell morphology, and label for melanocytic markers like Melan A.
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
A 72 year old male with an abnormal prostate exam but normal PSA.
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A 72 year old male presents with an abnormal prostate exam, but normal PSA. What is the diagnosis?
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Correct Answer: B
Histology: The lesion consists of glands with solid nests composed of cells with basophilic nuclei with scant cytoplasm. Some of the nests have a small glandular lumina. There is no necrosis or reaction of the stroma.
Discussion: Basal cell hyperplasia consists of glands with basophilic nuclei and scant cytoplasm and increased number of the basal layer, from a double-layer up to solid nest. It can range from small focal areas to florid. Glands can appear to form cribriform/pseudocribriform structures, but are actually small round hyperplastic glands crowded together. Well-formed lamellar intraluminal calcifications can be observed, which is extremely rare in carcinoma. Intracytoplasmic eosinophilic globules can also be present. The most frequent location is in the transition zone and therefore are more commonly seen in transurethral resections. In needle biopsies, the glands may appear to have an infiltrative growth pattern. Basal cell hyperplasia may have prominent nucleoli, further mimicking cancer. If cancer is suspected, immunohistochemistry is helpful in the differential diagnosis with adenocarcinoma because BCH is positive for basal cell markers, and negative for racemase. The differential diagnosis of BCH should also include basal cell carcinoma. The features that are seen in carcinoma but not in hyperplasia include large nests with necrosis, adenoid cystic pattern, variable sizes and shapes of the nests with infiltrating borders, extraprostatic extension or bladder neck invasion, and desmoplastic stromal reaction. Occasionally, basal cell hyperplasia can involve bladder neck muscle or present between normal prostatic glands, therefore these findings should not be considered in isolation, sufficient to make a diagnosis of carcinoma. By immunohistochemistry, diffuse staining for Bcl-2 and elevated Ki67 correlate have been reported to be associated with carcinoma and not hyperplasia.
References:
Am J Surg Pathol. 2002;26(2):237-243.
Am J Surg Pathol. 1992;16(12):1205-1214.
Hum Pathol. 2005;36(5):480-485.
Incorrect
Correct Answer: B
Histology: The lesion consists of glands with solid nests composed of cells with basophilic nuclei with scant cytoplasm. Some of the nests have a small glandular lumina. There is no necrosis or reaction of the stroma.
Discussion: Basal cell hyperplasia consists of glands with basophilic nuclei and scant cytoplasm and increased number of the basal layer, from a double-layer up to solid nest. It can range from small focal areas to florid. Glands can appear to form cribriform/pseudocribriform structures, but are actually small round hyperplastic glands crowded together. Well-formed lamellar intraluminal calcifications can be observed, which is extremely rare in carcinoma. Intracytoplasmic eosinophilic globules can also be present. The most frequent location is in the transition zone and therefore are more commonly seen in transurethral resections. In needle biopsies, the glands may appear to have an infiltrative growth pattern. Basal cell hyperplasia may have prominent nucleoli, further mimicking cancer. If cancer is suspected, immunohistochemistry is helpful in the differential diagnosis with adenocarcinoma because BCH is positive for basal cell markers, and negative for racemase. The differential diagnosis of BCH should also include basal cell carcinoma. The features that are seen in carcinoma but not in hyperplasia include large nests with necrosis, adenoid cystic pattern, variable sizes and shapes of the nests with infiltrating borders, extraprostatic extension or bladder neck invasion, and desmoplastic stromal reaction. Occasionally, basal cell hyperplasia can involve bladder neck muscle or present between normal prostatic glands, therefore these findings should not be considered in isolation, sufficient to make a diagnosis of carcinoma. By immunohistochemistry, diffuse staining for Bcl-2 and elevated Ki67 correlate have been reported to be associated with carcinoma and not hyperplasia.
References:
Am J Surg Pathol. 2002;26(2):237-243.
Am J Surg Pathol. 1992;16(12):1205-1214.
Hum Pathol. 2005;36(5):480-485.
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
A 64 year old male with a prostate mass.
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A 64 year old male presents with a prostate mass. What is the diagnosis?
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Correct Answer: C
Histology: This prostate tumor shows a proliferation of spindle stroma cells with small nuclei and variable amount of eosinophilic cytoplasm arranged in a whorled of haphazard pattern. The tumor is characterized by having thick walled vessels.
Discussion: One of the most common stromal proliferations identified in prostate needle biopsies are stromal nodules of benign prostatic hyperplasia (BPH). BPH is common among middle age and elder men and it affects up to 80% of men. BPH refers to the proliferation and enlargement of both the stromal and the glandular components but there is evidence that suggests that it is the stroma the one that leads to more pronounced enlargement and obstructive symptoms. By immunohistochemistry, the spindle cells are most commonly positive for vimentin and some cases with more prominent fibromuscular differentiation show positive staining for smooth muscle actin and desmin. The immunohistochemistry profile is not specific and of limited utility in the differential diagnosis. The main differential diagnoses include stromal tumor of uncertain malignant potential (STUMP) which, in contrast to stromal nodule of BPH, has more pronounced nuclear pleomorphism, often infiltrates around glands, and lacks the characteristic thick-walled blood vessels.
Histology: This prostate tumor shows a proliferation of spindle stroma cells with small nuclei and variable amount of eosinophilic cytoplasm arranged in a whorled of haphazard pattern. The tumor is characterized by having thick walled vessels.
Discussion: One of the most common stromal proliferations identified in prostate needle biopsies are stromal nodules of benign prostatic hyperplasia (BPH). BPH is common among middle age and elder men and it affects up to 80% of men. BPH refers to the proliferation and enlargement of both the stromal and the glandular components but there is evidence that suggests that it is the stroma the one that leads to more pronounced enlargement and obstructive symptoms. By immunohistochemistry, the spindle cells are most commonly positive for vimentin and some cases with more prominent fibromuscular differentiation show positive staining for smooth muscle actin and desmin. The immunohistochemistry profile is not specific and of limited utility in the differential diagnosis. The main differential diagnoses include stromal tumor of uncertain malignant potential (STUMP) which, in contrast to stromal nodule of BPH, has more pronounced nuclear pleomorphism, often infiltrates around glands, and lacks the characteristic thick-walled blood vessels.
Presented by Dr. Andres Matoso and prepared by Dr. Yembur Ahmad
75 year old male with an adrenal mass.
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A 75 year old male presents with an adrenal mass. What is your diagnosis?
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Correct answer: A
Histology: This tumor is composed of nests and cords of cells with eosinophilic and pale cytoplasm and marked degenerative nuclear atypia. There is extensive hemorrhage and thrombus formation that makes for the majority of the mass.
Discussion: This is an example of enlarged adrenal glands where the underlying diagnosis can be masked by a diffusely hemorrhagic process. The most common underlying lesion associated with diffuse hemorrhage are adrenocortical adenomas and benign non-neoplastic adrenal. Carcinomas and other rarer lesions can also show similar findings. Although there is a correlation between adrenocortical malignancy and size, hemorrhage into nonmalignant adrenal glands can result in markedly enlarged adrenals. Around the hemorrhage there is a proliferation of cortical cells with degenerative atypia, so called “endocrine atypia” which is a finding not associated with malignancy.
Histology: This tumor is composed of nests and cords of cells with eosinophilic and pale cytoplasm and marked degenerative nuclear atypia. There is extensive hemorrhage and thrombus formation that makes for the majority of the mass.
Discussion: This is an example of enlarged adrenal glands where the underlying diagnosis can be masked by a diffusely hemorrhagic process. The most common underlying lesion associated with diffuse hemorrhage are adrenocortical adenomas and benign non-neoplastic adrenal. Carcinomas and other rarer lesions can also show similar findings. Although there is a correlation between adrenocortical malignancy and size, hemorrhage into nonmalignant adrenal glands can result in markedly enlarged adrenals. Around the hemorrhage there is a proliferation of cortical cells with degenerative atypia, so called “endocrine atypia” which is a finding not associated with malignancy.
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