Presented by Dr. Epstein and prepared by Dr. J. David Peske.
Case 3. A 20 year-old man underwent a radical nephrectomy for a 7.2 cm renal mass.
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Case 3. A 20 year-old man underwent a radical nephrectomy for a 7.2 cm renal mass.
Choose the correct diagnosis:
Correct
Histological Description: At low magnification there is a large lobular tumor which is poorly circumscribed with extension into the surrounding renal parenchyma. The cells are arranged in sheets with high N/C ratio, speckled chromatin and inconspicuous nucleoli. Mitotic figures are present but not very prominent. Homer Wright rosettes are identifiable consisting of differentiated tumor cells grouped around a central region containing neuropil. The tumor falls apart giving rise to a pseudopapillary growth pattern.
Answer: C
Discussion: Primary Ewing sarcoma / primitive neuroectodermal tumor (ES) of the kidney are rare. The patients have no gender preference and a wide age range from children to the elderly with an average age of around 30 years. The average tumor size at presentation is large, approximately 12 cm. (range, 5-20 cm). The tumors often invade the renal sinus or perinephric fat or renal vein and less commonly the adrenal gland. Almost all patients develop metastases, commonly in the lungs and bone with a majority of them dead of disease in a mean of 21 months, although there are some long-term survivors. On a morphological basis, the presence of Homer Wright rosettes favors PNET compared to other tumors excluding neuroblastomas. In this case, the tumor most closely resembled a solid variant of papillary renal cell carcinoma. The work up of this case demonstrated negative cytokeratin 7, AE1/3, synaptophysin, WT-1, and PAX8, ruling out renal cell carcinoma, Wilms tumor, and neuroblastoma. A CD99 immunostain was positive as was NKX2.2, verifying the diagnosis of PNET. NKX2.2 is expressed in 80% of PNETs mostly with diffuse and strong staining pattern, and a minority of other tumors including olfactory neuroblastomas, extraskeletal myxoid chondrosarcoma, mesenchymal chondrosarcoma, small cell carcinomas, and Merkel cell carcinoma. When combined with CD99, the specificity of NKX2.2 increases to 98%.
Primary Ewing Sarcoma / Primitive Neuroectodermal Tumor of the Kidney: A Clinicopathologic Study of 23 Cases. Pathol Oncol Res. 2018 Jan;24(1):153-159.
Murugan P, Rao P, Tamboli P, Czerniak B, Guo CC.
Incorrect
Histological Description: At low magnification there is a large lobular tumor which is poorly circumscribed with extension into the surrounding renal parenchyma. The cells are arranged in sheets with high N/C ratio, speckled chromatin and inconspicuous nucleoli. Mitotic figures are present but not very prominent. Homer Wright rosettes are identifiable consisting of differentiated tumor cells grouped around a central region containing neuropil. The tumor falls apart giving rise to a pseudopapillary growth pattern.
Answer: C
Discussion: Primary Ewing sarcoma / primitive neuroectodermal tumor (ES) of the kidney are rare. The patients have no gender preference and a wide age range from children to the elderly with an average age of around 30 years. The average tumor size at presentation is large, approximately 12 cm. (range, 5-20 cm). The tumors often invade the renal sinus or perinephric fat or renal vein and less commonly the adrenal gland. Almost all patients develop metastases, commonly in the lungs and bone with a majority of them dead of disease in a mean of 21 months, although there are some long-term survivors. On a morphological basis, the presence of Homer Wright rosettes favors PNET compared to other tumors excluding neuroblastomas. In this case, the tumor most closely resembled a solid variant of papillary renal cell carcinoma. The work up of this case demonstrated negative cytokeratin 7, AE1/3, synaptophysin, WT-1, and PAX8, ruling out renal cell carcinoma, Wilms tumor, and neuroblastoma. A CD99 immunostain was positive as was NKX2.2, verifying the diagnosis of PNET. NKX2.2 is expressed in 80% of PNETs mostly with diffuse and strong staining pattern, and a minority of other tumors including olfactory neuroblastomas, extraskeletal myxoid chondrosarcoma, mesenchymal chondrosarcoma, small cell carcinomas, and Merkel cell carcinoma. When combined with CD99, the specificity of NKX2.2 increases to 98%.
Primary Ewing Sarcoma / Primitive Neuroectodermal Tumor of the Kidney: A Clinicopathologic Study of 23 Cases. Pathol Oncol Res. 2018 Jan;24(1):153-159.
Murugan P, Rao P, Tamboli P, Czerniak B, Guo CC.
Presented by Dr. Epstein and prepared by Dr. J. David Peske.
Case 2. A 4.2 cm mass was noted adjacent to the adrenal and was resected.
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Case 2. A 4.2 cm mass was noted adjacent to the adrenal and was resected.
Choose the correct diagnosis:
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Histological Description: With a compressed adrenal gland is a large vascular mass. The lesion is composed of vascular channels that connect with each other in an irregular fashion resulting in a sinusoidal vascular pattern. Cytologically, the cells lining the vessels are flattened without atypia and lacking mitotic activity. Areas of fibrin and recent hemorrhage are noted which at higher magnification consist of amorphous pink fibrillary material. In areas at the perimeter the lesion appears to involve and possibly arise in a large vein.
Answer: D
Discussion: The morphology seen in this case is typical of an anastomosing hemangioma which is a variant of hemangioma that has a predilection for genitourinary sites, such as the kidney, ovary, and testis. The only feature that is not that evident in this case which can be seen in this entity is the presence of areas of extramedullary hematopoiesis. Anastomosing hemangiomas are are benign and can either involve the parenchyma of an organ or can arise partly or entirely within a large vein, such as the renal vein. Anastomosing hemangiomas architecturally mimic malignant vascular neoplasms, in that they lack the individual discrete round vessels of a typical hemangioma and have anastomosing vascular channels that characterize well-differentiated angiosarcoma. All cases reveal a lack of endothelial atypia, lack of spindling, absence of multilayering and papillary endothelial tufting, and virtually absent mitotic activity to distinguish anastomosing hemangioma from malignant vascular neoplasms. One further needs to consider in the differential diagnosis a clear cell renal cell carcinoma that has sinusoid-like rich vascularity. We have reported unusual cases of clear cell renal cell carcinoma that have undergone degenerative changes leaving large areas of loose myxohyalinized stroma with complex anastomosing capillary networks and rare indistinct bland clear cell renal cell carcinoma cell. These changes may lead to a false impression of primary vascular neoplasm. Pancytokeratin and/or epithelial membrane antigen immunostaining may distinguish this pattern of renal cell carcinoma from a hemangioma. Angiomyolipoma could be considered in the differential diagnosis. However, even cases of angiomyolipoma with prominent vessels have totally different morphologic features characterized by large vessels with unique PEComa (perivascular epithelioid cell tumor) stromal cells radiating off the outer edge of the vessel walls.
Low-grade clear cell renal cell carcinoma mimicking hemangioma of the kidney: a series of 4 cases. Kryvenko ON, Roquero L, Gupta NS, Lee MW, Epstein JI. Arch Pathol Lab Med. 2013 Feb;137(2):251-4.
Anastomosing hemangioma of the genitourinary system: eight cases in the kidney and ovary with immunohistochemical and ultrastructural analysis. Kryvenko ON, Gupta NS, Meier FA, Lee MW, Epstein JI. Am J Clin Pathol. 2011 Sep;136(3):450-7
Anastomosing hemangioma of the genitourinary tract: a lesion mimicking angiosarcoma.
Montgomery E, Epstein JI. Am J Surg Pathol. 2009 Sep;33(9):1364-9
Incorrect
Histological Description: With a compressed adrenal gland is a large vascular mass. The lesion is composed of vascular channels that connect with each other in an irregular fashion resulting in a sinusoidal vascular pattern. Cytologically, the cells lining the vessels are flattened without atypia and lacking mitotic activity. Areas of fibrin and recent hemorrhage are noted which at higher magnification consist of amorphous pink fibrillary material. In areas at the perimeter the lesion appears to involve and possibly arise in a large vein.
Answer: D
Discussion: The morphology seen in this case is typical of an anastomosing hemangioma which is a variant of hemangioma that has a predilection for genitourinary sites, such as the kidney, ovary, and testis. The only feature that is not that evident in this case which can be seen in this entity is the presence of areas of extramedullary hematopoiesis. Anastomosing hemangiomas are are benign and can either involve the parenchyma of an organ or can arise partly or entirely within a large vein, such as the renal vein. Anastomosing hemangiomas architecturally mimic malignant vascular neoplasms, in that they lack the individual discrete round vessels of a typical hemangioma and have anastomosing vascular channels that characterize well-differentiated angiosarcoma. All cases reveal a lack of endothelial atypia, lack of spindling, absence of multilayering and papillary endothelial tufting, and virtually absent mitotic activity to distinguish anastomosing hemangioma from malignant vascular neoplasms. One further needs to consider in the differential diagnosis a clear cell renal cell carcinoma that has sinusoid-like rich vascularity. We have reported unusual cases of clear cell renal cell carcinoma that have undergone degenerative changes leaving large areas of loose myxohyalinized stroma with complex anastomosing capillary networks and rare indistinct bland clear cell renal cell carcinoma cell. These changes may lead to a false impression of primary vascular neoplasm. Pancytokeratin and/or epithelial membrane antigen immunostaining may distinguish this pattern of renal cell carcinoma from a hemangioma. Angiomyolipoma could be considered in the differential diagnosis. However, even cases of angiomyolipoma with prominent vessels have totally different morphologic features characterized by large vessels with unique PEComa (perivascular epithelioid cell tumor) stromal cells radiating off the outer edge of the vessel walls.
Low-grade clear cell renal cell carcinoma mimicking hemangioma of the kidney: a series of 4 cases. Kryvenko ON, Roquero L, Gupta NS, Lee MW, Epstein JI. Arch Pathol Lab Med. 2013 Feb;137(2):251-4.
Anastomosing hemangioma of the genitourinary system: eight cases in the kidney and ovary with immunohistochemical and ultrastructural analysis. Kryvenko ON, Gupta NS, Meier FA, Lee MW, Epstein JI. Am J Clin Pathol. 2011 Sep;136(3):450-7
Anastomosing hemangioma of the genitourinary tract: a lesion mimicking angiosarcoma.
Montgomery E, Epstein JI. Am J Surg Pathol. 2009 Sep;33(9):1364-9
Presented by Dr. Epstein and prepared by Dr. J. David Peske.
Case 1. A 65 year-old man underwent a radical orchiectomy for a large epididymal mass.
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Case 1. A 65 year-old man underwent a radical orchiectomy for a large epididymal mass.
Choose the correct diagnosis:
Correct
Histological Description: There is a nodule of dense inflammation with scattered atypical cells. Most of the inflammation is lymphocytic but there is an admixture of plasma cells, and a few eosinophils. In the surrounding dense sclerotic fibroadipose tissue are scattered markedly atypical spindle cells with large hyperchromatic nuclei seen at low magnification. These cells have degenerative nuclear atypia with smudgy chromatin and a lack of mitotic activity.
Answer: B
Discussion: First, it is critical to recognize that the most common soft tissue paratesticular tumor is well-differentiated liposarcoma. Most well-differentiated liposarcomas in this region are lipoma-like with mature adipose tissue intersected by broad fibrous bands containing atypical spindle cells identical to those seen in the current case. Lipoblasts are typically not seen and not necessary to establish the diagnosis. There is also a sclerotic variant of well-differentiated liposarcoma which is similar to the lipoma-like subtype except there is a much higher proportion of sclerosis to mature adipose tissue. A much less common variant of well-differentiated liposarcoma is the inflammatory subtype. Microscopically, these tumors were characterized by areas of ordinary well-differentiated liposarcoma, admixed with discrete nodules comprised of small germinal centers, and separated by an admixture of lymphocytes, spindled stromal cells, collagen, and blood vessels, in which highly atypical tumor cells were embedded. The inflammatory component can almost obscure the atypical cells mimicking an inflammatory process or raising the differential diagnosis of various lymphoid neoplasms. This case was seen in consultation and submitted immunohistochemical stains were negative for CK7, S100 protein, CD30, CD45, Cd15, Oct ¾, EMA, CD68 and CD34. At our institution, MDM2 immunohistochemistry and MDMD2 RNA in-situ hybridization were performed showing positivity not only in the large atypical spindle cells in the sclerotic stroma but also in scattered atypical cells in the lymphoid nodule, verifying that both the sclerotic and inflammatory foci were both well-differentiated liposarcoma.
Lymphocyte-rich well-differentiated liposarcoma: report of nine cases. Argani P, Facchetti F, Inghirami G, Rosai J. Am J Surg Pathol. 1997 Aug;21(8):884-95.
Incorrect
Histological Description: There is a nodule of dense inflammation with scattered atypical cells. Most of the inflammation is lymphocytic but there is an admixture of plasma cells, and a few eosinophils. In the surrounding dense sclerotic fibroadipose tissue are scattered markedly atypical spindle cells with large hyperchromatic nuclei seen at low magnification. These cells have degenerative nuclear atypia with smudgy chromatin and a lack of mitotic activity.
Answer: B
Discussion: First, it is critical to recognize that the most common soft tissue paratesticular tumor is well-differentiated liposarcoma. Most well-differentiated liposarcomas in this region are lipoma-like with mature adipose tissue intersected by broad fibrous bands containing atypical spindle cells identical to those seen in the current case. Lipoblasts are typically not seen and not necessary to establish the diagnosis. There is also a sclerotic variant of well-differentiated liposarcoma which is similar to the lipoma-like subtype except there is a much higher proportion of sclerosis to mature adipose tissue. A much less common variant of well-differentiated liposarcoma is the inflammatory subtype. Microscopically, these tumors were characterized by areas of ordinary well-differentiated liposarcoma, admixed with discrete nodules comprised of small germinal centers, and separated by an admixture of lymphocytes, spindled stromal cells, collagen, and blood vessels, in which highly atypical tumor cells were embedded. The inflammatory component can almost obscure the atypical cells mimicking an inflammatory process or raising the differential diagnosis of various lymphoid neoplasms. This case was seen in consultation and submitted immunohistochemical stains were negative for CK7, S100 protein, CD30, CD45, Cd15, Oct ¾, EMA, CD68 and CD34. At our institution, MDM2 immunohistochemistry and MDMD2 RNA in-situ hybridization were performed showing positivity not only in the large atypical spindle cells in the sclerotic stroma but also in scattered atypical cells in the lymphoid nodule, verifying that both the sclerotic and inflammatory foci were both well-differentiated liposarcoma.
Lymphocyte-rich well-differentiated liposarcoma: report of nine cases. Argani P, Facchetti F, Inghirami G, Rosai J. Am J Surg Pathol. 1997 Aug;21(8):884-95.
Presented by Dr. Epstein and prepared by Dr. J. David Peske.
A 45 year old man presented with a 3 cm testicular mass and an orchiectomy was performed.
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Clinical History: A 45 year old man presented with a 3 cm testicular mass and an orchiectomy was performed. At our institution, an extensive study was performed which was negative for multiple keratins, STAT6, desmin, and myogenin. FISH showed no evidence of X:18 translocation. SF-1, inhibin, and ER were diffusely positive.
Choose the correct diagnosis:
Correct
Histological Description: There was predominantly extratesticular tumor but it also had an intratesticular component. Microscopically, it was composed of a mixed storiform and short fascicular growth pattern. The lesion was very hypercellular with focal areas of a looser background. Nuclei were either plump-ovoid or spindled with small central nucleoli. Nuclear pleomorphism was absent. Mitotic figures were not frequent but readily identifiable. At our institution, an immunohistochemical stain for SF-1 was performed.
Answer: C
Discussion: Paratesticular synovial sarcoma and SFT exceedingly rarely affect the paratesticular region. Paratesticular embryonal rhabdomyosarcoma is the most common paratesticular tumor in childhood but would be uncommon in an older age group. The microscopic appearance of the tumor in this case is typical of fibrothecoma of the testis in that it is composed of a mixture of either storiform pattern and/or short fascicles. One half of the testicular fibrothecomas are very hypercellular. Cases are equally split between having plumper ovoid as opposed to spindled pointed nuclei, with all cases lacking prominent nucleoli. In the largest study to date, 11 testicular fibrothecomas had 0 to 2 mitoses per 10 HPF, 3 had 4 to 5 mitoses per 10 HPF, and 2 had 9 to 10 mitoses per 10 HPF. Collagen deposition either in bands or investing single cells ranged from none to extensive. The average size was 1.8 cm but ranged up to 7.6 cm. Given that some testicular fibrothecomas can be large, hypercellular, with increased mitotic activity, they can be confused with a malignant spindle cell tumor. Despite some worrisome histologic features, they appear uniformly benign in their behavior. The current case was unique in that the majority of the tumor protruded outside of the testis where the differential diagnosis had to expand to include paratesticular tumors. Testicular fibrothecomas typically abut the tunica albuginea such that it is not totally unexpected that in a rare case the tumor could expand outward to mimic a paratesticular tumor.
Incorrect
Histological Description: There was predominantly extratesticular tumor but it also had an intratesticular component. Microscopically, it was composed of a mixed storiform and short fascicular growth pattern. The lesion was very hypercellular with focal areas of a looser background. Nuclei were either plump-ovoid or spindled with small central nucleoli. Nuclear pleomorphism was absent. Mitotic figures were not frequent but readily identifiable. At our institution, an immunohistochemical stain for SF-1 was performed.
Answer: C
Discussion: Paratesticular synovial sarcoma and SFT exceedingly rarely affect the paratesticular region. Paratesticular embryonal rhabdomyosarcoma is the most common paratesticular tumor in childhood but would be uncommon in an older age group. The microscopic appearance of the tumor in this case is typical of fibrothecoma of the testis in that it is composed of a mixture of either storiform pattern and/or short fascicles. One half of the testicular fibrothecomas are very hypercellular. Cases are equally split between having plumper ovoid as opposed to spindled pointed nuclei, with all cases lacking prominent nucleoli. In the largest study to date, 11 testicular fibrothecomas had 0 to 2 mitoses per 10 HPF, 3 had 4 to 5 mitoses per 10 HPF, and 2 had 9 to 10 mitoses per 10 HPF. Collagen deposition either in bands or investing single cells ranged from none to extensive. The average size was 1.8 cm but ranged up to 7.6 cm. Given that some testicular fibrothecomas can be large, hypercellular, with increased mitotic activity, they can be confused with a malignant spindle cell tumor. Despite some worrisome histologic features, they appear uniformly benign in their behavior. The current case was unique in that the majority of the tumor protruded outside of the testis where the differential diagnosis had to expand to include paratesticular tumors. Testicular fibrothecomas typically abut the tunica albuginea such that it is not totally unexpected that in a rare case the tumor could expand outward to mimic a paratesticular tumor.
Presented by Dr. Epstein and prepared by Dr. J. David Peske.
A 65 year old man with an elevated serum PSA level underwent 12 core biopsy.
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Clinical History. A 65 year old man with an elevated serum PSA level underwent 12 core biopsy. Two cores had typical Grade Group 3 adenocarcinoma of the prostate. Three other cores had a more poorly differentiated component. At another institution, the following stains were performed on the poorly differentiated component: PSAP – focally positive; NKX3.1 – negative; P501S – negative; PSA – negative. Cystoscopy was normal.
What is the diagnosis of the cores with the poorly differentiated tumor?
Choose the correct diagnosis:
Correct
Histology: A poorly differentiated adenocarcinoma is present on the prostate biopsy. The tumor cells are pleomorphic, in that they not uniform one to another. Numerous mitotic figures and apoptotic bodies are identified. Large areas of cellular necrosis are present. In addition, Gleason score 4+3=7 (Grade Group 3) adenocarcinoma is present with cytologically bland cells arranged in acini and cribriform structures. Immunohistochemical stains for CDX2 are diffusely positive.
Answer: C.
Discussion. The poorly differentiated tumor does not resemble Grade Group 5 adenocarcinoma of the prostate. First, the tumor is more pleomorphic without prominent nucleoli, whereas typical high grade prostate cancer has a more uniform appearance where each nucleus is enlarged with prominent nucleoli yet not significant variation in size and shape. Second, there is extensive necrosis, which also differs from usual high grade prostate cancer. Grade Group 5 prostate cancer can show uncommonly rounded nests of carcinoma with central necrosis, which in most cases represents intraductal carcinoma but can also on occasion be invasive carcinoma with necrosis. However, one does not see sheets of tumor with large areas of necrosis in Grade Group 5 prostate adenocarcinoma. Third, it would be exceptional for high grade prostate cancer to be negative for NKX3.1 and P501S with positivity for PSAP, given the greater sensitivity and specificity of the NKX3.1 and P501S. At our institution, the tumor was confirmed to be negative for NKX3.1, P501S, PSA, and GATA3. The tumor was strongly diffusely positive for CDX2, SATB2, CK20, and CK7. These findings along with the morphology is typical of a gastrointestinal tumor, although uncommonly prostate adenocarcinoma can express CDX2. Although CK7 and CK20 positivity is more usual for an upper GI or pancreaticobiliary primary, colorectal carcinoma can express both of these cytokeratins in approximately 15% of cases. Given that the morphology of the tumor in the prostate looks more like a lower than upper GI tumor and that colorectal carcinoma involves the prostate much more commonly than an upper GI/pancreaticobiliary carcinoma, the most likely diagnosis is spread from the lower GI tract. A bladder or prostatic urethral adenocarcinoma would have identical morphology and immunoexpression, but the negative cystoscopy virtually rules out this possibility. A misleading finding in the case was the presence of usual prostate adenocarcinoma, which in part lead the outside institution to consider a unifying diagnosis of prostate adenocarcinoma involving all the parts. However, prostate adenocarcinoma is common, such that occasionally there may be both usual prostate adenocarcinoma and a tumor from another site co-existing in the prostate.
Incorrect
Histology: A poorly differentiated adenocarcinoma is present on the prostate biopsy. The tumor cells are pleomorphic, in that they not uniform one to another. Numerous mitotic figures and apoptotic bodies are identified. Large areas of cellular necrosis are present. In addition, Gleason score 4+3=7 (Grade Group 3) adenocarcinoma is present with cytologically bland cells arranged in acini and cribriform structures. Immunohistochemical stains for CDX2 are diffusely positive.
Answer: C.
Discussion. The poorly differentiated tumor does not resemble Grade Group 5 adenocarcinoma of the prostate. First, the tumor is more pleomorphic without prominent nucleoli, whereas typical high grade prostate cancer has a more uniform appearance where each nucleus is enlarged with prominent nucleoli yet not significant variation in size and shape. Second, there is extensive necrosis, which also differs from usual high grade prostate cancer. Grade Group 5 prostate cancer can show uncommonly rounded nests of carcinoma with central necrosis, which in most cases represents intraductal carcinoma but can also on occasion be invasive carcinoma with necrosis. However, one does not see sheets of tumor with large areas of necrosis in Grade Group 5 prostate adenocarcinoma. Third, it would be exceptional for high grade prostate cancer to be negative for NKX3.1 and P501S with positivity for PSAP, given the greater sensitivity and specificity of the NKX3.1 and P501S. At our institution, the tumor was confirmed to be negative for NKX3.1, P501S, PSA, and GATA3. The tumor was strongly diffusely positive for CDX2, SATB2, CK20, and CK7. These findings along with the morphology is typical of a gastrointestinal tumor, although uncommonly prostate adenocarcinoma can express CDX2. Although CK7 and CK20 positivity is more usual for an upper GI or pancreaticobiliary primary, colorectal carcinoma can express both of these cytokeratins in approximately 15% of cases. Given that the morphology of the tumor in the prostate looks more like a lower than upper GI tumor and that colorectal carcinoma involves the prostate much more commonly than an upper GI/pancreaticobiliary carcinoma, the most likely diagnosis is spread from the lower GI tract. A bladder or prostatic urethral adenocarcinoma would have identical morphology and immunoexpression, but the negative cystoscopy virtually rules out this possibility. A misleading finding in the case was the presence of usual prostate adenocarcinoma, which in part lead the outside institution to consider a unifying diagnosis of prostate adenocarcinoma involving all the parts. However, prostate adenocarcinoma is common, such that occasionally there may be both usual prostate adenocarcinoma and a tumor from another site co-existing in the prostate.
Presented by Dr. Epstein and prepared by Dr. J. David Peske
A 39 year old man presented with a 1 cm testicular mass. An orchiectomy was performed.
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Case 1. A 39 year old man presented with a 1 cm testicular mass. An orchiectomy was performed.
Choose the correct diagnosis:
Correct
Histological Description: The testis shows sheets of cytologically benign Leydig cells in the testis. These sheets are not only in the 1 cm lesion but in smaller foci scattered throughout the testis. Leydig cells are seen extending around nerves and rete testis in the hilum of the testis.
Answer: C
Discussion: The distinction between a benign Leydig cell tumor and Leydig cell hyperplasia is based on whether there is a solitary Leydig cell nodule with decreased or normal Leydig cells in the surrounding testis or there are multiple Leydig cell nodules of various size in the testis. In the latter setting, even in the presence of a fairly large nodule, the diagnosis is multinodular Leydig cell hyperplasia with a dominant nodule. It is analogous to the thyroid with the distinction of a follicular adenoma versus a dominant adenomatoid nodule in multinodular hyperplasia. In the current case, the outside contributor’s diagnosis of a Leydig cell tumor along with Leydig cells surrounding nerves in the hilum led to the consideration of a malignant Leydig cell tumor. It is a normal finding for Leydig cells to be situated around nerves in the hilum and when there is Leydig cell hyperplasia, the Leydig cells surrounding nerves can be hyperplastic as well. Multinodular Leydig cell hyperplasia can be seen in cryptorchid testes or pituitary conditions leading to a rise in luteinizing hormone or gonadotropin releasing hormone or impaired adrenal steroidogenesis. In adrenogenital syndrome, bilateral testes can be massively enlarged mimicking tumors due to marked Leydig cell hyperplasia. A misdiagnosis of Leydig cell tumors can result in bilateral orchiectomy as opposed to correcting the enzyme deficiency.
Incorrect
Histological Description: The testis shows sheets of cytologically benign Leydig cells in the testis. These sheets are not only in the 1 cm lesion but in smaller foci scattered throughout the testis. Leydig cells are seen extending around nerves and rete testis in the hilum of the testis.
Answer: C
Discussion: The distinction between a benign Leydig cell tumor and Leydig cell hyperplasia is based on whether there is a solitary Leydig cell nodule with decreased or normal Leydig cells in the surrounding testis or there are multiple Leydig cell nodules of various size in the testis. In the latter setting, even in the presence of a fairly large nodule, the diagnosis is multinodular Leydig cell hyperplasia with a dominant nodule. It is analogous to the thyroid with the distinction of a follicular adenoma versus a dominant adenomatoid nodule in multinodular hyperplasia. In the current case, the outside contributor’s diagnosis of a Leydig cell tumor along with Leydig cells surrounding nerves in the hilum led to the consideration of a malignant Leydig cell tumor. It is a normal finding for Leydig cells to be situated around nerves in the hilum and when there is Leydig cell hyperplasia, the Leydig cells surrounding nerves can be hyperplastic as well. Multinodular Leydig cell hyperplasia can be seen in cryptorchid testes or pituitary conditions leading to a rise in luteinizing hormone or gonadotropin releasing hormone or impaired adrenal steroidogenesis. In adrenogenital syndrome, bilateral testes can be massively enlarged mimicking tumors due to marked Leydig cell hyperplasia. A misdiagnosis of Leydig cell tumors can result in bilateral orchiectomy as opposed to correcting the enzyme deficiency.
Presented by Dr. Pedram Argani and prepared by Dr. J. David Peske.
This is an 83 year old male with a breast mass.
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Diagnosis:
Correct
Answer: C
Histologic Description: This is a spindle cell lesion associated with ectatic vessels. The nuclei focally appeared to palisade. There is focal atypia and mitotic figures are not difficult to identify. Lesional cells label for CD34 and desmin, and demonstrate diffuse nuclear labeling for estrogen receptor. These findings support the diagnosis of myofibroblastoma. The cytologic atypia and occasional mitotic activity support classification as a myofibroblastoma with atypical features, and suggest the need for complete but conservative excision.
Differential Diagnosis: Schwannomas would demonstrate diffuse immunoreactivity for S100 protein, and not label for desmin or estrogen receptor. Gastrointestinal stromal tumor would also label for CD34, but typically does not label for desmin or estrogen receptor. Solitary fibrous tumors also label for CD34, but not for desmin or estrogen receptor.
Incorrect
Answer: C
Histologic Description: This is a spindle cell lesion associated with ectatic vessels. The nuclei focally appeared to palisade. There is focal atypia and mitotic figures are not difficult to identify. Lesional cells label for CD34 and desmin, and demonstrate diffuse nuclear labeling for estrogen receptor. These findings support the diagnosis of myofibroblastoma. The cytologic atypia and occasional mitotic activity support classification as a myofibroblastoma with atypical features, and suggest the need for complete but conservative excision.
Differential Diagnosis: Schwannomas would demonstrate diffuse immunoreactivity for S100 protein, and not label for desmin or estrogen receptor. Gastrointestinal stromal tumor would also label for CD34, but typically does not label for desmin or estrogen receptor. Solitary fibrous tumors also label for CD34, but not for desmin or estrogen receptor.
Presented by Dr. Pedram Argani and prepared by Dr. J. David Peske.
This is a 61 year old female with a breast mass.
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Diagnosis:
Correct
Answer: D
Histologic Description: The small ducts in this biopsy contain fibrovascular cores, which supports the classification as micropapilloma. The epithelial proliferation filling the ducts is solid and is associated with central necrosis, which raises concern for carcinoma in situ. However, the cells filling the ducts have the classic features of usual duct hyperplasia; namely, ill-defined cell borders, syncytial growth pattern, nuclear size variation, hypochromasia, and occasional intranuclear inclusions. A known pitfall associated with papillomas is that they may show epithelial necrosis, likely due to an ischemia. This case also had biopsy site changes which also could have contributed to the necrosis.
Differential Diagnosis: Ductal carcinoma in situ cells would demonstrate more rigid cell borders, hyperchromatic nuclei, and typically polarized spaces. Atypical ductal hyperplasia would have some features of carcinoma in situ that are of insufficient in extent to diagnose ductal carcinoma in situ. Atypical lobular hyperplasia would feature discohesive cells with intracytoplasmic vacuoles that lack E-cadherin immunoreactivity.
Incorrect
Answer: D
Histologic Description: The small ducts in this biopsy contain fibrovascular cores, which supports the classification as micropapilloma. The epithelial proliferation filling the ducts is solid and is associated with central necrosis, which raises concern for carcinoma in situ. However, the cells filling the ducts have the classic features of usual duct hyperplasia; namely, ill-defined cell borders, syncytial growth pattern, nuclear size variation, hypochromasia, and occasional intranuclear inclusions. A known pitfall associated with papillomas is that they may show epithelial necrosis, likely due to an ischemia. This case also had biopsy site changes which also could have contributed to the necrosis.
Differential Diagnosis: Ductal carcinoma in situ cells would demonstrate more rigid cell borders, hyperchromatic nuclei, and typically polarized spaces. Atypical ductal hyperplasia would have some features of carcinoma in situ that are of insufficient in extent to diagnose ductal carcinoma in situ. Atypical lobular hyperplasia would feature discohesive cells with intracytoplasmic vacuoles that lack E-cadherin immunoreactivity.
Presented by Dr. Pedram Argani and prepared by Dr. J. David Peske
This a 32 year old female with a breast mass.
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1. Question
Diagnosis:
Correct
Answer: B
Histologic Description: The core biopsy shows a diffuse infiltrate of small round cells with effaced chromatin that permeate between benign breast ducts. Mitotic activity is evident. There is no in situ component. The lesional cells label for CD34, which raises the possibility of a vascular lesion or pseudoangiomatous stromal hyperplasia in its cellular form. However, the lesional cells also label for CD43 and myeloperoxidase, consistent with granulocytic sarcoma.
Differential Diagnosis: Granulocytic sarcoma involving the breast is a known mimic of invasive lobular carcinoma, in this case the mimic would be the solid variant of invasive lobular carcinoma. The absence of immunoreactivity for cytokeratin and estrogen receptor excludes the diagnosis of invasive lobular carcinoma. Pseudoangiomatous stromal hyperplasia would label for CD34, but would not label for CD43 and myeloperoxidase. Pseudoangiomatous stromal hyperplasia is essentially a spindle cell lesion with only rare epithelioid forms. Invasive ductal carcinoma would label for cytokeratin and demonstrate greater pleomorphism.
Incorrect
Answer: B
Histologic Description: The core biopsy shows a diffuse infiltrate of small round cells with effaced chromatin that permeate between benign breast ducts. Mitotic activity is evident. There is no in situ component. The lesional cells label for CD34, which raises the possibility of a vascular lesion or pseudoangiomatous stromal hyperplasia in its cellular form. However, the lesional cells also label for CD43 and myeloperoxidase, consistent with granulocytic sarcoma.
Differential Diagnosis: Granulocytic sarcoma involving the breast is a known mimic of invasive lobular carcinoma, in this case the mimic would be the solid variant of invasive lobular carcinoma. The absence of immunoreactivity for cytokeratin and estrogen receptor excludes the diagnosis of invasive lobular carcinoma. Pseudoangiomatous stromal hyperplasia would label for CD34, but would not label for CD43 and myeloperoxidase. Pseudoangiomatous stromal hyperplasia is essentially a spindle cell lesion with only rare epithelioid forms. Invasive ductal carcinoma would label for cytokeratin and demonstrate greater pleomorphism.
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