Presented by Dr. Pedram Argani and prepared by Dr. Robby Jones.
This is a 23 year female with a renal tumor.
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This is a 23 year female with a renal tumor.
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Answer: D. MIT family translocation carcinoma.
Histologic Description: Many areas of this tumor resemble a conventional clear cell carcinoma; that is, the tumor has a nested to tubular architecture and features cells with predominantly clear cytoplasm. However, one notes that the cytoplasm is finely granular in even the clear cell areas, and that there are mixed cells with oncocytic cytoplasm. On more careful examination of the tumor, one can appreciate clusters of small cells surrounding hyaline nodules of the basement membrane material within the center of the acini in this case. The neoplastic cells were immunoreactive for PAX8 and Melan A, and cathepsin k. They demonstrated rearrangement of the TFEB gene by break-apart FISH. Therefore, this represents a t(6;11) renal cell carcinoma, which is considered a member of the MiT family of translocation carcinomas. The latter family includes more common Xp11 translocation renal carcinomas.
Differential Diagnosis: Clear cell carcinoma would be unusual this age group, and would not be associated with the smaller cells clustered around basement membrane material. The immunoprofile of the current case (positive for melanocytic markers, negative for carbonic anhydrase 9) helps exclude clear cell carcinoma. Chromophobe carcinoma would have hyalinized vessels and more irregular nuclei. It would also lack expression of melanocytic markers seen in the current case. SDHB deficient renal cell carcinomas typically are oncocytic and have cytoplasmic vacuoles and inclusions, and show loss of SDHB immunoreactivity. They would lack the smaller cell component of the current case, as well as the melanocytic marker expression.
t(6;11) RCC are generally more indolent than the Xp11 translocation RCC. There are only approximately 4 cases of metastases and approximately 50 reported cases in the literature (Argani P Seminars and Diagnostic Pathology 2015; 32:103-113).
Incorrect
Answer: D. MIT family translocation carcinoma.
Histologic Description: Many areas of this tumor resemble a conventional clear cell carcinoma; that is, the tumor has a nested to tubular architecture and features cells with predominantly clear cytoplasm. However, one notes that the cytoplasm is finely granular in even the clear cell areas, and that there are mixed cells with oncocytic cytoplasm. On more careful examination of the tumor, one can appreciate clusters of small cells surrounding hyaline nodules of the basement membrane material within the center of the acini in this case. The neoplastic cells were immunoreactive for PAX8 and Melan A, and cathepsin k. They demonstrated rearrangement of the TFEB gene by break-apart FISH. Therefore, this represents a t(6;11) renal cell carcinoma, which is considered a member of the MiT family of translocation carcinomas. The latter family includes more common Xp11 translocation renal carcinomas.
Differential Diagnosis: Clear cell carcinoma would be unusual this age group, and would not be associated with the smaller cells clustered around basement membrane material. The immunoprofile of the current case (positive for melanocytic markers, negative for carbonic anhydrase 9) helps exclude clear cell carcinoma. Chromophobe carcinoma would have hyalinized vessels and more irregular nuclei. It would also lack expression of melanocytic markers seen in the current case. SDHB deficient renal cell carcinomas typically are oncocytic and have cytoplasmic vacuoles and inclusions, and show loss of SDHB immunoreactivity. They would lack the smaller cell component of the current case, as well as the melanocytic marker expression.
t(6;11) RCC are generally more indolent than the Xp11 translocation RCC. There are only approximately 4 cases of metastases and approximately 50 reported cases in the literature (Argani P Seminars and Diagnostic Pathology 2015; 32:103-113).
Presented by Dr. Pedram Argani and prepared by Dr. Robby Jones
This is a 52 year old female who presents with widespread metastatic cancer and is found to have a parotid tumor which is excised.
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This is a 52 year old female who presents with widespread metastatic cancer and is found to have a parotid tumor which is excised.
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Answer: Acinic cell carcinoma with high grade transformation
Histology:
Histologic Description: The submitted tissue represents a salivary gland with prominent tumor associated lymphoid proliferation, not a lymph node. The neoplasm has two components. One component is a fairly typical acinic cell carcinoma, featuring tubules, and cribriform areas of cells with abundant purple zymogen granules. These areas are low grade. Adjacent to this is a high grade basaloid carcinoma, with abundant mitotic activity and central necrosis. These are the characteristic features high grade transformation of acinic cell carcinoma. Unlike most acinic cell carcinomas which are low grade carcinomas, high grade transformation of acinic cell carcinoma is associated with metastasis and aggressive behavior (Skalova et al Am J Surg Pathol 2009; 33:1137-1145). The high grade component is likely responsibility for the disseminated tumor in this case.
Differential Diagnosis: Salivary duct carcinoma would typically have a morphologic appearance resembling that of an apocrine breast carcinoma with areas resembling comedo ductal carcinoma in situ. The areas of acinic cell differentiation seen in this case exclude that diagnosis. Metastatic HPV-related squamous cell carcinoma could be suggested by the high grade areas of this tumor, but that diagnosis does not account for the low grade acinic cell component of this case. Mammary analog secretory carcinomas is often confused with acinic cell carcinoma; however, it is essentially a low grade lesion which is morphologically and genetically identical to secretory carcinoma of the breast, and lacks the high grade component and acinic cell differentiation of the current lesion.
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Answer: Acinic cell carcinoma with high grade transformation
Histology:
Histologic Description: The submitted tissue represents a salivary gland with prominent tumor associated lymphoid proliferation, not a lymph node. The neoplasm has two components. One component is a fairly typical acinic cell carcinoma, featuring tubules, and cribriform areas of cells with abundant purple zymogen granules. These areas are low grade. Adjacent to this is a high grade basaloid carcinoma, with abundant mitotic activity and central necrosis. These are the characteristic features high grade transformation of acinic cell carcinoma. Unlike most acinic cell carcinomas which are low grade carcinomas, high grade transformation of acinic cell carcinoma is associated with metastasis and aggressive behavior (Skalova et al Am J Surg Pathol 2009; 33:1137-1145). The high grade component is likely responsibility for the disseminated tumor in this case.
Differential Diagnosis: Salivary duct carcinoma would typically have a morphologic appearance resembling that of an apocrine breast carcinoma with areas resembling comedo ductal carcinoma in situ. The areas of acinic cell differentiation seen in this case exclude that diagnosis. Metastatic HPV-related squamous cell carcinoma could be suggested by the high grade areas of this tumor, but that diagnosis does not account for the low grade acinic cell component of this case. Mammary analog secretory carcinomas is often confused with acinic cell carcinoma; however, it is essentially a low grade lesion which is morphologically and genetically identical to secretory carcinoma of the breast, and lacks the high grade component and acinic cell differentiation of the current lesion.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Jennifer Bynum
Clinical history: A 60 year-old male presents with a liver mass
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Week 635: Case 2
A 60 year-old male presents with a liver mass
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Answer: Metastatic melanoma
Histology: The resection of the liver mass reveals sheets of loosely cohesive epithelioid cells with abundant eosinophilic cytoplasm, atypical nuclei and prominent nucleoli. There is a brisk mitotic rate and tumoral necrosis. Scattered cells show intracytoplasmic pigment that is granular and golden to pale brown. There are admixed bland glandular structures consistent with reactive bile ductule proliferations. The adjacent hepatic parenchyma shows periportal inflammation but minimal to no fibrosis. Immunostains show the lesional cells to be positive for S100 protein and Sox10, and negative for AE1/AE3.
Discussion: The patient has a history of malignant melanoma, and the morphology and immunprofile of the lesion in the liver are consistent with metastatic melanoma. The metastatic melanoma displays rhabdoid morphology, which is one of the common histologic variants seen in metastatic melanoma, although this pattern is rarely seen in primary melanoma. Indeed, melanoma should always be considered high in the differential of a “pink cell tumor,” along with hepatocellular carcinoma, adrenocortical carcinoma, renal cell carcinoma, and other oncocytic neoplasms (such as Hurthle cell carcinoma, rhabdomyosarcoma, etc). Metastatic melanomas can also be loosely cohesive and have signet ring morphology, mimicking a metastatic signet ring cell carcinoma. In this case, the intracytoplasmic pigment is melanin pigment, although in the liver the differential includes bile pigment and can raise the possibility of a hepatocellular carcinoma.
Reference(s):
1. Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006 Feb;19 Suppl 2:S41-70.
Incorrect
Answer: Metastatic melanoma
Histology: The resection of the liver mass reveals sheets of loosely cohesive epithelioid cells with abundant eosinophilic cytoplasm, atypical nuclei and prominent nucleoli. There is a brisk mitotic rate and tumoral necrosis. Scattered cells show intracytoplasmic pigment that is granular and golden to pale brown. There are admixed bland glandular structures consistent with reactive bile ductule proliferations. The adjacent hepatic parenchyma shows periportal inflammation but minimal to no fibrosis. Immunostains show the lesional cells to be positive for S100 protein and Sox10, and negative for AE1/AE3.
Discussion: The patient has a history of malignant melanoma, and the morphology and immunprofile of the lesion in the liver are consistent with metastatic melanoma. The metastatic melanoma displays rhabdoid morphology, which is one of the common histologic variants seen in metastatic melanoma, although this pattern is rarely seen in primary melanoma. Indeed, melanoma should always be considered high in the differential of a “pink cell tumor,” along with hepatocellular carcinoma, adrenocortical carcinoma, renal cell carcinoma, and other oncocytic neoplasms (such as Hurthle cell carcinoma, rhabdomyosarcoma, etc). Metastatic melanomas can also be loosely cohesive and have signet ring morphology, mimicking a metastatic signet ring cell carcinoma. In this case, the intracytoplasmic pigment is melanin pigment, although in the liver the differential includes bile pigment and can raise the possibility of a hepatocellular carcinoma.
Reference(s):
1. Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006 Feb;19 Suppl 2:S41-70.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Jennifer Bynum
Clinical history: An 85 year-old male presents with lung collapse and bulky pleural masses
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Week 635: Case 3
An 85 year-old male presents with lung collapse and bulky pleural masses.
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Answer: Metastatic prostatic adenocarcinoma
Histology: The excisional biopsy specimen focal areas of fibrous tissue largely replaced by nests and sheets of uniform cells with clear to eosinophilic cytoplasm, uniform nuclei with punctate nucleoli and scattered mitotic figures. No necrosis is evident. There is no definite glandular differentiation, however in some areas there is a vaguely cribriform architecture. Immunostains for D2-40, WT1, calretinin, TTF1, napsin and p40 are all negative. Additional immunostains are performed, and the lesional cells are positive for PSA, P501S and NKX3.1.
Discussion: The clinical suspicion was malignant mesothelioma in an elderly male with occupational asbestos exposure and a new presentation of lung collapse with bulky pleural masses. The histologic features are in keeping with an epithelioid mesothelioma, or involvement by a non-small cell lung carcinoma, but all of the mesothelial (D2-40, WT1, calretinin), lung adenocarcinoma (TTF1), and squamous cell carcinoma (p40) markers are negative. Upon further review, the patient had a history of prostatic adenocarcinoma treated with radiation therapy. The morphologic features of the tumor are nonspecific but are compatible with high grade prostatic adenocarcinoma, and indeed the immunoprofile supports the diagnosis of metastatic high grade prostatic adenocarcinoma (PSA+, P501S+, NKX3.1+). This case illustrates the importance of clinical history, as well as the importance of keeping prostatic adenocarcinoma in the differential of any metastatic or new lesion in a male patient, particularly in elderly male patients (just as breast carcinoma should be in the differential diagnosis of carcinomas of unknown origin in female patients).
Reference(s):
1. Gurel B, Ali TZ, Montgomery EA, et al. NKX3.1 as a marker of prostatic origin in metastatic tumors. Am J Surg Pathol. 2010 Aug;34(8):1097-105.
Incorrect
Answer: Metastatic prostatic adenocarcinoma
Histology: The excisional biopsy specimen focal areas of fibrous tissue largely replaced by nests and sheets of uniform cells with clear to eosinophilic cytoplasm, uniform nuclei with punctate nucleoli and scattered mitotic figures. No necrosis is evident. There is no definite glandular differentiation, however in some areas there is a vaguely cribriform architecture. Immunostains for D2-40, WT1, calretinin, TTF1, napsin and p40 are all negative. Additional immunostains are performed, and the lesional cells are positive for PSA, P501S and NKX3.1.
Discussion: The clinical suspicion was malignant mesothelioma in an elderly male with occupational asbestos exposure and a new presentation of lung collapse with bulky pleural masses. The histologic features are in keeping with an epithelioid mesothelioma, or involvement by a non-small cell lung carcinoma, but all of the mesothelial (D2-40, WT1, calretinin), lung adenocarcinoma (TTF1), and squamous cell carcinoma (p40) markers are negative. Upon further review, the patient had a history of prostatic adenocarcinoma treated with radiation therapy. The morphologic features of the tumor are nonspecific but are compatible with high grade prostatic adenocarcinoma, and indeed the immunoprofile supports the diagnosis of metastatic high grade prostatic adenocarcinoma (PSA+, P501S+, NKX3.1+). This case illustrates the importance of clinical history, as well as the importance of keeping prostatic adenocarcinoma in the differential of any metastatic or new lesion in a male patient, particularly in elderly male patients (just as breast carcinoma should be in the differential diagnosis of carcinomas of unknown origin in female patients).
Reference(s):
1. Gurel B, Ali TZ, Montgomery EA, et al. NKX3.1 as a marker of prostatic origin in metastatic tumors. Am J Surg Pathol. 2010 Aug;34(8):1097-105.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Jennifer Bynum
Clinical history: A 60 year-old male presents with a liver mass
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Week 635: Case 2
A 60 year-old male presents with a liver mass
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Answer: Metastatic melanoma
Histology: The resection of the liver mass reveals sheets of loosely cohesive epithelioid cells with abundant eosinophilic cytoplasm, atypical nuclei and prominent nucleoli. There is a brisk mitotic rate and tumoral necrosis. Scattered cells show intracytoplasmic pigment that is granular and golden to pale brown. There are admixed bland glandular structures consistent with reactive bile ductule proliferations. The adjacent hepatic parenchyma shows periportal inflammation but minimal to no fibrosis. Immunostains show the lesional cells to be positive for S100 protein and Sox10, and negative for AE1/AE3.
Discussion: The patient has a history of malignant melanoma, and the morphology and immunprofile of the lesion in the liver are consistent with metastatic melanoma. The metastatic melanoma displays rhabdoid morphology, which is one of the common histologic variants seen in metastatic melanoma, although this pattern is rarely seen in primary melanoma. Indeed, melanoma should always be considered high in the differential of a “pink cell tumor,” along with hepatocellular carcinoma, adrenocortical carcinoma, renal cell carcinoma, and other oncocytic neoplasms (such as Hurthle cell carcinoma, rhabdomyosarcoma, etc). Metastatic melanomas can also be loosely cohesive and have signet ring morphology, mimicking a metastatic signet ring cell carcinoma. In this case, the intracytoplasmic pigment is melanin pigment, although in the liver the differential includes bile pigment and can raise the possibility of a hepatocellular carcinoma.
Reference(s):
1. Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006 Feb;19 Suppl 2:S41-70.
Incorrect
Answer: Metastatic melanoma
Histology: The resection of the liver mass reveals sheets of loosely cohesive epithelioid cells with abundant eosinophilic cytoplasm, atypical nuclei and prominent nucleoli. There is a brisk mitotic rate and tumoral necrosis. Scattered cells show intracytoplasmic pigment that is granular and golden to pale brown. There are admixed bland glandular structures consistent with reactive bile ductule proliferations. The adjacent hepatic parenchyma shows periportal inflammation but minimal to no fibrosis. Immunostains show the lesional cells to be positive for S100 protein and Sox10, and negative for AE1/AE3.
Discussion: The patient has a history of malignant melanoma, and the morphology and immunprofile of the lesion in the liver are consistent with metastatic melanoma. The metastatic melanoma displays rhabdoid morphology, which is one of the common histologic variants seen in metastatic melanoma, although this pattern is rarely seen in primary melanoma. Indeed, melanoma should always be considered high in the differential of a “pink cell tumor,” along with hepatocellular carcinoma, adrenocortical carcinoma, renal cell carcinoma, and other oncocytic neoplasms (such as Hurthle cell carcinoma, rhabdomyosarcoma, etc). Metastatic melanomas can also be loosely cohesive and have signet ring morphology, mimicking a metastatic signet ring cell carcinoma. In this case, the intracytoplasmic pigment is melanin pigment, although in the liver the differential includes bile pigment and can raise the possibility of a hepatocellular carcinoma.
Reference(s):
1. Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006 Feb;19 Suppl 2:S41-70.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Jennifer Bynum
Clinical history: A 50 year-old female presents with a lung mass
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Week 635: Case 1
A 50 year-old female presents with a lung mass
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Answer: Metastatic pleomorphic sarcoma, consistent with known uterine leiomyosarcoma
Histology: The specimen shows a wedge resection of lung with alveolated lung parenchyma and a discrete, fairly well circumscribed parenchymal nodule with no associated desmoplasia or reactive changes. The nodule is comprised of markedly pleomorphic and atypical cells, with variation in nuclear size and shape, hyperchromasia, nucleoli, and brisk mitotic activity including atypical mitotic figures. There is no necrosis. The cells in areas are loosely cohesive and have abundant eosinophilic, glassy cytoplasm. In areas, the cells have a pseudo-vascular growth pattern (i.e., appear to be making slit-like or vascular-like spaces). Immunostains for cytokeratins, smooth muscle markers, skeletal muscle markers, vascular markers, and melanoma markers, are all negative.
Discussion: The patient has a known history of a uterine leiomyosarcoma, however the lesion is in the lung does not display overt histologic or immunophenotypic evidence of smooth muscle differentiation. The slides from the hysterectomy were pulled and re-reviewed, and indeed the tumor in the uterus displayed the classic fascicular growth pattern along with atypia and mitoses of a leiomyosarcoma. However, there were also regions of marked pleomorphism comprised of cells with prominent eosinophilic, glassy cytoplasm. The lesion in the lung is therefore a metastatic pleomorphic sarcoma, consistent with spread from the patient’s uterine leiomyosarcoma. The differential diagnosis of the lung lesion on the basis of the histology should broadly include melanoma, sarcomatoid carcinoma and sarcoma (including angiosarcoma, rhabdomyosarcoma, and pleomorphic undifferentiated sarcoma), with a targeted immunopanel to evaluate any evidence of lineage of differentiation. The most useful component of this case is comparison of the new lung lesion with the patient’s prior hysterectomy slides, and the importance of both clinical history and comparison with prior histology cannot be overstated.
Reference(s):
1. Goldblum JR. An approach to pleomorphic sarcomas: can we subclassify, and does it matter? Mod Pathol. 2014 Jan;27 Suppl 1:S39-46.
2. Oda Y, Miyajima K, Kawaguchi K, et al. Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma. Am J Surg Pathol. 2001 Aug;25(8):1030-8.
Incorrect
Answer: Metastatic pleomorphic sarcoma, consistent with known uterine leiomyosarcoma
Histology: The specimen shows a wedge resection of lung with alveolated lung parenchyma and a discrete, fairly well circumscribed parenchymal nodule with no associated desmoplasia or reactive changes. The nodule is comprised of markedly pleomorphic and atypical cells, with variation in nuclear size and shape, hyperchromasia, nucleoli, and brisk mitotic activity including atypical mitotic figures. There is no necrosis. The cells in areas are loosely cohesive and have abundant eosinophilic, glassy cytoplasm. In areas, the cells have a pseudo-vascular growth pattern (i.e., appear to be making slit-like or vascular-like spaces). Immunostains for cytokeratins, smooth muscle markers, skeletal muscle markers, vascular markers, and melanoma markers, are all negative.
Discussion: The patient has a known history of a uterine leiomyosarcoma, however the lesion is in the lung does not display overt histologic or immunophenotypic evidence of smooth muscle differentiation. The slides from the hysterectomy were pulled and re-reviewed, and indeed the tumor in the uterus displayed the classic fascicular growth pattern along with atypia and mitoses of a leiomyosarcoma. However, there were also regions of marked pleomorphism comprised of cells with prominent eosinophilic, glassy cytoplasm. The lesion in the lung is therefore a metastatic pleomorphic sarcoma, consistent with spread from the patient’s uterine leiomyosarcoma. The differential diagnosis of the lung lesion on the basis of the histology should broadly include melanoma, sarcomatoid carcinoma and sarcoma (including angiosarcoma, rhabdomyosarcoma, and pleomorphic undifferentiated sarcoma), with a targeted immunopanel to evaluate any evidence of lineage of differentiation. The most useful component of this case is comparison of the new lung lesion with the patient’s prior hysterectomy slides, and the importance of both clinical history and comparison with prior histology cannot be overstated.
Reference(s):
1. Goldblum JR. An approach to pleomorphic sarcomas: can we subclassify, and does it matter? Mod Pathol. 2014 Jan;27 Suppl 1:S39-46.
2. Oda Y, Miyajima K, Kawaguchi K, et al. Pleomorphic leiomyosarcoma: clinicopathologic and immunohistochemical study with special emphasis on its distinction from ordinary leiomyosarcoma and malignant fibrous histiocytoma. Am J Surg Pathol. 2001 Aug;25(8):1030-8.
Presented by Dr. Jonathan Epstein and prepared by Dr. Jennifer Bynum
A 47 year old female was found to have an incidental 2.5 cm cystic renal mass.
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Week 631: Case 6
A 47 year old female was found to have an incidental 2.5 cm cystic renal mass.
Correct
Answer: C
Histological description: The tumor is cystic with solid areas composed predominantly of tubules lined by clear cells. Focally there are papillary and cystic areas with cells having the same cytology. The cells are bland with low nuclear grade and indistinct nucleoli. In areas, the cells show reverse polarity with nuclei oriented towards the surface of the cells with subnuclear clear cytoplasmic vacuoles.
Discussion: This case is a typical example of clear cell papillary renal cell carcinoma (RCC). As with most cases, the tubular component predominates which is one of the differentiating features from clear cell RCC which is composed mainly of small solid nests of cells separated by an anastomosing vascular network. Foci with solid nests may be a minor component of clear cell papillary RCC, in areas mimicking clear cell RCC. The other typical feature of clear cell papillary RCC is that at least focally cases will show the reverse polarity with subnuclear vacuoles. While translocation associated renal cell carcinoma also can have tumor with both clear cell and papillary areas, these tumors tend to be high grade, lack the prominent tubule formation, and don’t have reverse polarity. Translocation associated RCC was initially described in children but can also be seen in adults, which is the typical age for clear cell papillary RCC. A characteristic but not specific immunoprofile is positivity for CK7 (positive in papillary RCC) and CAIX (positive in clear cell RCC) and negative for AMACR (positive in papillary RCC) and negative for RCC (positive in clear cell RCC). However, in a case with classic morphology, such as the current case, immunohistochemistry is not essential for the diagnosis. Also unclassified tumors other than clear cell papillary RCC can be both CK7 and CAIX positive. The importance of diagnosing clear cell papillary RCC is that they have not been reported to exhibit metastatic behavior. We have seen a rare case with sarcomatoid differentiation, but otherwise both in our experience and in the literature they are virtually benign tumors and in the future their terminology may be modified to better reflect their behavior.
Incorrect
Answer: C
Histological description: The tumor is cystic with solid areas composed predominantly of tubules lined by clear cells. Focally there are papillary and cystic areas with cells having the same cytology. The cells are bland with low nuclear grade and indistinct nucleoli. In areas, the cells show reverse polarity with nuclei oriented towards the surface of the cells with subnuclear clear cytoplasmic vacuoles.
Discussion: This case is a typical example of clear cell papillary renal cell carcinoma (RCC). As with most cases, the tubular component predominates which is one of the differentiating features from clear cell RCC which is composed mainly of small solid nests of cells separated by an anastomosing vascular network. Foci with solid nests may be a minor component of clear cell papillary RCC, in areas mimicking clear cell RCC. The other typical feature of clear cell papillary RCC is that at least focally cases will show the reverse polarity with subnuclear vacuoles. While translocation associated renal cell carcinoma also can have tumor with both clear cell and papillary areas, these tumors tend to be high grade, lack the prominent tubule formation, and don’t have reverse polarity. Translocation associated RCC was initially described in children but can also be seen in adults, which is the typical age for clear cell papillary RCC. A characteristic but not specific immunoprofile is positivity for CK7 (positive in papillary RCC) and CAIX (positive in clear cell RCC) and negative for AMACR (positive in papillary RCC) and negative for RCC (positive in clear cell RCC). However, in a case with classic morphology, such as the current case, immunohistochemistry is not essential for the diagnosis. Also unclassified tumors other than clear cell papillary RCC can be both CK7 and CAIX positive. The importance of diagnosing clear cell papillary RCC is that they have not been reported to exhibit metastatic behavior. We have seen a rare case with sarcomatoid differentiation, but otherwise both in our experience and in the literature they are virtually benign tumors and in the future their terminology may be modified to better reflect their behavior.
Presented by Dr. Jonathan Epstein and prepared by Dr. Jennifer Bynum
A 1.5 cm. nodule was removed from the inguinal region of a 40 year old male.
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Week 631: Case 5
A 1.5 cm. nodule was removed from the inguinal region of a 40 year old male.
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Answer: A
Histological Description: Within the dermis is a well-circumscribed nodule composed of variably sized nests in dense collagen. The cells resemble benign urothelial cells. Focally, there is tubule formation and sebaceous differentiation.
Discussion: This case is a not uncommon consult I receive as a genitourinary pathologist because they can occur in the genital region and histologically the cells resemble urothelial cells. In addition to the solid sheets of cells, cases typically have focal tubular eccrine differentiation and can show other adnexal features, as with the focal sebaceous cells seen in the current case. Also urothelial carcinoma does not metastasize to the superficial inguinal region. Rather, like prostate carcinoma, it first spread to deep groin nodes located in the obturator fossa. The only epithelial tumors that typically spread to superficial inguinal nodes are cancers from the penis or scrotal skin or perianal region.
Incorrect
Answer: A
Histological Description: Within the dermis is a well-circumscribed nodule composed of variably sized nests in dense collagen. The cells resemble benign urothelial cells. Focally, there is tubule formation and sebaceous differentiation.
Discussion: This case is a not uncommon consult I receive as a genitourinary pathologist because they can occur in the genital region and histologically the cells resemble urothelial cells. In addition to the solid sheets of cells, cases typically have focal tubular eccrine differentiation and can show other adnexal features, as with the focal sebaceous cells seen in the current case. Also urothelial carcinoma does not metastasize to the superficial inguinal region. Rather, like prostate carcinoma, it first spread to deep groin nodes located in the obturator fossa. The only epithelial tumors that typically spread to superficial inguinal nodes are cancers from the penis or scrotal skin or perianal region.
Presented by Dr. Jonathan Epstein and prepared by Dr. Jennifer Bynum
A 15 year old male underwent resection of a 6.5 cm paratesticular mass.
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Week 631: Case 4
A 15 year old male underwent resection of a 6.5 cm paratesticular mass.
Correct
Answer: D
Histological Description: Areas of the tumor had a “small blue cell” appearance with others characterized by pleomorphic spindle cells with speckled chromatin and small nucleoli. Focally the cytoplasm was abundant and eosinophilic with the appearance of “strap cells”. Areas of necrosis and frequent mitotic figures, some atypical, were present.
Discussion: It is critical to recognize the paratesticular as opposed to testicular location of the tumor. In adults the most common paratesticular tumor is liposarcoma followed by leiomyosarcoma. In children and young adults almost all are rhabdomyosarcomas. Most are embryonal with a favorable prognosis with alveolar having a worse outcome. In the current case, there is a greater degree of anaplasia with atypical mitotic figures diagnostic of an anaplastic rhabdomyosarcoma, using the same criteria, as anaplasia in Wilms tumors. Anaplasia in rhabdmyosarcomas is associated with a worse prognosis and this patient subsequently developed distant metastases. Rhabdomyosarcomas can arise in testicular teratomas as one of the more common somatic (non-germ cell) malignancies to arise in a teratoma. However, these would be intratesticular not paratesticular.
Incorrect
Answer: D
Histological Description: Areas of the tumor had a “small blue cell” appearance with others characterized by pleomorphic spindle cells with speckled chromatin and small nucleoli. Focally the cytoplasm was abundant and eosinophilic with the appearance of “strap cells”. Areas of necrosis and frequent mitotic figures, some atypical, were present.
Discussion: It is critical to recognize the paratesticular as opposed to testicular location of the tumor. In adults the most common paratesticular tumor is liposarcoma followed by leiomyosarcoma. In children and young adults almost all are rhabdomyosarcomas. Most are embryonal with a favorable prognosis with alveolar having a worse outcome. In the current case, there is a greater degree of anaplasia with atypical mitotic figures diagnostic of an anaplastic rhabdomyosarcoma, using the same criteria, as anaplasia in Wilms tumors. Anaplasia in rhabdmyosarcomas is associated with a worse prognosis and this patient subsequently developed distant metastases. Rhabdomyosarcomas can arise in testicular teratomas as one of the more common somatic (non-germ cell) malignancies to arise in a teratoma. However, these would be intratesticular not paratesticular.
Presented by Dr. Jonathan Epstein and prepared by Dr. Jennifer Bynum
A 43 year old man presented with hematuria and underwent a TURB.
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Week 631: Case 3
A 43 year old man presented with hematuria and underwent a TURB.
Correct
Answer: A
Histological Description: The tumor consists of sheets of epithelioid cells with eosinophilic cytoplasm. Nuclear are enlarged, pleomorphic, with prominent nucleoli. Mitotic figures are frequent. Numerous areas are visible with extravasated red blood cells. The tumor was positive for cd31 and focally positive for pancytokeratin.
Discussion: Epithelioid angiosarcoma of the urinary bladder is very rare. The tumor is frequently mistaken as invasive high grade urothelial carcinoma. Misdiagnosis can
carry significant clinical consequences as the therapeutic approach between sarcoma and carcinoma can differ substantially. A clinical history of remote prior radiotherapy to the pelvis is frequently present. A hemorrhagic background and/or extravasated red blood cells located interspersed among epithelioid cells and/or the presence of intracytoplasmic vacuoles/
lumina is an important clue to guide toward the correct diagnosis. Most of the patients have muscle invasive disease at diagnosis and the prognosis is dismal.
Incorrect
Answer: A
Histological Description: The tumor consists of sheets of epithelioid cells with eosinophilic cytoplasm. Nuclear are enlarged, pleomorphic, with prominent nucleoli. Mitotic figures are frequent. Numerous areas are visible with extravasated red blood cells. The tumor was positive for cd31 and focally positive for pancytokeratin.
Discussion: Epithelioid angiosarcoma of the urinary bladder is very rare. The tumor is frequently mistaken as invasive high grade urothelial carcinoma. Misdiagnosis can
carry significant clinical consequences as the therapeutic approach between sarcoma and carcinoma can differ substantially. A clinical history of remote prior radiotherapy to the pelvis is frequently present. A hemorrhagic background and/or extravasated red blood cells located interspersed among epithelioid cells and/or the presence of intracytoplasmic vacuoles/
lumina is an important clue to guide toward the correct diagnosis. Most of the patients have muscle invasive disease at diagnosis and the prognosis is dismal.
Presented by Dr. Jonathan Epstein and prepared by Dr. Jennifer Bynum
An 80 year old man was noted to have a circumscribed 7 mm. mass in his scrotum.
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Week 631: Case 2
An 80 year old man was noted to have a circumscribed 7 mm. mass in his scrotum.
Correct
Answer: C
Histological Description: The lesion consists of a spindle cell tumor with alternating myxoid areas and more cellular areas concentrated around blood vessels. The individual cells are short spindle cells with uniform ovoid nuclei without prominent nucleoli. Many of the blood vessels have fibrin within their walls and lumina. Although it is difficult to determine boundaries of the lesion based on the section, the lesion was well circumscribed.
Discussion: The major differential diagnosis in the anogenital region for a lesion with this morphology is aggressive angiomyxoma. Whereas cellular angiofibromas are benign and do not recur, aggressive angiomyxomas locally recurs in 30% of cases requiring much larger excisions. There are several key differences between the two entities. 1) Cellular angiofibromas are tpyically well-circumscribed histologically compared to aggressive angiomyxomas which are usually infiltrative. 2) Aggressive angiomyxomas have uniformly low cellularity vs. cellular angiofibroma which will have areas of increased cellularity as in the current case. 3) The nature of the blood vessels are different between the two entities. In aggressive angiomyxoma, there are small bundles of smooth muscle that spin off of the vessels, a feature lacking in cellular angiofibroma. Also, the presence of fibrin within the vessel walls and lumina are characteristic of cellular angiofibroma and not seen in aggressive angiomyxoma. Both lesions have the same cytology, mitotic index, and similar immunohistochemistry with often CD34, SMA, desmin, ER, and PR.
Incorrect
Answer: C
Histological Description: The lesion consists of a spindle cell tumor with alternating myxoid areas and more cellular areas concentrated around blood vessels. The individual cells are short spindle cells with uniform ovoid nuclei without prominent nucleoli. Many of the blood vessels have fibrin within their walls and lumina. Although it is difficult to determine boundaries of the lesion based on the section, the lesion was well circumscribed.
Discussion: The major differential diagnosis in the anogenital region for a lesion with this morphology is aggressive angiomyxoma. Whereas cellular angiofibromas are benign and do not recur, aggressive angiomyxomas locally recurs in 30% of cases requiring much larger excisions. There are several key differences between the two entities. 1) Cellular angiofibromas are tpyically well-circumscribed histologically compared to aggressive angiomyxomas which are usually infiltrative. 2) Aggressive angiomyxomas have uniformly low cellularity vs. cellular angiofibroma which will have areas of increased cellularity as in the current case. 3) The nature of the blood vessels are different between the two entities. In aggressive angiomyxoma, there are small bundles of smooth muscle that spin off of the vessels, a feature lacking in cellular angiofibroma. Also, the presence of fibrin within the vessel walls and lumina are characteristic of cellular angiofibroma and not seen in aggressive angiomyxoma. Both lesions have the same cytology, mitotic index, and similar immunohistochemistry with often CD34, SMA, desmin, ER, and PR.
Presented by Dr. Jonathan Epstein and prepared by Dr. Jennifer Bynum
A 53 year old man presented with urinary obstructive symptoms and underwent a TURP.
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1. Question
Week 631: Case 1
A 53 year old man presented with urinary obstructive symptoms and underwent a TURP.
Correct
Answer: C
Histological Description: Infiltrating the TUR specimens are cribriform glands, nests and cords of cells, some with necrosis. The same tumor is seen growing with some of the prostatic ducts. Tumor involves thick muscle bundles suggestive of bladder neck involvement. The tumor cells have amphophilic cytoplasm with enlarged nuclei and prominent nucleoli but are relatively uniform from cell to cell. Focally, there are areas of squamous differentiation with keratin pearl formation.
Discussion. The presence of cribriform glands on a TUR is almost pathognomic for prostatic adenocarcinoma. Bladder adenocarcinoma, either by itself or as a pattern of divergent differentiation in urothelial carcinoma, resembles gastrointestinal adenocarcinoma, where a cribriform pattern is not seen. This tumor was stained with prostate markers and was positive but also labeled in the squamous areas with gata-3 and p63. The presence of these markers, which are negative in usual prostate adenocarcinoma, can be seen in areas of squamous differentiation and does not exclude the diagnosis of prostatic adenocarcinoma. Adenosquamous carcinoma is rare and typically seen following prior hormonal therapy for advanced prostate cancer, but can also be seen de novo without prior therapy. Typically this is an aggressive disease with most patients dead within a year.
Incorrect
Answer: C
Histological Description: Infiltrating the TUR specimens are cribriform glands, nests and cords of cells, some with necrosis. The same tumor is seen growing with some of the prostatic ducts. Tumor involves thick muscle bundles suggestive of bladder neck involvement. The tumor cells have amphophilic cytoplasm with enlarged nuclei and prominent nucleoli but are relatively uniform from cell to cell. Focally, there are areas of squamous differentiation with keratin pearl formation.
Discussion. The presence of cribriform glands on a TUR is almost pathognomic for prostatic adenocarcinoma. Bladder adenocarcinoma, either by itself or as a pattern of divergent differentiation in urothelial carcinoma, resembles gastrointestinal adenocarcinoma, where a cribriform pattern is not seen. This tumor was stained with prostate markers and was positive but also labeled in the squamous areas with gata-3 and p63. The presence of these markers, which are negative in usual prostate adenocarcinoma, can be seen in areas of squamous differentiation and does not exclude the diagnosis of prostatic adenocarcinoma. Adenosquamous carcinoma is rare and typically seen following prior hormonal therapy for advanced prostate cancer, but can also be seen de novo without prior therapy. Typically this is an aggressive disease with most patients dead within a year.
Presented by Dr. Pedram Argani and prepared by Dr. Jennifer Bynum
This is a 57 year old female with a giant polyp in the pharynx.
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Week 630: Case 3
This is a 57 year old female with a giant polyp in the pharynx.
Correct
Answer: D
Histologic Description: This is a polypoid lesion which demonstrates a benign appearing squamous epithelium under which there is a fibrolipomatous proliferation. Much of the proliferation is bland fat and collagen. Within the stroma of the lesion one sees occasional hyperchromatic nuclei (particularly in adipocytes), which raises the differential diagnosis of a reactive multi-nucleated stroma giant cell versus a lipoblast from a well differentiated liposarcoma. In the case, these cells were immunoreactive for MDM2, which supports the diagnosis of atypical lipomatous tumor/well differentiated liposarcoma.
Differential Diagnosis: Many lesions with this morphology have previously been described in the literature as giant fibrovascular polyp of the esophagus. Some of these lesions recur, and it is possible that some such cases actually represent atypical lipomatous tumors. Solitary fibrous tumor would demonstrate greater cellularity, hemangiopericytomatous vasculature, and more cellular spindled cells. Sclerosing epithelial fibrosarcoma would be highly cellular, composed of epithelioid neoplastic cells associated with ropy collagen.
Incorrect
Answer: D
Histologic Description: This is a polypoid lesion which demonstrates a benign appearing squamous epithelium under which there is a fibrolipomatous proliferation. Much of the proliferation is bland fat and collagen. Within the stroma of the lesion one sees occasional hyperchromatic nuclei (particularly in adipocytes), which raises the differential diagnosis of a reactive multi-nucleated stroma giant cell versus a lipoblast from a well differentiated liposarcoma. In the case, these cells were immunoreactive for MDM2, which supports the diagnosis of atypical lipomatous tumor/well differentiated liposarcoma.
Differential Diagnosis: Many lesions with this morphology have previously been described in the literature as giant fibrovascular polyp of the esophagus. Some of these lesions recur, and it is possible that some such cases actually represent atypical lipomatous tumors. Solitary fibrous tumor would demonstrate greater cellularity, hemangiopericytomatous vasculature, and more cellular spindled cells. Sclerosing epithelial fibrosarcoma would be highly cellular, composed of epithelioid neoplastic cells associated with ropy collagen.
Presented by Dr. Pedram Argani and prepared by Dr. Jennifer Bynum
This is a 48 year old female with breast fullness.
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Week 630: Case 2
This is a 48 year old female with breast fullness.
Correct
Answer: D
Histologic Description: This is a vascular lesion that has large areas which are very bland cytologically. The lesion consists of irregular anastomosing dilated vessels which are situated in fat and do not elicit a stromal reaction. These areas would suggest the diagnosis of hemangioma or angiomatosis. However, one can appreciate the infiltrative nature of the lesion as it permeates normal breast lobules. In addition, the lesion contains more solid areas composed of atypical spindle cells with hyperchromatic nuclei and prominent mitotic activity. These are the typical features of angiosarcoma of the breast parenchyma. The lesion has a prominent low grade periphery which can be mistaken for benign process, but it also has high grade areas in the center.
Differential Diagnosis: Angiomatosis is a bland but infiltrative vascular lesion. While this lesion may infiltrate breast lobules, it should show no evidence of cytologic atypia, and no solid areas. Perilobular hemangiomas involved the lobules, but are well circumscribed, lack atypia, and lack solid areas. Atypical vascular lesions are radiation associated vascular proliferations which occur in the dermis of the skin in patients who have undergone breast conserving therapy with adjuvant radiation therapy. They should not show cytologic atypia or solid areas.
Incorrect
Answer: D
Histologic Description: This is a vascular lesion that has large areas which are very bland cytologically. The lesion consists of irregular anastomosing dilated vessels which are situated in fat and do not elicit a stromal reaction. These areas would suggest the diagnosis of hemangioma or angiomatosis. However, one can appreciate the infiltrative nature of the lesion as it permeates normal breast lobules. In addition, the lesion contains more solid areas composed of atypical spindle cells with hyperchromatic nuclei and prominent mitotic activity. These are the typical features of angiosarcoma of the breast parenchyma. The lesion has a prominent low grade periphery which can be mistaken for benign process, but it also has high grade areas in the center.
Differential Diagnosis: Angiomatosis is a bland but infiltrative vascular lesion. While this lesion may infiltrate breast lobules, it should show no evidence of cytologic atypia, and no solid areas. Perilobular hemangiomas involved the lobules, but are well circumscribed, lack atypia, and lack solid areas. Atypical vascular lesions are radiation associated vascular proliferations which occur in the dermis of the skin in patients who have undergone breast conserving therapy with adjuvant radiation therapy. They should not show cytologic atypia or solid areas.
Presented by Dr. Pedram Argani and prepared by Dr. Jennifer Bynum
This is an adrenal tumor in a 41 year old male with a history of multifocal clear cell renal cell carcinoma.
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Week 630: Case 1
This is an adrenal tumor in a 41 year old male with a history of multifocal clear cell renal cell carcinoma.
Correct
Answer: A
Histologic Description: This is a highly vascular clear cell neoplasm in the adrenal, which certainly raises the differential diagnosis of clear cell RCC. However, the neoplastic cells in this case also have finely granular amphophilic cytoplasm in different areas, and irregular, coarse chromatin. This features support the diagnosis of pheochromocytoma. The neoplasm was immunoreactive for chromogranin and synaptophysin, but not for PAX8, supporting the above diagnosis.
Differential Diagnosis: Adrenal cortical neoplasms would have more vacuolated cytoplasm, with vacuoles that indent the nucleus as is of typical steroid-producing cellular lesions. These neoplasms would not label for chromogranin. Metastatic renal cell carcinoma would lack the amphophilic fine cytoplasmic granules in the current case, would typically not label for chromogranin and synaptophysin, and would label for PAX8.
This patient likely had von Hippel Lindau syndrome, which predisposes two multiple clear cell RCCs and pheochromocytoma.
Incorrect
Answer: A
Histologic Description: This is a highly vascular clear cell neoplasm in the adrenal, which certainly raises the differential diagnosis of clear cell RCC. However, the neoplastic cells in this case also have finely granular amphophilic cytoplasm in different areas, and irregular, coarse chromatin. This features support the diagnosis of pheochromocytoma. The neoplasm was immunoreactive for chromogranin and synaptophysin, but not for PAX8, supporting the above diagnosis.
Differential Diagnosis: Adrenal cortical neoplasms would have more vacuolated cytoplasm, with vacuoles that indent the nucleus as is of typical steroid-producing cellular lesions. These neoplasms would not label for chromogranin. Metastatic renal cell carcinoma would lack the amphophilic fine cytoplasmic granules in the current case, would typically not label for chromogranin and synaptophysin, and would label for PAX8.
This patient likely had von Hippel Lindau syndrome, which predisposes two multiple clear cell RCCs and pheochromocytoma.
Presented by Dr. Pedram Argani and prepared by Dr. Jennifer Bynum
This is a 64 year old male with a thyroid mass.
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Week 629: Case 3
This is a 64 year old male with a thyroid mass.
Correct
Answer: C
Histologic Description: This is a solid cellular nodule with areas of follicular formation which mimics a follicular adenoma. However, on closer inspection, one can appropriate that the nuclei are round and hyperchromatic, and are supported by delicate capillary vascular pattern. Oxalate crystals are not identified. Immunohistochemistry for parathyroid hormone confirms that tissue represents a parathyroid adenoma.
Differential Diagnosis: Follicular adenoma is distinguished from parathyroid adenoma in the thyroid by differences in cytology (follicular adenoma typically has more open chromatin), presence of calcium oxalate crystals, and absence of immunoreactivity for parathormone. Follicular carcinoma would demonstrate angioinvasion or capsular invasion which is not seen in the current case. Follicular variant of papillary thyroid carcinoma would demonstrate more irregular nuclei with open chromatin and prominent nuclear overlap. None of these features are seen in the current case.
Incorrect
Answer: C
Histologic Description: This is a solid cellular nodule with areas of follicular formation which mimics a follicular adenoma. However, on closer inspection, one can appropriate that the nuclei are round and hyperchromatic, and are supported by delicate capillary vascular pattern. Oxalate crystals are not identified. Immunohistochemistry for parathyroid hormone confirms that tissue represents a parathyroid adenoma.
Differential Diagnosis: Follicular adenoma is distinguished from parathyroid adenoma in the thyroid by differences in cytology (follicular adenoma typically has more open chromatin), presence of calcium oxalate crystals, and absence of immunoreactivity for parathormone. Follicular carcinoma would demonstrate angioinvasion or capsular invasion which is not seen in the current case. Follicular variant of papillary thyroid carcinoma would demonstrate more irregular nuclei with open chromatin and prominent nuclear overlap. None of these features are seen in the current case.
Presented by Dr. Pedram Argani and prepared by Dr. Jennifer Bynum
This is a 52 year old female with a nipple erosion and mass.
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Week 629: Case 2
This is a 52 year old female with a nipple erosion and mass.
Correct
Answer: C
Histologic Description: This is a sclerotic lesion which ulcerates the epidermis of the nipple, which accounts for the erosion and eczematous appearance seen clinically. The neoplasm has features of a sclerotic papilloma with florid usual duct hyperplasia. The proliferating epithelial cells are unevenly placed, have hypochromatic nuclei and indistinct cell membranes. Focally one sees punctate central necrosis which is typical of benign sclerotic lesions in the breast. These are the typical features of a nipple duct adenoma.
Differential Diagnosis: Invasive ductal carcinoma would demonstrate a more irregular growth pattern, and absence of myoepithelial cells. Myoepithelial cells were retained in the nipple duct adenoma. Low grade adenosquamous carcinoma may arise in association with papillomas of the breast; however, this is typically an infiltrative lesion demonstrating both glandular and squamous differentiation. Sclerosing adenosis is a lobulocentric process, but lacks a papillary component and is centrally composed of spindled myoepithelial cells with abundant cytoplasm.
Nipple duct adenomas are benign lesions that are generally treated by conservative excision.
Incorrect
Answer: C
Histologic Description: This is a sclerotic lesion which ulcerates the epidermis of the nipple, which accounts for the erosion and eczematous appearance seen clinically. The neoplasm has features of a sclerotic papilloma with florid usual duct hyperplasia. The proliferating epithelial cells are unevenly placed, have hypochromatic nuclei and indistinct cell membranes. Focally one sees punctate central necrosis which is typical of benign sclerotic lesions in the breast. These are the typical features of a nipple duct adenoma.
Differential Diagnosis: Invasive ductal carcinoma would demonstrate a more irregular growth pattern, and absence of myoepithelial cells. Myoepithelial cells were retained in the nipple duct adenoma. Low grade adenosquamous carcinoma may arise in association with papillomas of the breast; however, this is typically an infiltrative lesion demonstrating both glandular and squamous differentiation. Sclerosing adenosis is a lobulocentric process, but lacks a papillary component and is centrally composed of spindled myoepithelial cells with abundant cytoplasm.
Nipple duct adenomas are benign lesions that are generally treated by conservative excision.
Presented by Dr. Pedram Argani and prepared by Dr. Jennifer Bynum
This is a 68 year old female with a kidney tumor.
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Week 629: Case 1
This is a 68 year old female with a kidney tumor.
Correct
Answer: B
Histologic Description: This is a high grade adenocarcinoma involving the kidney. The tumor is associated with acutely inflamed desmoplastic stroma. The neoplastic cells form tubules and cribriform structures, and are characterized by vesicular chromatin with prominent nucleoli and occasional intracytoplasmic inclusions (rhabdoid features). The neoplastic cells label for PAX8 and show loss of labeling for INI-1, supporting the diagnosis of renal medullary carcinoma. Hemoglobin electrophoresis later showed evidence of sickle cell trait.
Differential Diagnosis: Urothelial carcinoma would feature transitional type stratified epithelium, and may involve the renal pelvis. Urothelial carcinoma would label for high molecular cytokeratin and generally has intact INI-1 protein. SDHB-RCC is typically an oncocytic tumor with intra cytoplasmic vacuoles and inclusions, dissimilar to the current case. HLRCC-associated RCC characteristically features cells with vesicular chromatin and extremely prominent nucleoli. These neoplasms often but not always demonstrate papillary architecture.
This patient is of more advanced age than the typical renal medullary carcinoma, but the typical morphologic features in this unusual age group led to subsequent hemoglobin electrophoresis, which demonstrated sickle cell trait.
Incorrect
Answer: B
Histologic Description: This is a high grade adenocarcinoma involving the kidney. The tumor is associated with acutely inflamed desmoplastic stroma. The neoplastic cells form tubules and cribriform structures, and are characterized by vesicular chromatin with prominent nucleoli and occasional intracytoplasmic inclusions (rhabdoid features). The neoplastic cells label for PAX8 and show loss of labeling for INI-1, supporting the diagnosis of renal medullary carcinoma. Hemoglobin electrophoresis later showed evidence of sickle cell trait.
Differential Diagnosis: Urothelial carcinoma would feature transitional type stratified epithelium, and may involve the renal pelvis. Urothelial carcinoma would label for high molecular cytokeratin and generally has intact INI-1 protein. SDHB-RCC is typically an oncocytic tumor with intra cytoplasmic vacuoles and inclusions, dissimilar to the current case. HLRCC-associated RCC characteristically features cells with vesicular chromatin and extremely prominent nucleoli. These neoplasms often but not always demonstrate papillary architecture.
This patient is of more advanced age than the typical renal medullary carcinoma, but the typical morphologic features in this unusual age group led to subsequent hemoglobin electrophoresis, which demonstrated sickle cell trait.
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