Presented by Dr. Jonathan Epstein and prepared by Dr. Katherine Fomchenko
An elderly male underwent a radical nephrectomy for a renal mass.
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1. Question
An elderly male underwent a radical nephrectomy for a renal mass.
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Answer: C
Histological Description: The lesion is fairly well-circumscribed. There is predominantly an admixture of compressed elongated tubules and cords of cells in either a myxoid or a scant collagenous stroma. The cells have light eosinophilic cytoplasm. Cytologically, the epithelial cells are bland with small ovoid-round nuclei and inconspicuous nucleoli. Mitotic activity is low. There is a variable amount of stromal and intratubular mucin present.
Discussion: Mucinous tubular spindle cell carcinoma (MTSC) is a well-established relatively newer described renal cell carcinoma variant. It predominantly occurs in females and has an excellent prognosis with only rare cases having metastases. Cases of MTSC can uncommonly be high grade with either nucleolar grade 3 morphology or with extensive necrosis, where the risk of metastatic behavior is increased. Although the classic case of MTSC, has all three components (mucinous, tubular, spindled), the presence of the elements may vary from case to case, and in some cases only two of the three features are present. In this case, the key to the correct diagnosis is recognizing the lightly eosinophilic secretions that are either between or in the tubules, as this is not seen in other renal cell carcinomas. The spindle cell component in this case is not well-developed. In cases with a more prominent spindle cell component, it is important not to misdiagnose MTSC as sarcomatoid renal cell carcinoma. The low grade cytology and other features of MTSC are key in this regard. Immunohistochemical stains are not helpful in establishing the diagnosis. Tubulocystic carcinoma contains much more dilated cysts with a “Swiss cheese” appearance at low power and have grade 3 nucleoli. Medullary renal cell carcinoma and collecting duct carcinoma share with MTSC the presence of tubules, but have more cytological atypia, a prominent desmoplastic reaction, and a very infiltrative interface with the normal kidney.
Incorrect
Answer: C
Histological Description: The lesion is fairly well-circumscribed. There is predominantly an admixture of compressed elongated tubules and cords of cells in either a myxoid or a scant collagenous stroma. The cells have light eosinophilic cytoplasm. Cytologically, the epithelial cells are bland with small ovoid-round nuclei and inconspicuous nucleoli. Mitotic activity is low. There is a variable amount of stromal and intratubular mucin present.
Discussion: Mucinous tubular spindle cell carcinoma (MTSC) is a well-established relatively newer described renal cell carcinoma variant. It predominantly occurs in females and has an excellent prognosis with only rare cases having metastases. Cases of MTSC can uncommonly be high grade with either nucleolar grade 3 morphology or with extensive necrosis, where the risk of metastatic behavior is increased. Although the classic case of MTSC, has all three components (mucinous, tubular, spindled), the presence of the elements may vary from case to case, and in some cases only two of the three features are present. In this case, the key to the correct diagnosis is recognizing the lightly eosinophilic secretions that are either between or in the tubules, as this is not seen in other renal cell carcinomas. The spindle cell component in this case is not well-developed. In cases with a more prominent spindle cell component, it is important not to misdiagnose MTSC as sarcomatoid renal cell carcinoma. The low grade cytology and other features of MTSC are key in this regard. Immunohistochemical stains are not helpful in establishing the diagnosis. Tubulocystic carcinoma contains much more dilated cysts with a “Swiss cheese” appearance at low power and have grade 3 nucleoli. Medullary renal cell carcinoma and collecting duct carcinoma share with MTSC the presence of tubules, but have more cytological atypia, a prominent desmoplastic reaction, and a very infiltrative interface with the normal kidney.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
Adult male with inguinal lymphadenopathy.
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Adult male with inguinal lymphadenopathy.
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Correct: B.
Histology: This lymph node is almost entirely replaced by a tumor composed of nests and sheets of cells with eosinophilic cytoplasm and large nuclei with prominent nucleoli. There are occasional glandular lumina and intracytoplasmic mucin vacuoles.
Discussion: The skin adnexal structures have a similar histogenesis to mammary glands. Accordingly, neoplasms arising from adnexal sweat glands and mammary glands look very similar histologically, as well as immunophenotypically. Apocrine sweat glands are concentrated in areas such as the axilla, eyelid, anogenital regions, and ear canal. Apocrine carcinoma is a rare form of malignancy that originates in sweat apocrine glands and, therefore, it is more common in regions with high density of such glands including the axilla and anogenital area. The definition of apocrine carcinoma varies in the literature. Some experts would require morphologic evidence of apocrine differentiation including tumor cells with granular eosinophilic cytoplasm and evidence of decapitation, while others would accept tumors with a wider range of morphologic features but with expression of GCDFP15 and occurring in the axillary or anogenital regions that are known to harbor apocrine glands. A lesion that is more common in men and shows the same immunophenotype is extramammary Paget disease (EMPD). Histologically, extramammary Paget disease is predominantly an intraepithelial (in-situ) lesion with superficial invasion in a minority of the cases. Clinically, patients with EMPD present with an insidious rash or erythema that is suspected to be a fungal infection or a dermatitis. In contrast, patients with apocrine carcinoma present with a nodule or mass. Lymph node metastases is rare in EMPD, and most patients have a favorable prognosis, with the main clinical challenge being to obtain negative margins to avoid local recurrence. Most patients with apocrine carcinoma of the scrotum present with metastatic disease. Similar to EMPD and breast carcinomas, apocrine carcinomas are positive for GATA3, GCDFP15, CK7 and mammaglobin. AR could also be positive, and tumors can occasionally show positive staining for NKX3.1 and PSA, as also seen in EMPD.
References:
Shabihkhani M et al. Appl Immunohistochem Mol Morphol. 2020 Aug;28(7):524-531.
Kamanda S et al. Am J Dermatopathol. 2022 Apr 1;44(4):260-266.
Incorrect
Correct: B.
Histology: This lymph node is almost entirely replaced by a tumor composed of nests and sheets of cells with eosinophilic cytoplasm and large nuclei with prominent nucleoli. There are occasional glandular lumina and intracytoplasmic mucin vacuoles.
Discussion: The skin adnexal structures have a similar histogenesis to mammary glands. Accordingly, neoplasms arising from adnexal sweat glands and mammary glands look very similar histologically, as well as immunophenotypically. Apocrine sweat glands are concentrated in areas such as the axilla, eyelid, anogenital regions, and ear canal. Apocrine carcinoma is a rare form of malignancy that originates in sweat apocrine glands and, therefore, it is more common in regions with high density of such glands including the axilla and anogenital area. The definition of apocrine carcinoma varies in the literature. Some experts would require morphologic evidence of apocrine differentiation including tumor cells with granular eosinophilic cytoplasm and evidence of decapitation, while others would accept tumors with a wider range of morphologic features but with expression of GCDFP15 and occurring in the axillary or anogenital regions that are known to harbor apocrine glands. A lesion that is more common in men and shows the same immunophenotype is extramammary Paget disease (EMPD). Histologically, extramammary Paget disease is predominantly an intraepithelial (in-situ) lesion with superficial invasion in a minority of the cases. Clinically, patients with EMPD present with an insidious rash or erythema that is suspected to be a fungal infection or a dermatitis. In contrast, patients with apocrine carcinoma present with a nodule or mass. Lymph node metastases is rare in EMPD, and most patients have a favorable prognosis, with the main clinical challenge being to obtain negative margins to avoid local recurrence. Most patients with apocrine carcinoma of the scrotum present with metastatic disease. Similar to EMPD and breast carcinomas, apocrine carcinomas are positive for GATA3, GCDFP15, CK7 and mammaglobin. AR could also be positive, and tumors can occasionally show positive staining for NKX3.1 and PSA, as also seen in EMPD.
References:
Shabihkhani M et al. Appl Immunohistochem Mol Morphol. 2020 Aug;28(7):524-531.
Kamanda S et al. Am J Dermatopathol. 2022 Apr 1;44(4):260-266.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
Adult male with kidney mass.
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Adult male with kidney mass.
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Correct: B
Histology: The tumor is composed of irregular nests of tumor cells with keratinization, with invasion of the kidney parenchyma, and surrounded by marked stromal desmoplasia.
Discussion: Primary squamous cell carcinoma of the renal pelvis is extremely rare. Risk factors are chronic inflammation of the renal pelvis, most commonly secondary to stones and chronic urinary infection. For the tumor to be designated as squamous cell carcinoma, it must show squamous differentiation in 100% of the tumor. Most patients present in advanced stage (pT3 or higher) but the prognosis is similar to urothelial carcinoma when compared stage by stage. Prognostic factors include vascular invasion, poorly differentiated histology and size of the tumor.
Reference:
Holmäng S, et al. J Urol. 2007. PMID: 17574059
Incorrect
Correct: B
Histology: The tumor is composed of irregular nests of tumor cells with keratinization, with invasion of the kidney parenchyma, and surrounded by marked stromal desmoplasia.
Discussion: Primary squamous cell carcinoma of the renal pelvis is extremely rare. Risk factors are chronic inflammation of the renal pelvis, most commonly secondary to stones and chronic urinary infection. For the tumor to be designated as squamous cell carcinoma, it must show squamous differentiation in 100% of the tumor. Most patients present in advanced stage (pT3 or higher) but the prognosis is similar to urothelial carcinoma when compared stage by stage. Prognostic factors include vascular invasion, poorly differentiated histology and size of the tumor.
Reference:
Holmäng S, et al. J Urol. 2007. PMID: 17574059
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
Adult male with bladder tumor
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Adult male with bladder tumor.
Correct
Correct: C
Histology: Highly atypical tumor cells invading in single cells through the muscularis propria or detrusor muscle.
Discussion: Plasmacytoid urothelial carcinoma is considered an aggressive variant of urothelial carcinoma that includes signet ring cell carcinoma and carcinomas with poorly cohesive cells that invade similarly to lobular carcinoma of the breast. When tumor cells closely resemble plasma cells, immunostaining for CD138 could be a diagnostic pitfall as both, plasmacytoid variant of urothelial carcinoma and plasma cell neoplasia, are both positive. In the absence of a surface papillary component, the main differential diagnosis is with breast lobular carcinoma in a female and gastrointestinal signet ring cell carcinoma in both males and females. Both plasmacytoid urothelial carcinoma and lobular breast carcinomas are positive for GATA3 and negative for e-cadherin; but in contrast to breast carcinomas, urothelial carcinoma is commonly negative for ER. When the main differential diagnosis is with gastrointestinal signet ring cell carcinoma, it is important to remember that plasmacytoid urothelial carcinoma can be positive for CDX2 in approximately 15% of the cases and that CDX2 does not necessarily exclude a gastrointestinal origin, for which clinical/radiologic correlation is essential.
References
Perrino CM et al. Hum Pathol. 2019 Aug;90:27-36.
Incorrect
Correct: C
Histology: Highly atypical tumor cells invading in single cells through the muscularis propria or detrusor muscle.
Discussion: Plasmacytoid urothelial carcinoma is considered an aggressive variant of urothelial carcinoma that includes signet ring cell carcinoma and carcinomas with poorly cohesive cells that invade similarly to lobular carcinoma of the breast. When tumor cells closely resemble plasma cells, immunostaining for CD138 could be a diagnostic pitfall as both, plasmacytoid variant of urothelial carcinoma and plasma cell neoplasia, are both positive. In the absence of a surface papillary component, the main differential diagnosis is with breast lobular carcinoma in a female and gastrointestinal signet ring cell carcinoma in both males and females. Both plasmacytoid urothelial carcinoma and lobular breast carcinomas are positive for GATA3 and negative for e-cadherin; but in contrast to breast carcinomas, urothelial carcinoma is commonly negative for ER. When the main differential diagnosis is with gastrointestinal signet ring cell carcinoma, it is important to remember that plasmacytoid urothelial carcinoma can be positive for CDX2 in approximately 15% of the cases and that CDX2 does not necessarily exclude a gastrointestinal origin, for which clinical/radiologic correlation is essential.
References
Perrino CM et al. Hum Pathol. 2019 Aug;90:27-36.
Presented by Dr. Pedram Argani and prepared by Dr. Harsimar Kaur
This is a 60 year old male with retroperitoneal mass.
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This is a 60 year old male with retroperitoneal mass.
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Answer: B
Histologic Description: The lesion is dominated by a prominent nodular lymphoid infiltrate, within are occasional atypical cells. In the fat surrounding the lesion, one can appreciate hyperchromatic nuclei that tend to be centered on fibrous septa. The lesion demonstrates MDM2 amplification by FISH.
Differential Diagnosis: This lesion resembles Rosai Dorfman disease in that emperipolesis may be seen. However, Rosai Dorfman disease would not be characterized by the atypical enlarged nuclei in the fibrous stroma of the lesion. The presence of single atypical cells in the background of lymphoid tissue raise the possibility of Hodgkin’s disease; however, the lesional cells label for MDM2 but not for CD30 or CD15. The density of infiltrate suggests lymphoma; however, the lesion contains a mixture of B cells and T cells (the latter predominating).
Incorrect
Answer: B
Histologic Description: The lesion is dominated by a prominent nodular lymphoid infiltrate, within are occasional atypical cells. In the fat surrounding the lesion, one can appreciate hyperchromatic nuclei that tend to be centered on fibrous septa. The lesion demonstrates MDM2 amplification by FISH.
Differential Diagnosis: This lesion resembles Rosai Dorfman disease in that emperipolesis may be seen. However, Rosai Dorfman disease would not be characterized by the atypical enlarged nuclei in the fibrous stroma of the lesion. The presence of single atypical cells in the background of lymphoid tissue raise the possibility of Hodgkin’s disease; however, the lesional cells label for MDM2 but not for CD30 or CD15. The density of infiltrate suggests lymphoma; however, the lesion contains a mixture of B cells and T cells (the latter predominating).
Presented by Dr. Pedram Argani and prepared by Dr. Harsimar Kaur
This is a 50 year old male with multiple renal tumors.
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This is a 50 year old male with multiple renal tumors.
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Answer: A
Histologic Description: This neoplasm has a predominantly tubular and focally papillary architecture. The neoplastic cells have low grade nuclei. They have clear cytoplasm which is often located at the base of the cell. The neoplastic cells label for CK7 and carbonic anhydrase 9 (the latter in a cup shaped pattern), but not for TFE3. The background kidney shows evidence of end stage renal disease.
Differential Diagnosis: Clear cell RCC typically would not label diffusely for CK7, though occasion low grade variants do. The subnuclear vacuoles of the current are not typical of clear cell RCC. Xp11 translocation RCC are typically associated with psammomatous calcifications, usually do not label for diffusely for cytokeratins, and demonstrate TFE3 immunoreactivity. Renal cell carcinomas with leiomyomatous stroma have a similar labeling pattern for CK7 and CA-IX as the current lesion; however, they typically have voluminous cytoplasm, and are associated with mutations in either the ELOC1 or TSC genes.
Incorrect
Answer: A
Histologic Description: This neoplasm has a predominantly tubular and focally papillary architecture. The neoplastic cells have low grade nuclei. They have clear cytoplasm which is often located at the base of the cell. The neoplastic cells label for CK7 and carbonic anhydrase 9 (the latter in a cup shaped pattern), but not for TFE3. The background kidney shows evidence of end stage renal disease.
Differential Diagnosis: Clear cell RCC typically would not label diffusely for CK7, though occasion low grade variants do. The subnuclear vacuoles of the current are not typical of clear cell RCC. Xp11 translocation RCC are typically associated with psammomatous calcifications, usually do not label for diffusely for cytokeratins, and demonstrate TFE3 immunoreactivity. Renal cell carcinomas with leiomyomatous stroma have a similar labeling pattern for CK7 and CA-IX as the current lesion; however, they typically have voluminous cytoplasm, and are associated with mutations in either the ELOC1 or TSC genes.
Presented by Dr. Pedram Argani and prepared by Dr. Harsimar Kaur
This is a 7 year old male with a renal mass.
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This is a 7 year old male with a renal mass.
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Answer: C
Histologic Description: This is a nested clear cell tumor associated abundant brown melanin pigment, leading to a black gross appearance. The neoplastic cells label for HMB45, but not for epithelial markers such as cytokeratins or for renal tubular markers like PAX8. Break-apart FISH demonstrates a TFE3 gene rearrangement.
Differential Diagnosis: Xp11 translocation renal cell carcinoma may express melanocytic markers, but should express PAX8 and often express some epithelial markers such as cytokeratins or EMA. Melanoma may have a balloon cell appearance, but is unassociated with TFE3 rearrangements. Clear cell sarcoma is typically characterized the gene fusion EWS-ATF1, but not with TFE3 gene rearrangements. It would also label for S100 protein unlike the current lesion.
The lesion illustrated herein was originally reported as melanotic Xp11 translocation renal cancer. With a greater experience, we believe these are closely related to Xp11 translocation PEComas, and represent a variant of that with melanin pigment.
References
Argani P, Illei P, Netto G, Ro J, Cho HY, Dogan S, Ladanyi M, Martignoni G, Aulmann S, Weiss SW. A Distinctive Subset of PEComas Harbor TFE3 Gene Fusions. Am J Surg Pathol 2010; 34: 1395-1406.
Argani P, Aulmann S, Karanjawala Z, Fraser RB, Ladanyi M, Rodriguez MM. Melanotic Xp11 translocation Renal Cancers: A Distinctive Neoplasm with overlapping features of PEComa, Carcinoma, and Melanoma. Am J Surg Pathol 2009; 33: 609-619.
Incorrect
Answer: C
Histologic Description: This is a nested clear cell tumor associated abundant brown melanin pigment, leading to a black gross appearance. The neoplastic cells label for HMB45, but not for epithelial markers such as cytokeratins or for renal tubular markers like PAX8. Break-apart FISH demonstrates a TFE3 gene rearrangement.
Differential Diagnosis: Xp11 translocation renal cell carcinoma may express melanocytic markers, but should express PAX8 and often express some epithelial markers such as cytokeratins or EMA. Melanoma may have a balloon cell appearance, but is unassociated with TFE3 rearrangements. Clear cell sarcoma is typically characterized the gene fusion EWS-ATF1, but not with TFE3 gene rearrangements. It would also label for S100 protein unlike the current lesion.
The lesion illustrated herein was originally reported as melanotic Xp11 translocation renal cancer. With a greater experience, we believe these are closely related to Xp11 translocation PEComas, and represent a variant of that with melanin pigment.
References
Argani P, Illei P, Netto G, Ro J, Cho HY, Dogan S, Ladanyi M, Martignoni G, Aulmann S, Weiss SW. A Distinctive Subset of PEComas Harbor TFE3 Gene Fusions. Am J Surg Pathol 2010; 34: 1395-1406.
Argani P, Aulmann S, Karanjawala Z, Fraser RB, Ladanyi M, Rodriguez MM. Melanotic Xp11 translocation Renal Cancers: A Distinctive Neoplasm with overlapping features of PEComa, Carcinoma, and Melanoma. Am J Surg Pathol 2009; 33: 609-619.
Presented by Dr. Jonathan Epstein and prepared by Dr. Harsimar Kaur
A 68 year old female underwent a resection of a 1.5 cm. adrenal mass. The lesion appeared to be adherent and to the adrenal, but not within the adrenal.
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A 68 year old female underwent a resection of a 1.5 cm. adrenal mass. The lesion appeared to be adherent and to the adrenal, but not within the adrenal.
Correct
Answer: A
Histological Description:
Adjacent to the adrenal is a nodule with a biphasic appearance. There are nests of cells with abundant eosinophilic cytoplasm, indistinguishable from Leydig cells. Between these nests is a very cellular spindle cell proliferation composed of bland cells with elongated nuclei, no atypia, and no mitotic activity. These cells are identical to thecal cells seen in ovarian or testicular thecomas.
Discussion: In this case there is unremarkable adrenal tissue with an adherent nodule of thecal/Leydig cells. Stains were performed at the outside institution demonstrating that the Leydig cell component was positive for SF1 and synaptophysin. The spindle cell component was positive for SMA (patchy) and desmin (focal). Both were negative for PAX8, inhibin, calretinin, S100, CD34, HMB45, p63, and chromogranin. Additional stains were performed at Johns Hopkins showing that the Leydig cell component was focally positive for PR and the spindle cell component was diffusely positive for ER and PR. This case represents a rare entity which could be regarded as either “ovarian thecal metaplasia of the adrenal gland” or “benign sex cord stromal tumor/nodule” arising adjacent to the adrenal gland.” The adrenal cortex is derived from the intermediate mesoderm in the region between the genital ridge and the root of the mesentery, such that embryologically gonadal tissue fused with the adrenal would be feasible. It is much more common to see this close relationship of adrenal and gonadal tissue manifest with adrenal cortical tissue in the inguinal or testicular region, representing adrenal cortical tissue that descends with the testis from the abdomen down to the scrotum during fetal development.
Incorrect
Answer: A
Histological Description:
Adjacent to the adrenal is a nodule with a biphasic appearance. There are nests of cells with abundant eosinophilic cytoplasm, indistinguishable from Leydig cells. Between these nests is a very cellular spindle cell proliferation composed of bland cells with elongated nuclei, no atypia, and no mitotic activity. These cells are identical to thecal cells seen in ovarian or testicular thecomas.
Discussion: In this case there is unremarkable adrenal tissue with an adherent nodule of thecal/Leydig cells. Stains were performed at the outside institution demonstrating that the Leydig cell component was positive for SF1 and synaptophysin. The spindle cell component was positive for SMA (patchy) and desmin (focal). Both were negative for PAX8, inhibin, calretinin, S100, CD34, HMB45, p63, and chromogranin. Additional stains were performed at Johns Hopkins showing that the Leydig cell component was focally positive for PR and the spindle cell component was diffusely positive for ER and PR. This case represents a rare entity which could be regarded as either “ovarian thecal metaplasia of the adrenal gland” or “benign sex cord stromal tumor/nodule” arising adjacent to the adrenal gland.” The adrenal cortex is derived from the intermediate mesoderm in the region between the genital ridge and the root of the mesentery, such that embryologically gonadal tissue fused with the adrenal would be feasible. It is much more common to see this close relationship of adrenal and gonadal tissue manifest with adrenal cortical tissue in the inguinal or testicular region, representing adrenal cortical tissue that descends with the testis from the abdomen down to the scrotum during fetal development.
Presented by Dr. Jonathan Epstein and prepared by Dr. Harsimar Kaur
A 55 year old man underwent a TURB for a bladder tumor.
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A 55 year old man underwent a TURB for a bladder tumor.
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Answer: B
Histological description. The TURB shows invasive high grade papillary urothelial carcinoma. In addition, there is CIS with involvement of Von Brun nests. There is extensive lamina propria invasion with no muscularis propria present. Scattered amongst the invasive carcinoma are multinucleated cells typical of syncytiotrophoblasts.
Discussion: Urothelial carcinoma with trophoblastic differentiation can manifest as: 1) invasive high grade pleomorphic urothelial carcinoma without syncytiotrophoblasts aberrantly expressing HCG; 2) invasive urothelial carcinoma or non-invasive papillary urothelial carcinoma of various grades with syncytiotrophoblasts; or rarely 3) choriocarcinoma. In high grade pleomorphic urothelial carcinoma, HCG can be present in tumor cells or elevated in the serum that lack the histological features of syncytiotrophoblasts. Aberrantly expression of HCG can be seen in in pleomorphic tumors in other organs, as well. As in this case, rarely, one can see cells with the typical appearance of syncytiotrophoblasts in various pattern of urothelial carcinoma. These cells will express HCG, but if there is elevated levels of serum HCG then often there is a lot of background staining immunohistochemically with HCG. A cleaner trophoblastic marker is HSD3B1 which will only label the syncytiotrophoblasts. There is no prognostic significance to the presence of syncytiotrophoblasts, yet if numerous can result in elevated serum HCG levels and gynecomastia in men. Choriocarcinoma of the bladder is very rare and has a dimorphic population of cytotrophoblasts and intimately admixed syncytiotrophoblasts, with a very poor prognosis.
Incorrect
Answer: B
Histological description. The TURB shows invasive high grade papillary urothelial carcinoma. In addition, there is CIS with involvement of Von Brun nests. There is extensive lamina propria invasion with no muscularis propria present. Scattered amongst the invasive carcinoma are multinucleated cells typical of syncytiotrophoblasts.
Discussion: Urothelial carcinoma with trophoblastic differentiation can manifest as: 1) invasive high grade pleomorphic urothelial carcinoma without syncytiotrophoblasts aberrantly expressing HCG; 2) invasive urothelial carcinoma or non-invasive papillary urothelial carcinoma of various grades with syncytiotrophoblasts; or rarely 3) choriocarcinoma. In high grade pleomorphic urothelial carcinoma, HCG can be present in tumor cells or elevated in the serum that lack the histological features of syncytiotrophoblasts. Aberrantly expression of HCG can be seen in in pleomorphic tumors in other organs, as well. As in this case, rarely, one can see cells with the typical appearance of syncytiotrophoblasts in various pattern of urothelial carcinoma. These cells will express HCG, but if there is elevated levels of serum HCG then often there is a lot of background staining immunohistochemically with HCG. A cleaner trophoblastic marker is HSD3B1 which will only label the syncytiotrophoblasts. There is no prognostic significance to the presence of syncytiotrophoblasts, yet if numerous can result in elevated serum HCG levels and gynecomastia in men. Choriocarcinoma of the bladder is very rare and has a dimorphic population of cytotrophoblasts and intimately admixed syncytiotrophoblasts, with a very poor prognosis.
Presented by Dr. Jonathan Epstein and prepared by Dr. Harsimar Kaur
A 65 year-old man underwent a radical nephrectomy for a renal hilar mass.
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A 65 year-old man underwent a radical nephrectomy for a renal hilar mass.
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Answer: B
Histological Description: Adjacent to the renal pelvis is a spindle cell tumor composed of well-formed fascicles. Nuclei are cigar-shaped with occasional nuclear hyperchromasia yet still relatively uniform. Scattered mitotic activity is present. The lesion lacks necrosis. Adjacent renal parenchyma is uninvolved.
Discussion: First, in terms of the distinction of AML and a smooth muscle tumor involving the kidney, there is a difference in location. AMLs involve the kidney or peri-renal tissue, but typically not the hilum of the kidney. In contrast, smooth muscle tumors arise from the large vessels of the renal hilum. Histologically, smooth muscle cells have identical nuclei to those in low grade leiomyosarcomas yet the cytoplasm is looser and filamentous, whereas in smooth muscle the overall appearance is more dense pink due to more compact eosinophilic cytoplasm. Smooth muscle tumors also tend to have a more regular fascicular growth pattern compared to AML. Immunohistochemically, both AML and smooth muscle tumors express desmin and smooth muscle actin. However, AMLs are also positive for HMB45 and Melan A, yet can be very focal. S100 protein can be positive. Typically, Cathepsin K is diffusely positive in AMLs but not smooth muscle tumors. A more recently described marker GPNMB is also positive in AML and negative in smooth muscle tumors. In the current case, immunohistochemistry confirmed the diagnosis of a smooth muscle tumor. Once it is recognized that this is a smooth muscle tumor, the differential is between a leiomyoma and leiomyosarcoma. In this site, a leiomyoma is diagnosed only if the lesion is virtually identical to normal smooth muscle in terms of cellularity and no atypia and no mitotic activity, yet recognizable as a tumor because it is forming a spherical mass. In this case, the lesion is hypercellular with occasional hyperchromatic nuclei and scatter mitotic activity diagnostic of a low grade (Grade 1) leiomyosarcoma.
Incorrect
Answer: B
Histological Description: Adjacent to the renal pelvis is a spindle cell tumor composed of well-formed fascicles. Nuclei are cigar-shaped with occasional nuclear hyperchromasia yet still relatively uniform. Scattered mitotic activity is present. The lesion lacks necrosis. Adjacent renal parenchyma is uninvolved.
Discussion: First, in terms of the distinction of AML and a smooth muscle tumor involving the kidney, there is a difference in location. AMLs involve the kidney or peri-renal tissue, but typically not the hilum of the kidney. In contrast, smooth muscle tumors arise from the large vessels of the renal hilum. Histologically, smooth muscle cells have identical nuclei to those in low grade leiomyosarcomas yet the cytoplasm is looser and filamentous, whereas in smooth muscle the overall appearance is more dense pink due to more compact eosinophilic cytoplasm. Smooth muscle tumors also tend to have a more regular fascicular growth pattern compared to AML. Immunohistochemically, both AML and smooth muscle tumors express desmin and smooth muscle actin. However, AMLs are also positive for HMB45 and Melan A, yet can be very focal. S100 protein can be positive. Typically, Cathepsin K is diffusely positive in AMLs but not smooth muscle tumors. A more recently described marker GPNMB is also positive in AML and negative in smooth muscle tumors. In the current case, immunohistochemistry confirmed the diagnosis of a smooth muscle tumor. Once it is recognized that this is a smooth muscle tumor, the differential is between a leiomyoma and leiomyosarcoma. In this site, a leiomyoma is diagnosed only if the lesion is virtually identical to normal smooth muscle in terms of cellularity and no atypia and no mitotic activity, yet recognizable as a tumor because it is forming a spherical mass. In this case, the lesion is hypercellular with occasional hyperchromatic nuclei and scatter mitotic activity diagnostic of a low grade (Grade 1) leiomyosarcoma.
Presented by Dr. Ezra Baraban and prepared by Dr. Harsimar Kaur
Elderly male status post cystoprostatectomy.
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Elderly male status post cystoprostatectomy.
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Sections show prostatic tissue with a solid intraductal proliferation of dyscohesive neoplastic cells with eosinophilic cytoplasm, nuclear pleomorphism and mitotic activity. Focally these cells undermine benign prostatic epithelium in a pagetoid distribution. Another area shows an infiltrating tumor composed predominantly of poorly formed glands with amphophilic cytoplasm, monotonous nuclei and prominent nucleoli. Intraductal carcinoma of the prostate shows the cytologic features of prostatic adenocarcinoma but conforms to the architecture of pre-existing benign prostate glands. The non-invasive proliferation in this case conforms to the architecture of pre-existing benign prostate glands but has the cytologic features of urothelial carcinoma, indicating in-situ urothelial carcinoma involving prostatic ducts and acini, which is regarded as pTis under the prostatic urethral staging system. GATA3, P40, or uroplakin, along with negativity for some combination of NKX3.1, P501S, and PSA would confirm the urothelial nature of these cells. Elsewhere there is invasive adenocarcinoma with cytologic features of prostatic adenocarcinoma – an incidental finding in this cystoprostatectomy performed for muscle invasive urothelial carcinoma.
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Sections show prostatic tissue with a solid intraductal proliferation of dyscohesive neoplastic cells with eosinophilic cytoplasm, nuclear pleomorphism and mitotic activity. Focally these cells undermine benign prostatic epithelium in a pagetoid distribution. Another area shows an infiltrating tumor composed predominantly of poorly formed glands with amphophilic cytoplasm, monotonous nuclei and prominent nucleoli. Intraductal carcinoma of the prostate shows the cytologic features of prostatic adenocarcinoma but conforms to the architecture of pre-existing benign prostate glands. The non-invasive proliferation in this case conforms to the architecture of pre-existing benign prostate glands but has the cytologic features of urothelial carcinoma, indicating in-situ urothelial carcinoma involving prostatic ducts and acini, which is regarded as pTis under the prostatic urethral staging system. GATA3, P40, or uroplakin, along with negativity for some combination of NKX3.1, P501S, and PSA would confirm the urothelial nature of these cells. Elsewhere there is invasive adenocarcinoma with cytologic features of prostatic adenocarcinoma – an incidental finding in this cystoprostatectomy performed for muscle invasive urothelial carcinoma.
Presented by Dr. Ezra Baraban and prepared by Dr. Harsimar Kaur
Elderly male with pleural mass.
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Elderly male with pleural mass.
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Sections show a low-grade cellular spindle cell neoplasm. The monotony and arcing vasculature could suggest low grade fibromyxoid sarcoma, however that lesion should lack keratin staining and express MUC4. Pleura is a typical location for solitary fibrous tumor, however SFT should typically express CD34 and STAT6 and typically features “staghorn” vasculature. Sarcomatoid carcinoma of lung origin or other primary sites is a strong consideration and expression of keratin and TTF1 would support this diagnosis. A recent publication suggested that MUC4 positivity and GATA3 negativity can be used to support sarcomatoid carcinoma versus sarcomatoid mesothelioma in the setting of a malignant spindled tumor involving pleura. In this case, an epithelioid component was present in other sections and both components labeled with cytokeratin as well as multiple mesothelial markers, confirming the diagnosis of biphasic (epithelioid and sarcomatoid) mesothelioma.
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Sections show a low-grade cellular spindle cell neoplasm. The monotony and arcing vasculature could suggest low grade fibromyxoid sarcoma, however that lesion should lack keratin staining and express MUC4. Pleura is a typical location for solitary fibrous tumor, however SFT should typically express CD34 and STAT6 and typically features “staghorn” vasculature. Sarcomatoid carcinoma of lung origin or other primary sites is a strong consideration and expression of keratin and TTF1 would support this diagnosis. A recent publication suggested that MUC4 positivity and GATA3 negativity can be used to support sarcomatoid carcinoma versus sarcomatoid mesothelioma in the setting of a malignant spindled tumor involving pleura. In this case, an epithelioid component was present in other sections and both components labeled with cytokeratin as well as multiple mesothelial markers, confirming the diagnosis of biphasic (epithelioid and sarcomatoid) mesothelioma.
Presented by Dr. Ezra Baraban and prepared by Dr. Harsimar Kaur
Adult male with shoulder mass.
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Adult male with shoulder mass.
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Sections show a spindle cell neoplasm infiltrating deep dermis and subcutis. Nodular fasciitis may involve the dermis but necrosis and fascicular architecture are not typical. A myofibroblastic immunophenotype would be expected and demonstration of a USP6 rearrangement can be used to support the diagnosis. Melanoma can be excluded with negativity for S100 and SOX10 as well as the lack of an overlying in-situ component. Angiosarcoma should label with at least two of the three endothelial markers CD31, ERG, or CD34. This patient had a history of squamous carcinoma at this site. A previous biopsy with similar morphology showed extensive expression of multiple keratins and P40, confirming the diagnosis of sarcomatoid squamous cell carcinoma.
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Sections show a spindle cell neoplasm infiltrating deep dermis and subcutis. Nodular fasciitis may involve the dermis but necrosis and fascicular architecture are not typical. A myofibroblastic immunophenotype would be expected and demonstration of a USP6 rearrangement can be used to support the diagnosis. Melanoma can be excluded with negativity for S100 and SOX10 as well as the lack of an overlying in-situ component. Angiosarcoma should label with at least two of the three endothelial markers CD31, ERG, or CD34. This patient had a history of squamous carcinoma at this site. A previous biopsy with similar morphology showed extensive expression of multiple keratins and P40, confirming the diagnosis of sarcomatoid squamous cell carcinoma.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
Adult female with kidney tumor.
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Adult female with kidney tumor.
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Correct: B.
Histology: This solid and cystic tumor is composed of tumor cells with abundant eosinophilic cytoplasm, enlarged nuclei and prominent nucleoli. The cysts are lined by cells exhibiting hobnail arrangement with voluminous eosinophilic cytoplasm. The cells in the solid areas typically showed diffuse and compact acinar or nested growth. The cytoplasm shows a characteristic granular, fine or coarse stippling, consisting of basophilic to purple inclusions.
Discussion: Eosinophilic solid and cystic RCC (ESC RCC)shows the characteristic morphology of the case presented here, with often tan, solid, and cystic gross appearance and cells exhibiting eosinophilic, voluminous cytoplasm with granular stippling. The tumors are typically low stage and often show prominent nucleoli. There is frequent CK20 positivity, whereas CK7 is usually negative or only focally positive. Cathepsin-K can be positive, which is also positive in epithelioid AMLs but AMLs are negative for PAX8 while ESC RCC is most frequently positive. ESCs RCC are associated with mutations in the TSC1 gene, with or without association with tuberous sclerosis syndrome. While most patients present with organ confined disease and have a favorable outcome, rare cases of metastatic ESC RCC have been documented.
References:
1. Trpkov K, Hes O, Bonert M, et al. Eosinophilic, solid, and cystic renal cell carcinoma: clinicopathologic study of 16 unique, sporadic neoplasms occurring in women. Am J Surg Pathol. 2016;40:60–71.
2. Trpkov K, Abou-Ouf H, Hes O, Lopez JI, Nesi G, Comperat E, Sibony M, Osunkoya AO, Zhou M, Gokden N, Leroy X, Berney DM, Werneck Cunha I, Musto ML, Athanazio DA, Yilmaz A, Donnelly B, Hyndman E, Gill AJ, McKenney JK, Bismar TA. Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC): Further Morphologic and Molecular Characterization of ESC RCC as a Distinct Entity. Am J Surg Pathol. 2017 Oct;41(10):1299-1308.
3. Palsgrove DN, Li Y, Pratilas CA, Lin MT, Pallavajjalla A, Gocke C, De Marzo AM, Matoso A, Netto GJ, Epstein JI, Argani P. Eosinophilic Solid and Cystic (ESC) Renal CellCarcinomas Harbor TSC Mutations: Molecular Analysis Supports an Expanding Clinicopathologic Spectrum. Am J Surg Pathol. 2018 Sep;42(9):1166-1181.
Incorrect
Correct: B.
Histology: This solid and cystic tumor is composed of tumor cells with abundant eosinophilic cytoplasm, enlarged nuclei and prominent nucleoli. The cysts are lined by cells exhibiting hobnail arrangement with voluminous eosinophilic cytoplasm. The cells in the solid areas typically showed diffuse and compact acinar or nested growth. The cytoplasm shows a characteristic granular, fine or coarse stippling, consisting of basophilic to purple inclusions.
Discussion: Eosinophilic solid and cystic RCC (ESC RCC)shows the characteristic morphology of the case presented here, with often tan, solid, and cystic gross appearance and cells exhibiting eosinophilic, voluminous cytoplasm with granular stippling. The tumors are typically low stage and often show prominent nucleoli. There is frequent CK20 positivity, whereas CK7 is usually negative or only focally positive. Cathepsin-K can be positive, which is also positive in epithelioid AMLs but AMLs are negative for PAX8 while ESC RCC is most frequently positive. ESCs RCC are associated with mutations in the TSC1 gene, with or without association with tuberous sclerosis syndrome. While most patients present with organ confined disease and have a favorable outcome, rare cases of metastatic ESC RCC have been documented.
References:
1. Trpkov K, Hes O, Bonert M, et al. Eosinophilic, solid, and cystic renal cell carcinoma: clinicopathologic study of 16 unique, sporadic neoplasms occurring in women. Am J Surg Pathol. 2016;40:60–71.
2. Trpkov K, Abou-Ouf H, Hes O, Lopez JI, Nesi G, Comperat E, Sibony M, Osunkoya AO, Zhou M, Gokden N, Leroy X, Berney DM, Werneck Cunha I, Musto ML, Athanazio DA, Yilmaz A, Donnelly B, Hyndman E, Gill AJ, McKenney JK, Bismar TA. Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC): Further Morphologic and Molecular Characterization of ESC RCC as a Distinct Entity. Am J Surg Pathol. 2017 Oct;41(10):1299-1308.
3. Palsgrove DN, Li Y, Pratilas CA, Lin MT, Pallavajjalla A, Gocke C, De Marzo AM, Matoso A, Netto GJ, Epstein JI, Argani P. Eosinophilic Solid and Cystic (ESC) Renal CellCarcinomas Harbor TSC Mutations: Molecular Analysis Supports an Expanding Clinicopathologic Spectrum. Am J Surg Pathol. 2018 Sep;42(9):1166-1181.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
Adult female with kidney tumor.
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Adult female with kidney tumor.
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Correct: B
Histology: The lesion shows a relatively well circumscribed mass composed of a mixed inflammatory infiltrate with sheets of foamy histiocytes.
Discussion: Xanthogranulomatous pyelonephritis is a variant of chronic pyelonephritis in the setting of chronic obstruction due to renal calculi, which may lead to massive unilateral destruction of the kidney with the presence of granulomatous tissue that contains lipid-filled macrophages. Clinically, the patients can present with back pain, fever, or incidentally found in imaging studies performed for another reason. Image studies reveal an infiltrative mass that is suspicious for carcinoma. Three forms of this condition have been described: diffuse, segmental, and focal. The diffuse type is the most common one, and there are three stages associated with it. The first one is the nephric stage, which is confined to the renal parenchyma; stage II, or the perinephric stage, involves the perirenal space and Gerota’s fascia; and stage III, or the paranephric stages, refers to the involvement of the pararenal area and retroperitoneal structures. The differential diagnosis include other histiocytic disorders such as Rosai Dorfman disease, Erdheim Chester disease and malakoplakia. Malakoplakia has similar histologic features but it is characterized by the presence of Michaelis Gutman bodies which are small targetoid concentrically layered basophilic inclusions. Histiocytes of Rosai Dorfman have eosinophilic cytoplasm and are positive for S100 by immunohistochemistry. Erdheim Chester disease is an extremely rare neoplastic process that could be diagnosed using immunohistochemistry to detect mutant BRAF V600E.
References:
1. Cureus. 2021 Oct; 13(10): e19133.
Incorrect
Correct: B
Histology: The lesion shows a relatively well circumscribed mass composed of a mixed inflammatory infiltrate with sheets of foamy histiocytes.
Discussion: Xanthogranulomatous pyelonephritis is a variant of chronic pyelonephritis in the setting of chronic obstruction due to renal calculi, which may lead to massive unilateral destruction of the kidney with the presence of granulomatous tissue that contains lipid-filled macrophages. Clinically, the patients can present with back pain, fever, or incidentally found in imaging studies performed for another reason. Image studies reveal an infiltrative mass that is suspicious for carcinoma. Three forms of this condition have been described: diffuse, segmental, and focal. The diffuse type is the most common one, and there are three stages associated with it. The first one is the nephric stage, which is confined to the renal parenchyma; stage II, or the perinephric stage, involves the perirenal space and Gerota’s fascia; and stage III, or the paranephric stages, refers to the involvement of the pararenal area and retroperitoneal structures. The differential diagnosis include other histiocytic disorders such as Rosai Dorfman disease, Erdheim Chester disease and malakoplakia. Malakoplakia has similar histologic features but it is characterized by the presence of Michaelis Gutman bodies which are small targetoid concentrically layered basophilic inclusions. Histiocytes of Rosai Dorfman have eosinophilic cytoplasm and are positive for S100 by immunohistochemistry. Erdheim Chester disease is an extremely rare neoplastic process that could be diagnosed using immunohistochemistry to detect mutant BRAF V600E.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
Adult male with bladder mass.
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Adult male with bladder mass.
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Correct: D
Histology: The lesion is composed of broad based polypoid and papillary projections lined by urothelium that is thickened in areas and has acute and chronic inflammation. There is edema of the lamina propria.
Discussion: Polypoid, or papillary cystitis is a reactive lesion occurring most frequently in the bladder but it can occur anywhere in the urinary tract. When it presents in the urethra, it is called polypoid urethritis; in the renal pelvis, polypoid pyelitis, and in the ureter, polypoid ureteritis. Clinically, patients may present with hematuria and the cystoscopy can show a papillary/polypoid lesion, suspicious for papillary urothelial carcinoma. Patients often have a history of injury to the bladder including a previous urologic procedure, urinary stones, or indwelling catheter. Histologically, the lesion is composed of broad based papillary/polypoid projections of the mucosa with edema in the stalk and lamina propria and associated acute and chronic inflammation. The urothelium can be hyperplastic, but in contrast to low grade papillary urothelial carcinoma, there is no nuclear hyperchromasia or significant nuclear enlargement. In. contrast to PUNLMP, polypoid cystitis is inflamed, the papillary projections are broad based and do not show branching. Given the presence of inflammation, mitoses can be seen in association with reactive epithelial changes.
Histology: The lesion is composed of broad based polypoid and papillary projections lined by urothelium that is thickened in areas and has acute and chronic inflammation. There is edema of the lamina propria.
Discussion: Polypoid, or papillary cystitis is a reactive lesion occurring most frequently in the bladder but it can occur anywhere in the urinary tract. When it presents in the urethra, it is called polypoid urethritis; in the renal pelvis, polypoid pyelitis, and in the ureter, polypoid ureteritis. Clinically, patients may present with hematuria and the cystoscopy can show a papillary/polypoid lesion, suspicious for papillary urothelial carcinoma. Patients often have a history of injury to the bladder including a previous urologic procedure, urinary stones, or indwelling catheter. Histologically, the lesion is composed of broad based papillary/polypoid projections of the mucosa with edema in the stalk and lamina propria and associated acute and chronic inflammation. The urothelium can be hyperplastic, but in contrast to low grade papillary urothelial carcinoma, there is no nuclear hyperchromasia or significant nuclear enlargement. In. contrast to PUNLMP, polypoid cystitis is inflamed, the papillary projections are broad based and do not show branching. Given the presence of inflammation, mitoses can be seen in association with reactive epithelial changes.
Presented by Dr. Pedram Argani and prepared by Dr. Harsimar Kaur
This is a 60 year old female with an exophytic renal mass.
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This is a 60 year old female with an exophytic renal mass.
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Answer: A
Histologic Description: This is a renal mass centered on the capsule which projects out to the perirenal fat. The neoplasm contains a bundled smooth muscle stroma with all the features of angiomyolipoma, and associated with epithelial cysts that represent entrapped renal tubules. The stroma consists of poorly formed fascicles of short spindle cells with eosinophilic to pale cytoplasm in a highly vascularized stroma. The epithelium has a hobnail appearance consistent with entrapped renal tubular epithelium; however, beneath it is a more cellular zone which resembles endometrial stroma. The stromal component labels for HMB45 and cathepsin K, whereas epithelium is PAX8 positive. Estrogen receptor immunoreactivity is accentuated beneath the cystic epithelium.
Differential Diagnosis: Mixed epithelial stromal tumor also is biphasic; however, the stroma is of conventional smooth muscle and doesn’t not label for HMB45 or Melan A. Endometriosis would not contain the angiomyolipomatous smooth muscle component seen in the current case, and would feature more hemorrhage and degenerative changes. Synovial sarcoma may entrapped renal tubules; however, the stromal component would be a primitive blue spindle cell lesion, not the angiomyolipomatous stroma of the current case.
AMLEC is typically subscapular and projects beyond the contour of the kidney into perirenal fat, raising clinical concerns for an aggressive capsule-invasive renal carcinoma.
Incorrect
Answer: A
Histologic Description: This is a renal mass centered on the capsule which projects out to the perirenal fat. The neoplasm contains a bundled smooth muscle stroma with all the features of angiomyolipoma, and associated with epithelial cysts that represent entrapped renal tubules. The stroma consists of poorly formed fascicles of short spindle cells with eosinophilic to pale cytoplasm in a highly vascularized stroma. The epithelium has a hobnail appearance consistent with entrapped renal tubular epithelium; however, beneath it is a more cellular zone which resembles endometrial stroma. The stromal component labels for HMB45 and cathepsin K, whereas epithelium is PAX8 positive. Estrogen receptor immunoreactivity is accentuated beneath the cystic epithelium.
Differential Diagnosis: Mixed epithelial stromal tumor also is biphasic; however, the stroma is of conventional smooth muscle and doesn’t not label for HMB45 or Melan A. Endometriosis would not contain the angiomyolipomatous smooth muscle component seen in the current case, and would feature more hemorrhage and degenerative changes. Synovial sarcoma may entrapped renal tubules; however, the stromal component would be a primitive blue spindle cell lesion, not the angiomyolipomatous stroma of the current case.
AMLEC is typically subscapular and projects beyond the contour of the kidney into perirenal fat, raising clinical concerns for an aggressive capsule-invasive renal carcinoma.
Presented by Dr. Pedram Argani and prepared by Dr. Harsimar Kaur
This is a 45 year old female with a renal mass.
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This is a 45 year old female with a renal mass.
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Answer: D
Histologic Description: This an unusual lesion with features heavy classification and ossification at its rim and internally. The neoplastic cells are set in a very hyalinized stroma, and have a nondescript eosinophilic cytoplasm. They form tubules with focal papillary areas. The neoplastic cells were immunoreactive for TFE3 and cathepsin K, and FISH confirmed a TFE3 rearrangement.
Differential Diagnosis: Heterotopic ossification would not contain the proliferated neoplastic epithelial component of the current case. Tubulocystic carcinoma could be suggested by the prominent tubular architecture and focally elastotic stroma; however, the extensive ossification is not typical of that lesion, and the diffuse cathepsin K immunoreactivity also excludes it. Carcinosarcoma is suggested by the prominent osseous component; however, the osseous component is histologically benign and metaplastic.
Xp11 translocation RCC may have variety of histologic patterns. One of the features occasionally seen is heavy eggshell-like classification and ossification, which can lead to the tumor being taken for a renal stone.
Incorrect
Answer: D
Histologic Description: This an unusual lesion with features heavy classification and ossification at its rim and internally. The neoplastic cells are set in a very hyalinized stroma, and have a nondescript eosinophilic cytoplasm. They form tubules with focal papillary areas. The neoplastic cells were immunoreactive for TFE3 and cathepsin K, and FISH confirmed a TFE3 rearrangement.
Differential Diagnosis: Heterotopic ossification would not contain the proliferated neoplastic epithelial component of the current case. Tubulocystic carcinoma could be suggested by the prominent tubular architecture and focally elastotic stroma; however, the extensive ossification is not typical of that lesion, and the diffuse cathepsin K immunoreactivity also excludes it. Carcinosarcoma is suggested by the prominent osseous component; however, the osseous component is histologically benign and metaplastic.
Xp11 translocation RCC may have variety of histologic patterns. One of the features occasionally seen is heavy eggshell-like classification and ossification, which can lead to the tumor being taken for a renal stone.
Presented by Dr. Pedram Argani and prepared by Dr. Harsimar Kaur.
This is a 51 year old male with a renal neoplasm.
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This is a 51 year old male with a renal neoplasm.
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Answer: D
Histologic Description: The neoplasm has both solid and cystic architecture, and is composed of cells that have variably clear to eosinophilic cytoplasm. There is a second population of smaller cells within the acini formed by the neoplasm. These focally surround hyaline basement membrane material. The neoplasm is diffusely immunoreactivity for cathepsin K and Melan A, focally immunoreactivity for HMB45, and demonstrated TFEB rearrangement by FISH.
Differential Diagnosis: The clear cell areas of this neoplasm closely resemble clear cell RCC; however, the latter would not have these small cell component and diffuse immunoreactivity for cathepsin K and Melan A. Low grade oncocytic tumor closely resembles eosinophilic chromophobe RCC, and labels for cytokeratin 7 but not CD117. It also would not label for diffusely for Melan A or HMB45. Eosinophilic solid and cystic renal cell carcinoma may have the solid cystic architecture of the current lesion; however, it features large polygonal cells with eosinophilic cytoplasm and basophilic cytoplasmic stippling, and focal immunoreactivity for cytokeratin 20. Both ESC RCC and low grade oncocytic tumors are associated with TSC gene mutations.
TFEB rearranged renal cell carcinomas typical harbor a t(6;11) (p21;q12) translocation resulting from a MALAT1-TFEB gene fusion. These tumors are more indolent than the Xp11 translocation RCC.
Incorrect
Answer: D
Histologic Description: The neoplasm has both solid and cystic architecture, and is composed of cells that have variably clear to eosinophilic cytoplasm. There is a second population of smaller cells within the acini formed by the neoplasm. These focally surround hyaline basement membrane material. The neoplasm is diffusely immunoreactivity for cathepsin K and Melan A, focally immunoreactivity for HMB45, and demonstrated TFEB rearrangement by FISH.
Differential Diagnosis: The clear cell areas of this neoplasm closely resemble clear cell RCC; however, the latter would not have these small cell component and diffuse immunoreactivity for cathepsin K and Melan A. Low grade oncocytic tumor closely resembles eosinophilic chromophobe RCC, and labels for cytokeratin 7 but not CD117. It also would not label for diffusely for Melan A or HMB45. Eosinophilic solid and cystic renal cell carcinoma may have the solid cystic architecture of the current lesion; however, it features large polygonal cells with eosinophilic cytoplasm and basophilic cytoplasmic stippling, and focal immunoreactivity for cytokeratin 20. Both ESC RCC and low grade oncocytic tumors are associated with TSC gene mutations.
TFEB rearranged renal cell carcinomas typical harbor a t(6;11) (p21;q12) translocation resulting from a MALAT1-TFEB gene fusion. These tumors are more indolent than the Xp11 translocation RCC.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur.
Adult female with kidney tumor.
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Adult female with kidney tumor.
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Correct: B.
Histology: This solid and cystic tumor is composed of tumor cells with abundant eosinophilic cytoplasm, enlarged nuclei and prominent nucleoli. The cysts are lined by cells exhibiting hobnail arrangement with voluminous eosinophilic cytoplasm. The cells in the solid areas typically showed diffuse and compact acinar or nested growth. The cytoplasm shows a characteristic granular, fine or coarse stippling, consisting of basophilic to purple inclusions.
Discussion: Eosinophilic solid and cystic RCC (ESC RCC)shows the characteristic morphology of the case presented here, with often tan, solid, and cystic gross appearance and cells exhibiting eosinophilic, voluminous cytoplasm with granular stippling. The tumors are typically low stage and often show prominent nucleoli. There is frequent CK20 positivity, whereas CK7 is usually negative or only focally positive. Cathepsin-K can be positive, which is also positive in epithelioid AMLs but AMLs are negative for PAX8 while ESC RCC is most frequently positive. ESCs RCC are associated with mutations in the TSC1 gene, with or without association with tuberous sclerosis syndrome. While most patients present with organ confined disease and have a favorable outcome, rare cases of metastatic ESC RCC have been documented.
References:
1. Trpkov K, Hes O, Bonert M, et al. Eosinophilic, solid, and cystic renal cell carcinoma: clinicopathologic study of 16 unique, sporadic neoplasms occurring in women. Am J Surg Pathol. 2016;40:60–71.
2. Trpkov K, Abou-Ouf H, Hes O, Lopez JI, Nesi G, Comperat E, Sibony M, Osunkoya AO, Zhou M, Gokden N, Leroy X, Berney DM, Werneck Cunha I, Musto ML, Athanazio DA, Yilmaz A, Donnelly B, Hyndman E, Gill AJ, McKenney JK, Bismar TA. Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC): Further Morphologic and Molecular Characterization of ESC RCC as a Distinct Entity. Am J Surg Pathol. 2017 Oct;41(10):1299-1308.
3. Palsgrove DN, Li Y, Pratilas CA, Lin MT, Pallavajjalla A, Gocke C, De Marzo AM, Matoso A, Netto GJ, Epstein JI, Argani P. Eosinophilic Solid and Cystic (ESC) Renal CellCarcinomas Harbor TSC Mutations: Molecular Analysis Supports an Expanding Clinicopathologic Spectrum. Am J Surg Pathol. 2018 Sep;42(9):1166-1181.
Incorrect
Correct: B.
Histology: This solid and cystic tumor is composed of tumor cells with abundant eosinophilic cytoplasm, enlarged nuclei and prominent nucleoli. The cysts are lined by cells exhibiting hobnail arrangement with voluminous eosinophilic cytoplasm. The cells in the solid areas typically showed diffuse and compact acinar or nested growth. The cytoplasm shows a characteristic granular, fine or coarse stippling, consisting of basophilic to purple inclusions.
Discussion: Eosinophilic solid and cystic RCC (ESC RCC)shows the characteristic morphology of the case presented here, with often tan, solid, and cystic gross appearance and cells exhibiting eosinophilic, voluminous cytoplasm with granular stippling. The tumors are typically low stage and often show prominent nucleoli. There is frequent CK20 positivity, whereas CK7 is usually negative or only focally positive. Cathepsin-K can be positive, which is also positive in epithelioid AMLs but AMLs are negative for PAX8 while ESC RCC is most frequently positive. ESCs RCC are associated with mutations in the TSC1 gene, with or without association with tuberous sclerosis syndrome. While most patients present with organ confined disease and have a favorable outcome, rare cases of metastatic ESC RCC have been documented.
References:
1. Trpkov K, Hes O, Bonert M, et al. Eosinophilic, solid, and cystic renal cell carcinoma: clinicopathologic study of 16 unique, sporadic neoplasms occurring in women. Am J Surg Pathol. 2016;40:60–71.
2. Trpkov K, Abou-Ouf H, Hes O, Lopez JI, Nesi G, Comperat E, Sibony M, Osunkoya AO, Zhou M, Gokden N, Leroy X, Berney DM, Werneck Cunha I, Musto ML, Athanazio DA, Yilmaz A, Donnelly B, Hyndman E, Gill AJ, McKenney JK, Bismar TA. Eosinophilic Solid and Cystic Renal Cell Carcinoma (ESC RCC): Further Morphologic and Molecular Characterization of ESC RCC as a Distinct Entity. Am J Surg Pathol. 2017 Oct;41(10):1299-1308.
3. Palsgrove DN, Li Y, Pratilas CA, Lin MT, Pallavajjalla A, Gocke C, De Marzo AM, Matoso A, Netto GJ, Epstein JI, Argani P. Eosinophilic Solid and Cystic (ESC) Renal CellCarcinomas Harbor TSC Mutations: Molecular Analysis Supports an Expanding Clinicopathologic Spectrum. Am J Surg Pathol. 2018 Sep;42(9):1166-1181.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur.
Adult male with prostate enlargement (TURP).
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Adult male with prostate enlargement (TURP).
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Histology: These prostate chips show glandular structures with areas of papillary formation lined by columnar pseudostratified epithelium. On high power, the epithelial cells have prominent nucleoli.
Discussion: Ductal adenocarcinoma, also called “prostatic duct adenocarcinoma” is accounts for about 3% of all prostate cancer and is most commonly associated with usual acinar adenocarcinoma but it can be pure in 0.2-0.4% of all prostate cancer cases. Ductal adenocarcinoma is characterized by an epithelial lining that is pseudostratified and columnar. The most common location for this tumor is in the large ducts around the prostatic urethra. Because tumor cells are columnar and tall it was originally described as adenocarcinoma with endometrioid features. While the cells are tall with elongated nuclei, most still show large prominent nucleoli as seen in acinar adenocarcinoma; a minority can have very bland cytology. Architecturally, most ductal adenocarcinomas are characterized by papillary formation and cribriform growth. The cribriform growth in ductal adenocarcinoma differs from the cribriform of usual acinar adenocarcinoma in that the cells in ductal adenocarcinoma still preserve the columnar pseudostratified morphology often with slit-like spaces while the acinar is cuboidal with basally located round nuclei and round lumina.
The differential diagnoses of ductal adenocarcinoma include prostatic urethral polyp, hyperplastic benign glands, urethral villous adenomas, PIN, and cribriform acinar adenocarcinoma. Prostatic urethral polyp is a benign entity most frequently found in transurethral resections and is composed of normal benign prostatic glands without any cytologic atypia or the columnar and pseudostratified organization of epithelial cells (see prostatic urethral lesions chapter). Detached fragments of ductal adenocarcinoma may mimic a prostatic urethral polyp. Benign prostatic glands can show exuberant epithelium, especially around the central zone of the prostate and could pose consideration of ductal adenocarcinoma to the unexperienced eye. However, in prostatic gland hyperplasia the cells are identical to normal benign secretory cells. The differential diagnosis with these benign entities can be easily resolved with the use of immunohistochemistry which will highlight the presence of intact basal cells and lack expression of racemase, contrary to ductal adenocarcinoma.
The differential diagnosis with villous adenoma can be challenging given that the adenomatous changes in a lesion with intestinal differentiation can mimic the cytology of ductal adenocarcinoma of the prostate. Furthermore, adenocarcinoma with intestinal differentiation, either spread from colon and rectum or primary from the urethra, can mimic ductal adenocarcinoma of the prostate. The presence of extracellular mucin will favor villous adenoma or adenocarcinoma from colonic origin, which can be confirmed by positive staining for CDX2 and negative staining for prostate markers in the adenocarcinoma with intestinal differentiation. It is also rare for ductal adenocarcinoma of the prostate to have mucinous goblet cells, in contrast to villous adenoma of the prostatic urethra. One must also be aware that ductal adenocarcinoma of the prostate can rarely express CDX2 such that prostate-specific stains such as NKX3.1, P501S, and PSA should be done to differentiate between the two entities if needed.
The differential diagnosis with PIN can be challenging in cases in which the focus of ductal adenocarcinoma is very small in needle biopsies. The presence of true papillary formation, cribriform architecture or comedo necrosis favors ductal adenocarcinoma. If the entire lesion has basal cells highlighted by immunohistochemistry, that rules out invasive ductal adenocarcinoma but still could be intraductal carcinoma with ductal cytology; the vast majority of these cases have associated invasive ductal adenocarcinoma. Finally, the differential diagnosis with adenocarcinoma with cribriform morphology is based in the lack of papillary formation and the tumor cells with more cuboidal shape instead of elongated as seen in ductal carcinoma. Given the presence of cribriform glands, most cases of ductal adenocarcinoma should be graded as Gleason score 4+4=8 (Grade Group 4). When the ductal adenocarcinoma shows solid areas or necrosis, then Gleason pattern 5 is assigned. Ductal adenocarcinoma is positive for prostate-specific in an analogous fashion to acinar adenocarcinoma, including PSA, NKX3.1 and prostein (p501s). When a PIN4 is performed, approximately 30% of cases will show focal positive staining for HMWCK and/or p63 highlighting basal cells. As noted above, this represents an intraductal component of ductal adenocarcinoma.
References
1. Humphrey PA. Histological variants of prostatic carcinoma and their significance. Histopathology. 2012;60(1):59-74.
2. Bostwick DG, Kindrachuk RW, Rouse RV. Prostatic adenocarcinoma with endometrioid features. Clinical, pathologic, and ultrastructural findings. Am J Surg Pathol. 1985;9(8):595-609.
3. Epstein JI, Woodruff JM. Adenocarcinoma of the prostate with endometrioid features. A light microscopic and immunohistochemical study of ten cases. Cancer. 1986;57(1):111-119.
Incorrect
Correct: D
Histology: These prostate chips show glandular structures with areas of papillary formation lined by columnar pseudostratified epithelium. On high power, the epithelial cells have prominent nucleoli.
Discussion: Ductal adenocarcinoma, also called “prostatic duct adenocarcinoma” is accounts for about 3% of all prostate cancer and is most commonly associated with usual acinar adenocarcinoma but it can be pure in 0.2-0.4% of all prostate cancer cases. Ductal adenocarcinoma is characterized by an epithelial lining that is pseudostratified and columnar. The most common location for this tumor is in the large ducts around the prostatic urethra. Because tumor cells are columnar and tall it was originally described as adenocarcinoma with endometrioid features. While the cells are tall with elongated nuclei, most still show large prominent nucleoli as seen in acinar adenocarcinoma; a minority can have very bland cytology. Architecturally, most ductal adenocarcinomas are characterized by papillary formation and cribriform growth. The cribriform growth in ductal adenocarcinoma differs from the cribriform of usual acinar adenocarcinoma in that the cells in ductal adenocarcinoma still preserve the columnar pseudostratified morphology often with slit-like spaces while the acinar is cuboidal with basally located round nuclei and round lumina.
The differential diagnoses of ductal adenocarcinoma include prostatic urethral polyp, hyperplastic benign glands, urethral villous adenomas, PIN, and cribriform acinar adenocarcinoma. Prostatic urethral polyp is a benign entity most frequently found in transurethral resections and is composed of normal benign prostatic glands without any cytologic atypia or the columnar and pseudostratified organization of epithelial cells (see prostatic urethral lesions chapter). Detached fragments of ductal adenocarcinoma may mimic a prostatic urethral polyp. Benign prostatic glands can show exuberant epithelium, especially around the central zone of the prostate and could pose consideration of ductal adenocarcinoma to the unexperienced eye. However, in prostatic gland hyperplasia the cells are identical to normal benign secretory cells. The differential diagnosis with these benign entities can be easily resolved with the use of immunohistochemistry which will highlight the presence of intact basal cells and lack expression of racemase, contrary to ductal adenocarcinoma.
The differential diagnosis with villous adenoma can be challenging given that the adenomatous changes in a lesion with intestinal differentiation can mimic the cytology of ductal adenocarcinoma of the prostate. Furthermore, adenocarcinoma with intestinal differentiation, either spread from colon and rectum or primary from the urethra, can mimic ductal adenocarcinoma of the prostate. The presence of extracellular mucin will favor villous adenoma or adenocarcinoma from colonic origin, which can be confirmed by positive staining for CDX2 and negative staining for prostate markers in the adenocarcinoma with intestinal differentiation. It is also rare for ductal adenocarcinoma of the prostate to have mucinous goblet cells, in contrast to villous adenoma of the prostatic urethra. One must also be aware that ductal adenocarcinoma of the prostate can rarely express CDX2 such that prostate-specific stains such as NKX3.1, P501S, and PSA should be done to differentiate between the two entities if needed.
The differential diagnosis with PIN can be challenging in cases in which the focus of ductal adenocarcinoma is very small in needle biopsies. The presence of true papillary formation, cribriform architecture or comedo necrosis favors ductal adenocarcinoma. If the entire lesion has basal cells highlighted by immunohistochemistry, that rules out invasive ductal adenocarcinoma but still could be intraductal carcinoma with ductal cytology; the vast majority of these cases have associated invasive ductal adenocarcinoma. Finally, the differential diagnosis with adenocarcinoma with cribriform morphology is based in the lack of papillary formation and the tumor cells with more cuboidal shape instead of elongated as seen in ductal carcinoma. Given the presence of cribriform glands, most cases of ductal adenocarcinoma should be graded as Gleason score 4+4=8 (Grade Group 4). When the ductal adenocarcinoma shows solid areas or necrosis, then Gleason pattern 5 is assigned. Ductal adenocarcinoma is positive for prostate-specific in an analogous fashion to acinar adenocarcinoma, including PSA, NKX3.1 and prostein (p501s). When a PIN4 is performed, approximately 30% of cases will show focal positive staining for HMWCK and/or p63 highlighting basal cells. As noted above, this represents an intraductal component of ductal adenocarcinoma.
References
1. Humphrey PA. Histological variants of prostatic carcinoma and their significance. Histopathology. 2012;60(1):59-74.
2. Bostwick DG, Kindrachuk RW, Rouse RV. Prostatic adenocarcinoma with endometrioid features. Clinical, pathologic, and ultrastructural findings. Am J Surg Pathol. 1985;9(8):595-609.
3. Epstein JI, Woodruff JM. Adenocarcinoma of the prostate with endometrioid features. A light microscopic and immunohistochemical study of ten cases. Cancer. 1986;57(1):111-119.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur.
Adrenal mass in a 20 yo female.
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Adrenal mass in a 20 yo female.
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Correct: C
Histology: This is an adrenal neoplasia that measured 12 cm in size and is composed of cords and sheets of epithelial cells with eosinophilic cytoplasm. There is mild nuclear pleomorphisms and mitoses are not frequent. Necrosis or vein invasion are not seen.
Discussion: Adrenocortical neoplasms are sometimes difficult to classify into benign or malignant and the Weiss criteria has been establish to predict malignant behavior.
Original Weiss criteria for malignancy, modified as indicated below, requires 3+ of these factors:
– Nuclear grade III or IV based on Fuhrman criteria
– > 5 mitotic figures/50 HPF (40x objective), counting 10 random fields in area of greatest number of mitotic figures on 5 slides with greatest number of mitoses
– Presence of atypical mitotic figures (abnormal distribution of chromosomes or excessive number of mitotic spindles)
– Clear or vacuolated cells comprising 25% or less of tumor
– Diffuse architecture (more than 1/3 of tumor forms patternless sheets of cells; trabecular, cord, columnar, alveolar or nesting pattern is not considered to be diffuse)
– Microscopic necrosis
– Venous invasion (veins must have smooth muscle in wall; tumor cell clusters or sheets forming polypoid projections into vessel lumen or polypoid tumor thrombi covered by endothelial layer)
– Sinusoidal invasion (sinusoid is endothelial lined vessel in adrenal gland with little supportive tissue; consider only sinusoids within tumor)
– Capsular invasion (nests or cords of tumor extending into or through capsule with a stromal reaction); either incomplete or complete
– Each criterion is scored 0 when absent and 1 when present in the tumor
Modified Weiss criteria:
– Mitotic rate > 5 per 50 high power fields
– Cytoplasm (clear cells comprising 25% or less of the tumor)
– Abnormal mitoses
– Necrosis
– Capsular invasion
– Calculate: 2x mitotic rate criterion + 2x clear cytoplasm criterion + abnormal mitoses + necrosis + capsular invasion (score of 3 or more suggests malignancy)
This criteria does not apply to neoplasms in children and oncocytic (eosinophilic) tumors. Because eosinophilia of more than 70% is a criterium in both original and modified, an oncocytic tumor will score points even when completely benign. In those situations, Ki67 can be helpful and more than 5% correlates with malignant behavior, although by itself, Ki67 is not used to render a diagnosis of malignancy. Below is the diagnostic criteria for oncocytic adrenocortical neoplasms.
Lin–Weiss–Bisceglia (LWB) system for diagnostic categorization of oncocytic adrenocortical neoplasms:
Major criteria:
– Mitotic count >5 per 50 high-power fields
– Atypical mitoses
– Venous invasion
Minor criteria:
– Size >10 cm and/or weight >200 g
– Necrosis
– Sinusoidal invasion
– Capsular invasion
The presence of one major criterion indicates malignancy, one to four minor criteria present indicates uncertain malignant potential, and the absence of all major and minor criteria is indicative of benign biological behavior
References:
– Am J Surg Pathol 2002; 26:1612
– Am J Surg Pathol 1984; 8:163
Incorrect
Correct: C
Histology: This is an adrenal neoplasia that measured 12 cm in size and is composed of cords and sheets of epithelial cells with eosinophilic cytoplasm. There is mild nuclear pleomorphisms and mitoses are not frequent. Necrosis or vein invasion are not seen.
Discussion: Adrenocortical neoplasms are sometimes difficult to classify into benign or malignant and the Weiss criteria has been establish to predict malignant behavior.
Original Weiss criteria for malignancy, modified as indicated below, requires 3+ of these factors:
– Nuclear grade III or IV based on Fuhrman criteria
– > 5 mitotic figures/50 HPF (40x objective), counting 10 random fields in area of greatest number of mitotic figures on 5 slides with greatest number of mitoses
– Presence of atypical mitotic figures (abnormal distribution of chromosomes or excessive number of mitotic spindles)
– Clear or vacuolated cells comprising 25% or less of tumor
– Diffuse architecture (more than 1/3 of tumor forms patternless sheets of cells; trabecular, cord, columnar, alveolar or nesting pattern is not considered to be diffuse)
– Microscopic necrosis
– Venous invasion (veins must have smooth muscle in wall; tumor cell clusters or sheets forming polypoid projections into vessel lumen or polypoid tumor thrombi covered by endothelial layer)
– Sinusoidal invasion (sinusoid is endothelial lined vessel in adrenal gland with little supportive tissue; consider only sinusoids within tumor)
– Capsular invasion (nests or cords of tumor extending into or through capsule with a stromal reaction); either incomplete or complete
– Each criterion is scored 0 when absent and 1 when present in the tumor
Modified Weiss criteria:
– Mitotic rate > 5 per 50 high power fields
– Cytoplasm (clear cells comprising 25% or less of the tumor)
– Abnormal mitoses
– Necrosis
– Capsular invasion
– Calculate: 2x mitotic rate criterion + 2x clear cytoplasm criterion + abnormal mitoses + necrosis + capsular invasion (score of 3 or more suggests malignancy)
This criteria does not apply to neoplasms in children and oncocytic (eosinophilic) tumors. Because eosinophilia of more than 70% is a criterium in both original and modified, an oncocytic tumor will score points even when completely benign. In those situations, Ki67 can be helpful and more than 5% correlates with malignant behavior, although by itself, Ki67 is not used to render a diagnosis of malignancy. Below is the diagnostic criteria for oncocytic adrenocortical neoplasms.
Lin–Weiss–Bisceglia (LWB) system for diagnostic categorization of oncocytic adrenocortical neoplasms:
Major criteria:
– Mitotic count >5 per 50 high-power fields
– Atypical mitoses
– Venous invasion
Minor criteria:
– Size >10 cm and/or weight >200 g
– Necrosis
– Sinusoidal invasion
– Capsular invasion
The presence of one major criterion indicates malignancy, one to four minor criteria present indicates uncertain malignant potential, and the absence of all major and minor criteria is indicative of benign biological behavior
References:
– Am J Surg Pathol 2002; 26:1612
– Am J Surg Pathol 1984; 8:163
Presented by Dr. Jonathan Epstein and prepared by Dr. Harsimar Kaur.
A 53 year-old female underwent a radical nephrectomy for a 7.3 cm renal mass.
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A 53 year-old female underwent a radical nephrectomy for a 7.3 cm renal mass.
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Answer: B
Histological Description: There are two slides. The one where there is an adjacent adrenal gland, there is usual chromophobe RCC with raisenoid nuclei with irregular, wrinkled, notched nuclear membrane and perinuclear halos. The cells have a relatively low nuclear to cytoplasmic ratio. Some of the cells have degenerative atypia. This area of the tumor lacks necrosis. There are very infrequent mitotic figures and lacks atypical mitotic figures. On the other slide, the tumor shows increased cellularity, cells with higher nuclear to cytoplasmic ratio, and focal necrosis. There are increased mitotic figures along with atypical mitotic figures. There is extensive extra-renal extension with multiple foci of vascular invasion.
Discussion: On the first slide, the findings are typical of usual Chromophobe RCC, which is not assigned a grade. We add the following note in these cases: “Chromophobe renal cell carcinoma is a well-defined variant that has a significantly better prognosis than conventional (clear cell) carcinoma. While chromophobe renal carcinomas are frequently large (mean diameter was 9.0 cm in one study), two-thirds of them are confined to the kidney at the time of diagnosis. While many of these tumors qualify as Fuhrman (ISUP) nuclear grade 3, the Fuhrman (ISUP) nuclear grading system does not accurately reflect their prognosis. In general, patients with stage pT1 and pT2 chromophobe tumors are almost always cured by surgery, while presentation with pT3 or pT4 disease is rare. Consequently, it is not recommended to assign a Fuhrman (ISUP) nuclear grade to chromophobe renal cell carcinomas (Delahunt B, et al. Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. Am J Surg Pathol, 2007 Jun;31(6):957-60.)” There are a minority of Chromophobe RCCs that are overtly high grade, as in this case. There is no accepted grading system for these cases, and it is appropriate to just diagnose them as “high grade Chromophobe RCC.” The other more common scenario of aggressive chromophobe RCC is when there is a sarcomatoid component, which is assigned Grade 4 based on the sarcomatoid component.
Incorrect
Answer: B
Histological Description: There are two slides. The one where there is an adjacent adrenal gland, there is usual chromophobe RCC with raisenoid nuclei with irregular, wrinkled, notched nuclear membrane and perinuclear halos. The cells have a relatively low nuclear to cytoplasmic ratio. Some of the cells have degenerative atypia. This area of the tumor lacks necrosis. There are very infrequent mitotic figures and lacks atypical mitotic figures. On the other slide, the tumor shows increased cellularity, cells with higher nuclear to cytoplasmic ratio, and focal necrosis. There are increased mitotic figures along with atypical mitotic figures. There is extensive extra-renal extension with multiple foci of vascular invasion.
Discussion: On the first slide, the findings are typical of usual Chromophobe RCC, which is not assigned a grade. We add the following note in these cases: “Chromophobe renal cell carcinoma is a well-defined variant that has a significantly better prognosis than conventional (clear cell) carcinoma. While chromophobe renal carcinomas are frequently large (mean diameter was 9.0 cm in one study), two-thirds of them are confined to the kidney at the time of diagnosis. While many of these tumors qualify as Fuhrman (ISUP) nuclear grade 3, the Fuhrman (ISUP) nuclear grading system does not accurately reflect their prognosis. In general, patients with stage pT1 and pT2 chromophobe tumors are almost always cured by surgery, while presentation with pT3 or pT4 disease is rare. Consequently, it is not recommended to assign a Fuhrman (ISUP) nuclear grade to chromophobe renal cell carcinomas (Delahunt B, et al. Fuhrman grading is not appropriate for chromophobe renal cell carcinoma. Am J Surg Pathol, 2007 Jun;31(6):957-60.)” There are a minority of Chromophobe RCCs that are overtly high grade, as in this case. There is no accepted grading system for these cases, and it is appropriate to just diagnose them as “high grade Chromophobe RCC.” The other more common scenario of aggressive chromophobe RCC is when there is a sarcomatoid component, which is assigned Grade 4 based on the sarcomatoid component.
Presented by Dr. Jonathan Epstein and prepared by Dr. Harsimar Kaur.
A 68 year old man underwent a partial nephrectomy for a 2 cm renal mass.
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A 68 year old man underwent a partial nephrectomy for a 2 cm renal mass.
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Answer: A
Histological Description: The lesion is well-circumscribed. The vast majority of the lesion is composed to hemorrhage and fibrin with scattered benign vascular channels. Focally, there are individual cells, clusters of 2-3 cells, or rows of cells with small round dark lymphocyte-like nuclei surrounded by a clear space.
Discussion: Rarely, clear cell renal cell carcinoma can be very pauci-cellular mimicking a hemangioma or just a clot. The key is to first recognize that when there is a circumscribed lesion with fibrin, the vast majority of the time it represents renal cell carcinoma. Then one has to look for areas of increased cellularity at low magnification, which on closer inspection has the lymphocyte-nuclei in clusters surrounded by clear spaces. As was done in the case, the diagnosis is confirmed with positive stains in these cells for keratin AE1/3, PAX8, and CAIX.
Reference: Kryvenko ON, ROquero L, Gupta NS. Low-grade clear cell renal cell carcinoma mimicking hemangioma of the kidney: A series of 4 cases. Arch Pathol Lab Med 2013: 137: 251-4.
Incorrect
Answer: A
Histological Description: The lesion is well-circumscribed. The vast majority of the lesion is composed to hemorrhage and fibrin with scattered benign vascular channels. Focally, there are individual cells, clusters of 2-3 cells, or rows of cells with small round dark lymphocyte-like nuclei surrounded by a clear space.
Discussion: Rarely, clear cell renal cell carcinoma can be very pauci-cellular mimicking a hemangioma or just a clot. The key is to first recognize that when there is a circumscribed lesion with fibrin, the vast majority of the time it represents renal cell carcinoma. Then one has to look for areas of increased cellularity at low magnification, which on closer inspection has the lymphocyte-nuclei in clusters surrounded by clear spaces. As was done in the case, the diagnosis is confirmed with positive stains in these cells for keratin AE1/3, PAX8, and CAIX.
Reference: Kryvenko ON, ROquero L, Gupta NS. Low-grade clear cell renal cell carcinoma mimicking hemangioma of the kidney: A series of 4 cases. Arch Pathol Lab Med 2013: 137: 251-4.
Presented by Dr. Jonathan Epstein and prepared by Dr. Harsimar Kaur.
A 55 year-old man underwent a TURB for a polypoid lesion in the bladder.
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A 55 year-old man underwent a TURB for a polypoid lesion in the bladder.
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Answer: B
Histological Description: The tumor consists predominantly of anastomosing thin columns of urothelium extending into the lamina propria. In some areas there is continuity with the surface but in most there is not. The periphery of the columns are lined by cells with a palisading appearance with cells streaming parallel to the basement membrane in center of nests. There is no cytological atypia and mitotic figures rare and when present only at the periphery of columns. Focally, there is an exophytic papillary component, where the lining is the same as the rest of the lesion. There is cyst formation filled with eosinophilic secretions common with intervening stroma lacking inflammation.
Discussion: The morphology of >95% of the lesion is typical of inverted papilloma. What makes this case somewhat unusual and more difficult is that there are rare exophytic papillary fronds raising the possibility of a low grade papillary urothelial carcinoma or PUNLMP with an inverted growth pattern. As long as the cytology in the fronds are identical to the rest of the lesion, and the lesion is otherwise classical for inverted papilloma, the diagnosis remain inverted papilloma. There is no risk of recurrence, and no risk of progression to urothelial carcinoma.
Incorrect
Answer: B
Histological Description: The tumor consists predominantly of anastomosing thin columns of urothelium extending into the lamina propria. In some areas there is continuity with the surface but in most there is not. The periphery of the columns are lined by cells with a palisading appearance with cells streaming parallel to the basement membrane in center of nests. There is no cytological atypia and mitotic figures rare and when present only at the periphery of columns. Focally, there is an exophytic papillary component, where the lining is the same as the rest of the lesion. There is cyst formation filled with eosinophilic secretions common with intervening stroma lacking inflammation.
Discussion: The morphology of >95% of the lesion is typical of inverted papilloma. What makes this case somewhat unusual and more difficult is that there are rare exophytic papillary fronds raising the possibility of a low grade papillary urothelial carcinoma or PUNLMP with an inverted growth pattern. As long as the cytology in the fronds are identical to the rest of the lesion, and the lesion is otherwise classical for inverted papilloma, the diagnosis remain inverted papilloma. There is no risk of recurrence, and no risk of progression to urothelial carcinoma.
Presented by Dr. Pedram Argani, M.D. and prepared by Dr. Harsimar Kaur, M.B.B.S.
This is a 56 year old female with a renal mass.
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This is a 56 year old female with a renal mass.
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Answer: C
Histologic Description: This is a multicystic lesion that appears fairly well delineated but at its periphery intermingles with the native renal tubules. These cysts are surrounded by a cellular, “ovarian-like” stroma associated with ropy collagen. The lining cells are bland and sometimes hobnailed, consistent with collecting duct epithelium. These stromal cells label for estrogen receptor and inhibin. These are the typical features of mixed epithelial stromal tumor.
Differential Diagnosis: Angiomyolipoma with epithelial cysts would demonstrate three layers; a peripheral stroma rich angiomyolipoma component, a subepithelial blue cell component that resembles endometrial stroma, and entrapped native renal tubules with a frequently hobnailed appearance. The stromal predominant angiomyolipoma component resembles smooth muscle but has shorter fascicles, clearer cytoplasm, and a prominent lymphatic investment. AMLEC would label for melanocytic markers like HMB45. Tubulocystic carcinoma features an elastotic stroma and numerous small cysts, giving rise to a “bubble wrap” gross appearance. The lining cells have a hobnail appearance but demonstrate greater cytologic atypia and nuclear irregularities. Multilocular clear cell renal neoplasm of low malignant potential is also exclusively cystic, but there are characteristically small clusters of clear cells within the septa that do not form expansile nodules.
Incorrect
Answer: C
Histologic Description: This is a multicystic lesion that appears fairly well delineated but at its periphery intermingles with the native renal tubules. These cysts are surrounded by a cellular, “ovarian-like” stroma associated with ropy collagen. The lining cells are bland and sometimes hobnailed, consistent with collecting duct epithelium. These stromal cells label for estrogen receptor and inhibin. These are the typical features of mixed epithelial stromal tumor.
Differential Diagnosis: Angiomyolipoma with epithelial cysts would demonstrate three layers; a peripheral stroma rich angiomyolipoma component, a subepithelial blue cell component that resembles endometrial stroma, and entrapped native renal tubules with a frequently hobnailed appearance. The stromal predominant angiomyolipoma component resembles smooth muscle but has shorter fascicles, clearer cytoplasm, and a prominent lymphatic investment. AMLEC would label for melanocytic markers like HMB45. Tubulocystic carcinoma features an elastotic stroma and numerous small cysts, giving rise to a “bubble wrap” gross appearance. The lining cells have a hobnail appearance but demonstrate greater cytologic atypia and nuclear irregularities. Multilocular clear cell renal neoplasm of low malignant potential is also exclusively cystic, but there are characteristically small clusters of clear cells within the septa that do not form expansile nodules.
Presented by Dr. Pedram Argani, M.D. and prepared by Dr. Harsimar Kaur, M.B.B.S.
This is a 20 year old female with a renal mass.
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This is a 56 year old female with a renal mass.
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Answer: B
Histologic Description: The kidney is overtaken by a small round blue cell tumor. The neoplastic cells have sheet like growth pattern, and are non-pleomorphic small round blue cells that focally seem to form rosettes. The neoplastic cells demonstrate nuclear labeling for NKX2.2 and membranous labeling for CD99, and demonstrated an EWSR1-ERG gene fusion.
Differential Diagnosis: In this age group, a primary Ewing sarcoma would be more common than a blastemal Wilms tumor. The latter would demonstrate nuclear molding, would not show membranous labeling for CD99, and lacks the typical gene fusions of Ewing sarcoma. Neuroblastoma would be a stronger consideration in a patient under the age of 1. Neuroblastoma may grow into the kidney from the adjacent adrenal gland or sympathetic ganglion, mimicking a primary renal neoplasm. Neuroblastoma would label for PHOX2B and not for CD99, and typically would demonstrate elevated serum and urine catecholamines. Poorly differentiated synovial sarcoma may, in areas, be morphologically indistinguishable from Ewing sarcoma; this is why some of these cases were mistakenly included in prior protocols for Ewing sarcoma. Synovial sarcoma would not label for NKX2.2 but would demonstrate labeling for TLE1, and is characterized by an t(X;18) translocation fusing the SS18 with the SSX1 or SSX2 genes.
Incorrect
Answer: B
Histologic Description: The kidney is overtaken by a small round blue cell tumor. The neoplastic cells have sheet like growth pattern, and are non-pleomorphic small round blue cells that focally seem to form rosettes. The neoplastic cells demonstrate nuclear labeling for NKX2.2 and membranous labeling for CD99, and demonstrated an EWSR1-ERG gene fusion.
Differential Diagnosis: In this age group, a primary Ewing sarcoma would be more common than a blastemal Wilms tumor. The latter would demonstrate nuclear molding, would not show membranous labeling for CD99, and lacks the typical gene fusions of Ewing sarcoma. Neuroblastoma would be a stronger consideration in a patient under the age of 1. Neuroblastoma may grow into the kidney from the adjacent adrenal gland or sympathetic ganglion, mimicking a primary renal neoplasm. Neuroblastoma would label for PHOX2B and not for CD99, and typically would demonstrate elevated serum and urine catecholamines. Poorly differentiated synovial sarcoma may, in areas, be morphologically indistinguishable from Ewing sarcoma; this is why some of these cases were mistakenly included in prior protocols for Ewing sarcoma. Synovial sarcoma would not label for NKX2.2 but would demonstrate labeling for TLE1, and is characterized by an t(X;18) translocation fusing the SS18 with the SSX1 or SSX2 genes.
Presented by Dr. Pedram Argani, M.D. and prepared by Dr. Harsimar Kaur, M.B.B.S.
This is a 63 year old male with a gastric mass that is cytokeratin negative and CD117 negative.
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This is a 63 year old male with a gastric mass that is cytokeratin negative and CD117 negative.
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Histologic Description: This is a myxoid lesion featuring epithelioid cells that have focally vacuolated cytoplasm. The neoplastic cells were negative for keratin, desmin, S100, and HMB45. The morphology was suggestive of gastrointestinal stromal tumor (GIST) but the CD117 stain being negative initially argued against this possibility. However, the neoplastic cells were diffusely positive for DOG1. Sequencing revealed a PDGFRA mutation. GISTs with the PDGFRA mutations often are epithelioid, have vacuolated cytoplasm and myxoid stroma, and are CD117 negative.
Differential Diagnosis: Myxoid liposarcoma would demonstrate a branching capillary vasculature as well as lipoblastic cells, and would be characterized by a t(12;16) translocation fusing the FUS gene with DDIT3. Low-grade fibromyxoid sarcoma may involve the gastrointestinal tract; however, these lesions are typically more fibrous than myxoid, and are composed of bland spindled cells. They demonstrate diffuse labeling for MUC4, and demonstrate fusions of either FUS or EWSR1 with CREB3L1 or CREB3L2. Myxoid melanoma would demonstrated immunoreactivity for S100 and HMB45, and typically demonstrate more pleomorphic cells.
Incorrect
Histologic Description: This is a myxoid lesion featuring epithelioid cells that have focally vacuolated cytoplasm. The neoplastic cells were negative for keratin, desmin, S100, and HMB45. The morphology was suggestive of gastrointestinal stromal tumor (GIST) but the CD117 stain being negative initially argued against this possibility. However, the neoplastic cells were diffusely positive for DOG1. Sequencing revealed a PDGFRA mutation. GISTs with the PDGFRA mutations often are epithelioid, have vacuolated cytoplasm and myxoid stroma, and are CD117 negative.
Differential Diagnosis: Myxoid liposarcoma would demonstrate a branching capillary vasculature as well as lipoblastic cells, and would be characterized by a t(12;16) translocation fusing the FUS gene with DDIT3. Low-grade fibromyxoid sarcoma may involve the gastrointestinal tract; however, these lesions are typically more fibrous than myxoid, and are composed of bland spindled cells. They demonstrate diffuse labeling for MUC4, and demonstrate fusions of either FUS or EWSR1 with CREB3L1 or CREB3L2. Myxoid melanoma would demonstrated immunoreactivity for S100 and HMB45, and typically demonstrate more pleomorphic cells.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur.
Adult female with kidney tumor.
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Adult female with kidney tumor.
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Histology: This is a biphasic tumor composed of solid stromal areas and cystic structures lined by cuboidal epithelium with areas with hobnailed appearance.
Discussion: Cystic nephroma (CN) and mixed epithelial and stromal tumors (MEST) are considered morphologic spectrums of the same lesion. Tumors that are composed entirely of cysts and cysts sepate without any solid expansile areas or mural nodules are called CN. Tumors with variable amounts of solid components are called MEST. There is a marked female predominance and tumors frequently express ER and PR in the mesenchymal cells. They are most commonly benign, well circumscribed and located near the hilum. Features of malignancy include irregular border, high cellularity, cytologic atypia and frequent mitoses. Immunohistochemistry highlights ER and PR in stromal cells and inhibin or calretinin in both epithelial cells and stromal cells.
References:
1. Chuang CK, Pan PY, Kao Y, Chou YC, Ng KF, Wang LJ, Tsai HY, Lee KH. Mixed epithelial stromal tumor of the kidney: The male case and literature review. Urol Case Rep. 2018 Jan 31;17:122-124.
Incorrect
Histology: This is a biphasic tumor composed of solid stromal areas and cystic structures lined by cuboidal epithelium with areas with hobnailed appearance.
Discussion: Cystic nephroma (CN) and mixed epithelial and stromal tumors (MEST) are considered morphologic spectrums of the same lesion. Tumors that are composed entirely of cysts and cysts sepate without any solid expansile areas or mural nodules are called CN. Tumors with variable amounts of solid components are called MEST. There is a marked female predominance and tumors frequently express ER and PR in the mesenchymal cells. They are most commonly benign, well circumscribed and located near the hilum. Features of malignancy include irregular border, high cellularity, cytologic atypia and frequent mitoses. Immunohistochemistry highlights ER and PR in stromal cells and inhibin or calretinin in both epithelial cells and stromal cells.
References:
1. Chuang CK, Pan PY, Kao Y, Chou YC, Ng KF, Wang LJ, Tsai HY, Lee KH. Mixed epithelial stromal tumor of the kidney: The male case and literature review. Urol Case Rep. 2018 Jan 31;17:122-124.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
30-year-old male with testicular mass.
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30-year-old male with testicular mass.
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Histology: There is a diffuse population of cells with clear cytoplasm separated by fibrous septae with prominent lymphocytic infiltration. There are cystic structures lined by cuboidal cells.
Discussion: Seminomas involving the rete testis can provoke cystic change or hyperplastic change in the rete testis epithelium and mimic a yolk sac tumor. This case demonstrates complete invasion of the rete and extension into the hilar soft tissue. Invasion of the hilum soft tissue is considered pT2, as is vascular invasion. Patients with a pT2 (but not pT1) tumor are considered for adjuvant chemotherapy to prevent recurrence, even if the retroperitoneal lymph nodes are not enlarged. Recognition of invasion of the rete testis is critical because the hilum is the area in which the tumor spreads outside of the testis most frequently.
References:
1. Fontes-Sousa M, Lobo J, Magalhães H, Cassis J, Malheiro M, Ramos S, Henrique R, Martins A, Maurício MJ. Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification. BMC Urol. 2020 Aug 20;20(1):127.
2. Cohn-Cedermark G, Stahl O, Tandstad T; SWENOTECA. Surveillance vs. adjuvant therapy of clinical stage I testicular tumors – a review and the SWENOTECA experience. Andrology. 2015 Jan;3(1):102-10.
Incorrect
Histology: There is a diffuse population of cells with clear cytoplasm separated by fibrous septae with prominent lymphocytic infiltration. There are cystic structures lined by cuboidal cells.
Discussion: Seminomas involving the rete testis can provoke cystic change or hyperplastic change in the rete testis epithelium and mimic a yolk sac tumor. This case demonstrates complete invasion of the rete and extension into the hilar soft tissue. Invasion of the hilum soft tissue is considered pT2, as is vascular invasion. Patients with a pT2 (but not pT1) tumor are considered for adjuvant chemotherapy to prevent recurrence, even if the retroperitoneal lymph nodes are not enlarged. Recognition of invasion of the rete testis is critical because the hilum is the area in which the tumor spreads outside of the testis most frequently.
References:
1. Fontes-Sousa M, Lobo J, Magalhães H, Cassis J, Malheiro M, Ramos S, Henrique R, Martins A, Maurício MJ. Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification. BMC Urol. 2020 Aug 20;20(1):127.
2. Cohn-Cedermark G, Stahl O, Tandstad T; SWENOTECA. Surveillance vs. adjuvant therapy of clinical stage I testicular tumors – a review and the SWENOTECA experience. Andrology. 2015 Jan;3(1):102-10.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur.
Renal mass in a 70-year-old female.
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Renal mass in a 70-year-old female.
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Histology: This is a predominantly cystic mass with areas of small solid tumor nests composed with clear cells. There are occasional papillary structures and psammomatous calcifications.
Discussion: The combination of papillary structures, lined by clear cells and associated psammomatous calcifications is a morphologic clue to translocation RCC. While translocation RCC are more predominant in children and adults under the age of 35 year, they can occur at any age. Translocation Xp11.2 RCC are usually negative or focally positive for cytokeratin stains and for CAIX while they exhibit nuclear expression of TFE3 and can be confirmed by FISH.
References:
1. Argani P, Zhong M, Reuter VE, et al. TFE3-Fusion Variant Analysis Defines Specific Clinicopathologic Associations Among Xp11 Translocation Cancers. Am J Surg Pathol. 2016;40:723-737.
2. Argani P, Lal P, Hutchinson B, et al. Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol. 2003;27:750-761.
Incorrect
Histology: This is a predominantly cystic mass with areas of small solid tumor nests composed with clear cells. There are occasional papillary structures and psammomatous calcifications.
Discussion: The combination of papillary structures, lined by clear cells and associated psammomatous calcifications is a morphologic clue to translocation RCC. While translocation RCC are more predominant in children and adults under the age of 35 year, they can occur at any age. Translocation Xp11.2 RCC are usually negative or focally positive for cytokeratin stains and for CAIX while they exhibit nuclear expression of TFE3 and can be confirmed by FISH.
References:
1. Argani P, Zhong M, Reuter VE, et al. TFE3-Fusion Variant Analysis Defines Specific Clinicopathologic Associations Among Xp11 Translocation Cancers. Am J Surg Pathol. 2016;40:723-737.
2. Argani P, Lal P, Hutchinson B, et al. Aberrant nuclear immunoreactivity for TFE3 in neoplasms with TFE3 gene fusions: a sensitive and specific immunohistochemical assay. Am J Surg Pathol. 2003;27:750-761.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
34 yo male with hydrocele.
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34 yo male with hydrocele.
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Correct answer: C.
Histology: The fibrous wall of this hydrocele sac is hyalinized and thickened and smal tubules or clusters of epithelioid cells arranged linearly and paralell to the mesothelial surface.
Discussion: The tunica vaginalis is an embryologically derived mesothelium-lined outpouching of the peritoneal cavity, which may develop neoplastic mesothelial proliferations similar to pleural or peritoneal surfaces. In contrast to the normal tunica consisting of a thin fibrous wall lined by a monolayer of flattened bland mesothelium and no significant inflammation, this case is characterized by background changes of fibroblastic organization and stromal chronic inflammation. The mesothelial proliferation within the fibrous stroma consists of linear arrays of widely spaced horizontally elongated tubules and small solid nests and cords that were well spaced apart. The entrapment of isolated mesothelial clusters within deep fibrous tissue may be the cause of significant diagnostic difficulty. However, morphologic clues such as linear arraying of widely spaced architecturally simple cell clusters that may aid in the correct identification of the benignity of these proliferations.
References:
1. Lee S, Illei PB, Han JS, Epstein JI. Florid mesothelial hyperplasia of the tunica vaginalis mimicking malignant mesothelioma: a clinicopathologic study of 12 cases. Am J Surg Pathol. 2014 Jan;38(1):54-9.
Incorrect
Correct answer: C.
Histology: The fibrous wall of this hydrocele sac is hyalinized and thickened and smal tubules or clusters of epithelioid cells arranged linearly and paralell to the mesothelial surface.
Discussion: The tunica vaginalis is an embryologically derived mesothelium-lined outpouching of the peritoneal cavity, which may develop neoplastic mesothelial proliferations similar to pleural or peritoneal surfaces. In contrast to the normal tunica consisting of a thin fibrous wall lined by a monolayer of flattened bland mesothelium and no significant inflammation, this case is characterized by background changes of fibroblastic organization and stromal chronic inflammation. The mesothelial proliferation within the fibrous stroma consists of linear arrays of widely spaced horizontally elongated tubules and small solid nests and cords that were well spaced apart. The entrapment of isolated mesothelial clusters within deep fibrous tissue may be the cause of significant diagnostic difficulty. However, morphologic clues such as linear arraying of widely spaced architecturally simple cell clusters that may aid in the correct identification of the benignity of these proliferations.
References:
1. Lee S, Illei PB, Han JS, Epstein JI. Florid mesothelial hyperplasia of the tunica vaginalis mimicking malignant mesothelioma: a clinicopathologic study of 12 cases. Am J Surg Pathol. 2014 Jan;38(1):54-9.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
55 yo male bladder neck tumor presenting with hematuria
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55 yo male bladder neck tumor presenting with hematuria
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Correct answer: C
Histology: Polypoid fragments of tissue lined by normal urothelium and underlying clusters of urothelial nests and prostatic glands surrounded by loose bland cellular stroma.
Discussion: Fibroepithelial polyps (FEPs) of the urinary tract are rare with most cases reported in children. Clinical symptoms were hematuria, urinary urgency, and hesitancy, all related to lower urinary tract obstruction. Most lesions are located near the verumontanum or the bladder neck. Histologically, they are lined by normal-appearing urothelium. There are three architectural patterns. The most common pattern (seen in this case) consists of a polypoid mass with club-like projections resembling a cloverleaf with florid cystitis cystica et glandularis. The second pattern consists of a papillary tumor composed of numerous small, rounded fibrovascular cores containing dense fibrous tissue. The last morphologic pattern consists of a polypoid lesion with secondary tall finger-like projections. FEPs lack prominent edema and inflammation seen in polypoid cystitis and contain broader stalks with dense fibrous tissue, in contrast to the thin delicate loose fibroconnective tissue seen in the stalk of papillomas. Occasionally, some lesions may contained atypical degenerative-appearing stromal cells. Because FEPs in adults are rare, some of these cases can be misdiagnosed as urothelial neoplasms or reactive conditions. Recognition of the precise histologic features can facilitate its correct diagnosis.
Reference:
1. Tsuzuki T, Epstein JI. Fibroepithelial polyp of the lower urinary tract in adults. Am J Surg Pathol. 2005 Apr;29(4):460-6.
Incorrect
Correct answer: C
Histology: Polypoid fragments of tissue lined by normal urothelium and underlying clusters of urothelial nests and prostatic glands surrounded by loose bland cellular stroma.
Discussion: Fibroepithelial polyps (FEPs) of the urinary tract are rare with most cases reported in children. Clinical symptoms were hematuria, urinary urgency, and hesitancy, all related to lower urinary tract obstruction. Most lesions are located near the verumontanum or the bladder neck. Histologically, they are lined by normal-appearing urothelium. There are three architectural patterns. The most common pattern (seen in this case) consists of a polypoid mass with club-like projections resembling a cloverleaf with florid cystitis cystica et glandularis. The second pattern consists of a papillary tumor composed of numerous small, rounded fibrovascular cores containing dense fibrous tissue. The last morphologic pattern consists of a polypoid lesion with secondary tall finger-like projections. FEPs lack prominent edema and inflammation seen in polypoid cystitis and contain broader stalks with dense fibrous tissue, in contrast to the thin delicate loose fibroconnective tissue seen in the stalk of papillomas. Occasionally, some lesions may contained atypical degenerative-appearing stromal cells. Because FEPs in adults are rare, some of these cases can be misdiagnosed as urothelial neoplasms or reactive conditions. Recognition of the precise histologic features can facilitate its correct diagnosis.
Reference:
1. Tsuzuki T, Epstein JI. Fibroepithelial polyp of the lower urinary tract in adults. Am J Surg Pathol. 2005 Apr;29(4):460-6.
Presented by Dr. Andres Matoso and prepared by Dr. Harsimar Kaur
56 yo Male with bladder neck tumor.
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56 yo Male with bladder neck tumor.
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Correct answer B.
Histology: Low power view shows bladder mucosa with nests of urothelium with central lumina and areas with intestinal differentiation and mucin extravasation. There is no dysplasia or invasion into the muscularis propria.
Discussion: Intestinal (mucinous) metaplasia (IM), or metaplastic replacement of urothelium by intestinal type epithelium, is an uncommon finding in the urinary bladder. It is far less common than cystitis cystica et glandularis, which is a benign condition usually related to inflammation or infection. Occasionally, both cystitis cystica et glandularis (CCG) and intestinal metaplasia coexist in the same patient/specimen. When the epithelium manifests colonic phenotype with goblet cell metaplasia, it also acquires an intestinal immunoprofile and may show dysplasia or adenocarcinoma.1 It is controversial if IM acts as a precursor of malignancy in the urinary system. IM can show mucin extravasation but that does not equal malignancy. In contrast to IM, well differentiated mucinous adenocarcinoma shows an irregular invasive frond, may involve the detrusor muscle and the strips of epithelium show dark dysplastic nuclei.
References:
1. Clouston D, Lawrentschuk N. Metaplastic conditions of the bladder. BJU Int. 2013;112 Suppl 2:27-31.
2. Xin Z, Zhao C, Huang T, et al. Intestinal metaplasia of the bladder in 89 patients: a study with emphasis on long-term outcome. BMC Urol. 2016;16:24.
3. Gordetsky J, Epstein JI. Intestinal metaplasia of the bladder with dysplasia: a risk factor for carcinoma? Histopathology. 2015;67:325-330.
Incorrect
Correct answer B.
Histology: Low power view shows bladder mucosa with nests of urothelium with central lumina and areas with intestinal differentiation and mucin extravasation. There is no dysplasia or invasion into the muscularis propria.
Discussion: Intestinal (mucinous) metaplasia (IM), or metaplastic replacement of urothelium by intestinal type epithelium, is an uncommon finding in the urinary bladder. It is far less common than cystitis cystica et glandularis, which is a benign condition usually related to inflammation or infection. Occasionally, both cystitis cystica et glandularis (CCG) and intestinal metaplasia coexist in the same patient/specimen. When the epithelium manifests colonic phenotype with goblet cell metaplasia, it also acquires an intestinal immunoprofile and may show dysplasia or adenocarcinoma.1 It is controversial if IM acts as a precursor of malignancy in the urinary system. IM can show mucin extravasation but that does not equal malignancy. In contrast to IM, well differentiated mucinous adenocarcinoma shows an irregular invasive frond, may involve the detrusor muscle and the strips of epithelium show dark dysplastic nuclei.
References:
1. Clouston D, Lawrentschuk N. Metaplastic conditions of the bladder. BJU Int. 2013;112 Suppl 2:27-31.
2. Xin Z, Zhao C, Huang T, et al. Intestinal metaplasia of the bladder in 89 patients: a study with emphasis on long-term outcome. BMC Urol. 2016;16:24.
3. Gordetsky J, Epstein JI. Intestinal metaplasia of the bladder with dysplasia: a risk factor for carcinoma? Histopathology. 2015;67:325-330.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Harsimar Kaur.
A 15 year-old female with Grave’s disease and a total thyroidectomy.
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A 15 year-old female with Grave’s disease and a total thyroidectomy.
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Correct Answer:
C. Intrathyroidal thymus
Discussion:
The total thyroidectomy specimen contains a grossly distinct nodular focus, which upon histologic review appears to be well demarcated and composed of a fairly uniform lymphocytic population. High-power examination reveals that the lymphocytes are are admixed with larger epithelioid cells as well as overtly epithelial nests with squamous-like pearls (Hassall’s corpuscles). The histologic features would be recognized instantaneously in the mediastinum as normal thymic gland; however, the unusual anatomic location can make the diagnosis challenging. This intrathyroidal thymus is an incidental finding in this young patient’s thyroidectomy performed for refractory Grave’s disease. Unlike lymph nodes, thymic gland lacks a distinct capsule or subcapsular sinus space. The Hassall’s corpuscles can be mistaken for the psammomatous calcifications seen in papillary thyroid carcinoma and thus can mimic metastatic papillary thyroid carcinoma to a lymph node; however, the bright pink eosinophilic material is in contrast to the purple, lamellated concretions of a psammatous calcification.
Incorrect
Correct Answer:
C. Intrathyroidal thymus
Discussion:
The total thyroidectomy specimen contains a grossly distinct nodular focus, which upon histologic review appears to be well demarcated and composed of a fairly uniform lymphocytic population. High-power examination reveals that the lymphocytes are are admixed with larger epithelioid cells as well as overtly epithelial nests with squamous-like pearls (Hassall’s corpuscles). The histologic features would be recognized instantaneously in the mediastinum as normal thymic gland; however, the unusual anatomic location can make the diagnosis challenging. This intrathyroidal thymus is an incidental finding in this young patient’s thyroidectomy performed for refractory Grave’s disease. Unlike lymph nodes, thymic gland lacks a distinct capsule or subcapsular sinus space. The Hassall’s corpuscles can be mistaken for the psammomatous calcifications seen in papillary thyroid carcinoma and thus can mimic metastatic papillary thyroid carcinoma to a lymph node; however, the bright pink eosinophilic material is in contrast to the purple, lamellated concretions of a psammatous calcification.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Harsimar Kaur.
A 30 year-old female with bilateral lung nodules.
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A 30 year-old female with bilateral lung nodules.
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Correct Answer:
C. Alveolar soft part sarcoma
Discussion:
Multiple elements inform a differential diagnosis, including: patient demographics (e.g., pediatric vs. adult, male vs. female), anatomic location, and tumor morphology. Here, we have a young adult, female patient with lesions in both lungs, suggesting infectious, systemic, or metastatic etiologies. The lesion is composed of cells with abundant eosinophilic cytoplasm and fairly uniform nuclei, arranged in nests with central discohesion (i.e., an “alveolar” pattern). The morphology raises the differential diagnosis of “pink cell tumors,” and immiunohistochemistry is often necessary to resolve the diagnosis. This tumor is immunoreactive for cathepsin K and TFE3, and is negative for S-100, desmin, myogenin, and cytokeratin. The morphologic and immunophenotypic features are in keeping with metastatic alveolar soft part sarcoma, of which the patient had a known history. Alveolar soft part sarcomas are translocation sarcomas, driven by translocations between the ASPL gene on chromosome 17 and the TFE3 gene on the X chromosome (Xp11). Tumors with recurrent genomic translocations are often deceptively bland cytologically, despite their aggressive clinical behavior; that is, they comprise nuclei of uniform size and shape, thereby lacking pleomorphism. To quote a beloved professor, “Translocation tumors are like designer shoes…they all look the same!” Each cell is driven by the exact same genomic alteration, thus each cell looks relatively the same. This can be a useful clue when formulating a differential diagnosis on the basis of the cellular morphology.
Incorrect
Correct Answer:
C. Alveolar soft part sarcoma
Discussion:
Multiple elements inform a differential diagnosis, including: patient demographics (e.g., pediatric vs. adult, male vs. female), anatomic location, and tumor morphology. Here, we have a young adult, female patient with lesions in both lungs, suggesting infectious, systemic, or metastatic etiologies. The lesion is composed of cells with abundant eosinophilic cytoplasm and fairly uniform nuclei, arranged in nests with central discohesion (i.e., an “alveolar” pattern). The morphology raises the differential diagnosis of “pink cell tumors,” and immiunohistochemistry is often necessary to resolve the diagnosis. This tumor is immunoreactive for cathepsin K and TFE3, and is negative for S-100, desmin, myogenin, and cytokeratin. The morphologic and immunophenotypic features are in keeping with metastatic alveolar soft part sarcoma, of which the patient had a known history. Alveolar soft part sarcomas are translocation sarcomas, driven by translocations between the ASPL gene on chromosome 17 and the TFE3 gene on the X chromosome (Xp11). Tumors with recurrent genomic translocations are often deceptively bland cytologically, despite their aggressive clinical behavior; that is, they comprise nuclei of uniform size and shape, thereby lacking pleomorphism. To quote a beloved professor, “Translocation tumors are like designer shoes…they all look the same!” Each cell is driven by the exact same genomic alteration, thus each cell looks relatively the same. This can be a useful clue when formulating a differential diagnosis on the basis of the cellular morphology.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Harsimar Kaur.
A 45 year-old female underwent a hemithyroidectomy for a thyroid nodule.
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A 45 year-old female underwent a hemithyroidectomy for a thyroid nodule.
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Correct Answer:
B. Hyalinizing trabecular adenoma
Discussion:
Hyalinizing trabecular adenoma (sometimes referred to as hyalinizing trabecular “tumor” or “neoplasm”) is a benign thyroid neoplasm with the nuclear features of papillary thyroid carcinoma; that is, the nuclei display elongation, overlap, clearing, grooves, and pseudoinclusions. However, the cells are arranged in a nested or trabecular architecture, resembling cords or ribbons of cells, and are invested by a collagenous (hyalinized) matrix. The tumor lacks papillary architecture or follicular-pattern growth. Hyalinizing trabecular adenomas have been recently characterized to have rearrangements between PAX8 and GLIS1 or GLIS3, which is unique and distinct from the genetic changes of papillary thyroid carcinomas. Hyalinizing trabecular adenomas are important to recognize as distinct from papillary thyroid carcinomas, because hyalinizing trabecular adenomas are uniformly benign and do not require any additional therapy or monitoring
References:
1. Nikiforova MN, et al. GLIS Rearrangement is a Genomic Hallmark of Hyalinizing Trabecular Tumor of the Thyroid Gland. Thyroid. 2019 Feb;29(2):161-173.
2. Marchiò C, et al. PAX8-GLIS3 gene fusion is a pathognomonic genetic alteration of hyalinizing trabecular tumors of the thyroid. Mod Pathol. 2019 Jul 4. [Epub ahead of print]
Incorrect
Correct Answer:
B. Hyalinizing trabecular adenoma
Discussion:
Hyalinizing trabecular adenoma (sometimes referred to as hyalinizing trabecular “tumor” or “neoplasm”) is a benign thyroid neoplasm with the nuclear features of papillary thyroid carcinoma; that is, the nuclei display elongation, overlap, clearing, grooves, and pseudoinclusions. However, the cells are arranged in a nested or trabecular architecture, resembling cords or ribbons of cells, and are invested by a collagenous (hyalinized) matrix. The tumor lacks papillary architecture or follicular-pattern growth. Hyalinizing trabecular adenomas have been recently characterized to have rearrangements between PAX8 and GLIS1 or GLIS3, which is unique and distinct from the genetic changes of papillary thyroid carcinomas. Hyalinizing trabecular adenomas are important to recognize as distinct from papillary thyroid carcinomas, because hyalinizing trabecular adenomas are uniformly benign and do not require any additional therapy or monitoring
References:
1. Nikiforova MN, et al. GLIS Rearrangement is a Genomic Hallmark of Hyalinizing Trabecular Tumor of the Thyroid Gland. Thyroid. 2019 Feb;29(2):161-173.
2. Marchiò C, et al. PAX8-GLIS3 gene fusion is a pathognomonic genetic alteration of hyalinizing trabecular tumors of the thyroid. Mod Pathol. 2019 Jul 4. [Epub ahead of print]
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Harsimar Kaur.
A 70 year-old altered mental status found to have a brain mass.
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A 70 year-old altered mental status found to have a brain mass.
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Correct Answer:
C. Metastatic melanoma
Discussion:
This high grade neoplasm consists of large cells with abundant eosinophilic cytoplasm, pleomorphic nuclei, prominent cherry-red nucleoli, and frequent atypical mitotic figures. Close examination reveals brown intracellular pigment; one might say that the tumor is “staining itself,” because this pigment is melanin. The histologic features are compatible with metastasis from the patient’s reported melanoma; in addition, the lesion is diffusely immunoreactive for S-100. Melanoma can also be called “the great mimicker” because of the wide range of histologic appearances it can display: spindled vs. epithelioid, pleomorphic vs. bland/nevoid, cohesive vs. discohesive, and others. Thus, due to both it’s variable histologic appearance and aggressive clinical behavior, melanoma should always be in the differential diagnosis during the work-up of a neoplasm regardless of body site. In this current case, the melanoma cells are displaying the features of a “big pink cell tumor.” When a tumor of unknown origin or classification is encountered that displays cells with abundant eosinophilic cytoplasm and prominent nucleoli (aka, “a big pink cell tumor”), melanoma must be excluded. The top four differential diagnoses for “big pink cell tumors” are: melanoma, renal cell carcinoma, adrenocortical carcinoma, and hepatocellular carcinoma. Other less common entities to consider include Hurthle cell or oncotytic carcinomas and PEComa family tumors such as angiomyolipoma.
Incorrect
Correct Answer:
C. Metastatic melanoma
Discussion:
This high grade neoplasm consists of large cells with abundant eosinophilic cytoplasm, pleomorphic nuclei, prominent cherry-red nucleoli, and frequent atypical mitotic figures. Close examination reveals brown intracellular pigment; one might say that the tumor is “staining itself,” because this pigment is melanin. The histologic features are compatible with metastasis from the patient’s reported melanoma; in addition, the lesion is diffusely immunoreactive for S-100. Melanoma can also be called “the great mimicker” because of the wide range of histologic appearances it can display: spindled vs. epithelioid, pleomorphic vs. bland/nevoid, cohesive vs. discohesive, and others. Thus, due to both it’s variable histologic appearance and aggressive clinical behavior, melanoma should always be in the differential diagnosis during the work-up of a neoplasm regardless of body site. In this current case, the melanoma cells are displaying the features of a “big pink cell tumor.” When a tumor of unknown origin or classification is encountered that displays cells with abundant eosinophilic cytoplasm and prominent nucleoli (aka, “a big pink cell tumor”), melanoma must be excluded. The top four differential diagnoses for “big pink cell tumors” are: melanoma, renal cell carcinoma, adrenocortical carcinoma, and hepatocellular carcinoma. Other less common entities to consider include Hurthle cell or oncotytic carcinomas and PEComa family tumors such as angiomyolipoma.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Harsimar Kaur.
A 50 year-old male with a breast mass.
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A 50 year-old male with a breast mass.
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Correct Answer:
C. Myofibroblasoma
Discussion:
Mammary myofibroblastoma is a benign neoplasm of the breast stromal myofibroblasts. Myofibroblastomas were initially thought to be more common in men, in whom they presented as palpable masses. However, with the initiation of routine mammographic screening of women, myofibroblastomas are known to occur equally in men and women. Classic myofibroblastomas are well-circumscribed nodules containing spindle cells with amphophilic cytoplasm, indistinct cell borders, bland nuclei, inconspicious nucleoli, minimal to no mitotic activity, and associated brightly eosinophilic cytoplasm. However, myofibroblastomas can display a wide range of variant morphologies, including collagenized/fibrotic, cellular, epithelioid, lipomatous, and others. Myofibroblastomas can be histologically indistinguishable from schwannomas, with nuclear palisading and hyalinized vessels. Immunohistochemistry can resolve the differential diagnosis, as myofibroblastomas are immunoreactive for CD34, ER, BCL-2, and calponin or desmin (variably), and are negative for S-100, cytokeratins, CD31 and ERG. Myofibroblastomas—as well as spindle cell lipomas—are characterized by chromosomal loss of 13q14, encompassing the Rb gene locus.
Incorrect
Correct Answer:
C. Myofibroblasoma
Discussion:
Mammary myofibroblastoma is a benign neoplasm of the breast stromal myofibroblasts. Myofibroblastomas were initially thought to be more common in men, in whom they presented as palpable masses. However, with the initiation of routine mammographic screening of women, myofibroblastomas are known to occur equally in men and women. Classic myofibroblastomas are well-circumscribed nodules containing spindle cells with amphophilic cytoplasm, indistinct cell borders, bland nuclei, inconspicious nucleoli, minimal to no mitotic activity, and associated brightly eosinophilic cytoplasm. However, myofibroblastomas can display a wide range of variant morphologies, including collagenized/fibrotic, cellular, epithelioid, lipomatous, and others. Myofibroblastomas can be histologically indistinguishable from schwannomas, with nuclear palisading and hyalinized vessels. Immunohistochemistry can resolve the differential diagnosis, as myofibroblastomas are immunoreactive for CD34, ER, BCL-2, and calponin or desmin (variably), and are negative for S-100, cytokeratins, CD31 and ERG. Myofibroblastomas—as well as spindle cell lipomas—are characterized by chromosomal loss of 13q14, encompassing the Rb gene locus.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Harsimar Kaur
A 45 year-old female presents with a breast mass.
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A 45 year-old female presents with a breast mass.
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Correct answer: Borderline phyllodes tumor
The lesion consists of biphasic epithelial and stromal components, falling into the diagnostic category of “cellular fibroepithelial neoplasm.” The neoplasm displays an irregular, infiltrative interface with the adjacent benign breast parenchyma; variably cellular stroma with abrupt transition between hypocellular and hypercellular areas; and moderate stromal cell atypia with readily apparent mitotic figures. The lesion lacks atypical mitotic figure, stromal overgrowth, and malignant heterologous elements. This combination of histologic features supports classification as a borderline phyllodes tumor. Phyllodes tumors are fibroepithelial neoplasms of the breast that have cellular stroma and a leaf-like architecture. They are subdivided into the categories of benign, borderline and malignant on the basis of the following features: 1) tumor circumscription, 2) degree and characteristics of stromal cellularity, 3) degree of stromal cell atypia, 4) mitotic activity, 5) and presence of malignant heterologous elements.
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Correct answer: Borderline phyllodes tumor
The lesion consists of biphasic epithelial and stromal components, falling into the diagnostic category of “cellular fibroepithelial neoplasm.” The neoplasm displays an irregular, infiltrative interface with the adjacent benign breast parenchyma; variably cellular stroma with abrupt transition between hypocellular and hypercellular areas; and moderate stromal cell atypia with readily apparent mitotic figures. The lesion lacks atypical mitotic figure, stromal overgrowth, and malignant heterologous elements. This combination of histologic features supports classification as a borderline phyllodes tumor. Phyllodes tumors are fibroepithelial neoplasms of the breast that have cellular stroma and a leaf-like architecture. They are subdivided into the categories of benign, borderline and malignant on the basis of the following features: 1) tumor circumscription, 2) degree and characteristics of stromal cellularity, 3) degree of stromal cell atypia, 4) mitotic activity, 5) and presence of malignant heterologous elements.
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