Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Kevan Salimian
An 80 year-old male with a history of pancreatic cancer presents with abdominal masses
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An 80 year-old male with a history of pancreatic cancer presents with abdominal masses
Choose the correct diagnosis:
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Diagnosis: B. Metastatic acinar cell carcinoma
Histology:
This section of the abdominal mass shows nests of cells arranged in acinar and trabecular patterns, with basal polarization of the nuclei and apical pink, granular cytoplasm. The nuclei are uniform with finely dispersed chromatin and occasional prominent nucleoli. There are frequent mitotic figures, but no atypical mitoses or necrosis. No normal structures/organs are identified in this section. The lesional cells are positive for cytokeratin, chymotrypsin, and BCL10.
Discussion:
This patient has a known history of pancreatic acinar cell carcinoma of the pancreas, and his metastatic disease involving the abdominal cavity displays characteristic histologic features of this entity. Pancreatic acinar cell carcinomas arise from the pancreatic acinar cells, which produce exocrine enzymes. Acinar cell carcinomas may have either an acinar growth pattern or solid growth pattern. The acinar growth pattern is easier to recognize as “acinar” in origin, whereas the solid pattern consists of sheets of atypical cells. By immunohistochemistry, acinar cell carcinomas are positive for cytokeratin, chymotrypsin, trypsin, lipase, and BCL10. Scattered cells may be synaptophysin or chromogranin positive, but this labeling is typically not diffuse. The differential diagnosis of other pancreatic neoplasms includes pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and Pancreatoblastoma (however, the latter typically effect children and contain squamoid nests). In metastatic sites, the differential diagnosis would also include neuroendocrine tumors with rosette formation, adenocarcinomas with gland formation, and other “pink cell tumors” such as melanoma and hepatocellular, renal and adrenocortical carcinomas. In general, acinar cell carcinomas have a more favorable prognosis that pancreatic ductal adenocarcinomas; however, acinar cell carcinomas can still metastasize and behave aggressively.
References:
1. Hackeng WM, Hruban RH, Offerhaus GJ, Brosens LA. Surgical and molecular pathology of pancreatic neoplasms. Diagn Pathol. 2016 Jun 7;11(1):47.
Incorrect
Diagnosis: B. Metastatic acinar cell carcinoma
Histology:
This section of the abdominal mass shows nests of cells arranged in acinar and trabecular patterns, with basal polarization of the nuclei and apical pink, granular cytoplasm. The nuclei are uniform with finely dispersed chromatin and occasional prominent nucleoli. There are frequent mitotic figures, but no atypical mitoses or necrosis. No normal structures/organs are identified in this section. The lesional cells are positive for cytokeratin, chymotrypsin, and BCL10.
Discussion:
This patient has a known history of pancreatic acinar cell carcinoma of the pancreas, and his metastatic disease involving the abdominal cavity displays characteristic histologic features of this entity. Pancreatic acinar cell carcinomas arise from the pancreatic acinar cells, which produce exocrine enzymes. Acinar cell carcinomas may have either an acinar growth pattern or solid growth pattern. The acinar growth pattern is easier to recognize as “acinar” in origin, whereas the solid pattern consists of sheets of atypical cells. By immunohistochemistry, acinar cell carcinomas are positive for cytokeratin, chymotrypsin, trypsin, lipase, and BCL10. Scattered cells may be synaptophysin or chromogranin positive, but this labeling is typically not diffuse. The differential diagnosis of other pancreatic neoplasms includes pancreatic neuroendocrine tumor, solid-pseudopapillary neoplasm, and Pancreatoblastoma (however, the latter typically effect children and contain squamoid nests). In metastatic sites, the differential diagnosis would also include neuroendocrine tumors with rosette formation, adenocarcinomas with gland formation, and other “pink cell tumors” such as melanoma and hepatocellular, renal and adrenocortical carcinomas. In general, acinar cell carcinomas have a more favorable prognosis that pancreatic ductal adenocarcinomas; however, acinar cell carcinomas can still metastasize and behave aggressively.
References:
1. Hackeng WM, Hruban RH, Offerhaus GJ, Brosens LA. Surgical and molecular pathology of pancreatic neoplasms. Diagn Pathol. 2016 Jun 7;11(1):47.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Kevan Salimian
A 50 year-old female presents with an intraluminal gallbladder mass
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A 50 year-old female presents with an intraluminal gallbladder mass
Choose the correct diagnosis:
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Diagnosis: D. Metastatic melanoma
Histology:
This section of gallbladder, which includes the mass in relation to the gallbladder mucosa and wall, displays a well-preserved gallbladder mucosa comprised of bland cuboidal cells with no atypia. The mucosa is intimately associated with, and in areas undermined by, a proliferation of atypical cells. The neoplastic cells are variably spindled to epithelioid, with abundant mitotic activity. The spindled cells have fairly uniform chromatin, while the epithelioid cells contain prominent nucleoli, discohesive growth, and abundant pink cytoplasm. The lesional cells are positive for S100 and Melan-A, and are negative for AE1/AE3.
Discussion:
This is an example of metastatic melanoma forming an intraluminal gallbladder mass that clinically mimicked a primary gallbladder polyp. This patient had a known history of metastatic melanoma, but melanoma was not expected in this site. The histologic features highlight the classic descriptor of melanoma as “the great mimicker”—this tumor has both spindled-type morphology and epithelioid-type morphology. The differential diagnosis of malignant lesions with spindled morphology includes leiomyosarcoma and sarcomatoid carcinoma, and similarly the differential diagnosis of epithelioid neoplasms includes both sarcomas and carcinoma. The differential diagnosis of “big pink cell tumors” should always include melanoma, hepatocellular carcinoma, adrenocortical carcinoma, and renal cell carcinoma. This is particularly challenging in the location of the gallbladder, as the liver, adrenal and kidneys are all in close proximity. By immunohistochemistry, most melanomas label for S100, SOX10, HMB45, Melan A and MITF, and are negative for cytokeratins. Melanomas may contain melanin pigment, however hepatocellular carcinomas may contain intracytoplasmic bile pigment, which is more yellow than melanin (which is more brown). In addition, hepatocellular carcinomas and adrenocortical carcinomas may be negative for broad spectrum cytokeratin, mimicking melanoma or sarcoma. A broad immunopanel and through clinical history is essential.
References:
1. Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006 Feb;19 Suppl 2:S41-70.
Incorrect
Diagnosis: D. Metastatic melanoma
Histology:
This section of gallbladder, which includes the mass in relation to the gallbladder mucosa and wall, displays a well-preserved gallbladder mucosa comprised of bland cuboidal cells with no atypia. The mucosa is intimately associated with, and in areas undermined by, a proliferation of atypical cells. The neoplastic cells are variably spindled to epithelioid, with abundant mitotic activity. The spindled cells have fairly uniform chromatin, while the epithelioid cells contain prominent nucleoli, discohesive growth, and abundant pink cytoplasm. The lesional cells are positive for S100 and Melan-A, and are negative for AE1/AE3.
Discussion:
This is an example of metastatic melanoma forming an intraluminal gallbladder mass that clinically mimicked a primary gallbladder polyp. This patient had a known history of metastatic melanoma, but melanoma was not expected in this site. The histologic features highlight the classic descriptor of melanoma as “the great mimicker”—this tumor has both spindled-type morphology and epithelioid-type morphology. The differential diagnosis of malignant lesions with spindled morphology includes leiomyosarcoma and sarcomatoid carcinoma, and similarly the differential diagnosis of epithelioid neoplasms includes both sarcomas and carcinoma. The differential diagnosis of “big pink cell tumors” should always include melanoma, hepatocellular carcinoma, adrenocortical carcinoma, and renal cell carcinoma. This is particularly challenging in the location of the gallbladder, as the liver, adrenal and kidneys are all in close proximity. By immunohistochemistry, most melanomas label for S100, SOX10, HMB45, Melan A and MITF, and are negative for cytokeratins. Melanomas may contain melanin pigment, however hepatocellular carcinomas may contain intracytoplasmic bile pigment, which is more yellow than melanin (which is more brown). In addition, hepatocellular carcinomas and adrenocortical carcinomas may be negative for broad spectrum cytokeratin, mimicking melanoma or sarcoma. A broad immunopanel and through clinical history is essential.
References:
1. Magro CM, Crowson AN, Mihm MC. Unusual variants of malignant melanoma. Mod Pathol. 2006 Feb;19 Suppl 2:S41-70.
Presented by Dr. Cimino-Mathews and prepared by Dr. Kevan Salimian
A 50 year-old female presents with a porcelain gallbladder
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A 50 year-old female presents with a porcelain gallbladder
Choose the correct diagnosis:
Correct
Diagnosis: E. Xanthogranulomatous cholecystitis
Histology:
This representative section of gallbladder wall from the patient’s cholecystectomy specimen shows gallbladder mucosa with changes of chronic cholecystitis including focal reactive atypia but no dysplastic changes. The striking feature here is the exuberant chronic inflammatory infiltrate containing an abundance of foamy histiocytes that involves the transmural thickness of the gallbladder wall. The histiocytes show no nuclear atypia. Within this histiocytic infiltrate, there is yellow bile pigment, multinucleated giant cells, and neutrophilic abscesses.
Discussion:
This is an example of a xanthogranulomatous cholecystitis, which often clinically mimics carcinoma due to the extensive thickening of gallbladder wall and “infiltration” or adhesion of the process into adjacent organs. Xanthogranulomatous cholecystitis is typically associated with cholelithiasis and bile duct obstruction, likely leading to rupture of the Rokitansky-Aschoff sinuses with extravasation of bile and the subsequent development of a florid inflammatory response. This is analogous to xanthogranulomatous pyelonephritis that develops in the kidney in association with kidney stones. Xanthogranulomatous cholecystitis is a non-neoplastic condition, however it can cause significant morbidity due to stricture formation and fistula/abscess formation. There is no clear association of xanthogranulomatous cholecystitis with the development of gallbladder carcinoma.
References:
1. Goodman ZD, Ishak KG. Xanthogranulomatous cholecystitis. Am J Surg Pathol. 1981;5(7):653.
2. Fligiel S, Lewin KJ. Xanthogranulomatous cholecystitis: case report and review of the literature. Arch Pathol Lab Med. 1982;106(6):302.
Incorrect
Diagnosis: E. Xanthogranulomatous cholecystitis
Histology:
This representative section of gallbladder wall from the patient’s cholecystectomy specimen shows gallbladder mucosa with changes of chronic cholecystitis including focal reactive atypia but no dysplastic changes. The striking feature here is the exuberant chronic inflammatory infiltrate containing an abundance of foamy histiocytes that involves the transmural thickness of the gallbladder wall. The histiocytes show no nuclear atypia. Within this histiocytic infiltrate, there is yellow bile pigment, multinucleated giant cells, and neutrophilic abscesses.
Discussion:
This is an example of a xanthogranulomatous cholecystitis, which often clinically mimics carcinoma due to the extensive thickening of gallbladder wall and “infiltration” or adhesion of the process into adjacent organs. Xanthogranulomatous cholecystitis is typically associated with cholelithiasis and bile duct obstruction, likely leading to rupture of the Rokitansky-Aschoff sinuses with extravasation of bile and the subsequent development of a florid inflammatory response. This is analogous to xanthogranulomatous pyelonephritis that develops in the kidney in association with kidney stones. Xanthogranulomatous cholecystitis is a non-neoplastic condition, however it can cause significant morbidity due to stricture formation and fistula/abscess formation. There is no clear association of xanthogranulomatous cholecystitis with the development of gallbladder carcinoma.
References:
1. Goodman ZD, Ishak KG. Xanthogranulomatous cholecystitis. Am J Surg Pathol. 1981;5(7):653.
2. Fligiel S, Lewin KJ. Xanthogranulomatous cholecystitis: case report and review of the literature. Arch Pathol Lab Med. 1982;106(6):302.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Kevan Salimian
A 30 year-old female with a breast mass
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A 30 year-old female with a breast mass
Choose the correct diagnosis:
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Diagnosis: A. Angiolipoma
Histology:
The soft tissue mass consists primarily of mature adipocytes with scattered capillaries; the capillaries are arranged in variable density, with some areas of low vascularity and some areas where the capillaries are clustered together in close proximity. The capillaries are lined by a single layer of bland endothelial cells and may show associated supportive stromal cells (smooth muscle cells and fibroblasts). Scattered capillaries show fibrin thrombi within their lumens.
Discussion:
The histologic features of mature adipose tissue with an associated bland vascular component containing fibrin thrombi are characteristic of a benign angiolipoma, which commonly present as painful subcutaneous masses. Angiolipomas can occur throughout the body and are occasionally encountered on core needle biopsy of the breast, both in male and female patients. In contrast to other body sites, the angiolipomas of the breast are not as commonly painful. The differential diagnosis of angiolipoma of the breast includes other fatty tumors such as lipoma or even a benign breast fat lobule, as well as vascular neoplasms such as hemangioma or angiosarcoma. The diagnosis can be particularly challenging on core needle biopsy of a breast mass with a clinical concern of low grade angiosarcoma, because the well circumscribed and encapsulated nature of a cellular angiolipoma may not be appreciated on the limited tissue sampling of a core biopsy. The presence of fibrin thrombi greatly favors an angiolipoma, whereas the presence of nuclear atypia, mitotic activity, and an infiltrative pattern favors a low grade angiosarcoma. Clinicoradiographic correlation of tumor size, location, and clinical history can be helpful. However, the distinction may not always be possible, and in some cases, an excisional biopsy is necessary for definitive classification. Many observers recommend conservative excision of any vascular lesion diagnosed on breast core needle biopsy to exclude the potential of lesional heterogeneity in an angiosarcoma. Clinicoradiographic correlation of any finding on breast core needle biopsy is always recommended.
References:
1. Kryvenko ON, Chitale DA, VanEgmond EM, Gupta NS, Schultz D, Lee MW. Angiolipoma of the female breast: clinicomorphological correlation of 52 cases. International journal of surgical pathology. 2011;19(1):35-43.
Incorrect
Diagnosis: A. Angiolipoma
Histology:
The soft tissue mass consists primarily of mature adipocytes with scattered capillaries; the capillaries are arranged in variable density, with some areas of low vascularity and some areas where the capillaries are clustered together in close proximity. The capillaries are lined by a single layer of bland endothelial cells and may show associated supportive stromal cells (smooth muscle cells and fibroblasts). Scattered capillaries show fibrin thrombi within their lumens.
Discussion:
The histologic features of mature adipose tissue with an associated bland vascular component containing fibrin thrombi are characteristic of a benign angiolipoma, which commonly present as painful subcutaneous masses. Angiolipomas can occur throughout the body and are occasionally encountered on core needle biopsy of the breast, both in male and female patients. In contrast to other body sites, the angiolipomas of the breast are not as commonly painful. The differential diagnosis of angiolipoma of the breast includes other fatty tumors such as lipoma or even a benign breast fat lobule, as well as vascular neoplasms such as hemangioma or angiosarcoma. The diagnosis can be particularly challenging on core needle biopsy of a breast mass with a clinical concern of low grade angiosarcoma, because the well circumscribed and encapsulated nature of a cellular angiolipoma may not be appreciated on the limited tissue sampling of a core biopsy. The presence of fibrin thrombi greatly favors an angiolipoma, whereas the presence of nuclear atypia, mitotic activity, and an infiltrative pattern favors a low grade angiosarcoma. Clinicoradiographic correlation of tumor size, location, and clinical history can be helpful. However, the distinction may not always be possible, and in some cases, an excisional biopsy is necessary for definitive classification. Many observers recommend conservative excision of any vascular lesion diagnosed on breast core needle biopsy to exclude the potential of lesional heterogeneity in an angiosarcoma. Clinicoradiographic correlation of any finding on breast core needle biopsy is always recommended.
References:
1. Kryvenko ON, Chitale DA, VanEgmond EM, Gupta NS, Schultz D, Lee MW. Angiolipoma of the female breast: clinicomorphological correlation of 52 cases. International journal of surgical pathology. 2011;19(1):35-43.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Kevan Salimian
A 45 year-old female with a breast mass
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A 45 year-old female with a breast mass
Choose the correct diagnosis:
Correct
Diagnosis: D. Schwannoma
Histology:
The core needle biopsy of the breast mass reveals a spindle cell proliferation comprised of bland cells with wavy nuclei, nuclear palisading resembling Verocay bodies, and indistinct cell borders. There is no overt epithelial component. There is no mitotic activity, no necrosis, and no cytologic atypia. An immunostain for S100 protein is diffusely positive, and immunostains for cytokeratin and CD43 are negative.
Discussion:
The histologic features of this spindle cell lesion are classic for a schwannoma, a benign peripheral nerve sheath tumor of the Schwann cells. Schwannomas can occur throughout the body and are occasionally seen on core needle biopsy of a “breast mass,” where they may be centered in the dermis, subcutaneous tissue, axillary soft tissue, chest wall soft tissue, or even in the breast parenchyma itself. The primary histologic differential diagnosis of any spindle cell proliferation of the breast on core needle biopsy is a spindle cell metaplastic carcinoma, which will display nuclear atypia, mitotic activity, and cytoerkatin immunoreactivity. In addition, the morphologic features of a schwannoma (i.e., nuclear palisading, indistinct cell borders, wavy nuclei, and hyalinized blood vessels) may be seen in variant forms of myofibroblastomas, a benign neoplasm of the breast stromal myofibroblasts. In contrast to schwannomas, myofibroblastomas are negative for S100 and variably positive for CD34, ER, desmin, and actin.
References:
1. Bellezza G, Lombardi T, Panzarola P, Sidoni A, Cavaliere A, Giansanti M. Schwannoma of the breast: a case report and review of the literature. Tumori. 2007;93(3):308-11.
2. Fisher C. Immunohistochemistry in diagnosis of soft tissue tumours. Histopathology 2011;58(7):1001-1012.
3. Magro G, Foschini MP, Eusebi V. Palisaded myofibroblastoma of the breast: a tumor closely mimicking schwannoma: Report of 2 cases. Human pathology. 2013;44(9):1941-6.
Incorrect
Diagnosis: D. Schwannoma
Histology:
The core needle biopsy of the breast mass reveals a spindle cell proliferation comprised of bland cells with wavy nuclei, nuclear palisading resembling Verocay bodies, and indistinct cell borders. There is no overt epithelial component. There is no mitotic activity, no necrosis, and no cytologic atypia. An immunostain for S100 protein is diffusely positive, and immunostains for cytokeratin and CD43 are negative.
Discussion:
The histologic features of this spindle cell lesion are classic for a schwannoma, a benign peripheral nerve sheath tumor of the Schwann cells. Schwannomas can occur throughout the body and are occasionally seen on core needle biopsy of a “breast mass,” where they may be centered in the dermis, subcutaneous tissue, axillary soft tissue, chest wall soft tissue, or even in the breast parenchyma itself. The primary histologic differential diagnosis of any spindle cell proliferation of the breast on core needle biopsy is a spindle cell metaplastic carcinoma, which will display nuclear atypia, mitotic activity, and cytoerkatin immunoreactivity. In addition, the morphologic features of a schwannoma (i.e., nuclear palisading, indistinct cell borders, wavy nuclei, and hyalinized blood vessels) may be seen in variant forms of myofibroblastomas, a benign neoplasm of the breast stromal myofibroblasts. In contrast to schwannomas, myofibroblastomas are negative for S100 and variably positive for CD34, ER, desmin, and actin.
References:
1. Bellezza G, Lombardi T, Panzarola P, Sidoni A, Cavaliere A, Giansanti M. Schwannoma of the breast: a case report and review of the literature. Tumori. 2007;93(3):308-11.
2. Fisher C. Immunohistochemistry in diagnosis of soft tissue tumours. Histopathology 2011;58(7):1001-1012.
3. Magro G, Foschini MP, Eusebi V. Palisaded myofibroblastoma of the breast: a tumor closely mimicking schwannoma: Report of 2 cases. Human pathology. 2013;44(9):1941-6.
Presented by Dr. Ashley Cimino-Mmathews and prepared by Dr. Kevan Salimian
A 60 year-old female with a breast mass
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A 60 year-old female with a breast mass
Choose the correct diagnosis:
Correct
Diagnosis E. Myofibroblastoma
Histology:
The excisional biopsy reveals bland epithelioid cells within an associated dense, eosinophilic collagenous stroma with some admixed adipose tissue. The cells are variably nested or arranged as single cells in cords. The nuclei are hypochromatic with punctate nucleoli. The cells have indistinct cell borders and amphophilic cytoplasm. The lesional cells do not infiltrate benign terminal duct lobular units. The cells are positive for CD34 and ER, and are negative for: AE1/AE3, Cam5.2, CK903, S100 and SMA
Discussion:
The morphology and immunoprofile are in keeping with a myofibroblastoma, which is a neoplastic proliferation of the breast stromal myofibroblasts. Classic-type myofibroblastomas are usually well-circumscribed, non-infiltrative nodules comprised of variable spindled to epithelioid cells with bland oval nuclei and amphophilic cytoplasm, arranged in nests with associated brightly eosinophilic collagen. There are multiple variant patterns, including epithelioid, myxoid, lipomatous, cellular, and collagenous/fibrous myofibroblastoma. Thus, the differential diagnosis varies with the histologic pattern, but in general the differential includes other spindle cell lesions such as spindle cell metaplastic carcinoma, phyllodes tumor, and fibromatosis. Notably, epithelioid myofibroblastomas can mimic infiltrating lobular carcinomas, which is especially treacherous since myofibroblastomas are typically strongly immunoreactive for ER. Hence, in this setting, a cytokeratin and CD34 immunostains should be included in the immunopanel to resolve the diagnosis. Mammary myofibroblastoma display similar genetic changes as spindle cell lipomas and mammary-type myofibroblastomas encountered elsewhere; specifically, they display recurrent loss or rearrangements of chromosomes 16q and 13q (encompassing the Rb gene).
References
1. Maggiani F, Debiec-Rychter M, Verbeeck G, et al. Extramammary myofibroblastoma is genetically related to spindle cell lipoma. Virchows Arch. 2006;449:244–247.
2. Howitt BE, Fletcher CDM. Mammary-type Myofibroblastoma: Clinicopathologic Characterization in a Series of 143 Cases. Am. J. Surg. Pathol. 2016;40:361–367.
3. Charu V, Cimino-Mathews A. Spindle cell lesions of the breast. Am J Surg Pathol: Reviews & Reports. 2017 Mar-Apr;22(2):116-124.
Incorrect
Diagnosis E. Myofibroblastoma
Histology:
The excisional biopsy reveals bland epithelioid cells within an associated dense, eosinophilic collagenous stroma with some admixed adipose tissue. The cells are variably nested or arranged as single cells in cords. The nuclei are hypochromatic with punctate nucleoli. The cells have indistinct cell borders and amphophilic cytoplasm. The lesional cells do not infiltrate benign terminal duct lobular units. The cells are positive for CD34 and ER, and are negative for: AE1/AE3, Cam5.2, CK903, S100 and SMA
Discussion:
The morphology and immunoprofile are in keeping with a myofibroblastoma, which is a neoplastic proliferation of the breast stromal myofibroblasts. Classic-type myofibroblastomas are usually well-circumscribed, non-infiltrative nodules comprised of variable spindled to epithelioid cells with bland oval nuclei and amphophilic cytoplasm, arranged in nests with associated brightly eosinophilic collagen. There are multiple variant patterns, including epithelioid, myxoid, lipomatous, cellular, and collagenous/fibrous myofibroblastoma. Thus, the differential diagnosis varies with the histologic pattern, but in general the differential includes other spindle cell lesions such as spindle cell metaplastic carcinoma, phyllodes tumor, and fibromatosis. Notably, epithelioid myofibroblastomas can mimic infiltrating lobular carcinomas, which is especially treacherous since myofibroblastomas are typically strongly immunoreactive for ER. Hence, in this setting, a cytokeratin and CD34 immunostains should be included in the immunopanel to resolve the diagnosis. Mammary myofibroblastoma display similar genetic changes as spindle cell lipomas and mammary-type myofibroblastomas encountered elsewhere; specifically, they display recurrent loss or rearrangements of chromosomes 16q and 13q (encompassing the Rb gene).
References
1. Maggiani F, Debiec-Rychter M, Verbeeck G, et al. Extramammary myofibroblastoma is genetically related to spindle cell lipoma. Virchows Arch. 2006;449:244–247.
2. Howitt BE, Fletcher CDM. Mammary-type Myofibroblastoma: Clinicopathologic Characterization in a Series of 143 Cases. Am. J. Surg. Pathol. 2016;40:361–367.
3. Charu V, Cimino-Mathews A. Spindle cell lesions of the breast. Am J Surg Pathol: Reviews & Reports. 2017 Mar-Apr;22(2):116-124.
Presented by Dr. Fausto Rodriguez and prepared by Daniel Miller
A 31 year-old male developed an enhancing left frontal lobe mass. What
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What molecular alteration has significant prognostic implications in the following tumor, and merits inclusion into the diagnosis under the current WHO Classification (2016)?
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Answer: C-IDH1 mutation
Histology: The neoplasm demonstrated parenchymal infiltration and pleomorphism consistent with an astrocytic neoplasm. Mitotic figures, and pseudopalisading necrosis with microvascular proliferation were also present.
Discussion: The tumorexpressed mutant IDH1 p.R132H protein, which was detected with a mutation specific antibody. The correct diagnosis is Glioblastoma, IDH-mutant.
Mutations in isocitrate dehydrogenase 1 (IDH1) or 2 (IDH2) genes are present in most grade II and grade III diffuse gliomas, as well as secondary glioblastomas. When present, they are associated with a better prognosis compared to IDH-wildtype tumors. Given the strong prognostic and biologic implication, IDH mutation status is added to the tumor diagnosis whenever possible (1).
Reference:
1. Louis DN, Ohgaki H, Wiestler OD, et al., eds. WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer; 2016.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is a 31 year old male with a chest wall/breast mass.
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This is a 31 year old male with a chest wall/breast mass. Choose the correct diagnosis.
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Answer: Nodular fasciitis
Histologic Description: This is a spindle cell proliferation characterized by loosely spaced cells with uniform chromatin and amphophilic cytoplasm. There are associated thin capillaries with extravasated red blood cells, along with lymphocytes. The nuclei are hypochromatic relative to the adjacent endothelial cells. These are the typical features of nodular fasciitis.
Differential Diagnosis: Fibromatosis would demonstrate more fibrous stroma, and more infiltrative borders. Nuclear labeling for beta-catenin would support the diagnosis of fibromatosis, but this was absent in the current case. Metaplastic carcinoma of the breast may be very bland and have a fasciitis-like pattern. However, these metaplastic carcinomas demonstrate strong immunoreactivity for high molecular cytokeratins. Leiomyomas would have more fascicular growth protein and less myxoid stroma. The neoplastic cells typically have dense eosinophilic cytoplasm and rectangular nuclei, and label diffusely for desmin.
Incorrect
Answer: Nodular fasciitis
Histologic Description: This is a spindle cell proliferation characterized by loosely spaced cells with uniform chromatin and amphophilic cytoplasm. There are associated thin capillaries with extravasated red blood cells, along with lymphocytes. The nuclei are hypochromatic relative to the adjacent endothelial cells. These are the typical features of nodular fasciitis.
Differential Diagnosis: Fibromatosis would demonstrate more fibrous stroma, and more infiltrative borders. Nuclear labeling for beta-catenin would support the diagnosis of fibromatosis, but this was absent in the current case. Metaplastic carcinoma of the breast may be very bland and have a fasciitis-like pattern. However, these metaplastic carcinomas demonstrate strong immunoreactivity for high molecular cytokeratins. Leiomyomas would have more fascicular growth protein and less myxoid stroma. The neoplastic cells typically have dense eosinophilic cytoplasm and rectangular nuclei, and label diffusely for desmin.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is a 48 year old male with a breast mass.
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This is a 48 year old male with a breast mass.
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Answer: Spindle cell lipoma
Histologic Description: This is a bland primarily fibrous lesion that involves soft tissue, with no breast epithelium present. One can focally appreciate areas of fat within the tumor. The collagen in areas has a ropey appearance, and there are associated mast cells. The cells associated with the fibrous tissue are bland and have minimal cytoplasm. These are the typical features of a spindle cell lipoma. The lesion was diffusely immunoreactive for CD34, supporting the diagnosis. Estrogen receptor was negative.
Differential Diagnosis: Like spindle cell lipoma, neurofibroma may demonstrate prominent collagen (though the latter has more of a “shredded carrot” appearance in neurofibroma) and mast cells, along with bland stromal cells. However, neurofibromas would label for S100, and have more angulated nuclei. Solitary fibrous tumors would also label for CD34, but would demonstrate a more prominent hemangiopericytomatous vasculature and label for STAT6. Low grade fibromyxoid sarcomas have more curvilinear vessels, greater nuclear atypia, and label for MUC4.
Incorrect
Answer: Spindle cell lipoma
Histologic Description: This is a bland primarily fibrous lesion that involves soft tissue, with no breast epithelium present. One can focally appreciate areas of fat within the tumor. The collagen in areas has a ropey appearance, and there are associated mast cells. The cells associated with the fibrous tissue are bland and have minimal cytoplasm. These are the typical features of a spindle cell lipoma. The lesion was diffusely immunoreactive for CD34, supporting the diagnosis. Estrogen receptor was negative.
Differential Diagnosis: Like spindle cell lipoma, neurofibroma may demonstrate prominent collagen (though the latter has more of a “shredded carrot” appearance in neurofibroma) and mast cells, along with bland stromal cells. However, neurofibromas would label for S100, and have more angulated nuclei. Solitary fibrous tumors would also label for CD34, but would demonstrate a more prominent hemangiopericytomatous vasculature and label for STAT6. Low grade fibromyxoid sarcomas have more curvilinear vessels, greater nuclear atypia, and label for MUC4.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is an inguinal lymph node in a 23 year old male.
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This is an inguinal lymph node in a 23 year old male. Choose the correct diagnosis.
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Answer: Kaposi sarcoma
Histologic Description: This lesion here is a bland spindle cell proliferation that primarily involves the capsule and extends both into the lymph node and perinodal soft tissue. One can appreciate in some foci an anastomosing vascular pattern. The lesional cells are not severely pleomorphic, they focally form fascicles, and there are admixed plasma cells present. There are focally extravasated red blood cells. The lesion demonstrates diffuse nuclear immunoreactivity for HHV8 by immunohistochemistry. These are the typical features of Kaposi sarcoma.
Differential Diagnosis: Angiosarcoma would demonstrate greater nuclear pleomorphism, and is HHV8 negative. Vascular transformation of the lymph node sinuses in a bland proliferation of vessels that involves the sinus, and is typically seen in obstructed lymph nodes or those which drain angiogenic neoplasms such as renal cell carcinoma. Malignant mesothelioma may focally have a pattern that mimics vascular neoplasms, but would be diffusely immunoreactive for cytokeratin and lack vascular markers.
Incorrect
Answer: Kaposi sarcoma
Histologic Description: This lesion here is a bland spindle cell proliferation that primarily involves the capsule and extends both into the lymph node and perinodal soft tissue. One can appreciate in some foci an anastomosing vascular pattern. The lesional cells are not severely pleomorphic, they focally form fascicles, and there are admixed plasma cells present. There are focally extravasated red blood cells. The lesion demonstrates diffuse nuclear immunoreactivity for HHV8 by immunohistochemistry. These are the typical features of Kaposi sarcoma.
Differential Diagnosis: Angiosarcoma would demonstrate greater nuclear pleomorphism, and is HHV8 negative. Vascular transformation of the lymph node sinuses in a bland proliferation of vessels that involves the sinus, and is typically seen in obstructed lymph nodes or those which drain angiogenic neoplasms such as renal cell carcinoma. Malignant mesothelioma may focally have a pattern that mimics vascular neoplasms, but would be diffusely immunoreactive for cytokeratin and lack vascular markers.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is a 65 year old male with a 4cm thyroid nodule.
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This is a 65 year old male with a 4cm thyroid nodule. Choose the correct diagnosis.
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Answer: Hurthle cell carcinoma
Histologic Description: This is a lesion of oncocytic cells that have both follicular and trabecular architecture. A worrisome feature of this lesion is the thickness of the capsule, which raises concern for a follicular pattern carcinoma. At least focally, one can appreciate tongues of tumor cells extending into vascular spaces within the capsule, and other areas there are signs of capsular penetration. These features of diagnostic of Hurthle cell carcinoma.
Differential diagnosis: Adenomatoid nodules typically demonstrate less cellularity than carcinomas and more variation in the presence/thickness of their capsules. Hurthle cell adenomas are well delineated from normal thyroid; however, they tend to have thinner capsules and importantly lack capsular/vascular invasion. Medullary carcinoma of the thyroid may have oncocytic and follicular patterns; however, this neoplasm is characterized by amphophilic cells with uniform chromatin that has a salt and pepper appearance.
Incorrect
Answer: Hurthle cell carcinoma
Histologic Description: This is a lesion of oncocytic cells that have both follicular and trabecular architecture. A worrisome feature of this lesion is the thickness of the capsule, which raises concern for a follicular pattern carcinoma. At least focally, one can appreciate tongues of tumor cells extending into vascular spaces within the capsule, and other areas there are signs of capsular penetration. These features of diagnostic of Hurthle cell carcinoma.
Differential diagnosis: Adenomatoid nodules typically demonstrate less cellularity than carcinomas and more variation in the presence/thickness of their capsules. Hurthle cell adenomas are well delineated from normal thyroid; however, they tend to have thinner capsules and importantly lack capsular/vascular invasion. Medullary carcinoma of the thyroid may have oncocytic and follicular patterns; however, this neoplasm is characterized by amphophilic cells with uniform chromatin that has a salt and pepper appearance.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is a 72 year old female with a hand mass and history of lymphoma.
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This is a 72 year old female with a hand mass and history of lymphoma. Choose the correct diagnosis.
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Answer: Merkel cell carcinoma
Histologic Description: This is sheet like proliferation of small uniform cells with fine chromatin. Nuclear membranes are generally thin, and the nuclei mold to each other. There is relatively little pleomorphism given the high mitotic activity of the lesion. The lesion demonstrates dot-like staining for cytokeratin, focal staining for synaptophysin, and perinuclear staining for neurofilament and cytokeratin 20. These findings support the diagnosis of Merkel cell carcinoma.
Differential Diagnosis: Metastatic small cell carcinoma may overlap immunophenotypically with Merkel cell carcinoma in that it would show dot-like cytokeratin labeling, high proliferation rate, and neuroendocrine marker labeling. However, small cell carcinomas usually do not label for neurofilament or cytokeratin 20 like Merkel cell carcinoma. Lymphomas would be expected to have more irregular, thicker nuclear membranes, and be less cohesive than Merkel cell carcinoma. The cytokeratin labeling in the absence of labeling for lymphoid markers helps exclude the diagnosis of lymphoma.
Incorrect
Answer: Merkel cell carcinoma
Histologic Description: This is sheet like proliferation of small uniform cells with fine chromatin. Nuclear membranes are generally thin, and the nuclei mold to each other. There is relatively little pleomorphism given the high mitotic activity of the lesion. The lesion demonstrates dot-like staining for cytokeratin, focal staining for synaptophysin, and perinuclear staining for neurofilament and cytokeratin 20. These findings support the diagnosis of Merkel cell carcinoma.
Differential Diagnosis: Metastatic small cell carcinoma may overlap immunophenotypically with Merkel cell carcinoma in that it would show dot-like cytokeratin labeling, high proliferation rate, and neuroendocrine marker labeling. However, small cell carcinomas usually do not label for neurofilament or cytokeratin 20 like Merkel cell carcinoma. Lymphomas would be expected to have more irregular, thicker nuclear membranes, and be less cohesive than Merkel cell carcinoma. The cytokeratin labeling in the absence of labeling for lymphoid markers helps exclude the diagnosis of lymphoma.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is a 72 year old female with abdominal pain.
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This is a 72 year old female with abdominal pain. Choose the correct diagnosis.
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Answer: Pneumatosis cystoides intestinalis
Histologic Description: Throughout the thickness of the bowel wall, extending from the submucosa to the subserosa, are gas filled spaces lined by multinucleate giant cells. These are the diagnostic features of pneumatosis cystoides intestinalis. In some cases, pneumatosis cystoides intestinalis is of unclear etiology, but most cases are associated with either mucosal damage or dissection of the air emanating from ruptured pressurized lung cysts from the mediastinum into the mesentery and on into the bowel.
Differential Diagnosis: Colitis cystica profunda is associated with prolapse, and features large spaces as seen in the current case except those spaces are filled with directing mucin. Artefactual air spaces associated with trauma from colonoscopy (colonic pseudolipomatosis) are not associated with giant cell reaction. The granulomas of tuberculosis would be associated with central necrosis, not central air spaces.
Incorrect
Answer: Pneumatosis cystoides intestinalis
Histologic Description: Throughout the thickness of the bowel wall, extending from the submucosa to the subserosa, are gas filled spaces lined by multinucleate giant cells. These are the diagnostic features of pneumatosis cystoides intestinalis. In some cases, pneumatosis cystoides intestinalis is of unclear etiology, but most cases are associated with either mucosal damage or dissection of the air emanating from ruptured pressurized lung cysts from the mediastinum into the mesentery and on into the bowel.
Differential Diagnosis: Colitis cystica profunda is associated with prolapse, and features large spaces as seen in the current case except those spaces are filled with directing mucin. Artefactual air spaces associated with trauma from colonoscopy (colonic pseudolipomatosis) are not associated with giant cell reaction. The granulomas of tuberculosis would be associated with central necrosis, not central air spaces.
Presented by Dr. Andres Matoso and prepared by Dr. Kevan Salimian
37 year old male with a testicular mass.
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37 year old male with a testicular mass. Choose the correct diagnosis.
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Answer: Nephroblastoma arising in teratoma
Histology: The tumor shows areas of primitive neural-type tubules lined by stratified epithelium and surrounded by poorly differentiated malignant cells.
Discussion: Somatic malignancies arising in teratomas with primitive appearing nests and tubules invites consideration of primitive neuroectodermal tumos (PNET) and nephroblastoma. PNET of the testis represent overgrowth of embryonic appearing neuroectodermal tissue. Some are pure but most have a small component of mixed germ cell tumor. Distinction with a teratoma with immature neural elements is based on the extent of the immature component (by consensus is >one 4x field or 5mm). Unlike peripheral PNETs, these tumors are not associated with chromosome 22 translocations. This case presented focal glomeruloid structures, diffuse cytokeratin stain and positive staining for WT1 which supports the diagnosis of neprhoblastoma.
Histology: The tumor shows areas of primitive neural-type tubules lined by stratified epithelium and surrounded by poorly differentiated malignant cells.
Discussion: Somatic malignancies arising in teratomas with primitive appearing nests and tubules invites consideration of primitive neuroectodermal tumos (PNET) and nephroblastoma. PNET of the testis represent overgrowth of embryonic appearing neuroectodermal tissue. Some are pure but most have a small component of mixed germ cell tumor. Distinction with a teratoma with immature neural elements is based on the extent of the immature component (by consensus is >one 4x field or 5mm). Unlike peripheral PNETs, these tumors are not associated with chromosome 22 translocations. This case presented focal glomeruloid structures, diffuse cytokeratin stain and positive staining for WT1 which supports the diagnosis of neprhoblastoma.
Presented by Dr. Andres Matoso and prepared by Dr. Kevan Salimian
59 year old female with a kidney tumor.
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59 year old female with a kidney tumor. Choose the correct diagnosis.
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Answer: Epithelioid angiomyolipoma
Histology: The tumor is composed of sheets of small round to oval tumor cells with scant eosinophilic cytoplasm. The nuclei have inconspicuous nucleoli. Tumor cells are organized in fascicles and radiate off of vessels walls.
Discussion: This is an angiomyolipoma (AML) with epithelioid features. While it is common to see a lipomatous component intermixed with the spindle smooth muscle component but in small biopsies as in this case, the lipomatous component might not be seen. In resection specimens, epithelioid AMLs and fat-poor AMLs could have little to no lipomatous component. Surgically resected AMLs tend to have more smooth muscle component because those are the lesions with ambiguous read on imaging studies. AMLs can involve lymph nodes but are benign unless epithelioid. Malignant behavior correlated with the presence of 3 of the 4 following criteria: (a) >70% atypical epithelioid areas, (b) 2 or more mitoses per 10 HPF, (c) atypical mitotic figures, or (d) necrosis.
References
Urology. 2017 Oct 6. pii: S0090-4295(17)31051-8.
Am J Surg Pathol. 2010 May;34(5):715-22
Incorrect
Answer: Epithelioid angiomyolipoma
Histology: The tumor is composed of sheets of small round to oval tumor cells with scant eosinophilic cytoplasm. The nuclei have inconspicuous nucleoli. Tumor cells are organized in fascicles and radiate off of vessels walls.
Discussion: This is an angiomyolipoma (AML) with epithelioid features. While it is common to see a lipomatous component intermixed with the spindle smooth muscle component but in small biopsies as in this case, the lipomatous component might not be seen. In resection specimens, epithelioid AMLs and fat-poor AMLs could have little to no lipomatous component. Surgically resected AMLs tend to have more smooth muscle component because those are the lesions with ambiguous read on imaging studies. AMLs can involve lymph nodes but are benign unless epithelioid. Malignant behavior correlated with the presence of 3 of the 4 following criteria: (a) >70% atypical epithelioid areas, (b) 2 or more mitoses per 10 HPF, (c) atypical mitotic figures, or (d) necrosis.
References
Urology. 2017 Oct 6. pii: S0090-4295(17)31051-8.
Am J Surg Pathol. 2010 May;34(5):715-22
Presented by Dr. Andres Matoso and prepared by Dr. Kevan Salimian
59 year old male who underwent prostatectomy.
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59 year old male who underwent prostatectomy. Choose the correct diagnosis.
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Answer: Nonspecific granulomatous prostatitis
Histology: Dilated ducts and acini filled with neutrophils, debris, foamy histiocytes and desquamated epithelial cells. Ruptured ducts surrounded by diffuse areas of granulomatous inflammation and chronic inflammatory infiltrate. Neutrophils and eosinophils can be seen but are the minority of the inflammatory cells.
Discussion: Granulomatous inflammation in the prostate can be subclassified into infectious granulomas, postbiopsy granulomas and nonspecific granulomatous prostatitis (NSGP). In most cases, the differential there is sufficient morphologic evidence to arrive to the diagnosis without the need for special stains for microorganisms. In contrast to infectious granulomatous prostatitis, the granulomas of NSGP are usually less well formed and composed of a mixed inflammatory infiltrate. Additionally, infectious granulomatous prostatitis surrounds intact acini. The presence of eosinophils should not prompt the diagnosis of allergic prostatitis as these are usually seen in NSGP and are not associated with allergic symptoms. Postbiopsy granulomas are composed of a central region of fibrinoid necrosis surrounded by palisading of epithelioid histiocytes.
References:
J Urol. 2012 Jun;187(6):2209-10.
Incorrect
Answer: Nonspecific granulomatous prostatitis
Histology: Dilated ducts and acini filled with neutrophils, debris, foamy histiocytes and desquamated epithelial cells. Ruptured ducts surrounded by diffuse areas of granulomatous inflammation and chronic inflammatory infiltrate. Neutrophils and eosinophils can be seen but are the minority of the inflammatory cells.
Discussion: Granulomatous inflammation in the prostate can be subclassified into infectious granulomas, postbiopsy granulomas and nonspecific granulomatous prostatitis (NSGP). In most cases, the differential there is sufficient morphologic evidence to arrive to the diagnosis without the need for special stains for microorganisms. In contrast to infectious granulomatous prostatitis, the granulomas of NSGP are usually less well formed and composed of a mixed inflammatory infiltrate. Additionally, infectious granulomatous prostatitis surrounds intact acini. The presence of eosinophils should not prompt the diagnosis of allergic prostatitis as these are usually seen in NSGP and are not associated with allergic symptoms. Postbiopsy granulomas are composed of a central region of fibrinoid necrosis surrounded by palisading of epithelioid histiocytes.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is a 46 year old male with polyp in gallbladder.
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This is a 46 year old male with polyp in gallbladder. The surrounding gallbladder mucosa was unremarkable. Choose the correct diagnosis.
Correct
Answer: Pyloric gland adenoma with high grade dysplasia
Histology Description: This is a polypoid lesion that is composed of cuboidal cells that have round nuclei. The architecture is complex, and there is increased nucleus to cytoplasm ratio. Focally, there is suggestion of squamoid morule formation. These features suggest the diagnosis of pyloric gland adenoma with superimposed high grade dysplasia. The diagnosis is supported by immunohistochemistry for beta-catenin, which demonstrates diffuse nuclear and cytoplasmic labeling of the lesion but not the surrounding mucosa.
Differential Diagnosis: Cholesterol polyp consists of unremarkable gallbladder epithelium and prominent cholesterol-laden macrophages. Adenocarcinoma of the gallbladder would demonstrate stromal reaction and greater cytologic atypia. Intestinal type dysplasias are associated with goblet cells, and importantly typically involve the surrounding gallbladder mucosa, not just the polyp.
Pyloric gland adenomas of the gallbladder typically arise in pristine mucosa, form polyps that often detach and simulate stones, have squamoid morules, and harbor beta-catenin mutations.
Reference: Chang Am J Surg Pathol 2002; 26:758-766.
Incorrect
Answer: Pyloric gland adenoma with high grade dysplasia
Histology Description: This is a polypoid lesion that is composed of cuboidal cells that have round nuclei. The architecture is complex, and there is increased nucleus to cytoplasm ratio. Focally, there is suggestion of squamoid morule formation. These features suggest the diagnosis of pyloric gland adenoma with superimposed high grade dysplasia. The diagnosis is supported by immunohistochemistry for beta-catenin, which demonstrates diffuse nuclear and cytoplasmic labeling of the lesion but not the surrounding mucosa.
Differential Diagnosis: Cholesterol polyp consists of unremarkable gallbladder epithelium and prominent cholesterol-laden macrophages. Adenocarcinoma of the gallbladder would demonstrate stromal reaction and greater cytologic atypia. Intestinal type dysplasias are associated with goblet cells, and importantly typically involve the surrounding gallbladder mucosa, not just the polyp.
Pyloric gland adenomas of the gallbladder typically arise in pristine mucosa, form polyps that often detach and simulate stones, have squamoid morules, and harbor beta-catenin mutations.
Reference: Chang Am J Surg Pathol 2002; 26:758-766.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is an 87 year old male with a retroperitoneum mass.
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This is an 87 year old male with a retroperitoneum mass. Choose the correct diagnosis.
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Answer: Well differentiated liposarcoma
Histologic Description: This an inflammation-rich lesion which contains large neoplastic cells with large irregular nucleoli and abundant cytoplasm in a background of predominantly chronic inflammation with lymphocytes and plasma cells. These large cells resemble those of Hodgkin lymphoma or Rosai Dorfman disease. However, in the adjacent fat, one can appreciate occasionally atypical cells which, in the retroperitoneum, raise the differential diagnosis of well differentiated liposarcoma. Immunohistochemistry for MDM2 supports the diagnosis of well differentiated liposarcoma, inflammatory type in this case. Myogenin immunostain did not label these cells; instead, it labeled regenerating skeletal muscle cells. Reference Argani P et al. Am J Surg Pathol 1997; 21:884-895.
Differential Diagnosis: The atypia in the fat surrounding the lesion essentially excludes the differential diagnosis of Hodgkin lymphoma, Rosai Dorfman disease and sclerosing low grade lymphoma. The majority of inflammatory cells in inflammatory well-differentiated liposarcomas are, in our experience T-lymphocytes. The neoplastic cells of Hodgkin disease typically have less abundant cytoplasm, and while emperilopoiesis is often seen in well-differentiated inflammatory liposarcoma, it is less prevalent than in Rosai Dorfman disease.
Incorrect
Answer: Well differentiated liposarcoma
Histologic Description: This an inflammation-rich lesion which contains large neoplastic cells with large irregular nucleoli and abundant cytoplasm in a background of predominantly chronic inflammation with lymphocytes and plasma cells. These large cells resemble those of Hodgkin lymphoma or Rosai Dorfman disease. However, in the adjacent fat, one can appreciate occasionally atypical cells which, in the retroperitoneum, raise the differential diagnosis of well differentiated liposarcoma. Immunohistochemistry for MDM2 supports the diagnosis of well differentiated liposarcoma, inflammatory type in this case. Myogenin immunostain did not label these cells; instead, it labeled regenerating skeletal muscle cells. Reference Argani P et al. Am J Surg Pathol 1997; 21:884-895.
Differential Diagnosis: The atypia in the fat surrounding the lesion essentially excludes the differential diagnosis of Hodgkin lymphoma, Rosai Dorfman disease and sclerosing low grade lymphoma. The majority of inflammatory cells in inflammatory well-differentiated liposarcomas are, in our experience T-lymphocytes. The neoplastic cells of Hodgkin disease typically have less abundant cytoplasm, and while emperilopoiesis is often seen in well-differentiated inflammatory liposarcoma, it is less prevalent than in Rosai Dorfman disease.
Presented by Dr. Pedram Argani and prepared by Dr. Kevan Salimian
This is a 62 year old male with a mediastinal adenopathy and a history of melanoma.
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This is a 62 year old male with mediastinal adenopathy and a history of melanoma. Choose the correct diagnosis.
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Answer: C. Metastatic melanoma and melanophages
Histologic Description: The majority of this lymph node is occupied by macrophages containing abundant melanin pigment (melanophages). These cells generally have small nuclei with thin nuclear membranes, and prominent cytoplasmic pigment. The prominent cytoplasmic pigment makes evaluation of cytoplasmic immunohistochemical markers for melanoma problematic. However, in addition to these cells, there are small clusters of neoplastic cells with prominent nucleoli and irregular, thick nuclear membranes, morphologically suggestive of melanoma. Immunohistochemistry for the nuclear marker SOX10 highlights these cells, confirming the diagnosis of metastatic melanoma in addition to melanophages.
Differential Diagnosis: The differential diagnosis of melanoma and melanophages is highlighted above. It is important recognize that some markers like HMB45 may actually stain melanophages due to phagocytosis of melanosomes (Modern Pathology 2002; 15: 1288-1293). Dermatopathic lymphadenopathy would be characterized by dendritic macrophages harboring melanin pigment in the paracortical zone of a lymph node typically draining inflamed skin.
Incorrect
Answer: C. Metastatic melanoma and melanophages
Histologic Description: The majority of this lymph node is occupied by macrophages containing abundant melanin pigment (melanophages). These cells generally have small nuclei with thin nuclear membranes, and prominent cytoplasmic pigment. The prominent cytoplasmic pigment makes evaluation of cytoplasmic immunohistochemical markers for melanoma problematic. However, in addition to these cells, there are small clusters of neoplastic cells with prominent nucleoli and irregular, thick nuclear membranes, morphologically suggestive of melanoma. Immunohistochemistry for the nuclear marker SOX10 highlights these cells, confirming the diagnosis of metastatic melanoma in addition to melanophages.
Differential Diagnosis: The differential diagnosis of melanoma and melanophages is highlighted above. It is important recognize that some markers like HMB45 may actually stain melanophages due to phagocytosis of melanosomes (Modern Pathology 2002; 15: 1288-1293). Dermatopathic lymphadenopathy would be characterized by dendritic macrophages harboring melanin pigment in the paracortical zone of a lymph node typically draining inflamed skin.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Kevan Salimian
75 year-old female with a leg skin lesion
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Clinical history: 75 year-old female with a leg skin lesion
Choose the correct diagnosis:
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Diagnosis: C. Melanoma with balloon cell change
Histology: The skin resection shows an epidermal and dermal based lesion of epithelioid cells with prominent nucleoli and irregular nuclear contours. A subset of the cells shows prominent pale, foamy, and histiocytoid cytoplasm.
Discussion: This is a nice example of a malignant melanoma with balloon cell change. On clinical exam or on gross exam, melanomas with balloon cell change do not look any different than melanomas with other growth patterns, and there is no clinical or prognostic significance to the balloon cell change. In melanomas with balloon cell change, the malignant melanoma cells display expanded, granular cytoplasm that looks like the cell “ballooned” out, and there are adjacent or admixed other conventional appearing malignant melanocytes. The cells with balloon cell change resemble the cells in benign “balloon cell nevi,” but the malignant melanomas also show atypia and mitoses. The histologic differential diagnosis of the cells with balloon cell change includes other clear cell lesions: histiocytic neoplasms, histiocytic chronic inflammation, sebaceous neoplasms, lipoma or adipocyte tumors, metastatic renal cell carcinoma, clear cell syringoma or other. The presence of the classic-type malignant melanoma cells confirms the diagnosis. If needed, particularly on the limited material of a biopsy, immunostains for melanocytic markers such as S100, HMB45, Melan A or Sox10 can confirm the melanocytic differentiation of the lesion.
References
1. Kao GF, Helwig EB, Graham JH. Balloon cell malignant melanoma of the skin. A clinicopathologic study of 34 cases with histochemical, immunohistochemical, and ultrastructural observations. Cancer. 1992 Jun 15;69(12):2942-52.
Incorrect
Diagnosis: C. Melanoma with balloon cell change
Histology: The skin resection shows an epidermal and dermal based lesion of epithelioid cells with prominent nucleoli and irregular nuclear contours. A subset of the cells shows prominent pale, foamy, and histiocytoid cytoplasm.
Discussion: This is a nice example of a malignant melanoma with balloon cell change. On clinical exam or on gross exam, melanomas with balloon cell change do not look any different than melanomas with other growth patterns, and there is no clinical or prognostic significance to the balloon cell change. In melanomas with balloon cell change, the malignant melanoma cells display expanded, granular cytoplasm that looks like the cell “ballooned” out, and there are adjacent or admixed other conventional appearing malignant melanocytes. The cells with balloon cell change resemble the cells in benign “balloon cell nevi,” but the malignant melanomas also show atypia and mitoses. The histologic differential diagnosis of the cells with balloon cell change includes other clear cell lesions: histiocytic neoplasms, histiocytic chronic inflammation, sebaceous neoplasms, lipoma or adipocyte tumors, metastatic renal cell carcinoma, clear cell syringoma or other. The presence of the classic-type malignant melanoma cells confirms the diagnosis. If needed, particularly on the limited material of a biopsy, immunostains for melanocytic markers such as S100, HMB45, Melan A or Sox10 can confirm the melanocytic differentiation of the lesion.
References
1. Kao GF, Helwig EB, Graham JH. Balloon cell malignant melanoma of the skin. A clinicopathologic study of 34 cases with histochemical, immunohistochemical, and ultrastructural observations. Cancer. 1992 Jun 15;69(12):2942-52.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Kevan Salimian
40 year-old female with a thyroid mass
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Clinical history: 40 year-old female with a thyroid mass
Choose the correct diagnosis:
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Diagnosis: B. Cribriform morular variant of papillary thyroid carcinoma
Histology: This lesion is centered in the thyroid and the background thyroid parenchyma lacks any significant abnormalities (i.e., no inflammation or no signs of Grave’s disease). Low power examination of the lesion reveals varying growth patterns, with some areas of papillary architecture and some areas of cribriform architecture, with areas of admixed squamous morules. High power examination confirms the presence of nuclear atypia in keeping with papillary thyroid carcinoma, including nuclear elongation, overlap, clearing and grooves. Immunostains show the lesion to have nuclear beta-catenin labeling, as well as diffuse ER positivity in the non-squamous areas.
Discussion: These findings all support the diagnosis of cribriform morular variant of papillary thyroid carcinoma (PTC). The cribriform morular variant of PTC can occur sporadically, or in association with familial adenomatous polyposis (FAP), a syndrome caused by mutations in the adenomatous polyposis coli (APC) gene. APC gene mutations lead to abnormal nuclear accumulation of the beta-catenin protein, which can be detected with immunohistochemistry for beta-catenin. Nuclear labeling for beta-catenin can be detected in any tumor type that has mutations or aberrations in the APC pathway, whether the aberrations are germline/syndromic or sporadic. Other lesions that can be seen in patients with FAP include intestinal adenomas and carcinomas, desmoid tumors (fibromatoses), retinal pigmentation, gastric fundic gland polyps, hepatoblastomas, medulloblastomas and glioma, osteomas, fibromas and others. Diagnosis of cribriform morular variant of PTC should prompt clinical evaluation for FAP in any patient. The differential diagnosis of the cribriform morular variant of PTC includes the other variants of PTC; however, the immunoprofile of nuclear beta-catenin labeling is specific for the diagnosis.
References
1. Hizawa K, Iida M, Yao T, et al. Association between thyroid cancer of cribriform variant and familial adenomatous polyposis. J Clin Pathol. 1996 Jul;49(7):611-3.
2. Xu B, Yoshimoto K, Miyauchi A, et al. Cribriform-morular variant of papillary thyroid carcinoma: a pathological and molecular genetic study with evidence of frequent somatic mutations in exon 3 of the beta-catenin gene. J Pathol. 2003 Jan;199(1):58-67.
Presented by Dr. Ashley Cimino-Mathews and prepared by Dr. Kevan Salimian
30 year-old female with a dural lesion
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Clinical history: 30 year-old female with a dural lesion
Choose the correct diagnosis:
Correct
Diagnosis: D. Plasmacytoma
Histology: The lesion consists of sheets of fairly monomorphic, discohesive cells with eccentrically located nuclei and eosinophilic cytoplasm. Some cells have “clock face” chromatin with clumps of chromatin arranged circumferentially around the periphery of the nucleus, and some nuclei have punctate nucleoli. There is no necrosis or atypia. The cells are immunoreactive for CD138 and show kappa light chain restriction by immunohistochemistry, and flow analysis confirms a monoclonal, kappa positive plasma cell population.
Discussion: The pre-operative clinical impression was of a meningioma, so the actual pathologic findings were unexpected. The features seen here, in the absence of additional lesions throughout the body, are in keeping with a solitary, extramedullary plasmacytoma. However, clinical, radiographic, and laboratory studies are needed to exclude a diagnosis of plasma cell myeloma. Indeed, subsequent clinical evaluation of this patient confirmed a diagnosis of multiple myeloma. The morphologic differential diagnosis includes metastatic carcinoma (such as lobular carcinoma or signet ring carcinoma), melanoma, lymphoma, and possibly a variant meningioma such as rhabdoid meningioma. In a patient with a known history of plasma cell myeloma, confirmatory immunostains are not necessary on a histologically classic plasmacytoma. However, in this patient with a new brain lesion, a targeted panel of immunostains can be helpful in confirming the diagnosis. This lesion is EMA negative (excluding a carcinoma and meningioma) but immunoreactive for CD138 with kappa light chain restriction, supporting the diagnosis of a monoclonal plasma cell population. A potential diagnostic pitfall is that CD138 can label carcinomas, but the constellation of histologic features is sufficient in this setting to ensure the correct diagnosis.
References
1. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48.
2. Palumbo A, Anderson K. Multiple Myeloma. N Engl J Med 2011; 364:1046-10
Incorrect
Diagnosis: D. Plasmacytoma
Histology: The lesion consists of sheets of fairly monomorphic, discohesive cells with eccentrically located nuclei and eosinophilic cytoplasm. Some cells have “clock face” chromatin with clumps of chromatin arranged circumferentially around the periphery of the nucleus, and some nuclei have punctate nucleoli. There is no necrosis or atypia. The cells are immunoreactive for CD138 and show kappa light chain restriction by immunohistochemistry, and flow analysis confirms a monoclonal, kappa positive plasma cell population.
Discussion: The pre-operative clinical impression was of a meningioma, so the actual pathologic findings were unexpected. The features seen here, in the absence of additional lesions throughout the body, are in keeping with a solitary, extramedullary plasmacytoma. However, clinical, radiographic, and laboratory studies are needed to exclude a diagnosis of plasma cell myeloma. Indeed, subsequent clinical evaluation of this patient confirmed a diagnosis of multiple myeloma. The morphologic differential diagnosis includes metastatic carcinoma (such as lobular carcinoma or signet ring carcinoma), melanoma, lymphoma, and possibly a variant meningioma such as rhabdoid meningioma. In a patient with a known history of plasma cell myeloma, confirmatory immunostains are not necessary on a histologically classic plasmacytoma. However, in this patient with a new brain lesion, a targeted panel of immunostains can be helpful in confirming the diagnosis. This lesion is EMA negative (excluding a carcinoma and meningioma) but immunoreactive for CD138 with kappa light chain restriction, supporting the diagnosis of a monoclonal plasma cell population. A potential diagnostic pitfall is that CD138 can label carcinomas, but the constellation of histologic features is sufficient in this setting to ensure the correct diagnosis.
References
1. Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014 Nov;15(12):e538-48.
2. Palumbo A, Anderson K. Multiple Myeloma. N Engl J Med 2011; 364:1046-10
Presented by Dr. Jonathan Epstein and prepared by Dr. Kevan Salimian
A 41 year old female presented with hematuria, and was found to have a polypoid 10.1 cm. mass projecting into the urethra. A radical nephrectomy was performed.
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A 41 year old female presented with hematuria, and was found to have a polypoid 10.1 cm. mass projecting into the urethra. A radical nephrectomy was performed.
Choose the correct diagnosis:
Correct
Answer: B. Polypoid endometrioma
Histology: A polypoid mass is seen projecting into the urethra. The mass has both solid and cystic components. The cystic components are lined variably by cuboidal cells w/o cilia, cuboidal or columnar cells with cilia, or urothelium. The intervening stroma has the appearance of endometrial stroma with condensation around the cysts. Clusters of prominent thick walled arterioles are evident. The tumor stroma was positive for estrogen receptor, progesterone receptor, and CD10.
Discussion: A characteristic features of spindle cell tumors in the kidney is that they tend to entrap native renal tubules, which then often become cystically dilated. This occurs in monophasic synovial sarcoma, angiomyolipoma, and in mixed epithelial and stromal tumor (MEST). In all these lesions, the tubules are lined by bland cuboidal epithelium which label with PAX8. Another feature of several renal lesions is that the stroma can undergo metaplasia to ovarian-like stroma which expresses estrogen receptor (ER) and progesterone receptor (PR). This metaplasia is associated with AMLEC and MEST. The major differential diagnosis in this case is MEST. As with the current case, MESTs can characteristically present as a polypoid mass protruding into the renal pelvis. MESTs would similarly have a mixture of tubules, often cystic, and stroma that resemble Mullerian stroma. The key feature in this case of polypoid endometriosis (polypoid endometrioma) is that the epithelium lining the tubules is Mullerian composed of cuboidal and columnar cells with prominent cilia, indicating tubal differentiation. The stroma also appears more typical of endometrial stroma than the fibroblastic appearing ovarian stroma seen in MEST. Another feature seen in this case that is classic for polypoid endometriosis is the clusters of thick walled arteries, identical to those seen in endometrial polyps. Polypoid endometriosis results in a tumor-like lesion of endometriosis occurring in a cavity allowing it to become polypoid. It has been most commonly seen in the colon, vagina, vulva, cervix, bladder, ureter, and ovary. As with usual endometriosis, a variety of epithelial and stromal neoplasms have been described arising in polypoid endometriosis.
Incorrect
Answer: B. Polypoid endometrioma
Histology: A polypoid mass is seen projecting into the urethra. The mass has both solid and cystic components. The cystic components are lined variably by cuboidal cells w/o cilia, cuboidal or columnar cells with cilia, or urothelium. The intervening stroma has the appearance of endometrial stroma with condensation around the cysts. Clusters of prominent thick walled arterioles are evident. The tumor stroma was positive for estrogen receptor, progesterone receptor, and CD10.
Discussion: A characteristic features of spindle cell tumors in the kidney is that they tend to entrap native renal tubules, which then often become cystically dilated. This occurs in monophasic synovial sarcoma, angiomyolipoma, and in mixed epithelial and stromal tumor (MEST). In all these lesions, the tubules are lined by bland cuboidal epithelium which label with PAX8. Another feature of several renal lesions is that the stroma can undergo metaplasia to ovarian-like stroma which expresses estrogen receptor (ER) and progesterone receptor (PR). This metaplasia is associated with AMLEC and MEST. The major differential diagnosis in this case is MEST. As with the current case, MESTs can characteristically present as a polypoid mass protruding into the renal pelvis. MESTs would similarly have a mixture of tubules, often cystic, and stroma that resemble Mullerian stroma. The key feature in this case of polypoid endometriosis (polypoid endometrioma) is that the epithelium lining the tubules is Mullerian composed of cuboidal and columnar cells with prominent cilia, indicating tubal differentiation. The stroma also appears more typical of endometrial stroma than the fibroblastic appearing ovarian stroma seen in MEST. Another feature seen in this case that is classic for polypoid endometriosis is the clusters of thick walled arteries, identical to those seen in endometrial polyps. Polypoid endometriosis results in a tumor-like lesion of endometriosis occurring in a cavity allowing it to become polypoid. It has been most commonly seen in the colon, vagina, vulva, cervix, bladder, ureter, and ovary. As with usual endometriosis, a variety of epithelial and stromal neoplasms have been described arising in polypoid endometriosis.
Presented by Dr. Jonathan Epstein and prepared by Dr. Kevan Salimian
A 21 year old man underwent an orchiectomy for a 1.5 cm. testicular mass.
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A 21 year old man underwent an orchiectomy for a 1.5 cm. testicular mass.
Choose the correct diagnosis:
Correct
Answer: D. Granulosa cell tumor
Histology: At low magnification, the lesion is well circumscribed and is separated by eosinophilic collagen bundles. At higher magnification, there are irregular nests of cells having round-ovoid nuclei and evenly dispersed chromatin without readily visible nucleoli. Many cells have nuclear grooves. Mitotic figures are infrequent. Occasional follicular structures containing watery eosinophilic secretions in the lumina are seen surrounded by cells with rounded nuclei.
Discussion: The tumor at low magnification has the typical appearance of a benign sex-cord stromal tumor of the testis. These tumors characteristically are well circumscribed and have bands of bright eosinophilic collagen dissecting the tumor. The key diagnostic criteria in this case resides in the nuclear appearance. In contrast to the last case, the nuclei in this case are not neuroendocrine. Instead of rounded nuclei with salt and pepper nuclei seen in a carcinoid tumor, the nuclei in this case are angulated with more dense chromatin. Sertoli cell tumor nuclei resemble those seen in normal Sertoli cells consisting of slightly ovoid uniform nuclei with delicate homogeneous chromatin and a single centrally located small but distinct nucleolus. In the current case, the nuclei lack these features and intead many have nuclear grooves typical of a granulosa cell tumor. Another unique feature diagnostic of a granulosa cell tumor is the presence of Call-Exner bodies described above with follicles containing eosinophilic secretions. Sertoli cell tumors often have ill defined lumina trying to recapitulate seminiferous tubules but not the well defined tubules with secretions of Call-Exner bodies. It is important to distinguish a benign Sertoli cell tumor from a granulosa cell tumor, as patients with the former can be told that they are cured following orchiectomy, whereas granulosa cell tumors as in the ovary are more unpredictable in their behavior. Although the majority of testicular granulosa cell tumors behave in a benign fashion, a few have not despite the lack of overt malignant histological features. Immunohistochemistry is not helpful to distinguish amongst sex-cord stromal tumors, as they stain similarly, The best and most commonly used markers that label these tumors are inhibin and steroid factor 1 (SF1).
Incorrect
Answer: D. Granulosa cell tumor
Histology: At low magnification, the lesion is well circumscribed and is separated by eosinophilic collagen bundles. At higher magnification, there are irregular nests of cells having round-ovoid nuclei and evenly dispersed chromatin without readily visible nucleoli. Many cells have nuclear grooves. Mitotic figures are infrequent. Occasional follicular structures containing watery eosinophilic secretions in the lumina are seen surrounded by cells with rounded nuclei.
Discussion: The tumor at low magnification has the typical appearance of a benign sex-cord stromal tumor of the testis. These tumors characteristically are well circumscribed and have bands of bright eosinophilic collagen dissecting the tumor. The key diagnostic criteria in this case resides in the nuclear appearance. In contrast to the last case, the nuclei in this case are not neuroendocrine. Instead of rounded nuclei with salt and pepper nuclei seen in a carcinoid tumor, the nuclei in this case are angulated with more dense chromatin. Sertoli cell tumor nuclei resemble those seen in normal Sertoli cells consisting of slightly ovoid uniform nuclei with delicate homogeneous chromatin and a single centrally located small but distinct nucleolus. In the current case, the nuclei lack these features and intead many have nuclear grooves typical of a granulosa cell tumor. Another unique feature diagnostic of a granulosa cell tumor is the presence of Call-Exner bodies described above with follicles containing eosinophilic secretions. Sertoli cell tumors often have ill defined lumina trying to recapitulate seminiferous tubules but not the well defined tubules with secretions of Call-Exner bodies. It is important to distinguish a benign Sertoli cell tumor from a granulosa cell tumor, as patients with the former can be told that they are cured following orchiectomy, whereas granulosa cell tumors as in the ovary are more unpredictable in their behavior. Although the majority of testicular granulosa cell tumors behave in a benign fashion, a few have not despite the lack of overt malignant histological features. Immunohistochemistry is not helpful to distinguish amongst sex-cord stromal tumors, as they stain similarly, The best and most commonly used markers that label these tumors are inhibin and steroid factor 1 (SF1).
Presented by Dr. Jonathan Epstein and prepared by Dr. Kevan Salimian
A 67 year old man was diagnosed with tumor on needle biopsy and underwent a radical prostatectomy. A ki67 was performed which showed 10% positivity.
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A 67 year old man was diagnosed with tumor on needle biopsy and underwent a radical prostatectomy. A ki67 was performed which showed 10% positivity.
Choose the correct diagnosis:
Correct
Answer: D. Carcinoid
Histology: The tumor consists of large islands of tumor with surrounding dense hyalinized stroma. Within the islands are ribbons of cells with round uniform nuclei with delicate “salt and pepper” chromatin and a moderate amount of eosinophilic cytoplasm. Scattered mitotic figures are noted. In the center of the nests are sheets of pyknotic dyscohesive tumor cells which looks different from the surrounding more organoid appearance. The tumor lacked necrosis, except for a small area that probably was from the prior biopsy. Extensive lymph-vascular space invasion and extraprostatic extension was present. Submitted immunohistochemical stains demonstrated the following results: The neoplastic cells were positive for synaptophysin, chromogranin, CK20 focally and negative for NKX3.1, CK7, GATA, p501S and p63.
Discussion:
Small cell carcinoma is a high grade tumor defined by characteristic nuclear features, including lack of prominent nucleoli, nuclear molding, fragility, and crush artifact. High nuclear to cytoplasmic ratio and indistinct cell borders are characteristic, as is a high mitotic rate and apoptotic bodies. In contrast to a small cell carcinoma, the tumor in this case has a prominent endocrine appearance with ribbons and cords of tumor, more typical of well-differentiated NE tumor (carcinoid) as opposed to small cell carcinoma. Many of the more solid sheet-like appearing areas are poorly preserved and are an artifact of poor cellular preservation. The absence of increased mitotic activity and lack of high Ki-67 proliferative index are also not consistent with a high grade NE carcinoma. The extensive lymph-vascular space invasion and extraprostatic extension is still consistent with an intermediate grade NE tumor, albeit one with an increased risk of aggressive behavior.
True carcinoid tumors of the prostate are extremely rare. In order to diagnose a carcinoid of the prostate and distinguish it from a prostate adenocarcinoma with carcinoid-like features, the following features should be present: 1) Not closely associated with concomitant adenocarcinoma of the prostate; 2) Immunohistochemically positive for NE markers and negative for PSA and other prostatic markers, and 3) Originating in the prostatic parenchyma. Of the cases in the literature, there are only 5 cases satisfy this definition. Two cases were in men in their 30s, younger than typically seen with adenocarcinoma of the prostate. The remaining three cases were in even younger males with multiple endocrine neoplasia (MEN) IIB syndrome. Patients were 7, 19, and 22 years of age. Although the data is limited, prostatic carcinoids tend to present with locally advanced disease, including some with regional lymph node metastases yet still have a favorable prognosis. It is reasonable for these true carcinoids to grade them in an analogous fashion to those of gastrointestinal tract based on mitotic rates and Ki-67 proliferation rates. Most cases reported with carcinoid-like morphology have admixed usual prostate cancer or the carcinoid-like tumor expressed PSA. Clinically, carcinoid-like adenocarcinomas have behaved like ordinary prostate carcinomas and in none of these cases has a carcinoid syndrome been present. Prostate-specific acid phosphatase immunoreactivity is not discriminatory in the assessment of whether a tumor is a true carcinoid or adenocarcinoma with carcinoid-like features as even some non-prostatic carcinoid tumors express PSAP.
Large cell neuroendocrine carcinoma (LCNEC) of prostate is exceptionally rare, particularly its pure form. The largest series by Evans et al. describes seven cases of LCNEC, only one pure and apparently de novo. Six other cases represented progression from prior typical prostate adenocarcinoma, following longstanding hormonal therapy. According to the authors, the large cell neuroendocrine component was composed of sheets and ribbons of amphophilic cells with large nuclei, coarse chromatin and prominent nucleoli. Mitotic activity was high, and foci of necrosis were present. The LCNEC component was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S. Ki67 proliferative index was >50%.
Incorrect
Answer: D. Carcinoid
Histology: The tumor consists of large islands of tumor with surrounding dense hyalinized stroma. Within the islands are ribbons of cells with round uniform nuclei with delicate “salt and pepper” chromatin and a moderate amount of eosinophilic cytoplasm. Scattered mitotic figures are noted. In the center of the nests are sheets of pyknotic dyscohesive tumor cells which looks different from the surrounding more organoid appearance. The tumor lacked necrosis, except for a small area that probably was from the prior biopsy. Extensive lymph-vascular space invasion and extraprostatic extension was present. Submitted immunohistochemical stains demonstrated the following results: The neoplastic cells were positive for synaptophysin, chromogranin, CK20 focally and negative for NKX3.1, CK7, GATA, p501S and p63.
Discussion:
Small cell carcinoma is a high grade tumor defined by characteristic nuclear features, including lack of prominent nucleoli, nuclear molding, fragility, and crush artifact. High nuclear to cytoplasmic ratio and indistinct cell borders are characteristic, as is a high mitotic rate and apoptotic bodies. In contrast to a small cell carcinoma, the tumor in this case has a prominent endocrine appearance with ribbons and cords of tumor, more typical of well-differentiated NE tumor (carcinoid) as opposed to small cell carcinoma. Many of the more solid sheet-like appearing areas are poorly preserved and are an artifact of poor cellular preservation. The absence of increased mitotic activity and lack of high Ki-67 proliferative index are also not consistent with a high grade NE carcinoma. The extensive lymph-vascular space invasion and extraprostatic extension is still consistent with an intermediate grade NE tumor, albeit one with an increased risk of aggressive behavior.
True carcinoid tumors of the prostate are extremely rare. In order to diagnose a carcinoid of the prostate and distinguish it from a prostate adenocarcinoma with carcinoid-like features, the following features should be present: 1) Not closely associated with concomitant adenocarcinoma of the prostate; 2) Immunohistochemically positive for NE markers and negative for PSA and other prostatic markers, and 3) Originating in the prostatic parenchyma. Of the cases in the literature, there are only 5 cases satisfy this definition. Two cases were in men in their 30s, younger than typically seen with adenocarcinoma of the prostate. The remaining three cases were in even younger males with multiple endocrine neoplasia (MEN) IIB syndrome. Patients were 7, 19, and 22 years of age. Although the data is limited, prostatic carcinoids tend to present with locally advanced disease, including some with regional lymph node metastases yet still have a favorable prognosis. It is reasonable for these true carcinoids to grade them in an analogous fashion to those of gastrointestinal tract based on mitotic rates and Ki-67 proliferation rates. Most cases reported with carcinoid-like morphology have admixed usual prostate cancer or the carcinoid-like tumor expressed PSA. Clinically, carcinoid-like adenocarcinomas have behaved like ordinary prostate carcinomas and in none of these cases has a carcinoid syndrome been present. Prostate-specific acid phosphatase immunoreactivity is not discriminatory in the assessment of whether a tumor is a true carcinoid or adenocarcinoma with carcinoid-like features as even some non-prostatic carcinoid tumors express PSAP.
Large cell neuroendocrine carcinoma (LCNEC) of prostate is exceptionally rare, particularly its pure form. The largest series by Evans et al. describes seven cases of LCNEC, only one pure and apparently de novo. Six other cases represented progression from prior typical prostate adenocarcinoma, following longstanding hormonal therapy. According to the authors, the large cell neuroendocrine component was composed of sheets and ribbons of amphophilic cells with large nuclei, coarse chromatin and prominent nucleoli. Mitotic activity was high, and foci of necrosis were present. The LCNEC component was strongly positive for CD56, CD57, chromogranin A, synaptophysin, and P504S. Ki67 proliferative index was >50%.
Presented by Dr. Andres Matoso and prepared by Dr. Robby Jones
This is a 71 year old male with a urethral polyp.
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This is a 71 year old male with a urethral polyp. Choose the correct diagnosis below.
Correct
Answer: 2. Prostatic duct adenocarcinoma
Histology: Exophytic papillary intraurethral lesion with areas of cribriform growth. The epithelial lining is characterized by pseudostratified epithelial cells with abundant cytoplasm and prominent nucleoli. There are conspicuous mitoses.
Discussion: When prostatic duct adenocarcinoma occurs in proximity to the veromontanum, it can show an exophytic and papillary growth into the lumen of the urethra. The clinician usually submits these lesions as “urethral polyp.” The presence of pseudostratified epithelium with papillary architecture should suggest this diagnosis. Occasionally, benign prostatic glands can show papillary architecture but the nuclei would be bland without prominent nucleoli and without the nuclear pseudostratification characteristic of prostatic duct adenocarcinoma. Prostate markers could be used to differentiate from an intestinal type polyp. PIN4 can be patchy positive for basal cells. In general, prostatic duct adenocarcinoma has a prognosis that is similar to Gleason 8 (grade group 4).
References:
Am J Surg Pathol. 1999;23:1471-79
J Urol. 2010;184:2303-07
Incorrect
Answer: 2. Prostatic duct adenocarcinoma
Histology: Exophytic papillary intraurethral lesion with areas of cribriform growth. The epithelial lining is characterized by pseudostratified epithelial cells with abundant cytoplasm and prominent nucleoli. There are conspicuous mitoses.
Discussion: When prostatic duct adenocarcinoma occurs in proximity to the veromontanum, it can show an exophytic and papillary growth into the lumen of the urethra. The clinician usually submits these lesions as “urethral polyp.” The presence of pseudostratified epithelium with papillary architecture should suggest this diagnosis. Occasionally, benign prostatic glands can show papillary architecture but the nuclei would be bland without prominent nucleoli and without the nuclear pseudostratification characteristic of prostatic duct adenocarcinoma. Prostate markers could be used to differentiate from an intestinal type polyp. PIN4 can be patchy positive for basal cells. In general, prostatic duct adenocarcinoma has a prognosis that is similar to Gleason 8 (grade group 4).
References:
Am J Surg Pathol. 1999;23:1471-79
J Urol. 2010;184:2303-07
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