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Presented by Dr. Ezra Baraban and prepared by Dr. Sintawat Wangsiricharoen.
A 77-year-old man with peritoneal carcinomatosis.
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1. Question
A 77-year-old man with peritoneal carcinomatosis. Choose the correct diagnosis:
Correct
Answer: C. Malignant mesothelioma.
Sections show an epithelioid neoplasm infiltrating adipose tissue, such that if this lesion were of mesothelial lineage, it would qualify as malignant mesothelioma. The main differential diagnosis is between metastatic adenocarcinoma and mesothelioma. Immunohistochemistry is critical, with positivity for multiple mesothelial markers (CK5/6, WT1, calretinin, and D240) and negativity for multiple carcinoma markers (claudin-4, MOC31, BerEP4) essential to support the mesothelial nature of this proliferation. Importantly, diffuse keratin expression is expected in mesothelial lesions, so cannot distinguish between adenocarcinoma and mesothelioma. If definitive invasion is not present, BAP1 or MTAP loss can support a diagnosis of mesothelioma, but retention of either of these does not exclude it. Desmoplastic small round cell tumor can have immunophenotypic overlap with mesothelioma (keratin, WT1 expression), but should lack calretinin and D240 expression, and would also typically label with desmin, and importantly, has an undifferentiated appearance morphologically, as opposed to the tubular morphology that predominates in this case. Rare mesotheliomas can have EWSR1 fusions, which are the hallmark of desmoplastic small round cell tumor, so the presence of an EWSR1 fusion alone does not distinguish between these two entities either.
Incorrect
Answer: C. Malignant mesothelioma.
Sections show an epithelioid neoplasm infiltrating adipose tissue, such that if this lesion were of mesothelial lineage, it would qualify as malignant mesothelioma. The main differential diagnosis is between metastatic adenocarcinoma and mesothelioma. Immunohistochemistry is critical, with positivity for multiple mesothelial markers (CK5/6, WT1, calretinin, and D240) and negativity for multiple carcinoma markers (claudin-4, MOC31, BerEP4) essential to support the mesothelial nature of this proliferation. Importantly, diffuse keratin expression is expected in mesothelial lesions, so cannot distinguish between adenocarcinoma and mesothelioma. If definitive invasion is not present, BAP1 or MTAP loss can support a diagnosis of mesothelioma, but retention of either of these does not exclude it. Desmoplastic small round cell tumor can have immunophenotypic overlap with mesothelioma (keratin, WT1 expression), but should lack calretinin and D240 expression, and would also typically label with desmin, and importantly, has an undifferentiated appearance morphologically, as opposed to the tubular morphology that predominates in this case. Rare mesotheliomas can have EWSR1 fusions, which are the hallmark of desmoplastic small round cell tumor, so the presence of an EWSR1 fusion alone does not distinguish between these two entities either.
