H&O What is the definition of neuroendocrine prostate cancer (NEPO? HB NEPC is an aggressive variant of prostate cancer that typically is diagnosed in the later stages of advanced disease. It is thought to arise as a function of treatment resistance.1 In its pure form, NEPC is histologically similar to other high-grade or small cell neuroendocrine carcinomas, often expressing classical neuroendocrine markers (eg, chromogranins) and lacking expression of typical prostate markers, such as prostate specific antigen (PSA).2 The prostate cancer-specific TMPRSS2-ERG gene fusion is present in approximately half of NEPC cases, which distinguishes NEPC tumors from neuroendocrine tumors that arise from other primary sites. A break-apart fluorescence in situ hybridization (FISH) assay can be used to assess patients for TMPRSS2-ERG fusion in cases of small cell carcinoma of unknown primary tumor site to confirm prostate origin, although a negative test does not rule out NEPC. Notably, a spectrum of morphologies are observed in advanced prostate cancer; we frequently see mixed or overlapping tumors with features of both prostate adenocarcinoma and NEPC.
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