De novo large cell neuroendocrine carcinoma of the prostate, case report and literature review

Large cell neuroendocrine carcinoma of the prostate (LCNEC), de novo in particular, is an extremely rare entity that has only been described in the literature in case reports. Historically, the majority of the cases of LCNEC reported in the literature represent typical prostatic adenocarcinomas that transformed after long standing androgen deprivation therapy (ADT). These cases were admixed with histological areas of usual adenocarcinoma and showed hybrid features of both neuroendocrine and usual adenocarcinoma. Here we present a case of an LCNEC without admixed areas of usual prostatic adenocarcinoma arising de novo in a patient without prior history of hormonal therapy. The tumor also shows morphologic evidence of neuroendocrine differentiation; composed of large sheets and nests of cells with moderate amphophilic cytoplasm with peripheral palisading, and vesicular clumpy chromatin with prominent nucleoli. The carcinoma's prostatic origin is indicated by positive immunohistochemical staining for PSA, PAP, PSMA, racemase, and Nkx3.1. Diffusely positive staining for chromogranin and synaptophysin, as well as the presence of secretory granules in the cytoplasm of the tumor cells demonstrated by electron microscopy supports the NE differentiation. NE prostate cancer usually does not express AR and is refractory to ADT therapy while AR and ERG are positive in this case. In summary, we report a de novo LCNEC of the prostate with review of literature, in particular, clinical implications.