Gastric large cell neuroendocrine carcinomas: a distinct clinicopathologic entity.

The current histologic classifications of gastric cancers define only carcinoids and small cell carcinomas in the neuroendocrine (NE) category. This study aimed to characterize the histologic and clinical features of high-grade gastric NE carcinomas of nonsmall cell type, tentatively named large cell neuroendocrine carcinoma (LCNEC). Tumors with histologic features suspicious of NE differentiation were selected by a histologic review of 2835 resected gastric cancers, and those with a NE phenotype in > 50% and 1% to approximately 50% tumor cells assessed by expressing chromogranin A and/or synaptophysin were defined as LCNEC and adenocarcinoma with neuroendocrine differentiation (ACNED), respectively. One hundred ninety-nine tumors were selected and of the 109 positive for chromogranin A and/or synaptophysin, 42 and 44 met the criteria for LCNEC and ACNED, respectively. Generally, LCNECs demonstrated less predominant NE morphology than carcinoids, and could be roughly divided into solid (30 cases), tubular (7 cases), and scirrhous (5 cases) subtypes with reference to their main growth pattern. The prognosis of LCNECs was significantly worse than that of conventional adenocarcinomas (P < 0.0001). Thus, this study shows that the spectrum of gastric NE tumors is broader than has previously been recognized and LCNEC is not only a distinct histopathologic entity, but also a distinct clinical entity. Furthermore, the prognosis of ACNEDs was also significantly worse than that of adenocarcinomas (P < 0.0001), and some ACNEDs might actually have been LCNECs, and survival analysis showed that > 20% positivity of NE markers could be enough to characterize LCNEC, as long as light microscopic NE morphology was present in the tumor.