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Composite neuroendocrine-exocrine carcinomas (NEECs) with two distinct components of adenocarcinoma and neuroendocrine (NE) carcinoma within the same tumor are rare but may have a clue for clarifying the pathogenesis of NE tumors arising from non-endocrine organs. This study was done to characterize histological and immunohistochemical features of NEECs of the stomach comparing with pure NE tumors of the gastrointestinal (GI) tract. Microscopically, adenocarcinoma components in 6 of 8 NEECs were well differentiated and located superficially, whereas NE components were poorly differentiated and located deeply. In the remaining two cases, smaller NE components were intermingled within adenocarcinoma components. Immunohistochemically, neural cell adhesion molecule (NCAM) was positive in 5 NE components, of which 3 cases were homogeneously positive, and 2 adenocarcinoma components of 8 NEECs, while 19 of 21 pure NE tumors of GI tract were homogeneously positive for NCAM. Ghrelin-immunoreactivity was found in 4 NE components and 2 adenocarcinoma components of NEECs, although 20 pure NE tumors were positive for ghrelin. Smad4 was positive in both components of 7 NEECs. These findings suggest that composite NEECs and pure NE tumors of GI tract may have different NE properties and that most NE components of composite NEECs of the stomach may originate from an adenocarcinoma precursor cell and occasional tumors from a pluripotent cell.

Histological and immunohistochemical study of composite neuroendocrine-exocrine carcinomas of the stomach