Neuroendocrine carcinoma of the stomach: morphologic and immunohistochemical characteristics and prognosis.

Neuroendocrine carcinoma (NEC) of the stomach has been recognized as a highly malignant tumor; however, because of its rarity, limited information is available regarding its clinicopathologic characteristics. Here, we investigated the morphologic and immunohistochemical features and prognosis of 51 cases of gastric NEC. Histologically, 40 lesions were large cell type, and 11 were small cell type. The large majority of the tumors exhibited a solid growth pattern (94%), with subsets of tumors showing trabecular (18%), scirrhous (10%), or tubular growth patterns (6%). Thirty-six cases (71%) had adenocarcinoma components and/or dysplasia. Among them, 26 cases (51%) were associated with intramucosal adenocarcinoma or dysplasia. Immunohistochemically, synaptophysin, chromogranin A, and CD56 were diffusely expressed in 48 (94%), 44 (86%), and 24 cases (47%), respectively. Two recently reported neuroendocrine markers, ASH1 and NKX2.2, were diffusely positive in 12 (24%) and 17 cases (33%), respectively. The diffuse or focal expression of TTF-1 was observed in 19 cases (37%). Among the 41 patients who underwent a curative resection, 16 patients (39%) developed radiologic recurrences, and the liver was the most frequent site of recurrence (11 patients, 27%). The 3- and 5-year overall survival rates were 57.8% and 44.7%, respectively. Regarding patient outcome, none of the histologic subclassifications, including small cell versus large cell types and the presence versus the absence of adenocarcinoma components and/or dysplasia, were significant. In a multivariate analysis, curative surgery was identified as the sole independent prognostic factor (P=0.03). Although gastric NECs exhibit significant morphologic diversity, their histologic subclassification is unlikely to be of immediate clinical relevance.