Insights into gastric mixed adenoneuroendocrine carcinoma: a novel comparative study of clinicopathological features and survival outcomes

Mixed adenoneuroendocrine carcinoma (MANEC) is a rare and histologically complex malignancy. Due to its low incidence, data on gastric MANEC (G-MANEC) are limited, and its clinicopathological characteristics and prognosis remain poorly defined. In this study, we performed a retrospective analysis of 168 G-MANEC patients and identified a median age of 64.7 years at diagnosis. Cases were classified into adenocarcinoma (AC)-predominant and neuroendocrine carcinoma (NEC)-predominant subtypes based on histological composition, with large-cell NEC accounting for 69.9% of NEC-predominant tumors. Patterns of lymph node metastasis (LNM) included involvement of either a single component (AC or NEC) or both components. Survival analysis revealed a median overall survival (OS) of 24 months, with 1-, 3-, and 5-year survival rates of 72.6%, 39.5%, and 29.7%, respectively. Univariate and multivariate analyses identified tumor size, LNM, and histological subtype as independent prognostic factors. Compared with a cohort of 328 patients with pure gastric adenocarcinoma, G-MANEC cases exhibited distinct clinicopathological features—particularly in terms of tumor size, Ki-67 index, and LNM. Collectively, these findings underscore that G-MANEC is associated with significantly poorer overall survival than that of conventional gastric adenocarcinoma.