Clinicopathological features and lymph node metastatic patterns of gastric mixed adenoneuroendocrine carcinoma.

Mixed adenoneuroendocrine carcinoma (MANEC), also known as high- grade mixed neuroendocrine-non-neuroendocrine neoplasm (MiNEN) in the World Health Organization (WHO) classification of tumors of the endocrine organs (2017), is a rare gastric malignancy. Here, we present 10 cases of gastric MANEC and analyse their clinicopathological features and lymph node metastatic patterns. Six patients were male, and four were female. The mean age of the patients was 67.9 years. Grossly, most tumors presented as ulcerative mass, located in gastric fundus or/and cardia. Microscopically, the neuroendocrine component, large cell neuroendocrine carcinoma in most cases (8/10), constituted 30-70% of the whole tumor. It was diffusely positive for CD56 or/and synaptophysin in all cases, but negative for chromogranin A in 9 cases. Ki-67 index was 50-80% in neuroendocrine component. The glandular component was moderately (6/10) or poorly (4/10) differentiated adenocarcinoma. Nine of 10 cases were positive for lymph node metastasis, with pure neuroendocrine component (6/9), or pure glandular component (1/9), or mixed components (2/9). The patients were treated with surgery, combining with chemotherapy (4/10), radiotherapy (2/10) and immunotherapy (1/10). Five patients died from tumor progress, with an average survival time of 18.6 months. The dead cases had predominant neuroendocrine component in primary tumor or in metastatic lymph nodes. Neuroendocrine component may determine the clinical behavior and outcome in gastric MANEC. Different metastatic component makes the selection of chemotherapy protocol more challenging.