Mixed Adenoneuroendocrine Carcinoma of the Pancreas

Abstract

Among the “mixed” carcinomas of the pancreas, mixed adenoneuroendocrine carcinomas (MANECs) are the least common. These extremely rare epithelial neoplasms are said to account for less than 2 % of all gastroenteropancreatic neuroendocrine (NE) tumors and are characterized by an intimate mixture of malignant ductal (glandular) and neuroendocrine tumor cells, both of which show variable degrees of differentiation (well– poorly differentiated) and have individually distinctive immunoprofiles. The World Health Organization (WHO) recommends that at least 30 % of either component be present in order for tumors to qualify as MANEC. In the vast majority of cases, the NE component is poorly differentiated/high grade (small or large cell type). Occasionally well-differentiated NE tumor (2010 WHO/ENETS grade 1 or 2) may be encountered in combination with adenocarcinoma. Patients with pancreatic MANEC range in age from 21 to 84 years (mean of 68 years) and males and females are equally affected. Tumors often arise in the head, followed by the tail and body, are often circumscribed, and range from 2 to 12 cm (mean, 5.6 cm). MANECs are often metastatic to lymphatics, regional lymph nodes, and perineural spaces with positive resection margins at diagnosis. Histologic differentials that should be excluded include peri-isletic invasion by pancreatic ductal adenocarcinoma, ductulo-insular neuroendocrine tumors (with entrapped or proliferating benign ductules), and pancreatoblastomas with predominant ductal and neuroendocrine differentiation. The optimal management of MANECs remains unclear, but for tumors with a poorly differentiated neuroendocrine carcinoma component, platinum-based regimens may be preferable. Not surprisingly, MANECs are highly aggressive tumors with a prognosis akin to and perhaps only slightly better than that of poorly differentiated neuroendocrine carcinoma.