Cytological features of mixed adenoneuroendocrine carcinoma of the ampulla: two case reports with review of literature.

Mixed adenoneuroendocrine carcinoma (MANEC) of ampulla is rare, with only 13 cases reported, and the diagnoses were all based on histology mostly after surgery. We describe two new cases with cytological features of signet ring-cell carcinoma mixed with small-cell carcinoma, and intestinal adenocarcinoma mixed with large-cell neuroendocrine carcinoma. Our cases and literature review demonstrate the higher frequency of periampullary-duodenum subtype in MANEC compared with non-MANEC ampullary carcinomas. In accordance, of the 14 MANEC cases with detailed morphology available, the most common glandular components are intestinal-type carcinoma (6/14), followed by goblet carcinoid tumor (3/14), signet ring-cell carcinoma (2/14), pancreatobiliary-type carcinoma (2/14), and pancreatic acinar cell carcinoma (1/14). The intestinal-type carcinoma and goblet carcinoid in MANEC are favorable histological types showing no distant metastasis or mortality (0/9) during 6-36 months follow-up. In contrast, the signet ring cell, pancreatobiliary-type carcinoma, and acinar cell carcinoma are unfavorable with distant metastatic rate and mortality rate of 80% (4/5) during 3-16 months follow-up. The combination of favorable glandular histological types with high-grade neuroendocrine tumors (neuroendocrine carcinoma) has a mortality rate of 0% (0/3), whereas the combination of unfavorable glandular types with low-grade neuroendocrine tumors (e.g., carcinoid, atypical carcinoid) has a mortality rate of 100% (3/3). In addition, younger age (<40 years) seems to be associated with high mortality rate of 100% (2/2). Overall, cytology preparations are able to make the diagnosis of MANEC and distinguish the subcomponents. Disease progression is apparently driven by the carcinomatous component of the tumor.