title: Clinicopathologic study of mixed adenoneuroendocrine carcinomas of hepatobiliary organs.
abstract: Neuroendocrine neoplasms in hepatobiliary organs are very rare, but several cases of mixed adenoneuroendocrine carcinoma (MANEC) have been reported. In this study, we characterized the neuroendocrine component of biliary MANEC. A total of 274 cases of biliary cancer including 17 intrahepatic cholangiocarcinomas (CCs), 15 hepatic hilar CCs without preceding hepatobiliary disease, 55 hepatic hilar CCs with hepatolithiasis, 49 gallbladder cancers, 53 extrahepatic CCs, and 85 hepatocellular carcinomas were examined for a neuroendocrine component using immunohistochemistry with neuroendocrine markers (chromogranin A and synaptophysin). In the MANEC cases, in addition to a close histological examination, the proliferative activity and the expression of somatostatin receptor 2A were also evaluated. In addition to an ordinary adenocarcinoma, a neuroendocrine component occupying more than 30% of the entire tumor was also found in 4% (2/55 cases) of hepatic hilar cholangiocarcinomas with hepatolithiasis, 10% (5/49 cases) of gallbladder cancers, and 4% (2/53 cases) of extrahepatic cholangiocarcinomas, but not in the intrahepatic cholangiocarcinomas, hilar cholangiocarcinomas without preceding hepatobiliary disease, and hepatocellular carcinomas. Two cases were positive for somatostatin receptor 2A. The adenocarcinoma components were predominately located at the surface of the tumors, and the majority of stromal and vascular invasion and lymph node metastasis involved neuroendocrine components, showing the features of neuroendocrine tumor G2 or neuroendocrine carcinomas (NECs). NEC components showed higher proliferative activity on Ki67 immunostaining, compared to the adenocarcinoma components. Biliary MANECs are found in hepatic hilar cholangiocarcinomas with hepatolithiasis, gallbladder cancers, and extrahepatic cholangiocarcinomas and show a characteristic histology. Since the neuroendocrine component in biliary MANEC defines the prognosis, it is important to identify it and consider the indications for adjunctive therapy with somatostatin analogues.
authors.affiliation: Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan. kenichih@med.kanazawa-u.ac.jp
authors.forename: Kenichi
authors.initials: K
authors.lastname: Harada
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ikeda
authors.forename: Hsu
authors.initials: H
authors.lastname: Maylee
authors.forename: Saya
authors.initials: S
authors.lastname: Igarashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okamura
authors.forename: Shinji
authors.initials: S
authors.lastname: Masuda
authors.forename: Yasuni
authors.initials: Y
authors.lastname: Nakanuma
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001650:Bile Duct Neoplasms / Q000378:metabolism / Q000473:pathology; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D001661:Biliary Tract Neoplasms / Q000378:metabolism / Q000473:pathology*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D018278:Carcinoma, Neuroendocrine / Q000378:metabolism / Q000473:pathology; D018281:Cholangiocarcinoma / Q000378:metabolism / Q000473:pathology; D005260:Female; D005706:Gallbladder Neoplasms / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D018193:Neoplasms, Complex and Mixed / Q000378:metabolism / Q000473:pathology*