Department of Human Pathology, Kanazawa University Graduate School of Medicine, Kanazawa 920-8640, Japan.
Virchows Arch. 2012 Mar;460(3):281-9. doi: 10.1007/s00428-012-1212-4. Epub 2012 Feb 23.
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.
肝胆器官的神经内分泌肿瘤非常罕见，但已有几例混合性腺神经内分泌癌（MANEC）的报道。本研究旨在对胆管 MANEC 的神经内分泌成分进行特征分析。本研究共分析了 274 例胆道癌病例，包括 17 例肝内胆管癌（ICC）、15 例无肝胆疾病史的肝门部 ICC、55 例伴有肝胆管结石的肝门部 ICC、49 例胆囊癌、53 例肝外胆管癌和 85 例肝细胞癌。采用神经内分泌标志物（嗜铬粒蛋白 A 和突触素）的免疫组织化学方法检测神经内分泌成分。在 MANEC 病例中，除了进行密切的组织学检查外，还评估了增殖活性和生长抑素受体 2A 的表达。除普通腺癌外，还在 4%（55 例中有 2 例）伴有肝胆管结石的肝门部胆管癌、10%（49 例中有 5 例）胆囊癌和 4%（53 例中有 2 例）肝外胆管癌中发现了神经内分泌成分占整个肿瘤的 30%以上，但在肝内胆管癌、无肝胆疾病史的肝门部胆管癌和肝细胞癌中未发现。有 2 例对生长抑素受体 2A 呈阳性。腺癌成分主要位于肿瘤表面，大多数间质和血管侵犯及淋巴结转移均涉及神经内分泌成分，表现为神经内分泌肿瘤 G2 或神经内分泌癌（NEC）的特征。与腺癌成分相比，NEC 成分在 Ki67 免疫染色中表现出更高的增殖活性。胆管 MANEC 见于伴有肝胆管结石的肝门部胆管癌、胆囊癌和肝外胆管癌，具有特征性的组织学表现。由于胆管 MANEC 中的神经内分泌成分决定了预后，因此识别它并考虑使用生长抑素类似物辅助治疗的适应证非常重要。
