Precancerous lesions of intrahepatic cholangiocarcinoma

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Abstract
Intrahepatic cholangiocarcinoma (ICC), also known as cholangiocellular carcinoma or peripheral bile duct carcinoma, is an intrahepatic malignant tumor that consists of cells resembling the biliary epithelium. The proportion of ICC among primary hepatic malignancies is approximately 10% worldwide. Although the etiology and pathogenesis remain unclear in a great majority of cases, preceding pathologic conditions or etiologies in the development of ICC are known or suspected in a proportion of these patients. Some forms of ICC, such as those associated with hepatolithiasis or liver fluke infestation, are endemic in parts of the world, particularly in East Asia. ICC is reportedly a late complication of primary sclerosing cholangitis. Most of these preceding pathologic conditions are forms of chronic cholangitis, and longstanding inflammation, chronic injury, and regenerative hyperplasia of the biliary epithelium may be causally related to malignant transformation. Biliary epithelial dysplasia is encountered in the intrahepatic bile ducts both near and remote from ICC foci in the liver and near and remote from the chronically inflamed biliary tree. This lesion could be a precancerous lesion, and it shows telomerase activity and increased proliferative activities. Furthermore, congenital and developmental disorders of the biliary system, such as Caroli's disease, congenital hepatic fibrosis, and pancreatico-biliary malformation are occasionally associated with ICC. Benign biliary tumors, such as biliary papillomatosis, may eventually undergo malignant transformation. These lesions could be regarded as precancerous or borderline lesions. Some ICCs may also develop in nonbiliary viral cirrhosis. In the majority of cases of ICC, however, the etiology, pathogenesis, and developmental processes and precancerous lesions of the ICC remain unclear.

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