Published online Nov 8, 2015. doi: 10.4254/wjh.v7.i25.2563
Peer-review started: May 30, 2015
First decision: June 18, 2015
Revised: July 22, 2015
Accepted: October 16, 2015
Article in press: October 19, 2015
Published online: November 8, 2015
Cholangiocarcinoma (CC) is primarily a malignant tumor of older adults most prevalent in Southeast Asia, where liver fluke infestation is high. However the etiology in western countries is unknown. Although the incidence of extrahepatic cholangiocarcinoma has remained constant, incidence of intrahepatic CC (ICC) which differs in morphology, pathogenesis, risk factors, treatment and prognosis is increasing. While this increase is associated with hepatitis C virus infection, chronic nonalcoholic liver disease, obesity, and smoking, the pathogenesis of ICC and molecular alterations underlying the carcinogenesis are not completely elucidated. Benign biliary lesions such as biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, von Meyenburg complex or bile duct hamartoma, and bile duct adenoma have been associated with ICC. For each of these entities, evidence suggests or supports a role as premalignant lesions. This article summarized the important biological significance of the precursor lesions of ICC and the molecular mechanisms that may be involved in intrahepatic cholangiocarcinogenesis.
Core tip: This manuscript highlights the important development in the research field of intrahepatic cholangiocarcinogenesis, and summarizes some key points related to progression from the precursor lesions to the intrahepatic cholangiocarcinoma, including their molecular genetics. Each individual precursor or potential precursor is linked to the cancer by the clinical, histological and molecular association.