Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Nov 8, 2015; 7(25): 2563-2570
Published online Nov 8, 2015. doi: 10.4254/wjh.v7.i25.2563
Clinical and biological significance of precursor lesions of intrahepatic cholangiocarcinoma
Mark Ettel, Ogechukwu Eze, Ruliang Xu
Mark Ettel, Ogechukwu Eze, Ruliang Xu, Department of Pathology, NYU School of Medicine, New York, NY 10016, United States
Author contributions: All the authors equally contributed to this work.
Conflict-of-interest statement: None.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Ruliang Xu, MD, PhD, Department of Pathology, NYU School of Medicine, 560 First Avenue, New York, NY 10016, United States. ruliang.xu@nyumc.org
Telephone: +1-212-2630728 Fax: +1-212-2637916
Received: May 27, 2015
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.

Keywords: Intraepithelial neoplasia, Von Meyenburg complex or bile duct hamartoma, Bile duct adenoma, Intrahepatic cholangiocarcinoma, Intraductal papillary neoplasm of the bile duct

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.