Review
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2022; 14(3): 607-627
Published online Mar 15, 2022. doi: 10.4251/wjgo.v14.i3.607
Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review
Mukul Vij, Yogesh Puri, Ashwin Rammohan, Gowripriya G, Rajesh Rajalingam, Ilankumaran Kaliamoorthy, Mohamed Rela
Mukul Vij, Gowripriya G, Department of Pathology, Dr Rela Institute and Medical center, Chennai 600044, Tamil Nadu, India
Yogesh Puri, Ashwin Rammohan, Rajesh Rajalingam, Ilankumaran Kaliamoorthy, Mohamed Rela, Institute of Liver Disease and Transplantation, Dr Rela Institute and Medical Center, Chennai 600044, Tamil Nadu, India
Author contributions: Vij M conceptualized the review, performed literature search and drafting of the manuscript; Puri Y, Rammohan A, G G, Rajalingam R, Kaliamoorthy I and Rela M edited and revised the review; All authors read and approved the manuscript for publication.
Conflict-of-interest statement: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Mukul Vij, MD, Department of Pathology, Dr Rela Institute and Medical Center, No. 7 CLC Works Road, Chromepet, Chennai 600044, Tamil Nadu, India. mukul.vij.path@gmail.com
Received: September 25, 2021
Peer-review started: September 25, 2021
First decision: December 4, 2021
Revised: December 13, 2021
Accepted: February 23, 2022
Article in press: February 23, 2022
Published online: March 15, 2022
Processing time: 166 Days and 11.4 Hours
Abstract

Cholangiocarcinomas are a heterogeneous group of highly aggressive cancers that may arise anywhere within the biliary tree. There is a wide geographical variation with regards to its incidence, and risk-factor associations which may include liver fluke infection, primary sclerosing cholangitis, and hepatolithiasis amongst others. These tumours are classified into intrahepatic, perihilar and distal based on their anatomical location. Morphologically, intrahepatic cholangiocarcinomas are further sub-classified into small and large duct variants. Perihilar and distal cholangiocarcinomas are usually mucin-producing tubular adenocarcinomas. Cholangiocarcinomas develop through a multistep carcinogenesis and are preceded by dysplastic and in situ lesions. While clinical characteristics and management of these tumours have been extensively elucidated in literature, their ultra-structure and tumour biology remain relatively unknown. This review focuses on the current knowledge of pathological characteristics, molecular alterations of cholangiocarcinoma, and its precursor lesions (including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and mucinous cystic neoplasm).

Keywords: Cholangiocarcinoma; Classification; Pathology; Molecular features; Precursors lesions; Treatment

Core Tip: Cholangiocarcinoma is a heterogeneous and aggressive epithelial malignancy of the biliary system. The majority of cholangiocarcinomas are diagnosed at an advanced stage when choice of treatment is limited. Cholangiocarcinoma is classified into intrahepatic, perihilar, and distal bile duct cancer, according to the anatomical location. This review focuses on the current knowledge of histopathological features, molecular alterations and clinical characteristics of cholangiocarcinoma and its precursor lesions (including biliary intraepithelial neoplasia, intraductal papillary neoplasms of the bile duct, intraductal tubulopapillary neoplasms and hepatobiliary mucinous cystic neoplasm. Recently, actionable genetic alterations, mainly IDH1 mutations and FGFR2 fusions have been described, in cholangiocarcinoma.