Pathological, molecular, and clinical characteristics of cholangiocarcinoma: A comprehensive review

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).