[Cholangiocarcinoma : Histopathological diagnosis, classification and molecular diagnostics-an update]

The term cholangiocarcinoma covers various malignant epithelial neoplasms with biliary differentiation. The aim of this article is to provide an update with new findings and developments on the etiology, pathogenesis, diagnosis, classification, and molecular diagnostics of intra- and extrahepatic cholangiocarcinomas based on the last review published in this journal in 2020. The basis is the currently available specialist literature, lectures, and discussions at congresses as well as our own findings.Cholangiocarcinomas are morphologically and molecularly diverse malignant epithelial neoplasms that can develop ubiquitously in the biliary tract. As there is a broad histological and immunohistochemical overlap with the frequent metastases in the liver, the definitive diagnosis should only be made in a clinical context. According to macroanatomical criteria, cholangiocarcinomas are subclassified into intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) tumors. In the case of iCCA, a distinction can be made in particular between small duct type tumors (SD-iCCA) and large duct type tumors (LD-iCCA). LD-iCCA are morphologically and molecularly practically equivalent to extrahepatic CCA (eCCA, including pCCA and dCCA), while SD-iCCA originate from the small bile ducts or precursor cells and often exhibit druggable molecular alterations. Cholangiocarcinogenesis is now better described by morphomolecular studies of precursor lesions and the various precursor lesions can be assigned not only according to anatomical classification but also to distinct etiologies. A precise classification of these neoplasms is therefore essential, especially with regard to the use of established and the development of novel targeted therapeutic approaches.