Pathological classification of cholangiocarcinomas and their possible molecular targets

Cholangiocarcinomas (CCA) are heterogeneous tumours arising from epithelial cells of the bile ducts with aggressive biological behaviour. They are the second most common malignant primary liver tumour after hepatocellular carcinoma. With an increasing incidence, a clear etiological cause has not been identified yet. Several classifications have been developed to investigate tumour localisation, origin, proliferative potential and biomarkers. According to the anatomical classification, we distinguish intrahepatic, perihilar and distal types of CCA. Perihilar and distal biliary tumours are called extrahepatic CCAs according to the latest WHO classification. The two subtypes of intrahepatic CCAs, in addition to their histological picture, differ in their etiology, risk factors, molecular characteristics and therapeutic options. Molecular classification of tumours using multiomic assays allows the separation of inflammatory and proliferative classes within intrahepatic CCA. The identification of various target molecules (FGFR, IHD 1/2 inhibitors) as a result of genomic studies, which are still ongoing on a large scale, could significantly help the oncological treatment of patients by the introduction of target therapies.