Pathology of Cholangiocarcinomas

Cholangiocarcinomas (CCA) are heterogeneous tumors that arise from epithelial cells of the biliary tract. They represent the second primary liver malignancy, after hepatocellular carcinoma. Recent epidemiological data show an increased incidence of intrahepatic CCA without any identified causes. According to their location on the biliary tract, intrahepatic, perihilar (p) and distal (d) CCA can be individualized. Intrahepatic CCA (iCCA) are subdivided into small duct type iCCA and large duct type iCCA, according to the level or size of the biliary duct affected. These two subgroups are characterized by distinct risk factors, gross aspect, histopathological and molecular features, and therapeutic management. The role of biopsy in iCCA is to confirm the diagnosis and to eliminate various differential diagnostics, in particular, metastases. In p/d CCA, biopsy requires more invasive approaches, and tissue samples are difficult to obtain, leading to a high rate of false negatives. In this review, we will discuss the different classifications of CCA (anatomical and macroscopic). We will describe the various microscopic and phenotypic subtypes of CCA. Finally, we will deal with their mode of extension, the role of biopsy and pre-neoplastic lesions.