Extrahepatic cholangiocarcinoma: Current concepts in histopathology, immunohistochemistry, and molecular diagnostics

Cholangiocarcinoma (CCA) makes up a diverse group of malignancies that originate from the biliary epithelium. Despite its rarity, this is a highly aggressive group of diseases with a high mortality, which has been increasing on a global scale. Classification of CCA is based on the anatomical site of origin and consists of intrahepatic (iCCA), perihilar (pCCA), and distal (dCCA) cholangiocarcinoma. The pathologic diagnosis of CCA can be challenging from multiple standpoints, including tissue acquisition and interpretation. Surgery is the only curative treatment, but patients often present at late stages, which may not be amenable to surgical treatment. Novel therapies are emerging for CCA, and early genetic testing is essential to identify candidate patients. There is a need for further developments in immunohistochemistry and molecular characterization of CCA to enable earlier diagnosis, especially from limited samples. This review provides a concise overview of current concepts in the pathology of CCA, focusing on diagnostic challenges, histology, staging, immunohistochemistry, and evolving molecular features.