Rare histotypes of epithelial biliary tract tumors: a literature review

Adenocarcinoma represents the most frequent biliary tract cancer. However, other rare histotypes can be found in the biliary tract, such as cholangiolocellular carcinoma, cholangiocarcinoma with ductal plate malformation pattern, adenosquamous carcinoma, mucinous carcinoma, signet ring cell carcinoma, clear cell carcinoma, mucoepidermoid carcinoma, lymphoepithelioma-like carcinoma, and sarcomatous cholangiocarcinoma. These cancer types account for less than 10% of all the already rare biliary tract tumors. Yet, they represent a relevant issue in everyday clinical practice, given the lack of therapeutic recommendations and the overall scarcity of data, mainly deriving from isolated small center-specific cohorts of patients.The shifts of such histotypes from the most common ones reflect genetic and molecular differences, determine changes in clinical aggressiveness, and suggest a possible variability in sensitivity to the standard treatments of biliary adenocarcinomas. The consistency and degree of these variables are still to be solidly demonstrated and investigated. Therefore, this paper aims to review the current literature concerning very infrequent and rare epithelial biliary tract cancers, focusing our attention on the clinical, molecular, and immunohistochemical features of these tumors.