Preneoplastic and Neoplastic Biliary Diseases

Preneoplastic and neoplastic biliary disease comprises biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasms, mucinous cystic neoplasms (MCNs), and cholangiocarcinoma and their variants. Correct recognition of these entities can be challenging, especially on small/needle biopsies, but is required to plan therapy and guide transplant in the setting of cirrhosis. Salient histologic features of these entities, along with ancillary use of immunostains and key molecular findings aiding in diagnosis, are discussed. Type 2 intraductal papillary neoplasm of the bile ducts is typically associated with an invasive malignancy and lack unique molecular features associated with the Type 1 intraductal papillary neoplasm, thus they are called “papillary cholangiocarcinoma” by some authors. Some of the cholangiocarcinoma variants, like enteroblastic and mucoepidermoid, are under-recognized and can pose diagnostic challenges. The tubulocystic and cholangioblastic variants are relatively recently described but are being increasingly recognized. The cholangioblastic variant has a novel NIBPL-NACC1 fusion described in the more recent larger series reported, making it a somewhat unique variant of cholangiocarcinoma. Nomenclature of the cholangioblastic variant is in evolution as is the link between adenofibroma and the tubulocystic variant. Correct recognition of these variant subtypes would aid in long-term studies to better determine the prognosis in these subtypes.