Epithelial precursor lesions of the bile duct

Biliary epithelial precursor lesions represent key initiating steps in the multistep pathogenesis of cholangiocarcinoma. The three commonly recognized entities-biliary intraepithelial neoplasia (BilIN), intraductal papillary neoplasm of the bile duct (IPNB), and intraductal tubulopapillary neoplasm of the bile duct (ITPN-B) -include both flat and mass-forming lesions and span a broad spectrum of morphologic, immunophenotypic, and molecular profiles. While their classification partially parallels that of pancreatic precursor lesions, biliary lesions exhibit unique architectural patterns, molecular alterations, and phenotypic variability. Accurate diagnosis is often complicated by overlapping histologic features, limited or fragmented sampling, and under-recognition of critical diagnostic criteria. This review synthesizes contemporary pathologic insights into biliary precursor lesions and provides a practical diagnostic framework based on detailed histologic evaluation, supported by ancillary immunohistochemical and molecular testing, differential diagnostic considerations, and integration of clinico-radiologic context. A nuanced understanding of the defining features and biological behavior of these lesions is essential to reduce diagnostic ambiguity, guide appropriate clinical decision-making, and enable effective risk stratification.