Benign Biliary Tumors and Precursor Neoplasms: An Updated Clinicopathological and Molecular Review Based on the 2026...

Benign biliary tumors and precursor neoplasms of the biliary tract are a heterogeneous group of uncommon neoplasms with significant clinical and diagnostic implications. Their importance lies in their variable malignant potential and morphological and molecular similarities to pancreatic neoplasms. The sixth edition of the World Health Organization Classification of Digestive System Tumours (WHO DST6), published online in 2026, introduced major revisions to the classification of these entities. According to WHO DST6, benign tumors and precursor neoplasms of the liver and intrahepatic bile ducts include bile duct adenoma, biliary adenofibroma, and mucinous cystic neoplasm, whereas those of the gallbladder and extrahepatic bile ducts include biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile ducts, intraductal tubulopapillary neoplasm of the bile ducts, intraductal oncocytic papillary neoplasm of the bile ducts, and mass-forming intracholecystic neoplasm. Despite these advances, their histological and molecular heterogeneity continues to pose significant diagnostic challenges, particularly in distinguishing them from malignant biliary tumors on limited biopsy specimens and in recognizing early invasive lesions. This review summarizes the clinicopathological and molecular features of benign biliary tumors and precursor neoplasms, emphasizing differential diagnosis and key updates introduced in WHO DST6.