Nakanuma Y, et al. - Researchers examined intestinal subtype of intraductal papillary neoplasm of the bile duct (iIPNB) showing columnar cells with pseudostratified, cigar-shaped nuclei, and basophilic or amphophilic cytoplasm with the diffuse immunohistochemical expression of CK20 and/or CDX2 regarding their pathologic and genetic characteristics. Pathological examination of a total of 34 cases of iIPNB was done according to their anatomic location (the bile duct) and the findings were then compared with the intestinal subtype of intraductal papillary mucinous neoplasm (iIPMN) of the pancreas (n = 22). They noted a less-complicated villous-papillary pattern in intrahepatic IPNBs, while a papillary pattern with tubular and/or villous components and predominant high-grade dysplasia with complicated architectures were noted in extrahepatic IPNBs. Intrahepatic iIPNBs and iIPMNs but not extrahepatic iIPNBs show MUC5AC frequently and extensively. Extrahepatic IPNBs but not intrahepatic iIPNBs or iIPMN frequently expressed CD10. iIPMNs lacked or infrequently showed genetic mutations of TP53 and PIK3CA, while these mutations were frequently identified in extrahepatic iIPNBs. KRAS and GNAS, which were commonly observed in iIPMNs, were frequently detected in intrahepatic iIPNBs. Villous-papillary growth with features reminiscent of iIPMNs were noted in intrahepatic iIPNBs, while papillary growth with tubular and/or villous components, complicated histology and variable differences from iIPMNs were observed in extrahepatic iIPNBs, suggesting differences in the tumorigenesis of iIPNBs along the biliary tree.