Pathological spectrum of intrahepatic cholangiocarcinoma arising in non-biliary chronic advanced liver diseases.

Intrahepatic cholangiocarcinoma (ICC) is reported to develop in non-biliary chronic advanced liver diseases (CALD). Herein, we characterize the pathological features of ICC arising in CALD in comparison with those in non-CALD livers. Of 471 surgically resected cases of ICC in Kanazawa, Japan and Seoul, Korea, 53 were associated with CALD (group A), while the remaining 418 arose in otherwise normal livers (group B). When ICC were classified into bile duct type, bile ductular type, variants, and intraductal papillary neoplasm of the bile duct (IPNB), the whole spectrum of subtypes were found in group A; the majority of ICC belonged to the bile duct type in both groups. In group A, bile ductular type was rather frequent (22.6%) compared with group B (8.4%). IPNB was more frequent in group B (22.5%) than group A (3.8%), and in group B, frequent in Seoul cases (24.8%), but rare in Kanazawa cases (2.3%). Variants of ICC were rare in both groups. These results imply that cholangiocarcinogenesis itself is upregulated in group A in comparison with group B and that the bile ductular type is specifically related to group A. Some unique environmental factors in Seoul may be responsible for the frequent development of IPNB.