title: Morphological subclassification of intrahepatic cholangiocarcinoma: etiological, clinicopathological, and molecular features.
abstract: On the basis of morphological features, we subclassified 189 intrahepatic cholangiocarcinomas into two subtypes: bile duct and cholangiolar. The cholangiolar type is composed of cuboidal to low columnar tumor cells that contain scanty cytoplasm. The bile duct type is composed of tall columnar tumor cells arranged in a large glandular pattern. In this study, 77 (41%) tumors were classified as the cholangiolar type and 112 (59%) tumors were classified as the bile duct type. The cholangiolar-type intrahepatic cholangiocarcinoma was more frequently associated with viral hepatitis, whereas all but one intrahepatic cholangiocarcinoma associated with intrahepatic lithiasis were classified as the bile duct type. Biliary intraepithelial neoplasm or intraductal papillary neoplasm of the bile duct could be identified in 50 bile duct-type intrahepatic cholangiocarcinomas (45%), but in only 3 cholangiolar-type intrahepatic cholangiocarcinomas (4%). Cholangiolar-type intrahepatic cholangiocarcinomas frequently expressed N-cadherin, whereas bile duct intrahepatic cholangiocarcinomas were more likely to express S100P, Trefoil factor 1, and anterior gradient 2. KRAS is mutated in 23 of 98 (23%) bile duct-type intrahepatic cholangiocarcinomas and in only 1 of 76 (1%) cholangiolar-type intrahepatic cholangiocarcinomas. Cholangiolar-type intrahepatic cholangiocarcinomas had a higher frequency of IDH1 or 2 mutations than did the bile duct-type intrahepatic cholangiocarcinomas. The molecular features of the bile duct-type intrahepatic cholangiocarcinoma were similar to those of hilar cholangiocarcinoma. Patients with the cholangiolar-type intrahepatic cholangiocarcinoma had higher 5-year survival rates than those of patients with the bile duct-type intrahepatic cholangiocarcinoma. Our results indicated that intrahepatic cholangiocarcinoma was a heterogeneous tumor. Subclassification of intrahepatic cholangiocarcinomas based on cholangiocytic differentiation divides them into two groups with different etiologies, clinical manifestations, and molecular pathogeneses.
authors.affiliation: 1] Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jau-Yu
authors.initials: JY
authors.lastname: Liau
authors.affiliation: 1] Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Jia-Huei
authors.initials: JH
authors.lastname: Tsai
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ray-Hwang
authors.initials: RH
authors.lastname: Yuan
authors.affiliation: 1] Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Chih-Ning
authors.initials: CN
authors.lastname: Chang
authors.affiliation: 1] Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Hsin-Jung
authors.initials: HJ
authors.lastname: Lee
authors.affiliation: 1] Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan [2] Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
authors.forename: Yung-Ming
authors.initials: YM
authors.lastname: Jeng
mesh_terms: D000368:Aged; D001650:Bile Duct Neoplasms / Q000737:chemistry / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D001653:Bile Ducts, Intrahepatic / Q000737:chemistry / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D018281:Cholangiocarcinoma / Q000737:chemistry / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D002769:Cholelithiasis / Q000150:complications; D005260:Female; D020022:Genetic Predisposition to Disease; D006525:Hepatitis, Viral, Human / Q000150:complications; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010641:Phenotype; D016016:Proportional Hazards Models; D012307:Risk Factors; D009626:Terminology as Topic; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor