Morphological subclassification of intrahepatic cholangiocarcinoma: Etiological, clinicopathological, and molecular features
Journal
Modern Pathology
Journal Volume
27
Journal Issue
8
Pages
1163-1173
Date Issued
2014
Author(s)
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. ? 2014 USCAP, Inc..
SDGs
Other Subjects
biological marker; intestinal trefoil factor; isocitrate dehydrogenase; isocitrate dehydrogenase 1; K ras protein; nerve cell adhesion molecule; protein S 100; protein S100P; unclassified drug; tumor marker; adult; aged; article; bile duct carcinoma; cancer surgery; female; gene mutation; human; human tissue; intraductal papillary mucinous tumor; major clinical study; male; molecular pathology; neoplasm; pathogenesis; priority journal; stone formation; survival rate; tumor classification; virus hepatitis; Bile Duct Neoplasms; chemistry; Cholangiocarcinoma; cholelithiasis; classification; comparative study; complication; genetic predisposition; genetics; intrahepatic bile duct; Kaplan Meier method; middle aged; mortality; mutation; nomenclature; pathology; phenotype; proportional hazards model; risk factor; time; treatment outcome; Aged; Bile Duct Neoplasms; Bile Ducts, Intrahepatic; Cholangiocarcinoma; Cholelithiasis; Female; Genetic Predisposition to Disease; Hepatitis, Viral, Human; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mutation; Phenotype; Proportional Hazards Models; Risk Factors; Terminology as Topic; Time Factors; Treatment Outcome; Tumor Markers, Biological
Publisher
Nature Publishing Group
Type
journal article