Clinicopathological, radiologic, and molecular study of 23 combined hepatocellular-cholangiocarcinomas with stem cell features, cholangiolocellular type

Hum Pathol. 2017 Jun:64:118-127. doi: 10.1016/j.humpath.2017.01.016. Epub 2017 Apr 18.

Abstract

Cholangiolocellular carcinoma is a type of intrahepatic cholangiocarcinoma (ICC). According to the 2010 World Health Organization classification, this carcinoma is a combined hepatocellular-cholangiocarcinoma with stem cell features, cholangiolocellular type (CHC-SC-CLC). The aim of this study was to compare the clinicopathological characteristics of CHC-SC-CLC and conventional ICC. Based on the gross and histologic characteristics, we divided consecutive ICC tumors into CHC-SC-CLC (n = 23), mass-forming (MF; n = 57), and non-MF (n = 22) groups. Compared with MF and non-MF groups, the CHC-SC-CLC group featured history of hepatolithiasis or bile duct operation in significantly fewer patients (4.3% versus 14.8% and 86.4%, respectively; P < .001) and was more common in the right lobe (70% versus 47% and 27%; P = .033) but lower frequency of invasive growth or peritumoral Glisson sheath invasion (61% and 22% versus 77% and 33% and 100% and 86%, respectively; P = .002 and P < .001) and absence of mucous production (0 versus 77% and 96%; P < .001). In CHC-SC-CLCs, the mutation rate of isocitrate dehydrogenase 1 (IDH1) or IDH2 was significantly higher (35%) than in MF (4%) or non-MF (0) ICCs (P < .001). The 1-, 3-, and 5-year postresection survival rates were also significantly better with CHC-SC-CLCs (93%, 79%, and 52%, respectively) than with MF (72%, 46%, and 40%) or non-MF (61%, 18%, and 0) ICCs (P = .041). Thus, CHC-SC-CLC tumors demonstrated an indolent growth pattern, more frequent IDH1/2 gene mutations, and better prognosis than did MF or non-MF ICC tumors.

Keywords: Bile ducts; Cholangiocarcinoma; Cholangiolocellular carcinoma; Hepatic tumors; Isocitrate dehydrogenase.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bile Duct Neoplasms / diagnosis*
  • Bile Duct Neoplasms / diagnostic imaging
  • Bile Duct Neoplasms / genetics
  • Bile Duct Neoplasms / pathology
  • Biomarkers, Tumor / genetics
  • Biopsy
  • Carcinoma, Hepatocellular / diagnosis*
  • Carcinoma, Hepatocellular / diagnostic imaging
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / pathology
  • Cell Proliferation
  • Cholangiocarcinoma / diagnosis*
  • Cholangiocarcinoma / diagnostic imaging
  • Cholangiocarcinoma / genetics
  • Cholangiocarcinoma / pathology
  • DNA Mutational Analysis
  • Female
  • Hepatectomy
  • Humans
  • Immunohistochemistry
  • Isocitrate Dehydrogenase / genetics
  • Kaplan-Meier Estimate
  • Liver Neoplasms / diagnosis*
  • Liver Neoplasms / diagnostic imaging
  • Liver Neoplasms / genetics
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • Molecular Diagnostic Techniques*
  • Mutation
  • Neoplasm Invasiveness
  • Neoplasms, Complex and Mixed / diagnosis*
  • Neoplasms, Complex and Mixed / diagnostic imaging
  • Neoplasms, Complex and Mixed / genetics
  • Neoplasms, Complex and Mixed / pathology
  • Neoplastic Stem Cells / pathology*
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Time Factors
  • Tomography, X-Ray Computed*
  • Treatment Outcome
  • Tumor Burden

Substances

  • Biomarkers, Tumor
  • IDH2 protein, human
  • Isocitrate Dehydrogenase
  • IDH1 protein, human