Distinctive clinicopathological features and KRAS and IDH1/2 mutation status of cholangiolocellular carcinoma.

Aim: Cholangiolocellular carcinoma (CLC) is classified as a subtype of combined hepatocellular cholangiocarcinoma with stem-cell features (CHC-SC) in the latest World Health Organization classification. This subclassification of CHC-SCs is controversial and the relevance of such classification is unclear.
Methods: We analyzed a series of CHC-SCs and intrahepatic cholangiocarcinoma (iCCA) to clarify the clinicopathological features and mutational status of each tumor.
Results: Background liver disease, fibrosis stage, microvascular invasion, nodal metastasis, and IDH1/2 mutation status were associated with their histology. Compared with the intermediate cell subtype of CHC-SC (CHCs-SC-int), CLCs were less frequently associated with chronic viral hepatitis, and showed lower levels of serum alpha-fetoprotein. Compared with iCCAs, CLCs showed lower levels of serum carbohydrate antigen 19-9 (CA19-9) and a lower frequency of expression of S100P. Patients with iCCA showed worse overall survival than those with CLC or CHC-SC-int. In patients with iCCA, CLC, or CHC-SC-int, a histology of iCCA, microvascular invasion, and serum CA19-9 value of >100 U/mL were significant poor prognostic factors for overall survival in univariate analysis. Multivariate analysis showed that a high serum CA19-9 value was an independent poor prognostic factor for overall survival.
Conclusions: Patients with CLC are likely to have a different etiology and mutational background from those with CHC-SC-int. Their clinicopathological manifestations are also different from those with classic iCCA. Our results suggest that CLC might be a distinct entity among primary liver carcinomas.
(© 2019 The Japan Society of Hepatology.)