Clinicopathologic Characteristics of Hepatocellular Carcinoma With Reactive Ductule-like Components, a Subset of Liver Cancer Currently Classified as Combined Hepatocellular-Cholangiocarcinoma With Stem-Cell Features, Typical Subtype.

The aim of this study was to elucidate the clinicopathologic characteristics of hepatocellular carcinoma with reactive ductule-like components (HCC-RD), corresponding to combined hepatocellular-cholangiocarcinoma (CHC) with stem cell features, typical subtype. Retrospective clinicopathologic analysis was performed on HCCs surgically treated at the University of Tokyo Hospital between 1995 and 2013. RD components were defined as neoplastic ductular structures composed of small "stem/progenitor-like" cells. There were 46 HCC-RDs, comprising about 3% of all HCCs. Thirty-eight cases of CHC, classical type (classical CHC), were identified during the study period. When compared with conventional HCC, HCC-RD was characterized by younger patient age (P=0.016), higher frequency of female patients (P<0.001), and higher serum α-fetoprotein levels (P=0.005). Serum carbohydrate antigen 19-9 elevation was also more frequently observed in HCC-RD than in conventional HCC (P=0.002). Histologically, clear cell constituents and interstitial fibrosis were more frequent in HCC-RD than in conventional HCC (P=0.003 and <0.001, respectively). When compared with HCC-RD and conventional HCC, classical CHC was characterized by a poorly differentiated HCC component, frequent vascular invasion, and lymph node metastasis (P<0.05). There was little prognostic difference between HCC-RD and conventional HCC, whereas overall and disease-free survival in classical CHC was significantly worse than in conventional HCC. In conclusion, although HCC-RDs do have some unique clinicopathologic characteristics, they have no prognostic significance, and it is not reasonable to include these tumors in the CHC category.