We investigated the clinicopathological and molecular characteristics of scirrhous hepatocellular carcinoma (HCC) to elucidate its uniqueness. Samples from 120 resected HCC cases underwent immunohistochemical analysis. Tumor area containing fibrous stroma and the percentage of steatotic cells within the tumor were evaluated. In our previous report, tumors were immunohistochemically subclassified as biliary/stem cell markers–positive (B/S) (cytokeratin 19 and/or sal-like protein 4 and/or epithelial cell adhesion molecule positive), Wnt/β-catenin signaling–related markers–positive (W/B) (β-catenin and/or glutamine synthetase positive), or all markers–negative (−/−) groups. Thirty-seven cases (31%) with fibrous stroma making up ≥50% of the largest tumor area were defined as scirrhous HCC (sHCC); the other 83 cases (69%) were categorized as common HCC (cHCC). Clinicopathologically, sHCC had fewer poorly differentiated tumors (P =.037) and a higher percentage of cases with steatosis (P =.025) than cHCC. sHCC cases were further divided into two subgroups: those with ≥5% steatotic cells (steatotic sHCC) and those with <5% steatotic cells (nonsteatotic sHCC). Hepatitis B virus infection was more frequent in nonsteatotic sHCC (P =.029), and non-B, non-C cases were more frequent in steatotic sHCC (P =.006). Steatotic sHCC tended to have a longer time to recurrence than nonsteatotic sHCC and cHCC. Most nonsteatotic sHCC cases belonged to B/S group, whereas most steatotic sHCC belonged to −/− group. The same tendency in sHCC was shown in another cohort. Distinct features were seen in steatotic and nonsteatotic sHCC, and both sHCC subgroups exhibited different clinicopathological and molecular features from cHCC. These findings support the hypothesis that sHCC is an independent entity.
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