Steatohepatitic features span molecular subclasses of hepatocellular carcinoma, while intracytoplasmic hyaline bodies associate with mutational status

BACKGROUND Hepatocellular carcinoma (HCC) is a molecularly and morphologically heterogeneous malignancy.Steatohepatitic (STH) morphology, defined by hepatocellular ballooning, Mallory-Denk bodies, intracytoplasmic hyaline bodies (IHBs), steatosis, and inflammation, has been associated with the G4 molecular subgroup.Its distribution across other molecular subclasses of HCC remains insufficiently characterized.AIM To investigate the distribution of STH morphological features across established molecular subclasses of HCC and to assess their associations with molecular alterations and clinical outcome.METHODS Thirty-nine HCCs were analyzed using a comprehensive next-generation sequencing panel and assigned to established molecular subgroups (G1-G6).Expert histopathological evaluation assessed the presence of STH features and background liver cirrhosis. RESULTSSTH features were observed across multiple molecular subclasses and were not confined to G4 tumors (n = 19).In non-G4 cases, inflammation was present in 35%, Mallory-Denk bodies in 30%, ballooning in 15%, IHBs in 20%, steatosis in 25%, and background liver cirrhosis in 53.8%.IHBs were numerically more frequent in tumors harboring pathogenic molecular alterations in this cohort.No significant differences in STH distribution were identified between proliferative and non-proliferative classes or between G4 and non-G4 tumors (P = 0.85).In this cohort, G3 tumors (n = 3) did not demonstrate classical STH features other than occasional steatosis, while TSC1/2-mutated tumors did not exhibit classical STH features.Survival analyses revealed no significant differences according to molecular class or STH morphology.4 / 29 CONCLUSION STH morphology is not restricted to the G4 subgroup.In this cohort, STH features were not associated with survival.IHB-positive HCCs may represent a potential morphological correlate of pathogenic molecular alterations.