Small hepatocellular carcinoma: its relationship to multistep hepatocarcinogenesis

Recent advances in imaging techniques have led to the discovery of small hepatocellular carcinomas (HCC). The small HCC most often exhibit low-grade malignant (LGM) or extremely well differentiated features, which are different from those of advanced, full-blown HCC. The LGM-HCC present a serious diagnostic challenge to pathologists and must be differentiated from benign (reactive) and atypical (borderline) hyperplastic nodules. Analysis of small HCC revealed that hepatocarcinogenesis frequently occurs stepwise from atypical hyperplasia to LGM-HCC and subsequently to advanced HCC. The HCC arise in irregular regeneration in chronic liver disease and in the essentially normal liver after steroid administration. Although the tumor suppressor gene, p53, is revealed to be often mutated in advanced HCC, the genetic events corresponding to each stage of multistep hepatocarcinogenesis are not clarified at all.