Liver cell atypias: a comparative study in cirrhosis with and without hepatocellular carcinoma

Various criteria have been proposed for the identification of early neoplastic changes in the setting of both small hepatocellular carcinomas and macroregenerative nodules. In this study we have applied those criteria to cases of liver cirrhosis without tumour (group I) and hepatocellular-carcinoma-associated cirrhosis (group II) to assess their discriminatory value in these two situations. Group I included 50 liver biopsies with uncomplicated cirrhosis while group II encompassed 48 liver biopsies of cirrhotic nodules adjacent to hepatocellular carcinomas. The histological changes sought were large cell dysplasia, small cell dysplasia, cytoplasmic basophilia, small microacinar structures, peripheral distribution of nuclei, nuclear irregularities and thickened liver cell plates. These changes were also assessed in macroregenerative nodules (nine in group I and seven in group II). None of these changes was useful to discriminate between group I and group II cirrhotic nodules when assessed separately. On the other hand, cirrhotic nodules showing three or fewer changes were never associated with malignancy, whereas those exhibiting four or more alterations were often located in the vicinity of a tumour. Acinar structures, thickened cell trabeculae, peripheral distribution of nuclei and nuclear irregularities seem to be the most specific indicators of proximity to a hepatocellular carcinoma. Similar results were obtained for macroregenerative nodules. These results may be helpful as guidelines to the probability of having a hepatocellular carcinoma elsewhere in livers containing atypical cirrhotic nodules, and may also prove valuable in the selection of appropriate material for investigating early molecular events in hepatic carcinogenesis.