DETECTION OF THE PRENEOPLASTIC LESIONS OF SMALL HEPATOCELLULAR-CARCINOMA IN CIRRHOTIC LIVERS

To identify the preneoplastic lesions of hepatocellular carcinoma and the fine structure of preneoplastic hepatocytes, we studied proliferat ive conditions in cirrhosis of the liver. In all, 46 foci of cellular alteration (FCA), three regions of adenomatous hyperplasia (ADH), and 21 small hepatocellular carcinomas (sHCC) were studied by published cr iteria for sHCC and by the proliferative activity of the lesions as ex amined with monoclonal antibodies against DNA polymerase alpha and pro liferating cell nuclear antigen. The four patients with FCA composed o f basophilic hepatocytes were classified by the criteria as having sHC C; cells had features similar to those of sHCC. Two of these four pati ents with FCA were found to have HCC several years later. The number o f hepatocytes stained for proliferating cell nuclear antigen was 72 an d 81 per 1000 hepatocyte nuclei in the two patients who developed HCC. In one of the three patients with ADH, a sHCC was found 1 year later, and dysplastic hepatocytes from the region of ADH in this patient had features similar to those of HCC cells by light and electron microsco py. In this patient, the number of hepatocytes stained for DNA polymer ase alpha was 452 per 1000 nuclei. Therefore, FCA and ADH might be pre neoplastic lesions of sHCC in cirrhosis of the liver. Preneoplastic he patocytes seem to be small cells with basophilic cytoplasm, with a lar ge nucleus to cytoplasm ratio, finely indented nuclei with a smaller a mount of condensed chromatin than normal, and poorly to moderately dev eloped organelles.