Cytophotometric DNA analysis of adenomatous hyperplasia in cirrhotic livers

The possibility of adenomatous hyperplasia (AH) being a precursor lesion of hepatocellular carcinoma (HCC) in human cirrhotic livers was investigated. Feulgen DNA cytophotometry was used to measure the DNA content of the hepatocytes in 13 AH nodules obtained from six cirrhotic livers. DNA distribution patterns were classified into types I (diploid pattern), II (hyperploid pattern) and III (aneuploid pattern). According to the cellular and structural atypia, AH nodules were divided into ordinary type (2 nodules) and atypical type (11 nodules), 6 of the latter possessing foci of apparent HCC within them. Two ordinary AH nodules showed a type I DNA distribution pattern, similar to the surrounding regenerative nodules. A major part of the atypical AH nodules also showed type I. However, small foci showing moderate and structural atypia within these atypical AH nodules presented a type I pattern with more hyperploid cells and some aneuploid cells and also a type II histogram pattern with some aneuploid cells. Neoplastic foci, found within 5 atypical AH nodules, displayed various patterns (type I, II, III) as seen in well-developed HCC nodules. These data may imply that atypical AH nodules are precursor lesions of HCC, or are actually undergoing malignant transformation. It is apparent that at least some HCCs occurring in liver cirrhosis evolve through AH.