Histopathological and morphometric analysis of atypical adenomatous hyperplasia of human cirrhotic livers.

Atypical adenomatous hyperplasia (AAH) is a hyperplastic parenchymal nodular change in the cirrhotic liver, in which overt hepatocellular carcinoma (HCC) occasionally arises. AAH is defined as a sizable hepatocellular nodule with a variable degree of hepatocellular atypia not regarded as HCC, and is different from ordinary adenomatous hyperplasia in which hepatocellular atypia is absent. In the present study, we attempted to evaluate carcinogenetic processes and to find histological variables which indicate malignant transformation in AAH, using 49 surgically resected or autopsied nodules. AAH frequently showed morphological heterogeneity. Atypical lesions within AAHs were divisible into the following three categories from overall histopathological appearances: malignant (A), equivocal (B), or non-malignant (C) lesions. Analysis of combination of these three lesions, which were frequently intermixed in a given AAH, suggested that B lesions appear subsequent to C lesions, and A lesions finally appear in AAH nodules. Among the 14 histological variables, enlargement, hyperchromasia and irregular contour of nuclei were found to correlate well with A lesions. Increased nuclear density, iron resistance, reduction of reticulin fibres, clear cell change, sinusoidal dilatation and presence of abnormal arteries were suggestive of A or B lesions. Nuclear deviation toward the sinusoids, acinar and compact arrangements, fatty change and Mallory's hyaline alone were not useful indicators of A or B lesions. These results indicate that AAH is a preneoplastic or borderline lesion in which overt HCC is likely to evolve through several steps. Although a needle liver biopsy is a useful tool for diagnosis of benign, equivocal and malignant hepatocellular nodular lesions, the needle biopsy specimen should be carefully evaluated by considering the morphological heterogeneity of the AAH and a variable combination of 14 histological variables.