DNA image cytometric analysis of macroregenerative nodules (adenomatous hyperplasia) of the liver: Evidence in support of their preneoplastic nature

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Abstract
Twenty-eight macroregenerative nodules from 14 cirrhotic patients who underwent orthotopic liver transplantation were evaluated for DNA ploidy by means of image analysis of Feulgen-stained tissue sections. The lesions were classified as type 1 (16 cases) or type 2 (12 cases) on the basis of the absence or presence of cellular or architectural atypia in the nodules. The surrounding cirrhotic nodules were evaluated for liver cell dysplasia. Aneuploid peaks were significantly more frequent in type 2 macroregenerative nodules (58.3%) than in the cirrhotic regenerative nodules (7.1%) (p < 0.007). In addition, aneuploid peaks occurred with increased frequency in type 2 nodules (58.3%) than in type 1 macroregenerative nodules (6.2%) (p < 0.02). Only two aneuploid peaks (14.2%) were found in dysplastic cirrhotic livers. The nuclear area of aneuploid hepatocytes (71.6 μm ± 10.1%, mean ± S.D.) differed significantly from that of diploid liver cells (45.4 μm ± 6.5%) (p < 0.0001). Tetraploid peaks occurred in three type 2 lesions (25%); they were also found in one type 1 macroregenerative nodule (6.2%), one cirrhotic liver without dysplasia (7.1%) and three cirrhotic livers with dysplasia (21.4%). These findings support the notion that macroregenerative type 2 nodules are directly implicated in hepatocarcinogenesis and that their presence should be sought as an indicator of malignant potential in cirrhotic livers. (Hepatology 1993;17:621-627.)