In order to reveal the precursor lesion of hepatocellular carcinoma, a histopathologic study was performed on 141 cases of liver cirrhosis with or without hepatocellular carcinoma. Exclusive of primary or metastatic hepatocellular carcinoma nodules, 94 nodular lesions (>5 mm) were detected in 53 cirrhotic livers. They consisted of 83 large regenerative nodules and 11 dysplastic nodules. Besides some common features with those observed in the former type, the dysplastic nodules presented increased cytoplasmic basophilia, nuclear and nucleolar enlargement, nuclear crowding, occasional microacinar formation and proliferation of the hepatocytes within fibrous septa. These changes were not substantial enough to allow the diagnosis of hepatocellular carcinoma. In one case, however, malignant transformation of hepatocytes was suspected because of their pattern of extranodular outgrowth. It is important to recognize these subtle abnormalities in order to define premalignant hepatic lesions. A possible connection between benign large regenerative nodules and dysplastic nodules is also discussed.
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