Iron-negative foci in siderotic macroregenerative nodules in human cirrhotic liver. A marker of incipient neoplastic lesions.

Resistance to iron accumulation is known as a phenotypic marker of neoplasia and preneoplasia in experimental hepatocarcinogenesis in rodents overloaded by iron. This study was aimed to evaluate whether such iron-free foci are present and valuable for identification of preneoplastic and incipient neoplastic lesions in human cirrhotic livers, especially within macroregenerative nodules in which hepatocellular carcinoma is known to arise. Iron-free foci were found in siderotic macroregenerative nodules in liver cirrhosis. These foci were classic and overt carcinoma or borderline lesions showing an expansive growth pattern. Borderline lesions were composed of hyperplastic or small basophilic hepatocytes with hyperchromasia and distinct nuclear membrane showing pseudoglandular, trabecular, compact, and scirrhous patterns. These data suggest that iron stain is valuable for identification of neoplastic or borderline lesions representing a transition from hyperplastic nodule to carcinoma in human liver cirrhosis.