Survey of iron-accumulative macroregenerative nodules in cirrhotic livers

Recently, macroregenerative nodules in cirrhotic livers have been suspected to be among the putative precancerous lesions in human hepatocarcinogenesis. We examined the morphologies of 99 macroregenerative nodules in 44 cirrhotic livers with special emphasis on stainable iron. In 26 macroregenerative nodules (26%), stainable iron selectively accumulated within the macroregenerative nodules themselves, and little or no iron was found in the surrounding regenerative nodules. In nine macroregenerative nodules (9%), an appreciable amount of stainable iron was present in both the macroregenerative nodules and the surrounding regenerative nodules. In the remaining 64 macroregenerative nodules (65%), stainable iron was absent in both the macroregenerative nodules and the surrounding regenerative nodules. Hyperplastic hepatocellular foci were present within 19 (73%) of the 26 iron-accumulative macroregenerative nodules, one (11%) of the nine iron-positive macroregenerative nodules and 20 (31%) of the 64 iron-negative macroregenerative nodules. These findings suggest that iron-accumulative macroregenerative nodules are frequently associated with hyperplastic hepatocellular foci and should be included among the precancerous lesions in human hepatocellular carcinoma.