Macroregenerative (dysplastic) nodules and hepatocarcinogenesis: theoretical and clinical considerations

Over the last decade or so, we have seen the development of an interesting new area of liver pathology, new because advanced imaging techniques coupled with careful screening of population at risk for HCC have focused attention on nodular hepatocellular lesions that have been previously ignored. Careful searching for these nodules has led to the acknowledgment that they are not restricted to the populations in which they were first identified and in which the association with HCC was first made, but are probably a universal phenomenon and one extremely important pathway for the development of HCC. Moving beyond these epidemiological associations, we see that careful consideration of the morphology of these lesions leads to insights into the early stages of human hepatocarcinogenesis, setting the stage for the development of a clinically useful system of nomenclature and, perhaps, new approaches to screening for early HCC. Additional important work lies ahead, as concepts from animal models of hepatocarcinogenesis are applied to these human lesions, molecular approaches to research and diagnostics are applied, and extensive prospective screening and clinicopathologic correlation studies are carried out.