Morphologic correlation between liver epithelium and mesenchyme allows insight into histogenesis of focal nodular hyperplasia (FNH) of the liver.

The microanatomic organization of focal nodular hyperplasia (FNH) of the liver was analyzed to obtain information about the histogenesis of this tumor-like lesion. All of the 11 examples of FNH studied showed subdivision into multiple pseudolobules, which were characterized by fibrovascular and ductular areas radiating from perilobular septa, and an expanding periphery of normal appearing hepatocytes. Immunohistochemical analysis showed continuous transitions from normal hepatocytes in the periphery of the pseudolobules, which expressed only the keratins 8 and 18, to small hepatocytes and ductular aggregates in the center of the pseudolobules, both of which also expressed the keratins 7 and 19. Ductular metaplasia of hepatocytes was always accompanied by sinusoidal endothelial cells stained by the endothelial markers BMA 120, M 616, and by an increase in collagenous fibers especially of type III. Further development of this fibrovascular and ductular transformation lead to subdivision of the involved pseudolobules. The pseudolobules had similar mean sizes, irrespective of their site in the periphery or the center of the FNHs, showing that proliferation, fibrovascular and ductular transformation and subdivision of these micronodules are a basic histogenetic phenomenon in FNH. The findings indicate that local changes in the interrelations between liver epithelial and mesenchymal cells influence substantially the abnormal but nevertheless regulated growth of liver parenchyma which gives rise to FNH.