Analysis of morphological variables and arterialization in the differential diagnosis of hepatic nodules in explanted cirrhotic livers

BACKGROUND Many terminologies have been given to dysplastic hepatocellular nodules, which are preneoplastic lesions. In 1995, the International Working Party meeting established the nomenclature and morphological criteria for hepatocellular nodular lesions. Nevertheless, an unequivocal differential diagnosis is sometimes difficult, particularly among large regenerative nodules, dysplastic nodules and hepatocellular carcinoma. Angiogenesis is observed during hepatocarcinogenesis and the presence of the isolated arteries may help to discriminate these nodules. The relevance of the International Working Party histological variables and presence of the isolated arteries were analyzed with regard to the diagnosis of large regenerative nodules, low and high grade dysplastic nodules and hepatocellular carcinoma, in order to evaluate which have a real contribution in such diagnoses. METHODS One hundred and seven nodular hepatocellular lesions over 5 mm (or smaller nodules with a different color) from explanted cirrhotic livers were analyzed and classified following the criteria of the International Working Party. Classifications were as follows: large regenerative nodules, low grade dysplastic nodules, high grade dysplastic nodules and hepatocellular carcinoma. The presence of isolated arteries (not related to the portal tracts or fibrosis) was verified for the nodules. RESULTS Among the 107 nodular lesions studied, 17 were classified as large regenerative nodules, 38 as low grade dysplastic nodules, 28 as high grade dysplastic nodules and 24 as hepatocellular carcinoma. The most relevant International Working Party variables in the differential diagnosis of the nodules were cellularity, trabeculae thickness, cytoplasmic staining, nuclear atypia, pseudoacinar pattern, portal tracts, nucleocytoplasmic ratio and mitosis. The isolated arteries, identified by hematoxylin and eosin staining, were important discriminating between two groups: low grade lesions (large regenerative nodules/low grade dysplastic nodules) and high grade lesions (high grade dysplastic nodules/hepatocellular carcinoma) (P < 0.001). CONCLUSION The International Working Party criteria allow for the classification of the majority of hepatocellular nodules. However, other features such as cytoplasmatic tintorial affinity and pseudoacinar pattern may contribute to these diagnoses. The finding of isolated arteries in a nodular lesion should be investigated carefully, since the nodule could be a dysplastic lesion or hepatocellular carcinoma.