Morphometric Analysis of Dysplastic Nodules in Hepatitis C Virus–Related Liver Cirrhosis: Comparison with Cirrhotic and Large Regenerative Nodules

Objective: To apply a computerized morphometric model to evaluate and quantify the morphologic features, including hepatic progenitor cells, in large regenerative nodules (LRN) and high grade dysplastic nodules (DN) in hepatitis C virus (HCV)–related cirrhosis. Study Design: Thirty-two cirrhotic nodules; 10 LRN; and 8 DN were identified in cirrhotic livers with HCV-related cirrhosis removed at transplantation. All specimens were stained for routine diagnosis with hematoxylin-eosin and immunohistochemically for CD31, CD34, cytokeratin 7 (CK7) and reticulin. We determined by a computerized morphometric model on hematoxylin-eosin slices the volume fractions occupied by hepatocyte nuclei and cytoplasm, sinusoids, portal triads, fibrosis and centrilobular veins. We also investigated volume fraction of hepatocytes expressing CK7, and volume fractions of capillary units and of sinusoid capillarization expressing CD31 and CD34, respectively, and surface fraction of reticulin. Results: Compared to LRN, DN showed higher volume fraction of hepatocyte nuclei, higher number of hepatocytes in unit volume, higher nuclear/cytoplasmic ratio, higher volume fractions of capillarized sinusoids, capillary units and CK7 positive hepatocytes and lower mean hepatocyte volume and surface reticulin fraction. Conclusion: Our morphometric model is an objective method of quantification of the morphologic changes of LRN and DN, including the hepatic progenitor compartment. (Anal Quant Cytol Histol 2010;32:106–113)