We examined pathomorphologically small nodular lesions in hepatitis C virus-related cirrhosis (type C cirrhosis). Small nodular lesions seen in the non-cancerous areas of 128 consecutively resected hepatocellular carcinomas (HCCs) associated with type C cirrhosis were selected for the study. From these, 18 large regenerative nodules (LRNs), 14 low-grade dysplastic nodules (LDNs), 10 high-grade DNs (HDNs), and 12 well-differentiated HCCs were detected. The diameters of HDN (11.7+/-4.3 mm) and well-differentiated HCC (12.3+/-3.5) were significantly larger than those of LRN (8.1+/-1.0) and LDN (8.6+/-2.7). Fatty change was not seen in LRNs and LDNs, while it was found in 4 HDNs (40%) and 8 well-differentiated HCCs (75%). Iron deposits were found in 2 LRNs (11%), 5 LDNs (36%), and 3 HDNs (30%), but not in the well-differentiated HCCs. The number of Kupffer cells in LDN and HDN was increased compared with that in the surrounding regenerative nodules. Cell density and the degree of neovascularization were well correlated with the progression from DN to HCC. The lack of neovascularization supports the concept that LRN has no neoplastic potency and can be regarded as the morphologic marker in the differentiation of LRN from DN.
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