Small hyperechoic nodules in chronic liver diseases include hepatocellularcarcinomas with low cyclin D1 and Ki-67 expression

In spite of the importance of periodic screening for hepatocellular carcino ma (HCC) by ultrasonography (US) in patients with underlying liver disease, the clinicopathological characteristics of hyperechoic nodules have not be en clearly evaluated. The aim of this study was to characterize the patholo gical and proliferating features of small hyperechoic nodules. Tissue speci mens of 55 hyperechoic and 107 hypoechoic nodules less than 20 mm in diamet er in patients with chronic liver disease were obtained by echo-guided need le biopsy and examined histopathologically, Of these, 42 (76%) hyperechoic and 56 (52%) hypoechoic nodules were diagnosed as HCC, and 82% of hyperecho ic HCCs contained fatty change and/or clear cell change. In addition, immun ohistochemical staining using cyclin D1, p53, and Ki-67 was examined. A hig h-level expression of cyclin D1 was found in only 5% of hyperechoic HCCs, i n contrast to 38% of hypoechoic HCCs (P < .02). The labeling index of Ki-67 in hyperechoic HCCs was lower than in hypoechoic HCCs (4.2% vs. 8.9%; P < .003). However, there was no difference on p53 staining between them. Retro spective follow-up study revealed that hyperechoic nodules showed slow grow th (doubling time, median: 1,403 days) initially, and came to show rapid gr owth (doubling time, median: 56 days). From these results, small hyperechoi c nodules in chronic Liver diseases are worth notice as candidates for well -differentiated HCC with low cyclin D1 and Ki-67 expression.