Hepatocellular dysplasia: large and small cell changes

Abstract

As potential precursor lesions of hepatocellular carcinoma (HCC), small cell changes (SCC) and large cell changes (LCC) are frequently noted. Recently, we discovered a progressive decrease in telomere length and a progressive increase in proliferative activity as normal looking cirrhotic hepatocytes transitioned towards LCC, SCC, and HCC. Cell cycle checkpoint markers, p21, p27, and pl6, were decreased in SCC and absent in HCC, whereas gamma-H2AX-DNA damage foci were present in both SCC and HCC. These data suggest the precancerous nature of SCC, whereas LCC is rather heterogeneous in nature, depending on the biological setting. Additionally, HBV-related LCC showed significantly high Tp53 labeling index, gamma-H2AX labeling index, and micronuclei index, as well as shorter telomere length, decreased SA-β-Gal activity, and increased net cellular gain, compared to cholestatic LCC. The characteristics of HBV-related LCC are more consistent with dysplastic lesions than reactive hepatocytes, whereas those of cholestatic LCC more likely highlight a reactive change of more stringent cell cycle checkpoint control. From a practical point of view, identification of SCC and LCC in liver biopsies may be related to an increased risk of HCC over time. Accordingly, the presence of such lesions should be noted in pathology reports.