Arterial elements and perisinusoidal cells in borderline hepatocellular nodules and small hepatocellular carcinomas

Borderline hepatocellular nodule in the human cirrhotic liver is considered a preneoplastic lesion of hepatocellular carcinoma (HCC). However, the angiogenetic process and changes in perisinusoidal cells (fat‐storing cells or Ito cells) during the borderline nodule‐HCC sequence have not been investigated. We have investigated intraparenchymal arterial elements and perisinusoidal cells in normal livers, chronic hepatitis, borderline nodules and small HCC, using an immunohistochemical staining for α‐smooth muscle actin. In normal livers, chronic hepatitis, cirrhotic nodules and large regenerative nodules, no or few arterial elements were present in the parenchyma, and α‐smooth muscle actin‐positive perisinusoidal cells were not increased. In borderline nodules, however, there were many intranodular arterial elements, and perisinusoidal cells were significantly increased. In small HCC, there were much more arterial elements, and perisinusoidal cells were increased further. These data suggest that angiogenesis first occurs in borderline hepatocellular nodules and it gradually proceeds during the nodule to HCC sequence along with an increase in perisinusoidal cells. The demonstration of arterial elements and perisinusoidal cells may be useful for the differential diagnosis of large regenerative nodule, borderline hepatocellular nodule and small HCC.