Analytical histopathological diagnosis of small hepatocellular nodules in chronic liver diseases

  • Yasuni Nakanuma
  • K. Hirata
  • S. Terasaki
  • K. Ueda
  • O. Matsui
Keywords: hepatocellular carcinoma, low-grade hepatocellular carcinoma, classical hepatocellular carcinoma, dysplastic nodule, large regenerative nodule


Due to the recent progress in radiology and increased clinical and pathological interest, small hepatocellular nodules about 1 cm in size are frequently being detected in patients with chronic liver disease, particularly liver cirrhosis. Two new types of small hepatocellular nodules are now known: low-grade hepatocellular carcinomas (HCC) and dysplastic nodules, in addition to the previously known HCC (classical) and regenerative nodules. Ultrasound-guided needle biopsies from these nodules are routinely used for the differential diagnosis. For comparison, a simultaneous needle biopsy from the liver remote from the nodule is strongly recommended. Low-grade HCC, which are different from classical HCC in their morphological atypia and also biological behaviors, show local invasion into the portal tracts and surrounding hepatic parenchyma, but not intrahepatic or extrahepatic metastasis. Dysplastic nodules show mild cellular and structural atypia, a finding which is not sufficient for making a diagnosis of malignancy. An increased nuclear/cytoplasmic (N/C) ratio and nuclear crowding, small cell-dysplasia, increased cytoplasmic staining, clear cell change, pseudogland formation, and fatty change of hepatocytes are variably seen in these nodules. Nuclear changes, local invasion to the portal tract and surrounding liver, and loss of the reticulum fibers along the hepatocytes are useful markers favoring low-grade HCC rather than dysplastic nodules. These low-grade HCC and dysplastic nodules should also be distinguished from classical HCC as well as large-sized regenerative nodules. A comparative analysis of the histological findings observed in individual nodules is a reasonable approach to differential diagnosis at present. The recognition and analysis of these two new hepatocellular nodules may augur a new horizon in the study of hepatocellular neoplasm.
Invited Reviews