• hepatocellular carcinoma;
  • dysplastic nodule;
  • multistep carcinogenesis



Advances in imaging technology have enhanced the detection of small nodular lesions during the course of chronic liver disease.


Between 1995 and 2002, the authors examined 154 consecutive patients with small hepatic nodules without hepatocellular carcinoma (HCC) over a median duration of 2.8 years. The median size of these nodules was 14 mm (range, 7–40 mm). The initial histopathologic diagnosis included high-grade dysplastic nodule (HGDN) (n = 13), low-grade dysplastic nodule (LGDN) (n = 42), and regenerative nodule (RN) (n = 99).


A total of 29 (18.8%) nodules developed into HCC during the observation period. Cumulative HCC development rates at the first, third, and fifth year were 46.2%, 61.5%, and 80.8% for HGDN; 2.6%, 30.2%, and 36.6% for LGDN; and 3.3%, 9.7%, and 12.4% for RN, respectively. The rate of HCC development was significantly higher in the HGDN group than for other types (P < 0.001). Multivariate analysis disclosed that histopathologic diagnosis (P < 0.001) and findings on computed tomographic arterial portography (CT-AP) (P = 0.004) were significantly associated with future HCC development. The hazard ratios of HGDN and LGDN were 16.8 (95% confidence interval [CI], 6.19–45.6) and 2.96 (95% CI, 1.20–7.31), respectively. A decrease in portal blood flow also showed a significantly high hazard ratio of 3.04 (95% CI, 1.42–6.50). Approximate annual development rate to HCC was 20% in patients with HGDN and 10% in LGDN.


HGDN should be considered a precancerous lesion when it appears during follow-up of chronic viral hepatitis or cirrhosis. Reduced portal blood flow in the nodule on computed tomography-AP is also an important predictor for development of hepatocellular carcinoma. Cancer 2006. © 2005 American Cancer Society.