Background/aims: The multistep development of overt hepatocellular carcinoma from very well-differentiated early hepatocellular carcinoma, and of early hepatocellular carcinoma from adenomatous hyperplasia has been strongly suggested. The clinicopathologic and immunohistochemical characteristics of solitary minute hepatocellular carcinomas smaller than 1 cm in size have yet to be clarified.
Methodology: Fourteen minute hepatocellular carcinomas were divided into 2 groups consisting of: 1) hepatocellular carcinoma of hepatitis B surface antigen positive patients (B-HCC) (n = 5), and 2) hepatocellular carcinoma of hepatitis C virus antibody positive patients (C-HCC) (n = 9), then they were all analyzed histopathologically and clinicopathologically. Immunohistochemical studies were also performed using the antibodies against p53 protein.
Results: Six of the 14 minute hepatocellular carcinoma were demonstrated to be moderately or poorly differentiated tumors. Among the 8 well-differentiated minute hepatocellular carcinomas, 2 tumors already contained less differentiated components. B-HCC tended to be less differentiated than C-HCC (P < 0.05). Adenomatous hyperplasia was detected in only 2 cases of C-HCC. Small cell liver dysplasia was detected significantly more frequently in C-HCC than in B-HCC (P < 0.05). The prognosis of the 14 minute hepatocellular carcinomas varied considerably. Immunohistochemically, some tumor cells were positive for p53 in 3 cases.
Conclusions: Our study suggests that 1) the multistep carcinogenesis through adenomatous hyperplasia may not be so frequent, 2) De novo carcinogenesis from not only well-differentiated hepatocellular carcinoma, but also from less differentiated hepatocellular carcinoma, especially B-HCC, may be present, 3) the carcinogenesis in the B-HCC cases may behave differently from that in C-HCC cases, and 4) minute hepatocellular carcinomas demonstrate varying prognoses after hepatectomy.