Clinicopathological characteristics of surgically resected minute hepatocellular carcinomas

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.

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.

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.

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.