Relationship of histologic grade of hepatocellular carcinoma (HCC) to tumor size, and demonstration of tumor cells of multiple different grades in single small HCC.

The histologic features of 65 surgically resected cases of hepatocellular carcinoma (HCC) were studied, and the cellular differentiation was graded from I to IV according to Edmondson-Steiner's classification. HCC cells of 2 or more grades were seen in 31 (47.7%) of the 65 cases. There was no significant difference in the proportion of HCC composed of tumor cells of more than one histologic grade between HCCs with association with liver cirrhosis and without cirrhosis. Among these 31 cases, extremely well-differentiated HCC, corresponding to Edmondson-Steiner's grade I carcinoma, was found in 9 of 11 tumors smaller than 3 cm in diameter, but it was not seen in 20 tumors larger than 3 cm in diameter. In the 34 HCCs with a uniform histologic pattern, all of two minute tumors smaller than 1 cm in diameter consisted of extremely well-differentiated HCC, but there were no cases consisting of extremely well-differentiated HCC in tumors larger than 2 cm in diameter. Taken together, these findings suggest that HCCs originate as relatively well-differentiated tumors, which may be difficult to distinguish from adenomatous regenerative nodules, and become progressively less differentiated at a later stage of their development.