Ninety-two nodules of surgically resected small hepatocellular carcinoma no larger than 3 cm in diameter were classified macroscopically into six types. Common types (type C) included four types; type 1 (single nodular type), type 2 (single nodular type with extranodular growth), type 3 (contiguous multinodular type) and type 4 (poorly demarcated nodular type). Early type (type e) was a nodule which had not destroyed the preexisting liver architecture. Common type in early type (type Ce) was defined as a nodule-in-nodule type which is composed of a type e element in the outer nodule and a type C element in the inner nodule. The respective frequencies were type 1 12%, type 2 20%, type 3 19%, type 4 3.3%, type e 22%, type Ce 25%. The incidence of type e was higher in smaller nodules and that of type C was higher in the larger nodules. Histologically, type e was well differentiated and rarely showed vascular invasion, whereas type C was moderately or poorly differentiated and often showed vascular invasion and intrahepatic metastasis, and type Ce was intermediate in character. It is suggested that as type e HCC grows larger, a more malignant component, i.e. the type C component, emerges inside the type e nodule, the tumor shows then nodule-in-nodule type, defined as type Ce. Finally, the outer nodule is destroyed by the growth of the inner nodule, resulting in a change of type Ce to type C. This constitutes a proposed model of multistep progression of human HCC.
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