Extracapsular Penetration is a New Prognostic Factor in Human Hepatocellular Carcinoma

The fibrous capsule is a unique characteristic of hepatocellular carcinoma (HCC) and acts as a barricade preventing the spread of cancer cells. Infiltration to the capsule (fc-inf) is the invasive feature in HCC; however, there are no reports of a detailed investigation regarding fc-inf. We selected 88 HCCs of <= 5 cm in diameter, when considered together with both the single nodular and the single nodular with extranodular growth types. We classified the infiltrating pattern into 2 types: extracapsular (EC) infiltrating type (n = 38), in which cancer cells infiltrated outside the capsule and touched the existing liver parenchyma, and intracapsular (IQ infiltrating type (n = 50), in which the infiltrating cancer cells stayed inside the capsule. The distance of infiltration and the capsular thickness were measured and the ratio of capsular infiltration (Cl index) was calculated. There were no clinicopathologic differences between the 2 types, but the capsular thickness of IC type was greater than that of EC type (P < 0.0001). EC type showed a poorer outcome for the overall survival and the disease-free survival (P = 0.0210 and P = 0.0115, respectively) and EC type was an independent prognostic factor for a disease-free survival (P = 0.0158). However, Cl index did not correlate with any clinicopathologic factors or the patient prognosis in IC type. We propose a new definition of fc-inf as a histologic feature of cancer cells penetrating to the liver parenchyma through the fibrous capsule. It may be closely related to the patient prognosis and may therefore, become a new and useful pathologic factor.