Prognostic histologic indicators of curatively resected hepatocellular carcinomas: A multi-institutional analysis of 425 patients with definition of a histologic prognostic index

Despite growing information on the clinical behavior of hepatocellular carcinoma, the histologic features associated with survival are not well characterized. Clinical and pathologic data on 425 patients who underwent complete resection for hepatocellular carcinoma were reviewed. Six microscopic features, namely, microvascular invasion, nuclear pleomorphism, mitosis, tumor architecture, growth interface, and tumor necrosis, were examined. Independent predictors of survival were identified and combined into a simple prognostic index. By univariate analysis, microvascular invasion, seen in 51.3% of patients (p <0.001), nuclear grade 3, present in 42% of the cases (p <0.001), and mitosis (p <0.008) were significant predictors of poor survival. Hepatocellular carcinoma with a compact growth pattern had a better prognosis as compared with macrotrabecular (p = 0.014) and acinar (p = 0.051) patterns. By multiple regression analysis, only microvascular invasion (p <0.001) and nuclear grade 3 (p = 0.008) were independent predictors of poor survival. The predictive values of microvascular invasion and nuclear grade allowed the construction of a hepatocellular prognostic index (HPI) whereby HPI = (microvascular invasion status × 0.459) + (nuclear grade × 0.287), with microvascular invasion either absent (0) or present (1) and nuclear grade scored as 1, 2, or 3. Using a cut-off of 0.746 (corresponding to at least nuclear grade 2 with microvascular invasion), two groups could be segregated: fair prognosis (HPI ≤0.746), with a 50% survival of 5.06 years, and poor prognosis (HPI >0.746) with a 50% survival of 2.71 years (p <0.001). HPI was more discriminating than Edmondson grade, with Edmondson II hepatocellular carcinomas dispersed in both fair and poor prognosis groups. Microvascular invasion and nuclear grade 3 emerge as strong prognostic indicators, and their combination provides adequate prognostic stratification. Practically, hepatocellular carcinoma can be stratified in two groups with regard to prognosis: 1) fair prognosis group (nuclear grade 1 with or without microvascular invasion and nuclear grade 2 without microvascular invasion), and 2) poor prognosis (nuclear grade 2 with microvascular invasion and nuclear grade 3 with or without microvascular invasion). The combination of these histologic parameters provides adequate prognostic stratification.