The Histologic Cut-off Point for Adjacent and Remote Non-neoplastic Liver Parenchyma of Hepatocellular Carcinoma in Chronic Hepatitis B Patients

Hepatitis B virus (HBV) is the most common cause of chronic liver disease in South Korea and is one of the major risk factors of hepatocellular carcinoma (HCC) worldwide. Although various radiologic techniques for early detection and medical or surgical methods have successfully controlled the primary tumor, HCC still shows unsatisfactory long-term prognosis after surgical resection probably due to high recurrence rate.1 Most studies reported greater than 70% recurrence rate within a 5-year period. This recurrence, rather than the underlying cirrhosis, is the major cause of death.2-4 Hence, many investigations have studied risk factors for HCC recurrence after curative resection. Clinicopathologic characteristics of HCC such as micrometastasis, vascular invasion, and positive resection margin are well-known risk factors for tumor recurrence.5 Recently, peritumoral non-neoplastic liver parenchyma (PNLP) has been suggested to be an important predictive marker of HCC recurrence after surgical resection.6-8 PNLP can be defined as hepatic parenchyma without histologic evidence of tumors. However, in patients with chronic liver disease, PNLP has two different levels; the first is adjacent parenchyma that is affected by tumors and the second one is remote parenchyma that is not affected by primary tumors. Adjacent PNLP is claimed to be influenced by mass effect of tumor proper and several tumor-producing factors via paracrine or autocrine manners, indirectly depicting the trait of tumors. Meanwhile, remote PNLP may express the patient's underlying chronic liver disease and indirectly the trait of tumorigenesis, implying new occurrence of HCCs. It is therefore important to determine the exact distance of adjacent PNLP that is directly influenced by the tumor, which differs from remote PNLP, the background liver parenchyma. However, published reports lack consistency on the precise distance that defines adjacent PNLP. Some authors used the farthest non-cancerous liver parenchyma in the entire surgical specimen.9 However, there were some other studies that have limited specimens to a distance of 10 mm from the tumor,10 while others have simply made use of the peritumoral liver tissue that was available at the time of the study.11 In this study, we sought the pathologic characteristics of PNLP of HCCs in chronic HBV patients in order to suggest a reasonable cut-off point between adjacent and remote PNLP from the histologic view point.