Clinicopathological study on hepatocellular carcinoma with lymphocytic infiltration.

We examined the clinicopathologic features of 11 surgically resected hepatocellular carcinomas (HCCs) less than 3 cm in diameter with marked inflammatory cell infiltration (LHCCs). In comparison with the other 152 HCCs without such an infiltration (controls), there were no significant differences in male/female ratio, age, serum alpha-fetoprotein levels, and laboratory and imaging findings. All the 11 LHCC cases were hepatitis B surface antigen (HBsAg) negative and hepatitis C virus antibody positive. Among the 152 controls, 116 cases were also HBsAg negative and HCVAb positive and were referred to as HCV-only controls. The clinical features were not significantly different between the LHCC and the HCV-only controls. The LHCC group tended to have higher numbers of lymphocytes and monocytes in pre- and post-operative peripheral blood, but there were no significant group differences. Recurrence rate was 9.1% in the LHCC group, 47.7% in the controls and 47.5% in the HCV-only controls (P < .01). Five-year survival rate was 100% in the LHCC group, 65.1% in the controls and 68.1% in the HCV-only controls (P < .01). Histologically, remarkable inflammatory cell infiltration, mostly lymphocytic, was observed in the cancerous tissue of the LHCC group. Varying degrees of piecemeal necrosis of cancer nests produced by infiltrating lymphocytes were observed in all the 11 cases. Lymph follicle formation was also found in 10 of 11 cases (90.9%). Liver cirrhosis was associated in 6 LHCC cases (54.5%), in 117 control cases (77.0%), and in 91 HCV-only controls (78.4%). Tumor invasion into the portal vein in the vicinity of the tumor was found in 1 LHCC case (9.1%), in 54 controls (35.5%), and in 34 HCV-only controls (29.3%). Immunohistochemically, most of the infiltrating lymphocytes, other than those in the lymph follicle, were identified as T lymphocyte, and CD8+ T lymphocyte was more predominant than CD4+ T lymphocyte. Better prognosis of the LHCC group could attribute to the anti-tumor effect induced by cellular immunity of CD8+ and CD4+ T lymphocytes, and partly by humoral immunity of B cells which formed lymph follicles.