Tumor-Associated Macrophages in Pediatric Classical Hodgkin Lymphoma: Association with Epstein-Barr Virus, Lymphocyte Subsets, and Prognostic Impact

Purpose: Tumor-infiltrating macrophages are associated with adverse outcome in adult classical Hodgkin lymphoma (cHL). We have previously shown age-related changes in the lymphocyte composition of pediatric cHL. We therefore hypothesized that the number, function, and prognostic impact of macrophages in pediatric cHL would be different from adult cases. Experimental Design: We analyzed the number of macrophages and dendritic cells (DC) in the tumor microenvironment of pediatric cHL by immunohistochemistry. Results were analyzed in context of age, histologic characteristics, Epstein-Barr virus (EBV) status, clinical follow-up, and our previous study of T-cell populations in these cases. Results: One hundred cHL cases were studied, including 69% nodular sclerosis and 23% mixed cellularity cases. A total of 44.8% of cases were EBV-positive. Patients <10 years displayed more CD14(+) cells (P = 0.025). In comparison with nodular sclerosis, mixed cellularity was characterized by higher numbers of CD14(+), (P = 0.003) and CD163(+) cells (P = 0.027). EBV+ cases exhibited higher numbers of CD14(+) (P < 0.0005), CD68(+) (P = 0.005), and CD163(+) cells (P = 0.02). CD68-positive cells did not display an effect on outcome. Worse overall survival was observed in cases with CD163/CD8 ratio >= 2 (P = 0.007). High numbers of CD163(+) cells were associated with worse progression-free survival (PFS; P = 0.015). Furthermore, high numbers of CD163(+) and granzyme B+ cells were associated with worse PFS in EBV-negative (P = 0.005) but not in EBV-positive cases. Conclusion: Our results suggest that macrophage composition in pediatric cHL is distinct from adults. Functional status of macrophages and their value as prognostic indicators in pediatric cHL may depend on EBV status. Clin Cancer Res; 18(14); 3762-71. (C)2012 AACR.