The correlation of Epstein-Barr virus expression and lymphocyte subsets with the clinical presentation of nodular sclerosing Hodgkin disease

BACKGROUND. The pathogenesis of nodular sclerosing Hodgkin disease (HD) has been correlated with Epstein-Barr virus (EBV). The phenotype of lymphocyte s in HD and its relations to clinical presentation and to EBV expression ha ve not been characterized fully. Grade II HD is a more aggressive form of t he disease. The authors studied cases of I-ID by flow cytometry (FCM) in an attempt to analyze the phenotype of lymphocytes in the involved lymph node s and to characterize the phenotype of these lymphocytes in relation to EBV expression, tumor grade, and clinical presentation. MATERIALS AND METHODS, The authors prospectively studied lymph nodes from 4 8 patients with the diagnosis of HD by FCM for T (CD3, CD4, and CD8) and B (CD19) lymphocytes. Ratios of helper to suppressor (CD4 to CD8) and ratios of T to B (CD3 to CD19) lymphocytes were calculated. In situ hybridization for EBV also was performed. The tumors were graded. Clinical data related t o age and stage of the disease were retrospectively analyzed. RESULTS, There were 30 male and 18 female patients with an age range of 7 t o 77 years (median, 17 yrs). EBV expression was seen in 24 (50%) cases. Ele ven (23%) cases were classified as Grade II disease. All Grade II cases sho wed EBV expression, whereas only 13 (39%) cases of Grade I disease were pos itive (P = 0.03). EBV-positive cases had a median CD4 to CD8 ratio of 1.62, whereas EBV-negative cases had a ratio of 3.86 (P = 0.01). Grade I cases h ad a median CD4 to CD8 ratio of 4.58, whereas Grade II cases had a ratio of 1.62 (P = 0.007). EBV-positive cases had a median T-lymphocyte to B-lympho cyte ratio of 2.72, whereas EBV-negative cases had a ratio of 3.17 (P = 0.7 7). Grade I cases had a median T-lymphocyte to B-lymphocyte ratio of 3.51, whereas Grade II cases had a ratio of 1.71 (P = 0.001). A higher percentage of children was seen in the EBV-positive cases than in the negative ones ( 58% vs. 29%). Cases with low (< 1.5) CD4 to CD8 ratios showed more incidenc e of high-stage disease (Stages III and IV) than patients with higher ratio s (81% vs. 51%). High-stage disease also was seen more frequently in patien ts with low (< 3) T- to B-lymphocyte ratios (71% vs. 50%). CONCLUSION, The authors found that the local immune response in HD may vary from one case to another. The findings also suggest that EBV may play a ro le in the pathogenesis of the disease in relation to T- and B-lymphocyte re sponse. A more profound immune suppression and decrease in overall T and he lper lymphocytes may be seen in aggressive EBV-positive variants of the dis ease. These changes may impact the initial presentation of the disease and perhaps its overall biologic behavior. Cancer 2001;91:1957-63. (C) 2001 Ame rican Cancer Society.