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

Abstract

The pathogenesis of nodular sclerosing Hodgkin disease (HD) has been correlated with Epstein-Barr virus (EBV). The phenotype of lymphocytes in HD and its relations to clinical presentation and to EBV expression have not been characterized fully. Grade II HD is a more aggressive form of the disease. The authors studied cases of HD by flow cytometry (FCM) in an attempt to analyze the phenotype of lymphocytes in the involved lymph nodes 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 48 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 to age and stage of the disease were retrospectively analyzed. There were 30 male and 18 female patients with an age range of 7 to 77 years (median, 17 yrs). EBV expression was seen in 24 (50%) cases. Eleven (23%) cases were classified as Grade II disease. All Grade II cases showed EBV expression, whereas only 13 (39%) cases of Grade I disease were positive (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 had 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-lymphocyte ratio of 2.72, whereas EBV-negative cases had a ratio of 3.17 (P = 0.77). 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 incidence of high-stage disease (Stages III and IV) than patients with higher ratios (81% vs. 51%). High-stage disease also was seen more frequently in patients with low (< 3) T- to B-lymphocyte ratios (71% vs. 50%). 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 role in the pathogenesis of the disease in relation to T- and B-lymphocyte response. A more profound immune suppression and decrease in overall T and helper lymphocytes may be seen in aggressive EBV-positive variants of the disease. These changes may impact the initial presentation of the disease and perhaps its overall biologic behavior.