Age-Related EBV-Associated B-Cell Lymphoproliferative Disorders: Comparison with EBV-Positive Classical Hodgkin Lymphoma in Elderly Patients

Age-related Epstein-Barr virus-associated (EBV⁺) B-cell lymphoproliferative disorder (LPD) is a disease group of EBV⁺ large B-cell lymphoma characteristically seen in elderly patients without predisposing immunodeficiency. This disease is now going to be listed in the up-coming WHO classification the 4^th version. Age-related EBV⁺ LPD, especially of a polymorphous subtype, which occupied about one-third of cases, is often featured by a rich infiltration of reactive cells in the background, posing the differential diagnostic issue with classical Hodgkin lymphoma (cHL) associated with EBV. However, the clinicopathological differentiation between these two EBV-positive diseases remains to be elucidated. The aim of this study is to clarify the clinicopathological differences between the polymorphic subtype of age-related EBV⁺ LPD (n=34) and EBV⁺ cHL (n=108) of patients of 50 years and more of age. Age-related LPD was more closely associated with the following clinical parameters than cHL: a higher age at onset (71 vs. 63 years), lower male predominance (male:female ratio, 1.4 vs. 3.3), and a higher ratio of involvement of the skin (18% vs. 2%), the gastrointestinal tract (15% vs. 4%) and the lung (12% vs. 2%). Furthermore, age-related LPD was histopathologically characterized by a higher ratio of geographical necrosis, a greater increase (>30%) of cytotoxic T cells in the background lymphocytes, a higher positive rate for CD20 and EBNA2 together with an absence of CD15 expression than EBV⁺ cHL. As predicted by the clinical profile, age-related LPD had a significantly poorer prognosis than EBV⁺ cHL (P = 0.0001). This analysis has clearly demonstrated that the polymorphous subtype of age-related LPD constitutes an aggressive group with an immune response distinct from those of EBV⁺ cHL.