Senile Epstein-Barr Virus-Associated B-Cell Lymphoproliferative Disorders: a Mini Review

Abstract

Epstein-Barr virus (EBV) is associated with a number of malignant lymphomas, including Burkitt lymphomas, Hodgkin lymphomas (HLS), immunodeficiency-associated lymphoproliferative disorders (LPDs), and subset of diffuse large B-cell lymphomas. We have recently identified a series of elderly patients afflicted with EBV-associated (EBV-positive) B-cell LPDs in the absence of predisposing immunodeficiencies ; we have named these neoplasms "senile" EBV + B-cell LPDs. The large series of patients with this disease (n=76) provided additional evidence that this neoplasia, with a median age of onset of 71 years, has the highest incidence in elderly patients aged>50 years, suggesting that this disease may be related to the immunological deterioration that occurs during the aging process. These lesions were pathologically characterized by varying numbers of Hodgkin and Reed-Sternberg (HRS)-like giant cells, often posing a diagnostic problem differentiating this condition from HL. Recent studies, however, have indicated that HL and non-Hodgkin lymphoma (NHL) may be more closely related than previously implied, promoting the general consensus that HRS cells are derived from B cells in most HL cases. The relationship between EBV + HL and EBV + B-cell LPDs remains to be clarified. This review provides a unique opportunity to highlight the gray areas between EBV + HL and EBV + B-cell LPDs. Further investigations are necessary to clarify the interrelationship, including their overlapping morphological and biological features.

Epstein-Barr virus-positive diffuse large B-cell lymphoma association is not only restricted to elderly patients

“…Moreover, in recent years, it has been proposed that defective immune surveillance for EBV may develop late in life and be associated with the development of EBV positive B-cell lymphoproliferative disorder. 47 This defective immune surveillance for EBV is associated with immunological deterioration as a result of aging process, 3,[48][49][50] and explains the correlation between an increased incidence of this lymphoma type together with the increased age of the patients found in the Eastern series. Surprisingly, we did not observe major differences linked with age of the relative numbers of any T-cell population analyzed (Supporting Information Fig.…”

EBV-positive diffuse large B-cell lymphoma of the elderly is an aggressive post-germinal center B-cell neoplasm characterized by prominent nuclear factor-kB activation

“…1 This defective immune surveillance for EBV is associated with immunological deterioration as a result of aging [3][4][5] and explains the correlation between the increased incidence of this lymphoma type and the increased age of the patients found in the Eastern series. However, the definitional cutoff of 50 years proposed by the WHO is arbitrary, 2,4 and cases below the age of 50 years can be found, provided an undiagnosed underlying immunodeficiency has been ruled out.…”

“…8,13,14 Published studies of clinical series have identified a high risk of treatment failure in these patients. 5,8 Among the clinical factors that have an impact on patient outcome, only B symptoms and an age of 70 þ years are independently predictive of survival, while the International Prognostic Index score did not seem to separate different risk groups as in conventional EBVnegative diffuse large B-cell lymphomas. 9 Among the biological features of the tumors that might influence patient survival, it seems clear that EBV positivity is a risk factor.…”

“…[3][4][5] This reduced immune surveillance could be related, at least in part, to the narrowly focused T-cell repertoire, which has limited functional activity against the EBV infection found in these patients. 1,6,7 Currently, age-related EBV-positive lymphoproliferative disorder accounts for 8-10% of diffuse large B-cell lymphoma cases among East Asian patients with no predisposing immunodeficiency; 4,8,9 however, little information is available about the frequency of this condition in western countries.…”

Epstein-Barr virus–associated lymphoproliferative disorders

“…The entity was further subdivided into a polymorphic category (broad range of B-cell differentiation in an inflammatory background) and a large cell category (monomorphic large cells) [69]. EBV was detected in all cases; and a latency III program was most often expressed, although some cases lacked EBNA2 expression (latency II) [69,70]. The variable presence of EBNA2 expression may be attributed to the variable degrees of immune surveillance in aging individuals.…”