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

Abstract

Diffuse large B-cell lymphoma (DLBCL), the most common group of malignant lymphomas, account for 30% of adult nonHodgkin lymphomas. The 2008 World Health Organization (WHO) classification included a new entity, Epstein-Barr virus (EBV)1 DLBCL of the elderly, affecting patients aged 50 years or older. However, some reports of younger EBV1 DLBCL cases, without evidence of underlying immunosuppression, can be found. The role of EBV in tumor microenvironment composition in DLBCL is still not well understood. Our aim was to assess EBV presence and latency pattern as well as tumor T-cell population in an adult DLBCL series of Argentina. The study was conducted on biopsies from 75 DLBCL patients. EBERs expression was performed by in situ hybridization, while EBV gene expression was analyzed using real-time polymerase chain reaction. LMP1, LMP2A, EBNA2, EBNA3A, CD4, CD8 and Foxp3 expression was assessed by immunohistochemistry. Nine percent of cases showed EBV expression, with similar frequency among patients younger than 50 years and 50 years or older (13% and 8%, respectively). T-cell subsets were not altered by EBV presence. Latency type II was the most frequently observed, together with lytic gene expression in EBV1 DLBCL, with 20% of EBERs1 cells. These findings suggest that EBV1 DLBCL in our series was similar to the previously described in Asia and Latin-America, displaying latency II or III expression profile and no agespecific characteristics. Finally, EBV1 DLBCL may be an entity that is not only restricted to patients who are older than 50 years of age, in consequence the age cutoff revision may be a current goal.

EBV-positive large B-cell lymphomas in young patients: a nodal lymphoma with evidence for a tolerogenic immune environment

“…The predominance of males in our series (male to female ratio of 3.6) is similar to what has been observed in the elderly. 4,5,9,24 However, all patients had nodal disease, with only 11% showing extranodal involvement as well. This is in contrast with the higher incidence of extranodal disease reported in the elderly population.…”

“…8 Our results are similar to those reported recently by Hong et al 25 and contrast with the poor prognosis observed by Beltran et al and Cohen et al in a limited number of patients. 22,24 Seventy-nine percent of patients received rituximab in addition to chemotherapy, likely contributing to the good outcome. It has been shown that rituximab chemotherapy improved survival of patients with THRLBCL 32 and EBV 1 DLBCL-E 7,21 and abolished the negative impact of EBV on the outcome of patients with DLBCL 16 and DLBCL-E.…”

“…Normal, n (%) 18 (58) 3 (60) 0 (0) 21 (55) Abnormal, n (%) 13 (42) 2 (40) 2 (100) 17 (45) IPI score, n Cohen et al, 23,24 using quantitative PCR to measure latency gene expression, found a higher incidence of latency III, but RNA levels may not correlate with actual protein expression. The low frequency of latency III in our cohort indirectly supports the immunocompetent status of our patients.…”

“…16,17,21 Few studies have identified EBV 1 LBCLs in pediatric and young patients without known immunodeficiency. 5,[21][22][23][24][25][26] The reported cases showed more frequent type III EBV latency and aggressive clinical behavior, [22][23][24] but the small number of cases analyzed and the inclusion of cases with a relatively low percentage of EBV 1 cells limits firm conclusions regarding this disease in young patients. We describe 46 cases of EBV 1 large B-cell lymphomas (LBCLs) in patients younger than 45 years of age with no significant prior history or identifiable causes of immunosuppression.…”

The Role of EBV in the Pathogenesis of Diffuse Large B Cell Lymphoma

“…EBV-positive DLBCL is defined as an EBV-positive monoclonal large B cell lymphoproliferation occurring in an immunocompetent patient greater than 50 years of age with no history of prior lymphoma. The age cutoff emphasizes the tendency of these tumors to arise in individuals of advanced age (Balague Ponz et al 2008;Cho et al 2008;Cohen et al 2014), though EBV-positive DLBCL has been reported in younger immunocompetent patients, albeit rarely (Cohen et al 2014;Ao et al 2014;Beltran et al 2011a). It is presently unclear whether elderly patients can be truly considered immune competent, and thus distinct from other EBV-positive DLBCL subtypes, or whether the EBV reactivation in these patients is due to age-related T cell dysfunction (Miller 1996).…”