Geographic variation in the prevalence of Epstein–Barr virus-positive diffuse large B-cell lymphoma of the elderly: a comparative analysis of a Mexican and a German population

Abstract

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma of the elderly was included as a provisional entity in the 2008 WHO lymphoma classification. Most reports of this disease come from Asia and little is known about it in other regions of the world, including Latin America. Therefore, in this study, 305 diffuse large B-cell lymphomas in patients above 50 years were analyzed, 136 from Mexico and 169 from Germany. EBV was detected by Epstein-Barr early RNA (EBER) in situ hybridization. Only cases with EBER þ in the majority of tumor cells were regarded as EBV þ diffuse large B-cell lymphoma. The prevalence of EBV þ diffuse large B-cell lymphoma in Mexican patients was found to be 7% (9 of 136), whereas only 2% (4 of 169) of the German cases were positive. The median age at diagnosis was 66 years in the Mexican cohort, as opposed to 77 years in the German group. The site of presentation was in both groups predominantly nodal in nine cases (70%) and extranodal in four cases (30%). Of the 13 EBV þ cases, 10 (77%) were classified as polymorphic and 3 (23%) as monomorphic type. The polymorphic cases showed a non-germinal center B-cell immunophenotype (CD10À MUM1 þ ). Twelve cases (92%) were LMP1 positive and two (15%) expressed EBNA2. An interesting finding was the high frequency of EBV type B with the LMP1 30 bp deletion found in the Mexican cases (50%). Eight of the 11 evaluable cases were B-cell monoclonal by polymerase chain reaction. In summary, we found a similar prevalence of EBV þ diffuse large B-cell lymphoma of the elderly in a Mexican population compared with what has been reported in Asian countries, and in contrast to the low frequency in Western populations (1-3%). However, compared with the Asian series, the Mexican patients were younger at diagnosis, presented predominantly with nodal disease and rarely expressed EBNA2 protein.Modern Pathology (2011Pathology ( ) 24, 1046Pathology ( -1054 doi:10.1038/modpathol.2011 published online 15 April 2011 Keywords: EBV; elderly; large cell lymphoma; Mexico Epstein-Barr virus (EBV) is a ubiquitous herpesvirus that infects 490% of the human population establishing persistent latent infection in the host. 1Although EBV infection is benign in most individuals, it has been linked to the etiology of a rather broad spectrum of B-cell lymphoproliferations both

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

“…10 In addition, EBV gene expression exhibited particular characteristics, given that previous studies suggested that EBV1 DLBCL in elderly patients generally have viral latency type II or III pattern. 8,10,14,15 We observed differences in the viral gene levels and protein expression, in cases with more than 20% of positive cells and those with less than 20% of positive cells. This fact leads us to define EBV patterns in the former group, whereas, due to the small amount of EBERs1 cells, the EBV latency could not be defined in the latter, even though morphological and immunophenotypic properties were similar in both groups.…”

“…27 In contrast to the first publications, 3,45 most recent reported series-including ours-have found a predominant nodal presentation. 9,10,14,46 Morphologically, the distinction between the polymorphic and the monomorphic subtype is no longer regarded as clinically relevant. 8 Although several pathological characteristics have been described in EBV1 LDBCL of the elderly, we also corroborated that there is no morphologic or immunohistochemical pattern that is specific of this entity.…”

“…2,13 Few studies focused on the analysis of EBV latency patterns in EBV1 DLBCL of the elderly, which reported viral latencies including patterns II and III. 8,10,14,15 It has been postulated that EBV1 DLBCL of the elderly might be caused by the senescence of the immune system as a part of the normal aging process, based largely on shared features with PTLDs, such as EBV infection and latency pattern, comparable morphology and presence of monoclonal Tcell populations. 8,[16][17][18] Of note, immunosenescence refers to a continuous remodeling process, where the distribution of CD41 and CD81 T-cell populations is altered; however, the changes in CD41 T-cell profile seem to be affected by advancing age at a higher degree than the one of CD81 T-cell.…”

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

“…1,6,7 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. 4,[10][11][12] The largest western series published to date, 11 including other EBV-positive lymphoproliferative lesions (reactive lymphoid hyperplasia, polymorphic extranodal, polymorphic nodal and diffuse large B-cell lymphoma), demonstrates that the spectrum of EBV-related lesions in western populations is wider than previously expected and mirrors the situation found in Asian countries. In addition, a direct comparison between the prevalence of this particular neoplasm between Mexican and German populations demonstrates that EBVpositive diffuse large B-cell lymphoma of the elderly in a Latin-American (Mexican) population has a similar prevalence, comparable with what has been reported in Asian countries, and in contrast to the low frequency in western populations (1-3%).…”

EBV‐positive diffuse large B‐cell lymphoma of the elderly: 2016 update on diagnosis, risk‐stratification, and management

“…Additionally, geographic differences could be explained by different strains of EBV. For example, a high frequency of EBV type B with the LMP1 30bp deletion was found in Mexican cases [6].…”