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

Abstract

Key Points• EBV 1 LBCLs in young patients resemble those seen in the elderly, but usually have a good outcome.• LBCLs affected predominantly males (male:female 5 3.6:1), with a median age of 23 years (range, 4-45 years). All patients presented with lymphadenopathy and 11% also had extranodal disease. Morphologically, 3 patterns were identified: T-cell/histiocyte-rich large B-cell lymphoma-like (n 5 36), gray zone lymphoma (n 5 7), and diffuse LBCL-not otherwise specified (n 5 3). Tumor cells (EBV 1 in >90% of cells) expressed B-cell antigens, were often CD30 and PD-L1 positive, and showed a nongerminal center immunophenotype. A total of 93% expressed EBV latency type II and 7% latency type III. Indoleamine 2,3-dioxygenase was expressed on background accessory cells. The most common treatment regimen was rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (58%), with local radiation therapy added in 21%. With a median follow-up of 22 months, 82% of patients are in clinical remission and only 8% died of disease. Younger patients achieved a significantly higher overall survival than prior series of EBV 1 LBCLs reported in the elderly (P < .0001). In conclusion, EBV 1 LBCLs are not restricted to the elderly. Young patients present with nodal disease and have a good prognosis.(Blood. 2015;126(7):863-872)

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

“…Recent evidence suggests that EBV-positive DLBCL can be seen in young, immunocompetent individuals [9][10][11][12]. These studies have shown similar virological and pathological findings between younger and older patients with EBV-positive DLBCL.…”

Immune-checkpoint expression in Epstein-Barr virus positive and negative plasmablastic lymphoma: a clinical and pathological study in 82 patients

“…In this regard, it has been shown that PD-L1 expression can be driven by intrinsic genetic aberrations of 9p24.1 (a genomic region including CD274, PDCD1LG2 and JAK2) and by the dysregulation of JAK/STAT pathway. 43,45,46 As suggested for EBV + CD20 + diffuse large B-cell lymphoma (DLBCL), 25,47 further genetic analyses of PD-L1 (CD274) locus are needed to identify the intrinsic mechanism of PD-L1 upregulation by malignant cells in PL.…”

The oncogenic membrane protein LMP1 sequesters TRAF3 in B-cell lymphoma cells to produce functional TRAF3 deficiency

“…2 Additionally, a rarer form of EBV-associated diffuse large BCL (DLBCL) occurs in immunocompetent patients .50 years 3 ; a similar type of DLBCL was recently reported in young patients. 4 The EBV protein latent membrane protein 1 (LMP1) is expressed in EBV latency II and III programs, characteristic of Hodgkin, posttransplant, AIDS-associated, 2 and DLBCL. 4 LMP1 was implicated as oncogenic in the 1980s by its ability to transform cultured cells.…”

“…4 The EBV protein latent membrane protein 1 (LMP1) is expressed in EBV latency II and III programs, characteristic of Hodgkin, posttransplant, AIDS-associated, 2 and DLBCL. 4 LMP1 was implicated as oncogenic in the 1980s by its ability to transform cultured cells. 5,6 Over the ensuing decade, it was revealed that B-cell LMP1 acts as a dysregulated mimic of CD40, inducing enhanced B-cell activation and survival via several pathways.…”