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

Abstract

Here, we report a retrospective series of 47 EBV-positive diffuse large B-cell lymphoma associated with advanced age. Histopathology allowed to the identification of different histological patterns: cases with polymorphic diffuse large B-cell lymphoma (29 cases), Hodgkin-like (8 cases) and polymorphic lymphoproliferative disorder-like (9 cases) patterns. One case was purely monomorphic diffuse large B-cell lymphoma. We show that this lymphoma type is a neoplasm with prominent classical and alternative nuclear factor-kB pathway activation in neoplastic cells (79% of the cases showed nuclear staining for p105/p50, 74% for p100/p52 and 63% for both proteins), with higher frequency than that observed in a control series of EBV-negative diffuse large B-cell lymphoma (v 2 o0.001). Most cases showed an activated phenotype (95% non-germinal center (Hans algorithm); 78% activated B cell (Choi algorithm)). Clonality testing demonstrated IgH and/or K/Kde/L monoclonal rearrangements in 64% of cases and clonal T-cell populations in 24% of cases. C-MYC (1 case), BCL6 (2 cases) or IgH (3 cases) translocations were detected by FISH in 18% cases. These tumors had a poor overall survival and progression-free survival (the estimated 2-year overall survival was 40±10% and the estimated 2-year progression-free survival was 36±9%). Thus, alternative therapies, based on the tumor biology, need to be tested in patients with EBV-positive diffuse large B-cell lymphoma of the elderly. Modern Pathology (2012) 25, 968-982;

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

“…The monomorphic subtype is less common, and is characterized by monotonous sheets of large transformed B-cells. Hodgkin and ReedSternberg-like cells can be admixed in both the polymorphic and monomorphic types [14]. Geographic necrosis is common.…”

“…1). However, no prognostic significance has been associated with the morphologic subgroups [14]. The lymphoma cells express B-cell markers such as CD19, CD20, CD22, and CD79.…”

“…CD30 is expressed in about 40% of cases. Most cases have an activated B-cell phenotype, expressing MUM1/IRF4, and are negative for CD10 and BCL6 [14]. Expression of NF-jB component p50 and phosphorylated signal transducer and activator of transcription (pSTAT3) are more commonly seen compared with EBV-negative DLBCL.…”

“…The gene set enrichment assay (GSEA) demonstrated an enhanced Toll-like receptor signaling pathway (which has many similarities to the NF-jB pathway) and the JAK-STAT pathway [16]. Clonal rearrangement of the immunoglobulin gene is seen in approximately 60% of cases, and a subset of cases shows rearrangements of the T-cell receptor [14].…”

Evaluation of NF-κB subunit expression and signaling pathway activation demonstrates that p52 expression confers better outcome in germinal center B-cell-like diffuse large B-cell lymphoma in association with CD30 and BCL2 functions

“…Moreover, most previous studies have evaluated only a subset of the NF-κB subunits. [8][9][10][11][12][13][14][15] There are only two studies using all five subunits in DLBCL-a cohort of 88 patients with DLBCL by Odqvist et al 16 and a cohort of 45 patients with testicular DLBCL by Menter et al 17 In the current study, we evaluated expression of all five subunits of the NF-κB protein by immunohistochemistry and its clinical implications in a large cohort of patients with de novo DLBCL.…”