Age Related EBV+ Diffuse Large B Cell Lymphoma Is a B Cell Neoplasm Characterized by Prominent NFkB Activation Evaluation of a Series of 47 Cases.
Santiago Montes-Moreno, Julio A Diaz-Perez, Raquel Pajares, Lydia Sanchez-Verde, Juan F Garcia, Manuela Mollejo, Carmen Ruiz-Marcellan, Magdalena Adrados, Nazario Ortiz, Renato Franco, Javier Menarguez, Miguel A Piris. Spanish National Cancer Centre (CNIO), Madrid, Spain
Background: Little data in western countries are available on Age related EBV+ DLBCL. Here we have studied a series of 47 EBV+ DLBCL in elderly patients (mean age 69 years old (48-91)) retrieved from the consultation files of the CNIO in a period of 6 years. We have also evaluated correlations with clinical variables.
Design: HE and IHQ was performed in both TMA and whole tissue sections, using conventional protocols and a panel of antibodies. ISH for EBV (EBER) was also performed. Cases were classified according to the COO using Choi's and Hans algorithms. A control series of EBV-DLBCL cases was used for comparison.
Results: Morphologically most of the cases here studied show a polymorphic B cell rich population. Only one case showed a pure monomorphic appearance. All cases were CD20+ and commonly coexpressed CD30 (41/46, 85% cases) and very rarely CD15 (4/42, 8% cases). EBER was always positive and only 4 cases were negative for EBV-LMP1. The median percentage of EBER positive cells was 80% of the neoplastic population (10-100%). Most cases belong to the NON-GC category (Hans) (39 NON GC (81 %) vs 2 GCB (4 %), 7 NV (14 %)). Choi's algorithm identifies a larger subset of GCB cases (27 ABC (56 %), 8 GCB (16%), 13 NV (27 %)). A shift towards a non-GC phenotype is observed in EBV+DLBCL when compared with EBV- DLBCL cases (n 324; χ2< 0.001). In 94% (45/48) of the cases there is overexpression of BCL2 and a high proliferation index (>50%, 84% of cases). Overexpression of both classical and alternative NFkB pathway related proteins p50 and p52, respectively, is found. 32 out of 37 (60.5%) cases evaluated showed nuclear expression of either p50 only (15% (7/36)), p52 only (8.5% (4/36) or both (45% (21/36) This increased NFkB activation is greater than the observed in the EBV-DLBCL, in both GC and ABC type cases (χ2< 0.001).Survival estimates using Kaplan Meier analysis demonstrate a poor OS and PFS survival for these patients (42% alive at median follow-up of 3 years and 27% without progression/dead at 3 years). When compared with EBV- DLBCL (n 240) these patients show shorter OS and PFS irrespective of age and COO phenotype (p < 0.001).
Conclusions: Our results demonstrate that age related EBV+ DLBCL is a B cell neoplasms that expresses a post GC B cell differentiation programme related with prominent classical and alternative NFkB pathway activation.Moreover, overexpression of BCL2 may lead to uncontrolled proliferation and this might explain the poor clinical outcome in these cases in comparison with EBV- DLBCL.
Wednesday, March 2, 2011 9:30 AM
Poster Session V # 175, Wednesday Morning