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

• Published in: Modern pathology Vol. 25; no. 7; pp. 968 - 982
• Main Authors: Montes-Moreno, Santiago, Odqvist, Lina, Diaz-Perez, Julio A, Lopez, Ana Batlle, de Villambrosía, Sonia Gonzalez, Mazorra, Francisco, Castillo, Maria E, Lopez, Mar, Pajares, Raquel, García, Juan F, Mollejo, Manuela, Camacho, Francisca I, Ruiz-Marcellán, Carmen, Adrados, Magdalena, Ortiz, Nazario, Franco, Renato, Ortiz-Hidalgo, Carlos, Suarez-Gauthier, Ana, Young, Ken H, Piris, Miguel A
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.07.2012; Nature Publishing Group US; Elsevier Limited
• Subjects: 692/699/67/1990/291/1621/1915; 692/700/139/422; 692/700/1518; Age; Aged; Aged, 80 and over; Algorithms; B-cell lymphoma; Bcl-6 protein; Blotting, Western; c-Myc protein; Cancer; Disease-Free Survival; DLBCL; EBV; elderly; Epstein-Barr Virus Infections - complications; Fluorescence in situ hybridization; Geriatrics; Germinal Center - pathology; Heavy chains; Humans; Immune system; Immunoglobulins; Immunohistochemistry; In Situ Hybridization, Fluorescence; Laboratory Medicine; Lymphocytes; Lymphocytes B; Lymphocytes T; Lymphoma; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Large B-Cell, Diffuse - virology; Medical prognosis; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Staging; NF- Kappa B protein; NF-kappa B - metabolism; NFkB; non-Hodgkin lymphoma; original-article; Pathology; Patients; Retrospective Studies; Tissue Array Analysis; Translocation; Tumors; Mexico; United States > US; Madrid Spain; Spain; EBV; DLBCL; non-Hodgkin lymphoma; NFkB; elderly
• ISSN: 0893-3952; 1530-0285; 1530-0285
• DOI: 10.1038/modpathol.2012.52

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 (χ2 <0.001). 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.