Increased Incidence of Epstein-Barr Virus Infection in Primary Central Nervous System Lymphoma of the Elderly
Siraj El Jamal, Renu Bajaj, Alina Dulau-Florea, Zixuan Wang, Lawrence Kenyon, Mark Curtis, Stephen Peiper, Jerald Gong. Thomas Jefferson University Hospital, Philadelphia, PA
Background: Epstein-Barr Virus (EBV) positive diffuse large B-cell lymphoma (DLBCL) in the immune competent population is mostly found in the elderly population. Its pathogenesis is believed to be caused by reduced immunity in older age. Primary central nervous system lymphoma (PCNSL) is a subtype of DLBCL with distinct clinicopathologic features. EBV infection in PCNSL was reportedly absent in Western countries but information is limited. We reviewed the EBV status as well as the clinicopathologic features of a series of PCNSL in the elderly.
Design: PCNSL in patients older than 50 years old were retrieved from the pathology archives at our institution from 2000 to 2010. All cases were classified based on the 2008 WHO classification. A panel of immunohistochemistry was performed, which included CD10, CD138, BCL2, BCL6, PAX5, MUM1, C-MYC, and Ki67. In-situ hybridization for Epstein-Barr virus encoded RNA (EBER) was performed in all cases. Immunoglobulin heavy chain gene (IGH) rearrangement was assessed by fluorescence in-situ hybridization (FISH) using an IGH break-apart probe. The histologic morphology, immunophenotype,proliferation rate, EBV status, and IGH rearrangement status were evaluated.
Results: Twenty-three cases of PCNSL were found to match the search criteria. The patients were from 55 to 92 years old (average 71 years) and included 10 men and 13 women. Morphologically, twenty cases (87%) showed a diffuse growth pattern while only 3 cases showed a perivascular pattern (angiotropic). All the cases were DLBCL and histologic variants included 15 centroblast/immunoblast, 4 anaplastic and 4 “Burkitt-like”. Prognostic subgrouping into germinal center and non-germinal center was assessed based on CD10, BCL6 and MUM1 expression using Hans algorithm. Five cases (26%) were germinal center type while 17 cases (74%) were non-germinal center type. Eighteen cases (78%) showed medium to high proliferation indices (>60%). IGH rearrangement was found in 6 of 15 cases (26%). EBV was detected in 2 of 23 cases (9%) by EBER.
Conclusions: PCNSL in the elderly are diffuse large B-cell lymphoma of non-germinal center type. Approximately 25% of patients have IGH rearrangement by FISH. An increased incidence of EBV infection was observed in our series. This finding indicates that EBV may play a role in the pathogenesis of a subset of PCNSL. Similar to DLBCL in other locations, reduced immunity due to older age may have contributed to the increased susceptibility to EBV. Further studies are necessary to evaluate additional cases to assess the clinical significance of EBV infection in PCNSL.
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 208, Tuesday Afternoon