Epstein-Barr Virus-positive Diffuse Large B-cell Lymphomas of the ElderlyAdam, Patrick MD; Bonzheim, Irina PhD; Fend, Falko MD; Quintanilla-Martínez, Leticia MDAdvances in Anatomic Pathology: September 2011 - Volume 18 - Issue 5 - p 349–355 doi: 10.1097/PAP.0b013e318229bf08 Review Articles Abstract Author Information Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly has been included in the 2008 WHO classification as a new provisional entity and is defined as blastic, clonal B-cell proliferation associated with EBV occurring in patients over 50 years of age, presumably due to senescence of the immune system. Secondary immunodeficiencies must be excluded. Morphologically, the predominant polymorphic subtype shows a mixed proliferation of large transformed cells, plasma cells, plasmablasts, lymphocytes, and commonly Reed-Sternberg (RS)-like cells, whereas the monomorphic subtype reveals sheets of large cells. An additional characteristic feature is large areas of “geographical” necrosis. EBV+ DLBCL of the elderly is positive for pan-B cell markers and often for CD30. EBV infection detected by Epstein Barr early RNA in situ hybridization should be present in the majority of tumor cells. Most cases express LMP1 and up to 32% EBNA2, the latter a sign of an impaired immune system. The most challenging differential diagnosis is EBV+ classical Hodgkin lymphoma in older patients. Strong, homogeneous expression of B-cell markers, including transcription factors OCT2 and BOB.1, and lack of CD15 support a diagnosis of EBV+ DLBCL. EBV+ DLBCL of the elderly accounts for 8% to 10% of DLBCL in Asian countries, but seems to be uncommon in Western populations, indicating an ethnic or geographic predisposition. Clinically, patients may present with nodal or extranodal involvement. B-symptoms and poor performance status are common, and prognosis is significantly inferior compared with EBV- cases. Whether EBV+DLBCL of the elderly represents a true entity or only a DLBCL variant remains to be determined. Institute of Pathology, Eberhard-Karls-University of Tuebingen, Tuebingen, Germany The authors have no conflicts of interest to disclose. Supported in part by a Grant from the Deutsche Forschungsgemeinschaft (SFB 685, TP B8) to L.Q.M and F.F. Reprints: Leticia Quintanilla-Martinez, MD, Institute of Pathology, University Hospital Tuebingen, Liebermeisterstrasse 8, Tuebingen 72076, Germany (e-mail: email@example.com). © 2011 Lippincott Williams & Wilkins, Inc.