Age cutoff for Epstein-Barr virus-positive diffuse large B-cell lymphoma–is it necessary?

// Chi Young Ok 1 , Qing Ye 1 , Ling Li 1 , Ganiraju C. Manyam 2 , Lijuan Deng 1 , Rashmi R. Goswami 1 , Xiaoxiao Wang 1 , Santiago Montes-Moreno 3 , Carlo Visco 4 , Alexandar Tzankov 5 , Karen Dybkaer 6 , Li Zhang 2 , Jeremy Abramson 7 , Aliyah R. Sohani 7 , April Chiu 8 , Attilio Orazi 9 , Youli Zu 10 , Govind Bhagat 11 , Kristy L. Richards 12 , Eric D. Hsi 13 , William W.L. Choi 14 , J. Han van Krieken 15 , Jooryung Huh 16 , Maurilio Ponzoni 17 , Andres J.M. Ferreri 17 , Shanxiang Zhang 18 , Ben M. Parsons 19 , Mina Xu 20 , Michael B. Moller 21 , Jane N. Winter 22 , Miguel A. Piris 3 , Zijun Y. Xu-Monette 1 , L. Jeffrey Medeiros 1 and Ken H. Young 1,23 1 Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 2 Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA 3 Hospital Universitario Marques de Valdecilla, Santander, Spain 4 San Bortolo Hospital, Vicenza, Italy 5 University Hospital, Basel, Switzerland 6 Aalborg University Hospital, Aalborg, Denmark 7 Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA 8 Memorial Sloan-Kettering Cancer Center, New York, New York, USA 9 Weill Medical College of Cornell University, New York, New York, USA 10 Houston Methodist Hospital, Houston, Texas, USA 11 Columbia University Medical Center and New York Presbyterian Hospital, New York, New York, USA 12 University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA 13 Cleveland Clinic, Cleveland, Ohio, USA 14 University of Hong Kong, Li Ka Shing Faculty of Medicine, Hong Kong, China 15 Radboud University, Nijmegen Medical Centre, Nijmegen, the Netherlands 16 Asan Medical Center, Ulsan University College of Medicine, Seoul, Korea 17 San Raffaele H. Scientific Institute, Milan, Italy 18 Indiana University School of Medicine, Indianapolis, Indiana, USA 19 Gundersen Lutheran Health System, La Crosse, Wisconsin, USA 20 Yale University, School of Medicine, New Haven, CT, USA 21 Odense University Hospital, Odense, Denmark 22 Feinberg School of Medicine, Northwestern University, Chicago, Illinois, USA 23 The University of Texas School of Medicine, Graduate School of Biomedical Sciences, Houston, Texas, USA Correspondence to: Ken H. Young, email: // Keywords : EBV, DLBCL, elderly, gene expression profiling Received : April 21, 2015 Accepted : May 12, 2015 Published : May 29, 2015 Abstract Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly (EBV+ DLBCL-e) is a molecularly distinct variant of DLBCL, characterized by a monoclonal B-cell proliferation that occurs in patients >50 years of age without a history or clinicopathologic evidence of immunodeficiency. However, patients with EBV+ DLBCL younger than 50-years-old also exist in Western countries. We evaluated the clinicopathologic, immunophenotypic and genetic features in Cacausian patients with EBV+ DLBCL who are ≤50 years of age and compared this patient group to patients who are >50 years. In patients who are ≤50 years, less frequent expression of BCL6 and a trend of more frequent expression of CD30 and pSTAT3 were found in patients with EBV+ DLBCL. In patients who are >50 years, common expression of CD30, p50, pSTAT3 and less frequent expression of BCL6 were observed. Older patients also more commonly had a poor performance status (ECOG≥2). Comparing EBV+ DLBCL patients in ≤50 years versus >50 years, both groups had similar clinicopathologic, immunophenotypic and genetic features. Gene expression profiling, microRNA profiling and treatment outcome of the younger patients with EBV+ DLBCL was not distinctive from tumors in older patients. Based on our data, we suggest that the arbitrary age cutoff for EBV+ DLBCL is unnecessary and should be eliminated in the WHO lymphoma classification scheme.