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Age cutoff for Epstein-Barr virus-positive diffuse large B-cell lymphoma–is it necessary?
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Chi Young Ok1, Qing Ye1, Ling Li1, Ganiraju C. Manyam2, Lijuan Deng1, Rashmi R. Goswami1, Xiaoxiao Wang1, Santiago Montes-Moreno3, Carlo Visco4, Alexandar Tzankov5, Karen Dybkaer6, Li Zhang2, Jeremy Abramson7, Aliyah R. Sohani7, April Chiu8, Attilio Orazi9, Youli Zu10, Govind Bhagat11, Kristy L. Richards12, Eric D. Hsi13, William W.L. Choi14, J. Han van Krieken15, Jooryung Huh16, Maurilio Ponzoni17, Andrés J.M. Ferreri17, Shanxiang Zhang18, Ben M. Parsons19, Mina Xu20, Michael B. Møller21, Jane N. Winter22, Miguel A. Piris3, Zijun Y. Xu-Monette1, L. Jeffrey Medeiros1 and Ken H. Young1,23
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
Ken H. Young, email:
Keywords: EBV, DLBCL, elderly, gene expression profiling
Received: April 21, 2015 Accepted: May 12, 2015 Published: May 29, 2015
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.
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