title: Reappraisal of Epstein-Barr virus (EBV) in diffuse large B-cell lymphoma (DLBCL): comparative analysis between EBV-positive and EBV-negative DLBCL with EBV-positive bystander cells.
abstract: OBJECTIVE
  Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) not otherwise specified is defined as monoclonal EBV+ B-cell proliferation affecting patients without any known immunosuppression. Non-neoplastic EBV+ cells proliferating in or adjacent to EBV- DLBCL were reported recently, but their clinical significance is unclear. Thus, the aim of this study was to investigate the prognostic impact of EBV+ cells in DLBCL.
  
  
  RESULTS
  We compared the clinicopathological characteristics of 30 EBV+ DLBCL patients and 29 and 604 EBV- DLBCL patients with and without EBV+ bystander cells (median age of onset 71, 67 and 62 years, respectively). Both EBV+ DLBCL patients and EBV- DLBCL patients with EBV+ bystander cells tended to have high and high-intermediate International Prognostic Index scores (60% and 59%, respectively), as compared with only 46% of EBV- DLBCL patients without EBV+ bystander cells. EBV- DLBCL patients with EBV+ bystander cells showed a significantly higher incidence of lung involvement than those without EBV+ bystander cells (10% versus 2%, P < 0.05). Furthermore, EBV+ DLBCL patients and EBV- DLBCL patients with EBV+ bystander cells had a poorer prognosis than patients without any detectable EBV+ cells [median overall survival (OS) of 100 months and 40 months versus not reached, P < 0.01]. Notably, EBV+ DLBCL patients and EBV- DLBCL patients with EBV+ bystander cells treated with rituximab showed overlapping survival curves (OS, P = 0.77; progression-free survival, P = 1.0).
  
  
  CONCLUSIONS
  EBV- DLBCL with bystander EBV+ cells has similar clinical characteristics to EBV+ DLBCL. DLBCL with EBV+ bystander cells may be related to both age-related and microenvironment-related immunological deterioration.
authors.affiliation: Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan.|Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Akiko
authors.identifier: http://orcid.org/0000-0002-0849-9665
authors.initials: A
authors.lastname: Ohashi
authors.affiliation: Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Kato
authors.affiliation: Department of Haematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Akinao
authors.initials: A
authors.lastname: Okamoto
authors.affiliation: Department of Haematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Inaguma
authors.affiliation: Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan.|Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Satou
authors.affiliation: Department of Surgical Pathology, Aichi Medical University Hospital, Nagakute, Japan.
authors.forename: Toyonori
authors.initials: T
authors.lastname: Tsuzuki
authors.affiliation: Department of Haematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Emi
authors.affiliation: Department of Haematology, Fujita Health University School of Medicine, Toyoake, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Okamoto
authors.affiliation: Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Nakamura
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D024201:Bystander Effect; D018572:Disease-Free Survival; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000473:pathology*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D053208:Kaplan-Meier Estimate; D016403:Lymphoma, Large B-Cell, Diffuse / Q000401:mortality / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011379:Prognosis
keywords: Epstein-Barr virus; bystander cells; diffuse large B-cell lymphoma; senescence