EBV-positive diffuse large B-cell lymphoma of the elderly: 2016 update on diagnosis, risk-stratification, and management

Am J Hematol. 2016 May;91(5):529-37. doi: 10.1002/ajh.24370.


Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) of the elderly is a provisional entity included in the 2008 WHO classification of lymphoid neoplasms. It is a disease typically seen in the elderly and thought to be associated with chronic EBV infection and severe immunosuppression with a component of immunosenescence. Recent research, however, has suggested that EBV-positive DLBCL can be seen in younger, immunocompetent patients. The diagnosis of EBV-positive DLBCL of the elderly is made through a careful pathological evaluation. The differential diagnosis includes infectious mononucleosis (specifically in younger patients), lymphomatoid granulomatosis, Hodgkin lymphoma, and gray zone lymphoma, among others. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The International Prognostic Index (IPI), and the Oyama score can be used for risk-stratification. The Oyama score includes age >70 years and presence of B symptoms. The expression of CD30 is emerging as a potential adverse, and targetable, prognostic factor. Patients with EBV-positive DLBCL should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. It has been suggested, however, that EBV-positive patients have a worse prognosis than EBV-negative counterparts in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV-positive DLBCL.

Publication types

  • Review

MeSH terms

  • Age of Onset
  • Aged
  • Aged, 80 and over
  • Animals
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antiviral Agents / therapeutic use
  • Combined Modality Therapy
  • Diagnosis, Differential
  • Disease Management
  • Epstein-Barr Virus Infections / diagnosis
  • Epstein-Barr Virus Infections / epidemiology
  • Epstein-Barr Virus Infections / therapy
  • Herpesvirus 4, Human / drug effects
  • Herpesvirus 4, Human / physiology
  • Humans
  • Immunotherapy, Adoptive
  • Infectious Mononucleosis / diagnosis
  • Lymphoma / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / diagnosis
  • Lymphoma, Large B-Cell, Diffuse / epidemiology
  • Lymphoma, Large B-Cell, Diffuse / therapy
  • Lymphoma, Large B-Cell, Diffuse / virology*
  • Mice
  • Middle Aged
  • Molecular Targeted Therapy
  • Prognosis
  • Risk Assessment
  • Rituximab / administration & dosage
  • Virus Activation


  • Antiviral Agents
  • Rituximab