EBV-positive diffuse large B-cell lymphoma, not otherwise specified: 2020 update on diagnosis, risk-stratification and management

Am J Hematol. 2020 Apr;95(4):435-445. doi: 10.1002/ajh.25760. Epub 2020 Feb 29.

Abstract

Disease overview: Epstein Barr virus-positive (EBV+) diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) is an entity included in the 2016 WHO classification of lymphoid neoplasms. EBV+ DLBCL, NOS, is an aggressive B-cell lymphoma associated with chronic EBV infection, and a poor prognosis with standard chemotherapeutic approaches.

Diagnosis: The diagnosis is made through a careful pathological evaluation. Detection of EBV-encoded RNA (EBER) is considered standard for diagnosis; however, a clear cutoff for positivity has not been defined. The differential diagnosis includes plasmablastic lymphoma (PBL), DLBCL associated with chronic inflammation and primary effusion lymphoma (PEL), among others.

Risk-stratification: 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 and PD-1/PD-L1 are emerging as potential adverse but targetable biomarkers.

Management: Patients with EBV+ DLBCL, NOS, should be staged and managed following similar guidelines than patients with EBV-negative DLBCL. EBV+ DLBCL, NOS, however, might have a worse prognosis than EBV-negative DLBCL in the era of chemoimmunotherapy. There is an opportunity to study and develop targeted therapy in the management of patients with EBV+ DLBCL, NOS.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor
  • Combined Modality Therapy
  • Diagnosis, Differential
  • Disease Management
  • Epstein-Barr Virus Infections* / diagnosis
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Immunotherapy
  • Immunotherapy, Adoptive
  • Lymphoma, Large B-Cell, Diffuse* / diagnosis
  • Lymphoma, Large B-Cell, Diffuse* / genetics
  • Lymphoma, Large B-Cell, Diffuse* / therapy
  • Lymphoma, Large B-Cell, Diffuse* / virology
  • Lymphoproliferative Disorders / diagnosis
  • Prognosis
  • Proteasome Inhibitors / therapeutic use
  • Risk Assessment
  • Signal Transduction
  • Therapies, Investigational

Substances

  • Biomarkers, Tumor
  • Immune Checkpoint Inhibitors
  • Proteasome Inhibitors