Expanding the Spectrum of EBV-positive Marginal Zone Lymphomas: A Lesion Associated With Diverse Immunodeficiency Settings

Am J Surg Pathol. 2018 Oct;42(10):1306-1316. doi: 10.1097/PAS.0000000000001113.

Abstract

Traditionally low-grade B-cell lymphomas have been excluded from the category of monomorphic posttransplant lymphoproliferative disorders. However, recent reports identified Epstein-Barr virus-positive (EBV) extranodal marginal zone lymphomas (MZL), almost exclusively seen in the posttransplant setting. Some reported cases responded to reduced immunosuppression, suggesting that they should be considered as a form of posttransplant lymphoproliferative disorders. We identified 10 cases of EBV MZL, 9 in extranodal sites and 1 presenting in lymph node. Two cases arose following solid organ transplantation, but other settings included iatrogenic immunosuppression for rheumatoid arthritis (2); prior chemotherapy (2); congenital immune deficiency (1); and increased age (3), as the only potential cause of immune dysfunction. There were 4 males and 6 females; age range 18 to 86. The atypical plasmacytoid and/or monocytoid B cells were positive for EBV in all cases, with either latency I or II in all cases tested. Monotypic light chain expression was shown in all with 6 cases positive for IgG, and 2 for IgM, undetermined in 2. Clonal immunoglobulin gene rearrangement was positive in all cases with successful amplification. MYD88 L265P was wild type in the 6 cases tested. We show that EBV MZLs can arise in a variety of clinical settings, and are most often extranodal. Treatment varied, but most patients had clinically indolent disease with response to reduction of immune suppression, or immunochemotherapy.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Antiviral Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Cell Transformation, Viral
  • DNA, Viral / genetics
  • Epstein-Barr Virus Infections / drug therapy
  • Epstein-Barr Virus Infections / immunology*
  • Epstein-Barr Virus Infections / virology*
  • Female
  • Gene Rearrangement
  • Genes, Immunoglobulin Light Chain
  • Herpesvirus 4, Human / drug effects
  • Herpesvirus 4, Human / genetics
  • Herpesvirus 4, Human / immunology*
  • Humans
  • Immunocompromised Host*
  • Immunoglobulin G / genetics
  • Immunoglobulin G / immunology
  • Immunoglobulin M / genetics
  • Immunoglobulin M / immunology
  • Immunologic Deficiency Syndromes / immunology
  • Immunosuppressive Agents / adverse effects
  • Lymphoma, B-Cell, Marginal Zone / drug therapy
  • Lymphoma, B-Cell, Marginal Zone / genetics
  • Lymphoma, B-Cell, Marginal Zone / immunology*
  • Lymphoma, B-Cell, Marginal Zone / virology*
  • Male
  • Maryland
  • Middle Aged
  • Mutation
  • Myeloid Differentiation Factor 88 / genetics
  • Prognosis
  • Risk Factors

Substances

  • Antiviral Agents
  • Biomarkers, Tumor
  • DNA, Viral
  • Immunoglobulin G
  • Immunoglobulin M
  • Immunosuppressive Agents
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88