Expanding the Spectrum of EBV-positive Marginal Zone Lymphomas

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.

Clinicopathologic Characteristics, Treatment, and Outcomes of Post-transplant Lymphoproliferative Disorders: A Single-institution Experience Using 2017 WHO Diagnostic Criteria

“…EBV+ MALT tends to occur late after transplant and is usually solitary with an overall good prognosis. 6,20,21 EBV+MALTs are rare in occurrence, and no cases were identified in our study. In our report, the cases where the available pathology material was sufficient to diagnose PTLD but insufficient to subclassify the lesion were classified as PTLD, NOS.…”

Case Report: EBV-Positive Extra-Nodal Marginal Zone Lymphoma Associated With XMEN Disease Caused by a Novel Hemizygous Mutation in MAGT1

“…A recent study by Gong S et al (2) identified that EBV+ EMZL can occur in diverse immune defects, but primary immunodeficiency is very uncommon. Until now, only 2 (2). We here report an additional case of EBV+ EMZL associated with another form of primary immunodeficiency, XMEN disease.…”

“…Epstein-Barr virus (EBV)-positive extra-nodal marginal zone lymphoma (EMZL) has been recognized as a rare type of monomorphic post-transplantation lymphoproliferative disorders in the current 2017 World Health Organization lymphoma classification (1). More recent studies broadened the spectrum of EBV+ EMZL not only in the post-transplant patients but also in various immunodeficiency settings (2).…”

Dangerous Liaisons: Gammaherpesvirus Subversion of the Immunoglobulin Repertoire

“…The key details that support this expanded model for the GHV are as follows: GHVs infect follicular and extrafollicular B cells [ 31 , 36 ]. The MZ is an established extrafollicular site that may provide a source of IgM+ memory B cell and plasmablasts observed in GHV-associated diseases [ 21 , 22 , 224 ]. The Ig repertoire of MHV68-infected cells is distinct from uninfected cells, indicating that infection of B cells in GC is not a stochastic event [ 88 , 89 ].…”

“…GHVs infect follicular and extrafollicular B cells [ 31 , 36 ]. The MZ is an established extrafollicular site that may provide a source of IgM+ memory B cell and plasmablasts observed in GHV-associated diseases [ 21 , 22 , 224 ].…”