EBV-Positive Lymphoproliferations of B- T- and NK-Cell Derivation in Non-Immunocompromised Hosts

Abstract

The contribution of Epstein-Barr virus (EBV) to the development of specific types of benign lymphoproliferations and malignant lymphomas has been extensively studied since the discovery of the virus over the last 50 years. The importance and better understanding of the EBV-associated lymphoproliferative disorders (LPD) of B, T or natural killer (NK) cell type has resulted in the recognition of new entities like EBV+ mucocutaneous ulcer or the addition of chronic active EBV (CAEBV) infection in the revised 2016 World Health Organization (WHO) lymphoma classification. In this article, we review the definitions, morphology, pathogenesis, and evolving concepts of the various EBV-associated disorders including EBV+ diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), EBV+ mucocutaneous ulcer, DLBCL associated with chronic inflammation, fibrin-associated DLBCL, lymphomatoid granulomatosis, the EBV+ T and NK-cell LPD of childhood, aggressive NK leukaemia, extranodal NK/T-cell lymphoma, nasal type, and the new provisional entity of primary EBV+ nodal T- or NK-cell lymphoma. The current knowledge regarding the pathogenesis of B-cell lymphomas that can be EBV-associated including Burkitt lymphoma, plasmablastic lymphoma and classic Hodgkin lymphoma will be also explored.

Approach to nodal-based T-cell lymphomas

“…129 In systemic chronic active EBV infection, there is a polyclonal, oligoclonal or often monoclonal T-or NK-cell lymphoproliferation of variable clinical severity and the lymph nodes show variable patterns including paracortical hyperplasia, follicular hyperplasia, focal necrosis and epithelioid microgranulomas. 133 In the paediatric population, the autoimmune lymphoproliferative syndrome (ALPS), a primary immune disorder due to mutations in the FAS/FAS-L and defective apoptosis, induces a marked paracortical expansion by a population of CD4-CD8-(double-negative) cytotoxic T cells. 134 This histological picture in lymph nodes may lead to an erroneous diagnosis of either T-cell lymphoblastic or peripheral T-cell lymphoma (PTCL), but the lymphoproliferation in ALPS is mature (TdT-negative) and polyclonal.…”

Prevalence, clinical characteristics and prognosis of EBV‐positive follicular lymphoma

“…1 These disorders represent a spectrum of entities which range from indolent conditions to highly aggressive lymphomas. 2 EBV-positive follicular lymphoma (FL) is an uncommon and poorly characterized disease. We previously reported the largest series of EBV-positive FL, occurring with a prevalence of 2.6% in an unselected cohort of 382 FL patients.…”

“…FES patients, to test their applicability in this context 2. The Institutional Review Board at our institution approved this study and granted a waiver of informed consent.Sixteen patients (8 males and 8 females) with BMN/FES were seen at our institution between April 2010 and January 2018.…”

Immune Landscape in Burkitt Lymphoma Reveals M2-Macrophage Polarization and Correlation between PD-L1 Expression and Non-Canonical EBV Latency Program

“…The constitutive association between EBV and BL, especially with endemic Burkitt lymphoma (eBL) rises questions regarding the role of the virus in altering and actively shaping the tumour microenvironment [16][17][18][19][20][21] . Indeed, EBV orchestrates a variety of complex mechanism favouring the escape of lymphoma cells from anti-tumour immune responses while promoting the creation of niches in which tumour cells may find support for their growth and survival [19][20][21][22][23] .…”