Abstract
Epstein-Barr virus (EBV) is a ubiquitous herpesvirus, affecting up to 90% of the population. EBV was first identified as an oncogenic virus in a Burkitt lymphoma cell line, though subsequently has been found to drive a variety of malignancies, including diffuse large B-cell lymphoma (DLBCL) and other lymphoma subtypes. EBV has a tropism for B-lymphocytes and has the unique ability to exist in a latent state, evading the host immune response. In cases of impaired cell mediated immunity, as in patients with advanced age or iatrogenic immune suppression, the virus is able to proliferate in an unregulated fashion, expressing viral antigens that predispose to transformation. EBV-positive DLBCL not otherwise specified, which has been included as a revised provisional entity in the 2016 WHO classification of lymphoid malignancies, is thought to commonly occur in older patients with immunosenescence. Similarly, it is well-established that iatrogenic immune suppression, occurring in both transplant and non-transplant settings, can predispose to EBV-driven lymphoproliferative disorders. EBV-positive lymphoproliferative disorders are heterogeneous, with variable clinical features and prognoses depending on the context in which they arise. While DLBCL is the most common subtype, other histologic variants, including Burkitt lymphoma, NK/T-cell lymphoma, and Hodgkin lymphoma can occur. Research aimed at understanding the underlying biology and disease prevention strategies in EBV-associated lymphoproliferative diseases are ongoing. Additionally, personalized treatment approaches, such as immunotherapy and adoptive T-cell therapies, have yielded encouraging results, though randomized trials are needed to further define optimal management.
Highlights
Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus, affecting up to 90% of the population depending on the region [1]
EBV-associated diffuse large B-cell lymphoma (DLBCL) of the elderly was subsequently included as a provisional entity in the 2008 World Health Organization (WHO) classification of lymphoid malignancies, defined as a monoclonal large B-cell proliferation occurring in patients over the age of 50 and without known immunodeficiency or history of lymphoma
In Western countries, in which rituximab was added to a CHOP chemotherapy backbone (R-CHOP) and EBV positivity was defined by Epstein-Barr- encoded RNAs (EBERs) >10% of cellular staining, there were no appreciable differences between the clinical characteristics of EBV+ and EBV– disease, CD30 positivity in conjunction with EBV positivity, was found to confer an inferior prognosis [32]
Summary
EBV is a ubiquitous human herpesvirus, affecting up to 90% of the population depending on the region [1]. EBV was the first oncogenic virus identified, initially identified in association with a Burkitt lymphoma (BL) cell line, though subsequently associated with a variety of malignancies, including a variety of lymphoma subtypes [2]. EBV initially infects epithelial cells of the oropharynx, prior to replication and spread to B-lymphocytes. A key feature that provides oncogenic potential is the capacity of the virus to exist in a latent state within B-cells [3, 4]. One theory of EBV pathogenesis involves the transit of infected
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