Abstract
Simple SummaryEpstein–Barr virus (EBV) infection usually occurs early in life. The virus persists throughout the lifespan in a latent phase mainly in B lymphocytes of immunocompetent hosts. Conditions of immunosuppression of variable origins may favor the emergence of EBV-linked lymphoid proliferations. This group of disorders, having EBV as common denominator, encompasses entities ranging from indolent diseases to aggressive lymphomas. In this review, consisting of three parts, we focus on EBV-linked lymphoid proliferations which may occur in the gastrointestinal tract. Our aim is to summarize the salient clinical, pathological, molecular and therapeutic data of this group of heterogeneous entities, often showing overlapping morphologic and immunophenotypic features despite the different clinical behavior. The correct diagnosis is essential in order to adopt the adequate treatment. In this part of the review, the available data on EBV biology, EBV-positive mucocutaneous ulcer, EBV-positive diffuse large B-cell lymphoma, not otherwise specified and classic Hodgkin lymphoma are discussed.EBV is the most common persistent virus in humans. The interaction of EBV with B lymphocytes, which are considered the virus reservoir, is at the base of the life-long latent infection. Under circumstances of immunosuppression, the balance between virus and host immune system is altered and hence, EBV-associated lymphoid proliferations may originate. These disorders encompass several entities, ranging from self-limited diseases with indolent behavior to aggressive lymphomas. The virus may infect not only B-cells, but even T- and NK-cells. The occurrence of different types of lymphoid disorders depends on both the type of infected cells and the state of host immunity. EBV-driven lymphoproliferative lesions can rarely occur in the gastrointestinal tract and may be missed even by expert pathologists due to both the uncommon site of presentation and the frequent overlapping morphology and immunophenotypic features shared by different entities. The aim of this review is to provide a comprehensive overview of the current knowledge of EBV-associated lymphoproliferative disorders, arising within the gastrointestinal tract. The review is divided in three parts. In this part, the available data on EBV biology, EBV-positive mucocutaneous ulcer, EBV-positive diffuse large B-cell lymphoma, not otherwise specified and classic Hodgkin lymphoma are discussed.
Highlights
EBV is a ubiquitous virus, infecting the majority of the world population [1,2,3,4,5,6,7,8,9,10,11,12]
Recent data have demonstrated that PD-1 ligand 1 (PD-L1) expression is a common feature of EBVlinked LPDs, supporting the concept that these diseases may benefit from checkpoint inhibitor treatment, blocking the interplay between PD-1 of T lymphocytes and PD-L1 on neoplastic cells and, enhancing anti-tumor immune response [56,57]
Helpful histological clues observed in EBVMCU and not in classic Hodgkin lymphoma (cHL) are the high number of EBV-positive cells of variable sizes and the small rim of CD8-positive T lymphocytes at the base of the ulcer [13]
Summary
EBV is a ubiquitous virus, infecting the majority of the world population [1,2,3,4,5,6,7,8,9,10,11,12]. Recent data have demonstrated that PD-L1 expression is a common feature of EBVlinked LPDs, supporting the concept that these diseases may benefit from checkpoint inhibitor treatment, blocking the interplay between PD-1 of T lymphocytes and PD-L1 on neoplastic cells and, enhancing anti-tumor immune response [56,57]. It remains not completely elucidated which viral-encoded proteins may affect PD-L1 expression and how they act, recent studies have shown that EBV alters PD-L1 expression mainly through EBNA2 [58].
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