Epstein-Barr Virus Positive B-Cell Lymphoproliferative Disorder of the Gastrointestinal Tract

SIMPLE SUMMARY: Epstein-Barr virus (EBV) contributes to the reactive and neoplastic lymphoid proliferation of B-, T-, and NK-cell lineages, which represent a vast clinicopathological spectrum ranging from indolent, self-limited disease to aggressive lymphomas. EBV-positive B-cell lymphoproliferative disorder (EBV(+) B-LPD) is the most common of these diseases, accounting for 3% to 15% of diffuse large B-cell lymphomas. The spectrum of EBV(+) B-LPD is expanding with advances in understanding immunosenescence and iatrogenic immunodeficiency in the era of immune-oncology. We review EBV(+) B-LPD affecting the gastrointestinal tract with a focus on the PD-L1 expression in tumor and non-malignant immune cells to better understand this peculiar disease. ABSTRACT: Epstein-Barr virus positive B-cell lymphoproliferative disorder (EBV(+) B-LPD) encompasses a broad clinicopathological spectrum and distinct clinical behavior that relatively favors the gastrointestinal (GI) tract. In this review, we provide an update on the clinicopathological features and biological behavior of EBV-positive mucocutaneous ulcer (EBVMCU) and primary EBV(+) diffuse large B-cell lymphoma (DLBCL) of the GI tract. EBVMCU is a newly recognized entity but well known as an indolent and self-limited EBV(+) B-LPD occurring in various immunodeficiencies. In contrast, EBV(+) DLBCL constitutes the largest group of EBV(+) B-LPDs and is regarded as an aggressive neoplasm. These two distinct diseases have historically been distinguished in the reappraisal of age-related EBV-associated B-LPDs but are challenging in routine practice regarding their differential diagnostic and therapeutic approaches. An increasing number of reports indicate that they are epidemiologically prevalent beyond western and eastern countries, but their comprehensive analysis is still limited. We also describe the PD-L1 positivity of tumorous large cells and non-malignant immune cells, which is relevant for the prognostic delineation among patients with primary DLBCL of the GI tract with and without EBV on tumor cells.