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

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.

EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 1)

“…The occurrence of EBVMCU in GIT is rather uncommon, with just about 30 cases reported so far [ 13 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ].…”

“…The most common setting is iatrogenic IS in inflammatory bowel disease (IBD) patients [ 13 , 18 , 19 , 20 , 28 ], followed by solid organ-transplanted patients [ 13 , 16 , 17 ], immune-related colitis (irColitis) [ 29 ], rheumatoid arthritis [ 13 ] and treated lymphoma [ 30 ]. Occasional cases are reported in patients with autoimmune thrombocytopenia, HIV, post-hematopoietic stem cell transplantation, hypogammaglobulinemia and rheumatic polymyalgia [ 21 , 22 , 37 ]. In a minority of GIT cases, EBVMCU develops in advanced age, without other known causes of IS [ 16 , 23 , 24 ].…”

“…The review consists of three parts. In this first part, EBVMCU [ 8 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 ], EBV-positive diffuse large B-cell lymphoma not otherwise specified (EBV-positive DLBCL, NOS) [ 8 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ] and classic Hodgkin lymphoma (cHL) [ 8 ] are discussed.…”

EBV-Driven Lymphoproliferative Disorders and Lymphomas of the Gastrointestinal Tract: A Spectrum of Entities with a Common Denominator (Part 2)

“…PBL is predominantly an extra-nodal disease, with a predilection for the oral cavity in HIV-positive individuals, with the GIT being the second most common site. Other extra-nodal sites such as the skin, bone, genitourinary tract, sino-nasal tract, central nervous system (CNS), liver, lung and orbits are more rarely reported [ 8 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 ].…”

“…Unlike PBL, EBV-positive DLBCL, NOS shows a pan B-cell phenotype, strongly expressing CD20 and PAX5, in the absence of plasma cell-associated markers [ 52 , 53 ].…”