Reappraisal of Primary Epstein-Barr Virus (EBV)-positive Diffuse Large B-Cell Lymphoma of the Gastrointestinal Tract

Abstract

Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoproliferation encompasses a broad range of clinicopathologic findings, including specific subtypes, for example, EBV+ mucocutaneous ulcer. Here we reassessed 36 cases of primary EBV+ diffuse large B-cell lymphomas (16 men and 20 women; median age, 69.5 y; range, 35 to 84 y), including 8 immunosuppressed patients (Lugano stage II-IV; median age, 74 y), 7 nonimmunosuppressed patients with stage I disease (median age, 69 y), and 21 nonimmunosuppressed patients with stage II-IV disease (median age, 69 y). All immunosuppressed patients exhibited iatrogenic immunodeficiency and an ulcerative appearance, with ulcer sites including the stomach (1 patient), small intestine (6 patients), and rectum (1 patient). Four patients were in the setting of treated lymphoma-associated immunosuppression. Immunosuppressed patients had higher incidences of intestinal involvement (P=0.001) and perforation (n=2) compared with advanced stage nonimmunosuppressed patients. Among nonimmunosuppressed stage I patients, lesions were restricted to the stomach, none showed multiple lesions or elevated serum lactate dehydrogenase, and the overall survival curve plateaued, although it was not statistically significant (P=0.0581). One nonimmunosuppressed stage I patient with a polypoid lesion exhibited spontaneous regression within 2 months after diagnosis, while another with bulky disease pursued an aggressive clinical course. Nonimmunosuppressed stage I cases without bulky masses may be considered EBV mucocutaneous ulcer with local progression. Our results demonstrated that primary EBV+ gastrointestinal diffuse large B-cell lymphoma could be delineated into 3 groups based on immune status and clinical stage, revealing distinguishing features useful as a pragmatic guide for diagnostic and therapeutic approaches.

Epstein-Barr Virus-positive Intestinal Diffuse Large B-cell Lymphoma in a Japanese Patient with Celiac Disease: First Reported Case and a Literature Review

“…human immunodeficiency virus, hepatitis C, and EBV) and genetic factors predisposing patients to both Ads and lymphomas may also play a substantial role (19). Eight of the 36 EBV+ gastrointestinal DLBCL patients were receiving therapeutic immune suppression for rheumatoid arthritis, Crohn's disease, and malignant lymphoma (20).…”

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

“…However, the identification of the disease even in younger adults (<50 years) and in children led to change the terminology in the current 2017 WHO classification [ 8 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 ].…”

“…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.…”

Recent advances in upper gastrointestinal lymphomas: molecular updates and diagnostic implications

“…The immunophenotype is usually of the activated B-cell type, with frequent CD30 expression, but a subset of cases are CD10+. 144 EBV+ DLBCL, NOS is generally reported in patients without any known immune deficiency disorder (after exclusion of 'specific' types of EBV+ DLBCL, such as plasmablastic lymphoma), and can occur at any age, but usually in older adults. In a series from Asia, EBV+ DLBCLs represented approximately 7-10% of gastric primaries, and the presence of EBV was negatively correlated with outcome.…”

“…[145][146][147] Whereas EBV+ mucocutaneous ulcer has a predilection for the lower GI tract, a recent study from Japan reported that GI EBV+ DLBCLs occurring in non-immunosuppressed individuals have a predilection for the stomach, which was the main localisation of disease for low-stage lesions and was often involved in cases with multifocal lesions. 144 Plasmablastic lymphoma is composed of large cells, ranging from immunoblasts to plasmablasts with or without a component of mature plasma cells, and is characterised by extinction of the B-cell transcription programme and a plasma cell immunophenotype. 148 Recent data provide evidence that the transcriptome of plasmablastic lymphoma is more closely related to that of multiple myeloma than to that of other B-cell malignancies.…”