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. 2022 Oct 1:54:101674.
doi: 10.1016/j.eclinm.2022.101674. eCollection 2022 Dec.

Lymphomas associated with Epstein-Barr virus infection in 2020: Results from a large, unselected case series in France

Marie Donzel  1 , Maxime Bonjour  1   2 , Jean-Damien Combes  2 , Florence Broussais  3 , Pierre Sesques  3   4 , Alexandra Traverse-Glehen  1   4 , Catherine de Martel  2
Affiliations

Lymphomas associated with Epstein-Barr virus infection in 2020: Results from a large, unselected case series in France

Marie Donzel et al. EClinicalMedicine. .

Abstract

Background: Despite mounting evidence for a causal role in an increasing number of lymphoma subtypes, very few studies have systematically tested the entire spectrum of Hodgkin and non-Hodgkin lymphomas for the presence of Epstein-Barr virus (EBV). Here, we describe the prevalence of EBV in a large, unselected series of patients diagnosed with any type of lymphoma during 2020, in the pathology department of a single University Hospital in France.

Methods: A total of 756 lymphoma cases (89% new diagnoses and 11% relapses), were registered in the department between Jan 1 and Sept 30, 2020 and 616 were successfully tested for EBV presence in tumour cells by EBV-encoding RNA in-situ hybridisation, using double-blinded assessment and a scoring system designed in accordance with the current state of knowledge in the literature.

Findings: A strong association with EBV was described in 27/87 (31%) classic Hodgkin lymphomas, 12/223 (5%) diffuse large B-cell lymphomas, and 18/71 (25%) NK and T-cell lymphomas: 4 extranodal NK/T-cell lymphomas, nasal type, 14 angioimmunoblastic T-cell lymphomas (48%). In Hodgkin and NK and T-cell lymphomas, there was a statistically significant association between EBER positivity and relapse (p < 0·01). Among other subtypes, a potential association with EBV (≥10% stained cells) was found in 2/97 (2%) follicular lymphomas, both of grades 1-2, 1/19 (5%) chronic lymphocytic leukaemia (CLL), 1/9 lymphoplasmacytic lymphomas (11%), and 2/47 (4%) marginal zone lymphomas.

Interpretation: When applied to the distribution of lymphomas in France as described in the Lymphopath database, our data suggested that at least 8% of all combined Hodgkin and non-Hodgkin lymphomas are associated with EBV.

Funding: International Agency for Research on Cancer (IARC/WHO).

Keywords: EBV; Epidemiology; Hodgkin lymphoma; Lymphoma; Non-Hodgkin lymphoma; Prevalence.

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Conflict of interest statement

PS has received personal fees from Incyte, Chugai, Kite, Novartis and Janssen, and support for attending meetings from Janssen and Kite Gilead. The other authors declare no competing interests.

Figures

Figure 1:
Figure 1
Flowchart of the study. *Not meeting criteria: 595 excluded patients, including 536 patients with non-lymphomatous lesions (389 reactional proliferations, 22 indolent lymphoproliferative disorders, and 125 tumours other than lymphomas (i.e., carcinoma, melanoma, sarcomas, myeloid proliferations and benign tumours)); 2 EBV-induced lymphoproliferations occurring in transplanted patients; 24 cases sent for DNA extraction or other analysis, and for whom no histological diagnosis was requested; and 33 unclassifiable lymphomas due to insufficient or damaged tissue.
Figure 2:
Figure 2
Positive results of EBER-ISH using a threshold of 2 (≥10% stained cells) in small B-cell lymphomas. Since small B-cell lymphomas are not accepted as being associated with EBV, a score of 3 was not possible in this category. (A-B) Grades 1–2 Follicular lymphomas (magnification x10); (C) Chronic lymphocytic leukaemia (magnification x10); (D) Lymphoplasmacytic lymphoma (magnification x10). (E) Nodal marginal zone lymphoma (magnification x10). EBER-ISH=EBV-encoding RNA in situ hybridisation. EBV=Epstein-Barr virus.
See this image and copyright information in PMC

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