# EBV-positive diffuse large B-cell lymphoma

Source: https://onco.cc/cancers/ebv-positive-dlbcl/  
OnCo record `ebv-positive-dlbcl` (Cancer). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

A diffuse large B-cell lymphoma in which Epstein-Barr virus, the virus of glandular fever, is present in the tumour cells. It is diagnosed by a stain on the biopsy, it is commoner in east Asia and Latin America than in Europe, and it is treated in the same way as diffuse large B-cell lymphoma without the virus.

## Summary

What it is. Epstein-Barr virus infects almost everybody by adulthood and then lives quietly inside B cells for life. In a small proportion of diffuse large B-cell lymphomas the virus is present in the tumour cells themselves, detectable by a stain called EBER in situ hybridisation. WHO-HAEM5 recognises that group as an entity in its own right and, in 2022, dropped the qualifier that had restricted it to older people.

How it differs from its family. Not much, in the clinic. It behaves as a diffuse large B-cell lymphoma and is treated as one. What differs is how it is recognised and how it is counted. The European study that found 3.1 per cent noted that no appearance and no immunohistochemical marker reliably identified the positive cases, and that only in situ hybridisation for the viral RNA found them; necrosis was present in two-thirds of positive cases and CD30 in half, but neither was specific. The practical recommendation that came out of that work was to run the stain on every new diffuse large B-cell lymphoma in a person over 50.

Why it is the hardest entity in the classification to place. WHO-HAEM5 reorganised the lymphomas of immune deficiency and dysregulation in 2022 around a three-part description: the histological diagnosis, the virus, and the immune setting. That created an unresolved boundary, which the classification states as a question rather than hiding: should an older person with a diffuse large B-cell lymphoma carrying Epstein-Barr virus be diagnosed with this entity, or with diffuse large B-cell lymphoma arising in immune deficiency, on the assumption that their immune system has aged? The classification says the answer awaits further data and that some of the terminology is arbitrary. A reader should take from that that a label of EBV-positive diffuse large B-cell lymphoma is a description of a finding, not a different disease requiring different treatment.

The boundary the other way. Lymphomatoid granulomatosis is a separate Epstein-Barr virus-driven B-cell disease that, by definition, involves the lung; a similar lesion confined to the brain or gut in somebody with an immune deficiency is classified as EBV-positive diffuse large B-cell lymphoma rather than as lymphomatoid granulomatosis. The International Consensus Classification also keeps nearly all EBV-positive diffuse large B-cell lymphomas out of the mediastinal grey zone category even when they contain Hodgkin-like cells, because the genomes differ.

How it is treated. As diffuse large B-cell lymphoma, with the same immunochemotherapy. The European series found no relationship between the virus and outcome except in the subgroup with the broadest pattern of viral gene expression. The regimens are on the diffuse large B-cell lymphoma page.

## Fields

- Kind: Cancer
- Last checked: 2026-09-29
- Also known as: EBV-positive DLBCL; EBV-positive diffuse large B-cell lymphoma, NOS; EBV-positive diffuse large B-cell lymphoma of the elderly; Epstein-Barr virus-positive diffuse large B-cell lymphoma; EBV+ DLBCL
- Tags: heme; lymphoma; subtype-page
- Group: haematologic
- Burden: How common it is depends on where the series was collected, which is the most useful thing to know about it. In a European tissue microarray study, 8 of 258 diffuse large B-cell lymphomas met the criteria, about 3.1 per cent. In a direct comparison of two populations, 9 of 136 Mexican cases (7 per cent) were positive against 4 of 169 German cases (2 per cent), with a median age of 66 years in Mexico and 77 in Germany. Series from east Asia, where the entity was first described, report higher proportions.
- Subtypes: Polymorphic type, which contains a mixture of cell sizes; Monomorphic type, which looks like ordinary diffuse large B-cell lymphoma
- Biomarkers: Epstein-Barr virus in the tumour cells by EBER in situ hybridisation, which is the only reliable way to find it; A non-germinal-centre phenotype in most cases: CD10 negative, MUM1 positive; LMP1, the viral membrane protein, expressed in most positive cases; CD30, expressed in about half of cases and not specific; The immune setting: transplant, HIV, immunosuppressive therapy or none identified, which decides whether the diagnosis is this entity or a lymphoma of immune deficiency

## Sections of this record

The page is a hub with ten sections in reading order; large sections have their own page. The same plan as JSON: https://onco.cc/api/v1/cancers/ebv-positive-dlbcl/sections.json

- Overview (on the hub): The TL;DR, the family this cancer belongs to, the organ, who gets it and what the state of the art is. https://onco.cc/cancers/ebv-positive-dlbcl/#overview
- Types and stages (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/ebv-positive-dlbcl/#what-it-is [2 subtypes]
- Symptoms and diagnosis (on the hub): How this cancer shows itself, how the diagnosis is confirmed, and the biomarkers clinicians test for. https://onco.cc/cancers/ebv-positive-dlbcl/#finding-it [5 biomarkers]
- Treatment (on the hub): The standard of care by setting, the medicines, surgery and radiotherapy named in it, and the regimens behind them. https://onco.cc/cancers/ebv-positive-dlbcl/#treating-it [2 settings]
- Trials and papers (on the hub): Trials recruiting now, the landmark trials, the trials held by this cancer's subtypes, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/ebv-positive-dlbcl/#evidence [3 milestones]
- Biology and targets (on the hub): The molecular landscape: the targets and how often each appears, the pathways, the mechanics stages and the preclinical models. https://onco.cc/cancers/ebv-positive-dlbcl/#science [2 targets, 1 pathway]
- Countries and centres (own page): Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes. https://onco.cc/cancers/ebv-positive-dlbcl/where-you-are/
- Decisions and support (on the hub): The decisions you may face, the aids that walk through them, the warnings on record, the first sixty days and the questions to ask. https://onco.cc/cancers/ebv-positive-dlbcl/#living-with-it [11 questions, 4 red cards]
- Pipeline and open problems (own page): Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/ebv-positive-dlbcl/coming/ [1 medicine, 3 open problems]
- Data (own page): Every connected record, the notes, the JSON, Markdown and RDF twins, and where the record came from and when it was checked. https://onco.cc/cancers/ebv-positive-dlbcl/data/ [17 connected records]

## Standard of care

- Finding it: In situ hybridisation for Epstein-Barr-encoded RNA on the biopsy. The European series that put the frequency at 3.1 per cent found that no morphological or immunohistochemical feature reliably identified the positive cases, and recommended running the stain on every new diffuse large B-cell lymphoma in a person over 50. Necrosis and CD30 expression are common in positive cases but neither is specific enough to select who to test. ([Epstein-Barr virus (EBV) in cancer](https://onco.cc/terms/ebv-term/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [CD30](https://onco.cc/targets/cd30/))
- Treatment: The same immunochemotherapy as diffuse large B-cell lymphoma without the virus; the presence of Epstein-Barr virus does not currently change the regimen. Where there is an identifiable cause of immune suppression, reducing it is part of the treatment, as it is for the post-transplant lymphoproliferative disorders. The regimens are on the diffuse large B-cell lymphoma page and in the treatment layer of this family. ([Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Rituximab](https://onco.cc/drugs/rituximab/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/), [Post-transplant lymphoproliferative disorder (PTLD)](https://onco.cc/cancers/post-transplant-lymphoproliferative-disorder/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/))

## Open problems

- The classification itself says the boundary between this entity and a lymphoma arising from an ageing immune system is arbitrary, and nobody has defined immune senescence in a way that could settle it.
- The virus is present in the tumour and no treatment aims at it. Virus-specific T cells and other approaches used after transplant have not been tested here.
- Almost all of the original evidence came from east Asia, and the frequency in European and North American populations is several times lower, so the entity's natural history outside Asia rests on small series.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Diffuse_large_B-cell_lymphoma
- WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022): https://doi.org/10.1038/s41375-022-01620-2
- International Consensus Classification of Mature Lymphoid Neoplasms (Campo, Blood 2022): https://doi.org/10.1182/blood.2022015851
- Epstein-Barr virus-positive diffuse large B-cell lymphoma in elderly patients is rare in Western populations (Human Pathology 2010): https://doi.org/10.1016/j.humpath.2009.07.024
- Geographic variation in the prevalence of Epstein-Barr virus-positive diffuse large B-cell lymphoma of the elderly, a comparison of a Mexican and a German population (Modern Pathology 2011): https://doi.org/10.1038/modpathol.2011.62

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [HIV-associated (AIDS-related) lymphomas](https://onco.cc/cancers/hiv-associated-lymphoma/), [Lymphomatoid granulomatosis](https://onco.cc/cancers/lymphomatoid-granulomatosis/), [Mediastinal grey zone lymphoma](https://onco.cc/cancers/mediastinal-grey-zone-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Post-transplant lymphoproliferative disorder (PTLD)](https://onco.cc/cancers/post-transplant-lymphoproliferative-disorder/)
- technologies: [FDG PET](https://onco.cc/technologies/fdg-pet/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/)
- targets: [CD30](https://onco.cc/targets/cd30/)
- terms: [B-cell, T-cell and NK-cell lymphoma](https://onco.cc/terms/lymphoma-b-versus-t-cell/), [Epstein-Barr virus (EBV) in cancer](https://onco.cc/terms/ebv-term/), [R-CHOP (lymphoma chemoimmunotherapy)](https://onco.cc/terms/r-chop/), [The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest](https://onco.cc/terms/lymphoma-tx-regimen-alphabet/), [The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)](https://onco.cc/terms/lymphoma-classification-2022/)
- pathways: [Oncogenic viruses](https://onco.cc/pathways/oncogenic-viruses/)
- drugs: [Rituximab](https://onco.cc/drugs/rituximab/)

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JSON: https://onco.cc/api/v1/entities/ebv-positive-dlbcl.json