# Primary large B-cell lymphoma of the testis

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

## TL;DR

A large B-cell lymphoma that starts in a testicle rather than in a lymph node, usually in a man over 60, and shows itself as a painless swelling. It is the commonest cancer of the testicle in older men, and it behaves as one disease with lymphoma of the brain and of the eye, which is why treatment deliberately protects both.

## Summary

What it is. A diffuse large B-cell lymphoma arising inside a testicle. It presents as a firm, usually painless swelling, and it is the commonest malignant tumour of the testis in men over 60, an age at which the germ cell tumours of younger men have become rare. The diagnosis is usually made on the testicle after it has been removed, because a solid testicular mass is removed rather than biopsied.

How it differs from its family, and this is the whole of the management. The testis is an immune-privileged site: a barrier of cells keeps the immune system out, which protects developing sperm from being attacked and also shelters a lymphoma from immune surveillance and from many drugs. The brain and the inside of the eye are protected in the same way. WHO-HAEM5 recognised in 2022 that large B-cell lymphomas at those three sites are one entity, which it called primary large B-cell lymphoma of immune-privileged sites, because they share an activated B-cell phenotype, concurrent MYD88 and CD79B mutations, loss of the machinery that displays antigen to the immune system, and a habit of relapsing in each other: a testicular lymphoma comes back in the brain or in the other testicle, and a lymphoma of the eye follows or precedes one in the brain.

Where the two classifications disagree. The International Consensus Classification discussed the same grouping and decided it was premature, on the grounds that lymphomas at some of those sites are heterogeneous and that a pathologist often does not know whether other sites are involved. It nevertheless recognises primary diffuse large B-cell lymphoma of the testis as a specific entity in its own right, closely related to lymphoma of the central nervous system and sharing the same genetic subgroup. So the two books agree about the biology and differ about the filing.

How it is treated, and why three things are done at once. The trial that set the standard, IELSG-10, treated 53 men with stage I or II disease with six to eight cycles of rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone, four doses of methotrexate into the spinal fluid, and 30 Gy of radiotherapy to the remaining testicle, with the regional lymph nodes irradiated in stage II. At a median follow-up of 65 months, five-year progression-free survival was 74 per cent and overall survival 85 per cent. Ten patients relapsed, three of them in the central nervous system, giving a five-year cumulative incidence of relapse in the brain or spinal cord of 6 per cent. No patient relapsed in the remaining testicle. Those last two numbers are the reason the regimen looks the way it does.

What is still unsettled. Irradiating the remaining testicle prevents relapse there but causes infertility and low testosterone, which matters to a minority of men who are diagnosed young. Whether methotrexate into the spinal fluid is the right prophylaxis against disease in the brain, or whether high-dose intravenous methotrexate would do better, has not been settled by a randomised trial. In the SEER analysis covering 1980 to 2005, survival in testicular lymphoma did not improve after rituximab came into use in the way it did in lymphoma of the lymph nodes, which the authors noted explicitly.

## Fields

- Kind: Cancer
- Last checked: 2026-09-29
- Also known as: Primary testicular lymphoma; PTL; Primary testicular diffuse large B-cell lymphoma; Testicular lymphoma; Primary diffuse large B-cell lymphoma of the testis; Primary large B-cell lymphoma of immune-privileged sites
- Tags: heme; lymphoma; subtype-page
- Group: haematologic
- Burden: In the United States SEER registries, 769 men with primary testicular diffuse large B-cell lymphoma were identified between 1980 and 2005, with a median age at diagnosis of 68.0 years and an incidence that rose over the period; a later SEER analysis identified 1,169 patients between 1973 and 2013, median age 70 years, of whom 82.9 per cent had diffuse large B-cell lymphoma and 68.6 per cent had stage I or II disease at diagnosis. The corpus does not quote a United Kingdom incidence figure, because no source it could verify publishes one for this entity.
- Biomarkers: An activated B-cell (non-germinal-centre) phenotype: CD10 negative, MUM1 positive, BCL6 positive; Concurrent MYD88 and CD79B mutations, the genetic signature shared with lymphoma of the brain and of the eye; Loss of MHC class I and II and of beta-2-microglobulin, which is how the tumour escapes immune recognition; Epstein-Barr virus, which is characteristically negative; Imaging of the brain and examination of the spinal fluid at diagnosis, because the central nervous system is where this disease relapses

## 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/primary-testicular-lymphoma/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/primary-testicular-lymphoma/#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/primary-testicular-lymphoma/#what-it-is
- 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/primary-testicular-lymphoma/#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/primary-testicular-lymphoma/#treating-it [3 settings, 3 decisions with options]
- 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/primary-testicular-lymphoma/#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/primary-testicular-lymphoma/#science [1 target]
- 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/primary-testicular-lymphoma/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/primary-testicular-lymphoma/#living-with-it [12 questions, 6 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/primary-testicular-lymphoma/coming/ [6 medicines, 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/primary-testicular-lymphoma/data/ [31 connected records]

## Standard of care

- Diagnosis and staging: A solid testicular mass is removed through the groin rather than biopsied, so the diagnosis is usually made on the removed testicle. Staging then has to cover the sites this disease travels to: computed tomography or PET-CT of the body, imaging of the brain, examination of the spinal fluid, and examination of the remaining testicle. Sperm banking is discussed before treatment where it is relevant, because radiotherapy to the remaining testicle causes infertility and low testosterone. ([FDG PET](https://onco.cc/technologies/fdg-pet/), [Fertility before lymphoma treatment: what to ask for, and when](https://onco.cc/terms/lymphoma-tx-fertility-preservation/), [Lugano classification / Ann Arbor staging](https://onco.cc/terms/lugano-classification/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/))
- First-line treatment of stage I and II disease: Rituximab with cyclophosphamide, doxorubicin, vincristine and prednisone for six to eight cycles, methotrexate into the spinal fluid, and radiotherapy to the remaining testicle. In IELSG-10, which treated 53 men this way, five-year progression-free survival was 74 per cent and overall survival 85 per cent at a median follow-up of 65 months; the five-year cumulative incidence of relapse in the central nervous system was 6 per cent and there were no relapses in the irradiated testicle. Grade 3 or 4 neutropenia occurred in 28 per cent and infection in 4 per cent. ([Rituximab](https://onco.cc/drugs/rituximab/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Vincristine](https://onco.cc/drugs/vincristine/), [Prednisone](https://onco.cc/drugs/prednisone/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Intrathecal therapy (lumbar puncture, Ommaya reservoir)](https://onco.cc/terms/intrathecal-therapy/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/), [CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it](https://onco.cc/terms/lymphoma-tx-cns-prophylaxis/))
- What happens at relapse: Relapse is most often in the central nervous system, and it is treated on the pathway for lymphoma of the brain rather than on the pathway for nodal lymphoma: regimens built around high-dose methotrexate that crosses into the brain, and consideration of high-dose therapy with an autologous stem cell transplant using a conditioning regimen that also reaches the brain. The detail is on the primary central nervous system lymphoma page. ([Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [Stem cell transplant in lymphoma: what it is still for](https://onco.cc/terms/lymphoma-tx-transplant-role/))

## Open problems

- Radiotherapy to the remaining testicle prevents relapse there and causes permanent infertility and low testosterone. Nobody has tested whether it can be omitted in men who receive modern systemic treatment.
- The best way to protect the brain is not known. IELSG-10 used methotrexate into the spinal fluid; high-dose intravenous methotrexate reaches the brain tissue better and has not been compared against it in a randomised trial.
- Survival in this disease did not improve after rituximab came into use in the way it did for lymphoma of the lymph nodes, and the reason is not established.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Primary_testicular_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
- First-line treatment for primary testicular diffuse large B-cell lymphoma with rituximab-CHOP, central nervous system prophylaxis and contralateral testis irradiation, IELSG-10 (Vitolo, J Clin Oncol 2011): https://doi.org/10.1200/JCO.2010.31.4187
- Primary testicular diffuse large B-cell lymphoma, a population-based study of 769 patients on incidence, natural history and survival (Gundrum, J Clin Oncol 2009): https://doi.org/10.1200/JCO.2009.22.5896
- NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional version): https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq

## Connected records

- cancers: [Diffuse large B-cell lymphoma](https://onco.cc/cancers/dlbcl/), [Intravascular large B-cell lymphoma](https://onco.cc/cancers/intravascular-large-b-cell-lymphoma/), [Non-Hodgkin lymphoma (all types)](https://onco.cc/cancers/non-hodgkin-lymphoma/), [Primary CNS lymphoma](https://onco.cc/cancers/primary-cns-lymphoma/), [Testicular germ cell tumours](https://onco.cc/cancers/testicular/)
- technologies: [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/)
- drugs: [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Prednisone](https://onco.cc/drugs/prednisone/), [Rituximab](https://onco.cc/drugs/rituximab/), [Vincristine](https://onco.cc/drugs/vincristine/)
- terms: [CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it](https://onco.cc/terms/lymphoma-tx-cns-prophylaxis/), [Fertility before lymphoma treatment: what to ask for, and when](https://onco.cc/terms/lymphoma-tx-fertility-preservation/), [International Prognostic Index (IPI)](https://onco.cc/terms/ipi-score/), [Intrathecal therapy (lumbar puncture, Ommaya reservoir)](https://onco.cc/terms/intrathecal-therapy/), [Lugano classification / Ann Arbor staging](https://onco.cc/terms/lugano-classification/), [MYD88 L265P and CXCR4 mutations](https://onco.cc/terms/myd88-l265p/), [Nodal and extranodal lymphoma](https://onco.cc/terms/lymphoma-nodal-versus-extranodal/), [Stem cell transplant in lymphoma: what it is still for](https://onco.cc/terms/lymphoma-tx-transplant-role/), [The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)](https://onco.cc/terms/lymphoma-classification-2022/)

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JSON: https://onco.cc/api/v1/entities/primary-testicular-lymphoma.json