{"entity":{"id":"primary-testicular-lymphoma","kind":"cancer","name":"Primary large B-cell lymphoma of the testis","aka":["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"],"tldr":"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.\n\nHow 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.\n\nWhere 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.\n\nHow 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.\n\nWhat 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.","asOf":"2026-09-29","wikipedia":"https://en.wikipedia.org/wiki/Primary_testicular_diffuse_large_B-cell_lymphoma","links":[{"label":"WHO Classification of Haematolymphoid Tumours, 5th edition: lymphoid neoplasms (Alaggio, Leukemia 2022)","url":"https://doi.org/10.1038/s41375-022-01620-2"},{"label":"International Consensus Classification of Mature Lymphoid Neoplasms (Campo, Blood 2022)","url":"https://doi.org/10.1182/blood.2022015851"},{"label":"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)","url":"https://doi.org/10.1200/JCO.2010.31.4187"},{"label":"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)","url":"https://doi.org/10.1200/JCO.2009.22.5896"},{"label":"NCI PDQ: adult non-Hodgkin lymphoma treatment (health professional version)","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}],"tags":["heme","lymphoma","subtype-page"],"related":["primary-cns-lymphoma","dlbcl","testicular","non-hodgkin-lymphoma","intravascular-large-b-cell-lymphoma"],"cancers":[],"sections":[],"technologies":["histopathology-ihc","fdg-pet","imrt-igrt"],"targets":[],"drugs":["rituximab","methotrexate"],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-nodal-versus-extranodal","lymphoma-classification-2022","lymphoma-tx-cns-prophylaxis","lymphoma-tx-fertility-preservation","myd88-l265p","ipi-score"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"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.","subtypes":[],"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"],"standardOfCare":[{"setting":"Diagnosis and staging","approach":"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.","refs":["fdg-pet","lymphoma-tx-fertility-preservation","lugano-classification","histopathology-ihc"],"guideline":{"version":"NCI PDQ: adult non-Hodgkin lymphoma treatment","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}},{"setting":"First-line treatment of stage I and II disease","approach":"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.","refs":["rituximab","cyclophosphamide","doxorubicin","vincristine","prednisone","methotrexate","intrathecal-therapy","imrt-igrt","lymphoma-tx-cns-prophylaxis"],"guideline":{"version":"IELSG-10 (J Clin Oncol 2011); NCI PDQ adult non-Hodgkin lymphoma treatment","url":"https://doi.org/10.1200/JCO.2010.31.4187"}},{"setting":"What happens at relapse","approach":"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.","refs":["primary-cns-lymphoma","methotrexate","autologous-stem-cell-transplant","lymphoma-tx-transplant-role"],"guideline":{"version":"NCI PDQ: adult non-Hodgkin lymphoma treatment","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}}],"stateOfArt":[],"history":[{"year":2009,"title":"A population picture, and a gain that did not arrive","note":"Across 769 men in the SEER registries diagnosed between 1980 and 2005, median overall survival was 4.6 years and disease-specific survival was 71.5 per cent at three years, 62.4 per cent at five and 43.0 per cent at fifteen. Unlike nodal diffuse large B-cell lymphoma, disease-specific survival did not improve after the year 2000, when rituximab came into use.","refs":["rituximab"]},{"year":2011,"title":"IELSG-10 sets the standard","note":"Fifty-three men with stage I or II disease treated with rituximab-containing chemotherapy, methotrexate into the spinal fluid and radiotherapy to the remaining testicle: five-year progression-free survival 74 per cent, overall survival 85 per cent, no relapse in the irradiated testicle and a 6 per cent five-year risk of relapse in the central nervous system.","refs":["rituximab","methotrexate"]},{"year":2022,"title":"Grouped with lymphoma of the brain and the eye, by one classification of two","note":"WHO-HAEM5 created primary large B-cell lymphoma of immune-privileged sites, covering the central nervous system, the vitreoretina and the testis. The International Consensus Classification judged the grouping premature but recognised testicular lymphoma as an entity closely related to the central nervous system disease.","refs":["primary-cns-lymphoma","lymphoma-classification-2022"]}],"pipeline":[],"openProblems":["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."],"parent":"non-hodgkin-lymphoma"},"route":"/cancers/primary-testicular-lymphoma/","neighbours":{"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"intravascular-large-b-cell-lymphoma","kind":"cancer","name":"Intravascular large B-cell lymphoma","route":"/cancers/intravascular-large-b-cell-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"primary-cns-lymphoma","kind":"cancer","name":"Primary CNS lymphoma","route":"/cancers/primary-cns-lymphoma/"},{"id":"testicular","kind":"cancer","name":"Testicular germ cell tumours","route":"/cancers/testicular/"}],"technology":[{"id":"autologous-stem-cell-transplant","kind":"technology","name":"Autologous stem cell transplant (high-dose therapy)","route":"/technologies/autologous-stem-cell-transplant/"},{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"},{"id":"imrt-igrt","kind":"technology","name":"IMRT / IGRT (modern external beam)","route":"/technologies/imrt-igrt/"}],"drug":[{"id":"cyclophosphamide","kind":"drug","name":"Cyclophosphamide","route":"/drugs/cyclophosphamide/"},{"id":"doxorubicin","kind":"drug","name":"Doxorubicin","route":"/drugs/doxorubicin/"},{"id":"methotrexate","kind":"drug","name":"Methotrexate","route":"/drugs/methotrexate/"},{"id":"prednisone","kind":"drug","name":"Prednisone","route":"/drugs/prednisone/"},{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"},{"id":"vincristine","kind":"drug","name":"Vincristine","route":"/drugs/vincristine/"}],"term":[{"id":"lymphoma-tx-cns-prophylaxis","kind":"term","name":"CNS prophylaxis in aggressive B-cell lymphoma, and the evidence against it","route":"/terms/lymphoma-tx-cns-prophylaxis/"},{"id":"lymphoma-tx-fertility-preservation","kind":"term","name":"Fertility before lymphoma treatment: what to ask for, and when","route":"/terms/lymphoma-tx-fertility-preservation/"},{"id":"ipi-score","kind":"term","name":"International Prognostic Index (IPI)","route":"/terms/ipi-score/"},{"id":"intrathecal-therapy","kind":"term","name":"Intrathecal therapy (lumbar puncture, Ommaya reservoir)","route":"/terms/intrathecal-therapy/"},{"id":"lugano-classification","kind":"term","name":"Lugano classification / Ann Arbor staging","route":"/terms/lugano-classification/"},{"id":"myd88-l265p","kind":"term","name":"MYD88 L265P and CXCR4 mutations","route":"/terms/myd88-l265p/"},{"id":"lymphoma-nodal-versus-extranodal","kind":"term","name":"Nodal and extranodal lymphoma","route":"/terms/lymphoma-nodal-versus-extranodal/"},{"id":"lymphoma-tx-transplant-role","kind":"term","name":"Stem cell transplant in lymphoma: what it is still for","route":"/terms/lymphoma-tx-transplant-role/"},{"id":"lymphoma-classification-2022","kind":"term","name":"The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)","route":"/terms/lymphoma-classification-2022/"}]}}