{"entity":{"id":"mediastinal-grey-zone-lymphoma","kind":"cancer","name":"Mediastinal grey zone lymphoma","aka":["Mediastinal gray zone lymphoma","MGZL","Grey zone lymphoma","Gray zone lymphoma","B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma","B-cell lymphoma unclassifiable","Intermediate DLBCL/CHL"],"tldr":"A lymphoma of the chest that sits between two diseases: it has some of the features of primary mediastinal B-cell lymphoma and some of classic Hodgkin lymphoma, and a pathologist cannot put it cleanly in either. It is recognised as an entity of its own, and the 2022 classifications restricted the name to lymphomas that involve the mediastinum.","summary":"What it is. The mediastinum is the space in the middle of the chest between the lungs, and it contains the thymus. Two lymphomas grow there in young adults: primary mediastinal large B-cell lymphoma and nodular sclerosis classic Hodgkin lymphoma. They are biologically related, and some tumours fall between them, with the cell size and sheet-like growth of one and the surface markers of the other. WHO-HAEM5 describes it as a single biological group with a spectrum running from classic Hodgkin lymphoma to primary mediastinal B-cell lymphoma, with mediastinal grey zone lymphoma straddling the two.\n\nHow it differs from its neighbours. The distinguishing feature is the mismatch between what the cells look like and what they express. Classic Hodgkin lymphoma has rare large cells in a sea of immune cells and has lost most of its B-cell programme; grey zone lymphoma keeps a high density of tumour cells and keeps the B-cell markers. The International Consensus Classification writes that requirement down: a diagnosis needs both a high density of tumour cells and strong expression of at least two B-cell markers. A tumour that looks like nodular sclerosis Hodgkin lymphoma and happens to express CD20 variably is still Hodgkin lymphoma.\n\nWhat changed in 2022, and it is the whole of the name. The previous name was B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma, and it could be applied anywhere in the body. Both 2022 classifications restricted it to the mediastinum, because cases with the same appearance arising elsewhere turned out to have different gene expression and different DNA changes. Those are now classified as diffuse large B-cell lymphoma, not otherwise specified. This is one of the few places where the two classifications agree completely, and it changes the diagnosis of a real group of patients.\n\nHow it presents. Almost always as a large mass in the front of the chest in a young adult, more often a man, sometimes causing swelling of the face and arms and breathlessness from pressure on the great veins, which is an emergency. Sequential cases of primary mediastinal B-cell lymphoma and nodular sclerosis Hodgkin lymphoma in the same person have been shown to share a clonal origin, which is part of the evidence that the three diseases are one biological family.\n\nHow it is treated. As an aggressive B-cell lymphoma rather than as Hodgkin lymphoma: regimens built for large B-cell lymphoma, with rituximab, are preferred, because the tumour keeps its B-cell markers. There is no randomised trial in this entity and the series are small. The treatment layer of this family and the primary mediastinal B-cell lymphoma page carry the regimens.","asOf":"2026-09-29","wikipedia":"https://en.wikipedia.org/wiki/Primary_mediastinal_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":"Lymphoma incidence, survival and prevalence 2004 to 2014, subtype analyses from the UK Haematological Malignancy Research Network (Smith, Br J Cancer 2015)","url":"https://doi.org/10.1038/bjc.2015.94"},{"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-mediastinal-b-cell-lymphoma","hodgkin-lymphoma","dlbcl","non-hodgkin-lymphoma","ebv-positive-dlbcl"],"cancers":[],"sections":[],"technologies":["histopathology-ihc","fdg-pet"],"targets":["cd30","cd20"],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["lymphoma-classification-2022","lymphoma-indolent-versus-aggressive","lugano-classification","deauville-score","lymphoma-tx-radiotherapy"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"group":"haematologic","burden":"In the United Kingdom population series that reports lymphoma by subtype, 24 of 5,796 lymphomas (0.4 per cent) were recorded in the category then called intermediate between diffuse large B-cell and classic Hodgkin lymphoma: a crude incidence of 0.22 per 100,000 a year and a European age-standardised rate of 0.08, with men affected about twice as often as women and a median age at diagnosis of 59.3 years. Five-year relative survival in that series was 84.0 per cent, although the numbers are small and the confidence interval ran from 61 to 94 per cent.","subtypes":[],"biomarkers":["A high density of tumour cells, which separates it from classic Hodgkin lymphoma","Strong expression of at least two B-cell markers (CD20, CD79a, PAX5), which the International Consensus Classification requires for the diagnosis","CD30 and often CD15, shared with classic Hodgkin lymphoma","Involvement of the mediastinum, which both 2022 classifications now require","Epstein-Barr virus, which is usually negative; an EBV-positive tumour with Hodgkin-like cells is classified as EBV-positive diffuse large B-cell lymphoma instead"],"standardOfCare":[{"setting":"Making the diagnosis, and the trap in it","approach":"The diagnosis needs a generous biopsy, because the appearance varies across a single tumour and a core needle may sample only the part that looks like one of the neighbouring diseases. Both 2022 classifications require involvement of the mediastinum: an identical-looking tumour elsewhere in the body is diffuse large B-cell lymphoma, not otherwise specified. A nodular sclerosis classic Hodgkin lymphoma with variable CD20 expression remains Hodgkin lymphoma and is not reclassified here.","refs":["histopathology-ihc","cd30","cd20","lymphoma-classification-2022"],"guideline":{"version":"WHO Classification of Haematolymphoid Tumours, 5th edition (2022), with the International Consensus Classification (2022) where they differ","url":"https://doi.org/10.1038/s41375-022-01620-2"}},{"setting":"Treatment","approach":"Treated with regimens designed for aggressive large B-cell lymphoma and containing rituximab, rather than with Hodgkin lymphoma chemotherapy, because the tumour retains its B-cell programme and the surface target with it. Radiotherapy to the residual mediastinal mass is used in some series. There is no randomised trial in this entity, the published series number in the tens, and the regimen is chosen in a multidisciplinary meeting; the detail sits on the primary mediastinal B-cell lymphoma page and in the treatment layer of this family.","refs":["primary-mediastinal-b-cell-lymphoma","rituximab","lymphoma-tx-regimen-alphabet","lymphoma-tx-radiotherapy","r-chop"],"guideline":{"version":"NCI PDQ: adult non-Hodgkin lymphoma treatment","url":"https://www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq"}}],"stateOfArt":[],"history":[{"year":2008,"title":"Named as an unclassifiable category","note":"The fourth edition of the WHO classification created B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and classic Hodgkin lymphoma, which could be diagnosed at any site.","refs":["hodgkin-lymphoma"]},{"year":2021,"title":"The mutational landscape of grey zone lymphoma","note":"Sequencing showed that cases arising outside the mediastinum carry different gene expression profiles and DNA alterations from those arising in it, which is the evidence both 2022 classifications used to restrict the name.","refs":["primary-mediastinal-b-cell-lymphoma"]},{"year":2022,"title":"Renamed and restricted to the mediastinum","note":"WHO-HAEM5 and the International Consensus Classification both adopted the name mediastinal grey zone lymphoma and both reassigned non-mediastinal cases to diffuse large B-cell lymphoma, not otherwise specified.","refs":["lymphoma-classification-2022"]}],"pipeline":[],"openProblems":["No randomised trial has been run in this entity and none is likely: it is about one lymphoma in 250, so the evidence will stay observational.","Pathologists disagree about the boundary with nodular sclerosis classic Hodgkin lymphoma more often than about almost any other lymphoma boundary, and the treatment that follows the two diagnoses is different.","Whether radiotherapy to a residual mediastinal mass adds anything after modern immunochemotherapy has not been tested here."],"parent":"non-hodgkin-lymphoma"},"route":"/cancers/mediastinal-grey-zone-lymphoma/","neighbours":{"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"ebv-positive-dlbcl","kind":"cancer","name":"EBV-positive diffuse large B-cell lymphoma","route":"/cancers/ebv-positive-dlbcl/"},{"id":"hodgkin-lymphoma","kind":"cancer","name":"Hodgkin lymphoma","route":"/cancers/hodgkin-lymphoma/"},{"id":"non-hodgkin-lymphoma","kind":"cancer","name":"Non-Hodgkin lymphoma (all types)","route":"/cancers/non-hodgkin-lymphoma/"},{"id":"primary-mediastinal-b-cell-lymphoma","kind":"cancer","name":"Primary mediastinal (thymic) large B-cell lymphoma","route":"/cancers/primary-mediastinal-b-cell-lymphoma/"},{"id":"t-cell-histiocyte-rich-large-b-cell-lymphoma","kind":"cancer","name":"T-cell/histiocyte-rich large B-cell lymphoma","route":"/cancers/t-cell-histiocyte-rich-large-b-cell-lymphoma/"}],"technology":[{"id":"fdg-pet","kind":"technology","name":"FDG PET","route":"/technologies/fdg-pet/"},{"id":"histopathology-ihc","kind":"technology","name":"Histopathology & immunohistochemistry","route":"/technologies/histopathology-ihc/"}],"target":[{"id":"cd20","kind":"target","name":"CD20","route":"/targets/cd20/"},{"id":"cd30","kind":"target","name":"CD30","route":"/targets/cd30/"}],"term":[{"id":"deauville-score","kind":"term","name":"Deauville five-point scale","route":"/terms/deauville-score/"},{"id":"lymphoma-indolent-versus-aggressive","kind":"term","name":"Indolent and aggressive lymphoma","route":"/terms/lymphoma-indolent-versus-aggressive/"},{"id":"lugano-classification","kind":"term","name":"Lugano classification / Ann Arbor staging","route":"/terms/lugano-classification/"},{"id":"r-chop","kind":"term","name":"R-CHOP (lymphoma chemoimmunotherapy)","route":"/terms/r-chop/"},{"id":"lymphoma-tx-radiotherapy","kind":"term","name":"Radiotherapy in lymphoma: involved-site fields, 24 Gy, 4 Gy and total skin electron therapy","route":"/terms/lymphoma-tx-radiotherapy/"},{"id":"lymphoma-tx-regimen-alphabet","kind":"term","name":"The lymphoma regimen alphabet: R-CHOP, pola-R-CHP, DA-EPOCH-R, ABVD, BEACOPP and the rest","route":"/terms/lymphoma-tx-regimen-alphabet/"},{"id":"lymphoma-classification-2022","kind":"term","name":"The two lymphoma classifications of 2022 (WHO-HAEM5 and ICC)","route":"/terms/lymphoma-classification-2022/"}],"drug":[{"id":"rituximab","kind":"drug","name":"Rituximab","route":"/drugs/rituximab/"}]}}