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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.
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.
How 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.
What 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.
How 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.
How 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.
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.
Averages across everyone diagnosed, often years ago. A median is the middle of a group: half the people counted lived longer than the figure shown, and some lived far longer. Your stage, subtype, age, fitness and the treatment you receive matter more than the average, and the numbers are improving quickly.
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Langerhans cell histiocytosis (LCH), Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
No subtypes recorded beyond the ones named in the family strip above.
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.
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.
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Query for this cancer: (TITLE:"Mediastinal grey zone lymphoma" OR ABSTRACT:"Mediastinal grey zone lymphoma" OR TITLE:"Mediastinal gray zone lymphoma" OR ABSTRACT:"Mediastinal gray zone lymphoma" OR TITLE:"MGZL" OR ABSTRACT:"MGZL" OR TITLE:"Grey zone lymphoma" OR ABSTRACT:"Grey zone lymphoma" OR TITLE:"Gray zone lymphoma" OR ABSTRACT:"Gray zone lymphoma" OR TITLE:"B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma" OR ABSTRACT:"B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Mediastinal grey zone lymphoma, not a curated reading list.
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.
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.
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.
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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.
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Anyone who has ever had hepatitis B can have the virus wake up when rituximab strips out their B cells, sometimes months later and sometimes fatally. A blood test before the first dose, and a tablet for those who need it, prevents almost all of it.
A shortage of antibodies because treatment has wiped out the B cells or plasma cells that make them, as CD19 CAR-T, CD20 antibodies and BCMA therapies deliberately do. It leaves patients prone to infections, sometimes for years, and is managed with immunoglobulin infusions.
Treatments that remove B cells also remove the antibodies B cells make, and some people never make them again. When repeated chest and sinus infections follow, donated antibody given monthly by drip or weekly under the skin prevents them.
Reactions around the moment a drug is given: chills, fever or breathlessness from antibodies (infusion reactions), true allergy (hypersensitivity, rarely anaphylaxis), and leakage of a damaging drug into tissue around the vein (extravasation).
See all on the product pages:Rituximab·Printable cards in the navigator
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