Rosai-Dorfman-Destombes disease
Rosai-Dorfman disease is a rare histiocytosis in which large immune cells called histiocytes fill the neck lymph nodes or grow in the skin, bones, nose, brain coverings or kidneys. Many cases fade without treatment, so it is watched unless it threatens an organ, when surgery, steroids, sirolimus or, for the third with a growth-pathway mutation, MEK inhibitors such as cobimetinib are used.
Overview
Rosai-Dorfman-Destombes disease was described in 1965 and 1969 as sinus histiocytosis with massive lymphadenopathy: large S100-positive, CD68-positive, CD1a-negative histiocytes with abundant pale cytoplasm containing intact lymphocytes (emperipolesis) distend the sinuses of lymph nodes. The classical form presents in children and young adults with enormous painless cervical nodes, fever and raised inflammatory markers; extranodal disease, commoner in adults, affects the skin, nasal cavity and sinuses, bone, orbit, meninges (mimicking meningioma), kidneys and retroperitoneum, and can occur without any node involvement. Long thought reactive, it was found from 2017 onward to carry activating KRAS, MAP2K1 and other MAPK pathway mutations in about a third of cases, which places it in the R group of the 2016 histiocytosis classification and among the histiocytic neoplasms in the 2022 WHO classification. Associations include IgG4-related disease, autoimmune cytopenias, a familial form due to SLC29A3 mutations (H syndrome) and, rarely, lymphoma.
Because many cases regress spontaneously, the 2018 consensus recommendations (Blood) advise observation for asymptomatic nodal or cutaneous disease and treatment only for symptoms or organ threat. Surgery is curative for a single extranodal lesion and relieves compressive disease; corticosteroids shrink nodes but the disease returns as they are withdrawn; sirolimus with prednisone, cladribine, methotrexate, lenalidomide and rituximab (for the IgG4-associated form) have all produced responses in small series; radiotherapy is used for localised refractory lesions, particularly in the orbit and airway. For patients with MAPK pathway mutations or multifocal refractory disease, MEK inhibition works: the cobimetinib phase 2 trial included patients with Rosai-Dorfman disease among its responders, and the 2022 United States approval of cobimetinib for histiocytic neoplasms covers the disease. Central nervous system involvement, which can cause seizures and cranial nerve palsies, is treated more aggressively, and long follow-up is needed because the course is relapsing and remitting over years.
State of the art
- The discovery of MAPK mutations moved the disease from reactive to neoplastic and opened MEK inhibition.
- Observation remains correct for many patients because the disease often resolves.
- Cobimetinib's 2022 approval is the first drug approval covering Rosai-Dorfman disease.
Red cards
From the labels and guidelines behind the standard of care. Your team's thresholds win.- Emergency services nowBleeding or bruising
Bleeding that will not stop, black or bloody stools, or unexplained bruising when platelets are expected to be low.
- Emergency services nowFainting or palpitations
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
- Check before combiningKidneys: Methotrexate
High-dose methotrexate requires normal renal function, hydration, urine alkalinisation and leucovorin rescue with level monitoring.
- Good to knowHypogammaglobulinaemia and infection risk after B-cell therapies
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.
- Good to knowInfusion reactions, hypersensitivity and extravasation
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:CladribineCobimetinibMethotrexateRituximab·Printable cards in the navigator
Anatomy and lymph node drainage
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sites
- Nodes: cervical
- Nodes: axillary
- Nodes: mediastinal
- Nodes: para-aortic and mesenteric
- Nodes: inguinal
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.
- Bone marrow (leukaemia, MDS, MPN, myeloma)
- Lymph node germinal centre (lymphomas)Classical nodal Rosai-Dorfman disease (massive cervical lymphadenopathy, children and young adults)
- Spleen
- Blood (leukaemic phase)
- Lytic bone lesions (myeloma)
- Skin and extranodal sitesExtranodal Rosai-Dorfman disease (skin, sinonasal, bone, orbit, kidney) · Cutaneous-only Rosai-Dorfman disease (often self-limiting)
- cervical
- axillary
- mediastinal
- para-aortic and mesenteric
- inguinal
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: 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, 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
A rare disorder classically of children and young adults with huge painless neck nodes, and of older adults with extranodal disease; many cases resolve on their own and only a minority need systemic treatment.
- MRIStandard of care
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Cases by country
No country-level case numbers. This cancer is not mapped to a GLOBOCAN site.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
Excisional biopsy with immunohistochemistry and MAPK pathway sequencing; FDG-PET/CT; MRI where neurological disease is suspected; immunoglobulins and autoimmune screen.
Observation, because spontaneous regression is common.
Surgical excision or debulking; radiotherapy for unresectable localised disease (orbit, airway).
Corticosteroids for rapid control; sirolimus with prednisone, cladribine, methotrexate or lenalidomide; rituximab for IgG4-associated disease.
Cobimetinib (approved 2022 for histiocytic neoplasms) or trametinib.
Subtypes & biomarkers
top- Classical nodal Rosai-Dorfman disease (massive cervical lymphadenopathy, children and young adults)
- Extranodal Rosai-Dorfman disease (skin, sinonasal, bone, orbit, kidney)
- Neurological Rosai-Dorfman disease (meningeal or parenchymal, mimics meningioma)
- Cutaneous-only Rosai-Dorfman disease (often self-limiting)
- Rosai-Dorfman disease with KRAS or MAP2K1 mutations (MEK inhibitor responsive)
- Familial Rosai-Dorfman disease (SLC29A3, H syndrome) and IgG4-associated disease
- S100 and CD68 positive, CD1a and langerin negative histiocytes with emperipolesis
- KRAS, MAP2K1 and other MAPK pathway mutations (about a third)
- FDG-PET/CT for extent and response
- IgG4-positive plasma cells (IgG4-related overlap)
- Immunoglobulin levels, autoimmune screen and SLC29A3 testing where familial disease is suspected
- MRI of brain and spine for neurological disease
How often this target appears
- 1965Destombes describes the disease in Paris
- 1969Rosai and Dorfman define sinus histiocytosis with massive lymphadenopathy
- 2016Revised histiocytosis classification creates the R group for Rosai-Dorfman disease
- 2017KRAS and MAP2K1 mutations identified, establishing a neoplastic subset
- 2018First consensus recommendations for diagnosis and treatment (Blood)
- 2022Cobimetinib approved for histiocytic neoplasms; WHO lists Rosai-Dorfman disease among histiocytic neoplasms
Dated changes read from the records linked to this cancer: approvals, regulatory steps, reported trials, guideline versions and milestones. Newest first; no date is inferred.
All 12 changes by month →- 2026-09-18This recordRosai-Dorfman-Destombes diseaseFacts on this page last checked
When this page itself was last checked or edited.
- 2022MilestoneCobimetinibCobimetinib approved for histiocytic neoplasms; WHO lists Rosai-Dorfman disease among histiocytic neoplasms
A milestone in how this cancer is treated.
- 2018GuidelineRosai-Dorfman-Destombes diseaseGuideline Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018): Asymptomatic nodal or cutaneous disease
Observation, because spontaneous regression is common.
- 2018GuidelineRosai-Dorfman-Destombes diseaseGuideline Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018): Diagnosis and staging
Excisional biopsy with immunohistochemistry and MAPK pathway sequencing; FDG-PET/CT; MRI where neurological disease is suspected; immunoglobulins and autoimmune screen.
- 2018GuidelineRosai-Dorfman-Destombes diseaseGuideline Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018): MAPK-mutant or refractory disease
Cobimetinib (approved 2022 for histiocytic neoplasms) or trametinib.
- 2018GuidelineRosai-Dorfman-Destombes diseaseGuideline Consensus recommendations for Rosai-Dorfman-Destombes disease (Blood 2018): Multifocal or organ-threatening disease
Corticosteroids for rapid control; sirolimus with prednisone, cladribine, methotrexate or lenalidomide; rituximab for IgG4-associated disease.
What is in development for Rosai-Dorfman-Destombes disease, drawn from the whole corpus: 0 items. Drugs are grouped by the most advanced trial phase they have reached anywhere; approved treatments sit under standard of care. Technologies are the methods being tested for this cancer, trials are the studies recorded here, and ideas are proposals not yet in a trial.
Nothing recorded in development for this cancer yet.
Open problems and what is being done
Which patients will regress spontaneously cannot be predicted.
Two thirds of cases have no identified driver mutation.
All systemic treatments rest on case series; there has never been a randomised trial.
Neurological disease can leave permanent deficits despite treatment.
Trials
topTrials recruiting now
Country and place are remembered in this browser only. A postcode is sent to OpenStreetMap's Nominatim service to find coordinates when you press the button; nothing else leaves your device.
Expert centres
topExpert centres
New York · cancer center | United States | 0 | 5,100 | 94,456 | #1 | ||
Boston · hospital | United States | 0 | 3,582 | 54,857 | #16 | ||
Utrecht · cancer center | Netherlands | none recorded | 0 | 1,422 | 20,323 | - | |
Barcelona · hospital | Spain | none recorded | 0 | 1,265 | 15,631 | - | |
Tianjin · cancer center | China | none recorded | 0 | 1,219 | 11,455 | - | |
Hangzhou · cancer center | China | none recorded | 0 | 1,219 | 17,635 | - | |
Lyon · cancer center | France | none recorded | 0 | 1,071 | 14,301 | - | |
Rozzano (Milan) · hospital | Italy | none recorded | 0 | 1,031 | 10,720 | - | |
Oslo · cancer center | Norway | none recorded | 0 | 936 | 11,600 | - | |
Changsha · cancer center | China | none recorded | 0 | 930 | 14,477 | - | |
Jinan · cancer center | China | none recorded | 0 | 920 | 7,804 | - | |
Taipei · hospital | Taiwan | none recorded | 0 | 746 | 8,966 | - | |
Marseille · cancer center | France | none recorded | 0 | 738 | 7,479 | - | |
Dresden · cancer center | Germany | none recorded | 0 | 728 | 7,984 | - | |
Guangzhou · hospital | China | none recorded | 0 | 704 | 7,832 | - |
These are the things we can measure; they are not a ranking of quality. Each column is a field on the institution record or a count over what OnCo has linked; a centre that treats many patients with Rosai-Dorfman-Destombes disease but is thinly recorded here will look small.
Not known: OnCo holds no case-volume or outcome figures for centres, so none are shown. Where a national audit or registry publishes them, the centre's page links to it. Default order: Newsweek rank, then trials for this cancer, then research output.
Questions to ask
topQuestions to ask your oncologist about Rosai-Dorfman-Destombes disease
Newly diagnosed
- What is my exact diagnosis, stage, and grade, and which tests established them?Why: Everything else follows from an accurate stage and subtype.
- Which biomarkers have been tested on my tumour (for example S100 and CD68 positive, CD1a and langerin negative histiocytes with emperipolesis, KRAS, MAP2K1 and other MAPK pathway mutations, FDG-PET/CT for extent and response, IgG4-positive plasma cells, Immunoglobulin levels, autoimmune screen and SLC29A3 testing where familial disease is suspected), and what were the results?Why: These results decide eligibility for targeted therapy, immunotherapy, and trials.
- Which subtype is my cancer, and does that change the recommended treatment?Why: Recognised subtypes for this cancer include Classical nodal Rosai-Dorfman disease, Extranodal Rosai-Dorfman disease, Neurological Rosai-Dorfman disease.
- Is germline (inherited) genetic testing recommended for me or my family?Why: Inherited variants can change treatment and matter for relatives.
Diagnosis and staging
- For my situation (diagnosis and staging), which of the standard options do you recommend and why?Why: Guideline options include: Excisional biopsy with immunohistochemistry and MAPK pathway sequencing; FDG-PET/CT; MRI where neurological disease is suspected; immunoglobulins and autoimmune screen.
Asymptomatic nodal or cutaneous disease
- For my situation (asymptomatic nodal or cutaneous disease), which of the standard options do you recommend and why?Why: Guideline options include: Observation, because spontaneous regression is common.
Single or compressive extranodal lesion
- For my situation (single or compressive extranodal lesion), which of the standard options do you recommend and why?Why: Guideline options include: Surgical excision or debulking; radiotherapy for unresectable localised disease (orbit, airway).
Multifocal or organ-threatening disease
- For my situation (multifocal or organ-threatening disease), which of the standard options do you recommend and why?Why: Guideline options include: Corticosteroids for rapid control; sirolimus with prednisone, cladribine, methotrexate or lenalidomide; rituximab for IgG4-associated disease.
- Am I a candidate for Cladribine, Methotrexate, Rituximab, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
MAPK-mutant or refractory disease
- For my situation (mapk-mutant or refractory disease), which of the standard options do you recommend and why?Why: Guideline options include: Cobimetinib (approved 2022 for histiocytic neoplasms) or trametinib.
- Am I a candidate for Cobimetinib, and what side effects should I expect?Why: Knowing the expected toxicities helps you plan work, family, and supportive care.
Any stage
- Are there clinical trials I could join, for example of Cobimetinib?Why: Trials are how the next standard of care is set; asking early keeps options open.
- Would a second opinion at a high-volume centre change anything, and can you help arrange it?Why: Rare or high-stakes decisions benefit from a centre that treats many similar patients.
- What supportive care (symptom control, nutrition, exercise, mental health, financial help) is available from the start?Why: Supportive care improves quality of life and helps patients complete treatment.
- I read that “Which patients will regress spontaneously cannot be predicted”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
- I read that “Two thirds of cases have no identified driver mutation”. How does that affect my plan?Why: Open problems are where trials and second opinions matter most.
Newly diagnosed? Read the first 60 days with Rosai-Dorfman-Destombes disease, then print the one-page appointment sheet with room for the answers.
Print this page for your appointment (your browser's print command). These prompts are for discussion; your clinical team knows your case.
Direct links plus the targets, companies, and technologies of this cancer's products.
technologies
9targets
2drugs
4companies
6pathways
1terms
2key papers
3The names and definitions on a marrow report (for example MDS with biallelic TP53 inactivation, or AML myelodysplasia-related) come from this document or from the parallel International Consensus Classification.
The treatment rows on the Rosai-Dorfman page, from watchful waiting to cobimetinib, follow these recommendations.
The way OnCo groups the histiocytoses, and the recognition that LCH and ECD are cancers rather than inflammatory conditions, come from this classification.
Latest papers
topQuery for this cancer: (TITLE:"Rosai-Dorfman-Destombes disease" OR ABSTRACT:"Rosai-Dorfman-Destombes disease" OR TITLE:"Rosai-Dorfman disease" OR ABSTRACT:"Rosai-Dorfman disease" OR TITLE:"RDD" OR ABSTRACT:"RDD" OR TITLE:"Sinus histiocytosis with massive lymphadenopathy" OR ABSTRACT:"Sinus histiocytosis with massive lymphadenopathy" OR TITLE:"R-group histiocytosis" OR ABSTRACT:"R-group histiocytosis" OR TITLE:"Destombes-Rosai-Dorfman disease" OR ABSTRACT:"Destombes-Rosai-Dorfman disease") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Rosai-Dorfman-Destombes disease, not a curated reading list.
Similar pages
not linked directly; found by shared links- CancerAdvanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia)
Shares WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms, Cladribine, Driver mutation, Histopathology & immunohistochemistry and the tags subtype-page, haematologic.
- CancerIndolent and smouldering systemic mastocytosis
Shares WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms, Cladribine, Driver mutation, Histopathology & immunohistochemistry and the tags subtype-page, haematologic.
- CancerNodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma)
Shares FDG PET, Active surveillance, Histopathology & immunohistochemistry, Rituximab and the tags subtype-page, haematologic.
- CancerEarly-stage classical Hodgkin lymphoma (stage I to II)
Shares FDG PET, IMRT / IGRT (modern external beam) and the tags subtype-page, haematologic.
- CancerRelapsed and refractory classical Hodgkin lymphoma
Shares FDG PET, IMRT / IGRT (modern external beam) and the tags subtype-page, haematologic.
- CancerAdvanced-stage classical Hodgkin lymphoma (stage III to IV)
Shares FDG PET, IMRT / IGRT (modern external beam) and the tags subtype-page, haematologic.
- CancerMultisystem Langerhans cell histiocytosis (with or without risk-organ involvement)
Shares Cladribine, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Erdheim-Chester disease, Cobimetinib and the tag subtype-page.
- CancerLangerhans cell histiocytosis (LCH)
Shares Cladribine, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Active surveillance and the tag haematologic.