# Rosai-Dorfman-Destombes disease

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

## TL;DR

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.

## Summary

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extranodal lesion and relieves compressive disease; corticosteroids shrink nodes but the disease returns as they are withdrawn; sirolimus with prednisone, cladribine, methotrexate, lenalidomide and rituximab (for the IgG4-associated form) have all produced responses in small series;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.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Rosai-Dorfman disease; RDD; Sinus histiocytosis with massive lymphadenopathy; R-group histiocytosis; Destombes-Rosai-Dorfman disease
- Tags: subtype-page; haematologic
- Group: haematologic
- Burden: 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.
- Subtypes: 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
- Biomarkers: 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

## 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/rosai-dorfman-disease/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/rosai-dorfman-disease/#overview [3 state-of-the-art points]
- 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/rosai-dorfman-disease/#what-it-is [6 subtypes]
- 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/rosai-dorfman-disease/#finding-it [6 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/rosai-dorfman-disease/#treating-it [5 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/rosai-dorfman-disease/#evidence [3 key papers, 6 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/rosai-dorfman-disease/#science [2 targets, 1 pathway]
- 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/rosai-dorfman-disease/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/rosai-dorfman-disease/#living-with-it [16 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/rosai-dorfman-disease/coming/ [4 medicines, 4 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/rosai-dorfman-disease/data/ [27 connected records]

## Standard of care

- Diagnosis and staging: Excisional biopsy with immunohistochemistry and MAPK pathway sequencing; FDG-PET/CT; MRI where neurological disease is suspected; immunoglobulins and autoimmune screen. ([Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [MRI](https://onco.cc/technologies/mri/))
- Asymptomatic nodal or cutaneous disease: Observation, because spontaneous regression is common. ([Active surveillance](https://onco.cc/technologies/active-surveillance/))
- Single or compressive extranodal lesion: Surgical excision or debulking; radiotherapy for unresectable localised disease (orbit, airway). ([IMRT / IGRT (modern external beam)](https://onco.cc/technologies/imrt-igrt/))
- Multifocal or organ-threatening disease: Corticosteroids for rapid control; sirolimus with prednisone, cladribine, methotrexate or lenalidomide; rituximab for IgG4-associated disease. ([Cladribine](https://onco.cc/drugs/cladribine/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Rituximab](https://onco.cc/drugs/rituximab/))
- MAPK-mutant or refractory disease: Cobimetinib (approved 2022 for histiocytic neoplasms) or trametinib. ([Cobimetinib](https://onco.cc/drugs/cobimetinib/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/))

## 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.

## Open problems

- 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.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Rosai%E2%80%93Dorfman_disease
- RDD consensus recommendations (Blood 2018): https://doi.org/10.1182/blood-2018-03-839753
- Wikipedia: https://en.wikipedia.org/wiki/Rosai%E2%80%93Dorfman_disease

## Connected records

- cancers: [Erdheim-Chester disease](https://onco.cc/cancers/erdheim-chester-disease/), [Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms](https://onco.cc/cancers/histiocytoses/), [Single-system Langerhans cell histiocytosis (bone, skin or one other organ)](https://onco.cc/cancers/lch-single-system/)
- technologies: [Active surveillance](https://onco.cc/technologies/active-surveillance/), [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [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/), [MRI](https://onco.cc/technologies/mri/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- drugs: [Cladribine](https://onco.cc/drugs/cladribine/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/), [Methotrexate](https://onco.cc/drugs/methotrexate/), [Rituximab](https://onco.cc/drugs/rituximab/)
- terms: [Driver mutation](https://onco.cc/terms/driver-mutation/), [Retroperitoneum](https://onco.cc/terms/retroperitoneum/)
- key papers: [Consensus recommendations for the diagnosis and clinical management of Rosai-Dorfman-Destombes disease](https://onco.cc/key-papers/paper-rosai-dorfman-destombes-consensus-recommendations-blood-2018/), [Revised classification of histiocytoses and neoplasms of the macrophage-dendritic cell lineages](https://onco.cc/key-papers/paper-emile-revised-classification-of-histiocytoses-blood-2016/), [WHO classification of haematolymphoid tumours, fifth edition: myeloid and histiocytic neoplasms](https://onco.cc/key-papers/paper-who-2022-myeloid-khoury-leukemia-2022/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)

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JSON: https://onco.cc/api/v1/entities/rosai-dorfman-disease.json