# Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms

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

## TL;DR

Histiocytoses are diseases in which immune scavenger cells build up in bone, heart, brain, kidneys and skin. They used to be treated as inflammatory conditions with steroids and interferon. The discovery that most carry mutations in the same growth pathway as melanoma turned them into targetable cancers: BRAF and MEK inhibitor pills now produce responses in nearly every treated patient.

## Summary

The histiocytic neoplasms are clonal disorders of macrophage or dendritic cell lineage. The 2016 revised Histiocyte Society classification groups them into L (Langerhans: LCH, ECD, mixed ECD-LCH), C (cutaneous non-LCH, including juvenile xanthogranuloma), R (Rosai-Dorfman disease), M (malignant histiocytoses such as histiocytic sarcoma) and H (haemophagocytic lymphohistiocytosis, a hyperinflammatory syndrome rather than a neoplasm). Erdheim-Chester disease (ECD) infiltrates long bones, the retroperitoneum ('hairy kidney'), the heart and aorta, the orbits and the brain; BRAF V600E is present in around half of patients, with most of the rest carrying other MAPK-pathway alterations (MAP2K1, ARAF, NRAS, KRAS, RAF1 fusions) or PIK3CA mutations. Rosai-Dorfman disease shows emperipolesis in S100-positive, CD1a-negative histiocytes and carries KRAS or MAP2K1 mutations in a large minority. The same mutations in the same lineage in adults and children unify these diseases with Langerhans cell histiocytosis, which has its own page.

Treatment was transformed by targeted therapy. Interferon alfa was the previous first line for ECD. Vemurafenib produced responses in essentially every BRAF-mutant ECD patient in the VE-BASKET trial, leading to FDA approval in November 2017, the first approval for any histiocytosis. Cobimetinib, a MEK inhibitor, gave responses regardless of mutation status in a phase 2 trial (Diamond and colleagues, Nature Medicine 2019) and was FDA-approved in October 2022 for adult histiocytic neoplasms including ECD, RDD and LCH. Responses are deep and durable but relapse follows discontinuation in most patients, so therapy is often prolonged at reduced doses. Rosai-Dorfman disease is observed if asymptomatic, and treated with surgery, steroids, sirolimus, cladribine or MEK inhibitors when it causes harm. Histiocytic sarcoma is treated with lymphoma-type chemotherapy, radiotherapy and, increasingly, MAPK-pathway inhibitors. Mixed ECD-LCH and the neurodegenerative complications of both are the hardest problems.

International consensus recommendations for ECD (Blood 2020) and the Histiocyte Society trials network coordinate care and research.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: ECD; Erdheim-Chester disease; Rosai-Dorfman disease; RDD; Rosai-Dorfman-Destombes disease; Histiocytic sarcoma; Juvenile xanthogranuloma; Mixed ECD-LCH; L-group and R-group histiocytoses
- Tags: nci-coverage; rare; haematologic; histiocytosis
- Group: haematologic
- Burden: Erdheim-Chester disease has been described in only a few thousand patients worldwide, mostly adults in their fifties and sixties; Rosai-Dorfman disease and histiocytic sarcoma are similarly rare (Histiocyte Society registries).
- Subtypes: Erdheim-Chester disease (BRAF V600E-mutant or wild-type); Mixed ECD-LCH; Rosai-Dorfman-Destombes disease (nodal, extranodal, cutaneous, familial); Juvenile xanthogranuloma and other C-group cutaneous histiocytoses; Histiocytic sarcoma and other malignant histiocytoses; ALK-positive histiocytosis (rare; responds to ALK inhibitors)
- Biomarkers: BRAF V600E (tissue; plasma ctDNA for monitoring); MAP2K1, ARAF, NRAS, KRAS, PIK3CA, RAF1 and ALK fusions on NGS; Immunophenotype: CD68, CD163, factor XIIIa positive; CD1a and langerin negative (ECD, RDD); S100 with emperipolesis (RDD); FDG-PET/CT for extent and response; Cardiac MRI and brain MRI for organ involvement; Clonal haematopoiesis (mutations shared with myeloid clones in some patients)

## 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/histiocytoses/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/histiocytoses/#overview [2 subtypes, 4 state-of-the-art points]
- What it is (on the hub): Anatomy, the subtypes and how they differ, how it is staged, and where advanced disease spreads. https://onco.cc/cancers/histiocytoses/#what-it-is [8 subtypes]
- Finding it (on the hub): How it shows itself, how it is confirmed, what screening exists, and the biomarkers clinicians test for. https://onco.cc/cancers/histiocytoses/#finding-it [6 biomarkers]
- Treating it (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/histiocytoses/#treating-it [4 settings, 4 decisions with options]
- Evidence (on the hub): Trials recruiting now, the landmark trials, the key papers and what they mean, the latest literature, and the milestones year by year. https://onco.cc/cancers/histiocytoses/#evidence [1 trial, 1 key paper, 7 milestones]
- The science (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/histiocytoses/#science [4 targets, 3 pathways]
- Where you are (own page): Cases by country, the UK and NHS pathway and other country lenses, and the expert centres with trials on record. https://onco.cc/cancers/histiocytoses/where-you-are/ [1 centre]
- Living with it (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/histiocytoses/#living-with-it [17 questions, 6 red cards]
- What is coming (own page): Everything in development, the open problems and what is being done about them, the roadmaps, and what changed on this record. https://onco.cc/cancers/histiocytoses/coming/ [9 medicines, 1 trial, 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/histiocytoses/data/ [44 connected records]

## Standard of care

- ECD, BRAF V600E-mutant, needing treatment: Vemurafenib (FDA approval 2017) or dabrafenib, often with a MEK inhibitor to reduce toxicity; long-term treatment at the lowest effective dose. ([Vemurafenib](https://onco.cc/drugs/vemurafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [BRAF](https://onco.cc/targets/braf/))
- ECD or RDD, BRAF wild-type or intolerant of BRAF inhibitors: Cobimetinib (FDA approval October 2022 for histiocytic neoplasms) or another MEK inhibitor; interferon alfa or pegylated interferon as an alternative. ([Cobimetinib](https://onco.cc/drugs/cobimetinib/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/))
- Rosai-Dorfman disease: Observation for asymptomatic nodal disease; surgery for isolated masses; steroids, sirolimus, cladribine or MEK inhibitors for symptomatic or multifocal disease. ([Cladribine](https://onco.cc/drugs/cladribine/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/))
- Histiocytic sarcoma: Lymphoma-type chemotherapy (CHOP, ICE, or similar), radiotherapy for localised disease, MAPK-pathway inhibitors where mutations are found; clinical trials. ([Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Etoposide](https://onco.cc/drugs/etoposide/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/))

## State of the art

- The MAPK pathway discovery (BRAF V600E in ECD, 2012) converted histiocytoses from mysterious inflammatory diseases into targetable neoplasms.
- Vemurafenib (2017) and cobimetinib (2022) are the first drugs ever approved for a histiocytosis, with responses in nearly every treated patient.
- Plasma BRAF V600E ctDNA and FDG-PET allow response monitoring and dose reduction without repeat biopsy.
- The remaining challenges are stopping therapy without relapse, neurodegeneration, and histiocytic sarcoma.

## Open problems

- Most patients relapse when BRAF or MEK inhibitors stop; intermittent dosing and ctDNA-guided discontinuation are being tested.
- Neurodegenerative ECD and LCH do not reverse with targeted therapy; earlier treatment and neuroprotective trials are the response.
- Histiocytic sarcoma remains aggressive; MAPK inhibitors and immunotherapy are being tried.
- Rarity: the Histiocyte Society, the ECD Global Alliance registry and NCCN's 2021 guideline coordinate what evidence exists.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Erdheim%E2%80%93Chester_disease
- NCI PDQ: Langerhans cell histiocytosis (histiocytic disorders): https://www.cancer.gov/types/langerhans
- Consensus recommendations for ECD (Blood 2020): https://doi.org/10.1182/blood.2019003507
- Cobimetinib in histiocytic neoplasms (Nature Medicine 2019): https://doi.org/10.1038/s41591-019-0653-6
- NCCN: Histiocytic Neoplasms: https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1518

## Connected records

- cancers: [Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms](https://onco.cc/cancers/cmml/), [Erdheim-Chester disease](https://onco.cc/cancers/erdheim-chester-disease/), [Langerhans cell histiocytosis (LCH)](https://onco.cc/cancers/langerhans-cell-histiocytosis/), [Melanoma](https://onco.cc/cancers/melanoma/), [Rosai-Dorfman-Destombes disease](https://onco.cc/cancers/rosai-dorfman-disease/)
- technologies: [Comprehensive genomic profiling](https://onco.cc/technologies/cgp/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/), [MRI](https://onco.cc/technologies/mri/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/)
- targets: [ALK](https://onco.cc/targets/alk/), [BRAF](https://onco.cc/targets/braf/), [PIK3CA / PI3K-alpha](https://onco.cc/targets/pik3ca/)
- drugs: [Cladribine](https://onco.cc/drugs/cladribine/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/), [Cyclophosphamide](https://onco.cc/drugs/cyclophosphamide/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Doxorubicin](https://onco.cc/drugs/doxorubicin/), [Emapalumab](https://onco.cc/drugs/emapalumab/), [Etoposide](https://onco.cc/drugs/etoposide/), [Interferon alfa-2a/2b](https://onco.cc/drugs/interferon-alfa/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/)
- companies: [Roche / Genentech](https://onco.cc/companies/roche-genentech/)
- institutions: [Histiocyte Society](https://onco.cc/institutions/histiocyte-society/)
- pathways: [Clonal haematopoiesis (CHIP)](https://onco.cc/pathways/clonal-haematopoiesis/), [PI3K / AKT / mTOR](https://onco.cc/pathways/pi3k-akt-mtor/), [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/), [Circulating tumour DNA (ctDNA)](https://onco.cc/terms/ctdna/), [Driver mutation](https://onco.cc/terms/driver-mutation/), [Retroperitoneum](https://onco.cc/terms/retroperitoneum/)
- bottlenecks: [No incentive to repurpose cheap drugs](https://onco.cc/bottlenecks/b-generic-repurposing/), [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)
- key papers: [Activating mutations in CSF1R and additional receptor tyrosine kinases in histiocytic neoplasms](https://onco.cc/key-papers/paper-durham-nat-med/)
- trials: [Mirdametinib in Histiocytic Disorders](https://onco.cc/trials/nct06153173/)

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JSON: https://onco.cc/api/v1/entities/histiocytoses.json