# Langerhans cell histiocytosis (LCH)

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

## TL;DR

Langerhans cell histiocytosis is a disorder in which a small group of immune cells with a faulty growth signal (most often a BRAF mutation) pile up in bone, skin, pituitary or organs. It ranges from a single bone lesion that heals after biopsy to a life-threatening disease of infants. A year of gentle chemotherapy cures most children, and BRAF or MEK inhibitors rescue those with resistant disease.

## Summary

LCH is now understood as an inflammatory myeloid neoplasm: clonal cells of the mononuclear phagocyte lineage carry activating MAPK-pathway mutations, most often BRAF V600E (about half of cases) and MAP2K1, with the remainder having other RAS-MAPK lesions. The cell of origin, a bone-marrow or blood myeloid precursor versus a tissue dendritic cell, determines extent: mutations arising early give multisystem disease with risk-organ involvement (liver, spleen, marrow), while later lesions give single bone or skin disease. Pituitary involvement causes diabetes insipidus, and a minority of children develop a late neurodegenerative syndrome from mutated cells in the brain.

Treatment is stratified. Single-system bone or skin disease often needs only biopsy or curettage, observation or local therapy. Multisystem disease is treated with vinblastine and prednisone: the Histiocyte Society trials LCH-I to LCH-III showed that early response predicts survival and that prolonging therapy to 12 months reduces reactivation (LCH-III, Blood 2013); LCH-IV is refining duration and testing intensification for non-responders. Children with risk-organ involvement who do not respond quickly move to salvage (cladribine and cytarabine, or clofarabine). For refractory BRAF V600E disease, vemurafenib produces rapid responses in almost all children (Donadieu, JCO 2019), and dabrafenib with or without trametinib is used; MEK inhibitors cover MAP2K1 and other mutations. Responses to targeted therapy are near universal but reactivation on stopping is common, so the durability and safety of long-term inhibitors in young children is the central question.

Adult LCH, including smoking-related pulmonary LCH, is managed with cladribine or cytarabine and MAPK inhibitors, and is now covered by the same Histiocyte Society and NCCN guidance. Neurodegenerative LCH, once untreatable, responds partially to MAPK inhibition, giving a reason to detect it early with MRI.

## Fields

- Kind: Cancer
- Last checked: 2026-09-10
- Also known as: LCH; Histiocytosis X; Eosinophilic granuloma; Hand-Schuller-Christian disease; Letterer-Siwe disease
- Tags: nci-coverage; paediatric; haematologic
- Group: paediatric
- Burden: Roughly 5 cases per million children per year, most under ten; also occurs in adults, often in the lung of smokers (NCI PDQ).
- Subtypes: Single-system LCH (bone, skin, lymph node); Multisystem LCH without risk-organ involvement; Multisystem LCH with risk-organ involvement (liver, spleen, haematopoietic); CNS-risk lesions and pituitary LCH (diabetes insipidus); Neurodegenerative LCH; Pulmonary LCH (adults, smoking-related); Mixed LCH / Erdheim-Chester disease (adults)
- Biomarkers: BRAF V600E in lesion tissue and cell-free DNA (disease burden and monitoring); MAP2K1 and other MAPK alterations; Risk-organ involvement at diagnosis; Response at week 6 (predicts outcome in LCH-III); Pituitary MRI and posterior pituitary function; Brain MRI for neurodegenerative change

## 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/langerhans-cell-histiocytosis/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/langerhans-cell-histiocytosis/#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/langerhans-cell-histiocytosis/#what-it-is [9 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/langerhans-cell-histiocytosis/#finding-it [6 biomarkers, 1 prevalence rows]
- 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/langerhans-cell-histiocytosis/#treating-it [4 settings, 3 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/langerhans-cell-histiocytosis/#evidence [3 trials, 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/langerhans-cell-histiocytosis/#science [2 targets, 1 pathway]
- 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/langerhans-cell-histiocytosis/where-you-are/ [2 centres]
- 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/langerhans-cell-histiocytosis/#living-with-it [18 questions, 5 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/langerhans-cell-histiocytosis/coming/ [4 medicines, 3 trials, 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/langerhans-cell-histiocytosis/data/ [25 connected records]

## Standard of care

- Single-system bone or skin: Biopsy or curettage with observation; intralesional steroid, topical therapy or indomethacin for symptomatic lesions; systemic therapy for multifocal bone or CNS-risk lesions. ([Active surveillance](https://onco.cc/technologies/active-surveillance/), [Vinblastine](https://onco.cc/drugs/vinblastine/))
- Multisystem LCH (first line): Vinblastine and prednisone for 12 months (LCH-III), with response assessment at 6 weeks; LCH-IV tests further tailoring of duration and intensity. ([Vinblastine](https://onco.cc/drugs/vinblastine/), [LCH-III](https://onco.cc/trials/lch-iii/))
- Refractory risk-organ disease or reactivation: Cladribine plus cytarabine or clofarabine salvage; BRAF inhibitor (vemurafenib or dabrafenib, with trametinib) for BRAF V600E, MEK inhibitor for MAP2K1-mutant disease. ([Cladribine](https://onco.cc/drugs/cladribine/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/))
- Neurodegenerative LCH: MAPK-pathway inhibition (BRAF or MEK inhibitor) with neurological monitoring; early MRI detection in children with pituitary or craniofacial disease. ([Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [MRI](https://onco.cc/technologies/mri/))

## State of the art

- LCH is a MAPK-driven myeloid neoplasm; BRAF V600E in tissue and blood is a diagnostic, prognostic and monitoring marker.
- Twelve months of vinblastine-prednisone cures most children with multisystem disease and early response is the key prognostic signal (LCH-III).
- BRAF and MEK inhibitors rescue nearly every child with refractory BRAF-mutant disease, but reactivation after stopping means duration is unresolved.
- Neurodegenerative LCH, the most feared late complication, is partially reversible with MAPK inhibition if caught early.

## Open problems

- How long to give BRAF or MEK inhibitors and how to stop them without reactivation; combination with chemotherapy to allow cessation is being tested in the Histiocyte Society and NACHO networks.
- Preventing and treating neurodegenerative LCH; MRI surveillance and early MAPK inhibition are the current approach.
- Permanent sequelae (diabetes insipidus, growth failure, hearing loss, sclerosing cholangitis) in survivors of risk-organ disease.
- Adult LCH is under-recognised and under-studied; shared paediatric-adult guidelines are a first step.

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Langerhans_cell_histiocytosis
- NCI PDQ: Langerhans cell histiocytosis: https://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq
- LCH-III: prolonged therapy in multisystem LCH (Blood 2013): https://doi.org/10.1182/blood-2012-09-455774
- Vemurafenib in refractory BRAF V600E LCH (JCO 2019): https://doi.org/10.1200/JCO.19.00456
- Histiocyte Society: https://histiocytesociety.org/

## Connected records

- cancers: [Acute myeloid leukaemia](https://onco.cc/cancers/aml/), [Blastic plasmacytoid dendritic cell neoplasm (BPDCN)](https://onco.cc/cancers/bpdcn/), [Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms](https://onco.cc/cancers/histiocytoses/), [Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)](https://onco.cc/cancers/lch-multisystem/), [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/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [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/), [Survivorship care and late-effects surveillance](https://onco.cc/technologies/survivorship-care-plan/)
- targets: [ARAF](https://onco.cc/targets/araf/), [BRAF](https://onco.cc/targets/braf/)
- drugs: [Cladribine](https://onco.cc/drugs/cladribine/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/), [Vinblastine](https://onco.cc/drugs/vinblastine/)
- companies: [Children's Oncology Group (COG)](https://onco.cc/companies/childrens-oncology-group/)
- institutions: [Histiocyte Society](https://onco.cc/institutions/histiocyte-society/), [SIOP Europe (European Society for Paediatric Oncology)](https://onco.cc/institutions/siop-europe/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)
- terms: [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- trials: [LCH-III](https://onco.cc/trials/lch-iii/), [LCH-IV, International Collaborative Treatment Protocol for Children and Adolescents With Langerhans Cell Histiocytosis](https://onco.cc/trials/nct02205762/), [Mirdametinib in Histiocytic Disorders](https://onco.cc/trials/nct06153173/)
- bottlenecks: [Rare and paediatric cancers without markets](https://onco.cc/bottlenecks/b-rare-cancers/)

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JSON: https://onco.cc/api/v1/entities/langerhans-cell-histiocytosis.json