# Single-system Langerhans cell histiocytosis (bone, skin or one other organ)

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

## TL;DR

Single-system Langerhans cell histiocytosis is the milder form of this rare histiocytosis, in which the abnormal immune cells affect only one organ, usually a bone or the skin, in a child or young adult. Single bone lesions often heal after biopsy or curettage, skin disease may fade by itself, and gentle vinblastine and prednisone is kept for multiple bone lesions or lesions near the brain.

## Summary

Langerhans cell histiocytosis is a clonal myeloid neoplasm of CD1a- and langerin-positive dendritic-like cells, driven in most cases by BRAF V600E or another MAPK pathway mutation. Its behaviour depends on how many organs are involved. Single-system disease, most often a lytic bone lesion of the skull, femur, ribs or vertebrae in a child of school age, or a skin eruption in an infant, carries almost no mortality; the classic eponyms eosinophilic granuloma (bone), Hand-Schüller-Christian and Letterer-Siwe disease have given way to a classification by organ count and risk-organ involvement. Pulmonary Langerhans cell histiocytosis in adults who smoke is a distinct single-system form that often improves with smoking cessation. The Histiocyte Society staging separates unifocal bone disease, multifocal bone disease, special-site lesions (skull base, orbit, mastoid and vertebrae with soft tissue extension, which carry a risk of later pituitary or neurodegenerative involvement) and single-system disease of skin, lymph node or lung.

Treatment is proportionate. A single bone lesion is treated by biopsy with curettage, sometimes with an intralesional steroid injection, and many heal spontaneously; indomethacin or bisphosphonates help painful bone disease; skin-only disease in infants is observed or treated topically and often resolves, though a proportion of infants later develop multisystem disease and must be followed. Multifocal bone disease and special-site lesions are treated with the same vinblastine and prednisone regimen used for multisystem disease, given for twelve months after LCH-III showed longer treatment reduced reactivation, in order to prevent recurrence and the late central nervous system complications. Reactivation is common but rarely dangerous. Adults with single-system disease may receive cytarabine or cladribine instead because vinblastine is more toxic in adults, and BRAF or MEK inhibitors are reserved for refractory disease. The main long-term concerns are diabetes insipidus and neurodegenerative disease after skull-base lesions, and orthopaedic sequelae after vertebral collapse, so follow-up continues for years.

## Fields

- Kind: Cancer
- Last checked: 2026-09-18
- Also known as: Single-system LCH; Eosinophilic granuloma; Unifocal bone LCH; Skin-only LCH; Pulmonary Langerhans cell histiocytosis (adult smokers)
- Tags: subtype-page; paediatric
- Group: paediatric
- Burden: About two thirds of childhood Langerhans cell histiocytosis is confined to one organ system, most often bone; the outlook is excellent and many lesions heal with minimal or no treatment.
- Subtypes: Unifocal bone Langerhans cell histiocytosis (eosinophilic granuloma; curettage or observation); Multifocal bone Langerhans cell histiocytosis (vinblastine and prednisone); Special-site Langerhans cell histiocytosis (skull base, orbit, mastoid, vertebra; treated to prevent CNS complications); Skin-only Langerhans cell histiocytosis in infants (observation, may progress); Single-system lymph node or thymic Langerhans cell histiocytosis; Pulmonary Langerhans cell histiocytosis in adult smokers (smoking cessation)
- Biomarkers: CD1a and langerin (CD207) positive histiocytes on biopsy; BRAF V600E in tissue (present in over half) and cell-free DNA; MAP2K1 and other MAPK alterations; Skeletal survey or whole-body MRI or PET for occult lesions; Pituitary MRI and water balance for special-site disease; Chest CT and pulmonary function in adult pulmonary disease

## Standard of care

- Diagnosis and staging: Biopsy with immunohistochemistry and BRAF testing; skeletal survey or whole-body imaging, blood count, liver tests and abdominal ultrasound to exclude multisystem disease. ([Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/), [MRI](https://onco.cc/technologies/mri/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Ultrasound](https://onco.cc/technologies/ultrasound/))
- Unifocal bone disease: Biopsy with curettage, with or without intralesional methylprednisolone; observation of healing; indomethacin for pain. ([Active surveillance](https://onco.cc/technologies/active-surveillance/))
- Multifocal bone or special-site disease: Vinblastine and prednisone for twelve months (LCH-III schedule) to reduce reactivation and central nervous system risk. ([Vinblastine](https://onco.cc/drugs/vinblastine/), [LCH-III](https://onco.cc/trials/lch-iii/))
- Skin-only disease: Observation or topical corticosteroids; systemic therapy only for extensive symptomatic disease; regular review for progression to multisystem disease. ([Active surveillance](https://onco.cc/technologies/active-surveillance/))
- Adult single-system or refractory disease: Cytarabine or cladribine; smoking cessation for pulmonary disease; BRAF or MEK inhibitors (vemurafenib, dabrafenib-trametinib, cobimetinib) for refractory disease. ([Cladribine](https://onco.cc/drugs/cladribine/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/))

## State of the art

- Most single-system disease is cured with minimal treatment and near-zero mortality.
- Special-site lesions are treated systemically to prevent the late neurological complications.
- BRAF testing links the mildest and the most severe forms of the disease as one neoplasm.

## Open problems

- Which infants with skin-only disease will progress cannot be predicted.
- Whether treating special-site lesions truly prevents neurodegeneration is inferred rather than proven.
- Adults have no trial-based standard.
- Reactivation rates remain high even after twelve months of therapy.

## 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
- Wikipedia: https://en.wikipedia.org/wiki/Langerhans_cell_histiocytosis

## Connected records

- cancers: [Langerhans cell histiocytosis (LCH)](https://onco.cc/cancers/langerhans-cell-histiocytosis/), [Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement)](https://onco.cc/cancers/lch-multisystem/), [Rosai-Dorfman-Destombes disease](https://onco.cc/cancers/rosai-dorfman-disease/)
- technologies: [Active surveillance](https://onco.cc/technologies/active-surveillance/), [Cytotoxic chemotherapy](https://onco.cc/technologies/cytotoxic-chemotherapy/), [FDG PET](https://onco.cc/technologies/fdg-pet/), [Histopathology & immunohistochemistry](https://onco.cc/technologies/histopathology-ihc/), [MRI](https://onco.cc/technologies/mri/), [Small-molecule kinase inhibitors](https://onco.cc/technologies/kinase-inhibitors/), [Ultrasound](https://onco.cc/technologies/ultrasound/)
- targets: [BRAF](https://onco.cc/targets/braf/)
- drugs: [Cladribine](https://onco.cc/drugs/cladribine/), [Cobimetinib](https://onco.cc/drugs/cobimetinib/), [Dabrafenib + trametinib](https://onco.cc/drugs/dabrafenib-trametinib/), [Vemurafenib](https://onco.cc/drugs/vemurafenib/), [Vinblastine](https://onco.cc/drugs/vinblastine/)
- terms: [BRAF V600E mutation](https://onco.cc/terms/braf-v600-mutation/), [Late effects and survivorship toxicity](https://onco.cc/terms/late-effects/)
- trials: [LCH-III](https://onco.cc/trials/lch-iii/)
- key papers: [LCH-III: therapy prolongation improves outcome in multisystem Langerhans cell histiocytosis](https://onco.cc/key-papers/paper-lch-iii-therapy-prolongation-multisystem-lch-blood-2013/), [Recurrent BRAF mutations in Langerhans cell histiocytosis](https://onco.cc/key-papers/paper-badalian-very-braf-mutations-lch-blood-2010/), [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/)
- pathways: [RAS / RAF / MEK / ERK (MAPK)](https://onco.cc/pathways/ras-mapk/)

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