[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [Conditions](https://durgical.com/en/conditions/) › Langerhans cell histiocytosis

[Conditions](https://durgical.com/en/conditions/) · [Hematology and oncology](https://durgical.com/en/conditions/)

# Langerhans cell histiocytosis

A rare disease, mostly of children, in which abnormal immune cells pile up and damage bones, [skin](https://durgical.com/en/anatomy/skin/), the pituitary or other organs.

Updated 2026-11-01

## Structures involved

Tap one to see what it is and open it in 3D.

- [Frontal bone](https://durgical.com/en/anatomy/frontal-bone/)
- [Femur](https://durgical.com/en/anatomy/femur/)
- [Parietal bones](https://durgical.com/en/anatomy/parietal-bone/)
- [Temporal bones](https://durgical.com/en/anatomy/temporal-bone/)
- [Mandible](https://durgical.com/en/anatomy/mandible/)
- [Pituitary gland](https://durgical.com/en/anatomy/pituitary-gland/)
- [Skin](https://durgical.com/en/anatomy/skin/)
- [Tibia](https://durgical.com/en/anatomy/tibia/)

## Why it happens

- [Oncogenes: RAS, MYC, HER2, BCR-ABL and the table to know](https://durgical.com/en/general-pathology/oncogenes-ras-myc-her2-bcr-abl-and-the-table-to-know/)
- [Tumours of infancy and childhood](https://durgical.com/en/general-pathology/tumours-of-infancy-and-childhood/)
- [Keratinocytes, melanocytes, Langerhans and Merkel cells](https://durgical.com/en/histology/keratinocytes-melanocytes-langerhans-and-merkel-cells/)

## What it is

A rare myeloid neoplasm in which clonal cells resembling Langerhans cells (CD1a and CD207/langerin positive) accumulate with inflammatory cells and destroy tissue. It ranges from a single bone lesion that heals on its own to life-threatening disease in many organs.

## Who gets it

Rare: a few cases per million children per year, with a peak at ages 1–3 years; adults are affected less often, typically with lung involvement linked to smoking. Single-system bone disease is the most common form. In Colombia and Latin America it is managed in paediatric oncology centres following international protocols.

## Causes

- Somatic mutations activating the MAPK pathway in myeloid precursors, most often BRAF V600E, and MAP2K1 in many others
- Adult pulmonary LCH is strongly associated with cigarette smoking
- Not infectious and not inherited

## Risk factors

- Early childhood (1–3 years)
- Smoking (adult pulmonary form)
- Possible association with perinatal infections and family history of thyroid disease (weak evidence)

## Pathophysiology

Mutated myeloid cells migrate to tissues and behave like immature Langerhans cells. They recruit lymphocytes, eosinophils and macrophages and release cytokines that activate osteoclasts and destroy tissue, producing 'punched-out' bone lesions, skin rashes and organ damage. Birbeck granules (tennis-racket-shaped organelles) are seen on electron microscopy. Involvement of the hypothalamic-pituitary [axis](https://durgical.com/en/anatomy/axis/) destroys the posterior pituitary, causing central diabetes insipidus, which may be permanent.

## Classification

- Single-system disease: unifocal (one bone) or multifocal (several bones, skin, lymph nodes)
- Multisystem disease without risk-organ involvement
- Multisystem disease with risk-organ involvement (bone marrow, liver, [spleen](https://durgical.com/en/anatomy/spleen/)), with the highest mortality
- CNS-risk lesions: skull base, orbit, mastoid and [temporal bone](https://durgical.com/en/anatomy/temporal-bone/) (higher risk of diabetes insipidus)
- Isolated pulmonary LCH in adult smokers

## Symptoms and signs

- Bone pain and a tender swelling, most often of the skull, [femur](https://durgical.com/en/anatomy/femur/), [ribs](https://durgical.com/en/anatomy/ribs/), vertebrae or [pelvis](https://durgical.com/en/anatomy/region/pelvis/)
- Scaly, crusted or seborrhoeic-like rash on the scalp, behind the ears and in skin folds, resistant to usual treatment
- Chronic ear discharge (mastoid and temporal bone involvement)
- Excessive thirst and urination (central diabetes insipidus)
- Loose teeth and gum swelling (jaw involvement)
- Fever, weight loss, enlarged lymph nodes, liver or spleen in multisystem disease; cough and breathlessness in pulmonary disease

## Red flags

- Pancytopenia, jaundice or a large liver or spleen (risk-organ disease)
- Sudden chest pain and breathlessness in a young smoker (spontaneous pneumothorax)
- Polyuria and polydipsia in a child with bone or skin lesions (diabetes insipidus)
- Vertebral collapse with back pain or neurological deficit

## Diagnosis

**Clinical**
Suspect LCH in a child with a lytic skull lesion, a stubborn scalp or diaper-area rash, chronic otitis or diabetes insipidus, and in a young adult smoker with cystic lung disease.

**Tests**
Biopsy of the most accessible lesion is required: Langerhans-type cells positive for CD1a and CD207 (langerin), with S100 positivity; BRAF V600E testing guides therapy. Baseline blood count, [liver](https://durgical.com/en/anatomy/liver/) function, albumin and coagulation, and urine osmolality or water deprivation testing when diabetes insipidus is suspected. Pulmonary function tests in lung disease.

**Imaging**
Plain X-ray shows sharply 'punched-out' lytic lesions of the skull, sometimes with a 'hole within a hole' (bevelled edge), and vertebra plana when a vertebral body collapses. Skeletal survey or PET-CT to find all lesions; MRI of the brain and pituitary (thickened pituitary stalk); high-resolution [chest](https://durgical.com/en/anatomy/region/chest/) CT showing nodules and cysts in the upper lobes in adult smokers.

## Differential diagnosis

- Osteomyelitis
- Ewing sarcoma and osteosarcoma
- Metastatic neuroblastoma (lytic skull and orbit lesions in young children)
- Seborrhoeic or atopic dermatitis (for the rash)
- Other histiocytic disorders (Erdheim-Chester disease, haemophagocytic lymphohistiocytosis)

## Goal of treatment

Control active lesions, prevent reactivation and permanent consequences (diabetes insipidus, hearing loss, orthopaedic and neurological sequelae), and treat risk-organ disease intensively.

## Treatment

**Conservative**
Observation for a single bone lesion that is not in a CNS-risk site, since many heal spontaneously after biopsy.

**Procedure**
Curettage at biopsy, or intralesional corticosteroid injection, for selected single bone lesions; low-dose radiotherapy is rarely used.

**Medical**
Multisystem, multifocal bone or CNS-risk disease: systemic chemotherapy, classically vinblastine with prednisone, with cytarabine or cladribine for refractory disease; BRAF or MEK inhibitors for refractory or BRAF-mutated disease.

**Medical**
Central diabetes insipidus: desmopressin replacement; hormone replacement for other pituitary deficits.

**Lifestyle**
Adult pulmonary LCH: complete smoking cessation, which can stabilise or reverse the disease.

**Follow-up**
Long-term follow-up for reactivation, growth, hearing, pituitary function and neurodegeneration; nursing care includes fluid balance in diabetes insipidus and chemotherapy safety.

## Complications

- Central diabetes insipidus and other pituitary hormone deficiencies
- Hearing loss and chronic ear disease
- Orthopaedic deformity, vertebral collapse and tooth loss
- Neurodegenerative LCH (ataxia, learning and behavioural problems) years later
- Lung cysts, pneumothorax and pulmonary hypertension; liver sclerosing cholangitis and cirrhosis

## Prognosis

Single-system disease has excellent survival, although reactivations are common. Multisystem disease with risk-organ involvement that does not respond early to chemotherapy carries significant mortality. Permanent consequences such as diabetes insipidus affect quality of life in many survivors.

## Test yourself

Think of the answer, then tap the question to see it.

## Which two immunohistochemical markers confirm Langerhans cell histiocytosis?

CD1a and CD207 (langerin).

## What organelle is seen on electron microscopy in LCH cells?

Birbeck granules, shaped like tennis rackets.

## What is the most common endocrine complication of LCH?

Central diabetes insipidus from posterior pituitary involvement.

## What is the classic X-ray appearance of LCH in the skull?

Sharply defined 'punched-out' lytic lesions, sometimes with a bevelled 'hole within a hole' edge.

## Which mutation is found in about half of LCH cases?

BRAF V600E, activating the MAPK pathway.

[Add to my cards (5)](https://durgical.app/estudiar/?add=/en/conditions/langerhans-cell-histiocytosis/)

## Related conditions

- [Diabetes insipidus (central and nephrogenic)](https://durgical.com/en/conditions/diabetes-insipidus/)
- [Hypopituitarism (incl. Sheehan syndrome and pituitary apoplexy)](https://durgical.com/en/conditions/hypopituitarism/)
- [Otitis media with effusion and chronic suppurative otitis media](https://durgical.com/en/conditions/otitis-media-with-effusion-and-chronic-suppurative-otitis-media/)
- [Seborrheic dermatitis](https://durgical.com/en/conditions/seborrheic-dermatitis/)
- [Osteomyelitis](https://durgical.com/en/conditions/osteomyelitis/)
- [Ewing sarcoma](https://durgical.com/en/conditions/ewing-sarcoma/)
- [Osteosarcoma](https://durgical.com/en/conditions/osteosarcoma/)
- [Neuroblastoma](https://durgical.com/en/conditions/neuroblastoma/)
- [Tobacco use disorder](https://durgical.com/en/conditions/tobacco-use-disorder/)
- [Pneumothorax](https://durgical.com/en/conditions/pneumothorax/)
- [Interstitial lung disease](https://durgical.com/en/conditions/interstitial-lung-disease/)

Educational information, not medical advice. For any symptom, see a health professional.

Sources: [Langerhans Cell Histiocytosis Treatment (PDQ®)–Health Professional Version](https://www.cancer.gov/types/langerhans/hp/langerhans-treatment-pdq) (National Cancer Institute, 2025).

[← All conditions](https://durgical.com/en/conditions/)

## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake

Representative model, for educational purposes only.

---
Source: https://durgical.com/en/conditions/langerhans-cell-histiocytosis/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/conditions/langerhans-cell-histiocytosis/