Langerhans cell histiocytosis !

A rare disease, mostly of children, in which abnormal immune cells pile up and damage bones, skin, the pituitary or other organs.

Updated 2026-11-01

Structures involved

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Why it happens

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 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), with the highest mortality
CNS-risk lesions: skull base, orbit, mastoid and 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, ribs, vertebrae or 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

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 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 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.

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

Sources: Langerhans Cell Histiocytosis Treatment (PDQ®)–Health Professional Version (National Cancer Institute, 2025).

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Representative model, for educational purposes only.

Frontal bone highlighted on the Durgical 3D model