Langerhans cell histiocytosis

Langerhans Cell Histiocytosis
Synonyms	Histiocytosis X, Hand-Schüller-Christian disease, Letterer-Siwe disease, Hashimoto-Pritzker disease
Pronounce	N/A
Field	Hematology, Oncology
Symptoms	Bone lesions, rash, swelling, pain, fatigue, fever, diabetes insipidus, lymphadenopathy
Complications	Endocrine dysfunction, diabetes insipidus, hepatosplenomegaly, bone fractures, neurological deficits, pulmonary fibrosis
Onset	Childhood (common), but may occur at any age
Duration	Chronic or progressive
Types	Unifocal, Multifocal Unisystem, Multifocal Multisystem, Pulmonary LCH
Causes	Clonal proliferation of Langerhans cells; association with BRAF mutation
Risks	Genetic susceptibility, smoking (in pulmonary LCH)
Diagnosis	Histopathology, immunohistochemistry, radiology, biopsy
Differential diagnosis	Leukemia, lymphoma, Eosinophilic granuloma, Tuberculosis, Osteomyelitis
Prevention	No known prevention; risk reduction in smoking-related cases
Treatment	Chemotherapy, radiation therapy, corticosteroids, targeted therapy (BRAF inhibitors), surgery for isolated lesions
Medication	Vinblastine, Prednisone, Cladribine, Methotrexate
Prognosis	Variable; dependent on extent of disease and response to treatment
Frequency	Rare; estimated 1 in 200,000 children, 1 in 560,000 adults
Deaths	Higher in multisystem disease; varies by disease severity and response to treatment

Langerhans Cell Histiocytosis (LCH) is a rare proliferative disorder involving abnormal clonal growth of Langerhans cells, a type of dendritic cell derived from the bone marrow. These abnormal cells accumulate in tissues, causing damage through inflammation and lesion formation. LCH can range from localized disease to multisystem involvement, affecting the bone, skin, lungs, liver, spleen, lymph nodes, and central nervous system.

Previously classified under the term Histiocytosis X, the disorder was later renamed to reflect its defining cellular pathology. It shares similarities with leukemia and lymphoma in its clonal nature, but exhibits a distinct immunological behavior.

Classification

Langerhans Cell Histiocytosis is classified based on extent and severity:

Types of LCH

Type	Description	Common Sites	Prognosis
Unifocal LCH (Eosinophilic Granuloma)	A single lesion affecting one organ, typically bone	Skull, femur, ribs	Good, often resolves with treatment
Multifocal Unisystem LCH	Multiple lesions in one organ system, often bone	Skull, vertebrae, long bones	Variable; can be chronic
Multifocal Multisystem LCH (Letterer-Siwe Disease)	Disseminated disease affecting multiple organs	Bones, skin, liver, spleen, lymph nodes	Poor prognosis if untreated
Pulmonary LCH (PLCH)	LCH affecting the lungs, mostly in adult smokers	Lungs	Can improve if smoking is ceased; risk of pulmonary fibrosis

Signs and Symptoms

Symptoms of LCH vary depending on disease location:

• Bone involvement – Painful bone lesions, swelling, pathological fractures
• Skin involvement – Scaly rash, red papules, ulceration (often on the scalp, flexural areas)
• Endocrine involvement – Diabetes insipidus, growth hormone deficiency
• Lymphatic involvement – Lymphadenopathy, hepatosplenomegaly
• Neurological involvement – Seizures, ataxia, cognitive impairment
• Lung involvement – Cough, dyspnea, pulmonary fibrosis

A classic triad of diabetes insipidus, exophthalmos, and skull lesions is characteristic of Hand-Schüller-Christian disease, a form of LCH.

Causes and Pathophysiology

The exact cause of LCH is unknown, but it is linked to clonal proliferation of Langerhans cells, possibly due to mutations in the BRAF gene. The abnormal cells secrete cytokines, leading to inflammation and tissue destruction.

LCH behaves both as:

• A neoplastic disorder, due to its clonal nature.
• An immune dysregulation disorder, due to its inflammatory characteristics.

Diagnosis

LCH is diagnosed using:

• Histopathology – Identification of Langerhans cells with reniform nuclei.
• Immunohistochemistry – Cells stain positive for CD1a, CD207 (Langerin), S-100.
• Radiology – Osteolytic lesions, lung nodules, pituitary stalk thickening.
• Biopsy – Confirms the presence of pathological Langerhans cells.
• MRI/CT scans – Assess organ involvement.

Treatment

Treatment depends on disease severity:

• Unifocal lesions – Surgical excision, steroids, radiotherapy.
• Multisystem disease – Chemotherapy (vinblastine, methotrexate, cladribine).
• Pulmonary LCH – Smoking cessation, steroids, BRAF inhibitors.
• Endocrine dysfunction – Hormone replacement therapy for diabetes insipidus.

Prognosis

Prognosis varies by extent of disease:

• Unifocal disease – Excellent prognosis, often resolves.
• Multisystem disease – 50–70% survival if treated early.
• Pulmonary LCH – Improves with smoking cessation, but risk of fibrosis remains.

Epidemiology

LCH is rare, with:

• Incidence – 1 in 200,000 children, 1 in 560,000 adults.
• Higher prevalence in Caucasians.
• More common in males (2:1 ratio).
• Pulmonary LCH is strongly linked to smoking.

Society and Culture

LCH has been featured in medical dramas:

• House M.D. – Episode "Merry Little Christmas" diagnosed a dwarf girl with LCH.
• The Good Doctor – Episode where Dr. Shaun Murphy considered LCH in a pediatric case.
• Mystery Diagnosis – Case of a woman with abdominal pain, later diagnosed with LCH.

See Also

• Histiocytosis
• Leukemia
• Lymphoma
• BRAF mutation

References

This article incorporates public domain text from the United States National Library of Medicine and the National Cancer Institute.

External Links

Classification	ICD-10: C96.5 OMIM: 604856
External resources	eMedicine: derm/216 Orphanet: 389

• GeneReviews entry on LCH
• Cancer.gov LCH resources

NIH genetic and rare disease info

• NIH info on Langerhans cell histiocytosis

Langerhans cell histiocytosis is a rare disease.

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