Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by activating mutations of the mitogen-activated protein kinase pathway. There is clonal proliferation of pathogenic Langerhans cells in single or multiple organs.
Clinical presentation is heterogeneous and ranges from self-healing bone lesions to multisystem, life-threatening disease.
Tissue biopsy of lesional cells showing the presence of CD1a and langerin (CD207) is definitive for diagnosis in the correct clinical setting.
Single-system disease may resolve without treatment and require careful monitoring only.
Single-system disease involving risk organs and multisystem disease is treated with systemic chemotherapy.
Targeted therapy has the potential to improve outcomes in otherwise refractory cases.
Adverse prognostic factors include poor response to therapy and risk-organ involvement.
LCH is a rare disease characterized by the clonal proliferation of pathogenic Langerhans cells, leading to inflammation and tissue destruction.
LCH affects both children and adults, with almost twice the incidence in the pediatric age group. The most commonly involved organs in children are the bone, skin, pituitary gland, liver, spleen, hematopoietic system, lungs, lymph nodes, and central nervous system.
LCH was previously called histiocytosis X.
History and exam
Key diagnostic factors
- age <15 years
- bone pain and/or swelling
- skin rash
- polyuria and polydipsia
- growth or sexual maturation failure
- vertebra plana
Other diagnostic factors
- cough, dyspnea
- chest pain
- orbital abnormalities
- weight loss
- ear pain
- ear discharge
- hearing loss
- perforated tympanic membrane
- neurologic signs
- bloody diarrhea
- oral mucosa lesions
- thyroid enlargement
- family history of thyroid disease
- perinatal infections
1st investigations to order
- serum albumin
- renal function
- serum electrolytes
- serum calcium
- inflammatory markers
- endocrine evaluation (adults)
- BRAF V600E mutation analysis
- skeletal survey (children)
- chest x-ray (children)
- abdominal ultrasound (children)
- fluorodeoxyglucose positron emission tomography (FDG-PET) (adults)
- MRI head with contrast (adults)
- tissue biopsy
Investigations to consider
- endocrine evaluation (children)
- coagulation studies (children)
- pulmonary function tests
- high-resolution CT chest
- bone marrow aspirate and biopsy
- MRI head with contrast (children)
- MRI spine
- CT head
single-system disease: bone involvement
single-system disease: skin involvement
single-system disease: isolated lymph node involvement
single-system disease: lung involvement
single-system disease: CNS involvement
single-system disease: neurodegenerative disease
- Seborrheic dermatitis
- Juvenile xanthogranuloma (JXG)
- Rosai-Dorfman disease (RDD)
- Clinical practice guidelines in oncology: histiocytic neoplasms
- International expert consensus recommendations for the diagnosis and treatment of Langerhans cell histiocytosis in adults
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