Langerhans cell histiocytosis is an inflammatory myeloid neoplasm characterised 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 multi-system, 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 multi-system disease is treated with systemic chemotherapy.
Adverse prognostic factors include poor response to therapy and risk-organ involvement.
Langerhans cell histiocytosis (LCH) is a rare disease characterised by the clonal proliferation of pathogenic Langerhans cells, leading to inflammation and tissue destruction.
LCH primarily affects children. The most commonly involved organs in children are the bone, skin, pituitary gland, liver, spleen, haematopoietic 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, dyspnoea
- chest pain
- orbital abnormalities
- weight loss
- ear pain
- ear discharge
- hearing loss
- perforated tympanic membrane
- neurological signs
- bloody diarrhoea
- 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 (adults)
- 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
- 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
Gaurav Goyal, MD
Assistant Professor of Medicine
University of Alabama at Birmingham
Department of Medicine
Division of Hematology/Oncology
GG is an author of a number of references cited in this topic.
Dr Gaurav Goyal would like to gratefully acknowledge Dr Oussama Abla and Professor Kimo Stine, previous contributors to this topic.
OA declares that he has no competing interests. KS declares that he serves on the Board of the Histiocytosis Association (a nonprofit organization), has provided advice for a legal firm reviewing a case of LCH, and receives honoraria for membership of advisory boards to Pfizer and Behring.
R. Maarten Egeler, MD, PhD
Director of Pediatric Immunology, Hematology, Oncology, Bone Marrow Transplantation, and Autoimmune Diseases
Leiden University Medical Center
RME has previously worked with Dr Abla on a review of LCH. RME is an author of several references cited in this topic.
Rima Jubran, MD, MPH
Assistant Professor of Pediatrics
Keck School of Medicine
University of Southern California
Children's Hospital Los Angeles
RJ declares that she has no competing interests.
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