Langerhans Cell Histiocytosis (LCH)
Granulomatous Lesions comprising langerin-positive histiocytes and an inflammatory infiltrate can arise in virtually any organ system but have a particular affinity for bone, skin, lungs, and the pituitary.
WHAT?
• Definition: LCH is a rare disorder characterized by the proliferation of Langerhans cells, a type of dendritic cell involved in immune responses. These cells accumulate in various tissues, leading to damage and the formation of granulomas.
• Not purely inflammatory or autoimmune – now classified as a myeloid neoplasm
• Nature of Disease: LCH exhibits features of both inflammatory and neoplastic processes.
• Clonal proliferation of CD1a+, CD207+ (langerin+) dendritic cells.
• Part of the histiocytic neoplasms, often driven by MAPK pathway mutations (e.g., BRAF V600E)
WHEN?
• Incidence: 4–5 cases per million children/year.
• Affects both children and adults, male > female.
• Increased risk in some ethnicities (e.g., Hispanic populations)
CLINICAL SPECTRUM
Common areas include the bones, skin, lungs, and pituitary gland
• Bone Lesions: Painful lytic lesions, commonly in the skull, ribs, and long bones.
• Skin Involvement: Rashes, seborrheic dermatitis-like lesions.
• Endocrine Dysfunction: Diabetes insipidus due to pituitary involvement.
• Lymphadenopathy: Swollen lymph nodes.
• Pulmonary Symptoms: Cough, dyspnea, particularly in adult smokers.
A. Single-System (Low Risk)
Bone: Lytic lesions.
Skin: Papules, rashes.
Lungs: Cysts (esp. in smokers).
B. Multisystem (High Risk)
Liver, Spleen, Bone marrow: Organ dysfunction, cytopenias.
Pituitary involvement: Diabetes insipidus.
CNS involvement: Neurodegeneration, behavioral changes.
Histology & Immunophenotyping:
• Large pale histiocytes with reniform nuclei
• Birbeck granules (EM)
• Immunohistochemistry: CD1a+, CD207+ (langerin), S100+.
DIAGNOSIS
• Imaging: X-rays, CT, or MRI to identify lesions. PET-CT / MRI: Staging, detecting occult lesions.
• Biopsy: Confirmation through histological examination showing Langerhans cells positive for CD1a and Langerin (CD207).
• Laboratory Tests: Blood tests to assess organ function and rule out other conditions.
TREATMENT OPTIONS
Localized Disease:
• Surgical curettage or limited radiation therapy.
Multisystem Disease:
• Chemotherapy regimens, commonly vinblastine and prednisone.
• Targeted therapies for cases with BRAF V600E mutations.
• Supportive Care:
• Hormone replacement for endocrine dysfunctions.
• Smoking cessation is crucial in pulmonary LCH.
PROGNOSIS
• Single-System Disease: Generally favorable with appropriate treatment.
• Multisystem Disease: Prognosis varies; involvement of risk organs like the liver, spleen, or bone marrow indicates a more guarded prognosis.
#LCH #Langerhans #Cell #Histiocytosis #Diagnosis #Management
