Snapshot A 12-year-old boy presents to the emergency room for pain in in his right forearm with minimal trauma while playing tag. Radiography shows a fracture of the radius. A skeletal survey also shows 2 other lytic bone lesions on the cranium. He is referred to the pediatric oncologist for further workup and possible biopsy for a Langerhans cell histiocytosis. Introduction Overview Langerhans cell histiocytosis (LCH) describes a group of conditions caused by proliferation of dendritic (Langerhans) cells traditionally classified by 4 subtypes, but more recent classification is based on extent of dissemination Langerhans Cell Histiocytosis (LCH) Letterer-Siwe Hand-Schuller-Christian Hashimoto-Pritzker (Congenital Self-Healing Reticulohistiocytosis) Eosinophilic Granuloma Demographics < 2 years of age 2-6 years of age Neonatal period 7-12 years of age Pulmonary involvement seen in ages 30-40 years Involvement Skin, bone, and viscera pulmonary infiltrates, lymph nodules, liver, and spleen Skin, bone, and viscera liver, spleen, and lymph nodes Skin-limited Primarily bone > skin Pulmonary involvemen Prognosis Poor prognosis with disseminated disease Chronic and progressive Rapid spontaneous resolution is likely Good prognosis Epidemiology incidence rare demographics males > females risk factor smoking pulmonary involvement Pathogenesis mechanism proliferation of Langerhans cells, which are immature and are unable to stimulate T-cells via antigen presentation thought to be reactive or neoplastic BRAF V600E mutation can be found in LCH Prognosis worse with BRAF V600E mutation worse if there’s failure to respond to 6 weeks of treatment Presentation Clinical Presentation of LCH Letterer-Siwe Hand-Schuller-Christian Hashimoto-Pritzker (Congenital Self-Healing Reticulohistiocytosis) Eosinophilic Granuloma Symptoms Acutely disseminated lesions affecting the skin, bone, and internal organs Fever Bone pain Triad of diabetes insipidus, osteolytic bone lesions (cranium), and exophthalmos Skin lesions that crust and resolves spontaneously Solitary indolent bone lesions (cranium most common) with spontaneous bone fractures Physical exam Pink papules, pustules, vesicles, petechiae, purpura, and erosions on the scalp, flexural surfaces, and trunk Secondary impetiginization common Skin findings similar to Letterer-Siwe Multipe red to brown papulonodules, some with erosions Tenderness at site of bone lesions Other symptoms recurrent ear infections dizziness headache limping (due to leg pain) failure to thrive developmental delay Imaging Bone radiograph views cranium or other skeletal survey findings punched out lytic lesions Chest radiograph findings may show pulmonary nodules or infiltrate Studies Serum studies liver function test to evaluate for liver involvement baseline complete blood count Urine studies to evaluate for diabetes insipidus Pulmonary function test o evaluate for pulmonary involvement Histology S100+, CD1a+, and Langerin+ proliferation of histiocytes with mixed inflammatory infiltrate Electron microscopy Birbeck granules or “tennis rackets" Differential Multiple myeloma key distinguishing factors may also have “punched out” lytic bone lesions typically affects older adults, and protein electrophoresis of the serum (SPEP) will reveal monoclonal gammopathy Treatment Medical corticosteroids indications to slow autoimmune reaction chemotherapy indications for severe cases in children drugs cyclophosphamide, etoposide, methotrexate, and vinblastine radiation therapy indications bone lesions vasopressin indications diabetes insipidus bisphosphonates indication prevent bone destruction from bone lesion Surgical curettage or excision indications bone lesions Complications Bone fractures Spontaneous pneumothorax Infections Hearing impairment