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10 slides generated from the cancer page, with a quiz from the open benchmark and speaker notes that cite the sources. Arrow keys move between slides; Print gives one slide per page.
Langerhans cell histiocytosis is a disorder in which a small group of immune cells with a faulty growth signal (most often a BRAF mutation) pile up in bone, skin, pituitary or organs. It ranges from a single bone lesion that heals after biopsy to a life-threatening disease of infants. A year of gentle chemotherapy cures most children, and BRAF or MEK inhibitors rescue those with resistant disease.
LCH is now understood as an inflammatory myeloid neoplasm: clonal cells of the mononuclear phagocyte lineage carry activating MAPK-pathway mutations, most often BRAF V600E (about half of cases) and MAP2K1, with the remainder having other RAS-MAPK lesions. The cell of origin, a bone-marrow or blood myeloid precursor versus a tissue dendritic cell, determines extent: mutations arising early give multisystem disease with risk-organ involvement (liver, spleen, marrow), while later lesions give single bone or skin disease. Pituitary involvement causes diabetes insipidus, and a minority of children develop a late neurodegenerative syndrome from mutated cells in the brain.
Treatment is stratified. Single-system bone or skin disease often needs only biopsy or curettage, observation or local therapy. Multisystem disease is treated with vinblastine and prednisone: the Histiocyte Society trials LCH-I to LCH-III showed that early response predicts survival and that prolonging therapy to 12 months reduces reactivation (LCH-III, Blood 2013); LCH-IV is refining duration and testing intensification for non-responders. Children with risk-organ involvement who do not respond quickly move to salvage (cladribine and cytarabine, or clofarabine). For refractory BRAF V600E disease, vemurafenib produces rapid responses in almost all children (Donadieu, JCO 2019), and dabrafenib with or without trametinib is used; MEK inhibitors cover MAP2K1 and other mutations. Responses to targeted therapy are near universal but reactivation on stopping is common, so the durability and safety of long-term inhibitors in young children is the central question.
| Setting | Approach | Guideline |
|---|---|---|
| Single-system bone or skin | Biopsy or curettage with observation; intralesional steroid, topical therapy or indomethacin for symptomatic lesions; systemic therapy for multifocal bone or CNS-risk lesions. | not mapped |
| Multisystem LCH (first line) | Vinblastine and prednisone for 12 months (LCH-III), with response assessment at 6 weeks; LCH-IV tests further tailoring of duration and intensity. | not mapped |
| Refractory risk-organ disease or reactivation | Cladribine plus cytarabine or clofarabine salvage; BRAF inhibitor (vemurafenib or dabrafenib, with trametinib) for BRAF V600E, MEK inhibitor for MAP2K1-mutant disease. | not mapped |
| Neurodegenerative LCH | MAPK-pathway inhibition (BRAF or MEK inhibitor) with neurological monitoring; early MRI detection in children with pituitary or craniofacial disease. | not mapped |