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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.
Adult LCH, including smoking-related pulmonary LCH, is managed with cladribine or cytarabine and MAPK inhibitors, and is now covered by the same Histiocyte Society and NCCN guidance. Neurodegenerative LCH, which had no treatment at all, responds partially to MAPK inhibition, giving a reason to detect it early with MRI.
Roughly 5 cases per million children per year, most under ten; also occurs in adults, often in the lung of smokers (NCI PDQ).
Leukaemias, myeloma and MDS live in the marrow and blood; lymphomas grow in lymph nodes and spleen. The node stations are the disease map, not a route of spread, and staging counts them.
In lymphoma the node stations are the disease itself; staging (Ann Arbor / Lugano) counts how many regions and sides of the diaphragm are involved.
Same organ: High-grade B-cell lymphoma with MYC and BCL2 rearrangements (double-hit lymphoma), Mediastinal grey zone lymphoma, Primary effusion lymphoma, Plasmablastic lymphoma, T-cell/histiocyte-rich large B-cell lymphoma, EBV-positive diffuse large B-cell lymphoma, Primary large B-cell lymphoma of the testis, Gastric MALT lymphoma, Ocular adnexal MALT lymphoma, Extranodal NK/T-cell lymphoma, Adult T-cell leukaemia/lymphoma, ALK-positive anaplastic large cell lymphoma, ALK-negative anaplastic large cell lymphoma, Breast implant-associated anaplastic large cell lymphoma, Primary cutaneous anaplastic large cell lymphoma, Lymphomatoid papulosis, Mycosis fungoides, Enteropathy-associated T-cell lymphoma, Monomorphic epitheliotropic intestinal T-cell lymphoma, Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), Splenic marginal zone lymphoma, Nodal marginal zone lymphoma, Primary cutaneous marginal zone lymphoma, Primary cutaneous follicle centre lymphoma, Sezary syndrome, Nodal T-follicular helper cell lymphoma, angioimmunoblastic type (angioimmunoblastic T-cell lymphoma), Hepatosplenic T-cell lymphoma, Intravascular large B-cell lymphoma, Lymphomatoid granulomatosis, T-cell prolymphocytic leukaemia, Splenic B-cell lymphoma/leukaemia with prominent nucleoli (formerly B-cell prolymphocytic leukaemia and hairy cell leukaemia variant), T-cell large granular lymphocytic leukaemia, Mixed-phenotype acute leukaemia, Myeloid leukaemia of Down syndrome, Burkitt leukaemia, Marginal zone lymphoma, Cutaneous T-cell lymphoma (mycosis fungoides and Sezary syndrome), Primary mediastinal (thymic) large B-cell lymphoma, Leukaemia (all types), Acute myeloid leukaemia, Acute lymphoblastic leukaemia, Chronic lymphocytic leukaemia, Chronic myeloid leukaemia (CML), Diffuse large B-cell lymphoma, Follicular lymphoma, Hodgkin lymphoma, Mantle cell lymphoma, Multiple myeloma, Non-Hodgkin lymphoma (all types), Myelodysplastic syndromes / neoplasms (MDS), Myeloproliferative neoplasms (PV, ET, myelofibrosis), Polycythaemia vera (PV), Essential thrombocythaemia (ET), Waldenström macroglobulinaemia, Hairy cell leukaemia, Peripheral T-cell lymphomas (including cutaneous T-cell lymphoma), Blastic plasmacytoid dendritic cell neoplasm (BPDCN), Burkitt lymphoma, HIV-associated (AIDS-related) lymphomas, Chronic myelomonocytic leukaemia and MDS/MPN overlap neoplasms, Systemic mastocytosis, Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, Post-transplant lymphoproliferative disorder (PTLD), FLT3-mutated acute myeloid leukaemia, IDH1- and IDH2-mutated acute myeloid leukaemia, NPM1-mutated and KMT2A-rearranged acute myeloid leukaemia, Secondary and therapy-related acute myeloid leukaemia, Acute promyelocytic leukaemia, Acute myeloid leukaemia in older or unfit patients, Smouldering multiple myeloma, Newly diagnosed multiple myeloma, transplant-eligible, Newly diagnosed multiple myeloma, transplant-ineligible, Relapsed or refractory multiple myeloma, Plasma cell leukaemia, Lower-risk myelodysplastic syndromes, Higher-risk myelodysplastic syndromes, Chronic lymphocytic leukaemia, first treatment, Relapsed or refractory chronic lymphocytic leukaemia, Richter transformation of chronic lymphocytic leukaemia, Chronic myeloid leukaemia, chronic phase, Chronic myeloid leukaemia, accelerated and blast phase, Primary myelofibrosis, Standard-risk B-cell acute lymphoblastic leukaemia in children, High-risk acute lymphoblastic leukaemia in children (high-risk B-ALL and T-ALL), Philadelphia chromosome-positive acute lymphoblastic leukaemia in children (Ph-positive ALL), Philadelphia chromosome-like acute lymphoblastic leukaemia (Ph-like or BCR::ABL1-like ALL), Infant acute lymphoblastic leukaemia (KMT2A-rearranged, under one year), Relapsed and refractory acute lymphoblastic leukaemia in children, Acute myeloid leukaemia in children, Erdheim-Chester disease, Rosai-Dorfman-Destombes disease, Single-system Langerhans cell histiocytosis (bone, skin or one other organ), Multisystem Langerhans cell histiocytosis (with or without risk-organ involvement), Indolent and smouldering systemic mastocytosis, Advanced systemic mastocytosis (aggressive SM, SM with an associated haematological neoplasm, mast cell leukaemia), Early-stage classical Hodgkin lymphoma (stage I to II), Advanced-stage classical Hodgkin lymphoma (stage III to IV), Nodular lymphocyte-predominant Hodgkin lymphoma (nodular lymphocyte-predominant B-cell lymphoma), Relapsed and refractory classical Hodgkin lymphoma
Nothing recorded yet.
Nothing recorded yet.
Also on OnCo: Symptoms and red flags · Early detection roadmap.
Biopsy or curettage with observation; intralesional steroid, topical therapy or indomethacin for symptomatic lesions; systemic therapy for multifocal bone or CNS-risk lesions.
Vinblastine and prednisone for 12 months (LCH-III), with response assessment at 6 weeks; LCH-IV tests further tailoring of duration and intensity.
Cladribine plus cytarabine or clofarabine salvage; BRAF inhibitor (vemurafenib or dabrafenib, with trametinib) for BRAF V600E, MEK inhibitor for MAP2K1-mutant disease.
MAPK-pathway inhibition (BRAF or MEK inhibitor) with neurological monitoring; early MRI detection in children with pituitary or craniofacial disease.
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Query for this cancer: (TITLE:"Langerhans cell histiocytosis" OR ABSTRACT:"Langerhans cell histiocytosis" OR TITLE:"LCH" OR ABSTRACT:"LCH" OR TITLE:"Histiocytosis X" OR ABSTRACT:"Histiocytosis X" OR TITLE:"Eosinophilic granuloma" OR ABSTRACT:"Eosinophilic granuloma" OR TITLE:"Hand-Schuller-Christian disease" OR ABSTRACT:"Hand-Schuller-Christian disease" OR TITLE:"Letterer-Siwe disease" OR ABSTRACT:"Letterer-Siwe disease") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Langerhans cell histiocytosis (LCH), not a curated reading list.
Nezelof finds Birbeck granules in the lesions.
First international randomised trial in LCH.
Badalian-Very and colleagues (Blood) show LCH is a clonal MAPK-driven neoplasm.
Gadner and colleagues (Blood 2013).
Berres and colleagues (JEM) show BRAF V600E in myeloid precursors in high-risk disease.
Donadieu and colleagues (JCO) report responses in nearly all BRAF V600E children, with reactivation after stopping.
The targets of this cancer's medicines and the ones linked to it directly.
How common each drug target or alteration is in this cancer. Population-level and approximate; see the target page for detail. Full matrix.
Cases by country, the UK and NHS pathway and other country lenses, the expert centres with trials on record, and the centres named on this cancer's subtypes.
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Bleeding that does not stop by itself, bleeding from more than one site, or new bruising in several places or one large area.
Fainting, near-fainting, or an irregular or racing heartbeat; several kinase inhibitors prolong the QT interval and the labels require ECG and electrolyte monitoring.
Dabrafenib: take on an empty stomach. Trametinib: take on an empty stomach; both cause pyrexia.
Severe photosensitivity: sun protection.
Known QT prolongation. Avoid other QT-prolonging drugs where possible; check ECG and correct potassium and magnesium before and during treatment.
Several lymphoma treatments knock out the part of the immune system that keeps a particular lung infection, Pneumocystis, at bay. A low-dose antibiotic three times a week prevents it, and a separate tablet prevents shingles.
See all on the product pages:CladribineDabrafenib + trametinibVemurafenibVinblastine·Printable cards in the navigator
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