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Histiocytoses are diseases in which immune scavenger cells build up in bone, heart, brain, kidneys and skin. They used to be treated as inflammatory conditions with steroids and interferon. The discovery that most carry mutations in the same growth pathway as melanoma turned them into targetable cancers: BRAF and MEK inhibitor pills now produce responses in nearly every treated patient.
The histiocytic neoplasms are clonal disorders of macrophage or dendritic cell lineage. The 2016 revised Histiocyte Society classification groups them into L (Langerhans: LCH, ECD, mixed ECD-LCH), C (cutaneous non-LCH, including juvenile xanthogranuloma), R (Rosai-Dorfman disease), M (malignant histiocytoses such as histiocytic sarcoma) and H (haemophagocytic lymphohistiocytosis, a hyperinflammatory syndrome rather than a neoplasm). Erdheim-Chester disease (ECD) infiltrates long bones, the retroperitoneum ('hairy kidney'), the heart and aorta, the orbits and the brain; BRAF V600E is present in around half of patients, with most of the rest carrying other MAPK-pathway alterations (MAP2K1, ARAF, NRAS, KRAS, RAF1 fusions) or PIK3CA mutations. Rosai-Dorfman disease shows emperipolesis in S100-positive, CD1a-negative histiocytes and carries KRAS or MAP2K1 mutations in a large minority. The same mutations in the same lineage in adults and children unify these diseases with Langerhans cell histiocytosis, which has its own page.
Treatment was transformed by targeted therapy. Interferon alfa was the previous first line for ECD. Vemurafenib produced responses in essentially every BRAF-mutant ECD patient in the VE-BASKET trial, leading to FDA approval in November 2017, the first approval for any histiocytosis. Cobimetinib, a MEK inhibitor, gave responses regardless of mutation status in a phase 2 trial (Diamond and colleagues, Nature Medicine 2019) and was FDA-approved in October 2022 for adult histiocytic neoplasms including ECD, RDD and LCH. Responses are deep and durable but relapse follows discontinuation in most patients, so therapy is often prolonged at reduced doses. Rosai-Dorfman disease is observed if asymptomatic, and treated with surgery, steroids, sirolimus, cladribine or MEK inhibitors when it causes harm. Histiocytic sarcoma is treated with lymphoma-type chemotherapy, radiotherapy and, increasingly, MAPK-pathway inhibitors. Mixed ECD-LCH and the neurodegenerative complications of both are the hardest problems.
International consensus recommendations for ECD (Blood 2020) and the Histiocyte Society trials network coordinate care and research.
Erdheim-Chester disease has been described in only a few thousand patients worldwide, mostly adults in their fifties and sixties; Rosai-Dorfman disease and histiocytic sarcoma are similarly rare (Histiocyte Society registries).
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, Langerhans cell histiocytosis (LCH), 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.
Vemurafenib (FDA approval 2017) or dabrafenib, often with a MEK inhibitor to reduce toxicity; long-term treatment at the lowest effective dose.
Cobimetinib (FDA approval October 2022 for histiocytic neoplasms) or another MEK inhibitor; interferon alfa or pegylated interferon as an alternative.
Observation for asymptomatic nodal disease; surgery for isolated masses; steroids, sirolimus, cladribine or MEK inhibitors for symptomatic or multifocal disease.
Lymphoma-type chemotherapy (CHOP, ICE, or similar), radiotherapy for localised disease, MAPK-pathway inhibitors where mutations are found; clinical trials.
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Query for this cancer: (TITLE:"Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms" OR ABSTRACT:"Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms" OR TITLE:"ECD" OR ABSTRACT:"ECD" OR TITLE:"Erdheim-Chester disease" OR ABSTRACT:"Erdheim-Chester disease" OR TITLE:"Rosai-Dorfman disease" OR ABSTRACT:"Rosai-Dorfman disease" OR TITLE:"RDD" OR ABSTRACT:"RDD" OR TITLE:"Rosai-Dorfman-Destombes disease" OR ABSTRACT:"Rosai-Dorfman-Destombes disease") AND (treatment OR therapy OR trial OR survival OR diagnosis). Results are unfiltered search hits about Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, not a curated reading list.
Destombes had reported cases in 1965.
Haroche and colleagues (Blood 2012) after Badalian-Very's LCH discovery (2010).
L, C, R, M and H groups (Emile et al., Blood 2016).
First approval for any histiocytosis (VE-BASKET); November 2017.
Diamond and colleagues, Nature Medicine 2019.
FDA approval October 2022 for adults with ECD, RDD and LCH.
The targets of this cancer's medicines and the ones linked to it directly.
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.
One section per setting: the options named, what each is for, the trials behind them, the recorded trade-offs and the questions to ask.
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.
Cumulative dose: risk rises steeply above 400-550 mg/m² (see the anthracycline calculator).
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.
See all on the product pages:CladribineCobimetinibCyclophosphamideDabrafenib + trametinibDoxorubicinEtoposideVemurafenib·Printable cards in the navigator
Newly diagnosed? Read the first 60 days with Erdheim-Chester disease, Rosai-Dorfman disease and other histiocytic neoplasms, then print the one-page appointment sheet with room for the answers.
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Everything in development, the medicines held by this cancer's subtypes, the open problems and what is being done about them, the roadmaps, and what changed on this record.
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