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Aggressive systemic mastocytosis
Aggressive systemic mastocytosis (ASM) is a severe and rare form of systemic mastocytosis (SM) characterized by considerable infiltration of mast cells in different tissues.
- Synonym(s): -
- Prevalence: 1-9 / 1 000 000
- Inheritance: Not applicable
- Age of onset: Adult
- ICD-10: C96.2
- OMIM: -
- UMLS: C1112486
- MeSH: -
- GARD: -
- MedDRA: 10056453
It represents less than 10% of cases of SM and the global prevalence is estimated in the order of between 1/400,000 and 1/250,000.
ASM doesn't usually develop in children. Cutaneous involvement is normally absent. Patients present with severe symptoms related to mast cell invasion and the intense release of mediators including syncope, recurrent flushing, diarrhea, pain, organomegaly and organ dysfunction, impairment of hematopoietic function (which may result in disruption of the blood count ranging from isolated cytopenia to more or less marked pancytopenia), bone involvement in the form of osteoporosis with the risk of fracture, and malabsorption. The most serious complication of ASM is potentially fatal anaphylactic shock. Patients do not show signs of non mast cell hematological disease.
The etiology of ASM is not well understood but there is evidence of an activating mutation of KIT, usually D816V, in the mast cells of the vast majority of patients with ASM.
Diagnosis is based on histological and cytological analysis of bone marrow. Cytological analysis reveals a proportion of bone marrow mast cells greater than 5% but less than 20% and, in most cases of ASM, bone marrow mast cells have an atypical immature appearance with a bi or multi-lobed core or, sometimes, a blast-like morphological appearance. Measurement of serum tryptase shows values consistently above 20ng/mL, and the search for activating mutations of KIT is positive in the vast majority of cases.
Differential diagnoses include all causes of cytopenias (myelofibrosis, myelodysplasia and other hematological malignancies; see these terms) and other abnormal types of mutation in JAK2, that are excluded by the detection of bone marrow infiltration by mast cells with an activation mutation of KIT.
Management and treatment
Treatment is partly symptomatic, mainly involving antihistamines (anti-H1 and anti-H2) and partly antiproliferative (interferon alpha with or without corticosteroid therapy using cladribine). For the few cases without the D816V KIT mutation, imatinib mesylate or masitinib can be used because they inhibit the non-mutated form of KIT. Molecules inhibiting the mutated D816V form are currently being studied in clinical trials and other therapeutic approaches (including using rapamycin, bortezomib or thalidomide) have been proposed. The use of iodinated contrast agents should be limited because they induce a massive release of mast cell mediators.
The prognosis is poor with a median survival of 2 to 4 years.
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