Systemic type characterized by infiltration of tissues by neoplastic mast cells.

A rare, heterogeneous disease caused by uncontrolled proliferation and accumulation of neoplatic mast cells.

Aggressive systemic mastocytosis, systemic mastocytosis with associated hematologic neoplasm, mast cell leukemia are considered advanced forms of systemic mastocytosis.

A rare myeloproliferative neoplasm, estimated to affect about 10 in 100,000 people.

Mast cells are granulocytes that play a critical role in immune responses, especially allergy and anaphylaxis, so their pathologic proliferation can result in a wide array of clinical presentations.

Systemic type associated with bone marrow, liver, spleen, and skin infiltration.

Systemic mastocytosis is an abnormal proliferation of mast cells that subsequently invades various organs and releases cellular mediators, such as interleukins and histamine, which results in systemic symptoms including headache, urticaria, diarrhea, flushing, and anaphylaxis.

In contrast to in the indolent variants the prognosis of advanced systemic mastocytosis is poor with an estimated median overall survival of 3 1/2 years with the above aggressive variant, and as little as 6 months with mast cell leukemia.

Systemic type associated with bone pain, cytopenias, pathologic bone fractures, rash, urticaria, diarrhea, nausea, hypotension, flushing and rarely anaphylaxis.

Symptoms are caused by the release of vasoactive vessel mediators and by organ damage from mast cell infiltration.

Clinical manifestations of organ infiltration include cytopenias, skeletal lesions, hepato-megaly, liver function impairment, portal hypertension, splenomegaly, hypersplenism, and weight loss due to gastrointestinal involvement.

Leukemic transformation can occur.

Emotional distress is the most common trigger of symptoms in systemic disease.

High clinical suspicion is the cornerstone of diagnosis.

Serum tryptase often elevated.

Biopsy of the bone marrow often required for diagnosis, and shows clusters of mast cells which stain positively for tryptase and CD117.

In the majority of patients the somatic KIT point mutation D1816V is detectable in mast cells.

Bone marrow evaluation may indicate the presence of coexistent disease including myelodysplasia, eosinophilia, and fibrosis.

Four types of systemic disease: 1-indolent, without end-organ damage, 2-aggressive, manifested by hepatosplenomegaly, cytopenias, and bone disease, 3-systemic mastocytosis associated with a hematological disorder and 4-mast cell-leukemia/sarcoma.

Most cases of systemic disease are indolent and the next most common type of systemic disease is associated with a hematological disorder.

Mast cell degranulation can occur with release of mast cell mediators such as histamine with flushing palpitations headache nausea and syncope, suggesting prominent vasodilatation as a result.

Cortical troponin-releasing hormone that is released under distress can activate mast cells

In aggressive systemic mastocytosis and in mast cell leukemia response to conventional therapy is poor and prognosis grave.

Treatment aimed at preventing mast cell degranulation by avoiding hot showers, physical trauma, adding antihistamines, cromolyn sodium, and having epinephrine injections and corticosteroid preparations easily available.

Patients with systemic mastocytosis associated with eosinophilia have a tyrosine kinase created from a fusion of PDGFRA and FIL1L1 genes, and such patients respond to low dose imatinib.

Patients may respond to alpha-interferon, and cladibrine.

Cutaneous type indicates skin-limited disease.

Subtypes of cutaneous mastocytosis include urticaria pigmentosa, telangiectasia macularis eruptiva perstans, mastocytoma, and diffuse cutaneous mastocytosis.

Imatinib is approved for adult aggressive systemic mastocytosid for aggressive systemic mastocytosis but is only relevant for 10% of such cases.

Avapritinib is a new standard of care for patients with advanced systemic mastocytosis: robust and durable responses, including complete remissions, and a favorable safety profile.


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