History
Patients with systemic mastocytosis (systemic mast cell disease) can have signs and symptoms related to involvement of the hematopoietic system, the gastrointestinal (GI) tract, the skin, and the immune system. Additional coexistent hematologic disorders may also be a source of clinical manifestations. Systemic mastocytosis is known to be associated with a number of other hematologic diseases, including the following:
The incidence of various symptoms reported in one of the largest case series of systemic mastocytosis is as follows [8] :
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GI symptoms - 65%
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Cutaneous symptoms - 53%
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Mediator-related symptoms - 47%
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Constitutional complaints - 42%
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Urticaria pigmentosa - 41%
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Musculoskeletal symptoms - 31%
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Idiopathic and/or recurrent anaphylactoid reactions - 17%
Many GI manifestations are observed in patients with systemic mastocytosis. Abdominal pain is the most common GI symptom, followed, by diarrhea, nausea, and vomiting. Symptoms and signs of gastroesophageal reflux disease (GERD) and malabsorption are noted in some patients. Duodenal ulceration and severe duodenitis is seen in 30% to 50% of untreated cases. [26]
Some studies show precipitation of GI manifestations by agents such as penicillin, narcotics, cocaine, aspirin, [35] nonsteroidal anti-inflammatory drugs (NSAIDs), and dipyridamole (Persantine). These drugs can also provoke anaphylaxis, vascular collapse, or syncope.
Pruritus seem to be as common as GI complaints in patients with systemic mastocytosis. Patients may present with pruritus and flushing if their mastocytosis is associated with cutaneous abnormalities.
While the risk of recurrent anaphylactoid reaction is well known, it appears that the association with Hymenoptera (eg, bee, wasp) stings is stronger than the association with other food- and drug-induced systemic reactions. [4]
Caution during anesthesia in the endoscopic and surgical suites is advised. Rare anaphylactoid reactions to intravenous contrast have been reported. [5]
Anemia and coagulopathy (eg, acquired von Willebrand syndrome [36] ) may be observed.
Physical Examination
Physical examination findings in patients with systemic mastocytosis (systemic mast cell disease) may include the following:
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Signs of anemia, such as pallor, can be noted in some patients.
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Hepatomegaly (27%), splenomegaly (37%), and lymphadenopathy (21%) can be found in adult patients. [8]
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GI bleeding may be present; contributing factors may include thrombocytopenia caused by splenomegaly, hypersplenism, and a rise in portal pressure; heparin release from mucosal mast cells; and vitamin K malabsorption resulting from mast cell involvement.
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Patients may have signs of urticaria (41%) if the mastocytosis is associated with cutaneous involvement; in these situations, flushing can be noted upon physical examination.
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Osteolysis and pathological fractures are rarely noted (7%).
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Systemic mastocytosis. Bone marrow aspirate, Romanowsky stain, high-definition magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cells. This is a bone marrow smear from a patient with systemic mastocytosis. Several mast cells are present in this photograph. These mast cells are larger than normal mast cells and have more irregularly shaped nuclear outlines and less densely packed mast cell granules. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
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Systemic mastocytosis. Bone marrow aspirate, toluidine stain, low magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cells. This is a toluidine blue stain of a bone marrow smear from a patient with marrow involvement by systemic mastocytosis. Five mast cells are present in this field. The mast cell granules are metachromatic with the toluidine blue reaction. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
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Systemic mastocytosis. Bone marrow biopsy, toluidine stain, low magnification. Diagnosis is mastocytosis, and morphology is abnormal mast cell infiltrate. This is a toluidine blue stain of a bone marrow biopsy from a patient with systemic mastocytosis. The mast cells are metachromatic with toluidine blue and contain numerous purple granules. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
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Systemic mastocytosis. Lymph node biopsy. Diagnosis is mastocytosis, morphology is mast cell infiltrate, and the organ is the lymph nodes. This is a lymph node biopsy from a person with systemic mastocytosis. The mast cells have a characteristic perifollicular distribution. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
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Systemic mastocytosis. Lymph node biopsy, chloroacetate esterase stain. Diagnosis is mastocytosis, and morphology is mast cell infiltrate. This is a portion of a lymph node biopsy from a patient with systemic mastocytosis. The mast cells are chloroacetate esterase positive, which is characterized by an orange granular appearance. Courtesy of the American Society of Hematology Slide Bank. Used with permission.
Tables
| Criteria | WHO | ICC |
|---|---|---|
| Major Criterion | Presence of multifocal and dense infiltrates of mast cells in bone marrow or in other extracutaneous tissues. Mast cells should be seen in aggregates of 15 cells or more. | Presence of multifocal dense infiltrates of tryptase- and/or CD117 positive mast cells detected in bone marrow or in other extracutaneous tissues. Mast cells should be seen in aggregates of 15 cells or more. |
Minor Criteria |
Spindle shape or atypical mast cell morphology (type I or type II) in 25% or more of the mast cells in biopsy sections of bone marrow or other extracutaneous organs | Spindle shaped or atypical immature morphology in more than 25% of mast cells in biopsy sections of bone marrow or other extracutaneous organs |
| Minor Criteria | Presence KIT-activating KIT point mutation(s) at codon 816 or in other critical regions of KIT in bone marrow or another extracutaneous organ |
Presence of KIT D816V mutation or other activating KIT mutation in bone marrow, peripheral blood, or other extracutaneous organs |
| Minor Criteria | Expression of CD25 and/or CD2 and/or CD30 in addition to normal mast cell markers |
Expression of CD25 and/or CD2 and/or CD30 in addition to normal mast cell markers |
| Minor Criteria | Serum/plasma total tryptase levels persistently greater than 20 ng/mL | Serum tryptase level persistently greater than 20 ng/mL. In cases of SM-AMN an elevated tryptase does not count as a SM minor criterion. |
