For MCAS:

The following three general diagnostic criteria are relevant in MCAS. Note that for a variety of reasons, many successful patients will never meet the third criteria. Diagnosis on the basis of the first two is most common.

1. The patient presents with otherwise unexplained symptoms consistent with a mast cell disorder in more than one organ system (see checklist). Other potential causes for these symptoms have been responsibly investigated (see initial testing recommendations).

2. The patient experiences a reduction in symptoms from mast cell treatment.

3. The patient's laboratory work confirms elevations in mast cell mediators in one of the following ways*

A) with the elevation of one or more mediators in blood or urine (see mediator testing), or

B) with an increase from the patient's baseline serum tryptase level of 20% +2 ng/ml during a period of increased symptoms.

*When relying on mediator testing, it is important to note how few mast cell mediators we are currently able to test at all (of several hundred known chemicals), the prevalence of false negative results, and the uncommon challenges of handling these specimens properly to increase the likelihood of their producing more accurate results. Mediators degrade very quickly. Additionally, one challenge with tryptase increases is that of identifying the patient's baseline level, as there's evidence to suggest that tryptase may remain elevated for up to two weeks after a reaction.

For Systemic Mastocytosis:

Patients must meet the major and one minor criterion or three minor criteria.

Major criterion:

Multifocal dense infiltrates of mast cells (15 or more in aggregate) detected in sections of bone marrow (typically excepting the GI tract due to a number of other and more common causes for infiltrates here; bone marrow is preferred)

Minor criteria:

A) In biopsy sections, more than 25% of mast cells in infiltrated space are spindle-shaped or otherwise morphologically abnormal or immature.

B) Detection of CKIT mutation at codon 816 in bone marrow, blood, or extracutaneous organ

C) Mast cells in bone marrow, blood, or extracutaneous organ that co-express CD-117 and CD2 and/or CD25

D) Baseline serum tryptase of 20 ng/mL or higher.*

Typing*:

Indolent Systemic Mastocytosis accounts for roughly 90% of all identified systemic mastocytosis cases. ISM is diagnosed when a patient meets the above criteria for diagnosis but does not meet the criteria for the types below. ISM has been found to have a higher prevalence of urticaria pigmentosa-like skin lesions (66-75%) and is less likely to produce constitutional symptoms or hepatosplenomegaly.

Smoldering Systemic Mastocytosis patient meets the above criteria in addition to at least two of the following:

A) Increased mast cell burden (>30% focal, dense mast cell aggregates on bone marrow biopsy and serum tryptase >200 ng/mL

B) Myeloproliferation or myleodysplasia dysplasia in absence of myelodysplastic syndrome or myeloproliferative neoplasm.

C) Organ swelling on palpitation without deficit of organ function (hepatomegaly without ascites, palpable splenomegaly or lymphadenopathy)

Aggressive Systemic Mastocytosis patient meets the above criteria in addition of one of the following and does not meet the criteria for mast cell leukemia:

A) Cytopenias (absolute neutrophil count < 1000/ul, hemoglobin <10 g/dL, platelets <100,000/ul)

B) Hepatomegaly on palpitation with impairment of liver function, ascites, and/or portal hypertension

C) Palpable splenomegaly with hypersplenism

D) Low albumin and weight loss from GI mast cell infiltrates

E) Large osteolysis and/or severe osteoporosis and pathologic fractures (two or more fractures as a direct result of mast cell activity).

Systemic Mastocytosis with Associated Hematologic Neoplasm patients meet criteria for SM and also for a WHO-defined hematologic neoplasm

*A note on SM progression:

Studies have suggested that perhaps 3% (newer data) to 8% of patients with ISM will “progress” to other forms of SM, and between 1.2% (newer data) and 4% may eventually progress to ASM. (Many monitor tryptase elevations with periodic testing.) Many cases of ISM are also found in entirely asymptomatic patients for whom these biopsies are ordered for other reasons, and as such, ISM may well account for a much greater percentage than the roughly 90% of SM cases currently proposed.

A note on prevalence:

The prevalence of SM is currently estimated to be 1 in roughly 10,000. The prevalence of ASM is estimated to be 1-2 in a million/year. The prevalence of MCAS, however, is much higher, estimated in 2020 at 17% of the population, or 1 in 5 or 6.