What blood tests are used to diagnose systemic mastocytosis?

Blood Tests for Systemic Mastocytosis

The primary blood test for diagnosing systemic mastocytosis is serum tryptase measurement, which should be performed in all patients with suspected mastocytosis, followed by molecular testing for KIT D816V mutation in peripheral blood when tryptase is elevated (>15 ng/mL). 1

Initial Diagnostic Approach

Serum Tryptase Testing

• Normal range: 1-15 ng/mL 2
• Persistently elevated serum tryptase (>20 ng/mL) is a minor criterion for systemic mastocytosis diagnosis 1
• Important considerations:
  • Tryptase may be transiently elevated during anaphylaxis or severe allergic reactions
  • Elevated levels can occur in other myeloid malignancies and hereditary alpha-tryptasemia
  • Some patients with systemic mastocytosis may have normal tryptase levels 1

KIT D816V Mutation Testing

• Should be performed using allele-specific quantitative PCR (ASO-qPCR) in peripheral blood when:
  • Serum tryptase >15 ng/mL, or
  • Strong clinical suspicion despite normal tryptase 1
• Positive KIT D816V mutation in peripheral blood strongly supports diagnosis and indicates need for bone marrow evaluation 1

Complete Blood Count with Differential

• Essential for screening for associated hematologic abnormalities
• Look for:
  • Monocytosis
  • Eosinophilia
  • Dysplasia
  • Cytopenias (may indicate advanced disease) 1

Additional Blood Tests

• Comprehensive metabolic panel with:
  • Uric acid
  • Lactate dehydrogenase (LDH)
  • Liver function tests 1
• Blood smear examination 1

Diagnostic Algorithm

1. Initial screening:

   • Serum tryptase measurement
   • KIT D816V mutation testing in peripheral blood (if tryptase >15 ng/mL)

2. If serum tryptase >20 ng/mL OR KIT D816V positive in peripheral blood:

   • Proceed to bone marrow biopsy and aspiration

3. If serum tryptase <15 ng/mL AND KIT D816V negative in peripheral blood:

   • Follow up the patient
   • Consider bone marrow evaluation only if tryptase increases or clinical symptoms/signs of mastocytosis develop 1

Bone Marrow Evaluation

While not a blood test, bone marrow evaluation is the definitive diagnostic procedure for systemic mastocytosis when blood tests suggest the diagnosis. This should include:

• Bone marrow aspirate and biopsy with:
  • Flow cytometry: CD34, CD117, CD25, CD2 (CD30 optional)
  • Immunohistochemistry: CD117, CD25, tryptase (CD30 optional)
  • Cytogenetics
  • FISH for associated hematologic neoplasm-related abnormalities
  • Molecular testing for KIT D816V by allele-specific PCR
  • Myeloid mutation panel (e.g., SRSF2, ASXL1, RUNX1) 1

Common Pitfalls

• Relying solely on serum tryptase: Some patients with systemic mastocytosis may have normal tryptase levels 1
• Misinterpreting transient tryptase elevations: Tryptase may be elevated during anaphylaxis or allergic reactions 1
• Overlooking bone marrow tryptase: Bone marrow tryptase levels >50 μg/L have shown 93% sensitivity and 90% specificity for systemic mastocytosis diagnosis 3
• Missing hereditary alpha-tryptasemia: This genetic condition can cause baseline tryptase elevation (typically >8 ng/mL) and mastocytosis-like symptoms 4
• Failing to repeat tryptase measurements: Comparing acute and baseline values is important to distinguish between transient elevation and persistent elevation 4

By following this systematic approach to blood testing, clinicians can effectively screen for systemic mastocytosis and determine when bone marrow evaluation is necessary for definitive diagnosis.