Can a bone biopsy be used to diagnose mast cell activation syndrome (MCAS)?

Bone Biopsy for MCAS Diagnosis

Bone marrow biopsy is NOT required to diagnose mast cell activation syndrome (MCAS), but it IS indicated when baseline serum tryptase is persistently >20 ng/mL or when clinical features suggest an underlying clonal mast cell disorder that needs to be excluded. 1, 2

Understanding the Role of Bone Marrow Biopsy in Mast Cell Disorders

The diagnostic approach differs fundamentally between systemic mastocytosis (SM) and MCAS:

For Systemic Mastocytosis

• Bone marrow biopsy is the gold standard for diagnosing SM, providing detection of multifocal dense mast cell infiltrates (≥15 mast cells in aggregates), immunohistochemistry with CD117, CD25, and tryptase, flow cytometry for aberrant CD25 and CD2 expression, and KIT D816V mutation analysis 1
• SM requires meeting WHO criteria: 1 major criterion plus 1 minor criterion, OR ≥3 minor criteria 3

For MCAS Diagnosis

MCAS is diagnosed clinically and biochemically WITHOUT requiring bone marrow biopsy in most cases 4

The three essential diagnostic criteria for MCAS are:

• Clinical symptoms: Episodic signs affecting ≥2 organ systems concurrently (cardiovascular, dermatologic, respiratory, gastrointestinal) 4, 2
• Laboratory evidence: Acute serum tryptase elevation of ≥20% above baseline PLUS ≥2 ng/mL, measured 1-4 hours after symptom onset 1, 2
• Treatment response: Improvement with medications blocking mast cell mediators 2

When Bone Marrow Biopsy IS Indicated for Suspected MCAS

Proceed to bone marrow evaluation when:

• Baseline serum tryptase persistently >20 ng/mL 1, 2
• Clinical features suggest systemic mastocytosis (skin lesions, organomegaly, abnormal blood counts) 2
• Need to distinguish clonal from non-clonal mast cell disorders 1
• High mast cell clonality prediction score 5

What the Bone Marrow Biopsy Reveals in MCAS Patients

Critical distinction: Patients with MCAS-T (MCAS with elevated baseline tryptase) show unique bone marrow findings that differ from both SM and normal controls:

• Larger mast cells with hypogranular appearance 6
• Paratrabecular and perivascular mast cell location 6
• Associated bone marrow eosinophilia 6
• However, these patients do NOT meet WHO criteria for SM (no multifocal dense infiltrates of ≥15 mast cells, negative for clonal markers) 6

Many of these patients have hereditary alpha-tryptasemia (HαT), which explains the elevated baseline tryptase without clonal disease 6

Practical Diagnostic Algorithm

Initial workup for suspected MCAS (no bone marrow biopsy needed):

1. Baseline serum tryptase when asymptomatic 1, 2
2. Acute serum tryptase 1-4 hours after symptom onset 1, 2
3. 24-hour urine for N-methylhistamine, 11β-PGF2α, and LTE4 1, 7
4. Complete blood count and peripheral smear 1

Add peripheral blood KIT D816V testing by ASO-qPCR if:

• Baseline tryptase >20 ng/mL 1, 2
• Clinical suspicion for clonal disease 2

Proceed to bone marrow biopsy only if:

• Baseline tryptase persistently >20 ng/mL 1, 2
• Positive peripheral blood KIT D816V 1
• Adult-onset skin lesions suggestive of mastocytosis 2

Common Pitfalls to Avoid

Do not order bone marrow biopsy routinely for MCAS diagnosis - this is a common overuse of invasive testing 4

Do not confuse elevated baseline tryptase alone as requiring bone marrow biopsy - first consider hereditary alpha-tryptasemia (TPSAB1 testing via buccal swab) 1, 2

Do not rely on bone marrow biopsy to diagnose MCAS - the diagnosis is made by documenting episodic mast cell mediator release during symptomatic episodes, not by tissue examination 4

Timing is critical: Acute tryptase must be drawn 1-4 hours after symptom onset and compared to baseline - this is far more diagnostically useful than bone marrow examination for MCAS 1, 2