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Published on: May 27, 2015
Clonal Mast Cell Disorders and Mutation Profile in Adults Initially Presenting with Mast Cell Activation
Patchara Pornsuthirat1, Weerapat Owattanapanich2, Chamard Wongsa1,3
1Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Purpose:
To compare the diagnostic yield, clinical, and molecular features of clonal mast cell disorders (CMCDs) in adults presenting with mast cell activation (MCA)/anaphylaxis versus non-anaphylactic phenotypes in a joint Allergy-Hematology cohort.
Patients And Methods:
In this single-center retrospective study, we reviewed clinician-selected adults (≥18 years) evaluated at a Thai tertiary center (2019-2024) who completed joint Allergy-Hematology evaluation and targeted 66-gene myeloid next-generation sequencing (NGS). Index presentations were classified as MCA/anaphylaxis versus non-MCA. Final diagnoses followed WHO 5th/International Consensus Classification criteria.
Results:
Of 24 sequenced adults, 14 (58.3%) had MCA/anaphylaxis and 10 (41.7%) had non-MCA presentations. Among sequenced MCA/anaphylaxis presentations, final diagnoses included idiopathic anaphylaxis (IA, n=11), secondary anaphylaxis (n=2), and systemic mastocytosis (SM, n=1). Conversely, all 10 non-MCA cases had CMCD (SM 6, cutaneous mastocytosis 4). Compared to non-mastocytosis cases, mastocytosis patients were older, predominantly male, with higher basal tryptase (median 22.4 vs 3.2 ng/mL). Pathogenic variants occurred in 12/24 (50%) patients: KIT D816V in 6/24 (25%), with heterogeneous TET2 co-mutations, DNMT3A R882H, and SRSF2 P95 hotspots clustering in SM. IA rarely harbored driver mutations.
Conclusion:
CMCD showed a low diagnostic yield (1/14, 7.1%) in the clinician-selected MCA/anaphylaxis subgroup escalated to marrow/NGS, but was universal in the hematologic non-MCA subset (10/10, 100%). These findings suggest that REMA-based, risk-stratified selection may be useful in this setting, but larger prospective studies are needed. While TET2 was the most frequently mutated gene overall, the mutational profile within the SM subgroup-characterized by KIT D816V and frequent TET2, DNMT3A, and SRSF2 co-mutations-parallels established molecular signatures in Western systemic mastocytosis cohorts, suggesting KIT-targeted therapies are biologically applicable in Thai patients.
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