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Updated: Nov 28, 2025
Author Spotlight: Analyzing Bone Marrow Microenvironment in Murine Hematological Malignancies
Published on: November 10, 2023
Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow
Matthew P Giannetti1, Cem Akin2, Raied Hufdhi3
1Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
Background:
Patients with mast cell (MC) activation symptoms and elevated baseline serum tryptase level (MCAS-T) may not necessarily have a clonal MC disorder. Many are diagnosed with hereditary α-tryptasemia (HαT), a genetic trait characterized by autosomal dominant inheritance of multiple copies of TPSAB1 encoding α-tryptase and increased risk for severe anaphylaxis.
Objective:
The aim of our study was to identify and characterize bone marrow MC histopathologic features specific for MCAS-T.
Methods:
A total of 43 patients with MCAS-T underwent evaluation, including bone marrow biopsy, for a MC disorder. The results of the work-up for clonal MC disorders such as systemic mastocytosis and monoclonal MC activation syndrome were negative. Bone marrow MC histopathology was reviewed to identify characteristic features of MCAS-T. A subgroup of patients was available for tryptase genotyping.
Results:
Patients with MCAS-T showed unique morphologic and histologic features when compared with controls. MCs were larger (P < .01), hypogranular (P < .01), frequently detected in paratrabecular (P < .05) and perivascular (P < .01) locations, and associated with bone marrow eosinophilia (P < .01). A total of 10 patients who were available for tryptase genotyping were all confirmed to have HαT. This subgroup was representative of the larger MCAS-T cohort.
Conclusion:
We report unique bone marrow MC phenotypic and histopathologic changes in patients with MCAS-T. These morphologic changes are associated with an elevated tryptase level that has been confirmed to be caused by HαT in all patients available for testing.
