Patients with mast cell activation symptoms and elevated baseline serum tryptase level have unique bone marrow morphology

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 a-tryptasemia (HaT), a genetic trait characterized by autosomal dominant inheritance of multiple copies of TPSAB1 encoding a-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 HaT. 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 HaT in all patients available for testing. (J Allergy Clin Immunol 2021;147:1497-501.