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

Abstract

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. The aim of our study was to identify and characterize bone marrow MC histopathologic features specific for MCAS-T. 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. Asubgroup of patients was available for tryptase genotyping. 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). Atotal 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. 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.