Matthew P Giannetti1, Cem Akin2, Raied Hufdhi3, Matthew J Hamilton4, Emily Weller5, Bjorn van Anrooij6, Jonathan J Lyons7, Jason L Hornick8, Geraldine Pinkus8, Mariana Castells9, Olga Pozdnyakova8. 1. Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass. Electronic address: mgiannetti@bwh.harvard.edu. 2. Division of Allergy and Immunology, University of Michigan, Ann Arbor, Mich. 3. Department of Medicine, University of Toledo, Toledo, Ohio. 4. Harvard Medical School, Boston, Mass; Division of Gastroenterology, Endoscopy, and Hepatology, Brigham and Women's Hospital, Boston, Mass. 5. Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass. 6. Department of Allergology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. 7. Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md. 8. Harvard Medical School, Boston, Mass; Department of Pathology, Brigham and Women's Hospital, Boston, Mass. 9. Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass; Harvard Medical School, Boston, Mass.
Abstract
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.
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.
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