{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:02:02Z","timestamp":1784224922174,"version":"3.55.0"},"reference-count":20,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,3,21]],"date-time":"2016-03-21T00:00:00Z","timestamp":1458518400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005677","name":"Jos\u00e9 Carreras Leuk\u00e4mie-Stiftung","doi-asserted-by":"publisher","award":["DJCLS H 11\/03"],"award-info":[{"award-number":["DJCLS H 11\/03"]}],"id":[{"id":"10.13039\/501100005677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005677","name":"Jos\u00e9 Carreras Leuk\u00e4mie-Stiftung","doi-asserted-by":"publisher","award":["13\/05"],"award-info":[{"award-number":["13\/05"]}],"id":[{"id":"10.13039\/501100005677","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["SFB F4704\u2010B20"],"award-info":[{"award-number":["SFB F4704\u2010B20"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Eur J Clin Investigation"],"published-print":{"date-parts":[[2016,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bone marrow (<jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content>) histology\/immunohistochemistry, <jats:italic><jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content><\/jats:italic> D816V mutation analysis and serum tryptase measurements are mandatory tools for diagnosis of systemic mastocytosis (<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Within the \u2018German Registry of Disorders on Eosinophils and Mast Cells\u2019, we identified 65 patients with <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> who had two consecutive <jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content> biopsies. The first biopsy was evaluated by a local pathologist (<jats:styled-content style=\"fixed-case\">LP<\/jats:styled-content>) and the second biopsy by a reference pathologist (<jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content>) of the \u2018European Competence Network on Mastocytosis (<jats:styled-content style=\"fixed-case\">ECNM<\/jats:styled-content>)\u2019.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Final diagnoses by <jats:styled-content style=\"fixed-case\">RP<\/jats:styled-content> were <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> (<jats:italic>n<\/jats:italic> = 27), <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> or aggressive <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> (<jats:styled-content style=\"fixed-case\">ASM<\/jats:styled-content>) with associated clonal haematological non\u2010mast cell lineage disease [(A)<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">AHNMD<\/jats:styled-content>,<jats:italic> n<\/jats:italic> = 34)] or mast cell leukaemia \u00b1 <jats:styled-content style=\"fixed-case\">AHNMD<\/jats:styled-content> (<jats:italic>n<\/jats:italic> = 4). In 15 of 65 patients (23%), initial diagnoses by <jats:styled-content style=\"fixed-case\">LP<\/jats:styled-content> were incorrect (by overlooking <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>), for example primary myelofibrosis (<jats:italic>n<\/jats:italic> = 3), myelodysplastic\/myeloproliferative neoplasm unclassified (<jats:italic>n<\/jats:italic> = 3) or B\u2010cell lymphoma (<jats:italic>n<\/jats:italic> = 2). Fourteen of 15 patients (93%) with incorrect diagnosis had an advanced <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>, mostly (A)<jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">AHNMD<\/jats:styled-content>. In the 50 concordantly diagnosed patients, immunohistochemical markers for quantitative assessment of mast cell infiltration, for example <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>117 (<jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content>) or <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>25, were applied by <jats:styled-content style=\"fixed-case\">LP<\/jats:styled-content> in only 34 of 50 patients (68%), and mutational analysis for <jats:italic><jats:styled-content style=\"fixed-case\">KIT<\/jats:styled-content><\/jats:italic> D816V was performed or recommended in only 13 of 50 patients (26%). Finally, the subclassification of <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> was discordant because <jats:styled-content style=\"fixed-case\">LP<\/jats:styled-content> did not diagnose <jats:styled-content style=\"fixed-case\">AHNMD<\/jats:styled-content> in nine of 50 (18%) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In summary, adequate diagnosis and subclassification of <jats:styled-content style=\"fixed-case\">SM<\/jats:styled-content> requires an in\u2010depth evaluation of the <jats:styled-content style=\"fixed-case\">BM<\/jats:styled-content> by experienced haematopathologists (preferably in a reference centre) in combination with molecular genetics, serum tryptase level and clinical 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