title: Impact of centralized evaluation of bone marrow histology in systemic mastocytosis.
abstract: BACKGROUND
  Bone marrow (BM) histology/immunohistochemistry, KIT D816V mutation analysis and serum tryptase measurements are mandatory tools for diagnosis of systemic mastocytosis (SM).
  
  
  METHODS
  Within the 'German Registry of Disorders on Eosinophils and Mast Cells', we identified 65 patients with SM who had two consecutive BM biopsies. The first biopsy was evaluated by a local pathologist (LP) and the second biopsy by a reference pathologist (RP) of the 'European Competence Network on Mastocytosis (ECNM)'.
  
  
  RESULTS
  Final diagnoses by RP were SM (n = 27), SM or aggressive SM (ASM) with associated clonal haematological non-mast cell lineage disease [(A)SM-AHNMD, n = 34)] or mast cell leukaemia ± AHNMD (n = 4). In 15 of 65 patients (23%), initial diagnoses by LP were incorrect (by overlooking SM), for example primary myelofibrosis (n = 3), myelodysplastic/myeloproliferative neoplasm unclassified (n = 3) or B-cell lymphoma (n = 2). Fourteen of 15 patients (93%) with incorrect diagnosis had an advanced SM, mostly (A)SM-AHNMD. In the 50 concordantly diagnosed patients, immunohistochemical markers for quantitative assessment of mast cell infiltration, for example CD117 (KIT) or CD25, were applied by LP in only 34 of 50 patients (68%), and mutational analysis for KIT D816V was performed or recommended in only 13 of 50 patients (26%). Finally, the subclassification of SM was discordant because LP did not diagnose AHNMD in nine of 50 (18%) patients.
  
  
  CONCLUSIONS
  In summary, adequate diagnosis and subclassification of SM requires an in-depth evaluation of the BM by experienced haematopathologists (preferably in a reference centre) in combination with molecular genetics, serum tryptase level and clinical parameters.
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Mohamad
authors.initials: M
authors.lastname: Jawhar
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Juliana
authors.initials: J
authors.lastname: Schwaab
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Horny
authors.affiliation: Institute of Pathology, Ludwig-Maximilians-University, Munich, Germany.
authors.forename: Karl
authors.initials: K
authors.lastname: Sotlar
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Nicole
authors.initials: N
authors.lastname: Naumann
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Fabarius
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Wessex Regional Genetics Laboratory, Salisbury, UK.|Faculty of Medicine, University of Southampton, Southampton, UK.
authors.forename: Nicholas C P
authors.initials: NC
authors.lastname: Cross
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Georgia
authors.initials: G
authors.lastname: Metzgeroth
authors.affiliation: Department of Hematology and Oncology, University Medical Centre Mannheim, Mannheim, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reiter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow / Q000473:pathology*; D004252:DNA Mutational Analysis; D003951:Diagnostic Errors; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D007946:Leukemia, Mast-Cell / Q000175:diagnosis / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000175:diagnosis; D008297:Male; D034721:Mastocytosis, Systemic / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008875:Middle Aged; D009154:Mutation; D009190:Myelodysplastic Syndromes / Q000175:diagnosis; D009196:Myeloproliferative Disorders / Q000175:diagnosis; D010338:Pathology, Clinical / Q000458:organization & administration* / Q000592:standards; D055728:Primary Myelofibrosis / Q000175:diagnosis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism; D012189:Retrospective Studies
chemical_list: C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D019009:Proto-Oncogene Proteins c-kit
keywords: Bone marrow histology; European Competence Network on Mastocytosis; misdiagnosis; systemic mastocytosis