title: Primary role of multiparametric flow cytometry in the diagnostic work-up of indolent clonal mast cell disorders.
abstract: BACKGROUND
  According to the World Health Organization (WHO) classification the diagnosis of systemic mastocytosis (SM) relies on bone marrow (BM) examination and is based on one major and four minor criteria. Herein, we used WHO criteria to compare flow cytometry (FC) with other available techniques in the diagnosis of SM after BM examination.
  
  
  METHODS
  We analyzed a cohort of 95 patients with suspect SM. All patients underwent comprehensive BM examination by using cytology, immunohistochemistry, FC and molecular study for mutation of c-Kit and serum tryptase dosage. FC evaluation was based on a combination of monoclonal antibodies, specifically CD25/CD2/CD45/CD34/CD117.
  
  
  RESULTS
  Seventy-four out of ninety-five patients were diagnosed with indolent SM (n = 59) or monoclonal mast cell activation syndrome (n = 15) because satisfying less than 3 minor criteria. Thirty-nine out of these seventy-four patients fulfilled the major histological criterion, whereas the presence of a minor criterion was assessed by FC, molecular study, cytology, and tryptase level in 70/74, 52/67, 56/74, and 42/74 patients, respectively. FC showed higher sensitivity than IHC in detection of CD25+ mast cells (MC) (92.9% vs. 73.8%; P = 0.019), especially in the absence of the major histological criterion (90.5% vs. 47.6%; P = 0.003). Moreover, CD2 expression was documented by FC and IHC in 97.1% and 35.3% of cases, respectively (P < 0.001).
  
  
  CONCLUSIONS
  FC showed the best sensitivity for identifying abnormal MC compared to other techniques, especially in cases with low MC burden. Therefore, we hope for a major role of FC in the diagnostic work-up of clonal MC disorders.
authors.affiliation: Department of Medicine, Section of Hematology, Azienda Ospedaliera Universitaria Integrata and University of Verona, Italy. omar.perbellini@univr.it
authors.forename: Omar
authors.initials: O
authors.lastname: Perbellini
authors.forename: Alberto
authors.initials: A
authors.lastname: Zamò
authors.forename: Sabrina
authors.initials: S
authors.lastname: Colarossi
authors.forename: Francesca
authors.initials: F
authors.lastname: Zampieri
authors.forename: Francesca
authors.initials: F
authors.lastname: Zoppi
authors.forename: Patrizia
authors.initials: P
authors.lastname: Bonadonna
authors.forename: Donatella
authors.initials: D
authors.lastname: Schena
authors.forename: Anna
authors.initials: A
authors.lastname: Artuso
authors.forename: Giovanni
authors.initials: G
authors.lastname: Martinelli
authors.forename: Marco
authors.initials: M
authors.lastname: Chilosi
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pizzolo
authors.forename: Roberta
authors.initials: R
authors.lastname: Zanotti
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D018801:CD2 Antigens / Q000032:analysis / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping / Q000379:methods*; D053645:Interleukin-2 Receptor alpha Subunit / Q000032:analysis / Q000276:immunology; D008297:Male; D008407:Mast Cells / Q000737:chemistry / Q000276:immunology; D034721:Mastocytosis, Systemic / Q000097:blood / Q000175:diagnosis* / Q000235:genetics / Q000276:immunology; D008875:Middle Aged; D009154:Mutation; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D012680:Sensitivity and Specificity; D014944:World Health Organization; D055815:Young Adult
chemical_list: D015415:Biomarkers; D018801:CD2 Antigens; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D019009:Proto-Oncogene Proteins c-kit