title: Multiparameter immunophenotyping by flow cytometry as a diagnostic tool in multiple myeloma and monoclonal gammopathy of undetermined significance.
abstract: BACKGROUND
  Immunophenotyping by multiparameter flow cytometry (MFC) provides relevant information about prognosis and minimal residual disease detection in multiple myeloma (MM) and might be used to distinguish MM from monoclonal gammopathies of undetermined significance (MGUS).
  
  
  METHODS
  We evaluated a possible usage of MFC to predict the differential diagnosis between MM and MGUS. One hundred consecutive patients were studied at diagnosis and underwent conventional diagnostic procedures. We carried out a double-blind study. Immunophenotyping was performed on samples from myeloaspirates before establishing diagnosis, while the final clinical diagnosis was established independently from MFC results. A five- or six-color method was carried out by means of monoclonal antibody combinations able to identify abnormal plasma cells (CD19-) and the most relevant immunophenotypic aberrations (loss of CD27; overexpression of CD117, CD56, CD28; asynchronous expression of CD20). MFC was applied following the indications of the European Myeloma Network. When abnormal plasma cells were </= 3% of the global plasma cell population, MM was predicted; when abnormal plasma cells were >/= 3.1%, MGUS was predicted.
  
  
  RESULTS
  MFC results predicted 63 cases of MM and 37 cases of MGUS. At the end of our study, 61 cases of MM and 39 cases of MGUS were diagnosed. Therefore, 4% of patients were misdiagnosed by MFC parameters alone, with sensitivity and specificity of 0.983 and 0.92, respectively.
  
  
  CONCLUSIONS
  Only a small proportion of patients with MM and MGUS were misdiagnosed by MFC alone and a possible systematic application of MFC in all patient with MM and MGUS at diagnosis might be proposed. Novel additional criteria could be necessary to improve the diagnostic impact of MFC in monoclonal gammopathies.
authors.affiliation: Division of Hematology, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy. giovannicarulli@alice.it
authors.forename: G
authors.initials: G
authors.lastname: Carulli
authors.forename: V
authors.initials: V
authors.lastname: Ottaviano
authors.forename: E
authors.initials: E
authors.lastname: Cannizzo
authors.forename: S
authors.initials: S
authors.lastname: Giuntini
authors.forename: C
authors.initials: C
authors.lastname: Manetti
authors.forename: E M
authors.initials: EM
authors.lastname: Ciancia
authors.forename: A
authors.initials: A
authors.lastname: Azzarà
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D016130:Immunophenotyping / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000175:diagnosis* / Q000276:immunology*; D009101:Multiple Myeloma / Q000175:diagnosis* / Q000276:immunology*