title: Molecular characterization of 54 cases of false-negative fine-needle aspiration among 1347 papillary thyroid carcinomas.
abstract: BACKGROUND
  Fine-needle aspiration (FNA) has been widely accepted as the most crucial step in the preoperative assessment of thyroid nodules, but the false-negative rates are generally reported to be between 3.6% and 10.2%. To lower the overall incidence of this false-negative testing, new reporting systems encourage the molecular testing of thyroid nodules. However, to the authors' knowledge, the role of molecular testing in false-negative FNA has not yet been evaluated.
  
  
  METHODS
  In total, 1347 consecutive papillary thyroid carcinomas (PTCs) with both cytological and histological diagnoses were collected from the same center. A blinded revision of the false-negative cases was performed. An analysis of the BRAF and Ras genes in the false-negative cases was then performed.
  
  
  RESULTS
  The false-negative rate at the time of primary FNA diagnosis was 4.8% (65 of 1347 cases). False-negative cases were 15 follicular variant PTCs, 2 classical variant, and 1 solid variant that lacked peculiar PTC cytomorphological features. Adequate cellular material for molecular analysis was available only in 54 of the 65 false-negative cases. Mutations were found in 6 cases (11%), and Ras alterations were present in 16 cases (29.6%). The addition of molecular analysis decreased the false-negative rate to 0.4% (5 of 1347 cases).
  
  
  CONCLUSIONS
  The results of the current study confirm the feasibility of BRAF and Ras analysis in routine FNA. However, when the false-negative FNA rate is low, the cost-benefit analysis of the detection of BRAF and Ras mutations should be carefully evaluated. Consequently, the authors suggest that preoperative molecular assessment could be helpful for benign nodules, but only in the presence of clinical suspicion of malignancy.
authors.affiliation: Department of Surgical, Medical, Molecular Pathology and Critical Area, Unit of Pathological Anatomy, University of Pisa, Pisa, Italy.
authors.forename: Agnese
authors.initials: A
authors.lastname: Proietti
authors.forename: Nicla
authors.initials: N
authors.lastname: Borrelli
authors.forename: Riccardo
authors.initials: R
authors.lastname: Giannini
authors.forename: Rossana
authors.initials: R
authors.lastname: Romani
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Di Coscio
authors.forename: Francesca
authors.initials: F
authors.lastname: Quilici
authors.forename: Teresa
authors.initials: T
authors.lastname: Rago
authors.forename: Paolo
authors.initials: P
authors.lastname: Miccoli
authors.forename: Paolo
authors.initials: P
authors.lastname: Vitti
authors.forename: Fulvio
authors.initials: F
authors.lastname: Basolo
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle / Q000379:methods*; D002277:Carcinoma / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D002291:Carcinoma, Papillary; D002648:Child; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D016208:Databases, Factual; D005188:False Negative Reactions; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D057089:Pathology, Molecular; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D012680:Sensitivity and Specificity; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D016606:Thyroid Nodule / Q000235:genetics / Q000473:pathology / Q000601:surgery; D013965:Thyroidectomy / Q000379:methods; D055815:Young Adult
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf
keywords: BRAF; Ras; cytology; false-negative; thyroid cancer