title: Suspicious ultrasound characteristics predict BRAF V600E-positive papillary thyroid carcinoma.
abstract: BACKGROUND
  Current American Thyroid Association (ATA) guidelines recommend routine cervical ultrasound (US) in thyroid nodule evaluation. Specific US characteristics can help diagnose papillary thyroid carcinoma (PTC). The aim of this blinded cohort study was to determine whether these specific US characteristics can also reliably detect the more aggressive variants of PTC that are often associated with the BRAF(V600E) mutation.
  
  
  METHODS
  After Institutional Review Board approval, we identified a cohort of patients from January 2007 to December 2009 with histologic PTC≥1 cm who had cervical US, initial thyroid surgery, and molecular testing for BRAF(V600E) on fine-needle aspiration biopsy or histology. Preoperative US images were evaluated by a single radiologist, who was blinded to BRAF status, for nodule size and the presence or absence of the following suspicious US features: taller-than-wide shape, ill-defined margins, hypoechogenicity, calcifications, noncystic composition, and absent halo.
  
  
  RESULTS
  BRAF-positivity was associated with most known suspicious US findings, including taller-than-wide shape (47% vs. 7%, p<0.001), ill-defined margins (42% vs. 9%, p<0.001), hypoechogenicity (83% vs. 36%, p<0.001), micro/macrocalcifications (87% vs. 24%, p<0.001), and absent halo (85% vs. 27%, p<0.001) but was not associated with noncystic composition. When ≥3 suspicious US features were present, BRAF-positivity was predicted with a positive predictive value of 82%. The absence of suspicious US features together with negative BRAF testing predicted PTC without extrathyroidal extension or lymph node metastasis (negative predictive value 88%).
  
  
  CONCLUSIONS
  With routine preoperative cervical US and molecular testing, a trained radiologist or surgeon can improve the preoperative characterization of PTC, potentially impacting risk stratification and initial surgical management.
authors.affiliation: Department of Surgery, University of Pittsburgh, 3471 Fifth Ave., Pittsburgh, PA 15213, USA.
authors.forename: Adam S
authors.initials: AS
authors.lastname: Kabaker
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Tublin
authors.forename: Yuri E
authors.initials: YE
authors.lastname: Nikiforov
authors.forename: Michaele J
authors.initials: MJ
authors.lastname: Armstrong
authors.forename: Steven P
authors.initials: SP
authors.lastname: Hodak
authors.forename: Michael T
authors.initials: MT
authors.lastname: Stang
authors.forename: Kelly L
authors.initials: KL
authors.lastname: McCoy
authors.forename: Sally E
authors.initials: SE
authors.lastname: Carty
authors.forename: Linwah
authors.initials: L
authors.lastname: Yip
mesh_terms: D044963:Biopsy, Fine-Needle; D002277:Carcinoma; D002291:Carcinoma, Papillary; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D011237:Predictive Value of Tests; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D015203:Reproducibility of Results; D012189:Retrospective Studies; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D016037:Single-Blind Method; D000077273:Thyroid Cancer, Papillary; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000473:pathology; D013964:Thyroid Neoplasms / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000473:pathology; D014463:Ultrasonography
chemical_list: C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf