title: UTILITY OF ULTRASOUND VERSUS GENE EXPRESSION CLASSIFIER IN THYROID NODULES WITH ATYPIA OF UNDETERMINED SIGNIFICANCE.
abstract: OBJECTIVE
  Thyroid nodules with fine-needle aspiration (FNA) cytology categorized as atypia of undetermined significance (AUS) often undergo additional diagnostic analysis with the Afirma Gene Expression Classifier (GEC), which classifies these as either high probability of being benign (GEC-B) or suspicious for malignancy (GEC-S). Our goal was to assess the clinical validity and utility of GEC in the evaluation of AUS cytology and evaluate the performance of ultrasonography (USG) for predicting malignancy in this subset.
  
  
  METHODS
  We conducted a study with a retrospective cohort of patients from January 2012 to January 2014 who had FNA of thyroid nodules >1 cm in size with AUS cytology.
  
  
  RESULTS
  Cleveland Clinic Florida has an overall prevalence of AUS of 5%. A total of 119 cases with nodules >1 cm in size were reported as AUS. Forty-eight (40.3%) had a GEC performed after the first FNA (AUS-1), and 27 of these were GEC-S. Of those 27, 21 went for surgery and 14 (66.6%) had thyroid cancer on histopathology. The remaining 71 with AUS-1 were sent for a second FNA: 19 nodules were benign and did not undergo further evaluation, while the remaining 52 were reported as AUS for the second consecutive time (AUS-2). AUS-2 samples were sent for GEC. Of these 52 AUS-2, 38 (73.1%) were reported as GEC-S. Thirty-five went for surgery and 32 (91.4%) had confirmed malignancy on histopathology. Positive predictive value (PPV) was 91.4% for AUS-2 and 66.6% for AUS-1. Moreover, AUS-2 nodules that were hypoechoic and solid on USG showed a PPV of 92% for malignancy.
  
  
  CONCLUSIONS
  In our practice, the diagnostic accuracy to predict malignancy with GEC for AUS-1 nodules was poor (PPV, 66.6%). The PPV of GEC testing was markedly higher at 91.4% performed after two consecutive AUS cytologies. AUS-2 nodules that were solid and hypoechoic on USG also had a high probability to be malignant (PPV, 92%). We recommend repeat FNA on AUS-1 nodules rather than proceeding directly to GEC testing. Also, we suggest that among AUS-2 nodules, surgery can be recommended when USG shows solid and hypoechoic features with GEC testing reserved for the remainder.
  
  
  BACKGROUND
  AUS = atypia of undetermined significance FNA = fine-needle aspiration GEC = gene expression classifier GEC-B = GEC-benign GEC-S = GEC-suspicious for malignancy NPV = negative predictive value PPV = positive predictive value USG = ultrasonography.
authors.forename: Carmen V
authors.initials: CV
authors.lastname: Villabona
authors.forename: Vineeth
authors.initials: V
authors.lastname: Mohan
authors.forename: Karla M
authors.initials: KM
authors.lastname: Arce
authors.forename: Julia
authors.initials: J
authors.lastname: Diacovo
authors.forename: Alisha
authors.initials: A
authors.lastname: Aggarwal
authors.forename: Jessica
authors.initials: J
authors.lastname: Betancourt
authors.forename: Hassan
authors.initials: H
authors.lastname: Amer
authors.forename: Tessey
authors.initials: T
authors.lastname: Jose
authors.forename: Pascual
authors.initials: P
authors.lastname: DeSantis
authors.forename: Jose
authors.initials: J
authors.lastname: Cabral
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D044963:Biopsy, Fine-Needle; D003937:Diagnosis, Differential; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013964:Thyroid Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016606:Thyroid Nodule / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D059467:Transcriptome; D014463:Ultrasonography; D055815:Young Adult