title: Malignancy rate in thyroid nodules classified as Bethesda category III (AUS/FLUS).
abstract: BACKGROUND
  The Bethesda System for Reporting Thyroid Cytopathology is the standard for interpreting fine needle aspiration (FNA) specimens. The "atypia of undetermined significance/follicular lesion of undetermined significance" (AUS/FLUS) category, known as Bethesda Category III, has been ascribed a malignancy risk of 5-15%, but the probability of malignancy in AUS/FLUS specimens remains unclear. Our objective was to determine the risk of malignancy in thyroid FNAs categorized as AUS/FLUS at a comprehensive cancer center.
  
  
  METHODS
  The management of 541 AUS/FLUS thyroid nodule patients treated at Memorial Sloan-Kettering Cancer Center between 2008 and 2011 was analyzed. Clinical and radiologic features were examined as predictors for surgery. Target AUS/FLUS nodules were correlated with surgical pathology.
  
  
  RESULTS
  Of patients with an FNA initially categorized as AUS/FLUS, 64.7% (350/541) underwent immediate surgery, 17.7% (96/541) had repeat FNA, and 17.6% (95/541) were observed. Repeat FNA cytology was unsatisfactory in 5.2% (5/96), benign in 42.7% (41/96), AUS/FLUS in 38.5% (37/96), suspicious for follicular neoplasm in 5.2% (5/96), suspicious for malignancy in 4.2% (4/96), and malignant in 4.2% (4/96). Of nodules with two consecutive AUS/FLUS diagnoses that were resected, 26.3% (5/19) were malignant. Among all index AUS/FLUS nodules (triaged to surgery, repeat FNA, or observation), malignancy was confirmed on surgical pathology in 26.6% [CI 22.4-31.3]. Among AUS/FLUS nodules triaged to surgery, the malignancy rate was 37.8% [CI 33.1-42.8]. Incidental cancers were found in 22.3% of patients. On univariate logistic regression analysis, factors associated with triage to surgery were younger patient age (p<0.0001), increasing nodule size (p<0.0001), and nodule hypervascularity (p=0.032).
  
  
  CONCLUSIONS
  In patients presenting to a comprehensive cancer center, malignancy rates in nodules with AUS/FLUS cytology are higher than previously estimated, with 26.6-37.8% of AUS/FLUS nodules harboring cancer. These data imply that Bethesda Category III nodules in some practice settings may have a higher risk of malignancy than traditionally believed, and that guidelines recommending repeat FNA or observation merit reconsideration.
authors.affiliation: 1 Head and Neck Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center , New York, New York.
authors.forename: Allen S
authors.initials: AS
authors.lastname: Ho
authors.forename: Evan E
authors.initials: EE
authors.lastname: Sarti
authors.forename: Kunal S
authors.initials: KS
authors.lastname: Jain
authors.forename: Hangjun
authors.initials: H
authors.lastname: Wang
authors.forename: Iain J
authors.initials: IJ
authors.lastname: Nixon
authors.forename: Ashok R
authors.initials: AR
authors.lastname: Shaha
authors.forename: Jatin P
authors.initials: JP
authors.lastname: Shah
authors.forename: Dennis H
authors.initials: DH
authors.lastname: Kraus
authors.forename: Ronald
authors.initials: R
authors.lastname: Ghossein
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Fish
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Wong
authors.forename: Oscar
authors.initials: O
authors.lastname: Lin
authors.forename: Luc G T
authors.initials: LG
authors.lastname: Morris
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology / Q000601:surgery; D044963:Biopsy, Fine-Needle; D002173:Cancer Care Facilities; D015331:Cohort Studies; D003937:Diagnosis, Differential; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D033162:Incidental Findings; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009389:Neovascularization, Pathologic; D009519:New York City / Q000453:epidemiology; D017410:Practice Guidelines as Topic; D012086:Reoperation; D012306:Risk; D013961:Thyroid Gland / Q000098:blood supply / Q000000981:diagnostic imaging / Q000473:pathology* / Q000601:surgery; D013964:Thyroid Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000473:pathology / Q000601:surgery; D016606:Thyroid Nodule / Q000098:blood supply / Q000175:diagnosis* / Q000473:pathology / Q000601:surgery; D047368:Tumor Burden; D014463:Ultrasonography