title: Thyroid cytology-nuclear versus architectural atypia within the "Atypia of undetermined significance/follicular lesion of undetermined significance" Bethesda category have significantly different rates of malignancy.
abstract: BACKGROUND
  The Bethesda System for Reporting Thyroid Cytopathology is the most widely used classification system for the reporting of thyroid fine-needle aspiration cytology (FNAC) specimens. However, the "atypical" category ("atypia of undetermined significance" [AUS] or "follicular lesion of undetermined significance" [FLUS]) continues to cause diagnostic and therapeutic dilemmas. The objectives of this study were to describe the differential malignancy rates of FNACs diagnosed as AUS/FLUS based on nuclear or architectural atypia and to assess the significance of demographic and ultrasonographic features in predicting malignancy in this category.
  
  
  METHODS
  A retrospective review was performed of all thyroid FNACs between 2008 and 2014 that were diagnosed as AUS/FLUS at a tertiary referral center in Singapore. Patient demographics, preoperative ultrasonographic features, and follow-up data were collected and correlated with the final histopathologic diagnosis in resected cases.
  
  
  RESULTS
  In total, 309 thyroid nodules were diagnosed as AUS/FLUS, and 137 (44%) were surgically excised. Final histology yielded 37 (27%) malignancies. The malignancy rate for nodules that featured nuclear atypia was significantly higher at 36.8% than the rate for nodules that had only architectural atypia at 14.7% (P < .01). After up to 3 repeat FNACs, 67.1% of cases had a more definitive diagnosis. The only predictive sonographic finding for malignancy was irregular margins (P < .01).
  
  
  CONCLUSIONS
  The disparity between malignancy risks within the Bethesda "atypical" category suggests that cytologic (nuclear) atypia is significantly more predictive of malignancy than architectural atypia. This supports the substratification of patients according to risk and a corresponding management approach within this category. A sonographic finding of irregular margins is also predictive for malignancy. Cancer Cytopathol 2017;125:245-256. © 2016 American Cancer Society.
authors.affiliation: Yong Loo Lin School of Medicine, Department of Surgery, National University of Singapore, Singapore.
authors.forename: Tiffany Rui Xuan
authors.initials: TR
authors.lastname: Gan
authors.affiliation: Department of Pathology, National University Hospital, Singapore.
authors.forename: Min En
authors.initials: ME
authors.lastname: Nga
authors.affiliation: Department of Pathology, National University Hospital, Singapore.
authors.forename: Jeffrey Huey Yew
authors.initials: JH
authors.lastname: Lum
authors.affiliation: Division of Thyroid and Endocrine Surgery, Department of Surgery, National University Hospital, Singapore.
authors.forename: Wendy Meihua
authors.initials: WM
authors.lastname: Wong
authors.affiliation: Division of Thyroid and Endocrine Surgery, Department of Surgery, National University Hospital, Singapore.
authors.forename: Wee Boon
authors.initials: WB
authors.lastname: Tan
authors.affiliation: Division of Thyroid and Endocrine Surgery, Department of Surgery, National University Hospital, Singapore.
authors.forename: Rajeev
authors.initials: R
authors.lastname: Parameswaran
authors.affiliation: Division of Thyroid and Endocrine Surgery, Department of Surgery, National University Hospital, Singapore.
authors.forename: Kee Yuan
authors.initials: KY
authors.lastname: Ngiam
mesh_terms: D044963:Biopsy, Fine-Needle / Q000379:methods; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D012846:Singapore / Q000453:epidemiology; D013961:Thyroid Gland / Q000000981:diagnostic imaging / Q000473:pathology*; D016606:Thyroid Nodule / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000473:pathology* / Q000601:surgery
keywords: Bethesda classification; atypia of undetermined significance (AUS); fine-needle aspiration cytology; follicular lesion of undetermined significance (FLUS); malignancy risk