Strategy to reduce unnecessary surgeries in thyroid nodules with cytology of Bethesda category III (AUS/FLUS): a retrospective analysis of 667 patients diagnosed by surgery

Endocrine. 2020 Sep;69(3):578-586. doi: 10.1007/s12020-020-02300-w. Epub 2020 Apr 15.


Purpose: Fine-needle aspiration (FNA) is widely used for the diagnosis of thyroid nodules detected by ultrasonography. However, the cytology of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) often leads to unnecessary thyroid surgery. This study aimed to identify a strategy to reduce unnecessary surgeries in patients with AUS/FLUS nodules.

Methods: Medical records of 667 patients with the cytology of AUS/FLUS who underwent surgery from January 2007 to December 2017 were retrospectively reviewed. Clinicopathological data were analyzed to identify malignant factors in thyroid nodules with AUS/FLUS. Factors were compared between patients with thyroid cancer and those with benign thyroid nodules, using stepwise multivariate logistic regression and decision tree model.

Results: Pathological thyroid cancer was identified in 193 (43.3%) patients. There was a significant difference in malignancy incidence with respect to family history, number of nodules, number of FNAs, ultrasonographic finding, lymphocytic thyroiditis, and BRAFV600E mutation. Multivariate analysis showed that ultrasonography (K-TIRADS 5) was the most influential independent predictor of malignancy in AUS/FLUS (odds ratio = 11.02, p < 0.001), followed by possessing BRAFV600E mutation (odds ratio = 4.54, p < 0.001). This strategy enabled 226 (89.3%) patients to avoid unnecessary surgeries based on the decision tree model. There was no node of repeated FNA in the decision tree model, which reduced the risk of malignancy (odds ratio = 0.35, p = 0.029).

Conclusion: K-TIRADS 5 and BRAFV600E mutation were predictive of malignancy in nodules of AUS/FLUS. These factors should be considered in strategies to reduce unnecessary surgeries for AUS/FLUS.

Keywords: Atypia of undetermined significance; Follicular lesion of undetermined significance; Surgery; Thyroid nodule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma, Follicular*
  • Biopsy, Fine-Needle
  • Humans
  • Retrospective Studies
  • Thyroid Neoplasms* / diagnostic imaging
  • Thyroid Neoplasms* / surgery
  • Thyroid Nodule* / diagnostic imaging
  • Thyroid Nodule* / surgery