High risk of malignancy in cases with atypia of undetermined significance on fine needle aspiration of thyroid nodules even after exclusion of NIFTP

Diagn Cytopathol. 2020 Nov;48(11):986-997. doi: 10.1002/dc.24533. Epub 2020 Aug 3.


Background: Fine needle aspiration cytopathology (FNAC) is the most reliable tool for evaluating thyroid nodules. However, diagnosing Bethesda category III, atypia/follicular lesion of undetermined significance (AUS/FLUS), is a major limitation. The aim of this study was to evaluate the risk of malignancy (RoM) in AUS/FLUS nodules. A systematic review was also carried out analyzing the largest series.

Methods: Totally 1750 cases (9%) diagnosed with AUS/FLUS were evaluated retrospectively out of 19 392 cases within last 13 years. All patients undergoing surgery for AUS/FLUS were included into the study. Histopathology results were correlated; the impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) diagnosis on RoM is evaluated.

Results: Of the 280 patients (16%) undergoing surgery, neoplasia were detected in 177 (RoN:63.2%) and malignancy in 119 (RoM:42.5%) of these neoplasia. Follicular variant of papillary thyroid carcinoma (FVPTC) was the commonest malignancy (55.5%). Additional 58 (20.7%) nodules were neoplastic, of which 26 (9.3%) were encapsulated follicular tumors with unknown malignancy potential (FT-UMP) and 32 (11.4%) were follicular adenomas. The remaining 103 patients (36.8%) had non-neoplastic nodules. After reevaluation of the encapsulated FVPTC cases, 20 of them were NIFTP and RoM dropped to 35.4% with a relative decrease of 16.7% and an absolute decrease of 7.1%.

Conclusion: In our series, 42.5% of nodules with AUS/FLUS were malignant; 63.2% of them were neoplastic. The RoM and RoN for AUS/FLUS nodules are still much higher than the revised expected RoM of international guidelines even after NIFTP cases excluded. Therefore, current recommendations should be reevaluated periodically in view of detailed clinicopathologic studies.

Keywords: AUS/FLUS; NIFTP; RoM; atypia of undetermined significance; fine needle aspiration.

Publication types

  • Systematic Review

MeSH terms

  • Adenocarcinoma, Follicular / diagnosis
  • Adenocarcinoma, Follicular / pathology*
  • Adult
  • Biopsy, Fine-Needle
  • Carcinoma, Papillary / diagnosis
  • Carcinoma, Papillary / pathology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Risk
  • Thyroid Cancer, Papillary / diagnosis
  • Thyroid Cancer, Papillary / pathology*
  • Thyroid Gland / pathology*
  • Thyroid Nodule / diagnosis
  • Thyroid Nodule / pathology*