Thyroid Nodules with Nuclear Atypia of Undetermined Significance (AUS-Nuclear) Hold a Two-Times-Higher Risk of Malignancy than AUS-Other Nodules Regardless of EU-TIRADS Class of the Nodule or Borderline Tumor Interpretation.

BACKGROUND/OBJECTIVES: The 2023 revision of the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) simplified the subcategorization of category III into two groups: "AUS-nuclear" and "AUS-other". The aim of this study was to investigate the risk of malignancy (ROM) of individual BSRTC categories with a particular emphasis on the "AUS-nuclear" and "AUS-other" subcategories and to check whether the low-risk follicular-cell-derived thyroid neoplasm (LRTN) interpretation or EU-TIRADS class of the nodule modify ROM.

METHODS

The analysis covered the FNA results of 18,225 nodules in 12,470 patients. The rate of malignancy (the upper limit of ROM) was established on the basis of the assessment of 1660 nodules treated surgically in 978 patients.

RESULTS

In the broadest variant, with all LRTNs regarded as malignant, the ROM for subsequent categories was as follows: I: 0.4-3.5%, II: 0.1-1.3%, III: 3.8-17.7%, IV: 23.3-27.8%, V: 79.6-90.1%, and VI: 86.3-100.0%. In AUS-nuclear nodules, the ROM was 10.5-28.9%, while in AUS-other nodules, it was 2.2-12.2%. The exclusion of NIFTP or all LRTNs from cancers mainly affected the ROM of AUS-nuclear nodules: 9.4-25.9% or 8.6-23.7%, respectively. EU-TIRADS 5 class increases the ROM in AUS-nuclear nodules to 78.3%, OR: 15.7 and in AUS-other to 40.7%, OR: 6.6.

CONCLUSIONS

The 2023 BSRTC is a welcome step towards simplification of the way nodules are classified within category III. The AUS-nuclear subcategory is associated with a two-times-higher incidence of malignancy than the AUS-other regardless of LRTN interpretation and EU-TIRADS class of the nodule. The EU-TIRADS 5 class of the nodule is helpful in the identification of category III nodules with a high risk of malignancy.