Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance (AUS/FLUS): Interpretation and Algorithm for Follow-Up

The Bethesda System for Reporting Thyroid Cytology (TBSRTC) has proven to be an effective and robust thyroid fine needle aspiration (FNA) classification scheme to guide the clinical treatment of patients with thyroid nodules. However, a tendency of increasing diagnosis of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) is observed. This is commensurate with the incorporation of new molecular tests for classifying indeterminate thyroid nodules. Moreover, a sizable portion of AUS/FLUS is correlated with follicular variant papil‐ lary carcinoma (FVPTC). A suggestion of reclassifying noninvasive FVPTC (NIFVPTC) or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) as a neoplasm rather than a carcinoma would significantly change the risk of malignancy in AUS/FLUS category. We review the diagnostic criterion and subclassi‐ fying suggestions of AUS/FLUS, features indicating follicular variant neoplasm in AUS/ FLUS category, and commercially available molecular tests for AUS/FLUS subgroup‐ ing. We propose a multidisciplinary approach to AUS/FLUS follow-up.