Atypia of Undetermined Significance

Abstract

Atypia of Undetermined Significance (AUS) was introduced in 2008 as one of three “indeterminate” (not clearly benign or malignant) diagnostic categories for reporting thyroid fine needle aspiration (FNA). The previous alternative term, Follicular Lesion of Undetermined Significance (FLUS), has been eliminated in this update to avoid confusion with reporting terminology and management. Each of the indeterminate categories has an elevated risk of malignancy (ROM) compared to a benign aspirate. The AUS category is reserved for cases with atypia that is insufficient for either of the other two indeterminate categories of “Follicular Neoplasm” and “Suspicious for Malignancy.” Among the three indeterminate categories, AUS has the lowest ROM (average 22%; range 13-30%) meriting its distinction from the other two. Furthermore, malignancy risk differs according to the nature of the atypia prompting the AUS interpretation. Specifically, AUS with nuclear atypia raising concern for papillary carcinoma has a higher ROM than AUS associated with other patterns, particularly those characterized by architectural atypia alone or a predominance of oncocytic cells. The introduction of noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) terminology in 2016 decreased the overall ROM for AUS. The clinical approach to a nodule with an initial AUS interpretation is a repeat FNA or molecular testing, although patient preference and clinical risk factors may also impact management with diagnostic lobectomy or active surveillance being alternative options. Based on published experience with AUS in clinical practice, this update describes: 1. appropriate use of the AUS diagnostic terminology. 2. subclassification of AUS with an emphasis on the importance of distinguishing nuclear atypia from other common AUS patterns to improve communication regarding the ROM, between cytopathologists and the clinical team managing the patient; and 3. updates to the management of AUS, including the role of molecular testing and discussion of concerns specific to pediatric patients.