Background: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) describes several subcategories within atypia of undetermined significance (AUS), including (1) presence of focal nuclear atypia (AUS-N), (2) focal microfollicular proliferation (AUS-F), (3) focal Hürthle cell proliferation (AUS-HC), and (4) other (AUS-O). Several publications suggest that 5-15% is an underestimate of the malignancy risk for AUS, and that the underestimation is owing to the similarity between AUS-N and suspicious for malignancy (SFM). Thus, we investigated the AUS subcategories during morphologic re-review at a tertiary care center and their associated malignancy risk.

Methods: Of 4,827 fine-needle aspiration specimens were sent between January 2009 and August 2013 for morphologic re-review, 806 were categorized as AUS. Comparison of AUS subcategory diagnoses were made between outside and re-review results. The malignancy risk was also determined for 255 nodules with available surgical pathology.

Result: The outside diagnoses of the 806 cases read as AUS on second review were as follows: 5 insufficient (0.1%), 149 benign (19%), 463 AUS (57%), 124 SFN or suspicious for follicular or Hürthle cell neoplasm (15%), 56 SFM (7%), and 9 malignant (1%). Of the 463 cases in which both the outside and re-review diagnosis was AUS, the distribution of the subcategories in order of increasing frequency was 53 AUS-HC (11%), 74 AUS-O (16%), 79 AUS-F (17%), and 257 AUS-N (56%). Of the 255 resected nodules, 99 (39%) were malignant. Subcategory malignancy rates were: AUS-HC, 19% (9/47); AUS-O, 26% (14/54); AUS-F, 39% (19/49); and AUS-N, 54% (57/105). Cases in which both the referring institution and re-review agreed about the AUS-N subcategory had an even greater risk of malignancy (68%; 17/25).

Conclusion: Disagreement about the diagnosis of AUS between institutions is frequent. The malignancy risk for AUS is higher than originally proposed by TBSRTC and attributable to the high risk of AUS-N. Furthermore, agreement on AUS-N after re-review portends a malignancy risk that borders on that of SFM. This suggests that AUS-N may have discrete features that can provide specific morphologic predictors and enable the consolidation of AUS-N into SFM.