Subclassification of the Bethesda Category III (AUS/FLUS): A Study of thyroid FNA cytology based on ThinPrep slides from the National Cancer Center in China

Background The atypia of an undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) category in the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) is a heterogeneous category, which includes various cell patterns. The subclassification of AUS/FLUS was suggested in the 2017 TBSRTC. However, the risk of malignancy (ROM) associated with different subgroups remains unresolved. Herein, AUS/FLUS aspirates were subclassified, from which the ROM of each subgroup was determined. Methods All cases undergoing fine-needle aspiration (FNA) from July 2013 to December 2018 were reviewed. Of 12,913 thyroid FNAs, 1053 (8.2%) were AUS/FLUS. The slides of 222 patients with AUS/FLUS with surgical follow-up were reviewed and subclassified according to the recommendations of the 2017 TBSRTC. There were 195 aspirates consistently diagnosed as AUS/FLUS and subclassified as cytologic atypia 1 (AUS-C1); cytologic atypia 2 (AUS-C2); architectural atypia (AUS-A); cytologic and architectural atypia (AUS-C & A); Hurthle cell aspirates (AUS-H); atypia, not otherwise specified (AUS-NOS); and atypical lymphoid cells, rule out lymphoma (AUS-L). Results Malignancy was identified in 83.3% (185 of 222) of the AUS/FLUS nodules. The AUS-C1 group was the most common (62.1%), followed by the AUS-C&A (12.8%), AUS-C2 (10.8%), AUS-H (6.7%), AUS-NOS (5.6%), AUS-L (1.5%), and AUS-A (0.5%) groups. AUS-C1 had the highest ROM (92.6%) among the groups and varied significantly from that of the AUS-C&A (P = .171), AUS-C2 (P = .001), AUS-H (P = .001), and AUS-NOS (P < .001) groups. Conclusions As a heterogeneous category of TBSRTC, the ROM for AUS/FLUS varies greatly among medical centers. Subclassification of AUS/FLUS might be helpful in identifying nodules with a high ROM in this category and improving the management of such nodules.