Atypia of Undetermined Significance-Nuclear versus Other: Does Stratification Improve Risk? Time will Tell.

Summary: Introduction: Recognizing the higher risk of malignancy for aspirates of atypical undetermined significance (AUS) with cytologic atypia compared to those with architectural atypia, the latest iteration of The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) encourages the classification of AUS into AUS-Nuclear (AUS-N) and AUS-Other (AUS-OTH). We prospectively examined the rate of reporting, risk of malignancy (ROM), as well as any trends between these categories and outcomes since the beginning of implementing such practice at our institution. Materials and Methods: Our database was queried from September 22, 2023 to March 7, 2024 for aspirates subcategorized as AUS-N and AUS-OTH. Gender, age, Thyroid Imaging Reporting & Data System (TI-RADS) score, nodule size, molecular testing results and histologic/cytologic follow-up were collected (Table 1 and 2). AUS-N and AUS-OTH were diagnosed based on criteria detailed in TBSRTC. Repeat benign aspirates, negative molecular testing results or surgical excision were considered final outcomes. Malignant interpretations included noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) or carcinoma. Results: A total of 41 cases of AUS were identified (AUS-N=23; AUS-OTH=18). Twenty-two (AUS-N=11; AUS-OTH=11) had either subsequent benign cytology (n=2), negative molecular testing results (n=6) or surgical excision (n=14). AUS-OTH was followed by benign cytology (n=2), negative molecular results (n=3), follicular thyroid carcinoma (n=4), and follicular adenoma/follicular nodular disease (n=2), for an ROM of 36.7%. AUS-N was followed by negative molecular results (n=3), papillary thyroid carcinoma (n=4), NIFTP (n=1) and follicular adenoma/follicular nodular disease (n=3), for an ROM of 45.5 %. All cases of papillary thyroid carcinoma were preceded by AUS-N, while all cases of follicular thyroid carcinoma by AUS-OTH. Conclusions: While the NIFTP/cancer prevalence for AUS-N was greater than that for AUS-OTH, it was not as high as anticipated. This may improve over time and with feedback to the cytopathologists on their individual rates of malignancy per AUS subgroup.