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Is The Bethesda Classification System Downplaying The Risk Of Malignancy In The Era Of Molecular Testing?
*Aaron Mack Delman, *Kevin M Turner, *Allison M AMMANN, *Stephanie Sisak, Tammy M Holm
University of Cincinnati, Cincinnati, OH

OBJECTIVE(S): The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) was formalized in 2007 and updated in 2017 in part to risk stratify the risk of malignancy of thyroid nodules based upon cytopathology. Over time, several single-center studies have reported significant variations with respect to institutional rate of malignancy (ROM) as compared to those implied based upon TBSRTC. The objective of this study was to determine the national ROM for Bethesda III (BIII), Bethesda IV (BIV), and Bethesda V (BV) thyroid nodules.
METHODS: From 2016-2019, patients with preoperative cytopathology and pathology results in The American College of Surgeons National Surgical Quality Improvement (NSQIP) targeted thyroid database were identified. The ROM and patient factors associated with malignancy were assessed for BIII, BIV, and BV specimens.
RESULTS: 13,121 patients with preoperative cytopathology and post-resection pathology results were identified. Compared to TBSRTC-2017, the rate of malignancy was significantly higher than the median implied risk of malignancy for BIII, BIV, and BV thyroid nodules. For BIII, 36.2% were malignant as compared to 12% (p<0.001). For BIV, the ROM was 36.7% as compared to 25% (p<0.001), and for BV the rate of malignancy was 91.1% as compared to 52.5%, (p<0.001). Male sex significantly associated with malignancy in BIII, BIV, and BV nodules (BIII, OR: 1.20, 95% CI: 1.01-1.42; BIV, OR: 1.47, 95% CI: 1.27-1.71; BV, OR: 1.28, 95% CI: 1.03-1.58). Age was also associated with malignancy with BIII patients under 55 (OR: 1.23, 95% CI: 1.07-1.42), BIV patients under 42 (OR:1.23, 95% CI: 1.06-1.43), and BV patients aged less than 47 (OR: 1.39, 95% CI: 1.15-1.67).
CONCLUSIONS: This is the largest study describing the rate of malignancy for Bethesda III, IV, and V nodules in the United States. The results of this work reveal that the overall ROM is significantly higher than the implied risk of malignancy commonly reported to patients and providers. We recommend counseling patients regarding this increased ROM to set appropriate expectations following surgery.


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