Developing a tool that could reliably refute total thyroidectomy for solitary Bethesda IV thyroid nodules

To assess the reliability of a simple, accessible, cost-effective rule-out tool, for use in triaging patients with Bethesda IV nodules to appropriate surgery.

The diagnostic tool was assembled by combining the negativity for suspicious ultrasound features (irregular margins, microcalcification, and a taller-than-wide orientation), and mutational marker negativity (BRAF and NRAS). The tool, (US^-/mutation^-), was tested on 167 patients with solitary Bethesda IV nodules. The primary outcome was its negative predictive value (NPV) for lesions requiring total thyroidectomy (TT). The impact of mutational marker negativity, as part of the tool, was evaluated by comparing the NPV of (US^-/mutation^-) to that of (US^-/mutation⁺).

10 out of 167 lesions were positive for a mutational marker. These underwent TT, and only 2/10 (20%) were benign, on final histology. In 6/8 malignant lesions, TT was concordant with current clinical guidelines. 157 patients comprised the negative study cohort, for both mutational markers and suspicious US features. These underwent thyroid lobectomy, and 17 cases resulted in malignancy, only 8 of which required completion thyroidectomy. Accordingly, the NPV of (US^-/mutation^-) for malignancy was 89% (140/157), and 95% (149/157) for malignancy requiring TT. However, the NPV of (US^-/mutation⁺) was 20% for malignancy, and 40% for malignancy requiring TT. These differences were statistically significant (89% vs. 20%; p < 0.0001, and 95% vs. 40%; p < 0.0001).

US^-/mutation^- is a reliable rule-out tool, with sufficient diagnostic accuracy to spare patients, with Bethesda IV nodules, an overly radical TT.