Association of patient characteristics, ultrasound features, and molecular testing with malignancy risk in Bethesda III–V thyroid nodules

OBJECTIVE: To evaluate the role of patient characteristics, ultrasound findings, and molecular testing in predicting risk of malignancy in Bethesda III, IV, and V thyroid nodules. DESIGN: Single institution retrospective review of 230 patients with Bethesda III, IV, and V cytopathology undergoing thyroidectomy between 2009 and 2018. SETTING: Private and public tertiary urban university hospitals at the same academic institution. SUBJECTS AND METHODS: Patients who underwent thyroidectomy with Bethesda III, IV, and V nodules were included. Patient demographics, presence of underlying thyroid disease, nodule size, sonographic features, gene expression results, and surgical procedure were documented. Correlation between these variables and final histopathologic diagnosis of malignancy was analyzed. RESULTS: The 230 patients (103 Bethesda III, 64 Bethesda IV, and 63 Bethesda V) were included for analysis. Bethesda III nodules harbored malignancy in 26.2% of cases compared with 26.6% of Bethesda IV nodules and 82.5% of Bethesda V nodules. On multivariate analysis, age was inversely correlated with a diagnosis of malignancy (OR: 0.98, 95% confidence interval [CI]: 0.96–0.99, p = .03) Although the presence of microcalcifications was positively associated with cancer (OR: 2.31, CI: 1.24–4.29, p = .008) The co‐occurrence of microcalcifications and irregular margins was associated with a higher odds of malignancy (OR: 4.42, 95% CI: 1.32–14.93, p = .016), whereas the combination of microcalcifications, irregular margins, and hypoechogenicity was associated with the greatest cancer risk (OR: 5.52, 95% CI: 1.12–27.78, p = .036). CONCLUSIONS: The presence of microcalcifications in thyroid nodules categorized as Bethesda III–V is an independent risk factor for malignancy. The combination of microcalcifications, irregular margins, and hypoechogenicity is associated with a greater malignancy risk in nodules indeterminate for thyroid cancer on cytopathology.