Indeterminate thyroid nodules. The role of ¹⁸F-FDG PET/CT in the "era" of ultrasonography risk stratification systems and new thyroid cytology classifications.

To evaluate the reliability of <sup>18</sup> F-FDG PET/CT in distinguishing differentiated thyroid cancers (DTCs) and follicular neoplasms (FNs) from nodular hyperplasias (NH) in thyroid nodules with indeterminate cytology according to the Italian consensus for the classification and reporting of thyroid cytology (ICCRTC). We also tested whether the <sup>18</sup> F-FDG PET/CT result was an independent risk factor for DTCs or FNs when sex, age, nodule dimensions, the European Thyroid Imaging and Reporting Data System (EU-TIRADS) and ICCRTC were considered. We evaluated all patients with thyroid nodules and indeterminate cytology from September 2015 to May 2019; nodules were classified as low risk (TIR3A) and high risk (TIR3B) according to the ICCRTC. Neck ultrasonography features according to EU-TIRADS were re-evaluated and <sup>18</sup> F-FDG PET/CT performed. All these patients were surgically treated. We included 111 patients; 67 nodules were classified as TIR3A and 44 as TIR3B. Overall, we found 27 DTCs, 57 NHs and 27 FNs. Among 73 FDG-negative nodules, we found four low-risk papillary thyroid cancers. All follicular thyroid cancers were identified by <sup>18</sup> F-FDG-PET/CT. All TIR3A with low-risk US and negative <sup>18</sup> F-FDG-PET/CT were NH. In TIR3A nodules, the sensitivity, specificity, negative and positive predictive values (NPV, PPV) of <sup>18</sup> F-FDG PET/CT and EU-TIRADS for DTCs were 77.8%, 41.4%, 92.3%, 17.1% and 66.7%, 56.9%, 91.7%, 19.4%, respectively. In TIR3B nodules, the sensitivity, specificity, NPV and PPV of <sup>18</sup> F-FDG PET/CT and EU-TIRADS for DTCs were 88.9%, 38.5%, 83.3%, 50% and 88.2%, 58.3%, 87.5%, 60%, respectively. On multivariate analysis, <sup>18</sup> F-FDG-PET/CT (OR 9.04), ICCRTC (O.R. 7.57) and EU-TIRADS (OR 4.41) were all independent risk factors associated to DTCs and FNs. <sup>18</sup> F-FDG-PET/CT is a reliable rule-out test for DTC even in thyroid nodules with indeterminate high-risk results. In this subgroup, PPV also tends to be considerable. <sup>18</sup> F-FDG-PET/CT results, ICCRTC and EU-TIRADS proved independent risk factors associated to DTCs and FNs