The malignancy risk of thyroid incidentalomas detected by [18F]FDG PET/CT lower than expected: a nationwide observational study in the Netherlands

Abstract

Background: The widespread use of 18F-fluorodeoxyglucose positron emission tomography/computed tomography ([18F]FDG PET/CT) has led to increased detection of thyroid incidentalomas (TIs). Current guidelines cite malignancy rates of 31–33% for [18F]FDG-positive thyroid nodules, but population-based data remain limited. This study aimed to assess the malignancy risk and cytological distribution of [18F]FDG PET TIs in a nationwide cohort. Methods: This retrospective observational study analyzed data from the Dutch nationwide pathology databank (Palga) for all patients who underwent thyroid fine-needle aspiration between January 2012 and December 2019, with follow-up until December 2022. Patients were classified as [18F]FDG PET TI based on documentation of [18F]FDG PET positivity in pathology reports. The primary outcome was malignancy risk compared between [18F]FDG PET TI and control groups. Secondary outcomes included distribution across Bethesda System categories and histological subtypes. Results: Among 64,706 patients analyzed, 3,938 (6.1%) underwent fine-needle aspiration for [18F]FDG PET thyroid incidentalomas. [18F]FDG PET TI detection increased 128% between 2012 (n = 281) and 2019 (n = 641). Patients with [18F]FDG PET TIs were older (median 64 vs. 52 years, p < 0.001) and more likely male (30.8% vs. 19.1%, p < 0.001). The overall malignancy rate was significantly higher in [18F]FDG PET TIs compared with controls (19.4% vs. 8.8%, p < 0.001). [18F]FDG PET TIs demonstrated higher proportions of suspicious cytological categories: atypia of undetermined significance (Bethesda III) (13.1% vs. 6.5%), follicular neoplasm (Bethesda IV) (10.2% vs. 4.3%), suspicious for malignancy (Bethesda V) (7.3% vs. 2.9%), and malignant cytology (Bethesda VI) (6.8% vs. 2.1%) (all p < 0.001). Among patients with indeterminate cytology, 36% of Bethesda IV and 29% of Bethesda V cases did not undergo surgery. Papillary thyroid carcinoma was the predominant malignant subtype (52.3%), with no anaplastic carcinomas observed. Conclusions: This largest population-based study demonstrates that [18F]FDG PET TIs have a malignancy rate of 19.4%, which is lower than the 31–33% cited in current guidelines. The substantial proportion of cytologically suspicious nodules that do not proceed to surgery suggests potential inefficiency in current diagnostic approaches. These findings support more selective FNA strategies and enhanced risk stratification to optimize patient care while minimizing unnecessary interventions.