Indeterminate thyroid cytology in an iodine-deficient population: Prevalence, operation rate, risk of malignancy anddiagnostic value of thyroid scintigraphy and 18F-FDG PET imaging parameters.

Objective: Patients with indeterminate thyroid cytology often have a diagnostic hemithyroidectomy. The role of molecular imaging, particularly fluorine-18-fluorodeoxyglucose (¹⁸F-FDG) positron emission tomography (PET), is controversial, and demographic variations in tumor prevalence and histology influence test performance and clinical utility. We retrospectively assessed the prevalence of indeterminate thyroid cytology and the malignancy rate in patients from an iodine deficient area, and evaluated the diagnostic value of preoperative thyroid scintigraphy and ¹⁸F-FDG PET/CT among operated patients.

Subjects and methods: From 2006-2018, all patients with indeterminate thyroid cytology from the North Denmark region were included in the study (population 600,000).Clinical data, including operation rate, preoperative molecular imaging, and histopathological diagnosis, were retrieved. The results from preoperative thyroid scintigraphy and ¹⁸F-FDG PET/CT-scanning were compared to the final histopathological diagnosis.

Results: Four hundred and thirty-three patients were found with indeterminate thyroid cytology.The main registered reasons for conducting a fine needle aspiration biopsy (FNAB) were "cold nodule", goiter or a palpable nodule (n=312). In 40 patients (9%), FNAB was registered as conducted due to a PET incidentaloma. Four hundred and two patients (93%) underwent diagnostic lobectomy, and this population formed the study population for the following explorative study: One-hundred and two patients (25%) had a malignant diagnosis. In 226 (56%) and 51 (25%) patients, respectively, preoperative thyroid scintigraphy and ¹⁸F-FDG PET/computed tomography (CT) was performed. Among patients with a final malignant disease who had a thyroid scintigraphy (40 patients), a cold nodule was seen in 90% of cases; one (atypical) patient presented a warm nodule. Among patients with a final malignant disease 16 patients (16%) had a ¹⁸F-FDG PET (incl. 3 missing PET scans). Among the 51 patients with preoperative ¹⁸F-FDG PET/CT, no difference in the PET-derived parameters was found between benign (n=33) and malignant tumors (n=13).

Conclusion: The prevalence of malignancy (25%) was comparable with that in other studies. In patients with a preoperative thyroid scintigraphy, 90% of malignant cases had a cold nodule on scintigraphy. In patients with a preoperative PET/CT-scanning presenting focal ¹⁸F-FDG-uptake, PET-derived parameters had no diagnostic value. However, the diagnostic value of ¹⁸F-FDG-avidity vs. non-avidity needs to be addressed prospectively.