An update on management of cytologically indeterminate thyroid nodules

Abstract

Thyroid nodules are common, but only 5-15% are cancerous. Fine-needle aspiration cytology is the gold-standard examination for determining the nature of a thyroid nodule, with results reported according to the Bethesda International Classification as updated in 2023. However, 20-30% of nodules are cytologically indeterminate. The challenge here is to avoid unnecessary diagnostic surgery, since 70% of these nodules are benign, although thyroid cancer remains a possibility. Nodule size, growth rate and ultrasonographic or elastographic characteristics can guide management, but have not been shown to have robust diagnostic performance. Thyroid scintigraphy with iodine-123, MIBI and 18F-FDG PET/CT have shown some usefulness, but their efficacy and cost-benefit ratio remain debatable. Artificial intelligence should help clarify the diagnosis of thyroid nodules, but these approaches have yet to be validated in routine clinical practice. Molecular tests performed during aspiration of a thyroid nodule, marketed mainly in the United States, offer robust prospects, as they show good negative predictive values to rule out malignancy when the test is negative, but their high cost limits widespread use in Europe. In France, the development of molecular tests for research purposes is being encouraged. In conclusion, although progress has been made, management of indeterminate thyroid nodules remains complex and relies on a medical decision shared with the patient, pending validation of new diagnostic tools.

Keywords: Bethesda classification; Fine-needle aspiration cytology; Molecular biology; Thyroid nodules.