From the Guidelines
Management of a Bethesda diagnostic category 3 thyroid nodule should involve molecular testing of the initial FNA sample or repeat fine-needle aspiration (FNA) biopsy in 3-6 months, with consideration of surgical consultation for possible diagnostic lobectomy in patients with higher risk factors. The 2017 Bethesda System for Reporting Thyroid Cytopathology categorizes FNA results into six categories, with category III indicating atypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) 1. Molecular diagnostic testing, such as detecting individual mutations (e.g., BRAF V600E, RET/PTC, RAS, PAX8/PPARγ) or using molecular classifiers, can be useful in evaluating FNA samples that are indeterminate to assist in management decisions 1.
Some key points to consider in the management of Bethesda category 3 thyroid nodules include:
- Molecular testing options, such as Afirma, ThyroSeq, or ThyGeNEXT/ThyraMIR, can help stratify malignancy risk and guide further management decisions
- Repeat FNA biopsy in 3-6 months may be considered, especially if molecular testing is not available or if the results are inconclusive
- Surgical consultation for possible diagnostic lobectomy may be appropriate for patients with higher risk factors, such as family history of thyroid cancer, prior radiation exposure, suspicious ultrasound features, or enlarging nodules
- Regular ultrasound monitoring is essential regardless of the initial management strategy chosen, with routine follow-up recommended in 12 months if repeat FNA yields benign results
- Patient preference should be considered in the decision-making process, with a thorough discussion of the risks and benefits of each approach, as the management approach balances the relatively low malignancy risk of these nodules (10-30%) against the morbidity of unnecessary surgery 1.
From the Research
Management of Bethesda Diagnostic Category 3 Thyroid Nodules
The management of Bethesda diagnostic category 3 thyroid nodules involves several steps, including:
- Ultrasonography to guide the next step in management 2
- Repeat fine-needle aspiration (FNA) or core needle biopsy (CNB) for nodules with low suspicion of malignancy 3
- Surgery for nodules with high suspicion of malignancy or those that are sonographically suspicious for malignancy 2, 3
- Consideration of risk-benefit analysis for nodules with low suspicion of malignancy before proceeding with surgery or repeat examination 3
Role of Ultrasonography
Ultrasonography plays a crucial role in the management of Bethesda diagnostic category 3 thyroid nodules, including:
- Predicting malignancy based on ultrasound features such as hypoechogenicity, irregular margins, and microcalcifications 2, 4
- Guiding the decision for repeat FNA or surgery 2, 3
- Assigning a Korean Thyroid Imaging Reporting and Data System (K-TIRADS) category to the thyroid nodule to predict malignancy 3
Repeat Fine-Needle Aspiration
Repeat FNA is often performed for nodules with Bethesda category 3 cytology, with a malignancy rate of 55.5% reported in one study 2
- The subclassification of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) can help predict malignancy 5
- Repeat FNA may be unnecessary for nodules with sonographically suspicious features, and surgery should be considered instead 2
Surgery
Surgery is often recommended for nodules with high suspicion of malignancy or those that are sonographically suspicious for malignancy 2, 3