From the Guidelines
Follicular cell with atypia of undetermined significance (AUS/FLUS), Bethesda Category 3, indicates a thyroid fine needle aspiration (FNA) result that shows cellular features that are not clearly benign but also not suspicious enough to be classified in higher risk categories, with a recommended approach of repeat FNA in 3-6 months or molecular testing to better assess cancer risk. This finding carries approximately a 5-15% risk of malignancy, as indicated by the Bethesda System for Reporting Thyroid Cytopathology 1. The management decision should be individualized based on the specific cellular features noted, the patient's risk factors for thyroid cancer, and other clinical findings such as nodule size, growth pattern, and ultrasound characteristics.
Key Considerations
- The estimated risk of malignancy for AUS/FLUS is 5-15% 1
- Molecular diagnostic testing may be useful in evaluating FNA samples that are indeterminate to assist in management decisions 1
- Clinical correlation with ultrasound findings and patient risk factors may guide whether more immediate surgical intervention is warranted
- The management decision should be individualized based on the specific cellular features noted, the patient's risk factors for thyroid cancer, and other clinical findings
Molecular Testing
Molecular testing of the sample may be performed to better assess cancer risk, with the choice of the precise molecular test depending on the cytology and the clinical question being asked 1. However, the predictive value of molecular diagnostics may be significantly influenced by the pretest probability of disease associated with the various FNA cytology groups.
Clinical Approach
The recommended approach is usually a repeat FNA in 3-6 months to see if the abnormality persists or changes, with active surveillance considered if the application of a specific molecular diagnostic test results in a predicted risk of malignancy that is comparable to the rate seen in cytologically benign thyroid FNAs (approximately ≤5%) 1. In some cases, clinical correlation with ultrasound findings and patient risk factors may guide whether more immediate surgical intervention is warranted.
From the Research
Follicular Cell with Atypia of Undetermined Significance: Bethesda Category 3 Meaning
- The Bethesda System for Reporting Thyroid Cytopathology categorizes thyroid nodules into several categories, with Category 3 being "Atypia of Undetermined Significance" (AUS) or "Follicular Lesion of Undetermined Significance" (FLUS) 2, 3, 4, 5, 6.
- This category is used when the cytological findings are not sufficient to diagnose a benign or malignant lesion, but are not entirely normal either.
- The risk of malignancy for nodules classified as AUS/FLUS is variable, ranging from 5-55% 3, 5.
- Several studies have shown that the combination of cytological subcategory (FLUS or AUS) and ultrasonography (US) can provide different risks of malignancy for nodules initially classified as Bethesda Category 3 2, 4.
- For example, one study found that the rate of malignancy was lower in nodules initially classified as FLUS (10.8% versus 41.3% with AUS) 4.
- Another study found that the malignancy rate for nodules that featured nuclear atypia was significantly higher at 36.8% than the rate for nodules that had only architectural atypia at 14.7% 6.
- Ultrasonography (US) has also been shown to be useful for predicting malignancy, with sensitivity, specificity, and positive and negative predictive values of 79.4%, 90.5%, 71%, and 93.75%, respectively 4.
- The management of nodules with a cytopathologic diagnosis of AUS/FLUS can be difficult, and may include observation, repeat fine-needle aspiration, and surgery 5.
- Institutional factors, molecular genetics, and the identification of suspicious US characteristics are all important in the development of an appropriate, tailored management approach 5.