Bethesda Category III, IV, and V Thyroid Nodules: Can Nodule Size Help Predict Malignancy?

The association of tumor size with malignancy in thyroid nodules with indeterminate cytology (atypia of undetermined significance [AUS]/follicular lesion of undetermined significance [FLUS], suspicious for follicular neoplasm [SFN]/Hürthle cell neoplasm [HCN], and suspicious for malignancy [SM]) has not been clearly studied.

We retrospectively identified 1,104, patients who underwent thyroid FNA and subsequent thyroidectomy. Patients with indeterminate cytology were reviewed. The size of the nodule was determined by ultrasound. Malignancy was confirmed by final histology. Logistic regression modeling was performed to determine if nodule size was associated with malignancy.

There were 461 (42%) patients who had indeterminate cytology by FNA. The median nodule size of all indeterminate lesions was 2.1 cm (range 0.5 to 10 cm). The median nodule size for AUS/FLUS was 2.1 cm (range 0.7 to 8 cm), for SFN was 2.4 cm (range 0.5 to 10 cm), for HCN was 2.2 cm (range 0.5 to 9.3 cm), and for SM was 1.6 cm (range 0.5 to 6 cm). On final histology, 121 (28%) index lesions were malignant (AUS 23%; FLUS 14%; SFN 22%; HCN 25%; SM 69%). On logistic regression, nodule size was not associated with increased odds of malignancy in all lesions with indeterminate cytology (odds ratio [OR] 0.83; 95% CI 0.76 to 1.00; p = 0.051). Nodule size was not associated with malignancy in the index nodule of AUS/FLUS, SFN, or SM lesions. Increased nodule size was associated with malignancy in HCN lesions (OR 2.17; 95% CI 1.16 to 4.04; p = 0.01).

The findings of this study suggest that larger HCN nodules are more likely to be malignant. Nodule size alone was not predictive of malignancy in patients with AUS/FLUS, SFN, or SM. Clinical picture, institution-specific malignancy rates, and molecular testing continue to be important factors guiding treatment.