47.21 False Negative Rate of FNA in Thyroid Nodules: Size and Accuracy for Papillary Thyroid Cancer

E.M. Henriksen1, E.A. Todd1, J. Chang1, E. Lopez1, C. Saghira2, A.C. Cioci1,2, T.M. Vaghaiwalla1,2, J.I. Lew1,2  1University of Miami, Leonard M. Miller School Of Medicine, Miami, FLORIDA, USA 2University Of Miami, DeWitt Daughtry Department Of Surgery, Division Of Endocrine Surgery, Miami, FL, USA

Introduction:
Fine needle aspiration (FNA) is a widely used diagnostic tool for assessing thyroid nodules for malignancy. However, its accuracy can be influenced by various factors, including thyroid nodule size. Since larger nodules are known to yield higher false negative (FN) rates for papillary thyroid cancer (PTC) by FNA, surgical excision is often recommended for thyroid nodules >4 cm. This study examines the performance of FNA for PTC across thyroid nodule sizes.

Methods:
A retrospective study of prospectively collected data from 2525 patients who underwent FNA and thyroidectomy at a single institution between 2000-2022 was performed. Patients ≥18 years of age who had Bethesda Category II or VI thyroid nodules and a diagnosis of papillary thyroid cancer (PTC) on final histopathology were included. Thyroid nodules were stratified based on their largest dimension: <1 cm, 1.0–1.99 cm, 2.0–2.99 cm, 3.0–3.99 cm, and ≥4.0 cm. Final histopathology of thyroid nodules for PTC were correlated with their initial preoperative FNA results. Statistical analysis was performed using ANOVA and post-hoc testing to assess the significance of FN rates across thyroid nodule sizes. A P-value <0.05 was considered statistically significant.

Results:
Of 762 patients, there were 638 women (83.7%) and 124 men (16.3%) with an average age of 49.3 years. For the overall study group, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), false positive (FP), and FN rates for FNA were 85.8%, 97.1%, 97.8%, 82.5%, 2.9%, and 14.2%, respectively. FN rates increased with thyroid nodule size: 3.6% (n=2) for nodules <1 cm and 15.7% (n=66) for nodules ≥1 cm. Specifically, FN rates were 3.6% (n=2) for <1 cm, 3.9% (n=8) for 1.0–1.99 cm, 16.2% (n=18) for 2.0–2.99 cm, 46.4% (n=26) for 3.0–3.99 cm, and 46.2% (n=12) for ≥4.0 cm (Figure 1). Statistical analysis revealed significant differences in the FN rate of FNA for thyroid nodules ≥3.0 cm (p<0.001). Post-hoc testing revealed a significant difference between both the ≥3 cm groups and the <3 cm groups. There was no significant difference between patients with thyroid nodules 3.0-3.99 cm and ≥4 cm.

Conclusion:
Most clinical guidelines use a thyroid nodule size of >4 cm for surgical excision because of the higher incidence of FN for PTC. This study, however, highlights the variability of the FN rate and increased thyroid nodule size for PTC, particularly for thyroid nodules ≥3 cm. While the current study findings indicate a lower thyroid nodule size cutoff, future studies should be considered to re-evaluate this size threshold to avoid missed thyroid cancer diagnosis.