Background: Thyroid nodules may be detected during the workup of thyroid hormone abnormalities and as incidental findings during unrelated imaging studies. The diagnosis of a thyroid nodule is mainly established by performing fine needle aspiration (FNA) under ultrasound guidance. Thyroid nodules are classified as nondiagnostic, defined in the Bethesda System for Reporting Thyroid Cytopathology as samples with excess blood, cyst fluid only, and lack of thyroid follicular cells. The current study evaluates a series of nondiagnostic FNAs to assess whether repeat sampling improves yield and what patient management, and outcomes are after a nondiagnostic FNA.

Methods: Thyroid FNAs from 2016 to 2023 were retrieved from our institution archives. All cases were performed under ultrasound guidance and with rapid on-site evaluation. Cases were assigned the Bethesda System Category. Nondiagnostic FNAs were further reviewed for repeat FNA procedures, potential molecular testing, or diagnostic resections.

Results: In total 3104 thyroid FNAs were reviewed, with 153 (4.9%) being nondiagnostic. Of the 154 FNAs, there were 129 patients with an average age of 60 and a male-to-female ratio of 1:3.2. Of the 130 patients, there were 50 patients who underwent 55 repeat FNAs. Thirty-seven (67%) of the repeats were benign, 13 (24%) were nondiagnostic again, and 5 (9%) were atypia of undetermined significance (AUS). Molecular testing was performed on repeat FNAs diagnosed AUS. Four cases showed no mutations and had a high likelihood of being benign. One case did have an NRAS Q61R mutation, and resection revealed a noninvasive follicular thyroid neoplasm with papillary-like nuclear features. Seventeen (13% of all cases) with nondiagnostic FNA were resected. Twelve (71%) thyroidectomies showed benign adenomatous nodules. The remainder showed incidental papillary thyroid microcarcinoma (0.1 cm), an infarcted follicular adenoma, a noninvasive follicular thyroid neoplasm with papillary-like nuclear features, and metastatic renal cell carcinoma (2×).

Conclusion: Thyroid nodules with nondiagnostic cytology are reassuring of being highly likely a benign nodule. Only 5 of the 55 (9%) repeat FNAs yielded abnormalities, with only one of those being truly a follicular neoplasm (confirmed by molecular testing and resection). No primary thyroid malignancies have been identified in follow-up (repeat FNA or surgery). Clinical and ultrasound follow-up may be more appropriate management for nondiagnostic thyroid FNAs.