The clinical value of repeat ultrasound-guided fine-needle aspiration biopsy in the management of Bethesda Category III thyroid nodules

TL;DR

Repeat ultrasound-guided biopsies improve diagnosis of thyroid nodules initially deemed indeterminate, with timing and ultrasound features influencing outcomes.

Contribution

Demonstrates that repeat FNAB increases diagnostic accuracy for Bethesda III nodules and identifies optimal timing and ultrasound features for follow-up.

Findings

93 out of 114 Bethesda III nodules received a definitive diagnosis through repeat FNAB.

TI-RADS score ≥8 and ultrasound features like microcalcifications guide effective repeat biopsy.

No significant difference in outcomes based on biopsy interval (under or over 3 months).

Abstract

This study aimed to evaluate the clinical value of repeat fine-needle aspiration biopsy (rFNAB) for thyroid nodules initially classified as Bethesda Category III, to explore the optimal timing for repeat biopsy, and to optimize the biopsy strategy by integrating ultrasonographic characteristics.

We retrospectively analyzed the clinical data of 109 patients (114 nodules) who underwent rFNAB at our hospital from December 2020 to December 2025, including 87 females and 22 males. Based on rFNAB results, the nodules were divided into a definitive diagnosis group (93 nodules) and a non-definitive diagnosis group (21 nodules). The definitive diagnosis group was further subdivided into a malignant group (62 nodules, Bethesda V/VI) and a benign group (31 nodules, Bethesda II). We recorded biopsy results, intervals between biopsies, postoperative pathological findings, and ultrasonographic features. Statistical differences between groups were analyzed. Statistical methods included the χ² test, Fisher’s exact test, binary logistic regression analysis, and ROC curve analysis.

Among the 114 Bethesda Category III nodules, 93 (81.6%) obtained a definitive diagnosis through rFNAB, including 62 malignant (66.7%) and 31 benign (33.3%) nodules; 21 nodules (18.4%) remained non-diagnostic. Forty-seven patients with malignant rFNAB results underwent surgical treatment, including 9 (19.1%) in the <3-month interval group and 38 (80.9%) in the ≥3-month interval group. No significant differences were observed in lymph node metastasis rates or recurrence risk stratification between the two groups. Among the ultrasonographic characteristics of the malignant, benign, and non-diagnostic groups, only calcification type showed a statistically significant difference (P < 0.05). Additionally, ROC curve analysis confirmed the diagnostic efficacy of the TI-RADS score for Bethesda Category III nodules (AUC = 0.746). The maximum Youden index (0.403) was achieved at a cut-off value of 8 points (specificity 83.9%, sensitivity 56.5%).

Repeat fine-needle aspiration biopsy (rFNAB) significantly improves the diagnostic rate for thyroid nodules initially diagnosed as Bethesda Category III, and the time interval between the two biopsies does not affect diagnostic performance. For the follow-up of nodules with an initial Bethesda Category III FNAB result, rFNAB is recommended when the TI-RADS score is ≥8, especially if suspicious ultrasonographic signs such as new or persistent microcalcifications are present. During the procedure, multi-point sampling should target non-calcified areas at the nodule periphery to improve the accuracy and reliability of rFNAB.

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