BACKGROUND
Thyroid nodules are very common, occurring in up to 50% of individuals that get any imaging test that includes the neck. The concern with a thyroid nodule is whether it is a cancer. Fortunately, only ~5% of thyroid nodules are cancerous, so the vasy majority of nodules are benign. However, there is some data that shows that large nodules (≥4 cm) have a higher cancer risk. Thyroid biopsy is the main test to determine whether a nodule is cancer or benign. However, some studies suggest that a thyroid biopsy is less reliable in evaluating large nodules. Larger nodules may have a higher rate of missed cancer, especially those nodules with different areas within the nodule as compared to nodules that appear to be the same throughout. As a result, clinicians remain divided on whether benign biopsy findings in large thyroid nodules can safely be followed as benign nodules or whether the need to consider surgery instead.

The goal of this study was to determine the cancer rate of large thyroid nodules and evaluate the diagnostic accuracy of biopsy results of large nodules by comparing the biopsy findings with the final surgical pathology results.

THE FULL ARTICLE TITLE
Swaminathan N , et al. Malignancy risk and diagnostic accuracy of fine-needle aspiration in thyroid nodules ≥4 cm: a retrospective analysis of incidental cancer. Am Surg. Epub 2025 Dec 9; doi: 10.1177/00031348251407348. PMID: 41363024.

SUMMARY OF THE STUDY
This study evaluated 95 adult patients with thyroid nodules ≥4 cm who underwent thyroid biopsy and then surgical removal of their nodules (partial or total thyroidectomy) at a large care center between January 2015 and December 2024. Of note, at this institution, patients with large thyroid nodules typically undergo thyroidectomy even when the biopsy results are benign.

The biopsy results were categorized according to the Bethesda System for Reporting Thyroid Cytopathology, an international standardized reporting system that includes six cytologic categories, each category having a different cancer risk. In this study, the cytology results were grouped as low-risk (Bethesda I-III) and high risk for malignancy (Bethesda IV-VI). The cytology results from thyroid biopsies were compared with the final surgical results.

Among patients with thyroid nodules ≥4 cm who underwent thyroid biopsy, 15% were cancer at surgery, while 85% had benign results. Thyroid biopsy results and surgery results were in agreement in 64 of 81 patients (79%) with benign nodules and in 12 of 14 patients (86%) with cancerous nodules. Notably, over one-third (36%) of cancers were not detected by thyroid biopsy prior to surgery, highlighting the potential for missed cancers in large thyroid nodules despite benign results. A total of 86% of the patients with biopsy results showing high-risk cytology (Bethesda IV-VI) had cancer on final pathology, while 79% of those with low-risk cytology (Bethesda I-III) had truly benign thyroid nodules.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
This study highlights that a benign biopsy result does not always guarantee the absence of cancer in large thyroid nodules. A larger study with better characterization of the nodule features on ultrasound may be helpful in determining the risk of a false benign biopsy result. Understanding this risk enables informed shared decisionmaking regarding following a large nodule with a benign biopsy with ultrasound versus referring for surgery.

— Elie Naous, MD
— Alina Gavrila, MD, MMSC

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