Nonsurgical Option for More Large Thyroid Nodule Patients?

False negative rates from fine needle aspiration (FNA) biopsies of large thyroid nodules are lower than commonly reported when studies are expanded to include all nodules (including those that were not operated on), compared with only those that were.

While more research is needed, "the risk of false negative FNA results for large nodules may not be as high as reported in previous studies if you include patients who do not have indication for surgery, such as compressive symptoms, suspicious ultrasound features, etc," senior author Tracy Tylee, MD, an associate professor of endocrinology at the University of Washington, Seattle, told Medscape Medical News.

The implication is that nonsurgical options such as radiofrequency ablation may be appropriate for more patients than realized, she added.

"Clinicians should consider following these patients more conservatively, either with a second FNA to confirm [the] nodule is benign, or with ultrasound follow-up for 5 years with intervention only if [there are] significant changes on imaging," she said.

The findings were presented at the American Thyroid Association (ATA) Annual Meeting and Centennial Celebration.

Concerns About Nodules > 4 cm Having High False Negative Rates

Management of large thyroid nodules over 4 cm that are classified as Bethesda II, indicative of being benign, is complicated by concerns of false negatives in such cases. While the false negative rate for thyroid nodules in general is approximately 3%, the rate for large nodules over 4 cm has been reported as high as 35%.

Importantly, however, most studies evaluating the issue only involve patients who have received thyroid surgery, whereas most benign nodules are not referred for surgery.

"This may overestimate the false negative FNA biopsy risk for this group," first author Melbin Thomas, MD, also of the University of Washington, said in her talk.

To better assess the false negative rate in the broader context of large nodules that did and did not undergo surgery, Thomas and her colleagues conducted a retrospective chart review of all patients undergoing FNA biopsy at her center between 2008 and 2014 for thyroid nodules larger than 4 cm and initially classified as Bethesda II, or benign.

With a follow-up of up to 10 years, nodules were considered accurately benign if they showed benign pathology on surgical resection, if they remained benign based on repeat FNA biopsy with Bethesda II results, or if there were no changes on imaging characteristics on ultrasound after at least 2 years.

Overall, 47 nodules over 4 cm and Bethesda II cytology were included, with an average follow-up of 5 years (range 2.2 to 9.7 years).

Of the nodules, 23 were treated with surgery, two of which were determined to have been malignant (8.7%) and, hence, false negatives. Nine of the nodules had repeat FNA, with none found to be malignant, and 15 received repeat ultrasound, also with no malignancies.

Overall, the false negative rate including all patients was 4.3%.

"False negative FNA biopsy results were not markedly elevated if nodules greater than 4 cm are evaluated, but rates were considerably higher if limited to surgical patients," Thomas said.

Clinicians may be compelled to perform more aggressive surgery on large but benign thyroid nodules for a number of reasons, Tylee noted.

"A concern is that we may discontinue follow-up on these larger nodules and fail to diagnose a cancer early on before there has been extrathyroidal extension or lymph node metastases," she said.

In such cases, patients could wind up presenting at a higher stage of disease and require more intensive therapy.

However, with a low false negative rate overall, "all of this can increase the long-term healthcare costs and anxiety for patients, so having a better understanding of the true benign rate for large nodules is important," she concluded.

Commenting on the research, Rodis D. Paparodis, MD, chief of Endocrinology, Diabetes, and Metabolism Clinics, in Patras, Greece, said the findings underscore that, as a surgical procedure, "thyroidectomy should be used cautiously, only when the benefit outweighs the risk."

In his own previous multicenter study, Paparodis conducted a review of nearly 2500 thyroidectomies that were performed based on size or long-term slow growth despite pre-operative benign FNA findings. The results showed that only 1.9% of patients had any form of thyroid cancer in the nodule that had led to surgery; however, multiple other significant cancers were often present in other locations in the gland.

"Therefore, we suggest that careful sonographic evaluation of all thyroid nodules is warranted prior to deciding and planning the extent of surgical management for multinodular goiter," he told Medscape Medical News.

"In addition, FNA of all suspicious nodules is required as well, to avoid unnecessary surprises in surgical pathology."

Tylee, Thomas, and Paparodis report no relevant financial relationships.

American Thyroid Association (ATA) Annual Meeting and Centennial Celebration. Oral Abstract #32. Presented September 30, 2023.

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