If a fine-needle aspiration (FNA) biopsy of the thyroid is negative, is a repeat biopsy indicated if the thyroid mass increases in size?

From the Guidelines

If a thyroid nodule with a previously negative fine needle aspiration (FNA) biopsy increases in size, a repeat biopsy is generally recommended. This recommendation is based on the understanding that FNA has inherent sampling limitations, with false negative rates of approximately 2-5% 1. A significant size increase, typically defined as growth of 20% or more in at least two nodule dimensions, with a minimum increase of 2 mm, or a 50% or greater increase in volume, is considered a concerning feature that warrants reevaluation 1. The timing of repeat biopsy depends on the rate of growth and risk factors, but generally occurs within 6-12 months of documented growth.

Some key points to consider when deciding to repeat a biopsy include:

• The initial FNA result was negative, but the nodule has increased in size, which may indicate potential malignancy that was missed on the initial sampling 1.
• Patient-specific risk factors, such as radiation exposure history, family history of thyroid cancer, or suspicious sonographic features, should also influence the decision to repeat biopsy 1.
• The use of ultrasound-guided FNA can increase specimen adequacy and improve the diagnostic yield, especially in cases with cystic or necrotic masses 1.
• On-site evaluation by a cytopathologist can reduce the inadequacy rate of FNA 1.

In terms of the specific criteria for repeat biopsy, the following should be considered:

• A significant size increase, as defined above, is a clear indication for repeat biopsy 1.
• The presence of suspicious sonographic features, such as hypoechogenicity, microcalcifications, or irregular borders, should also prompt repeat biopsy 1.
• A history of radiation exposure or family history of thyroid cancer should lower the threshold for repeat biopsy 1.

Overall, the decision to repeat a biopsy should be based on a careful consideration of the individual patient's risk factors, the characteristics of the nodule, and the results of the initial FNA biopsy. Repeat biopsy is a crucial step in the management of thyroid nodules, as it can help to detect potential malignancies that may have been missed on the initial sampling.

From the Research

Thyroid FNA Biopsy Results and Repeat Biopsy

• If a thyroid fine-needle aspiration (FNA) biopsy is negative, the decision to repeat the biopsy depends on various factors, including the size and characteristics of the nodule, as well as changes in its size over time 2, 3, 4.
• A study published in 1995 found that large, cystic/solid thyroid nodules have a higher probability of malignancy and a higher false-negative rate for FNA, suggesting that repeat biopsy or surgical excision should be considered in these cases 2.
• Another study published in 2014 found that the odds of malignancy increase with the size of the nodule, and that repeat FNA may not be necessary in cases where the nodule is stable or decreasing in size 3.
• A 2015 study found that repeat FNA biopsy changed clinical management in 9.5% of cases, but the prevalence of malignancy remained low, ranging from 1.2% to 4.1% depending on the gold standard used 4.

Characteristics of Thyroid Nodules and Biopsy Results

• The characteristics of the thyroid nodule, such as its size, composition, and echogenicity, can influence the likelihood of malignancy and the accuracy of FNA biopsy results 2, 3, 5, 6.
• A 2022 study found that core needle biopsy (CNB) has a higher sensitivity and positive predictive value than FNA for diagnosing anaplastic thyroid carcinoma and thyroid lymphoma, particularly in cases with rapidly enlarging thyroid masses 5.
• Another study published in 2014 found that using CNB as a first-line diagnostic procedure can reduce false-negative and inconclusive results compared to FNA, particularly in solid thyroid nodules at high risk of malignancy 6.

Management of Thyroid Nodules with Negative FNA Biopsy Results

• The management of thyroid nodules with negative FNA biopsy results depends on various factors, including the size and characteristics of the nodule, as well as changes in its size over time 2, 3, 4.
• Clinical guidelines recommend ultrasonographic follow-up of benign thyroid nodules, and repeat FNA biopsy or surgical excision may be considered in cases where the nodule is large, growing, or has suspicious characteristics 2, 3, 4.
• The use of CNB as a diagnostic tool may be considered in cases where FNA biopsy results are inconclusive or suspicious, particularly in cases with rapidly enlarging thyroid masses or solid thyroid nodules at high risk of malignancy 5, 6.