Do large thyroid nodules have a higher pre-test probability of malignancy than smaller thyroid nodules?
Background: Thyroid nodules affect 4% to 10% of the U.S. adult population, with 4% to 5% of nodules ultimately proving malignant. Fine needle aspiration (FNA) biopsy is the prevalent diagnostic modality for evaluating a thyroid nodule, but there is variability in cytology reporting schemes, indeterminate values sorting, and statistical calculations. Large thyroid nodules may be associated with higher risk of malignancy and less accurate FNA results, but there is currently no overarching consensus.
Study design: Review of 15 criterion-meeting studies (two prospective studies, two retrospective analyses of prospective databases, 11 retrospective studies) with a total of 13,180 participants published through July 2013.
Setting: PubMed, Embase, Cochrane Library.
Synopsis: The strongest data and the preponderance of data suggest that malignancy prevalence is higher within larger nodules, regardless of whether a cutoff of 3 cm or 4 cm is used. All studies showed a worse point estimate of sensitivity and false negative rate in large nodules in comparison to small ones. The data presented in multiple reports also suggest a trend toward a higher post-test probability of malignancy in larger nodules, where FNA results were follicular neoplasm, suspicious, indeterminate, or nondiagnostic. One of the largest studies demonstrated a statistically significant higher false negative rate in large versus small nodules. In all studies with corresponding data, the point estimate of the post-test malignancy probability was higher in benign nodules larger than 3 to 4 cm, as compared with those that were smaller. There were some limitations: Trends may not be true differences due to statistically insignificant results, a notable variability in how indeterminate results were categorized, and limited data interpretation due to insufficient FNA technique description.
Bottom line: Large nodules have a higher pre-test probability of malignancy, with a reduced FNA diagnostic accuracy in nodules larger than 3 cm to 4 cm in diameter.
Reviewed by Amy E. Hamaker