Impact of Thyroid Nodule Size on Prevalence and Post-test Probability of Malignancy: A Systematic Review

Objectives/HypothesisLarge thyroid nodules may be associated with higher risk of malignancy and less-accurate fine-needle aspiration (FNA) results, but there is currently no overarching consensus. We therefore tested two null hypotheses: 1) thyroid nodule size >3 to 4 cm is not associated with a higher baseline prevalence of malignancy (i.e., the associated pretest probability is the same, regardless of size), and 2) thyroid nodule size >3 to 4 cm is not associated with worse diagnostic accuracy (i.e., the associated sensitivity, false-negative rate, and post-test probability of malignancy is not affected by nodule diameter). Study DesignComputerized searches of PubMed, Embase, and The Cochrane Library through July 2013 were performed, supplemented with manual searches. MethodsA priori criteria were defined to determine inclusion and exclusion of studies. Searches and data extraction were performed by independent reviewers and focused on FNA histopathologic findings and their relationship to nodule size, study design, and potential confounders. ResultsCriterion-meeting studies (n=15) included a total of 13,180 participants. The preponderance of prospective comparative studies showed a statistically significantly higher prevalence of malignancy in large nodules. Although data are mixed, evidence from the best-reported studies suggests sensitivity, false-negative rates, and frequency of true negatives among benign FNA results are worse in large nodules. ConclusionsLarge nodules have a higher pretest probability of malignancy. Data from larger studies suggest reduced FNA diagnostic accuracy in nodules >3 to 4 cm in diameter. Surgery represents a reasonable clinical option for nodules >3 cm. Level of EvidenceNA Laryngoscope, 125:263-272, 2015