Ultrasound is helpful to differentiate Bethesda class III thyroid nodules: A PRISMA-compliant systematic review and meta-analysis

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Fine-needle aspiration (FNA) is the most dependable tool to triage thyroid nodules for medical or surgical management. However, Bethesda class III cytology, namely “follicular lesion of undetermined significance” (FLUS) or “atypia of undetermined significance” (AUS), is a major limitation of the US-FNA in assessing thyroid nodules. As the most important imaging method, ultrasound (US) has a high efficacy in diagnosing thyroid nodules. This meta-analysis aimed to assess the role of US in evaluating Bethesda class III thyroid nodules.


With keywords “Undetermined Significance,” “Bethesda Category III,” “Bethesda system,” “Cytological Subcategory,” “AUS/FLUS,” “Atypia of Undetermined Significance,” and “Ultrasound/US,” papers in PubMed, Cochrane Library, Medline, Web of Science, Embase, and Google Scholar from inception to December 2016 were searched. A meta-analysis of these trials was then performed for evaluating the diagnostic value of thyroid ultrasound in Bethesda Category III thyroid nodules.


Fourteen studies including 2405 nodules were analyzed. According to the criteria for US diagnosis of thyroid nodules in each article, with any one of suspicious features as indictors of malignancy, US had a pooled sensitivity of 0.75 (95% CI 0.72–0.78) and a pooled specificity of 0.48 (95% CI 0.45–0.50) in evaluating Bethesda Class III Nodules. The pooled diagnostic odds ratio was 10.92 (95% CI 6.04–19.74). The overall area under the curve was 0.84 and the Q* index was 0.77. With any 2 or 3 of US suspicious features as indictors of malignancy, the sensitivity and specificity were 0.77 (95% CI 0.71–0.83) and 0.54 (95% CI 0.51–0.58), 0.66 (95% CI 0.59–0.73) and 0.71 (95% CI 0.68–0.74), respectively.


US was helpful for differentiating benign and malignant Bethesda class III thyroid nodules, with the more suspicious features, the more likely to be malignant.

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