Thyroid nodule size and risk of malignancy: a systematic review

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Abstract
Background There is ongoing uncertainty about the association between thyroid nodule size and likelihood of malignancy. Researchers are divided, some proposing that risk is increased with nodule size while others claim the opposite. Numerous studies have been completed but there is at present no agreed consensus. Furthermore, the diagnostic accuracy of fine needle aspiration (FNA), the standard test for investigating thyroid nodules is disputed. Reported ranges of false negatives range from 2 to 20%. Aims The overall aims of this study were to investigate the relationship between thyroid nodule size and malignancy and to examine the association between FNA results and malignancy rates in small and large nodules. Design Systematic review and meta-analysis of observational studies examining the association between malignancy and thyroid nodule size. Methods A systematic review was completed using search words ‘thyroid, nodule and size’ in PubMed database. Criteria for inclusion were retrospective or prospective studies with nodule size and final pathology and/or FNA results that had a primary focus on adult populations. Results In total 17 studies were deemed eligible for inclusion. 16 studies were included in the first meta-analysis looking at the relationship between nodule size and malignancy rates. Overall, nodules over 4 cm were associated with a lower incidence of malignancy, 15% compared with 37%. A Random effects model meta-analysis was undertaken, which also indicated a trend towards a lower risk of malignancy in nodules over 4 cm, with a risk difference of 0.1 (95% CI − 0.01, 0.21). However, there was significant heterogeneity with an I2 of 99%, therefore caution has to be exercised when interpreting the results. 11 studies were included in the second meta- analysis, examining the impact of nodule size on the association between FNA results and malignancy. The meta-analysis showed that there was no statistically difference between the false negative rates of nodules less than or greater than 4 cm. Conclusion While there is a trend towards larger nodule being less likely to indicate malignancy, thyroid nodule size does not appear to have a significant influence on the accuracy of FNA in predicting cancer. Thyroid nodule size alone should not influence the decision to refer for further tests or surgery as it is an unreliable predictor of malignancy in isolation. However, taken in conjunction with clinical and radiological findings it may be a useful adjunct to guiding treatment.

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