Key Points
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Thyroid fine-needle aspiration cytology has the inherent limitation of yielding 20–30% indeterminate results, and thyroid surgery is required for a definitive diagnosis in these cases; however, this limitation could be overcome through molecular diagnostics
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'Rule-out' malignancy approaches aim to identify benign nodules that have an indeterminate cytology and to reduce the overtreatment of benign nodules
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'Rule-in' malignancy approaches aim to identify malignant nodules that have an indeterminate cytology and to optimize surgical planning
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MicroRNA classifiers are expected to enable the classification of malignancy in mutation-negative malignant nodules as part of the rule-in approach and could provide additional markers as part of a two-step diagnostic approach
Abstract
The differential diagnosis and malignancy risk stratification of thyroid nodules requires multidisciplinary expertise and knowledge of both local ultrasonography practices and the local malignancy rates for a given fine-needle aspiration (FNA) result. Even in such a multidisciplinary setting, FNA cytology has the inherent limitation that indeterminate cytology results cannot distinguish between follicular adenomas, follicular thyroid carcinomas or follicular variant papillary thyroid carcinomas. Accumulating evidence suggests that this limitation can be overcome by using molecular diagnostic approaches. In this Review, we present the advantages and disadvantages of the different molecular diagnostic methodologies, which can be divided into two approaches: those that 'rule out' malignancy (to reduce the overtreatment of benign nodules) and those that 'rule in' malignancy (to optimize surgical planning). We identify microRNA classifiers as potential additional markers for use in a two-step diagnostic approach, consider the potential implications of the reclassification of noninvasive encapsulated follicular variant papillary thyroid carcinomas to noninvasive follicular thyroid neoplasms with papillary-like nuclear features and discuss the cost-effectiveness of molecular testing. Molecular FNA diagnostics is an important complementary addition to FNA cytology that could substantially reduce unnecessary surgery and better define the need for appropriate surgery in patients who have thyroid nodules with indeterminate FNA cytology.
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R.P., M.E. and L.L. researched the data for the article. R.P. and M.E. wrote and revised the article. All authors made a substantial contribution to discussion of the content of the article.
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Eszlinger, M., Lau, L., Ghaznavi, S. et al. Molecular profiling of thyroid nodule fine-needle aspiration cytology. Nat Rev Endocrinol 13, 415–424 (2017). https://doi.org/10.1038/nrendo.2017.24
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DOI: https://doi.org/10.1038/nrendo.2017.24
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