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  • Review Article
  • Published:

Molecular profiling of thyroid nodule fine-needle aspiration cytology

Nature Reviews Endocrinology volume 13, pages 415–424 (2017)Cite this article

Subjects

Key Points

  • 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

  • 'Rule-out' malignancy approaches aim to identify benign nodules that have an indeterminate cytology and to reduce the overtreatment of benign nodules

  • 'Rule-in' malignancy approaches aim to identify malignant nodules that have an indeterminate cytology and to optimize surgical planning

  • 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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Figure 1: Ruling in and ruling out malignancy.

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Authors and Affiliations

  1. Department of Oncology, Cumming School of Medicine, University of Calgary, Tom Baker Cancer Centre, 1331 - 29th Street NW, Calgary, T2N 4N2, Alberta, Canada

    Markus Eszlinger, Shamir P. Chandarana & Ralf Paschke

  2. Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Health Research Innovation Centre, 3280 Hospital Drive, Calgary, T2T 4Z6, Alberta, Canada

    Markus Eszlinger & Ralf Paschke

  3. Division of Endocrinology, Department of Medicine, Cumming School of Medicine, University of Calgary, Richmond Road Diagnostic and Treatment Centre, 1820 Richmond Road SW, Calgary, T2T 5C7, Alberta, Canada

    Lorraine Lau, Sana Ghaznavi, Christopher Symonds & Ralf Paschke

  4. Department of Surgery, Cumming School of Medicine, University of Calgary, Foothills Medical Centre, North Tower 1012, 1403 - 29th Street NW, Calgary, T2N 2T9, Alberta, Canada

    Shamir P. Chandarana

  5. Department of Pathology and Laboratory Medicine, University of Calgary, Foothills Medical Centre, McCaig Tower, 1403 - 29th Street NW, Calgary, T2N 2T9, Alberta, Canada

    Moosa Khalil

  6. Department of Medicine, Cumming School of Medicine, University of Calgary, North Tower 9th floor, 1403 - 29th Street NW, Calgary, T2N 2T9, Alberta, Canada

    Ralf Paschke

  7. Department of Biochemistry and Molecular Biology, Cumming School of Medicine, University of Calgary, Health Research Innovation Centre, 3280 Hospital Drive, Calgary, T2N 4Z6, Alberta, Canada

    Ralf Paschke

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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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Correspondence to Ralf Paschke.

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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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