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Preoperative Role of RAS or BRAF K601E in the Guidance of Surgery for Indeterminate Thyroid Nodules

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Abstract

Background

RAS and K601E BRAF mutations are not a reliable indicator of malignancy in fine-needle aspirations (FNA) of thyroid indeterminate cytologic nodules. We aimed to evaluate the histologic characteristics, the risk of malignancy associated with such mutations in FNA and their potential interest for preoperative clinical management of nodules.

Methods

We evaluated 69 indeterminate thyroid nodules with RAS or K601E BRAF mutations with available histopathologic follow-up. All FNA specimens were indeterminate according to the thyroid Bethesda system. Diagnosis of malignant, benign or indolent neoplasms was classified according to 2017 WHO classification. Carcinoma, NIFTP (noninvasive follicular thyroid neoplasm with papillary-like features) and WDTUMP (well-differentiated tumor of uncertain malignant potential) were considered “surgical,” as they require surgical excision. Adenoma was considered “non-surgical.” The risk of malignancy and the risk of “surgical disease” were evaluated.

Results

Pathologic evaluation of the 69 mutated nodules demonstrated benign, indolent and malignant histology in 17 cases (25%), 21 cases (30%) and 31 cases (45%), respectively. The risk of malignancy was 45%, and the risk of surgical disease was 75%. The majority of carcinomas were a follicular variant of papillary thyroid carcinoma. On follow-up, there have been no recurrences to date.

Conclusion

Preoperative RAS or BRAF K601E mutations detection in cytologic indeterminate thyroid nodules carries a high risk of surgical disease and may benefit from surgical management. Most surgical lesions harboring those mutations are low-risk tumors, which may be in favor of an initial lobectomy.

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Acknowledgements

We would like to thank Garance Tondeur and Aurélie Gaultier for their excellent technical support.

Funding

No specific funding was disclosed.

Author information

Authors and Affiliations

  1. Pathology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France

    L. Ravella & M. Decaussin-Petrucci

  2. Biochemistry and Molecular Biology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France

    J. Lopez & F. Descotes

  3. Cancer Research Center of Lyon, Team EMT and Cancer Cell Plasticity, Lyon 1 University, Lyon, France

    J. Lopez

  4. CNRS, UMR 5558, Laboratoire de Biométrie et Biologie Evolutive, Equipe Biostatistique-Santé, 69622, Villeurbanne, France

    J. Giai

  5. Université Lyon 1, 69622, Villeurbanne, France

    J. Giai

  6. Service de Biostatistique et Bioinformatique, Hospices Civils de Lyon, 69003, Lyon, France

    J. Giai

  7. Radiology Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France

    V. Lapras & M.-L. Denier

  8. Endocrinology Department, Groupement Hospitalier Est, Hospices Civils de Lyon, Bron, France

    F. Borson-Chazot

  9. Endocrine Surgery Department, Centre Hospitalier Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France

    J.-C. Lifante

  10. Cancer Research Center of Lyon, INSERM1052, CNRS5286, Lyon 1 University, Lyon, France

    M. Decaussin-Petrucci

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  1. L. Ravella
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  2. J. Lopez
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  3. F. Descotes
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Contributions

MDP and LR contributed to study design, results analysis, manuscript draft, cytology and histology data; FD and JL contributed to molecular biology data; VL, MLD and JCL contributed to LB-FNA and surgical specimens; JG helped in statistical analysis; and MDP, JL and FBC helped in manuscript reviewing.

Corresponding author

Correspondence to M. Decaussin-Petrucci.

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The authors declared that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Ravella, L., Lopez, J., Descotes, F. et al. Preoperative Role of RAS or BRAF K601E in the Guidance of Surgery for Indeterminate Thyroid Nodules. World J Surg 44, 2264–2271 (2020). https://doi.org/10.1007/s00268-020-05487-1

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  • DOI: https://doi.org/10.1007/s00268-020-05487-1

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