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Correlation of ThyroSeq Results with Surgical Histopathology in Cytologically Indeterminate Thyroid Nodules

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Abstract

The ThyroSeq next-generation sequencing test refines the risk of malignancy in cytologically indeterminate thyroid nodules. Specific genetic alterations have distinct cancer probabilities and clinical phenotypes. There is limited data on the association between specific genetic alterations and histopathologic features. The aim of this study was to evaluate specific ThyroSeq alterations in prognosticating high-risk histopathologic characteristics. We performed a retrospective single-institution study of all patients diagnosed with indeterminate thyroid nodules (May 2016–December 2019) who had a mutation identified with ThyroSeq v2 or v3 and underwent surgical resection. Specific genetic alterations were correlated with surgical histopathology. The main outcomes were risk of malignancy and structural recurrence risk based on histopathologic features and the 2015 American Thyroid Association (ATA) risk stratification. Of the 78 nodules, 50 (64%) were thyroid cancer or noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) on surgical histopathology. Nodules with high-risk TERT or TP53 combination mutations (TERT/TP53) and those with BRAF-like mutations were associated with a 100% probability of cancer and higher rates of extrathyroidal extension and regional nodal involvement than nodules with RAS-like mutations. Among nodules with RAS-like mutations, there was an even distribution between benign, NIFTP, and malignant results, the latter of which were all ATA low risk for structural disease recurrence. Overall, TERT/TP53 and BRAF-like ThyroSeq mutations are associated with an increased cancer probability and risk of recurrence defined by histopathologic features, while RAS-like mutations are associated with lower cancer probability and indolent disease. Individualized management, including extent of surgery, should be considered based on specific genetic alterations found in cytologically indeterminate thyroid nodules.

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Acknowledgments

We thank Dr. Chi-Hong Tseng for performing statistical analysis on the data. We thank Dr. Gregory Brent and Dr. Jeffrey Krane for comments on the project and manuscript.

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Authors and Affiliations

  1. Section of Endocrine Surgery, University of California Los Angeles David Geffen School of Medicine, 10833 Le Conte Ave, Suite 72-228 CHS, Los Angeles, CA, 90095, USA

    Patrick D. Chin, Catherine Y. Zhu, Michael W. Yeh & Masha J. Livhits

  2. Division of Anatomic Pathology, Department of Pathology and Laboratory Medicine, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA

    Dipti P. Sajed & Gregory A. Fishbein

  3. Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, University of California Los Angeles David Geffen School of Medicine, Los Angeles, CA, USA

    Angela M. Leung

  4. Department of Medicine, Division of Endocrinology, Diabetes, and Metabolism, VA Greater Los Angeles Healthcare System, Los Angeles, CA, USA

    Angela M. Leung

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  1. Patrick D. Chin
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Contributions

Patrick D. Chin: data curation, formal analysis, investigation, methodology, visualization, writing– original draft, writing– review and editing. Catherine Y. Zhu: conceptualization, data curation, formal analysis, methodology, visualization, writing– original draft, writing– review and editing. Dipti P. Sajed: formal analysis, investigation, visualization, validation, writing– review and editing. Gregory A. Fishbein: formal analysis, investigation, visualization, validation, writing– review and editing. Michael W. Yeh: conceptualization, formal analysis, methodology, project administration, validation, visualization, writing– review and editing. Angela M. Leung: conceptualization, formal analysis, methodology, validation, visualization, writing– review and editing. Masha J. Livhits: conceptualization, data curation, formal analysis, methodology, project administration, validation, visualization, writing– review and editing, supervision.

All authors read and approved the final manuscript.

Corresponding author

Correspondence to Masha J. Livhits.

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The authors declare that they have no conflict of interest.

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This study was approved by the UCLA Institutional Review Board, and all procedures were in accordance with the ethical standards of the 1964 Helsinki declaration and its later amendments.

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Chin, P.D., Zhu, C.Y., Sajed, D.P. et al. Correlation of ThyroSeq Results with Surgical Histopathology in Cytologically Indeterminate Thyroid Nodules. Endocr Pathol 31, 377–384 (2020). https://doi.org/10.1007/s12022-020-09641-2

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