Molecular alterations in Hürthle cell nodules and preoperative cancer risk

in Endocrine-Related Cancer
Authors:
William R Doerfler Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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Alyaksandr V Nikitski Department of Pathology, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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Elena M Morariu Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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N Paul Ohori Department of Pathology, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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Simion I Chiosea Department of Pathology, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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Michael S Landau Department of Pathology, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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Marina N Nikiforova Department of Pathology, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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Yuri E Nikiforov Department of Pathology, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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Linwah Yip Division of Endocrine Surgery, University of Pittsburgh, Pittsburgh, Pennysylvania, USA

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Pooja Manroa Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennysylvania, USA
Division of Endocrinology, University of Texas Medical Branch, Galveston, Texas, USA

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Correspondence should be addressed to P Manroa: pomanroa@utmb.edu
DOI:
https://doi.org/10.1530/ERC-20-0435
Volume/Issue:
Volume 28: Issue 5
Article Type:
Research Article
Page Range:
301–309
Online Publication Date:
27 Apr 2021
Copyright:
© 2021 Society for Endocrinology 2021
Collections:
Top-cited articles of 2023
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Hürthle cell carcinoma (HCC) is a distinct type of thyroid cancer genetically characterized by DNA copy number alterations (CNA), typically of genome haploidization type (GH-type). However, whether CNA also occurs in benign Hürthle cell adenomas (HCA) or Hürthle cell hyperplastic nodules (HCHN), and have diagnostic impact in fine-needle aspiration (FNA) samples, remains unknown. To address these questions, we (1) analyzed 26 HCC, 24 HCA, and 8 HCHN tissues for CNA and other mutations using ThyroSeq v3 (TSv3) next-generation sequencing panel, and (2) determined cancer rate in 111 FNA samples with CNA and known surgical outcome. We identified CNA, more often of the GH-type, in 81% of HCC and in 38% HCA, but not in HCHN. Among four HCC with distant metastasis, all had CNA and three TERT mutations. Overall, positive TSv3 results were obtained in 24 (92%) HCC, including all with ATA high risk of recurrence or metastasis. Among 111 FNA cases with CNA, 38 (34%) were malignant and 73 (66%) benign. A significant correlation between cancer rate and nodule size was observed, particularly among cases with GH-type CNA, where every additional centimeter of nodule size increased the malignancy odds by 1.9 (95% CI 1.3–2.7; P = 0.001). In summary, the results of this study demonstrate that CNA characteristic of HCC also occur in HCA, although with lower frequency, and probability of cancer in nodules with CNA increases with nodule size. Detection of CNA, in conjunction with other mutations and nodule size, is helpful in predicting malignancy in thyroid nodules.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© 2021 Society for Endocrinology 2021
Page(s):
9
Received Date:
08 Jan 2021
Accepted Date:
31 Mar 2021
Print Publication Date:
01 May 2021
Online Publication Date:
27 Apr 2021
Keywords:
Hürthle cell carcinoma; copy number alterations; ThyroSeq v3; molecular profile; Hürthle cell adenoma

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