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Identification of Recurrent TERT Promoter Mutations in Intrathyroid Thymic Carcinomas

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Abstract

Intrathyroid thymic carcinoma (ITTC) is a rare malignant neoplasm considered to be a eutopic thymic carcinoma (TC) arising ectopically in the thyroid. Histopathologically, ITTC resembles squamous cell carcinoma of the thymus with positive TC markers such as CD5 and c-KIT. Despite these similar histological findings, ITTC is clinically less aggressive than TC. In this study, we compared clinical, histological, and genetic characteristics of ITTCs and TCs. We collected 9 ITTCs and 8 TCs with their clinicopathological profiles. Immunohistochemistry for CD5, p63, CD117/c-KIT, Ki-67, p53, TTF-1, thyroglobulin, PAX8, EGFR, and PD-L1/CD274 plus in situ hybridization for EBER was performed. We further investigated mutation status of KIT, EGFR, BRAF, and TERT promoter using Sanger sequencing. In our study, ITTCs affected significantly younger patients than TCs. After a mean follow-up of 86 months, all patients with ITTC were alive, while two patients with TC had died. Immunohistochemistry showed ITTCs and TCs had a similar immunophenotype except for EGFR and p53. Genetic analysis did not identify KIT or BRAF mutations in any ITTCs or TCs. EGFR mutations were positive in 11% (1/9) of ITTCs and 25% (2/8) of TCs. Notably, TERT promoter C228T mutation was identified in 22% (2/9) of ITTCs but none of the TCs. There were no significant differences in age, tumor size, or sex between TERT-mutated and TERT-wild-type ITTCs. Collectively, ITTC and TC have similar histopathologic and immunophenotypic features but different clinical outcomes. Recurrent TERT promoter mutation may be a key event related to cancer progression in ITTCs and warrants further investigation.

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All data generated or analyzed during this study are included in this article and its supplementary information files.

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Acknowledgments

We wish to thank Pam Zaber of Editdoc English Editing for her help with English editing of this article. We appreciate Ms. Wakaba Iha, Mr. Yoshihito Koshimizu, and Ms. Kayoko Kono for their technical assistance.

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Authors and Affiliations

  1. Department of Pathology, University of Yamanashi, Chuo, Yamanashi, Japan

    Ippei Tahara, Naoki Oishi, Kunio Mochizuki & Tetsuo Kondo

  2. Department of Pathology, Yamanashi Prefectural Central Hospital, Kofu, Yamanashi, Japan

    Toshio Oyama

  3. Department of Pathology, Kofu Municipal Hospital, Kofu, Yamanashi, Japan

    Kazuyuki Miyata

  4. Department of Surgery, Kuma Hospital, Kobe, Hyogo, Japan

    Akira Miyauchi

  5. Department of Diagnostic Pathology, Kuma Hospital, Kobe, Hyogo, Japan

    Mitsuyoshi Hirokawa

  6. Department of Pathology, Ito hospital, Tokyo, Japan

    Ryohei Katoh

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  1. Ippei Tahara
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Correspondence to Tetsuo Kondo.

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This study was conducted under the approval of the Institutional Ethical Review Board of University of Yamanashi (approval code: 1723).

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Tahara, I., Oishi, N., Mochizuki, K. et al. Identification of Recurrent TERT Promoter Mutations in Intrathyroid Thymic Carcinomas. Endocr Pathol 31, 274–282 (2020). https://doi.org/10.1007/s12022-020-09635-0

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