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Whole exome sequencing and establishment of an organoid culture of the carcinoma showing thymus-like differentiation (CASTLE) of the parotid gland

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Abstract

Carcinoma showing thymus-like differentiation (CASTLE) is a rare tumor, especially in the parotid gland. We encountered a CASTLE of the parotid gland and analyzed its clinicopathological features, as well as the genotype using whole exome sequencing (WES). Moreover, we successfully established an organoid culture cell line from the primary tumor tissue. The patient was a 23-year-old woman who underwent superficial parotidectomy with peripheral neck dissection, followed by radiotherapy. Pathologically, the resected specimen showed atypical epithelioid nests and trabeculae with squamous differentiation, separated by thick fibrous septa, accompanied by dense lymphocytes and plasma cell infiltration. Immunohistochemistry revealed that the tumor cells were positive for AE1/AE3, p40, p63, p16, CK5/6, and CD5, and the background lymphocytes were positive for CD5 and CD99. Based on these findings, the tumor was diagnosed as CASTLE. WES uncovered five nonsynonymous and splicing somatic mutations, namely, FREM2 p.Val861Phe, CLK3 p.Phe376Leu, DLGAP1 p.Lys294Asn, NOX1 p.Val165Met, and PSG9 c.430 + 4A > T. Organoid culture cells preserved the histopathological characteristics of the epithelioid component of CASTLE and harbored all five somatic mutations detected in the primary tumor. In conclusion, for the first time to the best of our knowledge, we successfully analyzed a comprehensive genotype and established an organoid culture cell line of a parotid gland CASTLE, which should serve for analyzing the nature of this rare tumor.

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Acknowledgments

We would like to thank Ms. Yayoi Aoyama (Department of Pathology, Tohoku University Hospital) for technical support in immunohistochemistry and the technical staff of Biomedical Research Core of Tohoku University Graduate School of Medicine for tissue sample preparation.

Funding

This work was supported in part by Grant-in-Aid from JSPS KAKENHI Grant Number of 16 K11221.

Author information

Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, Tohoku University Graduate School of Medicine, Sendai, Japan

    Tomohiko Ishikawa, Ayako Nakanome, Yasunari Yamauchi, Takuya Yoshida & Yukio Katori

  2. Department of Investigative Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan

    Tomohiko Ishikawa, Masahiro Shiihara, Takuya Yoshida & Toru Furukawa

  3. Department of Otolaryngology, Gifu University Graduate School of Medicine, Gifu, Japan

    Takenori Ogawa

  4. Department of Pathology, Sendai Kousei Hospital, Sendai, Japan

    Hajime Usubuchi

  5. Tohoku University Advanced Research Center for Innovations in Next-Generation Medicine, Sendai, Japan

    Yasunobu Okamura & Kengo Kinoshita

  6. Tohoku University Tohoku Medical Megabank Organization, Sendai, Japan

    Yasunobu Okamura & Kengo Kinoshita

  7. Tohoku University Graduate School of Information Sciences, Sendai, Japan

    Kengo Kinoshita

Authors
  1. Tomohiko Ishikawa
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  2. Takenori Ogawa
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  10. Yukio Katori
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  11. Toru Furukawa
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Contributions

T. I. developed the concept of the study; T. O., Y. K., and T. F. supervised the study; T. I. and H. U. performed the histological and immunohistochemical analysis; T. O., A. N., and Y. Y. collected clinical sample and data; Y. O. and K. K. analyzed next-generation sequencing data; T. I. and T. Y. performed HPV assay; T. I. and M. S. performed the organoid culture; T. I. and T. F. interpreted the experimental and clinical data; T. I. wrote the draft and all authors contributed to the final manuscript; T.F. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Corresponding author

Correspondence to Toru Furukawa.

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This study was approved by the ethical committee of Tohoku University Graduate School of Medicine (#2019-1-082), and the patient provided informed consent. All procedures involving human participants in this study were in accordance with the ethical standards of this institutional research committee and with the 1964 Helsinki Declaration.

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Ishikawa, T., Ogawa, T., Nakanome, A. et al. Whole exome sequencing and establishment of an organoid culture of the carcinoma showing thymus-like differentiation (CASTLE) of the parotid gland. Virchows Arch 478, 1149–1159 (2021). https://doi.org/10.1007/s00428-020-02981-8

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