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Potentially actionable FGFR2 high-level amplification in thymic sebaceous carcinoma

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Abstract

Our aim was to investigate sebaceous differentiation in thymus tumours and to identify new actionable genomic alterations. To this end we screened 35 normal and 23 hyperplastic thymuses, 127 thymomas and 41 thymic carcinomas for the presence of sebaceous differentiation as defined by morphology and expression of adipophilin and androgen receptor (AR). One primary thymic carcinoma showed morphology of sebaceous carcinomas (keratinizing and foam cells, calcifications, giant cells), a strong expression of adipophilin and AR together with squamous markers. NGS revealed high-level amplification of fibroblast growth factor receptor 2 (FGFR2). In thymuses and thymomas, no cells with sebaceous morphology were present. Occasionally, macrophages or epithelial cells showed adipophilin-positivity, however, without co-expression of AR. Thymic sebaceous carcinoma should be considered if a thymic carcinoma shows clear or foamy features. Testing for FGFR2 amplification might be warranted when searching for actionable genomic alterations in sebaceous carcinomas in the mediastinum and in other locations.

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Funding

This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.

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Authors and Affiliations

  1. Institute of Pathology, University Medical Centre Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany

    Stefan Porubsky & Alexander Marx

  2. Department of Pathology, Royal Hobart Hospital, Hobart, Australia

    Peter Jessup

  3. Department of Cancer Medicine, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    Damien Kee & Clare Scott

  4. Cancer and Stem Cell Division, Walter and Eliza Hall Medical Research Institute, Parkville, Victoria, Australia

    Damien Kee & Clare Scott

  5. Department of Cardiothoracic Surgery, Royal Hobart Hospital, Hobart, Australia

    Rajiv Sharma & Ashutosh A. Hardikar

  6. Menzies Institute for Medical Research, University of Tasmania, Hobart, Australia

    Ayame Ochi

  7. Department of Pathology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia

    Huiling Xu

  8. Department of Medical Imaging, Interventional and Neurointerventional Services, Royal Hobart Hospital, Hobart, Australia

    Jens J. Froelich

  9. Department of Medical Oncology, Royal Hobart Hospital, Hobart, Australia

    Louise Nott & Cristina Moldovan

  10. Department of Radiation Oncology, Royal Hobart Hospital, Hobart, Australia

    Raef Awad

  11. Institute of Pathology, University Medical Center Göttingen, University of Göttingen, Göttingen, Germany

    Hanibal Bohnenberger, Stefan Küffer & Philipp Ströbel

Authors
  1. Stefan Porubsky
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  2. Peter Jessup
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  3. Damien Kee
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  4. Rajiv Sharma
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  5. Ayame Ochi
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  6. Huiling Xu
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  7. Jens J. Froelich
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  8. Louise Nott
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  9. Clare Scott
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  10. Raef Awad
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  11. Cristina Moldovan
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  12. Ashutosh A. Hardikar
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  13. Hanibal Bohnenberger
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  14. Stefan Küffer
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  15. Philipp Ströbel
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  16. Alexander Marx
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Contributions

AM initiated the study and reviewed the manuscript. SP and AM designed the study. SP analysed data, prepared figures and wrote the manuscript. PJ, DK, RS, AO, HX, JJF, LN, CS, RA, CM, AAH, HB, SK and PS analysed data. All authors gave final approval for publication. SP takes responsibility for the work, including the study design, access to data and the decision to submit and publish the manuscript.

Corresponding author

Correspondence to Stefan Porubsky.

Ethics declarations

The authors/co-authors declare that the study complies with ethical standards. The study was approved by the local Ethics committee (Medical Ethics Committee II, Medical Faculty Mannheim of the Heidelberg University).

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All authors declare to have no conflict of interests.

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Porubsky, S., Jessup, P., Kee, D. et al. Potentially actionable FGFR2 high-level amplification in thymic sebaceous carcinoma. Virchows Arch 476, 323–327 (2020). https://doi.org/10.1007/s00428-019-02644-3

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  • DOI: https://doi.org/10.1007/s00428-019-02644-3

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