SpringerLink
Log in

Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature

  • Case Reports
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

Clear cell carcinoma (CCC) is a rare low-grade malignant salivary gland carcinoma. EWSR1-ATF1 fusion has been characterized as a consistent finding in CCC, with breakpoints described between EWSR1 exon 11 and ATF1 exon 3. So far, over 100 cases of CCC harboring EWSR1 rearrangement arising from salivary gland of the oral cavity have been reported. Although EWSR1 involvement in these cases was confirmed by EWSR1 break-apart FISH indicating the translocation, sequence analysis for EWSR1-ATF1 fusion type has been reported only in three cases of CCC so far. Herein, we report a CCC case with novel EWSR1-ATF1 fusion (EWSR1 exon 15 and ATF1 exon 5) arising in minor salivary gland and review the role of the chimeric variants in some malignancies with EWSR1-ATF1 rearrangement. Current tumor was composed of the small nests of clear tumor cells and hyalized fibrous stroma. Immunohistochemically, the tumor was positive for AE1/AE3, CK5/6 and p63, negative for S100, Melan-A, SMA and CD10. After 8 months of follow-up, there are no evidence of recurrence.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. El-Naggar AK, Chang JKC, Grandis JR, Takada T, Slootweg PJ. World Health Organization classification of head and neck tumours. 4th ed. Lyon: IARC; 2017. p. 168–69.

    Google Scholar 

  2. Antonescu CR, Katabi N, Zhang L, et al. EWSR1-ATF1 fusion is a novel and consistent finding in hyalinizing clear-cell carcinoma of salivary gland. Genes Chromosomes Cancer. 2011;50:559–70.

    Article  CAS  Google Scholar 

  3. ** R, Craddock KJ, Irish JC, Perez-Ordonez B, Weinreb I. Recurrent hyalinizing clear cell carcinoma of the base of tongue with high-grade transformation and EWSR1 gene rearrangement by FISH. Head Neck Pathol. 2012;6:389–94.

    Article  Google Scholar 

  4. Bilodeau EA, Weinreb I, Antonescu CR, et al. Clear cell odontogenic carcinomas show EWSR1 rearrangements: a novel finding and a biological link to salivary clear cell carcinomas. Am J Surg Pathol. 2013;37:1001–5.

    Article  Google Scholar 

  5. Shah AA, Legallo RD, van Zante A, et al. EWSR1 genetic rearrangements in salivary gland tumors: a specific and very common feature of hyalinizing clear cell carcinoma. Am J Surg Pathol. 2013;37:571–8.

    Article  Google Scholar 

  6. Albergotti WG, Bilodeau EA, Byrd JK, Mims MM, Lee S, Kim S. Hyalinizing clear cell carcinoma of the head and neck: case series and update. Head Neck. 2016;38:426–33.

    Article  Google Scholar 

  7. Nakano T, Yamamoto H, Nishijima T, et al. Hyalinizing clear cell carcinoma with EWSR1-ATF1 fusion gene: report of three cases with molecular analyses. Virchows Arch. 2015;466:37–433.

    Article  Google Scholar 

  8. Hernandez-Prera JC, Kwan R, Tripodi J, et al. Reappraising hyalinizing clear cell carcinoma: a population-based study with molecular confirmation. Head Neck. 2017;39:503–11.

    Article  Google Scholar 

  9. Chapman E, Skalova A, Ptakova N, et al. Molecular profiling of hyalinizing clear cell carcinomas revealed a subset of tumors harboring a novel EWSR1-CREM fusion: report of 3 cases. Am J Surg Pathol. 2018;42:1182–9.

    Article  Google Scholar 

  10. Yang XH, Liu L, Shi YY, Hu YJ, Hu QG, Zhang P. Hyalinizing clear cell carcinoma of salivary gland origin in the head and neck: clinical and histopathological analysis. Int J Oral Maxillofac Surg. 2018;47:692–8.

    Article  Google Scholar 

  11. Thway K, Fisher C. Tumors with EWSR1-CREB1 and EWSR1-ATF1 fusions: the current status. Am J Surg Pathol. 2012;36:e1–e11.

    Article  Google Scholar 

  12. Kujiraoka S, Tsunematsu T, Sato Y, et al. Establishment and characterization of a clear cell odontogenic carcinoma cell line with EWSR1-ATF1 fusion gene. Oral Oncol. 2017;69:46–55.

    Article  CAS  Google Scholar 

  13. Wang WL, Mayordomo E, Zhang W, et al. Detection and characterization of EWSR1/ATF1 and EWSR1/CREB1 chimeric transcripts in clear cell sarcoma (melanoma of soft parts). Mod Pathol. 2009;22:1201–9.

    Article  CAS  Google Scholar 

  14. Skálová A, Weinreb I, Hyrcza M, et al. Clear cell myoepithelial carcinoma of salivary glands showing EWSR1 rearrangement: molecular analysis of 94 salivary gland carcinomas with prominent clear cell component. Am J Surg Pathol. 2015;39:338–48.

    Article  Google Scholar 

  15. Bilodeau EA, Hoschar AP, Barnes LL, Hunt JL, Seethala RR. Clear cell carcinoma and clear cell odontogenic carcinoma: a comparative clinicopathologic and immunohistochemical study. Head Neck Pathol. 2011;5:101–7.

    Article  Google Scholar 

  16. Taylor BS, Barretina J, Maki RG, Antonescu CR, Singer S, Ladanyi M. Advances in sarcoma genomics and new therapeutic targets. Nat Rev Cancer. 2011;11:541–57.

    Article  CAS  Google Scholar 

  17. Cantile M, Marra L, Franco R, et al. Molecular detection and targeting of EWSR1 fusion transcripts in soft tissue tumors. Med Oncol. 2013;30:412.

    Article  Google Scholar 

  18. Rossow KL, Janknecht R. The Ewing’s sarcoma gene product functions as a transcriptional activator. Cancer Res. 2001;61:2690–5.

    CAS  PubMed  Google Scholar 

  19. Hailemariam K, Iwasaki K, Huang BW, Sakamoto K, Tsuji Y. Transcriptional regulation of ferritin and antioxidant genes by HIPK2 under genotoxic stress. J Cell Sci. 2010;123:3863–71.

    Article  CAS  Google Scholar 

Download references

Funding

The authors have no funding, financial relationships.

Author information

Authors and Affiliations

  1. Department of Oral Pathology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Katsutoshi Hirose, Yu Usami, Sunao Sato & Satoru Toyosawa

  2. Department of Pathology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Masaharu Kohara, Yumiko Hori & Eiichi Morii

  3. Department of Oral and Maxillofacial Radiology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Yuri Iwamoto & Shumei Murakami

  4. Department of Oral and Maxillofacial Surgery 1, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Toshihiro Uchihashi

  5. Unit of Dentistry, Osaka University Hospital, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Toshihiro Uchihashi

  6. Clinical Laboratory, Osaka University Dental Hospital, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan

    Kaori Oya & Yasuo Fukuda

Authors
  1. Katsutoshi Hirose
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yu Usami
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Masaharu Kohara
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Sunao Sato
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yuri Iwamoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Shumei Murakami
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Toshihiro Uchihashi
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Kaori Oya
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yasuo Fukuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Yumiko Hori
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Eiichi Morii
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Satoru Toyosawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

All authors contributed to this work. KH, and YU designed this study. KH, YU, SS, KO, YF, EM and ST interpreted the H&E and immunohistochemical findings. KH and MK performed the experiments and assembled data. KH, YU, YH and ST contributed to the writing of the manuscript. YI, SM and TU reviewed the radiological and clinical data. All authors reviewed and approved the manuscript for submission.

Corresponding author

Correspondence to Satoru Toyosawa.

Ethics declarations

Conflict of interest

All authors state that they have no conflicts of interest.

Ethical Approval

This case report was approved by the Ethical Review Board of the Graduate School of Dentistry, Osaka University (No. R1-E46) and was performed in accordance with the Committee guidelines and regulations.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hirose, K., Usami, Y., Kohara, M. et al. Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature. Head and Neck Pathol 15, 676–681 (2021). https://doi.org/10.1007/s12105-020-01211-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-020-01211-6

Keywords

Search

Navigation