Skip to main content

Advertisement

SpringerLink
Log in

New Insights into Tumor Heterogeneity: A Case of Solid-Oncocytic Epithelial-Myoepithelial Carcinoma of the Parotid Gland Harboring a HRAS and Heterogeneous Terminating ARID1A Mutation

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

Abstract

Epithelial-myoepithelial carcinoma (EMC) can be a challenging diagnosis due to a lack of obvious invasion and bland cytology. We report an unusual case of a low-grade EMC with prominent fibrous stroma, an extensive solid-oncocytic differentiation and limited areas of morphological clearly identifiable characteristic biphasic (tubular) differentiation, clear cells and PAS-positive secretions/calcifications. Both areas were investigated by next generation sequencing (Oncomine comprehensive assay) and revealed a typical concordant HRAS p.Q61R mutation. An additional heterogeneous ARID1A (p.E672*) terminating mutation with loss of heterozygosity, which could be visualized predominantly in the solid-oncocytic differentiation by immunohistochemical loss of ARID1A protein expression, was found. This is the first case of an EMC of the salivary gland to be described with two separate tumor clones involving concordant HRAS and heterogeneous ARID1A mutations. The latter seem to be a “second hit” and was predominantly found in the solid-oncocytic differentiation, suggesting a potential morpho-molecular association.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Seethala RR, Barnes EL, Hunt JL. Epithelial-myoepithelial carcinoma: a review of the clinicopathologic spectrum and immunophenotypic characteristics in 61 tumors of the salivary glands and upper aerodigestive tract. Am J Surg Pathol. 2007;31(1):44–57. https://doi.org/10.1097/01.pas.0000213314.74423.d8.

    Article  PubMed  Google Scholar 

  2. Yang GC, Soslow RA. Epithelial-myoepithelial carcinoma of the parotid. A case of ductal-predominant presentation with cytologic, histologic and ultrastructural correlations. Acta Cytol. 1999;43(6):1113–8. https://doi.org/10.1159/000331363.

    Article  CAS  PubMed  Google Scholar 

  3. El Hallani S, Udager AM, Bell D, Fonseca I, Thompson LDR, Assaad A, et al. Epithelial-myoepithelial carcinoma: frequent morphologic and molecular evidence of preexisting pleomorphic adenoma, common HRAS mutations in PLAG1-intact and HMGA2-intact cases, and occasional TP53, FBXW7, and SMARCB1 alterations in high-grade cases. Am J Surg Pathol. 2018;42(1):18–27. https://doi.org/10.1097/PAS.0000000000000933.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Seethala RR, Richmond JA, Hoschar AP, Barnes EL. New variants of epithelial-myoepithelial carcinoma: oncocytic-sebaceous and apocrine. Arch Pathol Lab Med. 2009;133(6):950–9. https://doi.org/10.1043/1543-2165-133.6.950.

    Article  PubMed  Google Scholar 

  5. Seethala RR. Oncocytic and apocrine epithelial myoepithelial carcinoma: novel variants of a challenging tumor. Head Neck Pathol. 2013;7(Suppl 1):S77–84. https://doi.org/10.1007/s12105-013-0461-0.

    Article  PubMed  Google Scholar 

  6. Chiosea SI, Miller M, Seethala RR. HRAS mutations in epithelial-myoepithelial carcinoma. Head Neck Pathol. 2014;8(2):146–50. https://doi.org/10.1007/s12105-013-0506-4.

    Article  PubMed  Google Scholar 

  7. Urano M, Nakaguro M, Yamamoto Y, Hirai H, Tanigawa M, Saigusa N, et al. Diagnostic significance of HRAS mutations in epithelial-myoepithelial carcinomas exhibiting a broad histopathologic spectrum. Am J Surg Pathol. 2019. https://doi.org/10.1097/PAS.0000000000001258.

    Article  PubMed  Google Scholar 

  8. Geyer FC, Li A, Papanastasiou AD, Smith A, Selenica P, Burke KA, et al. Recurrent hotspot mutations in HRAS Q61 and PI3 K-AKT pathway genes as drivers of breast adenomyoepitheliomas. Nat Commun. 2018;9(1):1816. https://doi.org/10.1038/s41467-018-04128-5.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Pareja F, Geyer FC, Brown DN, Sebastiao APM, Gularte-Merida R, Li A, et al. Assessment of HMGA2 and PLAG1 rearrangements in breast adenomyoepitheliomas. NPJ Breast Cancer. 2019;5:6. https://doi.org/10.1038/s41523-018-0101-7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Wu JN, Roberts CW. ARID1A mutations in cancer: another epigenetic tumor suppressor? Cancer Discov. 2013;3(1):35–43. https://doi.org/10.1158/2159-8290.CD-12-0361.

    Article  CAS  PubMed  Google Scholar 

  11. Wiegand KC, Shah SP, Al-Agha OM, Zhao Y, Tse K, Zeng T, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 2010;363(16):1532–43. https://doi.org/10.1056/NEJMoa1008433.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Weinreb I, Zhang L, Tirunagari LM, Sung YS, Chen CL, Perez-Ordonez B, et al. Novel PRKD gene rearrangements and variant fusions in cribriform adenocarcinoma of salivary gland origin. Genes Chromosomes Cancer. 2014;53(10):845–56. https://doi.org/10.1002/gcc.22195.

    Article  CAS  PubMed  Google Scholar 

  13. Sebastiao APM, Pareja F, Kumar R, Brown DN, Silveira C, da Silva EM, et al. Genomic analysis of recurrences and high-grade forms of polymorphous adenocarcinomas. Histopathology. 2019. https://doi.org/10.1111/his.13854.

    Article  PubMed  Google Scholar 

  14. Zehir A, Benayed R, Shah RH, Syed A, Middha S, Kim HR, et al. Mutational landscape of metastatic cancer revealed from prospective clinical sequencing of 10,000 patients. Nat Med. 2017;23(6):703–13. https://doi.org/10.1038/nm.4333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Jones S, Wang TL, Shih Ie M, Mao TL, Nakayama K, Roden R, et al. Frequent mutations of chromatin remodeling gene ARID1A in ovarian clear cell carcinoma. Science. 2010;330(6001):228–31. https://doi.org/10.1126/science.1196333.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Williamson CT, Miller R, Pemberton HN, Jones SE, Campbell J, Konde A, et al. ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A. Nat Commun. 2016;7:13837. https://doi.org/10.1038/ncomms13837.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Shen J, Peng Y, Wei L, Zhang W, Yang L, Lan L, et al. ARID1A deficiency impairs the DNA damage checkpoint and sensitizes cells to PARP inhibitors. Cancer Discov. 2015;5(7):752–67. https://doi.org/10.1158/2159-8290.CD-14-0849.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Samartzis EP, Gutsche K, Dedes KJ, Fink D, Stucki M, Imesch P. Loss of ARID1A expression sensitizes cancer cells to PI3 K- and AKT-inhibition. Oncotarget. 2014;5(14):5295–303. https://doi.org/10.18632/oncotarget.2092.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology and Molecular Pathology, University Hospital Zurich, Schmelzbergstr. 12, 8091, Zurich, Switzerland

    Niels J. Rupp, Muriel Brada, Beata Bode, Markus Rechsteiner & Sandra N. Freiberger

  2. Sikl’s Department of Pathology, Faculty of Medicine in Plzen, Charles University, Pilsen, Czech Republic

    Alena Skálová

  3. Institute of Pathology Enge, Zurich, Switzerland

    Beata Bode

  4. Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Zurich, Zurich, Switzerland

    Martina A. Broglie & Grégoire B. Morand

  5. University of Zurich, Zurich, Switzerland

    Niels J. Rupp, Muriel Brada, Beata Bode, Martina A. Broglie, Grégoire B. Morand, Markus Rechsteiner & Sandra N. Freiberger

Authors
  1. Niels J. Rupp
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Muriel Brada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alena Skálová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beata Bode
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Martina A. Broglie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Grégoire B. Morand
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Markus Rechsteiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Sandra N. Freiberger
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Niels J. Rupp.

Ethics declarations

Conflict of interest

The authors declare that no competing financial interests exist.

Ethical approval

The patient provided a written informed consent in accordance with the Declaration of Helsinki.

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

Rupp, N.J., Brada, M., Skálová, A. et al. New Insights into Tumor Heterogeneity: A Case of Solid-Oncocytic Epithelial-Myoepithelial Carcinoma of the Parotid Gland Harboring a HRAS and Heterogeneous Terminating ARID1A Mutation. Head and Neck Pathol 14, 554–558 (2020). https://doi.org/10.1007/s12105-019-01055-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-019-01055-9

Keywords

Search

Navigation