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First Reported Case of Malignant Ectomesenchymoma with p.Leu122Arg Mutation in MYOD1 Gene: Extensive Intra- and Extracranial Tumor in a 15-Year-Old Female

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Abstract

Background

Ectomesenchymomas (EMs) are extremely rare neoplasms composed of malignant mesenchymal components and neuroectodermal derivatives. They are described in a wide variety of locations, with the head and neck region being one of the most frequently involved areas. EMs are usually managed as high-risk rhabdomyosarcomas and have similar outcomes.

Methods

We present the case of a 15-year-old female with an EM that arose in the parapharyngeal space and extended into the intracranial space.

Results

Histologically, the tumor presented an embryonal rhabdomyosarcomatous mesenchymal component and the neuroectodermal component was constituted by isolated ganglion cells. Next-generation sequencing (NGS) revealed a p.Leu122Arg (c.365 T > G) mutation in the MYOD1 gene, a p.Ala34Gly mutation in the CDKN2A gene, and CDK4 gene amplification. The patient was treated with chemotherapy. She died 17 months after the debut of symptoms.

Conclusion(s)

To our knowledge, this is the first reported case in English literature of an EM with this MYOD1 mutation. We suggest combining PI3K/ATK pathway inhibitors in these cases. NGS should be performed in EMs cases to detect mutations with potential treatment options.

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Data Availability

Data will be available upon request from the authors.

References

  1. Boué DR, Parham DM, Webber B et al (2000) Clinicopathologic study of ectomesenchymomas from intergroup rhabdomyosarcoma study groups III and IV. Pediatr Dev Pathol 3(3):290–300. https://doi.org/10.1007/s100249910039

    Article  PubMed  Google Scholar 

  2. Holimon JL, Rosenblum WI (1971) “Gangliorhabdomyosarcoma”: a tumor of ectomesenchyme: case report. J Neurosurg 34(3):417–422. https://doi.org/10.3171/jns.1971.34.3.0417

    Article  CAS  PubMed  Google Scholar 

  3. Nael A, Siaghani P, Wu WW, Nael K, Shane L, Romansky SG (2014) Metastatic malignant ectomesenchymoma initially presenting as a pelvic mass: report of a case and review of literature. Case Rep Pediatr 2014:1–9. https://doi.org/10.1155/2014/792925

    Article  Google Scholar 

  4. Dantonello TM, Leuschner I, Vokuhl C et al (2013) Malignant ectomesenchymoma in children and adolescents: report from the cooperative weichteilsarkom studiengruppe (CWS): malignant pediatric ectomesenchymoma. Pediatr Blood Cancer 60(2):224–229. https://doi.org/10.1002/pbc.24174

    Article  PubMed  Google Scholar 

  5. Matsko TH, Schmidt RA, Milam AH, Orcutt JC (1992) Primary malignant ectomesenchymoma of the orbit. Br J Ophthalmol 76(7):438–441. https://doi.org/10.1136/bjo.76.7.438

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Bittinger A, Rossberg C, Rodehüser M (1997) Primary malignant ectomesenchymoma of the orbit. Gen Diagn Pathol 142(3–4):221–225

    CAS  PubMed  Google Scholar 

  7. Paikos P, Papathanassiou M, Stefanaki K, Fotopoulou M, Grigorios S, Tzortzatou F (2002) Malignant ectomesenchymoma of the orbit in a child. Surv Ophthalmol 47(4):368–374. https://doi.org/10.1016/S0039-6257(02)00313-2

    Article  PubMed  Google Scholar 

  8. Medina LS, Barnes PD, Donovan MJ, Taylor GA (1997) Radiologic-pathologic conference of children’s hospital boston: intraconal mass in the orbit of an infant. Pediatr Radiol 27(8):682–684. https://doi.org/10.1007/s002470050211

    Article  CAS  PubMed  Google Scholar 

  9. Patil CN, Cyriac S, Majhi U, Rajendranath R, Sagar TG (2011) Malignant ectomesenchymoma of the nasal cavity. Indian J Med Paediatr Oncol 32(04):242–243. https://doi.org/10.4103/0971-5851.95164

    Article  PubMed  PubMed Central  Google Scholar 

  10. Cergnul M, La Rosa S, Bandera M et al (2007) Malignant ectomesenchymoma of the nasal cavity. Lancet Oncol 8(4):358–360. https://doi.org/10.1016/S1470-2045(07)70105-5

    Article  PubMed  Google Scholar 

  11. Brehmer D, Overhoff HM, Marx A (2003) Malignant ectomesenchymoma of the nose. ORL 65(1):52–56. https://doi.org/10.1159/000068666

    Article  CAS  PubMed  Google Scholar 

  12. Majhi U, Murhekar K, Sundersingh S, Krishnamurthy A (2012) Malignant ectomesenchymoma of paranasal sinuses with proptosis and nodal involvement. J Can Res Ther 8(3):465. https://doi.org/10.4103/0973-1482.103541

    Article  Google Scholar 

  13. Vinck AS, Lerut B, Hermans R, Nuyts S, Sciot R, Jorissen M (2011) Malignant ectomesenchymoma of the paranasal sinuses with proptosis. B-ENT 7(3):201–204

    CAS  PubMed  Google Scholar 

  14. Shuangshoti S, Chutchavaree A (1980) Parapharyngeal neoplasm of mixed mesenchymal and neuroepithelial origin. Arch Otolaryngol 106(6):361–364. https://doi.org/10.1001/archotol.1980.00790300049010

    Article  CAS  PubMed  Google Scholar 

  15. Kasantikul V, Shuangshoti S, Cutchavaree A, Bunyaphiphat P (1987) Parapharyngeal malignant ectomesenchymoma: combined malignant fibrous histiocytoma and primitive neuroectodermal tumour with neuroglial differentiation. J Laryngol Otol 101(5):508–515. https://doi.org/10.1017/s0022215100102105

    Article  CAS  PubMed  Google Scholar 

  16. Milano GM, Orbach D, Casanova M et al (2020) Malignant ectomesenchymoma in children: the European pediatric Soft tissue sarcoma study group experience. Pediatric Blood & Cancer. https://doi.org/10.1002/pbc.30116

    Article  Google Scholar 

  17. VandenHeuvel KA, Carpentieri DF, Chen J, Fung KM, Parham DM (2014) Ectomesenchymoma with embryonal rhabdomyosarcoma and ganglioneuroma, arising in association with benign triton tumor of the tongue. Pediatr Dev Pathol 17(3):226–230. https://doi.org/10.2350/14-01-1433-CR.1

    Article  PubMed  Google Scholar 

  18. Karcioglu Z, Someren A, Mathes SJ (1977) Ectomesenchymoma: a malignant tumor of migratory neural crest (ectomesenchyme) remnants showing ganglionic, schwannian, melanocytic and rhabdomyoblastic differentiation. Cancer 39(6):2486–2496. https://doi.org/10.1002/1097-0142(197706)39

    Article  CAS  PubMed  Google Scholar 

  19. Schmidt D, Mackay B, Osborne BM, Jaffe N (1982) Recurring congenital lesion of the cheek. Ultrastruct Pathol 3(1):85–90. https://doi.org/10.3109/01913128209016628

    Article  CAS  PubMed  Google Scholar 

  20. Huang S, Antonescu C (2020) Ectomesenchymoma. In: WHO classification of tumours editorial board. Soft tissue and bone tumours, 5th edn. Agency for research on cancer pp 214–215

  21. Cornejo P, Egelhoff J, Kaye R et al (2020) Malignant ectomesenchymoma of the scalp. Appl Radiol 49(3):40–42

    Article  Google Scholar 

  22. Howley S, Stack D, Morris T et al (2012) Ectomesenchymoma with t(1;12)(p32;p13) evolving from embryonal rhabdomyosarcoma shows no rearrangement of ETV6. Hum Pathol 43(2):299–302. https://doi.org/10.1016/j.humpath.2011.03.010

    Article  CAS  PubMed  Google Scholar 

  23. Huang SC, Alaggio R, Sung YS et al (2016) Frequent HRAS mutations in malignant ectomesenchymoma: overlapping genetic abnormalities with embryonal rhabdomyosarcoma. Am J Surg Pathol 40(7):876–885. https://doi.org/10.1097/PAS.0000000000000612

    Article  PubMed  PubMed Central  Google Scholar 

  24. Griffin BB, Chou PM, George D, Jennings LJ, Arva NC (2018) Malignant ectomesenchymoma: series analysis of a histologically and genetically heterogeneous tumor. Int J Surg Pathol 26(3):200–212. https://doi.org/10.1177/1066896917734915

    Article  PubMed  Google Scholar 

  25. Kleinschmidt-DeMasters BK, Lovell MA, Donson AM et al (2007) Molecular array analyses of 51 pediatric tumors shows overlap between malignant intracranial ectomesenchymoma and MPNST but not medulloblastoma or atypical teratoid rhabdoid tumor. Acta Neuropathol 113(6):695–703. https://doi.org/10.1007/s00401-007-0210-0

    Article  CAS  PubMed  Google Scholar 

  26. PDQ Pediatric Treatment Editorial Board. Childhood Soft Tissue Sarcoma Treatment (PDQ®): Health Professional Version. In: PDQ Cancer Information Summaries. National Cancer Institute (US); 2002. Accessed 5 Feb 2022. http://www.ncbi.nlm.nih.gov/books/NBK65923/

  27. Bahrami A, Gown AM, Baird GS, Hicks MJ, Folpe AL (2008) Aberrant expression of epithelial and neuroendocrine markers in alveolar rhabdomyosarcoma: a potentially serious diagnostic pitfall. Mod Pathol 21(7):795–806. https://doi.org/10.1038/modpathol.2008.86

    Article  CAS  PubMed  Google Scholar 

  28. Apostolides PJ, Spetzler RF, Johnson PC (1995) Ectomesenchymal hamartoma (Benign “Ectomesenchymoma”) of the VIIIth nerve. Neurosurgery 37(6):1204–1207. https://doi.org/10.1227/00006123-199512000-00022

    Article  CAS  PubMed  Google Scholar 

  29. Kohsaka S, Shukla N, Ameur N et al (2014) A recurrent neomorphic mutation in MYOD1 defines a clinically aggressive subset of embryonal rhabdomyosarcoma associated with PI3K-AKT pathway mutations. Nat Genet 46(6):595–600. https://doi.org/10.1038/ng.2969

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Rekhi B, Upadhyay P, Ramteke MP, Dutt A (2016) MYOD1 (L122R) mutations are associated with spindle cell and sclerosing rhabdomyosarcomas with aggressive clinical outcomes. Mod Pathol 29(12):1532–1540. https://doi.org/10.1038/modpathol.2016.144

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Agaram NP, Chen CL, Zhang L, LaQuaglia MP, Wexler L, Antonescu CR (2014) Recurrent MYOD1 mutations in pediatric and adult sclerosing and spindle cell rhabdomyosarcomas: evidence for a common pathogenesis. Genes Chromosom Cancer 53(9):779–787. https://doi.org/10.1002/gcc.22187

    Article  CAS  PubMed  Google Scholar 

  32. Iolascon A, Faienza MF, Coppola B et al (1996) Analysis of cyclin-dependent kinase inhibitor genes (CDKN2A, CDKN2B, andCDKN2C) in childhood rhabdomyosarcoma. Genes Chromosom Cancer 15(4):217–222. https://doi.org/10.1002/(SICI)1098-2264(199604)15

    Article  CAS  PubMed  Google Scholar 

  33. Xia SJ, Pressey JG, Barr FG (2002) Molecular pathogenesis of rhabdomyosarcoma. Cancer Biol Ther 1(2):97–104. https://doi.org/10.4161/cbt.51

    Article  CAS  PubMed  Google Scholar 

  34. He Y, Sun MM, Zhang GG et al (2021) Targeting PI3K/Akt signal transduction for cancer therapy. Signal Transduct Target Ther 6(1):425. https://doi.org/10.1038/s41392-021-00828-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Funding

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

Author information

Authors and Affiliations

  1. Pathology Department, La Paz University Hospital, Paseo de La Castellana, 261, 28046, Madrid, Spain

    E. M. Pena-Burgos & J. J. Pozo-Kreilinger

  2. Pediatric Oncology Department, La Paz University Hospital, Madrid, Spain

    D Plaza-López De Sabando, A. Sastre, P. Rubio, A. Escudero & A. Pérez-Martínez

  3. Radiology Department, La Paz University Hospital, Madrid, Spain

    C. Utrilla

  4. La Paz University Hospital, Molecular Pathology and Therapeutic Targets Group, Instituto de Investigación del Hospital Universitario La Paz (IdiPAZ), Madrid, Spain

    M. Mendiola-Sabio

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  1. E. M. Pena-Burgos
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Contributions

Conception and design of the study and acquisition and analysis of data: P-BEM and P-KJJ. Drafting the manuscript: P-BEM, P-LDSD, UC, P-KJJ, SA, RP, EA, M-SM, and P-MA. Radiology images: UC. Pathology figures: P-BEM and P-KJJ. Molecular studies: M-SM.

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Correspondence to E. M. Pena-Burgos.

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Pena-Burgos, E.M., De Sabando, D.PL., Utrilla, C. et al. First Reported Case of Malignant Ectomesenchymoma with p.Leu122Arg Mutation in MYOD1 Gene: Extensive Intra- and Extracranial Tumor in a 15-Year-Old Female. Head and Neck Pathol 17, 855–863 (2023). https://doi.org/10.1007/s12105-023-01542-0

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