Skip to main content

Advertisement

SpringerLink
Log in

Chordoma of the Head and Neck: A Review

  • Invited Review
  • Published:
Head and Neck Pathology Aims and scope Submit manuscript

Abstract

Chordoma is a rare malignant bone tumor that can arise anywhere along the central neural axis and many involve head and neck sites, most commonly the skull base. The relative rarity of these tumors, combined with the complex anatomy of the head and neck, pose diagnostic challenges to pathologists. This article describes the pertinent clinical, pathologic, and molecular features of chordomas and describes how these features can be used to aid in formulating a differential diagnosis. Emphasis is placed on key diagnostic pitfalls and the importance of incorporating immunohistochemical information into the diagnosis.

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
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. McMaster ML, Goldstein AM, Bromley CM, Ishibe N, Parry DM. Chordoma: incidence and survival patterns in the United States, 1973–1995. Cancer Causes Control. 2001;12:1–11.

    Article  PubMed  CAS  Google Scholar 

  2. Smoll NR, Gautschi OP, Radovanovic I, Schaller K, Weber DC. Incidence and relative survival of chordomas: the standardized mortality ratio and the impact of chordomas on a population. Cancer. 2013;119:2029–37.

    Article  PubMed  Google Scholar 

  3. Mukherjee D, Chaichana KL, Gokaslan ZL, Aaronson O, Cheng JS, McGirt MJ. Survival of patients with malignant primary osseous spinal neoplasms: results from the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2003. J Neurosurg Spine. 2011;14:143–50.

    Article  PubMed  Google Scholar 

  4. Lauer SR, Edgar MA, Gardner JM, Sebastian A, Weiss SW. Soft tissue chordomas: a clinicopathologic analysis of 11 cases. Am J Surg Pathol. 2013;37:719–26.

    Article  PubMed  Google Scholar 

  5. Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S, De Maglio G, den Bakker MA, Di Francesco L, Kalil RK, Athanasou NA, O’Donnell P, McCarthy EF, Flanagan AM. Brachyury expression in extra-axial skeletal and soft tissue chordomas: a marker that distinguishes chordoma from mixed tumor/myoepithelioma/parachordoma in soft tissue. Am J Surg Pathol. 2008;32:572–80.

    Article  PubMed  Google Scholar 

  6. Gladstone HB, Bailet JW, Rowland JP. Chordoma of the oropharynx: an unusual presentation and review of the literature. Otolaryngol Head Neck Surg. 1998;118:104–7.

    Article  PubMed  CAS  Google Scholar 

  7. Kataria SP, Batra A, Singh G, Kumar S, Sen R. Chordoma of skull base presenting as nasopharyngeal mass. J Neurosci Rural Pract. 2013;4:S95-97.

    Google Scholar 

  8. Khurram SA, Biswas D, Fernando M. A parapharyngeal soft tissue chordoma presenting with synchronous cervical lymph node metastasis: an unusual presentation. Head Neck Pathol. 2016;10:400–4.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Lynn-Macrae A, Haines GK 3rd, Altman KW. Primary chordoma of the lateral nasal wall: case report and review. Ear Nose Throat J. 2005;84:593–5.

    PubMed  Google Scholar 

  10. Nguyen RP, Salzman KL, Stambuk HE, Ahuja AT, Harnsberger HR. Extraosseous chordoma of the nasopharynx. AJNR Am J Neuroradiol. 2009;30:803–7.

    Article  PubMed  CAS  Google Scholar 

  11. Tao ZZ, Chen SM, Liu JF, Huang XL, Zhou L. Paranasal sinuses chordoma in pediatric patient: a case report and literature review. Int J Pediatr Otorhinolaryngol. 2005;69:1415–8.

    Article  PubMed  Google Scholar 

  12. Bohman LE, Koch M, Bailey RL, Alonso-Basanta M, Lee JY. Skull base chordoma and chondrosarcoma: influence of clinical and demographic factors on prognosis: a SEER analysis. World Neurosurg. 2014;82:806–14.

    Article  PubMed  Google Scholar 

  13. Lee-Jones L, Aligianis I, Davies PA, Puga A, Farndon PA, Stemmer-Rachamimov A, Ramesh V, Sampson JR. Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2. Genes Chromosomes Cancer. 2004;41:80–5.

    Article  PubMed  CAS  Google Scholar 

  14. Oakley GJ, Fuhrer K, Seethala RR. Brachyury. SOX-9, and podoplanin, new markers in the skull base chordoma vs chondrosarcoma differential: a tissue microarray-based comparative analysis. Mod Pathol. 2008;21:1461–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. Fletcher CDM. World Health Organization., International Agency for Research on Cancer. (2013) WHO classification of tumours of soft tissue and bone. IARC Press, Lyon.

    Google Scholar 

  16. Heffelfinger MJ, Dahlin DC, MacCarty CS, Beabout JW. Chordomas and cartilaginous tumors at the skull base. Cancer. 1973;32:410–20.

    Article  PubMed  CAS  Google Scholar 

  17. Rosenberg AE, Brown GA, Bhan AK, Lee JM. Chondroid chordoma–a variant of chordoma. A morphologic and immunohistochemical study. Am J Clin Pathol. 1994;101:36–41.

    Article  PubMed  CAS  Google Scholar 

  18. Hoch BL, Nielsen GP, Liebsch NJ, Rosenberg AE. Base of skull chordomas in children and adolescents: a clinicopathologic study of 73 cases. Am J Surg Pathol. 2006;30:811–8.

    Article  PubMed  Google Scholar 

  19. Jambhekar NA, Rekhi B, Thorat K, Dikshit R, Agrawal M, Puri A. Revisiting chordoma with brachyury, a “new age” marker: analysis of a validation study on 51 cases. Arch Pathol Lab Med. 2010;134:1181–7.

    PubMed  Google Scholar 

  20. Miettinen M, Wang Z, Lasota J, Heery C, Schlom J, Palena C. Nuclear brachyury expression is consistent in chordoma, common in germ cell tumors and small cell carcinomas, and rare in other carcinomas and sarcomas: an immunohistochemical study of 5229 cases. Am J Surg Pathol. 2015;39:1305–12.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Sangoi AR, Karamchandani J, Lane B, Higgins JP, Rouse RV, Brooks JD, McKenney JK. Specificity of brachyury in the distinction of chordoma from clear cell renal cell carcinoma and germ cell tumors: a study of 305 cases. Mod Pathol. 2011;24:425–9.

    Article  PubMed  CAS  Google Scholar 

  22. Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R, Boshoff C, Flanagan AM. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol. 2006;209:157–65.

    Article  PubMed  CAS  Google Scholar 

  23. Chavez JA, Nasir Ud D, Memon A, Perry A. Anaplastic chordoma with loss of INI1 and brachyury expression in a 2-year-old girl. Clin Neuropathol. 2014;33:418–20.

    Article  PubMed  Google Scholar 

  24. Hasselblatt M, Thomas C, Hovestadt V, Schrimpf D, Johann P, Bens S, Oyen F, Peetz-Dienhart S, Crede Y, Wefers A, Vogel H, Riemenschneider MJ, Antonelli M, Giangaspero F, Bernardo MC, Giannini C, Ud Din N, Perry A, Keyvani K, van Landeghem F, Sumerauer D, Hauser P, Capper D, Korshunov A, Jones DT, Pfister SM, Schneppenheim R, Siebert R, Fruhwald MC, Kool M. Poorly differentiated chordoma with SMARCB1/INI1 loss: a distinct molecular entity with dismal prognosis. Acta Neuropathol. 2016;132:149–51.

    Article  PubMed  Google Scholar 

  25. Mobley BC, McKenney JK, Bangs CD, Callahan K, Yeom KW, Schneppenheim R, Hayden MG, Cherry AM, Gokden M, Edwards MS, Fisher PG, Vogel H. Loss of SMARCB1/INI1 expression in poorly differentiated chordomas. Acta Neuropathol. 2010;120:745–53.

    Article  PubMed  CAS  Google Scholar 

  26. Almefty K, Pravdenkova S, Colli BO, Al-Mefty O, Gokden M. Chordoma and chondrosarcoma: similar, but quite different, skull base tumors. Cancer. 2007;110:2457–67.

    Article  PubMed  Google Scholar 

  27. Pamir MN, Ozduman K. Analysis of radiological features relative to histopathology in 42 skull-base chordomas and chondrosarcomas. Eur J Radiol. 2006;58:461–70.

    Article  PubMed  Google Scholar 

  28. Rosenberg AE, Nielsen GP, Keel SB, Renard LG, Fitzek MM, Munzenrider JE, Liebsch NJ. Chondrosarcoma of the base of the skull: a clinicopathologic study of 200 cases with emphasis on its distinction from chordoma. Am J Surg Pathol. 1999;23:1370–8.

    Article  PubMed  CAS  Google Scholar 

  29. Folpe AL, Agoff SN, Willis J, Weiss SW. Parachordoma is immunohistochemically and cytogenetically distinct from axial chordoma and extraskeletal myxoid chondrosarcoma. Am J Surg Pathol. 1999;23:1059–67.

    Article  PubMed  CAS  Google Scholar 

  30. Sangoi AR, Dulai MS, Beck AH, Brat DJ, Vogel H. Distinguishing chordoid meningiomas from their histologic mimics: an immunohistochemical evaluation. Am J Surg Pathol. 2009;33:669–81.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Fischer C, Scheipl S, Zopf A, Niklas N, Deutsch A, Jorgensen M, Lohberger B, Froehlich EV, Leithner A, Gabriel C, Liegl-Atzwanger B, Rinner B. Mutation analysis of nine chordoma specimens by targeted next-generation cancer panel sequencing. J Cancer. 2015;6:984–9.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Akhavan-Sigari R, Gaab MR, Rohde V, Abili M, Ostertag H. Expression of PDGFR-alpha, EGFR and c-MET in spinal chordoma: a series of 52 patients. Anticancer Res. 2014;34:623–30.

    PubMed  Google Scholar 

  33. Chen K, Mo J, Zhou M, Wang G, Wu G, Chen H, Zhang K, Yang H. Expression of PTEN and mTOR in sacral chordoma and association with poor prognosis. Med Oncol. 2014;31:886.

    Article  PubMed  CAS  Google Scholar 

  34. Yang C, Schwab JH, Schoenfeld AJ, Hornicek FJ, Wood KB, Nielsen GP, Choy E, Mankin H, Duan Z. A novel target for treatment of chordoma: signal transducers and activators of transcription 3. Mol Cancer Ther. 2009;8:2597–605.

    Article  PubMed  CAS  Google Scholar 

  35. Zhang K, Chen H, Zhang B, Sun J, Lu J, Chen K, Yang H. Overexpression of Raf-1 and ERK1/2 in sacral chordoma and association with tumor recurrence. Int J Clin Exp Pathol. 2015;8:608–14.

    PubMed  PubMed Central  CAS  Google Scholar 

  36. Bayrak OF, Gulluoglu S, Aydemir E, Ture U, Acar H, Atalay B, Demir Z, Sevli S, Creighton CJ, Ittmann M, Sahin F, Ozen M. MicroRNA expression profiling reveals the potential function of microRNA-31 in chordomas. J Neurooncol. 2013;115:143–51.

    Article  PubMed  CAS  Google Scholar 

  37. Long C, Jiang L, Wei F, Ma C, Zhou H, Yang S, Liu X, Liu Z. Integrated miRNA-mRNA analysis revealing the potential roles of miRNAs in chordomas. PLoS ONE. 2013;8:e66676.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Zou MX, Huang W, Wang XB, Li J, Lv GH, Wang B, Deng YW. Reduced expression of miRNA-1237-3p associated with poor survival of spinal chordoma patients. Eur Spine J. 2015;24:1738–46.

    Article  PubMed  Google Scholar 

  39. Marucci G, Morandi L, Mazzatenta D, Frank G, Pasquini E, Foschini MP. MGMT promoter methylation status in clival chordoma. J Neurooncol. 2014;118:271–6.

    Article  PubMed  CAS  Google Scholar 

  40. Yang XR, Ng D, Alcorta DA, Liebsch NJ, Sheridan E, Li S, Goldstein AM, Parry DM, Kelley MJ. T (brachyury) gene duplication confers major susceptibility to familial chordoma. Nat Genet. 2009;41:1176–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Pillay N, Plagnol V, Tarpey PS, Lobo SB, Presneau N, Szuhai K, Halai D, Berisha F, Cannon SR, Mead S, Kasperaviciute D, Palmen J, Talmud PJ, Kindblom LG, Amary MF, Tirabosco R, Flanagan AM. A common single-nucleotide variant in T is strongly associated with chordoma. Nat Genet. 2012;44:1185–7.

    Article  PubMed  CAS  Google Scholar 

  42. Presneau N, Shalaby A, Ye H, Pillay N, Halai D, Idowu B, Tirabosco R, Whitwell D, Jacques TS, Kindblom LG, Bruderlein S, Moller P, Leithner A, Liegl B, Amary FM, Athanasou NN, Hogendoorn PC, Mertens F, Szuhai K, Flanagan AM. Role of the transcription factor T (brachyury) in the pathogenesis of sporadic chordoma: a genetic and functional-based study. J Pathol. 2011;223:327–35.

    Article  PubMed  CAS  Google Scholar 

  43. Brandal P, Bjerkehagen B, Danielsen H, Heim S. Chromosome 7 abnormalities are common in chordomas. Cancer Genet Cytogenet. 2005;160:15–21.

    Article  PubMed  CAS  Google Scholar 

  44. Le LP, Nielsen GP, Rosenberg AE, Thomas D, Batten JM, Deshpande V, Schwab J, Duan Z, Xavier RJ, Hornicek FJ, Iafrate AJ. Recurrent chromosomal copy number alterations in sporadic chordomas. PLoS ONE. 2011;6:e18846.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  45. Scheil S, Bruderlein S, Liehr T, Starke H, Herms J, Schulte M, Moller P. Genome-wide analysis of sixteen chordomas by comparative genomic hybridization and cytogenetics of the first human chordoma cell line, U-CH1. Genes Chromosomes Cancer. 2001;32:203–11.

    Article  PubMed  CAS  Google Scholar 

  46. Amary MF, Bacsi K, Maggiani F, Damato S, Halai D, Berisha F, Pollock R, O’Donnell P, Grigoriadis A, Diss T, Eskandarpour M, Presneau N, Hogendoorn PC, Futreal A, Tirabosco R, Flanagan AM. IDH1 and IDH2 mutations are frequent events in central chondrosarcoma and central and periosteal chondromas but not in other mesenchymal tumours. J Pathol. 2011;224:334–43.

    Article  PubMed  CAS  Google Scholar 

  47. Arai M, Nobusawa S, Ikota H, Takemura S, Nakazato Y. Frequent IDH1/2 mutations in intracranial chondrosarcoma: a possible diagnostic clue for its differentiation from chordoma. Brain Tumor Pathol. 2012;29:201–6.

    Article  PubMed  CAS  Google Scholar 

  48. Bloch OG, Jian BJ, Yang I, Han SJ, Aranda D, Ahn BJ, Parsa AT. A systematic review of intracranial chondrosarcoma and survival. J Clin Neurosci. 2009;16:1547–51.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Cho YH, Kim JH, Khang SK, Lee JK, Kim CJ. Chordomas and chondrosarcomas of the skull base: comparative analysis of clinical results in 30 patients. Neurosurg Rev. 2008;31:35–43 (discussion 43).

    Article  PubMed  Google Scholar 

  50. Di Maio S, Temkin N, Ramanathan D, Sekhar LN. Current comprehensive management of cranial base chordomas: 10-year meta-analysis of observational studies. J Neurosurg. 2011;115:1094–105.

    Article  PubMed  Google Scholar 

  51. Martin JJ, Niranjan A, Kondziolka D, Flickinger JC, Lozanne KA, Lunsford LD. Radiosurgery for chordomas and chondrosarcomas of the skull base. J Neurosurg. 2007;107:758–64.

    Article  PubMed  Google Scholar 

  52. Hindi N, Casali PG, Morosi C, Messina A, Palassini E, Pilotti S, Tamborini E, Radaelli S, Gronchi A, Stacchiotti S. Imatinib in advanced chordoma: A retrospective case series analysis. Eur J Cancer. 2015;51:2609–14.

    Article  PubMed  CAS  Google Scholar 

  53. Launay SG, Chetaille B, Medina F, Perrot D, Nazarian S, Guiramand J, Moureau-Zabotto L, Bertucci F. Efficacy of epidermal growth factor receptor targeting in advanced chordoma: case report and literature review. BMC Cancer. 2011;11:423.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Scheipl S, Barnard M, Cottone L, Jorgensen M, Drewry DH, Zuercher WJ, Turlais F, Ye H, Leite AP, Smith JA, Leithner A, Moller P, Bruderlein S, Guppy N, Amary F, Tirabosco R, Strauss SJ, Pillay N, Flanagan AM. EGFR inhibitors identified as a potential treatment for chordoma in a focused compound screen. J Pathol. 2016;239:320–34.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Singhal N, Kotasek D, Parnis FX. Response to erlotinib in a patient with treatment refractory chordoma. Anticancer Drugs. 2009;20:953–5.

    Article  PubMed  CAS  Google Scholar 

  56. Stacchiotti S, Longhi A, Ferraresi V, Grignani G, Comandone A, Stupp R, Bertuzzi A, Tamborini E, Pilotti S, Messina A, Spreafico C, Gronchi A, Amore P, Vinaccia V, Casali PG. Phase II study of imatinib in advanced chordoma. J Clin Oncol. 2012;30:914–20.

    Article  PubMed  CAS  Google Scholar 

  57. Forsyth PA, Cascino TL, Shaw EG, Scheithauer BW, O’Fallon JR, Dozier JC, Piepgras DG. Intracranial chordomas: a clinicopathological and prognostic study of 51 cases. J Neurosurg. 1993;78:741–7.

    Article  PubMed  CAS  Google Scholar 

  58. Jian BJ, Bloch OG, Yang I, Han SJ, Aranda D, Tihan T, Parsa AT. Adjuvant radiation therapy and chondroid chordoma subtype are associated with a lower tumor recurrence rate of cranial chordoma. J Neurooncol. 2010;98:101–8.

    Article  PubMed  Google Scholar 

  59. Mitchell A, Scheithauer BW, Unni KK, Forsyth PJ, Wold LE, McGivney DJ. Chordoma and chondroid neoplasms of the spheno-occiput. An immunohistochemical study of 41 cases with prognostic and nosologic implications. Cancer. 1993;72:2943–9.

    Article  PubMed  CAS  Google Scholar 

  60. Colli BO, Al-Mefty O. Chordomas of the skull base: follow-up review and prognostic factors. Neurosurg Focus. 2001;10:E1.

    Article  PubMed  CAS  Google Scholar 

  61. Gay E, Sekhar LN, Rubinstein E, Wright DC, Sen C, Janecka IP, Snyderman CH. Chordomas and chondrosarcomas of the cranial base: results and follow-up of 60 patients. Neurosurgery. 1995;36:887–96 (discussion 896–887).

    Article  PubMed  CAS  Google Scholar 

  62. Jian BJ, Bloch OG, Yang I, Han SJ, Aranda D, Parsa AT. A comprehensive analysis of intracranial chordoma and survival: a systematic review. Br J Neurosurg. 2011;25:446–53.

    Article  PubMed  Google Scholar 

  63. Romeo S, Hogendoorn PC. Brachyury and chordoma: the chondroid-chordoid dilemma resolved? J Pathol. 2006;209:143–6.

    Article  PubMed  CAS  Google Scholar 

  64. Borba LA, Al-Mefty O, Mrak RE, Suen J. Cranial chordomas in children and adolescents. J Neurosurg. 1996;84:584–91.

    Article  PubMed  CAS  Google Scholar 

  65. Coffin CM, Swanson PE, Wick MR, Dehner LP. Chordoma in childhood and adolescence. A clinicopathologic analysis of 12 cases. Arch Pathol Lab Med. 1993;117:927–33.

    PubMed  CAS  Google Scholar 

  66. Kaneko Y, Sato Y, Iwaki T, Shin RW, Tateishi J, Fukui M. Chordoma in early childhood: a clinicopathological study. Neurosurgery. 1991;29:442–6.

    Article  PubMed  CAS  Google Scholar 

  67. Matsumoto J, Towbin RB, Ball WS Jr. Cranial chordomas in infancy and childhood. A report of two cases and review of the literature. Pediatr Radiol. 1989;20:28–32.

    Article  PubMed  CAS  Google Scholar 

  68. Yadav R, Sharma MC, Malgulwar PB, Pathak P, Sigamani E, Suri V, Sarkar C, Kumar A, Singh M, Sharma BS, Garg A, Bakhshi S, Faruq M. Prognostic value of MIB-1, p53, epidermal growth factor receptor, and INI1 in childhood chordomas. Neuro Oncol. 2014;16:372–81.

    Article  PubMed  CAS  Google Scholar 

  69. Chambers PW, Schwinn CP. Chordoma. A clinicopathologic study of metastasis. Am J Clin Pathol. 1979;72:765–76.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Division of Anatomical Pathology, Department of Pathology and Laboratory Medicine, The Ottawa Hospital, University of Ottawa, 501 Smyth Road, 4th Floor CCW, Ottawa, ON, K1H 8L6, Canada

    Jason K. Wasserman, Denis Gravel & Bibianna Purgina

Authors
  1. Jason K. Wasserman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Denis Gravel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Bibianna Purgina
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Bibianna Purgina.

Ethics declarations

Ethical Approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wasserman, J.K., Gravel, D. & Purgina, B. Chordoma of the Head and Neck: A Review. Head and Neck Pathol 12, 261–268 (2018). https://doi.org/10.1007/s12105-017-0860-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12105-017-0860-8

Keywords

Search

Navigation