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Chordoma

Chordoma

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Chordomas are rare tumors that arise from embryonic notochordal remnants along the length of the neuraxis at developmentally active sites. These sites are the ends of the neuraxis and the vertebral bodies. Chordomas constitute less than 1% of CNS tumors and rarely occur in extra-axial locations. Chordomas are thought to arise from ectopic notochord remnants. Chordomas are optimally managed with aggressive surgery, while preserving key structures, and postoperative radiation. [1]  Chordomas are associated with significant morbidity because of their growth patterns and surgical constraints in resection. [2]

An image depicting a chordoma can be seen below.

In 1857, Virchow originally described chordomas when he named them ecchondrosis physaliphora, believing they were cartilaginous in origin. In 1895, Ribbert pierced a nucleus pulposus and found similar tumors. From this bit of evidence, he correctly surmised the notochordal origin of chordomas.

Ecchordosis physaliphora is a term that refers to small, well-circumscribed, gelatinous masses adherent to the brainstem. Although composed of notochordal remnants, ecchordosis physaliphora seldom, if ever, progresses into chordoma. Ecchordosis physaliphora is a reported finding in approximately 2% of autopsy examinations, whereas chordomas are quite rare.

Rare, benign intra-axial tumors of notochordal origin have been described as “intraosseous benign notochordal cell tumors.” [3, 4] These are distinguished from ecchordosis physaliphora by their intraosseous location and from chordoma by their well-demarcated radiographic appearance, bland histologic features, and lack of soft tissue extension.

Although chordomas are usually slow-growing tumors, they are locally aggressive with a tendency to infiltrate into adjacent tissues and organs. Local recurrence results in tissue destruction and generally is the cause of death. Metastases are recognized but are uncommon.

Chordomas are rare neoplasms. As primary intracranial neoplasms, they only constitute 0.2% of all CNS tumors; however, they constitute 2-4% of all primary bone neoplasms. Chordomas generally occur in 3 locations, which are, in descending order of frequency, the sacrum, intracranially at the clivus, and along the spinal axis. Fifty percent of chordomas occur in the sacrum, while spinal axis chordomas are rare. Occasional parasellar and sellar examples have been described, and extraaxial sites have been reported in the literature.

When considering all locations, the male-to-female ratio is 2:1. However, skull base tumors, as a subgroup, tend to have a more equal sex distribution.

A number of reports indicate that chordomas are seen in all age groups, with the peak incidence varying by site. Intracranial chordomas present in a much younger age group than their spinal counterparts because the relevant anatomy of the clival region produces earlier symptomatology. [5, 6] In one series of chordomas reviewed, the average age at diagnosis of all patients with chordomas was 56 years, with an age range of 27-80 years. When considered by site, the average age for intracranial chordomas is 48 years; as a subgroup, chordomas of the sphenoccipital area have an average occurrence age of 38 years. The average age for sacrococcygeal chordomas is 56 years. For chordomas occurring along the vertebrae, the average age is 46 years.

In a review of demographic and clinical data of pediatric patients 19 years or younger abstracted from the Surveillance, Epidemiology, and End Result (SEER) database, pediatric primary chordomas presented most often as small tumors less than 4 cm in the cranium. Survival among pediatric patients who underwent surgery was significantly longer than for adults (22.5 vs 14.3 yr; P< 0.001), and overall survival was longer (17.2 vs 12.6 yr). Overall mortality was lower in pediatric patients (38.4 vs 49.8%), but cancer-specific mortality was higher (37.2 vs. 28.6%). [7]

Chordomas are thought to arise from primitive notochordal remnants along the axial skeleton. During development, the notochord is surrounded by the developing vertebral column. In adults, remnants of the notochord are present as the nucleus pulposus of the intervertebral discs. Notochordal remnants that are extradural are most common at the sacrococcygeal region but can be found at any site along the length of the axial skeleton. The distribution of tumors matches the distribution of notochordal remnants.

A genetic basis has been described for some chordomas. However, most exhibit complex abnormal karyotypes including whole or partial losses of chromosomes 3, 4, 10, and 13, gains in chromosome 7, and rearrangements of chromosome 1p. [8] All have been implicated in the pathogenesis of chordomas. Also, microsatellite instability resulting from DNA mismatch repair deficiencies has been demonstrated; however, no chordoma-specific translocations have been identified.

In a study of 287 chordomas in 111 patients, expressions of a variety of markers were identified, including  EGFR, pSTAT3, VEGF, and mTOR pathway proteins in 85.9%, 79.1%, 85.7%, and 46%, respectively. [9]  In another study, 3 different variants accounting for 11 point mutations in 3 cancer-associated genes (KIT, KDR, and TP53) were detected. [10]

Chordomas are characterized by slow growth, with local destruction of the bone and extension into the adjacent soft tissue. Very rarely, distant metastases are encountered. These tumors usually have a relatively indolent but prolonged course with multiple local recurrences. Eventually, they may be responsible for mortality.

The clinical presentation is entirely dependent on the location of the chordoma. [11] At the sacrum, common presenting symptoms are back and/or lower extremity pain. About one half of patients with chordomas have autonomic symptoms, particularly rectal dysfunction or urinary incontinence. About one half of patients with chordomas have a palpable sacral mass.

With intracranial tumors, the most common presenting symptoms are diplopia and headache. Neurologic signs also occur in over one half of the patients, primarily as cranial nerve palsies. Palsies of cranial nerve VI and the sensory branch of V are the most common.

Uncommon clinical presentations of intracranial tumors include CSF rhinorrhea, nasal obstruction, nasal bleeding, and subarachnoid hemorrhage. [12]

Patients with tumors located along lower vertebrae may present with pain, bladder dysfunction, or lower extremity weakness. Patients with tumors located along cervical vertebrae present with hoarseness, dysphagia, and, occasionally, pharyngeal bleeding. Other rare or unique symptoms have been reported but are the exception. The time span from the onset of symptoms to diagnosis averages 10 months.

Surgical therapy for these tumors is indicated as they continuously grow, albeit slowly, and erode bone and adjacent soft tissue, causing marked destruction of surrounding tissues.

A meta-analysis by Di Maio et al confirmed that both 5-year progression-free survival and overall survival of skull-base chordomas are enhanced by complete resection of the tumor. [13] Furthermore, this analysis suggests that the addition of adjuvant radiation therapy is of no additional benefit to total surgical resection, but is warranted in cases of incomplete resection. No differences were found in overall survival between the different types of adjuvant radiation therapy. [13]

In a more recent retrospective case series of primary sacral chordomas that were treated with carbon ion therapy or proton therapy, Mima et al showed an improved local control of the tumor growth and a significant improvement for overall survival. [14]

The location of chordomas along the spinal canal is directly related to the location of notochord remnants, particularly at the ends of the spinal axis. Of chordomas, 49% occur at the sacrococcygeal region, and 30% occur at the sphenoccipital region, with nearly all of these occurring at the clivus. These tumors have a variable extension. Vertebral chordomas account for only 15% of total chordomas and occur in the lumbar, cervical, and thoracic regions in descending order of frequency.

Grossly, chordomas are variable in size. They are soft, gelatinous, smooth, or lobulated and are gray-white in color on their outer surface. On cut section, the tumor is homogeneous in color and consistency. Occasionally, calcifications or hemorrhages are present. Chordomas appear to be encapsulated when in soft tissue but not when they are located in bone.

Contraindications to surgery for excision of a chordoma primarily are related to general health of the patient and preexisting medical conditions. The patient should be evaluated for cardiac, pulmonary, hematological, or endocrine disorders as well as coagulation status. These disorders need to be addressed and managed prior to surgery.

Skull base chordomas (SBCs) are rare dysembryogenetic invasive tumors with a variable tendency for recurrence. In one study, the 5- and 10-year overall survival rates were 67% and 57%, respectively, and the 5- and 10-year progression-free survival rates were 58% and 44%, respectively. Extent of resection, adjuvant radiation therapy, and absence of rhinopharynx invasion were positive independent predictors of overall survival. Adjuvant radiation therapy, absence of rhinopharynx invasion, and younger patient age were positive independent predictors of progression-free survival. [15]

Campbell RG, Prevedello DM, Ditzel Filho L, Otto BA, Carrau RL. Contemporary management of clival chordomas. Curr Opin Otolaryngol Head Neck Surg. 2015 Apr. 23 (2):153-61. [Medline].

Ahmed R, Sheybani A, Menezes AH, Buatti JM, Hitchon PW. Disease outcomes for skull base and spinal chordomas: a single center experience. Clin Neurol Neurosurg. 2015 Mar. 130:67-73. [Medline].

Amer HZ, Hameed M. Intraosseus benign notochordal cell tumor. Arch Pathol Lab Med. 2010/02. 134:283-288. [Medline].

Uglialora AD, Beebe KS, Hameed M, Benevenia J. A rare case of intraosseous benign notochordal cell tumor of the coccyx. Orthopedics. 2009/06. 32:445-449. [Medline].

Fernandez-Miranda JC, Gardner PA, Snyderman CH, Devaney KO, Mendenhall WM, Suárez C, et al. Clival chordomas: A pathological, surgical, and radiotherapeutic review. Head Neck. 2013 Jun 26. [Medline].

Beccaria K, Sainte-Rose C, Zerah M, Puget S. Paediatric Chordomas. Orphanet J Rare Dis. 2015 Sep 22. 10 (1):116. [Medline].

Lau CS, Mahendraraj K, Ward A, Chamberlain RS. Pediatric Chordomas: A Population-Based Clinical Outcome Study Involving 86 Patients from the Surveillance, Epidemiology, and End Result (SEER) Database (1973-2011). Pediatr Neurosurg. 2016 Feb 17. [Medline].

Brandal P, Bjerkehagen B, Danielsen H, Heim S. Chromosome 7 abnormalities are common in chordomas. Cancer Genet Cytogenet. 2005 Jul 1. 160(1):15-21. [Medline].

Tauziède-Espariat A, Bresson D, Polivka M, et al. Prognostic and Therapeutic Markers in Chordomas: A Study of 287 Tumors. J Neuropathol Exp Neurol. 2016 Jan 4. [Medline].

Fischer C, Scheipl S, Zopf A, Niklas N, Deutsch A, Jorgensen M, et al. Mutation Analysis of Nine Chordoma Specimens by Targeted Next-Generation Cancer Panel Sequencing. J Cancer. 2015. 6 (10):984-9. [Medline].

Williams BJ, Raper DM, Godbout E, Bourne TD, Prevedello DM, Kassam AB, et al. Diagnosis and treatment of chordoma. J Natl Compr Canc Netw. 2013 Jun 1. 11(6):726-31. [Medline].

Hsieh CT, Liu MY, Su WF, Ju DT. Spontaneous cerebrospinal fluid rhinorrhea: a rare initial presentation of clival chordoma. Neurol India. 2009 Jul-Aug. 57(4):513-4. [Medline].

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 Dec. 115(6):1094-105. [Medline].

Mima M, Demizu Y, Jin D, et al. Particle therapy using carbon ions or protons as a definitive therapy for patients with primary sacral chordoma. Br J Radiol. 2014 Jan. 87(1033):20130512. [Medline]. [Full Text].

Boari N, Gagliardi F, Cavalli A, Gemma M, Ferrari L, Riva P, et al. Skull base chordomas: clinical outcome in a consecutive series of 45 patients with long-term follow-up and evaluation of clinical and biological prognostic factors. J Neurosurg. 2016 Jan 8. 1-11. [Medline].

Bergh P, Kindblom LG, Gunterberg B, Remotti F, Ryd W, Meis-Kindblom JM. Prognostic factors in chordoma of the sacrum and mobile spine: a study of 39 patients. Cancer. 2000 May 1. 88(9):2122-34. [Medline].

Chugh R, Tawbi H, Lucas DR, Biermann JS, Schuetze SM, Baker LH. Chordoma : the nonsarcomatous primary bone tumor. Oncologist. 2007/11. 12(11):1344-1350. [Medline].

Hanna SA, Tirabosco R, Amin A, Pollock RC, Skinner JA, Cannon SR, et al. Dedifferentiated chordoma: a report of four cases arising ‘de novo’. J Bone Joint Surg Br. 2008 May. 90(5):652-6. [Medline].

Giannoni CM. Chordomas. In: Grand Rounds Archives; Baylor College. The Bobby R Alford Department of Otorhinolaryngology and Communicative Sciences Web Site. 1992. [Full Text].

Naka T, Boltze C, Kuester D, Schulz TO, Schneider-Stock R, Kellner A, et al. Alterations of G1-S checkpoint in chordoma: the prognostic impact of p53 overexpression. Cancer. 2005 Sep 15. 104(6):1255-63. [Medline].

Casali PG, Stacchiotti S, Sangalli C, Olmi P, Gronchi A. Chordoma. Curr Opin Oncol. 2007 Jul. 19(4):367-70. [Medline].

Asklund T, Sandström M, Shahidi S, Riklund K, Henriksson R. Durable stabilization of three chordoma cases by bevacizumab and erlotinib. Acta Oncol. 2014 Jan 23. [Medline].

Presneau N, Shalaby A, Idowu B, Gikas P, Cannon SR, Gout I, et al. Potential therapeutic targets for chordoma: PI3K/AKT/TSC1/TSC2/mTOR pathway. Br J Cancer. 2009 May 5. 100(9):1406-14. [Medline]. [Full Text].

Stacchiotti S, Marrari A, Tamborini E, Palassini E, Virdis E, Messina A. Response to imatinib plus sirolimus in advanced chordoma. Ann Oncol. 2009 Nov. 20(11):1886-94. [Medline].

Yang C, Schwab JH, Schoenfeld AJ, Hornicek FJ, Wood KB, Nielsen GP. A novel target for treatment of chordoma: signal transducers and activators of transcription 3. Mol Cancer Ther. 2009 Sep. 8(9):2597-605. [Medline].

Xia M, Huang R, Sakamuru S, Alcorta D, Cho MH, Lee DH, et al. Identification of repurposed small molecule drugs for chordoma therapy. Cancer Biol Ther. 2013 May 10. 14(7):[Medline].

[Guideline] National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology. Bone Cancer. Version 1.2017. NCCN. Available at https://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. August 29, 2016; Accessed: September 9, 2016.

[Guideline] ESMO/European Sarcoma Network Working Group. Bone sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2014 Sep. 25 Suppl 3:iii113-23. [Medline]. [Full Text].

Fletcher CDM, Bridge JA, Hogendoorn P, Mertens F. World Health Organization Classification of Tumours of Soft Tissue and Bone. 4th Ed. Lyons, France: IARC; 2013.

Edge SB, Byrd DR, Compton CC, et al. Bone. AJCC Cancer Staging Manual. 7th Ed. New York: Springer; 2010. 281-290.

Enneking WF. A system of staging musculoskeletal neoplasms. Clin Orthop Relat Res. 1986 Mar. 9-24. [Medline].

Bailey P. Intracranial Tumors. 2nd ed. Springfield, Ill:. Charles C Thomas Publisher. 1948.

Bigner DD, McLendon RE, Bruner JM, eds. Russell & Rubinstein’s Pathology of Tumors of the Nervous System. 6th ed. Hodder Headline Group. 1998:421-423.

Boriani S, Bandiera S, Biagini R, Bacchini P, Boriani L, Cappuccio M. Chordoma of the mobile spine: fifty years of experience. Spine. 2006 Feb 15. 31(4):493-503. [Medline].

Breteau N, Demasure M, Lescrainier J, Sabbattier R, Michenet P. Sacrococcygeal chordomas: potential role of high LET therapy. Recent Results Cancer Res. 1998. 150:148-55. [Medline].

Burger PC, Scheithauer BW, Vogel FS. Chordoma. In: Surgical Pathology of the Nervous System and its Coverings. 2002. 4th ed Churchill Livingstone:23-26 and 508-509.

Casali PG, Messina A, Stacchiotti S, Tamborini E, Crippa F, Gronchi A, et al. Imatinib mesylate in chordoma. Cancer. 2004 Nov 1. 101(9):2086-97. [Medline].

Cheng EY, Ozerdemoglu RA, Transfeldt EE, Thompson RC Jr. Lumbosacral chordoma. Prognostic factors and treatment. Spine. 1999 Aug 15. 24(16):1639-45. [Medline].

Fuchs B, Dickey ID, Yaszemski MJ, Inwards CY, Sim FH. Operative management of sacral chordoma. J Bone Joint Surg Am. 2005 Oct. 87(10):2211-6. [Medline].

Lantos PL, Louis DN, Rosenblum MK and Kleihues P. Tumours of the nervous system. In: Graham DI, Lantos PL, eds. Greenfield’s Neuropathology. 7th ed. Arnold, a member of the Hodder Headline Group:2002:(Volume II) 960-964.

Maclean FM, Soo MY, Ng T. Chordoma: radiological-pathological correlation. Australas Radiol. 2005 Aug. 49(4):261-8. [Medline].

Munzenrider JE, Liebsch NJ. Proton therapy for tumors of the skull base. Strahlenther Onkol. 1999 Jun. 175 Suppl 2:57-63. [Medline].

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 Dec. 21(12):1461-9. [Medline].

Ozdemir MH, Gürkan I, Yildiz Y, Yilmaz C, Saglik Y. Surgical treatment of malignant tumours of the sacrum. Eur J Surg Oncol. 1999 Feb. 25(1):44-9. [Medline].

Ribbert H, Virchow R. Chordoma. In: Windeyer BW. Procedings of the Royal Society of Medicine. Vol 52. 1959:1088-1100.

Tirabosco R, Mangham DC, Rosenberg AE, Vujovic S, Bousdras K, Pizzolitto S. 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 Apr. 32(4):572-80. [Medline].

Vujovic S, Henderson S, Presneau N, Odell E, Jacques TS, Tirabosco R. Brachyury, a crucial regulator of notochordal development, is a novel biomarker for chordomas. J Pathol. 2006 Jun. 209(2):157-65. [Medline].

Wippold FJ 2nd, Koeller KK, Smirniotopoulos JG. Clinical and imaging features of cervical chordoma. AJR Am J Roentgenol. 1999 May. 172(5):1423-6. [Medline].

York JE, Kaczaraj A, Abi-Said D, Fuller GN, Skibber JM, Janjan NA, et al. Sacral chordoma: 40-year experience at a major cancer center. Neurosurgery. 1999 Jan. 44(1):74-9; discussion 79-80. [Medline].

Cheryl Ann Palmer, MD Professor of Pathology, Director of Neuropathology, Director of Pathology Residency Program, Department of Pathology, Huntsman Cancer Institute, University of Utah School of Medicine

Cheryl Ann Palmer, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuropathologists, Society for Neuro-Oncology, International Society of Neuropathology

Disclosure: Nothing to disclose.

James Robinson Hackney, MD Neuropathology Fellow, Department of Pathology, University of Alabama at Birmingham School of Medicine

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Ryszard M Pluta, MD, PhD Associate Professor, Neurosurgical Department Medical Research Center, Polish Academy of Sciences, Poland; Clinical Staff Scientist, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health (NIH); Fishbein Fellow, JAMA

Ryszard M Pluta, MD, PhD is a member of the following medical societies: Polish Society of Neurosurgeons, Congress of Neurological Surgeons

Disclosure: Nothing to disclose.

Brian H Kopell, MD Associate Professor, Department of Neurosurgery, Icahn School of Medicine at Mount Sinai

Brian H Kopell, MD is a member of the following medical societies: Alpha Omega Alpha, American Association of Neurological Surgeons, American Society for Stereotactic and Functional Neurosurgery, Congress of Neurological Surgeons, International Parkinson and Movement Disorder Society, North American Neuromodulation Society

Disclosure: Received consulting fee from Medtronic for consulting; Received consulting fee from Abbott Neuromodulation for consulting.

Duc Hoang Duong, MD Professor, Chief Physician, Departments of Neurological Surgery and Neuroscience, Epilepsy Center, Charles Drew University of Medicine and Science

Duc Hoang Duong, MD is a member of the following medical societies: American Neurological Association, Congress of Neurological Surgeons, North American Skull Base Society

Disclosure: Nothing to disclose.

The authors wish to acknowledge the contributions of Daniel Keith Harrison, MD, to prior versions of this article.

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