Updated: May 03, 2022
  • Author: Cheryl Ann Palmer, MD; Chief Editor: Brian H Kopell, MD  more...
  • Print

Practice Essentials

A chordoma is a low-grade, slow-growing, but locally invasive and locally aggressive tumor. Chordomas belong to the sarcoma family of tumors. They arise from remnants of the notochord and occur in the midline along the spinal axis from the clivus to the sacrum, anterior to the spinal cord. The location distribution of chordomas is 50% sacral, 35% skull base, and 15% vertebral bodies of the mobile spine (most commonly, the C2 vertebra, followed by the lumbar then the thoracic spine). Overall 5-year survival is approximately 50%, and treatment consists of en bloc surgical resection followed by high-dose conformal radiation therapy (RT) such as proton beam radiation. [1]

Chordomas can be divided into 4 subtypes: conventional, poorly differentiated, dedifferentiated, and chondroid. Conventional (classic) chordomas are the most common variety and may show areas of dedifferentiation. Poorly differentiated chordomas are more common in young adult and pediatric patients, as are skull base chordomas, and show loss of the INI1 gene. Dedifferentiated chordomas typically are the fastest growing and most aggressive chordomas and can also have loss of INI1; they are more common among pediatric patients. Chondroid describes chordomas that are difficult to distinguish from chondrosarcoma on histology. Typically, chordomas express the brachyury gene, whereas chondrosarcomas do not express this gene. [1]

Surgical therapy is indicated for these tumors, as they continuously grow, albeit slowly, and erode bone and adjacent soft tissue, causing marked destruction of surrounding tissue. Optimal therapy typically involves complete surgical resection, which is often technically difficult because of the anatomic location, leading to a high rate of recurrence. Lesions have generally been resistant to radiation and chemotherapy; however, experimental studies involving targeted therapy and immunotherapy are under way. [2]

Different histologic subtypes of chordoma differ in their prognosis. To date, no recurrent genetic drivers have been identified for this disease. Brachyury seems to play a key role in the pathogenesis of chordoma, although the detailed mechanism remains to be elucidated. Surgical en bloc resection with negative margins is the only curative treatment for chordoma. High-dose irradiation, particularly with protons and carbon ions, is a therapeutic alternative in cases of inoperable tumor. Currently, no medical treatment has been approved for treatment of chordoma. Clinical trials exploring additional therapeutic modalities are ongoing. [3]

(An image depicting a chordoma is shown below.)

This pelvic CT scan shows a large presacral mass e This pelvic CT scan shows a large presacral mass eroding bone.

History of the Disease

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." [4, 5] 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.

Chordoma is a clinically and histologically unique malignant neoplasm, and numerous diagnostic considerations must be excluded to establish the correct diagnosis. [2]  Although a chordoma is usually a slow-growing tumor, it is locally aggressive and has 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.



Chordoma is a rare tumor that occurs along the axial spine in children and in adults, with an incidence of approximately 350 cases per year in the United States [6]  and a reported annual worldwide incidence of 0.08 per 100,000 cases. [3]

Chordomas typically affect those in the 40- to 60-year age group but have been reported in children and in the very elderly. Most believe males are more commonly affected than females, at an approximately 2:1 ratio, with an annual incidence of 1:1,000,000 for new diagnoses. Chordomas account for approximately 20% of primary spinal tumors and only 3% of all bone tumors. The most common location is the sacrum/coccygeal region (50%), followed by the spheno-occipital region (35%) and the mobile spine (about 10-15%). [1]

Less than 5% of chordomas occur in children. In a population-based study comparing pediatric versus adult skull base chordoma, Xu and colleagues reviewed data from the National Cancer Database from 2004 to 2015 on patients 18 years of age and older versus those younger than 18 years. They found that pediatric patients were likely to have larger tumor size (41.4 ± 15.7 mm vs 34.1 ± 15.8 mm; P< 0.01) and were universally treated at academic facilities. They found no difference in overall survival. [7]



Chordoma is a rare bone cancer of unknown etiology. TBXT is the only chordoma susceptibility gene identified to date; germline single nucleotide variants and copy number variants in TBXT have been associated with chordoma susceptibility in familial and sporadic chordoma. However, the genetic susceptibility of chordoma remains largely unknown. [8]

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 in 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.

Genes implicated in chordoma formation include the brachyury gene and the mechanistic target of rapamycin (mTOR) signaling pathway, as well as deficiency of the phosphatase tensin homolog (PTEN) gene, INI1, and platelet-derived growth factor receptor-beta (PDGFR-beta), although no definitive genetic marker has yet been identified. Few familial clusters of chordomas have been reported. [1]

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. [9] All these have been implicated in the pathogenesis of chordoma. Also, microsatellite instability resulting from DNA mismatch repair deficiencies has been demonstrated; however, no chordoma-specific translocations have been identified.




Chordomas present as slow-growing, locally invasive tumors; distant metastases occur rarely and only late in the disease. Although they are considered indolent tumors, there is significant risk for multiple local recurrences. [1]

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 located in bone.

Ongoing research into the molecular pathophysiology of chordoma has led to the discovery of several pathways that may serve as potential targets for molecular therapy, including a multitude of receptor tyrosine kinases (eg, platelet-derived growth factor receptor [PDGFR], epidermal growth factor receptor [EGFR]), downstream cascades (eg, phosphoinositide 3-kinase [PI3K]/protein kinase B [Akt]/mechanistic target of rapamycin [mTOR]), brachyury—a transcription factor expressed ubiquitously in chordoma but not in other tissues, and the fibroblast growth factor (FGF)/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway. Continued research and advances in the field may lead to improved outcomes for patients with this challenging disease. [10]



Clinical presentation is entirely dependent on the location of the chordoma. [11]

Skull base and clival chordomas typically present with headaches and/or cranial nerve dysfunction, most often involving cranial nerve VI (abducens nerve), although the lower cranial nerves can also be affected. [1]  With intracranial tumors, the most common presenting symptoms are diplopia and headache. Neurologic signs also occur in over 50% of patients, primarily as cranial nerve palsies. Palsies of cranial nerve VI and the sensory branch of cranial nerve V are most common.

Uncommon clinical presentations of intracranial tumors include CSF rhinorrhea, nasal obstruction, nasal bleeding, and subarachnoid hemorrhage. [12]  Rarely, a clival chordoma will present with rhinorrhea due to a cerebrospinal fluid (CSF) leak.

Cervical chordomas typically present with nonspecific neck, shoulder, or arm pain. Cervical chordomas can invade cranially to cause lower cranial nerve dysfunction, as well as compression of the spinal cord or exiting nerves, resulting in myelopathy or radiculopathy, respectively. [1]  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.

Patients with tumors located along lower vertebrae may present with pain, bladder dysfunction, or lower extremity weakness. Thoracic and lumbar chordomas are seen with nonspecific localized pain and may be the cause of a pathologic fracture or of radiculopathy or myelopathy. Sacral chordomas share a similar presentation as thoracic and lumbar chordomas with localized pain and possible radiculopathy, as well as possible dysfunction of the bladder, bowel, or autonomic nervous system if the tumor involves the lumbosacral plexus. [1]

Chordomas often present late in the disease course and tend to encapsulate adjacent neurovascular anatomy, seed resection cavities, recur locally, and respond poorly to radiotherapy and conventional chemotherapy—all of which make them challenging to treat. Extent of surgical resection and adequacy of surgical margins are the most important prognostic factors; thus, patients with chordoma should be cared for by a highly experienced, multidisciplinary surgical team at a quaternary center. [10]  The time span from onset of symptoms to diagnosis averages 10 months.



Chordoma is a low-grade notochordal tumor of the skull base, mobile spine, and sacrum that behaves malignantly and confers a poor prognosis despite indolent growth patterns. [10]

This is a clinically and histologically unique malignant neoplasm, and numerous diagnostic considerations must be excluded to establish the correct diagnosis. Treatment options have largely been centered on surgical excision with marginal results; however, novel therapeutic options including targeted therapy and immunotherapy offer promise for improved outcomes. [2]

Identification of molecular factors that are associated with survival contributes to better prognostication of patients with chordoma. Given the rarity of chordoma, often only univariate analyses can be performed. Robust multivariate analyses are scarcer but provide independently significant prognostic factors. At 10-year follow-up, the average survival rate is 50%, although individual prognosis varies substantially. [13]

A study based on analysis of Surveillance, Epidemiology, and End Results (SEER) data found that (1) marital status was an independent prognostic indicator for adult patients with chordoma, (2) married status was conducive to patient survival, and (3) compared with married patients, widowed patients are at higher risk of death. [14]

Despite the low-grade status of chordomas, they have a high recurrence rate and involve significant mortality. Five-year survival is approximately 50% overall but is improved to 65% with complete resection with negative margins. Surgical resection with positive margins is associated with approximately 50% 5-year survival, and if the chordoma is inoperable, 5-year survival is approximately 40%. [1]

Due to high local recurrence of chordomas, most physicians recommend lifelong surveillance with magnetic resonance imaging (MRI) with and without gadolinium contrast. Metastatic chordoma should be on the differential if new lesions arise elsewhere in the body, as up to 20% of chordomas can metastasize. [1]

Researchers who completed a population-based multivariate analysis to evaluate prognostic factors for patients with chordoma reported that older age, greater tumor size, and distant metastasis were correlated with decreased survival, whereas surgical resection was correlated with increased survival. Patients receiving radiation therapy also showed decreased survival—likely an indication of the patients' advanced stage of disease, making them poor surgical candidates. [15]

Immunohistochemical analysis of brachyury expression revealed that for classical and chondroid chordomas, the disease course cannot be reliably determined using only morphologic criteria. Brachyury (T gene) was shown to play a central role in chordoma pathogenesis. Recurrence-free survival and total survival were compared between brachyury-overexpressing and non-expressing groups using Kaplan-Meier survival analysis. Study authors concluded that brachyury expression in tumor samples is not a sensitive indicator of prognosis for patients with chordoma. [16]

A review of chordoma stated that chordoma is a complex disease because of its rarity, biological heterogeneity, and peculiar clinical behavior. Despite progress, the outcome of this disease remains unsatisfactory, and identification of active systemic treatments remains an urgent, unmet medical need. Significant steps forward have enhanced our comprehension of chordoma complexity, with insights gained into the biology and morphology of this disease. New entities have been described, and potentially druggable molecular targets identified. [17]