A rare slow-growing primary bone malignancy.
Arises from transformed notochordal remnants and occurs along the spinal axis from the clivus skull to the sacrum.
Chordoma is a low-grade malignancy that arises from tissue of the primitive notochord and in normal development becomes the nucleus pulposus of the intervertebral disk.
The evidence for this is the location of the tumors which are along the neuraxis, the similar immunohistochemical staining patterns, and the demonstration that notochordal cells are preferentially left behind in the clivus and sacrococcygeal regions when the remainder of the notochord regresses during fetal life.
It is a type of spinal cancer.
Chordomas can arise from bone in the skull base and anywhere along the spine.
Approximately 40% of these tumors arise in the clivus, with the remainder developing along the vertebral axis, most commonly in the sacrococcygeal region.
Chordomas may develop in persons of any age, but they manifest most commonly in persons aged 20-40 years.
A slight male predominance exists.
Chordoma. T1-weighted MRI with contrast that demon
Chordoma. T1-weighted MRI with contrast that demonstrates an enhancing mass that replaced the clivus and invaded the right cavernous sinus. This lesion was subtotally resected using a sublabial approach. The patient was then treated with gamma knife radiosurgery (GKRS).
In the United States, the annual incidence of chordoma is approximately 1 in one million with about 300 new patients each year.
Sacral chordomas make up 2 to 4% of all primary bone tumors and 44% of all primary sacral tumors: it the most common malignant sacral tumor.
About 50 to 60% of chordomas are located in the sacrococcygeal region.
Males aged between 40 to 50 years are twice as more common than women to get sacral chordoma.
No known environmental risk factors for chordoma.
The two most common locations are cranially at the clivus and in the sacrum at the bottom of the spine.
Constitutes 1-4% a primary bone malignancies.
Incidencee of approximately 1 per million.
2:1 male to female ratio.
Peak age of presentation between 50-60 years.
Rare entity in pediatric patients.
Associated with nonspecific symptoms and insidious onset resulting in an initial diagnosis at a locally advanced stage.
Occur along the midline near the neuraxis.
Distribution is even among the sacrum, skull base, and spine.
Younger patients and women more likely to have skull base disease.
A small number of families have been reported in which multiple relatives have been affected by chordoma.
In these families, duplication of the brachyury gene was found to be responsible for causing chordoma.
A possible association with tuberous sclerosis complex (TSC1 or TSC2) has been suggested.
Partial or complete PTEN (gene) deficiency is observed in nearly all sacral chordomas.
In a study of 49 chordomas Akt, TSC2, and EIF4EBP1 were phosphorylated in 92%, 96% and 98% of cases, respectively.
In a tissue microarray containing 21 chordomas: Platelet-derived growth factor receptor-beta (PDGFR-b), epidermal growth factor receptor (EGFR), KIT (CD117) and HER2 were detected in 100%, 67%, 33% and 0% of cases, respectively.
The CDKN2A and CDKN2B loci on chromosome 9p21 are frequently deleted in chordomas
62% of chordomas express the High Molecular Weight Melanoma Associated Antigen, also known as Chondroitin sulfate proteoglycan 4 (CSPG4) which has been the target of immune therapy.
Am inherited gene duplication is responsible for the familial form of this disorder.
Familial chordoma are rare, with an estimated rate of 0.4% in all Chordomas.
These tumors express brachyury, which can be detected by immunohistochemistry.
Most common primary bone tumor is of the sacrum.
Sacral chordoma presents with chronic low back pain.
Accounts with 50% of all sacral tumors.
Typically of low histologic grade, but are highly invasive lesions and recur often locally.
There are three histological types of chordoma: classical, chondroid and dedifferentiated.
The histological appearance of classical chordoma:lobulated tumor composed of groups of cells separated by fibrous septa.
The cells have small round nuclei and abundant vacuolated cytoplasm.
Chondroid chordomas histologically show features of both chordoma and chondrosarcoma.
Clinical presentation dependence on the location of the primary lesion.
Symptoms may be related to invasion of surrounding tissues, compression of adjacent structures such as the rectum, esophagus, trachea, and nerves.
Diagnosis is usually late, and approximate 5% of patients have metastases to lungs, bone, skin, brain at the time of diagnosis.
In patients with more advanced disease metastases may be present in up to 65% of cases.
Patients with involvement of the skull base present with headaches and possibly diplopia.
Lesions of the spine and sacrum are associated with deep pain and associated neurologic compromise.
Sacral lesions frequently have involvement of adjacent neurologic structures with weakness, numbness, bowel dysfunction, bladder incontinence, and sexual dysfunction.
Sacral extension to the pre-sacral area may be associated with obstipation, constipation, tenesmus or hemorrhoids.
Cervical chordomas may present as a oropharyngeal mass, or be associated with Horner syndrome, dysphagia or dysphonia.
Radiographic imaging classically manifests as osteolytic lesions in the midline involving the skull, vertebral body or sacrum, associated with a soft tissue mass.
Manifests as extradural masses compressing or encasing adjacent neurovascular structures.
Vertebral lesions usually spared the intervertebral disc space.
CT imaging shows osteolytic and osteosclerotic bone destruction.
MRI results show heterogeneous contrast enhancement.
Bone scans have diminished abnormal uptake compared with other bone tumors.
Imaging with PET scans show heterogeneous uptake..
Diagnosis done with fine needle aspiration or core needle biopsy.
Tumor seeding may occur following biopsy, and the tract of biopsy site should be excised with the tumor.
Microscopically associated with 3 variants: Classical, chondroid, or dedifferentiated.
The presence of brachyury, a transcription factor necessary for mesodermal formation, combined with cytokeratin staining as a sensitivity and specificity for detecting chordoma in approximately 100% of cases.
Treatment is en bloc resection with wide margins.
If lesions can not be resected, external beam radiation can be offered.
In most cases, complete surgical resection followed by radiation therapy offers the best chance of long-term control.
Incomplete resection of the primary tumor increases the odds of recurrence.
Chordomas are relatively radioresistant, requiring high doses of radiation to be controlled, and the proximity of chordomas to vital neurological structures such as the brain stem and nerves limits the dose of radiation that can safely be delivered.
Highly focused radiation such as proton therapy and carbon ion therapy are more effective than conventional x-ray radiation.
No effective medical therapy presently approved.
The tyrosine kinase inhibitor imatinib demonstrated a modest response in some chordoma patients, and that the combination of imatinib and sirolimus caused a response in several patients whose tumors progressed on imatinib alone.
Erlotinib-like EGFR inhibitors have been also reported to be effective in chordoma.
A report of response to olaparib has been published.
Prognosis depends on extent of surgical resection and surgical margins.
In one study, the 10-year tumor free survival rate for sacral chordoma was 46%.
Chondroid chordomas appear to have a more indolent clinical course.