You are in: eMedicine Specialties > Neurosurgery > Neoplasm ChordomaArticle Last Updated: Jun 5, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 12
  Author: Cheryl Ann Palmer, MD, Professor, Departments of Pathology and Neurology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Departments of Pathology and Neurology, University of Alabama at Birmingham Hospital; Consulting Staff, Departments of Pathology and Neurology, Veteran Affairs Medical Center; Consulting Staff, Department of Pathology, Children's Hospital of Alabama Cheryl Ann Palmer is a member of the following medical societies: American Academy of Neurology, American Association of Neuropathologists, Medical Association of the State of Alabama, Society for Neuro-Oncology, and Southern Medical Association Coauthor(s): Daniel Keith Harrison, MD, Neuropathology Fellow, Department of Pathology, University of Alabama at Birmingham Editors: Duc Hoang Duong, MD, Professor, Chief Physician, Departments of Neurological Surgery and Neuroscience, Epilepsy Center, Charles R Drew University; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Ryszard M Pluta, MD, PhD, Associate Professor, Neurosurgical Department Medical Research Center, Polish Academy of Sciences at Warsaw, Poland; Senior Researcher, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, NIH; Paolo Zamboni, MD, Professor of Surgery, Chief of Day Surgery Unit, Chair of Vascular Diseases Center, University of Ferrara, Italy; Allen R Wyler, MD, Former Medical Director, Northstar Neuroscience, Inc Author and Editor Disclosure Synonyms and related keywords: cranial chordoma, intracranial chordoma, vertebral chordomas, sacrococcygeal chordoma, malignant midline tumor, embryonic notochordal remnants, ectopic notochord remnants, neuraxis, CNS tumors, ecchondrosis physaliphora, primary intracranial neoplasms, sacrum, clivus, spinal axis, rectal dysfunction, urinary incontinence, bladder dysfunction, diplopia, headache, lower extremity weakness, cranial nerve palsy, hoarseness, dysphagia, pharyngeal bleeding, physaliferous cells INTRODUCTIONSection 2 of 12
  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 comprise less than 1% of CNS tumors, though they can occur in extraaxial locations. Chordomas are thought to arise from ectopic notochord remnants. History of the ProcedureIn 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. ProblemEcchordosis 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, but chordomas are quite rare. Even though chordomas usually are 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. FrequencyChordomas 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, and 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. 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. EtiologyChordomas 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.1 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. PathophysiologyChordomas 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, and, eventually, they may be responsible for mortality. ClinicalThe clinical presentation is entirely dependent on the location of the chordoma. 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. 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. INDICATIONSSection 3 of 12
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. RELEVANT ANATOMYSection 4 of 12
The location of the notochord 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. CONTRAINDICATIONSSection 5 of 12
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. WORKUPSection 6 of 12
Lab StudiesNo laboratory studies are required for the evaluation of chordomas, except as needed for routine preoperative evaluation in patients scheduled to undergo surgical resection. Imaging Studies
Other TestsNo other tests are required in the evaluation of chordomas. Diagnostic Procedures
Histologic FindingsMicroscopically, chordomas are composed of uniform cells with small oval or round eccentric nuclei and dense chromatin. The hallmark microscopic features of chordomas are the numerous, variably sized vacuoles located in the tumor cell cytoplasm, the physaliphorous cells (see Image 2 and Image 3). Some tumor cells may have more solid or eosinophilic cytoplasm. Various histologic growth patterns can be seen in chordomas. The cells may be arranged in a diffuse or lobular pattern, or they may be clustered in groups or islands in a sheetlike pattern. Areas of tumor cells may be seen in a solid, perivascular, or even ribbonlike pattern. Between the cells or clusters, an abundant basophilic-to-metachromatic mucinous matrix exists. Mitoses, foci of pleomorphic cells, or focal hemorrhage rarely can be seen but are not prominent features. Fibrous tissue surrounds the neoplasm and extends projections into the tumor, usually without forming a true capsule. A chondroid variant of chordoma is well recognized. In these tumors, a significant cartilaginous component is present with features of either chondrosarcomas or chondromas. Some authors believe these entities are separate and that studies with both immunoperoxidase staining and electron microscopy can distinguish them. Also, patients with this variant were once thought to have a slightly better prognosis; however, recent large studies have shown this variant to be of no prognostic significance. With specialized histochemistry, chordoma tumor cells tend to be periodic acid-Schiff (PAS) positive. The matrix stains diffusely with mucicarmine and Alcian blue, and it stains metachromatically with toluidine blue; it is negative with Sudan black. In electron microscopy, ultrastructural features in chordomas include desmosomal attachments and prominent mucinous vacuoles. Immunohistochemically, the tumor cells label with cytokeratins and epithelial membrane antigen (EMA). Both chordomas and the embryologic notochord are S-100 positive, whereas most carcinomas are negative. This difference in S-100 positivity can be helpful in the differentiation of metastatic carcinomas from chordomas in instances in which the histologic pattern is similar. Positivity for cytokeratins and EMA can be helpful in distinguishing the chondroid variant of chordoma from chondrosarcoma. More recently, immunohistochemical and gene microarray studies reveal the presence of high levels of brachyury in axial chordomas. Brachyury is a key transcription factor in the development of posterior mesoderm which becomes restricted to the notochord and tailbud. Although research is ongoing, initial data indicate brachyury could be a novel biomarker in distinguishing chordomas from chondroid neoplasms as well as other histologically similar entities.3, 4 Recent investigations have looked at cell cycle alterations and the role of the p53 tumor suppressor gene in chordoma tumorigenesis. Early data suggest that p53 overexpression characterized by increased immunohistochemical staining for p53 protein is associated with a poor prognosis in patients with chordoma.5 StagingChordomas, like other bone tumors, have been subject to staging methods. Studies analyzing the prognosis and outcome in comparison to stage have not proven to be very useful. As discussed above, the local extent and degree of resection are much more important to the prognosis of a chordoma (see Problem). TREATMENTSection 7 of 12
Medical therapyClinical trials are underway to study the effectiveness of imatinib mesylate in the treatment of chordoma (Casali et al., 2004). Imatinib mesylate is a tyrosine kinase inhibitor targeting several enzymes including platelet-derived growth factor receptor--b (PDGFRB), which can be expressed in chordomas. This drug has been shown to have antitumor activity in chordomas; however, research is ongoing and surgery remains the standard treatment for chordomas. Adjuvant radiation therapy is used in cases where incomplete resection is suspected. Chemotherapy has not been shown to be effective. Surgical therapyThe treatment of chordomas depends on the extent and location of the tumor. In general, a more complete removal with wide excision delays the time interval between surgery and eventual recurrence. The natural history and the effectiveness of different kinds of therapy are not well understood in chordomas because of their rare incidence and slow-growing nature. Radical resections of tumors with clean margins are associated with a longer disease-free interval. If subtotal excision is the only option (generally due to location and proximity to delicate anatomy), the addition of radiation therapy can lengthen the interval to recurrence. In cases in which radiation therapy is utilized without surgical resection, an average of only 50% for 10-year local control is seen for skull-based and cervical spine tumors. Preoperative detailsImaging of the tumor prior to surgery can reveal the extent of the tumor by ascertaining both the amount of bone involvement or erosion and the extent of expansion of the tumor into adjacent soft tissues. This information can be important for planning the most advantageous resection possible. As for any surgical patient, the normal preoperative history and physical are required. Other medical problems need to be stabilized or addressed (eg, cardiovascular, respiratory). Laboratory studies, including electrolytes, coagulation status, and blood count, are needed. Radiological studies (x-ray, CT scan, MRI) can be used for both evaluation of the tumor and other medical problems. Chest x-rays, ECGs, and blood crossmatch also may be important. Intraoperative detailsThe evaluation of tumor margins is essential to assess the status of the resection as the resection proceeds. Knowledge of the completeness of the tumor resection helps predict patient outcome in terms of the length of the disease-free interval and assists in determination of the need for adjunctive therapy such as radiation. Postoperative detailsGeneral postoperative complications relevant to this or any surgery include wound infection or infection of the operative bed (abscess), shock, pulmonary complications (respiratory failure, atelectasis, infection), and bladder infection or urinary retention. Complications particular to cranial neurosurgery include the possibilities of intracranial hemorrhage, meningitis, osteomyelitis, seizures, hydrocephalus, increased intracranial pressure, hematoma formation, swollen eyelids, keratitis, and facial palsy. Rehabilitation may be necessary in the case of sacral surgeries, depending on the extent of damage to the spinal cord and the level of presurgical functioning. Recovery from either sacral or cranial procedures depends on the extent of tumor removal and intraoperative injury of adjacent neural structures. Problems may include, but are not limited to, facial palsies, incontinence, and difficulty walking. Follow-upFrequent follow-up is required because of the high rate of recurrence of these tumors. Tumor recurrence identified early is easier to treat. The average interval to recurrence is 3.8 years for radically resected tumors, 2.1 years for subtotal resection followed by radiation therapy, and 8 months for subtotal excision without adjuvant therapy. The interval of follow-up, including repeat MRI or CT scans, depends on the completeness of the resection. Because residual tumor drastically shortens the recurrence time, patients with known or suspected residual tumor need to be evaluated more frequently. COMPLICATIONSSection 8 of 12
Complications occur at a higher rate after radical resections than with subtotal resections and depend somewhat on the location of the tumor. Morbidity from surgery can be very mild or severe following tumor resection. With the resection of sacrococcygeal chordomas, bowel and bladder dysfunction are the most frequent complications. OUTCOME AND PROGNOSISSection 9 of 12
Chordomas are relatively benign-appearing neoplasms; however, because of their tendency to erode bone and invade soft tissues, they usually display malignant behavior. In addition, the location of the tumor influences the ability to achieve complete resection. Chordomas often grow in inaccessible sites, and their margins within soft tissue often are not well defined. As a result, complete excision of chordomas is difficult at best. The 5-year survival rate is estimated to be 51%, and the 10-year survival is estimated to be 35%. Factors that may improve prognosis are young age, complete resection, and the addition of radiation therapy in incompletely resected tumors. FUTURE AND CONTROVERSIESSection 10 of 12
Molecular and cytogenetic studies continue to explore new treatment modalities for chordoma, but the most significant dilemma remains the choice between a radical surgical procedure with the potential for serious morbidity and a subtotal resection with an increased potential for recurrence. The general health of the patient should be considered during planning for the surgical procedure. With explanations of the risks and benefits provided to the patient, an informed decision regarding therapy can be reached. MULTIMEDIASection 11 of 12
REFERENCESSection 12 of 12
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