Chordoma – Causes, Symptoms, Diagnosis, Treatment

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 the 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% occur in the vertebral bodies of the mobile spine (most commonly the C2 vertebrae followed by the lumbar then thoracic spine). Overall 5-year survival is approximately 50%, and treatment is en bloc surgical resection followed by high-dose conformal radiation therapy such as proton beam radiation.[rx][rx]

Classification

Based upon location, a chondroma can be described as an enchondroma or ecchondroma.

• enchondroma – tumor grows within the bone and expands it
• ecchondroma – grows outward from the bone (rare)

Causes of Chordoma

Chordomas arise from the notochord. The notochord is the mesodermal structure in the embryo, which serves to help signal tissues for organization and differentiation. The notochord ultimately becomes the nucleus pulposus in humans as it regresses. Genes implicated in chordoma formation include the brachyury gene, mechanistic target of rapamycin (mTOR) signing pathway, phosphatase, and tensin homolog (PTEN) gene deficiency, INI-1 and platelet-derived growth factor receptor beta (PDGFR-beta) although no definitive genetic marker has as of yet been identified.[rx]  There are currently a few reported familial clusters of chordomas.

History and Physical

The patient history and physical findings are dependent on the specific location of the chordoma. Skull base and clival chordomas typically present with headaches and or cranial nerve dysfunctions, most often cranial nerve VI (abducens nerve), although the lower cranial nerves can also be affected. Rarely a clival chordoma will present with rhinorrhea due to a cerebrospinal fluid leak. Cervical chordomas typically present with non-specific neck, shoulder or arm pain, and occasionally dysphagia due to mass effect. Cervical chordomas can also invade cranially to cause lower cranial nerve dysfunction as well as compression of the spinal cord or exiting nerves causing myelopathy or radiculopathy, respectively. Thoracic and lumbar chordomas also present with non-specific localized pain and, also, maybe the cause of a pathologic fracture or 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.

Evaluation

The following tests and procedures may be used

• Physical exam and history – An exam of the body to check general signs of health, including checking for signs of disease, such as high blood pressure or anything else that seems unusual. A history of the patient’s health habits and past illnesses and treatments will also be taken.
• Twenty-four-hour urine test – A test in which urine is collected for 24 hours to measure the amounts of catecholamines in the urine. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts of certain catecholamines may be a sign of pheochromocytoma.
• Blood catecholamine studies – A procedure in which a blood sample is checked to measure the amount of certain catecholamines released into the blood. Substances caused by the breakdown of these catecholamines are also measured. An unusual (higher than or lower than normal) amount of a substance can be a sign of disease in the organ or tissue that makes it. Higher-than-normal amounts of certain catecholamines may be a sign of pheochromocytoma.
• CT scan (CAT scan) – A procedure that makes a series of detailed pictures of areas inside the body, such as the neck, chest, abdomen, and pelvis, taken from different angles. The pictures are made by a computer linked to an x-ray machine. A dye may be injected into a vein or swallowed to help the organs or tissues show up more clearly. This procedure is also called computed tomography, computerized tomography, or computerized axial tomography.
• NMRI (Nuclear magnetic resonance imaging) – A procedure that uses a magnet, radio waves, and a computer to make a series of detailed pictures of areas inside the body such as the neck, chest, abdomen, and pelvis. This procedure is also called nuclear magnetic resonance imaging (NMRI).
• MIBG scan – A procedure used to find neuroendocrine tumors, such as pheochromocytoma and paraganglioma. A very small amount of a substance called radioactive MIBG is injected into a vein and travels through the bloodstream. Neuroendocrine tumor cells take up the radioactive MIBG and are detected by a scanner. Scans may be taken over 1-3 days. An iodine solution may be given before or during the test to keep the thyroid gland from absorbing too much of the MIBG.
• Scan – A type of radionuclide scan used to find certain tumors, including tumors that release catecholamine. A very small amount of radioactive (a hormone that attaches to certain tumors) is injected into a vein and travels through the bloodstream. The radioactive attaches to the tumor and a special camera that detects radioactivity is used to show where the tumors are in the body.
• FDG-PET scan (fluorodeoxyglucose-positron emission tomography scan) – A procedure to find malignant tumor cells in the body. A small amount of FDG, a type of radioactive glucose (sugar), is injected into a vein. The PET scanner rotates around the body and makes a picture of where glucose is being used in the body. Malignant tumor cells show up brighter in the picture because they are more active and take up more glucose than normal cells do.
• Immunohistochemistry – A laboratory test that uses antibodies to check for certain antigens (markers) in a sample of a patient’s tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. After the antibodies bind to a specific antigen in the tissue sample, the enzyme or dye is activated, and the antigen can then be seen under a microscope. This type of test looks for the enzyme SDH in a sample of the patient’s tissue. When SDH is not present, it is called SDH-deficient GIST. It is important to know whether the cancer is SDH-deficient in order to plan treatment.
• Bone scan – A nuclear imaging method to evaluate any degenerative and/or arthritic changes in the joints, to detect bone diseases and tumors and to determine the cause of bone pain or inflammation.
• Biopsy – The removal of cells or tissues so they can be viewed under a microscope by a pathologist to check for signs of cancer.
  • Fine-needle aspiration – The removal of tissue using a thin needle.
  • Endoscopy – A procedure to look at organs and tissues inside the body to check for abnormal areas. An endoscope is inserted through an incision (cut) in the skin or opening in the body, such as the mouth or anus. An endoscope is a thin, tube-like instrument with a light and a lens for viewing. It may also have a tool to remove tissue or lymph node samples, which are checked under a microscope for signs of disease.

Evaluation of chordomas revolves around imaging and biopsy. A plan x-ray will demonstrate a locally destructive lytic lesion. Computed tomography (CT) imaging is better for demonstrating the destructive lytic chordoma. Occasionally the chordoma will have sclerosis at the margin. Chordomas are hypodense compared to bones on CT and may demonstrate irregular dystrophic calcification. Chordomas demonstrate moderate to significant enhancement in contrasted CT imaging. Magnetic resonance imaging (MRI) best delineates the extent of a chordoma. Chordomas have lower signal intensity on T1-weighted imaging and may show foci of hyperintensity, which represents intratumoral hemorrhage. T1-weighted imaging with gadolinium contrast demonstrates heterogeneous contrast enhancement of the tumor with a honeycomb appearance. On T2-weighed imaging, chordomas tend to be hyperintense. Gradient-echo MRI imaging can confirm intratumoral hemorrhage. Bone scans are sometimes obtained during the workup, and chordomas have normal to decreased uptake.

Many times a needle or open biopsy is performed to confirm the diagnosis of chordoma. Care needs to be taken when planning and performing the biopsy as the chordoma can seed along the biopsy tract. Thus the biopsy tract should be included in the future chordoma resection to decrease the risk of local recurrence.

Treatment of Chordoma

The treatment which provides the longest survival is complete en bloc resection of the tumor with clean margins. This can prove to be challenging either due to the location of the chordoma or reconstructive needs after resection. Intratumoral resection and piecemeal resection may also provide a similar benefit if complete chordoma resection can be achieved without local seeding. Local debulking is sometimes advocated if complete resection is not technically feasible.  Local debulking can alleviate symptoms secondary to mass effect as well as provide a smaller target volume for future radiation therapy.

Most physicians advocate for radiation therapy after any type of chordoma resection due to the high local recurrence rate. Chordomas are relatively radioresistant, necessitating high-dose radiation therapy. As chordomas are found near neuronal structures, highly-conformal radiotherapy is used, including proton beam radiation or radiosurgery. Conventional photon radiation is currently thought to be of no benefit to chordoma patients.

The slow-growing nature of chordomas makes them resistant to most current conventional chemotherapeutic agents. If a chordoma is treated with chemotherapy, then treatment typically occurs within a clinical trial.

Due to the 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.[rx]

References