Chordoma

Overview

A chordoma is a form of sarcoma that is low-grade, slow-growing, but locally invasive and aggressive. Chordomas develop from notochord remnants and appear between the clivus and the sacrum, anterior to the spinal cord, along the midline spinal axis. 

Chordomas are most commonly seen in the lower back (sacral region) and the base of the skull ( one-third of chordomas). Chordomas develop from notochord remnants, the embryonic tissue that eventually forms the core of spinal disks.

Chordoma definition

Chordoma is an uncommon kind of bone cancer that most commonly affects the spine or skull bones. It usually appears where the skull sits atop the spine (skull base) or at the bottom of the spine (spine base) (sacrum)

Chordoma develops in cells that were formerly part of a group of cells in the developing embryo that later become the spine's disks. The majority of these cells die before or shortly after you are born. However, a few of these cells may persist and, in rare cases, become malignant.

Chordomas are found in the sacral region 50% of the time, the skull base 35% of the time, and the vertebral bodies of the mobile spine 15% of the time (most commonly the C2 vertebrae followed by the lumbar then thoracic spine). 

Epidemiology

Chordomas are most common in people aged 40 to 60, but they have also been found in youngsters and the elderly. Males are thought to be more typically affected than females in a 2:1 ratio, with a new diagnosis rate of 1:1,000,000 every year. Chordomas make up about 20% of primary spinal tumors and just 3% of all bone tumors.

The sacrum/coccygeal area is the most common location (50 percent), followed by the spheno-occipital region (35 percent), and the movable spine (approximately 10% to 15%).

Etiology 

Chordomas are hypothesized to develop from the axial skeleton's basic notochordal remains. The notochord is encircled by the developing spinal column during development. The nucleus pulposus of the intervertebral discs contains vestiges of the notochord in adults. Extradural notochordal remains are most prevalent in the sacrococcygeal area, but they can be found elsewhere along the axial skeleton. Tumors are distributed in the same way that notochordal remains are distributed.

Some chordomas have been linked to a genetic foundation. The majority, however, have complicated aberrant karyotypes with full or partial losses of chromosomes 3, 4, 10, and 13, gains in chromosome 7, and chromosome 1p rearrangements. All of these factors have been linked to the development of chordomas. Microsatellite instability has also been established as a result of DNA mismatch repair defects; however, no chordoma-specific translocations have been discovered.

EGFR, pSTAT3, VEGF, and mTOR pathway proteins were found to be expressed in 85.9%, 79.1%, 85.7 percent, and 46 percent of 287 chordomas in 111 patients, respectively, in a study of 287 chordomas in 111 patients. In another investigation, three distinct variations were discovered, accounting for 11 point mutations in three cancer-related genes (KIT, KDR, and TP53).

Relevant Anatomy

Notochord remnants, especially near the ends of the spinal axis, are closely associated to the position of chordomas along the spinal canal. The sacrococcygeal region accounts for 49% of chordomas, whereas the sphenoccipital region accounts for 30%, with the clivus accounting for nearly all of them. The extent of these tumors varies. Vertebral chordomas make up just 15% of all chordomas, and they can be found in the lumbar, cervical, and thoracic areas, in that order.

Chordomomas come in a variety of sizes. They are gray-white in color on the outside and soft, gelatinous, smooth, or lobulated. The tumor is homogenous in color and consistency in sliced sections. Calcifications or hemorrhages may appear on occasion. When found in soft tissue, Chordomas appear to be encapsulated, but not when found in bone.

Pathophysiology

Chordomas are slow-growing, locally invasive tumors that seldom form distant metastases and only do so late in the disease. Despite the fact that they are considered indolent tumors, they are highly likely to recur locally.

History and Physical

The patient's medical history and physical results are determined by the chordoma's exact location. Headaches and/or cranial nerve dysfunctions, most commonly cranial nerve VI (abducens nerve), but the lower cranial nerves can also be affected, are common symptoms of skull base and clival chordomas. Rhinorrhea is a rare symptom of a clival chordoma caused by a CSF fluid leak.

Cervical chordomas are characterized by nonspecific neck, shoulder, or arm pain, as well as dysphagia due to mass impact. Cervical chordomas can also infiltrate cranially, causing lower cranial nerve dysfunction, as well as compression of the spinal cord or leaving nerves, resulting in myelopathy or radiculopathy.

Chordomomas of the thoracic and lumbar spine can induce non-specific regional pain and can also be the cause of a pathologic fracture, radiculopathy, or myelopathy. Sacral chordomas appear similarly to thoracic and lumbar chordomas, with localized pain and possibly radiculopathy, as well as potential bladder, bowel, or autonomic nervous system dysfunction if the tumor affects the lumbosacral plexus.

Diagnosis

The diagnosis of chordomas is based on imaging and biopsy. A locally damaging lytic lesion will be visible on a plan x-ray. The destructive lytic chordoma is best visualized by computed tomography (CT) imaging. Sclerosis near the chordoma's edge occurs occasionally. Chordomas show uneven dystrophic calcification and are hypodense on CT compared to bones.

In contrasted CT imaging, Chordomas show a moderate to substantial increase. The best way to determine the extent of a chordoma is to use magnetic resonance imaging (MRI). On T1-weighted imaging, chordomas have a decreased signal intensity and may reveal areas of hyperintensity, indicating intratumoral hemorrhage. T1-weighted imaging with gadolinium contrast reveals a honeycomb pattern of heterogeneous contrast enhancement in the tumor.

Chordomomas are hyperintense on T2-weighted MRI. Intratumoral bleeding can be confirmed using gradient-echo MRI imaging. Chordomomas exhibit normal to decreased uptake on bone scans, which are sometimes obtained during the workup.

To confirm the diagnosis of chordoma, a needle or open biopsy is frequently used. The chordoma can seed along the biopsy path, therefore caution is required when planning and performing the biopsy. To reduce the chance of local recurrence, the biopsy tract should be included in subsequent chordoma resections.

Management

Complete en bloc excision of the tumor with clean margins is the treatment that delivers the longest survival. This can be difficult due to the chordoma's location or the requirement for reconstructive surgery after resection. If total chordoma resection can be done without local seeding, intratumoral and piecemeal resection may also provide a similar advantage.

If total resection is not technically possible, local debulking may be recommended. Local debulking can reduce the size of the target volume for future radiation therapy and improve symptoms caused by mass effect.

Because of the high incidence of local recurrence after any type of chordoma excision, most doctors recommend radiation therapy. Because chordomas are radioresistant, they require high-dose radiation therapy. Due of the proximity of chordomas to neural structures, highly conformal irradiation, such as proton beam radiation or radiosurgery, is performed. Chordoma patients are currently thought to benefit from conventional photon therapy. 

Chordomomas are resistant to most current conventional chemotherapeutic treatments due of their slow growth. When a chordoma is treated with chemotherapy, it is usually done as part of a clinical study.

Most doctors urge lifelong surveillance with magnetic resonance imaging (MRI) with and without gadolinium contrast because to the high local recurrence of chordomas. If additional lesions appear elsewhere in the body, a metastatic chordoma should be considered, as up to 20% of chordomas can spread.

Treatment for chordoma in the sacral spine

If the chordoma affects the lower portion of the spine (sacrum), treatment options may include:

• Surgery. The goal of surgery for a sacral spine cancer is to remove all of the cancer as well as some of the surrounding healthy tissue. Because the tumour is close to vital structures like nerves and blood vessels, surgery may be challenging. When cancer cannot be totally removed, surgeons may attempt to remove as much as feasible.
• Radiation therapy. To kill cancer cells, radiation therapy uses high-energy beams such as X-rays or protons. Radiation therapy involves lying down on a table while a machine moves around you, directing radiation beams to specific spots on your body.

Before surgery, radiation therapy can be used to reduce a malignancy and make it easier to remove. It can also be used following surgery to eliminate any remaining cancer cells. Radiation therapy may be advised instead of surgery if surgery is not an option.

Newer types of radiation therapy, such as proton therapy, allow doctors to utilize higher doses of radiation while protecting healthy tissue, potentially making chordoma treatment more effective.

• Radiosurgery. Multiple beams of radiation are used in stereotactic radiosurgery to kill cancer cells in a very narrow area. Each radiation beam isn't particularly powerful, but the chordoma, where all the beams meet, receives a huge dose of radiation that kills the cancer cells. Radiosurgery can be used to treat chordoma before or after surgery. Radiosurgery may be considered instead of surgery if surgery is not an option.
• Targeted therapy. Drugs that target specific defects within cancer cells are used in targeted therapy. Targeted medication treatments can kill cancer cells by addressing these anomalies. Chordomoma that has spread to other parts of the body is sometimes treated with targeted therapy.

Treatment for chordoma in the skull base

If the chordoma affects the area where the spine joins with the skull (skull base), treatment options may include:

• Surgery. An operation to remove as much of the cancer as possible without hurting neighboring healthy tissue or generating new issues, such as injury to the brain or spinal cord, is usually the first step in treatment. If the tumor is close to vital structures like the carotid artery, complete excision may be impossible.

In some cases, surgeons may employ specialized techniques to approach the cancer, such as endoscopic surgery. Endoscopic skull base surgery is a minimally invasive procedure that includes accessing the cancer with a long, thin tube (endoscope) introduced through the nose. To remove the cancer, special tools can be sent via the tube.

Occasionally, surgeons may prescribe a second operation to remove as much cancer as possible or to stabilize the area where the disease was previously located.

• Radiation therapy. To kill cancer cells, radiation therapy uses high-energy beams such as X-rays or protons. After surgery for skull base chordoma, radiation therapy is frequently indicated to eradicate any remaining cancer cells. Radiation therapy may be advised instead of surgery if surgery is not an option.

Higher radiation doses may be more successful for chordoma thanks to new radiation therapy techniques that target the treatment more precisely. Proton treatment and stereotactic radiosurgery are two examples.

New treatments. New treatments for skull base chordoma are being tested in clinical trials, including medicines that target specific vulnerabilities in chordoma cells. If you're interested in trying one of these newer treatments, talk to your doctor about your options.

Differential Diagnosis

Clival/Spheno-occipital lesions:

• Benign notochordal cell tumor
• Chondrosarcoma
• Ecchordosis physaliphora
• Meningioma
• Pituitary macroadenoma
• Plasmacytoma

Vertebral lesions:

• Chondrosarcoma
• Giant cell tumor
• Plasmacytoma
• Spinal metastases
• Spinal lymphoma

Prognosis

SBCs (skull base chordomas) are uncommon dysembryogenetic invasive tumors with a variable recurrence rate. Overall survival rates were 67 percent and 57 percent in one research, while progression-free survival rates were 58 percent and 44 percent, respectively. Overall survival was positively predicted by the extent of resection, adjuvant radiation therapy, and the lack of rhinopharyngeal invasion. The use of adjuvant radiation therapy, the absence of rhinopharyngeal invasion, and the patient's age were all found to be positive independent predictors of progression-free survival.

Conclusion 

If chordoma is considered a possibility in the differential diagnosis, any biopsy should be carefully planned, as the biopsy tract must be included in the chordoma's final resection to reduce the risk of local recurrence.

Despite their low grade, chordomas have a high recurrence rate and a high fatality rate. Overall, five-year survival is around 50%, but full resection with negative margins improves this to a 65 percent 5-year survival rate. If the chordoma is operative, the 5-year survival rate is approximately 50%, and if the chordoma is inoperable, the 5-year survival rate is roughly 40%.

Chordomomas are soft, gelatinous tumors that may exhibit bleeding under the microscope. Fibrous septa separate lobules of physaliferous (bubbly) cells with an extensive myxoid stroma and infrequent mitotic patterns under the microscope.  

Chordomas are classified as either conventional, poorly differentiated, dedifferentiated, or chondroid. The most common type of chordoma is conventional (classic), which can have areas of dedifferentiation. Skull base chordomas, as well as poorly differentiated chordomas, are more frequent in young adult and juvenile patients.

The gene INI-1 is lost in poorly differentiated chordomas. Dedifferentiated chordomas are the most aggressive and fastest developing chordomas. They can also feature a lack of INI-1 and are more common in children. On histology, chondroid chordoma refers to chordomas that are difficult to identify from chondrosarcoma. Chordomas usually express the brachyury gene, whereas chondrosarcomas do not.

Chordomas have been known to dedifferentiate into high-grade spindle cell tumors, which are associated with a poor prognosis Chordomoma is best treated by a multidisciplinary team that comprises an orthopedic surgeon, radiologist, neurologist, and pathologist. Other professionals, such as a neurosurgeon, oncology nurse, pediatrician, and ENT surgeon, may be involved depending on the locale. Chordomas are locally aggressive tumors that respond well to extensive en bloc excision. 

Perioperative care, recuperation, and rehabilitation are all handled by nurses. They keep track of the patient's condition, educate patients and their families, and keep the rest of the team informed. Pharmacists examine drugs, look for drug-drug interactions, and educate patients.