What Is Chordoma

Overview

The human body is composed of a framework of bone. Anatomically, the skeleton is studied by forming 2 main divisions: 

• Axial skeleton 
• Appendicular skeleton

In simple terms, the axial skeleton is the one that forms the central axis of bone which includes the skull, laryngeal skeletons, thoracic cage, and vertebrae. The appendicular skeleton includes all the bones of the upper and lower limbs, the pelvic girdle and the shoulder. The vertebrae encompasses the spinal cord (commonly called the spine or backbone).

Chordoma is the malignant tumour of the bone, mainly localised in the axial skeleton, where they can occur anywhere on the bones of the spinal cord, from the base of the skull (clivus) to the sacrococcygeal region (tail region at the end of the vertebrae). It is a rare bone and soft tissue tumour falling under the category of sarcomas.. Chordoma tumours are slow growing but destructively harm nearby structures. Majority of chordoma tumours are diagnosed in the sacrococcygeal region, and they are called sacral chordoma; followed by the skull base called skull base chordoma; and the mobile parts of the spine (cervical, thoracic, and lumbar vertebrae). In a rare case, a chordoma tumour can appear on the soft tissue surrounding the joints (juxta-articular soft tissue).

According to the Chordoma Foundation, chordoma constitutes 20% of spinal cord tumours and 3% of all bone cancer. 

Based on the WHO classification of tumours of soft tissue and bones, chordoma is classified into:

• Classical chordoma 
• Chondroid chordoma: found on the skull base or clival chordoma. They are also referred to as brain tumours because the chordoma tumours can grow within the skull towards the brain
• Dedifferentiated chordoma: found in the sacral region, which is rare 
• Low-differentiated chordomas: found on the skull base and cervical spine (neck bone)

Causes of chordoma

Chordoma is known to have derived from the notochord, a structure present during the embryonic development stages. In humans and higher organisms, these notochords regress and form the vertebrae which contains the spinal cord. Only a small remnant of notochord remains later on in life by adulthood. The exact pathogenesis and source of chordoma development are still under study. But it is known that these notochord cells transform into cancer cells. 

Chordoma patients show a  higher expression of a gene called brachyury which is normally expressed during the initial stages of notochord development.

Cancer can be distinguished as hereditary and sporadic (non-hereditary). The hereditary basis of chordoma is still under research. Sporadic chordoma appears  after the age of 50-60 years. Pediatric chordoma and adolescent chordoma is very rare, less than a 5% chance , and mainly with shows skull base chordoma and sacral chordoma. 

Signs and symptoms of chordoma

Chordoma tumors grow up very slowly and thus it takes quite a while to show up the symptoms. Symptoms start appearing as the chordoma tumor starts compressing the surrounding tissue and the nerves nearby.

In the case of clival chordoma, the symptoms include:

• Headache
• cranial neuropathy (the 12 cranial nerves get  damaged) because of which you see symptoms such as blurred vision or loss of vision, droopy eyelid (ptosis), hearing loss, facial paralysis or hypoesthesia (lack of sensation of a body part), dysphonia (hoarse voice), dysarthria (slurred slow speech), dysphagia (difficulty swallowing), dyspnea (breathing difficulty), anosmia (loss of smell) and vertigo(dizziness).
• Endocrinopathy (dysfunctioning of endocrine glands)
• In case of pituitary tumor diabetes insipidus is seen¹

In case of sacral chordoma and mobile spinal cord tumour:

• Chronic back pain
• Numbness, tingling, and weakness of arm and legs
• Urinary bladder dysfunction
• Radiculopathies (The pain caused by compression of nerves of the spinal cord by chordoma tumor)²

After a point of time the as the cancer stage advances, chordoma tumor starts to metastasize or spread to nearby regions such as the lungs, bones, liver or local lymph nodes, surrounding muscle and subcutaneous tissue especially sacral chordoma show metastatic features.

Management and treatment for chordoma

Diagnosis

Chordoma is diagnosed mainly through:

• Imaging: CT scan and MRI is important to identify chordoma tumors. CT scan is necessary to reveal the intraosseous  tumor and intratumoral  calcification i.e, to see the tumor inside the bone and the calcium accumulation within the tumour. Moreover, they provide a detailed picture of metastasized tumour  cells.

• Biopsy:
  • A conclusive diagnosis is possible through biopsy by a pathologist. A needle  biopsy is required for the histopathological evaluation of chordoma cells. Immunohistochemical staining can differentiate chordoma from other kinds of cancer such as chondrosarcoma since they show similar features. Cytokeratin and brachyury serve as a marker for distinguishing chordoma from chondrosarcoma³

Treatment 

The choice of chordoma treatment is planned based on the extent of the spread of tumour called as staging. As such, there are no standard treatments and clinical trials are undergoing on identifying newer therapeutic and treatment modalities. 

The mainstay treatment involves surgery and radiation therapy.

• Surgery:
  • En block resection of the tumor is the choice of treatment. En block surgery is the surgical resection of the tumor entirely along with the surrounding continuous tissue. It is very important to cautious as these healthy tissues may have a functional role.⁴ The surgery is challenging and requires experienced surgeon and medical professionals. In the case of an inoperable tumor, radiation therapy forms the alternative approach⁵

• Radiation therapy: either external radiation or proton therapy
• Proton therapy uses high energy positively charged particles called protons are generated which directly destroys the cancer cells⁶
• Targeted therapy, chemotherapy, and immunotherapy are under clinical trial

Chordoma treatment is  challenging because, firstly, the chordoma tumor is located within the vertebrae which have  got various links with the nerves such as cranial nerves, vessels, brainstem, and spinal cord. Secondly, resistance towards available chemotherapeutic drugs, thirdly unnotified growth until it reaches advanced stages, fourthly spreading onto various locations. Even after complete treatment, there are chances of regrowth in the area of the primary tumor.

However advances in imaging, targeted therapy, radiation therapy, and surgical approach can open new modalities for treating chordoma. 

FAQs

How is chordoma diagnosed?

Chordoma is diagnosed through MRI and CT scan accompanied by a biopsy.

Can chordoma be prevented?

There are no risk factors associated with chordoma and thus early identification of the condition may improve the survival rates.

What are the types of chordoma

• Classical chordoma 
• Chondroid chordoma
• Dedifferentiated chordoma
• Low-differentiated chordoma

Who is at risk of chordoma?

Chordoma does not have any influence on lifestyle, dietary or environmental factors. The genetic predisposition of chordoma is still under question. Patients with chordoma present with a higher expression of gene brachyury.

How common is chordoma?

Chordoma is a very rare type of bone cancer affecting 1 in 1,000,00 people annually. In the US the number of chondroma-diagnosed  patients are 300 and UK about 700 patient annually. 

Summary

The whole article summarises  the understanding of chordoma, its symptoms, and treatment. Chordoma arises from the notochord cells mainly affecting the bone of the spinal cord which includes the sacrum, skull base, and mobile parts of the vertebral column. Surgical resection followed by radiation therapy increases the survival chances and prognosis. However, there are no approved treatments available and clinical trials are continuing to find new treatment strategies.