Chordoma


Article Author:
Steven Tenny


Article Editor:
Matthew Varacallo


Editors In Chief:
Paul DiCesare


Managing Editors:
Frank Smeeks
Scott Dulebohn
Erin Hughes
Pritesh Sheth
Mark Pellegrini
James Hughes
Richard Ciresi
Phillip Hynes


Updated:
10/27/2018 12:31:28 PM

Introduction

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.

Etiology

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.  There are currently a few reported familial clusters of chordomas.

Epidemiology

Chordomas typically affect those in the 40-60 year-old age group but have been reported in children and the very elderly. Most believe males are more commonly affected than females in an approximately 2:1 ratio with an annual incidence of 1:1,000,000 for new diagnoses.  Chordomas account for approximately 20% of primary spinal tumors and only 3% of all bone tumors.  The most common location is in the sacrum/coccygeal region (50%), followed by 35% located in the spheno-occipital region, and the remaining chordomas (about 10% to 15%) located in the mobile spine. 

Pathophysiology

Chordomas present with slow-growing, locally invasive tumors with distant metastases are rarely occurring and only late in the disease. Although they are considered indolent tumors, there is a significant risk for multiple recurrences locally.

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 commonly 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 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, may be 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 lumbosacral plexus is involved by the tumor.

Evaluation

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 on 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 heterogenous 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 planing 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 / Management

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.

Pearls and Other Issues

It should be stressed that if chordoma is entertained in the differential diagnosis, there should be careful planning of any biopsy as the biopsy tract needs to be included in the ultimate resection of the chordoma to decrease the risk of local recurrence.

Despite the low-grade status of chordomas they have a high recurrence rate and significant mortality. Five-year survival is approximately 50% overall but improved with complete resection with negative margins to a 65% 5-year survival rate. Surgical resection with positive margins is approximately 50% 5-year survival and if the chordoma is inoperable 5-year survival is approximately 40%.

Macroscopically chordomas are soft, gelatinous tumors and may have hemorrhage present. Microscopically they consist of fibrous septa separating lobules of physaliferous (bubbly) cells with an extensive myxoid stroma and rare mitotic figures.

Chordomas can be divided into four four subtypes: conventional, poorly differentiated, dedifferentiated and chondroid. Conventional (classic) chordomas are the most common variety and may show areas of dedifferentiation. Poorly differentiated chordomas are more common in young adult and pediatric patients as well as skull base chordomas. Poorly differentiated chordomas show a loss of the gene INI-1. Dedifferentiated chordomas typically are the fastest growing and most aggressive chordomas and can also have a loss of INI-1 and are more common in pediatric patients. Chondroid chordoma describes chordomas that are difficult to distinguish from chondrosarcoma on histology. Typically chordomas express the gene bruchyury whereas chondrosarcomas do not express the bruchyury gene.

Chordomas have been reported to dedifferentiate into high-grade spindle cell tumors which portend a worse prognosis.


  • Image 5552 Not availableImage 5552 Not available
    Contributed by Steven Tenny, MD, MPH, MBA and Christopher Gillis, MD.
Attributed To: Contributed by Steven Tenny, MD, MPH, MBA and Christopher Gillis, MD.

Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE courses, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Chordoma - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following immunohistochemical stains are associated with chordoma?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Where are chordomas most commonly found?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Where are chordomas most commonly found?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the optimal treatment for a chordoma?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 47-year-old male presents with six months of increasing dull ache in his neck and right shoulder. He has no neurologic deficits. Workup reveals a mass of the C2 vertebra which is biopsied and reported as chordoma. Which of the following is the best imaging for pre-operative planning?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 59-year-old male has two months of worsening diplopia and a cranial nerve VI palsy on the right is identified. Imaging shows a clival mass which is heterogeneously enhancing on MRI T1 sequencing and hypodense on T1-weighted images without contrast. CT imaging shows a lytic lesion of the clivus with peripheral sclerosis and local invasion and contrast enhancement. Based on the possible differential diagnoses for a clival tumor which of the following is an important consideration prior to biopsy?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
The embryologic progenitor cell of a chordoma turns into what adult structure?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 42-year-old female presented with dysphagia. A lytic and exophytic tumor centered in the body of the second cervical vertebra was found on imaging. A needle biopsy demonstrated bubbly cells separated into lobules with fibrous septa and a myxoid stroma. Which of the following stains is expected to be positive in this tumor?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A 48-year-old male presented to an outside hospital with worsening back pain and urinary dribbling. Imaging demonstrated a large, heterogeneously enhancing sacral mass with lytic bone destruction and exophytic growth anteriorly. The outside hospital diagnosed a sacral chordoma based on a CT needle biopsy and referred the patient to you for treatment. What is an important concern for this patient during surgical planning?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Chordoma - References

References

Characteristics and Patterns of Metastatic Disease from Chordoma., Young VA,Curtis KM,Temple HT,Eismont FJ,DeLaney TF,Hornicek FJ,, Sarcoma, 2015     [PubMed]
Chordoma: The Quest for Better Treatment Options., Heery CR,, Oncology and therapy, 2016     [PubMed]
The molecular aspects of chordoma., Gulluoglu S,Turksoy O,Kuskucu A,Ture U,Bayrak OF,, Neurosurgical review, 2016 Apr     [PubMed]
Chordomas: A Review., George B,Bresson D,Herman P,Froelich S,, Neurosurgery clinics of North America, 2015 Jul     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of NP-Orthopedic. The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for NP-Orthopedic, it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in NP-Orthopedic, you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of NP-Orthopedic. When it is time for the NP-Orthopedic board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study NP-Orthopedic.