Chordoma

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms and keywords: Notochordoma; chordocarcinoma; chordoepithelioma

Overview

Chordoma is a rare bone cancer that is diagnosed in only about 300 patients in the U.S. each year. Chordoma accounts for 1% of intracranial tumors and 4% of all primary bone tumors. It develops at the base of the skull, in a vertebra, or at end of the spine (in the sacrum or the coccyx) with about equal frequency. The cells that give rise to chordoma come from the notochord. The notochord is an important structure in the early embryo that disappears before birth. However, even after birth, some cells from the notochord remain in bones at the base of the skull, in vertebrae, and in the tail bone. Rarely, one of these cells, which are called notochord remnants, undergoes changes that give rise to a chordoma. They originate from embryonic remnants of the primitive notochord (earliest fetal axial skeleton, extending from the Rathke's pouch to the coccyx). Since chordomas arise in bone, they are usually extradural and result in local bone destruction.

Pathophysiology

Gross Pathology

• Fluid and gelatinous mucoid substance (associated with recent and old haemorrhage) and necrotic areas are found within the tumor.
• In some patients, calcification and sequestered bone fragments are found as well.

Microscopic Pathology

• Photomicrograph demonstrating the typical chordoma cells with large, pleomorphic nuclei and vacuolated cytoplasm (hematoxylin and eosin stain) forming sheets or lobular structures that are embedded in a mucoid stroma.
• Ultrastructural studies have indicated that the vacuoles can be divided into two subtypes, smooth-walled and villous, based upon the absence or presence of microvilli, respectively.
• Characteristic of chordomas chondroids are the formation of lobules of neoplastic tissue separated by fibrous stroma and areas of chondroid tissue and vacuolated cell and lymphocytic infiltration.
• The tumor displays remarkable morphological variation, mainly based on the amount of interstitial matrix and vacuolated cells; these physaliphorous cells (arrow) with multivacuolated cytoplasm and sometimes pleomorphic nuclei are surrounded by mucinous extracellular matrix, some with chondroid aspect. Physaliphorous comes from the Greek word physalis (bubble).
• PAS stain: the cytoplasm of many tumor cells is strongly PAS positive (arrows), highlighting them against mucoid matrix. The vacuoles, however, are usually negative. To define the nature of PAS positive material (glycogen), the technique was repeated in cuts, one of which was previously handled by diastase. (c) Neoplastic physaliphorous cells with arrows.
• AE1/AE3: antibodies against keratins clearly show the ratio of neoplastic cells (dark brown) and interstitial tissue (in blue). The lobules of tumor tissue stand out, surrounded by strands of fibrous tissue.

Classification

Chordomas are classified on the basis of their location along the spine. Depending on their location, chordomas are predominantly subdivided into clival (or skull-base), sacrococcygeal, cervical, thoracic, and lumbar. Chordomas are relatively evenly distributed among three locations:

Sacrococcygeal: 30-50%

Spheno-occipital: 30-35%

Vertebral body: 15-30%

Sacrococcygeal

This is the most common location, accounting for approximately 30-50% of all chordomas and involving particularly the fourth and fifth sacral segments. In this location a male predilection has been reported (M:F ratio of 2:1) and the tumor may be particularly large at presentation. Chordoma is the most common primary malignant sacral tumor.

Spheno-occipital

The clival region is the next most common, accounting for 30-35% 2-3 of cases. Typically the mass projects in the midline posteriorly indenting the pons. This characteristic appearance has been termed the 'thumb sign". In contrast to sacrococcygeal tumours, there is currently no recognised gender difference.

Vertebral bodies

Chordomas of the vertebral bodies are rare but after lymphoproliferative tumours are nonetheless the most common primary malignancy of the spine in adults. They most commonly involve the cervical spine (particularly C2), followed by the lumbar spine then the thoracic spine. They often extend across the intervertebral disc space, involving more than one vertebral segment. They may extend into the epidural space, compressing the spinal cord, or along the nerve roots, enlarging the neural exit foramen.

Differential Diagnosis

For clival/spheno-occipitial lesions differentials to consider include: Chondrosarcoma of skull base Plasmacytoma Meningioma of skull base Pituitary macroadenoma Ecchordosis physaliphora

For vertebral lesions, consider: Chondrosarcoma ◦neural arch > vertebral body Thoracic spine is the most commonly involved spinal region Chondroid matrix (rings & arcs) Similar MRI appearance to chordomas (low to intermediate signal intensity on T1, hyperintense on T2, enhances)

• Giant cell tumour
  • F>M
  • Location: sacrum > thoracic spine > cervical spine > lumbar spine
  • No mineralised matrix
  • Heterogeneous intermediate to hyperintense T2 signal

• Spinal metastases
  • Hypointense on T1; variably hyperintense on T2
• Often multiple, involving vertebral bodies and posterior elements

• Plasmacytoma
  • Destructive vertebral body lesion (similar appearance to lytic metastases)

Spinal lymphoma

• Multifocal disease
• Heterogenous T2 signal

Epidemiology

Chordomas are rare neoplasms, occurring with an annual age-adjusted incidence of 0.02 per 100,000 person-years, and account for 1%–4% of all primary malignant bone tumors.

• Chordomas occur at any age but are usually seen in adults (30-70 years).
• Those located in the spheno-occipital region most commonly occur in patients 20-40 years of age.
• Sacrococcygeal chordomas are typically seen in a slightly older age group (peak around 50 years).
• The median age at presentation for cranial chordomas is in the sixth decade, slightly younger for sacral chordomas, and with rare occurrences in the pediatric population.
• They are commonly found in Caucasians.

Prognosis

• Prognosis is typically poor, due to the locally aggressive nature of these tumors, with the 10-year survival approximately 40%.
• The median survival of cranial base chordomas is estimated at 6.29 years, with 5-year overall survival and progression-free survival rates of 78.4% and 50.8%, respectively.
• The lethality of skull-base chordoma is largely due to local progression, although systemic metastasis has been reported in 12.5% of skull base/craniocervical tumors.

Complications

• Chordoma does not usually spread to other bones but can recur after treatment.
• Metastatic spread of chordoma is observed in 7-14% of patients and includes nodal, pulmonary, bone, cerebral or abdominal visceral involvement, predominantly from massive tumors.
• Incomplete delineation of the tumor and microscopic distal extension of tumor cells may explain the frequency of recurrences.

Diagnosis

CT

Findings on CT scan suggestive of chordoma include:

• Centrally located well-circumscribed destructive lytic lesion
• Marginal sclerosis
• Expansile soft-tissue mass (usually hyper-attenuating relative to the adjacent brain; however, inhomogenous areas may be seen due to cystic necrosis or hemorrhage; the soft-tissue mass is often disproportionately large relative to the bony destruction)
• Irregular intratumoral calcifications (thought to represent sequestra of normal bone rather than dystrophic calcifications)
• Moderate to marked enhancement

MRI

T1: Intermediate to low signal intensity small foci of hyperintensity (intratumoral haemorrhage or a mucus pool)

T2: most exhibit very high signal

T1 C+ (Gd): heterogeneous enhancement with a honeycomb appearance corresponding to low T1 signal areas within the tumour GE (gradient echo): confirms haemorrhage if present with blooming.

Treatment

• Traditionally surgical resection has been the first line of treatment in feasible scenarios, with radiotherapy offered for recurrent cases.
• The principal goals of surgery beyond histologic confirmation of the lesion are to achieve a maximal safe resection, provide symptomatic improvement, and to facilitate adjuvant treatment, such as radiotherapy, by minimizing the treatment volume and maximizing the distance between the target volume and critical surrounding neurovascular structures.
• Some advocate the combination of radiation therapy and complete or subtotal surgical resection for selected patients.
• Percutaneous radiofrequency ablation has been trialled as an adjunct.
• Recurrence, including seeding along the operative tract, is common.

References

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