Chordoma

Updated by Vincent J. Lee and Michelle Alonso-Basanta

BACKGROUND

What are chordomas?

Chordomas are rare, slow-growing, locally aggressive neoplasms of bone arising from embryonic remnants of the notochord.

Where do chordomas most commonly arise?

Chordomas most commonly arise in 3 locations in the axial skeleton:

1. Sacrococcygeal region (50%)

2. Spheno-occipital region of the skull base (35%)

3. Vertebral column (15%)

In craniocervical chordomas, the most common sites are the dorsum sellae, clivus, and nasopharynx.

What is the DDx of a tumor involving sacral bone?

Metastatic lesions and multiple myeloma make up the overwhelming majority of sacral and spinal neoplasms. Chordomas are the most frequently occurring primary malignant bone tumor in both the sacrum and the mobile spine. Other primary sacral tumors include chondrosarcoma, Ewing sarcoma, osteosarcoma, PNET, Paget sarcoma, and benign tumors including giant cell tumor and hemangioma.

What are the most common histologic subtypes seen for chordomas?

Most common histologic subtypes of chordoma:

1. Conventional: most common, no cartilaginous or mesenchymal components

2. Chondroid: 5%–15%, contains cartilaginous components but is distinct from chondrosarcoma

3. Dedifferentiated or sarcomatous transformation: 2%–8%, aneuploid tumors interspersed in areas of conventional chordomas, worse survival

What features characterize conventional chordomas?

Gelatinous, pink or gray masses with solid or cystic areas. Microscopically, characteristic physaliphorous cells are present.

What histologic types of chordomas are most commonly found in the skull base?

Conventional is still the most common, although the chondroid type has a predilection for the cranial region (one-third of cranial chordomas are chondroid).

What are the immunohistochemical findings that can help distinguish chordomas from other histologically similar lesions?

S-100 immunoreactivity distinguishes chordoma from metastatic adenocarcinoma and meningioma, and epithelial membrane antigen immunoreactivity distinguishes it from chondroma, chondrosarcoma, and melanoma.

What is the rate of distant metastases for chordoma, and what distant sites can be involved?

Distant metastases have been found in up to 5% of pts at the time of diagnosis. Site of metastasis include lungs, soft tissues, bone, and skin.

WORKUP/STAGING

How do pts with chordomas present clinically?

Depends on the site of origin, but pain of a gradual and insidious onset is reported to be the most common presenting symptom regardless of location. Chordomas encroaching on the spinal canal may cause compression of the spinal cord or nerve roots, resulting in neurologic symptoms. Chordomas involving the cervical region may cause dysphagia, dysphonia, or Horner syndrome. Chordomas in the sacral region can create nerve root dysfunction as well as obstipation, constipation, and tenesmus. Pts with base of skull chordomas present with intermittent diplopia, HA, neck pain, or other lower CN findings. Invasion of the cavernous sinus produces diplopia and facial numbness.

Is transrectal biopsy a recommended method to obtain tissue diagnosis for chordoma?

No. Due to a propensity to seed along biopsy tracts, transrectal biopsies should be avoided so as to prevent spread of chordoma into the rectum. All biopsy tracts should be marked and removed in subsequent surgery.

What comprises oncologic staging for chordoma?

A complete workup, advanced imaging (MRI/CT), lab studies, and biopsy.

What are the T1-T2 MRI features of chordomas?

T1-T2 MRI features of chordomas:

T1: intermediate to low signal intensity, with marked but heterogeneous enhancement with gadolinium

T2: very high signal intensity

What staging system is used for chordomas?

Per the AJCC (2011), chordoma is staged as a primary bone tumor.

TREATMENT/PROGNOSIS

What is the mainstay of Tx for chordomas?

Surgery is the mainstay of Tx of chordomas, with studies demonstrating a direct correlation between the extent of surgical resection and the length of RFS.

Why is intralesional excision for a vertebral body chordoma a suboptimal surgical treatment?

Intralesional excision has been shown to have a high rate of local recurrence and to negatively affect overall survival. En bloc spondylectomy is preferred.

How are sacral amputations classified?

Based on the location of the highest level of nerve root sacrificed: low (sacrifice of at least 1 S4 nerve root or below), middle (sacrifice of at least 1 S3 nerve root), or high (at least 1 S2 nerve root). Total sacrectomy is performed when both S1 nerve roots are sacrificed.

What Tx is most commonly employed after surgical resection?

Because most chordomas are not fully resectable, postop radiotherapy is often employed.

Is aggressive management of chordomas at initial presentation (surgery + adj RT) important to improve outcomes compared to the same Tx at the time of recurrence (salvage RT)?

Yes. Adj RT may improve outcomes compared to a strategy of observation, reserving RT for salvage.

A retrospective series from France (Carpentier A et al., J Neurosurg 2002) found that pts managed aggressively at initial presentation (surgery + RT) compared to those treated aggressively at the time of recurrence (after initial surgery) had improved outcomes (5- and 10-yr survival: 80% and 65% for aggressive vs. 50% and 0% for salvage). A prospective phase II trial incorporating high dose RT given pre- and/or post-operatively reported an 11% local recurrence rate for primary chordomas; findings favored a dose of ~77.4 Gy RBE for primary tumors, and ~70 Gy in the adjuvant setting. (Delaney TF et al., J Surg Oncol 2014).

Is conventional fractionated RT an effective Tx for chordomas?

Yes. Conventional fractionated RT is effective for palliating chordomas. Retrospective series of skull base chordomas demonstrated that with 50 Gy (photons only), 85% of pts achieved useful and prolonged pain palliation. However, LC was ∼27%, 5-yr PFS was ∼23%, and MS was ∼62 mos (Catton C et al., Radiother Oncol 1996).

What is the role of SRS in the management of chordomas?

There is growing evidence supporting the role of SRS for chordoma. A MSKCC series that included unresectable pts reported a 95% LC rate at a median follow-up of 24 mos with single fraction SRS with a median dose of 24 Gy. (Yamada Y et al., Neurosurg 2013)

What other RT modalities can be utilized for skull base chordomas?

Multiple series have reported 5-yr PFS of 59%–73% and 5-yr OS of 79%–80.5% for proton beam therapy, with comparable rates for charged ion therapy. Stereotactic radiosurgery has also been reported to provide improvement in presenting cranial neuropathy; tumor control rates have not yet been defined. (Muro S et al., Exp Rev Neurother 2007)

What factor determines the risk for recurrence after Tx with proton beam therapy?

The volume of residual Dz after surgical resection determines the risk of recurrence after Tx with proton beam therapy.

In a series from Loma Linda, for residual tumors abutting the brainstem or >25 cc, the control rate was about 50% in the follow-up period (mean, 33 mos); those not abutting the brainstem or <25 cc residual Dz did not have recurrence. (Hug EB et al., J Neurosurg 1999)

What is the pattern of recurrence of chordomas after Tx?

LR is most common (95%), while up to 40% of pts will have both LR and distant metastases. The most common sites of distant Dz are lung and bone. (Fagundes MA et al., IJROBP 1995; McPherson CM et al., J Neurosurg Spine 2006)

What is the typical LC and OS for chordomas compared to chondrosarcomas after 70 CGE of proton beam therapy?

In the Loma Linda series of 58 pts (33 chordomas and 25 chondrosarcomas), with a mean follow-up of 33 mos, LC was 76% for chordoma and 92% for chondrosarcoma. The 5-yr OS rates were 79% for chordoma and 100% for chondrosarcoma. (Hug EB et al., J Neurosurg 1999)

What is the role of chemo or molecularly targeted agents in the management of chordomas?

In chordomas, cytotoxic chemo has not shown clinically significant activity. However, chordomas have been found to overexpress PDGFR-β, and clinical series have reported imatinib to provide symptomatic improvement and stabilization of Dz in some pts.

What is the survival of pts with recurrent Dz who received salvage Tx compared to supportive care?

The outcomes after recurrence are generally poor, but salvage Tx (surgery + RT) can be used after recurrence, with 2-yr survival of 63% vs. 21% with supportive care. However, most pts die even with therapy, with 5-yr survival only 6% after recurrence. (Fagundes MA et al., IJROBP 1995).

Salvage RT alone is associated with a 2-yr actuarial LC rate of 33%. (Berson AM et al., IJROBP 1988)

What are 5 poor prognostic factors for chordomas?

Poor prognostic factors for chordoma:

1. Recurrent Dz

2. Base of skull tumors

3. Female sex

4. Presence of tumor necrosis in pre-Tx Bx

5. Large tumors (>70 cc)

TOXICITY

What are some common late toxicities that manifest after the Tx of skull base chordomas?

∼26% of skull base chordoma pts develop endocrine abnormalities, while 5%–10% of pts develop vision loss, brainstem injury, or temporal lobe injury in 2–5 yrs. (Berson AM et al., IJROBP 1988; Santoni R et al., IJROBP 1998). The risk for sacral neuropathy increases with doses >77 Gy (Delaney TF et al., J Surg Oncol 2014).

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