Chordoma Workup

No laboratory studies are required for the evaluation of chordomas, except as needed for routine preoperative evaluation in patients scheduled to undergo surgical resection.

• CT scan or MRI studies are indicated to evaluate the extent of the tumor and to identify the tissues that the chordoma has infiltrated. Knowledge of the extent of the tumor is important in planning the optimal surgical approach.

  • With CT scans, chordomas at any site appear as single or multiple areas of decreased attenuation within the clivus, vertebrae, or sacrum. Fingers of low density radiate throughout the mass and into the adjacent tissues. If the chordoma has a significant chondroid component, focal regions of hyperdensity may be present. The lesions are expansile with destructive or lytic lesions in the bone.
  • On MRI, the appearance of a chordoma is similar to the appearance on CT scan, with better resolution of the soft-tissue component, resulting in better anatomical definition, as depicted in the image below. Chordomas are hyperintense on T2 images and hypointense on T1 images. This pelvic CT scan shows a large presacral mass eroding bone.
• Plain radiographs may be useful to demonstrate the amount of bone involvement.

  • Plain-film radiographs may show an ill-defined endosteal margin or a bulky mass in the soft tissue. The lesions also may be lytic.
  • In general, and especially in clival chordomas, erosion of the bone, particularly the tip of the clivus, and a sclerotic bone reaction are seen radiographically. The mass appears as a destructive well-demarcated lesion. The discovery of these features can better clarify the diagnosis of chordomas in the differential of bony lesions.

No other tests are required in the evaluation of chordomas.

• As described above, imaging techniques of the clivus usually demonstrate features adequate for differentiating chordomas from other site-specific lesions. In the sacrum, radiographic features are more similar to other common bone tumors and while they may be suggestive of a chordoma, they are not diagnostic.
• Biopsies of chordomas are useful only when other bone lesions remain in the differential diagnosis after imaging studies are performed. In this instance, tissue diagnosis by biopsy can enable optimal planning for surgical resection of the tumor. Fine needle aspiration (FNA) is the preferred method for establishing the preoperative morphologic diagnosis of chordoma and has been reported to lower local recurrence rates when compared with open biopsy.^[6] The diagnostic criteria for chordoma in FNA include the presence of physaliphorous cells with round nuclei, bland chromatin and distinct cytoplasmic borders in a background of abundant myxoid ground substance.
• Surgical resection remains the primary mode of treatment for both diagnostic and therapeutic purposes. The prognosis of chordomas generally depends on the extent and completeness of the tumor excision.

Chordomas are divided into conventional, chondroid, and dedifferentiated types.

Microscopically, conventional chordomas are composed of uniform cells with small oval or round eccentric nuclei and dense chromatin. The hallmark microscopic features of chordomas are the numerous, variably sized vacuoles located in the tumor cell cytoplasm, the physaliphorous cells, as depicted in the images below. Some tumor cells may have more solid or eosinophilic cytoplasm.

Various histologic growth patterns can be seen in chordomas. The cells may be arranged in a diffuse or lobular pattern, or they may be clustered in groups or islands in a sheetlike pattern. Areas of tumor cells may be seen in a solid, perivascular, or even ribbonlike pattern. Between the cells or clusters, an abundant basophilic-to-metachromatic mucinous matrix exists. Mitoses, foci of pleomorphic cells, or focal hemorrhage rarely can be seen but are not prominent features.

Fibrous tissue surrounds the neoplasm and extends projections into the tumor, usually without forming a true capsule.

The chondroid variant of chordoma is well recognized. In these tumors, a significant cartilaginous component is present with features of either chondrosarcoma or chondroma. Some authors believe these entities are separate and that studies with both immunoperoxidase staining and electron microscopy can distinguish them. Also, patients with this variant were once thought to have a slightly better prognosis; however, recent large studies have shown this variant to be of no prognostic significance.

The dedifferentiated variant of chordoma is rare, comprising 2-8% of chordomas. These can occur de novo, or as a sarcomatoid transformation in recurrences of conventional chordoma, sometimes following radiation therapy.^{[7, 8]}

With specialized histochemistry, chordoma tumor cells tend to be periodic acid-Schiff (PAS) positive. The matrix stains diffusely with mucicarmine and Alcian blue, and it stains metachromatically with toluidine blue; it is negative with Sudan black.

In electron microscopy, ultrastructural features in chordomas include desmosomal attachments and prominent mucinous vacuoles.

Immunohistochemically, the tumor cells label with cytokeratins and epithelial membrane antigen (EMA). Both chordomas and the embryologic notochord are S-100 positive, whereas most carcinomas are negative. This difference in S-100 positivity can be helpful in the differentiation of metastatic carcinomas from chordomas in instances where the histologic pattern is similar. Positivity for cytokeratins and EMA can be helpful in distinguishing the chondroid variant of chordoma from chondrosarcoma.

More recently, immunohistochemical and gene microarray studies have revealed the presence of high levels of brachyury in axial chordomas. Brachyury is a key transcription factor in the development of posterior mesoderm which becomes restricted to the notochord and tailbud. Although the classic marker, cytokeratin, remains the single best diagnostic marker for chordoma, the addition of brachyury to the diagnostic panel slightly improves accuracy.{Ref27}

The role of MIB-1 immunohistochemical staining (a proliferation marker) as a prognostic indicator in chordomas is controversial, but data suggest that an increased MIB-1 labeling index correlates with recurrence.

Recent investigations have looked at cell cycle alterations and the role of the p53 tumor suppressor gene in chordoma tumorigenesis. Early data suggest that p53 overexpression characterized by increased immunohistochemical staining for p53 protein is associated with a poor prognosis in patients with chordoma.^[9]

Chordomas, like other bone tumors, have been subject to staging methods. Studies analyzing the prognosis and outcome in comparison to stage have not proven to be very useful. As discussed above, the local extent and degree of resection are much more important to the prognosis of a chordoma (see Problem).