Chordoma in Orthopedic Surgery Workup

No specific blood tests exist for the diagnosis of chordoma. Routine investigations may be ordered in the workup, as indicated.

The so-called systemic inflammation score (SIS), which is based on preoperative lymphocyte-to-monocyte ratio and albumin has been suggested as a potential prognostic indicator for chordoma. A study by Li et al found that a high SIS was associated with poorer overall survival in patients with skull-base chordoma. ^[16]

Plain radiography

Sacrococcygeal chordomas present as midline lobular or geographic areas of radiolucency, occasionally expansile with an osteosclerotic rim. Skull-base chordomas present as radiolucent areas destroying the clivus and parasellar parts of the middle cranial fossa. ^[10]

Computed tomography

In addition to radiolucent foci, chordomas have an expansile concomitant soft-tissue mass, which is best visualized on computed tomography (CT). The soft-tissue masses frequently are calcified (50-70% of skull-base chordomas). They can protrude to present as nasopharyngeal masses (one third of cranial chordomas) or can compress the intestines and urinary bladder (sacrococcygeal chordomas). ^{[10, 17]}

Magnetic resonance imaging

Magnetic resonance imaging (MRI) provides better delineation of the full extent of tumor by virtue of its excellent contrast resolution capabilities (see the image below). MRI also provides a better estimate of tumor volume than CT does. Both CT and MRI are vital for preoperative planning and staging of the disease.

Bone scanning

Technetium-99m (^99mTc) bone scans demonstrate hot areas within the tumor. In the rare cases of chordoma observed in the mobile vertebral column (cervical, thoracic, lumbar), evidence of bony destruction and vertebral collapse is present. Frequently, two or more vertebrae are involved, showing destructive changes with a sclerotic rim. A paraspinal soft-tissue mass with calcification may be present. ^[17]

A fine-needle aspiration biopsy (FNAB) or Tru-Cut needle biopsy may be obtained for diagnostic purposes. Both biopsies may require radiologic guidance, especially with skull-base tumors. With both types of biopsies, additional material should be obtained for ancillary studies. ^[18]

With FNAB, adequacy of material can be ascertained rapidly on site. ^[18]  If indicated, during Tru-Cut needle biopsy, intraoperative cytology or a frozen section can be performed to determine whether appropriate tissue has been obtained. A definitive diagnosis usually is delayed until permanent analysis.

Careful preoperative planning is required before the biopsy is attempted. The biopsy should be the final diagnostic or staging procedure because it can distort findings from imaging studies, particularly MRI findings.

Histopathology

On the basis of light microscopic morphology, chordomas are classified as conventional, chondroid, or dedifferentiated.

Conventional chordomas

These are the most common type, are slow-growing, and account for 1-4% of all malignant bone tumors. Grossly, conventional chordomas have a soft, tan, myxoid appearance with areas of hemorrhage. Microscopically, characteristic physaliphorous (ie, containing bubbles or vacuoles, from Greek physalis ["bubble"] and -phoros ["bearing"]) cells are present, which are large with vacuolated cytoplasm. These cells are arranged in nests, cords, or sheets in a background of myxoid stroma (see the image below).

Physaliphorous cells contain glycogen and mucin. Rarely, they can have a signet-ring appearance, with the cytoplasmic vacuole pushing the nucleus to the periphery. A second population of spindled stellate cells with no cytoplasmic mucin is also present. These are believed to be precursor cells. The myxoid stroma contains hyaluronidase-resistant sulfated mucopolysaccharides.

Chondroid chondromas

These are observed predominantly in the sphenoccipital location. They are slower growing than conventional chordomas and exhibit foci of chondroid (cartilaginous) differentiation adjacent to areas of conventional chordoma. In the chondroid areas, physaliphorous cells lie within lacunae surrounded by cartilaginous stroma. The tumors share ultrastructural features with chordoma, as well as cartilaginous tumors.

Some controversy exists regarding the histogenesis of these tumors. In a comparative light microscopic and immunohistochemical study of chordoma, chondroid chordoma, and chondrosarcoma involving the skull base, the immunohistochemical profile of chondrosarcoma was found to be different from that of the other two tumors (negative for cytokeratin [CK], epithelial membrane antigen [EMA], and carcinoembryonic antigen [CEA]). The authors concluded that chondroid chordoma is a variant of chordoma. Some authors have suggested using the term hyalinized chordoma to describe it, so as to clarify its histogenesis and avoid confusion with chondrosarcoma. ^[19]

Dedifferentiated chondromas

These are rapidly growing tumors with a poor prognosis. The tumors are biphasic, with areas of high-grade sarcoma that coexist alongside conventional or chondroid chordoma. The sarcomatous areas most commonly resemble malignant fibrous histiocytoma, though elements resembling fibrosarcoma, osteosarcoma, and high-grade chondrosarcoma have been described. Most studies appear to suggest that they arise from sarcomatous transformation of chordoma, with some reporting their occurrence following postoperative radiotherapy for conventional chordoma. ^{[20, 21, 22]}

Immunohistochemically, physaliphorous cells in all types of chordoma are positive for S-100 protein (as depicted below), CK, and EMA. CEA also is positive in most cases.

In the anaplastic spindle cell areas of dedifferentiated chordoma, the epithelial markers CK and EMA usually are negative. In one report, although bordering areas between conventional and dedifferentiated chordoma exhibited EMA and CK positivity, EMA and CK were negative in the center of the sarcomatous areas. Vimentin and alpha1-antichymotrypsin were positive in these areas, which appears to support the pathogenesis of sarcomatous transformation from chordoma. ^{[20, 21, 22, 23]}

Cytology

With the advent and development of FNAB cytology, FNAB has become a widely accepted technique for rapid, accurate, and economical diagnosis of a wide variety of lesions. In a study correlating cytologic findings in chordoma with histologic and radiologic features, commonly observed cytologic features included typical physaliphorous cells (see the first image below) and a second population of round-to-polygonal nonvacuolated epithelioid cells. The background had a myxoid or mucinous appearance (see the second image below). In the dedifferentiated variety, physaliphorous cells were more pleomorphic, with nuclear inclusions, binucleation or multinucleation, and mitotic figures. ^[18]

Additional material should be obtained routinely for ancillary studies, especially immunocytochemistry. On FNAB cytology smears alone, chordoma has the potential to be confused with other conditions, such as metastatic adenocarcinoma. Depending on initial interpretation and differential diagnosis of FNAB cytology and core biopsy (frozen section), additional material can be obtained for other tests, such as electron microscopy and cytogenetic analysis.

Cytogenetics

No specific or characteristic anomalies are described in chordoma. However, cytogenetics is useful in distinguishing other lesions, such as myxoid chondrosarcoma [which has a specific t(9;22) translocation], from chordoma.

Careful staging is a prerequisite for appropriate management. Tumor extent and soft-tissue involvement are gauged by radiologic modalities. Biopsies are obtained to confirm the diagnosis. Plain radiography and CT of the chest can be performed to detect pulmonary metastases. Technetium bone scanning is useful for detecting bone metastases.

Staging of lesions is based on imaging results and histopathologic and cytopathologic studies. The American Joint Committee on Cancer staging system usually is employed, ^[24]  which includes the following components:

• Size and extension of primary tumor (T)
• Involvement of lymph nodes (N)
• Presence of metastases (M)
• Type and grade of sarcoma (G)

In the TNMG staging system, primary tumor size and extension (T) are classified as follows:

• T1 - Tumor smaller than 5 cm
• T2 - Tumor 5 cm or larger

Regional lymph node involvement (N) is classified as follows:

• N0 - No histologically verified regional node metastasis
• N1 - Histologically verified regional node metastasis

Presence of distant metastasis (M) is classified as follows:

• M0 - No distant metastasis
• M1 - Distant metastasis

Histologic grade of malignancy is classified as follows:

• G1 - Well differentiated
• G2 - Moderately differentiated
• G3 - Poorly differentiated
• G4 - Undifferentiated