Chordoma in Orthopedic Surgery 

Updated: Mar 11, 2019
Author: Nagarjun Rao, MD, FRCPath; Chief Editor: Jeffrey A Goldstein, MD 

Overview

Background

Chordoma is a relatively rare malignant midline tumor that arises in the axial skeleton, primarily at its cranial and caudal ends; it is derived from persistent embryonic notochordal cell rests.[1, 2, 3]

The notochord is derived from the primitive ectoderm and defines the midline of the chordate embryos. As the human fetus grows, the notochord expands at the site of the future intervertebral disks and forms the nucleus pulposus. The notochord regresses to leave an acellular sheath, except at its cephalic and caudal ends, where cell rests persist. Although this explains the observed distribution of chordomas (sphenoccipital and sacrococcygeal), it does not explain why the cell rests should transform into tumors.

A resemblance exists between notochordal and chordoma cells morphologically and immunohistochemically (positivity for S-100 protein, cytokeratin [CK], and epithelial membrane antigen [EMA]).[4, 5, 6]

Chordomas have been divided into the following three subtypes:

  • Conventional
  • Chondroid
  • Dedifferentiated

Epidemiology

Chordomas can affect individuals of any age, including young children, but are most often diagnosed in individuals between the ages of 40 and 75 years (average age at diagnosis, 55 years). Chordoma is diagnosed in just one person per million per year. Thus, about 300 patients are diagnosed with chordoma each year in the United States and about 700 in all of Europe. At any given time, fewer than one in 100,000 people are living with chordoma.[7, 8]

Chordomas affect males more often than females, by a ratio of approximately 2:1; however, skull-base tumors have an equal (1:1) gender distribution. Children are more likely to have skull-base tumors, whereas spinal chordomas are more common in older individuals. Chordomas account for approximately 1-4% of all malignant bone tumors and 20% of primary tumors of the spinal column. Some reports state that these tumors are more common in individuals of European ancestry.[7, 8]

Prognosis

The 5-year and 10-year survival rates for conventional chordoma are approximately 50% and 25-30%, respectively. Conversely, chondroid chordoma has 5-year and 10-year survival rates of approximately 80%. Survival rates appear to be influenced more by local tumor progression than by metastasis.[9, 10]  A higher survival rate is associated with Hispanic race, smaller tumor size, and surgical intervention.

All three types of chordomas can metastasize, usually later in the course of the disease (except dedifferentiated chordomas, which can metastasize early). The usual metastatic sites are skin, bone, lung, and lymph nodes. Accurate prediction of metastatic potential is not possible, though certain clinical (local aggressiveness) and pathologic (anaplastic histology) features may be indicative. Vertebral body chordomas have a higher incidence of metastasis than do those arising in the clivus or sacrum.[11]

Some data suggest that female sex, tumor necrosis, and tumor volume of more than 70 mL are independent poor prognostic variables in skull-base chordomas. The difference in survival rate between the sexes suggests that hormone receptor status and hormone manipulation management may be areas for future investigation.[12]

 

Presentation

History and Physical Examination

Chordomas present clinically as destructive bony masses with soft-tissue involvement. They erode and impinge upon adjacent structures, giving rise to a wide variety of clinical symptoms.

In the cranial region, these lesions can cause cranial nerve palsies, hydrocephalus, and torticollis (reported in an infant).[13]  The sacral lesions can remain asymptomatic for a long time and/or present with a variety of nonspecific symptoms. These symptoms may involve back pain, changes in bowel habits, or a feeling of fullness in the rectal area. Physical examination must include a rectal examination to exclude a presacral mass.[14]

In children, the tumor may be more aggressive, with a variable histologic picture.

 

DDx

Diagnostic Considerations

Chondrosarcoma

Conventional chondrosarcoma is an important differential diagnostic consideration for skull-base chordoma, especially chondroid chordoma. The location, which usually is off of the midline, and the immunohistochemical features (see Histologic Findings) can help distinguish between the two lesions.[5]

Myxoid chondrosarcoma

These lesions are likely to be confused with chordoma based on pathology. The histology of this lesion closely simulates that of chordoma. However, characteristic physaliphorous cells are not observed. Immunohistochemically, the cells are positive for S-100 and negative for cytokeratin (CK) and epithelial membrane antigen (EMA). Clinically, these lesions arise in the extremities (mostly in soft tissue) and rarely involve the axial skeleton.

Metastatic adenocarcinoma

If a chordoma contains large numbers of cells with cytoplasmic vacuoles, it may be confused with metastatic adenocarcinoma.[15]  However, metastatic adenocarcinoma usually lacks physaliphorous cells, and the extracellular mucin is of the neutral epithelial type, compared with the hyaluronidase-resistant sulfated mucopolysaccharide stroma of chordoma.

Myxoid liposarcoma

These tumors possess vacuolated lipoblasts, which may be mistaken for physaliphorous cells. However, they lack the lobular architecture and evenly distributed physaliphorous cells of chordoma. Further, the myxoid stroma in this tumor is hyaluronidase-sensitive nonsulfated mucopolysaccharide. Although both tumors are S-100 positive, myxoid liposarcoma lacks epithelial markers EMA and CK.

Polyvinylpyrrolidone granuloma

Polyvinylpyrrolidone is a high-molecular-weight hydrophilic substance that generally is used as a plasma substitute. Its high molecular weight prevents renal excretion and promotes accumulation within histiocytes, usually at injection sites within soft tissue. The histology of such soft-tissue mass lesions can resemble chordoma, as the bubbly, polyvinylpyrrolidone-laden histiocytes can simulate physaliphorous cells. They stain strongly with a variety of stains, such as Sudan black B and Congo red. The stroma usually lacks the myxoid character of chordoma. Location and the association with injection sites can help distinguish the lesions clinically.

Spinal tumors

Spinal tumors should also be taken into account in the differential diagnosis.

 

Workup

Laboratory Studies

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

Imaging Studies

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, 16]

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.

MRI scan demonstrates an osteolytic lesion involvi MRI scan demonstrates an osteolytic lesion involving the vertebral body. This lesion occurred in the mobile vertebral column.

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.[16]

Biopsy

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.[17]

With FNAB, adequacy of material can be ascertained rapidly on site.[17]  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.

Histologic 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).

Histologic section demonstrating lobular arrangeme Histologic section demonstrating lobular arrangement of tumor cells surrounded by fibrous connective tissue septa. Cellularity is variable with cells present in a pale myxoid matrix.

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.[18]

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, although 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.[19, 20, 21]

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.

S-100 immunostain of physaliphorous cells demonstr S-100 immunostain of physaliphorous cells demonstrating strong nuclear staining.

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.[19, 20, 21, 22]

Cytology

With the advent and development of FNAB cytology, FNAB is becoming 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.[17]

Cytologic preparation demonstrating characteristic Cytologic preparation demonstrating characteristic physaliphorous cells with bubbly cytoplasm at higher magnification.
Cytologic preparation demonstrating a sheet of low Cytologic preparation demonstrating a sheet of low-grade polygonal large cells in a background of pale myxoid matrix.

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.

Staging

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,[23]  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
 

Treatment

Approach Considerations

Treatment options include the following:

  • Low-dose [24] or high-voltage radiation therapy
  • Combined radiation and surgery
  • Surgical excision alone [25]

It is generally accepted that complete surgical excision of the tumor is the only curative procedure. Because of local invasion, many tumors (especially skull-base chordomas) may not be amenable to complete surgical excision, and the local recurrence rate is high.[26, 27, 28, 29, 30, 31]

 

Surgical Care

Tumors detected and diagnosed early have a favorable prognosis if treated with a complete or en-bloc excision.[32]  A complete excision may involve a combined anterior-posterior operation, with anterior vertebrectomy, strut grafting, and possible stabilization with instrumentation. This is followed by a posterior decompression that also removes the pedicles and by stabilization of the spine with instrumentation above and below the excised levels.

Extension of the tumor beyond the confines of the vertebral body decreases the chances of a complete cure. Resection of the psoas muscle and sacrifice of lumbar or sacral nerve roots may be necessary. Preservation of both S3 nerve roots is required if normal bladder and bowel function are to be expected postoperatively. In these cases, surgical margin decisions are made on an individual basis. If complete resection of the tumor cannot be carried out and residual tumor is present either in bone or soft tissue, postoperative megavoltage radiation therapy is indicated.

The local recurrence rate is affected by tumor contamination of the surgical wound.[33]  In one study, the recurrence rate was 64% when contamination was present and 28% when no contamination was present.[34]