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

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Media Gallery

MRI scan demonstrates an osteolytic lesion involving the vertebral body. This lesion occurred in the mobile vertebral column.
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.
S-100 immunostain of physaliphorous cells demonstrating strong nuclear staining.
Cytologic preparation demonstrating characteristic physaliphorous cells with bubbly cytoplasm at higher magnification.
Cytologic preparation demonstrating a sheet of low-grade polygonal large cells in a background of pale myxoid matrix.

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Author

Nagarjun Rao, MD, FRCPath Pathologist, Great Lakes Pathologists, Aurora Clinical Laboratories

Nagarjun Rao, MD, FRCPath is a member of the following medical societies: American Society for Clinical Pathology, United States and Canadian Academy of Pathology, College of American Pathologists, Royal College of Pathologists

Disclosure: Nothing to disclose.

Coauthor(s)

Vivek Panikkar, MBBS, MS, MCh, FRCS Consulting Surgeon, Departments of Trauma and Orthopedics, Doncaster Royal Infirmary, UK

Disclosure: Nothing to disclose.

Raj Rao, MD Professor of Orthopaedic Surgery and Neurosurgery, Department of Orthopedic Surgery, Medical College of Wisconsin

Raj Rao, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, North American Spine Society

Disclosure: Nothing to disclose.

Vinod B Shidham, MD, FRCPath Professor, Vice-Chair-AP, and Director of Cytopathology, Department of Pathology, Wayne State University School of Medicine, Karmanos Cancer Center and Detroit Medical Center; Co-Editor-in-Chief and Executive Editor, CytoJournal

Vinod B Shidham, MD, FRCPath is a member of the following medical societies: American Association for Cancer Research, American Society of Cytopathology, College of American Pathologists, International Academy of Cytology, Royal College of Pathologists, United States and Canadian Academy of Pathology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Jeffrey A Goldstein, MD Clinical Professor of Orthopedic Surgery, New York University School of Medicine; Director of Spine Service, Director of Spine Fellowship, Department of Orthopedic Surgery, NYU Hospital for Joint Diseases, NYU Langone Medical Center

Jeffrey A Goldstein, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Orthopaedic Association, AOSpine, Cervical Spine Research Society, International Society for the Advancement of Spine Surgery, International Society for the Study of the Lumbar Spine, Lumbar Spine Research Society, North American Spine Society, Scoliosis Research Society, Society of Lateral Access Surgery

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Medtronic, Nuvasive, NLT Spine, RTI, Magellan Health<br/>Received consulting fee from Medtronic for consulting; Received consulting fee from NuVasive for consulting; Received royalty from Nuvasive for consulting; Received consulting fee from K2M for consulting; Received ownership interest from NuVasive for none.

Additional Contributors

James F Kellam, MD, FRCSC, FACS, FRCS(Ire) Professor, Department of Orthopedic Surgery, University of Texas Medical School at Houston

James F Kellam, MD, FRCSC, FACS, FRCS(Ire) is a member of the following medical societies: American Academy of Orthopaedic Surgeons, Orthopaedic Trauma Association, Royal College of Physicians and Surgeons of Canada

Disclosure: Nothing to disclose.

William O Shaffer, MD Former Orthopedic Spine Surgeon, Northwest Iowa Bone, Joint, and Sports Surgeons

William O Shaffer, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Orthopaedic Association, International Society for the Study of the Lumbar Spine, Kentucky Medical Association, Kentucky Orthopaedic Society, North American Spine Society, Southern Medical Association, Southern Orthopaedic Association

Disclosure: Nothing to disclose.