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Case Presentation - Spring, 2012

Chordoma

Patient Age and History: Male, age 77

Specimen type: FNA- Left Presacral Mass

History: Hypercalcemia and involuntary weight loss, peripheral neuropathy. CT showed two indeterminate anterior sacrococcygeal masses, 3 cm and 2 cm. Recent colonoscopy showed a tubular adenoma of the right colon, but was otherwise within normal limits. No known cancer history.

Cytologic diagnosis: Malignant neoplastic cells present; cytologic features consistent with a chordoma. The tumor showed positivity for cytokeratin 5/6, cytokeratin 19 and epithelial membrane antigen. The tumor was negative for GFAP and S100.

Case provided by: Milstead Pathology, Conyers, Georgia

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ThinPrep® Cytology:

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Etiology:
While in the womb, a fetus initially develops a precursor to the spine called the notochord. At about six months this becomes the largest part of the vertebral column called the vertebral body. Some of the notochord may remain present. Chordomas arise from this residual notochord. It is considered to be a type of primary bone tumor. Primary bone tumors are rare and chordomas make up 4% of these tumors. There are roughly 300 new cases of chordomas in the US annually and these lesions are more common in men than women at a 1.6 to 1 ratio, especially in the tumors that are located in the bottom of the spine. They exhibit slow, progressive growth with local destruction and tend not to spread, but when they do, the most common sites are lung, liver, lymph nodes, bone and skin. They can occur in the skull base and at any location of the spine with the two most common sites being a bone in the middle of the head called the clivus and vertebrae at the bottom of the spine, either the sacrum or the coccyx. There is no known cause or risk factor; however, a family history of chordoma, other certain childhood brain tumors or tuberous sclerosis are thought to be predisposing factors. Although the tumor can affect any age group, when it occurs at the base of the skull, the median age is 49 and when it occurs at the base of the spine, the median age is 69.

Clinical Features:
Because a chordoma is such a slow growing tumor, a person may develop symptoms over a long period of time and it may become difficult to diagnose. The symptoms will vary based on location. When occurring in the spine, the patient may exhibit some or all of the following symptoms - pain, numbness, incontinence, impotence, weak legs and changes in bowel habits. It is possible that the patient will not experience any symptoms and in this instance, the first presentation may be a lump. When occurring at the base of the skull, common symptoms are headache, diplopia, problems with hearing and swallowing as well as dizziness.

Treatment and Prognosis:
Complete surgical resection is the gold standard of treatment. This may require a very aggressive surgery. Possible side effects and complications must be taken into account when trying to achieve complete removal of the tumor. When surgery is not possible, radiotherapy along with chemotherapy can be used. Chemotherapy alone is not an effective tool in treating chordoma. Stereotactic radiotherapy and proton beam radiotherapy is sometimes used after surgery to destroy remaining tumor cells. Proton beam radiotherapy is the favored choice due to its ability to deliver high doses of radiation to the tumor while protecting critical surrounding structures. In some instances, a urostomy or colostomy may be necessary for some patients depending on the location of the tumor that is removed.

The overall survival rate of chordoma is 68% at 5 years and 40% at 10 years with a median survival of 7 years. Although metastasis is rare, the tumor is very difficult to completely eradicate and is potentially a life threatening tumor. Local reoccurrence is common and is treated with repeat surgery. The need for repeat surgery due to reoccurrence dramatically decreases survival rates.

Cytology:
Physaliphorous cells are the diagnostic cell type in a fine needle aspiration from a chordoma. The absence of these cells can make the diagnosis of chordoma difficult. These large, round to polygonal cells with ill defined cell borders occur in tight clusters and cord like arrangements and are often surrounded by a myxoid matrix. The cytoplasm in physaliphorous cells is abundant, multivacuolated with an occasional signet ring appearance. When stained with Diff -Quick, the large vacuoles may stain purple. The distinct outer edges of these vacuoles will often have a "spider leg" appearance. The nuclei of these cells are bland with fine to coarsely granular chromatin that is evenly distributed. They also have indistinct nucleoli, are round in shape and are either centrally or eccentrically placed. Bi-nucleation is not uncommon. Other cell types that may be present are bland appearing, eosinophilic staining, round, oval or spindle shaped cells which are non-vacuolated with granular cytoplasm.

Differential Diagnosis:
The two main tumors that must be distinguished from chordoma are chondrosarcoma and metastatic adenocarcinoma. In addition, myxopapillary ependymoma must also be ruled out. Both chordoma and chondrosarcoma will shed cells that are finely vacuolated, however, cells with large, multiple vacuoles are lacking in a chondrosarcoma. A key difference between myxopapillary ependymoma and chordoma is the presence of ciliated cells in myxopapillary ependymoma. Immunohistochemical staining can help in the differentiation of these lesions as well. Both chordoma and chondrosarcoma stain positive for S100, while only chordoma will be positive with EMA and panCK. A further distinction is that chondrosarcoma will be positive for D2-40. To distinguish between chordoma and myxopapillary ependymoma EMA and GFAP are the stains of choice. Myxopapillary ependymoma will stain negative for EMA but positive for GFAP. Chordoma will have the opposite staining results - positive for EMA and negative for GFAP. Because chordomas stain positive for some epithelial markers, metastatic adenocarcinoma must be ruled out. Combining the midline location of the tumor with cytological criteria such as physaliphorous cells that contain large, multiple vacuoles in the cytoplasm will lead to a diagnosis of chordoma.

References:
  1. Atkinson, B., Silverman, J. Atlas of Difficult Diagnoses in Cytopathology. 1998: 290, 485-6, 504.
  2. Atkinson, B., Silverman, J. Atlas of Difficult Diagnoses in Cytopathology, Second Edition. 2004: 182, 642, 659.
  3. Cibas, E., Ducatman, B. Cytology Diagnostic Principles and Clinical Correlates Second Edition. 2003: 435.
  4. McKee, G. Cytopathology. 1997: 351-3.
  5. Bibbo, M. Comprehensive Cytopathology, Second Edition. 1997: 534.
  6. www.international.macmillan.com
  7. Cho, HY., Lee, M., Takei, H., Dancer, J., Ro, JY., Zhai, QJ., Immunohistochemical comparison of chordoma with chondrosarcoma, myxopapillary ependymoma, and chordoid meningioma. Applied Immunohistochemistry and Molecular Morphology. 2009, March; 17(2): 131-8.
  8. www.chordomafoundation.org
  9. http://www.cancer.gov/cancertopics/factsheet/Therapy/radiation
  10. http://en.wikipedia.org/wiki/Notochord
  11. Koss, M.D., Woyke, S., Olszewski, W., Aspiration Biopsy, Cytologic Interpretation and Histologic Bases, Second Edition. 1992: 645-6