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Background

Chordoma is a slow-growing malignant neoplasm of the bone. Most arise in the axial skeleton, most commonly the sacrum, followed by the base of the skull and the mobile spine.

OUTLINE

Epidemiology  
Disease Associations  
Pathogenesis  
Laboratory/Radiologic/
Other Diagnostic Testing
 
Gross Appearance
and Clinical Variants
 
Histopathological Features
and Variants
 
Special Stains/
Immunohistochemistry/
Electron Microscopy
 
Differential Diagnosis  
Prognosis  
Treatment  
Commonly Used Terms  
Internet Links  

EPIDEMIOLOGY CHARACTERIZATION
INCIDENCE Less than 5% of primary bone tumors
AGE  
CHILDHOOD  
Base of Skull Chordomas in Children and Adolescents: A Clinicopathologic Study of 73 Cases.

Hoch BL, Nielsen GP, Liebsch NJ, Rosenberg AE.

*Department of Pathology, Mount Sinai Medical Center, New York, NY daggerJames Homer Wright Pathology Laboratories, Massachusetts General Hospital and Harvard Medical School, MA double daggerDepartment of Radiation Oncology, Massachusetts General Hospital, Boston, MA
.


Am J Surg Pathol. 2006 Jul;30(7):811-818. Abstract quote  

Chordomas in children and adolescents comprise <5% of all chordomas and most frequently develop in the skull base. These tumors are believed to behave more aggressively than chordomas in adults and may have unusual morphology.

This study examines a large series of pediatric skull base chordomas treated with a standardized protocol to characterize the behavior and morphology of these tumors. There were 31 males and 42 females ranging from 1 to 18 (mean 9.7) years. Forty-two cases (58%) were conventional chordomas, some of which had unusual histopathologic features. Chondroid chordomas comprised 23% of cases. Fourteen tumors (19%) were highly cellular and had a solid growth pattern with no myxoid matrix or lobular architecture.

Eight of these had cytologic features of conventional chordoma cells including physaliferous cells (cellular chordoma). The remaining cellular tumors were composed of poorly differentiated epithelioid cells set in a fibrous stroma and lacked physaliferous cells (poorly differentiated chordoma). All variants studied by immunohistochemistry showed positive staining for cytokeratin, epithelial membrane antigen, S100 protein, and vimentin. Mitoses and necrosis were seen in all variants.

Follow-up data were available for all patients and ranged from 1 to 21 (mean 7.25) years. The survival rate was 81%. All but 1 patient with poorly differentiated chordoma died of disease. Overall, base of skull chordomas in children and adolescents treated with proton beam radiation have better survival than chordomas in adults. However, poorly differentiated chordomas are highly aggressive tumors.
   

 

PATHOGENESIS CHARACTERIZATION
BENGIN NOTOCHORD CELL TUMORS Supported by the fact that the histologic, immunohistochemical, and ultrastructural characteristics of chordoma are similar to those of the notochord
Intraosseous Benign Notochord Cell Tumors (BNCT): Further Evidence Supporting a Relationship to Chordoma.

Departments of *Pathology †Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA.

 

Am J Surg Pathol. 2007 Oct;31(10):1573-1577. Abstract quote

BACKGROUND: Previous studies have documented the existence of intraosseous benign notochordal cell tumors (BNCTs) within the axial skeleton. Evidence suggests that they may be associated with the development of chordomas. To further investigate the relationship between BNCT and classic chordoma, we reviewed a large series of resected sacral/coccygeal chordomas in an attempt to identify the presence of coexisting BNCTs.

DESIGN: Eighty-two sacrectomy/coccygectomy specimens performed for chordoma were identified. Available hematoxylin and eosin slides were reviewed to identify BNCTs and assess their relationship with the coexisting chordoma. BNCTs were defined, in accordance with prior descriptions, as cohesive aggregates of large cells that appeared adipocytelike because of their vacuolated cytoplasm. The cells exhibited only minimal nuclear atypia and lacked lobulation and myxoid stroma.

RESULTS: We identified 6 BNCTs, each was adjacent to but separate from the sacral chordoma. There were 5 females and 1 male, and the mean age was 58 years. Five lesions arose in the sacrum. One lesion arose in the coccyx, and involved 2 contiguous vertebral levels. The BNCTs ranged in size from 1 to 20 mm with a mean size of 6.1 mm. The lesions were exclusively composed of adipocytelike nuclei without significant nuclear atypia or myxoid stroma. Three lesions contained sclerotic bony trabeculae and intralesional hematopoietic elements were identified in 1 case. In all cases the chordoma was of the conventional type and were morphologically different from the BNCT.

CONCLUSIONS: BNCTs were identified in 7.3% of sacral/coccygeal resections performed for primary chordoma. We speculate that this finding provides further evidence that BNCT is the precursor lesion for chordoma. Additional investigations are needed to further understand this relationship.

 

LABORATORY/
RADIOLOGY
CHARACTERIZATION
BETA hCG  


Metastatic dedifferentiated chordoma with elevated beta-hCG: a case report.

Munshi HG, Merajver SD, Valdez R, Baker LH, Cooney KA.

Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor 48109-0948, USA.

Am J Clin Oncol 2002 Jun;25(3):274-6 Abstract quote

Chordomas are relatively uncommon bone tumors, and fewer than 10% of cases are classified as dedifferentiated chordomas. These tumors tend to be more clinically aggressive than chordomas and have a higher incidence of early distant metastases.

In this case report, we describe a 24-year-old man with dedifferentiated chordoma and multiple pulmonary metastases. Further laboratory analysis revealed an elevated serum beta-human chorionic gonadotropin level. Unfortunately, the patient's clinical condition deteriorated rapidly and he died before receiving any treatment for his cancer.

However, chemotherapy may play a useful role in the management of systemic disease in patients with dedifferentiated chordoma.

 

GROSS APPEARANCE/
CLINICAL VARIANTS
CHARACTERIZATION
VARIANTS  
PARACHORDOMA

Cancer 1977;40:158692.
Ann Diagn Pathol 1997;1:310.
Am J Surg Pathol 1999;23:105967.

Most parachordomas have arisen in the soft tissues of the extremities and trunk, often in close proximity to tendons and aponeurosis. Rare cases have involved bone

Parachordomas express cytokeratin 8/18 but are negative for other cytokeratins, including CK 1/10, CK 7, CK 20, CK 19, and CK 1217

  Usually lobulated tumors <5 cm
CHORDOMA PERIPHERICUM

Am J Surg Pathol 2001;25:263-267

Term should be used strictly for tumors arising in an appendicular location and that have the features of a classic chordoma

EXTRA-AXIAL  
Extra-axial chordoma.

Department of Pathology and Laboratory Medicine, University of Calgary, Alberta.

Arch Pathol Lab Med. 2006 Dec;130(12):1871-4. Abstract quote

Chordomas are low-grade malignant tumors of bone that occur almost exclusively in the axial skeleton. Other neoplasms with a similar histologic picture but an extra-axial location have been described, including parachordoma, myxoid chondrosarcoma, and extra-axial chordoma.

We herein present another case of the rare extra-axial chordoma. A 41-year-old woman developed an 8.3 cm mass in the pubic bone. The gross, microscopic, and immunohistochemical findings were identical to those of a classic chordoma. Parachordoma and myxoid chondrosarcoma were excluded from the differential diagnosis.

Five previously reported cases of extra-axial chordoma were reviewed and found also to demonstrate clinical and pathologic features specific to chordoma, despite arising in an extra-axial location.

Although rare, extra-axial chordoma does exist and should be recognized and managed in a similar fashion to its well-described counterpart.

It must be differentiated from other histologic mimics, because the treatment and prognosis can differ significantly.

 

HISTOLOGICAL TYPES CHARACTERIZATION
General Cohesive epithelioid cells with abundant eosinophilic cytoplasm embedded in a myxoid stroma
Noninvasive sacral chordoma presenting as a benign soft tissue mass.

Baboiu OE, Taylor WM.

Department of Pathology and Laboratory Medicine, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA.
Ann Diagn Pathol. 2006 Apr;10(2):95-9. Abstract quote  

In this case report, we describe a sacral chordoma, which had an atypical presentation as a mobile, encapsulated, benign soft tissue mass. The patient was asymptomatic, except for the slight enlargement of this lesion.

Biopsy of this mass showed a lobulated tumor with bland neoplastic cells in a rich myxoid matrix with the classical immunohistochemical profile of chordoma. Opposite to this classical histological picture of chordoma, the imaging studies (computed tomography and magnetic resonance imaging) could not find any sacral involvement or lytic destruction. Surgical excision of this chordoma confirmed all preoperative findings and diagnoses, showing an encapsulated mass in the sacral soft tissue that has not invaded into the sacrum.

This chordoma originated from the sacrococcygeal joint and grew parallel to the sacrum and below the skin. At the same time, histological sections and immunostains reconfirmed diagnosis of chordoma.
VARIANTS  
CHORDOMA PERIPHERICUM

Am J Surg Pathol 2001;25:263-267

Histologically identical to classic chordoma

EPITHELIOID CELLULAR CHORDOMA  
Epithelioid cellular chordoma of the sacrum: a potential diagnostic problem.

Fan F, Templeton K, Damjanov I.

Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Ann Diagn Pathol. 2005 Jun;9(3):139-42. Abstract quote  

We describe a sacral chordoma composed of solid nests of epithelioid cells. The tumor originated in the presacral area. Extensive clinical workup did not reveal any other lesion in the patient. In contrast to typical chordomas, this tumor contained only rare physaliferous cells, had no myxoid stroma, and was immunohistochemically unreactive with the antibody to S-100.

The diagnosis of chordoma was supported by electron microscopy, which showed that the tumor cells contained numerous mitochondria surrounded by profiles of rough endoplasmic reticulum. The abundance of mitochondria, the narrow intercellular spaces, combined with a lack of glycogen, and a lack of extracellular myxoid material accounted for the epithelioid appearance of the tumor.

We report this case to point out that the cellular chordomas can appear epithelioid in the sacrum and they may resemble metastatic squamous or transitional cell carcinomas.
INCIPIENT CHORDOMA  
Incipient chordoma: a report of two cases of early-stage chordoma arising from benign notochordal cell tumors.

Yamaguchi T, Watanabe-Ishiiwa H, Suzuki S, Igarashi Y, Ueda Y.

1Department of Pathology, Koshigaya Hospital, Dokkyo University School of Medicine, Minami-Koshigaya, Koshigaya, Saitama, Japan.
Mod Pathol. 2005 Jul;18(7):1005-10. Abstract quote  

Chordomas are rare malignant bone tumors primarily involving both ends of the axial skeleton that present as destructive bone lesions with a large soft tissue mass. Chordomas were previously believed to arise from notochordal remnants. However, recent studies suggest the possibility that chordomas arise from benign notochordal cell tumors.

We present two cases of coccygeal incipient chordoma that strengthen the new hypothesis. The first case was an 83-year-old man who died of prostatic adenocarcinoma. The second case was a 79-year-old man who died of hepatocellular carcinoma. The coccygeal tumors were composed of intraosseous and extraosseous infiltrative lesions. The intraosseous lesions consisted of both benign notochordal cell tumor and incipient chordoma. The extraosseous lesions were consistent with incipient chordoma. In addition, two other small benign notochordal cell tumors were found at a different level in case 1.

It is conceivable that pre-existing intraosseous benign notochordal cell tumors transform into incipient chordoma and then extend through the cortex into the surrounding soft tissue. The incidence of incipient chordoma appears much higher than expected because chordomas are rare tumors with an incidence of one case per 1 000 000 persons per year.

We suspect that unknown factors transform incipient chordoma into classic chordoma.
INTRALESIONAL FIBROUS SEPTUM  
Intralesional fibrous septum in chordoma: a clinicopathologic and immunohistochemical study of 122 lesions.

Naka T, Boltze C, Kuester D, Samii A, Herold C, Ostertag H, Iwamoto Y, Oda Y, Tsuneyoshi M, Roessner A.

Department of Pathology, Faculty of Medicine, Magdeburg University, Magdeburg, Germany.

Am J Clin Pathol. 2005 Aug;124(2):288-94. Abstract quote  

Intralesional fibrous septum (IFS) generally is considered a reactive tissue in chordoma; however, little is known about its significance.

We studied 122 chordomas for IFS using immunohistochemical techniques and compared IFS and lobular growth patterns (LGPs) formed by IFS with clinicopathologic parameters. Seventy-nine tumors (64.8%) revealed IFS. However, IFS frequently was infiltrated and interrupted by tumor cells with increased expression of proteases; only 33 (42%) of 79 tumors had LGP. In non-skull base chordomas, IFS and LGP were associated with nuclear pleomorphism, a previously described prognostic indicator, mitosis, and the MIB-1 labeling index, indicating a role of IFS and LGP in tumor growth or progression. Paradoxically, patients without LGP tended to have a worse prognosis than those with LGP.

We believe that IFS exerts diverse influences on chordoma; however, invasion of IFS leading to loss of the LGP indicates advanced stages of tumor development, possibly predicting an unfavorable prognosis in chordoma.
LIPOID CHORDOMA

Mod Pathol 2000;13:15A.

Lobular pattern with the neoplastic cells containing abundant clear cytoplasm

PARACHORODOMA

Cancer 1977;40:1586–92.
Ann Diagn Pathol 1997;1:3–10.
Am J Surg Pathol 1999;23:1059–67.

Three cell types, including epithelioid cells, smaller glomoid cells, and spindle cells

Parachordomas express cytokeratin 8/18 but are negative for other cytokeratins, including CK 1/10, CK 7, CK 20, CK 19, and CK 12–17

S-100 and occasionally EMA also positive

 

SPECIAL STAINS/
IMMUNOPEROXIDASE
CHARACTERIZATION
Immunoperoxidase  
CHORDOMA

S100, Cytokeratin, and Vimentin
Express cytokeratin 8/18 and other cytokeratins, including CK 1/10, CK 7, CK 20, CK 19, and CK 1217

CEA positive


Apoptotic and proliferative markers in chordomas: A study of 26 tumors.

Kilgore S, Prayson RA.

Department of Anatomic Pathology, Cleveland Clinic Foundation, Cleveland, OH.

 

Ann Diagn Pathol 2002 Aug;6(4):222-8 Abstract quote

Few studies have examined the role of cell proliferation and apoptotic markers in chordomas. This study retrospectively reviews the clinicopathologic features of 26 chordomas and examines MIB-1, p53, bcl-2, and cyclin D1 immunoreactivity in these neoplasms. Patients ranged in age from 34 to 78 years (mean, 60.7 years) and included 14 females. The most common presentations included lower back pain (N = 15) and headaches (N = 10). Sixteen tumors arose in the lumbosacral region and 10 in the clivus. Initial surgery included biopsy (N = 17), subtotal resection (N = 4), and gross total resection (N = 5).

The single highest mitosis count per 10 high power fields ranged from 0 to 6 (mean, 1). Marked nuclear pleomorphism was identified in seven tumors. Marked hypercellularity was seen in two tumors. Focal necrosis was identified in seven tumors. MIB-1 labeling indices (LI) in 22 tumors ranged from 0 to 3.8 (mean, 0.5). Cyclin D1 LI ranged from 0 to 82.4 (mean, 35.6). Seven tumors had positive p53 immunostaining and three demonstrated focal positive staining with bcl-2 antibody. Five tumors locally recurred; two patients developed metastatic disease. Thirteen patients received adjuvant chemotherapy and/or radiation therapy. At last known follow-up, seven patients died with tumor (12 to 132 months follow-up).

Five additional patients died, two without tumor at 36 and 72 months follow-up and three patients in whom the tumor status at death was not known. Seven patients were alive with evidence of tumor (1 to 120 months) and five patients were alive without evidence of tumor (12 to 84 months). Clinical follow-up was not available in one patient. In conclusion, the low MIB-1 LIs and the lack of p53 and bcl-2 staining is in keeping with the low-grade nature of most chordomas.

High cyclin D1 LIs may be reflective of a tendancy to accumulate cyclin D1 protein; however, there appears to be a block in the effect of cyclin D1 on cell proliferation in these tumors. Cyclin D1, MIB-1, p53, and bcl-2 immunostaining does not appear to improve one's ability to predict behavior versus routine light microscopy.

PARACHORDOMA
Negative for CEA
Type IV collagen more frequently seen in parachordoma

DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES
GENERAL  
The surgical pathology of notochordal remnants in adult intervertebral disks: a report of 3 cases.

Department of Pathology, Massachusetts General Hospital, Boston, MA 02114, USA.

 

Am J Surg Pathol. 2008 Aug;32(8):1123-9. Abstract quote

The notochord plays a critical role in organizing and directing vertebral development. In humans, most notochordal cells are eventually sequestered into the nucleus pulposus and disappear within the first decade of life. Although notochordal remnants and related lesions have been described in the axial skeleton of adults, their presence in intervertebral disks is rare.

We describe herein 3 cases of incidental notochordal remnants identified in surgically removed adult intervertebral disks. Their histologic features were reminiscent of notochordal vestiges in the fetus. However, they raised the differential diagnosis of benign notochordal cell tumor and chordoma.

Notochordal rests can be a source of diagnostic confusion and should be distinguished from notochordal neoplasms because they do not necessitate resection or other forms of therapy.
Benign notochordal cell tumors: A comparative histological study of benign notochordal cell tumors, classic chordomas, and notochordal vestiges of fetal intervertebral discs.

Yamaguchi T, Suzuki S, Ishiiwa H, Shimizu K, Ueda Y.

Department of Pathology, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan.
Am J Surg Pathol. 2004 Jun;28(6):756-61. Abstract quote

Intraosseous benign notochordal cell tumors are recently recognized conditions that may undergo malignant transformation to classic chordomas.

This study attempts to define the morphologic and immunohistochemical characteristics of 34 benign notochordal cell tumors by contrasting them with classic chordomas and the notochordal vestiges in fetal intervertebral discs.

Benign notochordal cell tumors were characterized by well-demarcated though unencapsulated sheets of adipocyte-like vacuolated and less vacuolated eosinophilic cells within axial bones. The round nuclei were mildly polymorphic but bland. The tumor cells often contained cytoplasmic eosinophilic hyaline globules and lack any intercellular myxoid matrix or necrosis. The involved bone trabeculae were often sclerotic without evidence of bone destruction. The histologic features were different from those of both notochordal vestiges in fetal intervertebral discs and classic chordomas. There was overlap in immunohistochemical reactivity of benign notochordal cell tumors and chordomas, but notochordal vestiges failed to demonstrate cytokeratin 18 positivity.

A more appropriate term for the lesions is "benign notochordal cell tumor" rather than "notochordal rest" or "notochordal hamartoma" as they are not rests and do not fulfill the definition of hamartoma.

Benign notochordal cell tumors do not need any surgical procedure and must be adequately recognized to prevent unnecessary operations.

PROGNOSIS AND TREATMENT  
PROGNOSIS  
Cadherins and Catenins in Clival Chordomas: Correlation of Expression With Tumor Aggressiveness.

Triana A, Sen C, Wolfe D, Hazan R.

From the *Department of Neurosurgery, St.Luke's-Roosevelt Hospital, New York, NY; daggerDepartment of Pathology, Mount Sinai Hospital and School of Medicine, New York, NY; and double daggerDepartment of Pathology, Albert Einstein College of Medicine, Bronx, NY. Drs. Wolfe and Hazan contributed equally.
Am J Surg Pathol. 2005 Nov;29(11):1422-1434. Abstract quote  

The local invasiveness and occasional rapid growth of chordomas, despite optimal treatment, highlight the need to develop ways to predict their biologic behavior. Alterations in adhesion proteins have been shown to participate in proliferation, invasiveness, and metastasis in epithelial tumors.

We therefore analyzed the expression of E-cadherin, N-cadherin, as well as their cytosolic binding proteins alpha-catenin, beta-catenin, and gamma-catenin, in 51 paraffin archived and 17 cryopreserved chordoma specimens. In the majority of chordomas, E-cadherin and N-cadherin expression was inversely correlated, whereas beta-catenin and gamma-catenin expression was directly correlated. By multivariate analysis, N-cadherin up-regulation correlated with a diminished recurrence-free survival, and E-cadherin down-regulation strongly correlated with increased probabilities of death as determined by the Kaplan-Meier log-rank test. There was a 3.28-fold increased probability of having a tumor recurrence and a 10.98-fold increased probability of dying when, respectively, N-cadherin was up-regulated and E-cadherin down-regulated.

These results suggest that changes in the relative expression of the cadherin-catenin complex reflect chordoma aggressiveness; and that decreased expression of E-cadherin and increased expression of N-cadherin may underlie the transition from a less to a more aggressive tumor phenotype.
TREATMENT  

Macpherson and Pincus. Clinical Diagnosis and Management by Laboratory Methods. Twentyfirst Edition. WB Saunders. 2006.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fifth Edition. Mosby Elesevier 2008


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Last Updated August 4, 2008

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