Chordoma

“Wer Freude an Namen hat, könnte die Masse als chordoide Geschwult oder Chordoma bezeichnen”12

This is a slow-growing malignant neoplasm which accounts for about 1% of all primary malignant bone tumours11. It is thought to arise from notochordal remnants.

Clinical

This tumour almost exclusively involves the axial skeleton of adults (mean ranges from 47 to 57), most commonly the sacro-coccygeal and spheno-occipital regions5. About 40% occur in the clivus8. Males are more often affected than females. Only 5% of chordomas occur before the age of 20 years: in this age group they are most common in the skull base10.

Radiology

At diagnosis, there is usually radiological evidence of bone destruction (sometimes sclerosis) with extraosseous extension5.

Histopathology

There is an abundant fibrillary myxoid stroma within which there are nests, sheets and cords of univacuolated, multivacuolated (physalipherous) and granular cells. If the vacuoles are large enough, the cells may resemble adipocytes10. Atypia may be minimal but is usually moderate to severe5. Some variants appear spindled10, chondroid or epithelioid7. Rarely, the cells may appear rhabdoid10. Chondroid chordomas have areas of neoplastic hyaline cartilage10.

Variants

• Cellular chordoma. Highly cellular cases lack a lobular pattern or myxoid stroma. The cells have distinct border, conferring a plant-like appearance10.

• Poorly differentiated chordoma usually occurs before the age of five years10. Sheets of small epithelioid cells have a minimal amount of cytoplasm, which lacks vacuolation.

• Rare cases show dedifferentiation with areas of high-grade sarcoma.

Immunohistochemistry

Dedifferentiated foci may loose positivity for S-100, HBME-1 and cytokeratins7.

Differential diagnosis

• Giant vertebral notochordal rest (ecchordosis physaliphora vertebralis)5,9. This is a controversial entity. The diagnosis is favoured by a lesion in the mobile spine, where chordoma is rare, young age and lack of radiological bone destruction or progression. Bone trabeculae are preserved, with sheets of clear cells filling the intertrabecular spaces: these cells are positive for cytokeratin (AE1/AE3, Cam5.2), EMA and S-100. Histologically, there should be a lack of lobularity, mucin pools with syncytial cell cords, necrosis, nuclear atypia or mitotic activity.

• parachordoma is the equivalent tumour when found in soft tissues.

• Chondrosarcoma. E-cadherin, catenins and NCAM may help to distinguish chordoma from chondrosarcoma4:

• Metastatic carcinoma, particularly renal cell carcinoma. Renal cell carcinoma is usually positive for CD10 and RCCMa.

• Dedifferentiated chordoma: spindle cell sarcoma or dedifferentiated chondrosarcoma.

Management

Radical (if possible) surgical excision followed by conventional or proton beam irradiation8.

Prognosis

Chordomas are locally invasive but metastasis occur late in the course of the disease11: when they do, metastases most often occur in the lungs10. Poorly differentiated tumours are liable to recur10. A switch from E-cadherin to N-cadherin expression is associated with recurrence and tumour-associated death8. Childhood cases are said to be more aggressive10. 5% of tumours undergo dedifferentaition to high grade sarcoma11.

References

1 O'Hara, B. J., Paetau, A., Miettinen, M. Keratin subsets and monoclonal antibody HBME-1 in chordoma: immunohistochemical differential diagnosis between tumors simulating chordoma. Human Pathol 1998; 29:119-26.

2 Naka, T., Iwamoto, Y., Shinohara, N., Chuman, H., Fukui, M., Tsuneyoshi, M.Cytokeratin subtyping in chordomas and the fetal notochord: an immunohistochemical analysis of aberrant expression. Mod Pathol 1997;10:545-51.

3 Miettinen M. Keratin 20: immunohistochemical marker for gastrointestinal, urothelial and Merkel cell carcinomas. Mod Pathol 1995;8:384-388.

4 Naka, T., Oda, Y., Iwamoto, Y. Immunohistochemical analysis of E-cadherin, alpha-catenin, beta- catenin, gamma-catenin, and neural cell adhesion molecule (NCAM) in chordoma J Clin Pathol 2001;54:945-950.

5 Kyriakos, M., Totty, W.G. and Lenke, L.G. Giant vertebral notochordal rest: a lesion distinct from chordoma: discussion of an evolving concept. Am J Surg Pathol 2003;27:396-406.

6 Chu, P. G. and L. M. Weiss (2002). "Keratin expression in human tissues and neoplasms." Histopathology 40(5): 403-39. (Summary data from multiple papers)

7 Al-Adnani M, Cannon SR,Flanagan AM. Chordomas do not express CD10 and renal cell carcinoma (RCC) antigen: an immunohistochemical study. Histopathology 2005; 47:535-7

8 Triana A, Sen C, Wolfe D, et al. Cadherins and catenins in clival chordomas: correlation of expression with tumor aggressiveness. Am J Surg Pathol 2005; 29:1422-34

9 Chauvel A, Taillat F, Gille O, et al. Giant vertebral notochordal rest: a new entity distinct from chordoma. Histopathology 2005; 47:646-9

10 Hoch BL, Nielsen GP, Liebsch NJ, et al. Base of Skull Chordomas in Children and Adolescents: A Clinicopathologic Study of 73 Cases. Am J Surg Pathol 2006; 30:811-818

11 Tirabosco Brachyury Expression in Extra-axial Skeletal and Soft Tissue Chordomas: A Marker that Distinguishes Chordoma From Mixed Tumor/Myoepithelioma/Parachordoma in Soft Tissue AJSP 2008;32:572

12 Müller H. Ueber das Vorkommen von Resten der Chordadorsalis bei Menschen nach der Geburt und über ihr Verhältniss zu den Gallertgeschwülsten am Clivus. Z Rationelle Med 1858;2:202–229.

This page last revised 23.7.2006.

©SMUHT/PW Bishop