Chordoma

This is a slow-growing malignant neoplasm which accounts for less than 5% of primary bone tumours. 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

Immunohistochemistry

 

 

AE1/AE3

31/317, 47/4710

 
 

Cytokeratin 5

most of 351

 

Cytokeratin 7

1/162, 6/66

Cytokeratin 8

16/162

Cytokeratin 8/18

6/66

Cytokeratin 10

0/66

Cytokeratin 13

0/66

Cytokeratin 14

0/66

Cytokeratin 18

9/162

Cytokeratin 19

16/162, 5/66

Cytokeratin 20

0/162, 0/73, 0/76

HMWK

4/162

S-100

 usually positive, 10/317, 47/4710

CD10

0/317

Renal cell carcinoma antigen

0/317

EMA

positive, 47/4710

vimentin

positive, 47/4710

HBME-1

positive1

NSE

positive1, 9/1010

CEA

4/810

synaptophysin

occasionally positive1, 0/410

chromogranin

negative1, 0/410

CD45

0/410

GFAP

0/410

   

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

Differential diagnosis

 

chordoma

chondrosarcoma

E-cadherin

11/16

0/8

a-catenin

7/16

1/8

b-catenin

13/16

1/8

g-catenin

10/16

0/8

NCAM

14/16

2/8

Management

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

Prognosis

Chordomas are locally invasive but rarely metastasis: when they do, metastases most often occur in the lungs10. Poorly differentiated case 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.

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

This page last revised 23.7.2006.

©SMUHT/PW Bishop