Ewing family tumour

Definition

There was initially a sharp distinction between Ewing sarcoma of bone and extraskeletal primitive neuroectodermal tumour (PNET). However, both are now recognised to be members of the Ewing family of tumours, small round blue cell tumours characterised by positivity for CD99 and Fli1, with a translocation t(11;22)(q24;q12). There is a spectrum from undifferentiated Ewing sarcoma to PNET with neuroendocrine differentiation. This family includes malignant small cell tumour of the thoracopulmonary region (Askin tumour) and peripheral neuroepithelioma.

Epidemiology

Tumours of the Ewing family occur predominantly in children and young adults.

Histopathology

The cells of Ewing tumour contain glycogen.

Variants:

Immunohistochemistry

 

 

Usual Ewing tumour

Usual PNET

Spindle-cell sarcoma-like Ewing tumour

Spindle-cell sarcoma-like Ewing tumour

Atypical Ewing sarcoma

Adamantinoma-like

Overall

 

CD99

35/351

8/81

3/31

2/21

3/31

3/31

52/521

Fli1

29/321

5/51

3/31

2/21

3/31

3/31

44/471

AE1/AE3

7/371

4/81

2/31

1/21

1/31

3/31, 1/12

18/561

Pancytokeratin MAK-6

 

 

 

 

 

2/32

 

Cam5.2

 

 

 

 

 

1/12

 

Cam5.2 or AE1/AE3

 

 

 

 

 

 

10/504

34bE12

0/371

0/91

0/31

0/21

0/31

3/31

3/551

Cytokeratin, NOS

 

 

 

 

 

 

13/413

Desmin

1/371

0/91

0/31

0/21

0/31

0/31

1/561

CD99+/Fli1+/CK-/desmin-

24/321

 

 

 

 

 

 

CD117

9/381

2/81

1/31

0/21

0/31

1/21

13/541

NSE

 

 

 

 

 

 

35/413, 13/503

Synaptophysin

 

 

 

 

 

 

14/403

CD56

 

 

 

 

 

 

9/403

Mic-2

 

 

 

 

 

1/32

 

               

Cytogenetics

The cytogenetic abnormalities are highly specific to Ewing tumours:

 

translocation

gene fusion product

frequency in Ewing tumours

 
 

t(11;22)(q24;q12)

EWS-Fli1

>90%

t(21;22)(q22;q12)

EWS-ERG

5%

t(17;22)(q12;q12)

EWS-E1AF

<1%

t(2;22)(q33;q12)

EWS-FEV

<1%

t(7;22)(p22;q12)

EWS-ETV1

1%

 

EWS-ZSG

rare3

     

Typical Ewing tumour can be diagnosed on morphology and immunohistochemistry, but the variants need cytogenetic or molecular confirmation of the diagnosis. The EWS-Fli1 transcript has been reported in two polyphenotypic tumours and two rhabdomyosarcomas5

 

Ultrastructure

The cells appear undifferentiated. The adamantinoma-like variant shows epithelial differentiation in the form of tonofilaments and numerous desmosomes1,2.

Differential diagnosis

Management

Chemotherapy

Prognosis

Reportedly, type I fusion transcripts (junction between exon 7 of EWS and exon 6 of FLI-1) appear to have a survival advantage when compared with type II fusion transcripts (junction between exon 7 of EWS and exon 5 of FLI-1) independent of tumor site and stage2. The adamantinoma-like variant may be more aggressive2.

References

1 Folpe AL, Goldblum JR, Rubin BP, et al. Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol 2005; 29:1025-33

2 Bridge JA, Fidler ME, Neff JR, et al. Adamantinoma-like Ewing's sarcoma: genomic confirmation, phenotypic drift. Am J Surg Pathol 1999; 23:159-65

3 Collini P, Sampietro G, Bertulli R, et al. Cytokeratin immunoreactivity in 41 cases of ES/PNET confirmed by molecular diagnostic studies. Am J Surg Pathol 2001; 25:273-4

4 Gu M, Antonescu CR, Guiter G, et al. Cytokeratin immunoreactivity in Ewing's sarcoma: prevalence in 50 cases confirmed by molecular diagnostic studies. Am J Surg Pathol 2000; 24:410-6

5 Thorner P, Squire J, Chilton-MacNeil S, et al. Is the EWS/FLI-1 fusion transcript specific for Ewing sarcoma and peripheral primitive neuroectodermal tumor? A report of four cases showing this transcript in a wider range of tumor types. Am J Pathol 1996; 148:1125-38

 

This page last revised 19.11.2005.

©SMUHT/PW Bishop