9. Ewing sarcoma

Question 1

Definition of Ewing sarcoma

Answer 1

Also known as Primitive Neuroectodermal Tumour (PNET); a highly malignant neoplasm composed of small round, rather uniform cells that do not form matrix

Question 2

Epidemiology of Ewing sarcoma

Answer 2

Usually whites aged 5-20 years

Question 3

Pathogenesis of Ewing sarcoma

Answer 3

Unique karyotypic abnormality (seen in 90%):

1. t(11;22) (q24;q12)
2. Results in expression of chimeric protein EWSR1-FLI-1

Question 4

Morphology of Ewing sarcoma

Answer 4

1. Grossly:
   - Sites affected:
   i. Marrow of femur, tibia, humerus, fibula, pelvis, ribs, vertebra, mandible, clavicle
   ii. May permeate cortex into soft tissue
   - Soft white (fish flesh) mass of almost liquid consistency
2. Histologically:
   - Sheets of small round uniform cells 10-15 microns (larger than lymphocytes) with scant clear cytoplasm & small nucleoli
   - May have Homer-Wright rosettes (tumour cells arranged around a central fibrillary space) or pseudorosettes (cells arranged around vessels)
   - Immunohistochemistry:
   i. Positive membranous CD99 staining
   ii. PAS positive, diastase sensitive
   iii. NSE, Leu7, FLI1 protein, vimentin
   iv. Variable low molecular weight keratin & synaptophysin

Question 5

Clinical features of Ewing sarcoma

Answer 5

1. Xray findings:
   - Destructive lytic tumour
   - Onion-skin appearance (concentric layers of new bone formation incited by permeating of cortex by tumour)
2. Treatment:
   - Preoperative chemotherapy
   - Surgery
   - Radiation therapy
3. Prognosis:
   - 5-year survival rate: 75% (50% are cured)
   - Metastases to lung, skull, pleura, CNS
   - 10-25% have multiple lesions at presentation
   - Poor prognostic factors: high stage, direct extension into soft tissue, aneuploidy, metastases, grossly viable tumour post-chemotherapy (poor response)
4. Differential diagnoses (other small blue round tumours):
   - Sarcomas (neuroblastoma, desmoplastic small round cell tumour, rhabdomyosarcoma)
   - Carcinomas (small cell carcinoma)
   - Lymphomas