Ewing Sarcoma

Diagnosis

Indications for Testing

• Childhood tumor at appropriate site (eg, long bones, pelvis)

Histology

• Densely packed homogeneous small round cells – granular chromatin
  • Biopsy specimen may be difficult to assess because tumor cells resemble other similar sarcomatous or round-cell tumors (eg, lymphoma/leukemia, rhabdomyosarcoma, medulloblastoma, neuroblastoma)
• Immunohistochemistry
  • CD99 (MIC2, also known as O13) – cell surface glycoprotein expressed in 85-95% of ES
    • Also positive in acute lymphoblastic leukemia/lymphoma, synovial sarcoma and desmoplastic small round blue-cell tumor
    • May be helpful in differentiating ES and pPNET from other small round-cell neoplasms
    • Not an exclusive marker; also found in other sarcomas
  • Friend leukemia integration-1 (Fli-1) protein
  • Must differentiate from other neuroendocrine tumors
    • Consider NSE, PGP 9.5, synaptophysin
• Molecular studies (PCR, FISH) – may be crucial if tumor is in unusual location
  • EWSR1 rearrangements – supports diagnosis of ES
  • t(11;22)(q24;12) translocation (EWS-FLI1) – found in ~85% of Ewing sarcomas
    • Not as sensitive as other EWSR1 transcriptions seen in ES and in some other sarcomas, including desmoplastic small round-cell tumors, clear-cell sarcomas, and extraskeletal myxoid liposarcomas

Imaging Studies 

• MRI – standard imaging for ES
  • Both bony and soft tissue components may coexist
  •  “Onion skinning” of reactive periosteum

Prognosis

• Favorable
  • Normal serum LD
  • Distal site of primary disease
  • Absence of metastatic disease
• Unfavorable
  • Metastatic disease – most significant adverse factor
    • ~25% present with metastatic disease
    • Lungs, other bones, bone marrow are most common sites
  • Elevated serum LD
  • Primary tumor in pelvic bone
  • Large tumor
  • Age – lower survival rate in adults
• Other factors affecting prognosis
  • EWS gene fusion/translocation
  • Lower socioeconomic status – poor prognosis
  • Hispanic ethnicity – poor prognosis

Differential Diagnosis

• Similar-appearing sarcomatous tumors
  • Synovial sarcoma
  • Rhabdomyosarcoma
  • Mesenchymal chondrosarcoma
• Other childhood tumors
  • Neuroblastoma 
  • Lymphoblastic lymphoma
  • Undifferentiated small round cell tumors

Monitoring

Clinical Background

The Ewing sarcoma family of tumors (ESFT) are small round-cell neoplasms and include classic Ewing sarcoma (ES) of the bone, extraskeletal ES, small round-cell tumors of the thoracopulmonary region (Askin tumor), and peripheral primitive neuroectodermal tumors (pPNET).

Epidemiology

• Incidence – 4/1,000,000
• Age
  • Second most common neoplasm of the bone in children and adolescents
  • Peak incidence in adolescence
  • 20% diagnosed in patients <10 years and >20 years  
• Sex – M>F, 1.3:1
• Ethnicity – in U.S., more common in Caucasians; essentially absent in African Americans

Genetics

• ES is characterized by fusion of EWS chromosome 22q12 with chromosome in the ETS gene family
  • ETS genes include FLI1, ERG, ETV1, ETV4, FEV
• EWS-FLI1 t(11;22)(q24;q12) found in ~85% of ES
  • May be found in other sarcomas
• EWS-ERG t(21;22)(q22;q12) – more specific for ES and pPNET
• Numerous other EWS fusions rare

Pathophysiology

• Classic ES is a poorly differentiated, homogeneous population of small round-cells with high nuclear-to-cytoplasmic ratio
• Characterized by strong expression of glycoprotein MIC2 (CD99, also known as O13)

Clinical Presentation

• Symptoms based on location of tumor
• Primary tumor sites include
  • Pelvis (26%)
  • Femur (20%)
  • Tibia/fibula (18%)
  • Chest wall (16%)
  • Upper extremity (9%)
  • Spine (6%)
  • Other (5%)
• Pain may be intermittent and variable in intensity
  • Easily mistaken for bone growth or injury in children
• Palpable mass/swelling at affected site
• Constitutional – occasionally may present with fever, weight loss, fatigue

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory