Table 1.

Comparison of skeletal and extraskeletal ES clinical features.

	Skeletal ES	Extraskeletal ES
Age onset	Most often in 2nd decade	Usually under 35 years, mostly 2nd and 3rd decade
Sex predominance	Male	Male or female
Location	Long bones (diaphysis)	Thorax (32%), extremities (26%), head and neck (18%), retroperitoneum and pelvis (16%)
Symptoms	In 40% patients: pain, enlargement of the extremity, infection- like with increased body temperature 1/4–1/3 patients at diagnosis have metastatic disease (most common in lungs and bones)	In one third of patients pain, polisymptomatic (depending on the location)
Treatment	CTH (chemotherapy) with RTH (radiotherapy) play main role, surgery as additional treatment	No standards, multimodal considered to be the best approach – CTH plus local treatment (surgery/RTH)
5-year survival rate	60–70% when localized, 20–40% when metastatic	38–83%
Negative prognostic factors	Metastatic disease, size > 5 cm, located in pelvis and chest, infiltrating soft tissues, elevated LDH (lactate dehydrogenase)	Metastatic disease, elderly, pelvic location, incomplete resection, tumor size ≥ 8 cm, elevated LDH, poor histological response to CTH, RTH only as local treatment, positive surgical margins
Positive prognostic factors	Female, treatment within 1 month of diagnosis	Normal level of hemoglobin, LDH, complete response to CTH, younger age, total resection, type 1 of the fusion EWS/FLI 1, located in the extremities, adjuvant RTH