2. Introduction
Ewing, in 1921 described it as a tumor occuring in the
diaphysis of long bone, in children, asso. With febrile
attacks , anorexia and anaemia and which was radio-
sensitive.
He believed it arose from endothelial elements of bone
marrow and described it as diffuse endothelioma of bone
Willis found rosette formation and presence of primary
lesion, usually in adrenals, in many cases
Ewings sarcoma is thought to be of either neuro-
ectodermal or stem cell origin
All Ewings sarcoma’s are considered high grade malignancy
and categorized under Enneking Stage II or III
3. Epidemiology
9% of primary bone sarcomas
4th most common primary malignancy of bone but 2nd most
common below 30yrs and most common below 10 yrs of age.
Age Group – 95% patients age between 5 to 30 yrs
- of these most range between 5 to 15 yrs
• Sex - slight male prediliction – 60%
• More common in Whites (95%)
• No known predisposing factor
• Chromosomal translocation – t(11;22)(q24;q12)
leading to fusion of EWS and FLI gene.
also t(21;22) and t(7;22)
4. Clinical Features
Pain
Swelling
Fever
Weight loss
Anemia
Raised ESR and CRP
Leukocytosis
And, symptoms depending on area of involvement
5. Location
Can develop in any bone
Principally affects the lower segment of the skeleton in more
than 2/3 cases
In long tubular bones – proximal segment more frequently
involved than distal fragment (5:1 to 3:1)
Usually of diaphyseal origin. Sometimes dia-metaphyseal.
Rarely, metaphyseal.
In vertebrae, most commonly involved – Sacrum
Body is mainly affected with subsequent involvement of
intra and para-spinal tissues and posterior elements
mostly metastatic.
• Rarely may be localized to soft-tissue or peri-osteum.
7. Radiology
On Plain X-ray – In long bones-
Diaphyseal/metadiaphyseal
Cortical erosion
Periostitis
Soft-tissue mass
Osteolysis
Aggressive nature with permeative/moth-eaten type of bone
destruction
Peri-osteal response – may be lamellated (‘onion-skin’) or hair-
0n-end
Cortical changes – longitudinal cross striations, tunnelling and
saucerization.
Occasionally, osteosclerosis and pathological fractures
11. In Vertebrae –
Osteolysis
Fractures
Vertebra plana
Extension to posterior segment
Soft tissue mass
• In Ribs
Osteo-lytic/sclerotic/both
Direction of growth usually intrathoracic
Large extra-pleural mass
• Metastasis – Usually to Lungs(m.c.) and Bones.
12. • Bone Scan - uptake
- rarely cold spots
• Gallium scan
• CT scan – For extra-osseous and trans-articular spread
- for chest metastasis
- evaluation of response to therapy
• MRI – for extra-osseous and intramedullary extent of lesion
- metastasis
- pre-operative planning ( along with MR-angio)
- response to therapy
• PET scan
• Biopsy
13. Histo-pathology
Diaphyseal/dia-metaphyseal
Predominantly medullary, then extends to haversian
system and cortex
Greyish-white to pink in color
soft, friable
Often of semi-liquid consistency
Areas of hemorrhage, necrosis and cyst formation
present
Onion-skin periosteal reaction
14. Microscopy
Small round undifferentiated tumor cells with little
cytoplasm and indistinct borders
Round nuclei with stippled evenly distributed powder-like
chromatin and 1-2 nucleoli
Frequent mitosis
Necrosis and Ghost cells
Minimal inter-cellular substance
Rosette and psuedo-rosette formation
Perithelioma
NO GIANT CELLS
PAS +ve presence of glycogen
Reactive for vimentin
15. Ewings Family of Tumors
1. Ewings
2. PNET
3. Askins
Similarity between Ewings and PNET
• C/f, radiology, light microscopy
• Chromosomal translocation t(11:22)(q24:q12)
• Reactivity towards p30/32 MIC-2 in 90%
Differences : In PNET
• More frequent epiphyseal involvement, Pathological fractures, metastasis
• Rosette formation
• Electron microscopy – features of neural differentiation like dendritic
processes, abundance of cytoplasmic granules, intermediate
filaments, neurosecretory granules and microtubule formation.
• Immunohistochemistry - +ve for neural markers – S-
100, synaptophysin, NSE, neuro-filament protein.
17. Prognostic factors
Good prognosis in –
involvement of distal segment of extremities
No metastasis
Infants and young children
Females
Poor prognosis –
Proximal segment involvement
Sacral involvement
Patients above 18 yrs
LDH and ESR
18. Stage Grade Site Metastasis
IA Low G-1 Intracompartmental -
T1
IB Low G-1 Extracompartmental -
T2
IIA High G-2 Intracompartmental -
T1
IIB High G-2 Extracompartmental -
T2
III Any G Any T Regional/ distant
metastasis
19. Treatment
Goal – To eliminate tumor mass, prevent recurrence and
preserve function
Depends on Stage at presentation and Location of lesion
Modalities of treatment – Chemotherapy, Surgery and
radiotherapy
Chemotherapy alone, as adjuvant or neo-adjuvant to
surgical excision or debulking
Drugs used – Vincristine, Actinomycin-
D, Cyclophosphamide ( VAC regimen)
Also used - Doxorubicin, etoposide, ifosphamide
Radiotherapy - Generally, a dose of 45-50 Gy is administered
over a 5 week course to treat local disease.
20. Chemotherapy
Induction CT for 3-6 cycles followed by 6-10 cycles of maintenance
First Line therapy: VAC/IE
Given in cycles of 3 weeks
Vincristine 2.0 mg/m2 on D1-2
Adriamycin 75 mg/m2 on D1-2
Cyclophosphamide 1.2 gm/m2 on D1-2
Ifosphamide 1.8 gm/m2 on D3-7
Etoposide 100 mg/m2 on D3-7
Second line therapy (relapse and refractory disease
Cyclophosphamide (250 mg/m2)and topotecan(0.75 mg/m2) D1-D5
Temozolomide and irinotecan
Ifosfamide and etoposide
Ifosfamide ,etoposide and carboplatin
Docetaxel and gemcitabine
21. Radiotherapy
For,
Tumors where Resection is Impossible
For skull, face, vertebra, or pelvic primary
where only an intra-lesional resection is achievable
Patient with poor Surgical risk
Patient refusing surgery
Pre-op - Indicated when narrow resection margins are expected
To sterilize the tumor compartment before surgery & to potentially
reduce the risk of dissemination during surgery
Local recurrence with pre-op RT <5%
Post-op - For gross or microscopic positive margin
For marginal Resection
For wide-resection with Poor Histological response to Neo-adjuvant
Chemotherapy
