1. By : Dr. Utsav Agrawal

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.

6. 1
8
10%
12
3% 6
22
%
11%
F - 9%

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

8. Hair-on-end periosteal reaction
Onion skin formation

9. Metatarsal involvement
with moth-eaten
appearance, periostitis
Involvement of long bone with
lamellated
appearance, saucerisation, cortical
breach, periostitis

10. Ewings sarcoma with extensive soft tissue involvement

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.

16. Differential diagnosis
 Osteosarcoma
 Lymphoma
 Leukemia
 Osteomyelitis
 PNET

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

22. Newer Therapies
 Nutlin – 3a  MDM-2 antagonist
 Figitumumab – antibodies against IGF-R1
 mTOR inhibitors – everolimus, rapamycin
 Retinoids – Fenretinide
 Biphosphonates
 TRAIL receptor agonists
 Gene therapy

23. THANK YOU