1) Ewing's sarcoma is a rare type of cancer that affects bone or soft tissue. It was first described in 1921 and is thought to arise from stem cells or nerve tissue. 2) It most commonly affects children and young adults between 5-30 years old and presents with pain, swelling, fever, weight loss and anemia. Common sites are the lower limbs, pelvis, ribs, and spine. 3) Treatment involves chemotherapy, surgery, and radiation therapy. The standard chemotherapy regimen is VAC or IE. Prognosis is best if the cancer is localized and in younger patients, and worst if it has spread to other organs or the patient is older.

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