Ewing's sarcoma is a rare type of cancer that develops in bone or soft tissue. It is the second most common primary bone cancer in children and adolescents between 10-20 years old. The cancer presents with local swelling and tenderness at the affected site, most commonly the diaphysis of long bones. Metastasis is often present at diagnosis, with the lungs being the most common site. Diagnosis is confirmed through histopathological or cytogenetic testing. Treatment involves neoadjuvant chemotherapy followed by local tumor control through surgery or radiation therapy, along with adjuvant chemotherapy. Five-year survival rates have improved to around 70% with current multi-agent chemotherapy regimens.

1. Dr. Manish Shrestha
Orthopaedic Surgery

2. Dr. James Ewing
Ewing’s Sarcoma

3. Introduction
 Named after James Ewing who identified it in 1921.
 Was originally termed as diffuse endothelioma or
endothelial myeloma.
 Currently- part of peripheral primitive
neuroectodermal tumors as it shares common
cytogenetic translocation of chromosome 11 & 22.

4. Introduction
 Ewings sarcoma is a round-cell tumor typically
arising in the bones, rarely in soft tissues, of children
and adolescents.
 Most unfavorable prognosis of all primary
musculoskeletal tumors.
 Prior to the use of multi-drug chemotherapy, long-
term survival was less than 10%.

5.  Ewings sarcoma family of tumors:
 Ewing’s sarcoma
 Extraosseous Ewing’s sarcoma
 Peripheral PNET
 Askin’s tumor.

6. Prevalance
 Second most frequent bone sarcoma after
osteosarcoma in patients younger than 20 years.
 2% of cancer in childhood.
 Caucasians are more frequently affected than
asians, africans and african-americans rarely
affected.
 Common age- 10 – 20 years.
 M>F - (M:F = 1.4 : 1)

7. Sites
 Long bones diaphysis
involvement is
common.
 Ribs – frequently
manifests with
pneumonia or pleural
effusion.

9. SPREAD
 Generally spread through bloodstream
 Direct extension into adjacent bone or soft
tissue.
 Micromets is common in all patients.

10.  Approximately 50% of patients who present
with metastases have pulmonary
involvement.
 25% - bony metastases.
 20% - bone marrow involvement.
 Liver and lymph node metastases are rare.

11. staging
 No specific staging system for Ewings
sarcoma
 The AJCC staging systems for bone or soft-
tissue sarcomas may be used.

14. Pathology
 Poorly differentiated tumor
 Unknown origin.Thought to be of neural
crest progenitor cell origin.

15.  Gross
 whitish-gray soft tissue mass arises in the marrow
spaces of the affected bone.
 Necrotic and hemorrhagic areas are frequent.
 Periosteum elevated and is often perforated.
 Almost always a large soft tissue mass extending well
beyond the bony boundaries.
 Not encapsulated and invades the surrounding
muscle.

16. Gross & Microscopy

17.  Microscopic
 Compact sheets of small polyhedral cells with pale
cytoplasm and ill-defined boundaries.
 Nuclei- uniform, round or oval, and contains scattered
areas of chromatin.
 Cytoplasm is scant
 Presence of glycogen in the cell

18.  Occasional rosette or pseudorosette
formation may be present.
 Must be distinguished from neuroblastoma,
non-Hodgkin lymphoma and
rhabdomyosarcoma.

19. Cytogenetics
 80 to 90 % patient s with Ewing sarcoma have
a translocation of chromosomes 11 and 22 or
chromosomes 21 and 22.

20. Clinical features
 Local pain and swelling of affected area.
 Tender local mass is invariably present.
 Stiffness – common in involvement of long bone.
 Limp

21.  Weight loss
 Fever
 Anemia
 Occasionally presents with pathological fractures.
 Other symptoms depend on the site of the lesion.

22. Investigations - Radiographic
findings X-RAY
 Characteristic but not pathognomonic
 Permeative lesion with mottled rarefaction of the
medullary cavity and invasion through the overlying
cortex, reflecting rapid bone destructon.
 Periosteal new bone formation- laminated “onion
peel”.

23.  Moth eaten lesion
 Lytic or mixed
lytic-sclerotic
areas
 Codman’s triangle

25.  Radiographic findings resemble
 Osteomyelitis
 Osteosarcoma
 Histiocytosis
 Wilms tumor
 Lymphoma
 Metastatic neuroblastoma

26.  MRI is useful to determine the extent of the
lesion within the bone and adjacent soft tissue.
 Dynamic MRI have made it possible to use to
access the response to chemotherapy.
 CT – to search for metastatic disease in the
chest.

27.  Bone scan - to search for other areas of bone
involvement.
 RT-PCR – most definitive test by
demonstration of chromosomal translocation
t(11;22)

29.  Diagnosis is usually made from histologic study
of tissue sections by open or needle biopsy.
 And it is best to avoid making a cortical defect in
a long bone , because if radiation is chosen for
local control, the chances of pathologic fracture
are greater.
 Frozen section biopsy, to ensure adequate tissue
is obtained for histologic studies.

30.  The histologic differential diagnosis –
 Neuroblastoma
 Rhabdomyosarcoma
 Malignant lymphoma
 Small cell osteosarcoma
 Wilms tumor
 Desmoplastic small cell tumor.

31. Laboratory tests
 CBC
 Alkaline phosphatase
 LDH

32. prognosis
 With the advent of adjuvant chemotherapy
and proper local control, the outlook has
been considerably better
 approximately 70 % 5-year event free
survival rates
 Large Central Lesion (esp., Pelvis) – worse
outcome than those with distant tumors.

34. Prognostic factors
 Unfavourable factors
 Distant metastasis
 Older than 15 years
 Size larger than 8cm.
 Central lesions( pelvis or spine).
 Poor response to chemotherapy

35.  Favourable prognosis
 Distal extremity
 <8 cm in greatest diameter or <20o ml estimated
volume.
 Localized
 Absence of radiographically identifiable soft tissue
extension.

36.  Fever , weight loss, anemia and elevated
WBC, ESR, LDH indicate more extensive
disease and a poor prognosis.

37. Treatment
Multidisciplinary approach
 Includes chemotherapy, surgery, radiation
therapy.
 Depends on –
 Where in the body the tumor started.
 Where the tumor has spread.
 The size of the tumor.
 The result of the treatment.

38. CHEMOTHERAPY
 With Intensive chemotherapy reported long-term survival
rate is 60-70%.
 Can be given before surgery(neoadjuvant) or after(adjuvant) .
 Current drugs
 Doxorubicin(DXR),
 Cyclophsophamide (CPA),
 Vincristine(VCR)
 Actinomycin-D (ACT)
 Ifosfamide (IFM)
 Etoposide(VP16)

39.  VACD-IE regimen – the standard therapy for
localized ewings sarcoma . 10 year event-free
survival is around 50%.- first line therapy
 Second line therapy-
 Cyclophosphamide and topotecan
 Temozolomide and irinotecan
 Ifosafamide and etoposide
 Ifosfamide, etoposide and carboplatin
 Docetaxel and gemcitabine

40.  Preoperative 4 to 6 cycles of multiagent
chemotherapy is indicated
 Decrease in tumor size
 Decrease in LDH level
 Tumor necrosis
 Efficacy of limb salvage surgery
 Facilitates disease free survival

41.  Postoperatively, additional cycles of the same
regimen is given.
 Total 48 weeks.
 Chemotherapy in every 2 weeks demonstrated
improvement in event free survival than
chemotherapy in every 3 weeks.

42. RADIATION THERAPY
 Effectively controls local disease , when combined with
chemotherapy.
 Usual dose- 55.8 to 60 Gy.
 Adequate dosages result in local control in 53 to 86 %.
 Studies shows no difference in local control with 2cm
margin compared to whole bone irradiation.

43.  Definitive radiation therapy:
 Where resection is impossible
 Where only intra-lesional resection is achievable
 Patient refusing surgery
 Patient with poor surgical risk.

44. Problems with radiotherapy
 In younger children with lower extremity primary tumors,
irradiation of growth plates can lead to limb length
inequality.
 Fracture - if bone is irradiated.
 Late occurence of a secondary malignancy in the
involved bone.

45. Surgical treatment
 Resection of tumor. Best done after induction
chemotherapy, which often decreases the size of
the soft tissue mass.
 To avoid secondary malignancies.
 Margins and histologic necrosis in the resected
specimen are examined.

46.  If margin is positive postoperative radiation is
advised but the dose is lower than before .
 Amputaion – in bulky tumors that do not
respond to chemotherapy and irradiation.

47. Metastatic ewing sarcoma
 Worse prognosis.
 Survival rates – approximately 25% at 5 years.
 Addition of ifosfamide and etoposide to
vincristine, doxurubicin, cyclophosphamide
and actinomycin D would improve outcome.

48. New Treatment
 Chemotherapy with stem cell transplant
 Targeted therapy- monoclonal antibody
therapy

49. surveillance
 Physical examination, chest x-ray:
 Every 2-3 months
 Increase interval after 24 months
 Annually after 5 years
 CBC
 Bone scan

50. Relapse
 Early- less than 2 years:
 Change chemotherapy
 Late – more than 2 years:
 Continue the previously used CT.

51. Summary
 Second most common primary malignant bone tumors in children.
 Common Age group – 10-20 years (M>F)
 Commonly involves diaphysis of long bone.
 Presents with local swelling and tenderness.
 Metastasis is usually present at the time of presentation.
 Diagnosis is confirmed by histopathological studies or cytogenetic studies.
 Treatment modalities includes Neoadjuvant therapy followed by local control
of the tumor with surgery/radiotherapy and maintainence with adjuvant
chemotherapy.
 5-year event free survival has incresed from 10% to 70% with the advent of
multi-chemotheraputic agents.

52. Thank you