1. Ewings Tumor

2. History:
 1928 James Ewing described a rare lesion
 Diaphysis of long bones
 Childhood
 Febrile attacks,anorexia, weight loss & anaemia
 Rapidly involving other parts of skeleton
 Radiosensitive
 Histologically –endothelial elements in marrow

3.  Willis – All these tumors were not Ewing’s but
 Neuroblastomas
 Reticulum cell sarcomas
 Metastatic tumors

4. Ewing’s Sarcoma
 Epidemiology:
 4th. m.c. primary malignancy of bone
 2nd. m.c. in age < 30 yrs.
 Incidence < 1/ million / year
 9% of primary malignancies of bone
in the Mayo Clinic series.

5.  Age –
 Wide age range from infants to elderly
 m.c. 5 – 15 yrs.
 Male slightly more than females.
 Very rare in Africans

6. Location:
 M.c. in
 metaphysis of long bones ( often extending into
diaphysis),
 Flat bones of shoulder and pelvis.
 Rarely in spine or small hand & foot
bones.
 Long bones
 Tibia > fibula > humerus > femur.

7.  Spread –
 Whole of the skeleton.
 Regional lymph nodes.

8. Clinical features:
 Pain – Universal complaint
 Insidious in onset, long standing, intermittent
attacks, responding to analgesics.
 Often H/O preceding trauma.
 Slow growing tumor
 in relation to the shaft of long bones.

9.  Delay in diagnosis Av. 34 weeks
 Patient delay – 15 weeks
 Physician delay 19 weeks – Importance of Xrays & rpt. X
rays to compare.
 During attacks of pain tumor size may enlarge visibly.

10. Other clinical features:
 Fever, erythema & swelling ~ Osteomyelitis
 Skin – not involved unless surgical exploration done.
 Pathological # seldom.
 Later stage – multiple deposits in skull, ribs, sternum,
pelvis & other long bones – cachexia & sec. Anaemia.

11.  Vertebral involvement –
 severe root pain or paralysis
 Death –
 Metastatic involvement of lungs.

12. Radiological appearance:
 X-rays:
 Classically
 Destructive lesions, diaphysis
long bones, onion peel
appearance.
 Reality
 Metaphysis long bones frequently extending
into diaphysis.

13.  Diffuse rarefaction towards center of shaft extending
to considerable area peripherally.
 Flat bones:
 Non-specific destructive lesions & large
adjacent soft tissue mass.

15.  Early stage:
 Condensation
 Later
 Reactive irritation – Onion skin layers
 Last stage
 Gross tumor formation, destruction of
bone, pathological #s.

16. 

17. 

18.  MRI:
 Taken of entire bone involved
 Extent of diseased bone
 Soft tissue involvement

19. Other Investigations:
 Blood Ix:
 WBC Leukocytosis,
 ESR
 CRP
 LDH ~ suggestive of infective cause.
 FNAC – resembles Pus.

20.  Base line X ray & CT chest –
 m.c. site of metastasis
 Bone Scan
 Bone marrow aspiration – routine
 R/O diffuse systemic disease
 USG abdomen
 liver & spleen.

21. Pathology:
 Begins in - Marrow (Mid shaft)
 Gross –
 Color - Greyish-white
 Areas of necrosis & hemorrhage with cyst formation.
 Lamellae destruction.

22.  Medulla Haversian canals Surface.
 Sub periosteal compensatory layers of new bone are
deposited only to be destroyed Onion Skin
appearance.

23. Histology:
 Microscopic features – non
specific.
 Intensely cellular
 Cells –
 Usually one type
 Blue,
 Small, round & polyhedral
 Arrangement – solid
cords or sheets.

24.  Intercellular substance – minimal
 Necrosis
 Remaining cells arrange around the central blood
vessel – perithelioma.
 Nuclei – prominent
 Mitosis - frequent

25.  Rossette arrangement with central fibril
(Neuroblastoma)
 Pseudorosette (without fibril) more common.
 Despite bone destruction
 Giant cells/ osteoclasts are not found
 Nor new bone
 Except sub periosteal
deposits.

26.  Vessels & lymphatics Tumor emboli tumor
spread.

27. Cytogenetics &
Immunohistochemistry:
 To differentiate from other small blue cell tumors.
 m.c. translocations in >90% cases t(11;22)(q24;q12)
diagnostic of Ewing’s.
 Other diagnostic translocations include
 t(21;22)(q22;q12) &
 t(7;22)(p22;p12)

28. IHC
 Staining for MIC2 gene products – Specific
 PAS + usually (high intracellular glycogen).
 Reticulin – ( c.f. lymphomas)

29.  Histological D/D
 Lymphomas – PAS -, Reticulin +,
 Embryonal rhabdomyosarcoma – desmin , myoglobin,
muscle specific actins +
 Hemangeopericytomas – Factor VIII +
 Small cell metastatic carcinomas & Melanomas –
Cytokeratin +

30. Other D/D:
 Chronic Osteomyelitis
 Metastatic Neuroblastoma
 Histiocytosis
 Rarely Osteolytic Osteosarcoma

31. Treatment:
 Adjunct or Neoadjunct Chemotherapy or both – for
distant metastasis.
 Local Treatment: (Controversial)
 Highly radiosensitive
 Wide resection
 Decreases local recurrence to <10%
 Increases overall survival

32.  Large, central, unresectable – Radiation
 Small, more accessible lesions – Surgery
 Choice is individual based.
 Repeat Staging studies
 after neoadjunct chemotherapy.
 Repeat X rays - ossification
 Repeat MRI - soft tissue mass.

33.  At this stage –
 If Lesions can be resected with wide margins & an
acceptable functional deficit – SURGERY.
 If not – RADIATION.
 Radiation:
 Marginal Resection or
 Contaminated wide resection.

34.  Treatment Plan:
 After long D/W patients & parents
 Include expected function after amputation, limb
salvage & radiation
 Inherent short & long term risks with each option.
 Disease relapse – and its prognosis.

35. Survival rates :
 Long term survival rates reported from most studies –
60-70%
 Before the use of chemotherapy – 10 %

36. Prognostic factors:
 Location & Size of primary lesion.
 Older age of presentation & male gender.
 Distant metastasis – worst prognostic factor with 20%
long term survival even with aggressive therapy and
surgery.
 Disease relapse
 Time to relapse

37.  Histological grade is of no significance as ALL
EWING’S SARCOMAS ARE CONSIDERED TO BE
HIGH GRADE.
 Fever, anemia, WBC, ESR, LDH indicate extensive
disease so worse prognosis.
 Aberrant p53 expression & histological response to
chemotherapy.