Ewing’s sarcoma

Described by James Ewing in the year 1921/28

Defination:
Ewing’s sarcoma is a distinct round cell neoplasm arise from
reticuloendothelial tissue of marrow cavity of a skeletally immature
long bone

Epidemiology:
 4th most common primary malignancy of bone,
 2nd most common (after osteosarcoma) in patients younger than
30 years
 Most common in patients younger than 10 years of age.

Incidence:
 Around 9% of all primary malignant of bone
 Age: 5-25 years commonly in 2nd decade, most common <10 yr
 Race: Rare in african
 Sex: Male: Female (1.5: 1)
 Site: Mainly long bones – tibia, fibula, clavicle, No bone is
immune
Flat bones – pelvis, skull, ribs
Rarely – spine, small bones of hand & feet
 Location: Diaphysis of skeletally immature long bone

Clinical feature:
A. Symptom
a. Pain
i. Usually the onset is insidious
ii. initially mild and intermittent throbbing pain
iii. Exacerbation and remission
iv. Later pain become severe and constant
v. worst at night (night cry)
b. Swelling
i. Overlying skin is red, oedematous, with dilated
vein
ii. Warm
iii. Tender
iv. Fixed to underlying bone
c. Constitutional symptom
i. Fever - 101-105
ii. Anaemia
iii. Erythema
iv. Leukocytosis – 20000-40000
v. ↑ ESR
 vi. ↑ CRP
d. H/O trauma may draw attention towards the pathology
B. Symptom of metastasis – metastasis occurs
a. 1st in bone – skull, vertebra, ribs
b. then lungs
via lymphatic and blood stream

Differential diagnosis
1. Subacute osteomyelitis --------- Blood culture
2. Osteosarcoma --------- S. Alkaline phosphatase , Biopsy
3. reticular cell sarcoma --------- Biopsy, no staining with PAS
[does not contain glycogen]
4. Metastasis of adrenal neuroblastoma – urine contain VMA
(vanillyl mandelic acid]
5. Syphilitic osteoperiostitis – blood test for syphilis

Pathology:
A. Macroscopic:
a. The tumour is lobulated , grayish white (like brain) and
often fairly large.
b. If haemorrhage has occurred into it looks red (like
redcurrant jelly).
B. Microscopic:
a. sheets of small dark polyhedral cells with no regular
arrangement and no ground substance
b. Nucleus is larger (twice than lymphocyte) which are
hyperchromatic
c. A ring of tumor cell form pseudorosette Rosette – tumor
d. No interstitial stroma can be identified cells surrun - ding a
e. No multinucleated giant cell central, acellular region
 Pseudorosette –
f. Area of hemorrhage may found central part is not a part
g. Staining - They are PAS positive, silver stain -ve

Pathogenesis
 Tumor invades through the Haversian canals
causing
- Periosteal elevation and new reactive bone formation
 The process goes on and on giving “Onion peel”
appearance in x ray
 Ultimately tumor breaks through the periosteum
giving rise to soft tissue tumor in which space - reactive bone
formation is seen
 Since the tumor traverses through Haversian canal,
occlusion of nutrient vessels occur
 i. If occlusion is partial – scleosis in supplied area
(Ca ++ turn over is dreaded due to decreased blood
supply)
ii. If occlusion is complete – osteolytic area due to
osteonecrosis
Investigation –
1. Blood biochemistry
i. Hb% - ↓ , ESR - ↑
ii. CRP – markedly increase
iii. Leukocytosis
2. Plain radiograph
A. In a typical case,
i. there is mostly a osteolytic lesion in the
medullary zone of the mid- diaphysis of a long bone
ii. Onion-peel appearance – cortical destruction
and new bone formation appears as fusiform layers
of bone around the lesion
B. In atypical presentations,
i. The pattern of bone destruction varies from
permeative pin head sized holes, moth eaten, rotten
wood to pure lytic. Hence, it can mimic a variety of
bone tumors both benign and malignant
ii. It may have a predominant soft tissue
component with little cortical destruction, and may
resemble a soft- tissue sarcoma.
iii. the tumour may be located in the
metaphysis, and may be confused with osteomyelitis.
iv. as a late and advanced feature of the tumor.
Codman’s triangle sun burst appearance may be
present.
3. X – ray chest – to see pulmonary metastases
4. Bone scan – to show skip lesions
5. CT scan – to see extant of tumor, pulmonary metastasis
6. MRI – to see extant of tumor
7. Biopsy – to confirm the diagnosis and staging

Treatment:
1. Radiotherapy: it has a dramatic effect on the tumour
Highly sensitive.
It is called melting tumor
but recurrence is common
2. Chemotherapy: is much more effective,
offering a 5-year survival rate of about 50%
VCA vincristin, adriamycin and cyclophosphamide
3. Surgery: Amputation
  Primary radiation followed by amputation – 2 years survival rate
is 15%
 Combination of Radio+Chemo+amputation – 2-3 years survival
rate is 50 – 70%

The best results are achieved by combination of these methods

a) In less accessible site
- Raditherapy followed by local excision followed by Tripple
chemotherapy
for 1 year
b) In favorable site
- Neoadjuvent chemotherapy followed by wide excision
followed by
adjuvant chemotherapy for 1 year
- Postoperative radiotherapy may be added if the resected
specimen is
found not to have a sufficiently wide margin of normal
tissue.

Prognosis Ewing's tumour is

of Ewing’s the commonest malignant tumour of flat bones.
sarcoma
** Ewing's tumour is the commonest malignant bone tumour which has
multi-centric
It depends origin.
on severeal factors
1. Age – older child (12 -150
- bad prognosis
2. Sex – Male
– worst prognosis
3. Site of tumor – pelvic bone
– worst prognosis
4. Size of primary lesion – Large lesion
– bad prognosis
5. Metastases – distant metastasis
– worst prognosis

a. Prognosis without metastases

Radio + chemo + surgery – 5 years survival rate – 70%
Primary radiation + amputation – 2 years survival rate – 15%

b. Prognosis with metastasis

Pt with local recurrence – 5 years survival rate - 20%
Pt with distant metastases – 5 years survival rate – 10%

*** Pt who relapses within 1st year after primary treatment has a worst
prognosis than
those of more disease free interval
*** Presence of symptom 3-9 months before clinical diagnosis
*** Metastases occur within 6th month after diagnosis

Viva related
Slide identification point
1. Small rounded loosely packed cells [proliferated
from undifferentiated mesenchymal cell]
2. There are nest of tumor cells with intervening
fibrous septa
3. Polyhedral cell with no regular arrangement
with no ground substance
4. Have rounded centrally placed nuclei with
indistinct cytoplasm

Q. Difference between Reticulum cell sarcoma and Ewing’s

Sarcoma
Ans. Though both are histologically round cell tumor.
Ewing’s sarcoma has no ground substance which contain
reticulum fibre but sheet of cell rich of glycogen. So it is PAS + ve
but Silver stain – ve.
 On the other hand Reticulum cell sarcoma are reticulin +ve
(Silver
stain + • Ewing’s stains for glycogen positivity by PAS. [Glycogen rich cell;
ve) but no reticulum fibre]
• In reticulum cell sarcoma silver stain is positive.[reticulum fibre;
PAS –
ve.

Q. Other Round cell tumor

Ans. 1. Reticulum cell tumor (Non – Hodgkin’s sarcoma)
2. Metastatic neuroblastoma
3. Eosinophilic granuloma

Q. Difference between Osteosarcoma & Ewings sarcoma

Ans.
Osteosarcoma Ewing’s sarcoma
Arise from Mesenchymal origin Endothelial cells in
bone marrow
Age Bimodal – 2nd decade 2nd decade or earlier
& after 50
years(paget’s)
Site Metaphysis Diaphysis
Constitutional Less marked More marked
symptom
X ray – Sunray appearance & Onion peel
characteristic feature Codman’s triangle appeerance
Microscopical Malignant stromal Round cell stroma
characteristic feature tissue showing osteoid
formation
Intercellular Present Less or absent
substance
Soft tissue component Less Enormous
extraosseous
Metastasis Lung Bones and lungs
May excide physeal Never excides
plate
Radiosensitivity Less More (melting tumor)
S.Alk phospatase,LDH Raised - prognostic Not so
Prognosis Negatively better Worst (Fatal tumor)

Q. What is the importance of grading of Ewing sarcoma

Ans – It has no importance in prognosis as every Ewing sarcoma
regarded as high grade malignancy
Q. What are the drugs used in neoadjuvent chemotherapy
Ans – VCA
1. Vincristine
2. Cyclophosphamide
3. Adrenomycin

Q. Characteristic of swelling in ES
Ans. Swelling
1. Fusiform or diffuse
2. Overlying skin is warm and red
3. Dilated vein over skin

Q. What are the primary malignant tumor

Ans –
1. Multiple myeloma
2. Osteosarcoma
3. Ewing’s sarcoma
4. Condrosarcoma
5. Fibrosarcoma

Q. Young child reconstruction by prosthesis wrong or right

Ans – wrong as prosthesis can not be adopt with growing bones

Q. Amputation done where to give radiotherapy

Ans.
Indication of radiotherapy
a. Pre operative
i. where tumor resection is less accessible
ii. When marginal resection expected
iii. Patient refuse surgery ???
b. Post operative
i. After wide resection still contaminated margin [specimen
– histology]

Q. Metastesis present, amputation needed or not

Q. Common swelling around knee

Ans –
1. Acute swelling of entire joint
 i. Post traumatic haemarthrosis
ii. Bleeding disorder
iii. Acute septic arthritis
iv. Traumatic synovitis
v. Aseptic non traumatic synovitis
1. Gout
2. Pseudogout
2. Chronic swelling of
a. entire joint
i. Arthritis
ii. Synovial disorder
1. Synovial chondromatosis
2. Pigmented villonodular
synovitis
b. Infront of joint
i. Prepatellar bursitis (House maid’s
knee)
ii. Infrapatellar bursitis ( Clargyman’s
knee)
c. Back of knee
i. Semimembranosus bursitis
ii. Popliteal cyst
iii. Popliteal aneurysm
3. Bony swelling around knee
a. Benign
i. Cartilage capped exostosis
ii. Osgood schlater disease
iii. ABC
iv. Simple bone cyst
v. GCT
b. Malignant
i. Ewing’s sarcoma
ii. Osteosarcoma
iii. Malignant GCT

Q. Reticulum cell where to found

Ans: Bone Marrow

Marrow itself Supporting marrow

structure
(Reticuloendothelial tissue)
- Myeloma - Ewings tumor
- Round cell sarcoma
- Haemangioendothelioma
Ewing’s tumor /undifferentiated round cell
 Note: Onion peel appearance
seen in.
• Ewing’s sarcoma
• Osteomyelitis
• Osteosarcoma
• Malignant lymphoma
Unfavorable prognostic features are: appearance and
• Male patients.
• Humerus if involved.
• Pelvic bones if involved.
• Distant metastasis.
Quick facts of Ewing’s sarcoma
• Rare primary malignant tumor.
• Common between 5 and 15
years.
• Tumor of the diaphysis.
• Clinically may mimic acute
osteomyelitis.
• X-ray shows moth-eaten
onion peel appearance.
• Tumor is highly cellular.
• Highly radiosensitive (melts like
snow).
• High rate of recurrence.