Ewing Sarcoma - Gottipati Vaishnavi, Group 2

EWING
SARCOMA
PRESENTED BY
GOTTIPATI VAISHNAVI
GROUP 2
Introduction
• Ewing sarcoma is a type
of pediatric cancer that forms in
bone or soft tissue.
• Ewing sarcoma represents 'classic'
Ewing sarcoma of bone, extra-
skeletal Ewing sarcoma, malignant
small cell tumor of the chest wall
(Askin tumor), and soft tissue-
based primitive neuroectodermal
tumors. Due to their similar
histologic and
immunohistochemical
characteristics, these sarcomas
originate from unique
mesenchymal progenitor cells.
Epidemiology
• 9% of primary bone sarcomas
• 4th most common primary malignancy of
bone but 2nd most common below zoyrs.
• Age Group - 95% patients age between 5 to
30 yrs
• of these most range between 5 to 15 yrs
• Sex - slight male predilection - 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)
Clinical Features
• Pain
• Swelling
• Fever
• Weight loss
• Anemia
• Raised ESR and CRP
• Leukocytosis
• And, symptoms depending on area of involvement
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 periosteum.
Radiology
• Plain radiographs of the affected area may
show destructive confluent '' moth-eaten"
lesions, "Codman triangle" of the elevated
periosteum, or multilayered "onion-skin"
periosteal reaction.
• Imaging of primary sites includes MRI with or
without CT, with contrast is of prime
importance as this allows for determination
of the extent of disease, operability, degree
of edema, and adjacent organ involvement.
• Other imaging methods, including CT thorax,
positron emission tomography (PET)/CT,
bone scan, and MRI of the spine and pelvis,
can also be used to detect possible lymph
node involvement or metastatic sites.
Hair-on-end periosteal reaction Onion skin formation
Involvement of long
bone with lamellated
appearance,
saucerisation, cortical
breach, periostitis
Metatarsal involvement with

moth-eaten appearance,
periostitis
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.

• Bone Scan –
Increase uptake
rarely cold spots
• Gallium scan
• CT scan - to assess
cortical destruction
For extra-osseous and
trans-articular spread
for chest metastasis
evaluation of response
to therapy
• MRI - for extra-osseous(T2) and intramedullary(T1) extent of lesion
metastasis
relationship with neurovascular structures
pre-operative planning (along with MR-angio)
response to therapy
• PET scan
• Biopsy - For definitive diagnosis with histopathology,immuno-

histochemistry, cytogenetics, karyotyping, RT-PCR
should include incision within area of specimen to be resected
best to avoid making a cortical defect when planning RT for local
control of disease (increased risk of pathological fractures)
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
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
•Ewings sarcoma under
light microscopy H&E
stain. Intensely stained
cells with scant
intercellular matrix,
pseudo-rosette formation
•Ewings sarcoma under
light microscopy H&E
stain. Intensely stained
cells with scant
intercellular matrix,
pseudo-rosette formation
Ewings Family of Tumors
• 1. Ewings
• 2. PNET
• 3. Askins
Similarity between Ewings and PNET

• Clinical features, radiology, light microscopy
• Chromosomal translocation t11:22)(q24:12)
• 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.
Differential diagnosis
• Osteosarcoma
• Lymphoma
• Leukemia
• Osteomyelitis
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
• increased LDH and ESR
• Size greater than 8cm
Enneking
system for
malignant
tumors
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.
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
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
Newer Therapies
• Nutlin - 3a → MDM-2 antagonist
• Figitumumab - antibodies against IGF-R1
• mTOR inhibitors - everolimus, rapamycin
• Retinoids - Fenretinide
• Biphosphonates
• TRAIL receptor agonists
• Gene therapy

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EWING

Metatarsal involvement with

Metastasis - Usually to Lungs(m.c.) and Bones.

• Biopsy - For definitive diagnosis with histopathology,immuno-

Similarity between Ewings and PNET

First Line therapy: VAC/IE. Given in cycles of 3 weeks

Second line therapy (relapse and refractory disease)

Pre-op - Indicated when narrow resection margins are expected.

Post-op - For gross or microscopic positive margin

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