Ewing sarcoma was a feared cancer of childhood, with few survivors. The disease manifests as chronic increasing pain in flat bones or long bone diaphysis, with a lytic destructive lesion seen on imaging. The 5-year survival rate is 60-65% for non-metastatic disease and 25-30% for metastatic disease. Diagnosis involves biopsy showing small round blue cells staining positive for CD99. Treatment involves chemotherapy and surgery when possible, with improved local control using surgery versus radiation alone. The long-term survival and prognosis depends on presence of metastases at diagnosis.

1. BONE SARCOMA

2. OSTEOSARCOMA

3. Etiology
• most common sarcoma of bone in
young people
• tumor composed of a malignant
spindle cell stroma (background)
with malignant osteoblast that
produce tumor osteoid
• Factors: Mutation and genetic
abnormalities
• p53 (chromosome 17) and Rb
(chromosome 13)
• familial patterns
• Retinoblastoma and Li-Fraumeni
syndrome

5. Epidemiology
• Bimodal peak age incidence
• Crude incidence: 0.3 per 100,000 per year in United
States (roughly 900 per year)
• second decade (60%)
• age 30 (85%)
• Second peak age 55
• Postradiation osteosarcomas occur in bone that is in a
previously irradiated field  > 3 years
• Classic secondary osteosarcomas represent 5% to 7% of all
osteosarcomas  worse prognosis
• in relation to previous exposures or procedures as
well as in the presence of other primary diseases
• Paget’s osteosarcoma

6. Pathophysiology
• Local growth
• metaphyseal region of long bones
• Within or surface
• Metastases
• hematogenously
• Lymphnode  very late
• 15-20% with metastases
• Lung and bone
• Skip lesion
• Death  Superior vena cava obstruction, Pneumonia,
Hemorrhage into tumor, Sepsis, Chemotoxicity

7. Pathology • anaplastic (less differentiated),
• marked atypia and pleomorphic (widely
variable) nuclei, bizarre mitoses.
• areas of osteoblastic (osseous), fibroblastic
(fibrous), or chondroblastic (cartilage)
appearance
• malignant osteoid (wavy, lace-like,
uncalcified bone matrix produced by
malignant osteoblasts),

8. Grade
• To plan treatment and predict
prognosis
• Mostly high grade

9. STAGE
• stage IIB (high-grade and extracompartmental
Enneking/Musculoskeletal Tumor Society
Staging System)
• MSTS stage III

10. DIAGNOSIS
• Pain present or worse at night
• Pain that is worsening despite treatment
• Pain at rest
• Pain without history of trauma
• Antecedent pain, but worsened with minor injury
Pain  red flag
Second decade of life; middle to late adulthood
Distal femur (most common) >proximal tibia >proximal humerus
Metaphysis >diaphysis
Proximally in limb

11. DIAGNOSIS
• tender mass about the knee
• Mass is firm and fixed to bone, nonmobile.
• Warmth
• Fusiform swelling of extremity
• Dilated (ectatic) subcutaneous veins (large
tumors)
• Tenderness

12. Laboratory test
CRP and ESR to
differentiate with infection
Worse prognosis
elevated of:
• Serum lactate dehydrogenase
(LDH)
• Serum alkaline phosphatase

13. RADIOLOGIC
FEATURE
• destructive lesions
• malignant bone production
radiodensities
• Codman’s triangle
• Sunburst pattern

14. • Conventional Osteosarcoma
• Telangiectatic Osteosarcoma
• Small Cell Osteosarcoma
• Low-Grade Central Osteosarcoma
• Secondary Osteosarcomas
• Postradiation Osteosarcomas
• Various Bone Diseases
• Surface Osteosarcomas
• Parosteal Osteosarcoma
• Periosteal Osteosarcoma
• High-Grade Surface Osteosarcoma

15. STAGING WORK UP
• Appropriate staging work-up must include:
• History and physical
• Plain radiographs (of entire bone with joint above and below)
• Laboratory evaluation should include alkaline phosphatase and LDH
• Magnetic resonance imaging
• Determine the extent of the tumor intraosseously
• anatomic relationship to adjacent structures ■ Nerves ■ Vessels ■ Joints ■ Soft tissue
(e.g., muscles, skin)
• At least one sequence of entire bone (preferably coronal T1 images) to rule out skip
lesion in same bone (metastasis)
• Whole body scan
• CT scan of chest

16. TREATMENT
Chemotherapy and Surgery (Systemic and Local Therapy)
• doxorubicin (Adriamycin), cisplatin, high-dose methotrexate, and ifosfamide
• Side effect : mucositis, cardiomyopathy (doxorubicin), alopecia, myelosuppression,
nausea/vomiting, and relative immunocompromise, sepsis, and rarely even death.
Chemotherapy
Radiation therapy
• Limb salvage vs limb amputation
Surgery

17. OUTCOME
• Nonmetastatis 60% - 70% 5
years survival
• Important prognostic factors
• Metastatic disease
• Response to chemotherapy
• Tumor grade
• Subtype of osteosarcoma

18. EWING SARCOMA AND
PRIMITIVE NEUROECTODERMAL
TUMOR OF BONE

19. Ewing sarcoma was a feared cancer of childhood, with very few survivors
The 5-year survival rate is 60% to 65% for nonmetastatic disease and 25% to 30% for metastatic
disease.
The disease manifests as chronic increasing pain in the area of a lytic, destructive bone lesion of flat
bones and the diaphysis of long bones.

20. Etiology
• Unknown; associated with reciprocal translocation of chromosomes 11 and 22 (90% of cases),
which involves bands q24 and q12 of both chromosomes respectively.
• This results in a new chimeric EWS/FLI-1 fusion product, which produces the EWS/FLI-1 or MIC2
protein, stained for by the CD99 immunohistochemistry marker.

21. Epidemiology
• Third most common primary bone sarcoma (after osteosarcoma and chondrosarcoma)
• Three times less common than osteosarcoma
• Rare in African-Americans (0.5% of Ewing cases); peak incidence in the second decade of life
• Male : female ratio 1.3 : 1

22. • Sheets of monotonous, small, round blue
cells with indistinct cytoplasm
• Glycogen granules in the cytoplasm can be
seen after periodic acid Schiff (PAS) staining
or with electron microscopy.
• PAS-positive granules sensitive to digestion
with diastase
Pathophysiology

23. • The nuclear chromatin is finely granular,
with one to three small nucleoli per nuclei.
• CD99 immunohistochemistry marker stains
for EWS/ FLI1 fusion or MIC2 protein, which
is present in 90% of cases.
Pathophysiology

24. Classification
• Ewing sarcoma
• Most common, least differentiated, worst prognosis
• PNET
• More neural differentiation, better prognosis
• Askin’s tumor
• Primary in thoracopulmonary region, best prognosis

25. Diagnosis
Clinical Features
• Typical age at diagnosis: 5 to 30
years
• Rare in patients 5 years old; this
distinguishes it from metastatic
neuroblastoma
• Usually presents as a painful mass
• May be accompanied by fever
and weight loss, which are poor
prognostic signs

26. Diagnosis
Radiographic Features
• Location
• Typically originates in flat bones
(pelvis, rib, clavicle) or the diaphysis
of long bones (femur, tibia, humerus)
• Pelvis > femur > tibia > humerus
• Mostly, lytic destructive lesion with
‘‘onion-skinning’’ periosteal reaction
• 90% of patients have soft tissue mass.
• A destructive, lytic, diaphyseal lesion in a
child is two times more likely to be a
Ewing sarcoma than an osteosarcoma.
• A destructive, lytic, metaphyseal lesion in
a child is 12 times more likely to be an
osteosarcoma than Ewing sarcoma.
Anteroposterior pelvis radiograph of a 14-
year-old with a lytic destructive iliac lesion

27. Diagnosis
Computed tomographic scans demonstrating the lytic destructive changes of the ilium

28. Diagnosis
Anteroposterior radiograph of a
19-year-old with chronic hip
pain. Note the cortical
destruction and periosteal
changes.

29. Diagnosis
Magnetic resonance imaging shows
large area of soft tissue involvement
without a stress fracture. This was
diagnosed as a Ewing sarcoma of
bone and was treated with
chemotherapy, wide resection, and
bone grafting.

30. Diagnosis
Subtle distal fibula lytic lesion
without periosteal signs

31. Diagnosis
Magnetic resonance imaging shows
marrow replacement with tumor.
This was diagnosed as a Ewing
sarcoma.

32. Treatment
• Surgical Indication/Contraindication
• Traditionally surgery for Ewing
sarcoma was reserved for
expendable bones.
• Because of improved local control
with surgery compared to radiation
alone, most Ewing sarcoma patients
have surgical resection if adequate
margins are attainable and the defect
is reconstructable
• Spine and acetabulum are sites that
pose difficulties with resection and
reconstruction.
The patient was treated with wide resection and
chemotherapy. No reconstruction was performed, and
no instability of the ankle was noted on follow-up
examinations.

33. Treatment
• Most resections are reconstructed
with bone grafting procedures.
• Frequent diaphyseal location
lends itself to intercalary allograft
reconstruction.
• Young age (small skeletal size)
often requires expandable
prostheses if growth plate has to
be resected.

34. Result and Outcome
• Local relapse rate with radiation alone is
25%; with surgery and radiation it is 8%.
• It is unclear whether this difference
affects survival.
• Five-year disease-free survival rate for
non-metastatic Ewing sarcoma is 60%
to 65%.
• Recurrent disease after 5 years for
patients with nonmetastatic disease
is very unusual.
• Five-year survival rate for patients with
metastatic disease at the time of
diagnosis is 25% to 30%

35. Postoperative Management
• Early postoperative pain control is very
important.
• Patient-controlled analgesia
• Regional and epidural pain
management
• Early rehabilitation emphasizing range of
motion is critical
• Avoid weight bearing until after bony union
• Long-term antibiotics for segmental
allografts.

36. THANKYOU