Sarcoma

2. Introduction
Identified in 1921 by James Stephen Ewing
2nd most common malignant primary bone tumors of children
Ewing's Sarcoma Family of tumors (ESFT) :
Ewing's sarcoma(Bone -- 87%)
Extraosseous Ewing's sarcoma (8%)
Peripheral PNET(5%)
Askin's tumor

3. Epidemiology
2% of all childhood malignancy
Occurs most commonly in 2nd decade
80% occurs between ages 5 to 25
M:F
1.3:1 < 10 years
1.6:1> 10 years
Rare in African-Americans and Asians

4. Etiology
Neuroectodermal in origin
90% have t(11;22) (q24;q12) translocation
and rest t(21;22)(q22;q12) and t(7;22)(p22;q12).

5. Histopathology
Gross appearence :
Soft, gray white, occasionally shiny
Areas of haemorrhage and necrosis
Cortex may be partially or completely
destroyed and periosteum may be
reflected

6. Histological Features
One of many 'small round blue cell'
tumors seen in pediatrics
Poorly differentiated tumor
Unknown origin, Thought to be of
neural crest progenitor cells origin

7. Clinical Presentation
Pain & swelling of affected area
May also have systemic symptoms:
• Fever
• Anemia
• Weight loss
• Elevated WBC & ESR, LDH
Longest lag time in diagnosis for any
pediatric solid tumor (mean of 146
days)
Pathological fracture

8. Metastasis
High potential of metastasis
To lungs and bones
> 10% patients presents with bone metastasis - initial diagnosis
Metastasis to lymph nodes are rare

9. Routes of Spread
Direct extension into adjacent bone or soft tissue
Metastases generally spread through bloodstream
25% present with metastatic disease
• Lungs(38%)
• Bone(31%)
• Bone Marrow(11%)
Nearly all patients have micrometastasis at diagnosis, so all Need
chemotherapy

10. Differential Diagnoses
Osteosarcoma
Osteomyelitis
Eosinophilic granuloma

11. Approach to Diagnosis
Age
On plain Radiograph
• Morphology of bone lesion
• Location within the bone
• Periosteal reaction
• Zone of transition
• Cortical destruction
MRI & CT
Biopsy
Other investigation

12. Age
Most commonly in between 5-25
years of age, with a peak at 15 years

13. Skeletal Distribution

14. Plain Radiography
Irregular destructive lesion in diaphysis (Usually in lower extremity) , permeative
(76%) in its appearance with a wide zone of transition.
A delicate, laminated, onion skin or onion peel (57%) periosteal reaction
Cortical saucerization is an early and characteristic sign
Mixed lytic and sclerotic (40%) pattern predominating in tubular bones
Pathologic fracture (5%)
Occasional features : Codman triagles , Spiculated (Sunburst) or thick periostial
reaction.

15. Location within Bone
Mid-diaphysis : 33%
Metadiaphysis : 44%
Metaphysis: 15%

17. Permeative pattern
ill defined lesion
with multiple “worm-holes”
spread through marrow space
wide zone transition
implies aggressive malignancies
Round-cell lesions
Ewing's sarcoma
Leukaemia

18. Periosteal reaction (Periostitis)
A periosteal reaction is the formation of new bone in response to injury or other
stimuli of the periosteum surrounding the bone. It is most often identified on X-
ray films of the bones.
Non-specific reaction and will occur whenever the periosteum is irritated.
This may be due to malignant tumor, benign tumor, infection or trauma.
There are two patterns of periosteal reaction: benign and aggressive
Benign: None, Solid
Aggressive: Lamellated or Onion peel, Sunburst, codman's triangle

23. Zone of transition
Most reliable indicator in determining whether an osteolytic lesion is benign or
malignant .
“Narrow” zone of transition
• A small zone of transition results in a sharp, well-defined border and is a
sign of slow growth.
“Wide” zone of transition
• An ill-defined border with a wide zone of transition is a sign of aggressive
growth or malignancy.
• There are two tumor-like lesions which may mimic a malignancy and have
to be included in the differential diagnosis.
• These are infections and eosinophilic granuloma.

24. NARROW ZONE OF TRANSITION WIDE ZONE OF TRANSITION

25. Cortical Destruction

26. Cortical Destruction

27. Ewing's Sarcoma Osteosarcoma Ch. Osteomyelitis
Age 5-25 yrs (peak at 15 yrs) Double peak (1st - 10 to
20 yrs and 2nd - after 50
yrs)
At any age
Location within bone Diaphyseal,
metadiaphyseal
Metaphyseal Metaphyseal
Soft tissue involvement Extensive(80%) Extensive Less or no
Aggressiveness Very much Very much Not so

31. MRI
Essential tool to determine accurate local staging and in evaluating response to
treatment
Intra-medullary extention
Soft tissue extension
Skip lesions
Relation adjacent structures, vessels , nerves

32. MRI
MR imaging of Ewing's sarcoma of bone reveals- marrow replacement (100%)
and cortical destruction (92%) with an associated soft tissue mass in 96% of cases
T1 - weighted image : signal intensity of tumor is low to imtermediate
T1 post contrast (Gd) : heterogenous but prominant enhancement
T2 - weighted image : heterogenously high signal intensity

33. Axial T1-weighted (repetition time [TR] [msec]/echo time [msec] = 400/15) (d), contrast-
enhanced T1-weighted (617/15) (e), and T2-weighted (4766/34) (f) magnetic resonance (MR)
images demonstrate the lesion centered in the marrow canal (M) with circumferential soft-tissue
extension (S). The lesion is heterogeneously intermediate in signal intensity on both the T1-
weighted and T2-weighted images with diffuse enhancement on the postcontrast image.

35. In tumors like Ewing's sarcoma, lymphoma and small cell osteosarcoma, cortex may
appear normal radiographically, while there is permeative growth throughout Haversian
channels. These tumors may be accompanied by a large soft tissue mass while there is
almost no visible bone destruction.
MRI

36. CT Scanning
Bone destruction is best seen
Intramedullary space
Extraosseous involvement
In metastasis : Delenate the osseous extent of tumour
Also helpful in evaluating response to treatment

39. Axial (b) and sagittal (c) computed tomographic (CT) images of the fibula better depict both
the hair-on-end aggressive periosteal reaction (arrow) and Codman triangles (white
arrowheads in c) as well as the extensive involvement of the marrow. A pathologic fracture
is also seen. No large focal areas of cortical destruction are identified, but linear channels of
low attenuation are seen extending through the cortex (arrowhead in b, black arrowheads
in c), which allow continuity between the medullary and soft-tissue components.

40. Nuclear Imaging
Nuclear medicine studies show
increased radionuclide uptake at both
bone scintigraphy and gallium
scanning.
Blood flow, blood pool, and delayed
static images reveal increased
radionuclide uptake at bone
scintigraphy
Whole body radionuclide bone scan is
also of value in detecting recurrences
and metastasis

41. PET Scanning
FDG PET also shows increased radionuclide uptake in the primary lesion.
Coupled with the significantly improved spatial resolution of CT, FDG PET has
been shown to demonstrate high accuracy, sensitivity, and specificity in staging
and restaging of the Ewing sarcoma family of tumors .
FDG PET is superior to bone scintigraphy in identification of osseous metastases
in Ewing sarcoma (37%–88% sensitivity) and in primary bone sarcomas in general
(18% not evident at bone scintigraphy in comparison with FDG PET).

42. PET Scanning
Aggressive predominantly sclerotic marrow lesion of the mid left femoral shaft with
associated periosteal elevation and soft tissue extension. PET images reveal avid
tracer uptake and delineate surrounding soft tissue extension. No distant metastasis.

43. Angiography
Extensive soft tissue component and abnormal circulation is obvious.
Early arterial phase shows the reactive and a capsular vessel as well as extent of
the soft tissue mass

44. Other Investigations
Biopsy
• To confirm diagnosis
• FNAC
• Immunocytochemistry
For metastasis
• Chest X-Ray
Blood
• CBC
• ESR
• LDH

46. General Management
Effective local and systemic chemotherapy is necessary for cure
Induction chemotherapy preferred over starting the systemic and local therapy
Advantage of this approach :
• Evaluation of effectiveness of the regimen
• Decreases the vol. of local lesion for surgery or RT
• Some bone healing occurs during CT, diminish the risk of pathological fracture

48. Chemotherapy
All patients require chemotherapy
• Induction chemotherapy
• Maintenance chemotherapy
Effective chemotherapy has improved local control rates achieved with radiation
to 85-90%

49. Role of Surgery
Development of Innovative Surgical Techniques : Limb preservation and
Structural bone function preservation.
Chemo-Cytoreduction makes resection possible.
Local failure rates with RT in historical series : 9 - 25%
Concern over second malignancies.

50. Role of Surgery
Surgical Indications
• Expendable bone (fibula, rib, clavicle)
• Bone defect able to be recostructed with modest loss of function
• May consider amputation if considerable growth remaining
• After pre-op RT
Limb-salvage surgery is preffered
Curative surgery requires wide local excision and negetive margin
• Bony margins of at least 1 cm with a 2-5 cm margin recommend.
• Soft tissue at least 5 mm in fat or muscle with 2 mm through fascial planes.

51. Indications for RT: After induction chemotherapy
Definitive Radiation Therapy :
• Tumors where surgery is Impossible
• For skull, face, vertebrae or pelvic primary
• where only an intra-lesional resection is achievable
• Patient with poor Surgical risk
• Patient refusing surgery
Note : Surgery is preferred where wide or marginal resection is possible

52. Progonostic Factors

54. Survival