osteosarcoma

1. Osteo = bone/osteoid tissue
Sarcoma = malignant tumour of connective
tissue
02/04/12
Dr. Athish Jaims
1

2. What is osteosarcoma ?
⚫ Highly malignant tumor of mesenchymal origin.
⚫Spindle shaped cells that produce osteoid.
⚫2nd most common primary malignant bone tumor
after MM.
2

3. Epidemiology
3
⚫Incidence – 1 to 3 per million per year
⚫Any age
⚫But 75% in 12-25yrs of age
⚫Almost equal in both sexes, slightly more in
males.

4. Epidemiology
4
⚫Associated syndromes
o
o
o
Hereditary form of retinoblastoma
Li-Fraumeni syndrome (p53)
Rothmund-Thomson syndrome
(8q24)

5. Pathogenesis
5
⚫Unknown
⚫Modal incidence correlates with rapid bone
growth
⚫Radiation >2000 rads
⚫Chemicals – chlorantherene, Be compounds

6. Gross pathology
⚫Arise from multipotent mesenchymal cells
⚫Mixture of osteoid, fibrous, cartilaginous, necrotic,
hemorrhagic, cystic areas
⚫Destruction of cortex
6

7. Gross pathology
⚫Metaphyseal, Central.
⚫ Extension into medullary cavity and subperiosteal
extension.
⚫Restricted bu periosteun and epiphyseal plate, but
eventually crosses it
⚫ Reactive periosteal
new bone formation
⚫Metastasis – lungs
7

8. Microscopic appearance
⚫Stroma - Malignant connective tissue with anaplastic
spindle cells
⚫Matrix of osteoid/fibrous/cartilagenous tissue
8

9. Classification
9
⚫PRIMARY or SECONDARY
⚫PRIMARY OSTEOSARCOMAS are
 Conventional /classic osteosarcoma (high
grade, intra medullar y)
 Low-grade intramedullary osteosarcoma
 Parosteal osteosarcoma
 Periosteal osteosarcoma
 High-grade surface osteosarcoma
 Telangiectatic osteosarcoma, and
 Small cell osteosarcoma.

10. Classification
10
⚫ SECONDARY OSTEOSARCOMAS
⚫ Osteosarcomas occurring at the site of another disease
process.
⚫ more common in >50 years of age
The most common causes are
Paget disease
Previous radiation treatment
Other associated conditions are
Fibrous dysplasia
Bone infarcts
Osteochondromas
Chronic osteomyelitis
Dedifferentiated chondrosarcomas
Osteogenesis imperfecta

11. Classic High Grade
Osteosarcoma
⚫These aggressive, high-grade tumors begin in an
intramedullary location, but may break through the
cortex and form a soft-tissue mass.
⚫The histologic hallmark - malignant osteoblastic
spindle cells producing osteoid,presence of woven
bone with malignant appearing stromal cells
⚫subtypes -
o osteoblastic,
o chondroblastic and
o fibroblastic 12

12. Skeletal distribution
⚫Distal femur
⚫Proximal tibia
⚫Proximal humerus
(sites of rapid bone growth)
⚫ others
Metaphyseal(89%)>diaphyseal(10%)>epiphyseal(1%)
12

13. Clinical Presentation
⚫Pain– progresssive pain
due to microinfarction
night pain in 25 %
⚫Swelling - Palpable mass is noted in up to 1/3
of patients at the first visit
Fever, malaise or other constitutional symptoms
are not typical of osteosarcoma
13

14. Evaluation
⚫Suspected diagnosis by history and physical
examination
⚫Supported by investigations
14

15. Plain X-ray (Most valuable)
⚫sclerotic
⚫Lytic Mixed (most
common)
15

16. Plain X-ray
⚫Lesions are usually permeative
⚫Associated with destruction of the cancellous and
cortical elements of the bone
⚫Ossification within the soft tissue component, if
tumour has broken through cortex
⚫Intra medullary
⚫Borders are ill defined
16

17. Plain X-ray
⚫ Periosteal reaction may appear as the characteristic Codman triangle.
⚫ Extension of the tumor through the periosteum may result in a so-
called “sunburst” or “hair on end” appearance.
17

18. Other investigations
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⚫MRI
⚫CT
⚫ Angiogram
⚫Bone scan
⚫Laboratory studies
⚫Biopsy

19. MRI
⚫best to detect extent into bone and soft tissues
19

20. CT
⚫Not of much use
⚫ CT chest to detect lung metastasis
20

21. Angiogram
• Determine vascularity of the tumour
• Detect vascular displacement
• Relationship of vessels to the tumour
21

22. Bone scan
⚫A bone scan should be obtained
to look for skeletal metastases
or multi focal disease
⚫Thallium scan - Monitor effects of chemotherapy
Detect local recurrence of tumor
22

23. laboratory studies
23
Full blood count, ESR, CRP.
 LDH (elevated level is associated with
poor prognosis)
ALP (highly osteogenic)
Platelet count
Electrolyte levels
Liver function tests
Renal function tests
Urinalysis

24. Biopsy
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⚫to conform the diagnosis.
⚫Types



Fine needle aspiration
Core needle biopsy
Open incisional biopsy

25. Enneking staging system
25
The staging system is typically depicted as follows
⚫Stage I: Low grade tumors
I-A intra compartmental
I-B extra compartmental
⚫Stage II: High grade tumors
II-A intra compartmental
II-B extra compartmental
⚫Stage III: Any tumors with evidence of
metastasis

26. Differential Dx
⚫Giant Cell Tumor
⚫Chondrosarcoma
⚫Fibrosarcoma
⚫Aneursymal Bone Cyst
⚫Ewings sarcoma
⚫Osteoblastoma
⚫Metastasis
⚫Lymphoma
⚫Osteomyelitis
⚫Chondroblastoma
⚫Post traumatic callus
⚫Other variants 27

27. Surface osteosarcoma
⚫Parosteal
⚫Periosteal
⚫High grade surface osteosarcoma
27

28. Parosteal
⚫5% of osteosarcomas
⚫Posterior metaphysis of
distal femur
⚫Arises from surface,invade
medullary cavity in late stages
⚫Tends to encircle bone
⚫Low grade,Slow growing
⚫Large ossified mass in centre
28

29. Periosteal
n
⚫Arises from surface of diaphysis
⚫Most commonly femur and tibia
⚫Characterized by bony spicule formatio
perpendicular to shaft
Strands of osteoid producing spindle cells
radiating between lobules of cartilage
⚫Sunburst
⚫Low grade
29

30. High grade surface
⚫Very rare
⚫Age group 20-30’s
⚫Appearance as parosteal but histology high grade and
medullary involvement more common.
30

31. Telangiectatic Osteosarcoma
 Aggressive
 Presents with pathological fracture
 5% of all osteosarcomas
 arises within the diaphysis
⚫Radiology
Often entirely osteolytic
Bone and cortex destruction
Periosteal reaction
Codman's triangles
⚫Pathology
Gross appearance is a multi-cystic similar
to an aneurysmal bone cyst.
Microscopically it has large blood filled spaces
and thin septation. Within the septa there is scanty
osteoid production by the pleomorphic malignant cells 32

32. Prognostic Factors
32
⚫Extent of the disease
⚫ Pts with pulmonary, non pulmonry (bone) or skip metastasis have
poor prognosis
⚫Grade of the tumor
⚫ High grade tumor have poor prognosis
⚫Size of the primary lesion
⚫ Large size tumors have worse prognosis then small size tumors
⚫Skeletal location
⚫ proximal tumors do worse than distal tumors.
⚫Secondary osteosarcoma: Poor prognosis

33. Treatment
⚫Current standard of care
Radiological staging
Biopsy to confirm diagnosis
Preoperative chemotherapy
Repeat radiological staging (access chemo response, finalize surgical
treatment plan)
Surgical resection with wide margin
Reconstruction using one of many
techniques
Post op chemo based on preop response
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34. Chemotherapy
34
⚫Chemotherapy given preoperatively -Neoadjuvant
⚫Given postoperatively - Adjuvant
⚫Advantages of neoadjuvant chemotherapy -
 regression of the primary tumor, making a
successful limb salvage operation easier.
 may decrease the spread of tumor cells at the time of
surgery
 Effectively treating micrometastases at the earliest time
possible.
 It avoid tumor progression, which may occur during any
delay before surgery.
 Given for about 3-4 weeks before definitive procedure

35. Chemotherapy
35
⚫The drugs used most often to treat
osteosarcoma are:
Methotrexate with leucovorin (folinic acid)
Doxorubicin (Adriamycin)
Cisplatin or carboplatin
Etoposide
Ifosfamide
Cyclophosphamide
Actinomycin D (dactinomycin)
Bleomycin

36. Surgery
36
⚫The main goal of surgery is to safely and
completely remove the tumor.
⚫Historically – amputation.
⚫Over the past few years - limb-sparing procedures
have become the standard, mainly due to
advances in chemotherapy and sophisticated
imaging techniques
⚫Limb salvage procedures now can provide rates of
local control and long-term survival equal to
amputation.

37. Surgery choice
⚫Surgical procedures fall into three basic categories:
Amputation
Rotationplasty
Limb salvage
37

38. Decision ???
38
⚫ If the tumor can be removed safely while retaining
a viable extremity, a limb sparing procedure may be
appropriate.
⚫ If major nerves or blood vessels are involved, or if
complete tumor removal results in significant loss of
function, amputation may be a better choice.
⚫ Patient’s age, desired level of function, cosmetic
preference and long-term prognosis must also be
considered.

39. Amputation
⚫Amputation involves removal of the limb with a
safe margin between the end of
the retained portion and the
tumor
⚫It should not be viewed as a
failure of treatment, but rather
as the first step towards patient’s return to a more
comfortable and productive life.
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40. Amputation
40
Indication
1. Grossly displaced pathologic fracture
2. Encasement of neurovascular bundle
3.Tumor that enlarges during preop chemo and
is adjacent to neurovascular bundle
4. Palliative measure in metastatic disease
5.If the tumor has caused massive necrosis,
fungation, infection, or vascular compromise.

41. Limb salvage surgery
⚫Removing the tumor with a normal cuff of tissue
surrounding it while preserving vascular and
nerve supply to the extremity.
41

42. ⚫The skeletal defect must be reconstructed by
Endoprosthesis (most common) –
replacing the removed bone with
a metal implant
 Allograft (cadaveric) bone
 Vascularized bone acquired from the patient
 Allograft-prosthetic composite constructions
42

43. Rotationplasty
⚫compromise between amputation and limb
salvage
⚫most commonly used for osteosarcomas of the
distal femur in skeletally immature patients
⚫It is a procedure where the neurovascular
structures and distal aspect of the limb (leg) are
retained, and re-attached to the proximal portion
after the tumor has been removed.
43

44. ⚫For functional purposes, the distal segment is turned 180
degrees so that the ankle joint functions as a knee joint,
thus converting an above-knee to a below-knee
amputation in order for prosthetic use to be maximized
44

45. Radiotherapy
45
⚫Radiation therapy has no major role in
osteosarcoma
⚫Radiation therapy may be useful in some cases
where the tumor cannot be completely removed
by surgery. E.g. in pelvic bones or in the bones of
the face.
⚫Megavoltage (upto 6000-8000 rads)

46. Follow up and Prognosis
46
⚫Signs of recurrence, metastasis and treatment
related complications
⚫Physical examination,radiographs of the primary
site, serial chest imaging,bone scans and
laboratory examinations
⚫50 % cases with high grade osteosarcoma have
some type of relapse in 5 months
⚫If recurrence is detected, additional surgery
(radical amputation)and chemotherapy may be
warranted.
⚫5 year survival rate is 5% - 23%

47. THANK YOU !
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