a lil bit of osteosarcoma

1. Osteosarcoma

2. • Osteosarcoma (OS) is a primary skeletal malignancy characterized by
spindle cells of mesenchymal origin depositing immature osteoid
matrix
• Osteosarcoma is the most common primary malignancy of bone in
children and young adults.

3. Incidence
• Affects ~1/200,000 population
• Accounts for 21% of malignant primary bone tumours
• M:F 2:1
• 3rd most common malignancy in adolescents, after leukaemia &
lymphoma

4. • Peak incidence 10-20 yrs (age of rapid
growth), with 2nd peak at after 50 yrs
(80% <30 & those >40 usually secondary
to Paget's)
Epidemiology of conventional osteosarcoma. National Cancer Institute Surveillance, Epidemiology, and End Result
Program 1973-2009. Age-adjusted incidence rate and age-specific frequency, all races, both sexes, 4962 cases.

5. • 75% occur in distal
femur or around knee
• 90% metaphyseal in
long bones
• 10% present with
macroscopic
metastatic disease

6. Staging

7. Pathology
• most commonly diagnosed as Stage IIB (high grade, extra-
compartmental, no metastases)
• Over 75% of patients present with pulmonary metastases
•lung is most common site of metastasis
•bone is second most common site
• Metastasis via hematogenous

8. • Syndrome associated with OS
• Li–Fraumeni syndrome – Mutation of p53
gene, 30% will have OS.
• Bloom’s syndrome, Werner’s syndrome,
and Rothmund Thomsonsyndrome -
Loss of RecQ helicases that unwind DNA
• Retinoblastoma - loss of RB1 in13q14
microdeletion cause Loss of pRb which
induces unregulatedcell cycle progression

9. Poor prognostic factors
• Advanced stage of disease (most predictive of survival)
• Response to chemotherapy (as judged by percent tumor necrosis of
resected specimen)
• Tumor site and size
• Expression of P-glycoprotein
• High serum alkaline phosphatase
• High lactic dehydrogenase
• Neurovascular involvement
• Surgical margins
• Expression of multi-drug resistance (MDR) gene tends to have a poor
prognosis - tumor cells can pump chemotherapy out of cell with MDR
expression present in 25% of primary lesions and 50% of metastatic lesions

10. Types
• Intramedullary (classical) osteosarcoma (75%)
• Surface/juxtacortical osteosarcomas (1-6%)
• Parosteal osteosarcoma
• Periosteal osteosarcoma
• Telangiectatic/giant cell/small cell osteosarcoma
• Secondary osteosarcomas
• Paget’s (not well understood)
• Post-radiation (DNA damage)

11. Clinical
• Pain which is constant & worse at night
• May have a tender lump which may lack a definite edge & may be
attached to muscle
• Restricted ROM, pain with weight bearing
• If vascular may pulsatile & feel warm
• Be aware of # following minimal trauma as if secondary to
osteosarcoma often -> late diagnosis of tumour (5 to 10%)
• Constitutional sx – advance disease and not sensitive in children

16. Radiology
X-ray
• Variable with combination of bone destruction & bone formation
• 25% lytic
• 35% sclerotic
• 40% mixed
• Wide zone of transition, cortical breach common
• Sun ray spicules (radial ossification) & Codman's triangle (lifting
of periosteum)
• Adjacent soft tissue mass
• Joint space rarely involved

17. CT scan
• CT is inferior to MRI
• To detect radiographically occult pulmonary metastasis

18. MRI
• will clearly demonstrate the extent of the bone marrow invasion, the
presence and size of any soft-tissue mass, and the relationship to
surrounding vital structures.
• Hypointense on T1, hyperintense on T2 and STIR imaging.
• But most of time, exhibit mixed heterogeneity
• surrounding peri-tumor edema, and show abundant enhancement
with contrast administration.
• It is important to image the entire bone involved to detect potential
skip lesion and accurately plan resection and reconstruction efforts

21. Bone scan or PET scan
• Both recommended to detect metastatic bone and
soft-tissue disease
• Bone scan is more cost-effective and superior to
PET for bony disease
• PET allows for better detection in soft tissue, and
includes the chest and abdomen.
• Both are effective scanning techniques; the choice
made usually varies by institution.
• An additional advantage of PET is that it may be
able to identify tumors with higher metabolic
activity and, therefore, higher-grade malignancies

23. Lab Ix
• Nondiagnostic
• but high levels of alkaline phosphatase (ALK-P) and lactate
dehydrogenase (LDH) have been shown to predict a poorer prognosis

24. Biopsy
• Biopsy needed for tissue confirmation
• Can be obtained from
• Core needle biopsy
• Open biopsy

25. Histopathology
• malignant spindle mesenchymal cells with pleomorphic nuclei,
scattered mitotic figures, and varying levels of anaplasia (Fig. 3).
• Immature and disorganized osteoid production is a characteristic
hallmark and must be present for diagnosis.
• Classical osteosarcomas matrix dominated by osseous, cartilaginous
or fibrous elements.
• (50% -> osteoblastic, 25% -> chondroid, 25% -> fibroblastic)

28. Treatment
• Untreated -> 95% death in 2 years
• 10% have macro-metastasis and 90% micro-metastasis at
presentation
• Consider osteosarcoma as systemic disease, therefore
• Remove primary site by en bloc excision
• Treat microscopic disease by chemotherapy
• Even with metastatic (Stage 3) disease 5 years survival now 30-
40% (10-20% with surgery alone)
• Multiagent chemo -> survival rate up to 60%

29. Chemotherapy
• Multi-agent chemotherapy has significant impact on limb salvage & disease-free
survival for osteosarcoma
• Commonly used agents include doxorubicin, cisplatin, high-dose methotrexate,
ifosfamide, cyclophosphamide
• Methotrexate -> 80% response
• T10 regimen (methotrexate, vincristine, adriamycin) -> 60-75% survival
• 45% of patients with T10 regimen -> 100% kill rate -> 100% survival
• Survival >10 yrs = cure
• Neo-adjuvant chemotherapy x 8-12/52 (3 cycles)
Good response to chemotherapy is indicated by 90% tumor necrosis on biopsy
• Regimen continued postop or changed to cisplatin depending on histology
• Chemotherapy continues for 1 yr

30. Radiotherapy
• Indication
• Palliation of local pain, to treat surgically inaccessible lesions and painful
metastatic deposits
• Relatively radio-resistant tumour but radiotherapy may also be used
preop to decrease size & vascularity of tumour
• Prophylactic irradiation of chest has not been shown to be effective

31. Surgery
•Limb Salvage vs amputation
•No difference in local recurrence rate
•Better quality of life with limb salvage
•Better 5 years survival rate
•Limb salvage require:
•Preserve nerves
•Preserve or reconstruct vessels
•Preserve sufficient muscle for functional motor power & soft tissue coverage
•Achieve safe, tumour-free margins (wide)
•Reconstruction options
•Autografts/Allografts
•Endoprosthesis
•Combination

32. A 13-year-old girl presents with right thigh pain and constitutional symptoms for 8
weeks. The patient's serum LDH and alkaline phosphatase are elevated. A radiograph
of the right femur is shown in Figure A. Computed tomography (CT) of the chest
reveals no pulmonary metastases. Magnetic resonance imaging (MRI) of the right
femur shows erosion of the tumor through the cortex into the adjacent soft tissue, but
no skip lesions are seen. A biopsy specimen is shown in Figures B and C. What stage
does this patient's case most appropriately represent using the Enneking Staging
System for Musculoskeletal Tumors?
A.Ia
B.Ib
C.IIa
D.IIb
E.III

33. A 13-year-old girl presents with knee pain for 2
months especially at night. She denies fevers
and weight loss. Her physical exam reveals a
painful thigh mass. A radiograph is shown in
Figure A. What is the next most appropriate
step in management?
A. Repeat radiographs in 3 months with observation
B. External beam radiation and chemotherapy
C. Surgical biopsy and culture directed intravenous
antibiotics
D. Neoadjuvant chemotherapy followed by wide
excision and adjuvant chemotherapy
E. MRI of the entire bone, whole body bone scan and
CT chest

34. A 24-year-old male presents with
increasing knee pain over the last 6
months. He reports that he sustained a
non-contact twisting injury to the knee 7
months ago while playing softball. His knee
range of motion is full and his knee is
stable to varus and valgus at 0 and 30
degrees of knee flexion. There is a grade 1
Lachman examination. A radiograph is
shown in Figure A. A biopsy is performed
and is shown in Figure B. What is the most
appropriate definitive management?
A. Reassurance and observation in 6 months with repeat knee radiographs
B. Neoadjuvant external beam radiation, wide surgical resection, and adjuvant chemotherapy
C. Wide surgical resection
D. Neoadjuvant chemotherapy, wide surgical resection, adjuvant chemotherapy
E. Neoadjuvant chemotherapy, marginal surgical resection, adjuvant chemotherapy