Classic Osteosarcoma

Epidemiology

• Children
  • Most common, high grade, central, affects children
  • 85% of osteosarcomas
• M:F – 1.5:1
• Location
  • 90% in ends of long bones
  • 50% around knee
  • distal femur 34%
  • proximal tibia 17%
  • femoral shaft 5%
  • proximal femur 5%
  • proximal humerus 9%

C>Clinical Features

• Localised swelling & pain in children (usually teens)
• Pain & mass
• Warmth
• No systemic symptoms
• Mean symptom duration is 4/12
• 10% metastases at presentation
• Pathological fracture occasionally

P>Pathology

• Dependent on predominant type of matrix produced
• Lichenstein’s classification
  • Conventional
    • Bony (50% of all central OS)
    • Cartilaginous
    • Fibrous
  • Telangiectactic
  • Small cell
  • Giant cell (fibrohistiocytic)
• Therefore gross & micro appearance varies
• Osteosarcoma is the great histological imitator among bone tumours just as Ewings sarcoma is the great radiological imitator among bone tumours

Gro>Gross

• Starts with intramedullary focus
• Bony with areas of focus & haemorrhage
• Skip lesions common 5-20%
• Grows up & down medulla
• Penetration of cortex common
• Penetration of epiphysis less common
• Involvement of joint rare

His>Histology

• Diagnosis depends on production of malignant osteoid by the tumour
• Cellular areas with microscopic trabeculae of bone between cells
• Pleomorphic spindle cells with
  • Hyperchromatic nuclei
  • Atypical mitotic figures
  • May also see anaplastic cell matrix & mix of fibrous, cartilaginous & bony tissues

• Conventional form
  • Osteoblastic
    • Prominent osteoid
  • Chondroblastic
    • Prominent cartilage
  • Fibroblastic
    • Prominent fibrous tissue
    • Looks like fibrosarcoma
• Telangiectatic form (< 5%)
  • Similar to ABC
  • Large lytic defect filled with blood filled cavity
  • Dilated vascular channels with multinucleated giant cells
  • Anaplastic sarcomatous stroma with bone formation
  • Worse prognosis than conventional form
• Small cell form
  • Similar to Ewing’s sarcoma
  • Nests of small cells with spindle arrangement
  • Sparse osteoid
  • Worse prognosis than conventional form
  • Responds to chemotherapy like PNET
• Fibrohistiocytic variant (giant cell variant)
  • Similar to MFH
  • Higher age group in 3rd decade
  • Pleomorphic spindle cells & multinucleated giant cells
  • Osteoid with inflammatory matrix

Centr>Central Osteosarcoma Low Grade

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Unusual

Older patient

M=F

Bone around the knee most common sites

Spindle cells with appearance of fibrous dysplasia & desmoid

Radiology more ominous than the histology

Metas>Metastatic spread

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Primarily haematogenous

• Lung mets can be treated by chemotherapy & surgical excision
• Bone mets have very poor prognosis

Up to 80% have at least micrometastatic spread on presentation

Multifocal OS very rare (? actually represents metastatic OS)

Inves>Investigations

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Definitive Diagnosis in 55%

Differential Diagnosis in 35%

Wilner’s classification

• Sclerotic 30%
• Lytic 20%
• Mixed 45%

Central & destructive lesion in metaphysis

• Involves medullary canal
• Lytic & Blastic
• Permeative cortical destruction

Periosteal reaction of rapid growth

• Codman’s Triangle (benign reactive bone which should be avoided in biopsy)
• Sunburst Spicules
• Soft tissue component
• Fluffy neoplastic bone

Rarely in diaphysis or even epiphysis

Soft tissue extension the rule

CT sc>CT scan

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Defines extraosseous component

Identifies neoplastic bone in soft tissues

CT lung

• 10% of patients have pulmonary mets on presentation
• Best resolution for metastases

MRIMRI

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Best for

• Intraosseous limit
• Soft tissue component
• Relationship to NV structures
• Skip lesions (metastasis outside reactive zone)
• Whether joint is involved (rare)

Bone >Bone Scan

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Identifies

• Skip lesions
• Metastases
• Polyostotic disease
• Pulmonary metastases

Labor>Laboratory

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ALP & LDH can be ↑

• Worst prognosis

May be mild ↑ in ESR

Different>Differential Diagnosis

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Bone island

Osteoma

Osteoblastoma

Ewing’s sarcoma

Chondrosarcoma

Fibrosarcoma

Myositis ossificans

Osteochondroma

Juxtacortical chondroma

Fracture callous

TreatmentTreatment

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Systemic treatment

Goals of chemotherapy

• Shrink tumour size
• Treat micrometastases
• Assess tissue response
• Allow Limb Salvage Surgery (LSS)
• Time to manufacture custom prosthesis

Neoadjuvant & Adjuvant (pre & post-op chemotherapy)

• Marked improvement in the 5 year survival rates with this
• Response to chemotherapy best indicator of survival
• Necrosis Response (Huvos Grade: Grade 1 < 50%, Grade IV > 90%)
  • > 90% necrosis correlates with good prognosis
  • Greater the necrosis » better the survival
• Some osteosarcomas have P-Glycoprotein Pump
  • Which remove chemotherapy from the cell

2 cycles Preoperative

• Rosen T 10 Regime outdated
• Current regimen “MACI”
  • MTX
  • Adriamycin
  • Cisplatin
  • I-Phosphamide

Postoperative regimen

• Similar
• Can add VP16 & CPM (? Only if surgical excision shows > 10% tumour viability)

Surgery

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Usually 3/12 after diagnosis

Usually 2/52 after end neoadjuvant chemotherapy

Consists of wide excision

• 7cm proximally, 5cm distally
• Can be in form of amputation or limb salvage procedures

Reconstructive Technique

• Endoprothesis ~ Best Results
• Arthrodesis
• Allograft
• DXRT to prevent local recurrence
• Adjuvant Chemotherapy for systemic treatment

Reasons for amputation

• Soft-tissue & neurovascular involvement
• Gross leg-length inequality (young child)
• Infected tumour
• Unstable pathological fracture
• Disadvantaged situation (environment, patient variables)

Poor outcome with any local recurrence after surgery

Poor outcome in presence of pathological fracture

Isolated Lung metastasis can be resected with good long term outcome

Outcome

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Prior to 1971

• 20% 5 year survival rate

Now

• 70% 5 year survival rate (80% some centres)

Due to

• Improved resection techniques
• Adjuvant chemotherapy (Mayo clinic – 40% 5 year survival without chemo)
• Resection of lung metastases early (some thoracic surgeons happy to do multiple metastectomies for osteosarcoma)

Limb salvage now viable option

• Local recurrence rate the same in distal femoral OS with limb salvage vs AKA
  • 74% LSS vs 64% amputation at distal femur
• Local recurrence rates are the same at 5-10%

Local Recurrence

• Incidence 5-10%
• Survival 5-10% at 5 years
• Treat with local measures only
• Dickinson says » recurrence = death

Worse prognosis if

• > 15cm (3x)
• Symptoms < 6/12
• Age < 10 years
• Males
• Elevated ALP & LDH
• Osteoblastic/ Chondroblastic
• Proximal or Central lesion
• Pathological fracture
• NV involvement

Late Presenter

• Paradoxically better survivor
• Less aggressive tumour
• Main indicator of survival is nature of tumour
  • Rather than nature of treatment

Death due to

• Local recurrence
• Lung secondaries