Osteosarcoma

Definition

 

Highly malignant spindle cell sarcoma of bone in which the malignant cells produce osteoid

- aggressive

- most High grade (II)

- most extracompartmental (IIB)

 

Exception is Juxtacortical (IA)

 

Epidemiology 

 

Most common malignant primary bone tumour excluding myeloma

 

Bimodal peak

 

1.  Second decade / teenagers

- 75%

 

2.  Elderly / 7th decade

- Paget's

 

In fact very rare to see under 13 years

- if looks like OS in this age group then probably Ewing's

 

M > F 3:2

 

Aetiology

 

Li-Fraumeni syndrome

Retinoblastoma - FHx / p53 Defect

Radiotherapy

Paget's disease

 

Classifications

 

Anatomical

 

Classic Central 

- classic high grade

- rare low grade

 

Juxtacortical

- parosteal

- periosteal

 

Extraskeletal

- Jaw

 

Pathological / Lichenstein's

- see below

 

Aetiological 

 

Secondary

- Paget's

- previous radiotherapy

- OM

- Fibrous Dysplasia

- Chondrosarcomatous dedifferentiation

 

Classic Central Osteosarcoma

 

Location

 

Metaphysis of long bones

- distal femur 35%

- proximal tibia 20%

- proximal humerus 10%

 

Osteosarcoma Proximal Tibial Xray0001Osteosarcoma Proximal Tibial Xray0002

 

Can cross into epiphysis / occasionally in diaphysis

 

Presentation

 

Pain

- often activity related

- likely due to microfracture

- most patients relate onset of pain to some minor trauma

- sometimes at night

 

No systemic symptoms

 

Mean symptom duration is 4/12

- 10% metastasis on presentation

- 1% pathological fracture

 

X-ray

 

Usually diagnostic 

 

Osteosarcoma Distal Femur0001Osteosarcoma Distal Femur0002

 

1.  Metaphyseal - involves medullary canal

 

2.  Permeative cortical destruction

 

3.  New bone formation / osteoid

 

4.  Wide / permeative zone of transition / non geographic

 

5.  Codman's Triangle

- triangular periosteal new bone formation

- at proximal and distal cortical margins

- non specific

- reaction to rapid growth

 

6.  Soft tissue component

 

MRI 

 

Osteosarcoma MRI0001Osteosarcoma MRI0002

 

1.  Determines the marrow extent of tumour

- helpful in determining appropriate resection level

- satellite lesions 

- metastasis within reactive zone

 

2.  Identify skip lesions 

- metastasis outside reactive zone

- sagittal and coronal images of the entire bone

 

3.  Soft tissue component

 

Osteosarcoma Proximal Tibial MRI0001Osteosarcoma Proximal Tibial MRI0002

 

4.  Relationship to NV structures

 

5.  Articular involvement

- usually runs along ACL / PCL

 

CT 

 

Complementary to MRI / very useful in the pelvis

 

Bone Scan

 

1.  Resect with 3-4cm margin from bone scan uptake

- resect skip lesions

 

Osteosarcoma Bone Scan

 

2.  Identifies metastatic disease

 

CT Chest / abdomen

 

10% present with pulmonary metastasis

- lungs most common site

- detect > 3 mm

- if resectable then resect lung metastasis via sternotomy

 

Laboratory

 

ALP & LDH

- can be increased 

- worse prognosis 

 

ESR

- May be mild increase

 

Pathology

 

Gross Pathology

 

Starts with intramedullary focus

- bony with areas of focus & haemorrhage

- skip lesions common 5-20% 

- grows up & down medulla

 

Histology

 

Must see malignant spindle cell stroma producing osteoid

- can be difficult to find osteoid

- therefore adequate sampling is essential

 

Osteosarcoma Nephron GNU Free Documentation License Version 1.3Osteosarcoma High Mag Nephron GNU Free Documentation License Version 1.3

 

Pleomorphic spindle cells 

- hyperchromatic nuclei 

- atypical mitotic figures

 

Can mistake fracture callous or periosteal new bone for that produced by malignant cells

 

Low grade central / parosteal OS

- much less cellular

 

Lichenstein Pathological Classification

 

1.  Osteoblastic (50%)

- prominent osteoid 

- delicate network of eosinophilic matrix with both benign and malignant osteoblasts throughout

 

2.  Chondroblastic 

- prominent cartilage

- still have malignant osteoid 

 

3.  Fibroblastic 

- prominent fibrous tissue

- look like fibrosarcoma

 

4. Telangiectatic 

- worst prognosis

- cystic pools of RBC / Giant cells

- may look completely lytic & expansile on Xray

- often with benign giant cells

- can mistake for ABC or GCT

- however see cellular atypia etc amongst stroma

 

5. Giant Cell Rich Osteosarcoma

- older patients

- similar to MFH

- difficult diagnosis

 

6. Small Cell Osteosarcoma

- similar appearance to Ewings

- responds to chemotherapy like PNET

- nests small cells

 

Management 

 

Prognosis

 

Historically

- amputation 

- 1970's 5 year survival 20%

 

Now

- 70% overall survival

- 90% limb sparing surgery 

 

Algorithm

 

1.  Accurate clinical staging

- local (cross sectional imaging - CT / MRI)

- systemic (bone scan & CT chest / abdomen

- biopsy

2.  Neoadjuvant chemotherapy

3.  Restage

- locally and systemic (MRI / CT Chest)

4.  Wide resection 

5.  Post operative chemotherapy +/- radiotherapy if positive margins

 

Chemotherapy

 

Concept

 

Systemic treatment

- treats micrometastasis

- allows limb salvage

 

Rosen in vivo response dictates outcome

 

Outcome best predicted by response as per Rosen

- some OS have P-Glycoproteins pump

- remove chemo from the cell

 

Grade 1 = no cell death

Grade 2 = Partial <90%

Grade 3 = Necrosis >90%

Grade 4 = Complete necrosis

 

Grade 1 & 2 

- < 50% survival

 

Grade 3 & 4 

- > 75% long term survival in OS and MFH

 

Regimen

 

Neoadjuvant & Adjuvant

 

2 cycles pre-operative MACI

- MTX

- Adriamycin (Doxorubicin)

- Cisplatin

- Ifosphamide

 

Surgery

 

Timing

- usually 3/12 after diagnosis

- usually 2/52 after end neoadjuvant chemotherapy

- post chemotherapy tumour is smaller & tends to have a "rind" that makes resection much easier

 

Goal

- resection with wide margin

- 7cm proximally, 5cm distally

 

Options

 

Amputatation

Limb Salvage Surgery

 

Limb Salvage Surgery

 

80% patients can have limb salvage

 

Contraindications / PIN LEG

 

1. Pathological fracture

2. Infection

3. N/V involvement 

4. Immature skeletal age if LLD >6-8cm

5. Extensive muscle involvement

6. Poor biopsy (instead of Good)

 

Technique

 

1. Resection of tumour & biopsy tract

- major N/V bundle must be free of tumour

- wide resection of affected bone 

- normal muscle cuff in all planes

- biopsy tract removed en bloc

- 5cm margin on MRI

- adjacent joint and capsule should be resected

- extra-articular resection preferred

- articular resection mandatory if effusion present

- use tourniquet --> if site contaminated at histology allows amputation to be performed above tourniquet level

- motor reconstruction by local transfer

 

2. Skeletal reconstruction 

- usually 15-20 cm defect

- endoprothesis / arthrodesis / allograft

 

Osteosarcoma Distal Femur Tumour ProsthesisOsteosarcoma Distal Femur Tumour Prosthesis0001

 

Osteosarcoma Proximal Tibial Resection0001Osteosarcoma Proximal Tibial Resection0002

 

3. Local soft tissue and muscle transfers

- adequate soft tissue cover mandatory

 

 

Local recurrence post OT 

 

Incidence 12%

- poor outcome

- DXRT to prevent local recurrence if +ve margin

 

Can still treat with an attempt at cure

- resectable disease =< 15 pulmonary metastasis + extremity tumour

- treatment is along similar lines

- neoadjuvent chemo

- tumour resection / amputation + median sternotomy and resection of mets

- aim is to relieve tumour burden

- if unresectable then chemotherapy is more appropriate

 

Prognosis

 

Single most predictive factor is the presence or absence of detectable metastasis at presentation

 

Survival

 

IIB 60% 5 year

III  50% 5 year

 

Significant improvement recently

- improved surgical resection

- early resection of lung metastasis

- improved adjuvant chemotherapy

 

Metastasis - 10 - 20% 5 year

 

Resectable pulmonary metastasis post treatment

- 20 - 40% 5 year 

 

CT Chest Solitary Metastasis

 

Local recurrence

- 5 - 10 % 5 year

 

Basic Principles

 

If survive 2 years probably will survive

- no difference in survival between amputation & limb salvage

- long-term survivors 7% risk of developing second tumour due to treatment

 

Poor Prognostic Signs

 

Age < 10 years

Proximal humerus / central lesion

Poor response to chemotherapy

Tumour size > 15cm

Symptoms < 6/12 = aggressive

Pathological fracture

NV involvement

Pelvis much worse than femur which is worse than tibia

Telangiectatic worst

Secondary OS