Osteosarcoma

Osteosarcoma

By Dr. KM Liau

Osteogenic Sarcoma (osteosarcoma) is a bone forming cancer.

It is the most frequent type of bone tumour and is most common between the ages of 15 to 25.

Over 90% of tumours are located in the metaphysis (the growing ends of the bone), the most common sites are the bones around the knee which account for 80% of cases.

Most are high grade intramedullary osteosarcomas, about 5% are low grade lesions, some are secondary osteosarcomas (for example those caused by radiation therapy).

Incidence

Affects about 1/200,000 population

Accounts for 21% of malignant primary bone tumours

Male : Female 2:1

Peak incidence 10 - 20 years (age of rapid growth), with a second peak at 50 - 70 years (80% less than 30 and those more than 40 years usually secondary to Pagets)

3rd most common malignancy in adolescents, after leukaemia & lymphoma.

75% occur in the distal femur or around the knee

90% are metaphyseal in long bones

10% present with macroscopic metastatic disease

Types:

1. Intramedullary (classical or ordinary) osteosarcoma (see picture)

2. Surface osteosarcomas:
a) Parosteal osteosarcoma
b) Periosteal osteosarcoma

3. Telangiectatic osteosarcoma

4. Secondary osteosarcomas:
a) Paget's
b) Post-radiation

Clinically

Pain which is constant and worse at night not relieved by pain killers. (non-mechanical pain)

Presence of a palpable mass

In smaller children, a limp may be the only symptom.

The pain may be present for many months, and initially be confused with more common sources such as muscle soreness.

Be aware of a fracture following minimal trauma - patient may present as pathological fracture secondary to osteosarcoma.(see picture)

Diagnosis

Clinical diagnosis can usually be made from plain x-ray.

The definitive diagnosis is established from biopsy of the affected limb.

• Chemotherapy: One of the goals of treatment before limb-sparing surgery is to shrink the tumor, allowing for a more successful surgical outcome. Chemotherapy drugs have been developed to kill malignant (cancerous) cells, while hopefully shrinking the tumor. Specific chemotherapy drugs are part of the treatment plan before and after surgery for the patient with primary bone cancer. Pre-surgical chemotherapy is used in an effort to increase the number of patients who are considered candidates for limb-sparing surgery and to provide a more positive outcome for surgery. Chemotherapy usually is administered for approximately three or four months before the limb-sparing surgery.

Plain X-ray

Features of osteosarcoma:

1. Osteoblastic (bone forming)

(note a rare variant which is osteolytic and
resemble aneurysmal bone cyst - telangiectatic
osteosarcoma)

2. Sun ray spicules (Radial ossification) and Codmans triangle (lifting of periosteum)

3. Wide zone of transition.

4. Cortical breach common

5. Adjacent soft tissue mass

6. Joint space rarely involved

Codman's Triangle

The tumour initially extends within the medulla but soon perforates the cortex -> raise periosteum -> Codman's triangle.

As the tumour mass expands new bone forms along vascular channels -> appearance of sunray spicules

Biologic behaviour

Sarcoma grows radially (centrifugally) and compresses the surrounding soft tissues, forming a pseudocapsule layer (inflammatory layer) referred to as the 'reactive zone'.

The reactive zone contains microscopic extensions of the main tumor mass, termed 'satellite lesions'.

Regional metastases within the same bone (intraosseous) or across the adjacent joint (transarticular) are referred to as "skip metastases."

Management

1. Staging - local and systemic

2. Biopsy

3. Neoadjuvant chemotherapy

4. Definitive surgery - limb salvage vs amputation

5. Adjuvant chemotherapy

6. Follow up

Local Staging

MRI:

1. Determine extent of tumor

2. Detect soft tissue mass or skip lesion

3. Determine relationship of tumor to neurovascular bundle

CT of affected extremity (if MRI not available):

1. Determine extent of tumor, especially in the presence of excessive tumoral oedema

2. Visualize vessels (using contrast medium)

Systemic Staging

1. CT Lung - Detect pulmonary metastasis

2. Bone scan - Determine sites of bone metastasis

Enneking Staging

Stage Grade and anatomic extent

I Low-grade tumor

IA Intracompartmental

IB Extracompartmental

II High-grade tumor

IIA Intracompartmental

IIB Extracompartmental

III Either grade with metastases

Biopsy

Biopsy is performed as the last part of staging

The biopsy should be performed by an orthopedic surgeon who is familiar with the management of malignant bone tumors and preferably by the surgeon who will perform the limb-sparing surgery.

Principle of biopsy

1. Should know the probable diagnosis and stage of tumour before biopsy is taken (biopsy is the last step in the staging of the patient)

2. Performed by the surgeon who will perform the definitive surgery.

3. Biopsy tract orientation & location is critical - will need to be included in the definitive surgery if lesion is malignant.

4. Meticulous haemostasis to avoid tracking haematomas

5. Send samples for microbiological analysis

Open Biopsy

1. Longitudinal incision

2. Sharp dissection should proceed directly to the tumour, through muscle, not between muscle planes

3. Uninvolved anatomic compartments should not be exposed

4. Avoid all major neurovascular structures to prevent contamination

5. Excise block of reactive tissue, pseudo capsule, capsule, and block of tumour -> formalin +/- frozen section

6. Windows in bone should be as small as possible and oval to avoid stress risers and pathological fracture

7. Release tourniquet prior to closure -> haemostasis

8. Close with a subcut. stitch

9. Drains should come out through the wound

10. If proceed following biopsy -> new instruments and drapes to stop seeding

Pathology

The histologic hallmark of osteosarcoma is the presence of frankly malignant osteoblastic spindle cells producing osteoid.

Variations are common.

3 distinct subtypes of conventional osteosarcoma:

a) Osteoblastic

b) Chondroblastic

c) Fibroblastic

The presence of woven bone with malignant appearing stromal cells, regardless of associated chondroid or fibrous matrix production, makes the diagnosis of osteosarcoma.

Chemotherapy

Neo-adjuvant chemotherapy is given prior to surgery as an effort to increase the number of patients who are eligible for limb-sparing surgery and to provide a more positive outcome for the surgery.

Goals of neo-adjuvant chemotherapy:

1. Kill micrometastasis to the lung (we must always presume micrometastasis has already occurred at the time of presentation).

2. Shrink the tumour size.

3. Sterilize the reactive zone.

Chemotherapy usually is administered for approximately 3 cycles (1 cycle/month) before the limb-sparing surgery.

The 2 combination of chemo used here is Adriamycin and Cisplatin.

Limb Salvage Surgery

Twenty years ago the standard of care for a patient with an osteosarcoma was to amputate the affected extremity; limb-salvage was an exceptional treatment.

Now, it is the exception that a child loses a limb as part of the treatment regimen for an osteosarcoma.

This dramatic change is attributable to improvements in surgical technique (both resection and reconstruction), imaging methods (first, computed tomography and later, magnetic resonance imaging), and survival rates of patients treated with adjuvant chemotherapy, particularly preoperative or "neoadjuvant" chemotherapy.

Today, patients who are advised to have an amputation are those who have tumors that extend into all surrounding compartments with encasement of the neurovascular bundle, or those who have had local recurrence after a limb-sparing operation.

Prognosis

Prognosis is separated into three groups.

Stage I osteosarcoma is rare and includes parosteal osteosarcoma or low-grade central osteosarcoma. It has an excellent prognosis (>90% 5 year survival) with wide resection.

Stage IIb prognosis depends on the site of the tumor (proximal tibia, femur, pelvis, etc.) size of the tumor mass (in cm.), and the degree of necrosis from neoadjuvant chemotherapy (chemotherapy prior to surgery).

Stage III osteosarcoma with lung metastates:

Prognosis depends on the resectability of the primary tumor and lung nodules, degree of necrosis of the primary tumor, and maybe the number of metastases.

Overall prognosis is 30% or greater depending.

Those with a longer length of time(>24months) and few nodules (2 or fewer) have the best prognosis with a 2-year survival after the metastases of 50% 5-year of 40% and 10 year 20%.

If metastases are both local and regional, the prognosis is worse.

Case Study

This patient presented with the complain of left thigh swelling for 2 months duration.

The swelling was initially small and was not taken noticed by the patient.

He first began to notice the swelling after a fall from bicycle when he injured his left knee.

There was no bony injury at that time and the patient could still ambulate normally.

However, since then he began experiencing a dull aching pain over the knee region and the swelling began to grow in size.

At the time of presentation it was 8x6 cm.

He was still able to walk normally and there was no limitation of left knee movement at that time.

Femur X- Ray -AP View

The AP and Lateral radiographs show a radiolucent destructive cortical lesion over the distal 1/3 of left femur.

It has a wide zone of transition with thinning of cortex as well as evidence of cortical destruction. However there is no cortical break seen.

Periosteal reaction is present over the posterior cortex with sunburst appearance.

There is also amorphous soft tissue calcification and swelling seen.

X-Ray Lateral View

The finding is suggestive of osteosarcoma of the distal 1/3 of left femur.

MRI - T1 Weighted Image

There is presence of an intramedullary as well as an extramedullary mass lesion in the distal end of right femur with cortical destruction.

The mass is heterogenously isointense to muscle on T1

MRI - T2 Weighted Image

The mass shows heterogenous enhancement post intravenous gadolinium.

CT Lung

No evidence of metastasis noted.

Whole Body Bone Scan

IV 99m Technetium was given and scan was performed 3 hours post injection.

Presence of increased tracer uptake in the left distal femur (at the metadiaphysis).

The increase tracer accumulation in the right thigh is due to the urinary catheter and the urine bag.

No other abnormal tracer uptake seen.

Physiological tracer uptake in kidneys and urinary bladder.

Biopsy

Biopsy done over the medial aspect of left thigh, 2cm above patella.

2cm incision made and the soft tissue was opened layer by layer through vastus medialis muscle up to the bone.

Cone biopsy done.

Haemostasis secured with bone wax.

Histology report:

The section of bone shows a malignant tumour within the marrow spaces and destroying the bone in a few areas.

The tumour cells are pleomorphic, hyperchromatic with scattered tumour osteoids noted.

Consistent with diagnosis of Osteosarcoma.

Pathological Fracture

He sustained a pathological fracture after a trivial fall at home.

AP view shows cortical break at the site of the tumour.

X-Ray Lateral View

Lateral view shows a cortical break of distal 1/3 of Left femur through the site of lesion.

He was treated conservatively while undergoing chemotherapy.

Treatment of Pathological Fracture

He was treated with a Thomas splint and non- weight bearing regime for 3 months while continuing chemotherapy.

Union of pathological Fracture

After 4 cycles of chemotherapy, the pathological fracture shows evidence of union with callus formation.

There is also marked reduction of soft tissue swelling and calcification as compared with the previous radiograph.

This is a good sign as it shows that the patient is responding well with the chemotherapy and this also makes the patient a suitable candidate of limb salvage procedure.

Limb Salvage Surgery

Incision made extending from mid thigh till upper 1/3 of left leg.

Soft tissue and muscle opened layer by layer.

Wide resection of tumour done with 3 cm of normal tissue cuff.

The femoral neurovascular bundle was carefully preserved.

The arrows point to the femoral artery.

Wide Resection

The widely resected tumour includes 5 cm of proximal and distal margin.

The femoral condyle together with the articular surface are resected as well.

The total length of resected femur measures 26 cm.

Allograft Preparation

The allograft is first immersed in povidone soak for 30 minutes.

The muscular attachments and periosteum were then stripped clean from the femur.

Injection of Bone Cement

Bone cement was injected into the medullary canal of the reamed allograft under high pressure.

Insertion of Femoral Component of Knee Replacement

The femoral component of total knee replacement being inserted into the allograft.

Insertion of Tibial Component

Bone cement was injected into the proximal tibia as a preparation for insertion of tibial component.

Plating of Allograft

Dynamic Compression Plate used to fix the allograft to proximal femur.

Final Fixation

The final fixation is shown here.

The femoral-allograft interface is reinforced with extracortical bone bridge using autogenous bone graft harvested from Iliac crest.

Post Surgery

After surgery, the wound will be covered in a bulky, sterile dressing.

A drain, which was placed in the wound during surgery to allow drainage of blood and reactive exudates outside the skin, may be removed within 3 to 5 days after the surgery.

The extremity will be placed in an immobilizer which supports the extremity and allows access to dressing changes.

After the wound has healed, and depending on the surgeon's protocol, a solid cast may be placed on the extremity for a period of time.

When the cast no longer is needed, a removable brace may be fitted to provide support to the limb.

Regular physiotherapy to mobilise the joint and to strengthen the anti-gravity muscles to get the patient mobilise and ambulate independently.

Post Surgery Advice To Patient

The patient is advised to watch out for these signs:

1. Pain.

2. Swelling.

3. Temperature (fever).

4. An open wound over the operation site.

5. A cracking sound in the joint.

Subsequent Follow Up

Follow up schedule:

1. 4 monthly follow up for the 1st year post-op with a repeat CT Lung every 4 months to detect lung metastasis (tumour doubling time is around 100 days)

2. 6 monthly follow up from the 2nd year onwards, with repeat CT Lung 6 monthly.

Useful Link

OSTEOSARCOMA DIAGNOSIS AND TREATMENT

A good source for further reading

OSTEOSARCOMA INITIATIVE

A good source for further reading