Osteosarcoma

Osteosarcoma is a high grade primary malignant bone tumour in which malignant mesenchymal cells directly produce osteoid or immature bone.

It occurs most commonly in adolescents and young adults during periods of rapid skeletal growth.

Typical sites are the metaphyses of long bones, particularly:

Distal femur
Proximal tibia
Proximal humerus

In older adults, osteosarcoma can arise secondary to:

Paget disease
Previous radiotherapy
Preexisting abnormal bone

Conventional high grade intramedullary osteosarcoma is the dominant form.

Clinically relevant variants include:

Conventional osteoblastic, chondroblastic or fibroblastic osteosarcoma
Telangiectatic osteosarcoma
Parosteal osteosarcoma, generally low grade
Periosteal osteosarcoma, usually intermediate grade
High grade surface osteosarcoma

The key staging distinction is localised versus metastatic disease.

The lungs are the commonest site of metastasis.

Typical presentation is progressive localised bone pain.

Pain may initially be activity related but becomes:

Persistent
Nocturnal
Present at rest

A firm enlarging mass may develop.

Joint movement can become restricted when the tumour approaches a joint.

A pathological fracture can occur but is not the commonest presentation.

Do not repeatedly treat persistent focal bone pain in an adolescent as a sports injury when symptoms are progressive or associated with swelling.

Plain radiograph: first investigation; an aggressive metaphyseal destructive lesion with osteoid matrix and aggressive periosteal response should trigger urgent sarcoma referral.

MRI of the entire involved bone and adjacent joint: define intramedullary extent, soft tissue extension, neurovascular relationship and skip lesions.

CT chest: mandatory for pulmonary metastatic staging.

PET CT or bone scintigraphy can evaluate distant skeletal disease according to the treatment protocol.

Biopsy principle

Complete imaging and staging before biopsy.

Biopsy should be performed by, or planned with, the sarcoma surgeon who will undertake definitive resection.

The biopsy tract must:

Pass directly through tissue that will be removed during definitive surgery
Avoid crossing uninvolved anatomical compartments
Avoid contaminating neurovascular structures
Avoid transverse incisions that compromise future limb salvage

Core needle biopsy is usually sufficient.

An improperly planned biopsy can contaminate tissues that would otherwise have been preserved.

Treatment requires systemic chemotherapy plus complete surgical resection for conventional high grade osteosarcoma.

Neoadjuvant chemotherapy

A major reference regimen in children, adolescents and young adults is MAP:

Methotrexate

12 g/m² IV over approximately 4 hours

with:

Aggressive IV hydration
Urine alkalinisation
Serial serum methotrexate concentrations
Leucovorin rescue adjusted according to methotrexate clearance

Doxorubicin

37.5 mg/m² IV daily on days 1 and 2

Total 75 mg/m² per course.

Cisplatin

60 mg/m² IV daily on days 1 and 2

Total 120 mg/m² per course.

High dose methotrexate must only be delivered where therapeutic drug monitoring, leucovorin rescue, renal monitoring and intensive supportive care are available.

Monitor:

Renal function
Liver function
Blood counts
Cardiac function with anthracycline exposure
Hearing with cisplatin

Surgery

Definitive resection usually follows neoadjuvant chemotherapy.

The objective is an R0 wide resection with an intact tumour specimen.

Do not enter the tumour.

Do not dissect directly along the pseudocapsule.

Remove:

Tumour
Biopsy tract
Contaminated tissues

with an adequate cuff of normal tissue.

Limb salvage

Limb salvage is preferred when an oncologically adequate margin can be achieved while maintaining a useful functional extremity.

Reconstruction options include:

Modular endoprosthetic replacement
Biological allograft
Autograft
Allograft prosthetic composite
Rotationplasty in selected children
Vascularised fibular reconstruction in selected anatomical sites

Preservation of a limb is inappropriate if obtaining a safe margin would leave a nonfunctional extremity or uncontrollable tumour contamination.

Amputation

Indications include selected cases with:

Major unreconstructible neurovascular involvement
Extensive contamination
Infection preventing safe tumour reconstruction
Nonfunctional limb after required resection
Recurrence unsuitable for further limb salvage

Histological response

The resected tumour is assessed for chemotherapy induced necrosis.

At least approximately 90% tumour necrosis represents a favourable histological response and is prognostically important.

A poor response does not justify arbitrary escalation to more toxic therapy. Adding ifosfamide and etoposide to postoperative MAP for poor responders did not improve outcome sufficiently to establish it as routine therapy.

Postoperative chemotherapy

Continue systemic chemotherapy after recovery from surgery according to the established protocol.

Do not omit postoperative systemic treatment merely because the tumour has been completely resected.

Pulmonary metastases

Patients with isolated resectable lung metastases can still be treated with curative intent.

Complete surgical resection of all detectable pulmonary disease is important when technically feasible.

Repeated pulmonary metastasectomy may be appropriate in carefully selected recurrent disease.

Radiotherapy

Conventional osteosarcoma is relatively radioresistant.

Radiotherapy has a limited role, including:

Unresectable disease
Positive margins when further surgery is impossible
Palliation
Selected axial tumours

Follow up

Surveillance must focus particularly on:

Pulmonary metastasis
Local recurrence
Reconstruction failure
Chemotherapy cardiotoxicity
Cisplatin ototoxicity and renal toxicity
Second malignancy

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Giant Cell Tumour of Bone

Giant cell tumour of bone is a locally aggressive primary bone neoplasm composed of neoplastic stromal cells and numerous osteoclast like giant cells.

It most commonly affects skeletally mature young adults.

Typical sites are the epiphysis and metaphysis of long bones, particularly:

Distal femur
Proximal tibia
Distal radius

The lesion usually extends to the subchondral bone.

Although conventionally classified as intermediate or locally aggressive rather than a conventional high grade sarcoma, it can:

Destroy bone extensively
Recur locally
Metastasise to lung
Rarely undergo malignant transformation

Campanacci classification

This is the main useful radiographic severity classification.

Grade I

Well defined lesion with intact cortex.

Grade II

Well defined lesion with cortical thinning and expansion but no major cortical breakthrough.

Grade III

Aggressive lesion with cortical destruction and soft tissue extension.

The grade assists operative planning but should not be used as the sole determinant of treatment.

Plain radiographs: classically demonstrate an eccentric expansile lytic epiphyseal lesion extending toward the articular surface.

A mature GCT generally has little surrounding sclerosis.

MRI: define:

Subchondral involvement
Soft tissue extension
Neurovascular relationships
Joint involvement

CT chest: obtain for pulmonary staging in aggressive or confirmed disease.

Biopsy is required before definitive treatment.

H3.3 G34W immunohistochemistry can support the diagnosis in appropriate lesions.

Intralesional surgery

For most Campanacci I and II lesions, and selected III lesions in which the joint can be preserved, perform extended intralesional curettage.

The quality of curettage determines recurrence risk.

Technique should include:

Large cortical window providing full visual access
Removal of all gross tumour
High speed burr extending treatment into cavity margins
Careful inspection for residual tumour in recesses

Local adjuncts can include:

Hydrogen peroxide
Phenol in selected practice
Argon beam
Cryotherapy

The evidence does not establish one universally superior local adjunct.

Defect reconstruction

Fill the cavity with:

PMMA bone cement
Autologous bone graft
Allograft
Bone substitute

PMMA provides immediate structural support and allows recurrent lysis at the cement interface to be recognised relatively easily.

In lesions immediately beneath articular cartilage, a layer of cancellous graft beneath the subchondral plate can reduce direct thermal or mechanical stress from cement.

Add plate fixation when curettage leaves the bone mechanically weak or pathological fracture risk is high.

Wide resection

Consider en bloc resection when there is:

Massive cortical destruction
Nonreconstructible joint surface
Extensive soft tissue extension
Repeated local recurrence
Pathological fracture with gross contamination that prevents reliable curettage
Anatomical location where recurrence would be catastrophic

Reconstruction can require:

Endoprosthesis
Osteoarticular allograft
Arthrodesis
Structural graft

Wide resection lowers local recurrence but sacrifices more normal tissue and joint function.

Denosumab

Denosumab blocks RANKL and profoundly suppresses giant cell mediated bone resorption.

Use primarily for:

Unresectable disease
Sacral or spinal lesions where surgery would cause major neurological morbidity
Tumours where initial resection would require highly morbid surgery

A standard regimen is:

Denosumab 120 mg subcutaneously every 4 weeks

with additional doses on:

Days 8 and 15 during the first month.

Provide:

Calcium supplementation
Vitamin D supplementation

unless hypercalcaemia is present.

Before treatment:

Correct hypocalcaemia
Assess dental health
Address significant dental infection

Monitor for:

Hypocalcaemia
Osteonecrosis of the jaw
Atypical femoral fracture with prolonged therapy
Rebound hypercalcaemia after discontinuation, particularly in younger patients

Denosumab does not eliminate the neoplastic stromal cells. It can produce a thick sclerotic shell that makes later tumour boundaries difficult to identify during curettage.

Therefore, routine preoperative denosumab before an otherwise straightforward joint preserving curettage should not be automatic. Its role is most valuable when it meaningfully reduces surgical morbidity.

Pulmonary metastases

Small stable pulmonary metastases may behave indolently.

Resect progressing or technically suitable pulmonary disease when appropriate.

Denosumab can be used for unresectable metastatic GCT.

Surveillance

Local recurrence occurs most frequently during the first several years.

Follow with:

Local radiographs
Clinical examination
Chest imaging according to disease severity

Rapid destructive progression during or after denosumab warrants reassessment and repeat biopsy because malignant transformation or an initially missed sarcoma must be considered.

Osteosarcoma

Overview

Clinical Features

Diagnosis

Management

Overview

Clinical Features

Diagnosis

Management