Orthopaedic Surgery - Osteosarcoma

Basics

Osteosarcoma is a high-grade primary malignant bone tumor characterized by malignant cells that directly produce osteoid or immature bone.

It is one of the most important primary bone sarcomas in:

Children

Adolescents

Young adults

and is particularly associated with periods of rapid skeletal growth.

Osteosarcoma can also occur in older adults, although in this population other primary bone malignancies, including chondrosarcoma, become relatively more common.

Synonym

Osteosarcoma is also called:

Osteogenic sarcoma.

Biological Behavior

Conventional high-grade osteosarcoma is an aggressive malignancy characterized by:

Rapid local invasion

Cortical destruction

Soft-tissue extension

Early hematogenous metastasis

The most common site of distant metastasis is the:

Lung.

Bone metastases may also occur.

Common Sites

Osteosarcoma most often develops in rapidly growing metaphyseal regions of long bones.

Historical distributions include:

Femur – approximately 41.5%

Tibia – approximately 16.5%

Humerus – approximately 15%

The classic location is:

Around the knee, particularly the distal femur and proximal tibia.

Classification

Osteosarcoma can be classified according to:

Anatomic location

Histologic grade

Degree of differentiation

Relationship to the bone surface or medullary cavity

Conventional High-Grade Intramedullary Osteosarcoma

This is the:

Most common form.

It arises within the medullary cavity and usually behaves aggressively.

Low-Grade or Well-Differentiated Intramedullary Osteosarcoma

This is uncommon and generally has:

Less aggressive histologic features

than conventional high-grade disease.

Surface Osteosarcomas

Surface osteosarcomas arise from the external surface of bone.

They include:

Parosteal osteosarcoma

Periosteal osteosarcoma

High-grade surface osteosarcoma

Parosteal Osteosarcoma

Parosteal osteosarcoma is the most common surface subtype.

It is generally:

Low grade

Well differentiated

and most frequently occurs around the:

Distal femur

although other metaphyseal locations can be involved.

Periosteal Osteosarcoma

Periosteal osteosarcoma is typically:

Intermediate grade

and arises from the bone surface beneath the periosteum.

It often demonstrates:

Prominent chondroid differentiation with malignant bone formation.

It more frequently involves the:

Diaphyseal or metadiaphyseal region.

High-Grade Surface Osteosarcoma

High-grade surface osteosarcoma is rare and behaves more aggressively than parosteal or many periosteal lesions.

Osteosarcoma of the Jaw

Osteosarcoma can involve the:

Mandible

or

Maxilla.

Jaw osteosarcomas often occur at an older age and may behave somewhat differently from conventional high-grade extremity osteosarcoma.

Secondary Osteosarcoma

Osteosarcoma can occasionally develop in previously abnormal bone.

Examples include:

Paget disease

Previous radiation exposure

Bone infarction

Fibrous dysplasia

and, rarely, other pre-existing skeletal disorders.

These are referred to as:

Secondary osteosarcomas.

Staging

Musculoskeletal sarcomas have historically been staged using the Enneking system.

Many conventional osteosarcomas present as:

Stage IIB – high-grade extracompartmental disease with soft-tissue extension

whereas patients with distant metastases are classified as:

Stage III.

Approximately 10–20% of patients historically have had detectable metastatic disease at diagnosis.

Epidemiology

Osteosarcoma occurs most commonly during:

The second decade of life.

The median age at presentation has historically been approximately:

13–17 years.

A slight male predominance has been reported.

Incidence

Primary sarcomas of bone are uncommon.

Osteosarcoma accounts for only a small fraction of all cancers but is one of the more common primary malignant bone tumors in children and adolescents.

Older U.S. estimates described several hundred new osteosarcoma cases annually.

Risk Factors

Most patients have no identifiable predisposing condition.

Recognized risk factors include:

Previous therapeutic radiation

Paget disease of bone

Bone infarction

Certain hereditary cancer syndromes

Pre-existing abnormal bone in selected disorders

Etiology

The cause of conventional high-grade osteosarcoma is usually unknown.

Its increased frequency during periods of:

Rapid skeletal growth

has long suggested a relationship between growth rate and tumor development, although rapid growth itself is not considered a direct cause.

Genetic Abnormalities

Osteosarcoma frequently contains complex genomic abnormalities.

Important tumor-suppressor pathways include:

RB1

and

TP53.

Retinoblastoma

Patients with hereditary retinoblastoma have an increased risk of developing osteosarcoma because of germline abnormalities involving the:

RB1 tumor-suppressor gene.

The risk may be further increased after radiation exposure.

Other Hereditary Syndromes

Osteosarcoma can also occur more frequently in rare cancer-predisposition syndromes involving:

TP53

and other genes controlling:

Cell-cycle regulation and DNA repair.

Associated Conditions

Important associated conditions include:

Hereditary retinoblastoma

Paget disease

Prior radiotherapy

Certain hereditary cancer syndromes

Diagnosis

Diagnosis is based on:

Clinical features

Plain radiographs

MRI

Staging studies

and

Biopsy.

Signs and Symptoms

The most common symptoms are:

Pain

and

Swelling.

Pain

Pain usually develops:

Gradually

and becomes:

Persistent and progressive.

It may initially be attributed to:

Sports activity

Minor trauma

or

Growing pains.

Night Pain

Many patients report:

Pain at night, sometimes severe enough to interrupt sleep.

Persistent night pain in a child or adolescent with a focal bone lesion should prompt further evaluation.

Swelling

As the tumor expands through the cortex, patients may notice:

Localized swelling

or

A palpable mass.

Physical Examination

A soft-tissue mass may be:

Firm

Tender

Warm

and associated with:

Reduced motion of the adjacent joint.

Range of Motion

Large lesions near a joint may cause:

Painful limitation of motion

because of local mass effect and inflammation.

Direct joint invasion is relatively uncommon early because articular cartilage and other joint structures initially act as barriers.

Pathologic Fracture

Occasionally, patients present with a:

Pathologic fracture through the tumor.

This complicates local treatment because fracture hematoma may contaminate surrounding tissue planes.

Staging Evaluation

Once osteosarcoma is suspected or diagnosed, staging commonly includes:

MRI of the primary tumor

CT of the chest

and

Whole-body assessment for additional skeletal disease, traditionally with bone scintigraphy and increasingly with other appropriate staging modalities.

Biopsy

Definitive diagnosis requires tissue biopsy.

The biopsy should be planned by or in consultation with the:

Musculoskeletal oncologic surgeon who will perform definitive resection.

Poor biopsy placement can contaminate compartments and complicate limb-salvage surgery.

Laboratory Tests

There is no single diagnostic blood test for osteosarcoma.

Alkaline Phosphatase

Serum alkaline phosphatase may be elevated.

A markedly elevated pretreatment value has historically been associated with:

Greater tumor burden and less favorable prognosis.

Serial measurements can occasionally help monitor disease when the level was elevated initially.

Lactate Dehydrogenase

Serum LDH may also be elevated.

An elevated LDH has likewise been associated with:

Higher tumor burden and poorer prognosis in some studies.

Imaging

Plain Radiographs

Osteosarcoma most commonly arises in the:

Metaphysis of a long bone.

Typical radiographic features include a mixture of:

Bone destruction

Tumor bone formation

Aggressive periosteal reaction

Soft-tissue mass

Destructive Bone Lesion

The classic lesion is:

Aggressively destructive while simultaneously producing abnormal mineralized osteoid or bone.

There may be:

Poorly defined margins

Cortical destruction

Mixed lytic and sclerotic change

Tumor Bone Formation

Malignant osteoid may appear radiographically as:

Cloud-like or dense mineralization

within the lesion or soft-tissue mass.

Codman Triangle

Rapid tumor growth may lift the periosteum away from the cortex.

Reactive bone formation at the edge of this elevated periosteum can produce a:

Codman triangle.

This is an aggressive periosteal reaction but is not specific to osteosarcoma.

Sunburst Appearance

Radiating spicules of mineralized tumor or reactive bone extending perpendicular to the cortex can create the classic:

Sunburst or sunray appearance.

Again, this is suggestive but not pathognomonic.

Soft-Tissue Extension

A mineralized soft-tissue mass strongly supports an aggressive bone-forming lesion.

MRI

MRI is the preferred modality for defining:

Intramedullary tumor extent

Soft-tissue extension

Relationship to neurovascular structures

Relationship to the joint

Skip lesions within the involved bone

This information is essential for surgical planning.

Chest CT

CT of the chest is important because:

The lungs are the most common site of metastasis.

Small pulmonary nodules may be detected before they are visible on routine chest radiography.

Skeletal Staging

Whole-body imaging is used to evaluate for:

Bone metastases

and

Additional skeletal lesions.

Pathological Findings

The defining histologic feature of osteosarcoma is:

Malignant mesenchymal cells directly producing osteoid or immature bone.

This malignant osteoid is required for diagnosis.

Histologic Subtypes

Conventional osteosarcoma may demonstrate varying dominant patterns.

Broad histologic patterns include:

Osteoblastic

Chondroblastic

Fibroblastic

Regardless of subtype, malignant osteoid production is the essential feature.

Differential Diagnosis

Important differential diagnoses include:

Osteomyelitis

Ewing sarcoma

Giant cell tumor

Metastatic bone disease

Eosinophilic granuloma

Other bone-forming tumors

Osteomyelitis

Infection may mimic osteosarcoma because both can produce:

Pain

Swelling

Bone destruction

Periosteal reaction

Clinical findings, inflammatory markers, MRI, and biopsy help distinguish the two.

Ewing Sarcoma

Ewing sarcoma frequently affects children and adolescents and can also present with:

Pain

Swelling

Aggressive bone destruction

However, its typical location and histologic appearance differ from osteosarcoma.

Giant Cell Tumor

Giant cell tumor generally occurs in:

Skeletally mature patients

and typically involves the:

Epiphysis extending to the subchondral bone.

Metastatic Disease

Metastatic bone lesions become increasingly important in the differential diagnosis in older adults.

Treatment

General Principles

Any patient with an aggressive destructive lesion that also demonstrates:

Tumor bone formation

should be referred promptly to an experienced:

Musculoskeletal oncology team.

Biopsy or definitive surgery should not be undertaken casually before appropriate staging and multidisciplinary planning.

Activity

Once osteosarcoma is suspected, the affected extremity should be protected from:

High-impact activity

Falls

Excessive weight bearing

to minimize the risk of:

Pathologic fracture.

Lower-Extremity Lesions

Patients with tumors of the lower extremity are often instructed to use:

Crutches or another protected-weight-bearing aid.

Upper-Extremity Lesions

For upper-extremity tumors, efforts should be made to maintain:

Hand

Wrist

and

Elbow function

while avoiding activities that risk fracture through the tumor.

Chemotherapy

Modern treatment of conventional high-grade osteosarcoma combines:

Systemic chemotherapy

with

Wide surgical resection.

Neoadjuvant Chemotherapy

Chemotherapy is often administered:

Before surgery

to treat microscopic metastatic disease and begin systemic tumor control.

A typical preoperative phase lasts several weeks.

Common Chemotherapy Agents

Common multiagent regimens may include combinations of:

High-dose methotrexate

Doxorubicin

Cisplatin

with other agents used in selected protocols.

The exact regimen depends on:

Age

Tumor characteristics

Treatment center

National or cooperative-group protocol

Adjuvant Chemotherapy

Chemotherapy is continued after surgery for several months.

Postoperative treatment addresses:

Micrometastatic disease

and reduces the risk of systemic recurrence.

Histologic Response

The amount of tumor necrosis following preoperative chemotherapy is an important prognostic factor.

A high percentage of necrosis generally indicates:

A favorable chemotherapy response.

Surgery

Historically, amputation was the standard treatment.

With modern imaging, chemotherapy, reconstruction, and oncologic surgical techniques, most appropriately selected patients can undergo:

Limb-salvage surgery.

Wide Resection

The primary tumor must be removed with:

A wide margin of uninvolved tissue.

The goal is complete local control without leaving microscopic tumor at the surgical margin.

Limb Salvage

Limb salvage is feasible in a large majority of patients when:

Adequate margins can be achieved

Critical neurovascular structures can be preserved or reconstructed

and

The limb can remain functional.

Reconstruction

After tumor resection, the skeletal defect may be reconstructed using:

Large-segment endoprostheses

Allograft

Allograft-prosthetic composites

Other biological reconstruction techniques

depending on the site and age of the patient.

Amputation

Amputation may still be required when:

Adequate oncologic margins cannot be achieved with limb salvage

Major neurovascular contamination exists

Severe infection or tissue loss prevents reconstruction

Functional limb salvage would be inferior to amputation

Pulmonary Metastasectomy

Selected patients with resectable lung metastases may benefit from:

Surgical removal of pulmonary metastatic lesions, particularly when complete resection is possible.

Follow-Up

Long-term surveillance is required because osteosarcoma can recur:

Locally

or

At distant sites.

The lungs are monitored especially closely.

Prognosis

Before effective chemotherapy, survival for high-grade osteosarcoma was poor, with historical 5-year survival rates of only:

Approximately 20–30%.

The major problem was occult pulmonary metastatic disease.

Modern Outcomes

For patients with:

Localized high-grade disease

treated with multiagent chemotherapy and complete surgical resection, long-term survival is substantially better, historically in the range of:

Approximately 60–70% or higher in selected contemporary series.

Outcomes are significantly worse when metastatic disease is present at diagnosis.

Favorable Prognostic Factors

Better outcomes are associated with:

Localized disease

Complete surgical resection

Good histologic response to chemotherapy

Smaller tumor burden

Resectable pulmonary metastases when present

Poor Prognostic Factors

Less favorable factors include:

Metastatic disease at diagnosis

Large tumor volume

Poor chemotherapy response

Elevated alkaline phosphatase or LDH in some series

Inability to achieve clear surgical margins

Complications

Pulmonary Metastases

The lungs are the most frequent site of metastatic spread.

Pulmonary metastases may occur:

At diagnosis

or

During follow-up after treatment.

Most recurrences occur within the first several years, although later recurrence is possible.

Bone Metastases

Osteosarcoma may also metastasize to:

Other bones.

Multifocal skeletal involvement generally indicates a less favorable prognosis.

Local Recurrence

Local recurrence after limb-salvage treatment is uncommon when adequate margins are obtained but remains a serious complication.

Older series reported local recurrence in approximately:

5–10% of patients.

Pathologic Fracture

Fracture through the tumor can:

Increase pain

Complicate local control

Contaminate surrounding tissues

It does not automatically require amputation, but it may make limb salvage more difficult.

Infection

Major reconstruction after tumor resection carries a meaningful risk of:

Deep infection.

This may require:

Débridement

Revision reconstruction

or occasionally

Amputation.

Prosthetic Complications

Endoprosthetic reconstruction may be complicated by:

Aseptic loosening

Mechanical failure

Periprosthetic fracture

Joint instability

Wear

Need for revision surgery

Wound Complications

Large oncologic resections may lead to:

Wound breakdown

Skin necrosis

Delayed healing

particularly after extensive soft-tissue resection.

Chemotherapy-Related Complications

Systemic treatment may cause:

Myelosuppression

Infection

Renal toxicity

Cardiac toxicity

Hearing impairment

and other drug-specific adverse effects.

Patient Monitoring

Post-treatment surveillance should assess for:

Pulmonary metastasis

Local recurrence

Bone metastasis

Reconstruction failure

Long-term chemotherapy effects

Chest Surveillance

Because pulmonary metastases are particularly common, chest imaging is performed regularly.

Historically, chest CT was obtained approximately every:

3–4 months during the first 2 years, with progressively longer intervals afterward.

The exact modern surveillance schedule depends on:

Treatment protocol

Disease stage

Age

Institutional practice

Local Imaging

Plain radiographs of the treated extremity are used to assess:

Local recurrence

Prosthetic or graft integrity

Fracture

Mechanical complications

MRI may be added when recurrence is suspected.

Key Principle

Osteosarcoma is an aggressive malignant bone-forming tumor that most commonly arises in the metaphyses of rapidly growing long bones in adolescents.

The defining pathologic feature is:

Malignant osteoid production.

Optimal treatment requires:

Prompt referral to musculoskeletal oncology, carefully planned biopsy, systemic multiagent chemotherapy, wide surgical resection, appropriate reconstruction, and long-term surveillance for pulmonary and local recurrence.