High Yield Overview

Osteosarcoma

Most Common Primary Bone Cancer

Distal Femur Most Common (50%)Location

Adolescents 10-20 (Peak)Age

Sunburst + Codman TriangleX-ray

60-70% (Localized Disease)Survival

Osteosarcoma Subtypes

Conventional (75%)

PatternHigh-grade intramedullary, produces osteoid.

TreatmentNeoadjuvant + Surgery + Adjuvant chemo

Telangiectatic (10%)

PatternLytic, hemorrhagic, mimics ABC.

TreatmentSame protocol as conventional

Parosteal (4%)

PatternLow-grade surface tumor.

TreatmentWide resection only - no chemo

Periosteal (2%)

PatternIntermediate-grade surface.

TreatmentMay need adjuvant chemo

Critical Must-Knows

Distal Femur: Most common location (50%), then proximal tibia (25%).
Bimodal Age: Adolescents (primary) and over 60 (secondary - Paget's).
Sunburst: Spiculated periosteal reaction - pathognomonic radiographic sign.
Codman Triangle: Elevated periosteum at tumor margin.
MAP Protocol: Methotrexate (high-dose), Adriamycin, cisPlatin.
Histologic Response: Over 90% necrosis = good prognosis (75-80% survival).

Examiner's Pearls

"
Distal femur most common primary bone cancer location
"
Sunburst + Codman triangle = osteosarcoma until proven otherwise
"
Neoadjuvant chemo BEFORE surgery - treats micrometastases
"
Over 90% necrosis = good response and better prognosis
"
Biopsy tract must be excised with specimen - plan with surgeon

Clinical Imaging

Imaging Gallery

A 12-year-old girl presented with pain after exercise (case 5). (A) The plain radiograph showed focal cortical breakage and faint sclerosis in the proximal tibia (arrow). (B) Under the assumption of a — A 12-year-old girl presented with pain after exercise (case 5). (A) The plain radiograph showed focal cortical breakage and faint sclerosis in the proCredit: Song WS et al. via Clin Orthop Surg via Open-i (NIH) (Open Access (CC BY))

A 42-year-old patient with an adamantinoma of the left proximal tibia. a X-ray showed the lesion located at the proximal part of the left tibia. b MRI showed the knee joint was not involved by the tum — A 42-year-old patient with an adamantinoma of the left proximal tibia. a X-ray showed the lesion located at the proximal part of the left tibia. b MRICredit: Qu H et al. via World J Surg Oncol via Open-i (NIH) (Open Access (CC BY))

Data of radiography. A, B) Anteroposterior and lateral radiographs and C) magnetic resonance imaging studies were consistent with an osteosarcoma of the left distal femur. — Data of radiography. A, B) Anteroposterior and lateral radiographs and C) magnetic resonance imaging studies were consistent with an osteosarcoma of tCredit: Ding HW et al. via BMC Musculoskelet Disord via Open-i (NIH) (Open Access (CC BY))

Radiographs showing pathognomonic periosteal reactions in osteosarcoma — Classic osteosarcoma radiographic findings: (A) Codman triangle - elevated periosteum at tumor margin in proximal tibia osteosarcoma (arrows). (B) Sunburst periosteal reaction - spiculated pattern in distal femur osteosarcoma (arrows). These aggressive periosteal reactions are highly characteristic of high-grade osteosarcoma.Credit: Messiou C et al. - PMC11477067 (CC-BY 4.0)

Critical Treatment Principle

Osteosarcoma treatment REQUIRES CHEMOTHERAPY.

Surgery alone results in 80% recurrence (micrometastases at presentation).
Neoadjuvant chemotherapy: Shrinks tumor, treats micrometastases, allows histologic assessment.
Adjuvant chemotherapy: Completes treatment, improves survival from 20% to 60-70%.
Exception: Parosteal osteosarcoma (low-grade surface) - wide resection only.

At a Glance Table

Feature	Details
Definition	Primary malignant bone tumor producing osteoid by malignant cells
Incidence	3-4 per million per year (most common primary bone cancer in adolescents)
Peak Age	Bimodal: 10-20 years (primary), over 60 (secondary - Paget's)
Sex Ratio	Male to Female = 1.5:1
Most Common Location	Distal femur (50%), proximal tibia (25%), proximal humerus (10%)
Classic Triad	Pain + Mass + Restricted ROM
Pathognomonic X-ray	Sunburst periosteal reaction + Codman triangle
Treatment Protocol	Neoadjuvant chemo → Wide resection → Adjuvant chemo
5-Year Survival	60-70% localized, 20-30% metastatic at presentation
Key Prognostic Factor	Histologic necrosis (over 90% = good response)

Mnemonic Cards

Mnemonic

Osteosarcoma Sites - DPHF

Distal femur

50% - Most common location around knee

Proximal tibia

25% - Second most common, also knee

Humerus (proximal)

10% - Third most common site

Flat bones

Pelvis, skull in older patients

Memory Hook:DPHF - 'Down Past the Hip to Flat' - Remember location distribution by frequency.

Mnemonic

Radiographic Signs - SCAM

Sunburst

Spiculated periosteal reaction (pathognomonic)

Codman triangle

Elevated periosteum at tumor margin

Aggressive

Wide zone of transition, cortical destruction

Mixed

Mixed lytic and sclerotic (osteoid production)

Memory Hook:SCAM the X-ray - Classic aggressive bone tumor appearance on radiographs.

Mnemonic

MAP Chemotherapy

Methotrexate

High-dose with leucovorin rescue

Adriamycin

Doxorubicin - cardiotoxicity limit

cisPlatin

Platinum agent - nephrotoxicity

Memory Hook:MAP your treatment - All 3 drugs needed for optimal survival in osteosarcoma.

Mnemonic

Enneking Staging - GTM

Grade

G1 (low) vs G2 (high grade)

Tumor site

T1 (intra) vs T2 (extracompartmental)

Metastases

M0 (none) vs M1 (present)

Memory Hook:GTM staging - Grade, Tumor site, Mets determine prognosis and margin requirements.

Overview/Epidemiology

Osteosarcoma is the most common primary malignant bone tumor, characterized by direct formation of osteoid or immature bone by malignant mesenchymal cells.

Epidemiology

Incidence

3-4 per million per year
400 new cases in USA annually
Most common in adolescents
Second peak over 60 years

Risk Factors

Prior radiation therapy
Paget's disease (1% transform)
Li-Fraumeni syndrome (p53)
Hereditary retinoblastoma (Rb1)
Rothmund-Thomson syndrome

Location Distribution

Distal femur: 50%
Proximal tibia: 25%
Proximal humerus: 10%
Other long bones: 15%
Metaphyseal predilection

Bimodal Age Distribution

Peak	Age Range	Characteristics	Association
Primary Peak	10-20 years	Rapid skeletal growth	Metaphyseal location, conventional type
Secondary Peak	Over 60 years	Paget's sarcoma	Axial skeleton, poor prognosis

Exam Pearl

Paget's Sarcoma: Secondary osteosarcoma in Paget's disease occurs in 1% of patients. Presents with sudden increase in pain, rapid enlargement, or rising alkaline phosphatase in known Paget's. Very poor prognosis (5-year survival under 10%).

Anatomy/Biomechanics

Anatomic Considerations for Tumor Location

Metaphyseal Predilection:

Osteosarcoma arises from primitive mesenchymal bone-forming cells
Metaphyses have highest osteoblastic activity during growth
Rich blood supply to metaphyses facilitates tumor growth
Growth plate initially acts as barrier to epiphyseal extension

Compartmental Anatomy

Tumor Extension Patterns:

Direction	Barrier	Clinical Significance
Intramedullary	Cortical bone	Skip lesions possible - MRI entire bone
Extraosseous	Soft tissue planes	Neurovascular involvement risk
Transphyseal	Growth plate	Less effective barrier than previously thought
Intra-articular	Joint capsule	Rare but indicates Stage IIB/III

Neurovascular Relationships

Distal Femur (Most Common Site):

Popliteal artery/vein: Posterior to femur, at risk with posterior extension
Femoral artery/vein: In Hunter's canal - anterior/medial approach consideration
Sciatic nerve: Posterolateral - divides to tibial and common peroneal above knee

Proximal Tibia:

Popliteal vessels: Posterior, trifurcate below knee
Anterior tibial vessels: Pass through interosseous membrane
Common peroneal nerve: Wraps around fibular neck - high risk

Classification Systems

WHO Histologic Classification:

Osteosarcoma Subtypes by Grade and Location

Subtype	Grade	Location
High	Intramedullary	Yes - MAP protocol
High	Intramedullary	Yes - Same as conventional
High	Intramedullary	Yes - May add Ewing's protocol
Low	Surface (posterior femur)	No - Wide resection only
Intermediate	Surface (diaphysis)	Consider adjuvant
High	Surface	Yes - Full protocol

Key point: Conventional osteosarcoma (75%) requires full chemotherapy protocol.

MRI of telangiectatic osteosarcoma showing fluid-fluid levels — Telangiectatic osteosarcoma: MRI demonstrating characteristic fluid-fluid levels (arrows) representing blood products of different ages within cystic spaces. This appearance can mimic aneurysmal bone cyst - biopsy is essential to avoid misdiagnosis. Despite lytic appearance, treatment follows the same protocol as conventional osteosarcoma.Credit: Messiou C et al. - PMC11477067 (CC-BY 4.0)

Clinical Presentation

History

Primary Symptoms

Pain: Progressive, worse at night
Initially activity-related
Becomes constant
May wake from sleep
NSAIDs initially helpful

Mass/Swelling

Develops over weeks-months
May be warm to touch
Firm, fixed to bone
Skin changes rare
Visible deformity late

Red Flags

Pathological fracture (10%)
Weight loss (late)
Night sweats (rare)
Respiratory symptoms (mets)
Duration under 6 months typical

Physical Examination

Systematic Assessment:

Inspection:
- Swelling/mass location
- Skin changes (rare, late)
- Muscle wasting (adjacent)
- Limb length (if growth plate involved)
Palpation:
- Mass characteristics: Firm, fixed to bone, tender
- Warmth (increased vascularity)
- Range of motion (reduced if near joint)
- Lymph nodes (rarely involved - under 3%)
Neurovascular:
- Pulses (rarely compromised)
- Sensation (late involvement)
- Motor function
- Compartment tension

Pathological Fracture

10% of osteosarcomas present with pathological fracture. This does NOT automatically preclude limb salvage but:

Creates surgical challenge (contamination of fracture hematoma)
May require modified chemotherapy timing
Still achieves similar survival with careful planning

Pathological fracture through osteosarcoma: Radiograph demonstrating fracture through a destructive bone lesion. While historically considered a poor prognostic sign, modern chemotherapy and careful surgical planning can still achieve limb salvage and comparable survival outcomes in many patients.Credit: Messiou C et al. - PMC11477067 (CC-BY 4.0)

Differential Diagnosis

Diagnosis	Key Distinguishing Features
Ewing Sarcoma	Diaphyseal, permeative, onion-skin periosteal, smaller cell
Chondrosarcoma	Older patients (40-60), axial, chondroid matrix (arcs/rings)
Giant Cell Tumor	Epiphyseal, eccentrically lytic, no matrix
Osteomyelitis	Systemic symptoms, sequestrum, involucrum
Stress Fracture	Transverse, no soft tissue mass, healing callus
Aneurysmal Bone Cyst	Eccentric, expansile, fluid levels on MRI

Investigations

Imaging Protocol

First-Line Investigation - Essential Characteristics:

Location:
- Metaphyseal (most common)
- Eccentric or central
Matrix:
- Osteoid production (cloud-like density)
- "Cumulus cloud" appearance
- Dense sclerotic areas
Periosteal Reaction:
- Sunburst/Spiculated: Pathognomonic
- Codman Triangle: Elevated periosteum at margins
- Indicates aggressive behavior
Margins:
- Permeative/moth-eaten (aggressive)
- Wide zone of transition
- Cortical destruction
Soft Tissue:
- Extraosseous mass
- May show calcification

These findings together create the classic "aggressive bone lesion" appearance.

Chronological progression of osteosarcoma on X-ray and MRI correlation — Osteosarcoma imaging evolution and multimodal assessment: (A-C) Serial plain radiographs showing chronological changes of proximal tibia osteosarcoma - note the progressive periosteal reaction and Codman triangle (arrow in panel A indicates subtle early periosteal elevation). The metaphyseal location and aggressive permeative pattern are characteristic. (D) Coronal MRI demonstrating the full tumor extent, critical for surgical planning to determine appropriate resection margins and assess for skip lesions.Credit: Open-i/PMC - CC BY 4.0

Classic distal femur osteosarcoma with X-ray and MRI — 3-panel (A-C) classic distal femur osteosarcoma. Panels A-B: AP and lateral radiographs showing large destructive lesion with sunburst periosteal reaction, soft tissue mass, and osteoid matrix production. Panel C: Coronal MRI demonstrating full extent of intramedullary involvement and soft tissue extension for surgical planning.Credit: Ding HW et al., BMC Musculoskelet Disord (CC-BY)

Biopsy Principles

Biopsy Planning - CRITICAL

The biopsy is the MOST IMPORTANT step in diagnosis:

MUST be planned with definitive surgeon
Wrong approach contaminates compartments
Biopsy tract excised with specimen
Violating these principles may necessitate amputation

Biopsy Technique:

Approach	Pros	Cons	Indication
Core Needle	Less contamination, outpatient	May miss diagnosis (sampling)	Preferred in most centers
Open Incisional	More tissue, higher accuracy	More contamination	If core non-diagnostic
Excisional	Diagnostic + therapeutic	Contraindicated	Never for suspected osteosarcoma

Biopsy Rules:

Longitudinal incision along planned resection
Avoid contaminating neurovascular structures
Through muscle (not between compartments)
Meticulous hemostasis
Mark biopsy site for excision

Management Algorithm

Osteosarcoma treatment algorithm flowchart — Treatment pathway: Staging → Neoadjuvant chemotherapy (8-12 weeks) → Restaging → Wide resection → Histologic assessment → Adjuvant chemotherapy.

Standard Treatment Pathway:

DIAGNOSIS CONFIRMED
        ↓
STAGING (MRI, CT Chest, Bone Scan)
        ↓
    ┌───────────────────┐
    │ NEOADJUVANT CHEMO │ → 8-12 weeks MAP protocol
    │   (Pre-operative) │
    └─────────┬─────────┘
              ↓
         RESTAGING
              ↓
    ┌───────────────────┐
    │  WIDE RESECTION   │ → Limb salvage (80-90%) or Amputation
    │    ± Recon        │
    └─────────┬─────────┘
              ↓
    HISTOLOGIC ASSESSMENT
    (% tumor necrosis)
              ↓
    ┌───────────────────┐
    │  ADJUVANT CHEMO   │ → Continue/modify based on response
    │ (Post-operative)  │
    └───────────────────┘

Key point: Surgery is performed AFTER neoadjuvant chemotherapy to assess histologic response.

Non-Operative Management

Chemotherapy Protocol

Mnemonic

MAP Chemotherapy

Methotrexate

High-dose with leucovorin rescue

Adriamycin

Doxorubicin - cardiotoxicity limit

cisPlatin

Platinum agent - nephrotoxicity

Memory Hook:MAP your treatment - all 3 drugs needed for optimal survival.

Neoadjuvant Chemotherapy (Pre-operative):

Duration: 8-12 weeks (2-4 cycles)
Purpose: Shrink tumor, treat micrometastases, assess response
Response assessment: Tumor shrinkage on imaging (not reliable)

Adjuvant Chemotherapy (Post-operative):

Duration: 12-29 weeks additional
Total treatment: Approximately 1 year
Modifications based on histologic response

Chemotherapy Toxicities

Agent	Major Toxicity	Monitoring	Management
Methotrexate	Mucositis, nephrotoxicity, hepatotoxicity	Levels, renal function	Leucovorin rescue, hydration
Doxorubicin	Cardiotoxicity (dose-dependent)	Echo/MUGA	Lifetime dose limit 450mg/m²
Cisplatin	Nephrotoxicity, ototoxicity, neuropathy	Cr, audiometry	Hydration, dose adjustment

Exam Pearl

Doxorubicin Cardiotoxicity: Cumulative dose-dependent. Lifetime limit typically 450mg/m². Echo/MUGA before each cycle. Irreversible cardiomyopathy if exceeded.

Indications for Chemotherapy

Subtype	Neoadjuvant	Adjuvant	Notes
Conventional	Yes	Yes	Standard MAP protocol
Telangiectatic	Yes	Yes	Same as conventional
Parosteal (Low-grade)	No	No	Wide resection only
Periosteal	Consider	Consider	Case-by-case decision
High-grade Surface	Yes	Yes	Full protocol

Surgical Technique

Surgical Principles

Margin Requirements:

Wide Margin: Minimum 1-2cm of bone beyond tumor
Cuff of Normal Tissue: Must include reactive zone
Biopsy Tract: Excise with specimen
Skip Lesions: Must be included in resection

Limb Salvage Options

Modular Metal Replacement:

Indications:

Most common reconstruction
Distal femur, proximal tibia, proximal humerus
Allows early mobilization

Advantages:

Immediate stability
Early weight-bearing
No donor site morbidity

Disadvantages:

Mechanical failure (5-10 year revision)
Infection (5-15%)
Aseptic loosening
Limited lifespan in young patients

Growing Prostheses:

For skeletally immature patients
Non-invasive lengthening available
Multiple lengthening procedures required

Endoprosthesis remains the gold standard for most limb salvage reconstructions.

Amputation Considerations

When Amputation is Indicated:

Neurovascular encasement (not reconstructable)
Massive soft tissue involvement
Poor response to chemotherapy with progression
Pathological fracture with contamination
Patient preference
Infection precluding salvage
Expected non-functional limb

Amputation Levels:

Above-knee for distal femur tumors
Hip disarticulation for proximal femur
Forequarter for proximal humerus (rarely needed)

Exam Pearl

Survival Equal: Multiple studies confirm limb salvage and amputation have equivalent oncologic outcomes when appropriate margins achieved. Limb salvage preferred when feasible due to better function and quality of life.

Complications

AP X-ray showing pathological fracture through distal femur osteosarcoma — Pathological fracture through distal femur osteosarcoma (arrow). Note the extensive bone destruction with mixed sclerotic/lytic pattern characteristic of osteosarcoma. Pathological fractures historically worsened prognosis due to tumor contamination, but modern neoadjuvant chemotherapy and surgical techniques have improved outcomes. Immobilization is required until surgery, and the fracture site must be included in the resection specimen.Credit: Messiou C et al. - PMC11477067 (CC-BY 4.0)

Chemotherapy Complications

Complication	Agent	Incidence	Prevention/Management
Cardiotoxicity	Doxorubicin	5-10%	Dose limit 450mg/m², serial Echo
Nephrotoxicity	Cisplatin, MTX	10-20%	Hydration, dose adjustment
Ototoxicity	Cisplatin	10-30%	Audiometry, dose modification
Mucositis	MTX	40-60%	Leucovorin rescue, supportive care
Myelosuppression	All agents	Universal	G-CSF, transfusions
Secondary Malignancy	All agents	2-5%	Long-term surveillance

Surgical Complications

Early Complications

Wound infection/dehiscence (10-15%)
Flap necrosis
Deep vein thrombosis
Neurovascular injury
Periprosthetic fracture

Late Complications

Aseptic loosening (30% at 10 years)
Prosthesis failure/breakage
Infection (5-15% lifetime)
Leg length discrepancy
Amputation (10-15% conversion)

Allograft Specific

Non-union (15-30%)
Fracture (15-20%)
Resorption
Disease transmission (rare)
Infection (10-15%)

Local Recurrence

Risk Factors:

Inadequate margins
Poor histologic response
Skip lesion missed
Pathological fracture
Biopsy tract violation

Management:

Re-staging (local + systemic)
Further resection if possible
Amputation if no salvage option
Chemotherapy if not previously given
Prognosis worse (30-40% survival)

Postoperative Care

Immediate Postoperative Period

Day 0-7:

ICU/HDU for 24-48 hours (major surgery)
DVT prophylaxis (mechanical + chemical)
Wound assessment (skin flaps, drain output)
Pain management (multimodal analgesia)
Limb elevation

Week 1-6:

Physiotherapy: ROM exercises
Weight-bearing: Depends on reconstruction
- Endoprosthesis: Touch weight-bearing → progressive
- Allograft: Protected weight-bearing 6-12 weeks
Wound care: Watch for infection/dehiscence
Chemotherapy: Resumes when wound healed (usually week 3-4)

Rehabilitation Protocol

Phase	Timeline	Goals	Activities
Acute	0-6 weeks	Wound healing, ROM	Bed exercises, transfer training
Intermediate	6-12 weeks	Strength, progressive WB	Gait training, strengthening
Advanced	3-6 months	Full function	Sport-specific training
Maintenance	Ongoing	Monitor function	Activity modification as needed

Follow-up Surveillance

Year 1-2:

Every 3 months: Clinical exam, chest X-ray
Every 6 months: CT chest, local imaging

Year 3-5:

Every 6 months: Clinical exam, chest X-ray
Annual: CT chest

Beyond 5 years:

Annual clinical and radiographic review
Late recurrence possible (rare after 10 years)
Monitor for late effects of chemotherapy

Outcomes/Prognosis

Survival Rates

Disease Status	5-Year Survival	Notes
Localized Disease	60-70%	Majority of presentations
Metastatic at Diagnosis	20-30%	15-20% have lung mets at presentation
Good Response (over 90% necrosis)	75-80%	Strongest prognostic factor
Poor Response (under 90% necrosis)	50-55%	Still benefits from adjuvant chemo
Local Recurrence	30-40%	Depends on resectability

Prognostic Factors

Favorable vs Unfavorable Prognostic Factors

Factor	Favorable	Unfavorable
Over 90% necrosis	Under 90% necrosis
Localized disease	Metastatic at diagnosis
Extremity	Axial skeleton, pelvis
Under 8cm	Over 8cm, skip lesions
Normal	Elevated
Wide/negative	Marginal/positive

Mnemonic

Osteosarcoma Prognosis

Size

Under 8cm better

Metastases

Absence = better

ALP

Normal = better

Response

Over 90% necrosis = best

Type/Site

Extremity, conventional = better

Memory Hook:SMART prognosis assessment.

Functional Outcomes

Limb Salvage:

MSTS functional score: 70-85%
Most return to normal daily activities
Competitive sports: Limited/modified
Prosthesis revision: Expected at 10-15 years

Amputation:

Prosthetic fitting: 2-3 months post-op
Above-knee: 60-70% MSTS score
Quality of life: Similar to limb salvage
Energy expenditure: Higher for ambulation

Evidence Base

Landmark

📚 Rosen G et al - T10 Protocol

Key Findings:

Introduced neoadjuvant chemotherapy concept
Demonstrated survival improvement from 20% to 60%
Established histologic response as prognostic factor
Foundation for all modern osteosarcoma protocols

Clinical Implication: Chemotherapy is absolutely essential - surgery alone inadequate.

Source: Cancer 1976

Level I

📚 EURAMOS-1

Key Findings:

Largest osteosarcoma trial ever (2,260 patients)
Intensifying chemo for poor responders did not improve survival
Adding ifosfamide/etoposide did not help poor responders
Histologic response remains strongly prognostic

Clinical Implication: Poor responders still benefit from standard adjuvant chemo - don't escalate.

Source: Lancet Oncol 2016

Level III

📚 Simon MA et al - Limb Salvage vs Amputation

Key Findings:

Compared limb salvage to amputation for osteosarcoma
No significant difference in survival
Better function with limb salvage
Local recurrence rates similar with adequate margins

Clinical Implication: Limb salvage preferred when technically feasible - equivalent survival.

Source: JBJS 1986

Level III

📚 Bacci G et al - Prognostic Factors

Key Findings:

Over 1,700 patients analyzed for prognostic factors
Histologic response strongest predictor
Tumor size, site, ALP independent predictors
Axial tumors have worse prognosis

Clinical Implication: Response-adapted treatment may be future direction.

Source: Cancer 2006

Level IV

📚 Jeys LM et al - Endoprosthesis Survival

Key Findings:

Long-term endoprosthesis outcomes (661 patients)
10-year implant survival: 77%
20-year implant survival: 51%
Infection most common mode of failure

Clinical Implication: Counsel patients about long-term revision risk.

Source: JBJS Br 2008

Viva Scenarios

Practice these scenarios to excel in your viva examination

VIVA SCENARIOStandard

Distal Femur Mass in Adolescent

EXAMINER

"A 14-year-old boy presents with 3 months of worsening right knee pain. X-ray shows an aggressive metaphyseal lesion in the distal femur with a sunburst periosteal reaction and Codman triangle. How do you manage this patient?"

EXCEPTIONAL ANSWER

This presentation is highly suspicious for osteosarcoma - the combination of adolescent age, metaphyseal location, sunburst periosteal reaction, and Codman triangle is classic.

Immediate Management:

Staging workup: MRI of entire femur (skip lesions), CT chest (lung mets), whole body bone scan
Laboratory: FBC, U&E, LFTs, alkaline phosphatase, LDH
Biopsy: Planned with definitive surgeon - longitudinal incision through planned resection approach, core needle preferred, meticulous hemostasis

Treatment Protocol (if confirmed):

Neoadjuvant chemotherapy: MAP protocol (high-dose Methotrexate, Adriamycin, cisPlatin) for 8-12 weeks
Restaging: Assess response before surgery
Wide resection: Limb salvage if feasible (endoprosthesis most common), minimum 2cm bone margin, excise biopsy tract
Histologic assessment: Percent necrosis (over 90% = good response)
Adjuvant chemotherapy: Complete treatment protocol

Prognosis: Localized disease has 60-70% 5-year survival. Good histologic response improves this to 75-80%.

KEY POINTS TO SCORE

Classic presentation: Adolescent + metaphyseal + sunburst + Codman

Biopsy MUST be planned with definitive surgeon

MRI entire femur for skip lesions

Neoadjuvant chemo essential before surgery

Over 90% necrosis indicates good response

COMMON TRAPS

✗Biopsy through wrong approach contaminating compartments

✗Surgery without chemotherapy

✗Missing skip lesions by not imaging entire bone

✗Forgetting to excise biopsy tract

LIKELY FOLLOW-UPS

"What chemotherapy agents are used?"

"What are the surgical reconstruction options?"

"What defines a good histologic response?"

VIVA SCENARIOStandard

Parosteal Osteosarcoma

EXAMINER

"A 35-year-old woman has a slowly enlarging mass on the posterior aspect of her distal femur for 2 years. X-ray shows a densely ossified surface lesion attached to the posterior cortex. Biopsy confirms low-grade parosteal osteosarcoma. How does management differ from conventional osteosarcoma?"

EXCEPTIONAL ANSWER

Parosteal osteosarcoma is a low-grade surface variant with distinctly different management from conventional osteosarcoma.

Key Differences:

No chemotherapy required - low-grade tumor with minimal metastatic potential
Wide surgical resection alone is curative in most cases
Excellent prognosis: 90-95% 5-year survival

Surgical Considerations:

Wide resection with adequate margins (can be marginal in some cases for function)
May allow joint preservation if not involving articular surface
Posterior approach for posterior distal femur lesions
Reconstruction depends on residual bone stock

Important Caveats:

Dedifferentiation can occur (10-15%) - high-grade areas require chemotherapy
Biopsy must adequately sample for high-grade component
If dedifferentiated, treat as conventional osteosarcoma

Surveillance: Regular imaging to detect local recurrence or dedifferentiation.

KEY POINTS TO SCORE

Low-grade surface tumor - NO chemotherapy needed

Wide resection alone is curative (90-95% survival)

Watch for dedifferentiation (requires full treatment)

Posterior distal femur classic location

Densely ossified appearance on X-ray

COMMON TRAPS

✗Giving unnecessary chemotherapy

✗Missing dedifferentiated component on biopsy

✗Inadequate margins due to favorable histology

LIKELY FOLLOW-UPS

"How does periosteal osteosarcoma differ?"

"What percentage dedifferentiate?"

"How do you counsel regarding prognosis?"

VIVA SCENARIOStandard

Metastatic Osteosarcoma

EXAMINER

"A 16-year-old presents with a distal femur osteosarcoma. Staging CT chest reveals 3 pulmonary nodules consistent with metastatic disease. How does this change your management approach?"

EXCEPTIONAL ANSWER

Metastatic osteosarcoma at diagnosis occurs in 15-20% of patients and significantly impacts prognosis (5-year survival 20-30%).

Key Management Principles:

Treatment is NOT palliative - still aim for cure in selected patients
Complete resection of ALL disease (primary + metastases) improves survival

Modified Treatment Approach:

Neoadjuvant chemotherapy: Standard MAP protocol (may be intensified)
Assess response: Both primary and metastatic disease
Surgical resection:
- Primary tumor: Wide resection with limb salvage if feasible
- Pulmonary metastases: Thoracotomy/VATS for complete metastasectomy
- Both can be done simultaneously or staged
Adjuvant chemotherapy: Complete treatment protocol

Favorable Features for Metastatic Disease:

Unilateral lung involvement
Small number of metastases (under 4-5)
Good response to chemotherapy
Complete surgical resection achievable

Prognosis: If complete resection of all disease achieved, 5-year survival can reach 30-40%. Incomplete resection has poor outcomes.

KEY POINTS TO SCORE

15-20% present with pulmonary mets

Still aim for cure - NOT palliative

Complete resection of ALL disease essential

Thoracotomy for pulmonary metastasectomy

5-year survival 20-30% (better if complete resection)

COMMON TRAPS

✗Treating as palliative - should aim for cure

✗Failing to resect pulmonary metastases

✗Proceeding without adequate staging (PET/bone scan)

LIKELY FOLLOW-UPS

"What if pulmonary mets appear during treatment?"

"What if mets are bilateral?"

"What is the role of stereotactic radiotherapy?"

MCQ Practice Points

MCQ Pearl 1: Location

Q: What is the most common site for osteosarcoma? A: Distal femur (50%), followed by proximal tibia (25%), proximal humerus (10%). Remember: "Around the knee" in adolescents.

MCQ Pearl 2: X-ray Findings

Q: What are the pathognomonic radiographic features of osteosarcoma? A: Sunburst periosteal reaction and Codman triangle. Also look for: permeative destruction, osteoid matrix (cloud-like), soft tissue mass.

MCQ Pearl 3: Chemotherapy Protocol

Q: What is the standard chemotherapy regimen for osteosarcoma? A: MAP - high-dose Methotrexate (with leucovorin rescue), Adriamycin (doxorubicin), cisPlatin.

MCQ Pearl 4: Histologic Response

Q: What defines a good histologic response in osteosarcoma? A: Over 90% tumor necrosis in resected specimen. This is the strongest prognostic factor (5-year survival 75-80% vs 50-55% for poor response).

MCQ Pearl 5: Parosteal Exception

Q: Which osteosarcoma subtype does NOT require chemotherapy? A: Parosteal osteosarcoma - low-grade surface tumor treated with wide resection alone. 90-95% 5-year survival. Watch for dedifferentiation.

Common MCQ Scenarios

Scenario	Key Answer Point
Adolescent + metaphyseal + sunburst	Osteosarcoma - biopsy with surgeon
Densely ossified posterior femur surface	Parosteal osteosarcoma - no chemo
Under 90% necrosis post-neoadjuvant	Continue standard adjuvant chemo
Skip lesion on MRI	Include in resection, not contraindication to limb salvage
Pathological fracture	Still attempt limb salvage with modified approach
Elevated ALP/LDH	Poor prognostic factor
Paget's disease + sudden pain	Suspect secondary osteosarcoma

Australian Context

Australian Incidence and Epidemiology

Approximately 100-150 new cases per year in Australia
Most common primary bone cancer in adolescents
Treated at specialized sarcoma units (major tertiary centers)
Multidisciplinary team essential (orthopaedic oncologist, medical oncologist, radiation oncologist, pathologist)

Key Australian Treatment Centers

Specialized Sarcoma Units:

Peter MacCallum Cancer Centre (VIC)
Royal Prince Alfred Hospital (NSW)
Princess Alexandra Hospital (QLD)
Royal Adelaide Hospital (SA)
Sir Charles Gairdner Hospital (WA)

Australian Guidelines and Protocols

Clinical Practice Guidelines:

Australian and New Zealand Sarcoma Association (ANZSA) guidelines
eviQ Cancer Treatments Online (chemotherapy protocols)
NCCN guidelines adapted for Australian context

Pharmaceutical Benefits Scheme (PBS):

Chemotherapy agents subsidized under PBS
Methotrexate, doxorubicin, cisplatin all PBS-listed
High-cost drugs require specialist authorization

Tumour Banking and Research

Australian Sarcoma Study Group (ASSG)
Tumour banking at major centers
Participation in international trials (EURAMOS, etc.)

Follow-up Surveillance

Medicare Considerations:

Bulk-billed imaging at public hospitals
Private imaging may have gap payments
Long-term surveillance covered under Medicare

Prosthesis Funding:

Complex prostheses funded through hospital budgets
Growing prostheses (non-invasive) increasingly available
Rehabilitation covered under public hospital system

Exam Pearl

Australian Practice: Osteosarcoma requires treatment at a specialized sarcoma center with multidisciplinary team. Don't manage at peripheral centers - refer to tertiary oncology unit.

Summary Points

High-Yield Take-Home Messages

Osteosarcoma = Most common primary bone cancer in adolescents, defined by osteoid production
Distal femur most common site (50%), "around the knee" in growing skeleton
Sunburst + Codman triangle on X-ray = osteosarcoma until proven otherwise
Biopsy MUST be planned with definitive surgeon - wrong approach contaminates compartments
MRI entire bone - skip lesions occur in 1-5%, change surgical planning
Neoadjuvant chemotherapy essential - MAP protocol (Methotrexate, Adriamycin, Platinum)
Histologic response is strongest prognostic factor - over 90% necrosis = good response
Limb salvage in 80-90% - equivalent survival to amputation
Parosteal = exception - low-grade surface tumor, wide resection alone, no chemo
Metastatic disease still aim for cure - complete resection of ALL disease improves survival

Self-Assessment Quiz

OSTEOSARCOMA

High-Yield Exam Summary

CLINICAL FEATURES

•Distal femur most common (50%)
•Bimodal: adolescents + over 60 (Paget's)
•Sunburst + Codman triangle on X-ray
•Pain worse at night, progressive swelling

STAGING WORKUP

•MRI entire bone (skip lesions)
•CT chest (lung mets - 80% of distant disease)
•Bone scan (systemic staging)
•Biopsy planned with definitive surgeon

TREATMENT PROTOCOL

•Neoadjuvant: MAP chemo 8-12 weeks
•Wide resection (limb salvage 80-90%)
•Assess histologic necrosis (over 90% = good)
•Adjuvant chemotherapy to complete

SUBTYPES

•Conventional (75%): High-grade, needs chemo
•Telangiectatic: Lytic, same treatment
•Parosteal: Low-grade, NO chemo needed
•Periosteal: Intermediate, consider chemo

PROGNOSIS

•Localized: 60-70% 5-year survival
•Metastatic: 20-30% survival
•Over 90% necrosis: 75-80% survival
•Under 90% necrosis: 50-55% survival

EXAM TRAPS

•Biopsy through wrong approach
•Surgery without chemotherapy
•Missing skip lesions (MRI entire bone)
•Giving chemo for parosteal type

Feature

Details

Definition

Primary malignant bone tumor producing osteoid by malignant cells

Incidence

3-4 per million per year (most common primary bone cancer in adolescents)

Peak Age

Bimodal: 10-20 years (primary), over 60 (secondary - Paget's)

Sex Ratio

Male to Female = 1.5:1

Most Common Location

Distal femur (50%), proximal tibia (25%), proximal humerus (10%)

Classic Triad

Pain + Mass + Restricted ROM

Pathognomonic X-ray

Sunburst periosteal reaction + Codman triangle

Treatment Protocol

Neoadjuvant chemo → Wide resection → Adjuvant chemo

5-Year Survival

60-70% localized, 20-30% metastatic at presentation

Key Prognostic Factor

Histologic necrosis (over 90% = good response)

Peak

Age Range

Characteristics

Association

Primary Peak

10-20 years

Rapid skeletal growth

Metaphyseal location, conventional type

Secondary Peak

Over 60 years

Paget's sarcoma

Axial skeleton, poor prognosis

Direction

Barrier

Clinical Significance

Intramedullary

Cortical bone

Skip lesions possible - MRI entire bone

Extraosseous

Soft tissue planes

Neurovascular involvement risk

Transphyseal

Growth plate

Less effective barrier than previously thought

Intra-articular

Joint capsule

Rare but indicates Stage IIB/III

Subtype

Grade

Location

Chemotherapy

High

Intramedullary

Yes - MAP protocol

High

Intramedullary

Yes - Same as conventional

High

Intramedullary

Yes - May add Ewing's protocol

Low

Surface (posterior femur)

No - Wide resection only

Intermediate

Surface (diaphysis)

Consider adjuvant

High

Surface

Yes - Full protocol

Diagnosis

Key Distinguishing Features

Ewing Sarcoma

Diaphyseal, permeative, onion-skin periosteal, smaller cell

Chondrosarcoma

Older patients (40-60), axial, chondroid matrix (arcs/rings)

Giant Cell Tumor

Epiphyseal, eccentrically lytic, no matrix

Osteomyelitis

Systemic symptoms, sequestrum, involucrum

Stress Fracture

Transverse, no soft tissue mass, healing callus

Aneurysmal Bone Cyst

Eccentric, expansile, fluid levels on MRI

Approach

Pros

Cons

Indication

Core Needle

Less contamination, outpatient

May miss diagnosis (sampling)

Preferred in most centers

Open Incisional

More tissue, higher accuracy

More contamination

If core non-diagnostic

Excisional

Diagnostic + therapeutic

Contraindicated

Never for suspected osteosarcoma

DIAGNOSIS CONFIRMED ↓ STAGING (MRI, CT Chest, Bone Scan) ↓ ┌───────────────────┐ │ NEOADJUVANT CHEMO │ → 8-12 weeks MAP protocol │ (Pre-operative) │ └─────────┬─────────┘ ↓ RESTAGING ↓ ┌───────────────────┐ │ WIDE RESECTION │ → Limb salvage (80-90%) or Amputation │ ± Recon │ └─────────┬─────────┘ ↓ HISTOLOGIC ASSESSMENT (% tumor necrosis) ↓ ┌───────────────────┐ │ ADJUVANT CHEMO │ → Continue/modify based on response │ (Post-operative) │ └───────────────────┘

Agent

Major Toxicity

Monitoring

Management

Methotrexate

Mucositis, nephrotoxicity, hepatotoxicity

Levels, renal function

Leucovorin rescue, hydration

Doxorubicin

Cardiotoxicity (dose-dependent)

Echo/MUGA

Lifetime dose limit 450mg/m²

Cisplatin

Nephrotoxicity, ototoxicity, neuropathy

Cr, audiometry

Hydration, dose adjustment

Subtype

Neoadjuvant

Adjuvant

Notes

Conventional

Yes

Standard MAP protocol

Telangiectatic

Yes

Same as conventional

Parosteal (Low-grade)

Wide resection only

Periosteal

Consider

Case-by-case decision

High-grade Surface

Yes

Full protocol

Surgical Principles

Margin Requirements:

Wide Margin: Minimum 1-2cm of bone beyond tumor
Cuff of Normal Tissue: Must include reactive zone
Biopsy Tract: Excise with specimen
Skip Lesions: Must be included in resection

Limb Salvage Options

Modular Metal Replacement:

Indications:

Most common reconstruction
Distal femur, proximal tibia, proximal humerus
Allows early mobilization

Advantages:

Immediate stability
Early weight-bearing
No donor site morbidity

Disadvantages:

Mechanical failure (5-10 year revision)
Infection (5-15%)
Aseptic loosening
Limited lifespan in young patients

Growing Prostheses:

For skeletally immature patients
Non-invasive lengthening available
Multiple lengthening procedures required

Endoprosthesis remains the gold standard for most limb salvage reconstructions.

Amputation Considerations

When Amputation is Indicated:

Neurovascular encasement (not reconstructable)
Massive soft tissue involvement
Poor response to chemotherapy with progression
Pathological fracture with contamination
Patient preference
Infection precluding salvage
Expected non-functional limb

Amputation Levels:

Above-knee for distal femur tumors
Hip disarticulation for proximal femur
Forequarter for proximal humerus (rarely needed)

Exam Pearl

Complication

Agent

Incidence

Prevention/Management

Cardiotoxicity

Doxorubicin

5-10%

Dose limit 450mg/m², serial Echo

Nephrotoxicity

Cisplatin, MTX

10-20%

Hydration, dose adjustment

Ototoxicity

Cisplatin

10-30%

Audiometry, dose modification

Mucositis

MTX

40-60%

Leucovorin rescue, supportive care

Myelosuppression

All agents

Universal

G-CSF, transfusions

Secondary Malignancy

All agents

2-5%

Long-term surveillance

Phase

Timeline

Goals

Activities

Acute

0-6 weeks

Wound healing, ROM

Bed exercises, transfer training

Intermediate

6-12 weeks

Strength, progressive WB

Gait training, strengthening

Advanced

3-6 months

Full function

Sport-specific training

Maintenance

Ongoing

Monitor function

Activity modification as needed

Disease Status

5-Year Survival

Notes

Localized Disease

60-70%

Majority of presentations

Metastatic at Diagnosis

20-30%

15-20% have lung mets at presentation

Good Response (over 90% necrosis)

75-80%

Strongest prognostic factor

Poor Response (under 90% necrosis)

50-55%

Still benefits from adjuvant chemo

Local Recurrence

30-40%

Depends on resectability

Factor

Favorable

Unfavorable

Over 90% necrosis

Under 90% necrosis

Localized disease

Metastatic at diagnosis

Extremity

Axial skeleton, pelvis

Under 8cm

Over 8cm, skip lesions

Normal

Elevated

Wide/negative

Marginal/positive

Scenario

Key Answer Point

Adolescent + metaphyseal + sunburst

Osteosarcoma - biopsy with surgeon

Densely ossified posterior femur surface

Parosteal osteosarcoma - no chemo

Under 90% necrosis post-neoadjuvant

Continue standard adjuvant chemo

Skip lesion on MRI

Include in resection, not contraindication to limb salvage

Pathological fracture

Still attempt limb salvage with modified approach

Elevated ALP/LDH

Poor prognostic factor

Paget's disease + sudden pain

Suspect secondary osteosarcoma

Factor	Limb Salvage	Amputation
Good response to chemo	Poor response, progression
Not encased	Encased, not reconstructable
Adequate coverage possible	Massive soft tissue loss
Expected functional limb	Non-functional limb
No active infection	Severe infection
Accepts risks, compliant	Non-compliant, prefers amputation

Necrosis	Response	Prognosis	Action
Over 90%	Good	75-80% 5-year survival	Continue same protocol
Under 90%	Poor	45-55% 5-year survival	Consider intensification

Factor	Limb Salvage	Amputation
Good response to chemo	Poor response, progression
Not encased	Encased, not reconstructable
Adequate coverage possible	Massive soft tissue loss
Expected functional limb	Non-functional limb
No active infection	Severe infection
Accepts risks, compliant	Non-compliant, prefers amputation

Necrosis	Response	Prognosis	Action
Over 90%	Good	75-80% 5-year survival	Continue same protocol
Under 90%	Poor	45-55% 5-year survival	Consider intensification

Stage	Grade	Site	Metastases	Surgical Margin
IA	Low (G1)	Intracompartmental (T1)	M0	Wide
IB	Low (G1)	Extracompartmental (T2)	M0	Wide
IIA	High (G2)	Intracompartmental (T1)	M0	Wide
IIB	High (G2)	Extracompartmental (T2)	M0	Wide
III	Any	Any	M1	Palliative/Wide

Osteosarcoma

Osteosarcoma

Osteosarcoma

Osteosarcoma Subtypes

Critical Must-Knows

Examiner's Pearls

Clinical Imaging

Imaging Gallery

Critical Treatment Principle

At a Glance Table

Mnemonic Cards

Osteosarcoma Sites - DPHF

Radiographic Signs - SCAM

MAP Chemotherapy

Enneking Staging - GTM

Overview/Epidemiology

Epidemiology

Incidence

Risk Factors

Location Distribution

Bimodal Age Distribution

Anatomy/Biomechanics

Anatomic Considerations for Tumor Location

Compartmental Anatomy

Neurovascular Relationships

Classification Systems

Osteosarcoma Subtypes by Grade and Location

Clinical Presentation

History

Primary Symptoms

Mass/Swelling

Red Flags

Physical Examination

Pathological Fracture

Differential Diagnosis

Investigations

Imaging Protocol

Skip Lesions

Biopsy Principles

Biopsy Planning - CRITICAL

Management Algorithm

Limb Salvage vs Amputation Criteria

Non-Operative Management

Chemotherapy Protocol

MAP Chemotherapy

Chemotherapy Toxicities

Indications for Chemotherapy

Surgical Technique

Surgical Principles

Limb Salvage Options

Amputation Considerations

Complications

Chemotherapy Complications

Surgical Complications

Early Complications

Late Complications

Allograft Specific

Local Recurrence

Postoperative Care

Immediate Postoperative Period

Rehabilitation Protocol

Follow-up Surveillance

Outcomes/Prognosis

Survival Rates

Prognostic Factors

Favorable vs Unfavorable Prognostic Factors

Osteosarcoma Prognosis

Functional Outcomes

Evidence Base

Viva Scenarios

Distal Femur Mass in Adolescent

Parosteal Osteosarcoma

Metastatic Osteosarcoma

MCQ Practice Points

Common MCQ Scenarios

Australian Context

Australian Incidence and Epidemiology

Key Australian Treatment Centers

Australian Guidelines and Protocols

Tumour Banking and Research