# CIM Case: Osteosarcoma of Knee ## Clinical Scenario **Patient:** 15-year-old male student **Presentation:** 6-month history of progressive pain and swelling around the left knee, worsening over time **Relevant history:** No history of trauma, no previous medical problems, no family history of cancer, no weight loss, no night sweats **Examination findings:** - Visible swelling over distal femur, non-fluctuant - Firm, tender mass fixed to bone - Restricted knee flexion (90°, limited by pain and mass effect) - No overlying skin changes - No regional lymphadenopathy - Popliteal pulse palpable but reduced compared to contralateral - Full neurovascular status of foot - No limp at rest, antalgic gait --- ## Investigations Provided ### Laboratory Results | Test | Result | Normal Range | Interpretation | |------|--------|--------------|----------------| | WCC | 8.2 x10⁹/L | 4.0-11.0 x10⁹/L | Normal | | Haemoglobin | 138 g/L | 130-175 g/L | Normal | | Platelets | 310 x10⁹/L | 150-400 x10⁹/L | Normal | | ESR | 28 mm/hr | 0-10 mm/hr | Elevated | | CRP | 15 mg/L | <5 mg/L | Mildly elevated | | ALP | 320 U/L | 40-150 U/L | Elevated (bone turnover) | | LDH | 450 U/L | 120-250 U/L | Elevated (tumour marker) | | Calcium | 2.40 mmol/L | 2.15-2.55 mmol/L | Normal | | Creatinine | 65 µmol/L | 60-110 µmol/L | Normal | ### Imaging **Image 1: AP and Lateral Radiographs of Left Knee** **Radiological features:** - Large aggressive lesion in distal femoral metaphysis - Mixed lytic and sclerotic pattern (osteoblastic predominant) - Sunburst periosteal reaction - Codman's triangle present - Cortical destruction medially - Soft tissue mass extending beyond cortex - No pathological fracture - Physis still open (skeletal immaturity) - No skip lesion visible **Image 2: MRI Left Knee (T1, T2, and post-gadolinium)** **MRI findings:** - Large tumour mass in distal femoral metaphysis (8 x 6 x 7 cm) - Extension to within 2cm of physis but NOT crossing it - No epiphyseal involvement - Extra-osseous soft tissue mass (5cm maximum dimension) - Neurovascular bundle displaced posteriorly but no encasement - No skip lesions in femur - No joint involvement - Marrow oedema extends proximally 3cm beyond main mass **Image 3: CT Chest** **CT findings:** - No pulmonary metastases - No mediastinal lymphadenopathy - Clear lung fields bilaterally **Image 4: Technetium-99m Bone Scan** **Findings:** - Intense uptake in distal left femur - No other areas of abnormal uptake - No skip lesions - No distant bone metastases ## Questions & Model Answers **Diagnosis: High-Grade Osteosarcoma of Distal Femur** This is a classic presentation of osteosarcoma - the most common primary malignant bone tumour in adolescents. **Epidemiology:** | Factor | Osteosarcoma | |--------|--------------| | **Peak incidence** | 10-25 years (second peak >60 years - Paget's associated) | | **Male:Female** | 1.5:1 | | **Most common site** | Distal femur (40%) > proximal tibia (20%) > proximal humerus | | **Annual incidence** | 3-4 per million | **X-ray Features of Aggressive/Malignant Lesion:** | Feature | This Patient | Significance | |---------|--------------|--------------| | **Location** | Metaphysis of distal femur | Classic site for osteosarcoma | | **Sunburst periosteal reaction** | Present | Malignant - tumour grows faster than periosteum | | **Codman's triangle** | Present | Lifted periosteum = aggressive lesion | | **Mixed lytic/sclerotic** | Yes (osteoblastic) | Tumour osteoid production | | **Cortical destruction** | Present | Aggressive behaviour | | **Soft tissue mass** | Present | Extra-osseous extension | | **Wide zone of transition** | Yes | Aggressive lesion | **Pattern Recognition - Periosteal Reactions:** | Type | Pattern | Implication | |------|---------|-------------| | **Sunburst** | Radiating spicules | Highly aggressive (osteosarcoma) | | **Onion skin** | Lamellated layers | Aggressive (Ewing, infection, osteosarcoma) | | **Codman's triangle** | Triangular elevation | Aggressive - tumour outgrew periosteum | | **Solid periosteal** | Smooth, uniform | Benign or slow-growing | **Differential Diagnosis:** | Diagnosis | Distinguishing Features | |-----------|------------------------| | **Osteosarcoma** | Osteoid production, sunburst, adolescent | | **Ewing sarcoma** | More diaphyseal, onion skin, younger age | | **Chondrosarcoma** | Older age, chondroid matrix | | **Osteomyelitis** | Fever, acute history, sequestrum | > **Consultant Tip:** Sunburst periosteal reaction + Codman's triangle + soft tissue mass in a teenager = osteosarcoma until proven otherwise. **Staging Workup for Osteosarcoma:** **Essential Investigations:** | Investigation | Purpose | This Patient | |---------------|---------|--------------| | **Plain X-ray** | Initial assessment, lesion characterisation | Done - aggressive features | | **MRI of primary** | Local staging, soft tissue extent, skip lesions | Done - 8cm tumour, no skip | | **CT chest** | Pulmonary metastases (most common site) | Done - clear | | **Bone scan** | Skeletal metastases, skip lesions | Done - isolated to distal femur | | **Biopsy** | Histological diagnosis and grading | Pending | **Additional Investigations:** | Investigation | Purpose | |---------------|---------| | **Bloods** | ALP, LDH (baseline and for response monitoring) | | **PET-CT** | May add to staging, useful for response assessment | | **Angiography** | Pre-operative if vascular involvement suspected | | **ECHO** | Baseline before chemotherapy (cardiotoxicity) | | **Audiometry** | Baseline before cisplatin (ototoxicity) | | **Renal function** | Baseline before methotrexate, cisplatin | **Enneking Staging System for Malignant Bone Tumours:** | Stage | Grade | Compartment | Metastasis | |-------|-------|-------------|------------| | **IA** | Low (G1) | Intracompartmental (T1) | None (M0) | | **IB** | Low (G1) | Extracompartmental (T2) | None (M0) | | **IIA** | High (G2) | Intracompartmental (T1) | None (M0) | | **IIB** | High (G2) | Extracompartmental (T2) | None (M0) | | **III** | Any | Any | Metastases (M1) | **This Patient's Stage:** - High-grade (histologically confirmed - pending) - Extracompartmental (soft tissue extension) - No metastases (CT chest clear, bone scan clear) - **Stage IIB** (assuming high-grade on biopsy) **Prognostic Significance of Staging:** | Stage | 5-Year Survival | |-------|-----------------| | **IA** | 80-90% | | **IB** | 70-80% | | **IIA** | 60-70% | | **IIB** | 50-70% | | **III (pulmonary)** | 20-30% | | **III (bone/multifocal)** | <10% | > **Consultant Tip:** 20% of osteosarcomas have detectable metastases at presentation. Assume ALL patients have micrometastatic disease - this is why chemotherapy is essential. **Biopsy Principles in Musculoskeletal Oncology:** **CRITICAL: Biopsy Should Be Performed at the Definitive Treatment Centre** | Principle | Rationale | |-----------|-----------| | **Tertiary centre** | Expertise, MDT available, avoids errors | | **Done by surgeon who will do definitive surgery** | Biopsy tract excised with specimen | | **Image-guided** | Ensures representative sample | | **Minimise contamination** | Avoid spreading tumour cells | **Biopsy Technique Options:** | Technique | Advantages | Disadvantages | |-----------|------------|---------------| | **Core needle biopsy** | Less invasive, less contamination | Smaller sample, may miss heterogeneity | | **Open incisional biopsy** | Larger sample, more tissue | Greater contamination risk | | **Excisional biopsy** | Complete removal | NEVER appropriate for suspected malignancy | **Core Needle Biopsy (Preferred for Most Cases):** - Image-guided (ultrasound or CT) - 11-14G needle - Multiple passes (3-5) - Through muscle that will be excised - Avoid neurovascular structures - Adequate material for diagnosis and molecular studies **Biopsy Tract Placement - Key Rules:** | Rule | Rationale | |------|-----------| | **Longitudinal incision** | Allows excision with definitive resection | | **Through single muscle compartment** | Limits contamination | | **Avoid intermuscular planes** | Limits tumour spread | | **Avoid neurovascular structures** | Prevents contamination of NV bundle | | **Direct approach** | Shortest path to tumour | | **Mark the tract** | Tattoo or suture for identification | **Distal Femur Osteosarcoma - Preferred Approach:** - Anterolateral or anteromedial approach - Through vastus lateralis or rectus femoris - Avoid intermuscular septum - Avoid popliteal fossa approach **Consequences of Poorly Placed Biopsy:** - May require amputation instead of limb salvage - Contamination of additional compartments - Local recurrence - Worse prognosis **Biopsy Results Expected:** - High-grade conventional osteosarcoma (most common) - Subtypes: osteoblastic (50%), chondroblastic (25%), fibroblastic (25%) > **Consultant Tip:** Mankin's study showed 18% error rate with biopsies done at non-specialist centres, with 4.5% requiring unnecessary amputation. ALWAYS refer to a sarcoma centre before biopsy. **Role of Chemotherapy in Osteosarcoma:** **Historical Context:** - Before chemotherapy: 5-year survival 15-20% (lung metastases) - With chemotherapy: 5-year survival 60-70% - Confirms presence of micrometastatic disease at diagnosis **Chemotherapy Regimen (MAP Protocol):** | Agent | Mechanism | Major Toxicity | |-------|-----------|----------------| | **Methotrexate (high-dose)** | Antifolate | Mucositis, renal, hepatic | | **Adriamycin (Doxorubicin)** | Anthracycline | Cardiotoxicity (cumulative) | | **Cisplatin** | Platinum | Ototoxicity, nephrotoxicity | **Treatment Timeline:** | Phase | Duration | Purpose | |-------|----------|---------| | **Neoadjuvant chemotherapy** | 10-12 weeks (3-4 cycles) | Shrink tumour, treat micrometastases | | **Restaging** | After neoadjuvant | MRI to assess response | | **Surgery** | Week 12 | Wide resection or amputation | | **Adjuvant chemotherapy** | 6-9 months | Complete treatment, based on response | **Benefits of Neoadjuvant Chemotherapy:** | Benefit | Explanation | |---------|-------------| | **Tumour shrinkage** | May convert inoperable to operable | | **Assess chemotherapy response** | Histological necrosis guides adjuvant therapy | | **Treat micrometastases** | Present in most patients | | **Limb salvage planning** | Better delineation of margins | | **Patient preparation** | Time to optimize for surgery | **Monitoring During Chemotherapy:** - Weekly bloods (FBC, renal, liver) - ECHO (cumulative doxorubicin effect) - Audiometry (cisplatin) - MRI at 6 weeks and pre-operatively - ALP/LDH trending > **Consultant Tip:** Chemotherapy response (tumour necrosis >90%) is the single most important prognostic factor after resection. **Surgical Options for Osteosarcoma:** **1. Limb Salvage Surgery (Preferred - 85-90% of cases)** | Reconstruction Option | Indications | Considerations | |-----------------------|-------------|----------------| | **Endoprosthetic replacement** | Most common, large defects | Growing child may need expandable prosthesis | | **Allograft** | Biological reconstruction | Union concerns, infection risk | | **Allograft-prosthesis composite** | Soft tissue attachment | Combined benefits | | **Rotationplasty** | Paediatric, distal femur/proximal tibia | Ankle becomes "knee" - excellent function | | **Distraction osteogenesis** | Small defects | Prolonged treatment | **2. Amputation** | Indication | Rationale | |------------|-----------| | **Major neurovascular involvement** | Cannot achieve clear margins | | **Extensive soft tissue contamination** | Poor biopsy, pathological fracture | | **Unable to achieve wide margin** | Risk of local recurrence | | **Infection** | May compromise reconstruction | | **Patient preference** | After appropriate counselling | **Decision Making - Limb Salvage vs Amputation:** | Factor | Favours Limb Salvage | Favours Amputation | |--------|---------------------|-------------------| | **Tumour extent** | No NV involvement | NV encasement | | **Response to chemo** | Good response (>90% necrosis) | Poor response | | **Margin achievable** | Wide margin possible | Cannot achieve negative margin | | **Patient age** | Older child/adult | Very young child (multiple revisions) | | **Function expected** | Good function with reconstruction | Better function with prosthesis | | **Biopsy quality** | Good tract placement | Contaminated multiple compartments | **This Patient's Considerations:** - 15 years old - near skeletal maturity - No NV encasement (displaced but not involved) - No skip lesions - No metastases - Stage IIB - likely limb salvage candidate **Expected Surgical Plan:** 1. Complete neoadjuvant chemotherapy (MAP) 2. Restaging MRI 3. Wide resection with 2cm bone margin, soft tissue cuff 4. Distal femoral endoprosthetic replacement 5. May consider expandable prosthesis if significant growth remaining **Margins in Osteosarcoma:** | Margin Type | Definition | Local Recurrence Risk | |-------------|------------|----------------------| | **Wide** | >2cm bone, cuff of normal tissue | 5-10% | | **Marginal** | Through reactive zone | 20-30% | | **Intralesional** | Through tumour | 50-90% | > **Consultant Tip:** The goal is identical local recurrence rates with limb salvage versus amputation. If you can't achieve a wide margin, amputation is the safer option. **Prognosis in Osteosarcoma:** **Overall Survival:** | Presentation | 5-Year Survival | |--------------|-----------------| | **Localised disease** | 60-70% | | **Metastatic at presentation** | 20-30% | | **Relapsed disease** | 20-30% | **Prognostic Factors:** **1. Chemotherapy Response - Most Important (Huvos Grading):** | Huvos Grade | Tumour Necrosis | Prognosis | |-------------|-----------------|-----------| | **I** | <50% | Poor (5-year survival 40%) | | **II** | 50-89% | Intermediate (55%) | | **III** | 90-99% | Good (75%) | | **IV** | 100% | Excellent (90%) | **2. Other Prognostic Factors:** | Factor | Favourable | Unfavourable | |--------|------------|--------------| | **Stage** | Localised (IIB) | Metastatic (III) | | **Tumour size** | <8cm | >8cm | | **Location** | Extremity | Axial skeleton | | **Response to chemo** | >90% necrosis | <90% necrosis | | **Margins** | Wide/negative | Marginal/positive | | **ALP** | Normal or normalises | Persistently elevated | | **LDH** | Normal | Elevated | | **Histological subtype** | Chondroblastic | Conventional osteoblastic | **3. Metastatic Disease:** | Pattern | Prognosis | |---------|-----------| | **Single pulmonary metastasis** | 30-40% (resectable) | | **Multiple pulmonary** | 20% | | **Bone metastases** | <10% | | **Multifocal disease** | <10% | **Follow-up Protocol:** | Time Period | Frequency | Investigations | |-------------|-----------|----------------| | **Year 1-2** | Every 3 months | CXR, local imaging | | **Year 3-5** | Every 6 months | CXR, annual CT chest | | **Year 5-10** | Annually | CXR, clinical review | **This Patient's Prognosis:** - Stage IIB (localised, extracompartmental) - No metastases - Elevated ALP and LDH (will monitor for response) - Expected 5-year survival: 60-70% if good chemotherapy response - Key prognostic determinant: Huvos grade after neoadjuvant therapy **Long-term Considerations:** - Endoprosthesis: revision rate 30-50% at 10 years - Late effects of chemotherapy: cardiotoxicity, hearing loss, fertility - Surveillance for second malignancy - Functional outcomes generally good with modern limb salvage > **Consultant Tip:** Counsel families that 60-70% survival means 30-40% will die from their disease. Honest prognostic discussions are essential. --- ## Key Teaching Points ### Pattern Recognition **This pattern suggests Osteosarcoma:** - Adolescent with metaphyseal bone pain and swelling - Sunburst periosteal reaction - Codman's triangle - Mixed lytic/sclerotic lesion with osteoid - Elevated ALP and LDH - Soft tissue mass **Comparison - Primary Bone Tumours in Adolescents:** | Feature | Osteosarcoma | Ewing Sarcoma | |---------|--------------|---------------| | Age | 10-25 years | 5-20 years | | Location | Metaphysis | Diaphysis (or flat bones) | | Matrix | Osteoid (sunburst) | None | | Periosteal | Sunburst, Codman's | Onion skin | | Systemic features | Uncommon | Fever, elevated ESR (mimics infection) | | Radiosensitive | No | Yes | | Primary treatment | Surgery + chemo | Chemo + surgery/radiation | ### Critical Management Points 1. **Biopsy at sarcoma centre** - poorly placed biopsy may necessitate amputation 2. **Full staging before treatment** - MRI, CT chest, bone scan 3. **Neoadjuvant chemotherapy is standard** - MAP protocol 4. **Chemotherapy response is key prognostic factor** - Huvos grading 5. **Limb salvage achievable in 85-90%** - when wide margins possible 6. **MDT approach essential** - orthopaedic oncology, medical oncology, radiology, pathology --- ## Common Examiner Follow-ups **Q: "What if this patient presents with a pathological fracture?"** Pathological fracture in osteosarcoma: - Historically considered indication for amputation (contamination) - Modern approach: neoadjuvant chemotherapy, then reassess - If fracture heals and good response, limb salvage may still be possible - Worse prognosis than non-fractured tumours - Higher local recurrence risk --- **Q: "What is the role of radiotherapy in osteosarcoma?"** | Role | Indication | |------|------------| | **Primary treatment** | NOT standard - osteosarcoma is radioresistant | | **Positive margins** | May be used if surgical margins positive | | **Unresectable disease** | Palliation for axial tumours | | **Metastatic disease** | Palliation for symptomatic metastases | Contrast with Ewing sarcoma which is radiosensitive. --- **Q: "What about surveillance after treatment completion?"** Post-treatment surveillance focuses on: 1. **Local recurrence** - clinical examination, MRI of operative site 2. **Pulmonary metastases** - most common site, CXR or CT chest 3. **Late effects of chemotherapy** - cardiac function, hearing, renal 4. **Prosthetic complications** - loosening, infection, fracture Detection of early pulmonary metastases allows potential curative metastasectomy. --- ## Related Topics - Ewing Sarcoma - Chondrosarcoma - Giant Cell Tumour of Bone - Pathological Fractures - Limb Salvage Surgery - Endoprosthetic Reconstruction - Bone Tumour Biopsy Principles