# CIM Case: De-differentiated Chondrosarcoma ## Clinical Scenario **Patient:** 62-year-old retired engineer **Presentation:** 3-month history of progressive right hip and groin pain following a minor fall, now requiring walking stick, night pain disturbing sleep **Relevant history:** Known enchondroma in proximal right femur monitored with X-rays for 10 years (stable until now), no previous surgery, no other medical conditions, non-smoker, independent mobility prior to current symptoms **Examination findings:** - Slim man, looks well but uncomfortable - Antalgic gait, using single-point stick - Palpable fullness over anterolateral right proximal thigh - Firm mass, fixed to deep structures - No overlying skin changes - Tenderness over greater trochanter region - Hip ROM: flexion 90° (limited by pain), internal rotation 10° (limited), external rotation 20° - No lymphadenopathy (inguinal) - Neurovascularly intact distally - No stigmata of Ollier disease or Maffucci syndrome --- ## Investigations Provided ### Laboratory Results | Test | Result | Normal Range | Interpretation | |------|--------|--------------|----------------| | Hb | 128 g/L | 130-170 g/L | ↓ Mildly low | | WCC | 8.2 ×10⁹/L | 4-11 ×10⁹/L | Normal | | Platelets | 285 ×10⁹/L | 150-400 ×10⁹/L | Normal | | CRP | 15 mg/L | <5 mg/L | ↑ Mildly elevated | | ESR | 28 mm/hr | <20 mm/hr | ↑ Elevated | | ALP | 165 U/L | 30-120 U/L | ↑ Elevated | | LDH | 310 U/L | 120-250 U/L | ↑ Elevated | | Calcium | 2.45 mmol/L | 2.2-2.6 mmol/L | Normal | | Albumin | 38 g/L | 35-50 g/L | Normal | | Creatinine | 95 μmol/L | 60-110 μmol/L | Normal | ### Imaging **Image 1: AP and Lateral Radiographs of Right Hip/Proximal Femur** **Radiological features:** - Large destructive lesion in proximal femur (intertrochanteric region) - **Biphasic appearance**: areas of chondroid matrix (rings and arcs) AND areas of aggressive osteolysis - Cortical destruction with breakthrough - Periosteal reaction (Codman triangle, sunburst pattern) - Soft tissue mass extending medially and laterally - No pathological fracture yet but high risk - Size approximately 10 x 8cm - Extends from lesser trochanter to subtrochanteric region **Image 2: MRI of Right Proximal Femur** **Findings:** - Large heterogeneous mass in proximal femur - **Bimorphic pattern**: high T2 signal lobulated component (cartilage) adjacent to aggressive solid component - Abrupt transition between components (diagnostic feature) - Extensive medullary involvement - Cortical destruction with extra-osseous extension - Soft tissue mass 6cm in maximum dimension - No skip lesions - Neurovascular bundle displaced but appears intact - Edema in adjacent muscles **Image 3: CT Chest (Staging)** **Findings:** - Two pulmonary nodules (right lower lobe 8mm, left lower lobe 5mm) - Suspicious for pulmonary metastases - No mediastinal lymphadenopathy - No pleural effusion --- ## Questions & Model Answers **Diagnosis: Dedifferentiated Chondrosarcoma of the Proximal Right Femur** **Key Diagnostic Features:** - Previously stable enchondroma now showing aggressive transformation - Biphasic radiological appearance (cartilage matrix + aggressive lysis) - Abrupt transition on MRI between components - Elderly patient with longstanding cartilage lesion **Differential Diagnosis:** | Diagnosis | Supporting Features | Against | |-----------|---------------------|---------| | **Dedifferentiated chondrosarcoma** | Known enchondroma, biphasic appearance, age | - | | Conventional chondrosarcoma Grade III | Cartilage matrix, age | Usually uniform appearance, not biphasic | | Osteosarcoma | Aggressive appearance, ALP elevated | No prior cartilage lesion, usually younger | | Metastatic carcinoma | Age, destructive lesion | Known pre-existing lesion, biphasic pattern | | Chondroblastic osteosarcoma | Mixed pattern | Age, history of enchondroma | **Definition of Dedifferentiated Chondrosarcoma:** - High-grade biphasic tumour - Low-grade cartilaginous component (Grade I-II chondrosarcoma or enchondroma) - High-grade non-cartilaginous sarcoma (osteosarcoma, fibrosarcoma, MFH pattern) - **Abrupt transition** between components (pathognomonic) > **Consultant Tip:** The key to diagnosis is recognising the biphasic pattern - a low-grade cartilage component with abrupt transition to high-grade sarcoma. This has dramatically different prognosis from conventional chondrosarcoma. **Epidemiology:** | Feature | Detail | |---------|--------| | Age | Peak 50-70 years (older than conventional chondrosarcoma) | | Sex | Slight male predominance | | Incidence | 10-15% of all chondrosarcomas | | Common sites | Pelvis (40%), femur (30%), humerus (15%) | | Pre-existing lesion | 30-40% arise from prior benign lesion (enchondroma, osteochondroma) | **Pathophysiology:** | Mechanism | Description | |-----------|-------------| | De novo | Arises as biphasic tumour from the start | | Secondary | Transformation from pre-existing cartilage tumour | | Genetic changes | p53 mutation, Rb pathway dysfunction in high-grade component | | Clonal origin | Both components arise from same clone (molecular studies) | **Histological Patterns of High-Grade Component:** | Pattern | Frequency | |---------|-----------| | Osteosarcoma-like | 40% | | Fibrosarcoma/MFH-like | 40% | | Undifferentiated pleomorphic | 15% | | Other (angiosarcoma, leiomyosarcoma) | 5% | **Risk of Transformation:** - Solitary enchondroma: <1% lifetime risk - Ollier disease (multiple enchondromas): 25-50% risk - Maffucci syndrome (enchondromas + hemangiomas): 100% risk > **Consultant Tip:** Always ask about multiple enchondromas (Ollier) or associated hemangiomas (Maffucci). These syndromic patients have much higher risk of malignant transformation and need surveillance. **Complete Staging Protocol:** | Investigation | Purpose | This Patient's Findings | |---------------|---------|-------------------------| | Plain radiographs | Local extent, matrix pattern | Biphasic lesion, cortical destruction | | MRI of lesion | Intramedullary extent, soft tissue, neurovascular | 10cm lesion, soft tissue mass, no skip lesions | | CT chest | Pulmonary metastases | Two suspicious nodules | | CT abdomen/pelvis | Lymph nodes, visceral metastases | Consider adding | | Bone scan or PET-CT | Skeletal metastases, other sites | Recommended | | Whole-body MRI | Skip lesions, distant bone mets | Alternative to bone scan | | Biopsy | Histological confirmation | Essential before treatment | **Staging Systems:** **AJCC/Enneking Staging for Bone Sarcomas:** | Stage | Grade | Local Extent | Metastases | |-------|-------|--------------|------------| | IIA | High | Intracompartmental | None | | IIB | High | Extracompartmental | None | | III | Any | Any | Present | **This Patient: Stage III** (pulmonary metastases) **Biopsy Considerations:** | Principle | Rationale | |-----------|-----------| | Performed at treating centre | Prevents contamination of surgical field | | Longitudinal incision | Excisable with definitive resection | | Avoid neurovascular structures | Prevent tumour seeding | | Sample BOTH components | Critical for diagnosis | | Core needle preferred | Lower contamination risk than open | > **Consultant Tip:** Biopsy must sample the high-grade component. If only low-grade cartilage sampled, diagnosis will be missed. Multiple cores from different areas essential. **Management Approach:** **Step 1: MDT Discussion** - Orthopaedic oncology surgeon - Medical oncologist - Radiation oncologist - Musculoskeletal radiologist - Pathologist - Palliative care (given metastatic disease) **Step 2: Staging Status** - This patient has **Stage III disease** (pulmonary metastases) - Changes treatment intent from curative to palliative/life-prolonging **Management Options for Metastatic Disease:** | Approach | Indication | Goal | |----------|------------|------| | Surgical resection | Symptomatic primary, impending fracture | Palliation, prevent fracture | | Chemotherapy | Metastatic disease | Limited evidence, consider for high-grade component | | Radiotherapy | Inoperable, positive margins | Local control | | Pulmonary metastasectomy | Limited lung metastases, controlled primary | Possible survival benefit | | Best supportive care | Poor performance status | Symptom control | **Surgical Options for Proximal Femur:** | Procedure | Indication | Reconstruction | |-----------|------------|----------------| | Wide excision + prosthesis | Resectable, good performance status | Proximal femoral replacement (megaprosthesis) | | Internal hemipelvectomy | Extension to acetabulum | Saddle prosthesis or custom implant | | Hindquarter amputation | Neurovascular involvement, massive soft tissue | No reconstruction | | Stabilisation + RT | Palliative, high surgical risk | Intramedullary nail or plate | **Chemotherapy Considerations:** | Regimen | Agent | Evidence | |---------|-------|----------| | Osteosarcoma-type | Doxorubicin, cisplatin, high-dose methotrexate | May benefit osteosarcoma-like component | | Soft tissue sarcoma-type | Doxorubicin, ifosfamide | For MFH/fibrosarcoma pattern | | Response rate | 20-30% | Lower than conventional osteosarcoma | > **Consultant Tip:** Despite metastatic disease, surgical resection of the primary may be worthwhile for pain control and fracture prevention. Discuss realistic expectations with patient and family. **Prognosis:** | Outcome Measure | Dedifferentiated Chondrosarcoma | |-----------------|--------------------------------| | 5-year overall survival | 7-18% | | 10-year overall survival | <10% | | Local recurrence rate | 20-40% | | Metastatic rate | 50-90% (often at diagnosis) | | Median survival (metastatic) | 6-12 months | **Compare to Other Chondrosarcomas:** | Type | 5-Year Survival | |------|-----------------| | Conventional Grade I | 90% | | Conventional Grade II | 60-80% | | Conventional Grade III | 30-50% | | **Dedifferentiated** | **7-18%** | | Clear cell | 70-90% | | Mesenchymal | 50-70% | **Prognostic Factors:** | Factor | Favourable | Unfavourable | |--------|------------|--------------| | Size | <8cm | >8cm (this patient: 10cm) | | Location | Extremity | Pelvis/axial | | Margins | Wide (R0) | Positive (R1/R2) | | Metastases | Absent | Present (this patient) | | Response to chemo | Good (rare) | Poor | | High-grade component | Small percentage | Predominant | | Performance status | ECOG 0-1 | ECOG 2+ | **This Patient's Prognosis:** - Stage III (metastatic at presentation) - Large tumour (10cm) - Unfavourable site (proximal femur, close to pelvis) - Expected survival: 6-12 months median > **Consultant Tip:** Be honest but compassionate when discussing prognosis. Emphasise quality of life goals, pain control, and maintaining function. Involve palliative care early. **Surveillance for Solitary Enchondroma:** | Feature | Recommendation | |---------|----------------| | Asymptomatic, classic features | No routine imaging | | Symptomatic or atypical features | MRI, consider biopsy | | New pain in known lesion | Urgent investigation - assume transformation | **Warning Signs of Malignant Transformation:** | Clinical | Radiological | |----------|--------------| | New pain (especially night pain) | Lesion growth on serial imaging | | Swelling | Cortical destruction | | Pathological fracture | Periosteal reaction | | | Soft tissue mass | | | Loss of matrix calcification (dedifferentiation) | **Surveillance for Multiple Enchondromatosis (Ollier/Maffucci):** | Protocol | Detail | |----------|--------| | Baseline | MRI whole body at diagnosis | | Routine | Annual clinical review | | Imaging | MRI of concerning lesions every 2-3 years | | Trigger for urgent imaging | New symptoms, growth, pain | **Considerations for Primary Prevention:** | Approach | Rationale | |----------|-----------| | Curettage of concerning enchondromas | Removes at-risk tissue | | Observation of stable lesions | Surgery has morbidity | | Patient education | Recognise warning symptoms | **Key Learning: When to Worry** | Reassuring | Concerning | |------------|------------| | Stable on serial imaging | Growing lesion | | Asymptomatic | New pain, especially night pain | | Typical location (hands/feet) | Long bone/pelvis location | | <5cm | >5cm | | No cortical involvement | Cortical destruction | > **Consultant Tip:** Any new pain in a known cartilage lesion should be treated as malignant transformation until proven otherwise. Urgent MRI and biopsy are indicated. --- ## Key Teaching Points ### Pattern Recognition **This pattern suggests Dedifferentiated Chondrosarcoma:** - Elderly patient with longstanding cartilage lesion - New aggressive symptoms (night pain, rapid progression) - Biphasic radiological appearance - Abrupt transition between low-grade and high-grade components on imaging/histology - Elevated ALP and LDH **Distinguish from Conventional Chondrosarcoma:** | Feature | Conventional | Dedifferentiated | |---------|--------------|------------------| | Appearance | Uniform cartilage pattern | Biphasic (two distinct components) | | Transition | Gradual grade variation | Abrupt transition | | Prognosis | Grade-dependent (30-90%) | Uniformly poor (7-18%) | | Chemo response | None | May respond (high-grade component) | | Behaviour | Primarily local | Early metastases | ### Critical Management Points 1. **Recognise biphasic pattern** - key to diagnosis 2. **Biopsy BOTH components** - sampling error can miss diagnosis 3. **Stage completely** - high rate of metastases at presentation 4. **MDT discussion essential** - complex decision-making 5. **Discuss prognosis honestly** - poor survival, palliative care involvement 6. **Surgical resection if feasible** - even in metastatic disease for palliation 7. **Chemotherapy role limited** - may benefit high-grade component --- ## Common Examiner Follow-ups **Q: "What is the difference between dedifferentiated and high-grade conventional chondrosarcoma?"** | Feature | Dedifferentiated | Conventional Grade III | |---------|------------------|------------------------| | Pattern | Biphasic (two distinct components) | Uniform high-grade cartilage | | Matrix | Absent in high-grade component | Cartilage matrix present | | Chemo sensitivity | Partial (high-grade component) | Chemoresistant | | Prognosis | 7-18% 5-year | 30-50% 5-year | | Transition | Abrupt | Not applicable | The key distinction is the abrupt transition between recognisable low-grade cartilage and high-grade non-cartilaginous sarcoma. --- **Q: "Would you offer chemotherapy to this patient?"** Chemotherapy considerations: Arguments for: - Metastatic disease - some treatment better than none - High-grade component may respond (osteosarcoma-like or MFH-like) - 20-30% response rate reported Arguments against: - Overall survival benefit unproven - Significant toxicity - Limited performance status impact - Resources for likely palliative outcome **Decision:** Discuss with patient, offer if good performance status and willing. Consider doxorubicin-based regimen. Realistic expectation is disease stabilisation rather than cure. --- **Q: "The patient asks about survival. How do you counsel them?"** Approach to prognostic discussion: 1. **Assess patient's understanding and wishes** - "What do you understand about your condition?" 2. **Provide honest information** - "This is a serious condition with limited treatment options" 3. **Frame realistically** - "Survival is typically measured in months rather than years" 4. **Focus on goals** - "What's most important to you right now?" 5. **Emphasise quality of life** - "We can control pain and maintain your independence" 6. **Introduce palliative care** - "Our palliative care team helps with symptom control" 7. **Leave hope without false promises** - "Everyone is different, but we need to plan realistically" Key message: Honest but compassionate communication, focus on achievable goals. --- **Q: "What reconstruction would you use for proximal femoral resection?"** | Option | Advantages | Disadvantages | |--------|------------|---------------| | **Proximal femoral replacement (megaprosthesis)** | Immediate stability, early weight-bearing, predictable | Infection risk, dislocation, implant complications | | Allograft-prosthetic composite | Bone stock restoration, soft tissue attachment | Nonunion, fracture, longer rehab | | Intercalary allograft | Biological reconstruction | High complication rate | | Arthrodesis | Durable if united | Loss of motion, difficult surgery | For this patient with metastatic disease and limited prognosis: **Megaprosthesis** - provides rapid rehabilitation and function for remaining life. --- ## Related Topics - Conventional Chondrosarcoma - Enchondroma - Ollier Disease and Maffucci Syndrome - Proximal Femoral Replacement - Bone Metastases Management - Osteosarcoma - Bone Sarcoma Staging