# CIM Case: Pathological Fracture - Unknown Primary ## Clinical Scenario **Patient:** 68-year-old man **Presentation:** Sudden onset left thigh pain after standing from chair, unable to weight-bear, preceded by 6-week history of dull aching left thigh pain **Relevant history:** 40 pack-year smoking history (stopped 5 years ago), 8kg weight loss over 3 months, decreased appetite, productive cough for 2 months, no prior malignancy diagnosed, retired carpenter (asbestos exposure) **Examination findings:** - Cachectic appearance - Left leg shortened and externally rotated - Obvious deformity at mid-thigh level - Palpable mass around fracture site - Exquisitely tender at fracture site - Unable to perform SLR - Neurovascularly intact distally - Finger clubbing noted - Scattered rhonchi on chest auscultation - No palpable lymphadenopathy --- ## Investigations Provided ### Laboratory Results | Test | Result | Normal Range | Interpretation | |------|--------|--------------|----------------| | Hb | 98 g/L | 130-170 g/L | ↓ Anaemia of chronic disease | | WCC | 11.2 ×10⁹/L | 4-11 ×10⁹/L | ↑ Mildly elevated | | Platelets | 425 ×10⁹/L | 150-400 ×10⁹/L | ↑ Reactive | | CRP | 85 mg/L | <5 mg/L | ↑ Elevated | | ESR | 95 mm/hr | <20 mm/hr | ↑ Markedly elevated | | Calcium | 2.85 mmol/L | 2.2-2.6 mmol/L | ↑ Hypercalcaemia | | ALP | 320 U/L | 30-120 U/L | ↑ Elevated (bone/liver) | | Albumin | 28 g/L | 35-50 g/L | ↓ Hypoalbuminaemia | | Creatinine | 125 μmol/L | 60-110 μmol/L | ↑ Mild renal impairment | | PSA | 2.5 ng/mL | <4 ng/mL | Normal | | Protein electrophoresis | No paraprotein | - | Excludes myeloma | ### Imaging **Image 1: AP and Lateral Radiographs of Left Femur** **Radiological features:** - Transverse fracture through mid-diaphysis of left femur - Large lytic lesion at fracture site (5cm) - Cortical destruction >75% - Moth-eaten/permeative margins - No matrix mineralisation (not bone-forming) - Pathological fracture through tumour - No periosteal reaction **Image 2: CT Chest/Abdomen/Pelvis** **Findings:** - 4.5cm spiculated mass in right upper lobe (highly suspicious for primary lung carcinoma) - Ipsilateral hilar lymphadenopathy - Multiple small pulmonary nodules bilaterally - Lytic lesion in L3 vertebral body - No liver metastases - No renal mass - No adrenal masses --- ## Questions & Model Answers **Differential Diagnosis:** | Diagnosis | Supporting Features | Against | |-----------|---------------------|---------| | **Metastatic lung carcinoma** | Smoker, lung mass on CT, weight loss, lytic lesion | - | | Metastatic renal cell carcinoma | Lytic lesion, age | No renal mass on CT | | Multiple myeloma | Lytic lesion, age, hypercalcaemia | Normal protein electrophoresis | | Metastatic prostate carcinoma | Age, male | PSA normal, lesion is lytic (not blastic) | | Primary bone tumour | Lytic lesion | Age >40, weight loss, lung mass | **Most Likely Diagnosis: Pathological fracture through metastatic lung carcinoma** **Key Supporting Features:** - 40 pack-year smoking history - Productive cough, weight loss - Spiculated lung mass with hilar lymphadenopathy (CT chest) - Lytic bone lesion (typical of lung metastases) - Hypercalcaemia (paraneoplastic or bone destruction) **Key Principle:** In adults over 40 with a destructive bone lesion and constitutional symptoms, assume metastatic carcinoma until proven otherwise. Metastasis is 25× more common than primary bone tumour. > **Consultant Tip:** Smoking + weight loss + lytic bone lesion = think lung cancer first. It's the most common occult primary in males with bone metastases. **Systematic Workup for Unknown Primary:** **History and Examination:** | System | Clinical Features | |--------|------------------| | Lung | Cough, haemoptysis, smoking history | | Prostate | Urinary symptoms, DRE | | Kidney | Haematuria, flank mass | | Thyroid | Neck mass, dysphagia | | Breast (even in males) | Nipple discharge, mass | | Skin | Melanoma history, suspicious lesions | **Laboratory Investigations:** | Test | Purpose | |------|---------| | PSA | Prostate carcinoma (male) | | AFP, β-hCG | Germ cell tumour (young patients) | | Thyroid function + thyroglobulin | Thyroid carcinoma | | Protein electrophoresis | Myeloma | | LDH | Lymphoma, prognosis | | Calcium | Hypercalcaemia workup | | Liver function | Hepatic metastases | **Imaging:** | Modality | Purpose | |----------|---------| | **CT chest/abdomen/pelvis** | Find primary, stage disease | | **Whole body bone scan** | Skeletal extent | | **PET-CT** | If primary unclear, occult primary detection | | **Mammogram** | Females, breast primary | **Tissue Diagnosis:** - CT-guided biopsy of most accessible lesion - Immunohistochemistry to determine origin: - TTF-1 = lung adenocarcinoma - PSA/PSAP = prostate - PAX8 = renal, thyroid - GATA3 = breast, urothelial **Most Common Occult Primaries:** - Lung: 30-40% - Kidney: 10-15% - Unknown remains: 10-15% > **Consultant Tip:** Don't delay fracture stabilisation for exhaustive workup. Stabilise first, then complete staging. Tissue from fracture site can be diagnostic. **Mirels Scoring System:** | Variable | 1 Point | 2 Points | 3 Points | |----------|---------|----------|----------| | **Site** | Upper limb | Lower limb | Peritrochanteric | | **Pain** | Mild | Moderate | Functional (weight-bearing) | | **Lesion type** | Blastic | Mixed | Lytic | | **Size (cortical destruction)** | <1/3 | 1/3-2/3 | >2/3 | **Interpretation:** - Score ≤7: Low risk (~5%) → radiotherapy alone - Score 8: Intermediate (~15%) → consider prophylactic fixation - Score ≥9: High risk (~33%) → prophylactic fixation recommended **This Patient (Before Fracture Would Have Been):** - Site: Lower limb = 2 - Pain: Functional = 3 - Lesion type: Lytic = 3 - Size: >2/3 cortical destruction = 3 - **Total: 11 - would have indicated prophylactic fixation** **Key Point:** This patient had prodromal pain for 6 weeks before fracture. Earlier diagnosis and prophylactic fixation could have prevented pathological fracture. **Impending Fracture Features:** - Cortical destruction >50% - Lesion >2.5cm - Progressive pain despite radiotherapy - Any peritrochanteric lytic lesion > **Consultant Tip:** Mirels ≥9 = prophylactic stabilisation. Lower limb lytic lesions with functional pain are high risk. Don't wait for fracture. **Treatment Goals (Palliative Intent):** - Pain relief - Restore function and mobility - Allow immediate weight-bearing - Single procedure (avoid revisions) - Improve quality of life for remaining survival **Surgical Options for Diaphyseal Femur:** | Option | Indication | Considerations | |--------|------------|----------------| | **Long cephalomedullary nail** | Standard for diaphyseal metastases | Load-sharing, immediate WB, protects entire bone | | **Plate fixation** | Short lesion, need for open biopsy | Load-bearing, requires healing | | **Endoprosthetic replacement** | Extensive bone loss, poor bone quality | Good for larger defects, no need for healing | **Recommended Treatment:** **Long cephalomedullary nail (e.g., long Gamma nail)** - Spans entire femur from hip to knee - Load-sharing device - Allows immediate full weight-bearing - Protects against future proximal/distal lesions (common) - Can be done closed or with limited open approach **Surgical Technique Considerations:** - Send tissue from lesion for histology (confirms diagnosis) - Prophylactic femoral neck fixation (cephalomedullary design) - Consider cement augmentation if poor bone stock - Post-operative radiotherapy to lesion **Adjuvant Treatment:** - **Radiotherapy:** 30 Gy in 10 fractions, or 8 Gy single fraction (palliative) - **Bisphosphonates/Denosumab:** Reduce skeletal events - **Systemic therapy:** Based on primary tumour type (oncology input) > **Consultant Tip:** For femoral shaft metastases, use a LONG nail from greater trochanter to distal femur. Short nails leave bone at risk proximally and distally. **Prognosis by Primary Tumour:** | Primary | Median Survival | Characteristics | |---------|-----------------|-----------------| | **Lung** | 3-6 months | Poor prognosis, often extensive disease | | Prostate | 12-24+ months | Often hormone-sensitive, better prognosis | | Breast | 12-36 months | Often responsive to hormonal/targeted therapy | | Kidney | 6-12 months | Variable, may be more aggressive | | Thyroid | 24-60 months | Best prognosis of common primaries | | Unknown | 3-6 months | Generally poor | **This Patient's Prognosis:** - Likely lung primary with hilar nodes and bone metastases - Median survival: 3-6 months - Poor prognostic features: weight loss, hypercalcaemia, multiple metastases **Surgical Decision-Making Based on Prognosis:** | Expected Survival | Surgical Approach | |-------------------|-------------------| | <6 weeks | Consider non-operative (splinting, RT), or minimally invasive | | 6 weeks - 6 months | Intramedullary nailing (standard) | | >6-12 months | Consider more durable reconstruction, or prosthesis | | Curative intent (rare) | Wide resection if solitary metastasis | **Key Principles:** - Surgery is palliative - balance morbidity against benefit - Aim for single procedure (avoid returns to theatre) - Immediate weight-bearing crucial for rehabilitation - Quality of life more important than longevity **Despite poor prognosis, surgery is beneficial because:** - Converts bedridden patient to mobile - Reduces analgesia requirements - Allows discharge home - Preserves independence - Enables palliative radiotherapy and systemic treatment > **Consultant Tip:** Even with 3-6 month prognosis, surgical stabilisation improves quality of remaining life. A mobile patient dies at home; an immobile patient dies in hospital. **Special Considerations for Renal Cell Carcinoma:** **Unique Features:** - Often presents as solitary skeletal metastasis - May be curative with complete resection - Highly vascular (bleeding risk) - Resistant to radiotherapy and chemotherapy - May have long disease-free interval **Workup for Solitary Renal Metastasis:** - Complete staging (CT/PET) to confirm truly solitary - Renal MRI/CT to assess primary - Cardiopulmonary fitness for major surgery - Oncology MDT discussion **Surgical Options:** | Scenario | Treatment | |----------|-----------| | Solitary metastasis, operable primary | Wide excision + reconstruction + nephrectomy (curative intent) | | Solitary metastasis, inoperable primary | Palliative stabilisation, targeted therapy | | Multiple metastases | Palliative stabilisation as per other metastases | **Preoperative Embolisation:** - Strongly recommended for RCC metastases - Reduces intraoperative blood loss by 50-70% - Perform 24-48 hours before surgery - Done by interventional radiology **Reconstruction Options:** - Endoprosthetic replacement (most common for appendicular skeleton) - Wide excision with allograft - En bloc resection (rarely achievable) **5-Year Survival with Solitary RCC Metastasis (Resected):** - 35-50% with complete resection - Much better than other carcinomas > **Consultant Tip:** Renal cell carcinoma is unique - curative surgery may be possible for solitary metastasis. Always embolise before operating (highly vascular). --- ## Key Teaching Points ### Pattern Recognition **This pattern suggests Metastatic Carcinoma:** - Adult >40 years with destructive bone lesion - Constitutional symptoms (weight loss, fatigue) - Lytic lesion without matrix production - Risk factors for primary malignancy (smoking) - Hypercalcaemia **Common Lytic Metastases (Mnemonic: "Kidney-Thyroid-Lung-Breast-Lick-Bone"):** - **K**idney (renal cell) - **T**hyroid - **L**ung - **B**reast **Common Blastic Metastases:** - Prostate (most common) - Breast (can be mixed) - Carcinoid - Medulloblastoma ### Critical Management Points 1. **Stabilise fracture first** - don't delay for exhaustive workup 2. **Tissue diagnosis from fracture site** - confirms primary 3. **Long nail for femoral shaft** - protects entire bone 4. **Mirels score for impending fractures** - ≥9 needs prophylactic fixation 5. **Adjuvant radiotherapy** - improves local control 6. **MDT discussion** - oncology, palliative care, radiation oncology 7. **Quality of life focus** - palliative intent in most cases --- ## Common Examiner Follow-ups **Q: "What are the most common sites for bone metastases?"** Most common sites (in order): 1. Spine (thoracic > lumbar > cervical) 2. Pelvis 3. Proximal femur 4. Ribs 5. Proximal humerus 6. Skull Metastases occur in red marrow areas due to rich blood supply and Batson's venous plexus. --- **Q: "When would you consider curative resection for bone metastases?"** Curative resection may be considered when: - **Solitary skeletal metastasis** confirmed on staging - **Primary controlled or controllable** (nephrectomy for RCC) - **Long disease-free interval** (>2 years) - **Favourable histology** (RCC, thyroid, breast) - **Patient fit for major surgery** - **Acceptable limb function** expected post-resection Most common scenario: solitary renal cell carcinoma metastasis --- **Q: "What is the role of radiotherapy in bone metastases?"** | Indication | Dose | Purpose | |------------|------|---------| | Palliation (pain) | 8 Gy single fraction | Quick pain relief | | Post-operative | 30 Gy in 10 fractions | Local control | | Spinal cord compression | 20-30 Gy | Decompression if non-surgical | | Impending fracture (low Mirels) | 30 Gy | Prevent fracture | Most bone metastases are radiosensitive except renal cell and melanoma. --- **Q: "How do you differentiate a pathological fracture from a traumatic fracture in the elderly?"** | Feature | Pathological | Traumatic | |---------|--------------|-----------| | Mechanism | Minimal trauma | Significant trauma | | Prodromal pain | Common (weeks) | Absent | | X-ray | Lytic lesion, cortical destruction | Normal bone prior to fracture | | Constitutional symptoms | Weight loss, fatigue | Absent | | Risk factors | Malignancy history, smoking | Falls risk, osteoporosis | Any fracture with minimal trauma or visible lesion on X-ray should be considered pathological until proven otherwise. --- ## Related Topics - Mirels Scoring System - Bone Metastasis Management - Intramedullary Nailing for Pathological Fractures - Renal Cell Carcinoma Metastases - Preoperative Embolisation - Palliative Orthopaedics