# CIM Case: Metastatic Renal Cell Carcinoma to Humerus ## Clinical Scenario **Patient:** 58-year-old man **Presentation:** Progressive left arm pain for 8 weeks, now with difficulty lifting objects, pain at night disturbing sleep **Relevant history:** Renal cell carcinoma diagnosed 2 years ago (right nephrectomy, clear cell type, T3aN0M0 at diagnosis), recent surveillance CT showed no recurrence in renal bed, no prior chemotherapy, otherwise well, smoker (20 pack-years), no other medical history **Examination findings:** - Well-appearing man, no cachexia - Tender mass palpable over mid-left humerus (firm, fixed to bone) - Overlying skin normal, warm to touch - Full shoulder and elbow range of motion (limited by pain) - No wasting of deltoid or arm muscles - Neurovascularly intact distally (radial pulse normal) - Lungs clear on auscultation - Abdomen soft, left nephrectomy scar healed --- ## Investigations Provided ### Laboratory Results | Test | Result | Normal Range | Interpretation | |------|--------|--------------|----------------| | Hb | 125 g/L | 130-170 g/L | ↓ Mildly low | | WCC | 7.8 ×10⁹/L | 4-11 ×10⁹/L | Normal | | Platelets | 245 ×10⁹/L | 150-400 ×10⁹/L | Normal | | CRP | 12 mg/L | <5 mg/L | ↑ Mildly elevated | | ESR | 35 mm/hr | <20 mm/hr | ↑ Elevated | | Calcium | 2.75 mmol/L | 2.2-2.6 mmol/L | ↑ Elevated | | ALP | 185 U/L | 30-120 U/L | ↑ Elevated | | Albumin | 38 g/L | 35-50 g/L | Normal | | LDH | 280 U/L | 120-250 U/L | ↑ Mildly elevated | | Creatinine | 115 μmol/L | 60-110 μmol/L | ↑ Mildly elevated (single kidney) | | eGFR | 58 mL/min | >60 | ↓ Stage 3 CKD | ### Imaging **Image 1: AP and Lateral Radiographs of Left Humerus** **Radiological features:** - Large lytic lesion in mid-diaphysis of humerus - Geographic destruction with moth-eaten margins - Cortical erosion (>50% circumference involved) - No matrix mineralisation - Soft tissue mass visible extending from bone - No periosteal reaction - No pathological fracture yet - Lesion spans approximately 8cm longitudinally **Image 2: CT Chest/Abdomen/Pelvis (Staging)** **Findings:** - Right nephrectomy (known) - No renal bed recurrence - No liver metastases - Solitary 5mm pulmonary nodule in right lower lobe (indeterminate) - No other bone lesions on CT - No lymphadenopathy **Image 3: Bone Scan (Whole Body)** **Findings:** - Hot lesion in mid-left humerus - Cold centre (photopenic) with hot rim - No other skeletal lesions - Normal uptake in kidneys/bladder --- ## Questions & Model Answers **Differential Diagnosis:** | Diagnosis | Supporting Features | Against | |-----------|---------------------|---------| | **Metastatic renal cell carcinoma** | Known RCC, lytic lesion, hypervascular appearance, hypercalcaemia | - | | Primary bone tumour (chondrosarcoma) | Lytic lesion, age | Known RCC, no matrix | | Metastasis from unknown primary | Lytic lesion, age | Known RCC is more likely source | | Multiple myeloma | Lytic lesion, hypercalcaemia | Single lesion, no paraprotein on history | | Infection (osteomyelitis) | Lytic lesion, elevated CRP/ESR | No systemic symptoms, known malignancy | **Most Likely Diagnosis: Solitary Metastatic Renal Cell Carcinoma to Left Humerus** **Supporting Evidence:** - Known clear cell RCC (most common type to metastasise to bone) - Classic lytic, hypervascular appearance - Solitary skeletal lesion on bone scan - Hypercalcaemia (PTHrP production by RCC) - Hot lesion with cold centre (highly vascular tumour) **Key Principle:** In a patient with known malignancy and new bone lesion, metastasis is the most likely diagnosis until proven otherwise. > **Consultant Tip:** RCC can metastasise late (even 10-20 years after nephrectomy). A new bone lesion in a patient with RCC history should be considered metastatic until proven otherwise. **Mirels Scoring System:** | Variable | Score 1 | Score 2 | Score 3 | This Patient | |----------|---------|---------|---------|--------------| | **Site** | Upper limb | Lower limb | Peritrochanteric | 1 (upper limb) | | **Pain** | Mild | Moderate | Functional (with use) | 3 (pain limiting function) | | **Lesion type** | Blastic | Mixed | Lytic | 3 (lytic) | | **Size (cortical destruction)** | <1/3 | 1/3-2/3 | >2/3 | 3 (>50%) | **Total Score: 10** **Fracture Risk by Score:** | Mirels Score | Fracture Risk | Recommendation | |--------------|---------------|----------------| | ≤7 | ~5% | Radiotherapy alone | | 8 | ~15% | Consider prophylactic fixation | | ≥9 | ~33% | Prophylactic fixation recommended | | 10 | ~72% | HIGH RISK - definite fixation | | 11-12 | >90% | Impending/established fracture | **This Patient: Score 10 = 72% fracture risk** **Prophylactic stabilisation is indicated.** **Additional Impending Fracture Features:** - Lesion >2.5cm - Cortical destruction >50% - Pain with activity - Progressive pain despite treatment > **Consultant Tip:** Mirels ≥9 means prophylactic fixation. A pathological fracture through RCC metastasis is a much bigger operation than prophylactic stabilisation. Operate before it breaks. **Complete Staging Protocol:** | Investigation | Purpose | This Patient's Findings | |---------------|---------|-------------------------| | CT chest/abdomen/pelvis | Visceral staging, local recurrence | No recurrence, 5mm lung nodule | | Bone scan | Skeletal staging | Solitary humerus lesion | | MRI of lesion | Local extent, soft tissue involvement | Consider for surgical planning | | PET-CT | If solitary metastasis confirmed | May detect occult disease | | Brain MRI | If neurological symptoms | Not indicated currently | **Significance of Solitary Metastasis:** | Feature | Implication | |---------|-------------| | Solitary skeletal metastasis | Potentially CURATIVE with complete resection | | Long disease-free interval (2 years) | Better prognosis | | Clear cell histology | Responds to targeted therapy | | No visceral metastases | Better prognosis | | 5mm lung nodule | Needs follow-up; may change staging | **Curative Potential:** - Solitary RCC metastasis can be cured with metastasectomy - 5-year survival with complete resection: 35-50% - Compare to non-resected/multiple metastases: <10% 5-year survival **For This Patient:** - Confirm solitary lesion with PET-CT - If truly solitary: wide excision with limb salvage - If multiple: palliative fixation > **Consultant Tip:** RCC solitary metastasis is unique - curative resection is possible. Confirm truly solitary with PET-CT before planning surgery. The 5mm lung nodule may change the approach. **Preoperative Embolisation for RCC Metastases:** **Rationale:** - RCC metastases are **highly vascular** (among the most vascular of all metastases) - Arteriovenous shunting within tumour - Massive blood loss possible without embolisation - Embolisation reduces intraoperative bleeding by 50-70% **Tumours Requiring Embolisation Consideration:** | Primary | Vascularity | Embolisation Recommendation | |---------|-------------|----------------------------| | Renal cell carcinoma | Very high | STRONGLY recommended | | Hepatocellular carcinoma | Very high | STRONGLY recommended | | Thyroid carcinoma | High | Often recommended | | Melanoma | Moderate | Consider | | Breast/Prostate/Lung | Low-moderate | Usually not needed | **Embolisation Technique:** - Performed by interventional radiology - Angiography to identify feeding vessels - Selective embolisation with particles (PVA, microspheres) or coils - Aim for devascularisation of tumour **Timing:** - Ideally 24-48 hours before surgery - Allows tumour necrosis and reduced vascularity - Not >72 hours (revascularisation begins) **Risks of Embolisation:** - Post-embolisation syndrome (pain, fever, swelling) - Skin necrosis (rare) - Non-target embolisation - Incomplete devascularisation > **Consultant Tip:** NEVER operate on an RCC bone metastasis without considering preoperative embolisation. The blood loss can be catastrophic. **Treatment Goals:** | If Solitary (Curative Intent) | If Not Solitary (Palliative) | |-------------------------------|------------------------------| | Wide excision of tumour | Intralesional curettage | | Limb salvage if possible | Stabilise bone | | Long-term disease-free survival | Prevent/treat fracture | | May consider amputation if needed | Pain relief | **Surgical Options:** | Option | Indication | Reconstruction | |--------|------------|----------------| | **Wide excision + endoprosthesis** | Solitary metastasis, curative intent | Humeral shaft/proximal humeral prosthesis | | **Curettage + cement + nail** | Palliative, impending fracture | Locked humeral nail + PMMA cement | | **Curettage + cement + plate** | Palliative, metaphyseal location | Plate fixation + PMMA | | **Amputation** | Massive local extension, neurovascular involvement, uncontrollable bleeding | - | **For This Patient (Assuming Solitary Lesion Confirmed):** **Wide Intercalary Resection + Reconstruction:** - Anterior approach to humerus - Identify and protect radial nerve - Resect segment of humerus with tumour + 2-3cm margins - Reconstruction options: - Endoprosthetic replacement (modular intercalary prosthesis) - Allograft reconstruction - Allograft-prosthetic composite **Surgical Steps:** 1. Preoperative embolisation (24-48h before) 2. Anterior approach, protect radial nerve 3. Identify tumour extent with imaging correlation 4. Mark resection margins (2-3cm from tumour) 5. Ligate feeding vessels 6. Perform osteotomies proximal and distal 7. Remove specimen en bloc 8. Reconstruct with prosthesis 9. Ensure stable fixation 10. Close in layers, drain > **Consultant Tip:** For curative resection, wide margins (2-3cm) are essential. Intralesional procedures have higher local recurrence. Endoprosthesis gives immediate stability and function. **Prognosis:** | Scenario | 5-Year Survival | |----------|-----------------| | Solitary bone metastasis, complete resection | 35-50% | | Limited metastases on targeted therapy | 15-30% | | Multiple metastases, historical (pre-TKI era) | <10% | | Bone-only metastases | Better than visceral | **Prognostic Factors:** - Disease-free interval from nephrectomy (longer = better) - Number of metastatic sites (fewer = better) - IMDC/Heng prognostic score - Performance status - Histological subtype (clear cell most common, responds to therapy) **Systemic Treatment Options:** | Class | Examples | Mechanism | |-------|----------|-----------| | **TKIs (Tyrosine Kinase Inhibitors)** | Sunitinib, Pazopanib, Cabozantinib, Axitinib | Block VEGF receptor | | **mTOR Inhibitors** | Everolimus, Temsirolimus | Block mTOR pathway | | **Immune Checkpoint Inhibitors** | Nivolumab, Ipilimumab, Pembrolizumab | Enhance T-cell response | | **Combination Therapy** | Nivolumab + Ipilimumab; TKI + checkpoint inhibitor | Current standard for many patients | **Adjuncts:** - Bone-modifying agents (Zoledronic acid or Denosumab) - reduce skeletal events - Radiotherapy (RCC is relatively radioresistant, but SBRT effective) - Surveillance of 5mm lung nodule (serial CT) **MDT Discussion Essential:** - Medical oncology input for systemic therapy - Orthopaedic oncology for surgical planning - Interventional radiology for embolisation - Radiology for staging interpretation > **Consultant Tip:** RCC survival has dramatically improved with targeted therapies. Median survival for metastatic disease now exceeds 2-3 years with modern treatment. Don't be nihilistic - aggressive local control for solitary metastasis combined with systemic therapy can achieve long-term survival. --- ## Key Teaching Points ### Pattern Recognition **This pattern suggests Renal Cell Carcinoma Bone Metastasis:** - History of RCC (even remote) - Lytic, expansile bone lesion - Hypercalcaemia - Hypervascular appearance on imaging - Hot lesion with cold centre on bone scan (vascular tumour necrosis) - Late presentation (years after primary) **Lytic Bone Metastases Mnemonic: "Lots of Trouble Kills Patients Badly":** - **L**ung - **T**hyroid - **K**idney - **P**rostate (usually blastic, can be lytic) - **B**reast ### Critical Management Points 1. **Confirm solitary** - PET-CT before planning curative surgery 2. **Preoperative embolisation** - ESSENTIAL for RCC (highly vascular) 3. **Mirels score ≥9** - prophylactic fixation indicated 4. **Wide excision for curative intent** - if truly solitary, 2-3cm margins 5. **MDT approach** - oncology, orthopaedics, IR, radiology 6. **Bone-modifying agents** - reduce skeletal events 7. **Long-term surveillance** - RCC can recur late --- ## Common Examiner Follow-ups **Q: "What is the 'cold in hot' sign on bone scan and what does it indicate?"** The "cold in hot" or "doughnut" sign: - Peripheral hot rim with central photopenic (cold) area - Indicates highly vascular tumour with central necrosis - Classic for renal cell carcinoma metastases - Also seen in aggressive vascular tumours Mechanism: The centre has outgrown its blood supply leading to necrosis, while the periphery remains hypervascular and metabolically active. --- **Q: "Why is RCC relatively radioresistant and what are the implications?"** RCC is considered radioresistant because: - Conventional fractionated RT has limited efficacy - May relate to hypoxic tumour microenvironment - VHL pathway mutations affect hypoxia response Implications: - Surgery preferred for local control when feasible - Stereotactic body radiotherapy (SBRT) more effective (high dose per fraction) - Radiotherapy alone not reliable for local control - Post-operative RT role is limited --- **Q: "How do you manage the 5mm lung nodule?"** Management of indeterminate lung nodule: - Repeat CT in 3-6 months (Fleischner Society guidelines) - If stable for 2 years: likely benign - If growing: biopsy or resection - PET-CT has limited sensitivity for lesions <8mm - Changes surgical plan if proven metastatic (no longer solitary) For this patient: - If nodule is stable/benign: proceed with curative resection of humerus - If nodule is metastatic: palliative approach more appropriate --- **Q: "What are the indications for amputation in this scenario?"** Amputation indications for bone metastasis (rare): - Massive neurovascular involvement not reconstructable - Failed limb salvage with infection - Uncontrollable haemorrhage - Fungating tumour with skin breakdown - Patient preference after informed discussion For this patient with localised disease, limb salvage should be achievable with modern techniques. --- ## Related Topics - Pathological Fractures - Mirels Scoring System - Preoperative Embolisation - Endoprosthetic Reconstruction - Bone Metastasis Management - Immunotherapy in Oncology