A 58-year-old man with a 40-pack-year smoking history presents with progressive proximal muscle weakness, difficulty climbing stairs, and myalgia. Serum creatine kinase is elevated at 2800 U/L. Chest X-ray reveals a 3 cm left hilar mass. Which investigation is most appropriate to confirm the suspected paraneoplastic syndrome?

## Paraneoplastic Myositis and Autoantibody Detection ### Clinical Context The patient presents with: - Proximal muscle weakness (myositis pattern) - Elevated CK (muscle necrosis) - Lung malignancy (smoking history + hilar mass) - This constellation suggests **paraneoplastic inflammatory myositis** ### Why Serum Autoantibody Panel Is Correct **Key Point:** Anti-Jo-1 (histidyl-tRNA synthetase) antibodies are the most common myositis-specific antibodies, found in ~30% of paraneoplastic myositis cases, particularly associated with lung cancer. **High-Yield:** The myositis panel includes: - Anti-Jo-1 (most frequent) - Anti-PL-7, Anti-PL-12 - Anti-Mi-2 - Anti-SRP (signal recognition particle) - Anti-HMGCR These are: 1. **Specific** — directly diagnostic of myositis 2. **Sensitive** — positive in 50–80% of inflammatory myositis 3. **Prognostic** — certain antibodies (e.g., anti-SRP) correlate with malignancy risk ### Diagnostic Algorithm ```mermaid flowchart TD A[Proximal weakness + elevated CK + lung mass] --> B{Confirm myositis} B -->|Serology first| C[Autoantibody panel] C -->|Positive| D[Paraneoplastic myositis confirmed] C -->|Negative| E[Proceed to EMG/biopsy] D --> F[Treat cancer + immunosuppression] ``` **Clinical Pearl:** Anti-Jo-1 positivity in a patient with lung cancer and myositis has ~90% specificity for paraneoplastic myositis and guides both diagnosis and prognosis. ### Why Serology Before Biopsy? - Non-invasive - High specificity - Guides biopsy interpretation if needed - Faster turnaround than biopsy [cite:Robbins 10e Ch 7]