A 32-year-old woman from Delhi presents with a 3-month history of progressive ptosis and diplopia. She reports that symptoms worsen towards the evening and improve after rest. On examination, she has bilateral ptosis that worsens with sustained upward gaze (positive fatigability sign). Serum anti-acetylcholine receptor (AChR) antibodies are positive. Chest CT shows a 2 cm anterior mediastinal mass. What is the most appropriate next step in management?

Explanation

## Clinical Diagnosis and Pathophysiology **Key Point:** This patient has seropositive myasthenia gravis (MG) with evidence of thymoma on imaging — a critical finding that mandates thymectomy. ### Why Thymectomy is Indicated The presence of a thymoma in a patient with MG is an **absolute indication for thymectomy**, regardless of disease severity. Thymomas are found in 10–15% of MG patients and are associated with: - Persistent anti-AChR antibodies - More severe disease phenotype - Risk of myasthenic crisis - Potential malignant transformation if left untreated ### Management Algorithm ```mermaid flowchart TD A[MG + Thymoma on imaging]:::outcome --> B{Surgical candidate?}:::decision B -->|Yes| C[Thymectomy + perioperative immunosuppression]:::action B -->|No| D[Medical management only]:::action C --> E[Start pyridostigmine pre-op]:::action E --> F[Thymectomy]:::action F --> G[Remission or improvement in 50-60% of cases]:::outcome ``` ### Rationale for Correct Answer 1. **Pyridostigmine** is the first-line symptomatic agent — it inhibits acetylcholinesterase, prolonging acetylcholine action at the neuromuscular junction. 2. **Thymectomy** is the definitive treatment for thymoma-associated MG and should be performed urgently after stabilization with pyridostigmine. 3. This two-step approach addresses both immediate symptom relief and the underlying pathology. **High-Yield:** Thymoma + MG = thymectomy is non-negotiable. Do not delay with medical management alone. ### Why Other Options Are Suboptimal - **IVIG** is reserved for acute exacerbations or myasthenic crisis, not initial management of stable disease with thymoma. - **Corticosteroids + plasmapheresis** are immunosuppressive options but do not address the thymoma, which requires surgical removal. - **Azathioprine monotherapy** is too slow-acting (weeks to months) and does not treat the underlying thymoma. **Clinical Pearl:** Thymectomy improves or remits symptoms in 50–60% of MG patients, with best outcomes when performed early in seropositive disease with thymoma. [cite:Harrison 21e Ch 385]