Thymoma & Myasthenia Gravis

Thymus — anatomy

The thymus is a specialised primary lymphoid organ that involutes after puberty. It weighs approximately 15–20 grams in adults. Embryonically, thymic epithelium develops from the ventral diverticulum of the 3rd pharyngeal pouch at 6 weeks, descending into the anteroinferior mediastinum and fusing at 8 weeks. This embryological origin explains why inferior parathyroids may be embedded in the thyrothymic ligament (ectopic parathyroid).

The thymus is bilobed (H-shaped), with two upper and two lower horns. It lies in the superior and anterior mediastinum, extending from the inferior pole of the thyroid gland superiorly to the 4th costal cartilage inferiorly. Isolated microscopic thymic islets may extend from the neck to the diaphragm — this explains incomplete resection during thymectomy for myasthenia gravis.

Thymoma

Thymomas are the most common epithelial tumours of the anterior mediastinum, representing 20% of all mediastinal masses in adults. Encapsulated in 40–70% of cases; invasive in 30–60%. Peak incidence in the 3rd to 5th decades; equal sex incidence; rare in children.

Paraneoplastic associations

About 35–40% of thymoma patients have an associated paraneoplastic syndrome. Myasthenia gravis is the most common (see below). Others include:

• Neurological: limbic encephalitis, neuromyotonia, stiff person syndrome, myotonic dystrophy, polymyositis
• Haematological: pure red cell aplasia, hypogammaglobulinaemia, blood dyscrasias
• Autoimmune: myocarditis, graft-versus-host disease, mixed connective tissue disease, thyroiditis

WHO classification and Masaoka staging

Investigations

• CT chest: investigation of choice — determines extent, pleural/pericardial involvement, nodules
• MRI: useful for surgical planning in invasive thymomas — superior for vascular invasion
• PET-CT: SUV in thymic carcinomas significantly higher than in high-risk or low-risk thymomas
• Biopsy: NOT required for clinically suspected, resectable, encapsulated thymoma — biopsy risks capsule breach and seeding. Biopsy IS indicated for: unresectable or invasive disease planned for neoadjuvant therapy; diagnostic dilemma (lymphoma vs GCT vs thymoma). Options: CT-guided core biopsy, mediastinoscopy, anterior mediastinotomy (Chamberlain), or VATS-guided
• Always check: MG symptoms/signs; AFP and β-hCG (exclude GCT in young patients); haematological indices (pure red cell aplasia)

Treatment

Complete surgical excision (CSE) with R0 resection — including total thymectomy en bloc with involved surrounding tissue — is indicated in all resectable thymomas (Masaoka I–III).

• Lung involvement: en-bloc lung resection
• Unilateral phrenic nerve involvement: nerve resection acceptable if patient can tolerate hemidiaphragm palsy and R0 resection otherwise achievable
• Neoadjuvant therapy: indicated for Masaoka stage III and above — reassess resectability after induction
• Post-operative radiotherapy: indicated for incomplete resection (R1/R2) and post-resection stage III and above

Thymic carcinoma

Rare, highly aggressive thymic epithelial malignancy. Squamous cell carcinoma is the most common variant. Growth is locally invasive with aggressive metastatic potential — most are unresectable at presentation. Surgery only where R0 resection is feasible.

Myasthenia gravis

Pathophysiology

Acetylcholine (ACh) released from nerve terminals binds AChR on the motor end plate to initiate muscle contraction. In MG, autoantibodies bind and destroy AChR — reducing the number of functional receptors and blocking ACh binding, leading to reduced muscle action potential and fatigable weakness.

Clinical features

Peak incidence in the 5th decade; equal sex incidence. Characteristic fatigable weakness — worsens with sustained effort and improves with rest. Commonly involved muscle groups:

• Ocular (most common): ptosis, diplopia — may be the only muscles affected (ocular MG)
• Oropharyngeal: difficulty chewing tough foods, dysphagia, dysarthria, nasal voice
• Limb: proximal myopathy — difficulty raising arms, climbing stairs
• Respiratory: myasthenic crisis — acute respiratory failure; life-threatening; triggered by infection, surgery, certain drugs

Investigations

• Tensilon (edrophonium) test: IV edrophonium transiently inhibits acetylcholinesterase — weakness caused by NMJ dysfunction improves dramatically within 30–60 seconds; objective improvement in ptosis or eye movements is the endpoint
• Serum antibodies: AChR antibodies (85%); anti-MuSK (in seronegative patients)
• CT chest: mandatory in all MG patients — characterise thymic pathology
• Electromyography: repetitive nerve stimulation shows decremental response (>10% amplitude fall); single-fibre EMG is the most sensitive test
• Pulmonary function tests: baseline and during exacerbations; FVC <1L signals impending respiratory crisis

Thymectomy for MG

Thymectomy is recommended for all MG patients with thymoma. For non-thymomatous MG, thymectomy is recommended in AChR antibody-positive patients under 65 years of age. The goal is maximum removal of all thymic tissue — the thymus and all mediastinal and cervical fat that may contain ectopic thymic islands.

Outcomes: One-year remission rate <20%, but over 7–10 years the rate increases substantially. Maximum response typically at 2–5 years post-surgery. Best responses in young patients early in the disease course. Patients with onset after 60 rarely show substantial improvement.

Surgical approaches to thymectomy

No convincing data currently favour any one approach over another for long-term MG remission rates — choice is based on tumour size, invasiveness, surgeon experience, and patient factors.