Thymoma

Thymoma is an epithelial tumor of the thymus and the commonest tumor of the anterior mediastinum in adults. Incidence is about 0.15 per 100,000 people a year, with a peak at 40 to 60 years and no sex predominance.

Histologic types by epithelial and lymphocytic content: A (spindle cell), AB (mixed), B1 (lymphocyte-rich), B2 (cortical) and B3 (epithelial, well-differentiated thymic carcinoma-like). Invasiveness, not histology alone, defines behavior.

Stages by invasion

• I: encapsulated
• II: microscopic capsular invasion or invasion into mediastinal fat or pleura
• III: invasion of pericardium, great vessels or lung
• IVA: pleural or pericardial implants
• IVB: lymphatic or hematogenous metastasis

Paraneoplastic syndromes are frequent: myasthenia gravis (30 to 50%), pure red cell aplasia (about 5%), hypogammaglobulinemia (Good syndrome, about 5%), and others (autoimmune encephalitis, lupus, thyroiditis). Five-year survival is over 95% for stage I and II, 70 to 80% for stage III and 40 to 70% for stage IV. Recurrence after resection is up to 5 to 30% and may occur after 10 years. Complications: superior vena cava syndrome, pleural spread (drop metastases), pericardial effusion and myasthenic crisis.

• Many tumors are incidental findings on chest imaging (30 to 40%)
• Cough, chest pain, dyspnea and dysphagia from local effect, with superior vena cava obstruction in invasive disease
• Myasthenia: ptosis, diplopia, bulbar weakness, fatigable limb weakness and respiratory weakness
• Pure red cell aplasia: pallor and fatigue
• Recurrent sinopulmonary infections in Good syndrome
• Red flags: myasthenic crisis, superior vena cava obstruction, hemoptysis and rapid enlargement

1. CT chest with intravenous contrast: a well-circumscribed anterior mediastinal mass, enhancing, with calcification or cystic change. Look for fat plane loss, pleural nodules and vessel invasion.
2. MRI for invasion into vessels or pericardium, and to separate cysts from solid tumors.
3. Biopsy: avoid in a resectable, encapsulated mass because of the risk of pleural seeding. Use core needle biopsy (or anterior mediastinotomy) for unresectable or doubtful tumors, since lymphoma and germ cell tumors need different treatment.
4. Serology and bloods: acetylcholine receptor antibodies (positive in about 85% of generalized myasthenia), full blood count with reticulocytes, immunoglobulin levels, AFP and beta-hCG (germ cell tumor), LDH, thyroid function.
5. Fluorodeoxyglucose PET-CT for staging in invasive disease. Pulmonary function tests for planning.

Differentials: lymphoma, germ cell tumor, thymic carcinoma, thymic hyperplasia, thymic cyst, substernal goiter, neurogenic tumor.

1. Optimize myasthenia before surgery: pyridostigmine 60 mg orally three to four times daily (maximum 360 mg a day), with prednisolone started at 10 to 20 mg daily and raised slowly. Severe or bulbar disease needs intravenous immunoglobulin 0.4 g/kg daily for 5 days or plasma exchange. Avoid drugs that worsen weakness (aminoglycosides, fluoroquinolones, magnesium, beta blockers).
2. Complete en bloc surgical resection (thymectomy with the surrounding fat and the tumor): median sternotomy for large or invasive tumors, or video-assisted or robotic surgery for stage I and II tumors under about 5 cm. Resect involved pericardium, pleura or lung, and implants where possible. Cefazolin 2 g IV before incision (3 g if over 120 kg), and enoxaparin 40 mg SC daily until mobile.
3. Adjuvant radiotherapy for stage III disease or positive margins: 45 to 50 Gy in 25 fractions after complete resection with risk features, 54 Gy for microscopic residual disease, and 60 to 66 Gy for gross residual disease.
4. Locally advanced unresectable disease: induction chemotherapy with cisplatin 50 mg/m2 day 1, doxorubicin 50 mg/m2 day 1 and cyclophosphamide 500 mg/m2 day 1 every 3 weeks for 3 to 4 cycles (or carboplatin AUC 6 with paclitaxel 225 mg/m2 every 3 weeks), then surgery or radiotherapy. Check echocardiogram, creatinine and blood count.
5. Recurrent or metastatic disease: re-resection of limited recurrence, chemotherapy, and octreotide 0.5 mg SC three times daily with prednisolone 0.6 mg/kg daily for octreotide-scan-positive tumors. Avoid immune checkpoint inhibitors in thymoma, which cause severe autoimmune toxicity.
6. Paraneoplastic disease:
   • Pure red cell aplasia: ciclosporin 5 mg/kg daily in 2 divided doses (trough 100 to 200 ng/mL) with prednisolone 1 mg/kg daily.
   • Good syndrome: immunoglobulin replacement 0.4 to 0.6 g/kg IV every 3 to 4 weeks, with infection treatment.

Follow-up: CT chest every 6 months for 2 years, then yearly for at least 10 years. Counsel on late recurrence and on monitoring for new autoimmune symptoms.