What is the recommended management for an adult aged 40‑60 years with thymoma, especially if associated with myasthenia gravis, including surgical resection, radiotherapy, and chemotherapy according to disease stage?

Management of Thymoma in Adults Aged 40-60 Years

Complete surgical resection via open median sternotomy with total thymectomy is the cornerstone of treatment for all resectable thymomas, with adjuvant radiotherapy and chemotherapy determined by disease stage and completeness of resection. 1

Pre-Operative Evaluation

All patients with suspected thymoma must have serum anti-acetylcholine receptor antibody levels measured preoperatively, even if asymptomatic for myasthenia gravis, to prevent potentially fatal respiratory failure during anesthesia. 2, 3

• Obtain contrast-enhanced CT chest to evaluate tumor extent, mediastinal invasion, and pleural involvement 2, 3
• Perform complete blood count, serum protein electrophoresis, and anti-nuclear antibodies as part of immunological workup 3
• If myasthenia gravis is detected, mandatory neurologist consultation and medical optimization before surgery to prevent perioperative respiratory complications 3
• Avoid surgical biopsy if resectable thymoma is suspected on imaging, as small biopsies cannot determine invasion status and transpleural approaches risk pleural seeding 3

Stage-Specific Treatment Algorithm

Stage I (Encapsulated, Non-Invasive)

• Complete resection of entire thymus without neoadjuvant or adjuvant therapy 1
• Surgery alone achieves 10-year survival of approximately 90% 3

Stage II (Microscopic Capsular Invasion)

• Complete resection of entire thymus with consideration of adjuvant radiation (50-55 Gy) for high-risk tumors 1
• 10-year survival approximately 70% with complete resection 3

Stage III (Macroscopic Invasion to Adjacent Structures)

Stage IIIA (Resectable):

• Surgery initially or after neoadjuvant chemotherapy, followed by adjuvant radiotherapy at minimum 55 Gy 1
• Consider neoadjuvant cisplatin-based chemotherapy for advanced disease to increase resectability 4

Stage IIIB (Bulky/Borderline Resectable):

• Combination chemotherapy, radiation, and/or surgery 1
• For bulky tumors, sequential chemotherapy followed by radiation, then surgical re-evaluation 1
• If technically possible, surgery with concurrent cisplatin-based chemoradiotherapy 1
• Incomplete resection requires postoperative radiotherapy at 55-60 Gy with boost to residual tumor marked by operative clips 1

Stage IVA (Pleural/Pericardial Metastases)

• Neoadjuvant chemotherapy followed by surgery and radiotherapy if metastases can be completely resected 1
• If completely resected, postoperative radiotherapy to mediastinum and pleura at 55 Gy 1
• Incomplete resection: chemotherapy then surgical re-evaluation and/or subsequent radiotherapy 1

Stage IVB (Distant Metastases)

• Treatment individualized on case-by-case basis with no generic recommendations 1
• Chemotherapy with surgical re-evaluation if response achieved 1

Surgical Technique

• Perform total thymectomy via open median sternotomy, removing entire thymus from phrenic nerve to phrenic nerve laterally and from diaphragm to thyroid gland superiorly 4
• Achieve complete (R0) resection whenever technically feasible, as completeness predicts outcomes 4
• Avoid bilateral phrenic nerve resection due to severe respiratory morbidity 3
• Surgery should be performed by board-certified thoracic surgeons with multidisciplinary team evaluation for locally advanced cases 3

Radiation Therapy Specifications

• Adjuvant radiation doses: 45-70 Gy to primary tumor bed for incomplete resection or advanced stage 4
• Limit total cardiac dose to ≤30 Gy given younger patient age and long survival expectations 4
• Stage II high-risk tumors: 50-55 Gy 1
• Stage III complete resection: minimum 55 Gy 1
• Stage III incomplete resection: 55-60 Gy with boost to residual disease 1

Chemotherapy Regimens

• Cisplatin-based polychemotherapy is superior to monotherapy 1
• Indicated for metastatic disease, local recurrence after radiotherapy, and neoadjuvant treatment for advanced stages 1
• Consider adjuvant chemotherapy with cisplatin-based regimens for Stage III/IVA disease with incomplete resection 4

Special Considerations for Myasthenia Gravis

• 30-50% of thymoma patients have myasthenia gravis, and approximately 20% of mortality in these patients is directly attributable to myasthenia gravis rather than tumor 2, 3
• Complete thymectomy is mandatory as both oncological necessity and may substantially reduce myasthenia gravis symptoms 3
• However, thymectomy alone is insufficient to resolve paraneoplastic syndromes like pure red cell aplasia in the vast majority of cases; immediate cyclosporine therapy should follow surgery 4

Recurrent Disease

• Consider surgery, radiation, and/or chemoradiation 1
• Chemoradiation should be considered in all medically inoperable and technically inoperable patients 1

Long-Term Surveillance

• Perform chest CT with contrast every 6 months for 2 years, then annually until at least 10 years to monitor for recurrence 4, 2
• Surveillance must continue for at least 15 years given possibility of very late relapses 1
• Appearance of signs/symptoms of autoimmune syndrome, particularly myasthenia gravis, should prompt early search for recurrence 1

Critical Pitfalls to Avoid

• Never proceed to surgery without checking anti-acetylcholine receptor antibodies, even in asymptomatic patients, due to risk of subclinical myasthenia gravis 3
• Avoid transpleural biopsy if thymoma suspected, as this violates oncologic principles and risks pleural seeding 3, 5
• Do not assume benign disease simply because patient is asymptomatic; thymomas often have indolent presentation 3
• Avoid bilateral phrenic nerve resection during surgery 3