Thymoma-associated autoimmune disease involves an alteration in circulating T-cell subsets.[12,13] The primary T-cell abnormality appears to be related to the acquisition of the CD45RA+ phenotype on naive CD4+ T cells during terminal intratumorous thymopoiesis, followed by export of these activated CD4+ T cells into the circulation. In addition to T-cell defects, B-cell lymphopenia has been observed in thymoma-related immunodeficiency, with hypogammaglobulinemia (Good syndrome) and opportunistic infection.[15,16] Patients with thymoma-associated myasthenia gravis can produce autoantibodies to a variety of neuromuscular antigens, particularly the acetylcholine receptor and titin, a striated muscle antigen.[17,18]
Approximately 50% of thymomas are diagnosed when they are localized within a capsule and do not infiltrate.
At the time of diagnosis, the majority of patients with thymoma or thymic carcinoma are asymptomatic. Typical clinical symptoms and signs that are indicative of anterior mediastinal mass effects include the following:
- Chest pain.
- Signs of upper airway congestion.
Paraneoplastic autoimmune syndromes are associated with thymoma and are rarely associated with thymic carcinomas.[19,20,21]
- Myasthenia gravis is the most common autoimmune disease associated with thymoma. Approximately 30% to 65% of patients with thymoma have been diagnosed with myasthenia gravis in reported series.[22,23]
- Autoimmune pure red cell aplasia and hypogammaglobulinemia are the next most common paraneoplastic syndromes after myasthenia gravis, and affect approximately 5% and 5% to 10%, respectively, of patients with thymoma.
Other autoimmune disorders associated with thymoma include the following:[7,15,24]
- Acute pericarditis.
- Addison disease.
- Alopecia areata.
- Cushing syndrome.
- Hemolytic anemia.
- Limbic encephalopathy.
- Nephrotic syndrome.
- Pernicious anemia.
- Aplastic anemia.
- Rheumatoid arthritis.
- Sensorimotor radiculopathy.
- Sjögren syndrome.
- Stiff-person syndrome.
- Systemic lupus erythematosus.
- Ulcerative colitis.
Prognosis and Survival
Although the oncologic prognosis of thymoma is reported to be more favorable in patients with myasthenia gravis than in patients without myasthenia gravis,[8,25] data are conflicting as to whether the presence of myasthenia gravis is an independent predictor of better outcome. Patients with myasthenia gravis are diagnosed with earlier stage disease and more often undergo complete surgical resection. Treatment with thymectomy may not significantly improve the course of thymoma-associated myasthenia gravis.[26,27]