Note: Information on thymoma in children is available in the PDQ summary on Unusual Cancers of Chilhood.

Thymomas are epithelial tumors of the thymus, which may or may not be extensively infiltrated by nonneoplastic lymphocytes. The term, thymoma, is customarily used to describe neoplasms that show no overt atypia of the epithelial component. A thymic epithelial tumor that exhibits clear-cut cytologic atypia and histologic features no longer specific to the thymus is known as a thymic carcinoma (also known as type C thymoma).[1]

Invasive thymomas and thymic carcinomas are relatively rare tumors, which together represent about 0.2% to 1.5% of all malignancies.[2] Thymic carcinomas are rare and have been reported to account for only 0.06% of all thymic neoplasms.[3] In general, thymomas are indolent tumors with a tendency toward local recurrence rather than metastasis. Thymic carcinomas, however, are typically invasive, with a high risk of relapse and death.[4,5]

Most patients with thymoma or thymic carcinoma are aged 40 through 60 years.[6] The etiology of these types of tumors is not known. In about 50% of the patients, thymomas/thymic carcinomas are detected by chance with plain-film chest radiography.[6] Ninety percent occur in the anterior mediastinum.[7]

Approximately 30% of the patients with thymoma/thymic carcinoma are asymptomatic at the time of diagnosis.[6] In other cases, the presenting clinical signs of these types of tumors may include coughing, chest pain, and signs of upper airway congestion. Paraneoplastic autoimmune syndromes associated with thymoma include myasthenia gravis, polymyositis, lupus erythematosus, rheumatoid arthritis, thyroiditis, and Sjögren syndrome, among others.[6,8,9] Autoimmune pure red cell aplasia and hypogammaglobulinemia affect approximately 5% and 5% to 10%, respectively, of patients with thymoma.[7] Thymoma-associated autoimmune disease involves an alteration in circulating T-cell subsets.[10,11] 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.[12] In addition to T-cell defects, B-cell lymphopenia has been observed in thymoma-related immunodeficiency, with hypogammaglobulinemia (Good syndrome) and opportunistic infection.[13-15] In contrast to thymoma, the association of thymic carcinoma and autoimmune diseases is rare.[8,16]

In a large retrospective study, approximately 47% of thymoma cases (excluding thymic carcinoma) were found to be associated with myasthenia gravis.[17] Although the oncologic prognosis of thymoma is reported to be more favorable in patients with myasthenia gravis than in patients without myasthenia gravis,[7] treatment with thymectomy may not significantly improve the course of thymoma-associated myasthenia gravis.[18,19]

Thymoma and thymic carcinoma should be differentiated from a number of nonepithelial thymic neoplasms, including neuroendocrine tumors, germ cell tumors, lymphomas, stromal tumors, tumor-like lesions (such as true thymic hyperplasia), thymic cysts, metastatic tumors, and lung cancer.[1,20] Standard primary treatment for these types of tumors is surgical with en bloc resection for invasive tumors, if possible.[4,6,7,21] Depending on tumor stage, multimodality treatment includes the use of radiation therapy and chemotherapy with or without surgery.[6,22]

Thymoma has been associated with an increased risk for second malignancies, which appears to be unrelated to thymectomy, radiation therapy, or a clinical history of myasthenia gravis.[19,23,24] Because of this increased risk for second malignancies and the fact that thymoma can recur after a long interval, it has been recommended that surveillance should be lifelong.[19] The measurement of interferon-alpha and interleukin-2 antibodies is helpful to identify patients with a thymoma recurrence.[25]

Although the classification of thymomas remains a source of debate, some general guidelines for a more coherent classification have emerged. The World Health Organization pathologic classification of tumors of the thymus emphasizes the importance of independent evaluations of the degree of tumor invasiveness and the tumor histology.[1] Although some thymoma histologic types are more likely to be invasive and clinically aggressive, treatment outcome and the likelihood of recurrence appear to correlate more closely with the invasive/metastasizing properties of the tumor cells.[1,17] Therefore, some thymomas that appear to be relatively benign by histologic criteria may behave very aggressively. Independent evaluations of both the tumor invasiveness (using staging criteria) and tumor histology should be combined to predict the clinical behavior of a thymoma.

References

1. Rosai J: Histological Typing of Tumours of the Thymus. New York, NY: Springer-Verlag, 2nd ed., 1999. 
   
   
2. Fornasiero A, Daniele O, Ghiotto C, et al.: Chemotherapy of invasive thymoma. J Clin Oncol 8 (8): 1419-23, 1990.  [PUBMED Abstract]
   
   
3. Greene MA, Malias MA: Aggressive multimodality treatment of invasive thymic carcinoma. J Thorac Cardiovasc Surg 125 (2): 434-6, 2003.  [PUBMED Abstract]
   
   
4. Ogawa K, Toita T, Uno T, et al.: Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 94 (12): 3115-9, 2002.  [PUBMED Abstract]
   
   
5. Blumberg D, Burt ME, Bains MS, et al.: Thymic carcinoma: current staging does not predict prognosis. J Thorac Cardiovasc Surg 115 (2): 303-8; discussion 308-9, 1998.  [PUBMED Abstract]
   
   
6. Schmidt-Wolf IG, Rockstroh JK, Schüller H, et al.: Malignant thymoma: current status of classification and multimodality treatment. Ann Hematol 82 (2): 69-76, 2003.  [PUBMED Abstract]
   
   
7. Cameron RB, Loehrer PJ Sr, Thomas CR Jr: Neoplasms of the mediastinum. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds.: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2005, pp 845-58. 
   
   
8. Levy Y, Afek A, Sherer Y, et al.: Malignant thymoma associated with autoimmune diseases: a retrospective study and review of the literature. Semin Arthritis Rheum 28 (2): 73-9, 1998.  [PUBMED Abstract]
   
   
9. Thomas CR, Wright CD, Loehrer PJ: Thymoma: state of the art. J Clin Oncol 17 (7): 2280-9, 1999.  [PUBMED Abstract]
   
   
10. Hoffacker V, Schultz A, Tiesinga JJ, et al.: Thymomas alter the T-cell subset composition in the blood: a potential mechanism for thymoma-associated autoimmune disease. Blood 96 (12): 3872-9, 2000.  [PUBMED Abstract]
    
    
11. Buckley C, Douek D, Newsom-Davis J, et al.: Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis. Ann Neurol 50 (1): 64-72, 2001.  [PUBMED Abstract]
    
    
12. Ströbel P, Helmreich M, Menioudakis G, et al.: Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas. Blood 100 (1): 159-66, 2002.  [PUBMED Abstract]
    
    
13. Tarr PE, Sneller MC, Mechanic LJ, et al.: Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature. Medicine (Baltimore) 80 (2): 123-33, 2001.  [PUBMED Abstract]
    
    
14. Montella L, Masci AM, Merkabaoui G, et al.: B-cell lymphopenia and hypogammaglobulinemia in thymoma patients. Ann Hematol 82 (6): 343-7, 2003.  [PUBMED Abstract]
    
    
15. Cucchiara BL, Forman MS, McGarvey ML, et al.: Fatal subacute cytomegalovirus encephalitis associated with hypogammaglobulinemia and thymoma. Mayo Clin Proc 78 (2): 223-7, 2003.  [PUBMED Abstract]
    
    
16. Ritter JH, Wick MR: Primary carcinomas of the thymus gland. Semin Diagn Pathol 16 (1): 18-31, 1999.  [PUBMED Abstract]
    
    
17. Okumura M, Ohta M, Tateyama H, et al.: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 94 (3): 624-32, 2002.  [PUBMED Abstract]
    
    
18. Budde JM, Morris CD, Gal AA, et al.: Predictors of outcome in thymectomy for myasthenia gravis. Ann Thorac Surg 72 (1): 197-202, 2001.  [PUBMED Abstract]
    
    
19. Evoli A, Minisci C, Di Schino C, et al.: Thymoma in patients with MG: characteristics and long-term outcome. Neurology 59 (12): 1844-50, 2002.  [PUBMED Abstract]
    
    
20. Strollo DC, Rosado-de-Christenson ML: Tumors of the thymus. J Thorac Imaging 14 (3): 152-71, 1999.  [PUBMED Abstract]
    
    
21. Moore KH, McKenzie PR, Kennedy CW, et al.: Thymoma: trends over time. Ann Thorac Surg 72 (1): 203-7, 2001.  [PUBMED Abstract]
    
    
22. Ogawa K, Uno T, Toita T, et al.: Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients. Cancer 94 (5): 1405-13, 2002.  [PUBMED Abstract]
    
    
23. Pan CC, Chen PC, Wang LS, et al.: Thymoma is associated with an increased risk of second malignancy. Cancer 92 (9): 2406-11, 2001.  [PUBMED Abstract]
    
    
24. Engels EA, Pfeiffer RM: Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer 105 (4): 546-51, 2003.  [PUBMED Abstract]
    
    
25. Buckley C, Newsom-Davis J, Willcox N, et al.: Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence? Neurology 57 (9): 1579-82, 2001.  [PUBMED Abstract]
    
    

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