General Information About Thymoma and Thymic Carcinoma.

Thymoma and Thymic Carcinoma

Definition of thymoma: A tumor of the thymus, an organ that is part of the lymphatic system and is located in the chest, behind the breastbone. 

Definition of thymic carcinoma: A rare type of thymus gland cancer. It usually spreads, has a high risk of recurrence, and has a poor survival rate. Thymic carcinoma is divided into subtypes, depending on the types of cells in which the cancer began. Also called type C thymoma.

·         Disease Overview

·         Incidence and Mortality

o    Age at onset

o    Unique disease features

·         Anatomy

·         Histology

·         Pathology

·         Diagnostics

·         Prognosis and Survival

·         Follow-up

·         Related Summary

Disease Overview

Thymomas and thymic carcinomas are epithelial tumors of the thymus. 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]

Incidence and Mortality

Invasive thymomas and thymic carcinomas are relatively rare tumors, which together represent about 0.2% to 1.5% of all malignancies.[2] The overall incidence of thymoma is 0.15 cases per 100,000, based on data from the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Program.[3] Thymic carcinomas are rare and have been reported to account for only 0.06% of all thymic neoplasms.[4] In general, thymomas are indolent tumors with a tendency toward local recurrence rather than metastasis. Thymic carcinomas, however, are typically invasive, with a higher risk of relapse and death.[5,6]

Age at onset

Most patients with thymoma or thymic carcinoma are aged 40 through 60 years.[7]

Unique disease features

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.[7]

Anatomy

Ninety percent of thymomas and thymic carcinomas occur in the anterior mediastinum.[8] They are the most common malignancies of the anterior mediastinum.[9]

Histology

World Health Organization pathologic classification of tumors of the thymus and stage correlate with prognosis.[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.[1,10] 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.

Thymoma and thymic carcinoma should be differentiated from a number of nonepithelial thymic neoplasms, including the following:[1,11]

·         Neuroendocrine tumors.

·         Germ cell tumors.

·         Lymphomas.

·         Stromal tumors.

·         Tumor-like lesions (such as true thymic hyperplasia).

·         Thymic cysts.

·         Metastatic tumors.

·         Lung cancer.

Pathology

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.[14] 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]

Diagnostics

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.[7] Typical clinical symptoms and signs that are indicative of anterior mediastinal mass effects include the following:

·         Coughing.

·         Chest pain.

·         Signs of upper airway congestion.

Paraneoplastic autoimmune syndromes are associated with thymoma and are rarely associated with thymic carcinomas.[19-21]

·         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.[8]

Other autoimmune disorders associated with thymoma include the following:[7,15,24]

·         Acute pericarditis.

·         Addison disease.

·         Agranulocytosis.

·         Alopecia areata.

·         Cushing syndrome.

·         Hemolytic anemia.

·         Limbic encephalopathy.

·         Myocarditis.

·         Nephrotic syndrome.

·         Parahypopituitarism.

·         Pernicious anemia.

·         Aplastic anemia.

·         Polymyositis.

·         Rheumatoid arthritis.

·         Sarcoidosis.

·         Scleroderma.

·         Sensorimotor radiculopathy.

·         Sjögren syndrome.

·         Stiff-person syndrome.

·         Systemic lupus erythematosus.

·         Thyroiditis.

·         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.[25] Treatment with thymectomy may not significantly improve the course of thymoma-associated myasthenia gravis.[26,27]

Thymoma has been associated with an increased risk for second malignancies. In a review of the SEER database of thymoma cases in the United States between 1973 and 1998, 849 cases were identified (overall incidence 0.15 per 100,000 person-years).[3] In this study, there was an excess risk of non-Hodgkin lymphoma and soft tissue sarcomas.

Risk of second malignancy appears to be unrelated to any of the following:[3,27,28]

·         Thymectomy.

·         Radiation therapy.

·         A clinical history of myasthenia gravis.

Standard primary treatment for patients with these types of tumors is surgical resection with en bloc resection for invasive tumors, if possible.[5,7,8,29] Depending on tumor stage, there are multimodality treatment options, which include the use of radiation therapy and chemotherapy with or without surgery.[7,30]

Thymic carcinomas have a greater propensity to capsular invasion and metastases than thymomas. Patients more often present with advanced disease, with a 5-year survival of 30% to 50%.[31] Owing to the paucity of cases, optimal management of thymic carcinoma has yet to be defined. As with thymoma, primary treatment is surgical resection; however, multimodality treatment with surgery, radiation, and chemotherapy are often used because of the more advanced stage and greater risk of relapse.

Follow-up

Because of the 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.[27] The measurement of interferon-alpha and interleukin-2 antibodies is helpful to identify patients with a thymoma recurrence.[32]

Related Summary

Another PDQ summary containing information related to thymoma includes the following:

·         Unusual Cancers of Childhood (thymoma in children).

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.     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]

4.     Greene MA, Malias MA: Aggressive multimodality treatment of invasive thymic carcinoma. J Thorac Cardiovasc Surg 125 (2): 434-6, 2003. [PUBMED Abstract]

5.     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]

6.     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]

7.     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]

8.     Cameron RB, Loehrer PJ, Thomas CR Jr: Neoplasms of the mediastinum. In: DeVita VT Jr, Lawrence TS, Rosenberg SA: Cancer: Principles and Practice of Oncology. 9th ed. Philadelphia, Pa: Lippincott Williams & Wilkins, 2011, pp 871-81.

9.     Detterbeck FC, Parsons AM: Thymic tumors. Ann Thorac Surg 77 (5): 1860-9, 2004. [PUBMED Abstract]

10.                       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]

11.                       Strollo DC, Rosado-de-Christenson ML: Tumors of the thymus. J Thorac Imaging 14 (3): 152-71, 1999. [PUBMED Abstract]

12.                       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]

13.                       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]

14.                       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]

15.                       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]

16.                       Ritter JH, Wick MR: Primary carcinomas of the thymus gland. Semin Diagn Pathol 16 (1): 18-31, 1999. [PUBMED Abstract]

17.                       Voltz RD, Albrich WC, Nägele A, et al.: Paraneoplastic myasthenia gravis: detection of anti-MGT30 (titin) antibodies predicts thymic epithelial tumor. Neurology 49 (5): 1454-7, 1997. [PUBMED Abstract]

18.                       Gautel M, Lakey A, Barlow DP, et al.: Titin antibodies in myasthenia gravis: identification of a major immunogenic region of titin. Neurology 43 (8): 1581-5, 1993. [PUBMED Abstract]

19.                       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]

20.                       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]

21.                       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]

22.                       Morgenthaler TI, Brown LR, Colby TV, et al.: Thymoma. Mayo Clin Proc 68 (11): 1110-23, 1993. [PUBMED Abstract]

23.                       Souadjian JV, Enriquez P, Silverstein MN, et al.: The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch Intern Med 134 (2): 374-9, 1974. [PUBMED Abstract]

24.                       Thomas CR, Wright CD, Loehrer PJ: Thymoma: state of the art. J Clin Oncol 17 (7): 2280-9, 1999. [PUBMED Abstract]

25.                       Kondo K, Monden Y: Thymoma and myasthenia gravis: a clinical study of 1,089 patients from Japan. Ann Thorac Surg 79 (1): 219-24, 2005. [PUBMED Abstract]

26.                       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]

27.                       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]

28.                       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]

29.                       Moore KH, McKenzie PR, Kennedy CW, et al.: Thymoma: trends over time. Ann Thorac Surg 72 (1): 203-7, 2001. [PUBMED Abstract]

30.                       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]

31.                       Eng TY, Fuller CD, Jagirdar J, et al.: Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys 59 (3): 654-64, 2004. [PUBMED Abstract]

32.                       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]