Showing posts with label THYMOMA. Show all posts
Showing posts with label THYMOMA. Show all posts

THYMOMA AND THYMIC CARCINOMA- CELLULAR CLASSIFICATION

Cellular Classification of Thymoma and Thymic Carcinomas




The following cellular classification of thymoma and thymic carcinoma is largely based on the classification scheme presented in a World Health Organization (WHO) monograph published in 1999.[1] Malignant thymoma is invasive disease (as defined either macroscopically or microscopically) that continues to retain typically "bland" cytologic characteristics. Thymomas are a mixture of epithelial cells and lymphocytes, often T-cells, and the malignant component is represented by the epithelial cells. Malignant cytologic characteristics are considered thymic carcinomas.
Both histologic classification of thymomas and stage may have independent prognostic significance.[2,3] A few series have reported the prognostic value of the WHO classifications. In large, retrospective analyses of 100 and of 178 thymoma cases, disease-free survivals at 10 years were 95% to 100% for type A, 90% to 100% for type AB, 83% to 85% for type B1, 71% to 83% for type B2, 36% to 40% for type B3, and 28% for type C.[4,5] In both series, stage and complete resection were significant independent prognostic factors. An analysis of 273 patients treated over a 44-year period found 20-year survival rates of 100%, 87%, 91%, 59%, and 36% for patients with type A, AB, B1, B2, and B3 tumors, respectively.[2]
Recurrent karyotype abnormalities have been documented in thymomas.[6] Type A thymomas have chromosome 6q deletions including the HLA locus and p21. Type B2 and B3 thymomas have additional chromosome 5q (adenomatous polyposis coli locus), 13q (retinoblastoma locus), and 17p (p53) deletions.[7] Amplifications in regions of chromosome 16 (cadherin-encoding gene) and chromosome 18 (bcl-2) have also been seen.[8] Gene expression profiling study has shown a correlation of expression of a number of genes including adhesion molecule cten, ets-1 oncogene and glycosylphosphatidyl inositol-anchored protein with thymoma stage.[9-11]
Thymoma
Thymoma is a thymic epithelial tumor in which the epithelial component exhibits no overt atypia and retains histologic features specific to the normal thymus.[1] Immature non-neoplastic lymphocytes are present in variable numbers depending on the histologic type of thymoma. The histologic types of thymoma are as follows:
·         Type A thymoma
Type A thymoma (also known as spindle cell thymoma and medullary thymoma) accounts for approximately 4% to 7% of all thymomas.[2,3] Approximately 17% of this type may be associated with myasthenia gravis.[2] Morphologically, the tumor is composed of neoplastic thymic epithelial cells that have a spindle/oval shape, lack nuclear atypia, and are accompanied by few, if any, nonneoplastic lymphocytes.[1] The appearance of this tumor can be confused with that of a mesenchymal neoplasm, but the immunohistochemical and ultrastructural features are clearly those of an epithelial neoplasm. Most type A thymomas are encapsulated. (Refer to the Stage Information for Thymoma and Thymic Carcinomas of this summary for more information). Some, however, may invade the capsule and, on rare occasion, may extend into the lung. Chromosome abnormalities, when present, may correlate with an aggressive clinical course.[12] The prognosis for this tumor type is excellent and have long-term survival rates (15 years or more) that are reported to be close to 100% in retrospective studies.[2,3]
·         Type AB thymoma
Type AB thymoma (also known as mixed thymoma) accounts for approximately 28% to 34% of all thymomas.[2,3] Approximately 16% of this type may be associated with myasthenia gravis.[2] Morphologically, type AB thymoma is a thymic tumor in which foci having the features of type A thymoma are admixed with foci rich in nonneoplastic lymphocytes.[1] The segregation of the different foci can be sharp or indistinct, and a wide range exists in the relative amount of the two components. The prognosis for this tumor type is good and have long-term survival rates (15 years ) that are recently reported to be approximately 90%.[2,3]
·         Type B1 thymoma
Type B1 thymoma (also known as lymphocyte-rich thymoma, lymphocytic thymoma, predominantly cortical thymoma, and organoid thymoma) accounts for approximately 9% to 20% of all thymomas and depends on the study cited.[2,3] Approximately 57% of cases may be associated with myasthenia gravis.[2] Morphologically, this tumor resembles the normal functional thymus because it contains large numbers of cells that have an appearance almost indistinguishable from normal thymic cortex with areas resembling thymic medulla.[1] The similarities between this tumor type and the normal active thymus are such that distinction between the two may be impossible on microscopic examination. The prognosis for this tumor type is good and has a long-term survival rate (20 years or more) of approximately 90%.[2,3]
·         Type B2 thymoma
Type B2 thymoma (also known as cortical thymoma and polygonal cell thymoma) accounts for approximately 20% to 36% of all thymomas and depends on the study cited.[2,3] Approximately 71% of cases may be associated with myasthenia gravis.[2] Morphologically, the neoplastic epithelial component of this tumor type appears as scattered plump cells with vesicular nuclei and distinct nucleoli among a heavy population of nonneoplastic lymphocytes.[1] Perivascular spaces are common and on occasion very prominent. A perivascular arrangement of tumor cells that results in a palisading effect may be seen. This type of thymoma resembles type B1 thymoma in its predominance of lymphocytes, but foci of medullary differentiation are less conspicuous or absent. Long-term survival is decidedly worse than for thymoma types A, AB, and B1. The 20-year survival rate (as defined by freedom-from-tumor death) for this thymoma type is approximately 60%.[2]
·         Type B3 thymoma
Type B3 thymoma (also known as epithelial thymoma, atypical thymoma, squamoid thymoma, and well-differentiated thymic carcinoma) accounts for approximately 10% to 14% of all thymomas. Approximately 46% of this type of tumor may be associated with myasthenia gravis.[2] Morphologically, this tumor type is predominantly composed of epithelial cells that have a round or polygonal shape and that exhibit no atypia or mild atypia.[1] The epithelial cells are admixed with a minor component of nonneoplastic lymphocytes, which results in a sheet-like growth of neoplastic epithelial cells. The 20-year survival rate (as defined by freedom-from-tumor death) for this thymoma type is approximately 40%.[2]
Thymic Carcinoma
Thymic carcinoma (also known as type C thymoma) is a thymic epithelial tumor that exhibits a definite cytologic atypia and a set of histologic features no longer specific to the thymus but rather similar to those histologic features observed in carcinomas of other organs.[1] In contrast to type A and B thymomas, thymic carcinomas lack immature lymphocytes. Any lymphocytes that are present are mature and usually admixed with plasma cells. Hypothetically, thymic carcinoma may arise from malignant transformation of a pre-existing thymoma.[13] This hypothetical evolution could account for the existence of thymic epithelial lesions that exhibit combined features of thymoma and thymic carcinoma within the same tumor.[14]
Thymic carcinomas are usually advanced when diagnosed and have a higher recurrence rate and worse survival compared with thymoma.[15,16] In a retrospective study of 40 patients with thymic carcinoma, the 5-year and 10-year actuarial overall survival rates were 38% and 28%, respectively.[15] In contrast to the thymomas, the association of thymic carcinoma and autoimmune disease is rare.[17]
Histologic subtypes of thymic carcinoma include the following:
·         Squamous cell (epidermoid) thymic carcinoma
This type of thymic carcinoma exhibits clear-cut cytologic atypia. In routinely stained sections, the keratinizing form exhibits equally clear-cut evidence of squamous differentiation in the form of intercellular bridges and/or squamous pearls, while the nonkeratinizing form lacks obvious signs of keratinization. Another subtype, basaloid carcinoma, is composed of compact lobules of tumor cells that exhibit peripheral palisading and an overall basophilic staining pattern caused by the high nucleocytoplasmic ratio and the absence of keratinization.
·         Lymphoepithelioma-like thymic carcinoma
This type of thymic carcinoma has morphologic features indistinguishable from those of lymphoepithelial carcinoma of the respiratory tract. The differential diagnosis with germ cell tumors, particularly seminomas, can be difficult but important for treatment.
·         Sarcomatoid thymic carcinoma (carcinosarcoma)
This is a type of thymic carcinoma in which part or all of the tumor resembles one of the types of soft tissue sarcoma.
·         Clear cell thymic carcinoma
This is a type of thymic carcinoma composed predominantly or exclusively of cells with optically clear cytoplasm.
·         Mucoepidermoid thymic carcinoma
This type of thymic carcinoma has an appearance similar to that of mucoepidermoid carcinoma of the major and minor salivary glands.
·         Papillary thymic adenocarcinoma
This type of thymic carcinoma grows in a papillary fashion. This histology may be accompanied by psammoma body formation, which may result in a marked similarity with papillary carcinoma of the thyroid gland.
·         Undifferentiated thymic carcinoma
This is a rare type of thymic carcinoma that grows in a solid undifferentiated fashion but without exhibiting sarcomatoid (spindle cell or pleomorphic) features.
Combined Thymoma
Combinations of the above histologic types can occur within the same tumor. For these cases, the term, combined thymoma, can be used, followed by a listing of the components and the relative amount of each component.[1]

References

1.     Rosai J: Histological Typing of Tumours of the Thymus. New York, NY: Springer-Verlag, 2nd ed., 1999.
2.     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]
3.     Chen G, Marx A, Wen-Hu C, et al.: New WHO histologic classification predicts prognosis of thymic epithelial tumors: a clinicopathologic study of 200 thymoma cases from China. Cancer 95 (2): 420-9, 2002. [PUBMED Abstract]
4.     Kondo K, Yoshizawa K, Tsuyuguchi M, et al.: WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 77 (4): 1183-8, 2004. [PUBMED Abstract]
5.     Rena O, Papalia E, Maggi G, et al.: World Health Organization histologic classification: an independent prognostic factor in resected thymomas. Lung Cancer 50 (1): 59-66, 2005. [PUBMED Abstract]
6.     Zettl A, Ströbel P, Wagner K, et al.: Recurrent genetic aberrations in thymoma and thymic carcinoma. Am J Pathol 157 (1): 257-66, 2000. [PUBMED Abstract]
7.     Inoue M, Starostik P, Zettl A, et al.: Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas. Cancer Res 63 (13): 3708-15, 2003. [PUBMED Abstract]
8.     Hirabayashi H, Fujii Y, Sakaguchi M, et al.: p16INK4, pRB, p53 and cyclin D1 expression and hypermethylation of CDKN2 gene in thymoma and thymic carcinoma. Int J Cancer 73 (5): 639-44, 1997. [PUBMED Abstract]
9.     Sasaki H, Kobayashi Y, Tanahashi M, et al.: Ets-1 gene expression in patients with thymoma. Jpn J Thorac Cardiovasc Surg 50 (12): 503-7, 2002. [PUBMED Abstract]
10.                       Sasaki H, Yukiue H, Kobayashi Y, et al.: Cten mRNA expression is correlated with tumor progression in thymoma. Tumour Biol 24 (5): 271-4, 2003 Sep-Oct. [PUBMED Abstract]
11.                       Sasaki H, Ide N, Sendo F, et al.: Glycosylphosphatidyl inositol-anchored protein (GPI-80) gene expression is correlated with human thymoma stage. Cancer Sci 94 (9): 809-13, 2003. [PUBMED Abstract]
12.                       Penzel R, Hoegel J, Schmitz W, et al.: Clusters of chromosomal imbalances in thymic epithelial tumours are associated with the WHO classification and the staging system according to Masaoka. Int J Cancer 105 (4): 494-8, 2003. [PUBMED Abstract]
13.                       Suster S, Moran CA: Thymic carcinoma: spectrum of differentiation and histologic types. Pathology 30 (2): 111-22, 1998. [PUBMED Abstract]
14.                       Suster S, Moran CA: Primary thymic epithelial neoplasms showing combined features of thymoma and thymic carcinoma. A clinicopathologic study of 22 cases. Am J Surg Pathol 20 (12): 1469-80, 1996. [PUBMED Abstract]
15.                       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]
16.                       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]
17.                       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]

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]