General Thoracic and Cardiovascular Surgery

, Volume 56, Issue 1, pp 10–16 | Cite as

Clinical and pathological aspects of thymic epithelial tumors

  • Meinoshin Okumura
  • Hiroyuki Shiono
  • Masato Minami
  • Masayoshi Inoue
  • Tomoki Utsumi
  • Yoshihisa Kadota
  • Yoshiki Sawa
Current Topics Review Article


A histological classification of thymic epithelial tumors was presented by the World Health Organization (WHO) in 1999 and again in 2004 following slight modifications, in which thymic epithelial tumors were categorized as thymomas and thymic carcinomas. Whereas thymoma is defined as an organotypic (thymuslike) tumor, thymic carcinoma is a malignant epithelial neoplasm with a morphology similar to that of malignant neoplasms arising from other organs. Herein, the recent progress in research of thymic epithelial tumors is reviewed with reference to the WHO histological classification system, with the focus on thymomas. Thymomas are classified into five types—A, AB, B1, B2, B3—according to the shape and atypia of their epithelial cells as well as the abundance of lymphocytes. The invasiveness, prognosis, and genetic imbalance of thymomas have been shown to be related to this classification system. Myasthenia gravis is frequently associated with types B1 and B2. The WHO histological classification of thymomas is not only useful for treatment but reflects their biological characteristics, including genetic alterations. Advances are expected in future studies of thymomas from the standpoint of their clinical, pathological, and biological aspects.

Key words

Thymoma Thymic carcinoma World Health Organization (WHO) histological classification Myasthenia gravis Paraneoplastic autoimmunity 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Rosai J, Levine GD. Tumors of the thymus. In: Atlas of tumor pathology. 2nd series, Fascicle 13. Washington, DC: Armed Forces Institute of Pathology; 1976.Google Scholar
  2. 2.
    Shimosato Y, Mukai K. Tumors of the mediastinum. In: Atlas of tumor pathology, 3rd series, Fascicle 21. Washington, DC: Armed Forces Institute of Pathology; 1997.Google Scholar
  3. 3.
    Rosai J, Sobin LH. Histological typing of tumours of the thymus. In: International histological classification of tumours, 2nd edition. Berlin: Springer; 1999.Google Scholar
  4. 4.
    Detterbeck FC. Clinical value of the WHO classification system of thymoma. Ann Thorac Surg 2006;81:2328–2334.PubMedCrossRefGoogle Scholar
  5. 5.
    World Health Organization Classification of Tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. Lyon: International Agency for Research on Cancer (IARC) Press; 2004.Google Scholar
  6. 6.
    Suster S, Moran CA. Micronodular thymoma with lymphoid B-cell hyperplasia: clinicopathologic and immunohistochemical study of eighteen cases of a distinctive morphologic variant of thymic epithelial neoplasm. Am J Surg Pathol 1999;23:955–962.PubMedCrossRefGoogle Scholar
  7. 7.
    Tateyama H, Saito Y, Fujii Y, Okumura M, Nakamura K, Tada H, et al. The spectrum of micronodular thymic epithelial tumours with lymphoid B-cell hyperplasia. Histopathology 2001;38:519–527.PubMedCrossRefGoogle Scholar
  8. 8.
    Suster S, Moran CA, Chan JK. Thymoma with pseudosarcomatous stroma: report of an unusual histologic variant of thymic epithelial neoplasm that may simulate carcinosarcoma. Am J Surg Pathol 1997;21:1316–1323.PubMedCrossRefGoogle Scholar
  9. 9.
    Yoneda S, Marx A, Heimann S, Shirakusa T, Kikuchi M, Müller-Hermelink HK. Low-grade metaplastic carcinoma of the thymus. Histopathology 1999;35:19–30.PubMedCrossRefGoogle Scholar
  10. 10.
    Kuo T. Sclerosing thymoma—a possible phenomenon of regression. Histopathology 1994;25:289–291.PubMedCrossRefGoogle Scholar
  11. 11.
    Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48:2485–2492.PubMedCrossRefGoogle Scholar
  12. 12.
    Okumura M, Ohta M, Tateyama H, Nakagawa K, Matsumura A, Maeda H, et al. The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer 2002;94:624–632.PubMedCrossRefGoogle Scholar
  13. 13.
    Nakahara K, Ohno K, Hashimoto J, Maeda H, Miyoshi S, Sakurai M, et al. Thymoma: results with complete resection and adjuvant postoperative irradiation in 141 consecutive patients. J Thorac Cardiovasc Surg 1988;95:1041–1047.PubMedGoogle Scholar
  14. 14.
    Regnard J-F, Magdeleinat P, Dromer C, Dulmet E, De Montpreville V, Levi J-F, et al. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg 1996;112:376–384.PubMedCrossRefGoogle Scholar
  15. 15.
    Maggi G, Casadio C, Cavallo A, Cianci R, Molinatti M, Ruffini E. Thymoma: results of 241 operated cases. Ann Thorac Surg 1991;51:152–156.PubMedCrossRefGoogle Scholar
  16. 16.
    Wilkins KB, Sheikh E, Green R, Patel M, George S, Takano M, et al. Clinical and pathologic predictors of survival in patients with thymoma. Ann Surg 1999;230:562–574.PubMedCrossRefGoogle Scholar
  17. 17.
    Wilkins EW Jr, Edmunds LH, Castleman B. Cases of thymoma at the Massachusetts General Hospital. J Thorac Cardiovasc Surg 1966;52:322–330.PubMedGoogle Scholar
  18. 18.
    Monden Y, Nakahara K, Kagotani K, Fujii Y, Masaoka A, Kawashima Y. Myasthenia gravis with thymoma: analysis of and postoperative prognosis for 65 patients with thymomatous myasthenia gravis. Ann Thorac Surg 1984;38:46–52.PubMedCrossRefGoogle Scholar
  19. 19.
    Wilkins EW Jr, Grillo HC, Scannell JG, Moncure AC, Mathisen DJ. Role of staging in prognosis and management of thymoma. Ann Thorac Surg 1991;51:888–892.PubMedCrossRefGoogle Scholar
  20. 20.
    Blumberg D, Port JL, Weksler B, Delgado R, Rosai J, Bains MS, et al. Thymoma: a multivariate analysis of factors predicting survival. Ann Thorac Surg 1995;60:908–914.PubMedCrossRefGoogle Scholar
  21. 21.
    Okumura M, Miyoshi S, Takeuchi Y, Yoon H-E, Minami M, Takeda S, et al. Results of surgical treatment of thymomas with special reference to the involved organs. J Thorac Cardiovasc Surg 1999;117:605–613.PubMedGoogle Scholar
  22. 22.
    Quintanilla-Martinez L, Wilkins EW Jr, Choi N, Efird J, Hug E, Harris NL. Thymoma: histologic subclassification is an independent prognostic factor. Cancer 1994;74:606–617.PubMedCrossRefGoogle Scholar
  23. 23.
    Okumura M, Miyoshi S, Fujii Y, Takeuchi Y, Shiono H, Inoue M, et al. Clinical and functional significance of WHO classification on human thymic epithelial neoplasms: a study of 146 consecutive tumors. Am J Surg Pathol 2001;25:103–110.PubMedCrossRefGoogle Scholar
  24. 24.
    Chen G, Marx A, Wen-Hu C, Yong J, Puppe B, Stroebel P, et al. New WHO histological classification predicts prognosis of thymic epithelial tumors: a clinicopathological study of 200 thymoma cases from China. Cancer 2002;95:420–429.PubMedCrossRefGoogle Scholar
  25. 25.
    Nakagawa K, Asamura H, Matsuno Y, Suzuki K, Kondo H, Maeshima A, et al. Thymoma: a clinicopathologic study based on the new World Health Organization classification. J Thorac Cardiovasc Surg 2003;126:1134–1140.PubMedCrossRefGoogle Scholar
  26. 26.
    Kondo K, Yoshizawa K, Tsuyuguchi M, Kimura S, Sumitomo M, Morita J, et al. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 2004;77:1183–1188.PubMedCrossRefGoogle Scholar
  27. 27.
    Park MS, Chung KY, Kim KD, Yang WI, Chung JH, Kim YS, et al. Prognosis of thymic epithelial tumors according to the new World Health Organization histologic classification. Ann Thorac Surg 2004;78:992–997.PubMedCrossRefGoogle Scholar
  28. 28.
    Kim DJ, Yang WI, Choi SS, Kim KD, Chung KY. Prognostic and clinical relevance of the World Health Organization schema for the classification of thymic epithelial tumors: a clinicopathologic study of 108 patients and literature review. Chest 2005;127:755–761.PubMedCrossRefGoogle Scholar
  29. 29.
    Okumura M, Shiono H, Inoue M, Tanaka H, Yoon H-E, Nakagawa K, et al. Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to World Health Organization histologic classification system. J Surg Oncol 2007;95:40–44.PubMedCrossRefGoogle Scholar
  30. 30.
    Suster S, Moran CA. Thymoma classification: the ride of the Valkyries? Am J Clin Pathol 1999;112:308–310.PubMedGoogle Scholar
  31. 31.
    Tomiyama N, Johkoh, T, Mihara N, Honda O, Kozuka T, Koyama M, et al. Using the World Health Organization classification of thymic epithelial neoplasms to describe CT findings. AJR Am J Roentgenol 2002;179:881–886.PubMedGoogle Scholar
  32. 32.
    Zettl A, Strobel P, Wagner K, Katzenberger T, Ott G, Rosenwald A, et al. Recurrent genetic aberrations in thymoma and thymic carcinoma. Am J Pathol 2000;157:257–266.PubMedGoogle Scholar
  33. 33.
    Inoue M, Starostik P, Zettl A, Strobel P, Schwarz S, Scaravilli F, et al. Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas. Cancer Res 2003;63:3708–3715.PubMedGoogle Scholar
  34. 34.
    Penzel R, Hoegel J, Schmitz W, Blaeker H, Morresi-Hauf A, Aulmann S, 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 2003;105:494–498.PubMedCrossRefGoogle Scholar
  35. 35.
    Ionescu DN, Sasatomi E, Cieply K, Nola M, Dacic S. Protein expression and gene amplification of epidermal growth factor receptor in thymomas. Cancer 2005;103:630–636.PubMedCrossRefGoogle Scholar
  36. 36.
    Sogawa K, Kondo K, Fujino H, Takahashi Y, Miyoshi T, Sakiyama S, et al. Increased expression of matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 is correlated with poor prognostic variables in patients with thymic epithelial tumors. Cancer 2003;98:1822–1829.PubMedCrossRefGoogle Scholar
  37. 37.
    Yukiue H, Sasaki H, Kobayashi Y, Nakashima Y, Moriyama S, Yano M, et al. Clinical significance of tissue inhibitor of metalloproteinase and matrix metalloproteinase mRNA expression in thymoma. J Surg Res 2003;109:86–91.PubMedCrossRefGoogle Scholar
  38. 38.
    Sasaki H, Ide N, Fukai I, Kiriyama M, Yamakawa Y, Fujii Y. Gene expression analysis of human thymoma correlates with tumor stage. Int J Cancer 2002;101:342–347.PubMedCrossRefGoogle Scholar

Copyright information

© The Japanese Association for Thoracic Surgery 2008

Authors and Affiliations

  • Meinoshin Okumura
    • 1
  • Hiroyuki Shiono
    • 1
  • Masato Minami
    • 1
  • Masayoshi Inoue
    • 1
  • Tomoki Utsumi
    • 1
  • Yoshihisa Kadota
    • 1
  • Yoshiki Sawa
    • 2
  1. 1.Department of General Thoracic Surgery (L5)Osaka University Graduate School of MedicineOsakaJapan
  2. 2.Department of Cardiovascular SurgeryOsaka University Graduate School of MedicineOsakaJapan

Personalised recommendations