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Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Clinicopathological analysis of thymic malignancies with a consistent retrospective database in a single institution: from Tokyo Metropolitan Cancer Center

Authors: Yusuke Okuma, Yukio Hosomi, Kageaki Watanabe, Yuko Yamada, Hirotoshi Horio, Yoshiharu Maeda, Tatsuru Okamura, Tsunekazu Hishima

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

Thymic epithelial tumors (TETs), which comprise thymoma and thymic carcinoma, are rare cancers with specific morphological and clinical features. Their clinical characteristics and outcomes have gradually been clarified by assessing large-scale, retrospective data obtained with international cooperation.

Methods

The study is a retrospective review of 187 Japanese patients with TETs who attended our institution from 1976 to 2012. Relevant clinical features of patients with TETs and their tumors, including histology, staging, treatment strategies, and overall survival, were investigated. Differences in survival were assessed by the Kaplan–Meier method and uni- and multi-variate Cox proportional hazards regression analyses.

Results

The 187 patients included 52 patients with stage I, 37 with stage II, 22 with stage III, and 76 with stage IVa/IVb tumors according to the Masaoka–Koga Staging System. As to histological type, five patients had type A, 33 type AB, 19 type B1, 39 type B2, and 15 type B3 thymomas, whereas 68 patients had thymic carcinoma, including 11 with neuroendocrine carcinomas according to the 2004 WHO classification. Either insufficient data were available to classify the tumors of the remaining eight patients or they had rare types. Immunological abnormalities were present in 26 patients, most of whom had thymomas (21.8% of the thymoma group). Most of the patients who presented with symptoms had myasthenia gravis or extensive thymic carcinoma. Secondary cancers were present in 25 patients (13.3%). The overall 5- and 10-year survival rates for thymoma were 85.4 and 71.5%, respectively, and those for thymic carcinoma were 33.8 and 2.3%, respectively. OS differed significantly between stage IVa thymomas and thymic carcinomas. The stage and whether the tumors were thymomas or thymic carcinomas were significant determinants of survival according to multivariate analysis.

Conclusion

The efficacy of treatments for thymoma and thymic carcinoma should be investigated separately because these tumors differ in their clinical features and prognosis.
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Literature
1.
go back to reference Engels EA, Pfeiffer RM: Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003, 105 (4): 546-551. 10.1002/ijc.11099.CrossRefPubMed Engels EA, Pfeiffer RM: Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003, 105 (4): 546-551. 10.1002/ijc.11099.CrossRefPubMed
2.
go back to reference de Jong WK, Blaauwgeers JL, Schaapveld M, Timens W, Klinkenberg TJ, Groen HJ: Thymic epithelial tumours: a population-based study of the incidence, diagnostic procedures and therapy. Eur J Cancer. 2008, 44 (1): 123-130. 10.1016/j.ejca.2007.11.004.CrossRefPubMed de Jong WK, Blaauwgeers JL, Schaapveld M, Timens W, Klinkenberg TJ, Groen HJ: Thymic epithelial tumours: a population-based study of the incidence, diagnostic procedures and therapy. Eur J Cancer. 2008, 44 (1): 123-130. 10.1016/j.ejca.2007.11.004.CrossRefPubMed
4.
go back to reference Huang J, Detterbeck FC, Wang Z, Loehrer PJ: Standard outcome measures for thymic malignancies. J Thorac Oncol. 2010, 5 (12): 2017-2023. 10.1097/JTO.0b013e3181f13682.CrossRefPubMed Huang J, Detterbeck FC, Wang Z, Loehrer PJ: Standard outcome measures for thymic malignancies. J Thorac Oncol. 2010, 5 (12): 2017-2023. 10.1097/JTO.0b013e3181f13682.CrossRefPubMed
7.
go back to reference Travis W, Brambilla W, Müller-Hermelink H, Harris C: Chapter 3. Tumours of the Thymus. World Health Organization classification of tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. 2004, Lyon: IARC press, 3 Travis W, Brambilla W, Müller-Hermelink H, Harris C: Chapter 3. Tumours of the Thymus. World Health Organization classification of tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. 2004, Lyon: IARC press, 3
8.
go back to reference Ettinger DS, Riely GJ, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, D’Amico TA, Demmy TL, Govindan R, Grannis FW, Grant SC, Horn L, Jahan TM, Komaki R, Kong FM, Kris MG, Krug LM, Lackner RP, Lennes IT, Loo BW, Martins R, Otterson GA, Patel JD, Pinder-Schenck MC, Pisters KM, Reckamp K, Rohren E, Shapiro TA, Swanson SJ: Thymomas and thymic carcinomas: clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2013, 11 (5): 562-576.PubMed Ettinger DS, Riely GJ, Akerley W, Borghaei H, Chang AC, Cheney RT, Chirieac LR, D’Amico TA, Demmy TL, Govindan R, Grannis FW, Grant SC, Horn L, Jahan TM, Komaki R, Kong FM, Kris MG, Krug LM, Lackner RP, Lennes IT, Loo BW, Martins R, Otterson GA, Patel JD, Pinder-Schenck MC, Pisters KM, Reckamp K, Rohren E, Shapiro TA, Swanson SJ: Thymomas and thymic carcinomas: clinical practice guidelines in oncology. J Natl Compr Canc Netw. 2013, 11 (5): 562-576.PubMed
9.
go back to reference Muller-Hermelink HK, Marino M, Palestro G: Pathology of thymic epithelial tumors. Curr Top Pathol. 1986, 75: 207-268. 10.1007/978-3-642-82480-7_7.CrossRefPubMed Muller-Hermelink HK, Marino M, Palestro G: Pathology of thymic epithelial tumors. Curr Top Pathol. 1986, 75: 207-268. 10.1007/978-3-642-82480-7_7.CrossRefPubMed
10.
go back to reference Rosai J, Sobin L: Histological Typing of Tumors of the Thymus. WHO International Histological Classification of Tumours. 1999, Berlin, Heidelberg: Springer-Verlag, 2 Rosai J, Sobin L: Histological Typing of Tumors of the Thymus. WHO International Histological Classification of Tumours. 1999, Berlin, Heidelberg: Springer-Verlag, 2
11.
go back to reference Okumura M, Ohta M, Tateyama H, Nakagawa K, Matsumura A, Maeda H, Tada H, Eimoto T, Matsuda H, Masaoka A: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer. 2002, 94 (3): 624-632. 10.1002/cncr.10226.CrossRefPubMed Okumura M, Ohta M, Tateyama H, Nakagawa K, Matsumura A, Maeda H, Tada H, Eimoto T, Matsuda H, Masaoka A: The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients. Cancer. 2002, 94 (3): 624-632. 10.1002/cncr.10226.CrossRefPubMed
12.
go back to reference Kondo K, Yoshizawa K, Tsuyuguchi M, Kimura S, Sumitomo M, Morita J, Miyoshi T, Sakiyama S, Mukai K, Monden Y: WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg. 2004, 77 (4): 1183-1188. 10.1016/j.athoracsur.2003.07.042.CrossRefPubMed Kondo K, Yoshizawa K, Tsuyuguchi M, Kimura S, Sumitomo M, Morita J, Miyoshi T, Sakiyama S, Mukai K, Monden Y: WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg. 2004, 77 (4): 1183-1188. 10.1016/j.athoracsur.2003.07.042.CrossRefPubMed
13.
go back to reference Rea F, Marulli G, Girardi R, Bortolotti L, Favaretto A, Galligioni A, Sartori F: Long-term survival and prognostic factors in thymic epithelial tumours. Eur J Cardiothorac Surg. 2004, 26 (2): 412-418. 10.1016/j.ejcts.2004.04.041.CrossRefPubMed Rea F, Marulli G, Girardi R, Bortolotti L, Favaretto A, Galligioni A, Sartori F: Long-term survival and prognostic factors in thymic epithelial tumours. Eur J Cardiothorac Surg. 2004, 26 (2): 412-418. 10.1016/j.ejcts.2004.04.041.CrossRefPubMed
14.
go back to reference Rieker RJ, Hoegel J, Morresi-Hauf A, Hofmann WJ, Blaeker H, Penzel R, Otto HF: Histologic classification of thymic epithelial tumors: comparison of established classification schemes. Int J Cancer. 2002, 98 (6): 900-906. 10.1002/ijc.10255.CrossRefPubMed Rieker RJ, Hoegel J, Morresi-Hauf A, Hofmann WJ, Blaeker H, Penzel R, Otto HF: Histologic classification of thymic epithelial tumors: comparison of established classification schemes. Int J Cancer. 2002, 98 (6): 900-906. 10.1002/ijc.10255.CrossRefPubMed
15.
go back to reference Suster S, Moran CA: Problem areas and inconsistencies in the WHO classification of thymoma. Semin Diagn Pathol. 2005, 22 (3): 188-197. 10.1053/j.semdp.2006.02.004.CrossRefPubMed Suster S, Moran CA: Problem areas and inconsistencies in the WHO classification of thymoma. Semin Diagn Pathol. 2005, 22 (3): 188-197. 10.1053/j.semdp.2006.02.004.CrossRefPubMed
16.
go back to reference Suster S, Moran CA: Thymoma classification: current status and future trends. Am J Clin Pathol. 2006, 125 (4): 542-554. 10.1309/CAV8-RNU5-TKNA-CKNC.CrossRefPubMed Suster S, Moran CA: Thymoma classification: current status and future trends. Am J Clin Pathol. 2006, 125 (4): 542-554. 10.1309/CAV8-RNU5-TKNA-CKNC.CrossRefPubMed
17.
go back to reference Detterbeck FC, Parsons AM: Thymic tumors. Ann Thorac Surg. 2004, 77 (5): 1860-1869. 10.1016/j.athoracsur.2003.10.001.CrossRefPubMed Detterbeck FC, Parsons AM: Thymic tumors. Ann Thorac Surg. 2004, 77 (5): 1860-1869. 10.1016/j.athoracsur.2003.10.001.CrossRefPubMed
18.
go back to reference Thomas CR, Wright CD, Loehrer PJ: Thymoma: state of the art. J Clin Oncol. 1999, 17 (7): 2280-2289.PubMed Thomas CR, Wright CD, Loehrer PJ: Thymoma: state of the art. J Clin Oncol. 1999, 17 (7): 2280-2289.PubMed
19.
go back to reference Petrini I, Zucali PA, Lee HS, Pineda MA, Meltzer PS, Walter-Rodriguez B, Roncalli M, Santoro A, Wang Y, Giaccone G: Expression and mutational status of c-kit in thymic epithelial tumors. J Thorac Oncol. 2010, 5 (9): 1447-1453. 10.1097/JTO.0b013e3181e96e30.CrossRefPubMed Petrini I, Zucali PA, Lee HS, Pineda MA, Meltzer PS, Walter-Rodriguez B, Roncalli M, Santoro A, Wang Y, Giaccone G: Expression and mutational status of c-kit in thymic epithelial tumors. J Thorac Oncol. 2010, 5 (9): 1447-1453. 10.1097/JTO.0b013e3181e96e30.CrossRefPubMed
20.
go back to reference Huang J, Rizk NP, Travis WD, Riely GJ, Park BJ, Bains MS, Dycoco J, Flores RM, Downey RJ, Rusch VW: Comparison of patterns of relapse in thymic carcinoma and thymoma. J Thorac Cardiovasc Surg. 2009, 138 (1): 26-31. 10.1016/j.jtcvs.2009.03.033.CrossRefPubMedPubMedCentral Huang J, Rizk NP, Travis WD, Riely GJ, Park BJ, Bains MS, Dycoco J, Flores RM, Downey RJ, Rusch VW: Comparison of patterns of relapse in thymic carcinoma and thymoma. J Thorac Cardiovasc Surg. 2009, 138 (1): 26-31. 10.1016/j.jtcvs.2009.03.033.CrossRefPubMedPubMedCentral
21.
go back to reference Gaur P, Leary C, Yao JC: Thymic neuroendocrine tumors: a SEER database analysis of 160 patients. Ann Surg. 2010, 251 (6): 1117-1121. 10.1097/SLA.0b013e3181dd4ec4.CrossRefPubMed Gaur P, Leary C, Yao JC: Thymic neuroendocrine tumors: a SEER database analysis of 160 patients. Ann Surg. 2010, 251 (6): 1117-1121. 10.1097/SLA.0b013e3181dd4ec4.CrossRefPubMed
22.
go back to reference Crona J, Bjorklund P, Welin S, Kozlovacki G, Oberg K, Granberg D: Treatment, prognostic markers and survival in thymic neuroendocrine tumours: a study from a single tertiary referral centre. Lung Cancer. 2013, 79 (3): 289-293. 10.1016/j.lungcan.2012.12.001.CrossRefPubMed Crona J, Bjorklund P, Welin S, Kozlovacki G, Oberg K, Granberg D: Treatment, prognostic markers and survival in thymic neuroendocrine tumours: a study from a single tertiary referral centre. Lung Cancer. 2013, 79 (3): 289-293. 10.1016/j.lungcan.2012.12.001.CrossRefPubMed
23.
go back to reference Oberg K, Hellman P, Ferolla P, Papotti M, Group EGW: Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012, 23 (Suppl 7): vii120-vii123.PubMed Oberg K, Hellman P, Ferolla P, Papotti M, Group EGW: Neuroendocrine bronchial and thymic tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2012, 23 (Suppl 7): vii120-vii123.PubMed
24.
go back to reference Weksler B, Dhupar R, Parikh V, Nason KS, Pennathur A, Ferson PF: Thymic carcinoma: a multivariate analysis of factors predictive of survival in 290 patients. Ann Thorac Surg. 2013, 95 (1): 299-303. 10.1016/j.athoracsur.2012.09.006.CrossRefPubMed Weksler B, Dhupar R, Parikh V, Nason KS, Pennathur A, Ferson PF: Thymic carcinoma: a multivariate analysis of factors predictive of survival in 290 patients. Ann Thorac Surg. 2013, 95 (1): 299-303. 10.1016/j.athoracsur.2012.09.006.CrossRefPubMed
25.
go back to reference Takeda K, Hirai F, Yamanaka T, Taguchi T, Daga T, Shimizu J, Kogure Y, Kimura T, Tanaka K, Iwamoto Y, Ono A, Sasaki H, Fukuoka J, Nishiyama K, Seto T, Ichinose Y, Nakagawa K, Nakanishi Y, West Japan Oncology Group: A multicenter prospective study of carboplatin and paclitaxel for advanced thymic carcinoma: West Japan Oncology Group 4207L. J Clin Oncol. 2013, 31 (suppl; abstr 7529): Takeda K, Hirai F, Yamanaka T, Taguchi T, Daga T, Shimizu J, Kogure Y, Kimura T, Tanaka K, Iwamoto Y, Ono A, Sasaki H, Fukuoka J, Nishiyama K, Seto T, Ichinose Y, Nakagawa K, Nakanishi Y, West Japan Oncology Group: A multicenter prospective study of carboplatin and paclitaxel for advanced thymic carcinoma: West Japan Oncology Group 4207L. J Clin Oncol. 2013, 31 (suppl; abstr 7529):
26.
go back to reference Sugiura H, Fujiwara Y, Ando M, Kawai A, Ogose A, Ozaki T, Yokoyama R, Hiruma T, Ishii T, Morioka H, Mugishima H: Multicenter phase II trial assessing effectiveness of imatinib mesylate on relapsed or refractory KIT-positive or PDGFR-positive sarcoma. J Orthop Sci. 2010, 15 (5): 654-660. 10.1007/s00776-010-1506-9.CrossRefPubMed Sugiura H, Fujiwara Y, Ando M, Kawai A, Ogose A, Ozaki T, Yokoyama R, Hiruma T, Ishii T, Morioka H, Mugishima H: Multicenter phase II trial assessing effectiveness of imatinib mesylate on relapsed or refractory KIT-positive or PDGFR-positive sarcoma. J Orthop Sci. 2010, 15 (5): 654-660. 10.1007/s00776-010-1506-9.CrossRefPubMed
27.
go back to reference Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, Kitamura Y: Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology. 2003, 125 (3): 660-667. 10.1016/S0016-5085(03)01046-1.CrossRefPubMed Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, Kitamura Y: Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology. 2003, 125 (3): 660-667. 10.1016/S0016-5085(03)01046-1.CrossRefPubMed
28.
go back to reference Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA: PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003, 299 (5607): 708-710. 10.1126/science.1079666.CrossRefPubMed Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA: PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003, 299 (5607): 708-710. 10.1126/science.1079666.CrossRefPubMed
29.
go back to reference Masaoka A, Monden Y, Nakahara K, Tanioka T: Follow-up study of thymomas with special reference to their clinical stages. Cancer. 1981, 48 (11): 2485-2492. 10.1002/1097-0142(19811201)48:11<2485::AID-CNCR2820481123>3.0.CO;2-R.CrossRefPubMed Masaoka A, Monden Y, Nakahara K, Tanioka T: Follow-up study of thymomas with special reference to their clinical stages. Cancer. 1981, 48 (11): 2485-2492. 10.1002/1097-0142(19811201)48:11<2485::AID-CNCR2820481123>3.0.CO;2-R.CrossRefPubMed
30.
go back to reference Mariano C, Ionescu DN, Cheung WY, Ali RH, Laskin J, Evans K, Carolan H, Murray N: Thymoma: a population-based study of the management and outcomes for the province of British Columbia. J Thorac Oncol. 2013, 8 (1): 109-117. 10.1097/JTO.0b013e318276241c.CrossRefPubMed Mariano C, Ionescu DN, Cheung WY, Ali RH, Laskin J, Evans K, Carolan H, Murray N: Thymoma: a population-based study of the management and outcomes for the province of British Columbia. J Thorac Oncol. 2013, 8 (1): 109-117. 10.1097/JTO.0b013e318276241c.CrossRefPubMed
31.
go back to reference Kondo K: Report of ITMIG databese - Japan. J Thorac Oncol. 2012, 7 (11 suppl 5): S416- Kondo K: Report of ITMIG databese - Japan. J Thorac Oncol. 2012, 7 (11 suppl 5): S416-
Metadata
Title
Clinicopathological analysis of thymic malignancies with a consistent retrospective database in a single institution: from Tokyo Metropolitan Cancer Center
Authors
Yusuke Okuma
Yukio Hosomi
Kageaki Watanabe
Yuko Yamada
Hirotoshi Horio
Yoshiharu Maeda
Tatsuru Okamura
Tsunekazu Hishima
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-349

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