Ann Thorac Surg 2009;87:339-341. doi:10.1016/j.athoracsur.2008.02.013
© 2009 The Society of Thoracic Surgeons
Key References
Thymoma
Joseph B. Shrager, MD*
Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University School of Medicine, Stanford, California
* Address correspondence to Dr Shrager, Department of Cardiothoracic Surgery, Division of Thoracic Surgery, Stanford University School of Medicine, Falk Building, 300 Pasteur Dr, Stanford, CA 94305-5407 (Email: shrager{at}stanford.edu).
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Historical
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- 1 Blalock A, Harvey AM, Ford FR, Lilienthal J Jr. The treatment of myasthenia gravis by removal of the thymus gland. JAMA 1941;117:1529–33.
- 2 Bernatz PE, Harrison EG, Clagett OT. Thymoma: a clinico-pathologic study. J Thorac Cardiovasc Surg 1961;42:424–44.
- 3 Lattes R. Thymoma and other tumors of the thymus. An analysis of 107 cases. Cancer 1962;15:1224–60.
- 4 Wilkins EW Jr, Edmunds LH, Castleman B. Cases of thymoma at the Massachusetts General Hospital. J Thorac Cardiovasc Surg 1966;52:322–30.
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Relationship to Myasthenia Gravis
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- 5 Goldman AJ, Hermann C Jr, Kessey JC, Mulder DG, Brown WJ. Myasthenia gravis and invasive thymoma: a 20-year experience. Neurology 1975;25:1021–5.
- 6 Wilkins EW Jr, Castleman B. Thymoma: a continuing survey at the Massachusetts General Hospitals. Ann Thorac Surg 1979;28:252–6.
- 7 Monden Y, Uyama T, Taniki T, et al. The characteristics of thymoma with myasthenia gravis: a 28-year experience. J Surg Oncol 1988;38:151–4.
- 8 Somnir FE. Exacerbation of myasthenia gravis after removal of thymomas. Acta Neurol Scand 1994;90:56–66.
- 9 De Perrot M, Liu J, Bril V, et al. Prognostic significance of thymomas in patients with myasthenia gravis. Ann Thorac Surg 2002;74:1658–62.
- 10 Lopez-Cano M, Ponseti-Bosch JM, Espin-Basany E, Sanchez-Garcia JL, Armengol-Carrasco M. Clinical and pathologic predictors of outcome in thymoma-associated myasthenia gravis. Ann Thorac Surg 2003;76:1643–9.
- 11 Kondo K, Monden Y. Myasthenia gravis appearing after thymectomy for thymoma. Eur J Cardiothorac Surg 2005;28:22–5.
- 12 Kondo K, Monden Y. Thymoma and myasthenia gravis: a clinical study of 1,089 patients from Japan. Ann Thorac Surg 2005;79:219–24.
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Other Paraneoplastic Syndromes
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- 13 Souadjian JV, Enriquez P, Silverstein MN, Pepin JM. The spectrum of diseases associated with thymoma: coincidence or syndrome? Arch Intern Med 1974;134:374–9.
- 14 Welsh JS, Wilkins KB, Green R, et al. Association between thymoma and second neoplasms. JAMA 2000;283:1142–3.
- 15 Tarr PE, Lucey DR. Infectious complications of immunodeficiency with thymoma investigators. Good's syndrome: the association of thymoma with immunodeficiency. Clin Infect Dis 2001;32:323–5.
- 16 Karras A, de Montpreville V, Fakhouri F, et al. Renal and thymic pathology in thymoma-associated nephropathy: report of 21 cases and review of the literature. Nephrol Dial Transplant 2005;20:1075–82.
- 18 Thompson CA, Steensma DP. Pure red cell aplasia associated with thymoma: clinical insights from a 50-year single-institution experience. Br J Haematol 2006;135:405–7.
- 19 Evoli A, Minicuci GM, Vitaliani R, et al. Paraneoplastic diseases associated with thymoma. J Neurol 2007;254:756–62.
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Imaging and Other Diagnostic Techniques
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Computed Tomography
- 20 Zerhouni EA, Scott WW Jr, Baker RR, Wharam MD, Siegelman SS. Invasive thymomas. Diagnosis and evaluation by computed tomography. J Comput Assist Tomogr 1982;6:92–100.
- 21 Lee JD, Choe KO, Kim SJ, Kim GE, Im JG, Lee JT. CT findings in primary thymic carcinoma. J Comput Assist Tomogr 1991;15:429–33.
- 22 Verstandig AG, Epstein DM, Miller WT Jr, Aronchik JA, Gefter WB, Miller WT. Thymoma—report of 71 cases and a review. Crit Rev Diagn Imaging 1992;33:201–30.
- 23 Do YS, Im JG, Lee BH, et al. CT findings in malignant tumors of thymic epithelium. J Comput Assis Tomogr 1995;19:192–7.
- 24 Jeong YJ, Lee KS, Kim J, Shim YM, Han J, Kwon OJ. Does CT of thymic epithelial tumors enable us to differentiate histologic subtypes and predict prognosis? Am J Roentgenol 2004;183:283–9.
Magnetic Resonance Imaging
- 25 Sakai F, Stone S, Kiyono K, et al. MR imaging of thymoma. Radiologic-pathologic correlation. Am J Roentgenol 1992;158:751–6.
- 26 Inoue A, Tomiyama N, Fujimoto K, et al. MR imaging of thymic epithelial tumors: correlation with World Health Organization classification. Radiat Med 2006;24:171–81.
Positron Emission Tomography
- 27 Liu RS, Yeh SH, Huang MH, et al. Use of fluorine-18 fluorodeoxyglucose positron emission tomography in the detection of thymoma. A preliminary report. Eur J Nucl Med 1995;22:1402–7.
- 28 Kubota K, Yamada S, Kondo T, et al. PET imaging of primary mediastinal tumours. Br J Cancer 1996;73:882–6.
- 29 Sasaki M, Kuwabara Y, Ichiya Y, et al. Differential diagnosis of thymic tumors using a combination of 11C methionine PET and FDG PET, J Nucl Med 1999;40:1595–601.
- 30 Wittram C, Fischman AJ, Mark E, Ko J, Shepard JA. Thymic enlargement and FDG uptake in three patients. CT and FDG positron emission tomography correlated with pathology. Am J Roentgenol 2003;180:519–22.
Needle Biopsy
- 31 Morrissey B, Adams H, Gibbs AR, Crane MD. Percutaneous needle biopsy of the mediastinum: review of 94 procedures. Thorax 1993;48:632–7.
- 32 Yonemori K, Tsuta K, Tateishi U, et al. Diagnostic accuracy of CT-guided percutaneous cutting needle biopsy for thymic tumours. Clin Radiol 2006;61:771–5.
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Classification and Staging Systems/Histology
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Masaoka Classification
- 33 Bergh NP, Gatzkinsky P, Larsson S, Lundin P, Rindell B. Tumor of the thymus and thymic region. I. Clinicoathological studies on thymoma. Ann Thorac Surg 1978;25:91–8.
- 34 Masaoka A, Monden Y, Nakahara K, Tanioka T. Follow-up study of thymomas with special reference to their clinical stages. Cancer 1981;48:2485–92.
- 35 Masaoka A, Yamakawa Y, Niwa H, et al. Thymectomy and malignancy. Eur J Cardiothorac Surg 1994;8:251–3.
- 36 Asamura N, Nakagawa K, Matsuno Y, et al. Thymoma needs a new staging system. Interact Cardiovasc Thorac Surg 2004;3:163–7.
Muller-Hermelink Classification
- 37 Marino M, Müller-Hermelink HK. Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus. Virchows Arch A Pathol Anat Histopathol 1985;407:119–49.
- 38 Pescarmona E, Rendina EA, Venuta F, et al. Analysis of prognostic factors and clinicopathologic staging of thymoma. Ann Thorac Surg 1990;50:534–8.
- 39 Quintilla-Martinez L, Wilkins EW Jr, Ferry JA, Harris NL. Thymoma—morphologic subclassification correlates with invasiveness and immunohistologic features: a study of 122 cases. Hum Pathol 1993;24:958–69.
World Health Organization Classification
- 40 Rosai J, Sobin L. Histological typing of tumours of the thymus. In: J Rosai and L Sobin, eds. World Health Organization, international histological classification of tumours. Berlin, New York: Springer, 1999:9–14.
- 41 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 2002;94:624–32.
- 42 Rieker RJ, Hoegel J, Morresi-Hauf, et al. Histologic classification of thymic epithelial tumors: comparison of established classification schemes. Int J Cancer 2002;98:900-6.
- 43 Kondo K, Yoshizawa K, Tsuyuguchi, et al. WHO histologic classification is a prognostic indicator in thymoma. Ann Thorac Surg 2004;77:1183–8.
- 44 Park MS, Chung KY, Kim KD, et al. Prognosis of thymic epithelial tumors according to the new World Health Organization histologic classification. Ann Thorac Surg 2004;78:992–8.
- 45 Wright CD, Wain JC, Wong DR, et al. Predictors of recurrence in thymic tumors: importance of invasion, WHO histology and size. J Thorac Cardiovasc Surg 2005;130:1312–21.
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Thymic Carcinoma
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- 46 Suster S, Rosai J. Thymic carcinoma: a clinincopathologic sudy of 60 cases. Cancer 1991;67:1025–32.
- 47 Lucchi M, Mussi A, Basolo F, Ambrogi MC, Fontanini G, Angeletti CA. The multimodality treatment of thymic carcinoma. Eur J Cardiothorac Surg 2001;19:566–9.
- 48 Ogawa K, Toita T, Uno T, et al. Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer 2002;94:3115–9.
- 49 Hernandez-Ilizaliturri FJ, Tan D, Cipolla D, Connolly G, Debb G, Ramnath N. Multimodality therapy for thymic carcinoma: results of a 30-year single-institution experience. Am J Clin Oncol 2004;27:68–72.
- 50 Chen YY, Huang CH, Tang Y, Eng HL. Concurrent chemoradiotherapy for unresectable thymic carcinoma. Chang Gung Med J 2004;27:515–22.
- 51 Lin JT, Wei-Shu W, Yen CC, Liu JH, Chen PM, Chiou TJ. Stage IV thymic carcinoma: a study of 20 patients. Am J Med Sci 2005;330:172–5.
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Ectopic Thymoma
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- 52 Chan JK, Rosai J. Tumors of the neck showing thymic or related branchial pouch differentiation: a unifying concept. Hum Pathol 1991;22:349–67.
- 53 Moran CA, Travis WD, Rosado-de-Christenson M, Loss MN, Rosai J. Thymomas presenting as pleural tumors. Report of eight cases. Am J Surg Pathol 1992;16:138–44.
- 54 Moran CA, Suster S, Fishback NF, Koss MN. Primary intrapulmonary thymoma. A clinicopathologic and immunohistochemical study of eight cases. Am J Surg Pathol 1995;19:304–12.
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Additional Large Surgical Series
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- 55 Verley JM, Hollmann KH. Thymoma: a comparative study of clinical stages, histologic features, and survival in 2000 cases. Cancer 1985;55:1074–86.
- 56 Lewis JE, Wick MR, Scheith Auer BW, Bernatz PE, Taylor WF. Thymoma. A clinicopathologic review. Cancer 1987;60:2727–43.
- 57 Elert O, Buchwald J, Wolf K. Epithelial thymus tumors—therapy and prognosis. Thorac Cardiovasc Surg 1988;36:109–13.
- 58 Maggi G, Casadio C, Cavallo A, Cianci R, Molinatti M, Ruffini E. Thymoma: results of 241 operated cases. Ann Thorac Surg 1991;51:152–6.
- 59 Wilkins EW, Grillo HC, Scannell JG, Moncure AC, Mathisen DJ. Role of staging in prognosis and management of thymoma. Ann Thorac Surg 1991;51:888–92.
- 60 Crucitti F, Doglietto GB, Bellantone R, Perri V, Tommasini O, Tonali P. Effects of surgical treatment in thymoma with myasthenia gravis: our experience in 103 patients. J Surg Oncol 1992;50:43–6.
- 61 Blumberg D, Port JL, Weksler B, et al. Thymoma: a multivariate analysis of factors predicting survival. Ann Thorac Surg 1995;60:908–14.
- 62 Regnard J-F, Magdeleinat P, Dromer C, et al. Prognostic factors and long-term results after thymoma resection: a series of 307 patients. J Thorac Cardiovasc Surg 1996;112:376–84.
- 63 Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1320 patients from Japan. Ann Thorac Surg 2003;76:878–85.
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Specific Surgical Techniques
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Robotic Video-Assisted Thoracic Surgery
- 64 Landreneau RJ, Dowling RD, Castillo WM, Ferson PF. Thoracoscopic resection of an anterior mediastinal tumor. Ann Thorac Surg 1992;54:142–4.
- 65 Roviaro G, Rebuffat C, Varoli F, Vergani C, Maciocco M, Scalambra SM. Videothoracoscopic excision of mediastinal masses: indications and techniques. Ann Thorac Surg 1994;58:1679–84.
- 66 Bodner J, Wykypiel H, Greiner A, et al. Early experience with robot-assisted surgery for mediastinal masses. Ann Thorac Surg 2004;78:259–65.
- 67 Cheng YJ, Kao EL, Chou SH. Videothoracoscopic resection of stage II thymoma; prospective comparison of the results between thoracoscopy and open methods. Chest 2005;128:3010–2.
Resection of Locally Advanced Tumors
- 68 Yagi K, Hirata T, Fukuse T, et al. Surgical treatment for invasive thymoma, especially when the superior vena cava is invaded. Ann Thorac Surg 1996;61:521–4.
- 69 Akaogi E, Ohara K, Mitsui K, et al. Preoperative radiotherapy and surgery for advanced thymoma with invasion to the great vessels. J Surg Oncol 1996;63:17–22.
- 70 Wright CD. Pleuropneumonectomy for the treatment of Masaoka stage IVA thymoma. Ann Thorac Surg 2006;82:1234–9.
- 71 Chen KN, Xu SF, Gu ZD, et al. Surgical treatment of complex malignant anterior mediastinal tumors invading the superior vena cava. World J Surg 2006;30:162–70.
- 72 Huang J, Rizk NP, Travis WD, et al. Feasibility of multimodality therapy including extended resections in stage IVA thymoma. J Thorac Cardiovasc Surg 2007;134:1477–83.
Reoperation for Recurrence
- 73 Kirschner PA. Reoperation for thymoma: report of 23 cases. Ann Thorac Surg 1990;49:550–4.
- 74 Landreneau RJ, Dowling RD, Castillo WM, et al. Thoracoscopic resection of an anterior mediastinal tumor. Ann Thorac Surg 1992;54:142–4.
- 75 Regnard JF, Zinzindohoue F, Magdeleinat P, Guibert L, Spaggiari L, Levasseur P. Results of re-resection for recurrent thymomas. Ann Thorac Surg 1997;64:1593–8.
- 76 Haniuda M, Kondo R, Numanami H, Makiuchi A, Machida E, Amano J. Recurrence of thymoma: clinicopathological features, re-operation, and outcome. J Surg Oncol 2001;78:183–8.
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Adjuvant and Nonsurgical Therapies
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Definitive Chemotherapy and Chemoradiation
- 77 Fornasiero A, Daniele O, Ghiotto C, et al. Chemotherapy for invasive thymoma. A 13-year experience. Cancer 1991;68:30–3.
- 78 Loehrer PJ, Chen M, Kim K, et al. Cisplatin, doxorubicin and cyclophosphamide plus thoracic radiation therapy for limited stage unresectable thymoma: an intergroup trial. J Clin Oncol 1997;15:3093–9.
- 79 Loehrer PJ Sr, Jiroutek M, Aisner S, et al. Combined etoposide, ifosfamide, and cisplatin in the treatment of patients with advanced thymoma and thymic carcinoma: an intergroup trial. Cancer 2001;91:2010–5.
- 80 Loehrer PJ Sr, Wang W, Johnson DH, et al. Octreotide alone or with prednisone in patients with advanced thymoma and thymic carcinoma; an Eastern Cooperative Oncology Group phase II trial. J Clin Oncol 2004;22:293–9.
- 81 Yokoi K, Matsuguma H, Nakahara R, et al. Multidisciplinary treatment for advanced invasive thymoma with cisplatin, doxorubicin, and methylprednisolone. J Thorac Oncol 2007;2:73–8.
- 82 Palmieri G, Marino M, Salvatore M, et al. Cetuximab is an active treatment of metastatic and chemorefractory thymoma. Front Biosci 2007;12:757–61.
Postoperative Radiation
- 83 Curran WJ Jr, Kornstein MJ, Brooks JJ, Turrisi AT III. Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol 1988;6:1722–7.
- 84 Nakahara K, Ohno K, Hashimoto J, et al. Thymoma: results with complete resection and adjuvant postoperative irradiation in 141 consecutive patients. J Thorac Cardiovasc Surg 1988;95:1041–7.
- 85 Urgesi A, Monetti U, Rossi G, Ricardi U, Casidio C. Role of radiation therapy in locally advanced thymoma. Radiother Oncol 1990;19:273–80.
- 86 Arakawa A, Yasunga T, Saitoh Y, et al. Radiation therapy of invasive thymoma. Int J Radiat Oncol Biol Phys 1990;18:529–34.
- 87 Cowen D, Richaud P, Mornex F, et al. Thymoma. Results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. Radiother Oncol 1995;34:9–16.
- 88 Haniuda M, Miyazawa M, Yoshida K, et al. Is postoperative radiotherapy for thymoma effective? Ann Surg 1996;224:219–24.
- 89 Latz D, Schraube P, Oppitz U, et al. Invasive thymoma: treatment with postoperative radiotherapy. Radiology 1997;204:859–64.
- 90 Myojin M, Choi NC, Wright CD, et al. Stage III thymoma. Pattern of failure after surgery and postoperative radiotherapy and its implication for future study. Int J Radiat Oncol Biol Phys 2000;46:927–33.
- 91 Ogawa K, Uno T, Toita T, et al. Postoperative radiotherapy for patients with completely resected thymoma. Cancer 2002;94:1405–13.
- 92 Mangi AA, Wright CD, Allan JS, et al. Adjuvant radiation therapy for stage II thymoma. Ann Thorac Surg 2002;74:1033–7.
- 93 Singhal S, Shrager JB, Rosenthal DI, LiVolsi VA, Kaiser LR. Comparison of stage II thymoma treated by complete resection with or without adjuvant radiation. Ann Thorac Surg 2003;76:1635–42.
- 94 Mangi AA, Wain JC, Donahue DM, Grillo HC, Mathisen DJ, Wright CD. Adjuvant radiation of stage III thymoma: is it necessary? Ann Thorac Surg 2005;79:1834–9.
- 95 Kundell Y, Yellin A, Popovtzer A, et al. Adjuvant radiotherapy for thymic epithelial tumors: treatment results and prognostic factors. Am J Clin Oncol 2007;30:389–94.
Neoadjuvant Therapies for Aggressive but Operable Tumors
- 96 Macchiarini P, Chella A, Ducci F, et al. Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer 1991;68:706–13.
- 97 Rea F, Sartori F, Loy M, et al. Chemotherapy and operation for invasive thymoma. J Thorac Cardiovasc Surg 1993;106:543–9.
- 98 Venuta F, Rendina EA, Longo F, et al. Long-term outcome after multimodality treatment for stage III thymic tumors. Ann Thorac Surg 2003;76:1866–72.
- 99 Bretti S, Berruti A, Loddo C, et al. Multimodal management of stages III-IVa malignant thymoma. Lung Cancer 2004;44:69–77.
- 99 Kim ES, Putnam JB, Komaki R, et al. Phase II study of a multidisciplinary approach with induction chemotherapy, followed by surgical resection, radiation therapy, and consolidation chemotherapy for unresectable malignant thymomas: final report. Lung Cancer 2004;44:369–79.
- 100 Lucchi M, Melfi F, Dini P, et al. Neoadjuvant chemotherapy for stage III and IVa thymomas: a single-institution experience with a long follow-up. J Thorac Oncol 2006;1:308–13.
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Review Articles
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- 101 Kirschner PA (guest editor) The Thymus. Chest Surg Clin N Am 2001;11.
- 102 Kesler KA, Wright CD, Loehrer PJ Sr. Thymoma: current medical and surgical management. Semin Neurol 2004;24:63–73.
- 103 Detterbeck FC, Parsons AM. Thymic tumors. Ann Thorac Surg 2004;77:1860–9.
- 104 Eng TY, Fuller CD, Jagirdar J, Bains Y, Thomas CR Jr. Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys 2004;59:654–64.
- 105 Detterbeck F. Clinical value of the WHO classification system of thymoma. Ann Thorac Surg 2006;81:2328–34.
- 106 Wright CD (guest editor) Thymic Tumors. Sem Thorac Cardiovasc Surg 2005;17.
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Historical
Relationship to Myasthenia...