Pediatric Thymoma Treatment & Management
- Author: Richard A Bickel, MD; Chief Editor: Harumi Jyonouchi, MD more...
Postoperative radiotherapy has been used for invasive thymoma and incompletely resected thymoma.
Commonly, radiotherapy has treated T tumors demonstrated to be unresectable on CT scan or with supraclavicular extension.
Primary radiotherapy in unresectable stage III or stage IVa disease has controlled local disease with a 5-year survival rate of 45-50%. 
Combination chemotherapy using cisplatin has been reported to have a response rating of 70-80%. Doxorubicin, vincristine, and cyclophosphamide have been used in combination chemotherapy.
The acquired immunodeficiency associated with thymoma should be treated with monthly replacement immunoglobulin (Ig) therapy. Replacement Igs may be intravenously or subcutaneously administered. Doses of intravenous Igs should be 300-400 mg/kg every 3 weeks or 400-500 mg/kg every 4 weeks with dose adjustment to maintain trough IgG levels above 500-600 mg/dL. In addition, prophylactic antibiotics may be required in addition to Ig replacement therapy to prevent bacterial infections in immunodeficient patients. Aggressive and long-term antibiosis is often required to treat bacterial infections in these patients.
See Thymoma Treatment Protocols for more information.
Because thymoma is usually well encapsulated and characterized by local spread, thymectomy can be curative in the early stages.
Encapsulated (stage I) tumors can usually be completely excised, and the local relapse rate is less than 5%. Currently, adjuvant radiotherapy and chemotherapy are not recommended for stage I thymomas that are completely resected. The relapse rate increases in more invasive stages.
Surgery can be challenging because of the tendency of the tumor to surround blood vessels, bronchi, and other mediastinal structures. Excessive bleeding can complicate thymectomy of large tumors that have become vascular or lacunar.
Tumor recurrence can occur even after complete resection.
Eighty-five percent of patients with myasthenia gravis (MG) have some histologic abnormality of the thymus.
Thymectomy is considered a routine treatment for MG. Reportedly, resection of the thymoma is associated with improvement in weakness in 25% of patients, and almost one half of patients without thymoma improve after thymectomy.
A study of 153 patients by Werneck et al compared thymectomy with conservative treatment groups in paired patients at similar stages and found no statistical difference between the conservative treatment and thymectomy groups.
Thymectomy is believed to improve muscle weakness in 25% of individuals with MG and thymoma and in 50% of patients with MG without thymoma.
Thymectomy results in resolution of red cell aplasia in 30% of persons with this disorder.
The acquired immunodeficiency phenotype does not improve after thymectomy, and, in some persons, immunodeficiency has occurred years after resection of a thymoma.
Stites DP. Diseases of the thymus. Wyngaarden J, Smith LH, eds. Cecil Textbook of Medicine. WB Saunders Co; 1988.
Rich RR. Clinical Immunology, Principles and Practice. 2nd ed. Mosby; 1996.
Roitt IM, Brostoff J, Male DK. Immunology. 5th ed. Mosby; 1998.
Temes R, Chavez T, Mapel D, et al. Primary mediastinal malignancies: findings in 219 patients. West J Med. 1999 Mar. 170(3):161-6. [Medline].
Agarwala SS. Paraneoplastic syndromes. Med Clin North Am. 1996 Jan. 80(1):173-84. [Medline].
Mygland A, Vincent A, Newsom-Davis J, et al. Autoantibodies in thymoma-associated myasthenia gravis with myositis or neuromyotonia. Arch Neurol. 2000 Apr. 57(4):527-31. [Medline].
Fauci AS, Braunwald E, Isselbacher KJ. Harrison’s Principles of Internal Medicine. 14th ed. McGraw-Hill; 1998.
Hart IK. Acquired neuromyotonia: a new autoantibody-mediated neuronal potassium channelopathy. Am J Med Sci. 2000 Apr. 319(4):209-16. [Medline].
Evoli A, Minicuci GM, Vitaliani R, et al. Paraneoplastic diseases associated with thymoma. J Neurol. 2007 Jun. 254(6):756-62. [Medline].
Takamori M, Komai K, Iwasa K. Antibodies to calcium channel and synaptotagmin in Lambert-Eaton myasthenic syndrome. Am J Med Sci. 2000 Apr. 319(4):204-8. [Medline].
Ammann AJ, Stiehm ER, Roberts RL. Antibody (B-cell) immunodeficiency disorders. Stites DP, Terr A, eds. Medical Immunology. Appleton & Lange; 1997.
Casadevall N, Dupuy E, Molho-Sabatier P, et al. Autoantibodies against erythropoietin in a patient with pure red-cell aplasia. N Engl J Med. 1996 Mar 7. 334(10):630-3. [Medline].
Frank K, Austin M. Samter’s Immunologic Diseases. Little Brown & Co; 1995.
Gay CM, William WN Jr, Wang SA, Oo TH. Thymoma complicated by acquired amegakaryocytic thrombocytopenia and pure red cell aplasia. J Natl Compr Canc Netw. 2014 Nov. 12(11):1505-9. [Medline].
Strollo DC, Rosado de Christenson ML, Jett JR. Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum. Chest. 1997 Aug. 112(2):511-22. [Medline].
Stiehm ER. Immunologic disorders in infants and children. Ochs HD, Winkelstein J, eds. Disorders of the B-Cell System. 4th ed. 1996. 320.
Watts RG, Kelly DR. Fatal varicella infection in a child associated with thymoma and immunodeficiency (Good's syndrome). Med Pediatr Oncol. 1990. 18(3):246-51. [Medline].
Middleton E, Reed CE, Ellis EF, et al, eds. Allergy: Principles and Practice. 5th ed. Mosby; 1998.
Loehrer PJ Sr. Current approaches to the treatment of thymoma. Ann Med. 1999 Oct. 31 Suppl 2:73-9. [Medline].
Takeda S, Miyoshi S, Akashi A. Clinical spectrum of primary mediastinal tumors: a comparison of adult and pediatric populations at a single Japanese institution. J Surg Oncol. 2003 May. 83(1):24-30. [Medline].
Takanami I, Takeuchi K, Naruke M. Noninvasive large thymoma with a natural history of twenty-one years. J Thorac Cardiovasc Surg. 1999 Dec. 118(6):1134-5. [Medline].
Bonilla FA, Bernstein IL, Khan DA, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005 May. 94(5 Suppl 1):S1-63. [Medline].
Kelleher P, Misbah SA. What is Good's syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003 Jan. 56(1):12-6. [Medline].
Camera L, Brunetti A, Romano M, et al. Morphological imaging of thymic disorders. Ann Med. 1999 Oct. 31 Suppl 2:57-62. [Medline].
Lastoria S, Palmieri G, Muto P, Lombardi G. Functional imaging of thymic disorders. Ann Med. 1999 Oct. 31 Suppl 2:63-9. [Medline].
Panitch HS. Neurologic diseases. Stites DP, Terr AI, Parslow TG, eds. Medical Immunology. Appleton & Lange; 1997.
Muller-Hermelink HK, Marx A. Pathological aspects of malignant and benign thymic disorders. Ann Med. 1999 Oct. 31 Suppl 2:5-14. [Medline].
Bott-Kothari T, Aron BS, Bejarano P. Malignant thymoma with metastases to the gastrointestinal tract and ovary: a case report and literature review. Am J Clin Oncol. 2000 Apr. 23(2):140-2. [Medline].
Das A, Pandit S, Choudhury S, Das SK, Basuthakur S. Superior vena caval syndrome and ipsilateral pleural effusion: A rare presentation of anterior mediastinal thymoma. Lung India. 2014 Oct. 31(4):383-6. [Medline].
Kim DJ, Yang WI, Choi SS. 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 Mar. 127(3):755-61. [Medline].
[Guideline] NCCN Clinical Practice Guidelines in Oncology. Thymomas and Thymic Carcinomas. V.2.2012. 11/9/2011. [Full Text].
Okumura M, Shiono H, Inoue M, et al. Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to world health organization histologic classification system. J Surg Oncol. 2007 Jan 1. 95(1):40-4. [Medline].
Werneck LC, Cunha FM, Scola RH. Myasthenia gravis: a retrospective study comparing thymectomy to conservative treatment. Acta Neurol Scand. 2000 Jan. 101(1):41-6. [Medline].
Raschal S, Siegel JN, Huml J, Richmond GW. Hypogammaglobulinemia and anemia 18 years after thymoma resection. J Allergy Clin Immunol. 1997 Dec. 100(6 Pt 1):846-8. [Medline].
Detterbeck FC, Zeeshan A. Thymoma: current diagnosis and treatment. Chin Med J (Engl). 2013. 126(11):2186-91. [Medline].
Davenport E, Malthaner RA. The role of surgery in the management of thymoma: a systematic review. Ann Thorac Surg. 2008 Aug. 86(2):673-84. [Medline].
Fornasiero A, Daniele O, Ghiotto C, et al. Chemotherapy of invasive thymoma. J Clin Oncol. 1990 Aug. 8(8):1419-23. [Medline].
Macchiarini P, Chella A, Ducci F, et al. Neoadjuvant chemotherapy, surgery, and postoperative radiation therapy for invasive thymoma. Cancer. 1991 Aug 15. 68(4):706-13. [Medline].
Loehrer PJ Sr, 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 Sep. 15(9):3093-9. [Medline].
Venuta F, Rendina EA, Pescarmona EO, et al. Multimodality treatment of thymoma: a prospective study. Ann Thorac Surg. 1997 Dec. 64(6):1585-91; discussion 1591-2. [Medline].
Kunitoh H, Tamura T, Shibata T, Takeda K, Katakami N, Nakagawa K, et al. A phase II trial of dose-dense chemotherapy, followed by surgical resection and/or thoracic radiotherapy, in locally advanced thymoma: report of a Japan Clinical Oncology Group trial (JCOG 9606). Br J Cancer. June 29, 2010. 103(1):6-11. [Medline].
Palmieri G, Lastoria S, Montella L, et al. Role of somatostatin analogue-based therapy in unresponsive malignant thymomas. Ann Med. 1999 Oct. 31 Suppl 2:80-5. [Medline].
Verley JM, Hollmann KH. Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases. Cancer. 1985 Mar 1. 55(5):1074-86. [Medline].
Pollack A, Komaki R, Cox JD. Thymoma: treatment and prognosis. Int J Radiat Oncol Biol Phys. 1992. 23(5):1037-43. [Medline].
Wright CD, Wain JC, Wong DR. Predictors of recurrence in thymic tumors: importance of invasion, World Health Organization histology, and size. J Thorac Cardiovasc Surg. 2005 Nov. 130(5):1413-21. [Medline].
Kondo K, Monden Y. Thymoma and myasthenia gravis: a clinical study of 1,089 patients from Japan. Ann Thorac Surg. 2005 Jan. 79(1):219-24. [Medline].
Park MS, Chung KY, Kim KD. Prognosis of thymic epithelial tumors according to the new World Health Organization histologic classification. Ann Thorac Surg. 2004 Sep. 78(3):992-7; discussion 997-8. [Medline].
Rena O, Papalia E, Maggi G. World Health Organization histologic classification: an independent prognostic factor in resected thymomas. Lung Cancer. 2005 Oct. 50(1):59-66. [Medline].
Huang J, Rizk NP, Travis WD, et al. Feasibility of multimodality therapy including extended resections in stage IVA thymoma. J Thorac Cardiovasc Surg. 2007 Dec. 134(6):1477-83; discussion 1483-4. [Medline].
Curran WJ Jr, Kornstein MJ, Brooks JJ, Turrisi AT 3rd. Invasive thymoma: the role of mediastinal irradiation following complete or incomplete surgical resection. J Clin Oncol. 1988 Nov. 6(11):1722-7. [Medline].
Goldman L, Cecil RL, Bennett JC, eds. Cecil Textbook of Internal Medicine. WB Saunders Co; 2000.
Graeber GM, Tamim W. Current status of the diagnosis and treatment of thymoma. Semin Thorac Cardiovasc Surg. 2000 Oct. 12(4):268-77. [Medline].
Inoue M, Okumura M, Miyoshi S, et al. Impaired expression of MHC class II molecules in response to interferon- gamma (IFN-gamma) on human thymoma neoplastic epithelial cells. Clin Exp Immunol. 1999 Jul. 117(1):1-7. [Medline].
Monden Y, Nakahara K, Iioka S, et al. Recurrence of thymoma: clinicopathological features, therapy, and prognosis. Ann Thorac Surg. 1985 Feb. 39(2):165-9. [Medline].
Spigland N, Di Lorenzo M, Youssef S, et al. Malignant thymoma in children: a 20-year review. J Pediatr Surg. 1990 Nov. 25(11):1143-6. [Medline].
Stephan JL, Galambrun C, Boucheron S, et al. Epstein-Barr virus--positive undifferentiated thymic carcinoma in a 12- year-old white girl. J Pediatr Hematol Oncol. 2000 Mar-Apr. 22(2):162-6. [Medline].
|Clinicopathologic Classification||WHO Type||Terminology of the Histogenetic Classification for the Histologic Subtypes of Thymic Epithelial Tumors|
|Predominantly cortical thymoma
Well-differentiated thymic carcinoma
|C||Epidermoid keratinizing (squamous cell) carcinoma
Epidermoid nonkeratinizing carcinoma
Sarcomatoid carcinoma (carcinosarcoma)
Clear cell carcinoma
|Cisplatin||75 mg/m2 on day 1||3 courses repeated q3wk|
|Epirubicin||100 mg/m2 on day 1|
|Etoposide||120 mg/m2 on days 1, 3, and 5|
|Surgery and radiation
in patients with
complete or partial
response to chemotherapy
|4500 cGy if complete
6000 cGy if incomplete
|Cisplatin||50 mg/m2||2-4 cycles q3wk|
|Followed by radiation||54 Gy to the primary tumor and lymph nodes|
|Cisplatin||75-100 mg/m2 on day 1||Repeated q3wk 3 times before surgery and 2 or 3 times after surgery|
|Epirubicin hydrochloride||100 mg/m2 on day 1|
|Etoposide||120 mg/m2 on days 1, 3, and 5|
|Postoperative radiation in patients with radical resection||30 Gy||Delivered in 3 wk with 5 fractions per wk|
|Postoperative radiation in
patients with incomplete resection
|50 Gy||Delivered in 5 wk with 5 fractions per wk|
|Octreotide||1.5 mg/d SC||In patients shown to have
|Lanreotide||30 mg/d SC q14d||Switch to this longer-acting
somatostatin analogue or depot form of octreotide if short-acting octreotide
is well tolerated
|Prednisone||0.6 mg/kg/d PO
for 3 mo, then
decreasing to 0.2 mg/kg