BASICS
DESCRIPTION
- The thymus gland is located in the anterior portion of the mediastinum; its function is to induce T-lymphocytes. It is largest in the teenage years and slowly regresses through adulthood.
- Primary neoplasms of the thymus include thymoma and thymic carcinoma, which arise from thymic epithelial cells.
- Thymomas are uncommon tumors that are benign but can be locally invasive.
- Thymic carcinomas are rare and aggressive malignant tumors with generally a much poorer prognosis.
EPIDEMIOLOGY
- Thymic cancers are uncommon: 0.2 " 1.5% of all malignancies (1).
- Majority of thymic tumors are thymomas; these account for 20% of mediastinal tumors and 50% of all anterior mediastinal masses in adults.
- Thymomas present between ages of 40 and 60 years (2).
- Thymomas are slightly more common in males and Asians/Pacific Islanders (1).
- Thymic carcinomas are rare: 0.06% of all neoplasms.
Incidence
Thymoma incidence is 0.15/100,000 person/year (1).
ETIOLOGY AND PATHOPHYSIOLOGY
- Embryologically, the thymus derives from the third pharyngeal pouch, which gradually is replaced with adipose tissue in adulthood.
- Thymomas originate from either the cortical or medullary epithelial cells of the thymus. These tumors are considered histologically benign. They are slow-growing and typically have an indolent course. However, they can exhibit invasive and locally aggressive behavior. Tumor spread can occur by local extension or by regional pleural implants. Distant metastatic spread is not seen.
- Thymic carcinomas are also epithelial in origin but have a high degree of atypical and invasiveness.
- Thymic carcinomas are malignant tumors with potential for local, regional, and distant spread.
- At presentation, 80% of thymic carcinomas invade into adjacent structures, and 40% have metastasis to mediastinal lymph nodes.
- For thymic carcinomas, histologic grade is an important prognostic factor.
- WHO pathologic classification for thymomas and thymic carcinoma (3)
- Type A: composed of spindle or oval cells, medullary thymoma
- Type AB: composed of two components, mixed thymoma
- Type B1: composed of predominantly cortical thymoma
- Type B2: cortical thymoma
- Type B3: atypical thymoma
- Type C: thymic carcinoma
RISK FACTORS
None known (1)
COMMONLY ASSOCIATED CONDITIONS
- Thymoma
- Myasthenia gravis: 30 " 40% of patients with thymomas. 10 " 15% of those with myasthenia gravis have a thymoma. Usually have less advanced disease because the symptoms favor earlier detection
- Pure red cell aplasia (5 " 10%)
- Hypogammaglobinemia (3 " 6%)
- Epstein-Barr virus
- Thymic carcinoma
- Occasionally associated with paraneoplastic syndromes
DIAGNOSIS
HISTORY
- 1/3 of patients are asymptomatic and diagnosed by incidental finding on imaging.
- Symptoms include fatigue, chest pain, shortness of breath, stridor, and cough.
- Superior vena cava syndrome may arise from local compression (2).
- 40% of patients have associated systemic autoimmune syndrome, myasthenia gravis being the most common.
- Symptoms of myasthenia gravis include diplopia, ptosis, dysphagia, and weakness with repetitive effort.
PHYSICAL EXAM
Usually normal
DIFFERENTIAL DIAGNOSIS
Must be differentiated from other causes of anterior mediastinal mass, both malignant and benign
- Malignant: thyroid carcinoma, lung cancer, teratoma, lymphoma, metastatic cancer
- Benign: thyroid goiters, benign cyst, thymus hyperplasia
- Anterior mediastinal masses (4 T 's): thymoma, teratoma, thyroid carcinoma, "terrible " lymphoma
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
- Rule out germ cell tumor with lactate dehydrogenase (LDH), erythrocyte sedimentation rate (ESR),α-fetoprotein (AFP), beta human chorionic gonadotropin ( ²-hCG).
- Pulmonary function test (PFT) as indicated
- Tensilon test (edrophonium) to test for myasthenia gravis
- Plain-film chest x-ray can detect 50% of thymomas and thymic carcinomas.
- CT scan is the imaging study of choice to detect and characterize anterior mediastinal mass and thymic tumors. CT can also be useful to demonstrate invasion (4,5).
- MRI may be helpful in determining invasion of mediastinal and vascular structures (4,5).
Diagnostic Procedures/Other
- Biopsy: Fine-needle aspiration, bronchoscopy, mediastinoscopy, video-assisted thoracoscopy, or open biopsy can be performed. Fine-needle aspiration does not indicate if invasion is present.
- Preoperative biopsy is not necessary if thymoma is strongly suspected based on clinical features and imaging.
Test Interpretation
Thymoma Staging System of Masaoka: most widely used staging criteria for thymomas (6)
- Stage I: macro- and microscopically completely encapsulated
- Stage II: A. Microscopic transscapular invasion; B. Macroscopic invasion into surrounding fatty tissue or grossly adherent to, but not through, mediastinal pleura or pericardium
- Stage III: macroscopic invasion into neighboring organs. A. Without invasion into great vessels; B. With invasion of great vessels
- Stage IV: A. Pleural or pericardial dissemination; B. Lymphogenous or hematogenous metastases
TREATMENT
- Thymoma
- Complete surgical resection is the most important therapeutic intervention.
- Adjuvant treatment with radiation depends on extent of resection and degree of tumor invasiveness.
- Chemotherapy is used in advanced disease. It can be used neoadjuvantly, with or without radiation, to convert unresectable tumor to resectable ones.
- Thymic carcinomas
- Typically, these tumors are aggressive, and multimodality approach with surgery, chemotherapy, and radiation therapy is used.
SURGERY/OTHER PROCEDURES
- Surgery
- Extent of resection based on degree of invasion
- Resection of the entire tumor and capsule with negative margins is the goal of surgery.
- Resection of the pericardium or lung parenchyma may be needed to achieve negative margins.
- Completeness of surgical resection is an important prognostic factor (7,8)[B].
- Radiation therapy
- Postoperative radiation is used to prevent tumor recurrence (9).
- Adjuvant radiation should be offered for patients with positive surgical margins (10,11)[B].
- Patients with stage III disease are also likely to benefit from adjuvant radiation therapy. Patients with high-risk stage II should be considered for adjuvant treatment, but this is an area of uncertainty (10,11)[B].
- Typical doses are 45 to 50 Gy for thymomas adjuvantly. Higher doses can be used for macroscopic residual disease. Thymic carcinoma: usually 50 to 60 Gy. Unresectable total dose of 60 to 70 Gy (9)[B]
- Radiation can also be used for local disease control and palliation of symptoms in unresectable disease.
- Chemotherapy
- Thymomas are sensitive to chemotherapy with demonstrated clinical response (12).
- Cisplatin-based regimens are most commonly used.
- Chemotherapy is typically used in unresectable and advanced disease.
- Treatment based on stage of thymomas (13)[B]
- Stage I: Complete surgical resection with negative margins results in a high rate of local control, and no adjuvant treatment is generally needed.
- Stage II: complete surgical resection. Adjuvant radiation therapy may improve the rate of local control, but due to the rarity of this disease and lack of randomized clinical trials, the benefit of radiation in this setting remains an area of uncertainty.
- Stage III: Surgical resection followed by adjuvant radiation therapy. Neoadjuvant or adjuvant chemotherapy should also be considered.
- Stage IV: Induction chemotherapy or chemoradiation to optimize surgical resectability followed by radiation therapy if not given preoperatively and consideration of consolidative chemotherapy (14)[B]
ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
- Annual imaging with chest CT scan for at least 10 years (4)
- Long-term follow-up is needed because late recurrence >5 years is not uncommon.
PROGNOSIS
- 5-year overall survival for thymomas based on Masaoka staging (15)
- Stage I: 94 " 100%
- Stage II: 86 " 95%
- Stage III: 56 " 69%
- Stage IV: 11 " 50%
- Thymic carcinomas have a poor prognosis.
- 5-year survival 30 " 50% (2)
REFERENCES
11 Engels EA. Epidemiology of thymoma and associated malignancies. J Thorac Oncol. 2010;5(10 Suppl 4):S260 " S265.22 Eng TY, Fuller CD, Jagirdar J, et al. Thymic carcinoma: state of the art review. Int J Radiat Oncol Biol Phys. 2004;59(3):654 " 664.33 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(3):624 " 632.44 Marom EM. Imaging thymoma. J Thorac Oncol. 2010;5(10 Suppl 4):S296 " S303.55 Rosado-de-Christenson ML, Strollo DC, Marom EM. Imaging of thymic epithelial neoplasms. Hematol Oncol Clin North Am. 2008;22(3):409 " 431.66 Masaoka A, Monden Y, Nakahara K, et al. Follow-up study of thymomas with special reference to their clinical stages. Cancer. 1981;48(11):2485 " 2492.77 Kondo K, Monden Y. Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan. Ann Thorac Surg. 2003;76(3):878 " 884.88 Filosso PL, Guerrera F, Rendina AE, et al. Outcome of surgically resected thymic carcinoma: a multicenter experience. Lung Cancer. 2014:83(2):205 " 210.99 Gomez D, Komaki R, Yu J, et al. Radiation therapy definitions and reporting guidelines for thymic malignancies. J Thorac Oncol. 2011;6(7 Suppl 3):S1743 " S1748.1010 Forquer JA, Rong N, Fakiris AJ, et al. Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease. Int J Radiat Biol Phys. 2010;76(2):440 " 445.1111 Utsumi T, Shiono H, Kadota Y, et al. Postoperative radiation therapy after complete resection of thymoma has little impact on survival. Cancer. 2009;115(23):5413 " 5420.1212 Schmitt J, Loehrer PJSr. The role of chemotherapy in advanced thymoma. J Thorac Oncol. 2010;5(10 Suppl 4):S357 " S360.1313 Schmidt-Wolf IG, Rockstroh JK, Sch Όller H, et al. Malignant thymoma: current status of classification and multimodality treatment. Ann Hematol. 2003;82(2):69 " 76.1414 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(3):369 " 379.1515 Kim DJ, Yang WI, Choi SS, et al. 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(3):755 " 761.
ADDITIONAL READING
National Comprehensive Cancer Network. Thymomas and Thymic Carcinomas: NCCN Guidelines Version 1.2014. Fort Washington, PA: National Comprehensive Cancer Network; 2013.
CODES
ICD10
C37 Malignant neoplasm of thymus
ICD9
164.0 Malignant neoplasm of thymus
SNOMED
- Primary malignant neoplasm of thymus
- Secondary malignant neoplasm of thymus
CLINICAL PEARLS
- Thymoma is an uncommon benign tumor arising in the thymus gland.
- Thymomas grow slowly but can be locally invasive and are susceptible to pleural implants but not metastasis.
- Surgery with complete resection of thymoma and capsule results in a high rate of long-term tumor control; adjuvant radiation is used for high-risk tumors.
- Chemotherapy is used in advanced and unresectable disease.
- Late recurrences are common, and long-term follow-up is needed.
- Thymic carcinomas are rare and aggressive malignant tumors arising in the thymus gland.
- Thymic carcinomas are generally treated with a multimodality approach using surgery, chemotherapy, and radiation.