Thymoma is a rare mediastinal tumor that occurs mainly in the anterosuperior mediastinum. Because thymic malignancies are rare, a multidisciplinary team of clinicians and basic scientists formed the International Thymic Malignancy Interest Group (ITMIG). ITMIG participants can pool their clinical experiences and outcomes in an international database to identify prognostic factors and effective treatments. ITMIG members published consensus papers proposing standardized definitions, terminology, and procedures for staging, imaging, surgery, radiation therapy, chemotherapy, and pathologic evaluations of patients with thymic malignancies.
The tumor affects both sexes equally.
Thymoma is most often seen in people in the fourth and fifth decades of life.
The etiology of thymoma is unknown, and the risk factors have not been identified. Thymoma is a tumor originating within the epithelial cells of the thymus. One-third to half of patients present with an asymptomatic anterior mediastinal mass, one-third of patients present with local symptoms (eg, cough, chest pain, superior vena cava syndrome, and/or dysphagia), and one-third of cases are detected during the evaluation of myasthenia gravis. Distant metastases are distinctly uncommon at initial presentation of this tumor.
In addition to myasthenia gravis, which occurs in approximately 30% of patients with thymoma, a host of paraneoplastic syndromes have been seen in association with thymoma. These other syndromes, which occur in fewer than 5% of patients, include pure red cell aplasia, hypogammaglobulinemia, and a variety of other autoimmune disorders.
The most commonly described symptoms are pleuritic chest pain or discomfort, dry cough, and dyspnea. Physical examination may reveal adenopathy, wheezing, fever, superior vena cava syndrome, vocal cord paralysis, and other paraneoplastic syndromes.
Chest radiography and CT
A chest radiograph provides an initial basis for diagnosis. The location, size, density, and presence of calcification within the mass can all be determined. Comparison of the film to previously obtained films is usually helpful.
Following identification of a mediastinal mass on conventional radiography, contrast-enhanced CT scanning should be performed. CT scanning can differentiate the cystic form from a solid lesion as well as the presence of fat, calcium, or fluid within the lesion. Magnetic resonance imaging (MRI) is increasingly available for use in the evaluation of mediastinal pathology, but it is less frequently used than CT. MRI is superior to CT scanning in defining the relationship between mediastinal masses and vascular structures and is useful in the assessment of vascular invasion by the tumor.
Invasive diagnostic tests
CT-guided percutaneous needle biopsy specimens are obtained using fine-needle aspiration techniques and cytologic evaluation or with larger-core needle biopsy and histologic evaluation. Fine-needle specimens are usually adequate to distinguish carcinomatosis lesions, but core biopsies may be necessary to distinguish most mediastinal neoplasms. Immunohistochemical techniques and electron microscopy have greatly improved the ability to differentiate the cell of origin in mediastinal neoplasms. Most series report diagnostic yields for percutaneous needle biopsy of 70% to 100%.
This is a relatively simple surgical procedure accomplished with the patient under general anesthesia. It is an adequate approach to the superior, middle, and upper posterior mediastinum, and most series report a diagnostic accuracy of 80% to 90%. Anterior mediastinotomy (Chamberlain approach) provides for direct biopsy of tissue and has a diagnostic yield of 95% to 100%. Thoracotomy is occasionally necessary to diagnose mediastinal neoplasms, but its indications have been largely supplanted by video-assisted thoracoscopic techniques, which yield an accuracy of 100%.
The most common tumors in the differential diagnosis of an anterior mediastinal tumor are lymphomas and germ-cell tumors. Immunohistochemical markers are helpful to differentiate thymoma from tumors originating from other cell types.
Two of the most common classification schemes for thymoma are listed in Table 5. Verley and Hollman propose a classification system based on tumor architecture, cellular differentiation, and predominant cell type. Bernatz et al describe a simpler classification by presenting thymoma based on the percentage of epithelial cells and lymphocytes. In both of these systems, thymoma with a predominance of epithelial cells is associated with a greater incidence of invasion and a subsequently worse prognosis.
The staging system proposed by Masaoka et al has been widely adopted. Stage is an independent predictor of recurrence and long-term survival. The 5-year survival rates are 96% for stage I thymoma, 86% for stage II, 69% for stage III, and 50% for stage IV.
All patients whose tumors are potentially resectable should undergo surgery. If the patient has evidence of myasthenia gravis, a preoperative consultation with a clinical neurologist should be considered. The incision of choice is almost always a median sternotomy, which is quick and easy to make and provides excellent exposure to the anterior mediastinum and neck. Although the surgeon is considered the best judge of a tumor's invasiveness, it is often difficult to grossly separate tumor invasion from tumor adherence to surrounding tissue. Experience with minimally invasive approaches (such as transcervical thymectomy; video-assisted, or VATS, thymectomy; and robotic-assisted thymectomy) is growing; however, until longer-term data become available, sternotomy should still be considered the standard surgical approach.
Complete resection of thymoma has been found to be the most significant predictor of long-term survival. Several studies have examined the extent of surgical resection on survival and disease-free survival rates. In 241 operative cases, Maggi and colleagues found an 82% overall survival rate in those whose tumors underwent complete resection and a 26% survival rate at 7 years in those who underwent biopsy alone. Other investigators reported similar results in surgical patients. Therefore, regardless of stage, tumor resectability is one of the important predictors of treatment outcome.
Thymomas are generally radiosensitive tumors, and the use of radiation therapy in their treatment is well established. It has been used to treat all stages of thymoma, either before or after surgical resection. General agreement exists regarding the postoperative treatment of invasive thymoma (stages II and III). The value of adjuvant radiation therapy for invasive thymomas is well documented and should be included in the treatment regimen regardless of the completeness of tumor resection.
Chemotherapy has been used in the treatment of invasive thymomas with increasing frequency during the past decade (Table 6). The most active agents appear to be cisplatin(Drug information on cisplatin), doxorubicin(Drug information on doxorubicin), ifosfamide(Drug information on ifosfamide), and corticosteroids. Combination chemotherapy has generally shown higher response rates and has been used in both neoadjuvant and adjuvant settings and in the treatment of metastatic or recurrent thymomas. CAP or CAPPr (cyclophosphamide, Adriamycin [doxorubicin], Platinol [cisplatin], and prednisone(Drug information on prednisone)) regimens have been used in neoadjuvant and/or adjuvant settings. These regimens have also been used for recurrent thymoma.
Advanced-stage (III/IVA) thymomas usually are difficult to remove completely. Multidisciplinary approaches, including induction chemotherapy followed by surgical resection, postoperative radiation therapy, and consolidation chemotherapy, have been reported.
Induction chemotherapy consists of cyclophosphamide(Drug information on cyclophosphamide) (500 mg/m2 IV on day 1), doxorubicin (20 mg/m2/d, by continuous infusion, on days 1 to 3), cisplatin (30 mg/m2/d IV on days 1 to 3), and prednisone (100 mg/d PO on days 1 to 5), repeated every 3 to 4 weeks for 3 courses. Twenty-two evaluable patients were consecutively treated from 1990 to 2000 in a prospective phase II study at MD Anderson Cancer Center. After induction chemotherapy, 17 of 22 patients (77%) had major responses, including 3 complete responses.
Twenty-one patients underwent surgical resection. All patients received postoperative radiation therapy and consolidation chemotherapy. With a median follow-up of 50.3 months, overall survival rates at 5 years and 7 years were 95% and 79%, respectively. The rate of disease-progression-free survival was 77% at 5 and 7 years. The multidisciplinary approaches to unresectable thymoma appear to be promising.
Sidebar: A single-arm study was performed to evaluate the response of octreotide(Drug information on octreotide) LAR plus prednisone in patients with inoperable or locally recurrent thymoma. Response was defined as a decrease in tumor volume by more than 20% at 3 months. Seventeen patients with Masaoka stage III thymoma were recruited. The response rate was 88%. Five patients (29%) were found to be operable for radical resection (Schalke B, Boy S, Hofmann H, et al: J Clin Oncol 30(S):abstract 7105, 2012).