The thymus is derived from the third and fourth pharyngeal pouches and is located in the anterior mediastinum. It is composed of epithelial and stromal cells derived from the pharyngeal pouch and lymphoid precursors derived from mesodermal cells. It is the site to which bone marrow precursors that are committed to differentiate into T cells migrate to complete their differentiation. Like many organs, it is organized into functional regions, in this case the cortex and the medulla. The cortex of the thymus contains ~85% of the lymphoid cells, and the medulla contains ~15%. It appears that the primitive bone marrow progenitors enter the thymus at the corticomedullary junction and migrate first through the cortex toward the periphery of the gland and then toward the medulla as they mature. Medullary thymocytes have a phenotype that cannot be distinguished readily from that of mature peripheral blood and lymph node T cells.
Several things can go wrong with the thymus, but thymic abnormalities are very rare. If the thymus does not develop properly, serious deficiencies in T cell development ensue and severe immunodeficiency is seen (e.g., DiGeorge syndrome, Chap. 316). If a lymphoid cell within the thymus becomes neoplastic, the disease that develops is a lymphoma. The majority of lymphoid tumors that develop in the thymus are derived from the precursor T cells, and the tumor is a precursor T cell lymphoblastic lymphoma (Chap. 110). Rare B cells exist in the thymus, and when they become neoplastic, the tumor is a mediastinal (thymic) B cell lymphoma (Chap. 110). Hodgkin's disease, particularly the nodular sclerosing subtype, often involves the anterior mediastinum. Extranodal marginal zone (MALT) lymphomas have been reported to involve the thymus in the setting of Sjögren's syndrome or other autoimmune disorders, and the lymphoma cells often express IgA instead of IgM on their surface. Castleman's disease can involve the thymus. Germ cell tumors and carcinoid tumors occasionally may arise in the thymus. If the epithelial cells of the thymus become neoplastic, the tumor that develops is a thymoma.
Clinical Presentation and Differential Diagnosis
Thymoma is the most common cause of an anterior mediastinal mass in adults, accounting for ~40% of all mediastinal masses. The other major causes of anterior mediastinal masses are lymphomas, germ cell tumors, and substernal thyroid tumors. Carcinoid tumors, lipomas, and thymic cysts also may produce radiographic masses. After combination chemotherapy for another malignancy, teenagers and young adults may develop a rebound thymic hyperplasia in the first few months after treatment. Granulomatous inflammatory diseases (tuberculosis, sarcoidosis) can produce thymic enlargement. Thymomas are most common in the fifth and sixth decades, are uncommon in children, and are distributed evenly between men and women.
About 40–50% of patients are asymptomatic; masses are detected incidentally on routine chest radiographs. When symptomatic, patients may have cough, chest pain, dyspnea, fever, wheezing, fatigue, weight loss, night sweats, or anorexia. Occasionally, thymomas may obstruct the superior vena cava. About 40% of patients with thymoma have another systemic autoimmune illness related to the thymoma. About 30% of patients with thymoma have myasthenia gravis, 5–8% have pure red cell aplasia, and ~5% have hypogammaglobulinemia. Thymoma with hypogammaglobulinemia also is called Good's syndrome. Among patients with myasthenia gravis, ~10–15% have a thymoma. Thymoma more rarely may be associated with polymyositis, systemic lupus erythematosus, thyroiditis, Sjögren's syndrome, ulcerative colitis, pernicious anemia, Addison's disease, scleroderma, and panhypopituitarism. In one series, 70% of patients with thymoma were found to have another systemic illness.
Once a mediastinal mass is detected, a surgical procedure is required for definitive diagnosis. An initial mediastinoscopy or limited thoracotomy can be undertaken to get sufficient tissue to make an accurate diagnosis. Fine-needle aspiration is poor at distinguishing between lymphomas and thymomas but is more reliable in diagnosing germ cell tumors and metastatic carcinoma. Thymomas and lymphomas require sufficient tissue to examine the tumor architecture to assure an accurate diagnosis and obtain prognostic information.
Once a diagnosis of thymoma is defined, subsequent staging generally occurs at surgery. However, chest CT scans can assess local invasiveness in some instances. MRI has a defined role in the staging of posterior mediastinal tumors, but it is not clear that it adds important information to the CT scan in anterior mediastinal tumors. Somatostatin receptor imaging with indium-labeled somatostatin analogues may be of value. If invasion is not distinguished by noninvasive testing, an effort to resect the entire tumor should be undertaken. If invasion is present, neoadjuvant chemotherapy may be warranted before surgery (see “Approach to Treatment,” below).
Some 90% of thymomas are in the anterior mediastinum, but some may be in other mediastinal sites or even the neck, based on aberrant migration of the developing thymic enlage.
The staging system for thymoma was developed by Masaoka and colleagues (Table e20-1). It is an anatomic system in which the stage is increased on the basis of the degree of invasiveness. The 5-year survival of patients in the various stages is as follows: stage I, 96%; stage II, 86%; stage III, 69%; stage IV, 50%. The French Study Group on Thymic Tumors (GETT) has proposed modifications to the Masaoka scheme based on the degree of surgical removal because the extent of surgery has been noted to be a prognostic indicator. In their system, stage I tumors are divided into A and B on the basis of whether the surgeon suspects adhesions to adjacent structures; stage III tumors are divided into A and B based on whether disease was subtotally resected or only biopsied. The concurrence between the two systems is high.
Table e20-1 Masaoka Staging System for Thymomas
| Save Table
Table e20-1 Masaoka Staging System for Thymomas
|I||Macroscopically and microscopically completely encapsulated; no invasion ...|
Log In to View More
If you don't have a subscription, please view our individual subscription options
below to find out how you can gain access to this content.
Want access to your institution's subscription?
Sign in to your MyAccess Account while you are actively authenticated on this website
via your institution (you will be able to tell by looking in the top right corner
of any page – if you see your institution’s name, you are authenticated). You will
then be able to access your institute’s content/subscription for 90 days from any
location, after which you must repeat this process for continued access.
If your institution subscribes to this resource, and you don't have a MyAccess account,
please contact your library's reference desk for information on how to gain access
to this resource from off-campus.
AccessMedicine Full Site: One-Year Subscription
Connect to the full suite of AccessMedicine content and resources including more than 250 examination and procedural videos, patient safety modules, an extensive drug database, Q&A, Case Files, and more.
Pay Per View: Timed Access to all of AccessMedicine
48 Hour Subscription
Pop-up div Successfully Displayed
This div only appears when the trigger link is hovered over.
Otherwise it is hidden from view.