Thymic Tumors Workup

Updated: Feb 22, 2021
  • Author: Dale K Mueller, MD; Chief Editor: Mary C Mancini, MD, PhD, MMM  more...
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Approach Considerations

Various advances have been made in rthe areas of diagnostic imaging and biologic analysis.

Diagnostic modalities such as positron emission tomography (PET) and other radionuclide studies may assist in the diagnosis of specific neoplasms and in posttherapy surveillance for recurrent disease. In preliminary studies, PET demonstrated the ability to differentiate benign thymomas from malignant thymomas.

Numerous biologic markers have been identified for many tumors and will play a vital role in better identifying individual neoplasms so that treatment can be optimized.


Laboratory Studies

Red blood cell (RBC) aplasia is found in approximately 5% of patients with thymoma and manifests as a normochromic-normocytic anemia. These studies are not routinely performed for evaluation of a mediastinal mass, but RBC aplasia may be an abnormality found in association with a mediastinal mass. Neutropenia, though rare, can be found in association with thymomas. These studies are also not part of the routine evaluation of a mediastinal mass, but neutropenia may be an associated abnormality.

Hypogammaglobulinemia is associated with some cases of thymoma.

The thorax should always be investigated for the source of ectopic adrenocorticotropic (ACTH) production. If the workup of a patient with Cushing syndrome calls for investigation for an extra-adrenal source, a neuroendocrine tumor (NET) or carcinoid tumor of the thorax should be excluded. These tumors occur in the mediastinum, particularly in the thymus gland, and in the lung.

Antidiuretic hormone (ADH) levels may be elevated with some NETs of the thymus.


Imaging Studies

Chest radiography

Posteroanterior and lateral radiographs of the chest taken for an unrelated cause are the usual means by which an asymptomatic mediastinal mass is identified (see the image below). Chest radiography is obviously the first radiologic study that would be performed in an individual with symptoms referable to the thorax. Most thymic neoplasms are visualized on standard chest radiography.

Posteroanterior chest film of a 34-year-old woman Posteroanterior chest film of a 34-year-old woman with large anterior mediastinal mass. Pathology results indicated malignant thymoma.

The lateral chest radiograph is very helpful in the determination of the involved compartment of the mediastinum (see the image below). This information, combined with the age, sex, and associated clinical findings, aids the physician in the proper choice of subsequent diagnostic studies.

Lateral view of tumor in the image above (a 34-yea Lateral view of tumor in the image above (a 34-year-old woman with anterior mediastinal mass found to be a malignant thymoma). Note the fullness and haziness above the heart shadow.

Computed tomography

Computed tomography (CT) of the chest and mediastinum is a routine part of the diagnostic evaluation of mediastinal tumors, cysts, and other masses (see the image below).

CT scan view of tumor in the images above (a 34-ye CT scan view of tumor in the images above (a 34-year-old woman with large anterior mediastinal mass found to be a malignant thymoma). Arrow indicates the area in which the tumor (malignant thymoma) is invading the anterior chest wall.

CT scans can greatly assist in determining the exact location of the mediastinal tumor and its relationship to adjacent structures. These images are also useful in differentiating masses that originate in the mediastinum from those that encroach on the mediastinum from the lung or other structures.

CT is very useful for helping differentiate tissue densities. This greatly assists in distinguishing structures that are cystic or vascular from those that are solid.

CT is the preferred imaging modality for visualizing a thymoma. However, thymomas have no absolute diagnostic features; they are usually homogeneous and enhance with contrast. CT scans can reveal evidence of local invasion of adjacent structures by a mass or the presence of intrathoracic metastases. CT has been found to be capable of differentiating stage I/II from stage III/IV and may be useful for predicting the need for neoadjunctive therapy. [2]

Magnetic resonance imaging

Magnetic resonance imaging (MRI) is useful both for initial diagnosis of a mediastinal mass and for follow-up evaluation after treatment. MRI can help differentiate between a possible mediastinal mass and a vascular abnormality such as an aortic aneurysm.

MRI offers direct multiplanar imaging. It can be used when iodinated contrast cannot be given. MRI provides increased detail in the subcarinal and aortopulmonary window areas and in the inferior aspects of the mediastinum at the level of the diaphragm.

MRI adds little that CT does not provide and should not be performed except under special circumstances.

Radionuclide scanning

The origin of a mass located at the thoracic inlet can occasionally be difficult to identify. At times, additional testing may be required to better identify such a mass and help differentiate whether it is of thymic, thyroid, or other origin.

Although the iodine 131 or iodine 123 scans are specific for thyroid tissue, they are worth mentioning in the context of thymic tumors because they are very helpful in distinguishing thyroid tissue from other masses. These scans are often used in identifying an anterior mediastinal mass located at the level of the thoracic inlet as the substernal extension of a cervical thyroid goiter. A radioactive iodine scan may also help identify ectopic thyroid tissue within the mediastinum. These studies must be performed before any tests requiring the administration of iodinated contrast because this material may interfere with thyroid uptake and scanning.

The octreotide scan, using indium 111In-labeled pentetreotide, is useful for localizing various neuroendocrine neoplasms, including carcinoid tumors, pheochromocytomas, and paragangliomas. Carcinoid tumors, though uncommon, can occur in the thymus.

Echocardiography and ultrasonography

Ultrasonographic methods have been used to differentiate solid from cystic mediastinal masses and to assist in determining whether a connection is present between a mass and adjacent structures. These studies are more useful in the evaluation of cardiac abnormalities than in the evaluation of mediastinal tumors.

Given the accuracy and detail provided by CT, MRI, and selected radionuclide scanning, ultrasound techniques are generally not used as primary tools in the evaluation of mediastinal tumors and cysts.

Positron emission tomography

PET has been studied extensively for the evaluation of a number of neoplasms (eg, lung cancer, colorectal cancer, breast cancer, lymphoma, and melanoma). Its usefulness in the evaluation of mediastinal tumors has not been definitively established.

Some results of using PET for thymomas suggest that a high 18-fluorodeoxyglucose (FDG) uptake on PET reflects the invasiveness of malignant nature of thymic tumors and can be used to differentiate these from benign thymomas. [3] A preliminary report suggested that PET is a sensitive test for thymomas. [4]



Transthoracic needle biopsy

In the past, percutaneous biopsy methods were believed to be too dangerous to use in the evaluation of mediastinal masses, and open surgical biopsy was the diagnostic procedure of choice.

Despite some degree of controversy, CT-guided fine-needle aspiration biopsy (FNAB) and core needle biopsy (CNB) techniques have been used with increasing success at several centers. [5, 6]  Differentiation between thymomas, lymphomas, and germ cell tumors can be achieved in a number of cases when tissue obtained from a CNB is subjected to special histologic staining methods, including immunohistochemical techniques. In some cases, lymphoma subtypes can also be identified.

Expert clinical judgment is necessary in the selection of appropriate cases for this diagnostic method. In addition, considerable expertise in tissue processing and analysis is necessary for diagnostic accuracy. Many consider tumor size an important factor when deciding to proceed with needle biopsy. Tumors larger than 5 cm can be considered for biopsy because preoperative chemotherapy may be considered for invasive thymoma and thymic carcinoma.

Cervical mediastinoscopy and substernal extended mediastinotomy

Cervical mediastinoscopy is a commonly used surgical diagnostic procedure for the evaluation of the retrovascular pretracheal area of the mediastinum. It is used most often for staging of bronchogenic carcinoma and for evaluation of hilar and paratracheal lymphadenopathy, but it can be modified into what has been termed a substernal extended mediastinoscopy to evaluate the prevascular area of the mediastinum.

The thymus and any tumors or cysts found in this area, as well as lymph nodes of the aortopulmonary window, are accessible for biopsy via this approach.

Anterior mediastinotomy

This parasternal approach to the mediastinum has been used most commonly in situations in which standard cervical mediastinoscopy was believed or found to be inadequate. The classic approach is to the upper left parasternal area in order to obtain access to the aortopulmonary window and areas of the anterior mediastinum inferior to the aortic arch. Anterior mediastinotomy is being replaced in many centers, either by extended cervical mediastinoscopy or by video-assisted thoracoscopic surgery (VATS). [7]

Video-assisted thoracoscopy

VATS techniques have been used successfully for biopsy of various masses in all areas of the mediastinum. [8]  VATS is commonly used for the sampling of perihilar lymph nodes or masses that are accessible via either thoracic cavity. VATS is superior to the various indirect biopsy techniques because it allows direct visualization of the mass or lesion from where the biopsy sample will be taken and a view of nearby structures and organs. This gives the surgeon an excellent idea of tumor extent and resectability.

Sternotomy and thoracotomy

In spite of the numerous minimally invasive options available for histologic diagnosis of mediastinal tumors and cysts, situations still arise for which open surgical access is needed. In some cases, standard sternotomy or thoracotomy may be the safest method available for obtaining an adequate tissue diagnosis. Ministernotomy can also be used for complete resection of a localized thymoma.


Histologic Findings


Thymomas arise from thymic epithelial cells and are generally composed of two cell types, epithelial and lymphocytic. The morphology of the epithelial cells can be round, oval, or spindle-shaped. The cells are rather large and tend to organize into clusters. They have vesicular nuclei with small nucleoli and cytoplasm that is eosinophilic or amphophilic. The spindle-shaped variety of epithelial cell is often arranged in a whorl-type pattern. Individual cells have an appearance similar to that of fibroblasts. The lymphocytic component of thymomas is made up of mature lymphocytes with no significant atypia.

Thymomas are generally classified as predominantly epithelial, predominantly lymphocytic, mixed lymphoepithelial, and spindle-cell type, which is a variant of the epithelial type and is composed mostly of the spindle-shaped epithelial cells. Other microscopic features that have been noted include Hassall corpuscles, keratinizing squamous epithelium, rosettes, glands and pseudoglands, cysts, papillary structures, and germinal centers. These features do not appear to have any significance in predicting the activity of the tumor.

Cellular makeup is not the prime consideration in the determination of a thymoma's malignant or indolent potential. The most important features are the gross pathologic characteristics. These include encapsulation of the tumor and fixation or invasion of adjacent structures. Although no thymoma is truly benign, well-encapsulated thymomas with no evidence of invasion of the capsule are considered much less aggressive. Any evidence of invasion of the capsule or adjacent structures suggests a much more malignant level of activity.

Immunohistochemical staining methods with antikeratin antibodies can be helpful in the histologic identification of a thymoma. A number of thymic epithelial markers, such as cytokeratin, thymosin beta-3, thymosin alpha-1, and epithelial membrane antigen, have also been used.

Thymic carcinomas

The various types of carcinoma that occur in the thymus are quite rare. Squamous cell carcinoma (SCC) of the thymus resembles typical SCC. Well-differentiated tumors display prominent lobulation and are composed of large polygonal cells in groups or cords connected by intercellular bridges. The nuclei are vesicular or densely pigmented and have distinct nucleoli. The cytoplasm is eosinophilic, and keratin "pearls" are common. These tumors may be only locally invasive.

Poorly differentiated squamous cell tumors are more aggressive locally, have little of the lobular architecture found in the well-differentiated form, and may metastasize to distant sites. These tumors have a more disarrayed architecture and cellular atypia. Distinct fibrous septa or bridges within the tumor often are lacking. Cytoplasm is sparse and amphophilic. Keratin pearls are not seen.

Lymphoepitheliomalike carcinoma of the thymus is made up of dense sheets of polygonal epithelial cells with indistinct cytoplasmic membranes. These cells have round vesicular nuclei, large eosinophilic nucleoli, and amphophilic cytoplasm. The tumors always have groups of lymphocytes interspersed throughout. These tumors are virtually identical to lymphoepitheliomas located in the nasopharynx.

Neuroendocrine tumors of thymus

NETs of the thymus have features virtually identical to those of NETs identified in other parts of the body. A spectrum of disease exists for this type of tumor, ranging from the well-differentiated or typical carcinoid tumor to the highly aggressive small cell carcinoma.

In the more well-differentiated or typical carcinoid type, cells are arranged in nests surrounded by fibrovascular septa or are situated in cords or ribbons with minimal septation. Cells are small and have a regular shape with round nuclei that have clumped chromatin within them. The cytoplasm is abundant and acidophilic.

Less well-differentiated NETs have more pronounced atypia. Nuclei are larger and have nucleoli that are more prominent. Mitotic figures are more frequent. The general architecture of these tumors takes on a more monotonous sheetlike appearance. Areas of necrosis are common.

Poorly differentiated tumors equivalent to small cell carcinoma have sheets or cords of remarkably atypical cells, large areas of necrosis, and high mitotic activity. Immunohistochemical staining, particularly using chromogranin, can be very helpful in identifying neuroendocrine tumors.



A great deal of controversy has been raised about the staging of thymomas. More than one staging system has been used for these lesions, based on the specific feature of the tumor. In the most commonly used system, thymomas are staged according to gross and microscopic features of the encapsulation or invasiveness of the tumor. This staging system is referred to as the Masaoka system, and several other authorities (eg, Koga) have modified it further.

Another staging method, put forth by Marino and Müller-Hermelink, is based on the cell type found within a given thymoma. Thymomas are classified as cortical, medullary, or mixed. The most accurate method of staging is likely some combination of these systems.

In the Masaoka system, thymomas are staged as follows:

  • Stage I - Grossly, the tumor is completely encapsulated; microscopically, no invasion of the capsule is seen
  • Stage IIA - Microscopically, tumor invasion is seen extending into the capsule
  • Stage IIB - Grossly, invasion is seen into the surrounding fatty tissues or mediastinal pleura
  • Stage III - Gross evidence of invasion into an adjacent organ or structure (eg, pericardium, lung, great vessels, including vena cava) is seen
  • Stage IVA - Tumor dissemination is seen in the pleura or pericardium
  • Stage IVB - Evidence of hematogenous or lymphogenous metastases is present

A staging system based on TNM (tumor-node-metastasis) classification has been developed by the American Joint Committee on Cancer (AJCC). [9]