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Journal of Thoracic Oncology:
doi: 10.1097/JTO.0b013e3181f209ca
Malignancies of the Thymus Supplement

Imaging Thymoma

Marom, Edith M. MD

Free Access
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Author Information

Department of Diagnostic Radiology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.

Disclosure: The author declares no conflicts of interest.

Address for correspondence: Dr. Edith M. Marom, Department of Diagnostic Imaging, The University of Texas M. D. Anderson Cancer Center, 1400 Pressler - Unit 1478, Houston, TX 77030. E-mail: emarom@mdanderson.org

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Abstract

Thymoma is a rare tumor, although it is the most common primary neoplasm of the anterior mediastinum. In the majority of thymoma patients, imaging is requested for investigation of symptoms related to their tumor, although an increasing number of asymptomatic patients are discovered incidentally due to the increased utilization of computed tomography for screening or for imaging of other unrelated diseases. This review will focus on the goals of imaging thymoma, the imaging features of thymoma, as well as the advantages and limitations of each imaging modality in establishing the diagnosis, staging, and prognosis of thymoma.

Thymomas are the most common primary neoplasm of the anterior mediastinum but account for less than 1% of all adult malignancies.1 The majority arise in the upper anterior mediastinum in proximity to the pulmonary artery and/or ascending aorta, corresponding to the position of the normal thymus. Rarely, however, they can be found in unusual locations such as the posterior mediastinum or lower neck.2,3 Thymomas are usually slow-growing tumors manifesting with local extension, which tend to spread along the serosal surfaces, i.e., along the pleura and pericardium, whereas extrathoracic metastases are uncommon.4,5 In the majority of patients with thymoma, imaging is requested for investigation of symptoms related to their tumors: either due to local compression or invasion of thoracic structures or due to systemic paraneoplastic disease. There is, however, an increasing number of asymptomatic patients incidentally discovered to have thymoma due to the increased utilization of computed tomography (CT) for screening and the investigation of other symptoms of unrelated diseases. The goal of imaging is to identify the tumor and stage it appropriately, with emphasis on local invasion and distant spread because invasion has been known as the most significant factor for survival.6,7 The objectives of this review are to discuss the imaging features of thymoma, the advantages, and limitations of each imaging modality in establishing the diagnosis, staging, and prognosis of thymoma.

Initial investigation of a thymoma starts with a chest radiograph, which is followed by chest CT for further characterization and staging. Rarely, in selected cases, additional imaging is used such as magnetic resonance imaging (MRI) or nuclear medicine studies.

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CHEST RADIOGRAPHY

Between 45 and 80% of thymomas are visible by chest radiography.8 Thymomas usually appear as an ovoid or lobulated, smooth, well-marginated mass, projecting over the mediastinum typically protruding unilaterally (Figure 1), although rarely may be seen to protrude bilaterally over the mediastinum.8,9 The mass can be seen from the thoracic inlet to the cardiophrenic angle. At times, the chest radiograph may appear entirely normal and at other times changes may be more subtle. The presence of a normal structure in the anterior mediastinum, the anterior junction line, negates the presence of an anterior mediastinal mass in the retrosternal region. Unfortunately, the anterior junction line is seen in the minority of normal individuals. This is a 1 to 3 mm line created by four layers of pleura as the lungs approximate anteriomedially, anterior to the heart and great vessels (Figure 2). Thickening of this line is a sign of a space-occupying lesion in the anterior mediastinum (Figure 3). The lateral film is of help for confirmation as often a mass will be seen in the retrosternal region, and when small, may be more easily detected on the lateral film without the superimposition of the heart and mediastinum.

Figure 1
Figure 1
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Figure 2
Figure 2
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Figure 3
Figure 3
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Chest radiographic signs for tumor invasiveness are limited but should be searched for. These include an irregular border with the adjacent lung, suggestive of invasion into the lung; elevation of the hemidiaphragm, suggestive of phrenic nerve involvement; and pleural nodularity.9

The advantage of the chest radiograph is in its low-radiation dose, low price, and its availability. It lacks sensitivity for smaller tumors and lacks specificity for differentiating a thymoma from other anterior mediastinal masses, such as metastatic disease, lymphoma, or for example, germ cell tumor. Thus, once an anterior mediastinal mass is identified by chest radiography, patients should be further characterized and staged by cross-sectional imaging, usually CT. Patients with a normal chest radiograph but strong clinical suspicion for thymoma are also referred for CT due to its great sensitivity.

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COMPUTED TOMOGRAPHY

CT is more definite in the diagnosis of thymoma, with its increased sensitivity in identifying mediastinal masses, when compared with chest radiography. Thymomas have a typical CT appearance that when seen is highly suggestive of the diagnosis. In addition to the appearance of the primary tumor, their pattern of spread differs from other tumors that may be found in the anterior mediastinum. Thymoma rarely presents with metastatic lymphadenopathy or with metastatic pulmonary nodules where as other tumors, which commonly present with an anterior mediastinal mass, such as lung cancer, do. Although intravenous contrast is not needed for identification of the thymic mass, its role is important with locally invasive tumors when evaluation of the abutting vessels is crucial for preoperative staging and therapeutic planning. Multiplannar reformatting of the axial CT images is easily performed with the current use of multidetector CT scanners and may aid in surgical planning.

Typically, thymomas are closely related to the superior pericardium that is anterior to the aorta, pulmonary artery, or superior vena cava, although they have been described anywhere from the lower neck to the cardiophrenic border (Figure 3). The tumor is usually well defined, round or lobulated, homogenous, and enhances after contrast injection.8 Nevertheless, at times, it can be heterogeneous, or even cystic, because of areas of hemorrhage and necrosis. The tumor can be partially or completely outlined by fat and may contain punctuate, course, or curvilinear calcifications8,9 (Figure 4). At presentation, thymomas are usually 5 to 10 cm large although have been described from a few millimeters to 34 cm.8

Figure 4
Figure 4
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One of the important though challenging roles of CT is to determine local tumor invasiveness. This is crucial as tumor invasiveness has been shown to strongly correlate with prognosis10,11 and dictates the therapeutic approach. The most common staging system used today, which guides the CT interpretation, is the Masaoka staging system.12 Briefly, stage I is when the tumor is macroscopically and microscopically completely encapsulated. Stage IIa is when there is macroscopic invasion into surrounding fatty tissue or mediastinal pleura, whereas stage IIb is when there is microscopic invasion into the capsule. Stage III is when there is macroscopic invasion into a neighboring organ such as pericardium, great vessels, or lung. Stage IVa is when there is pleural or pericardial dissemination and stage IVb when there is lymphogenous or hematogenous metastatic disease. Stage IV is readily identified by CT (Figure 4), and at times, local invasion into neighboring organs can readily be seen such as direct invasion into the superior vena cava, brachiocephalic veins, heart, or encasement of coronary arteries (Figure 5). It has been clinically known that CT cannot differentiate local disease accurately, and indeed, involvement of the pericardium (stage III) versus abutment of it and identification of capsular or pericapsular involvement (stage II) cannot be visualized directly. Unfortunately, there have been very few studies looking at CT predictors of invasiveness, and those that have been performed are small.

Figure 5
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There has been one study published so far, comparing the CT appearance of 50 thymoma tumors to their Masaoka staging.13 In this study, the authors attempted to separate stage I disease from any capsular invasion. They found that larger tumors were more likely to be invasive, although no cutoff value was established. In their study, invasive tumors were more likely to be heterogeneous with low-attenuation areas within the tumor, which was seen in 60% of invasive tumors (16/27), when compared with 22% (5/23) of stage I tumors. Similarly, calcifications were more common in invasive tumors, seen in 54% versus only 6% of stage I tumors. Lobulated contours were more common in invasive tumors (59%), when compared with stage I tumors (35%). Partial or complete obliteration of fat planes around the tumor was not helpful in distinguishing invasive (stages II-IV) from noninvasive (stage I) thymomas. Most of the CT features showed overlap, and a reliable distinction between stage I or higher remains difficult.

There have been surgical series, trying to establish a relationship between the size of thymoma and survival. Because size is readily available by CT, they should be mentioned. Smaller series looking at up to 70 patients with thymoma found no correlation between tumor size and survival.14,15 On the other hand, larger surgical series looking at 118 to 179 patients found that larger tumors were associated with worse outcome.6,16,17 There was no total agreement between these studies on the cutoff value that would best distinguish between the less favorable tumors as one suggested 8 cm, another 10 cm, and the other 11 cm as the ideal cutoff value. These cutoff values may be problematic, knowing that at CT most thymomas at presentation are 5 to 10 cm, and thus fall within the uncertainty zone as to their prognosis.

Perhaps, the most important role of the initial CT is not necessarily to distinguish stage I (purely encapsulated tumor) from higher stages but to distinguish between those tumors that should be treated with neoadjuvant therapy and those that should proceed directly to surgery. Currently, it is recommended that patients with stages III and IV should receive neoadjuvant therapy.18–23 In an internal review of 57 surgically treated patients in M. D. Anderson Cancer Center, we found that CT was able to distinguish early disease (stages I and II) from more advanced disease (stages III and IV), data that should be published shortly. Similar to the published surgical series, we found that size was useful but only for the extreme tumors. Tumors smaller than 5 cm were unlikely to be invasive. Tumors larger than 11 cm were much more likely to be advanced disease (stages III or IV). Nevertheless, there was substantial overlap for those presenting with tumors from 5 to 11 cm, and within this range, size could not reliably distinguish between early and advanced disease.

There are few studies focusing on the CT appearance of thymomas, when compared with the World Health Organization (WHO) classification. Unfortunately, in these studies, thymic cancers were included in the evaluation.24–27 When excluding the thymic cancers, CT could not distinguish between the different histologic subtypes of the WHO classification for thymoma.24–27 This may be due to the inherent problems within the WHO classification of thymoma, rather than due to the imaging itself.11 Such problems include (a) the poor interobserver and intraobserver reproducibility of the pathology classifications; (b) the morphologic heterogeneity and variations in morphology from field to field in thymoma; and (c) the inability of the WHO classification system to predict clinical outcome.7,28,29

CT is currently the cross-section modality of choice for evaluating patients with a suspected anterior mediastinal mass, and this is despite the relatively large radiation dose, when compared with chest radiographs. CT is readily available and is quite accurate in distinguishing a mediastinal mass caused by thymoma compared with other mediastinal tumors, which usually differ in the appearance of the primary and the pattern of metastatic spread, both of which are readily detected by chest CT.

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MAGNETIC RESONANCE IMAGING

The routine role of MRI in the identification and staging of thymoma is limited but is valuable in select circumstances. MRI features of thymoma are not specific. Thymoma has signal characteristics similar to or higher than muscle on T1-weighted images, and on T2-weighted images, the signal is higher than muscle and may approach that of fat, making it difficult to differentiate the thymoma from the surrounding fat.8,30 Fat-suppression techniques may be useful in this scenario (Figure 6). Heterogeneity of the tumor on MRI, similar to what was seen in CT studies, is indeed associated with more of an invasive status, but there is a great overlap, and noninvasive tumors may also show this heterogeneity, making this feature unreliable to distinguish invasive status using this feature alone.26,31 In fact, such MRI features are more useful for distinguishing thymic cancer rather than invasive status of thymoma.26 Dynamic MRI looking at time to peak contrast enhancement, although used in other tumors, cannot distinguish between thymoma and other major anterior mediastinal masses such as thymic carcinoma, lymphoma, or germ cell tumor32 and, thus, is not used clinically. Although MRI has the capabilities of multiplanar imaging, this is easily obtained with multidetector chest CT with its improved spatial resolution.

Figure 6
Figure 6
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Under certain circumstances, MRI may prove valuable. Patients, who cannot receive iodinated contrast material used at CT, can have their vessels evaluated for possible invasion by MRI. This can be performed with or without the use of MRI contrast material (Figure 7). Because of MRIs superior contrast resolution, when compared with CT, in select cases, MRI can prove useful in identifying the nodular wall thickening seen in cystic thymomas, absent from congenital cysts.9,33 Rarely, thymic hyperplasia may be difficult to distinguish from diffuse thymoma. In cases where history is most suspicious for thymoma and not for hyperplasia, chemical shift MRI helps differentiate thymic hyperplasia from thymic malignancy in patients 16 years of age or older.34,35 This technique relies on the difference in resonance frequency between protons in water and those of protons in trigyceride molecules. This technique is much more sensitive in detecting microscopic fat within tissue as compared with the detection of microscopic fat by fat-suppressed MR techniques or with CT detection of fat. Finally, in patients in whom detailed imaging of the lung is not of interest, and radiation is to be avoided, MRI could prove a good substitute to imaging instead of CT.

Figure 7
Figure 7
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The advantage of MRI in investigating the anterior mediastinum is the lack of radiation, the fact that vessel involvement can be investigated without the use of intravenous contrast and its superior contrast resolution. The disadvantage is that the examination is relatively lengthy and provides poor investigation of the lung parenchyma. Thus, if the etiology of the anterior mediastinal mass is not known, complete investigation of it by MRI, including the lungs is not optimal.

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NUCLEAR MEDICINE

Although nuclear medicine techniques have been used in the past for the evaluation of various thymic lesions, the diagnostic criteria overlap considerably.36–38 Evaluation of the thymus with thallium 201 (201Tl) is equal or superior to that with CT. Using the early (15 minutes) and delayed phases (180 minutes) after injection is helpful in differentiating between the normal thymus, hyperplastic thymus, and thymoma, in patients with myasthenia gravis.36 However, the examination suffers from low resolution, low throughput, and overlap in criteria.

Indium 111 octreotide shows increased uptake with thymoma but does not differentiate hyperplasia from normal thymus. Once again, its low spatial resolution limits its use (Figure 8), but it has one advantage over morphologic imaging. It is sometimes used to determine thymic tumor uptake to identify patients who may respond to treatment with octreotide, an octapeptide somatostatin analog that has a high affinity for a selective somatostatin subtype (SST2) receptor. In normal human thymus, the thymic epithelial cells seem to be the major site of the SST production. Neuroendocrine tumors show high affinity for octreotide and can be treated with it. Octreotide alone or in combination with prednisone is sometimes used as salvage therapy for patients with relapse of advanced thymoma.39

Figure 8
Figure 8
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During the last decade, positron emission tomography (PET), in particular with [18F]fluorodeoxyglucose (FDG) has proven useful for staging and imaging many tumors. Studies assessing the evaluation of thymoma with FDG-PET are small, but the data are not promising. Although FDG uptake was found to be much higher in thymic cancer than thymoma, the amount of uptake, or as it is termed standardized uptake value (SUV), overlaps between the low-grade and high-grade thymomas.40–43 Neither the FDG SUV nor another tracer used with PET, carbon 11-labeled acetate can differentiate between early thymoma, Masaoka stage I/II tumors, and stage III/IV tumors. Thus, it cannot aid in trying to establish who may benefit from neoadjuvant therapy. In addition, the FDG activity of some thymomas can be similar to the mediastinal blood activity and increased FDG uptake, similar to that seen in thymomas that can be seen in patients with thymic hyperplasia. The latter is more common in the pediatric population, found in 73% of untreated patients up to the age of 13 years and in 8% of patients in their fourth decade.44 Patterns of FDG activity and not just the SUV itself, in conjunction with the CT appearance of the mediastinal abnormality, are helpful in establishing the nature of disease. As with other malignancies, FDG-PET was shown in a small thymoma study to be particularly useful in the detection of distant malignant spread41 (Figure 8). Whether this will prove to be cost beneficial has not yet been shown.

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FOLLOW-UP

There are no published recommendations as to the frequency and timing of follow-up after treatment of thymoma nor is there consensus as to the imaging modality to be used in this follow-up. Because late recurrence in thymoma is not uncommon, seen even more than 5 or 10 years after resection, follow-up may be lengthy. Because complete resection of recurrence obtains similar outcome compared with those patients without recurrence, this follow-up may be justified.45–47 Currently, CT is most commonly used for this follow-up. With the increased public concern of radiation in young patients, it is unknown whether MRI will take a greater role in this follow-up, despite its lower spatial resolution and lengthy examination, when compared with CT. It also remains to be seen whether FDG-PET will be used in this follow-up or it will be reserved for selected cases such as differentiating between nodular radiation changes and recurrence within the radiation field. If FDG uptake values will be used to monitor disease progression/response, the FDG PET scan must be performed in a meticulous matter, in the same institution adhering to a strict imaging protocol, as SUV measurements can be affected by many technical factors.

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CONCLUSION

Imaging plays a crucial role in the diagnosis, staging, and follow-up of patients with thymoma. The advantages and disadvantages of each imaging modality were discussed. Currently, CT is the cross-sectional modality of choice for imaging thymoma. Whether MRI and/or PET-CT will play an increasing role in this disease remains to be seen. Hopefully, collaborative international studies48 will improve our understanding of this disease and enable us to predict local staging by imaging to individualize patient care before surgery.

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Keywords:

Thymomas; Computed tomography (CT); Chest radiography; Magnetic resonance imaging; Nuclear medicine

© 2010International Association for the Study of Lung Cancer

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