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Imaging findings of expansile lesions of the thymus
Imaging Findings of Expansile Lesions of the Thymus Carlos S. Restrepo, MD, Meenakshi Pandit, MD, MBA, Isabel C. Rojas, MD, Miguel A. Villamil, MD, Hernan Gordillo, MD, Diego Lemos, MD, Luciano Mastrogiovanni, MD, and Lisa Diethelm, MD
The purpose of this article is to review the imaging findings of the different expansile lesions of the thymus. Almost 50% of all mediastinal masses are located in the anterior mediastinum. The thymus is the most common site of origin of these masses. Several kinds of lesions can arise from this gland because it derives from the three embryonic germ cell layers. Primary neoplasms of the thymus are thymoma, thymolipomas, carcinoma, carcinoid, primary germ cell tumors, and lymphoma. The latter can also involve the organ in a secondary fashion. Other lesions that cause thymic enlargement and that can be confused with neoplasia are thymic cysts and thymic hyperplasia. Even though anterior mediastinal masses are first found on conventional radiographs, computed tomography and magnetic resonance are very useful additional studies for assessing the origin and extension of these masses. The basic concepts regarding embryology, anatomy, and histology relevant for the differential diagnosis of an enlarged thymic gland are also described.
Embryologically, the paired primordial of the thymus (epithelial portion) develops from the ventral wings of the bilateral third and probably 4th brachial pouches, which start to differentiate at the 5th to 6th week of gestational life. When the thymus loses its connection with the pharynx at week 7, it begins to migrate caudally and medially to its normal position into the anterior mediastinum below the left brachiocephalic vein. The normal thymus is bi-lobed and triangularshaped in cross-section (like an arrowhead).1,2 How-
From the Department of Radiology, Louisiana State University, Health Sciences Center, New Orleans, LA. Reprint requests: Carlos S. Restrepo, MD, Department of Radiology, Louisiana State University, Health Sciences Center, 1542 Tulane Avenue, Room 212, New Orleans, LA 70112. E-mail: [email protected]. Curr Probl Diagn Radiol 2005;34:22-34. © 2005 Elsevier Inc. All rights reserved. 0363-0188/2005/$30.00 ⫹ 0 doi:10.1067/j.cpradiol.2004.10.001
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ever, it may have a variable appearance on radiological studies. Histologically, the organ is composed of lymphocytes, epithelial cells, and bare myxoid cells that are distributed in the cortex and medulla. From birth until 2 years of age, the thymus almost completely fills the anterior mediastinum, recognizable on chest radiographs, with some features listed in Table 1. It continues growing until puberty when it attains its maximum size. Thereafter, it gradually diminishes in size and is often visible on computed tomography (CT) as a soft-tissue structure up until the 40s, when it starts to involute, becoming fatty and fibrous by about age 60.3,4 Most commonly, the gland is homogeneous. However, when it is being replaced by fat, it may show a lobular and speckled appearance.5,6 Features of the normal thymus on magnetic resonance (MR) images change depending on the age and the pulse sequence employed. In young patients, it is homogeneous, of low signal intensity but slightly greater than that of muscle on T1-weighted images (T1WI), and of high signal intensity on T2-weighted images (T2WI) approaching that of fat.6,7 An important indicator of pathology of the gland is its thickness of the left lobe, which is measured perpendicular to the axis of the aortic arch. Normally, in patients younger than 20 years, its maximum dimension is 18 mm, and after 20 years, its maximum dimension is 13 mm. Changes in the shape and heterogeneity are also important signs of abnormality, since an enlarged thymus has convex and lobulated margins, is heterogeneous, and frequently produces mass effect.7-10
Thymic Hyperplasia There are two different histological types: true thymic hyperplasia and lymphoid hyperplasia. True
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TABLE 1. Characteristics of the thymus on plain chest radiographs1 Notch sign Sail sign
Wave sign
Indentation at the junction of the thymus and the heart. Unilateral or bilateral. Triangular density of thymic tissue extending from the superior mediastinum. Usually right-sided. Rippled border of the thymus due to the indentation of the anterior ribs on the soft thymic tissue. Usually on the left.
thymic hyperplasia involves the cortex and the medulla; it presents as a diffuse and symmetric enlargement of the gland and is histologically normal (Fig 1).1,4 It can be spontaneous or secondary to different stress situations, such as recovering from an acute illness or corticosteroid therapy, and after radiation or chemotherapy. This condition has been termed “thymic rebound.”2 Such thymic rebound may simulate neoplastic degeneration or recurrent disease; however, it normally decreases in size after a certain time.4 Thymic hyperplasia may also occur associated with idiopathic thyromegaly, Grave’s disease, thyrotoxicosis, acromegaly, and red cell aplasia.4,9,11,12 Thymic lymphoid follicular hyperplasia is characterized by normal size and weight of the gland, with proliferation of lymphoid follicles with active germinal centers in the medulla. There is also an increase in the number of lymphocytes and epithelial cells and accelerated antibody production.4,13 This is more common than true hyperplasia and is highly associated with myasthenia gravis (MG). Almost 65% of patients with MG have lymphoid hyperplasia, 15% have thymoma, and 20% present with an involute or normal thymus.14 Thymic lymphoid follicular hyperplasia has also been associated with other autoimmune and endocrine diseases such as systemic lupus erythematosus, rheumatoid arthritis, thyrotoxicosis, and Addison’s disease, among others.1,4 On cross-sectional images, there are no specific characteristics for this condition. It presents as diffuse enlargement of the gland with shape preservation (Fig 2). Attenuation on CT and signal intensity on MR do not differ from those of the normal thymus (Figs 3 and 4). Lymphoid hyperplasia is difficult to differentiate from the normal thymus since these patients usually have a grossly normal gland. However, it can present as a mass up to 5 cm in diameter, making it important to differentiate it
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FIG 1. Thymic hyperplasia demonstrated on a PA chest radiograph in a 44-year-old female patient appearing as a triangular opacity in the right mid hemithorax (arrows).
FIG 2. Thymic hyperplasia in a 3-year-old child. Axial T1-weighted MR image of the chest demonstrate diffuse homogeneous hypointense enlargement of the thymus (arrows).
from a thymoma.4,9,11,13 The use of intravenous iodinated contrast in patients with MG is not contraindicated, but extra care is advised because at least one report mentions increased respiratory muscle weakness attributed to contrast infusion.14 Thymic hyperplasia may also be gallium-avid when evaluated on nuclear scan.4
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FIG 3. Thymic hyperplasia demonstrated on axial contrast-enhanced CT appearing as a lobulated heterogeneous soft-tissue mass in the anterior mediastinum.
Thymic Cysts Thymic cysts are uncommon mediastinal lesions representing barely 3% of all anterior mediastinal masses. The cysts can be congenital or acquired. Congenital thymic cysts may be present at any point along the pathway of the thymus migration during embryologic development and are thought to arise from a remnant of the thymopharyngeal duct. They are usually unilocular, thin-walled with thymic tissue in their lining, and filled with a clear fluid, without inflammatory changes.4,10,15 Acquired cysts are the most common form of thymic cysts. They are secondary to inflammatory, degenerative, or neoplastic diseases and are typically multilocular, hence the name “multilocular thymic cysts.” They have thicker walls containing turbid fluid or gelatinous material and measure 3 to 17 cm in diameter. They result from cystic dilation, fibrosis, or degeneration of Hassal corpuscles or glandular epithelium. Multilocular thymic cysts are associated with human immunodeficiency virus (HIV) infection, thymic neoplasms, such as thymoma, lymphoma, and carcinoma, following radiation therapy for Hodgkin’s disease, Sjögren syndrome, MG, and aplastic anemia.1,2,4,11,15,16 However, they may be idiopathic as well.15 Patients with HIV may present with other concomitant thymic abnormalities such as dysplasia, premature involution, and thymitis.16 Thymic cysts are most often asymptomatic and discovered incidentally on chest radiograph. However, they may present with pleuritic chest pain, usually due to spontaneous hemorrhage of the cyst.11
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FIG 4. Thymic hyperplasia. (A) Axial T1-weighted MR image of the chest demonstrates an intermediate signal intensity mass located anterior to the ascending aorta (arrows). (B) Sagittal T1-weighted MR image clearly demarcates the limits of the lesion.
On CT, they appear as well-circumscribed unilocular or multilocular homogeneous masses with septations and attenuation of water, although it may be heterogeneous and with high attenuation if hemorrhage is present. The wall of congenital cysts may be very thin, barely visible on CT examination. The presence of calcifications is rare in these kinds of cysts, but has been reported in the literature (Fig 5).2,4,10,11,13 On MR imaging, the cysts show diverse signal intensity depending on the kind of fluid they contain. When the fluid has low protein content, the cysts present low signal intensity on T1WI and high signal intensity on T2WI. Conversely, cysts filled with hemorrhagic or highly proteinaceous fluid show high signal intensity on both T1WI and T2WI. MR is more
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FIG 5. (A and B) Thymic cyst demonstrated on selected axial images from a noncontrast helical CT of the chest reveal a low density lesion in the anterior mediastinum to the left of the midline; lesion has linear calcifications. (C) Contrast-enhanced CT demonstrates a nonenhancing central area within the lesion. (D) Photomicrograph shows thymic tissue (Hassal’s corpuscle) with the typical architecture of a multilocular thymic cyst. (Color version of figure is available online.)
useful than CT when addressing such cysts, since they may appear solid on the latter (Fig 6).9,10,17,18
Thymoma Thymoma is the most common primary neoplasm of the anterior mediastinum and the most common primary tumor of the thymus.19 This tumor affects men and women equally and usually presents after 40 years of age; it is rare in children. Thymomas are derived from thymic epithelial cells. When they arise in the cortex, they are of ectodermal origin, but when they originate from the medulla, they are of endodermal origin. There are several classifications of thymomas in the published literature, based on histologic and immunophenotypic resemblance to cortical or medullary areas of the thymus. The
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recently published World Health Organization (WHO) classification of thymomas divides them into six categories: type A (medullary thymoma); type AB (mixed thymoma); type B1 (predominantly cortical thymoma); type B2 (cortical thymoma); type B3 (well-differentiated thymic carcinoma); and type C (thymic carcinoma). The first two types are considered benign, and the rest demonstrate either malignant features or behavior.20 The benign types are the most common. They can be solid and encapsulated; in approximately onethird of the cases, they invade the adjacent mediastinal fat, pleura, pericardium, great vessels, heart, or lung, receiving the name of invasive thymoma. Despite this invasive behavior, they histologically lack the features of malignancy, hence the name invasive but not malignant. Pleural and pericardial
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FIG 6. Multilocular thymic cyst. (A) Axial T1-weighted image after gadolinium injection demonstrates the fluid contents of low signal intensity. (B) Axial balanced FFE and (C) coronal balanced FFE images delineated a multicystic lesion, adjacent to the right cardiophrenic angle, with high signal intensity of its fluid contents. The multiple septations are clearly identified (arrows).
implants, extension through the diaphragm to the abdomen and lymphatic, and hematogenous metastases to liver, lymph nodes, bone, kidneys, and brain may occur.2,21-23 Although usually found in the anterior mediastinum, thymomas may be located anywhere from the neck to the cardiophrenic angle and, less frequently, in other mediastinal compartments. They are slow growing and have variable sizes, ranging from a few millimeters up to 34 cm, with a mean of 5 to 10 cm at the time of diagnosis. These tumors are round or ovoid
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and septated; their surface may be smooth or lobulated. Occasionally areas of necrosis and hemorrhage can be found within the tumor, which sometimes gives rise to cyst formation or degeneration found in approximately 40% of the cases.23,24 Most patients are asymptomatic and are diagnosed on routine chest radiograph. However, nearly one-third present with symptoms related to compression or invasion of adjacent structures. Recurrent respiratory infections can be another clinical manifestation of this tumor. It is also associated
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FIG 7. Benign lymphocytic thymoma in a 50-year-old male presenting with chest pain. (A) PA and (B) lateral chest radiographs demonstrate a prominent anterior lobulated soft-tissue mass in the right hemithorax in contact with the right heart border, and with no obvious pleural thickening or fluid. (C) Noncontrast CT of the chest and (D) contrast-enhanced helical CT at the level of the pulmonary hila demonstrate a homogeneous soft-tissue mediastinal mass, with little enhancement, compressing the right pulmonary artery, and mediastinal structures. A small amount of pleural fluid is seen posteriorly.
with paraneoplastic syndromes such as myasthenia gravis, red blood cell aplasia, and hypogammaglobulinemia. Thirty to fifty percent of the patients with thymoma develop MG, but only 15% of patients with MG have a thymoma. From patients with red cell aplasia, approximately 50% have a thymoma, and 5% of patients with thymoma develop red cell aplasia. Up to 10% of patients with thymoma have hypogammaglobulinemia, and onethird has pure red cell aplasia. Thymomas are also
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associated with connective tissue disorders such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, and myocarditis, among others. In addition, unusual infections are associated with thymomas. These include multifocal leukoencephalopathy, disseminated herpes, listeria, and cryptococcal meningitis, and candidiasis. Almost 20% of patients with thymoma present with other concomitant malignancy, most commonly lymphoma, and lung or thyroid neoplasms.4,21,25,26
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Chest radiographs demonstrate a mass in the anterior mediastinum in 45 to 80% of the patients. If the tumor is small, the chest radiograph may be completely normal. Eighty percent of the cases present with a portion of the tumor projecting over one of the pulmonary hila, which may be mistaken as a pulmonary outflow tract or part of the heart border, simulating cardiac enlargement. Lateral radiographs can aid in demonstrating the mass and differentiating it from the vascular structures.21,23,26 The tumor appears as a well-defined, rounded, or lobulated mass that usually involves one lobe protruding into one hemithorax, although it may grow through both sides (Fig 7). Calcification in the tumor capsule or within the mass can be seen in up to 40% of patients with thymoma, mainly in the invasive type. The calcification may be curvilinear, rim-like and peripheral, or punctuate in appearance.21,23,25,27 CT is more definitive in the diagnosis of thymomas. It may detect masses that are not seen on conventional chest radiographs. Thymomas are typically well-defined, spherical, oval, or lobulated homogeneous soft-tissue masses that usually enhance after injection of contrast media. However, they can also present with heterogeneous areas of low attenuation secondary to hemorrhage, necrosis, or cyst formation. They can be completely or partially outlined by fat; if the mediastinal fat is preserved, it is an unequivocal sign of noninvasion. Highly suggestive signs of capsular invasion include irregular interface with the adjacent lung, irregular tumor margins, midline crossing, encroachment of vascular structures, and encasement of mediastinal structures. Pleural effusion is uncommon, even with extensive pleural involvement. Inclusion of the upper abdomen in the evaluation for thymomas is important to rule out transdiaphragmatic invasion of the tumor.4,21,22,23,25 Large size of the tumor, multifocal calcifications, and necrotic foci are characteristics more commonly seen with invasive thymomas.27 These tumors may cause irregularity of the lung surface as they invade along the parietal pleura. They typically manifest as unilateral pleural thickening or pleural masses, which may mimic malignant mesothelioma or adenocarcinoma metastatic to the pleura (Fig 8).23 All of these features of invasion are more rapidly and accurately identified on CT than on chest radiographs. On MRI, the signal characteristics of thymomas are similar to that of normal thymus. They can present as oval, round, or lobulated masses with intermediate signal intensity on T1WI, slightly higher than that of skeletal muscle, and high signal intensity, approaching that of fat, on T2WI. En-
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FIG 8. Malignant thymoma in a 62-year-old woman. Contrast-enhanced helical CT of the chest shows an anterior mediastinal mass with inhomogeneous enhancement; the presence of pericardial fluid and pleural effusion are findings suggestive of the malignant nature of this tumor.
hancement after gadolinium injection is usually homogeneous, although areas of hemorrhage, necrosis, and cystic degeneration can give a heterogeneous appearance to the mass. Internal septations may also be seen on T2WI. MR can best depict the mediastinal spread of invasive thymomas because of its multiplanar capability and high contrast resolution (Figs 9 and 10).4,9,18,21,23,28
Thymolipoma Thymolipoma is an unusual benign mediastinal mass composed of thymic and adipose tissue that accounts for 2 to 9% of all thymic tumors. It presents equally in men and women with a wide range of age distribution (2 to 60 years); however, there is predominance in young adults. Almost half of patients are asymptomatic, and the tumor is discovered on routine chest radiographs. Patients who present with symptoms are usually related to compression of adjacent structures by the tumor. Thymolipomas are lobulated, pliable, encapsulated tumors that may reach large sizes and weigh over 500 g (70% of the cases). They are usually located in the anterior mediastinum. It grows downward in a pedunculary fashion toward the diaphragm, covering the heart or insinuating itself between the lungs, mediastinum, heart, and diaphragm. Other possible but uncommon locations for this tumor are the anterosuperior mediastinum and the posterior mediastinum. Malignant transformation or invasion has not
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FIG 9. Benign thymoma in a 60-year-old female patient with myasthenia gravis. (A) Axial T1-weighted MR image of the chest demonstrates a round intermediate signal intensity mass surrounded by mediastinal fat in the right cardiophrenic angle (arrows). (B) Gross specimen after surgical resection. (Color version of figure is available online.)
been reported; however, they may adhere to the pericardium or pleura. This tumor is rarely associated with paraneoplastic syndromes such as MG.2,4,29,30 On chest radiographs, a typically bulky, pendulous, teardrop-shaped, radiolucent mass occupying the anterior inferior mediastinum can be observed. It may mimic cardiomegaly on PA films or elevation of the hemidiaphragm on lateral radiographs, but visualizing the diaphragm through the mass is useful to confirm the diagnosis. In addition, the tumor may change its shape with changes in the patient position.2,4,25,29,30 CT findings of thymolipoma correspond to a fatcontaining mass with strands, whorls, or rounded areas of soft tissue embedded in this fat (Fig 11). They usually contain equal amounts of fat and soft tissue; however, some cases show fat predominance simulating mediastinal lipoma.25,29,30 An important clue for differentiating them is to look for the connection
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FIG 10. Benign thymoma. MR of the chest. (A) Axial T1-weighted image demonstrates an oval to round soft-tissue mass seen in the anterior mediastinum with intermediate to high signal intensity producing extrinsic compression of the right atrium. (B) Coronal T1-weighted image demonstrates the extension of the mass to the right cardiophrenic angle.
between the mass and the normal position of the thymus. Although calcifications have been seen in histological examination of thymolipomas, it is unusual to visualize on radiologic examinations, with only one reported case in the literature.29 The typical features of thymolipomas in MR evaluation are of masses of high signal intensity equal to fat on T1WI and T2WI with areas of intermediate signal intensity corresponding to fibrous or thymic tissue.9,18
Thymic Carcinoma Thymic carcinoma is a malignant epithelial tumor with loss of the organotypical features and cytologic atypia.
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FIG 12. Thymic carcinoma in a 70-year-old female patient with chest pain. Contrast-enhanced CT of the chest reveals an inhomogeneous enhancing mass in the anterior mediastinum.
FIG 11. Thymolipoma. (A) Contrast-enhanced CT of the chest reveals the presence of a fatty density mass in the anterior mediastinum, with some ill-defined whorls of soft-tissue density within the mass. (B) Photograph of the specimen in cross-section. Note the extensive fatty tissue within this thymolipoma is seen as low attenuation similar to subcutaneous fat. (Color version of figure is available online.)
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The most common histological types are squamous cell carcinoma and lymphoepithelioma-like carcinoma.25 There is a variety of these tumors that present with mild cytologic atypia, but has preserved organotypical features of the normal thymus. This variety of tumors is commonly termed “atypical thymoma” and, as previously mentioned, are classified as well-differentiated thymic carcinoma (types B3 and C according to the WHO classification).20,31 Thymic carcinoma is an uncommon and highly aggressive tumor, with strong propensity to local invasion, that metastasizes to regional lymph nodes and distant sites such as lung, bone, liver, and brain. It usually presents at the age of 50 years, with slightly greater prevalence in men. Symptoms of mediastinal compression, invasion, or distant metastases (50-65% of patients) can be the initial manifestations. This neoplasm is rarely associated with paraneoplastic syndromes such as MG. Exceptions to this are atypical thymomas, which are associated with this syndrome with the same frequency as thymomas are, suggesting that normal thymic tissue is probably a prerequisite for development of MG.4,9,31 Radiological evaluation of the tumor shows a large, poorly defined, anterior mediastinal mass, associated with intrathoracic adenopathy, vascular invasion, and pleural and pericardial effusions.9,25 On CT, the tumor appears as a mass with irregular margins with areas of low attenuation related to necrosis, hemorrhage, or cystic degeneration and may show curvilinear and punctuate calcifications4,31 (Figs 12 and 13). Intermediate signal intensity on T1W1 and high signal intensity on T2WI are typical findings on MR; however, if hemorrhage or necrosis is present, heterogeneous signal intensity on
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FIG 13. Thymic carcinoma extending to the right atrium. (A) Axial images from a contrast-enhanced CT scan of the chest at different levels demonstrate tumoral tissue in the anterior mediastinum with partial occlusion of the SVC (arrow). (B and C) The invasive tumor extends through the SVC lumen into the right atrium (arrow). Pleural fluid is seen in the right posterior costophrenic angle.
both sequences is found. MR is a useful tool in identifying local and vascular invasion by the tumor.4,9 According to Jung and coworkers, invasion of the great vessels, lymph node enlargement, extrathymic metastases, and phrenic nerve palsy are seen in patients with thymic carcinoma and not in atypical thymoma, helping to differentiate one from another (Fig 14).31
Thymic Carcinoid Carcinoids usually involve the gastrointestinal tract and lungs and rarely affect the thymus. Thymic carcinoids are highly aggressive neoplasms, histologically similar to atypical bronchial carcinoids. Typically, they affect men between 40 and 60 years of age. Almost 50% are encapsulated and well-circumscribed masses that may show areas of necrosis, with a size of 6 to 20 cm, and usually invade adjacent tissues. Up to 50% are functionally active and manifest themselves
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as an endocrinopathy. Among them, Cushing’s syndrome is the most frequently encountered (33-40% of the cases). Other associated syndromes include multiple endocrine neoplasia types 1 and 2, inappropriate secretion of antidiuretic hormone, polymyositis, and myocarditis. Interestingly, carcinoid syndrome has not been reported in association with this neoplasm. Patients can also present with signs and symptoms of invasion or compression of mediastinal structures, metastases to regional lymph nodes, or distant sites such as skin, adrenal glands, bone, lung, pleura, brain, and kidney, in 20% of the cases.4,25,32 One-third of the patients are asymptomatic. On chest radiographs, these tumors appear as large mediastinal masses. CT demonstrates an irregular soft-tissue mass with heterogeneous enhancement after contrast administration, which may present with calcifications or invading adjacent structures. These findings make it very difficult to distinguish these
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FIG 14. Metastasic thymic carcinoma. (A-D) Transverse contrast-enhanced CT of the chest illustrates both metastatic lesions infiltrating the posterior wall of the left atrium (long arrows) as well as the pericardium (short arrows) associated with pleural and pericardial effusion.
tumors from a thymoma. CT and MR may be helpful in identifying masses in cases of asymptomatic patients (Fig 15).4,25,32
Thymic Lymphoma Hodgkin’s disease and non-Hodgkin’s lymphomas may affect the gland primarily or secondarily through infiltration from the mediastinal lymph nodes. Despite the fact that Hodgkin’s disease is less common than non-Hodgkin’s lymphoma, it affects the thymus and mediastinum more frequently. Ten to forty percent of the patients with
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Hodgkin’s disease have involvement of the thymus. Histologically, nodular sclerosing Hodgkin’s disease is the most common type that involves the mediastinum and the thymus, while large B cell lymphoma and lymphocytic lymphoma are the most common non-Hodgkin’s types.1,4 On imaging studies, primary thymic lymphoma appears as a discrete or lobulated mass with associated intrathoracic adenopathy that may show mass effect or invasion of mediastinal structures. It has typically homogeneous low attenuation, although sometimes it can appear heterogeneous secondary to necrosis, hemorrhage, or cystic changes (Fig 16). Presence of
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FIG 15. Thymic carcinoid in a 70-year-old male with pulmonary embolism, in a patient who also had brain metastases. Contrastenhanced helical CT of the chest demonstrates the tumor in the anterior mediastinum, and the filling defect in the right pulmonary artery from the pulmonary embolus (arrow).
calcifications is rare, and if they are seen, is usually secondary to treatment. On MR, the findings are similar to thymoma: low signal intensity on T1WI and high signal intensity on T2WI. In this last sequence, the tumor may show heterogeneity due to dense fibrosis (low signal intensity), edema, inflammation, and necrosis or cyst formation (high signal intensity).4,18,19 After completion of therapy, thymic enlargement can be secondary to recurrent lymphoma, thymic hyperplasia, or thymic cyst.4 MR is more accurate than CT in the follow-up and evaluation of the tumor after therapy, since slight changes in signal intensity within the tumor and surrounding tissues are frequently observed. However, it is still difficult to differentiate between recurrent tumor and benign residual fibrosis.19
Conclusion This article provides an overview of abnormal imaging findings of the thymus and gives a systematic approach to the differential diagnosis of the various expansile lesions affecting this gland. Thymic lesions, especially thymoma, correspond to the most common anterior mediastinal masses. They may be found incidentally on radiological examinations performed for other purposes, or they may manifest themselves by compressing adjacent structures. For an accurate evaluation of a thymic lesion, CT scan, or preferably MRI
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FIG 16. Sclerosing lymphoma of the mediastinum in a 19-year-old male patient. (A and B) Contrast-enhanced helical CT of the chest demonstrates inhomogeneous enhancement of the mediastinal mass with compression of the trachea. Patient presented with superior vena cava syndrome. Note the increased diameter and collateral flow through the azygos vein (arrows).
scan, of the chest must be performed to characterize the tumor and evaluate tumoral invasion or extension to the adjacent structures. Although the imaging methods cannot provide a definitive diagnosis, they can certainly aid in diminishing the differential diagnosis of a thymic lesion and in planning further treatment for these tumors.
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19. Santana L, Givica A, Camacho C. Thymoma. Radiographics 2002;22:S95-S102. 20. Chan J. Tumors of the lymphoreticular system, including spleen and thymus. In: Fletcher C. Diagnostic Histopathologic of Tumors, vol. 2, 2nd ed. Philadelphia, PA: Churchill Livingstone, 2000. p. 1270-95. 21. Morgenthaler TI, Brown LR, Colby TV, et al. Thymoma. Mayo Clin Proc 1993;68:1110-23. 22. Ros PR, Rosado-de-Christenson ML, Buetow PC, et al. Image interpretation session: 1997. Invasive thymoma with mediastinal, pleural, and transdiaphragmatic extension producing myasthenia gravis. Radiographics 1998;18:195-9. 23. Rosado-de-Christenson ML, Galobardes J, Moran CA. Thymoma: radiologic-pathologic correlation. Radiographics 1992;12:151-68. 24. Suster S, Rosai J. Cystic thymomas. A clinicopathologic study of ten cases. Cancer 1992;69:92-7. 25. Strollo DC, Rosado-de-Christenson ML, Jett JR. Primary mediastinal tumors. Part 1 tumors of the anterior mediastinum. Chest 1997;112:511-22. 26. Loehrer PJ, Wick MR. Thymic malignancies. Cancer Treat Res 2001;105:277-302. 27. Tomiyama N, Müller NL, Ellis SJ, et al. Invasive and noninvasive thymoma: distinctive CT features. J Comput Assist Tomogr 2001;25:388-93. 28. Camera L, Brunetti A, Romano M, et al. Morphological imaging of thymic disorders. Ann Med 1999;31(Suppl 2):57-62. 29. Rosado-de-Christenson ML, Pugatch RD, Moran CA, et al. Thymolipoma: analysis of 27 cases. Radiology 1994;193: 121-6. 30. Casullo J, Palayew MJ, Lisbona A. General case of the day. Radiographics 1992;12:1250-4. 31. Jung KJ, Lee KS, Han J, et al. Malignant thymic epithelial tumors: CT-pathologic correlation. Am J Roentgenol 2001; 176:433-9. 32. Rosado-de-Christenson ML, Abbott GF, Kirejczyk WM, et al. Thoracic carcinoids: radiologic-pathologic correlation. Radiographics 1999;19:707-36.
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The purpose of this article is to review the imaging findings of the different expansile lesions of the thymus. Almost 50% of all mediastinal masses are located in the anterior mediastinum. The thymus is the most common site of origin of these masses. Several kinds of lesions can arise from this gland because it derives from the three embryonic germ cell layers. Primary neoplasms of the thymus are thymoma, thymolipomas, carcinoma, carcinoid, primary germ cell tumors, and lymphoma. The latter can also involve the organ in a secondary fashion. Other lesions that cause thymic enlargement and that can be confused with neoplasia are thymic cysts and thymic hyperplasia. Even though anterior mediastinal masses are first found on conventional radiographs, computed tomography and magnetic resonance are very useful additional studies for assessing the origin and extension of these masses. The basic concepts regarding embryology, anatomy, and histology relevant for the differential diagnosis of an enlarged thymic gland are also described.
Embryologically, the paired primordial of the thymus (epithelial portion) develops from the ventral wings of the bilateral third and probably 4th brachial pouches, which start to differentiate at the 5th to 6th week of gestational life. When the thymus loses its connection with the pharynx at week 7, it begins to migrate caudally and medially to its normal position into the anterior mediastinum below the left brachiocephalic vein. The normal thymus is bi-lobed and triangularshaped in cross-section (like an arrowhead).1,2 How-
From the Department of Radiology, Louisiana State University, Health Sciences Center, New Orleans, LA. Reprint requests: Carlos S. Restrepo, MD, Department of Radiology, Louisiana State University, Health Sciences Center, 1542 Tulane Avenue, Room 212, New Orleans, LA 70112. E-mail: [email protected]. Curr Probl Diagn Radiol 2005;34:22-34. © 2005 Elsevier Inc. All rights reserved. 0363-0188/2005/$30.00 ⫹ 0 doi:10.1067/j.cpradiol.2004.10.001
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ever, it may have a variable appearance on radiological studies. Histologically, the organ is composed of lymphocytes, epithelial cells, and bare myxoid cells that are distributed in the cortex and medulla. From birth until 2 years of age, the thymus almost completely fills the anterior mediastinum, recognizable on chest radiographs, with some features listed in Table 1. It continues growing until puberty when it attains its maximum size. Thereafter, it gradually diminishes in size and is often visible on computed tomography (CT) as a soft-tissue structure up until the 40s, when it starts to involute, becoming fatty and fibrous by about age 60.3,4 Most commonly, the gland is homogeneous. However, when it is being replaced by fat, it may show a lobular and speckled appearance.5,6 Features of the normal thymus on magnetic resonance (MR) images change depending on the age and the pulse sequence employed. In young patients, it is homogeneous, of low signal intensity but slightly greater than that of muscle on T1-weighted images (T1WI), and of high signal intensity on T2-weighted images (T2WI) approaching that of fat.6,7 An important indicator of pathology of the gland is its thickness of the left lobe, which is measured perpendicular to the axis of the aortic arch. Normally, in patients younger than 20 years, its maximum dimension is 18 mm, and after 20 years, its maximum dimension is 13 mm. Changes in the shape and heterogeneity are also important signs of abnormality, since an enlarged thymus has convex and lobulated margins, is heterogeneous, and frequently produces mass effect.7-10
Thymic Hyperplasia There are two different histological types: true thymic hyperplasia and lymphoid hyperplasia. True
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TABLE 1. Characteristics of the thymus on plain chest radiographs1 Notch sign Sail sign
Wave sign
Indentation at the junction of the thymus and the heart. Unilateral or bilateral. Triangular density of thymic tissue extending from the superior mediastinum. Usually right-sided. Rippled border of the thymus due to the indentation of the anterior ribs on the soft thymic tissue. Usually on the left.
thymic hyperplasia involves the cortex and the medulla; it presents as a diffuse and symmetric enlargement of the gland and is histologically normal (Fig 1).1,4 It can be spontaneous or secondary to different stress situations, such as recovering from an acute illness or corticosteroid therapy, and after radiation or chemotherapy. This condition has been termed “thymic rebound.”2 Such thymic rebound may simulate neoplastic degeneration or recurrent disease; however, it normally decreases in size after a certain time.4 Thymic hyperplasia may also occur associated with idiopathic thyromegaly, Grave’s disease, thyrotoxicosis, acromegaly, and red cell aplasia.4,9,11,12 Thymic lymphoid follicular hyperplasia is characterized by normal size and weight of the gland, with proliferation of lymphoid follicles with active germinal centers in the medulla. There is also an increase in the number of lymphocytes and epithelial cells and accelerated antibody production.4,13 This is more common than true hyperplasia and is highly associated with myasthenia gravis (MG). Almost 65% of patients with MG have lymphoid hyperplasia, 15% have thymoma, and 20% present with an involute or normal thymus.14 Thymic lymphoid follicular hyperplasia has also been associated with other autoimmune and endocrine diseases such as systemic lupus erythematosus, rheumatoid arthritis, thyrotoxicosis, and Addison’s disease, among others.1,4 On cross-sectional images, there are no specific characteristics for this condition. It presents as diffuse enlargement of the gland with shape preservation (Fig 2). Attenuation on CT and signal intensity on MR do not differ from those of the normal thymus (Figs 3 and 4). Lymphoid hyperplasia is difficult to differentiate from the normal thymus since these patients usually have a grossly normal gland. However, it can present as a mass up to 5 cm in diameter, making it important to differentiate it
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FIG 1. Thymic hyperplasia demonstrated on a PA chest radiograph in a 44-year-old female patient appearing as a triangular opacity in the right mid hemithorax (arrows).
FIG 2. Thymic hyperplasia in a 3-year-old child. Axial T1-weighted MR image of the chest demonstrate diffuse homogeneous hypointense enlargement of the thymus (arrows).
from a thymoma.4,9,11,13 The use of intravenous iodinated contrast in patients with MG is not contraindicated, but extra care is advised because at least one report mentions increased respiratory muscle weakness attributed to contrast infusion.14 Thymic hyperplasia may also be gallium-avid when evaluated on nuclear scan.4
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FIG 3. Thymic hyperplasia demonstrated on axial contrast-enhanced CT appearing as a lobulated heterogeneous soft-tissue mass in the anterior mediastinum.
Thymic Cysts Thymic cysts are uncommon mediastinal lesions representing barely 3% of all anterior mediastinal masses. The cysts can be congenital or acquired. Congenital thymic cysts may be present at any point along the pathway of the thymus migration during embryologic development and are thought to arise from a remnant of the thymopharyngeal duct. They are usually unilocular, thin-walled with thymic tissue in their lining, and filled with a clear fluid, without inflammatory changes.4,10,15 Acquired cysts are the most common form of thymic cysts. They are secondary to inflammatory, degenerative, or neoplastic diseases and are typically multilocular, hence the name “multilocular thymic cysts.” They have thicker walls containing turbid fluid or gelatinous material and measure 3 to 17 cm in diameter. They result from cystic dilation, fibrosis, or degeneration of Hassal corpuscles or glandular epithelium. Multilocular thymic cysts are associated with human immunodeficiency virus (HIV) infection, thymic neoplasms, such as thymoma, lymphoma, and carcinoma, following radiation therapy for Hodgkin’s disease, Sjögren syndrome, MG, and aplastic anemia.1,2,4,11,15,16 However, they may be idiopathic as well.15 Patients with HIV may present with other concomitant thymic abnormalities such as dysplasia, premature involution, and thymitis.16 Thymic cysts are most often asymptomatic and discovered incidentally on chest radiograph. However, they may present with pleuritic chest pain, usually due to spontaneous hemorrhage of the cyst.11
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FIG 4. Thymic hyperplasia. (A) Axial T1-weighted MR image of the chest demonstrates an intermediate signal intensity mass located anterior to the ascending aorta (arrows). (B) Sagittal T1-weighted MR image clearly demarcates the limits of the lesion.
On CT, they appear as well-circumscribed unilocular or multilocular homogeneous masses with septations and attenuation of water, although it may be heterogeneous and with high attenuation if hemorrhage is present. The wall of congenital cysts may be very thin, barely visible on CT examination. The presence of calcifications is rare in these kinds of cysts, but has been reported in the literature (Fig 5).2,4,10,11,13 On MR imaging, the cysts show diverse signal intensity depending on the kind of fluid they contain. When the fluid has low protein content, the cysts present low signal intensity on T1WI and high signal intensity on T2WI. Conversely, cysts filled with hemorrhagic or highly proteinaceous fluid show high signal intensity on both T1WI and T2WI. MR is more
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FIG 5. (A and B) Thymic cyst demonstrated on selected axial images from a noncontrast helical CT of the chest reveal a low density lesion in the anterior mediastinum to the left of the midline; lesion has linear calcifications. (C) Contrast-enhanced CT demonstrates a nonenhancing central area within the lesion. (D) Photomicrograph shows thymic tissue (Hassal’s corpuscle) with the typical architecture of a multilocular thymic cyst. (Color version of figure is available online.)
useful than CT when addressing such cysts, since they may appear solid on the latter (Fig 6).9,10,17,18
Thymoma Thymoma is the most common primary neoplasm of the anterior mediastinum and the most common primary tumor of the thymus.19 This tumor affects men and women equally and usually presents after 40 years of age; it is rare in children. Thymomas are derived from thymic epithelial cells. When they arise in the cortex, they are of ectodermal origin, but when they originate from the medulla, they are of endodermal origin. There are several classifications of thymomas in the published literature, based on histologic and immunophenotypic resemblance to cortical or medullary areas of the thymus. The
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recently published World Health Organization (WHO) classification of thymomas divides them into six categories: type A (medullary thymoma); type AB (mixed thymoma); type B1 (predominantly cortical thymoma); type B2 (cortical thymoma); type B3 (well-differentiated thymic carcinoma); and type C (thymic carcinoma). The first two types are considered benign, and the rest demonstrate either malignant features or behavior.20 The benign types are the most common. They can be solid and encapsulated; in approximately onethird of the cases, they invade the adjacent mediastinal fat, pleura, pericardium, great vessels, heart, or lung, receiving the name of invasive thymoma. Despite this invasive behavior, they histologically lack the features of malignancy, hence the name invasive but not malignant. Pleural and pericardial
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FIG 6. Multilocular thymic cyst. (A) Axial T1-weighted image after gadolinium injection demonstrates the fluid contents of low signal intensity. (B) Axial balanced FFE and (C) coronal balanced FFE images delineated a multicystic lesion, adjacent to the right cardiophrenic angle, with high signal intensity of its fluid contents. The multiple septations are clearly identified (arrows).
implants, extension through the diaphragm to the abdomen and lymphatic, and hematogenous metastases to liver, lymph nodes, bone, kidneys, and brain may occur.2,21-23 Although usually found in the anterior mediastinum, thymomas may be located anywhere from the neck to the cardiophrenic angle and, less frequently, in other mediastinal compartments. They are slow growing and have variable sizes, ranging from a few millimeters up to 34 cm, with a mean of 5 to 10 cm at the time of diagnosis. These tumors are round or ovoid
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and septated; their surface may be smooth or lobulated. Occasionally areas of necrosis and hemorrhage can be found within the tumor, which sometimes gives rise to cyst formation or degeneration found in approximately 40% of the cases.23,24 Most patients are asymptomatic and are diagnosed on routine chest radiograph. However, nearly one-third present with symptoms related to compression or invasion of adjacent structures. Recurrent respiratory infections can be another clinical manifestation of this tumor. It is also associated
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FIG 7. Benign lymphocytic thymoma in a 50-year-old male presenting with chest pain. (A) PA and (B) lateral chest radiographs demonstrate a prominent anterior lobulated soft-tissue mass in the right hemithorax in contact with the right heart border, and with no obvious pleural thickening or fluid. (C) Noncontrast CT of the chest and (D) contrast-enhanced helical CT at the level of the pulmonary hila demonstrate a homogeneous soft-tissue mediastinal mass, with little enhancement, compressing the right pulmonary artery, and mediastinal structures. A small amount of pleural fluid is seen posteriorly.
with paraneoplastic syndromes such as myasthenia gravis, red blood cell aplasia, and hypogammaglobulinemia. Thirty to fifty percent of the patients with thymoma develop MG, but only 15% of patients with MG have a thymoma. From patients with red cell aplasia, approximately 50% have a thymoma, and 5% of patients with thymoma develop red cell aplasia. Up to 10% of patients with thymoma have hypogammaglobulinemia, and onethird has pure red cell aplasia. Thymomas are also
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associated with connective tissue disorders such as systemic lupus erythematosus, rheumatoid arthritis, dermatomyositis, and myocarditis, among others. In addition, unusual infections are associated with thymomas. These include multifocal leukoencephalopathy, disseminated herpes, listeria, and cryptococcal meningitis, and candidiasis. Almost 20% of patients with thymoma present with other concomitant malignancy, most commonly lymphoma, and lung or thyroid neoplasms.4,21,25,26
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Chest radiographs demonstrate a mass in the anterior mediastinum in 45 to 80% of the patients. If the tumor is small, the chest radiograph may be completely normal. Eighty percent of the cases present with a portion of the tumor projecting over one of the pulmonary hila, which may be mistaken as a pulmonary outflow tract or part of the heart border, simulating cardiac enlargement. Lateral radiographs can aid in demonstrating the mass and differentiating it from the vascular structures.21,23,26 The tumor appears as a well-defined, rounded, or lobulated mass that usually involves one lobe protruding into one hemithorax, although it may grow through both sides (Fig 7). Calcification in the tumor capsule or within the mass can be seen in up to 40% of patients with thymoma, mainly in the invasive type. The calcification may be curvilinear, rim-like and peripheral, or punctuate in appearance.21,23,25,27 CT is more definitive in the diagnosis of thymomas. It may detect masses that are not seen on conventional chest radiographs. Thymomas are typically well-defined, spherical, oval, or lobulated homogeneous soft-tissue masses that usually enhance after injection of contrast media. However, they can also present with heterogeneous areas of low attenuation secondary to hemorrhage, necrosis, or cyst formation. They can be completely or partially outlined by fat; if the mediastinal fat is preserved, it is an unequivocal sign of noninvasion. Highly suggestive signs of capsular invasion include irregular interface with the adjacent lung, irregular tumor margins, midline crossing, encroachment of vascular structures, and encasement of mediastinal structures. Pleural effusion is uncommon, even with extensive pleural involvement. Inclusion of the upper abdomen in the evaluation for thymomas is important to rule out transdiaphragmatic invasion of the tumor.4,21,22,23,25 Large size of the tumor, multifocal calcifications, and necrotic foci are characteristics more commonly seen with invasive thymomas.27 These tumors may cause irregularity of the lung surface as they invade along the parietal pleura. They typically manifest as unilateral pleural thickening or pleural masses, which may mimic malignant mesothelioma or adenocarcinoma metastatic to the pleura (Fig 8).23 All of these features of invasion are more rapidly and accurately identified on CT than on chest radiographs. On MRI, the signal characteristics of thymomas are similar to that of normal thymus. They can present as oval, round, or lobulated masses with intermediate signal intensity on T1WI, slightly higher than that of skeletal muscle, and high signal intensity, approaching that of fat, on T2WI. En-
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FIG 8. Malignant thymoma in a 62-year-old woman. Contrast-enhanced helical CT of the chest shows an anterior mediastinal mass with inhomogeneous enhancement; the presence of pericardial fluid and pleural effusion are findings suggestive of the malignant nature of this tumor.
hancement after gadolinium injection is usually homogeneous, although areas of hemorrhage, necrosis, and cystic degeneration can give a heterogeneous appearance to the mass. Internal septations may also be seen on T2WI. MR can best depict the mediastinal spread of invasive thymomas because of its multiplanar capability and high contrast resolution (Figs 9 and 10).4,9,18,21,23,28
Thymolipoma Thymolipoma is an unusual benign mediastinal mass composed of thymic and adipose tissue that accounts for 2 to 9% of all thymic tumors. It presents equally in men and women with a wide range of age distribution (2 to 60 years); however, there is predominance in young adults. Almost half of patients are asymptomatic, and the tumor is discovered on routine chest radiographs. Patients who present with symptoms are usually related to compression of adjacent structures by the tumor. Thymolipomas are lobulated, pliable, encapsulated tumors that may reach large sizes and weigh over 500 g (70% of the cases). They are usually located in the anterior mediastinum. It grows downward in a pedunculary fashion toward the diaphragm, covering the heart or insinuating itself between the lungs, mediastinum, heart, and diaphragm. Other possible but uncommon locations for this tumor are the anterosuperior mediastinum and the posterior mediastinum. Malignant transformation or invasion has not
Curr Probl Diagn Radiol, January/February 2005
FIG 9. Benign thymoma in a 60-year-old female patient with myasthenia gravis. (A) Axial T1-weighted MR image of the chest demonstrates a round intermediate signal intensity mass surrounded by mediastinal fat in the right cardiophrenic angle (arrows). (B) Gross specimen after surgical resection. (Color version of figure is available online.)
been reported; however, they may adhere to the pericardium or pleura. This tumor is rarely associated with paraneoplastic syndromes such as MG.2,4,29,30 On chest radiographs, a typically bulky, pendulous, teardrop-shaped, radiolucent mass occupying the anterior inferior mediastinum can be observed. It may mimic cardiomegaly on PA films or elevation of the hemidiaphragm on lateral radiographs, but visualizing the diaphragm through the mass is useful to confirm the diagnosis. In addition, the tumor may change its shape with changes in the patient position.2,4,25,29,30 CT findings of thymolipoma correspond to a fatcontaining mass with strands, whorls, or rounded areas of soft tissue embedded in this fat (Fig 11). They usually contain equal amounts of fat and soft tissue; however, some cases show fat predominance simulating mediastinal lipoma.25,29,30 An important clue for differentiating them is to look for the connection
Curr Probl Diagn Radiol, January/February 2005
FIG 10. Benign thymoma. MR of the chest. (A) Axial T1-weighted image demonstrates an oval to round soft-tissue mass seen in the anterior mediastinum with intermediate to high signal intensity producing extrinsic compression of the right atrium. (B) Coronal T1-weighted image demonstrates the extension of the mass to the right cardiophrenic angle.
between the mass and the normal position of the thymus. Although calcifications have been seen in histological examination of thymolipomas, it is unusual to visualize on radiologic examinations, with only one reported case in the literature.29 The typical features of thymolipomas in MR evaluation are of masses of high signal intensity equal to fat on T1WI and T2WI with areas of intermediate signal intensity corresponding to fibrous or thymic tissue.9,18
Thymic Carcinoma Thymic carcinoma is a malignant epithelial tumor with loss of the organotypical features and cytologic atypia.
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FIG 12. Thymic carcinoma in a 70-year-old female patient with chest pain. Contrast-enhanced CT of the chest reveals an inhomogeneous enhancing mass in the anterior mediastinum.
FIG 11. Thymolipoma. (A) Contrast-enhanced CT of the chest reveals the presence of a fatty density mass in the anterior mediastinum, with some ill-defined whorls of soft-tissue density within the mass. (B) Photograph of the specimen in cross-section. Note the extensive fatty tissue within this thymolipoma is seen as low attenuation similar to subcutaneous fat. (Color version of figure is available online.)
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The most common histological types are squamous cell carcinoma and lymphoepithelioma-like carcinoma.25 There is a variety of these tumors that present with mild cytologic atypia, but has preserved organotypical features of the normal thymus. This variety of tumors is commonly termed “atypical thymoma” and, as previously mentioned, are classified as well-differentiated thymic carcinoma (types B3 and C according to the WHO classification).20,31 Thymic carcinoma is an uncommon and highly aggressive tumor, with strong propensity to local invasion, that metastasizes to regional lymph nodes and distant sites such as lung, bone, liver, and brain. It usually presents at the age of 50 years, with slightly greater prevalence in men. Symptoms of mediastinal compression, invasion, or distant metastases (50-65% of patients) can be the initial manifestations. This neoplasm is rarely associated with paraneoplastic syndromes such as MG. Exceptions to this are atypical thymomas, which are associated with this syndrome with the same frequency as thymomas are, suggesting that normal thymic tissue is probably a prerequisite for development of MG.4,9,31 Radiological evaluation of the tumor shows a large, poorly defined, anterior mediastinal mass, associated with intrathoracic adenopathy, vascular invasion, and pleural and pericardial effusions.9,25 On CT, the tumor appears as a mass with irregular margins with areas of low attenuation related to necrosis, hemorrhage, or cystic degeneration and may show curvilinear and punctuate calcifications4,31 (Figs 12 and 13). Intermediate signal intensity on T1W1 and high signal intensity on T2WI are typical findings on MR; however, if hemorrhage or necrosis is present, heterogeneous signal intensity on
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FIG 13. Thymic carcinoma extending to the right atrium. (A) Axial images from a contrast-enhanced CT scan of the chest at different levels demonstrate tumoral tissue in the anterior mediastinum with partial occlusion of the SVC (arrow). (B and C) The invasive tumor extends through the SVC lumen into the right atrium (arrow). Pleural fluid is seen in the right posterior costophrenic angle.
both sequences is found. MR is a useful tool in identifying local and vascular invasion by the tumor.4,9 According to Jung and coworkers, invasion of the great vessels, lymph node enlargement, extrathymic metastases, and phrenic nerve palsy are seen in patients with thymic carcinoma and not in atypical thymoma, helping to differentiate one from another (Fig 14).31
Thymic Carcinoid Carcinoids usually involve the gastrointestinal tract and lungs and rarely affect the thymus. Thymic carcinoids are highly aggressive neoplasms, histologically similar to atypical bronchial carcinoids. Typically, they affect men between 40 and 60 years of age. Almost 50% are encapsulated and well-circumscribed masses that may show areas of necrosis, with a size of 6 to 20 cm, and usually invade adjacent tissues. Up to 50% are functionally active and manifest themselves
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as an endocrinopathy. Among them, Cushing’s syndrome is the most frequently encountered (33-40% of the cases). Other associated syndromes include multiple endocrine neoplasia types 1 and 2, inappropriate secretion of antidiuretic hormone, polymyositis, and myocarditis. Interestingly, carcinoid syndrome has not been reported in association with this neoplasm. Patients can also present with signs and symptoms of invasion or compression of mediastinal structures, metastases to regional lymph nodes, or distant sites such as skin, adrenal glands, bone, lung, pleura, brain, and kidney, in 20% of the cases.4,25,32 One-third of the patients are asymptomatic. On chest radiographs, these tumors appear as large mediastinal masses. CT demonstrates an irregular soft-tissue mass with heterogeneous enhancement after contrast administration, which may present with calcifications or invading adjacent structures. These findings make it very difficult to distinguish these
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FIG 14. Metastasic thymic carcinoma. (A-D) Transverse contrast-enhanced CT of the chest illustrates both metastatic lesions infiltrating the posterior wall of the left atrium (long arrows) as well as the pericardium (short arrows) associated with pleural and pericardial effusion.
tumors from a thymoma. CT and MR may be helpful in identifying masses in cases of asymptomatic patients (Fig 15).4,25,32
Thymic Lymphoma Hodgkin’s disease and non-Hodgkin’s lymphomas may affect the gland primarily or secondarily through infiltration from the mediastinal lymph nodes. Despite the fact that Hodgkin’s disease is less common than non-Hodgkin’s lymphoma, it affects the thymus and mediastinum more frequently. Ten to forty percent of the patients with
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Hodgkin’s disease have involvement of the thymus. Histologically, nodular sclerosing Hodgkin’s disease is the most common type that involves the mediastinum and the thymus, while large B cell lymphoma and lymphocytic lymphoma are the most common non-Hodgkin’s types.1,4 On imaging studies, primary thymic lymphoma appears as a discrete or lobulated mass with associated intrathoracic adenopathy that may show mass effect or invasion of mediastinal structures. It has typically homogeneous low attenuation, although sometimes it can appear heterogeneous secondary to necrosis, hemorrhage, or cystic changes (Fig 16). Presence of
Curr Probl Diagn Radiol, January/February 2005
FIG 15. Thymic carcinoid in a 70-year-old male with pulmonary embolism, in a patient who also had brain metastases. Contrastenhanced helical CT of the chest demonstrates the tumor in the anterior mediastinum, and the filling defect in the right pulmonary artery from the pulmonary embolus (arrow).
calcifications is rare, and if they are seen, is usually secondary to treatment. On MR, the findings are similar to thymoma: low signal intensity on T1WI and high signal intensity on T2WI. In this last sequence, the tumor may show heterogeneity due to dense fibrosis (low signal intensity), edema, inflammation, and necrosis or cyst formation (high signal intensity).4,18,19 After completion of therapy, thymic enlargement can be secondary to recurrent lymphoma, thymic hyperplasia, or thymic cyst.4 MR is more accurate than CT in the follow-up and evaluation of the tumor after therapy, since slight changes in signal intensity within the tumor and surrounding tissues are frequently observed. However, it is still difficult to differentiate between recurrent tumor and benign residual fibrosis.19
Conclusion This article provides an overview of abnormal imaging findings of the thymus and gives a systematic approach to the differential diagnosis of the various expansile lesions affecting this gland. Thymic lesions, especially thymoma, correspond to the most common anterior mediastinal masses. They may be found incidentally on radiological examinations performed for other purposes, or they may manifest themselves by compressing adjacent structures. For an accurate evaluation of a thymic lesion, CT scan, or preferably MRI
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FIG 16. Sclerosing lymphoma of the mediastinum in a 19-year-old male patient. (A and B) Contrast-enhanced helical CT of the chest demonstrates inhomogeneous enhancement of the mediastinal mass with compression of the trachea. Patient presented with superior vena cava syndrome. Note the increased diameter and collateral flow through the azygos vein (arrows).
scan, of the chest must be performed to characterize the tumor and evaluate tumoral invasion or extension to the adjacent structures. Although the imaging methods cannot provide a definitive diagnosis, they can certainly aid in diminishing the differential diagnosis of a thymic lesion and in planning further treatment for these tumors.
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