Approaching the Patient with an Anterior Mediastinal Mass: a Guide for Radiologists

ITMIG Definitions and Policies

Approaching the Patient with an Anterior Mediastinal Mass: A Guide for Radiologists

Brett W. Carter, MD,* Meinoshin Okumura, MD,† Frank C. Detterbeck, MD,‡ and Edith M. Marom, MD*

Abstract: Mediastinal masses are relatively uncommon, yet include abnormalities are discovered with increasing frequency due to increased imaging of asymptomatic patients, either for a large variety of entities. Some tumors can be diagnosed with con- 1 fidence based on imaging alone; others when a typical appearance is screening or staging of extrathoracic primary malignancies. combined with the right clinical presentation. A structured approach To address this need, the International Thymic Malignancy for radiologists is presented to facilitate evaluation of patients with Interest Group (ITMIG) began an initiative to develop such anterior mediastinal tumors. The approach focuses first on the more a structured approach. This article represents the output of this project primarily addressed to radiologists; a companion common tumors and on imaging features that strongly suggest a par- 2 ticular diagnosis. Discussion with the clinician can be very helpful in paper focused on the clinician has also been produced. formulating a presumptive diagnosis. This article also discusses that confirmatory imaging or biopsy tests are most beneficial in particular METHODS situations. The algorithm outlined in this document represents a consensus among radiologists and clinicians with a par- Key Words: Mediastinum, Anterior, CT, MRI, PET. ticular interest in anterior mediastinal diseases. The ITMIG (J Thorac Oncol. 2014;9: S110–S118) Education Committee assembled a core workgroup (E.M.M., B.W.C., F.D., and M.O.) to review the existing literature as well as standards for imaging and clinical investigation of ediastinal masses are relatively uncommon. patients with an anterior mediastinal mass. This group drafted MFurthermore, because there is such a wide variety of a proposed approach to the patient presenting with an ante- pathologic entities that can occur in this region, the average rior mediastinal mass. The document was then refined by an radiologist or clinician will encounter many of these specific extended workgroup (Ami Rubinowitz, Wentao Fang, Jeanne lesions only infrequently. Imaging is a critical part of estab- B. Ackman, and Stephen Cassivi). lishing a presumptive diagnosis, which will guide whether and what type of confirmatory testing is needed. When classic fea- GENERAL CONSIDERATIONS tures are present, a presumptive diagnosis can be made with a Slightly more than half of all mediastinal masses are high degree of confidence based on imaging alone. However, located in the anterior mediastinum. One-fourth of medias- the appearance of anterior mediastinal lesions is often less tinal masses are discovered in the middle mediastinum, and specific. Nevertheless, when combined with a typical clinical another one-fourth of masses are found in the posterior medi- presentation, a particular entity can be strongly suggested. astinum.3–11 Assignment of lesions to particular mediastinal Developing an appropriate differential diagnosis for compartments has been quite useful in narrowing the dif- a particular patient can be very useful in avoiding unneces- ferential diagnosis. In the past, this classification was based sary and sometimes misleading biopsies or additional tests. on varying definitions based on the lateral chest radiograph. A framework to guide the image interpretation and addi- A modern, computed tomography (CT)-based definition of tional testing improves the efficiency of the evaluation. This mediastinal compartments has been developed by ITMIG12 is particularly pertinent since incidental anterior mediastinal building upon work done by radiologists associated with the Japanese Association for Research in the Thymus.13 *Department of Diagnostic Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX; †Department of General Thoracic Surgery, INCIDENCE Osaka University Graduate School of Medicine, Suita-City, Osaka, The most common tumors of the anterior mediastinum Japan; and ‡Division of Thoracic Surgery, Department of Surgery, Yale include thymic malignancies and lymphoma, but the preva- University School of Medicine, New Haven, CT. Disclosure: The authors declare no conflict of interest. lence of the different abnormalities varies markedly according Address for correspondence: Brett W. Carter, MD, Department of Diagnostic to both age and gender. Thymoma is the most common ante- Radiology, The University of Texas MD Anderson Cancer Center, 1515 rior mediastinal mass and primary tumor of the anterior medi- Holcombe Blvd., Unit 1478, Houston, TX 77030. E-mail: bcarter2@ astinum, with the highest incidence in middle aged patients. mdanderson.org Copyright © 2014 by the International Association for the Study of Lung Other tumors of the anterior mediastinum include benign Cancer teratomas and malignant germ cell tumors such as semino- ISSN: 1556-0864/14/0909-S110 mas and nonseminomatous germ cell tumors (NSGCTs).

S110 Journal of Thoracic Oncology ® • Volume 9, Number 9, Supplement 2, September 2014 Journal of Thoracic Oncology ® • Volume 9, Number 9, Supplement 2, September 2014 Anterior Mediastinal Mass: Radiographic Approach

Malignant teratomas, which are residual lesions after treat- normal mediastinal structure is lost. This loss of normal bor- ment of NSGCTs, are typically grouped in the same category der is termed the silhouette sign (Figure 1B). However, the as NSGCTs. Thymic cysts and benign cystic lesions (usually identification of a small mediastinal mass requires a more acquired, often related to surgery and radiation therapy) are methodical approach. The presence of the anterior junction among the most common nonneoplastic lesions of the anterior line, representing the point of contact between the anterior mediastinum. Additional nonneoplastic masses include vas- lungs and their pleural surfaces anterior to the cardiovascu- cular abnormalities, substernal extension of thyroid goiters, lar structures, can help exclude the presence of an anterior other cystic lesions such as pericardial or bronchogenic cysts, mediastinal mass. This line is seen in 20% of normal chest and lesions related to infection such as tuberculosis. radiographs (Figure 2A). Thickening of this line indicates an The true incidence of anterior mediastinal masses is dif- anterior mediastinal mass (Figure 2B). ficult to ascertain from the existing literature for numerous Once an abnormality is identified by chest radiography, reasons. One of the most important of these is that different cross-sectional imaging is used to characterize the lesion, gen- clinical and/or radiologic classification schemes have been erate a differential diagnosis, assess for other abnormalities, used to define the mediastinal compartments. Additionally, the and guide further management. CT with intravenous (IV) con- inclusion of nonneoplastic lesions such as thymic and pericar- trast has traditionally been the imaging modality of choice in dial cysts differs between series. Finally, there is variability in the evaluation and characterization of an anterior mediastinal the inclusion of lymphomas in different series. More detail on mass. One study analyzing 127 anterior mediastinal masses the relative incidence of anterior mediastinal tumors is pro- of various etiologies demonstrated that CT was equal or supe- vided elsewhere.2 rior to magnetic resonance imaging (MRI) in the diagnosis of anterior mediastinal masses except for thymic cysts.14 Indeed, ROLE OF IMAGING when a cystic mass is suspected or is to be investigated, MRI A large anterior mediastinal mass is readily identified is the most useful imaging modality, because MRI is supe- by chest radiography as it typically manifests as an extra soft rior to CT in distinguishing cystic from solid masses (e.g., tissue mass or opacity. The use of the silhouette sign, which thymic cysts from thymic neoplasms), discerning cystic/ describes the loss of normal borders of intrathoracic struc- necrotic components within solid masses, and discerning thy- tures, increases the sensitivity of detecting mediastinal abnor- mic hyperplasia from thymic tumors.15 For patients unable to malities. The borders of the anterior mediastinum, that is, the undergo contrast-enhanced CT due to renal failure or allergy ascending aorta, right and left heart border, are visualized by to IV contrast, non-contrast MRI may be performed to char- radiography because they are delineated by natural contrast: acterize the lesion and evaluate for involvement of vascular the air containing lung (Figure 1A). The density of soft tis- structures. Chemical shift techniques used in MRI can also sue masses is similar to the anterior mediastinal structures be used to differentiate thymic hyperplasia from thymoma and the image produced by the X-rays cannot differentiate in adult patients.16,17 18F-FDG positron emission tomography between the abnormal mass and the normal mediastinal struc- (PET)/CT is not routinely performed to evaluate or character- ture. However, since the mass displaces the air-containing ize an anterior mediastinal mass, but may be used to stage lung from the normal mediastinal structure, the border of the patients with specific malignant lesions and monitor response

FIGURE 1. Normal anatomy and the silhouette sign. A, Coned-down posteroanterior chest radiograph demonstrates the normal boundaries of the anterior mediastinum: the right heart border (white arrow), left heart border (black arrow), and ascending aorta (arrowheads). These structures are normally visible on chest radiography because they are delineated by air-filled lung. B, Coned-down posteroanterior chest radiograph of a different patient demonstrates obscuration of the right heart border and ascending aorta by a large right anterior mediastinal mass found to represent lymphoma at the time of surgery. This loss of normal boundaries and structures, known as the silhouette sign, may be used to localize an abnormality to a specific mediastinal compartment such as the anterior mediastinum in this case.

FIGURE 2. Normal and abnormal anterior junction line. A, Coned-down posteroanterior chest radiograph demonstrates the normal anterior junction line (arrows), representing the point of contact between the anterior lungs and their pleural surfaces anterior to the cardiovascular structures. B, Coned-down posteroanterior chest radiograph of a different patient demonstrates thickening of the anterior junction line (arrows) consistent with a biopsy-proven thymoma in the anterior mediastinum. to therapy and in some cases can help distinguish between cer- Lesions Identifiable on Imaging tain malignancies. However, it is important to note that imag- A heterogeneous anterior mediastinal mass that is intrin- ing with FDG-PET can be misleading, given that normal and sically hyperdense, enhances following the administration of IV hyperplastic thymus and inflammatory lesions in the medias- contrast, and demonstrates continuity with the cervical thyroid tinum are often FDG-avid. gland can reliably be diagnosed as a mediastinal goiter. Most mediastinal goiters demonstrate high attenuation on non-con- IMAGING APPROACH TO AN ANTERIOR trast CT, with Hounsfield Units measuring 70–85, due to the MEDIASTINAL MASS presence of iodine (Figure 3A). Following the administration of Evaluation of an anterior mediastinal mass may seem IV contrast, prolonged and sustained enhancement is typically difficult because of the number of different entities and the seen. Regions of low attenuation within goiters are commonly rarity with which most of them are encountered by the average seen and represent cystic changes. Calcifications may also be radiologist. A discussion between the clinician and the radi- present. The majority of substernal goiters can be reliably diag- ologist is exceedingly important, and it is best if this happens nosed by CT imaging alone. However, it is important to note at the time the images are interpreted. The degree of confi- that mediastinal goiters are not always connected to the thyroid dence in the presumptive diagnosis depends on how well it gland; nevertheless, when they are separate, they often demon- fits from a variety of viewpoints (imaging, demographics, and strate similar imaging features. As thyroid goiters may result clinical presentation) and has significant bearing on the need in compression and deviation of the trachea, evaluation of the for biopsy and if so, which type of biopsy approach is best. airways should be performed. When a goiter exhibits loss of To structure the approach to patients with an anterior distinct mediastinal fascial planes or is associated with cervi- mediastinal mass, we begin with identification of certain imag- cal or mediastinal lymphadenopathy, the possibility of thyroid ing characteristics that allow a fairly certain diagnosis to be malignancy should be investigated.19 Although patients may be made on imaging alone. Then we discuss imaging features that asymptomatic, symptoms related to compression of mediastinal are fairly common, and, while not definite by imaging appear- structures (particularly the airways) should be reported. ance alone, can nevertheless lead to a fairly reliable presump- The presence of visible areas of intralesional fat (which tive diagnosis in the appropriate clinical setting. We focus typically measures between ‒40 and ‒120 Hounsfield Units initially on the more commonly seen features and tumors, in on CT) within a heterogeneous anterior mediastinal mass is order to present a practical way of structuring an approach highly suggestive of a benign teratoma, as these lesions char- to patients. Unusual tumors and features are discussed last; acteristically demonstrate varying amounts of fat, fluid, cal- because of the rarity of such tumors the degree of certainly of cification (including bone and tooth-like elements), and soft the presumed diagnosis will always be somewhat limited. tissue.20,21 Fat is identified in approximately 50% of cases21 A highly reliable clinical diagnosis of an anterior medi- (Figure 3B). Although a fat–fluid level is highly specific for astinal lesion can be made when certain characteristic fea- teratoma, this finding is much less common, and formation tures are found on cross-sectional imaging and/or are noted of bone or a tooth is rare.22 Benign teratomas can sometimes in the clinical presentation (Table 1). Specific findings such be mostly cystic. Most benign teratomas are sufficiently char- as hyperdense and enhancing lesions that communicate with acteristic to be diagnosed reliably based on imaging charac- the thyroid gland, intralesional fat, cystic components, and teristics alone by an experienced thoracic radiologist. Benign soft tissue attenuation may be used to narrow the differential teratomas are typically seen in younger patients and account diagnosis. The presence of calcifications, whether punctate, for approximately 25% of anterior mediastinal masses in ages coarse, or curvilinear, cannot discriminate benign from malig- 10–19, 10–15% in ages 20–49, and less than 5% over age 50 nant anterior mediastinal masses and may be seen in a benign in both men and women. Patients are typically asymptomatic, lesion (such as a benign teratoma) as well as in a malignant but may report symptoms due to compression of mediastinal lesion (such as a thymoma or treated lymphoma).18 structures.

S112 Copyright © 2014 by the International Association for the Study of Lung Cancer Journal of Thoracic Oncology ® • Volume 9, Number 9, Supplement 2, September 2014 Anterior Mediastinal Mass: Radiographic Approach

TABLE 1. Imaging Algorithm for Anterior Mediastinal Masses

A proposed structured approach for radiologists in evaluating patients with an anterior mediastinal mass. This table focuses on the most common entities first and on entities in which imaging is often particularly helpful. However, the incidence varies according to age and gender, and the level of confidence in a presumptive clinical diagnosis varies according to whether the radiographic features are seen with a congruent clinical setting. aThis refers to which factors play a prominent role in establishing the presumptive clinical diagnosis. “B” symptoms, fever, sweats, and weight loss; HD, Hodgkin disease; LB-NHL, lymphoblastic non-Hodgkin lymphoma; LDH, lactose dehydrogenase; MLC-NHL, mediastinal large cell non-Hodgkin lymphoma; MRI, magnetic resonance imaging; NSGCT, nonseminomatous germ cell tumor.

When well-circumscribed, round/oval/saccular, and (Figure 3C), they can manifest as higher density lesions. This homogeneous lesions are present in the anterior mediastinum feature is responsible for CT’s inability to reliably distinguish near the thymic bed, the possibility of thymic cyst should be cystic lesions from solid masses. In the case of suspected considered. Although thymic cysts may measure water or thymic cyst, MRI should be performed. Purely cystic lesions fluid attenuation (between 0 and 20 Hounsfield Units) on CT in the anterior mediastinum with no soft tissue nodules and

FIGURE 3. Lesions identifiable on imaging. A, Coronal reformat- ted contrast-enhanced coned-down CT of an asymptomatic 54-year-old man demonstrates a high attenuation and enhancing mass (M) in the anterior mediastinum that is con- tiguous with the right lobe of the thyroid gland (arrow) and extends substernally, consistent with a goiter. Note the presence of coarse calcifications (arrowheads). B, Coned-down contrast-enhanced axial CT of an asymptomatic 34-year-old man demonstrates a well-circumscribed mass (arrow) in the right anterior mediastinum that contains both fat (asterisk) and fluid. This appearance is highly suggestive of a benign teratoma. C, Coned-down contrast-enhanced axial CT of an asymptomatic 49-year-old woman demonstrates a well-defined mass (M) in the anterior mediastinum that is fluid attenuation. No soft tissue components or internal septations are present in this lesion, which represents a thymic cyst. D, Coned-down non- contrast axial CT of an asymptomatic 51-year-old man shows a lobular fluid attenuation mass (M) in the right cardiophrenic angle, consistent with a pericardial cyst. no internal septations on MRI can reliably be diagnosed as a low attenuation anterior mediastinal mass is identified. unilocular thymic cysts.23 Cystic lesions that contain soft tis- Although the most common manifestation of thymic hyper- sue components may represent mulitlocular thymic cysts or plasia is diffuse, symmetric enlargement of the thymus on cystic thymoma. The diagnosis of cystic thymoma should be CT, intralesional fat may be present and result in ill-defined strongly considered in patients with a cystic anterior mediasti- regions of low attenuation (Figure 4A). In most patients, thy- nal lesion and symptoms related to myasthenia gravis or other mic hyperplasia can be diagnosed reliably when there is a typ- paraneoplastic syndromes, especially men and women older ical CT appearance (e.g., enlarged but maintaining the shape than 40 years of age. A well-circumscribed lesion measuring of the thymus) in a patient following stress. However, some- water or fluid density with thin or imperceptible walls in one times the CT appearance is not straightforward and it may of the cardiophrenic angles can be confidently diagnosed as a appear more nodular or bulky in configuration, resembling a pericardial cyst24,25 (Figure 3D). thymoma or lymphoma. When the findings are not classic for thymic hyperplasia, one can either re-image after a sufficiently Lesions Identifiable by a Combination long period (~3 months) to let the thymus decrease in size on of Imaging and Clinical Context its own or perform chemical shift MRI with in- and out-of- Normal thymic tissue is usually seen in young patients phase gradient echo sequences. Thymic hyperplasia and the and should decrease in prominence with age. By age 40, the normal thymus demonstrate loss of signal on out-of-phase thymus should be replaced by fat. Thymic hyperplasia should images due to the suppression of microscopic fat interspersed be considered in young patients with uniform enlargement between nonneoplastic thymic tissue, whereas thymic malig- of the thymus compared with prior imaging, or in patients nancies and lymphoma do not suppress on out-of-phase imag- over the age of 40 with soft tissue in the thymic bed without ing26,27 (Figure 4B–D). With either confirmatory approach an focal mass or contour abnormality similar to normal thymus. unnecessary biopsy or surgery can be avoided. In patients who have been treated with chemotherapy, radia- A homogeneous or slightly heterogeneous anterior tion therapy, or corticosteroids, have been exposed to stresses mediastinal mass in men and women older than 40 years of such as burns or injuries, or who have known disorders such age likely represents a thymoma28 (Figure 5A). When this as myasthenia gravis, hyperthyroidism, collagen vascular dis- appearance is combined with symptoms of myasthenia gra- eases, or HIV, thymic hyperplasia should be considered when vis or other paraneoplastic syndrome (such as pure red cell

S114 Copyright © 2014 by the International Association for the Study of Lung Cancer Journal of Thoracic Oncology ® • Volume 9, Number 9, Supplement 2, September 2014 Anterior Mediastinal Mass: Radiographic Approach

FIGURE 4. Thymic hyperplasia. A, Coned-down contrast-enhanced axial CT of a 23-year-old woman treated with chemotherapy for lymphoma demonstrates foci of low attenuation within hyperplastic thymic tissue (arrow), consistent with thymic hyperplasia. B–D, Coned-down contrast- enhanced axial CT (B) of a 38-year-old woman with chest pain and shortness of breath shows a soft tissue mass (arrow) in the anterior mediastinum. Because fat was difficult to detect by the CT alone to confirm the diagnosis of thymic hyperplasia, an MRI with chemical shift sequences was ordered. Axial in-phase (C) and out-of-phase (D) T1-weighted MRI of the same patient demonstrate soft tissue (arrow) in the anterior mediastinum that is similar in signal intensity to muscle on the in- phase image but shows complete loss of signal intensity on the out-of-phase image, compatible with thymic hyperplasia. Thymic hyperplasia and normal thymus (as opposed to thymoma or other soft tissue masses in this region) demonstrate loss of signal on out-of- phase imaging secondary to the suppression of microscopic fat interspersed between normal thymic tissue. aplasia/Diamond-Blackfan syndrome or hypogammaglobu- and especially when combined with “B” symptoms such as linemia), there is little doubt about the diagnosis. As more fever, weight loss, and night sweats (present in ~50% of medi- than 80% of thymomas are accurately diagnosed on CT or astinal lymphomas), one can be quite confident of the clinical MRI due to their typical cross-sectional appearance, tissue diagnosis. Further evaluation is typically performed with core diagnosis is typically unnecessary.14 Lymphadenopathy is needle biopsy combined with aspiration for flow cytometry or typically absent, but pleural and/or pericardial spread may be surgical biopsy. identified in advanced (stage IV) disease and is often quite For patients diagnosed with lymphoma, FDG-PET/CT pathognomonic for thymic malignancy. In the setting of a has become the modality of choice for staging. FDG-PET/CT large anterior mediastinal mass with features such as hetero- is more accurate than CT at detecting lymphomatous involve- geneity, local invasion, lymphadenopathy, and pleural effu- ment of lymph nodes, with a sensitivity of 94% and a specific- sion, thymic epithelial neoplasms other than thymoma such ity of 100%, respectively, compared with 88% and 86% for as thymic carcinoma (Figure 5B) and carcinoid should be CT. 32 FDG-PET/CT is also effective at identifying intranodal considered.29 On 18F-FDG PET/CT, thymic carcinomas and and extranodal disease within the remainder of the body. The carcinoids typically demonstrate greater FDG uptake than sensitivity and specificity of FDG-PET/CT in detecting organ thymomas.30,31 involvement are 88% and 100%, respectively, compared with In patients with enlarged lymph nodes or lobulated soft 50% and 90% for CT.32 tissue masses in the mediastinum on cross-sectional imaging, When patients present with a large anterior mediastinal which may or may not be seen in association with lymph- mass, pleural effusion, “B” symptoms, and elevated serum lev- adenopathy in the lower neck or axilla, a lymphoma such els of lactate dehydrogenase, then lymphoblastic non-Hodgkin as Hodgkin disease and mediastinal large cell non-Hodgkin lymphoma should be considered (Figure 5C). A rapid onset lymphoma should be considered. Although it may be difficult of symptoms is characteristically seen. Cytology of the pleu- to distinguish lymphoma from other soft tissue lesions in the ral effusion (when present) or bone marrow biopsy is almost mediastinum, the infiltrative nature of some lymphomas helps always sufficient to confirm the presumptive diagnosis. distinguish it from thymic epithelial neoplasms. Mediastinal When a large, lobular homogeneous anterior mediasti- lymphomas often encircle but “respect” the great vessels. nal mass is identified on cross-sectional imaging in a young When this is seen in the right age cohort, lymphoma being the man 10–39 years of age, seminoma should be considered33 most common anterior mediastinal mass in young patients, (Figure 5D). These lesions may be indistinguishable from

FIGURE 5. Lesions identifiable on imaging with clinical context. A, Coned-down contrast-enhanced axial CT of a 43-year-old man with myasthenia gravis demonstrates a well-defined, lobular soft tissue mass (arrow) in the anterior mediastinum. In a patient older than 40 years of age, the imaging appearance and clinical history are typical of a thymoma, which was confirmed at the time of surgery. B, Coned-down contrast-enhanced axial CT of a 38-year-old with chest pain demonstrates a large, lobular mass (M) originating in the left anterior mediastinum. The central regions of low attenuation represent necrosis. Note the extension of tumor around the left heart with obliteration of the adjacent fat plane. CT-guided biopsy revealed thymic carcinoma and cardiac invasion was confirmed at the time of surgery. C, Coned-down contrast-enhanced axial CT of a 33-year- old woman presenting with fever and weight loss demonstrates a large soft tissue mass (M) in the anterior mediastinum that extends into the middle mediastinum and insinuates itself around the great vessels. The infiltrative nature of this mass is characteristic of lymphoma and enables differentiation from other anterior mediastinal masses, such as thymoma. D, Coned-down contrast-enhanced axial CT of a 37-year-old man presenting with chest pain demonstrates a large, homogeneous, lobular mass (M) in the anterior mediastinum. Elevated serum lactate dehydrogenase and slightly elevated serum β-HCG levels were present and seminoma was confirmed at biopsy. E, Coned-down contrast-enhanced axial CT of a 28-year-old man presenting with chest pain, weight loss, and elevated serum α-FP demonstrates a large heterogeneous mass (M) originating in the left anterior mediastinum and extending into the left hemithorax. Regions of low density represent tumor necrosis. Biopsy revealed NSGCT. Note the loculated left pleural effusion (E), which was found to represent metastatic disease to the left pleura at the time of surgery.

S116 Copyright © 2014 by the International Association for the Study of Lung Cancer Journal of Thoracic Oncology ® • Volume 9, Number 9, Supplement 2, September 2014 Anterior Mediastinal Mass: Radiographic Approach

lymphoma.33 Although pleural effusions are rare, pulmonary with reasonable confidence is not possible. In such scenarios, metastases are relatively common (this is distinctly unusual extensive speculation is usually not helpful; acquisition of tis- for Hodgkin disease or mediastinal large cell non-Hodgkin sue through core needle, surgical biopsy, or resection is gener- lymphoma). Approximately 10% of patients with seminoma ally of greater benefit to guide subsequent management than demonstrate slightly elevated serum β-HCG but α-FP is typi- additional imaging studies. cally normal.34,35 Serum lactate dehydrogenase levels are usually elevated, but this is true for many lymphomas as well.36,37 CONCLUSION Further evaluation with core needle or surgical biopsy is Certain anterior mediastinal tumors can be reliably iden- usually performed. When a heterogeneous anterior mediasti- tified by imaging alone, including substernal goiters, benign nal mass is present with lung metastases in women and men teratoma, and benign cysts. However, many anterior medias- below the age of 40, NSGCTs should be included in the differ- tinal tumors exhibit suggestive but inconclusive imaging fea- 38,39 entiation diagnosis (Figure 5E). Markedly elevated serum tures; when the imaging correlates with the typical clinical α-FP or β-HCG levels are present in 90% of patients and are features a presumptive diagnosis can be quite reliable. This 35,36,40,41 pathognomonic for this diagnosis. Primary mediastinal underscores the need for a discussion between the clinician seminoma or NSGCTs are well-recognized entities; there is and the radiologist when evaluating most anterior mediastinal no documented reason to search for an occult testicular pri- tumors. The suggested approach, therefore, is to initially rule mary lesion via testicular ultrasound. in or out those lesions that can be reliably identified purely on the basis of characteristic imaging features. Less conclusive Evaluation of Rare Tumors imaging features should be correlated with specific clinical When an anterior mediastinal mass contains intral- features; in many cases this will strongly suggest a particu- esional fat, several rare tumors can be clinically diagnosed lar diagnosis and a further evaluative or treatment strategy. with a high degree of confidence. In the setting of a large Additional detail regarding clinical features, evaluation and fat-containing mass in the anterior mediastinum or at one of treatment is provided in the companion paper Approaching the cardiophrenic angles, thymolipoma should be considered. the Patient with an Anterior Mediastinal Mass: A Guide for These benign encapsulated lesions usually contain 50–85% fat Clinicians.2 This approach provides structure to the radiologic (although up to 95% has been reported) and a small amount of evaluation of anterior mediastinal masses, and facilitates a solid tissue and fibrous septa, and are typically very large with more streamlined and efficient discussion and further work- an average size of 20 cm.42,43 Direct connection with the thy- up of these patients. mus may be visualized and confirms the diagnosis.44 Patients may have symptoms related to mass effect such as dyspnea or be asymptomatic, and anecdotal cases of associations between REFERENCES thymolipomas and myasthenia gravis, Grave’s disease, and 1. 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