Chest Imaging - 413 - - - - 1 [email protected] Introduction radiographics.rsna.org • The existing schemes used in radiologic practice represent ar- RSNA, 2017 RSNA, be suggested when radiologic are combined with specific features authors the this article, In the new present clinical information. of mediastinal compartmentsmultidetector CT–based classification introduced by ITMIG and a structured approach to imaging evalu of mediastinal abnormalities. ation © in clinical practice. Most classifications have been based have radiology classifications Most in clinical practice. A on arbitrary chest radiograph. landmarks outlined on the lateral imaging,new scheme based on cross-sectional principally multi by the has been developed (CT), detector computed tomography Interest Group (ITMIG) andThymic International This clinical division scheme defines accepted as a new standard. and paravertebral compartments visceral, unique prevascular, structuresbased on boundaries by specific anatomic at delineated an importantThis new definition plays role in multidetector CT. and characterization mediastinal abnormalities, identification of although uncommon and encompassing a wide variety of which, can often be diagnosed with confidence based on location entities, a diagnosis may In other scenarios, and imaging alone. features Division of the into specific compartmentsDivision of the mediastinum is ben of a focused including generation of reasons, eficial for a number on imag for mediastinal masses identified differential diagnosis surgicalassistance in planning for biopsies and ing examinations, clinicians between and facilitation of communication procedures, schemes for classification Several in a multidisciplinary setting. used to varying and been created degreesthe mediastinum have bitrary divisions of the chest based primarily nonanatomic on the scheme based on The lack of a classification chest radiograph. lateral as multidetector computed cross-sectional imaging is problematic, The mediastinum contains vital vascular and nonvascular structures and nonvascular The mediastinum contains vital vascular Division of the mediastinum into specific compartments and organs. characterization, in the identification, has traditionally been valuable Numerous and management of various mediastinal abnormalities. varyingand used to been developed de systems have classification The most commonly and radiologists. surgeons, grees by anatomists, system, used scheme in clinical practice is the Shields classification and Zylak, Heitzman, Felson, whereas the traditional Fraser and Paré, One scheme Whitten models are used in radiologic practice (1–7). has been devised to bridge the various models (8). the gap between Significant differences in the terminology and methods of mediastinal resulteddivision or compartmentalization among these schemes have in confusion among health care providers and the inability to reliably localize some lesions to a specific mediastinal compartment because of in each classification. inherent limitations - - - -

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FDG = fluorodeoxyglucose, = fluorodeoxyglucose, FDG ea ). L ITMIG Classification of Mediastinal of Mediastinal Classification ITMIG Compartments and Multidisciplinary Masses Mediastinal to Approach activity, participants will be able to: See www.rsna.org/education/search/RG. Understand basic approaches to diag Identify the boundaries and contents Describe the role of imaging modalities ■ ■ ■ RSNA, 2017 RSNA, SA-CME From the Departmentthe From Radiol Diagnostic of After completing this journal-based SA-CME standardized uptake value RadioGraphics 2017; online Published Content Codes: such as multidetector CT, MR imaging, such as multidetector CT, medias- and FDG PET/CT in evaluating tinal masses. nosing mediastinal masses on the basis of imaging and clinical information. features of the mediastinal compartments mul- at tidetector CT as outlined in the ITMIG system. classification © Research on the , SUV Thymus, Research on the 1 Mylene T. Truong, MD Truong, Mylene T. MD Rosado-de-Christenson, Melissa L. MD Marom, Edith M. Abbreviations: Malignancy In Thymic ITMIG = International forAssociation = Japanese JART terest Group, Brett W. Carter, MD Carter, W. Brett MD Benveniste, Marcelo F. MD Rachna Madan, PhD MD, Godoy, Myrna C. MD de Groot, M. Patricia ■ ■ ■ correspondence to mdanderson.org Schil and Van See discussion on this article by Heyman (pp 436–438). Israel (E.M.M.). Recipient of a Certificate of Israel (E.M.M.). 2015the at exhibit education an for Meritaward 2016; April 8, Received Annual Meeting. RSNA August revision requested July 12 and received this journal- For accepted September 20. 30; M.L.R.d.C. the author based SA-CME activity, all disclosures (see end of article); has provided have reviewers the and editor, the other authors, relationships. disclosed no relevant ogy, University of Texas MD Anderson Can MD Texas University of ogy, Unit 1478, 1515 Holcombe Blvd, cer Center, M.G., M.F.B., (B.W.C., TX 77030 Houston, Department of Radiology, M.T.T.); P.M.d.G., Mass Boston, Hospital, Women’s Brigham and Luke’s Saint Department of Radiology, (R.M.); Missouri–of University City, Kansas of Hospital Kansas City, Kansas City School of Medicine, and Department of Radiol Mo (M.L.R.d.C.); Aviv, Tel Chaim Sheba Medical Center, ogy, 414 March-April 2017 radiographics.rsna.org

describe mediastinal abnormalities and formulate Teaching Points relevant differential diagnoses. ■■ The lack of a classification scheme based on cross-sectional im- In 2014, the Japanese Association for Research aging is problematic, as multidetector computed tomography on the Thymus (JART) developed a four-com- (CT) and magnetic resonance (MR) imaging are predominantly used for diagnosis, evaluation, and management of mediasti- partment multidetector CT–based classification nal abnormalities and a growing number of mediastinal le- scheme for division of the mediastinal compart- sions are detected with multidetector CT studies performed for ments, which was derived from a retrospective screening, cardiac screening, and other purposes. analysis of 445 nonconsecutive pathologically Therefore, a standardized classification scheme based on mul- proved mediastinal masses (11). On the basis of tidetector CT is necessary to appropriately describe mediastinal abnormalities and formulate relevant differential diagnoses. discussions with experts in the field of mediastinal ■■ In some cases, the multidetector CT appearance of thymic hy- diseases, the International Thymic Malignancy perplasia is not straightforward and a more nodular or bulky Interest Group (ITMIG) has modified the JART configuration may be present, which can mimic a thymic model and introduced a new definition of medias- epithelial tumor, , or other soft-tissue . In tinal compartments to be used with cross-sectional this setting, two options are available: (a) follow-up multide- imaging and adopted as a new standard (12). tector CT can be performed in ~3 months to allow a decrease in thymic size or (b) chemical shift MR imaging with in-phase In this article, we describe the new ITMIG and out-of-phase gradient-echo sequences. Thymic hyperpla- mediastinal compartment classification system sia and the normal thymus characteristically demonstrate loss based on cross-sectional imaging that can be used of signal on out-of-phase images due to the suppression of to accurately localize and characterize mediastinal fat interspersed between nonneoplastic hyperplastic thymus, lesions and assist in the formulation of focused whereas thymic epithelial , lymphoma, and other soft-tissue do not demonstrate suppression on differential diagnoses and management strategies. out-of-phase images. Use of either of these options ensures Specific approaches to evaluation of abnormalities that unnecessary biopsies or surgeries can be avoided. in the prevascular, visceral, and paravertebral com- ■■ Internal heterogeneity resulting in soft-tissue attenuation at partments are presented here and primarily based multidetector CT may be due to hemorrhagic or protein- on multidetector CT. It is important to note that aceous components or infection of the bronchogenic cyst; in these approaches are not intended to include every this setting, MR imaging can be performed to confirm the possible entity that may be encountered in the me- cystic nature of the lesion, which demonstrates high signal intensity on T2-weighted images regardless of the other con- diastinum, but instead to provide a practical and tents. The presence of hemorrhagic, proteinaceous, or mu- realistic algorithm for the radiologist. Although coid content results in variable patterns of signal intensity on management strategies such as biopsy and surgery T1-weighted images. may be included when necessary, detailed treat- ■■ When a previously stable neurofibroma suddenly increases in ment strategies for individual lesions are beyond size, develops regions of heterogeneity, and/or invades ad- the scope of this article. jacent tissues, malignant transformation to a malignant pe- ripheral nerve sheath tumor should be strongly considered. In patients with neurofibromatosis type 1, there is a 10% life- Rationale and Methodology time risk of developing a malignant peripheral nerve sheath ITMIG has an established method of develop- neoplasm, and these lesions account for most cancer-related ing international standards for mediastinal dis- deaths in these patients. FDG PET/CT has demonstrated utility eases, which was used in this instance to develop in distinguishing malignant peripheral nerve sheath tumors from benign neurofibromas, with sensitivity of 95% and a practical division of the mediastinum based on specificity of 72%. cross-sectional imaging. A thorough analysis of the ■■ Tuberculosis associated with involvement of the posterior ele- existing literature regarding the various compart- ments, the presence of a large prevertebral and paravertebral ment schemes was performed, with specific atten- soft-tissue component out of proportion to the degree of os- tion given to the model developed by JART. In an seous destruction, and disk space narrowing enable differentia- effort to develop a standard representing a con- tion of tuberculous from pyogenic infection. Additionally, the sensus among clinicians and researchers interested presence of calcification without new bone formation or sclero- sis strongly suggests the diagnosis of Pott disease of the spine. in mediastinal diseases, a working group within ITMIG identified and surveyed a multidisci- plinary group of experts in thoracic surgery, medi- cal , diagnostic radiology, and pathology tomography (CT) and magnetic resonance (MR) regarding their preferences for specific details imaging are predominantly used for diagnosis, regarding a multidetector CT–based compartment evaluation, and management of mediastinal ab- model. Information requested included the follow- normalities and a growing number of mediastinal ing: (a) preference for a three-compartment or a lesions are detected with multidetector CT stud- four-compartment model and (b) specific reasons ies performed for screening, cardiac for this preference. After drafting of a proposed screening, and other purposes (9,10). Therefore, multidetector CT–based compartment model by a standardized classification scheme based on an ITMIG work group, it was further refined by multidetector CT is necessary to appropriately an extended work group and ultimately dissemi- RG • Volume 37 Number 2 Carter et al 415 nated to the active ITMIG members (~225) for Among the surveyed multidisciplinary group review. The final document, which we present in of experts, 72% preferred a three-compartment this article, was approved and adopted as a new model, 23% preferred a four-compartment standard by the ITMIG members. model, and 5% did not have a specific preference. Mediastinal classification models have tra- Reasons for selecting one model over another ditionally divided the mediastinum into three included the following: (a) optimal distinction or four compartments depending on whether a of disease entities (67%), (b) similarity to what superior mediastinal compartment is included is currently used (63%), (c) anatomic nature in the description. Four-division models include (53%), and (d) ease of use (48%). On the basis superior, anterior, middle, and posterior compart- of this feedback, a three-compartment model was ments, whereas three-division models include selected as the foundation for the cross-sectional anterior, middle, and posterior compartments. In classification scheme developed by ITMIG. describing a cross-sectional imaging approach, both types of models have specific advantages ITMIG Definition of and disadvantages. The principal advantages of a Mediastinal Compartments four-compartment cross-sectional imaging model The three-compartment cross-sectional imaging include similarity to anatomic and radiologic model of the mediastinal compartments developed four-compartment models, the efficacy of such a by ITMIG includes prevascular (anterior), visceral system as demonstrated by the JART proposal, (middle), and paravertebral (posterior) compart- and the fact that most cases of thyroid goiter are ments (Table). Specific compartment boundaries typically located in the superior mediastinum and the anatomic structures they contain can be and can be distinguished from other mediastinal readily identified at multidetector CT (Fig 1). masses on this basis. Significant disadvantages of a four-compart- Prevascular Compartment ment cross-sectional imaging model include In the ITMIG classification system, the following the relative complexity compared with a more boundaries of the prevascular compartment are streamlined three-compartment model, the per- defined:(a) superiorly, the thoracic inlet; (b) infer­ ception that most clinicians and radiologists do iorly, the diaphragm; (c) anteriorly, the posterior not use the existing four-compartment schemes, border/cortex of the sternum; (d) laterally, the and several nonanatomic features that limit ap- parietal mediastinal pleura; and (e) posteriorly, plicability. For example, the division between the the anterior aspect of the pericardium as it wraps superior and inferior compartments is entirely around the in a curvilinear fashion (Table). artificial and nonanatomic; thus, neoplastic, Briefly, the thoracic inlet has been defined as a thin infectious, and inflammatory disease processes plane of tissue outlined by specific osseous struc- can spread unimpeded within these two areas tures, including the superior border of the manu- without fascial plane restrictions. Furthermore, brium anteriorly and inferiorly, the body of the first neurogenic neoplasms in the posterior aspect of thoracic vertebra posteriorly and superiorly, and the the chest do not respect this arbitrary separation first pair of ribs and their costal cartilages. of compartments. These factors limit the imple- On the basis of these landmarks, the major mentation and dissemination of any four-com- contents of the prevascular compartment in- partment cross-sectional imaging model. clude the thymus, fat, lymph nodes, and the left The primary advantages of a three-compart- brachiocephalic vein. Therefore, the most com- ment cross-sectional imaging model include mon abnormalities encountered in the prevascu- similarity to the published anatomic, clinical, and lar compartment include thymic lesions (cysts, radiologic three-compartment models previously hyperplasia, and malignancies such as , developed and in current use, less complicated thymic , and neuroendocrine neo- design relative to four-compartment models, and plasms); germ cell neoplasms (which arise from the fact that specific compartmental boundaries germ cell rest remnants in the mediastinum); are established along true anatomic planes. The lymphoma; metastatic ; and principal disadvantage of a three-compartment intrathoracic goiter. cross-sectional imaging model is that blending the superior and anterior compartments may not Visceral Compartment result in sufficient separation of lesions that occur In the ITMIG classification system, the following in each of these locations. However, this is not boundaries of the visceral compartment are de- a significant issue in clinical practice, as specific fined: (a) superiorly, the thoracic inlet; (b) inferi- lesions that typically occupy the superior medias- orly, the diaphragm; (c) anteriorly, the posterior tinum, in particular thyroid goiter, can be readily boundaries of the prevascular compartment; and identified at multidetector CT. (d) posteriorly, a vertical line connecting a point 416 March-April 2017 radiographics.rsna.org

ITMIG Multidetector CT–based Classification of Mediastinal Compartments

Compartment Boundaries Major Contents Prevascular Superior: thoracic inlet Thymus Inferior: diaphragm Fat Anterior: sternum Lymph nodes Lateral: parietal mediastinal pleura Left brachiocephalic vein Posterior: anterior aspect of the pericardium as it wraps around the heart in a curvilinear fashion Visceral Superior: thoracic inlet Nonvascular: , carina, , Inferior: diaphragm lymph nodes Anterior: posterior boundaries of the prevascu- Vascular: heart, ascending thoracic , aor- lar compartment tic arch, descending thoracic aorta, superior Posterior: vertical line connecting a point on vena cava, intrapericardial pulmonary arter- each thoracic vertebral body 1 cm posterior ies, thoracic duct to its anterior margin Paravertebral Superior: thoracic inlet Thoracic spine Inferior: diaphragm Paravertebral soft tissues Anterior: posterior boundaries of the visceral compartment Posterolateral: vertical line against the posterior margin of the chest wall at the lateral margin of the transverse process of the thoracic spine

on the thoracic vertebral bodies 1 cm posterior to Paravertebral Compartment the anterior margin of the spine—this is referred In the ITMIG classification system, the follow- to as the visceral-paravertebral compartment ing boundaries of the paravertebral compart- boundary line (Table). This vertical line was ment are defined: (a) superiorly, the thoracic selected as the posterior boundary of the visceral inlet; (b) inferiorly, the diaphragm; (c) ante- compartment and the anterior boundary of the riorly, the posterior boundaries of the visceral paravertebral compartment because most abnor- compartment; and (d) posterolaterally, a vertical malities in the latter are neurogenic neoplasms line along the posterior margin of the chest wall that arise from the dorsal root ganglia/neurons at the lateral aspect of the transverse processes adjacent to the intervertebral foramina. (Table). The major contents of the paraverte- The major contents of the visceral compart- bral compartment include the thoracic spine ment fall into two main categories: (a) vascular and paravertebral soft tissues; therefore, most structures including the heart, , abnormalities in this region are neurogenic neo- ascending thoracic aorta, aortic arch, descend- plasms that arise from the dorsal root ganglia/ ing thoracic aorta, intrapericardial pulmonary neurons adjacent to the intervertebral foramina. arteries, and thoracic duct; and (b) nonvascular Other potential lesions in this compartment are structures including the trachea, carina, esopha- of infectious (discitis/osteomyelitis) or traumatic gus, and lymph nodes. In contrast to the JART (hematoma) origin, or miscellaneous lesions model, the ITMIG model includes all structures related to other underlying conditions (such as within the pericardium (ie, heart and great ves- extramedullary hematopoiesis). sels) in the visceral compartment. Note that the extrapericardial pulmonary arteries and veins Approach to Mediastinal Masses are considered to be pulmonary structures and not mediastinal in location; thus, these are not General Considerations included in the visceral compartment. Employing the existing nomenclature regarding The most common abnormalities in the the mediastinal compartments, slightly more than visceral compartment include lymphadenopathy half of all mediastinal masses are located in the (related to lymphoma or metastatic disease), anterior compartment, whereas one-fourth each duplication cysts, tracheal lesions, and esophageal are identified in the middle and posterior medias- neoplasms. Additionally, vascular lesions arising tinal compartments (10,13–21). These compart- from the heart, pericardium, and great vessels ments and the frequency of lesions located therein may also be present. approximate the ITMIG compartment scheme. In RG • Volume 37 Number 2 Carter et al 417

Figure 1. ITMIG definition of mediastinal compartments. Sagittal reformatted multidetector CT image(a) and axial multidetector CT images at the levels of the aortic arch (b), left (c), and left atrium (d) demonstrate the classification scheme. Note that the prevascular compartment (purple) wraps around the heart and pericardium, which are located in the visceral compartment (blue). Yellow = paravertebral compartment, green line = visceral-paravertebral compartment boundary line.

many instances, localization and characterization of consider findings suggestive of a mediastinal a mediastinal abnormality using multidetector CT abnormality at chest , as it remains are sufficient to make the diagnosis. In other cases, the most common imaging examination per- correlation between imaging findings and clinical formed. Although small lesions may not be context, as well as additional imaging examina- visible or produce subtle findings, large medi- tions such as MR imaging and fluorodeoxyglucose astinal abnormalities may manifest in a variety (FDG) positron emission tomography (PET)/CT of ways, such as a soft-tissue mass, often ac- and histologic sampling through image-guided or companied by loss of the normal mediastinal surgical biopsy, is necessary to make a definitive contours or interfaces or thickening of specific diagnosis and guide further management. lines or stripes. The lateral chest radiograph can be especially useful in detecting lesions that may Role of Imaging not be visible on the posteroanterior radiograph, since mediastinal lesions may be visible only in Radiography.—Although the ITMIG classifica- the retrosternal space or overlying the upper tion of mediastinal compartments is applicable thoracic spine. only to multidetector CT and other cross- The “silhouette sign,” which describes the loss sectional imaging modalities, it is important to of normal borders of intrathoracic structures, 418 March-April 2017 radiographics.rsna.org can aid in detection of mediastinal abnormalities. MR Imaging.—MR imaging is not typically For instance, a lesion in the right aspect of the performed for evaluation of all mediastinal ab- anterior mediastinum may obscure cardiovascular normalities; however, its effectiveness in specific structures such as the superior vena cava or right scenarios has been demonstrated. For instance, heart border, whereas a mass in the posterior MR imaging is the most useful imaging modality mediastinum may result in loss of the normal for distinguishing cystic from solid lesions (eg, paraspinal stripes. The “hilum overlay” sign may thymic cysts from solid neoplasms), discerning help differentiate a mediastinal mass from cardio- cystic and/or necrotic components within solid megaly or enlarged pulmonary vessels. masses, distinguishing cystic neoplasms from be- The “cervicothoracic sign” as described by Fel- nign cysts, and identifying septa and/or soft tissue son (4) is useful for localizing mediastinal abnor- within cystic lesions (24,25). malities identified at radiography and for formulat- For patients unable to undergo contrast-en- ing a focused differential diagnosis. In such cases, hanced multidetector CT due to renal failure or obscuration of the lateral borders of an upper allergy to intravenous contrast material, nonen- mediastinal mass as it extends above the clavicles hanced MR imaging with specific fluid-sensitive into the neck implies that the lesion has both intra- sequences may be performed to characterize the thoracic and cervical components. Although often lesion and evaluate for involvement of vascular misinterpreted as a manifestation of the cervico- structures (26). Chemical shift MR imaging using thoracic sign, an upper paravertebral (or posterior in-phase and out-of-phase sequences is the best mediastinal) mass with borders visible above the modality for differentiating thymic hyperplasia from clavicles is located entirely within the chest but thymoma and other thymic neoplasms in adult does not exhibit the cervicothoracic sign. patients (27,28). Thymic hyperplasia can be identi- fied when the microscopic fat interspersed between Multidetector CT.—Once an abnormality is thymic tissue loses signal on out-of-phase images. identified at chest radiography, cross-sectional imaging is employed to characterize the lesion, FDG PET/CT.—The role of fluorine 18 FDG PET/ formulate a focused differential diagnosis, as- CT in the evaluation of many mediastinal ab- sess for other abnormalities, and guide further normalities remains controversial. Several stud- management. Multidetector CT with intrave- ies have been performed to investigate the ability nous contrast material is the imaging modality of PET/CT to allow distinction between benign of choice for evaluation and characterization of and malignant mediastinal lesions and between most mediastinal lesions. One study that analyzed various types of malignant primary mediastinal 127 anterior mediastinal masses from various neoplasms. In one of these, malignant neoplasms causes demonstrated that multidetector CT was demonstrated significantly higher FDG uptake equal or superior to MR imaging in diagnosis of than benign lesions when a maximal standardized anterior mediastinal masses except for thymic uptake value (SUVmax) equivalent value of 3.5 was cysts (22). For this reason, ITMIG uses multide- used as a threshold (29). Others have used higher tector CT as the gold standard/reference modal- SUVmax thresholds such as 4.67 and suggested that ity for defining the mediastinal compartments. PET/CT is complementary to other conventional Specific imaging characteristics that should imaging techniques and could potentially avoid un- be noted at multidetector CT include (a) loca- necessary investigations, but noted that histologic tion, size, and configuration of mediastinal sampling is required to confirm PET findings (30). lesions; (b) descriptive features such as attenua- There is significant overlap between the SUVmax tion, heterogeneity, and enhancement; (c) pres- of malignant neoplasms demonstrating increased ence of intralesional fat, cystic components, soft FDG uptake, particularly high-risk thymic epithe- tissue, and calcification; and (d) any connection lial neoplasms (World Health Organization [WHO] with or invasion of adjacent structures. Some of types B2 and B3), lymphoma, paraganglioma, and these findings are more important than others; nonseminomatous germ cell neoplasms (31). for instance, the presence of fat in a prevascular Regarding thymic epithelial neoplasms, Sung mediastinal lesion is highly suggestive of a small et al (32) suggested that PET/CT could be used number of entities, whereas calcifications— to distinguish low-risk (WHO types whether punctate, coarse, or curvilinear—are A, AB, and B1) from . Other nonspecific and cannot be used to discriminate groups have reported that PET/CT could be used benign from malignant prevascular mediastinal to distinguish low-risk thymomas from high-risk masses, as they may be associated with malig- thymomas (WHO types B2 and B3) and thymic nant neoplasms such as thymoma or treated carcinoma (33). However, other studies have been lymphoma, as well as benign lesions such as less definitive, with PET/CT not demonstrating a mature (10,23). significant benefit in the staging of patients with RG • Volume 37 Number 2 Carter et al 419

thymic epithelial neoplasms. It has been observed sons, the most significant of which is that different that thymic epithelial neoplasms tend to demon- classification schemes have been used to define strate variable, often only low-grade FDG uptake, the mediastinal compartments in published stud- making histologic differentiation between the vari- ies (35). Additionally, there is variability in the ous types of neoplasms unreliable. inclusion of nonneoplastic lesions such as thymic A significant factor limiting the ability of PET/ hyperplasia and thymic and pericardial cysts and CT to accurately characterize mediastinal lesions other neoplastic lesions such as lymphoma (35). is the potential for false-positive and false-negative The most common neoplasms of the pre- examinations. Some benign processes such as thy- vascular mediastinum include thymic epithelial mic hyperplasia and inflammatory diseases such as neoplasms (thymoma, thymic carcinoma, and fibrosing mediastinitis may demonstrate increased thymic neuroendocrine tumors) and lymphoma. FDG uptake and mimic malignancy. Jerushalmi et Thymoma is the most common prevascular al (34) demonstrated that FDG uptake in thymic mediastinal mass and primary neoplasm of the hyperplasia is highly variable and in many instances prevascular mediastinum, with the highest inci- can significantly overlap with that of mediastinal dence in middle-aged patients. Other neoplasms that may arise in the prevascular compartment malignancies, with SUVmax as high as 7.3. In such cases, a combination of clinical history, focality include mature teratoma, nonteratomatous germ of FDG uptake at PET/CT, and morphologic cell malignancies such as seminoma and nonsem- features at multidetector CT is necessary to deter- inomatous germ cell neoplasms, and metastatic mine whether the lesion is benign or malignant. disease. Nonneoplastic lesions of the prevascular mediastinum include substernal extension of Localization of thyroid goiter, thymic hyperplasia, cystic lesions Mediastinal Abnormalities such as thymic and pericardial cysts, and vascu- Although localization of mediastinal lesions to a lar-lymphatic abnormalities. specific compartment is an important component of characterization, this may be difficult in some Lesions Identifiable at Imaging instances. For example, a large mediastinal lesion may appear to involve multiple compartments or Thyroid Goiter.—A heterogeneous prevascular extend from one compartment to another, making mediastinal mass that demonstrates continuity identification of the precise site of origin challeng- with the cervical thyroid gland, is intrinsically ing. Two tools have been described by ITMIG and hyperattenuating (with Hounsfield unit values are recommended to help identify the compart- of 70–85 due to the presence of iodine), and ment from which these lesions originate. demonstrates intense and sustained enhance- One of these tools is known as the “center ment after administration of intravenous con- method” and states that the center of a medias- trast material can dependably be diagnosed as a tinal lesion, defined as the center point of the le- mediastinal goiter. Cystic changes manifesting sion on the axial CT image that demonstrates the as internal foci of low attenuation and calcifi- largest size of the abnormality, localizes the lesion cations may be present. For cases in which a to a specific mediastinal compartment (12). The definitive connection with the cervical thyroid JART study used this method and resulted in ac- gland cannot be identified, these other findings curate localization of all 445 mediastinal masses at multidetector CT should strongly suggest the in the study to specific compartments. diagnosis (Fig 2). When additional findings such The second tool is known as the “structure dis- as loss of mediastinal tissue planes or associ- placement tool” and is useful in scenarios in which ated cervical or mediastinal lymphadenopathy very large mediastinal lesions displace organs from accompany a mediastinal goiter, then thyroid other mediastinal compartments, typically those malignancy should be suspected and further that abut the compartment from which the lesion evaluation performed (10,36). originated (11). For instance, a very large prevas- cular mediastinal mass may posteriorly displace Fat-containing Lesions.—The presence of visible organs of the visceral mediastinal compartment regions of intralesional fat measuring between such as the trachea, esophagus, or heart. −40 and −120 HU at multidetector CT within a heterogeneous prevascular mediastinal mass is Approach to the highly suggestive of a mature teratoma. These be- Prevascular Compartment nign lesions characteristically demonstrate vary- ing amounts of fat, fluid, calcification, and soft General Considerations tissue; in rare cases, bone and tooth-like elements The true incidence of prevascular mediastinal may be identified (23,37) (Fig 3a). Intralesional masses is difficult to ascertain for multiple rea- fat is identified in 50% of cases (37). Fat-fluid 420 March-April 2017 radiographics.rsna.org

Figure 2. Thyroid goiter in an 83-year-old woman. Coned-down axial contrast-enhanced multide- tector CT image of the upper chest below the thoracic inlet shows a heterogeneous mass with enhanc- ing soft tissue (black *) and cystic components (white *) in the pre- vascular mediastinum. Note the focus of calcification anteriorly (arrow). Although a definitive con- nection with the cervical thyroid gland could not be identified, these multidetector CT findings strongly suggest the diagnosis of mediastinal goiter.

Figure 3. Fat-containing masses. (a) Mature teratoma in a 42-year-old man. Coned-down axial contrast-en- hanced multidetector CT image at the level of the pulmonary arteries shows a large, lobular, heterogeneous prevascular mass with a large macroscopic fat component (M). Regions of soft tissue and fluid *( ) are also pres- ent. These findings are virtually pathognomonic for a mature teratoma, which was confirmed at surgical resec- tion. (b) Thymolipoma in a 43-year-old man. Coned-down axial contrast-enhanced multidetector CT image at the level of the left atrium shows a predominantly fat-containing mass (M) in the left prevascular mediastinum. Minimal internal soft tissue is present (arrows), and the lesion extended inferiorly into the left cardiophrenic angle (not shown). When a large fat-containing lesion is identified in a cardiophrenic angle with scattered re- gions of solid tissue and/or fibrous septa, thymolipoma should be considered. Establishment of a connection to the anatomic location of the thymus supports the diagnosis. levels are highly specific for mature teratoma but represent a thymolipoma, an uncommon lesion are much less common (38). These neoplasms accounting for less than 5% of prevascular medi- typically affect young patients, accounting for astinal masses in all age groups (Fig 3b). These 25% of prevascular masses in patients 10–19 benign encapsulated neoplasms are comprised of years of age, 10%–15% in patients 20–49 years of 50%–85% fat—although a fat composition of up age, and less than 5% in patients over 50 years of to 95% has been reported—and scattered regions age in both men and women (10). of solid tissue and fibrous septa (37,39). Thymo- Other fat-containing lesions originating from lipomas tend to be very large at presentation with the prevascular mediastinum are much less com- an average reported size of 20 cm, and a direct mon and include a wide variety of benign and ma- connection with the anatomic location of the lignant neoplasms such as thymolipoma, lipoma, thymus may be identified. Patients may be asymp- and liposarcoma. A predominantly fat-containing tomatic or have symptoms related to local mass lesion present in a cardiophrenic angle may effect; rare associations between thymolipoma and RG • Volume 37 Number 2 Carter et al 421

Figure 4. Thymic cyst in a 43-year-old man. (a) Coned-down axial contrast-enhanced multidetector CT im- age below the level of the carina shows a well-defined low-attenuation lesion (arrow) in the thymic bed of the prevascular mediastinum. The internal Hounsfield unit value was 15.(b) Coned-down axial T2-weighted MR image shows high signal intensity in the lesion (arrow) and no evidence of internal septa or soft tissue. These findings are compatible with a benign unilocular thymic cyst. MR imaging is the most useful imaging modality for distinguishing cystic from solid lesions, discerning cystic and/or necrotic components within solid masses, and identifying septa and/or soft tissue in cystic lesions.

myasthenia gravis, Graves disease, and hemato- regions of higher attenuation than that of fluid logic disorders have been reported (40). due to hemorrhagic or proteinaceous compo- Lipomas represent 2% of all primary mediasti- nents. In such a scenario, MR imaging should be nal neoplasms and manifest at multidetector CT performed, given its ability to allow distinction as encapsulated lesions composed predominantly between cystic and solid lesions and identifica- of fat with a small amount of soft tissue and blood tion of solid internal components. vessels in the prevascular compartment. Although Prevascular masses that are purely cystic mediastinal liposarcomas are also comprised with no soft-tissue components or internal septa predominantly of fat, these lesions may be distin- can reliably be diagnosed as unilocular thymic guished from lipomas, thymolipomas, and other cysts (43) (Fig 4). However, when cystic lesions fat-containing lesions by the presence of aggressive contain internal soft-tissue components and/or features, including a greater proportion of soft- internal septa, the differential diagnosis should tissue components, local invasion, intrathoracic include multilocular thymic cysts, cystic tera- lymphadenopathy, and metastatic disease (41,42). toma, lymphangioma, and cystic thymoma. In the Fat-containing masses with attenuation values clinical setting of symptoms related to myasthenia overlapping with those of other tissues at multi- gravis or other paraneoplastic syndromes, espe- detector CT can be further evaluated with MR cially in men and women older than 40 years, the imaging. Fat demonstrates high signal intensity diagnosis of cystic thymoma should be strongly on T1- and T2-weighted images, low signal inten- considered (Fig 5). sity on fat-saturated images, and loss of signal on In the setting of a large multilocular cystic out-of-phase images (37). lesion with internal septa and/or soft-tissue components that extends into the neck, axilla, or Cystic Lesions.—Cystic lesions of the mediasti- chest wall, the diagnosis of lymphangioma should num are those that have water or fluid attenua- be considered. Although mature may tion at multidetector CT, with Hounsfield unit demonstrate internal fat at multidetector CT, values between 0 and 20. A well-circumscribed a large percentage of these lesions manifest as homogeneous lesion in the prevascular medias- predominantly or entirely unilocular or multiloc- tinum near the thymic bed that is round, oval, ular thin-walled cystic masses in the prevascular or saccular likely represents a thymic cyst. Most mediastinum. In contrast to simple cysts, cystic of these lesions are acquired and due to inflam- teratomas are typically associated with additional mation; iatrogenic processes such as surgery, features such as internal septa and soft-tissue radiation therapy, or chemotherapy; or malignant components and may enhance after administra- neoplasms. Some thymic cysts may demonstrate tion of intravenous contrast material. 422 March-April 2017 radiographics.rsna.org

Figure 5. Cystic thymoma in a 59-year-old woman. (a) Coned-down axial contrast-enhanced multidetector CT image at the level of the pulmonary valve shows a lobular low-attenuation mass (arrow) in the right pre- vascular mediastinum. Although a thymic cyst was suspected on the basis of the CT appearance, the internal Hounsfield unit value was 45.(b, c) Coned-down axial fat-saturated T2-weighted (b) and coned-down axial contrast-enhanced T1-weighted (c) MR images confirm that portions of the lesion are cystic (arrow inb ); how- ever, peripheral enhancement (arrows in c) and an internal enhancing soft-tissue septum (arrowhead in c) are identified. These imaging findings, in combination with the clinical history of myasthenia gravis, were highly suggestive of cystic thymoma, which was confirmed at surgical resection. A cystic lesion containing internal soft-tissue components and/or internal septa may represent a multilocular thymic cyst, lymphangioma, cystic teratoma, or cystic thymoma. In the clinical setting of symptoms related to myasthenia gravis or other paraneo- plastic syndromes, as in this case, the diagnosis of cystic thymoma can reliably be made.

A well-circumscribed unilocular mass of fluid attenuation with thin or imperceptible walls local- ized to a cardiophrenic angle can be confidently diagnosed as a pericardial cyst (Fig 6). These benign nonneoplastic lesions arise from aber- rations in the formation of coelomic or somatic cavities and more commonly arise in the right costophrenic angle than in the left, although they may be seen as high as the pericardial recesses at the level of the proximal aorta and pulmonary ar- teries (44). Although pericardial cysts are always connected to the pericardium, only a small num- ber of cases demonstrate this communication at the time of surgery.

Lesions Identifiable with a Combination of Imaging and Clinical Context

Thymic Hyperplasia.—Normal prevascular thy- Two distinct histologic types of thymic hy- mic tissue is seen in young individuals and de- perplasia have been described: true and thymic creases in prominence with advancing age, with lymphoid (follicular) hyperplasia. In patients who complete fatty replacement usually achieved by have been treated with chemotherapy, radiation 40 years of age. Thymic hyperplasia should be therapy, or corticosteroids or exposed to stresses considered in young patients with uniform en- such as burns or injuries, true thymic hyperplasia largement of the thymus that is new compared should be considered when there is diffuse sym- with the appearance on earlier imaging studies, metric enlargement of the thymus at multidetector or in patients greater than 40 years of age with CT (10). True thymic hyperplasia is also known soft tissue in the thymic bed that has a con- as “rebound hyperplasia” and is characterized by figuration similar to that of the normal bilobed an increase in thymic volume of greater than 50% triangular thymus. over baseline after a causative stressor; approxi- RG • Volume 37 Number 2 Carter et al 423

Figure 6. Pericardial cyst in a 48-year-old man. Coned-down axial contrast-enhanced multidetector CT image at the level of the ventricles shows a well-circumscribed, ho- mogeneous, fluid attenuation lesion(M) with imperceptible walls in the right cardiophrenic angle. These findings are pathognomonic for a pericardial cyst. mately 10%–25% of patients undergoing chemo- women older than 40 years with immunologic therapy may develop rebound hyperplasia (45). diseases such as myasthenia gravis (most com- Thymic lymphoid (follicular) hyperplasia is a mon) or other paraneoplastic syndromes such as histologic diagnosis defined as the presence of an pure red cell aplasia/Diamond-Blackfan syn- increased number of lymphoid follicles, which may drome, hypogammaglobulinemia, or aplastic ane- or may not be associated with an increase in the mia likely represents a thymoma (46) (Fig 8a). size of the gland and is typically associated with More than 80% of thymomas can be accurately immunologic diseases such as myasthenia gravis, diagnosed with multidetector CT or MR imag- hyperthyroidism, collagen vascular diseases, or hu- ing in this setting, and tissue diagnosis is typically man immunodeficiency virus (HIV) infection (10). unnecessary (22). Pleural or pericardial dissemi- At multidetector CT, follicular hyperplasia results nation may be present in advanced disease and is in a normal appearance of the thymus, thymic highly suggestive of thymoma; however, lymph- enlargement, or a focal soft-tissue thymic mass. A adenopathy is typically absent. rare manifestation of thymic hyperplasia at multi- A thymic epithelial neoplasm other than detector CT is a heterogeneously hypoattenuating thymoma, such as thymic carcinoma or thymic prevascular mediastinal mass that results from de- carcinoid, should be considered when a large position of fat between hyperplastic thymic tissue. soft-tissue mass is present in the prevascular In some cases, the multidetector CT appearance mediastinum with accompanying features such of thymic hyperplasia is not straightforward and a as increased heterogeneity, local invasion, lymph- more nodular or bulky configuration may be pres- adenopathy, and/or distant metastasis (Fig 8b). ent, which can mimic a thymic epithelial tumor, Specifically regarding thymoma, studies have lymphoma, or other soft-tissue neoplasm. In this shown that lobulated or irregular contours, cystic setting, two options are available: (a) follow-up or necrotic regions within the lesion, and multifo- multidetector CT can be performed in ~3 months cal calcifications are more suggestive of invasive to allow a decrease in thymic size or (b) chemical thymoma than noninvasive thymoma (47,48). shift MR imaging with in-phase and out-of-phase gradient-echo sequences. Thymic hyperplasia and Lymphoma.—A mildly enhancing lobular soft- the normal thymus characteristically demonstrate tissue mass or group of enlarged lymph nodes in loss of signal on out-of-phase images due to the the prevascular mediastinum at multidetector CT, suppression of fat interspersed between nonneo- especially in the setting of lymphadenopathy in the plastic hyperplastic thymus, whereas thymic epi- neck, axilla, or elsewhere in the body, may represent thelial neoplasms, lymphoma, and other soft-tissue lymphoma. Primary mediastinal lymphoma may be malignancies do not demonstrate suppression on due to or non-Hodgkin lym- out-of-phase images (27,28) (Fig 7). Use of either phoma, encompassing entities such as diffuse large of these options ensures that unnecessary biopsies B-cell lymphoma, gray zone lymphoma, and T-cell or surgeries can be avoided. lymphoblastic lymphoma. Enlarged lymph nodes, often affecting several different groups Thymic Epithelial Neoplasms.—A solid, homo- or stations, without a focal mediastinal mass suggest geneous or slightly heterogeneous mass in the secondary involvement by non-Hodgkin lymphoma prevascular mediastinal compartment in men and arising from another location. 424 March-April 2017 radiographics.rsna.org

Figure 7. Thymic hyperplasia in a 34-year-old woman with hyperthyroidism. (a) Coned-down axial contrast- enhanced multidetector CT image below the level of the aortic arch shows a lobular soft-tissue mass (M) in the thymic bed of the prevascular mediastinum. (b, c) Axial in-phase (b) and out-of-phase (c) T1-weighted MR images show complete loss of signal in the mass (M) on the out-of-phase image, indicating the presence of mi- croscopic fat interspersed between hyperplastic thymic tissue in thymic hyperplasia. In some cases, the multide- tector CT appearance of thymic hyperplasia is not straightforward and a nodular or bulky configuration may be present, as in this case. Chemical shift MR imaging with in-phase and out-of-phase gradient-echo sequences can be used to differentiate thymic hyperplasia and normal thymus from thymic epithelial neoplasms, lymphoma, and other soft-tissue malignancies, as the latter do not show suppression on out-of-phase images. Use of this imaging technique ensures that unnecessary biopsies or surgeries can be avoided.

Although it may be difficult to distinguish needle biopsy combined with aspiration for flow lymphoma from other soft-tissue mediastinal cytometry or surgical biopsy. masses, the infiltrative nature of some types of FDG PET/CT has become the modality of lymphoma enables differentiation from thymic choice for staging and restaging of disease for epithelial neoplasms and germ cell tumors. many types of lymphoma, as it is more accurate In many cases, encase or encircle than multidetector CT in detecting involvement vascular structures but do not result in invasion. of lymph nodes, with sensitivity of 94% and When such findings are present in young pa- specificity of 100% compared with 88% and tients who present with “B” symptoms such as 86%, respectively, for multidetector CT (Fig 9). , , and , which occur PET/CT is also effective in identifying intra- in ~50% of cases, the diagnosis of mediastinal nodal and extranodal disease within the body, lymphoma can be reliably made (Fig 9). Fur- with sensitivity of 88% and specificity of 100% ther evaluation is typically performed with core compared with 50% and 90%, respectively, RG • Volume 37 Number 2 Carter et al 425

Figure 8. Thymic epithelial neoplasms. (a) Thymoma in a 64-year-old man. Coned-down axial contrast-en- hanced multidetector CT image at the level of the left pulmonary artery shows a homogeneous soft-tissue mass (M) in the prevascular mediastinum. The clinical presentation was significant for progressive worsening of myasthenia gravis. This combination of clinical and imaging information enabled prospective diagnosis of a thymoma. Thymoma should be strongly suspected when a prevascular soft-tissue mass is identified in a patient older than 40 years and in the clinical setting of myasthenia gravis or another paraneoplastic syndrome such as pure red cell aplasia/Diamond-Blackfan syndrome or hypogammaglobulinemia. (b) Thymic carcinoma in a 52-year-old man. Coned-down axial contrast-enhanced multidetector CT image at the level of the aortic arch shows a heterogeneous soft-tissue mass (M) in the prevascular mediastinum, ipsilateral and contralateral mediastinal lymphadenopathy (*), and pleural metastatic disease in the right hemithorax (arrow). CT-guided biopsy revealed advanced thymic carcinoma. When a prevascular mediastinal mass is accompanied by features such as local invasion, lymphadenopathy, or distal metastasis, a diagnosis other than thymoma, such as thymic carcinoma or thymic carcinoid, should be considered.

for multidetector CT for detecting end-organ evaluation with core needle or surgical biopsy is involvement (49). usually performed. When a heterogeneous prevascular mediastinal Nonteratomatous Germ Cell Neoplasms.—Non- mass is present with lung metastases in men below teratomatous germ cell neoplasms include a wide the age of 40 years, NSGCTs should be included in variety of lesions, the most common of which the differential diagnosis (23,53) (Fig 10b). Ap- include seminoma and nonseminomatous germ proximately 90% of patients present with markedly cell tumors (NSGCTs). These lesions typically elevated serum levels of a-FP or b-HCG, which is manifest as large soft-tissue masses in the pre- often highly suggestive of the disease (54,55). vascular mediastinum, and it can be difficult to distinguish these entities from lymphoma. How- Ectopic Parathyroid Adenoma.—In a patient ever, the addition of demographic and clinical/ with a clinical history of primary hyperparathy- serologic information usually enables diagnosis. roidism, elevated serum calcium levels and/or ele- The presence of a large, lobular, homoge- vated serum parathyroid hormone, with or without neous soft-tissue mass in the prevascular me- prior surgical parathyroidectomy, and a soft-tissue diastinum at multidetector CT in men 10–39 nodule in the prevascular mediastinum at multide- years of age should raise suspicion for seminoma tector CT, an ectopic parathyroid adenoma should (50) (Fig 10a). Approximately 10% of patients be suspected. Although most parathyroid adeno- with seminoma demonstrate slightly elevated mas are juxtathyroid in location, they may occur serum levels of b–human chorionic gonadotro- in an ectopic location, with the mediastinum being pin (b-HCG); however, a-fetoprotein (a-FP) the most common such site (56). level is usually normal. Although serum lactate Many different imaging modalities can assist dehydrogenase (LDH) levels are usually el- in diagnosis of these lesions, including high-reso- evated, this may be seen with other malignancies lution ultrasonography (US) with color Doppler, such as lymphoma (51,52). Pleural effusions technetium 99m (99mTc) sestamibi single photon are rare but pulmonary metastases are relatively emission CT (SPECT), multidetector CT, and common, which also helps distinguish semi- MR imaging. Recently, four-dimensional (4D) noma from many types of lymphoma. Further multidetector CT has been shown to be more 426 March-April 2017 radiographics.rsna.org

Figure 9. Mediastinal lymphoma in a 20-year-old man who presented with classic “B” symptoms, including fever, night sweats, and weight loss. (a) Coned-down axial contrast-enhanced multide- tector CT image at the level of the pulmonary ar- teries shows a large soft-tissue mass (M) in the pre- vascular mediastinum, resulting in leftward shift of the heart. CT-guided core needle biopsy revealed Hodgkin lymphoma. (b, c) Coned-down axial FDG PET/CT images before (b) and after (c) one cycle of chemotherapy show that the lymphoma is hetero- geneously FDG avid due to the presence of internal necrosis, but decreases markedly in size and FDG uptake on the restaging PET/CT image. FDG PET/ CT is the imaging modality of choice for staging and restaging many types of lymphoma, as it is more ac- curate than multidetector CT for detecting lymph node and end-organ involvement.

sensitive than US and scintigraphy for preopera- and esophageal duplication cysts. A discussion tive identification and localization of parathyroid of all visceral compartment abnormalities is adenomas. The typical findings at 4D multidetec- beyond the scope of this article; the approach tor CT include intense contrast enhancement in described here is based primarily on whether the arterial phase, washout of contrast material in lesions can be identified at imaging alone or the delayed phase, and low attenuation at nonen- with a combination of radiologic and clinical hanced multidetector CT (57,58). An enlarged information, and to a lesser extent by organ of feeding artery or draining vein, referred to as the origin and composition. polar vessel, associated with the hypervascular parathyroid adenoma may also be seen (59). Lesions Identifiable at Imaging

Approach to the Visceral Cystic Lesions.—A well-circumscribed, homoge- Compartment neous, fluid attenuation lesion measuring 0–20 HU at multidetector CT in the visceral mediastinal General Considerations compartment is compatible with a benign dupli- As the visceral compartment contains both cation cyst, the most common of which include nonvascular and vascular structures, a wide bronchogenic and esophageal duplication cysts. variety of abnormalities may originate from Bronchogenic cysts result from abnormal budding this region. The most significant lesions in- of the primitive foregut, which also gives rise to the clude neoplasms of the airways, esophagus, and tracheobronchial tree, during embryologic develop- lymph nodes; enhancing masses; and non- ment. Although bronchogenic cysts may arise from neoplastic abnormalities such as bronchogenic any mediastinal compartment, they typically occur RG • Volume 37 Number 2 Carter et al 427

Figure 10. Nonteratomatous germ cell neoplasms. (a) Seminoma in a 37-year-old man. Coned-down axial contrast-enhanced multidetector CT image at the level of the aortic arch shows a large soft-tissue mass (M) in the prevascular mediastinum. The clinical presentation was significant for elevated serum levels ofb –human chorionic gonadotropin (b-HCG) and lactate dehydrogenase (LDH) but normal a-fetoprotein (a-FP) level. This combination of radiologic and clinical information strongly suggested a seminoma, which was confirmed with CT-guided biopsy. (b) NSGCT in a 29-year-old man. Coned-down axial contrast-enhanced multidetector CT image at the level of the pulmonary arteries shows a heterogeneous soft-tissue mass (M) in the right prevascular mediastinum that exerts mass effect on the right side of the heart. Note the presence of right pleural metastasis and a right (arrow). The clinical presentation was significant for elevated serum levels of a-FP, which, in a patient of this age, was suggestive of an NSGCT, as confirmed with CT-guided biopsy. in the visceral compartment near the carina or, less bronchogenic cysts, esophageal duplication cysts commonly, the right paratracheal region (44). may have thick walls. At multidetector CT, bronchogenic cysts manifest as a single, smooth, round or ovoid Lesions Identifiable with a Combination mass with internal low attenuation (Fig 11). The of Imaging and Clinical Context wall has variable perceptibility and may enhance or demonstrate intrinsic calcifications. Internal Enhancing Masses.—Several entities should be heterogeneity resulting in soft-tissue attenuation considered when a visceral compartment mass at multidetector CT may be due to hemorrhagic demonstrates enhancement after administration or proteinaceous components or infection of the of intravenous contrast material. Paragangliomas bronchogenic cyst; in this setting, MR imaging can or extra-adrenal are highly be performed to confirm the cystic nature of the vascular neoplasms that arise from chromaffin lesion, which demonstrates high signal intensity on tissue located in the para-aortic ganglia that may T2-weighted images regardless of the other con- secrete catecholamines; however, the majority of tents. The presence of hemorrhagic, proteinaceous, these neoplasms are nonfunctional. Typical clinical or mucoid content results in variable patterns of symptoms include hoarseness, dysphagia, shortness signal intensity on T1-weighted images (Fig 11). of breath, and chest pain (61,62). Paragangliomas Esophageal duplication cysts are uncommon usually manifest as intensely and homogeneously developmental anomalies that manifest as well- enhancing mediastinal masses at multidetector CT, circumscribed, homogeneous, fluid attenuation le- although regions of internal heterogeneity repre- sions adjacent to the esophagus or associated with senting necrosis may be present (Fig 13a). Further the esophageal wall at multidetector CT (44) (Fig diagnostic studies such as MR imaging, at which 12). As with other cystic lesions, internal hetero- paragangliomas demonstrate intermediate signal geneity may be present, in this case typically due intensity on T1-weighted images and high signal to hemorrhage or infection caused by the presence intensity on T2-weighted images, and iodine 123 of ectopic gastric mucosa. The presence of ectopic (123I) metaiodobenzylguanidine (MIBG) scintigra- gastric mucosa can render these lesions visible phy can help support the diagnosis. on 99mTc sodium pertechnetate scans and may be represents a form of non- helpful in diagnosing these lesions in pediatric pa- clonal lymph node hyperplasia and is classified as tients, in 50% of whom thoracic duplication cysts hyaline vascular, plasma cell, or human herpesvi- contain ectopic gastric mucosa (60). In contrast to rus 8 (HHV-8) types (63) and may be unicentric 428 March-April 2017 radiographics.rsna.org

Figure 11. Bronchogenic cyst in a 33-year-old woman. (a) Coned-down axial contrast-enhanced multidetector CT image at the level of the left atrium shows a well-circumscribed homogeneous subcari- nal mass (arrow). The internal Hounsfield unit value was 45, suggesting a soft-tissue mass. (b, c) Coned- down axial T2-weighted (b) and nonenhanced T1- weighted (c) MR images show that the lesion (ar- row) is entirely cystic with a dependent fluid-fluid level (arrowhead). Although many bronchogenic cysts manifest as homogeneous fluid attenuation lesions at multidetector CT, internal heterogeneity may be due to hemorrhagic or proteinaceous com- ponents or infection. In this scenario, MR imaging can be performed to confirm the cystic nature of the abnormality, which demonstrates high signal inten- sity on T2-weighted images regardless of the other contents. Hemorrhagic, proteinaceous, or mucoid content results in variable patterns of signal intensity on T1-weighted images.

or multicentric. Unicentric hyaline vascular type the possibility of esophageal malignancy must be is the most common and may manifest as a non- considered. Any portion of the esophagus may be invasive mass, an infiltrative mass with associated affected, although the distal esophagus is typically lymphadenopathy, or matted lymphadenopathy involved due to the rising incidence of adenocar- with intense enhancement (64) (Fig 13b). cinoma due to gastroesophageal reflux disease. Finally, metastatic disease from vascular pri- The differential diagnosis for esophageal wall mary malignancies such as renal cell and thyroid thickening is broad and includes inflammatory, neoplasms, , choriocarcinoma, and infectious, and neoplastic causes. The presence of some may result in intensely enhanc- a focal esophageal mass is more concerning for an ing lymphadenopathy in the visceral compart- esophageal neoplasm such as adenocarcinoma or ment. The diagnosis of metastatic lymphadenop- squamous cell carcinoma; however, multidetector athy can be inferred when the clinical history CT may not allow differentiation between malig- is significant for one of these neoplasms. In the nant and benign esophageal lesions. absence of such information, further evalua- Although the diagnosis can often be strongly tion with histologic sampling may be necessary; suggested by a combination of imaging and clini- however, this should be done carefully, as biopsy cal history, further evaluation with upper endos- of mediastinal vascular lesions may result in copy and biopsy is ultimately required for defini- significant intrathoracic hemorrhage. tive diagnosis (Fig 14). Multidetector CT can be useful in differentiating some benign lesions such Esophageal Lesions.—When an abnormality of as fibrovascular polyp and lipoma from esophageal the thoracic esophagus such as wall thickening cancer. The former manifests as an intraluminal or a focal mass is identified at multidetector CT, mass with smooth margins (as compared with RG • Volume 37 Number 2 Carter et al 429

Figure 12. Esophageal duplica- tion cyst in a 33-year-old woman. Coned-down axial contrast-en- hanced multidetector CT image at the level of the aortic arch shows a well-circumscribed, homoge- neous, fluid attenuation mass(M) adjacent to and intimately as- sociated with the upper thoracic esophagus. The location of the ab- normality enables definitive diag- nosis of an esophageal duplication cyst with imaging alone.

Figure 13. Enhancing masses. (a) Paraganglioma in a 29-year-old man. Coned-down axial contrast-enhanced multidetector CT image at the level of the aortic valve shows a heterogeneous mass (M) in the visceral com- partment with internal regions of intense enhancement. The patient presented with clinical symptoms related to catecholamine secretion by the neoplasm, and the catecholamines in blood and urine samples were confir- matory of paraganglioma. (b) Castleman disease in a 42-year-old man. Coned-down axial contrast-enhanced multidetector CT image at the level of the pulmonary trunk shows a large mass (M) in the visceral mediastinum with intense central enhancement and peripheral hypoenhancement. A small right pleural effusion (arrow) is also present. As the patient did not have specific symptoms suggestive of a paraganglioma or a known vascular primary neoplasm, surgical biopsy was performed for diagnostic purposes and revealed Castleman disease.

the irregular margins and lobulated appearance include composition (soft tissue, fat, calcium, of many esophageal ), and both of these and attenuation), behavior (well-defined or benign lesions may demonstrate internal fat attenu- infiltrative), and enhancement characteristics ation due to the presence of adipose tissue (65). after administration of intravenous contrast material. Cardiac Masses.—When a mass involving the In the setting of a known primary malig- heart or pericardium is identified at multi- nancy, the presence of a cardiac mass is com- detector CT, a wide variety of malignant and patible with metastatic disease until proven benign lesions should be considered. One of otherwise. In the absence of known malignancy, the most important features is the location of a cardiac mass represents either thrombus or a the abnormality, as masses can be categorized benign or malignant neoplasm. It is beyond the as intracavitary, valvular, intramural, or epi- scope of this article to discuss the distinguishing cardial/pericardial. Other significant features characteristics of individual cardiac neoplasms; 430 March-April 2017 radiographics.rsna.org

Figure 14. Esophageal cancer in a 49-year-old man. Coned-down axial contrast-enhanced multidetector CT im- age at the level of the left atrium shows marked thickening of the distal thoracic esophagus and an eccentric mass (M) in the right esophageal wall. Upper endoscopy, endoscopic US, and biopsy revealed primary adenocarcinoma of the distal esophagus. The presence of a focal esophageal mass should raise concern for an esophageal neoplasm such as adenocarcinoma or squamous cell carcinoma; however, multidetector CT does not allow differentiation between malignant and benign esophageal lesions, and further im- aging and histologic sampling are ultimately required for definitive diagnosis.

Figure 15. Cardiac angiosarcoma in a 34-year-old man. Coned-down axial contrast-enhanced multidetector CT image shows a large heterogeneous mass (M) arising from the right atrium and extending into the adjacent pericar- dium and mediastinum, compatible with biopsy-proven angiosarcoma. In contrast to the JART model of mediastinal compartments, the heart and pericardium are included in the visceral compartment in the ITMIG model, as are abnor- malities arising from these structures. Once a cardiac mass is identified at multidetector CT, advanced imaging such as ECG-gated cardiac CT, cardiac MR imaging, and/or echo- cardiography is necessary for full characterization.

however, it is important to emphasize that when these lesions are identified at multidetector CT, further evaluation with more advanced imaging such as electrocardiographically (ECG) gated cardiac CT, cardiac MR imaging, and/or echo- cardiography is necessary for full characteriza- tion (Fig 15). may be included in the differential diagnosis on Approach to the the basis of imaging features, clinical information Paravertebral Compartment is necessary in most cases.

General Considerations Soft-Tissue Lesions As the paravertebral compartment includes the thoracic spine and paravertebral soft tissues, most Neurogenic Neoplasms.—When a smooth, round, lesions originating in this region are neoplasms of or oval mass is present in the paravertebral region neurogenic origin. Other less common neoplastic at multidetector CT, the most likely diagnosis is a conditions in this compartment include lym- neurogenic neoplasm, typically a benign periph- phoma, primary osseous tumors, and metastases. eral nerve sheath tumor such as schwannoma or Nonneoplastic causes include thoracic spinal neurofibroma. Neurogenic neoplasms, 70%–80% infections due to bacterial and mycobacterial of which are benign, are the most common cause agents, cystic lesions such as thoracic meningo- of paravertebral compartment masses and account cele and neurenteric cyst, and extramedullary for 20% and 35% of all adult and pediatric me- hematopoiesis. diastinal neoplasms, respectively (66). Peripheral The approach outlined in this section is based nerve sheath neoplasms typically arise from spinal primarily on the composition of the mediastinal or proximal intercostal nerves, less commonly abnormality, as there are a limited number of from the vagus, recurrent laryngeal, or phrenic structures from which lesions can arise in the nerves, and account for 70% of mediastinal neu- paravertebral compartment. While specific masses rogenic tumors (66). At multidetector CT, periph- RG • Volume 37 Number 2 Carter et al 431

Figure 16. Neurogenic neoplasm in a 39-year-old asymptomatic woman. Coned-down axial contrast- enhanced multidetector CT image at the level of the aortic arch shows a well-defined heterogeneous soft- tissue mass (arrow) in the right paravertebral medi- astinum, compatible with a benign peripheral nerve sheath tumor, in this case a schwannoma. When a smooth, round, or oval mass is present in the para- vertebral region at multidetector CT, the most likely diagnosis is a neurogenic neoplasm, typically a be- nign peripheral nerve sheath tumor arising from spinal or intercostal nerves. As in this case, internal heterogeneity may be due to cystic changes or hem- orrhage and is more common in schwannomas than in neurofibromas.

eral nerve sheath neoplasms may demonstrate a greater than 3.5 should be considered malignant,

dumbbell morphology and communication with and those with SUVmax of 2.5–3.5 should be fol- the spinal canal. Regions of heterogeneity may be lowed with surveillance imaging (68). due to cystic changes or hemorrhage and are more Other neurogenic neoplasms that may originate common in schwannomas than in neurofibromas in the paravertebral compartment include sympa- (66) (Fig 16). thetic ganglion neoplasms such as ganglioneuro- Neurogenic neoplasms may cause benign pres- mas, ganglioneuroblastomas, and neuroblastomas sure erosion of adjacent ribs or vertebrae and en- and neuroendocrine neoplasms such as paragan- largement of the neural foramina. These findings gliomas and are much less common. The imag- are suggestive of a benign lesion, compared with ing features of other neurogenic neoplasms are the osseous invasion and destruction typical of often nonspecific, and histologic sampling is often malignancies. MR imaging optimally demonstrates necessary for diagnosis. The presence of intense the extent of intraspinal/extradural extension, and homogeneous enhancement in a paravertebral several imaging signs for peripheral nerve sheath mass should raise suspicion for a paraganglioma. tumors have been described. The “fascicular sign” describes multiple hypointense, small, ring-like Extramedullary Hematopoiesis.—In the setting structures corresponding to fascicular bundles of paravertebral masses adjacent to thoracic and is typically associated with schwannomas. The vertebrae and/or ribs at multidetector CT in a “target sign” is characterized by central low signal patient with imaging and clinical evidence of a intensity and surrounding peripheral high signal hematologic disorder resulting in bone marrow intensity and is more commonly seen with neurofi- replacement (myelofibrosis or chronic myelog- bromas than with schwannomas. enous leukemia) or hemolytic anemia (thalas- When a previously stable neurofibroma sud- semia, sickle cell anemia, or hereditary sphero- denly increases in size, develops regions of het- cytosis), extramedullary hematopoiesis should erogeneity, and/or invades adjacent tissues, ma- be strongly considered (69). These masses lignant transformation to a malignant peripheral may be large or small and unilateral or bilat- nerve sheath tumor should be strongly consid- eral and typically enhance after administration ered (Fig 17). In patients with neurofibromatosis of intravenous contrast material due to high type 1, there is a 10% lifetime risk of developing vascularity. Heterogeneous attenuation and/or a malignant peripheral nerve sheath neoplasm, enhancement may be seen in the setting of iron and these lesions account for most cancer-related deposition and fat infiltration in long-standing deaths in these patients. FDG PET/CT has lesions (70) (Fig 18). demonstrated utility in distinguishing malignant In the absence of specific osseous findings peripheral nerve sheath tumors from benign neu- suggesting an underlying hematologic disorder, rofibromas, with sensitivity of 95% and specificity functional imaging with 99mTc sulfur colloid of 72% (67). Another study revealed sensitivity bone marrow scanning and SPECT/CT bone of 97% and specificity of 87% for detection of marrow scanning may noninvasively confirm the malignant peripheral nerve sheath tumors and presence of functioning hematopoietic tissue,

suggested that lesions with SUVmax less than 2.5 thus avoiding biopsy. In patients with sickle cell should be considered benign, those with SUVmax disease, the ancillary finding of autosplenectomy 432 March-April 2017 radiographics.rsna.org

Figure 17. Malignant peripheral nerve sheath tumor in a 37-year-old woman with neurofibromatosis type 1. (a) Coned-down axial nonenhanced multidetector CT image of the lower thoracic spine shows a well-circum- scribed homogeneous soft-tissue mass (arrow) in the left paravertebral region, compatible with a biopsy-proven benign peripheral nerve sheath neoplasm. Note the benign pressure erosion exerted on the vertebral body, which further supports the diagnosis. (b) Coned-down axial FDG PET/CT image 2 years later shows marked in- terval increase in the size of the lesion, which demonstrates increased FDG uptake and invasion and destruction of the thoracic spine, left lower lobe, and chest wall—in contrast to the benign pressure erosion seen earlier— findings consistent with malignancy. Findings suggestive of malignant degeneration of a neurofibroma include sudden increase in size, development of internal regions of heterogeneity, invasion of adjacent structures, and increased FDG uptake at PET/CT. serves as a clue to the diagnosis of extramedul- mass is identified at multidetector CT in a pa- lary hematopoiesis. tient after surgery or esophageal perforation or in the setting of infection in the adjacent . Cystic Lesions Internal foci of air may be present, and commu- nication may be seen with coexisting subphrenic Intrathoracic Meningocele.—When a smooth and abscesses or empyema (73). In the majority of unilocular mass with fluid attenuation at multide- situations, the clinical context permits definitive tector CT is present in the paravertebral medias- diagnosis; however, in selected cases, percuta- tinum and is associated with vertebral anomalies neous needle aspiration may be necessary to such as hemivertebrae, butterfly vertebra, or spina differentiate between abscess and postoperative bifida, the likely diagnosis is an intrathoracic me- seroma or hematoma. ningocele. An intrathoracic meningocele represents anomalous herniation of the leptomeninges through Pancreatic Pseudocyst.—A cystic mass in the an intervertebral foramen or vertebral body defect paravertebral mediastinum that develops over and is more common in adults than in children a short period of time in the clinical setting of (56,71). Associated findings include enlargement pancreatitis may represent intrathoracic extension of intervertebral foramina and vertebral and/or rib of a pancreatic pseudocyst (74). These uncom- anomalies or scoliosis (Fig 19). mon lesions contain pancreatic secretions, blood, Although it may be difficult to distinguish and necrotic material and spread through the intrathoracic meningoceles from other low- esophageal or aortic hiatus (69). At multidetector attenuation paravertebral masses such as CT, these lesions typically manifest as thin-walled neurenteric cysts or neurogenic neoplasms, masses that may be isoattenuating or hyperatten- the clinical setting of neurofibromatosis type uating depending on the presence of hemorrhage 1 should clinch the diagnosis. However, in or infection. Separate intra-abdominal pseudo- uncertain cases, multidetector CT, MR imag- cysts may or may not be present. ing, or myelography performed after intraspinal injection of contrast material will reveal filling Spinal Infections of the meningocele (72). When ill-defined soft tissue, unorganized fluid, and/or a loculated collection are present in the Mediastinal Abscess.—Mediastinal abscess paravertebral compartment in a patient with should be considered when a low-attenuation clinical symptoms such as back pain, fever, and RG • Volume 37 Number 2 Carter et al 433

Figure 18. (a) Extramedullary hematopoiesis in a 51-year-old man with myelofibrosis. Coned-down coronal nonenhanced multidetector CT image through the thoracic spine shows numerous paravertebral soft-tissue nodules and masses (arrows), compatible with extramedullary hematopoiesis. (b) Extramedullary hematopoi- esis in a 62-year-old woman with bone marrow replacement due to a chronic myeloid neoplasm. Coned-down axial contrast-enhanced multidetector CT image at the level of the aortic arch shows multiple heterogeneous paravertebral masses (M) composed of both fat and soft tissue, which is characteristic of extramedullary hemato- poiesis. Note the expansion of the marrow spaces of the ribs and vertebral bodies (*), supporting the diagnosis. At multidetector CT, the lesions of extramedullary hematopoiesis may appear as soft-tissue lesions that enhance after administration of intravenous contrast material due to high vascularity or heterogeneous masses due to iron deposition and fat infiltration in long-standing disease.

Figure 19. Intrathoracic meningocele in a 49-year-old woman with neurofibromatosis type 1.(a) Coned- down axial contrast-enhanced multidetector CT image at the level of the aortic arch shows a large fluid attenu- ation mass (M) in the posterior right hemithorax that communicates with the spinal canal. Note the irregularity of the adjacent vertebral body and expansion of the spinal canal. (b) Coned-down axial contrast-enhanced multidetector CT image at the level of the kidneys shows multiple cutaneous neurofibromas (arrows). When a homogeneous low-attenuation paravertebral mass is present in a patient with neurofibromatosis type 1 and as- sociated with vertebral anomalies such as hemivertebrae, butterfly vertebra, or spina bifida, a definitive diagnosis of intrathoracic meningocele can be made.

malaise, spinal infection should be included in the use (75). Early multidetector CT findings include differential diagnosis. These infections are typically paravertebral fat infiltration and intervertebral disk due to bacterial organisms, and significant risk fac- hypoattenuation, whereas osseous erosion, disk tors include diabetes, autoimmune diseases, malig- space narrowing, and sequestrum formation may nancy, immunosuppression, and intravenous drug be present in later stages (75) (Fig 20). 434 March-April 2017 radiographics.rsna.org

Figure 20. Discitis/osteomyelitis in a 62-year-old woman. Coned-down axial nonenhanced multidetector CT image (soft-tissue [a] and bone [b] windows) of the lower thoracic spine shows paravertebral soft tissue (arrows in a) and extensive osseous destruction. The clinical presentation was significant for methicillin-resistantStaphy - lococcus aureus (MRSA) bacteremia and back pain. The combination of imaging features and clinical findings enables definitive diagnosis of spinal infection, which may manifest at multidetector CT as ill-defined soft tissue, unorganized fluid, and/or a loculated fluid collection.

In the setting of immunodeficiency, particu- able identification with imaging alone, whereas larly human immunodeficiency virus (HIV) others may demonstrate suggestive but incon- infection, tuberculous involvement of the spine clusive imaging characteristics. In many cases, a should be considered. It has been demonstrated combination of clinical and imaging information that up to 60% of HIV-positive patients with permits a presumptive diagnosis. Therefore, the tuberculosis have skeletal involvement, and the approaches presented here recommend initial spine is the most commonly affected site, in- inclusion or exclusion of lesions on the basis of volved in approximately 50% of cases. Tubercu- multidetector CT features and correlation of losis associated with involvement of the posterior less conclusive imaging features with specific elements, the presence of a large prevertebral clinical information. In many cases, this will and paravertebral soft-tissue component out of strongly suggest a particular diagnosis and a proportion to the degree of osseous destruction, further evaluative or treatment strategy. and disk space narrowing enable differentiation of tuberculous from pyogenic infection. Addition- Disclosures of Conflicts of Interest.—M.L.R.d.C. Activities related to the present article: disclosed no relevant relationships. ally, the presence of calcification without new Activities not related to the present article: royalties from Amir- bone formation or sclerosis strongly suggests the sys Elsevier, Thieme Medical Publishers, and the American diagnosis of Pott disease of the spine (76,77). Registry of Pathology. Other activities: disclosed no relevant relationships. Conclusion The new mediastinal division scheme devel- References 1. Shields TW. Primary tumors and cysts of the mediastinum. oped by ITMIG is designed to enable precise In: Shields TW, ed. General thoracic surgery. Philadelphia, identification of mediastinal abnormalities at Pa: Lea & Febiger, 1983; 927–954. cross-sectional imaging by radiologists and 2. Fraser RS, Müller NL, Colman N, Paré PD, eds. The me- diastinum. In: Fraser and Paré’s diagnosis of diseases of the consistent communication between health care chest. 4th ed. Philadelphia, Pa: Saunders, 1999; 196–234. providers. It is anticipated that this system 3. Fraser RG, Paré PA, eds. The normal chest. In: Diagnosis will improve lesion localization, help generate of diseases of the chest. 2nd ed. Philadelphia, Pa: Saunders, 1977; 1–183. a focused differential diagnosis, and assist in 4. Felson B. Chest roentgenology. Philadelphia, Pa: Saunders, tailoring biopsy and treatment plans. Although 1973. mediastinal masses are uncommon, this article 5. Heitzman ER. The mediastinum. 2nd ed. New York, NY: Springer-Verlag, 1988. presents approaches that radiologists may find 6. Zylak CJ, Pallie W, Jackson R. Correlative anatomy and helpful when faced with a mediastinal abnor- computed tomography: a module on the mediastinum. mality at multidetector CT. RadioGraphics 1982;2(4):555–592. 7. Whitten CR, Khan S, Munneke GJ, Grubnic S. A diagnos- Some mediastinal masses manifest with tic approach to mediastinal abnormalities. RadioGraphics specific features at multidetector CT that en- 2007;27(3):657–671. RG • Volume 37 Number 2 Carter et al 435

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