Prevascular masses (Box 14.1) are located anterior to the ascending aorta and branch vessels. Almost all masses in this location³³ are thyroid or thymic masses, germ cell tumors, or lymphadenopathy. Thyroid masses can usually be specifically diagnosed or excluded based on their contiguity with the thyroid gland in the neck and their high CT attenuation on both pre- and postcontrast scans. In addition, most thyroid lesions are heterogeneous and have focal cysts as well as one or more areas of discrete calcification. A mass located superiorly in the anterior mediastinum that causes lateral deviation of the trachea is likely to be of thyroid origin.

The likely diagnoses for paracardiac masses (Box 14.2) that contact the diaphragm are pericardial cyst, diaphragmatic hernia, fat pad, lymphadenopathy, or, in patients with portal hypertension, cardiophrenic varices.^{34. and 35.} Most pericardial cysts are diagnosable by their uniform water attenuation on CT and their thin walls. Morgagni hernias are recognized by the omental fat within the hernia and sometimes by opacified bowel either within the mass or leading into it. If the mass is not in contact with the diaphragm, the differential diagnosis broadens to include germ cell tumors, mesenchymal and pericardial tumors, and thymic masses. Approximately 20% of thymomas are found in a paracardiac location, though contact with the diaphragm is very unusual. Lack of contact with the diaphragm excludes diaphragmatic hernia.

Paratracheal, subcarinal, and paraesophageal masses (Box 14.3) are considered together because the trachea, central bronchi, and esophagus are contained within a common fascial sheath. This compartment continues into the neck around the airway, the esophagus, and pharynx. Prime considerations for nonvascular masses in these locations are lymphadenopathy, intrathoracic thyroid mass, foregut cysts, esophageal tumors, hiatal hernias, and paraspinal masses encroaching on the middle mediastinum. In terms of frequency, lymphadenopathy is by far the most frequent. Masses deep to the azygos vein in either the right paratracheal area or in the pretracheal or precarinal space are almost invariably enlarged lymph nodes. For masses arising in the aortopulmonary window, the only other alternative is aortic aneurysm – a diagnosis that can be readily confirmed or excluded with contrast-enhanced CT or MRI. As mentioned earlier, lymphadenopathy is frequently multifocal and, in the case of metastatic carcinoma, the primary tumor is usually already known. Bronchogenic cyst can be diagnosed with confidence if the criteria of a simple cyst are met. But many bronchogenic cysts do not meet these criteria and these, therefore, are included in the differential diagnosis of a solid mediastinal mass. ³⁶ Thyroid masses that pass lateral to or posterior to the trachea are distinctive, partly because of the signs discussed below, but also because thyroid masses show far greater contact, displacement, and compression of the trachea than do lymph nodes. Separation of the trachea from the esophagus is a characteristic shared only by thyroid masses, bronchogenic cysts, esophageal tumors, and an aberrant origin of the left pulmonary artery. Aortic arch anomalies, though they deform the trachea and esophagus in various ways, do not pass between these two structures.

Strictly speaking, masses situated on either side of the vertebral column (Box 14.4) are outside the mediastinum since, according to anatomists’ definitions, the mediastinum lies anterior to the spine. However, it is standard practice among radiologists and thoracic surgeons to label paraspinal masses as posterior mediastinal masses.

Bronchogenic cysts are discussed on page 1089–1093.

Esophageal duplication cysts are uncommon. They may present in adults or children. ⁴² The cysts are located in the middle or posterior mediastinum, have muscular coats, and contain mucosa that resembles esophagus, stomach, or small intestine. Esophageal duplication cysts usually occur within the wall, or are adherent to the wall, of the esophagus, are either spherical or tubular in shape, and are usually located along the lateral aspect of the distal esophagus.^{43. and 44.} Many cysts are clinically silent and are first discovered as asymptomatic masses on chest imaging. The remainder manifest with symptoms of dysphagia or chest pain or symptoms due to compression of adjacent structures. ⁴² Ectopic gastric mucosa in the cyst may cause bleeding into the cyst or perforation of the cyst and the cyst may become infected.

On chest radiographs, esophageal duplication cysts manifest as well-defined round or lobular masses in the middle or posterior mediastinum (Figs 14.1 and 14.2).^{43. and 44.} The masses are usually solid, unless they are infected and contain air. Calcification is rarely detected in the cyst walls. On CT, the cysts manifest as round or tubular water attenuation masses, usually in close proximity to the esophageal wall. These features are similar to those seen in cases of bronchogenic cysts, except that the wall of the esophageal duplication cyst may appear thicker and the mass may have more of a tubular shape than the typical bronchogenic cyst (Fig. 14.2).^{42.45.46. and 47.} On barium swallow examination, the cyst may manifest as either an intramural or extrinsic mass. ⁴² Although esophageal duplication cysts are usually of water attenuation on CT (Fig. 14.1), some contain proteinaceous fluid or blood and thus appear as soft tissue masses.^{43. and 44.} On MRI, the cysts have similar signal intensity characteristics to bronchogenic cysts, being of variable signal intensity on T1-weighted images, depending on intracystic content, and of markedly increased signal intensity on T2-weighted images (Figs 14.1 and 14.2). ⁴⁸ Endoscopic ultrasonography can be used to diagnose and treat esophageal duplication cysts. ⁴⁹

Pericardial cysts are anomalous outpouchings of parietal pericardium, but only rarely have an identifiable communication with the pericardial sac. Pericardial diverticula are related anomalies of the visceral pericardium that communicate with the pericardial space. ⁵⁰ Rapid change in size, particularly a decrease in size, suggests a pericardial diverticulum rather than a pericardial cyst. ⁵¹ The cysts contain clear yellow fluid. The interior is usually unilocular but can be trabeculated. In one series, 20% of cases examined pathologically were multilocular, ⁵² though in another large series of 72 patients, only one pericardial cyst was truly loculated. ⁵³ The wall of the cyst is composed of collagen and scattered elastic fibers lined by a single layer of mesothelial cells. ⁵² Most affected patients are asymptomatic at presentation, but in series derived from surgical case material, symptoms such as chest pain, cough, and dyspnea are reported in up to a third of patients.^{38.52. and 53.}

There is a strong predilection for the anterior cardiophrenic angles and the cysts typically contact the heart, the diaphragm, and the anterior chest wall. They are more frequent on the right than on the left. In one large series of 72 patients with pericardial cysts, 37 (51%) were in the right cardiophrenic angle (Figs 14.3 and 14.4) and 17 were in the left. ⁵³ The remaining 18 arose higher in the mediastinum (Fig. 14.5), and 11 extended into the superior mediastinum. In a review of chest radiographs of 41 patients with pericardial cysts, the right-to-left ratio was 4 : 3. ⁵²

On radiographic studies, the cysts are seen as smooth round or oval well-defined masses in contact with the heart (Fig. 14.3, Fig. 14.4, Fig. 14.5 and Fig. 14.6). Occasionally, the cysts may be large enough to compress adjacent structures such as heart. ⁵⁴ A pointed oval shape has been observed in some cases.^{52.55. and 56.} Calcification is exceptional on chest radiographs. On CT, the cysts are usually homogeneous water attenuation masses with thin or imperceptible walls (Figs 14.4 and 14.5). The cyst contents should not enhance after administration of intravenous contrast. ⁵⁷ Soft tissue attenuation pericardial cysts are quite rare. ⁵⁵ The size of the cysts is quite variable, with very large cysts occasionally reported (Figs 14.3 and 14.4).^{52. and 53.} Ultrasonography can be used to demonstrate the cystic nature of these lesions. MRI shows the mass to be homogeneous and of low signal intensity on T1-weighted images and of high signal intensity on T2-weighted images (Fig. 14.6), similar to water. ³² Cyst puncture and aspiration can be diagnostic in difficult cases or therapeutic in symptomatic patients, although the frequency of recurrence after such intervention is unknown (Fig. 14.4). ⁵⁸

Neurenteric cysts result from incomplete separation of endoderm from notochord, resulting in a diverticulum of endoderm. Neurenteric cysts are pathologically identical to esophageal duplication cysts and usually have either a fibrous connection to the spine or an intraspinal component. ⁵⁹ These cysts are typically associated with vertebral body anomalies such as hemivertebra, butterfly vertebra or spina bifida that occur at or above the level of the cyst. Most neurenteric cysts occur in the posterior, rather than middle, mediastinum, and usually above the level of the carina. ³⁸ Neurenteric cysts are quite rare.^{14.38. and 60.}

Radiographically (Fig. 14.7),^{61. and 62.} neurenteric cysts are round, oval, or lobulated masses of water density situated in the posterior mediastinum or paravertebral region. Their cystic nature can be demonstrated by ultrasonography. The CT and MRI appearance of these lesions (Fig. 14.7) is similar to that of other foregut cysts. ⁴⁴ MRI is useful for optimally demonstrating the extent of spinal abnormality and degree of intraspinal involvement. Because the cysts may communicate with the subarachnoid space, CT myelography can also be diagnostic.

On rare occasions, a pancreatic pseudocyst extends into the mediastinum.^{63. and 64.} Most affected patients are adults and have clinical features of chronic pancreatitis. In children, the usual etiology is trauma. ⁶⁵ Radiographically, most patients have either bilateral or left-sided pleural effusions. ⁶⁶ The mediastinal component of the pseudocyst is almost always in the middle and posterior mediastinum, having gained access to the chest via the esophageal or aortic hiatus. The pseudocyst in many instances, therefore, deforms the esophagus. CT is the optimum method of demonstrating the full extent of these pseudocysts. ⁶⁷ CT shows a thin-walled cyst containing fluid within the mediastinum in continuity with the pancreas (Fig. 14.8), as well as any peripancreatic fluid collections. ⁶⁸ Magnetic resonance cholangiopancreaticography (MRCP) has been used to successfully diagnose a mediastinal pancreatic pseudocyst. ⁶⁹ The cyst may, on rare occasion, rupture into the pericardium resulting in tamponade. ⁷⁰ Hemothorax and esophagobronchial fistula have also been reported as complications of mediastinal pseudocyst. ⁷¹ Mediastinal pseudocysts have been successfully treated by endoscopic ultrasonography.^{72. and 73.}

Intrathoracic meningoceles are protrusions of spinal meninges through the intervertebral foramina. ⁷⁴ They are usually detected in patients between 30 and 60 years of age as asymptomatic masses on chest radiographs. They are rarely associated with pain or neurological abnormalities. ⁷⁵ Approximately two-thirds of cases occur in association with neurofibromatosis. ⁷⁵ On rare occasions, multiple or bilateral intrathoracic meningoceles are encountered.^{76. and 77.}

On chest radiographs, ⁷⁸ these lesions manifest as well-defined paravertebral masses, usually associated with scalloping and deformity of the adjacent ribs, pedicles, or vertebral bodies. Enlargement of the adjacent intervertebral foramen is an important diagnostic feature. Kyphoscoliosis is often present. These findings are identical to those seen in patients with so-called ‘dumbbell’ nerve sheath tumors – a diagnostic problem that is complicated by the fact that both conditions are so frequently associated with neurofibromatosis. CT^{79. and 80.} better demonstrates these features and also shows that the ‘mass’ is of water attenuation, since the bulk of the lesion consists of cerebrospinal fluid (Fig. 14.9). If CT is performed with intrathecal contrast medium, the contrast will enter the meningocele, confirming the diagnosis. Similarly, uniform cerebrospinal fluid (CSF) signal is seen throughout the lesion on MRI. ⁷⁹

Thoracic lymphoceles are usually due to trauma and are discussed on page 1140. Mediastinal thoracic duct cysts are extremely rare lesions that may be due to either congenital or degenerative weaknesses in the wall of the thoracic duct. ³⁷ The cysts can occur anywhere along the course of the thoracic duct, but have also been reported in the neck. ⁸¹ Very large cysts are reported. ⁸² In a review of 30 reported cases, approximately half of affected patients were asymptomatic. ⁸³ The remainder presented with symptoms such as chest pain, dysphagia, and dyspnea due to compression of adjacent structures.^{83.84. and 85.} CT usually shows a homogeneous mass of water attenuation along the course of the thoracic duct (Fig. 14.10). ⁸³

Hiatal hernias are frequent incidental findings on chest radiographs and CT. Pain as a result of gastroesophageal reflux or anemia due to upper gastrointestinal bleeding may be presenting complaints. On chest radiography, they produce a smooth, focal widening of the posterior junction anatomy extending down to the diaphragm. Varying amounts of fat surround the hernia itself, and in most instances some air can be appreciated within the hernia and there may be a visible air–fluid level (Fig. 14.12). When air is present within the hernia, a definitive diagnosis can be made by chest radiography. In the absence of air, however, the differential diagnosis includes other lower paraesophageal masses including lymphadenopathy, and CT or barium swallow examination may be required for confirmation.

At CT, the esophagus can be traced down into the hernia, and air (and contrast material) within the lumen usually enables the diagnosis to be made without difficulty (Fig. 14.12). The fat surrounding the hernia may be a striking feature. Hiatus hernias can be huge and may contain a major portion of the stomach. With large paraesophageal hernias, the stomach not infrequently undergoes organoaxial rotation. ¹⁰³

On occasion, ascitic fluid under tension may herniate into the mediastinum at the gastroesophageal junction, usually contained by the parietal peritoneum. ¹⁰⁴ This so-called ‘communicating thoracic hydrocele’ can occur in the absence of a hiatal hernia and manifests as a mass on chest radiographs. ¹⁰⁴ Because the fluid freely communicates with the abdominal cavity, the ‘mass’ may spontaneously disappear. CT shows a water-attenuation middle mediastinal mass closely associated with the esophageal hiatus in a patient with ascites (Fig. 14.13). ¹⁰⁵

Excessive deposition of fat may result in mediastinal widening, a condition known as mediastinal lipomatosis.125. ^{and 126.} When associated with generalized obesity, mediastinal lipomatosis does not usually pose a diagnostic problem. However, in patients on steroid therapy or in those with Cushing disease, focal collections of histopathologically normal, but unencapsulated, fat can deposit in many sites, including the mediastinum, and simulate mass lesions on chest radiographs.^{127.128. and 129.} Furthermore, a similar phenomenon is occasionally encountered in patients with normal steroid hormone levels.^{130. and 131.}

On chest radiographs, mediastinal lipomatosis usually manifests as smooth, diffuse widening of the superior mediastinum (Fig. 14.19). There is usually no mass effect upon the trachea or other mediastinal structures. In addition to findings of mediastinal fat deposition, chest radiographs also usually show a symmetric increase in extrapleural fat and the costophrenic angle fat pads may be enlarged as well. When mediastinal fat deposition is symmetric and diffuse, the radiographic appearance is characteristic enough to pose no significant diagnostic difficulty (Fig. 14.19). On the other hand, when deposition is asymmetric or more focal, CT may be required to exclude a soft tissue mass (Fig. 14.20). This may be the case in patients with lymphoma who are being treated with corticosteroids. At CT, the uniform low attenuation of fat is diagnostic (Figs 14.19 and 14.20).^{130.132. and 133.}

A rare inherited condition termed multiple symmetric lipomatosis, also known as Madelung disease or Lanois–Bensaude syndrome, radiologically resembles mediastinal lipomatosis. In this condition, multiple masses of benign fat tissue proliferate at various sites including the mediastinum. ¹³⁴ Unlike mediastinal lipomatosis, however, these masses occasionally compress mediastinal structures such as the trachea¹³⁵ or larynx. ¹³⁶ Although the pathogenesis is unclear, the disease may be due to defective regulation of brown fat.^{137.138.139. and 140.}

Increased use of combined FDG-PET-CT imaging in oncology patients has led to the recognition that metabolically active fat, known as brown fat, can accumulate FDG and lead to false-positive interpretations. ¹⁴¹ Brown fat is more commonly found in young patients and in women. It is most commonly seen in the neck and paravertebral regions, but can also be found in the mediastinum. ¹⁴² Careful correlation between the CT image and foci of FDG uptake should prevent misinterpretation (Fig. 14.21).

Mediastinal tumors of fatty origin are uncommon, accounting for less than 1% of 1064 surgically proved mediastinal masses. ¹⁴ On chest radiographs, both benign and malignant fat-containing tumors manifest as well-defined, round or oval, mediastinal masses. ¹⁴³ Benign lipomas usually do not compress surrounding structures unless they are very large. Quinn et al. ¹⁴⁴ reported one unusual case where a mediastinal lipoma extended into the spinal canal and caused pressure deformity of the adjacent bones. Large mediastinal lipomas may mold so completely to mediastinal contours as to simulate the appearance of an enlarged heart. ¹⁴⁵ CT of mediastinal lipomas usually shows a homogeneous mass of fat attenuation. The lesion may contain a very few strands of soft tissue or septa, but these should be quite thin (<1.0 mm).^{144. and 146.} Lipoblastomas are benign fat-containing tumors that usually occur in childhood.^{147. and 148.} On CT, both fat and soft tissue components are seen.^{29.149. and 150.} Occasionally, the amount of fat seen on CT is relatively small and the mass is primarily of soft tissue attenuation. ¹⁵¹ Hibernomas are very rare benign tumors that contain brown fat. ¹⁵² The CT features of mediastinal hibernomas are the subject of case reports only.^{152. and 153.} Based upon these reports, the masses appear as mixed fat, water, and soft tissue attenuation. The amount of fat that is identifiable seems to be variable. ¹⁵⁴ As hibernomas contain metabolically active brown fat, they can show considerable FDG uptake on FDG-PET imaging.^{152. and 155.} Angiolipoma and myelolipomas are also very rare benign tumors that can occur in the mediastinum. They also manifest as masses of mixed soft tissue and fat attenuation on CT, and are thus indistinguishable from liposarcoma.^{156. and 157.}

Liposarcomas are malignant fat-containing tumors that occur more often in the anterior than the posterior mediastinum (when they occur in the mediastinum).^{158. and 159.} Most affected patients are middle-aged adults who present with symptoms of chest pain and dyspnea. The masses are typically large and may diffusely infiltrate the mediastinum. Well-differentiated liposarcomas may have large amounts of fat admixed with soft tissue components on CT or MR images (Fig. 14.22). ¹²⁴ On occasion, the lesions may be almost completely fatty with only a minimal soft tissue component. ¹⁶⁰ High-grade tumors usually do not have significant amounts of fat demonstrable on CT or MRI; instead, these lesions manifest as infiltrative masses of heterogeneous soft tissue attenuation (Fig. 14.22) or signal intensity. ¹⁵⁸ Myxoid liposarcomas of the mediastinum may contain regions of near water attenuation on CT (Fig. 14.23) and may have calcified stroma. ¹⁶¹

It can be difficult to confidently differentiate benign lipomas from well-differentiated liposarcomas of the mediastinum. This question has not specifically been addressed in regard to mediastinal lesions. However, numerous studies of peripheral fatty tumors suggest that large size (>10.0 cm), male sex, fat content less than 75% of the lesion, thick internal septa (>1.0 mm), and nodular or globular soft tissue components favor liposarcoma.162.^{163.164. and 165.} Areas of high signal intensity on fluid-sensitive MRI sequences are also a suggestive feature of liposarcoma. ¹⁶² FDG-PET-CT imaging features of mediastinal liposarcomas have not been reported. Based on experience with extremity tumors, however, the degree of FDG uptake likely correlates with likelihood of malignancy, histopathologic grade, and aggressiveness of the lesion (Fig. 14.24).^{166. and 167.} When in doubt, histopathologic sampling is required.

Herniation of omental or perigastric fat is a common cause of a localized fatty mass in the mediastinum. The fat may herniate through the esophageal hiatus, the foramen of Morgagni, or the foramen of Bochdalek. Such herniations are usually readily diagnosed on chest radiographs because of their characteristic locations. The masses are of fat attenuation or signal intensity on CT²⁹ or MRI¹⁶⁸ and may contain linear or nodular foci due to contained omental vessels (Fig. 14.25).

Extramedullary hematopoiesis in potential blood-forming organs such as the liver, spleen, and lymph nodes is common in patients with severe anemia. Thoracic manifestations are rare and usually consist of paravertebral soft tissue masses, although pulmonary parenchymal involvement has been described. ¹⁶⁹ The masses are caused by extrusion of the marrow through the thinned cortex of the posterior ribs. Histopathologically the masses resemble splenic tissue with hematopoietic elements mixed with fat. The masses themselves are usually asymptomatic, though paraplegia from cord compression may occur.^{170. and 171.} Massive hemothorax secondary to rupture of the hematopoietic masses has been described. ¹⁷² The most common conditions that result in extramedullary hematopoiesis are the congenital hemolytic anemias, notably thalassemia, hereditary spherocytosis, and sickle cell disease. ¹⁷³ However, it may rarely occur in other anemias and may even occur in patients without anemia. ¹⁷⁴

Thoracic extramedullary hematopoiesis manifests on chest radiographs,171.^{174. and 175.} CT,^{175. and 176.} and MRI¹⁷⁷ as focal paravertebral masses, usually in the lower half of the thorax (Fig. 14.26). The masses are usually well marginated because they are covered by pleura, are bilateral in distribution, contain no calcification, and show no rib destruction. Further foci of extramedullary hematopoiesis can also be seen as subpleural masses adjacent to ribs. These subpleural masses may be continuous or discontinuous with the paravertebral masses. The adjacent bone is usually normal or shows findings of marrow expansion; pressure erosions or bone destruction do not occur. ¹⁷⁴ CT is particularly useful for demonstrating the lacelike marrow expansion in the adjacent bones (Fig. 14.26). ¹⁷⁵ On CT, the lesions manifest as heterogeneous or homogeneous soft tissue attenuation masses (Figs 14.26 and 14.27). There may be some fat within the mass (Fig. 14.27), ¹⁷⁸ but calcification is uncommon. ¹⁷⁹ On MRI, the masses are usually heterogeneous with increased signal intensity on T1-weighted images because of contained fat. ¹⁷⁷ Radionuclide studies using agents that show erythropoiesis or the reticuloendothelial system may demonstrate activity in the mass,^{175.180.181. and 182.} but can be negative.^{175. and 183.} Diagnosis can also be established by fine needle aspiration biopsy. ¹⁸⁴

Teratomas are the most common mediastinal germ cell tumors and are derived from more than one embryonic germ layer. Most mediastinal teratomas arise in cell rests within, or in intimate contact with, the thymus.192. ^{and 193.} Teratomas are classified histopathologically as mature or immature. Immature teratomas are further subclassified as immature teratoma, immature teratoma – malignant, or immature teratoma with additional malignant components.¹⁹⁴ The term teratocarcinoma is now discouraged. ¹⁹⁰Mature teratomas are composed of different tissue types (ectoderm, endoderm, mesoderm), with ectodermal derivatives predominating. ¹⁹⁵ The term dermoid cyst is commonly used when the tumor contains primarily ectodermal components such as skin, sebaceous material, hair and calcification.^{189. and 196.} Such lesions are typically unilocular; multilocular lesions with intervening solid portions are less common. ¹⁴ Tumors with more than 10% immature elements are classified as immature teratoma and are considered potentially malignant. ¹⁹⁰Immature teratoma – malignant is such a lesion that develops metastases after diagnosis. Teratomas that contain malignant components such as other malignant germ cell neoplasia, sarcoma, or adenocarcinoma, are termed immature teratoma with additional malignant components and are frequently metastatic at presentation.190.^{194. and 197.} Such tumors have a very poor prognosis.

Mature teratomas account for 70% of germ cell tumors in childhood and 60% of mediastinal germ cell tumors in adults. Mature teratomas occur most frequently in children and young adults.^{14.185. and 198.} About half of affected patients are asymptomatic at presentation, with the lesion being detected on chest radiographs obtained for other purposes. In the remainder, symptoms due to local compression, rupture, or infection occur. The most common presenting complaints are chest pain, productive cough, dyspnea, or fever. ¹⁹⁹ Rarely, affected patients present with pneumonia, hemoptysis, or the superior vena cava syndrome. Trichoptysis (the expectoration of hair) is a dramatic, but extremely rare, symptom that occurs when the lesion ruptures into the airway.^{14. and 189.} Patients with mature teratoma usually have normal serum levels of β-hCG and AFP. Complete resection is the treatment for mature teratomas and usually results in a complete cure. Despite a benign histology, these tumors may be difficult to remove when they are adherent to local structures.

On chest radiographs, mature teratomas manifest as well-defined, rounded, or lobulated masses that usually project to one side of the midline (Fig. 14.28). ¹⁴ They most commonly occur in the anterior mediastinum, typically in the prevascular space. On occasion, they occur in the posterior mediastinum or the lung parenchyma itself.^{14.186.199.200.201. and 202.} The lesions tend to grow very slowly, but may increase in size rapidly if intratumoral hemorrhage occurs. Calcification, ossification, or even teeth^{199. and 200.} may be visible on chest radiographs (Fig. 14.29) and, occasionally, sufficient fat is present within the lesion to be detectable radiographically.

The CT appearance of mature teratoma is quite variable because it depends upon the content of the lesion (Figs 14.28 and 14.29).^{203. and 204.} Almost all lesions have some areas of water attenuation on CT. Regions of fat attenuation are seen on CT in up to three-quarters of lesions and are the predominant tissue type in 15%. ¹⁹⁹ Fat–fluid levels within the lesion, while uncommon, are virtually diagnostic of teratoma (Fig. 14.30).^{205. and 206.} More often, however, the fat is interspersed with regions of water and soft tissue attenuation. A definite cyst wall, which may have curvilinear calcification, may be visible on CT (Fig. 14.28), as is characteristic intralesional calcification (Fig. 14.29). ¹⁹⁹

On rare occasions, the lesions rupture into the airway, pleural space, or pericardium. When the tumor ruptures into the airway, air may enter the cyst and become visible on imaging examination; severe chemical pneumonitis or lung abscess can also result. ³⁸ In a review of 17 patients with seven ruptured and 10 unruptured teratomas, those lesions that ruptured were noted to be more internally heterogeneous on CT than were those that were not ruptured. ²⁰⁷ Additional findings suggestive of rupture were adjacent consolidation, atelectasis, pleural, or pericardial effusion. ²⁰⁷ In two cases, fat was seen in the lung parenchyma. Rupture into the pericardium²⁰⁸ or pleura can result in the appearance of a fat–fluid level within these spaces on imaging examinations. ²⁰⁹

As is the case with CT, the MRI appearance of mature mediastinal teratomas is quite variable (Fig. 14.29). Because the contents of the cyst are typically rich in proteinaceous fluid, the cystic component of the lesion may be of high signal intensity on T1-weighted images.^{32.199. and 210.} Furthermore, the lesion may be of high signal on T1-weighted images because of fat or hemorrhage. On ultrasonography, the lesions may appear as completely cystic or solid masses or as mixed cystic and solid masses. ²¹¹ The pattern on ultrasonography is often quite complex because of intralesional calcification (densely echogenic), hair (hyperechoic dots), and fat (dense echo pattern). ²¹² One case that showed echogenic floating spherules in the mass has been described. ²¹³

Information regarding FDG-PET imaging features of mediastinal mature teratoma is scant. Based upon limited experience with germ cell tumors in other sites, it is likely that these lesions, unless complicated, show little or no FDG accumulation. ²¹⁴ Any foci of increased FDG accumulation should suggest a more aggressive lesion, such as immature teratoma, until proven otherwise.

Imaging features of immature teratoma or teratoma with malignant components are less well-described. ¹⁹⁰ Masses are typically described as large, invasive, and quite heterogeneous on CT or MRI, and may or may not contain areas of fat or calcification (Fig. 14.31). ¹⁹⁰

In addition to teratomas with malignant features, other types of malignant germ cell tumors that occur in the mediastinum include seminoma, embryonal cell carcinoma, endodermal sinus tumor, choriocarcinoma, and mixed germ cell tumors.^{215. and 216.} Seminoma is the most common pure histopathologic type in men and accounts for 40% of such tumors. ²¹⁶ However, tumors of mixed histology are more common than pure seminoma. ²¹⁵ Malignant mediastinal germ cell tumors are usually encountered in young adults and are much more common in men than women. ¹⁹² In a review of 103 cases of primary mediastinal seminoma, only five occurred in women. ²¹⁷ Even mediastinal choriocarcinoma in adults is more common in men than women; in children, the male–female ratio is more evenly distributed. ¹⁹² Because of marked differences in prognosis and treatment, nonteratomatous malignant germ cell tumors are frequently grouped as seminoma and nonseminomatous germ cell malignancies.¹⁹¹

Malignant mediastinal germ cell tumors are more frequently symptomatic than mature teratomas.^{187.190. and 192.} Common presenting complaints include cough, dyspnea, and chest pain. ²¹⁷ Superior venal cava obstruction is reported in up to 10% of affected patients.^{217. and 218.} Weight loss may also be a notable feature. However, between 10% and 30% of affected patients are asymptomatic at presentation, with the mass discovered on routine chest radiographs. ¹⁹¹

Serum levels of hCG and AFP are useful for diagnosis and monitoring of some mediastinal germ cell malignancies.^{187. and 190.} Both hCG and AFP levels are typically normal in cases of pure seminoma; slight elevation in hCG levels are occasionally encountered; elevation of AFP indicates a nonseminomatous component of the tumor. Up to 80% of patients with nonseminomatous germ cell malignancies have elevated levels of AFP and 54% have elevated levels of hCG.^{187. and 190.} There is an association between malignant nonseminomatous germ cell tumors of the mediastinum and hematologic malignancies^{219. and 220.} and up to 20% of affected patients may have Klinefelter syndrome.^{221. and 222.}

Seminomas typically manifest on chest radiographs as focal, unilateral or bilateral, mediastinal masses (Fig. 14.32). On CT or MRI, they are usually large lobulated masses of homogeneous attenuation or signal intensity, often indistinguishable from lymphoma (Fig. 14.32).^{187. and 190.} Cysts or areas of necrosis may also be seen in association with mediastinal seminoma.^{187. and 190.} Invasion of adjacent structures may occur but calcification is rare. Metastases to regional nodes or lung can occur (Fig. 14.32).

Nonseminomatous germ cell malignancies usually manifest as large lobular or ill-defined anterior mediastinal masses (Figs 14.33 and 14.34). ¹⁹⁰ The mass is typically asymmetric and projects to one side of the thorax.^{185.223. and 224.} Calcification is an exceptional finding on chest radiographs. On CT or MRI, the mass may be quite heterogeneous and may contain cysts or areas of necrosis and hemorrhage (Figs 14.33 and 14.34).^{225. and 226.} These features may be accentuated following administration of intravenous contrast. Coarse tumor calcification is rarely seen on CT.^{225. and 227.} Adjacent mediastinal fat planes are often obliterated and extensive local invasion may be identified. ²²⁸ Invasion of the adjacent mediastinal structures, chest wall, and lung, as well as metastases to the regional lymph nodes and distant sites, is common (Figs 14.33 and 14.34). ¹⁹⁰

The FDG-PET imaging features of mediastinal germ cell malignancies are not well described. Most of the literature on the subject describes findings in patients with testicular or ovarian primary tumors.^{11.229.230.231. and 232.} Extrapolation of such results to patients with mediastinal primary tumors is difficult, as the nonseminomatous mediastinal tumors tend to behave quite differently from their testicular or ovarian counterparts. Nevertheless, it is likely, based upon these results, that pure teratoma will show little if any increased metabolic activity. ²³⁰ Malignant tumors (seminoma or nonseminomatous), on the other hand, should show metabolic activity (Figs 14.33 and 14.35). Results of staging studies with testicular primary tumors are mixed, with one multicenter randomized trial showing only a slight positive benefit for FDG-PET over CT. ²²⁹ Marked FDG uptake in a residual mass after treatment, however, does seem to predict viable tumor. ²³²

A residual mediastinal mass is sometimes seen on CT after successful treatment of a primary mediastinal nonseminomatous germ cell malignancy or after treatment of metastatic disease from a gonadal primary (Fig. 14.36). This mass may be cystic in nature, contain residual mature teratoma, and enlarge with time.^{233. and 234.} This phenomenon is known as the ‘growing teratoma’ syndrome.235.^{236.237. and 238.} The benign or malignant nature of the residual mass cannot be confidently determined based upon the CT appearance alone. However, elevation of serum tumor markers suggests a malignant component. Andre et al. ²³⁶ followed 30 patients with growing teratoma syndrome. All 30 lesions were biopsied or resected and 86% of lesions were found to have a mature teratoma component. All but one patient who underwent curative resection survived disease-free. Five of the six patients who had only partial resection developed recurrent disease and one died of progressive tumor. These authors and others²³³ concluded that complete surgical resection was the treatment of choice.

Lymphadenopathy (Box 14.10) can be caused by a variety of infectious, inflammatory, and neoplastic conditions. Neoplastic causes include lymphoma, leukemia, and metastatic carcinoma. Lymph node metastases frequently occur in the setting of thoracic malignancies such as lung (Fig. 14.37), esophagus, and breast cancer. Extrathoracic tumors that frequently spread to intrathoracic lymph nodes include renal, testicular, and head and neck malignancies.^{239. and 240.} The most common infections that result in intrathoracic lymphadenopathy are tuberculosis (Fig. 14.38) and fungal disease (particularly histoplasmosis and coccidioidomycosis). Lymph node enlargement is frequent in acquired immune deficiency syndrome (AIDS) patients (see Chapter 6) and can be caused by lymphoma or granulomatous infection. Rare infections such as tularemia, anthrax, and plague can also cause lymphadenopathy. Enlarged nodes in patients with anthrax are characteristically of high attenuation on CT due to extensive hemorrhage. ²⁴¹ Significant lymphadenopathy is quite uncommon in other infections, particularly bacterial pneumonia, and, when present, suggests an unusual organism or alternative diagnosis.

Sarcoidosis is a particularly frequent cause of intrathoracic lymph node enlargement in young adults (Fig. 14.39). When multiple lymph node groups in the hila and mediastinum are symmetrically enlarged in a young patient, sarcoid is the most likely diagnosis. Lymph nodes in patients with sarcoidosis are frequently positive on FDG-PET scans (Fig. 14.40). ²⁴² Lymphoma is the most important differential diagnosis in such patients, but lymphoma is rarely so symmetrically distributed with equal involvement of the hilar and mediastinal lymph node groups (Fig. 14.41). Isolated paracardiac node enlargement is unusual in cases of sarcoid or infection, and are often due to lymphoma or metastatic carcinoma.^{243. and 244.} Lymphoma and sarcoidosis are discussed further in Chapters 13 and 11, respectively.

Reactive hyperplasia is a term used to describe an acute or chronic nonspecific inflammatory response in which both inflammation and hyperplasia are present. Lymph nodes undergo reactive changes whenever challenged by infection, cell debris, or foreign substances. Thus, nodal enlargement due to reactive hyperplasia is seen in nodes draining areas of pulmonary infection, bronchiectasis, and a variety of inflammatory and chronic interstitial lung diseases,^{245. and 246.} and also in nodes draining neoplasms. Reactive hyperplasia is a common cause of false-positive lymph nodes on FDG-PET scans in patients with nonsmall cell carcinoma. ²⁴⁷ In such cases, high FDG uptake has been attributed to overexpression of the glucose transporter-1 enzyme in regions of follicular lymphoid hyperplasia.^{248. and 249.}

Chronic left heart failure is an important and perhaps underrecognized cause of mediastinal lymphadenopathy.^{250.251.252. and 253.} Between 42% and 66% of patients with left heart failure will have enlarged lymph nodes (>1 cm short axis, see below) on CT.^{250.252. and 253.} Most (63%) are in the pretracheal regions and the mean short axis diameter in one series was 1.3 cm. ²⁵² Node margins may be ill-defined and mediastinal fat may be of increased attenuation (‘hazy’) in up to 33%. ²⁵⁰ Presence of enlarged nodes has been shown to correlate with decreased left ventricular ejection fraction.^{252. and 253.} Node enlargement may resolve after treatment for heart failure. ²⁵³ The etiology for lymph node enlargement in this setting is unknown. Histopathologic sampling in three patients with congestive heart failure and mediastinal lymphadenopathy showed only sinus histiocytosis. ²⁵¹ It has been speculated, however, that mediastinal lymph nodes hypertrophy in response to chronic mediastinal edema and lymphatic congestion. ²⁵¹

Mediastinal lymph node enlargement is also common in patients with pulmonary fibrosis that occurs either idiopathically^{254. and 255.} or in the setting of collagen vascular disease (Fig. 14.42)^{245. and 256.} or asbestos exposure. ²⁵⁷ In one series, 13 (93%) of 14 patients with usual interstitial pneumonia had enlarged mediastinal lymph nodes on CT. ²⁵⁵ Nodes larger than 2 cm in short axis diameter were seen in three (21%). ²⁵⁵ In another series, enlarged nodes were found on CT in 67% of 175 patients with diffuse infiltrative lung disease. ²⁴⁵ These authors noted that the vast majority of patients had only a few enlarged nodes and that they rarely exceeded 15 mm in short axis diameter. ²⁴⁵ Jung et al. ²⁵⁴ reported enlarged nodes on CT in 86% of 30 patients with pulmonary fibrosis and also found that the number of enlarged nodes correlated with disease severity. Histopathologic analysis of enlarged lymph nodes in patients with fibrosis usually shows reactive change or sinus histiocytosis. ²⁴⁵

Castleman disease (Box 14.11), also known as giant lymph node hyperplasia or angiofollicular lymph node hyperplasia, is a rare cause of often massive lymph node enlargement in the chest. ²⁸⁵ Although intrathoracic lymph nodes are most commonly affected, nodes at any location can be involved.^{276. and 286.} Extranodal involvement, including spleen and lung parenchyma, can also occur.^{287.288. and 289.}

There are two major histopathologic variants of Castleman disease: hyaline-vascular and plasma cell. The hyaline-vascular type is the most common (80–90%) and shows a follicular structure with tumor nodules composed predominantly of small lymphocytes and with large numbers of blood vessels in the interfollicular areas. The plasma cell type (10%) shows sheets of interfollicular cells and fewer blood vessels. ²⁹⁰ Mixed hyaline-vascular and plasma cell types can also occur, particularly in patients with multifocal disease.^{287.288. and 289.} Furthermore, hyaline-vascular and plasma cell lesions can occur concomitantly at separate sites. ²⁸⁵

The pathogenesis of Castleman disease remains a subject of investigation. Although clonal expansion of certain lymphocyte populations is seen in some cases, Castleman disease is generally regarded as a reactive process that can eventually lead to lymphoma, particularly in patients with multifocal disease. There is evidence that some cases may be mediated by abnormal production of B lymphocyte growth factors, such as interleukin 6, leading to abnormal lymphoid proliferation. ²⁸⁵ There is also an association with infection by human herpes-8 virus (HHV-8), also known as the Kaposi sarcoma associated virus, particularly in HIV-positive individuals.^{291. and 292.}

Castleman disease is currently best classified as unifocal, multifocal or HIV-associated disease.^{287.288. and 289.} Patients with unifocal Castleman disease typically present in the fourth decade of life with a mass detected either incidentally or by virtue of symptoms related to mass-effect on neighboring mediastinal structures.^{276. and 286.} Systemic symptoms, laboratory abnormalities, peripheral lymphadenopathy, or organomegaly are rare. About 90% of cases of unifocal Castleman disease are of the hyaline vascular variant. Unifocal disease is usually resected in toto and patients typically have a benign course thereafter.

Patients with multifocal Castleman disease typically present in the sixth decade of life with diffuse lymphadenopathy and systemic complaints such as fever, night sweats, and weight loss.^{287.288.289.293. and 294.} Organomegaly, peripheral neuropathy, anemia, gamma globulin abnormalities, and elevated lactic dehydrogenase are common. ²⁹⁰ About 80% of cases of multifocal Castleman disease are of the plasma cell or mixed variants. Some patients with multifocal Castleman disease are infected with HHV-8, an association that increases in the HIV-positive population.^{287.288. and 289.} Affected patients are usually treated with chemotherapy or radiation therapy with mixed results. Disease usually pursues an aggressive course, and development of frank lymphoma can occur.

Castleman disease that develops in HIV-positive individuals is almost always multifocal and pursues a very aggressive course. ²⁹⁵ There is a strong association with HHV-8 viral infection, and affected individuals may also develop Kaposi sarcoma.^{287.288.289.296.297. and 298.} HIV-positive patients with multifocal Castleman disease have a very high risk of developing lymphoma as well. Prognosis is poor.

On chest radiographs, localized Castleman disease usually manifests as a focal, well-defined, smooth or lobular mediastinal or hilar mass (Fig. 14.43). The mass is typically quite large and most commonly occurs in the middle mediastinum or hila.^{276.299. and 300.} Occasionally, the lesion is found in other sites, including the posterior mediastinum and chest wall.^{276.286. and 300.} On noncontrast-enhanced CT, the mass is usually homogeneous and of soft tissue attenuation (Fig. 14.44). Calcification is uncommon (5–10%) and, when it occurs, is typically coarse and central in location (Fig. 14.45). Multifocal Castleman disease usually manifests on chest radiographs with diffuse mediastinal widening. On CT or MRI, multifocal lymph node enlargement is noted.

Because of its highly vascular nature, hyaline-vascular Castleman disease usually enhances intensely following administration of intravenous iodinated or gadolinium-based contrast material (Fig. 14.45)^{276.286.293.301.302.303.304.305. and 306.} – a distinctive feature that helps differentiate Castleman disease from many other mediastinal lesions including lymphoma. The lesions are also found to be highly vascular at angiography.^{299.301. and 307.} Plasma cell Castleman disease is less vascular, and typically shows less enhancement after contrast administration. ²⁵⁸

On MRI, hyaline-vascular Castleman disease lesions are typically heterogeneous and have increased signal intensity compared with skeletal muscle on T1-weighted sequences (Figs 14.43 and 14.45).^{307.308. and 309.} They become markedly hyperintense on T2-weighted sequences (Fig. 14.45). Low signal intensity septa are occasionally visible within the lesions. In larger lesions, flow voids in and around the mass may be identified and are important clues to the hypervascular nature of the mass. Because the lesions are hypervascular, diffuse enhancement following administration of intravenous gadolinium is common (Fig. 14.45). The FDG-PET imaging findings of Castleman disease have been described only in small series or case reports.^{310.311.312. and 313.} In these reports, the lesions are usually quite metabolically active, whether uni- or multifocal in nature (Fig. 14.46).

Castleman disease may, very rarely, involve the lung parenchyma (Fig. 14.44). Reported manifestations include a pulmonary mass,^{290. and 314.} centrilobular nodules, ³¹⁵ septal thickening, ³¹⁵ and thin-walled cysts. ³¹⁵ Most patients with diffuse lung involvement have multifocal disease and the lung findings are usually due to associated lymphoid interstitial pneumonitis. ³¹⁵

Important clues to the presence and sometimes the cause of mediastinal or hilar lymph node disease include enlargement and abnormal density on chest radiographs, attenuation on CT, or signal intensity on MRI. It is important to remember, however, that lymph nodes of normal size and attenuation or signal intensity can harbor disease, including malignancy.

Calcification of intrathoracic lymph nodes (Box 14.12) is a common sequela of certain infections, particularly tuberculosis and histoplasmosis (Fig. 14.47). It can also be seen in other benign conditions such as sarcoidosis, silicosis, coal worker’s pneumoconiosis, amyloidosis, and Castleman disease. Lymph node calcification is very rarely due to neoplastic disease. Lymph node metastases from calcifying primary malignancies such as osteosarcoma, chondrosarcoma, carcinoid tumors, and mucinous colorectal and ovarian carcinomas (Fig. 14.48) may calcify.^{316. and 317.} Lymph node calcification can occur after treatment of mediastinal lymphoma (Fig. 14.49), but is quite rare prior to treatment.^{318. and 319.} CT clearly demonstrates lymph node calcification to better advantage than chest radiographs. MRI is limited, however, in its ability to show calcification, a notable disadvantage. ³²⁰

Various patterns of lymph node calcification can be seen. Coarse irregular clumplike calcification of a part of the node and homogeneous calcification of the entire node are the two most common patterns. Lymph node calcification due to tuberculosis tends to involve the entire node whereas calcification due to sarcoid tends to be more punctate. Further, calcified lymph nodes due to tuberculosis tend to involve the mediastinum asymmetrically (usually unilateral), corresponding to the drainage patterns of primary infection; whereas diffuse, bilateral nodal involvement is more common in sarcoidosis. ³²¹ A strikingly foamy pattern of calcification is described in AIDS patients with disseminated Pneumocystis jirovecii infection322. ^{and 323.} and in patients with metastatic mucinous neoplasms. Thin peripheral calcification – so-called ‘eggshell calcification’ (Fig. 14.50) – is seen in patients with coal worker’s pneumoconiosis, silicosis, and sarcoidosis.^{321.324. and 325.} In one series, eggshell calcification was seen on chest radiographs in 3% of coal workers with greater than 30 years’ experience. ³²⁵ Eggshell calcification is rarely seen in other conditions, but has been reported in patients with amyloidosis, histoplasmosis, blastomycosis, and treated lymphoma. ²⁷⁷

Areas of low CT attenuation within enlarged nodes, likely due to necrosis (Fig. 14.51), is seen in a variety of conditions, including tuberculosis,^{326. and 327.} nontuberculous mycobacterial infection, metastatic disease, particularly testicular tumor,^{328. and 329.} and lymphoma. In one series, 16 of 76 patients with Hodgkin disease had low-attenuation lymphadenopathy on CT at presentation. ³³⁰ Some nodes have a prominent fatty hilum on CT. This feature is associated with benign disease and is usually thought to be the result of previous inflammation. Conversely, obliteration of the fatty hilum has been associated with metastatic disease. ³³¹ Low-attenuation or even fatty nodes have also been described in patients with Whipple disease. ²⁸³

Contrast enhancement in enlarged nodes, when moderate in degree, is nonspecific and seen in patients with tuberculosis,^{327. and 332.} fungal infection, ³²⁶ sarcoidosis, and metastatic neoplasm. When enhancement is dramatic, however, it suggests metastatic neoplasm from a highly vascular primary tumor such as melanoma, renal or thyroid carcinoma, carcinoid tumor, or leiomyosarcoma. Castleman disease is a further, though rare, cause of markedly enhancing lymph nodes (see Fig. 14.44). Peripheral, or rim, enhancement and central necrosis are features of tuberculosis (see Fig. 14.38) ³²⁷ and can be of diagnostic value in situations where tuberculosis is likely and metastatic carcinoma is not. ³³²

How large a mediastinal or hilar node has to be in order to be detected on chest radiographs is not easily established. It is likely that this size threshold depends upon the location of the node in the mediastinum, the presence of other mediastinal abnormalities such as tortuous great vessel or lipomatosis, and radiographic technique. Most nodes with a short-axis diameter of 2 cm or greater in the right paratracheal region, the aortopulmonary window, the hilar or the paravertebral regions should be detected on appropriately exposed posteroanterior chest radiographs. However, nodes in the pretracheal, left paratracheal, subcarinal, and paracardiac regions may be considerably larger than 2 cm in diameter and yet not be identified on chest radiographs.^{243. and 333.}

Upper right paratracheal node enlargement (Fig. 14.52) (station 2R of the AJCC/UICC nomenclature) ³³⁴ (see p 69) manifests as uniform or lobular widening of the right paratracheal stripe. ³³⁵ When the paratracheal nodes become substantially enlarged, the lateral border of the superior vena cava may become convex rather than flat or concave. The apparent density of the superior vena cava may be increased and equal that of the aortic arch (normally the density of the superior vena cava in the right paratracheal area is less than that of the aortic arch). When the lower right paratracheal (azygos) nodes (station 4R) enlarge, they displace the azygos vein laterally so that the diameter of the combined shadow of the azygos node and vein enlarges (the normal diameter on an upright chest film should be 7 mm or less). ³³⁶

Enlargement of the upper left paratracheal nodes (station 2L) is frequently obscured by the shadows of the left carotid and subclavian arteries. These nodes have to be quite large to be detected on chest radiographs. If the aortopulmonary nodes (station 5) are substantially enlarged, they project beyond the aortopulmonary window and appear as a mass in the angle between the aortic arch and the main pulmonary artery (Fig. 14.53). ³³⁷ Enlargement of the anterior mediastinal nodes, i.e. nodes anterior to the aorta (station 6), the brachiocephalic artery (station 3), and the trachea (stations 2 and 4), must be substantial to be recognizable on chest radiographs. The resulting mediastinal abnormality is frequently bilateral and lobulated in contour (Fig. 14.54). Sometimes, the only finding of lymph node enlargement in these areas is increased opacity of the retrosternal area on the lateral view. Enlargement of the anterior intercostal, or internal mammary, nodes is best recognized on the lateral chest radiograph as well-marginated, retrosternal soft tissue masses along the course of the internal mammary arteries. Significant enlargement may result in upper parasternal opacities on the frontal radiograph. ³³⁸

The most useful sign of subcarinal node (station 7) enlargement on chest radiographs is a change from the normally concave contour of the superior portion of the azygoesophageal interface (Fig. 14.55) into a convex bulge. ³³⁹ Alteration of the contour of the azygoesophageal interface is, unfortunately, a relatively insensitive sign of subcarinal lymphadenopathy. It was noted in only 23% of the patients with subcarinal lymph node enlargement reported by Müller et al. ³³³ Effacement of the interface, without a focal bulge, can be seen with smaller volume nodes, but is a less specific finding for subcarinal pathology, particularly in children.^{340. and 341.} Other chest radiographic findings of subcarinal node enlargement include increased opacity in the subcarinal region³⁴² and obscuration of the medial margin of the bronchus intermedius. ³³³ Since the esophagus passes immediately behind the carina, subcarinal node enlargement may cause posterior displacement of the esophagus.

Enlarged paraesophageal nodes (station 8) and posterior mediastinal nodes result in displacement of the azygoesophageal and paraspinal interfaces.

CT more readily demonstrates lymph node enlargement than chest radiography. The optimal CT technique for detection of enlarged mediastinal lymph nodes remains a subject of debate and is related to the rapidly changing nature of CT technology. In general, the thinner the slice collimation used, the better individual nodes will be shown. Thin-collimation images obtained on a multidetector spiral CT scanner will likely show more nodes than relatively thick-collimation images on a single-slice spiral or non-spiral scanner. However, whether this improvement in node detection makes a significant clinical difference to the patient is less certain and depends upon the specific clinical circumstances. Furthermore, although CT images are traditionally reviewed in axial format, several studies have shown that coronal reformat images from multidetector CT datasets obtained using thin slice collimation (0.5 mm or 2 mm collimation) performed better for the detection of enlarged lymph nodes than conventional 5 mm postcontrast scans.^{343. and 344.} Again, whether this improvement translates into improved patient outcome is uncertain.

Whether or not intravenous contrast is necessary for detection of mediastinal lymphadenopathy also remains a subject of debate and is, for the most part, a decision that rests upon the experience of the interpreter and individual preference. One group compared contrast-enhanced with noncontrast CT for staging lung cancer and found that contrast-enhanced CT revealed more enlarged lymph nodes, particularly at the 2R station. ³⁴⁵ However, they also reported excellent overall agreement between the two studies for the presence and total number of enlarged lymph nodes, suggesting that the observed differences might not be clinically relevant. Another study compared contrast-enhanced with noncontrast CT for staging lung cancer and found that contrast-enhanced CT rarely changed the tumor stage determined by noncontrast CT. ³⁴⁶ These authors concluded that intravenous contrast was not needed for routine CT for lung cancer staging. A more recent study compared noncontrast with contrast-enhanced FDG-PET-CT for lung cancer staging, and found no difference for assessment of nodal metastases. ³⁴⁷

CT findings of mediastinal lymphadenopathy (Fig. 14.50, Fig. 14.51, Fig. 14.52, Fig. 14.53, Fig. 14.54, Fig. 14.55 and Fig. 14.56) include: an increase in size of individual nodes; focal mediastinal contour abnormalities or lobulations of the interface between the mediastinum and lung; invasion of surrounding mediastinal fat; coalescence of adjacent and enlarged nodes to form larger masses; and diffuse soft tissue attenuation throughout the mediastinum obliterating the mediastinal fat. Individually enlarged nodes are seen as round or oval soft tissue lesions in the mediastinum. Distinguishing enlarged nodes from normal vascular structures requires thorough knowledge of the normal arrangement of blood vessels and an understanding of the various anomalies and variations in the arrangement of the mediastinal vessels. Intravenous contrast enhancement may be needed to help distinguish vessels from lymph nodes in problematic cases.

Many authors have studied CT scans in normal patients in order to establish normal size criteria for mediastinal or hilar lymph nodes (see p 68).^{348.349.350. and 351.} These studies suggest that the upper limit of normal for short-axis lymph node diameter is about 1 cm. Short-axis diameter is considered the standard for diagnosis because it is the most reproducible measurement and has the best correlation with lymph node volume at autopsy. ³⁵² These studies must be interpreted with caution, however, as the importance of both ‘enlarged’ and ‘nonenlarged’ nodes varies depending upon node location, the clinical scenario, and the presence or absence of known or suspected malignancy. For example, nodes between 10 mm and 15 mm in short-axis diameter may be normally found in certain areas, such as the subcarinal region. Furthermore, nodes considerably smaller than 10 mm can harbor metastatic disease in patients with lung cancer. ³⁵³ Use of size alone to predict presence or absence of nodal malignancy is fraught with error, particularly in patients with lung cancer. ³⁵⁴

It is easier to identify and measure right-sided mediastinal lymph nodes than to evaluate the left-sided nodes, because of the more abundant mediastinal fat and less complex vascular anatomy on the right. ³⁵² Subcarinal lymph node enlargement may be difficult to recognize at noncontrast CT. Important signs include: a soft tissue mass between the esophagus and either the left atrium or the intramediastinal portions of the right or left pulmonary arteries; or a soft tissue mass that extends into the azygoesophageal recess, posterior to the bronchus intermedius and the left lower lobe bronchus.

For the most part, MRI and CT provide comparable information regarding enlarged mediastinal nodes. However, MRI is frequently more time-consuming, more difficult for patients, and more limited in availability than CT at many centers. It can also be difficult to distinguish a cluster of small normal nodes from a single enlarged node or to detect intranodal calcification at MRI. ³²⁰ Furthermore, differences in signal intensity at spin-echo MRI have not proved to be a reliable method for differentiating benign from malignant lymphadenopathy. For these reasons, MRI is currently used primarily for patients for whom the use of iodinated intravenous contrast material is contraindicated.^{247. and 355.}

There has been considerable recent interest, however, in developing new MR techniques for imaging nodal metastases from a variety of malignancies including lung cancer. One group reported increased accuracy for differentiating benign from malignant nodes at 3.0 T field strength. ³³¹ Others have reported positive results with contrast agents such as gadolinium-DTPA^{356. and 357.} or molecular imaging techniques such as small superparamagnetic iron oxide (USPIO) particles.^{358.359. and 360.} In a recent series, USPIO-enhanced MRI was shown to be more accurate that FDG-PET for detection of nodal metastases in a rabbit model. ³⁶⁰ Furthermore, new pulse sequences such as diffusion-weighted MRI are being investigated and have also been recently shown to be more accurate than FDG-PET for mediastinal nodal staging in patients with lung cancer. ³⁶¹ While these results are promising, their impact and eventual role in staging patients with suspected mediastinal nodal metastases remains to be seen.

PET imaging, using a variety of positron-emitting agents, most commonly FDG, has assumed a dominant role in the assessment of mediastinal lymph nodes, especially in patients with known or suspected malignancy. The role and influence of FDG-PET imaging in this regard very much depends upon the clinical scenario and source of primary malignancy and is considered in more detail in sections dealing with specific conditions. However, a few caveats are appropriate. First, while FDG-PET greatly improves the accuracy of assessment of suspected mediastinal nodal metastases, it is not perfect; false positives and negatives occur and are not infrequent. ³⁵⁴ Second, a variety of benign causes of lymph node enlargement also show increased metabolic activity on FDG-PET imaging, including sarcoidosis, tuberculosis, and histoplasmosis (see Fig. 14.40).^{242.362. and 363.} Third, combined PET-CT is probably more accurate for assessment of mediastinal lymph nodes than either CT or PET alone, especially in patients with lung cancer.^{363.364. and 365.}

The findings of hilar node enlargement on chest radiographs are enlargement of the hilum, increased lobulation of the hilar contours, a rounded mass in a portion of the hilum that does not contain major vessels (Fig. 14.56; see also Figs 14.37 and 14.39), and increased density of the hilum. ³⁶⁶ In certain highly vascular regions of the hila (e.g. the intersection of the right superior pulmonary vein and interlobar artery and the inferior aspect of the hilum where the inferior pulmonary veins intersect the lower lobe segmental arteries), nodal enlargement must be substantial to be recognized radiographically. Enlarged nodes adjacent to the lower lobe arteries increase the overall diameter of the hilum (the transverse diameter of each lower lobe artery should be no greater than 16 mm) and result in a lobular rather than the normal tubular configuration. Lymph node enlargement in the upper portions of the hila is often easily detected because the vessels in these regions are normally small. Even mild nodal enlargement can be recognized on the lateral view when the enlarged nodes lie posterior to the right main bronchus and bronchus intermedius (Fig. 14.57), because lung normally contacts the posterior wall of the airway in this region. Another important region to evaluate for hilar lymphadenopathy on the lateral view is the angle formed by the lower lobe bronchi and the middle lobe or lingular bronchus (Fig. 14.58) – the so-called inferior hilar window. ³⁶⁷

It may, at times, be very difficult to distinguish enlarged hilar lymph nodes from enlargement of the hilar arteries due to pulmonary hypertension (Fig. 14.59). Correct diagnosis depends on determining that the abnormality is truly centered on the pulmonary arteries and on evaluating the degree of lobulation. A hilar mass in a location that is normally devoid of vessels clearly favors nodal enlargement. Enlarged central pulmonary arteries usually retain their tubular configuration. Lobulated hilar enlargement favors lymphadenopathy. If needed, contrast-enhanced CT will answer the question.

The recognition of hilar node enlargement at CT is facilitated by intravenous contrast opacification of the hilar vessels (see Fig. 14.37). ³⁶⁸ Lymph nodes generally do not enhance to the same degree as blood vessels. The majority of nodes in the hilum, except those around the lower hilum, are normally less than 3 mm in short-axis diameter. ³⁶⁹ Nonenhancing hilar tissue that is up to 7 mm in short-axis diameter is commonly seen in the lower hila, however. ³⁶⁹ If the examination is performed without contrast, then the recognition of nodal enlargement depends on demonstrating rounded soft tissue densities that are too large to be blood vessels (see Figs 14.56 and 14.58).^{370.371.372. and 373.} The smallest node that can be reliably detected on noncontrast CT varies with location. Some portions of the hilum are normally devoid of vessels greater than 5 mm in diameter and thus relatively small nodes may be detected as contour abnormalities in these regions. In other regions of the hila, however, the vessel diameters may be 15 mm, or greater if there is increased pulmonary blood flow or pulmonary arterial hypertension, limiting detection of all but the largest nodes. Perhaps the most sensitive area for detection of hilar lymphadenopathy on noncontrast CT is the region immediately behind the right main bronchus and its divisions – the right upper lobe bronchus and the bronchus intermedius – because, in these regions, the lung normally contacts the posterior wall of the airway. ³⁷⁴ Increased soft tissue opacity, especially if it is lobulated, in this region is suggestive of lymphadenopathy. The equivalent area in the left hilum is occupied by the descending aorta and left descending pulmonary artery; therefore, only a small portion of lung contacts the posterior wall of the left main bronchus, ³⁷⁵ limiting detection of lymphadenopathy in this region. The most difficult, and therefore the least sensitive, area for detection of hilar lymphadenopathy is the central portion of the right hilum, where the right superior pulmonary vein crosses directly anterior to the right pulmonary artery and its major divisions. Additionally, there are fat pads at the bifurcation of the right pulmonary artery that can resemble lymph node enlargement on axial CT (Fig. 14.60). It can be difficult to recognize the fatty nature of these pads because of partial volume averaging with the adjacent arteries and lung. ³⁷⁶

As is the case with imaging mediastinal lymph node enlargement, MRI and CT provides comparable information regarding enlarged hilar nodes. However, hilar node enlargement may be more easily recognized with MRI than with noncontrast CT.320.^{326.377. and 378.} For the most part, MRI is used primarily in patients for whom the use of iodinated intravenous contrast material is contraindicated.^{247. and 355.}

A variety of anatomic structures can be confused with mediastinal lymph node enlargement,^{379.380. and 381.} including enlarged blood vessels and vascular variants such as aortic anomalies (p 979), azygos continuation of the inferior vena cava, varices of the azygos or pulmonary vein,^{382.383.384. and 385.} and aneurysmal dilatation of the brachiocephalic vein or superior vena cava.^{385.386. and 387.} Fluid in the various pericardial recesses can occasionally mimic lymphadenopathy or other mediastinal masses.^{388. and 389.} Choi et al. ³⁸⁸ described a series of patients with posterior superior pericardial recesses that extended cephalad to the level of the aortic arch (‘high-riding’) and were misdiagnosed as lymphadenopathy. Some of these pitfalls are illustrated in Fig. 14.61, Fig. 14.62 and Fig. 14.63.

Mediastinal lymphangioma (cystic hygroma) is discussed in Chapter 16.

Blood vessel tumors in the mediastinum are rare and frequently benign. Capillary or cavernous hemangiomas³⁹⁰ are the most common lesions. Hemangioendothelioma, ³⁹¹ hemangiosarcoma, hemangiopericytoma, ³⁹² hemangioendothelioma, ³⁹³ and mixed lymphatic and blood vessel lesions, such as lymphangiohemangiomas,^{394.395. and 396.} are very rare.

Hemangiomas are rare mediastinal tumors that account for less than 0.5% of all mediastinal masses. ³⁹⁷ Mediastinal hemangiomas usually occur in the anterior (68%) or posterior mediastinum (22%), although multicompartment involvement is found in up to 14% of cases.398.^{399.400. and 401.} Most mediastinal lesions are cavernous hemangiomas and are composed of large interconnecting vascular spaces with varying amounts of interposed stromal elements such as fat and fibrous tissue. Focal areas of organized thrombus can calcify as phleboliths. Affected patients are usually asymptomatic.

On chest radiographs, hemangiomas manifest as sharp, well-marginated mediastinal masses (Fig. 14.64). Phleboliths are seen in less than 10% of cases but, when present, are diagnostic. CT typically reveals a heterogeneous mass with intense central and peripheral rim-like enhancement after administration of intravenous contrast.^{391.397.398.402. and 403.} Hemangiomas typically have heterogeneous signal intensity on T1-weighted images. In lesions with significant stromal fat, linear areas of increased signal intensity on T1-weighted images can occasionally be identified. The central vascular spaces typically become markedly hyperintense on T2-weighted images, a suggestive feature (Fig. 14.64). ⁴⁰⁴

Mixed lymphangioma/hemangioma is a variant of hemangioma seen most frequently in children and young adults. ⁴⁰⁵ The lesion may be localized to the thorax or occur as a more systemic process. When it occurs in the chest, the lesion may involve the mediastinum, pleura, and chest wall as a single process causing widespread lobular soft tissue swelling, bone destruction, and chylous pleural effusion. This destructive form of the disease is known as Gorham disease.^{406. and 407.} Cystic angiomatosis is another, probably distinct form of widespread lymphangiomatosis⁴⁰⁸ in which lymphangiomas and hemangiomas may coexist. Many different sites in the body are involved, including the mediastinum, pericardium, and pleura. Multiple lytic lesions may be seen in the bones. ⁴⁰⁹ The condition is most frequently seen in children and young adults. Lymphangiomatosis is discussed further in Chapter 16.

Acute mediastinitis is a potentially life-threatening, but fortunately rare, condition that requires prompt diagnosis and treatment. Spontaneous or iatrogenic esophageal rupture is the most common cause, accounting for up to 90% of cases.^{419. and 420.} Other causes of acute mediastinitis include necrosis of neoplasm, extension of infection from the neck, pharynx, teeth,^{421.422.423.424. and 425.} retroperitoneum, lungs, pleura, or adjacent bones and joints, ⁴²⁶ and mediastinitis after cardiac surgery. ⁴²⁷ Acute mediastinitis may also be associated with empyema or subphrenic abscess. Clinically, affected patients are often very ill with chills, high fever, tachycardia, and chest pain. Circulatory shock is frequent. Dysphagia is common in those patients in whom the mediastinitis is caused by perforation of the esophagus. Diffuse mediastinitis has a particularly high mortality.

Esophageal perforation is usually caused by penetrating trauma, particularly from surgery, endoscopy, or swallowing sharp objects such as chicken bones. In young children, the possibility of child abuse as a cause of pharyngeal or esophageal perforation must be considered. ⁴²⁸ Spontaneous perforation may occur, as in the Boerhaave syndrome, when forceful vomiting causes a tear in the esophageal wall. The tear in the esophagus is usually just above the gastroesophageal junction. It may be of any depth, but is usually confined to the mucosa, in which case bleeding may occur but there is no immediate danger of mediastinitis. If the tear is complete, however, air, alimentary juices, and food leak into the mediastinum resulting in mediastinitis.

The primary imaging features of acute mediastinitis are mediastinal widening, pneumomediastinum, obliteration of fat planes, localized fluid collections, and abscess formation (Figs 14.67 and 14.68). ⁴²⁹ Mediastinal widening is the result of inflammatory swelling or abscess formation within the mediastinum. Because so many cases of acute mediastinitis are secondary to esophageal perforation, an important clue to the diagnosis is air within the mediastinum, a feature that may be difficult to appreciate on chest radiographs. The air may be bubbly or streaky and may be localized or widespread in distribution. As with all types of pneumomediastinum, the air may extend into the neck or retroperitoneum. Accompanying pleural effusions in one or both pleural cavities are also common. Pleural effusion tends to be right sided in patients with iatrogenic, mid-esophageal perforation and left sided in patients with spontaneous, distal esophageal perforation (Boerhaave syndrome). In patients with Boerhaave syndrome, the effusion is particularly striking on the left and is often accompanied by consolidation of the left lower lobe (Fig. 14.67). ⁴³⁰ All these features are better demonstrated on CT than on chest radiographs.^{429.431. and 432.} Findings of esophageal perforation on CT include periesophageal fluid collections (100%), extra-luminal mediastinal air (100%), esophageal wall thickening (82%), and pleural effusion (82%). ⁴³³ The site of perforation is rarely identifiable on CT (18%). ⁴³³ Contrast esophagography can be critical in determining the presence and precise location of esophageal perforation. ⁴³⁰ In cases of acute mediastinitis without discrete abscess formation, CT may show diffuse obliteration of normal fat planes, and gas bubbles may be scattered throughout the mediastinum (Fig. 14.69). When a walled-off abscess develops, the gas may be seen in discrete rounded collections or as air–fluid levels (Fig. 14.70). Mediastinal abscesses may be solitary, but are frequently multiple. CT is an invaluable guide should percutaneous drainage be indicated.^{429. and 434.} CT may also show important associated abnormalities such as jugular vein thrombosis, pericardial effusion, or rupture of the hypopharynx or esophagus.

Descending cervical mediastinitis is an uncommon, but potentially life-threatening, cause of mediastinitis.^{423.424.425. and 435.} These infections begin in the head and neck region and spread via fascial planes (usually in the prevertebral space) into the middle and posterior mediastinum. Typical causes include odontogenic infection, suppurative tonsillitis, and retropharyngeal abscess. CT in cases of descending cervical mediastinitis shows fluid collections in the mediastinum that may be contiguous with a fluid collection in the cervical region. ⁴³⁵ CT is essential for confirming the diagnosis, assisting in fluid aspiration to confirm infection, and for monitoring response to therapy.

Mediastinitis after cardiac surgery is uncommon, occurring in only 0.5–3% of patients.^{427.429.436.437.438.439. and 440.} Mediastinitis often occurs in the setting of sternal dehiscence. Radiographic features of sternal dehiscence include the midsternal stripe and the wandering wire signs (Fig. 14.71). A very thin vertical lucency (midsternal stripe) in the upper third of the sternum can often be seen on well-centered radiographs of patients after uncomplicated sternotomy. This lucent line should not exceed 2 mm in thickness, nor extend below the first sternal wire. Progressive mid-sternal lucency or a mid-sternal stripe greater than 3 mm in thickness after sternotomy suggests possible dehiscence. ⁴⁴¹ Changes in position or orientation of sternal wires (wandering wire sign) also suggest dehiscence. ⁴⁴² However, neither sign is predictive of mediastinitis complicating dehiscence. ⁴⁴³

CT is therefore frequently performed in patients with clinically suspected mediastinitis but can be difficult to interpret since fluid and air collections, hematomas, pleural effusions, and increased attenuation of anterior mediastinal fat, all potential findings of mediastinitis, are common expected findings in the immediate postoperative period (Fig. 14.72). These findings generally resolve, however, in the first days and weeks after median sternotomy. One study found that mediastinal air or fluid collections seen on CT in the first 2 weeks after sternotomy were not specific for mediastinitis. ⁴³⁷ However, such findings were highly indicative of mediastinitis after 2 weeks. Air or fluid collections that appear de novo or that progressively increase without other explanation are also suggestive of mediastinitis (Figs 14.70 and 14.73). ⁴⁴⁴ Needle aspiration of fluid collections may be necessary to rule out infection when mediastinitis is suspected (Fig. 14.72). CT is most useful for distinguishing patients with substantial retrosternal fluid collections that require open drainage from those that have only superficial wound infections. CT has limited ability for detecting early changes of sternal osteomyelitis. As noted above, minor degrees of sternal separation are common in asymptomatic patients after uncomplicated operations.^{436. and 438.} However, gross sternal destruction, indicative of osteomyelitis, is occasionally seen on CT (Fig. 14.73). Radiolabeled leukocyte scanning (indium-111, ^99mTc-hexamethylpropylene amine oxime [HMPAO]) can also be used to help diagnose sternal osteomyelitis in the setting of mediastinitis.^{445. and 446.}

Fibrosing mediastinitis (sclerosing mediastinitis or mediastinal fibrosis; Box 14.13) is a rare disorder caused by proliferation of acellular collagen and fibrous tissue within the mediastinum. ⁴⁴⁷ It is thought that most cases in the USA are caused by an abnormal immunologic response to Histoplasma capsulatum antigens in genetically susceptible individuals.^{448.449. and 450.} However, fibrosing mediastinitis is rare, even in areas where histoplasmosis is endemic, and recovery of organisms in affected specimens is unusual. Other etiologies that are likely more important in other parts of the world where H. capsulatum is rare include M. tuberculosis, autoimmune disease, Behçet disease, radiation therapy, trauma, and drugs such as methysergide.451.^{452. and 453.} Importantly, an idiopathic form of fibrosing mediastinitis is also now recognized.^{454. and 455.} A rare familial form associated with retroperitoneal fibrosis, sclerosing cholangitis, Riedel thyroiditis, and pseudotumor of the orbit has also been reported. ⁴⁵⁶

Fibrosing mediastinitis is characterized by progressive proliferation of fibrous tissue within the mediastinum that encases and eventually obstructs vital structures such as the vena cava, the pulmonary arteries and veins, and the airways. Fibrosis due to histoplasmosis is often focal in nature. In older reports, idiopathic disease was described as more diffuse in distribution. ⁴⁵⁷ However, more recent reports describe more focal mediastinal involvement in cases of idiopathic fibrosis.^{454. and 455.}

In areas where histoplasmosis is endemic, affected patients usually present in the second through fifth decades of life with signs and symptoms of cough, recurrent pulmonary infection, hemoptysis, or chest pain. ⁴⁴⁹ Pulmonary venous obstruction may result in symptoms that mimic mitral stenosis. Patients with superior vena cava obstruction may present with swelling of the face and distension of the neck veins. ⁴⁵⁸ In other parts of the world where histoplasmosis is unusual, the age range at presentation is much broader. ⁴⁵¹

Chest radiographs frequently underestimate the extent of mediastinal disease (Fig. 14.74) and can be normal.^{459.460.461.462.463.464.465.466. and 467.} When abnormal, chest radiographic findings vary somewhat depending on the etiology of fibrosis and the site and nature of the mediastinal abnormality. Disease due to infection, usually histoplasmosis, typically results in focal or diffuse calcified mediastinal masses that may be evident radiographically (Fig. 14.75). Idiopathic fibrosis results in either a focal^{454. and 455.} or diffuse mediastinal abnormality without evident calcification (Fig. 14.76). ⁴⁶⁸ In either setting, the secondary effects of mediastinal fibrosis may also be evident on chest radiographs. These include findings of airway narrowing, parenchymal consolidation or atelectasis due to airway obstruction, oligemia due to pulmonary artery obstruction, or septal thickening and pleural effusion due to pulmonary venous obstruction (Fig. 14.77).

CT or MRI are most useful for evaluation of fibrosing mediastinitis.^{259.449.451.465.469.470. and 471.} When disease is due to histoplasmosis or tuberculosis, CT usually shows a focal, infiltrative mediastinal or hilar mass that is often extensively calcified (Figs 14.74, 14.75 and 14.77). When disease occurs idiopathically, CT may show either a focal masslike opacity^{454. and 455.} or more diffuse encasement of mediastinal structures by soft tissue attenuation masses that obliterate normal fat planes (Fig. 14.76). Calcification is uncommon in lesions due to idiopathic fibrosis. In either setting, CT is also useful for demonstrating airway, pulmonary arterial and venous involvement.

On MRI, the process is typically of heterogeneous signal intensity on T1- and T2-weighted images. ⁴⁴⁷ Markedly decreased signal intensity on T2-weighted images is occasionally seen and is suggestive of the fibrotic or calcific nature of the process.^{472. and 473.} MRI can demonstrate the infiltrative nature of the fibrosis and the narrowing of the major vessels and bronchi as well as, if not better than, CT.^{460.470.472.474. and 475.} However, CT is better for demonstrating calcification within the lesion, a finding that is critical for differentiating fibrosing mediastinitis from other infiltrative disorders of the mediastinum such as metastatic carcinoma or lymphoma.

Radionuclide ventilation–perfusion scanning can be used to diagnose pulmonary arterial or airway obstruction (Fig. 14.77).^{473. and 476.} Venography, pulmonary arteriography (Fig. 14.74), or CT angiography may show smooth, tapered narrowing of the superior vena cava and brachiocephalic veins, together with numerous dilated collateral veins, and may also show narrowing of the central pulmonary arteries.^{449. and 467.} Lesions can be either metabolically active^{477. and 478.} or negative⁴⁷⁹ on FDG-PET imaging. Barium swallow may show narrowing of the esophagus and, in rare instances, may show varices resulting from esophageal venous collaterals, so-called downhill varices.

The prognosis for affected patients is often unpredictable; disease may progress, remain stable for many years, or even spontaneously regress. ⁴⁴⁷ Mortality rates up to 30% are reported. ⁴⁴⁹ Patients with subcarinal or bilateral fibrosis may have a slightly higher mortality than patients with more localized disease. ⁴⁴⁹ Causes of death include recurrent pneumonia, hemoptysis, or cor pulmonale. ⁴⁴⁷ Because many cases in the USA are caused by an inflammatory reaction to H. capsulatum infection, some patients have been treated with systemic antifungal agents or corticosteroids, with variable success. ⁴⁴⁷ If disease is localized, surgical resection can be curative or result in symptomatic improvement. Bilateral mediastinal involvement may preclude surgery, however. Symptomatic patients may also be treated by percutaneous therapies directed at occluded or severely stenosed airways, pulmonary arteries, or vena cava.^{480. and 481.} Laser therapy, balloon dilation, and intravascular or endobronchial stent placement have all been used with success to treat affected patients (Fig. 14.78). ⁴⁴⁷

Panniculitis is an inflammatory process of fat leading to focal fat necrosis. It is most commonly encountered in subcutaneous mesenteric fat. Mediastinal panniculitis is a very rare condition that is usually seen in patients with Weber–Christian disease, it may cause focal mediastinal widening, and may therefore be mistaken for neoplasm. CT in one case showed masslike accumulations of soft tissue (shown to be fibrosis and inflammation on histopathologic examination) interspersed with fat in the mediastinum. ⁴⁸² On MRI, the mass was very heterogeneous. ⁴⁸²

Most neurogenic tumors manifest as well-defined masses with smooth or lobulated contours (Fig. 14.82, Fig. 14.83 and Fig. 14.84).^{487.500. and 503.} When localized, it is not possible to distinguish benign from malignant lesions. The tumors may be almost any size and some are very large, occupying most of a hemithorax. Except for vagal and phrenic nerve tumors, and the occasional neuroblastoma, neurogenic tumors are typically situated in the posterior mediastinum⁵⁰¹ or grow along intercostal nerves. Those that arise adjacent to the upper thoracic spine may occupy the lung apex and appear as a well-marginated apical mass (Fig. 14.84).

Most neurogenic tumors are spherical in nature, but some ganglion cell tumors are elongated along the spine, paralleling the vertical orientation of the sympathetic chain (Fig. 14.85). It may be possible to distinguish between a ganglion cell tumor and a nerve sheath tumor by observing: (1) the shape of the tumor mass, since the ganglion cell tumors are frequently elongated along the mediastinum with tapered superior and inferior margins, whereas nerve sheath tumors are more spherical in shape with more acute angles at their margins; and (2) that ganglion cell tumors arise slightly more anteriorly with their center alongside the vertebral body, whereas nerve sheath tumors are centered on the neural foramen, or are closely adherent to the chest wall.

Calcification can be seen in all types of neurogenic tumors (Figs 14.85 and 14.86). Approximately 10% of primary mediastinal neuroblastomas are visibly calcified on chest radiographs,^{487. and 497.} a figure considerably lower than that reported for neuroblastomas arising in the abdomen. The frequency of calcification detectable at CT is substantially higher. In neuroblastoma, the calcification is usually finely stippled, whereas in ganglioneuroblastoma and ganglioneuroma (Fig. 14.85), it is denser and coarser, occurring most frequently in the larger, more benign lesions. Nerve sheath tumors rarely calcify.^{487. and 488.} When present, calcification is typically curvilinear and peripheral in nature and is seen in only very large masses.

Because neurogenic tumors tend to arise adjacent to bone and grow slowly, they can cause pressure erosions of adjacent ribs and vertebrae (Figs 14.81, 14.83 and 14.85) – an important diagnostic feature. The bone in immediate contact with the tumor shows a scalloped edge; usually the bony cortex is preserved, and frequently it is thickened. The ribs may be thinned and splayed apart, and the intervertebral foramina may appear enlarged. With larger lesions, the absence of changes in the adjacent bones argues against the diagnosis of a neurogenic tumor. Bone changes are most frequently seen with the tumors of ganglion cell origin, perhaps because these tumors are frequently large at presentation and occur in pediatric patients with a rapidly growing skeleton. Large tumors may be associated with scoliosis. ⁴⁸⁸ Frank destruction of bone appears to be a sign of malignancy,^{487.488. and 504.} as is associated pleural effusion. ⁵⁰¹

On noncontrast CT, schwannomas are often of mixed attenuation, and may have regions that are close to water attenuation^{485.500.504.505.506. and 507.} due either to hypocellularity or to cystic degeneration (Fig. 14.83).^{508. and 509.} Neurofibromas tend to be more homogeneous on noncontrast CT.^{485. and 506.} Nerve sheath tumors are typically vascular and enhance after administration of intravascular contrast. A variety of enhancement patterns have been described including homogeneous, diffuse heterogeneous (with cystlike regions of nonenhancement), rim enhancement, and central enhancement with a hypoattenuating rim.^{485. and 504.} Malignant nerve sheath tumors are typically heterogeneous on both contrast-enhanced and noncontrast CT; local invasion and bone destruction as well as metastatic foci to the pleura or lungs suggest the diagnosis (Fig. 14.87).^{485. and 509.} Ganglioneuromas usually manifest as homogeneous or heterogeneous masses of low-attenuation lesions on both contrast-enhanced and noncontrast CT (Fig. 14.85). ⁴⁸⁵ Neuroblastomas manifest as heterogeneous soft tissue masses that show extensive local invasion (Fig. 14.88). ⁴⁸⁵

CT can show spinal and intraspinal involvement (Fig. 14.81),^{510. and 511.} particularly if intrathecal contrast has been administered (rarely performed). However, MRI is considered the standard for imaging neurogenic tumors because it better demonstrates spinal and intraspinal involvement (Fig. 14.81).^{404. and 512.} The signal pattern at MRI is variable (Fig. 14.89, Fig. 14.90 and Fig. 14.91). Neurogenic tumors may show uniform signal intensity similar to muscle on T1-weighted sequences and signal intensity considerably higher than muscle on T2-weighted sequences. Neurofibromas, on occasion, show the so-called ‘target pattern’ with different signal in the central portion of the lesion compared with the periphery (see Fig. 14.79).^{507.513.514. and 515.} On T1-weighted images, the central portion is of higher signal, whereas on T2-weighted spin-echo images, the periphery is of higher intensity than the center, corresponding to the histopathologic finding of central nerve tissue and peripheral myxoid degeneration. ⁵¹⁶ Schwannomas and ganglioneuromas may show heterogeneous high signal intensity throughout the lesion on T2-weighted images, and low to intermediate signal intensity on T1-weighted images. ³² In these cases, the signal high intensity on T2-weighted images is probably due to cystic degeneration.^{507. and 516.} Ganglioneuromas may have a whorled appearance on MRI, corresponding to whorls of collagenous fibrous tissue and neural tissue.

Because most neurogenic tumors in adults are benign, the role of imaging is to facilitate differential diagnosis and to evaluate local extent prior to resection. MRI is probably the technique of choice for imaging neurogenic tumors because it best shows intraspinal extension. For malignant tumors, notably neuroblastoma, chest radiography and MRI appear to be the best imaging techniques for staging (Fig. 14.91).^{502. and 517.} Radionuclide imaging with agents such as meta-iodobenzylguanidine (MIBG) or FDG-PET scanning can also be used to assess the extent of tumor and for staging.^{518. and 519.} FDG-PET imaging is likely of little benefit for differentiation of benign from malignant nerve sheath tumors, as benign schwannomas may show increased metabolic activity (Fig. 14.82).^{520. and 521.}

Paragangliomas (Box 14.16) are rare tumors that arise from chromaffin cells and may be either benign or malignant.^{522.523. and 524.} Most such tumors arise in the adrenal glands and are known as pheochromocytomas. Those that arise elsewhere are known collectively as paragangliomas. ⁵²³ Mediastinal paragangliomas are rare, constituting less than 2% of thoracic neurogenic tumors in one large series. ⁴⁸⁷ In a review of 51 mediastinal paragangliomas, two-thirds arose in the region of the aortic arch (aortic body tumors) and one-third arose in the paravertebral region (Figs 14.92 and 14.93). ⁵²⁵ Aortic body tumors may occur in one of four locations: lateral to the brachiocephalic artery; anterolateral to the aortic arch; at the angle of the ductus arteriosus; or above and to the right of the right pulmonary artery.^{524. and 525.} Tumors may also arise in the wall of the left atrium or the interatrial septum (Fig. 14.94).^{526.527. and 528.} Multifocal lesions are also reported. ⁵²⁹ Most mediastinal paragangliomas are nonfunctional and are detected either incidentally or because of signs and symptoms related to compression or invasion of mediastinal structures. ⁵²⁴

Mediastinal paragangliomas manifest as round soft tissue masses on CT that, because they are highly vascular, can enhance intensely after administration of intravenous contrast.^{30. and 524.} Smaller lesions tend to be of homogeneous attenuation, while larger lesions may be more heterogeneous, due to necrosis (Fig. 14.92). ⁵²⁴ Arteriography demonstrates enlarged feeding vessels, pathologic vessels within the tumor, and an intense tumor blush. ⁵³⁰ Radioiodine MIBG (Fig. 14.93) and somatostatin receptor scintigraphy all show increased activity in paragangliomas.^{526.531.532.533. and 534.}

The MR findings of thoracic paragangliomas are the subjects of case reports only.^{535.536. and 537.} Based on these reports, it seems that the MR appearance of thoracic lesions is similar to that of lesions more commonly encountered in the head and neck: the masses are isointense to muscle on T1-weighted images and are of substantially higher signal than muscle on T2-weighted images (Fig. 14.95). ⁵³⁸ Numerous serpiginous vascular channels may also be seen coursing through the larger lesions. MRI is particularly advantageous for showing intracardiac paragangliomas (Fig. 14.94). Lesions can be metabolically active on FDG-PET scans (Fig. 14.92).