Thymoma

Thymoma is the most common primary mediastinal neoplasm in adults and the most frequent tumor of the anterior mediastinum. It usually affects adults older than 40 years, with no gender predilection. Approximately 30% of patients with thymoma have thoracic symptoms of cough, dyspnea, and/or chest pain; 40% to 70% have symptoms related to one or more of the parathymic syndromes, typically myasthenia gravis (MG), but hypogammaglobulinemia, pure red cell aplasia, and nonthymic malignancies may also occur. Some affected patients are asymptomatic and are discovered incidentally because of abnormal chest radiographs. Although the association of thymoma and MG is well recognized, approximately 85% of patients with MG have thymic lymphoid hyperplasia, and only 15% are found to have thymoma. In contrast, 30% to 50% of patients with thymoma may develop MG. Hypogammaglobulinemia and pure red cell aplasia occur in 10% and 5% of patients who have thymoma, respectively. Nonthymic malignancies occur in 12% to 20% of patients with thymoma and include thyroid carcinoma, lung cancer, and lymphoma.

Thymomas manifest on radiography as rounded, well-circumscribed, unilateral, anterior mediastinal masses (Figure 71-2). They are typically located anterior to the aortic root but may be found anywhere from the thoracic inlet to the diaphragm and rarely in the neck. On cross-sectional imaging, thymomas are often homogeneous, soft tissue masses but may exhibit heterogeneity because of cystic change, hemorrhage, or necrosis, especially in large neoplasms. Drop metastases to the ipsilateral pleura, pericardium, or upper abdomen through a diaphragmatic hiatus are well documented and represent invasive disease (Figure 71-3). Pleural drop metastases may encase the lung and mimic diffuse malignant mesothelioma, although associated pleural effusion is infrequent. Lymph node and hematogenous metastases are rare. Mediastinal invasion may be detected with CT and may manifest as an irregular tumoral surface, contralateral extension of thymoma across the midline, and obvious invasion of mediastinal fat and structures. Imaging evidence of local invasion must be correlated with microscopic evidence of capsular transgression and tissue invasion, because encapsulated thymomas may produce fibrous adhesions to adjacent structures. MRI is more sensitive than CT in the detection of vascular invasion. When evaluating a thymic mass, PET-CT may be useful for depicting tumoral invasion, differentiating subgroups of thymic epithelial neoplasms, and staging extent of disease. The maximum standard uptake values (SUVs) of thymoma are typically lower than those of thymic carcinoma. Guided needle biopsy, mediastinotomy, mediastinoscopy, and video-assisted thoracoscopy may establish the diagnosis. However, histologic diagnosis before excisional surgery may not be required in classic cases of thymoma.

Figure 71-2 Elderly woman with thymoma with microscopic capsular invasion. A, Posteroanterior (PA) chest radiograph; B, lateral chest radiograph; C, contrast-enhanced chest computed tomography (CT) scan (mediastinal window). A 6 × 5 cm discrete homogeneous thymoma (arrows) extends inferiorly in the mediastinum without invasion. Thymomas may occur in any location between the thoracic inlet and the diaphragm.

Figure 71-3 Invasive thymoma. A, Posteroanterior chest radiograph; B, unenhanced chest CT (mediastinal window). Thymoma manifests as a lobular right anterior mediastinal mass (solid arrows) with multiple drop metastases to ipsilateral pleura (open arrows).

Thymomas represent neoplastic proliferation of thymic epithelial cells, intermixed with mature lymphocytes. The histologic typing has been complex and challenging. The Revised 2004 World Health Organization (WHO) classification divides thymic epithelial neoplasms into A, B, and C types on the basis of epithelial cell morphology, the ratio of lymphocytes to epithelial cells, and prognosis. Types A and B correlate with the traditional major histologic cell types of thymoma—epithelial, lymphocytic, mixed lymphoepithelial, and spindle cell. Type C refers to thymic carcinoma. The multidisciplinary International Thymic Malignancy Group (ITMG) assesses diagnostic and therapeutic options of thymoma. Anatomic staging is based on the presence or absence of capsular invasion, determined macroscopically during surgery and confirmed microscopically. Thymomas are now considered malignant neoplasms, and all stages have the potential to metastasize. Most thymomas are completely encapsulated; however, approximately 30% are invasive and grow through the capsule into surrounding adipose tissue, pleura, pericardium, great vessels, and/or heart. Encapsulated and invasive thymomas are microscopically identical, and “invasive” is used to denote capsular invasion.

The treatment of choice for encapsulated and invasive thymomas confined to the mediastinum is surgical resection. Postoperative radiation therapy is included in the treatment of invasive thymoma, but the role of preoperative irradiation is controversial. Chemotherapy with cisplatin-based regimens is generally recommended for metastatic or unresectable recurrent disease, with an overall response rate of 50% to 70% in small studies.

The prognosis of patients with thymoma varies with the stage and extent of surgical resection. Patients with completely resected, encapsulated lesions have the best prognosis. Overall 5-year and 10-year survival rates in patients who have encapsulated thymomas are 75% and 63%, respectively, whereas patients with invasive thymoma have survival rates of 50% and 30%, respectively. Delayed recurrence of thymomas may occur, even in patients with completely resected encapsulated lesions, which emphasizes the importance of long-term follow-up.

The role of thymectomy in the treatment of parathymic syndromes is controversial. Thymectomy is more effective in patients with MG in the absence of a thymoma, with a clinical remission rate of approximately 35% and improvement in another 50%. Neurologic improvement is less likely when MG is associated with thymoma. Thymectomy in patients with pure red cell aplasia results in a 40% to 50% remission rate, in contrast to those with hypogammaglobulinemia, who do not benefit from thymic resection.

Thymic Carcinoma

Thymic carcinomas are a heterogeneous group of aggressive epithelial malignancies with a tendency for early local invasion and distant metastases. Men are more often affected (mean age, 46 years). The Revised 2004 WHO classification of thymic epithelial neoplasms describes thymic carcinomas as “nonorganotypic” malignancies (type C) that resemble carcinomas of extrathymic origin, such as lung carcinomas. By traditional histopathologic classification, the two most common cell types are squamous cell and lymphoepithelial-like carcinoma. Unlike thymoma, thymic carcinoma has malignant histologic features and typically manifests as a large, poorly defined, infiltrative, anterior mediastinal mass, frequently with regional lymph node and pulmonary metastases, and pleural and/or pericardial effusions (Figure 71-4).

Figure 71-4 Unenhanced chest CT image (mediastinal window) of patient with thymic carcinoma. The heterogeneous left anterior thymic carcinoma extends across the midline of the chest and exhibits multi-cystic change (arrow) and an eccentric mural soft tissue component (open arrow).

The histologic grade and neoplastic staging determine the therapy and prognosis for the patient with thymic carcinoma. Surgical resection, when feasible, is the preferred treatment. Adjuvant cisplatin-based chemotherapy and concurrent radiotherapy may be used. Response rates are generally poor, with 5-year survival rates of approximately 30%.

Thymic Carcinoid

Thymic carcinoid is a rare, aggressive neuroendocrine neoplasm that typically affects men in the fourth and fifth decades of life. These are large, symptomatic, locally invasive neoplasms with frequent distant metastases. Approximately 35% of affected patients develop endocrine abnormalities caused by ectopic hormone production, most often Cushing syndrome. Multiple endocrine neoplasia syndrome type I (MEN-I) may also occur. However, the syndrome of inappropriate antidiuretic hormone secretion (SIADH) and the carcinoid syndrome are rare. Radiologically, thymic carcinoid is a large, lobular, heterogeneous, and usually invasive anterior mediastinal mass indistinguishable from thymic carcinoma or thymoma (Figure 71-5). There may be associated intrathoracic metastatic lymphadenopathy. Surgical resection, when feasible, is the treatment of choice, and response to chemotherapy and radiotherapy is poor.

Figure 71-5 Thymic carcinoid. A, Posteroanterior chest radiograph; B, contrast-enhanced chest CT (mediastinal window). The 6-cm, discrete, rounded left anterior mediastinal thymic carcinoid (arrow) exhibits central low attenuation and circumferential mural enhancement. C, Fluorodeoxyglucose positron emission tomography (FDG-PET) scan. Multiple FDG-avid foci within the cyst wall (arrows) correspond with malignancy.

Mediastinal Lymphoma

Lymphoma represents 10% to 20% of all mediastinal neoplasms in adults. Approximately two thirds of all lymphomas are non-Hodgkin lymphoma (NHL). Mediastinal involvement typically denotes systemic lymphoma but may also represent primary disease. Although both Hodgkin disease (HD) and NHL may affect the mediastinum, mediastinal involvement from systemic lymphoma is much more common in HD than in NHL. Nodular sclerosis is the most common subtype of HD to affect the mediastinum. Diffuse, large B-cell lymphoma and lymphoblastic lymphoma represent the most common primary mediastinal subtypes of NHL. Patients affected by NHL have a higher incidence of systemic symptoms and concomitant involvement of extrathoracic and extranodal lymphoid tissue. PET-CT is superior to CT alone in depicting the extent of disease involvement and plays an important role in assessing disease response to therapy and residual viable neoplasm.

Hodgkin Disease

Hodgkin disease is most often seen in adults age 20 to 30 and in those older than 50. Even though the nodular sclerosis subtype is more common in women, HD in general does not exhibit a gender predilection in young patients. Patients who have mediastinal lymphoma tend to be younger. The usual presenting finding is cervical and supraclavicular lymphadenopathy. In less than 25% of patients, HD is limited to the thorax. Approximately one third of patients have systemic symptoms. Patients with mediastinal involvement are generally asymptomatic, although bulky lymphadenopathy may induce symptoms related to mediastinal compression.

Radiologically, most patients with HD have bilateral, asymmetric, mediastinal lymphadenopathy, which frequently involves the prevascular and paratracheal lymph nodes and rarely the posterior mediastinal or juxtacardiac lymph nodes. Nodular sclerosis HD can manifest as a discrete, unilateral anterior mass (Figure 71-6) or bilateral mediastinal mass (Figure 71-7) or as large, lobular, coalescent lymphadenopathy in the anterior mediastinum (Figure 71-8). Invasion, compression, and displacement of mediastinal structures, lung, pleura, and chest wall may occur. Affected lymph nodes usually exhibit homogeneous attenuation but may be heterogeneous because of hemorrhage, necrosis, or cystic change. De novo lymph node calcification rarely occurs but may develop 1 to 5 years after radiation therapy. Direct invasion of the lung occurs in 8% to 14% of untreated patients and is usually associated with hilar lymphadenopathy. The diagnosis is established with either core biopsy or surgical excision of affected palpable lymph nodes or masses found on imaging.

Figure 71-6 Primary mediastinal Hodgkin lymphoma in 45-year-old man. A, Posteroanterior chest radiograph; B, contrast-enhanced chest CT (mediastinal window). Hodgkin lymphoma manifests as a smooth, homogeneous, right anterior mediastinal mass (arrow), without lymphadenopathy.

Figure 71-7 Mediastinal mass in Hodgkin disease (HD). A, Posteroanterior chest radiograph; B, contrast-enhanced chest CT (mediastinal window). Homogeneous central anterior mediastinal mass (arrows) extends across the midline bilaterally in woman with HD.

Figure 71-8 Contrast-enhanced chest CT (mediastinal window) of patient with mediastinal Hodgkin disease. A dominant right anterior mediastinal nodal mass (arrow) has associated enlarged bilateral contiguous mediastinal nodal groups (open arrows).

Hodgkin disease spreads by means of contiguous nodal chains and is staged anatomically according to the modified Ann Arbor classification, combined with histologic staging: nodular sclerosis, mixed cellularity, lymphocyte predominant, lymphocyte depletion, and unclassified. Stages IA and IIA HD (asymptomatic disease on same side of diaphragm, without bulky lymphadenopathy) have historically been treated with radiation therapy alone. At this time, limited chemotherapy and limited radiotherapy are being evaluated for early-stage disease. More advanced stages are treated with systemic chemotherapy. Bulky mediastinal lymphoma from HD is treated with chemotherapy followed by radiation therapy. Prognosis depends on the stage of the disease, with cure rates of more than 90% achieved in stage IA and IIA disease; even with diffuse or disseminated involvement of one or more extranodal tissues (stage IV), 50% to 60% of patients can be cured with combination chemotherapy. Recurrences may be cured with salvage chemotherapy.

Non-Hodgkin Lymphoma

Non-Hodgkin lymphoma typically affects older patients (compared with those affected by HD) and exhibits a slight male predilection. Diffuse, large B-cell and lymphoblastic lymphomas, the most commonly diagnosed subtype in the mediastinum, occur in younger patients. Diffuse large B-cell lymphoma is more common in women, and lymphoblastic lymphoma is more common in men and is frequently associated with acute lymphoblastic leukemia (Figure 71-9). Both may produce symptoms related to rapid growth and mediastinal invasion, including the superior vena cava syndrome. In addition, diffuse large B-cell lymphoma and lymphoblastic lymphoma may manifest as a primary mediastinal mass without extrathoracic lymphadenopathy. Most patients with NHL are initially seen with advanced disease and systemic symptoms, and approximately half have intrathoracic lymph node enlargement. Thoracic lymphadenopathy is typically isolated or noncontiguous and tends to occur in unusual sites, such as the paravertebral, juxtacardiac, and retrocrural lymph node groups (Figure 71-10). Anterior mediastinal involvement is less common than in HD, but imaging features are similar to those of HD.

Figure 71-9 Diffuse large B-cell non-Hodgkin lymphoma (NHL). A, Posteroanterior chest radiograph; B and C, contrast-enhanced chest PET-CT images. Heterogeneous right anterior mediastinal NHL (arrows) extends across the midline (open arrow) and exhibits marked FDG avidity. A moderate right pleural effusion has developed.

Figure 71-10 Unenhanced chest CT (mediastinal window) of patient with mediastinal non-Hodgkin lymphoma. NHL manifests as multiple enlarged mediastinal and axillary lymph nodes (arrows).

Non-Hodgkin lymphoma is usually systemic on presentation and spreads unpredictably; thus histologic classification has a better prognostic value than anatomic staging. According to the Revised European-American Classification of Lymphoid Neoplasms, NHL can be classified as indolent, aggressive, or highly aggressive. Indolent NHLs are associated with a more favorable histology and a higher likelihood of nodal disease, but a more advanced clinical stage than the aggressive variety, with a propensity to transform into higher-grade lymphomas. Aggressive NHLs have a less favorable histology, with a tendency for extranodal involvement. Although the prognosis is poor if untreated, aggressive NHLs are potentially more curable than indolent lymphomas. The treatment of indolent NHLs is palliative, and use of radiotherapy or chemotherapy depends on disease stage. PET-CT is an accurate method of assessing remission and prognosis after therapy of aggressive NHL.

Mediastinal Germ Cell Neoplasms

The most common primary extragonadal site of germ cell neoplasms is the anterior mediastinum. These lesions account for 10% to 15% of anterior mediastinal neoplasms in adults. Mediastinal germ cell neoplasms are a diverse group of benign and malignant neoplasms that may originate from ectopic primitive germ cells “misplaced” in the mediastinum during embryogenesis. Most neoplasms that occur in adulthood are benign, but childhood neoplasms are more often malignant. Adults in the third decade of life are most frequently affected. Benign, mature teratomas affect males and females equally, but most malignant mediastinal germ cell neoplasms affect males. Although malignant germ cell neoplasms that manifest as mediastinal masses are typically primary lesions, secondary neoplasia from a primary gonadal germ cell neoplasm should be excluded. Elevation of serum levels of tumor markers, such as alpha fetoprotein (AFP) and beta subunit of human chorionic gonadotropin (β-HCG), in a male with an anterior mediastinal mass strongly suggests the diagnosis of a malignant, nonseminomatous germ cell neoplasm.

Mediastinal Teratomas

Teratomas represent the most common mediastinal germ cell neoplasms, accounting for 60% to 70% of cases, and consist of tissues that may be derived from more than one of the embryonic germ cell layers. Most teratomas are well differentiated and benign, thus the term mature teratoma. Uncommon categories include immature teratoma and malignant teratoma or teratocarcinoma. Mature teratoma typically affects children and young adults. Although large tumors may result in symptoms related to local compression, patients with mature teratoma are frequently asymptomatic. Characteristic, but uncommon, symptoms include expectoration of hair (trichoptysis), sebum, or fluid as a result of communication between the tumor and the airways. Radiologically, teratomas are spherical, lobular, well-circumscribed, anterior mediastinal masses that may exhibit calcification on radiography (Figure 71-11). CT typically demonstrates a multilocular cystic mass, and 75% of lesions contain fat attenuation (Figure 71-12). The treatment of choice is surgical excision, and the prognosis is excellent.

Figure 71-11 Posteroanterior chest radiograph of child with mediastinal mature teratoma. A large mass occupies the entire left hemithorax with mass effect on the mediastinum. Well-formed teeth within the mass, although highly specific for the diagnosis, are an extremely unusual finding.

Figure 71-12 Unenhanced chest CT (mediastinal window) of child who has teratoma with immature elements. Teratoma manifests as a large, left anterior mediastinal mass with multicystic (asterisks) and fat (arrow) components.

Seminomas

Mediastinal seminomas typically affect men in the third and fourth decades of life and represent 40% to 50% of mediastinal malignant germ cell neoplasms of a pure histology. Most patients are symptomatic. β-HCG levels are elevated in 10% of the patients, but AFP level is normal in pure seminomas. The tumor manifests as a large, lobular, well-defined, anterior mediastinal mass. Invasion of mediastinal structures is uncommon, but lymph node, lung, and skeletal metastases may occur. Cisplatin-based chemotherapy for four cycles has largely replaced previously used radiotherapy alone and results in cure rates of approximately 80%. Radiotherapy is still used in combination with chemotherapy to treat bulky disease and residual neoplasm after chemotherapy.

Nonseminomatous, Malignant Germ-Cell Neoplasms

Nonseminomatous, malignant germ cell neoplasms affect young, symptomatic men and include choriocarcinoma, embryonal carcinoma, endodermal sinus (yolk sac) tumor, and mixed germ-cell neoplasms. Tumor markers (AFP and HCG) are elevated in most patients. A significantly elevated AFP level is usually found in endodermal sinus tumor and embryonal carcinoma, whereas HCG is typically elevated in choriocarcinoma. Nonseminomatous, malignant germ-cell neoplasms may be associated with various hematologic neoplasms, such as acute leukemia or myelodysplastic syndrome, and up to 20% of affected patients have Klinefelter syndrome. These tumors manifest radiologically as large, heterogeneous masses with internal low-attenuation areas corresponding to central necrosis, surrounded by enhancing nodular, irregular soft tissue. Invasion of adjacent structures, pleural and pericardial effusions, and lymph node and distant metastases are common.

Standard treatment involves systemic chemotherapy with cisplatin-containing regimens, followed by surgical resection of residual neoplasm if a positive response is achieved. Patients who respond to therapy are followed with serum tumor markers, which are expected to normalize after treatment. Compared with seminoma, the prognosis is less favorable; however, complete remission rates of 50% to 70% and 5-year survival of approximately 50% can be achieved in patients with nonseminomatous, malignant germ cell neoplasms.

Thymolipoma

Thymolipoma is a rare, benign thymic neoplasm composed of mature adipose and thymic tissues. It usually affects young adults and has no gender predilection. Thymolipomas grow slowly, frequently reaching a large size before diagnosis, and almost half of the patients are asymptomatic. Thymolipomas manifest as large, anterior, inferior mediastinal masses that conform to adjacent thoracic structures and may mimic diaphragmatic elevation and cardiac enlargement on radiography (Figure 71-13). These lesions may also exhibit positional changes in shape. CT and MRI demonstrate soft tissue and adipose tissue components and establish an anatomic connection between the lesion and the thymus (Figure 71-14). The treatment of choice is surgical resection. The prognosis is excellent.

Figure 71-13 A and B, Posteroanterior and lateral chest radiographs of woman with thymolipoma. Large, soft, left mediastinal thymolipoma (arrows) conforms to lower left side of heart and diaphragmatic contours and exhibits multiple punctate calcifications.

Figure 71-14 Unenhanced chest CT (mediastinal window) of a young woman with thymolipoma. Large anterior mediastinal thymolipoma drapes down into inferior right hemithorax. Note anatomic connection of the thymus and an admixture of fat (+) and soft tissue (S) elements within the lesion.

Thymic Cyst

Thymic cysts are rare anterior mediastinal masses that may be congenital or acquired. Congenital thymic cysts are usually found in the first two decades of life, whereas acquired thymic cysts are seen in association with the acquired immunodeficiency syndrome (AIDS) or thymic inflammation or malignancy (e.g., carcinoma, HD). Radiologically, thymic cysts are well-defined anterior mediastinal masses with cystic unilocular or multilocular appearances on cross-sectional imaging (Figure 71-15). Surgical excision is the recommended treatment. The diagnosis of cystic neoplasm should always be considered and excluded, and inflammatory cysts must be carefully examined to exclude associated malignancy.

Figure 71-15 Unenhanced chest CT (mediastinal window) of asymptomatic woman with unilocular thymic cyst (arrows), showing water-attenuation contents, an imperceptible wall, and no soft tissue component.

Pericardial Cyst

Pericardial cysts, also termed spring water cysts or clear water cysts because of their clear-fluid contents, are uncommon developmental lesions that occur in the radiographic anterior mediastinum. Most are discovered incidentally in asymptomatic middle-aged adults. These cysts are well circumscribed and usually abut the heart, the diaphragm, and the anterior chest wall, typically in the right cardiophrenic angle. CT typically demonstrates a nonenhancing cystic mass of water attenuation and an imperceptible wall (Figure 71-16). Unless significant symptoms or atypical imaging features are found, pericardial cysts are followed clinically and radiologically.

Figure 71-16 Pericardial cyst in asymptomatic man. A and B, Posteroanterior and lateral chest radiographs; C, contrast-enhanced chest CT (mediastinal window). Right cardiophrenic angle pericardial cyst manifests as a unilocular water-attenuation mass (arrow) with an imperceptible wall.

Thymic Hyperplasia

Thymic hyperplasia most often occurs as a rebound phenomenon in patients who have received chemotherapy for treatment of lymphoma or germ cell neoplasms. Diffuse hyperplasia occurs within 2 weeks to 12 months after chemotherapy and may manifest with mediastinal enlargement on radiography or may mimic thymic neoplasia on cross-sectional imaging. On PET-CT, thymic hyperplasia typically exhibits only mild FDG uptake, in contrast to marked uptake by recurrent malignancy. Chemical-shift MRI (in-phase and out-of-phase gradient-echo sequences) may be used successfully to differentiate thymic hyperplasia from thymic neoplasia.

Intrathoracic Goiter

Most intrathoracic goiters result from extension of cervical thyroid goiters into the mediastinum and typically affect women. Although patients are usually asymptomatic, compression of the trachea or esophagus rarely causes symptoms such as dyspnea or dysphagia. The risk of malignant degeneration is small. Most intrathoracic goiters are located in the anterosuperior mediastinum, usually on the right side, but other compartments may be affected. Ectopic intrathoracic goiter without a cervical component rarely occurs. Chest radiography often reveals a cervicothoracic mass that produces mass effect on the trachea. CT demonstrates a lobular, well-defined mass with heterogeneous attenuation resulting from hemorrhage, cystic change, and calcification (Figure 71-17). Intense and sustained contrast enhancement is common. In functioning goiters, uptake of radioactive iodine (iodine 123 [¹²³I] or iodine 131 [¹³¹I]) and technetium 99 m (^99mTc) pertechnetate is diagnostic. Symptomatic or large goiters may be surgically excised.

Figure 71-17 A to C, Contrast-enhanced chest CT (mediastinal window) in elderly woman with goiter (arrows). The goiter arises from right lobe of thyroid, extends into upper thorax, and exhibits exuberant contrast enhancement.

Parathyroid Adenoma

Ectopic parathyroid glands in the mediastinum are usually located within or near the thymus gland. Most are encapsulated, functioning, benign adenomas, most often seen in older women who have persistent hyperparathyroidism after surgical parathyroidectomy. Because of their small size, parathyroid adenomas are rarely detected on chest radiography and frequently mimic lymph nodes on CT. Localization may be achieved by ^99mTc sestamibi scintigraphy or dual-isotope digital subtraction imaging with ^99mTc pertechnetate and thallium-201 chloride. Scintigraphic (functional) localization is correlated with CT or MRI (anatomic) identification of a mediastinal soft tissue nodule or mass. Selective venous sampling for parathyroid hormone levels may be necessary. Surgical excision is the treatment of choice.

Benign Mediastinal Lymphadenopathy

Infectious and noninfectious granulomatous diseases may involve the mediastinal lymph nodes. Infectious granulomatous diseases include tuberculosis and fungal infections, such as histoplasmosis and coccidioidomycosis. The most important noninfectious granulomatous diseases include sarcoidosis and silicosis. Lymphadenopathy associated with granulomatous infection is usually unilateral and asymmetric, in contrast to bilateral and symmetric lymph node enlargement with sarcoidosis and silicosis. Many of these disorders cause lymph node calcification, which may exhibit an “eggshell” configuration, characteristic of silicosis and less often sarcoidosis. Although calcified lymph nodes generally represent a benign process, definitive exclusion of malignant lymphadenopathy may be impossible by CT alone, and histologic examination may be required.

Other benign causes of lymph node enlargement include reactive hyperplasia from bacterial or viral lung infections, amyloidosis, drugs such as phenytoin, and Castleman disease (angiofollicular lymphoid hyperplasia or giant lymph node hyperplasia). Castleman disease usually manifests in young, asymptomatic adults as incidental, large, well-circumscribed, middle-posterior mediastinal lymph nodes. Nodal hypervascularity results in intense, homogeneous enhancement after intravenous (IV) contrast administration on cross-sectional imaging. The hyaline vascular histologic type accounts for 80% to 90% of cases, whereas the plasma cell and multicentric types represent only 10%. Patients with the hyaline vascular type are typically asymptomatic, although symptoms of compression may occur. The plasma cell variety may be associated with constitutional symptoms and signs of fever, weight loss, fatigue, anemia, and hypergammaglobulinemia, which may improve after surgical excision. The multicentric type is rare and associated with severe systemic symptoms in older patients, generalized lymphadenopathy, and hepatosplenomegaly, with eventual development of NHL.

Metastatic Mediastinal and Hilar Lymphadenopathy

Primary lung, breast, renal cell, gastrointestinal, and prostate carcinomas and malignant melanoma may metastasize to mediastinal or hilar lymph nodes and may manifest as a solitary mass, a dominant mass with lymphadenopathy, or multifocal enlarged lymph nodes (Figure 71-18). Ipsilateral mediastinal metastases from lung carcinoma represent N2 disease and may be operable. The diagnosis of metastases is established by a history of a known primary malignancy and confirmed by biopsy. The treatment depends on the underlying neoplasm and its stage.

Figure 71-18 Contrast-enhanced chest CT (mediastinal window) in patient with mediastinal squamous cell cancer (SCCA) of lung. SCCA manifests as an anterior mediastinal mass (m) that insinuates between the ascending aorta (a) and trachea and invades the superior vena cava (arrow).

Foregut Cysts

Congenital foregut cysts represent 20% of mediastinal masses, and 50% to 60% of these are bronchogenic cysts. Enteric cysts, which include esophageal duplication and neurenteric cysts, account for approximately 10% to 15%. Up to 20% of foregut cysts cannot be histologically classified and are termed nonspecific or indeterminate cysts.

Bronchogenic Cysts

Bronchogenic cysts are thought to originate from abnormal ventral budding of the primitive foregut. Most are located in the mediastinum, most often in subcarinal or paratracheal locations. Up to 15% are reported to arise in the lung; other locations (pleura, diaphragm, pericardium) are rare. These cysts are usually lined by a pseudostratified, columnar, ciliated (respiratory) epithelium; exhibit cartilage and smooth muscle in their walls; and may contain serous fluid, mucus, milk of calcium, blood, or purulent material.

Bronchogenic cysts typically occur in adult men and women but may affect all age groups. Patients are usually asymptomatic, but infection or bleeding eventually produces symptoms in up to two thirds of cases. Radiography usually reveals a well-circumscribed, spherical, middle-posterior mediastinal mass. On CT, these cysts are unilocular homogeneous, nonenhancing masses of variable attenuation, depending on the composition of the fluid (Figures 71-19 and 71-20). The cyst wall may contain calcification or enhance after IV administration of contrast. A gas-fluid level within the cyst is exceptionally rare in mediastinal cysts but frequently occurs in pulmonary cysts and indicates communication with the airways or infection. Large cysts in children may compress the airways, with resultant atelectasis, bronchopneumonia, or air trapping.

Figure 71-19 Contrast-enhanced chest CT (mediastinal window) of patient with bronchogenic cyst. The cyst (arrow) arises in azygoesophageal recess of middle-posterior mediastinum and exhibits water-attenuation contents with an imperceptible wall. Cyst contents do not enhance.

Figure 71-20 Subcarinal bronchogenic cyst. A, On contrast-enhanced chest CT (mediastinal window), the cyst (arrows) exhibits smooth mural enhancement and “fluid-fluid” level (open arrow) from recent hemorrhage. B, On T2-weighted coronal magnetic resonance imaging (MRI), the cyst (c) splays the main bronchi and exhibits high signal intensity.

The treatment of choice is surgical resection (even in the absence of symptoms), although incidental cysts in asymptomatic adults have been followed clinically and radiologically. Bronchoscopic or thoracoscopic needle drainage of cyst fluid typically reveals mucus and bronchial epithelial cells and is reserved for patients with a high risk of surgical complications.

Enteric Cysts

Enteric (esophageal duplication and neurenteric) cysts originate from the dorsal foregut, are usually located in the middle-posterior mediastinum or paravertebral region, and typically manifest in childhood. Enteric cysts are lined by squamous or enteric epithelium and may contain gastric mucosa and/or pancreatic and neural tissue. The cyst walls have two well-defined, smooth muscle layers with a myenteric plexus. Esophageal duplication cysts almost always adhere to the esophagus or are located within its wall and can be associated with gastrointestinal (GI) malformations. Similarly, neurenteric cysts may be associated with GI and cervical or upper thoracic vertebral anomalies, occasionally with a fibrous attachment to the spine or intraspinal extension.

Most enteric cysts are diagnosed during childhood. Hemorrhage or rupture may occur, especially when gastric epithelium or pancreatic tissue is present. The radiologic features of enteric cysts are similar to those of bronchogenic cysts. Esophageal duplication cysts are usually located close to the distal esophagus on the right side. Most neurenteric cysts are located in the paravertebral region, above the level of the carina on the right side, and approximately one half are associated with scoliosis, anterior spina bifida, vertebral fusion, hemivertebrae, and other vertebral anomalies. MRI is indicated to exclude intraspinal extension. Surgical excision is the treatment of choice. Prognosis after complete resection is excellent.

Vascular Lesions

Vascular lesions constitute approximately 10% of all mediastinal masses and may originate from the arterial or venous portions of the systemic or pulmonary circulation. They may mimic neoplasms on chest radiographs and should be considered in the differential diagnosis before biopsy is performed. The diagnosis is usually established with contrast-enhanced CT, MRI, and angiography.

Herniation

Hiatal hernias are common and result when an abdominal structure, usually the stomach, extends through the esophageal hiatus into the thorax and manifests as a retrocardiac mass. Morgagni hernias are congenital defects in the diaphragm that allow herniation of omentum or other abdominal contents into the thorax and typically manifest as right cardiophrenic angle masses. Diagnosis is typically established by identification of abdominal contents in the hernia sac on cross-sectional imaging studies. Treatment of symptomatic cases is surgical.

Neurogenic Neoplasms

Neurogenic neoplasms constitute 15% to 20% of adult and 40% of pediatric mediastinal tumors. Approximately 90% occur in the paravertebral region. Neurogenic neoplasms are the most common cause of a paravertebral mass and account for 75% of primary paravertebral “mediastinal” neoplasms. Approximately 50% of neurogenic neoplasms in children are malignant, whereas in adults most are benign. Approximately half of affected patients are asymptomatic. Neurogenic neoplasms are generally grouped into three categories according to their structure of origin: peripheral nerve, sympathetic ganglia, and paraganglionic neoplasms.

Schwannoma and Neurofibroma

Schwannoma (also termed neurilemmoma) and neurofibroma are the most common mediastinal neurogenic neoplasms. More than 90% are benign, and 10% are multiple. They are slow-growing neoplasms and usually arise from a posterior spinal nerve root but can involve any nerve in the thorax. Schwannoma and solitary neurofibroma affect men and women equally in the third and fourth decades. Although these neoplasms may attain large sizes, most patients are asymptomatic. Approximately 30% to 45% of neurofibromas occur in individuals who have neurofibromatosis (von Recklinghausen disease). The presence of multiple neurofibromas or a single plexiform neurofibroma is pathognomonic of neurofibromatosis. Malignant transformation of a solitary schwannoma is extremely rare. Patients with neurofibromatosis and neurogenic neoplasms are at increased risk for malignant transformation of one or more lesions. Patients with neurofibromatosis may also have ganglion cell neoplasms develop.

Radiologically, schwannomas and neurofibromas are sharply marginated, spherical, and occasionally lobular paravertebral masses, which usually span one to two rib interspaces but can attain large sizes (Figure 71-21). Up to one half of the cases cause splaying and benign pressure erosion of the ribs, vertebral bodies, and neural foramina. Approximately 10% of schwannomas and neurofibromas grow through and widen adjacent neural foramina and expand on either end with a “dumbbell” or hourglass configuration (Figure 71-22). Typically, CT reveals a heterogeneous mass that may contain punctate calcification or areas of low attenuation. MRI should always be performed to exclude intraspinal growth of the neoplasm (Figure 71-23). The treatment of choice is surgery. Recurrences are uncommon, even when excision is incomplete.

Figure 71-21 Neurofibroma. A, Posteroanterior chest radiograph; B, unenhanced chest CT (mediastinal window). Rounded, homogeneous left paravertebral neurofibroma (arrow) does not exhibit intraspinal extension or skeletal pressure erosion.

Figure 71-22 Unenhanced chest CT (mediastinal window) of patient with neurofibroma. A spherical mass of heterogeneous attenuation exhibits intraspinal extension (arrow) with enlargement and pressure erosion of adjacent neural foramen.

Figure 71-23 Gadolinium-enhanced T1-weighted coronal MR image of patient with neurofibroma. Spherical, heterogeneously enhancing paravertebral neurofibroma exhibits intraspinal extension (arrow) and mass effect on spinal cord.

Malignant Peripheral Nerve Sheath Neoplasms

Malignant peripheral nerve sheath neoplasms are a rare group of spindle cell sarcomas thought to represent the malignant counterparts of schwannomas and neurofibromas. These nerve sheath lesions occur equally in men and women in the third to fifth decades, and approximately half occur in patients with neurofibromatosis. The incidence of malignant degeneration of neurogenic neoplasms in patients with neurofibromatosis is approximately 5%. Malignant peripheral nerve sheath neoplasms may also occur sporadically or be induced by radiation. Pain and an enlarging mass are common at presentation. Radiologically, mediastinal malignant peripheral nerve sheath neoplasms manifest as sharply marginated, spherical, heterogeneous masses on cross-sectional imaging and may exhibit explosive growth.

Ganglioneuromas

Ganglioneuromas are benign neoplasms that affect males and females equally. Affected patients are older children (typically >5 years of age) and young adults. One half of patients are symptomatic from local effects of the tumor or intraspinal growth. Radiologically, ganglioneuromas are well-circumscribed, oblong, paravertebral masses that usually span three to five vertebrae and may exhibit skeletal displacement or pressure erosion (Figure 71-24). MRI is indicated to exclude intraspinal extension. Surgical excision is the treatment of choice and may necessitate a combined thoracic and neurosurgical approach.

Figure 71-24 Ganglioneuroma in adolescent patient. A, Coned-down chest CT scout scan; B, contrast-enhanced CT scan (mediastinal window). Oblong, smooth, homogeneous paravertebral ganglioneuroma (arrow) does not exhibit intraspinal extension.

Ganglioneuroblastomas

Ganglioneuroblastomas are malignant neoplasms that usually affect children younger than 10 years, with no gender predilection. They demonstrate composite histologic, biologic, and radiologic features of ganglioneuromas and neuroblastomas and are not usually distinguishable on imaging. Symptoms, when present, are caused by local mass effect, invasion of adjacent structures, or metastases. Staging and treatment are the same as for neuroblastomas. The prognosis for patients with ganglioneuroblastomas is generally more favorable than in those with neuroblastomas.

Neuroblastomas

Neuroblastomas are highly malignant neoplasms that affect children younger than 5 years, typically boys. Neuroblastomas in children older than 5 have no gender predilection. Two thirds of patients have constitutional symptoms, pain, cough, dyspnea, paraplegia, opsoclonus, and Horner syndrome. Systemic effects, such as hypertension, tachycardia, perspiration, flushing, and severe watery diarrhea, may result from elevation of catecholamine and vasoactive intestinal peptide levels. Radiologically, the masses are paravertebral, occasionally with local invasion, contralateral extension, and skeletal erosion. Approximately 10% exhibit extensive calcification on radiography. On CT, the tumors are heterogeneous because of hemorrhage and necrosis, and calcification may be detected in 80% of cases. MRI should always be used to exclude intraspinal extension and vascular or skeletal involvement. Metaiodobenzylguanidine (MIBG) scintigraphy (¹²³I or ¹³¹I) may demonstrate uptake in both primary and metastatic sites.

Neuroblastomas and ganglioneuroblastomas are treated with surgical resection. Adjuvant chemotherapy and irradiation may be used for residual disease or as a primary treatment modality in advanced cases. Radiotherapy in children can lead to delayed complications such as myelitis and scoliosis. The prognosis is generally poor and depends on the age at diagnosis, the size, the degree of histologic differentiation, and the neoplastic stage. Patients with congenital and thoracic lesions have the best prognosis.

Pheochromocytoma

Pheochromocytomas are functioning paragangliomas that most often arise from the adrenal glands and occur more frequently in men in the third to fourth decades. Approximately 10% of pheochromocytomas are extraadrenal, and less than 2% are intrathoracic; the latter tend to be more aggressive and multicentric. Symptoms relate to excessive systemic catecholamines or local mass effect. Pheochromocytomas may be part of a multisystem endocrine syndrome (e.g., MEN IIA or IIB). Diagnosis can be established by measurement of urine catecholamines and their metabolites (vanillylmandelic acid, homovanillic acid, metanephrine, normetanephrine). Typically, CT and MRI reveal a well-delineated, enhancing, paravertebral mass. The neoplasm is typically ¹²³I and ¹²³I MIBG avid (Figure 71-25). Treatment includes sympathetic α- and β-blockade for 1 to 2 weeks, followed by surgical excision. Chemotherapy and radiotherapy can be used to treat metastatic disease.

Figure 71-25 A, ¹³¹I-MIBG scintigraphy of patient with pheochromocytoma. Two foci of pheochromocytoma (arrows) in the chest and abdomen exhibit marked uptake of radiotracer. B, Contrast-enhanced chest CT (mediastinal window) of left paravertebral pheochromocytoma, manifesting as a smooth nodule (arrow) with moderate enhancement.

Paraganglioma

Paragangliomas are rare neoplasms of paraganglionic tissue. Most are benign, asymptomatic, and nonfunctioning. Radiologically, they typically manifest as sharply marginated, middle-posterior mediastinal nodules or masses, usually located adjacent to the aorta, pulmonary arteries, heart, or costovertebral sulci or within the left atrial wall (Figure 71-26). Paragangliomas are hypervascular lesions and demonstrate marked contrast enhancement. The treatment is surgical excision.

Figure 71-26 A and B, Contrast-enhanced chest positron emission tomography-computed tomography scan of patient with mediastinal paraganglioma (arrow) in the aorticopulmonary region, manifesting as a smooth, rounded mass with moderate homogeneous enhancement and FDG avidity.

Lateral Thoracic Meningocele

Lateral thoracic meningoceles are rare and consist of redundant meninges that protrude through the neural foramen and contain cerebrospinal fluid (CSF). These meningoceles do not exhibit a gender predilection and typically occur in association with neurofibromatosis. Patients are usually asymptomatic adults in the fourth to fifth decades. Radiologic studies demonstrate a well-circumscribed, paravertebral, cystic lesion, frequently associated with vertebral erosion, kyphoscoliosis, and/or widening of adjacent neural foramina (Figure 71-27). Cross-sectional imaging may demonstrate continuity with the thecal sac. CT demonstrates a homogeneous nonenhancing mass of water attenuation, and MRI shows signal intensity equal to that of adjacent CSF. Symptomatic lateral thoracic meningoceles are treated with surgical excision.

Figure 71-27 Unenhanced contrast CT (mediastinal window) of patient with lateral thoracic meningocele. The rounded meningocele (arrow) has attenuation that parallels that of cerebrospinal fluid, an imperceptible wall, and pressure erosion with expansion of neural foramen.

Mediastinitis

The term mediastinitis is used to refer to a variety of infectious and inflammatory conditions. Acute mediastinitis is more common than the chronic form and may be caused by esophageal or tracheobronchial perforation, penetrating chest trauma, postoperative sternal wound infection, extension of an oropharyngeal infection or a paravertebral or vertebral abscess, radiation therapy, malignancy, and rarely anthrax. Patients with acute mediastinitis usually have had sudden onset of high fever, chills, chest pain, dyspnea, and dysphagia. Physical examination may reveal systemic toxicity, respiratory distress, Hamman sign, subcutaneous emphysema, chest wall tenderness, and edema. Chest radiography and CT show mediastinal widening, pneumomediastinum, mediastinal air–fluid levels or fluid collections, and pleural effusions. An esophagram may reveal perforation. Acute mediastinitis is a generally diffuse process but may be localized when secondary to sternal wound infection. The treatment includes surgical drainage, débridement, repair of the traumatic injury, and broad-spectrum antibiotics. The mortality rate is high, especially when the diagnosis is delayed.

Chronic mediastinitis, also termed fibrosing or granulomatous mediastinitis, is caused by various infectious and inflammatory processes. Histoplasmosis and tuberculosis account for most cases. Noninfectious causes include mediastinal hematoma, radiation therapy, and drugs such as methysergide and hydralazine. Chronic mediastinitis can be associated with various idiopathic and autoimmune diseases, such as retroperitoneal fibrosis, Riedel thyroiditis, pseudotumor of the orbit, sclerosing cholangitis, systemic lupus erythematosus, and rheumatoid arthritis. Dense fibrous tissue, usually located in the paratracheal, carinal, and hilar regions, compresses and obstructs mediastinal structures, such as the superior vena cava, pulmonary vessels, airways, and esophagus. Superior vena cava syndrome is the most common clinical manifestation. Chest radiographs, CT, MRI, and perfusion scintigraphy, in addition to endoscopy, help to suggest the diagnosis. The typical CT finding is an infiltrative mediastinal soft tissue mass with calcification and coexistent pulmonary or hepatosplenic calcified granulomas. Noncalcified lesions present a diagnostic dilemma and require exclusion of malignancy. Histologic examination of mediastinal tissue may be necessary to exclude a malignant neoplasm or active infection. Treatment is ineffective and mostly palliative; the benefit of corticosteroids is controversial. In the presence of viable fungal organisms or rising serum antibody titers, antifungal agents can be administered. For patients with superior vena cava syndrome, long-term anticoagulation and vascular stents may be effective.

Pneumomediastinum

Pneumomediastinum is typically caused by overdistention and rupture of alveoli because of increased intrathoracic volume or pressure that results from mechanical ventilation, blunt trauma, asthma, or spontaneous rupture. Air dissects along the pulmonary interstitium into the peribronchovascular tissues and mediastinum and frequently decompresses into the soft tissues of the neck. Less often, pneumomediastinum can be secondary to tracheobronchial or esophageal perforation, a gas-forming infection, traumatic direct entry of air, cervical soft tissue air, or pneumoperitoneum that tracks into the mediastinum.

Mediastinal Hemorrhage

Mediastinal hemorrhage can be spontaneous from rupture of a thoracic or other vascular aneurysm or dissection or can result from blunt or penetrating trauma or invasive medical procedures. Chest radiography typically reveals mediastinal widening. Unenhanced chest CT may show hyperdense areas within the mediastinum or aortic wall, and contrast-enhanced chest CT may reveal an intimal flap or dissection, a contained pseudoaneurysm, or frank extravasation of blood into the mediastinum, pericardium, or pleural space. The treatment depends on the cause and location of the source of bleeding and typically involves surgical repair, especially when the ascending thoracic aorta is involved.