Thymus

The function of the thymus is to produce T lymphocytes, which are crucial components of cell-mediated immunity. The primordia of the thymus develop from the third pharyngeal pouches during the fifth to sixth gestational weeks. The paired primordia then migrate medially and caudally where they meet at the midline by the eighth embryonic week. Connective tissue extends between the lobes, but the thymic tissue itself is not completely fused. Each lobe of the thymus maintains a thin fibrous connection to the adjacent inferior lobe of the thyroid gland. Incomplete or excessive migration of the thymic primordia can lead to ectopic or aberrant locations of thymic tissue.

Prior to puberty, the predominant constituents of the thymic cortex are lymphocytes. The central medulla is predominantly composed of epithelial cells (especially Hassall corpuscles). Other tissue components include plasma cells, eosinophils, histiocytes, and chromaffin cells. Although the thymus is at its greatest size relative to overall body mass during infancy, there is continued growth of the gland during childhood such that its maximum size occurs around the age of puberty. Soon after the onset of puberty, growth slows, and the interlobular septa of the thymus become thicker. Around the age of 15 years, gradual involution begins, with infiltration of the gland by fatty tissue and progressive decrease in the number of cortical lymphocytes.

In young children, the thymus has a quadrilateral shape and convex lateral margins. There is a triangular or a bilobed configuration in older children, with the left lobe more prominent than the right. There is considerable variability in position, size, and configuration of the normal thymus. In children, the thymus usually abuts the sternum, and there is no plane of delineation between the thymus and the sternum on lateral radiographs. The thymus may obscure the heart on frontal radiographs of infants, and correlation with a lateral view is essential for accurately assessing cardiac size (Figure 7-1). Occasionally, a normal thymus mimics an anterior mediastinal mass or lung consolidation. On standard chest radiographs, the sail sign and thymic wave sign suggest that a mediastinal soft-tissue density is actually caused by the thymus (Figure 7-2). Frontal oblique radiographs are useful for selected patients to confirm that a density projecting over the lung actually represents the thymus rather than lung pathology.

A homogeneous composition and well-defined margins are important characteristics of the normal thymus on cross-sectional imaging studies. After puberty, the thymus becomes slightly heterogeneous because of infiltration with fat. A lack of compression or displacement of adjacent structures is an additional important imaging feature of the normal thymus. On sonography, the normal thymus is homogeneous aside from scattered echogenic strands; it is slightly hypoechoic in comparison to the thyroid gland. On unenhanced CT, the attenuation of the thymus is approximately equal to or slightly greater than that of adjacent normal chest wall muscle. On T1-weighted MR images, the normal thymus is slightly hyperintense to other soft-tissue structures in young children; the signal intensity increases with age as a consequence of fat deposition. The thymus is usually slightly hypointense to fat on T2-weighted images, and is hyperintense on fat-suppression T2-weighted images.¹

Variations in thymic size in response to systemic stresses of infants are common. Rapid involution can occur in response to chemotherapy, steroid therapy, burns, sepsis, heart surgery, respiratory distress syndrome, and a variety of other severe systemic diseases. Endogenous corticosteroid production apparently mediates this process. With resolution of the underlying condition, the thymus regenerates and sometimes attains a slightly larger size than existed prior to the initial event. This is termed rebound growth or rebound hyperplasia. This regeneration occurs in both the cortex and medulla of the thymus. Rebound thymic enlargement sometimes results in an atypical shape of the structure. Some degree of gallium uptake is common in patients with rebound thymic enlargement, complicating the differentiation from residual or recurrent tumor in children with lymphoma. Thyromegaly can occur in children with Beckwith-Wiedemann syndrome. There is also a rare idiopathic condition termed giant thymic hyperplasia or massive true thymic hyperplasia, which is apparently caused by endocrine dysregulation.^2–5

In addition to rare forms of hyperplasia, developmental abnormalities of the thymus include aplasia, hypoplasia, congenital cyst, ectopic location, and aberrant location. Aplasia and hypoplasia of the thymus result in diminished T-cell–related immune function, and are often associated with immunological deficiency syndromes such as DiGeorge syndrome, ataxia-telangiectasia, severe combined immunodeficiency syndrome, and Nezelof disease. In children with DiGeorge syndrome (more properly, 22q11 deletion syndrome), the severity of T-cell deficiency correlates with the morphology of the thymus. Severe immune deficiency occurs in individuals with thymic aplasia (approximately 20% of patients with DiGeorge syndrome). Absence of normal thymic tissue is a universal finding in children with severe combined immunodeficiency syndrome.⁶

Anomalies of thymic position are classified as ectopic or aberrant locations. Aberrant thymus refers to the presence of thymic tissue anywhere along the normal pathway of embryological descent of the gland. An ectopic thymus is located in any position except along the normal pathway of descent. Anomalous thymic tissue can be located in the neck, superior mediastinum, or posterior mediastinum. The abnormally located tissue may or may not be contiguous with the main mass of the thymus. However, ectopic thymic tissue in the mediastinum usually is contiguous with the normally positioned thymus at some point. Posterior mediastinal ectopic thymus is usually located between the superior vena cava and the trachea. Thymic tissue is considered to be in an abnormally cephalad position if it is above the left brachiocephalic vein. The term cervical thymus refers to anomalous herniation of the thymus into the lower portion of the neck. In most children, however, cervical thymus should be considered a developmental variation rather than symptom-producing pathology. Protrusion of the thymus into the anterior chest wall can occur in association with a congenital defect of the sternum.^1,7

The diagnosis of ectopic or aberrant thymus should be considered when cross-sectional imaging studies show a cervical or mediastinal mass that has similar or identical imaging characteristics to the normal thymus; i.e., similar echogenicity on sonography, attenuation on CT, and signal intensity on MRI (Figure 7-3). A connection to the orthotopic thymus is sometimes present (Figure 7-4). Ectopic thymus in the mediastinum usually produces little or no mass effect on adjacent structures. Aberrant or ectopic tissue in the neck is usually lateral or anterolateral in location and may cause mild mass effect on adjacent structures, depending on the size and location of the lesion. The lesion occasionally mimics a thyroid tumor. A cervical mass as a result of aberrant or ectopic thymus is sometimes cystic. Surgical excision is generally recommended for isolated anomalous thymic tissue in the neck because of rare reports of malignant degeneration.^8–10

Neurenteric Cyst

Neurenteric cyst is a developmental lesion that results from delayed closure of the connection from the yolk sac to the amniotic cavity. This anterior paraspinal cyst contains both neural and GI elements. A stalk extends from the cyst to the meninges via a vertebral defect. Spinal cord anomalies are common in these children, such as syringohydromyelia and tethered cord. Additional vertebral anomalies are also common. There is additional discussion of neurenteric cyst in Chapter 22.

The diagnosis of a neurenteric cyst should be considered when radiographs show a posterior mediastinal mass adjacent to vertebral anomalies. MR imaging usually affords a specific diagnosis. CT allows optimal evaluation of the vertebral anomalies. With sonography, a neurenteric cyst appears as a well-defined anechoic lesion with thin walls. Higher echogenicity occurs if there is blood, proteinaceous fluid, or mucus within the lesion.

Bronchogenic Cyst

Bronchogenic cyst is a developmental lesion that results from anomalous budding of the ventral diverticulum of the foregut, with isolation of the resultant cyst from the normal airway. Because of this developmental pathophysiology, most mediastinal bronchogenic cysts are located near the carina. The cyst sometimes shares a common wall with the adjacent airway or is attached by a fibrous stalk. Communication with the airway does not occur, however, except as an occasional secondary phenomenon related to infection or instrumentation. Mediastinal bronchogenic cysts may be clinically silent or produce symptoms related to airway compression or esophageal compression. Infection of a bronchogenic cyst within the mediastinum is much less common than with those located in the lungs. Bronchogenic cysts are lined with pseudostratified columnar respiratory epithelium. The walls usually contain cartilage, smooth muscle, and mucous gland tissue. The cyst may contain serous fluid or thick mucoid material.^11–13

Bronchogenic cyst is the most common cystic mass of the mediastinum in children. Approximately two-thirds of bronchogenic cysts are located within the mediastinum, and one-third within the lung parenchyma. The lesion is most often in the middle mediastinum, although posterior mediastinal locations are also common (Figure 7-5). Standard radiographs usually show a well-defined, solitary mediastinal or hilar mass. Rapid increase in size or accumulation of gas within the cyst may be visible if the lesion becomes infected. Esophagography demonstrates extrinsic compression or deviation of the esophagus in about half of patients with a mediastinal bronchogenic cyst.^14,15

Cross-sectional imaging with CT, MR, or sonography serves to document the fluid composition of a mediastinal bronchogenic cyst. Most often, the contents of the cyst have characteristics of clear fluid, although debris or proteinaceous fluid sometimes alters the appearance, particularly on MRI (i.e., increased signal intensity on T1-weighted images). The contents of the cyst do not enhance with intravenous contrast (Figure 7-6). Rarely, CT demonstrates high attenuation within the cyst because of milk of calcium. The borders of a bronchogenic cyst are well-defined and smooth or lobulated. Calcification of the wall is rare. The wall may enhance with intravenous contrast.

Most mediastinal bronchogenic cysts are not detectable with prenatal sonography. When this lesion is visible, it usually appears as a unilocular fluid-filled cyst in the middle or posterior mediastinum. The differential diagnosis in this situation includes other cystic mediastinal lesions, such as esophageal duplication cyst and neurenteric cyst.^16,17

The treatment of bronchogenic cyst is surgical resection. Even small asymptomatic lesions may become symptomatic later in childhood or adulthood. Malignant degeneration (rhabdomyosarcoma) has been reported within bronchogenic cysts.^18,19

Enteric Cyst

Approximately 10% to 15% of enteric duplications occur in the posterior mediastinum. This is a cystic or tubular structure that has smooth muscle walls and GI tract mucosa. Ectopic gastric mucosa is present in about half of these lesions. Communication with the esophageal lumen is rare. Many mediastinal enteric duplications are asymptomatic; potential clinical manifestations include airway obstruction, cough, dysphagia, and pain. Approximately two-thirds of thoracic enteric duplication cysts are located on the right side. Occasionally, a duplication traverses the diaphragm, resulting in both thoracic and abdominal components.

A mediastinal enteric duplication cyst is demonstrated on esophagography as an extrinsic mass; occasionally, there are characteristics of an intraluminal lesion. CT or MRI serves to document the cystic character of the mass and to assess compression or displacement of adjacent mediastinal structures. The lesion produces attenuation values of water or soft tissue on CT, and there is no enhancement (Figure 7-7). The cyst has high T2 signal intensity on MR images. Most often, the lesion is round or oval; a tubular duplication cyst is uncommon. In those cysts with ectopic gastric mucosa, uptake of technetium-99m pertechnetate can be demonstrated scintigraphically.²⁰

Anatomic Compartments

The mediastinum is defined as the central portion of the thorax that lies between the pleural cavities, the diaphragm, and the thoracic inlet. Division of the mediastinum into anterior, middle, and posterior compartments is arbitrary, as there are no fascial separations between these areas. The anterior mediastinum is the portion anterior to the heart, ascending aorta, and brachiocephalic vessels on a lateral chest radiograph. The anterior mediastinum contains the thymus, adipose tissue, and lymph nodes. The middle mediastinum consists of the structures contained within the pericardium, and includes the heart, the ascending and transverse portions of the aortic arch, the brachiocephalic vessels, the vena cava, the main pulmonary artery and proximal aspects of the right and left pulmonary arteries, the right and left pulmonary veins, the trachea, the main bronchi, and lymph nodes. The posterior mediastinum extends from the thoracic vertebral margin to the heart and trachea, and contains the descending thoracic aorta, esophagus, azygos veins, autonomic ganglia and nerves, thoracic duct, and lymph nodes.²¹

The majority of mediastinal masses in young infants are located in the posterior mediastinum. Posterior mediastinal masses include neurogenic tumors, neurenteric cyst, and enteric duplication cyst (Table 7-1). The most common mediastinal mass in older children is lymphadenopathy caused by lymphoma or leukemia; this is usually most prominent in the middle compartment of the mediastinum (Table 7-2). Adenopathy related to metastatic disease or inflammatory conditions is usually most prominent in the right paratracheal region of the middle mediastinum. With massive adenopathy, there may be extension from the middle mediastinum into the anterior mediastinum. The differential diagnosis of an anterior mediastinal mass in a child includes thymoma, teratoma, dermoid cyst, hemangioma, lymphatic malformation, and tumors of thyroid origin (Table 7-3). The most common cysts of the mediastinum in children are bronchogenic cyst and enteric duplications (Table 7-4). A bronchogenic cyst is most often located in the middle mediastinum, but posterior locations also occur. Duplications are usually in the posterior mediastinum, with a predilection for the right side.^22,23

Clinical Presentations

Stridor or Respiratory Distress Because of a Mediastinal Lesion

Extrinsic tracheobronchial compression in children occurs because of great vessel anomalies and mediastinal masses (Table 7-5). The most common symptomatic vascular ring in infants is the double aortic arch. The components of the aortic arch completely encircle the esophagus and trachea, and cause narrowing of both of these structures. Symptomatic tracheal narrowing can also result from a right aortic arch with a left ligamentum arteriosum. Some degree of focal intrathoracic tracheal abnormality nearly always occurs in children with pulmonary artery sling. This anomaly consists of a left pulmonary artery origin from the right pulmonary artery, with the left pulmonary artery passing over the right main bronchus and between the trachea and esophagus, causing compression of the right upper lobe bronchus and/or trachea. Associated tracheal stenosis caused by abnormal development of the tracheal cartilage or localized tracheomalacia is common in children with pulmonary sling. Other vascular abnormalities that can cause tracheobronchial compression include right aortic arch with anomalous left subclavian artery, origin of the innominate artery to the left of the midline, and enlarged or displaced vessels following cardiac surgery.^24–26

Mediastinal malignant tumors, such as lymphoma, are often quite large and rapidly growing at the time of clinical presentation. They are also frequently associated with deviation and narrowing of the airway. Therefore, patients with these masses are at significant risk for cardiopulmonary complications when general anesthesia is administered. Careful evaluation of the airway on preoperative imaging studies is essential for these patients. The peak expiratory flow rate and the tracheal cross-section area are useful markers to identify children at high risk for anesthetic complications. General anesthesia is particularly dangerous if the peak expiratory flow rate is less than 50% of the predicted value and the tracheal cross sectional area is narrowed greater than 50%.²⁷

Superior Vena Cava Syndrome

Superior vena cava syndrome is caused by intraluminal occlusion or extrinsic compression of the superior vena cava. The most common mechanism is catheter-related thrombosis, often related to malposition of a central venous catheter. Other potential etiologies of symptomatic superior vena cava obstruction include compression by a mediastinal neoplasm, abscess, or hematoma. The rare syndrome of fibrosing mediastinitis is an additional cause. The dominant clinical characteristic of superior vena cava syndrome is edema of the face, neck, upper extremities, and upper portion of the thorax. Dilated chest wall veins are usually visible.^28,29

Standard chest radiographs of children with superior vena cava syndrome may show enlargement of the azygos vein. A specific diagnosis is usually provided by venography, contrast-enhanced CT, or MR (Figure 7-8). Systemic anticoagulation and catheter directed thrombolysis are useful treatments for patients with acute superior vena cava syndrome. Imaging evaluation for an underlying stenosis is often useful after recanalization.³⁰

Germ Cell Tumors

The mediastinum is the third most common site of germ cell tumors, following sacrococcygeal and gonadal locations. Most mediastinal germ cell tumors are located in the anterior mediastinum, sometimes arising in the thymus. Teratoma is the most common, accounting for approximately 80% of these lesions. Germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, and mixed germ cell tumor are other primary germ cell tumors of the mediastinum. Malignant germ cell tumors often cause elevations of serum β-human chorionic gonadotropin and α-fetoprotein. Teratomas occur with an equal frequency in boys and girls, but malignant germ cell tumors are much more common in males.^31-34

Mediastinal germ cell tumors apparently arise from multipotent germ cells that fail to migrate properly during embryogenesis. The primitive germ cells normally descend along the midline from the yolk sack endoderm to the gonads. It is also possible that some of these tumors arise from myoid cells within the thymus. These germ cells retain the ability to proliferate and differentiate into embryonic or extraembryonic tissue.

Teratoma

Teratoma is a benign developmental neoplasm that contains tissues that either represent more than one of the embryonic germ layers or are foreign to the site of the lesion. Approximately 10% of all teratomas arise in the mediastinum. Many of these lesions are asymptomatic. If the mass is of sufficient size to compress the airway, patients may experience cough, wheezing, dyspnea, chest pain, or shortness of breath. Manifestations of superior vena cava obstruction can occur with a large mass. Hemoptysis has been reported in infants with mediastinal teratoma.^35,36

Teratoma is an encapsulated mass that typically contains a mixture of tissue types, including cystic and solid areas (Figure 7-9). Attempted tissue differentiation and organ formation may result in the presence of skin, hair, teeth, cartilage, bone, bronchial tissue, or intestinal tissue. On diagnostic imaging studies, the margins of a teratoma are usually well-defined, and may be rounded or lobulated. The mass is usually predominantly located within the anterior compartment of the mediastinum. Most contain one or more cysts with thick well-defined walls. Fat–fluid levels can occur, and there may be calcifications within the walls. The presence of fat and calcification or ossification within the mass is highly specific for the diagnosis of teratoma.³⁷

Intrapericardial Teratoma

Intrapericardial teratoma is a rare lesion that presents in the neonatal period with congestive cardiac failure as a consequence of mass effect on the great vessels. This lesion is located within the pericardium adjacent to the bases of the great vessels. Neonates with intrapericardial teratoma have a markedly enlarged cardiac silhouette on chest radiographs, and there are often indications of congestive heart failure. Cross-sectional imaging with sonography, CT, or MRI shows a mass in the superior aspect of the pericardium, with a heterogeneous tissue composition.³⁸

Malignant Germ Cell Tumors

Malignant germ cell tumors of the mediastinum are uncommon. In teenagers and young adults, this tumor is more common in males. The frequency is approximately equal between boys and girls in younger children. There are a variety of histological types, including germinoma, embryonal carcinoma, yolk sac tumor, choriocarcinoma, mixed germ cell tumor, and polyembryoma. The evaluation of serum tumor markers is helpful in the diagnosis and followup monitoring of these lesions; at least 90% of nonseminomatous malignant germ cell tumors elaborate α-fetoprotein and/or β-human chorionic gonadotropin. Endodermal sinus tumor results in elevated α-fetoprotein; choriocarcinoma elaborates β-human chorionic gonadotropin; embryonal carcinoma and polyembryoma elaborate both α-fetoprotein and β-human chorionic gonadotropin; neither of these tumor markers is usually elevated in the presence of germinoma.^31,34,36,39

A malignant germ cell tumor is usually a large, unencapsulated mass that contains hemorrhage, necrosis, and cysts. There is usually a nonspecific appearance on chest radiographs: a lobulated unilateral mediastinal mass. CT and MR imaging may show evidence of invasion of adjacent structures and violation of tissue planes. The large cysts and well-formed calcifications that are common in benign teratomas are typically lacking in malignant germ cell tumors. However, hemorrhage and necrosis are frequent findings. Cysts with irregular thick walls are sometimes present. Other potential findings are pleural effusion and pulmonary nodules (Figure 7-10).^32,40

Seminoma is a malignant germ cell tumor that occurs nearly exclusively in males. Although most seminomas of the mediastinum are primary lesions, seminoma can also occur at this location as a metastatic lesion from a testicular primary. The peak prevalence of mediastinal seminoma is from the second to fourth decades of life. The most common presenting complaints are a result of tumor compression of the trachea or superior vena cava. Patients may report chest pain, dyspnea, cough, and weight loss. The α-fetoprotein is never elevated with pure seminoma, and β-human chorionic gonadotropin is elevated in a minority of patients. The prognosis for appropriately treated mediastinal seminoma is excellent; the 5-year survival rate is greater than 90%.

The imaging features of seminoma are similar to those of other malignant germ cell tumors. Cross-sectional imaging studies typically demonstrate a bulky, lobular anterior mediastinal mass; this lesion only rarely arises in the posterior mediastinum. Cysts are occasionally present. The tumor matrix tends to be more homogeneous than other malignant germ cell tumors. Calcifications are rare. Contrast enhancement is minimal. Local structures may be encased or invaded. The most common sites of metastasis are regional lymph nodes and the skeletal system.⁴¹

Thymic Enlargement

The differential diagnosis of enlargement of the thymus includes a variety of developmental, neoplastic, and idiopathic conditions. Enlargement of an otherwise normal thyroid thymus can occur as a rebound phenomenon after stress-related atrophy, or as an idiopathic process. Masses that can be located within the thymus include thymoma, cysts, hemangioma, lymphatic malformation, hematoma, and thymic carcinoma. The thymus is a common site of involvement with lymphoma and leukemia. Infiltration of the thymus can occur with Langerhans cell histiocytosis, particularly in young infants. Infiltration and enlargement of the thymus can be part of Castleman disease. Cystic lesions of the thymus include primary epithelial cysts, cystic teratoma, and Hodgkin disease.

Enlargement of the thymus can occur in children with autoimmune diseases. This is termed lymphoid follicular hyperplasia of the thymus. The hyperplasia only occurs in the medulla. Lymphoid follicular hyperplasia of the thymus is common in children with HIV infection.