Mean values and standard deviations (SD) of thymic thickness (measured perpendicular to the craniocaudal axis of a lobe), length (measured along the craniocaudal axis), and width (measured from outer border to outer border in the transverse dimension) have been reported. These vary with age. Length increases directly with age, whereas width shows little change. Thymic thickness decreases in size with advancing age. Mean thickness is 1.50 6 0.46 (SD) cm for patients between 0 and 10 years and 1.05 6 0.36 cm for the 10- to 20-year age group (5). Thickness is the best indicator of an infiltrative disease, but it is usually not required for the diagnosis of thymic abnormality. Most abnormal thymuses can be recognized by qualitative assessment of thymic shape and lateral borders.

In some individuals, the thymus will extend either superiorly above the level of the brachiocephalic vessels or into the posterior thorax (6). The abnormally posteriorly positioned thymus can be recognized on CT by its continuity with the anterior mediastinal thymic tissue, an attenuation value similar to that of normal thymic tissue, and the absence of compression of adjacent mediastinal vessels or the tracheobronchial tree (Figs. 2.3 and 2.4).

In the mediastinum, Hodgkin lymphoma is more common than non-Hodgkin lymphoma. The most frequent
type of Hodgkin lymphoma, the nodular sclerosing form, constituting 60% to 70% of all cases, can present as a large anterior mediastinal mass. The other histologic subtypes, the mixed cellularity subtype (20% to 40%), the lymphocytic predominant subtype (8% to 20%) and the lymphocytic depletion subtype (1% to 8%), usually manifest as mediastinal adenopathy rather than as a thymic mass (17). The subtypes of non-Hodgkin lymphoma that involve the mediastinum are the precursor T lymphoblastic and diffuse large B-cell types (18,19). In the pediatric population, Hodgkin lymphoma is uncommon before the second decade of life, whereas non-Hodgkin lymphoma is common in both the first and second decade of life.

Intrathoracic involvement is present in ≤85% of patients with Hodgkin lymphoma at initial presentation. Thymic involvement is seen in >70% of patients with Hodgkin lymphoma. By comparison, thoracic involvement in non-Hodgkin lymphoma is about half as common as it is in Hodgkin lymphoma. Approximately 40% to 45% of patients with non-Hodgkin lymphoma have intrathoracic disease at the time of initial diagnosis and ≤25% may have thymic involvement. In both forms of lymphoma, thymic involvement is not an isolated finding and is associated with nodal enlargement elsewhere in the mediastinum.

In patients with lymphoma, CT is used to determine the extent and stage of disease, plan radiation therapy ports, and evaluate response to treatment. In several series, CT findings altered staging or treatment planning, usually radiation portals, in 10% to 20% of patients with Hodgkin lymphoma (20,21). CT demonstration of unsuspected chest wall or pericardial disease and subcarinal, cardiophrenic or paravertebral nodes is likely to have the greatest impact on therapy planning. Partial-transmission lung blocks or localized boost therapy may be given when disease lies outside the standard field of radiation.

On CT, the infiltrated thymus appears as an enlarged, quadrilateral gland with convex or lobulated margins (Fig. 2.8) (22,23). Usually, both lobes of the thymus are diffusely enlarged, but asymmetric thymic infiltration, predominantly affecting one lobe, may be seen (Fig. 2.9). Mean thickness of an infiltrated lobe ranges from 2.1 to 7.5 cm (normal, 0.4 to 2.1 cm). Thymic masses are usually of homogeneous soft tissue attenuation, but areas of low attenuation or cystic components, due to ischemic necrosis, can be present (Fig. 2.10) (3,24,25,26,27). These cystic changes can persist unchanged or enlarge following successful treatment, despite regression of disease elsewhere. Thymic calcification can be seen in untreated lymphoma, but more often it is a posttreatment sequela (Fig. 2.11) (28,29). As noted above, thymic involvement is not an isolated finding and is associated with nodal enlargement elsewhere in the mediastinum.

Nodal disease ranges from mildly enlarged, discrete nodes in a single area to large conglomerate masses in multiple regions (Figs. 2.12 and 2.13). Lymphomatous nodes are usually soft tissue attenuation and show little if any enhancement after administration of intravenous contrast material.

There are two distinct histologic types of thymic hyperplasia: true thymic hyperplasia and lymphoid hyperplasia (30). True thymic hyperplasia involves both the cortex and medulla and results in increase in size and weight of the thymus and preservation of the normal architecture. Rebound hyperplasia following chemotherapy is the most common cause of true thymic hyperplasia. Less commonly, true hyperplasia occurs in association with red cell hypoplasia or aplasia, Graves disease, or Addison disease (30).

Thymic hyperplasia, defined as >50% increase in thymic volume over baseline, is a well-recognized effect of chemotherapy, especially when corticosteroids have been given as part of the treatment plan. The increased levels of glucocorticoids cause lymphocyte depletion from the cortical portion of the gland. Thymic regrowth results when the cortisone levels return to normal and the cortex is repopulated with lymphocytes. Nearly all patients exhibit thymic involution after the start of chemotherapy (3). Following involution, the thymus returns to normal size in most patients, but in up to 25% of patients, it exhibits rebound or a substantial increase in volume. Thymic rebound usually occurs between courses of chemotherapy
or from 1 to 10 months after cessation of chemotherapy. On CT, the thymus is diffusely enlarged, but it maintains its triangular configuration (Fig. 2.14).

None of the currently available imaging examinations (CT, MRI, gallium-67 scintigraphy, or positron emission tomography) are able to reliably distinguish thymic hyperplasia from recurrent disease. Patients who are doing well clinically with no other evidence of disease and who have isolated thymic enlargement that coincides with the timing of chemotherapy can be followed with serial CT scans, rather than undergo biopsy. A gradual reduction in thymic size supports the diagnosis of benign thymic hyperplasia (31). On the other hand, the presence of lymph node enlargement in association with thymic enlargement should raise the suspicion of recurrent tumor.

Thymic lymphoid or follicular hyperplasia refers to the presence of an increased number of lymphoid follicles (30). This condition is most commonly associated with myasthenia gravis and HIV infection. The thymus usually is of normal size and weight. On CT, patients can have a normal-appearing thymus, an enlarged thymus with a normal shape, or a focal mass (30). In myasthenia gravis, the diagnosis of lymphoid hyperplasia is made at histologic examination at the time that patients undergo thymectomy to induce remission.

Thymoma, also referred to as lymphoepithelioma, is a neoplasm of thymic epithelial cells and histologically contains various proportions of epithelial cells and lymphocytes. Thymomas are rare in the pediatric population, accounting for only 1% to 2% of mediastinal tumors (32). Patients may be asymptomatic or have symptoms related to compression of mediastinal structures. Most thymomas in children arise sporadically, but they can be found in association with myasthenia gravis, red cell aplasia, or hypogammaglobulinemia.

Pathologically, thymomas are classified as noninvasive (encapsulated) or invasive (extending through the capsule into the adjacent mediastinum). Typically, they are cytologically benign and show no atypia, and thus, the terms noninvasive and invasive, rather than benign and malignant, are used to characterize thymomas. Approximately 10% to 15% of thymomas are invasive.

CT findings of thymoma range from a focal soft tissue mass extending beyond the lateral thymic margin to a large lobulated mass, replacing the thymus (32). They are typically homogeneous, but some masses may contain low-attenuation areas, representing necrosis, cystic degeneration or old hemorrhage, (Figs. 2.15 and 2.16) (25,26,33). Calcifications also may be noted. Most thymomas exhibit mild contrast enhancement. The presence of well-defined fat planes between the tumor and adjacent mediastinal structures suggests the absence of gross invasion, but microscopic invasion cannot be excluded. Conversely, the obliteration of fat planes does not always indicate local invasion.

CT features of invasive thymoma include invasion or encasement of mediastinal structures, pulmonary metastases, and pleural or pericardial implants or thickening, most commonly limited to one side of the thoracic cavity
(Fig. 2.17). Transdiaphragmatic spread is a late finding of invasive thymoma. Lymphadenopathy is unusual in thymomas and should raise concern for lymphoma rather than thymoma.

Thymic carcinomas are a rare type of epithelial tumor of the thymus that exhibit cytologic atypia and anaplasia and histologic features not specific to the thymus. They differ from thymomas, which are also epithelial tumors but are cytologically benign. CT findings include a large anterior mediastinal, soft tissue mass with aggressive features of central necrosis, great vessel invasion, mediastinal/hilar lymphadenopathy, and pleural and pericardial metastases (Fig. 2.18). The CT features are similar to thymoma, but the presence of vascular invasion or lymphatic or hematogenous metastases supports the diagnosis of carcinoma.

Langerhans cell histiocytosis can produce an anterior mediastinal soft tissue mass. Following chemotherapy, the thymus may exhibit cavitary or cystic changes, occasionally with air–fluid levels (34,35,36).

Extragonadal germ cell tumors constitute approximately 10% of all mediastinal masses in children and follow lymphoma in frequency as a cause of an anterior mediastinal mass (15,16). Most are found within or adjacent to the thymus. Rarely, they arise in the posterior mediastinum (37,38,39). Most germ cell tumors present during the second to forth decades of life. Germ cell tumors in children are usually symptomatic because they compress adjacent structures.

Germ cell tumors may be classified as teratomatous or nonteratomatous tumors. Teratomatous tumors can be further classified as mature (including the dermoid cyst), immature, and malignant. Mature teratomas are well differentiated and contain elements of all three germinal layers: ectoderm (skin, hair), endoderm (fat), and mesoderm (cartilage, muscle). Dermoid cysts contain elements of only two germinal layers. Immature teratomas contain both immature tissue, usually fetal brain, and mature tissues. Malignant teratomas contain frankly malignant elements in addition to mature elements. The nonteratomatous tumors are malignant and include seminomas, embryonal carcinoma, endodermal sinus tumor, choriocarcinoma, and mixed cell types. Serum levels of serum human chorionic gonadotropin or alpha-fetoprotein are elevated in malignant germ cell tumors.

The mature teratoma is the most common mediastinal germ cell tumor, accounting for approximately 90% of cases. On CT, dermoid cysts and mature teratomas are well-circumscribed, smoothly marginated, heterogeneous masses with predominance of low-attenuation components (Fig. 2.19) (39). Fluid is the dominant component in 80% of masses (38,39,40). Fat is seen in approximately 76% of mature teratomas, a fat–fluid level in 10% of cases, and foci of calcification or ossification in approximately 50% of cases. About 15% of teratomas are purely cystic lesions without identifiable fat or calcification (38,39,40). Soft tissue elements may be present, but they are
typically not a dominant component. A specific diagnosis of teratoma can be made with certainty by CT when calcifications and fat are demonstrated within an anterior mediastinal mass.

Immature and malignant teratomas tend to have irregular or nodular walls and a predominance of soft tissue attenuation components (Fig. 2.20). Compared with mature teratomas, a smaller number contain fat. Malignant teratomas also may show pulmonary and/or liver metastases and chest wall invasion.

Seminomas are the most common nonteratomatous germ cell tumor. On CT, they are usually large, homogeneous, soft tissue attenuation masses (39,40,41) (Fig. 2.21). Occasionally, low-attenuation foci, attributed to necrosis or hemorrhage, may be noted. Nonseminomatous germ cell tumors appear as large masses with areas of low attenuation and irregular borders (Fig. 2.22) (39,41). Both seminomatous and nonseminomatous tumors may contain areas of calcification, and they may invade locally and infiltrate adjacent fat planes. On occasion, nonseminomatous germ cell tumors enlarge after treatment. Such enlargement most often represents fibrosis or benign teratomatous tissue rather than tumor (42).

Thymolipoma is a rare benign tumor occurring most frequently in adolescents and young adults. It accounts for <5% of all thymic tumors. Histologically, thymolipoma is composed of mature adipose and thymic tissue (43). The tumor is typically large (average diameter, 20 cm). It may be confined to the anterior mediastinum, but because of its soft and pliable nature, it often extends inferiorly, abutting the cardiac border. It is often detected incidentally at routine chest radiography and may mimic cardiac enlargement or an elevated hemidiaphragm (43).

CT findings of thymolipoma are an anterior mediastinal or paracardiac fatty mass with strands or whorls of soft tissue (Fig. 2.23). It does not compress or invade adjacent structures, but instead it conforms to the shape of adjacent mediastinal structures (43). By

comparison, mature teratomas contain fat, but they commonly also have fluid and calcification, are round, and do not conform to the shape of adjacent structures.

Thymic cysts can be congenital or acquired (25,26). Congenital thymic cysts are believed to arise from remnants of the thymopharyngeal duct and as such, may be found in the neck or mediastinum (44). Acquired cysts have been reported in association with HIV infection and with thymic neoplasms, including lymphoma, Langerhans cell histiocytosis, and thymoma (25,26,45,46). They also have been reported following radiation therapy and thoracotomy (47).

CT findings of congenital thymic cysts are similar to those of cysts elsewhere. They usually appear as a well-defined water-attenuation mass with thin or imperceptible walls, which do not enhance (25,26) (Fig. 2.24). The attenuation may be higher and equal to that of soft tissue if the contents are proteinaceous or hemorrhagic. Cysts associated with neoplasia, inflammation, and trauma usually show a thick wall or soft tissue attenuation components. Most thymic cysts are unilocular with the exception of inflammatory cysts, which tend to be multilocular (Fig. 2.25) (48).

Lymphangioma is a benign congenital malformation of the lymphatic system. It is lined by endothelium and contains chylous fluid. Most are discovered in the first 2 years of life. Approximately 75% of lymphangiomas arise in the neck, 20% in the axilla, and the remainder in the retroperitoneum or presacral areas. Between 5% and 10% of cervical lymphangiomas extend into the mediastinum, usually the anterior or superior mediastinum (5,26). Approximately 1% of all lymphangiomas are confined to the chest. These usually are found in older children and adolescents (49).

Lymphangiomas typically appear as thin-walled, multiloculated, near-water attenuation masses, which often encase and displace the adjacent mediastinal structures (Figs. 2.26 and 2.27). On occasion, they may be unilocular or they may have higher attenuation caused by the presence of hemorrhage or infection. Contrast enhancement is absent unless the lesions contain vascular components or are infected. Calcification is rare. Other findings include cervical and thoracic venous aneurysms (50). Although CT
can detect lymphangioma, MRI is best for showing the extent of tumor, particularly vessel encasement (51).

Hilar and mediastinal lymph node enlargement is commonly seen in children with active tuberculosis. Typically, the enlargement is unilateral and on the side of lung disease. The right paratracheal and tracheobronchial lymph nodes are involved most often (57). Large nodes commonly show central areas of low attenuation on contrast-enhanced CT scans, with surrounding rim enhancement (Fig. 2.36) (57). The latter findings indicate active tuberculosis and resolve after successful treatment.

Infection by Histoplasma capsulatum is another cause of mediastinal and hilar lymphadenopathy. Paratracheal, subcarinal, and hilar lymph node enlargement and associated atelectasis or pneumonitis are commonly seen at the time of initial infection. Most often, histoplasmosis resolves with only residual nodal or parenchymal calcifications (Fig. 2.37). Occasionally, it results in fibrosing mediastinitis, which is thought to result from an abnormal immunologic response to H. capsulatum antigens rather than from direct infection of the mediastinum by H. capsulatum (58,62). The result of this reaction is the proliferation of dense fibrous tissue within the mediastinum, which may obliterate mediastinal fat planes and encase or invade adjacent structures (superior vena cava, pulmonary arteries and veins, tracheobronchial tree, and esophagus) (62). There are two patterns of involvement: focal and diffuse. The focal pattern appears as a localized soft tissue attenuation mass that is often calcified and usually found in the right paratracheal or subcarinal regions or in the hila (Fig. 2.38). The diffuse pattern appears as a diffusely infiltrating mass that involves multiple mediastinal compartments (Fig. 2.39). It may or may not be calcified. Pulmonary opacities, representing pneumonia secondary to airway obstruction or venous obstruction with infarction, may also be seen.

Sarcoidosis is characterized by nonnecrotizing granulomatous inflammation (63). Typically, CT shows symmetric bilateral hilar lymphadenopathy, usually with right
paratracheal lymphadenopathy (Fig. 2.40). Subcarinal and anterior or posterior mediastinal adenopathy also may be seen, but rarely without hilar disease (64). Nodal calcifications are usually a late manifestation of disease and have been reported in 25% to 50% of cases. Unlike nodes in neoplastic disorders, which tend to coalesce, the lymph nodes in patients with sarcoidosis usually maintain their configuration and borders as they enlarge (63).

Castleman disease (also known as angiofollicular lymph node hyperplasia, angiomatous lymphoid hamartoma, and giant mediastinal lymph node hyperplasia) is a disease of unknown cause. There are two histologic types (60,61): the hyaline-vascular type, accounting for 80% to 90% of cases, and the plasma cell type. The former has a predilection for the mediastinum, although it can involve other areas such as the axilla and retroperitoneum. The plasma cell type usually is multicentric and commonly arises in extramediastinal sites, especially the neck, mesentery, and retroperitoneum, producing generalized lymphadenopathy. In the chest, it produces multifocal lymphadenopathy. On CT, the hyaline type usually appears as a mediastinal and/or hilar mass (Fig. 2.41) that enhances intensely after contrast administration. Multiple masses are less common. The plasma cell type more often appears as bilateral nodal enlargement. The degree of nodal enhancement is mild compared with the hyaline type (60,61).

The malignancies with a higher propensity to metastasize to the mediastinum and hilum are lymphoma, leukemia, Wilms tumor, rhabdomyosarcoma, and testicular cancer. Lymph node involvement is typically asymmetric. Most nodal masses have an attenuation equal to that of soft tissue, although low-attenuation nodes can be seen in testicular and ovarian cancers and rhabdomyosarcoma (Fig. 2.42).

Hodgkin lymphoma spreads in a contiguous manner from one nodal group to another (65). At presentation, approximately 85% of patients with thoracic involvement by Hodgkin lymphoma have intrathoracic disease (19,21,27). In almost all patients (>95%), the superior mediastinal (prevascular) lymph nodes are involved. Other sites of lymph node enlargement, in order of
decreasing frequency, include hilar lymph nodes (33% of cases), subcarinal nodes (20% of cases), cardiophrenic angle nodes (8% of cases), and posterior mediastinal nodes (5% of cases) (Fig. 2.12) (21).

In non-Hodgkin lymphoma, nodal involvement is often noncontiguous. Intrathoracic disease is initially present in 40% to 50% of patients. Superior mediastinal nodes are involved in about 75% of patients (20). Hilar nodes are involved in 9%, subcarinal nodes in 13%, posterior mediastinal nodes in 10%, and cardiophrenic nodes in 7% (Fig. 2.13).

Mediastinal neuroblastoma, a malignant tumor composed of immature ganglion cells, is typically seen in young children under the age of 5 years (69). Ganglioneuroblastoma, a tumor containing both mature and immature cell, is often encountered in children between 5 and 10 years of age. Ganglioneuroma, a
benign tumor made up of mature ganglion cells, is a more common neoplasm in older children and adolescents.

On CT, ganglion tumors tend to be sharply marginated, fusiform paraspinal masses that are oriented vertically along the direction of the sympathetic chain (70) (Fig. 2.46). Approximately 40% of neuroblastomas and 20% of ganglioneuromas contain calcifications. Enlargement and invasion of the neural foramina (Fig. 2.47), smooth pressure erosions of adjacent vertebral bodies or ribs, and spread into the abdomen, either via the aortic and esophageal hiatus or by direct invasion,
also may be seen. The ganglion cell tumors may show heterogeneous enhancement following administration of intravenous contrast material. Differentiation among the different tumor types is not possible on the basis of their CT appearances and requires tissue sampling (Fig. 2.48).

Nerve sheath tumors include neurofibroma and schwannomas. They are more common in adolescents than they are in young children (71). They commonly arise from intercostal nerves and are generally benign. Rare instances of malignant transformation of benign neurofibromas have been described, especially in children with neurofibromatosis (71).

Nerve sheath tumors are usually solitary lesions. They tend to have a round or oval shape and a short craniocaudal diameter, in contradistinction to ganglion tumors, which have a fusiform shape and extend over several vertebral body levels. They may be of homogeneous soft tissue attenuation or they may contain areas of low attenuation due to the presence of cystic degeneration, xanthomatous (fatty) components, or areas of hypocellularity or myxoid stroma (Fig. 2.49) (72). Enlargement of adjacent neural foramina, small areas of calcification, and minimal heterogeneous or peripheral enhancement following contrast administration also may be seen.

Plexiform neurofibromas are associated with neurofibromatosis. On CT, these lesions can appear as multiple soft tissue masses or as an extensive fusiform or infiltrating mass following the distribution of the sympathetic chains or mediastinal or intercostal nerves (73). They often have lobulated, ill-defined margins, surround mediastinal vessels, and have a lower attenuation than muscle. Calcification and enhancement following administration of intravenous contrast material may be present.

Malignant nerve sheath tumors (e.g., neurofibrosarcoma) are rare. In the absence of associated pulmonary or pleural metastases, CT features of benign plexiform neurofibromas and malignant nerve sheath tumors are indistinguishable and tissue sampling is required for differentiation. Heterogeneity, mediastinal infiltration, ill-defined margins, and areas of calcifications may be noted in both types of tumors.