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A diagnostic approach to the mediastinal masses
Insights into Imaging volume 4, pages29–52 (2013)
Multiple different types of mediastinal masses may be encountered on imaging techniques in symptomatic or asymptomatic patients. The location and composition of these lesions are critical to narrowing the differential diagnosis.
Radiological compartmentalisation of the mediastinum helps in focusing the diagnosis of masses on the basis of their site. Some diseases, however, do not occur exclusively in any specific compartment and can spread from one compartment to another.
Tissular components of the mass, the degree of vascularisation and the relationships with mediastinal structures assessed by computed tomography (CT) or magnetic resonance imaging (MRI) are a leading edge of the radiological diagnosis. Special applications at MRI have been developed over the recent years in order to identify accurately tissular components of the mediastinal masses. The likelihood of malignancy of the mediastinal masses is influenced by the symptomatology and the age of the patient. This article reviews the most commonly encountered mediastinal masses considering clinical history and manifestations, anatomical position and certain details seen on different imaging modalities that allow correct diagnosis in many cases.
Familiarity with the radiological features of mediastinal masses facilitates accurate diagnosis, differentiation from other mediastinic processes and, thus, optimal patient treatment.
• CT and MRI are important for the diagnosis of mediastinal masses.
• The location and tissue characteristics on imaging studies are critical to narrow down the differential diagnosis of mediastinal masses.
• Symptomatology and patient age affect the likelihood of malignancy.
Mediastinal masses span a wide histopathological and radiological spectrum. The most frequent lesions encountered in the mediastinum are thymoma, neurogenic tumours and benign cysts, altogether representing 60% of patients with mediastinal masses . Neurogenic tumours, germ cell neoplasms and foregut cysts represent 80% of childhood lesions, whereas primary thymic neoplasms, thyroid masses and lymphomas are the most common in adults .
The mediastinum is demarcated by the pleural cavities laterally, the thoracic inlet superiorly and the diaphragm inferiorly. It is further divided into anterior, middle and posterior compartments by many anatomists . Anterior mediastinal tumours account for 50% of all mediastinal masses, including thymoma, teratoma, thyroid disease and lymphoma . Masses of the middle mediastinum are typically congenital cysts while those arising in the posterior mediastinum are often neurogenic tumours .
Usual symptoms at presentation are cough, chest pain, fever/chills and dyspnea. Localising symptoms are secondary to tumour invasion (respiratory compromise; paralysis of the limbs, diaphragm and vocal cords; Horner syndrome; superior vena cava syndrome), while systemic symptoms are typically due to the release of excess hormones, antibodies or cytokines.
Many mediastinal reflections can be appreciated at conventional radiography (CR), and their presence or distortion is the key to the interpretation of mediastinal abnormalities . However, computed tomography (CT) is the most important tool in the evaluation of a mediastinal mass . Characterisation on CT is based on specific attenuation of air, fat, water and calcium (Fig. 1). High-resolution multiplanar reformation images display the detailed anatomical relationship of the tumour with the adjacent structures. An excellent soft tissue contrast also designates magnetic resonance imaging (MRI) as an ideal tool to evaluate tumours of the mediastinum . Assessment of preoperative relationships with the pericardium, heart cavities, spinal cord and vascular involvement is a common indication. Chemical-shift MRI has been shown to be useful in distinguishing normal thymus and thymic hyperplasia from thymic neoplasms and lymphoma . Diffusion-weighted MRI (DWI) is another special application that unveils minute metabolic and biophysical differences between tissues. According to Gumustas et al. , the mean apparent diffusion coefficient for the malignant mediastinal entities could be significantly lower than that for the benign diseases.
Many entities that involve the mediastinum correspond to anatomical variants or masses arising from the spine or from the digestive tract, and should not be considered true mediastinal masses (Figs. 2 and 3). Lymph node enlargement represents a frequent cause of mediastinal masses .
Lipomas predominantly occur in the anterior mediastinum and are reported to represent 1.6–2.3% of all primary mediastinal tumours . At CT, lipomas have homogeneous fat attenuation of approximately -100 HU. Liposarcoma frequently occurs in the posterior mediastinum and it is usually symptomatic at the time of presentation, in contrast to lipoma . Inhomogeneous appearance on CT or MRI differentiates liposarcoma from lipoma .
Thymolipoma is a rare, benign, well-encapsulated thymic tumour that accounts for about 2–9% of thymic neoplasms [10, 12–14]. Tumours occur most frequently in the cardiophrenic angle of asymptomatic young adults without sex predilection. The fat content usually constitutes 50–85% of the lesion but has been reported to account for as much as 95% of the tumour . Associations with myasthenia gravis, Graves disease and haematological disorders have been reported . At CR, thymolipomas may mimic cardiomegaly, excessive epicardial fat, diaphragmatic elevation, lobar collapse or a pericardial cyst. CT or MRI is required to establish the diagnosis by showing a well-defined encapsulated mass that has extensive fat content and contains small amounts of solid areas and fibrous septa  (Fig. 4).
Mediastinal primary cysts represent 15–20% of all primary mediastinal masses [1, 15]. A smooth or oval mass with a homogeneous attenuation, with no enhancement of cyst contents and no infiltration of adjacent structures are the usual CT features of benign mediastinal cyst (Fig. 5). Any cyst may have a higher attenuation due to its calcic, proteinaceous, mucous or haemorrhagic content. Cysts typically show high signal intensity on T2-weighted MR images. True cystic lesions should be differentiated from the cystic degenerative changes observed in many solid tumours, in lymphomas before or after treatment, or in abscesses (Fig. 6).
Bronchogenic cysts result from abnormal ventral budding or branching of the tracheobronchial tree during embryologic development [15–17]. They are lined by respiratory epithelium and their capsule contains cartilage, smooth muscle and mucous gland tissue. They are stable in size, except when complicated by infection or haemorrhage. Approximately 40% of bronchogenic cysts are symptomatic, resulting in cough, dyspnea or chest pain . The bronchogenic cyst is commonly located in the near carina (52%) and in the paratracheal region (19%) . The anterior mediastinum is a rare location of the bronchogenic cyst  (Fig. 7). Air within the cyst is suggestive of secondary infection and communication with the tracheobronchial tree.
Duplication cysts are uncommon lesions lined by gastrointestinal tract mucosa and generally asymptomatic. However, if they contain gastric or pancreatic mucosa, there is the added risk of haemorrhage or rupture of the cyst from mucosal secretions. The majority of them are detected adjacent to or within the oesophageal wall (Fig. 8). Duplication cysts are indistinguishable from bronchogenic cysts on CT and MRI.
Mediastinal neuroenteric cysts are anomalous protrusions of the leptomeninges through intervertebral foramen or defects in the vertebral body. They are associated with multiple vertebral anomalies and with neurofibromatosis [15, 16].
Pericardial cyst is a benign lesion accounting for 5–10% of all mediastinal tumours . Most pericardial cysts are unilocular and commonly located in the right cardiophrenic space (Fig. 9). However, they may occur anywhere in relation to the pericardium.
Thymic cyst represents 1% of all mediastinal masses . Congenital cysts derive from remnants of the thymopharyngeal duct, they are typically unilocular and contain clear fluid (Fig. 10). In contrast, acquired thymic cysts are much more common, tend to be multilocular (Fig. 11) and may arise in association with neoplasms such as thymomas, lymphomas or germ cell tumours. Thymic cysts may also be seen in the anterior mediastinum after radiation therapy of Hodgkin’s disease, after inflammatory processes and occasionally in patients with AIDS, particularly in children .
Lymphangioma is a rare benign lesion of lymphatic origin that represents 0.7–4.5% of all mediastinal tumours in adult population . Lymphangiomas involve the neck or the axillary region in more than 80% of the cases and the thorax in 10% of the cases  (Fig. 12).
Pancreatic pseudocyst can extend into the mediastinum via the oesophageal or aortic hiatus. CT shows a thin-walled, fluid-containing cyst within the posterior mediastinum which may be in continuity with the intrapancreatic or peripancreatic fluid collections (Fig. 13).
Mediastinal goitre generally represents direct contiguous growth of a goitre into the anterior or superior mediastinum. Typical features of mediastinal goitres are encapsulated and lobulated mass with inhomogeneous appearance with cystic areas, calcifications and marked contrast enhancement. (Fig. 14). An intrathoracic thyroid mass developing from heterotopic thyroid tissue without any connection to the thyroid in the neck is extremely rare (Fig. 15a). The presence of ill-defined margins, invasion of adjacent structures and nearby lymph node enlargement suggests the diagnosis of thyroid cancer  (Fig. 15b).
Thymic hyperplasia can be divided into two distinct histological types [13, 14]. True thymic hyperplasia is defined as enlargement of the thymus, which generally retains its normal shape. This disease entity is observed when a patient is recovering from some recent stress (such as chemotherapy, corticosteroid therapy, irradiation or thermal burns). The phenomenon known as rebound hypeplasia is defined as a greater than 50% increase in thymic volume over baseline after such stress . Among patients who undergo chemotherapy, approximately 10–25% may develop rebound hyperplasia . Thymic lymphoid (follicular) hyperplasia of the thymus refers to the presence of an increased number of lymphoid follicles. It is commonly associated with autoimmune diseases, being seen in up to 65% of cases with myasthenia gravis , and it has been reported to occur in the early stages of human immunodeficiency virus infection. At CT it may appear normal (45%), enlarged (35%) (Fig. 16) or as a focal thymic mass (20%) .
It is important for radiologists to be able to distinguish thymic hyperplasia from neoplasm. Diffuse symmetric enlargement of the gland, a smooth contour and normal vessels are the key morphological features of hyperplasia, whereas neoplasm tends to manifest as a focal mass with nodular contour and necrotic or calcified foci. Detecting fat in the thymus is particularly relevant in these situations. According to Takahashi et al. , chemical-shift MRI can be useful in this situation. Thymic hyperplasia reveals a relative signal loss on opposed-phase chemical-shift MRI that it is different from no significant signal change between in-phase and opposed-phase chemical-shift MR images in patients with malignancy (Fig. 17).
Thymoma is the most common primary neoplasm of the anterior mediastinum but accounts for less than 1% of all adult malignancies [22, 23]. Thymomas typically occur in patients older than 40 years of age, being rare in children, and affecting men and women equally . Between 20% and 30% of patients with thymoma have pressure-induced symptoms . Myasthenia gravis associated with thymoma occurs most frequently in women. Between 30% and 50% of patients with a thymoma have myasthenia gravis, whereas 10–15% of patients with myasthenia gravis have a thymoma.
The updated histological classification elaborated by WHO in 2004 classified different types of thymomas (Table 1) on the basis of the morphology of the neoplastic epithelial cells together with the lymphocyte-epithelial cell ratio [23, 24]. In contrast to histological classification, the stage of thymoma has clinical implications and it is a useful tool for management decisions. The Masaoka-Koga staging system is the most commonly used and describes thymomas in terms of the local extension of the tumour [14, 23–26] (Table 2). The Masaoka staging system is one of the two factors, including completeness of surgical resection, that most strongly correlates with prognosis of thymomas . The role of imaging is to initially diagnose and properly stage thymoma, with emphasis on the detection of local invasion and distant spread of disease. Between 45 and 80% of thymomas are visible by chest radiography . On CT scans, thymomas usually appear as homogeneous solid masses with soft-tissue attenuation and well-demarcated borders, located anywhere from the thoracic inlet to the cardiophrenic angle. Thymomas may be oval, round or lobulated and when they are large, cystic or necrotic degeneration may be shown (Fig. 18). Calcification may be present in the capsule or throughout the mass. Certain findings, such as encasement of mediastinal structures, infiltration of fat planes, irregular interface between the mass and lung parenchyma, and direct signs of vascular involvement are highly suggestive of invasion (Fig. 19). Pleural dissemination (“drop metastases”) manifests as one or more pleural nodules or masses, and they are almost always ipsilateral to the tumour  (Fig. 20). Thymoma rarely presents with metastatic lymphadenopathy, metastatic pulmonary nodules or pleural effusion. At MRI, thymomas commonly appear as homogeneous or heterogeneous masses with low to intermediate signal intensity on T1-weighted images and with high signal intensity on T2-weighted images (Fig. 21). MRI can prove useful in identifying the nodular wall thickening detected in cystic thymomas, absent from congenital cysts .
Thymic carcinoma accounts for about 20% of thymic epithelial tumours with a mean age of 50 years . Typical appearance is a multilobulated and heterogeneous mass that may contain areas of calcification or haemorrhage. Distant metastasis are present at the initial diagnosis in 50–65% . Sadohara et al.  found that irregular contour, necrotic or cystic components, heterogeneous enhancement, lymphadenopathy and great vessel invasion strongly favoured thymic carcinoma.
Thymic carcinoids are rare, well-differentiated neuroendocrine tumours, which have a male predilection of 3:1 [13, 14]. They often present with endocrine disorder. Thymic carcinoid usually manifests as a large anterior mediastinal mass often with metastases.
Lymphoproliferative disorders. Primary mediastinal lymphoma usually occurs in the anterior mediastinum. Malignant lymphoma accounts for nearly 20% of all mediastinum neoplasms in adults and 50% in children . Lymphomas are the most common cause of masses in the paediatric mediastinum . Hodgkin lymphoma (Fig. 22) represents approximately 50–70% of mediastinal lymphomas, while non-Hodgkin lymphoma comprises 15–25% . Pleural and pericardial effusions are often common features in all types of lymphoma.
Hodgkin disease (HD) has a bimodal distribution of incidence peaking in young adulthood and again after the age of 50 years . Most patients experience constitutional symptoms. Four subtypes of HD are described: nodular sclerosis (by far the most common histological subtype) (Fig. 23), lymphocyte-rich, mixed cellularity and lymphocyte depleted HD [4, 5]. CR is abnormal in up to 76% of patients with HD, often showing enlargement of the prevascular and paratracheal nodes . Characteristic features on imaging are a homogeneous soft-tissue anterior mediastinal mass with mild to moderate contrast enhancement, irregular contours, surface lobulation, absence of vascular involvement, and high prevalence of associated mediastinal lymphadenopathy . Cystic and necrotic changes can be identified.
The two most common forms of mediastinal non-Hodgkin disease (NHD) include diffuse large B-cell lymphoma and T-cell lymphoblastic lymphoma. T-cell lymphoblastic lymphoma mainly occurs in children and adolescents. The most common CT appearance is a large mediastinal mass representing thymic and lymph node enlargement, which compresses the airway and cardiovascular structures (Fig. 24). Low attenuation areas reflecting necrosis are commonly seen. Primary mediastinal diffuse large B-cell lymphomas tend to occur in young to middle-aged adults with a mean age of 30 . It accounts for 7% of all cases of NHD and about 10% of all cases of high-grade NHD . The tumours appear as a large, smooth or lobulated, anterior mediastinal mass in nearly all patients. On CT the tumours show low attenuation areas, representing haemorrhage, necrosis or cystic degeneration in 50% of the cases and heterogeneous enhancement in about 40% of the cases  (Fig. 25). Primary mediastinal B-cell lymphoma recurs in the chest. Consequently, chest CT examination alone is sufficient for routine follow-up of these patients .
Germ cell tumours (GCTs) mainly arise in gonads and in the midline of the body as well, the mediastinum being the most common extragonadal site. GCTs account for 10–15% of anterior mediastinal masses in adults and 25% in children . Only 3% of them arise in the posterior mediastinum . Pathological classifications include teratomas and non-teratomatous germ cell tumours.
Teratoma is the most common mediastinal GCT . Mature teratomas are usually asymptomatic and represent 60–70% of all mediastinal GCTs . They are composed of well-differentiated benign tissues with predominant ectodermal element. If a teratoma contains fetal tissue or neuroendocrine tissue, it is defined as immature and malignant with a poor prognosis. On CT, teratoma most commonly appears as a well-defined unilocular or multilocular cystic lesion containing fluid, soft tissue and fat attenuation (Fig. 26). Calcifications may be focal, rim-like or, in rare cases, representative of teeth or bone. Common combinations of internal components of mature teratomas include soft tissue, fluid, fat and calcification in 39%; soft tissue, fluid and fat in 24%; and soft tissue and fluid in 15%. In 15% of the cases, mature teratomas appear as non-specific cystic lesions without fat or calcium . On MRI, teratomas typically demonstrate heterogeneous signal intensity, representing various internal elements. Fat-fluid levels within the lesion are virtually diagnostic of teratoma. Ruptured teratomas show an adjacent consolidation, atelectasis and pleural or pericardial effusion than do unruptured teratomas.
The non-teratomatous germ cell tumours (NTGCT) are rare and malignant tumours which usually occur in young males and most frequently affect the anterosuperior mediastinum . These tumours grow rapidly and develop large, bulky, ill-circumscribed masses with lobulated shape. Primary mediastinal seminomas comprise 25–50% of malignant mediastinal GCTs  and occur almost exclusively in males during the period from the second to fourth decades of life . At imaging, the tumours typically have homogenous appearance and show minimal contrast enhancement. Areas of degeneration due to haemorrhage and coagulation necrosis may be present (Fig. 27). Metastasis to lymph nodes and bone does occur. Non-seminomatous germ cell tumours include yolk sac tumours, endodermal sinus tumours, embryonal carcinomas, choriocarcinomas and mixed germ cell tumours, which present as large masses typically with marked heterogeneous attenuation. At diagnosis, 85% of patients are symptomatic . Invasion of adjacent structures and distant metastasis may occur. Pleural and pericardial effusions are common. Measuring AFP and ß-hCG levels is important when making the diagnosis (Fig. 28).
Neurogenic tumours represent approximately 20% of all adults and 35% of all paediatric mediastinal tumours and they are the most common cause of a posterior mediastinal mass . Seventy to eighty percent of neurogenic tumours are benign, and nearly half are asymptomatic . These tumours are generally grouped into:
Peripheral nerve tumours, which are the most common (70%) mediastinal neurogenic tumours and originate from spinal or proximal intercostal nerve; however, they rarely arise from the vagus, recurrent laryngeal and phrenic nerve  (Fig. 29). Schwannomas are the most common (50%) mediastinal neurogenic tumours and frequently affect patients from 20 to 30 years old . They are usually solitary and encapsulated masses, but multiple schwannomas may be associated with neurofibromatosis type 2. The tumour may grow through the adjacent intervertebral foramen and spinal canal to produce a “dumbbell” or “hourglass” configuration. Cystic changes and haemorrhage are more common in schwannomas than in neurofibromas. Neurofibromas are non-encapsulated soft tissue tumours and account for approximately 20% of mediastinal neurogenic tumours . A sudden increase in the size of a previously stable neurofibroma and the presence of neurological symptoms suggests malignant transformation to malignant peripheral nerve sheath tumour. These tumours are closely associated with neurofibromatosis and show more heterogeneous signal intensity and contrast enhancement on MRI.
Sympathetic ganglion tumours, which comprise 25% of mediastinal neurogenic tumours and arise from neuronal cells rather than from the nerve sheath . Ganglioneuromas are the most benign and differentiated of the autonomic ganglionic tumours. Radiographically, the tumours are well-marginated, occurring along the anterolateral aspect of the spine and spanning three to five vertebrae. The “whorled appearance” is due to curvilinear bands of low signal intensity that reflects collagenous fibrous tissue in the mass on T2-weighted images. Most ganglioneuromas show gradual and heterogeneous contrast enhancement. Ganglioneuroblastomas are the least common type of neurogenic tumour and show intermediate features in cellular maturity between neuroblastoma and ganglioneuroma. Neuroblastomas are highly aggressive and readily metastasising tumours of neuroectodermal origin with a median age at diagnosis of 22 months . They are heterogeneous and non-encapsulated lesions, often exhibiting haemorrhage, necrosis, calcification or cystic degeneration (Fig. 30).
Mediastinal paraganglia. Paraganglioma is a rare neuroendocrine tumour of chromaffin cell origin. One to two percent of extra-adrenal paragangliomas occur in the thorax . Aortopulmonary paragangliomas are usually asymptomatic, while aortosympathetic paragangliomas (along the sympathetic chain in the posterior mediastinum) occur in symptomatic patients related to the functional activity of the tumour. These masses commonly enhance brightly at enhanced CT (Fig. 31). A characteristic MRI finding of paragangliomas is the presence of multiple curvilinear and punctate signal voids, which reflect high velocity flow in the intratumoral vessels, described as “salt-and-pepper” appearance.
Clinical and radiological features of the most common mediastinal masses are detailed in Table 3.
Uncommon mediastinal masses
Parathyroid adenomas may be seen in ectopic locations, the mediastinum being the most commonly site. High-resolution ultrasonography (US) is recognised as a tool for detecting cervical parathyroid lesions. As it enlarges, an abnormal gland appears as a hypoechoic, and often anechoic, lesion, often posterior in location to the thyroid. As the gland enlarges, it can develop lobularity and foci of echogenicity. Colour Doppler assessment of parathyroid lesions is a useful integration of grey-scale US and may be helpful in featuring parathyroid lesions. The colour Doppler patterns termed “parenchymal” (pattern IV, internal flow) and “vascular pole” (pattern II, focal peripheral flow) are typical of parathyroid lesions . The different colour Doppler US patterns seem to be influenced by many factors as the location of the gland and the degree of vascularity. These tumours tend to be small and may contain calcifications at CT. Technetium-99 Sestamibi SPECT scans are more effective for their diagnosis (Fig. 32). Fibrosing mediastinitis is a dense fibrosis which progressively encases and eventually obliterates the lumen of the mediastinal vessels and airways (Fig. 33). Haematoma. High attenuation of haematomas can be observed on unenhanced CT scans during the first 72 h (Fig. 34). When the hematoma ages its attenuation decreases at CT in a centripetal fashion. Haemangiomas in the mediastinum are rare and the may be associated with Rendu-Osler syndrome. Sarcomas other than vascular or neural origin, including fibrosarcomas, osteosarcomas and chondrosarcomas, are also very uncommon. Extramedullary haematopoiesis in posterior mediastinum is another entity to take into account.
In assessment of mediastinal disease, cross-sectional imaging techniques allow excellent visualisation of the mediastinum. CT is generally the first-choice modality of diagnostic imaging. MRI plays an increasing role in this disease due to the existence of new available MR techniques on mediastinum imaging.
On each of CT and MR scanning, the size of tumour, contour, perimeter of capsule, septum, haemorrhage, necrotic or cystic component, homogeneity within tumour, presence of mediastinal lymphadenopathy, pleural effusion and great vessel invasion are assessed. In addition, presence of calcification are assessed on CT and signal intensities of the tumour are assessed on MRI.
Imaging plays an essential role in the diagnosis, staging and follow-up of mediastinal disease. Complete resection is the mainstay of treatment in many mediastinal tumours and the ability to accomplish a complete resection appears to be the most important prognostic factor. Currently, CT is the modality most commonly used for follow-up after treatment. The goal of follow-up is to detect recurrence as early as possible. CT findings may serve as predictors of tumour invasiveness and of postoperative recurrence or metastases.
In Table 4 we summarise some teaching points and imaging pitfalls for the diagnostic approach to mediastinal masses before and after treatment.
Tumours of the mediastinum represent a wide diversity of disease state. The location and composition of a mass is critical to narrowing the differential diagnosis. The clinical spectrum of mediastinal masses can range from being asymptomatic to producing compressive symptoms. Although many of these masses have similar imaging appearances, clinical history, anatomical position and certain details seen at CT and MRI imaging allow correct diagnosis in many cases.
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The authors gratefully acknowledge the contribution of technicians, surgeons and pathologists of the hospitals listed above, without whose efforts this work would not have been possible. The authors thank Isabel Coll for the English correction and assistance.
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