Mediastinal mass (suspected)

• The mediastinum is the thoracic space between the visceral pleura of the lungs, from the thoracic inlet to the diaphragm. It is bordered anteriorly by the sternum and posteriorly by the vertebral column and contains the heart, great vessels, trachea, oesophagus, thymus gland, lymphatic tissue and nerves. Masses may arise from any of these structures 1-5

• Most patients with mediastinal masses are asymptomatic, although symptoms are more commonly experienced in patients with malignant masses (80-90% compared with 46% in patients with benign masses). 1, 3

• 83% of incidentally discovered masses are benign 3

• The  most frequent lesions encountered in the mediastinum in adults are primary thymic neoplasms, thyroid masses and lymphoma 3

• Imaging plays an essential role in the investigation of mediastinal masses. Some tumours of the mediastinum can be diagnosed based on imaging alone, and others may require biopsy and histopathological diagnosis 5

• Benign appearing tumours of the mediastinum are usually resected for cure - for example thymomas. Malignant appearing lesions usually require biopsy in the first instance and may be treated with chemotherapy and/or radiotherapy– for example lymphomas and germ cell tumours 6-10

• The Thymic Malignancy Interest Group have developed a CT-based division of the mediastinum into three compartments 11, 12

• Prevascular - includes all structures anterior to the pericardium and proximal ascending aorta

• Visceral - includes all major mediastinal visceral structures extending from anterior pericardium to a vertical line drawn 1 cm posterior to the anterior margin of the spine

• Paravertebral - includes all mediastinal structures posterior to this vertical line

• The Table below lists mediastinal lesions based on where they are most commonly found 2, 6, 13-16

• It is important to note that some diseases, however, do not occur exclusively in one compartment and can spread from one compartment to another. Compartments are not separated by fascial planes and communicate freely with one another 4, 10

• Masses are found to be malignant in 60% of anterior mediastinal masses, 30% of middle mediastinal masses and 15% of posterior mediastinal masses 1

• A plain chest radiograph represents the first imaging investigation in the majority of cases. Often a mediastinal mass will be an incidental finding on chest radiography performed for other reasons 2

• Deformation of  mediastinal contours and lines, and/or displacement of normal structures can be seen 3

• From chest radiography the location (anterior, middle, or posterior mediastinum) and basic characteristics of the mass can often be established. These findings, in conjunction with the clinical history and patient demographics, can provide a limited differential diagnosis 3

• CT with IV contrast is the most important imaging investigation in the evaluation of a mediastinal mass 3, 6, 17-19

• May be the only imaging investigation required before deciding on further management 3

• Generally, has a high accuracy in determining size, characteristics (solid or cystic), content (calcium, fat or necrotic tissue), location, and adjacent organ involvement of a mediastinal mass 1, 2

• Traditionally the mediastinum has been compartmentalised into anterior, middle, and posterior compartments based on lateral radiograph anatomy (Felson’s classification). More recently the International Thymic Malignancy Interest Group developed a CT-based division of the mediastinum into three compartments: 11

• Prevascular - includes all structures anterior to the pericardium and proximal ascending aorta

• Visceral - includes all major mediastinal visceral structures extending from anterior pericardium to a vertical line drawn 1 cm posterior to the anterior margin of the spine

• Paravertebral - includes all mediastinal structures posterior to this vertical line

• In conjunction with the patient’s demographics and symptoms, the location and characteristics of the mediastinal mass on CT may be diagnostic (50-60% of cases) or at least focus the differential diagnosis 2, 3, 7, 9

• Some diseases, however, do not occur exclusively in one compartment and can spread from one compartment to another. Compartments are not separated by fascial planes and communicate freely with one another 4, 10

• Masses are found to be malignant in 60% of anterior mediastinal masses, 30% of middle mediastinal masses and 15% of posterior mediastinal masses 1

• The table below lists mediastinal lesions based on where they are most commonly found: 2, 6, 13-16

• Where available, dual energy CT may be a helpful complementary tool to differentiate between benign and malignant mediastinal tumours when conventional contrast CT is inconclusive 20

• One study which analysed 127 anterior mediastinal masses found that CT was equal or superior to MRI in the diagnosis of lesions of various aetiologies apart from thymic cysts – correctly diagnosing the lesion in 61% compared with 56% of cases 5, 19, 21

• Although there is no consensus for its routine use, MRI is an important adjunctive imaging modality when a lesion is indeterminate or incompletely characterised by CT 22-24

• MRI is superior to CT in assessing chest wall invasion, neural foramen involvement or spinal canal invasion, and cardiac/vascular invasion. It is therefore recommended for all posterior mediastinal masses 1, 4, 10, 25

• MRI is superior to CT to distinguish cystic from solid masses, discern cystic/necrotic components within solid masses, and discern thymic hyperplasia from thymic tumours 21-23, 26-30

• MRI is also useful in patients with contraindications to contrast-enhanced CT 5

• Some studies have investigated the ability of MRI to distinguish benign from malignant mediastinal tumours and lymph nodes. Although there is no firm consensus for its routine use, these studies have all shown that MRI can differentiate between benign and malignant lesions in the majority of cases. This may be helpful in those patients who are not fit for more invasive biopsy techniques 25, 31-34

• MRI can aid diagnosis of indeterminate mediastinal lesions on CXR and CT 35

• The MRI techniques and imaging findings in non-vascular thoracic MRI have been reviewed in recent Canadian guidelines 36

• The MRI appearances of anterior compartment lesions have been reviewed by Nakazono 37

• Although there is no current consensus recommending its routine use, a number of small studies have found that PET/CT can be useful to distinguish between benign and malignant neoplasms in the anterior mediastinum. This may be particularly useful in patients who are in a poor physical condition for obtaining a pathological diagnosis and when the diagnosis remains uncertain after other imaging modalities have been performed 5, 9, 29, 38-42

• One retrospective study of 94 patients found a significantly higher uptake of FDG in thymic cancer compared with thymoma 9

• A separate multicentre retrospective study with 134 patients found that PET/CT had a sensitivity and specificity of 83% and 58% to correctly classify an anterior mediastinal mass as malignant. The positive and negative predictive values were 90% and 42% respectively. The authors of this study concluded that PET/CT was therefore moderately useful to rule out the diagnosis of malignancy when the test result was negative, but unable to rule in the diagnosis of malignancy when the result was positive 38

• PET/CT is important for tumour staging and for monitoring treatment response in lymphoma 2, 43

• When diagnosis remains uncertain, fine needle aspiration or core biopsy is usually necessary to guide subsequent surgical and/or medical treatment 44, 45

• Access to the mediastinum can pose significant technical challenges. There are a number of modalities which can be used to obtain a pathological diagnosis, each with its advantages and limitations 45-47

Ultrasound or CT-guided percutaneous biopsy

• Particularly useful for anterior mediastinal masses 1

• Minimally invasive and cost-effective, can be performed under local anaesthesia or with conscious sedation 45, 48

• Diagnostic success rates for ultrasound guided percutaneous biopsy in anterior mediastinal lesions range from 71 to 100% 48. Use of contrast enhanced ultrasound has been trialled and is thought to increase diagnostic accuracy of biopsies - tumour tissue and necrotic tissue are better identified based on microvascularity and blood flow which improves one’s ability to obtain adequate and representative specimens 48

• Overall CT-guided mediastinal lesion biopsy has a diagnostic yield sensitivity of 77-97.4% 8, 45, 49-51

• A recent systematic review/meta-analysis reported the pooled diagnostic yield and accuracy of core needle biopsy of mediastinal masses to be 92% and 94%, respectively.52

• The same study reported a total complication rate of 13% and major complication rate of 2%. 52

• The authors recommend 20G core biopsies to improve diagnostic outcomes and decrease complication rates.52

Endobronchial ultrasound-guided transbronchial biopsy

• A minimally invasive, relatively low risk technique for diagnosis of lymphadenopathies and/or mediastinal masses 46, 47, 53

• Recommended for indeterminate paratracheal lesions 50

• Has a reported diagnostic yield sensitivity between 84-96% 46

• Has the capability to access lymph nodes traditionally sampled by mediastinoscopy including the paratracheal, subcarinal, hilar and parenchymal lymph node stations 53

• Although EBUS-guided aspiration biopsy has moderately good sensitivity in the diagnosis of metastatic disease in the context of Non-Small Cell Lung Cancer 54, it is somewhat less sensitive for lymphoproliferative disease 55. However, specificity is high in both contexts.

• EBUS is considered a first line examination for invasive mediastinal evaluation in Non-Small Cell Lung Cancer (NSCLC)56.

• EBUS- guided transbronchial needle aspiration is highly sensitive and specific for mediastinal staging in NSCCL 57, 58 and small cell carcinoma of the lung 56 is effective in the diagnosis of mediastinal masses of unknown aetiology 47.

• EBUS-guided intranodal forceps and cryobiopsy may provide more optimal specimens for patients with benign disease such as sarcoidosis and in those with lymphoproliferative disease 56.

Endoscopic ultrasound guided biopsy

• A minimally invasive, relatively low risk technique for diagnosis of lymphadenopathies and/or mediastinal masses 59, 60

• Recommended for indeterminate paraoesophageal lesions 50, 61

• Sensitivity and specificity reported to be 80-93% and 100% respectively 61, 62

• Endoscopic ultrasound allows better access to the posterior/inferior mediastinum, including to sub-carinal and paraoesophageal lymph nodes 62, 63

Surgical mediastinoscopy/mediastinotomy and video-assisted thoracoscopic surgery

• Mediastinoscopy is a commonly used approach requiring general anaesthesia. An incision is made just above the manubrium and the scope passed along the pretracheal plane into the mediastinum.1 There is a reported 2.5% risk of pneumothorax and haemorrhage 61(61)

• Mediastinotomy is typically performed for anterior mediastinal masses or masses within the aortopulmonary window. A small transverse parasternal incision is made to give excellent exposure. It has a high diagnostic yield but it is an invasive procedure requiring general anaesthesia 1

• Video-assisted thoracoscopic surgery (VATS) allows excellent exposure of all compartments of the mediastinum for diagnostic biopsy or therapeutic excision and can accurately determine local invasion or intrapleural metastatic spread. Procedures which were previously performed using an open technique can now be performed via VATS including thymectomy, duplication cyst excision, pericardial cyst excision and posterior mediastinal mass resection 1

• Accurate in the diagnosis of mediastinal cysts and can facilitate diagnostic/therapeutic aspiration 10

• Endoscopic ultrasound can be used to differentiate between oesophageal intramural or extramural masses and delineate the relation of the lesion to surrounding structures 1

• Concurrent FNA can be performed for tissue diagnosis 63

• For oesophageal tumours, endoscopy with endoscopic ultrasound provides the most accurate imaging modality to assess depth of tumour infiltration in the wall 64

• To assess the location and extent of a central tumour when it is abutting the trachea or central bronchi as well as an accurate assessment of mediastinal lymph nodes 47, 53

• Endobronchial ultrasound can help to establish the degree of tracheal invasion 1

• It has capability to access lymph nodes traditionally sampled by mediastinoscopy including paratracheal, subcarinal, hilar and parenchymal lymph node stations 53

• Aortic dissection and associated vascular abnormalities can be visualised. True and false lumens, intimal flap, aortic regurgitation and coronary arteries can be visualised to help in operative planning 1

• CT angiogram is the most commonly used investigation to evaluate the aorta 65, 66

• MR angiography is particularly useful in imaging of younger patients with aortic pathology 65

• Both transthoracic and transoesophageal echocardiography have been used to assess masses within the mediastinum, and are particularly useful in assessing pericardial disease or when there is suspected invasion by a mass into the pericardium or heart 67, 68

• Transoesophageal echocardiography is more invasive but can provide additional details (mass size, composition, associated lymph nodes and the anatomic relation of the mass to other structures) which can be used in conjunction with cross-sectional imaging in pre-operative planning

• It can also assess haemodynamic consequences of compression, possible obstruction of the great vessels and involvement of the heart cavities 68

• Assesses the relationship of an oesophageal cyst to the oesophagus proper and determines whether there is a communication with the lumen 1

• Can also assess for extrinsic compression of the oesophagus from a mediastinal mass or stricturing from an oesophageal mass

• Thymic lesions range from the benign (thymic remnant, thymic hyperplasia and thymic cysts) to localised thymomas to more aggressive malignancy (thymic carcinoma, lymphoma and germ cell tumours)69.

• The classification of thymic epithelial, germ cell, and mesenchymal tumours has been recently (2021) updated by WHO 70.

• Non-epithelial lesions of the thymus include thymic lymphomas, thymic carcinoids, thymic germ cell tumors, and thymic lipomas 71.

• A diagnostic algorithm for suspected thymic lesions  (and their imaging characteristics) has been recently proposed by the BTOG Thymic Malignancies Special Interest Group 69 and is summarised below, based on initial CT findings.

• Thymic hyperplasia is often seen in the context of an acute illness, cancer treatment or a connective tissue disease.

• If there is doubt regarding the diagnosis of thymic hyperplasia, contrast-enhanced MRI and chemical shift MRI are advised

• If thymic cyst is suspected, contrast-enhanced MRI is recommended.

• If there are atypical features present within the cyst on MRI, further management including discussion at a multidisciplinary meeting and possible minimally invasive thymectomy may be required

• Suspected early stage/localised thymoma: minimally invasive thymectomy if appropriate after discussion multidisciplinary meeting. An alternative may be surveillance with portal venous phase post-contrast CT.

• Suspected more aggressive/higher stage malignancy: PET-CT and biopsy

• The diagnosis can often be made on the clinical picture, the patient’s demographics and the CT appearance.

• The imaging characteristics of the various pathological entities have been recently reviewed by Taka et al 72 and by Gentili et al 71.

• The MRI appearances of anterior compartment lesions have been reviewed by Nakazono 37

• The imaging modalities (CT, MRI, PET-CT) of use in the various mediastinal compartments and their related pathologies have been reviewed in recent articles 35, 36, 69, 71-76