Imaging features and differential diagnoses of non-neoplastic diffuse mediastinal diseases

Pneumomediastinum, defined as free gas located within the mediastinum, may dissect along fascial sheaths (Fig. 1) to create a cervical and thoracic subcutaneous emphysema [3]. Pneumorrachis, pneumoperitoneum, or rarely, retropneumoperitoneum, and even air within the esophageal wall that mimics an esophageal dissection (Fig. 2), may be observed [4].

The Macklin effect, or pulmonary interstitial emphysema, which is responsible for more than 95% of cases, corresponds to an alveolar rupture with air dissection along the interstitial sheaths toward the mediastinum (Fig. 1), eventually leading to a pneumomediastinum [5]. The Macklin effect, more frequent than esophageal or tracheobronchial disruptions, has been reported in 39% of cases of severe, blunt trauma pneumomediastinum. It has been associated with a significantly prolonged intensive care stay, reflecting severe trauma [3, 5]. Importantly, its identification does not rule out a tracheobronchial injury (Fig. 2), which must be excluded in cases of traumatic as well as post-procedure pneumomediastinum [4] (Fig. 3).

At least half of all esophageal perforations are estimated to be iatrogenic in nature. This can result from endoscopic or surgical procedures, as well as thermal injury during left atrial ablation. Typical imaging findings include pneumomediastinum, pleural effusion on the left side more commonly than on the right side, and mediastinal hematoma [6] with extravasation of swallowed water-soluble contrast.

Spontaneous rupture, known as Boerhaave’s syndrome, occurs when incomplete crico-pharyngeal relaxation during vomiting results in a sudden increase in intraluminal esophageal pressure (Fig. 4). Rupture is most common in the distal left posterior wall immediately above the diaphragm. It may be suspected on a chest X-ray in patients with esophageal rupture but is not specific to that condition. Esophageal rupture is characterized by a V-shaped air collection, with one limb of the V produced by mediastinal gas that outlines the left lower lateral mediastinal border, and the other limb produced by gas between the parietal pleura and medial left hemidiaphragm. Mortality is high without prompt thoracotomy [6].

Tracheobronchial lesions are rare, occurring in 1 to 3% of patients with blunt trauma and 2 to 9% of those who suffer penetrating cervical and/or thoracic injuries. The former preferentially causes lesions in the intra-thoracic trachea and main-stem bronchus, 80% of which are up to 2.5 cm from the carina, most commonly on the right side, and are considered less protected by the mediastinal structures. Uncommon causes include iatrogenic injuries, such as intubation-related trauma [7] (Fig. 3).

Other causes of pneumomediastinum include acute exacerbation of severe asthma, excessive coughing, diabetic ketoacidosis, physical exertion, the Valsalva maneuver, or inhalational drug abuse [5], as well as extra-thoracic causes, such as facial fracture. In young individuals, the absence of other etiological factors should raise the suspicion of free-base cocaine use [8]. Rare circumstances, such as a lightning strike or insufflation of the content of a dry chemical fire extinguisher, have also been reported.

Most cases of acute mediastinitis are encountered following cardiovascular or other thoracic surgical procedures. Risk factors for post-sternotomy mediastinitis may be categorized into patient-related, including age as well as co-morbidities, such as obesity, diabetes, history of smoking, COPD, and renal failure, and operative factors or environmental elements (operating room and medical devices) [9].

Other cau ses typically comprise either esophageal perforation or the contiguous spread of odontogenic or retropharyngeal infections (Fig. 5). Rarely, mediastinitis may result from a penetrating trauma or hematogenous spread of infection.

In a retrospective study that included 40 various causes of acute mediastinitis, the most common abnormal findings were represented by increased attenuation of fat and pleural effusion, followed by free gas bubbles in the mediastinum, localized mediastinal fluid collections, sternal dehiscence, mediastinal lymph nodes, pericardial effusion, lung infiltrates, and pleuro-mediastinal fistula [10]. There was a high sensitivity and specificity for CT after day 17 in post-operative patients, with a low diagnostic yield in the early post-operative period. The normal post-operative appearance of the mediastinum during the first 2–3 weeks after surgery may mimic mediastinitis (Fig. 6) and may not return to normal for as long as 2 months after surgery. This lack of specificity of CT during the first 2 weeks requires a careful correlation between clinical and radiological findings that require contrast-enhanced CT.

In any case, careful analysis of cartilage and bone is necessary to detect loco-regional involvement, such as a cartilaginous abscess or focal osteitis (Fig. 6).

Fatal aortic arch ruptures (Fig. 7) have been reported in the context of mediastinitis that originated from several conditions, including odontogenic infection, foreign body ingestion, endoscopic botulinum toxin injection, or after open heart surgery [11].

Fibrosing mediastinitis (FM), also known as sclerosing mediastinitis, is a condition related to an abnormal immunologic reaction that results in the proliferation of fibro-inflammatory tissue in the mediastinum and/or hila [12]. It leads to a variable constriction of systemic veins, pulmonary arteries and veins, the airways and/or the esophagus, with a morbidity related to location and extent of fibrosis. The pleura, pericardium, and coronary arteries may also be involved [12].

The most common form is the focal or granulomatous subtype of fibrosing mediastinitis, mainly due to histoplasmosis (less frequently tuberculosis), and other fungal or inflammatory conditions, such as sarcoidosis. This form usually manifests as a localized, calcified mass in the paratracheal or subcarinal regions of the mediastinum or in the pulmonary hila, commonly responsible for a superior vena cava syndrome. Diagnosis can be made based on imaging findings, preventing the need for tissue sampling.

The diffuse or non-granulomatous subtype accounts for about 10 to 20% of cases of fibrosing mediastinitis. It may be idiopathic or can originate in association with autoimmune disorders, methysergide exposure, or prior radiation exposure [12]. Fibrosing processes in other locations, such as retroperitoneal fibrosis, may also be encountered [12]. This subtype, which affects multiple mediastinal compartments and which is sometimes diagnosed after considerable delay, manifests as diffusely infiltrated soft tissue, rarely calcified, with heterogeneous enhancement after intravenous administration of contrast material. Each structure can be surrounded, encased, and/or occluded. It is noteworthy that a sequential occurrence is observed in this setting, with a primary involvement of the pulmonary veins, then the pulmonary arteries, and finally the airways. While extrinsic compression of the pulmonary arteries and/or veins is a major cause of pulmonary hypertension (Figs. 8 and 9), longstanding pulmonary venous occlusion may also lead to secondary pulmonary arterial hypertension and cor pulmonale. In addition, arterial and venous compression may lead to an imaging appearance of unilateral pulmonary edema (Fig. 10) [13], and hemoptysis may occur due to hypertrophy of the systemic arteries. With regard to airway involvement, the trachea and the main, lobar, and/or segmental bronchi may be involved and are characterized by volume loss, chronic post-obstructive pneumonitis, endoluminal mucus plugs, or bronchiectasis [12]. Although surgical biopsies are more appropriate, the role of percutaneous CT-guided core tissue biopsies should be emphasized.

Fibrosing mediastinitis has been reported as an unusual mediastinal manifestation of IgG4-related disease (Fig. 11) [14]. The diagnosis requires a comprehensive evaluation for other disease manifestations, including Riedel’s thyroiditis, retroperitoneal fibrosis, sclerosing cholangitis, or autoimmune pancreatitis [12], which may precede and/or suggest the diagnosis. Improvement with corticosteroid therapy has been described in this setting in contrast to numerous other forms of fibrosing mediastinitis.

In addition to IgG4 disease, some disorders, such as Erdheim-Chester disease, must be suspected in case of multisystemic involvement. This rare, non-inherited, non-Langerhans form of histiocytosis, commonly with a BRAF mutation, is characterized by xanthomatous infiltration of the involved tissues with foamy histiocytes surrounded by fibrosis, and appears with heterogeneous systemic manifestations. A common peri-aortic infiltration that extends to the pericardium, the right coronary sulci, and/or the myocardium of the right atrium with pleural involvement may point toward this rare entity. Furthermore, bone, renal, and retroperitoneal involvement (Fig. 12) [15] have been observed. Cardiac-gated CT is required to detect coronary involvement.

The radiological differential diagnosis of diffuse fibrosing mediastinitis is extensive (Fig. 14) [16] and includes lymphoma (Fig. 13) [11], primary lung cancer, metastases, Castleman disease, and uncommonly, atypical sarcoidosis or granulomatosis with polyangiitis. Benign disorders, such as amyloidosis or lymphangiomatosis, may also diffusely infiltrate into the mediastinum (Fig. 15) [17]. The latter affects the lymphatic channels from the mediastinum to the pleura, with an associated thickening of the pulmonary peribronchovascular bundles and interlobular septae, reflecting the lymphatic distribution. Infectious disorders, such as actinomycosis, aspergillosis, zygomycosis, coccidioidomycosis, nocardiosis, mycobacterial infection, or syphilis, should also be excluded.

In addition to CT and 18F-FDG PET/CT, diffusion and dynamic contrast-enhanced MRI sequences may be useful to ensure an exhaustive assessment of the disease, particularly its cardiovascular extent. Moreover, these sequences may point out the optimal areas to biopsy (Fig. 14) [18].

Due to the histological complexity of these various entities, cytological sampling with fine-needle aspirations should be avoided and surgical biopsy sampling is often required to ensure sufficient material for detailed histologic analysis, immunohistochemical staining, molecular analyses, and culturing [11], if needed (Fig. 15) [12].

In all cases, a systematic analysis of the pulmonary veins and arteries, as well as the tracheobronchial tree and esophagus, is advised when encountering any infiltrative soft tissue density within the mediastinum. This may help to suggest the diagnosis of chronic mediastinitis and, thus, avoid delayed recognition of this condition. Such an approach has to be combined with an overall analysis of the retroperitoneum, liver, thyroid, and pancreas.