Mediastinal tissue biopsy of a patient affected by idiopathic mediastinal fibrosis with elevated serum IgG4 levels. The pictures show fibrotic tissue with linfo-plasmacellular infiltration (a). IgG4 (b) and CD138 (c) immunohistochemical stainings demonstrate that a significant proportion of total plasma cells are IgG4+. (a) Hematoxylin and eosin; (b) IgG4 immunostaining; (c) CD138 immunostaining. Original magnification is × 10 in (a) and (b) and × 4 in (c)
This finding further suggests the possibility of common pathogenetic mechanisms in idiopathic and infective secondary forms of mediastinal fibrosis.
10.5 Clinical Characteristics
The clinical presentation and the severity of the disorder are determined by the compression of vital mediastinal structures, i.e., central airways, superior or inferior vena cava, pulmonary veins, and arteries. However, patients are often asymptomatic. When present, typical symptoms include dyspnea, cough, hemoptysis, and pleuritic chest pain . The occlusion of airways can lead to recurrent or persistent pneumonia with or without lung atelectasis distal to the occlusion . If the compression of the superior or inferior vena cava is significant, superior or, much less frequently, inferior vena cava syndromes can occur, with their typical signs . The compression of pulmonary veins and less frequently of pulmonary arteries can lead to secondary pulmonary hypertension and subsequent right heart failure [35, 36].
10.6 Laboratory Findings
Laboratory findings are usually nonspecific or absent. Elevation of ESR and/or of CRP can be observed. A case has been reported of idiopathic mediastinal fibrosis with high serum IgG4 level . However, in a recent series of 40 cases of idiopathic mediastinal fibrosis, none had high serum IgG4 level. The authors concluded that since mediastinal fibrosis is a focal process, the quantity of IgG4-producing plasma cells might not be sufficient to cause an increase in serum IgG4 levels .
Chest radiographs usually show nonspecific widening of the mediastinum (most frequently the middle mediastinum). Findings consistent with superior vena cava obstruction, compression of central airways, pulmonary arterial obstruction, or pulmonary venous obstruction can be seen if these structures are involved .
The typical manifestation on computed tomography (CT) scans is an infiltrative mass of soft-tissue attenuation obliterating normal mediastinal planes, invading or encasing adjacent structures. The middle mediastinal compartment is frequently involved, although involvement of the posterior mediastinum is not uncommon .
Several authors highlighted two different patterns on CT scans: a focal pattern, usually located in the hila or in the right paratracheal/subcarinal regions; and a diffuse pattern, which consists of a diffuse infiltration of multiple mediastinal compartments. The focal pattern is the most frequent and is probably associated with histoplasmosis, while the diffuse pattern is more frequently associated with the idiopathic form, a finding that is consistent with CT scan appearance of other disorders such as retroperitoneal fibrosis or Riedel thyroiditis [2, 29, 43] (Fig. 10.2).
Coronal (a), sagittal (b), and axial (c) views of contrast-enhanced CT scans of the chest showing mediastinal fibrosis from D4 to D12 (red arrows)
As already stated for chest radiographs, complications due to the compression of mediastinal structures by the mediastinal mass can be seen on CT scans. Contrast-enhanced CT scans are particularly useful if arterial or venous obstruction are present, with or without pulmonary infarcts .
Magnetic resonance (MR) imaging can help distinguish between mediastinal fibrosis and neoplastic forms, as the latter typically show increased signal intensity on T2-weighted images .
18FDG Positron emission tomography
The diagnosis of idiopathic mediastinal fibrosis is a diagnosis of exclusion. As patients are often asymptomatic, mediastinal masses can be incidental findings on CT scans or chest radiographs. Whether symptoms are present or not, neoplastic and infective forms must be carefully excluded if idiopathic mediastinal fibrosis is suspected. The association with other fibroinflammatory disorders makes the diagnosis more likely. Nonetheless, if feasible a biopsy should always be performed. As already noted, the histological features of mediastinal fibrosis are not unique to the idiopathic form. Thus, a final diagnosis can be made only by integrating clinical, histological, and imaging findings.
10.9 Overlap with Other Disorders
As already noted, cases of idiopathic mediastinal fibrosis associated with retroperitoneal fibrosis, Riedel thyroiditis, pseudotumor of the orbit, and sclerosing cholangitis have been reported since the 1960s [17–20, 24, 47]. Familial cases have also been reported [15, 23]. Such fibroinflammatory disorders are now thought to be part of the IgG4-RD spectrum and to share a common pathogenesis [22, 48]. However, it is still unclear which proportion of cases of idiopathic mediastinal fibrosis can actually be classified as being IgG4-related, because systematic histological studies are lacking and also because patients with idiopathic mediastinal fibrosis are not routinely screened for other conditions belonging to the spectrum of IgG4-RD. It seems clear, however, that IgG4-RD lesions and idiopathic mediastinal fibrosis share many histological features, such as a chronic inflammatory infiltrate rich in plasma cells, B cells, and CD4+ T cells, abundant and irregular fibrosis.
In addition, the frequently reported association with autoimmune disorders such as ANCA-associated vasculitides, Behçet disease, and others further suggests the systemic nature of the disease and the central role of an abnormal immune response in the pathogenesis of idiopathic mediastinal fibrosis [9–13].
10.10 Treatment and Prognosis
It has been reported that idiopathic mediastinal fibrosis, in contrast with neoplastic forms and similarly to prior histoplasmosis form, has a relatively benign course, even when left untreated. However, compression of vital mediastinal structures can lead to life-threatening complications. Once believed to be frequent, probably because only the most severe cases were reported in literature, these complications (airway obstruction with or without recurrent pulmonary infections, superior vena cava syndrome, secondary pulmonary hypertension and cor pulmonale, inferior vena cava syndrome, pulmonary infarcts, myocardial infarction) are usually best addressed with surgical procedures or nonsurgical procedural interventions .
10.11 Surgical Management of Complications
When the disease is refractory to immunosuppressive therapy, surgical procedures or nonsurgical interventions become mandatory. However, they are both associated with high complication and mortality rates.
Surgical procedures include: debulking procedures; superior vena cava bypass procedures such as positioning of spiral vein grafts, PTFE grafts, conduits between right ventricle to pulmonary artery; pulmonary resection for uncontrollable hemoptysis (lobectomies and pneumonectomies); and pulmonary vein reconstruction [1, 50].
Peikert T, Colby TV, Midthun DE, Pairolero PC, Edell ES, Schroeder DR et al (2011) Fibrosing mediastinitis. Medicine (Baltimore) 90(6):412–423CrossRef