Introduction

Fibrosing mediastinitis (FM), also known as mediastinal fibrosis or sclerosing mediastinitis, is a rare, non-cancerous condition where scar-like tissue grows aggressively in the mediastinum.¹ Over time, this scarring can tighten and spread into nearby structures like the heart, large blood vessels such as the aorta, and the tracheobronchial tree, which may lead to severe complications. There are two major pathological forms: focal FM, which accounts for almost 80% of the cases, and diffuse FM, which accounts for approximately 20% of the cases.^2,3

Focal FM occurs as localised areas of fibrous tissue growth within the mediastinum. The fibrotic tissue creates discrete masses or nodules. Whereas diffuse FM is characterised by predominant growth of the fibrous tissue and its penetration into large areas of the mediastinum. There may be diffuse infiltration, leading to wide engagement of the mediastinal structures.

The mediastinum contains the heart, trachea, major nerves, and vessels. It also forms a covered passage for structures that are present from the neck to the abdomen. The aftereffect of fibrosing mediastinitis may cause obstruction of the airway, vascular sequelae, and multiple pulmonary complications.

Etiology and pathophysiology

Mediastinal fibrosis may be idiopathic, familial, or associated with various disorders. It is most commonly associated with a previous histoplasmosis infection. Other causes include infection with fungi, such as Aspergillus, Cryptococcus, tuberculosis or sarcoidosis. Focal mediastinal fibrosis (also known as chronic fibrosing mediastinitis) is considered to be caused by remote infection, such as tuberculosis or histoplasmosis. The underlying mechanism has not been elucidated, but an aberrant inflammatory response to residual Histoplasma capsulatum antigens within mediastinal tissues has been postulated.⁴

Fibrosing mediastinitis is a condition of abnormal proliferation of fibrous tissue in the mediastinum, usually resulting from chronic inflammation or infection. This inflammatory process invites immune cells that produce cytokines and growth factors, which in turn activate fibroblasts, leading to the excessive accumulation of collagen. This finally leads to the formation of dense, fibrous tissue that gradually presses on and obstructs the surrounding structures in the mediastinum. Since these are vital structures, the progressive nature of the disease can result in dangerous complications and potentially be life-threatening if both lungs are affected.⁴

Pulmonary complications

Airway obstruction

Airway obstruction refers to the blockage of respiration in the airway, hindering the free flow of air. Bronchial compression secondary to mediastinal fibrosis is a condition whereby the mediastinum's fibrotic tissue causes narrowing or obstruction of the bronchi, large air passages connecting the trachea to the lungs. This may give rise to symptoms such as shortness of breath, cough, wheezing, or recurrent respiratory infections.

Vascular complications

Mediastinal fibrosis can result in compression of intrathoracic structures, including the pulmonary vasculature, leading to clinical symptoms and complications like pulmonary hypertension.⁵

Pulmonary hypertension is a serious condition where there is abnormally high pressure in the blood vessels between the lungs and the heart. Pulmonary hypertension makes the heart work harder than normal to pump blood into the lungs. This can damage the heart and cause symptoms such as shortness of breath, chest pain, and lightheadedness.

Other pulmonary manifestations

Patients with chronic pulmonary vein stenosis present with atypical dyspnea and fatigue, and its late form is characterised by asymmetric pulmonary edema, recurrent appearance of pleural effusion, chest pain, and hemoptysis.⁶ Pleural effusion refers to the abnormal accumulation of fluid within the pleural space, the thin cavity between the layers of pleura covering the lungs, whereas hemoptysis is the coughing up of blood from some part of the lungs.

Diagnostic evaluation

Symptoms

The symptoms of fibrosing mediastinitis can vary depending on the structures affected, but common symptoms include:

Respiratory symptoms

•   Cough
•   Shortness of breath (dyspnea)
•   Wheezing
•   Recurrent respiratory infections

Vascular symptoms

• Swelling of the face, neck, or upper extremities due to superior vena cava syndrome
• Cyanosis (bluish discoloration of the skin due to lack of oxygen)
• Varicose veins in the chest and neck

Cardiac symptoms

• Chest pain
• Palpitations

Esophageal symptoms

• Difficulty swallowing (dysphagia)

General symptoms

• Fatigue
• Unexplained weight loss
• Fever (in some cases)

Tests

Imaging studies

Computed tomography (CT) of the chest provides a detailed map of the soft tissue in the mediastinum and bronchial involvement. CT angiography is helpful to assess vascular involvement with more detail. The role of conventional chest X-rays is limited due to non-specific findings. Enlarged or calcified lymph nodes suggest exposure to Histoplasma capsulatum infection and may help in the differential diagnosis. Vascular involvement secondary to compression and obstruction of mediastinal structures is best identified by contrast angiography studies that clearly demonstrate abnormal narrowing of vessels.

Magnetic resonance imaging of the chest and positron emission tomography (PET) in the assessment and management of FM may provide additional information about disease location and activity but needs more study.⁷

Pulmonary function tests

Pulmonary function tests (PFTs) include different kinds of breathing tests that measure how well your lungs exchange air. 

Histological confirmation via biopsy

A biopsy may be performed to confirm the diagnosis of fibrosing mediastinitis and to rule out other potential causes of mediastinal masses or fibrosis, such as malignancy or infections.

Management and treatment

Medical management

As the exact pathogenesis for fibrosing mediastinitis is unknown, the treatment course lacks a standardised regimen. Although there is little evidence on successful medication therapy, most current strategies will use an immunosuppressant, corticosteroid, or antifungals as there are limited treatment options for these patients.⁸

Corticosteroids and immunosuppressive therapy

Used to reduce inflammation and manage autoimmune aspects, though effectiveness varies. Based on case reports, there are different medical options that have provided significant symptom relief in idiopathic FM, which include steroids, methotrexate, and rituximab to target B-cell proliferation in selected patients, especially if they have an underlying autoimmune disease. The combination of corticosteroids and methotrexate has been reported to provide the resolution of symptoms and improvement of haemodynamic parameters related to pulmonary hypertension.¹⁰

Antibiotic therapy

Administered if an underlying infection, like histoplasmosis, is identified. If fibrosing mediastinitis is caused by histoplasmosis, antifungal treatment with itraconazole or amphotericin B may be considered, especially in active infections. If tuberculosis is the underlying cause, standard antitubercular therapy (a combination of isoniazid, rifampicin, pyrazinamide, and ethambutol) should be administered.

Bronchoscopic interventions

Bronchoscopic interventions address airway obstruction by removing or bypassing blockages. Different techniques are used to restore airway patency, either by ablation, debulking, or dilation.⁸

Debulking

Debulking is done to remove excessive fibrotic tissue or granulation that compresses or obstructs the airway. It is typically performed using rigid bronchoscopy. Mechanical instruments or lasers may be used to excise or vaporise the obstructive tissue. It is usually done in cases where significant airway obstruction is not amenable to stenting or when stent placement is insufficient.

Ablation

Ablation is done to destroy unwanted tissue using thermal energy or other methods. There are various types of ablation procedures. Laser ablation, which uses laser energy to vaporise obstructive tissue, electrocautery, which employs electrical current to remove tissue and cryotherapy which uses extreme cold to ablate tissue, are less commonly used for FM. It is usually conducted to reduce tumour burden or obstructive lesions in the airway and when tissue needs to be removed with minimal damage to surrounding structures.

Dilatation

The purpose of dilatation is to widen narrowed airways or vessels affected by fibrotic encroachment. The procedure involves balloon bronchoplasty, where a balloon catheter is inserted into the narrowed area and inflated to stretch and widen the airway. This procedure is conducted when short-segment strictures or stenoses cause significant symptoms and where non-invasive methods are preferred or as a prelude to stenting.¹¹

Vascular stenting

Vascular stenting is primarily used to relieve the compression of major blood vessels caused by fibrosing mediastinitis. It helps restore adequate blood flow and alleviates symptoms associated with vascular obstruction.

Surgical management

Surgical management is considered when significant compression affects vital structures or when other treatments fail. It may involve resection of fibrotic tissue to alleviate pressure on organs and structures.

Supportive care

Supportive care is provided by oxygen therapy, which provides supplemental oxygen to improve breathing, and pulmonary rehabilitation, which helps patients enhance lung function and overall respiratory health.

Prognosis

The prognosis for patients with fibrosing mediastinitis (FM) varies based on factors such as the underlying cause, the extent of mediastinal involvement, and the severity of complications like pulmonary hypertension (PH). A study focusing on FM patients with associated PH reported survival rates of 88%, 73%, and 56% at 1, 3, and 5 years, respectively.⁹ However, the effectiveness of corticosteroid therapy in FM is not well-established. Some reports suggest potential benefits in certain cases while others indicate limited efficacy. Therefore, treatment plans should be individualised, considering the patient's specific condition and response to therapy.¹⁰

Summary 

Fibrosing mediastinitis (FM) is characterised by the excessive proliferation of fibrous tissue in the mediastinum. It appears in focal or diffuse forms and is often related to prior infections like histoplasmosis or tuberculosis. Pulmonary complications include airway obstruction and vascular issues such as pulmonary hypertension and embolism, alongside other manifestations like pleural effusion and haemoptysis. Diagnosis can be done through imaging and biopsy if needed. Although treatment lacks a standardised approach, medical management includes corticosteroids, antifungals, or immunosuppressants. Surgical options, such as bronchoscopic interventions and vascular stenting, are considered for severe cases. The prognosis varies, influenced by the underlying cause and severity of complications.