Description
Amyloidosis is a group of diseases characterised by extracellular deposition of insoluble, fibrillar proteins known as amyloid in various organs and tissues. Pulmonary amyloidosis refers to the accumulation of these amyloid proteins within the lung parenchyma. Although amyloidosis can affect many different organ systems, this article will focus primarily on pulmonary manifestations of the disease.
Pathogenesis
Amyloidosis results from a failure of the body’s protein quality control mechanisms, leading to an accumulation of amyloid, a misfolded, insoluble protein in one specific organ or systemically. Within the chest, cardiac involvement is the most commonly seen, with patients presenting with variable symptoms ranging from arrhythmias to cardiac failure. In the case of pulmonary amyloidosis, this protein accumulation typically occurs in the setting of multiple previous chest infections.
Epidemiology, Risk Factors & Associations
Pulmonary amyloidosis is relatively rare, with most cases occurring as a part of systemic amyloidosis (80-90%). The two primary forms of amyloidosis, AL (primary) and AA (secondary), can both affect the lungs. Nodular pulmonary amyloidosis is often associated with Sjögren’s syndrome and, less frequently, with rheumatoid arthritis.
Clinical Features
Patients with pulmonary amyloidosis may be asymptomatic or may present with non-specific symptoms such as cough, shortness of breath, and chest pain. Haemoptysis can occur but is relatively rare. Physical examination may be normal or may reveal crackles, wheezing, or signs of pulmonary hypertension.
Complications
Pulmonary amyloidosis can lead to several complications including pulmonary hypertension, restrictive lung disease, and respiratory failure. In rare cases, amyloidosis can also cause hemoptysis or pulmonary nodules leading to pneumothorax.
Subtypes
Pulmonary amyloidosis can present in various forms:
- Nodular pulmonary amyloidosis: presents as solitary or multiple nodules or masses.
- Diffuse alveolar-septal amyloidosis: a rare form, usually associated with systemic AL amyloidosis.
- Tracheobronchial amyloidosis: amyloid deposits primarily affecting the trachea and bronchi.
Pathological Features
Morphology
The amyloid deposits are typically eosinophilic, homogeneous, and acellular. They are often located around blood vessels or within alveolar septa.
Histopathology
Amorphous, eosinophilic material within the alveolar spaces and walls, which is positive with Congo red staining and exhibits apple-green birefringence under polarised light.
Biochemistry
Biochemical analysis of the amyloid deposits can determine the specific protein subtype, with AL (lambda or kappa light chains) and AA (serum amyloid A protein) being the most common.
Radiological Features
CT
- Nodular pulmonary amyloidosis: Solitary or multiple nodular or tree-in-bud opacities can be seen, which may calcify (approximately 20-30% of cases) or cavitate. These are usually seen in a peripheral location at sites of previous pneumonia1.
- Diffuse alveolar-septal amyloidosis: Interlobular septal thickening, ground-glass opacities, and pleural effusions are typical.
- Tracheobronchial amyloidosis: Within the tracheobronchial tree, mass-like lesions arising from the internal wall, often significantly compromising the airway lumen are seen. Thickening of the tracheal and bronchial walls also seen.
PET
PET scanning may show uptake in nodular pulmonary amyloidosis but is usually not the first line of imaging for this condition.
Grading and Staging
There is no specific grading or staging system for pulmonary amyloidosis. The severity of the disease is usually assessed based on the extent of lung involvement and the presence of systemic disease.
Differential Diagnosis
- Sarcoidosis: Characterised by non-caseating granulomas involving various organs, including lungs. Often presents with systemic symptoms and bilateral hilar lymphadenopathy.
- Silicosis: Occupational lung disease caused by inhalation of silica dust, presenting with nodular pulmonary fibrosis. History of exposure is critical in differentiation.
- Tuberculosis: May present with cavitation or upper lobe nodules and infiltrates. Diagnosis is confirmed with positive cultures or nucleic acid amplification tests.
- Lung Cancer: May present as a solitary pulmonary nodule. Diagnosis is typically confirmed with biopsy showing malignancy.
- Lymphangioleiomyomatosis (LAM): Rare disease that typically affects women and presents with thin-walled cysts scattered throughout the lungs.
- Pulmonary Langerhans Cell Histiocytosis (PLCH): Rare disease causing nodules and cysts, typically in young smokers. Histopathology will reveal characteristic Langerhans cells.
- Pulmonary metastases: Metastases from various primary cancers can present with multiple lung nodules, although these tend to be more irregular in shape and size.
- Pulmonary Rheumatoid Nodules: May be seen in patients with severe rheumatoid arthritis. Can present as multiple well-defined nodules on imaging.
- Granulomatosis with Polyangiitis: Multiple nodules or masses, often cavitated, and can mimic infectious or malignant processes.
Management
- A multidisciplinary approach involving pulmonologists, pathologists, and radiologists is needed.
- The treatment of pulmonary amyloidosis is primarily based on the management of systemic disease, with chemotherapy being the mainstay of treatment for AL amyloidosis.
- Localised forms can be managed with surgery or radiotherapy.
- Regular follow-ups are essential given the potential for disease progression and the development of systemic involvement.
- Lung transplantation might be considered for severe cases with respiratory failure.
References