From the Guidelines
The diagnostic approach for pulmonary amyloidosis should begin with clinical suspicion based on symptoms and imaging findings, followed by tissue confirmation through biopsy, with a focus on early diagnosis to prevent irreversible organ damage, as emphasized in the comprehensive review of AL amyloidosis 1. The diagnosis of pulmonary amyloidosis requires a combination of clinical evaluation, imaging studies, and tissue confirmation. Key steps in the diagnostic approach include:
- Clinical suspicion based on symptoms such as dyspnea, cough, and chest pain
- Imaging findings on chest X-ray or computed tomography (CT) scan
- Tissue confirmation through biopsy, with bronchoscopy with transbronchial lung biopsy being a common first approach, and surgical lung biopsy being necessary for definitive diagnosis in some cases
- Staining of the biopsy specimen with Congo red to identify the characteristic apple-green birefringence under polarized light
- Additional testing, including serum and urine protein electrophoresis, free light chain assay, and cardiac biomarkers to determine the type of amyloidosis and assess for systemic involvement, as recommended by the European Myeloma Network 1. Management of pulmonary amyloidosis depends on the type and extent of disease, with options including:
- Bronchoscopic interventions like laser ablation, mechanical debulking, or stent placement for localized tracheobronchial amyloidosis
- Chemotherapy regimens such as bortezomib, cyclophosphamide, and dexamethasone, or daratumumab-based regimens, sometimes followed by autologous stem cell transplantation in eligible patients for AL amyloidosis, as discussed in the comprehensive review of AL amyloidosis 1
- Tafamidis (20 mg daily) or patisiran for ATTR amyloidosis
- Supportive care, including bronchodilators, supplemental oxygen, pulmonary rehabilitation, and vaccination against respiratory pathogens.
From the Research
Diagnostic Approach
- The diagnosis of pulmonary amyloidosis can be made by transbronchial biopsy, provided the appropriate histologic stains are employed 2.
- Computed tomography (CT) of the chest, bronchoscopy, and biopsy are needed to establish the diagnosis of airway amyloidosis, and systemic amyloidosis should be ruled out 3.
- CT scan of the chest is typically the first step in suspecting pulmonary amyloidosis, and tissue biopsy with immunohistochemical staining is required for diagnosis 4.
- High-resolution CT shows reticular opacities, interlobular septal thickening, and small, well-defined nodules of 2 to 4-mm in diameter predominantly in the subpleural regions 5.
Management
- Treatment of amyloidosis requires a multidisciplinary approach 3.
- External beam radiotherapy is a common treatment modality for airway amyloidosis 3.
- Systemic treatment for pulmonary AL amyloidosis has evolved to include the combination of daratumumab, bortezomib, cyclophosphamide, and dexamethasone (dara-VCD) as first-line therapy, with the goal of quickly attaining complete hematologic response 4.
Clinical Presentation
- Shortness of breath and cough are the most common presenting symptoms of airway amyloidosis 3.
- Patients with localized amyloidosis tend to have a better prognosis than those with systemic amyloidosis 3.
- Clinical data and CT findings' frequencies differ significantly between patients with local pulmonary parenchymal amyloidosis and those with tracheobronchial amyloidosis 6.
Radiologic Features
- CT findings in pulmonary amyloidosis include nodules, plaques, or diffuse thickening of the airways with calcification, and postobstructive collapse in case of diffuse airway involvement 5.
- Parenchymal nodules have sharp and lobulated margins with peripheral or subpleural locations 5.
- Tracheobronchial amyloidosis leads to wall thickening of the bronchi and the trachea 6.