Pulmonary Amyloidosis

Pulmonary amyloidosis is the deposition of insoluble amyloid protein fibrils in the lungs and tracheobronchial tree. Amyloid types relevant to pulmonary involvement include AL amyloidosis (immunoglobulin light chain, most common in pulmonary involvement, often systemic with cardiac/renal involvement), AA amyloidosis (serum amyloid A, secondary to chronic inflammation), ATTR amyloidosis (transthyretin, hereditary or wild-type/age-related), and localized amyloidoma (often AL, no systemic disease).

Three main pulmonary patterns exist: (1) Nodular pulmonary amyloidosis — single or multiple parenchymal nodules, often peripheral and lower lobe, mimicking malignancy on imaging, usually localized AL with excellent prognosis after biopsy/excision; (2) Diffuse alveolar-septal amyloidosis — diffuse interstitial deposits in alveolar septa and small vessel walls, presenting as restrictive lung disease with hypoxemia, almost always systemic AL with cardiac involvement and poor prognosis; (3) Tracheobronchial amyloidosis — localized submucosal deposits in airways causing wheeze, cough, hemoptysis, and obstruction, may need bronchoscopic resection or stent.

Diagnosis requires histologic confirmation by biopsy (apple-green birefringence under polarized light after Congo red staining is pathognomonic), followed by amyloid typing (immunohistochemistry, mass spectrometry — gold standard) to distinguish AL/AA/ATTR (critical for treatment). Workup for systemic disease: serum/urine immunofixation electrophoresis with free light chain assay (AL), echocardiogram with cardiac MRI, NT-proBNP/troponin, renal function, autonomic and peripheral neuropathy assessment. Treatment: AL — chemotherapy (bortezomib, daratumumab) ± autologous hematopoietic stem cell transplant; ATTR — stabilizers (tafamidis, diflunisal) and gene-silencing (patisiran, inotersen for hereditary); AA — treat underlying inflammation; localized — excision/observation; tracheobronchial — bronchoscopic resection, stent, external beam radiation.