ADOPTING ORPHAN DISEASES RARE INTERSTITIAL LUNG DISEASES

adoptingorphandiseaseskapak

PULMONARY AMYLOIDOSIS

Yonca Sekibağ1 Şermin Börekçi2

1Maltepe University, Faculty of Medicine, Department of Chest Diseases, İstanbul, Türkiye
2İstanbul University, Cerrahpaşa Faculty of Medicine, Department of Chest Diseases, İstanbul, Türkiye

Sekibag Y, Borekci S. Pulmonary Amyloidosis. In: Altinisik G, McCormack FX, editors. Adopting Orphan Diseases: Rare Interstitial Lung Diseases. 1st ed. Ankara: Türkiye Klinikleri; 2025. p.147-157.

ABSTRACT

Pulmonary amyloidosis is a rare and heterogeneous group of disorders characterized by the extracellular accumulation of misfolded and insoluble protein fibrils within the lung parenchyma and airways. While systemic amyloidosis and its pulmonary manifestations have been extensively discussed in the hematology literature, isolated pulmonary involvement remains exceedingly uncommon. In most instances, it has been described through case reports, small case series, or autopsy-based studies. From a clinical perspective, pulmonary amyloidosis is classified into three principal subtypes: tracheobronchial, nodular parenchymal, and diffuse alveolar-septal forms. Tracheobronchial amyloidosis is localized predominantly to the central airways and leads to progressive luminal narrowing, presenting with symptoms such as chronic cough, wheezing, recurrent respiratory infections, or hemoptysis. The nodular parenchymal type is often asymptomatic and is typically detected incidentally during thoracic imaging. It may appear as solitary or multiple nodules, occasionally demonstrating calcification, and can radiologically mimic primary or metastatic malignancies. The diffuse alveolar-septal subtype almost invariably reflects pulmonary involvement of systemic AL amyloidosis. Radiologically, this form closely resembles interstitial lung disease, with high-resolution computed tomography (HRCT) demonstrating ground-glass opacities, interlobular septal thickening, and a reduction in diffusing capacity as characteristic findings. Diagnostic evaluation requires an integrated approach combining clinical, radiologic, and histopathological modalities. HRCT represents the cornerstone of radiological assessment and diagnostic work-up. Definitive diagnosis, however, relies on histological demonstration of amyloid deposits using Congo red staining, which reveals the pathognomonic apple-green birefringence under polarized light. While immunohistochemistry may assist in fibril subtyping, laser microdissection coupled with mass spectrometry-based proteomic analysis is currently regarded as the gold standard. The differential diagnosis is broad, encompassing malignant neoplasms, granulomatous diseases, and a range of interstitial lung disorders, thereby underscoring the necessity of tissue confirmation in cases of clinical suspicion. Therapeutic strategies are closely related to the subtype. Localized tracheobronchial disease may be managed with bronchoscopic debulking, stent placement, or, in refractory cases, external beam radiotherapy. Nodular parenchymal amyloidosis generally requires no intervention unless progressive growth or symptomatic disease develops. In contrast, diffuse alveolar-septal involvement is almost invariably associated with systemic AL amyloidosis and necessitates hematology-directed regimens, including bortezomib-, daratumumab-, or lenalidomide-based protocols. Prognosis varies substantially: localized forms frequently pursue an indolent course, whereas pulmonary involvement in systemic AL amyloidosis is strongly associated with adverse outcomes. Future research priorities include the establishment of standardized diagnostic algorithms, the development of noninvasive biomarkers for earlier recognition, and the identification of novel therapeutic targets to improve long-term clinical outcomes in this rare but clinically important condition.

Keywords: Pulmonary amyloidosis; Tracheobronchial amyloidosis; Lung nodules; Systemic amyloidosis; Immunoglobulin light chains

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