May 02, 2026
Amyloidosis and light chain deposition disease (LCDD) are monoclonal immunoglobulin deposition diseases (MIDD) caused by abnormal production of monoclonal immunoglobulin components, most commonly light chains, that deposit in tissues and lead to organ dysfunction. Although the kidneys and heart are most frequently affected, pulmonary involvement can occur and may be underrecognized.
Pulmonary disease may present as diffuse alveolar-septal amyloidosis, nodular pulmonary amyloidosis, tracheobronchial amyloidosis, pulmonary hypertension or pleural effusions. "In LCDD, similar light chain deposition can occur within lung parenchyma and pulmonary vasculature, producing respiratory symptoms and structural lung abnormalities," says Misbah Baqir, M.B.B.S., a pulmonologist and critical care specialist at Mayo Clinic in Rochester, Minnesota.
These conditions are clinically important because pulmonary manifestations often mimic more common diseases, including interstitial lung disease, malignancy or chronic airway disorders. Diagnosis therefore requires a high index of suspicion and tissue confirmation. Early recognition is essential, as pulmonary findings may be the first indication of systemic disease, particularly AL amyloidosis, for timely evaluation and treatment.
Study methodology and major findings
A review recently published in Clinics in Chest Medicine, summarizes current literature on pulmonary manifestations of amyloidosis and LCDD and draws largely from case series and observational studies due to the rarity of these disorders.
Diagnosis requires histopathologic confirmation typically through biopsy with Congo red staining, which demonstrates apple-green birefringence under polarized light. Mass spectrometry is used to identify the specific amyloid subtype. Additional evaluation may include serum and urine protein electrophoresis, lig, and bone marrow biopsy to detect plasma cell disorders. Imaging studies such as high-resolution CT (HRCT) help characterize pulmonary findings, while echocardiography or technetium-pyrophosphate scintigraphy assess cardiac involvement.
Pulmonary manifestations vary widely. Diffuse alveolar-septal amyloidosis, usually associated with systemic AL disease, involves amyloid deposition within alveolar septa and pulmonary vessels and may be clinically silent. Nodular pulmonary amyloidosis presents as solitary or multiple nodules that can mimic malignancy and are often associated with localized disease or lymphoproliferative disorders. Tracheobronchial amyloidosis involves amyloid deposition in airway walls, producing symptoms such as cough, dyspnea, wheezing, hemoptysis and recurrent infections.
Other thoracic manifestations include pulmonary hypertension and pleural effusions, particularly in patients with cardiac amyloidosis. Pulmonary light chain deposition disease (PLCDD) is extremely rare and typically presents as nodular or cystic lung disease, sometimes discovered incidentally on imaging.
Interpretation of results and notable limitations
Pulmonary amyloidosis demonstrates marked clinical heterogeneity, with presentations ranging from asymptomatic disease to airway obstruction or parenchymal abnormalities. Diffuse alveolar-septal disease is particularly difficult to diagnose during life because it is often silent, while localized nodular or airway disease may be detected through imaging or bronchoscopy.
"Radiological findings are frequently nonspecific and may resemble malignancy or interstitial lung disease, making biopsy essential for diagnosis," Dr. Baquir comments. "Prognosis varies by subtype, with localized nodular pulmonary amyloidosis often having a favorable course."
A major limitation is the rarity of these disorders, resulting in limited prospective data. Most available evidence derives from case reports or small retrospective series, leaving gaps in knowledge regarding optimal diagnostic strategies and long-term outcomes. Additionally, overlapping histopathologic features between amyloidosis and LCDD can complicate classification.
Relevance to current practice in pulmonary and critical care medicine
For clinicians in Pulmonary and Critical Care Medicine at Mayo Clinic, maintaining clinical suspicion is essential when evaluating patients with unexplained pulmonary nodules, cystic lung disease, airway obstruction or atypical interstitial lung abnormalities. HRCT imaging, bronchoscopy and tissue biopsy are key diagnostic tools.
"Management typically requires a multidisciplinary approach, involving pulmonologists, hematologists, pathologists, radiologists and oncologists," Dr. Baquir says. "Treatment focuses on reducing production of pathogenic immunoglobulin chains and managing organ dysfunction. Systemic disease may require chemotherapy, proteasome inhibitors or stem cell transplantation, while localized airway disease may require bronchoscopic or surgical intervention."
Key takeaways and how Mayo Clinic contributes
Pulmonary amyloidosis and LCDD are rare but clinically important conditions that frequently mimic other pulmonary diseases. Accurate diagnosis depends on tissue confirmation and amyloid typing, which are critical for distinguishing localized from systemic disease.
"Institutions such as Mayo Clinic play an important role through advanced diagnostic capabilities, multidisciplinary expertise and ongoing research," Dr. Baquir states. "Collaboration among pulmonary, hematology, pathology and radiology specialists enables accurate diagnosis, tailored treatment and improved outcomes for patients with these uncommon but significant disorders."
For more information
Baqir M, et al. Amyloid and light chain deposition disorders. Clinics in Chest Medicine. 2025;46:711.
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