Pulmonary amyloidosis: clinicopathologic spectrum and diagnostic pitfalls in a 12-patient case series

Pulmonary amyloidosis is a rare, underrecognized manifestation of amyloid disease that may present as nodular, tracheobronchial, or diffuse alveolar-septal involvement and can mimic common pulmonary conditions. This study aimed to characterize the clinicopathologic features, diagnostic patterns, and management approaches of patients with pulmonary amyloidosis in a real-world setting.

We performed a retrospective review of patients with pathology-confirmed pulmonary amyloidosis diagnosed between January 2020 and December 2024 at a tertiary academic medical center in Detroit, Michigan. Data included demographics, presenting symptoms, imaging and histopathologic findings, amyloid typing, treatment, and outcomes.

Twelve patients were included (median age 76 years; 50% female; 42% Black); 67% were former smokers. Nodular pulmonary amyloidosis was the predominant pattern (92%), and half of cases were diagnosed incidentally (50%). Amyloid typing was completed in 25% [immunoglobulin light-chain amyloidosis (AL) 17%, transthyretin-related amyloidosis (ATTR) 8%]; typing was incomplete or not performed in the remainder due to ongoing evaluation, patient preference, loss to follow-up, or death. Management was heterogeneous, including systemic therapy (25%), surgical resection with surveillance (8%), and supportive/palliative care (8%); several patients were undergoing evaluation at last follow-up. At analysis, 75% were alive at the last known follow-up.

Pulmonary amyloidosis commonly presents as nodular disease and is frequently detected incidentally. Incomplete amyloid typing and variable management highlight diagnostic and care gaps. Systematic amyloid subtyping is essential to guide treatment.