Diagnosing Pulmonary Amyloidosis

Initial Clinical Suspicion

The American Thoracic Society suggests suspecting pulmonary amyloidosis in middle-aged to older adults (average diagnosis age ~55 years) with chronic cough, wheezing, or hemoptysis 3
The American College of Physicians recommends considering pulmonary amyloidosis in patients with unexplained dyspnea or respiratory symptoms and constitutional symptoms including weight loss and fatigue, particularly if systemic involvement is suspected 1

The American College of Chest Physicians recommends bronchoscopy with biopsy for tracheobronchial disease showing diffuse submucosal infiltration (nodular, tumor-like, or polypoid appearance) 3

The International Society of Amyloidosis recommends Congo red staining showing red deposits under normal light, and apple-green birefringence under polarized light, which is pathognomonic and the gold standard for diagnosis 1, 2
The College of American Pathologists suggests eosinophilic (pink) hyaline material on routine H&E staining is also a required finding 2

The American Society for Clinical Pathology recommends mass spectrometry as the gold standard (88% sensitivity, 96% specificity) to identify the protein subtype 2
The European Hematology Association suggests alternative methods include immunohistochemistry, immunofluorescence, or immunogold electron microscopy 1, 4

The American College of Cardiology recommends serum and urine immunofixation to detect monoclonal protein in systemic AL amyloidosis workup 1
The National Kidney Foundation suggests serum free light chain (FLC) assay with abnormal kappa/lambda ratio (reference 0.26-1.65 for normal renal function) 5
The European Society of Cardiology recommends cardiac biomarkers: NT-proBNP (>332 ng/L has >99% sensitivity for cardiac involvement) and troponin T for staging 1, 5
The American Heart Association suggests echocardiography or cardiac MRI if cardiac involvement is suspected 6
The National Institute of Diabetes and Digestive and Kidney Diseases recommends 24-hour urine protein and eGFR for renal assessment 6
The International Myeloma Society suggests considering fat aspirate or bone marrow biopsy with Congo red staining as accessible alternative sites 6, 1

The American Thoracic Society warns against relying on imaging alone and recommends tissue diagnosis with Congo red staining and polarized light microscopy as mandatory 2
The American Society of Hematology emphasizes the importance of always performing amyloid typing, as treatment differs fundamentally between AL and TTR amyloidosis 1, 4