CONTENTS
- Amyloidosis basics
- Interstitial lung disease
- Tracheobronchial amyloidosis
- Parenchymal nodular amyloidomas
- Other pulmonary manifestations
- Amyloid pleural effusion ➡️
- Questions & discussion
abbreviations used in the pulmonary section: 8
- ABPA: Allergic bronchopulmonary aspergillosis 📖
- AE-ILD: Acute exacerbation of ILD 📖
- AEP: Acute eosinophilic pneumonia 📖
- AFB: Acid-fast bacilli
- AIP: Acute interstitial pneumonia (Hamman-Rich syndrome) 📖
- ANA: Antinuclear antibody 📖
- ANCA: Antineutrophil cytoplasmic antibodies 📖
- ARDS: Acute respiratory distress syndrome 📖
- ASS: Antisynthetase syndrome 📖
- BAL: Bronchoalveolar lavage 📖
- BiPAP: Bilevel positive airway pressure 📖
- CEP: Chronic eosinophilic pneumonia 📖
- CF: Cystic fibrosis 📖
- COP: Cryptogenic organizing pneumonia 📖
- CPAP: Continuous positive airway pressure 📖
- CPFE: Combined pulmonary fibrosis and emphysema 📖
- CTD-ILD: Connective tissue disease associated interstitial lung disease 📖
- CTEPH: Chronic thromboembolic pulmonary hypertension 📖
- DAD: Diffuse alveolar damage 📖
- DAH: Diffuse alveolar hemorrhage 📖
- DIP: Desquamative interstitial pneumonia 📖
- DLCO: Diffusing capacity for carbon monoxide 📖
- DRESS: Drug reaction with eosinophilia and systemic symptoms 📖
- EGPA: Eosinophilic granulomatosis with polyangiitis 📖
- FEV1: Forced expiratory volume in 1 second 📖
- FVC: Forced vital capacity 📖
- GGO: Ground-glass opacity 📖
- GLILD: Granulomatous and lymphocytic interstitial lung disease 📖
- HFNC: High flow nasal cannula 📖
- HP: Hypersensitivity pneumonitis 📖
- IPAF: Interstitial pneumonia with autoimmune features 📖
- IPF: Idiopathic pulmonary fibrosis 📖
- IVIG: Intravenous immunoglobulin 📖
- LAM: Lymphangioleiomyomatosis 📖
- LIP: Lymphocytic interstitial pneumonia 📖
- MAC: Mycobacterium avium complex 📖
- MCTD: Mixed connective tissue disease 📖
- NIV: Noninvasive ventilation (including CPAP or BiPAP) 📖
- NSIP: Nonspecific interstitial pneumonia 📖
- NTM: Non-tuberculous mycobacteria 📖
- OHS: Obesity hypoventilation syndrome 📖
- OP: Organizing pneumonia 📖
- OSA: Obstructive sleep apnea 📖
- PAP: Pulmonary alveolar proteinosis 📖
- PE: Pulmonary embolism 📖
- PFT: Pulmonary function test 📖
- PLCH: Pulmonary Langerhans cell histiocytosis 📖
- PPFE: Pleuroparenchymal fibroelastosis 📖
- PPF: Progressive pulmonary fibrosis 📖
- PVOD/PCH Pulmonary veno-occlusive disease/pulmonary capillary hemangiomatosis 📖
- RB-ILD: Respiratory bronchiolitis-associated interstitial lung disease 📖
- RP-ILD: Rapidly progressive interstitial lung disease 📖
- TNF: Tumor necrosis factor
- UIP: Usual interstitial pneumonia 📖
amyloidosis basics
- Amyloidosis is a disorder that involves the deposition of protein conglomerates in the extracellular tissue.
- Different types of amyloidosis result from the deposition of different types of protein. A common type is AL amyloidosis, which results from plasma cells' overproduction of light chain proteins.
systemic vs. localized AL amyloidosis
- Systemic AL amyloidosis reflects an underlying hematologic malignancy. Other organ systems are involved (e.g., infiltrative cardiomyopathy, nephrotic syndrome, renal failure, and autonomic neuropathy). Treatment involves chemotherapy directed towards the underlying malignancy. Prognosis is often poor.
- Localized AL amyloidosis may result from a localized overgrowth of plasma cells producing light chains. The prognosis is much better. Treatment often focuses on the management of the focal amyloid disorder. There usually is a localized lymphoproliferative process (e.g., MALT lymphoma), even if the process is subtle. (Fishman 2023)
basics
- This is nearly always associated with systemic disease (usually AL-type amyloidosis, but it may also occur with AA-type amyloidosis).
- This is extremely rare.
clinical presentation
- Progressive dyspnea may occur.
- The overall clinical picture is usually dominated by the involvement of other organs (e.g., cardiac amyloidosis).
radiology: several abnormalities may occur
- Interlobular septal thickening (especially in the bases).
- Multiple subpleural micronodules.
- Patchy ground-glass opacities.
- Honeycombing and traction bronchiectasis.
- Mediastinal and hilar lymphadenopathy (this is rare in localized amyloidosis but occurs in ~75% of patients with AL-type systemic amyloidosis). (Walker 2019)
- Extensive calcification may occur.
treatment
- Treatment generally focuses on the management of the underlying systemic amyloidosis.
- Patients have a poor prognosis but usually don't die from respiratory failure.
basics
- Tracheobronchial amyloidosis is usually a localized form of light-chain amyloidosis. It's not associated with systemic amyloidosis, nor with lung parenchymal amyloidosis. (Murray 2022)
epidemiology
- This is the most common form of localized pulmonary amyloidosis (although it remains rare overall, accounting for only 1% of all amyloidosis).
- Peak age of onset is 50-60 years old. (Murray 2022)
- There is a 2:1 male predominance. (35256089)
clinical presentation
- Patients are usually asymptomatic.
- However, symptoms may include:
- Dyspnea, wheezing, and/or stridor.
- Cough, sometimes with hemoptysis.
- Bronchus involvement may cause atelectasis or recurrent pneumonia.
- Laryngeal or vocal cord involvement can cause hoarseness, stridor, choking, dysphagia, or even aspiration. (28483133)
- Progression may occur over time.
radiology
- Anatomic distribution is variable:
- Any portion of the tracheobronchial tree can be involved. (25786151)
- Most often, the trachea and central bronchi are involved (typically the entire trachea, including the posterior membrane). (Shepard 2019)
- Radiological findings:
- Multifocal nodular protrusions usually occur, but smooth tracheal thickening may also be seen. Focal deposits of amyloid enhance following IV contrast. (Shepard 2019)
- The posterior tracheal wall is often involved.
- Calcification can occur.
- Tracheobronchomalacia may be seen. (25786151)
- Obstruction can cause bronchiectasis, atelectasis, consolidation, and/or hyperinflation. (Rosado-de-Christenson 2022)
bronchoscopy
- Small erythematous or yellow nodules or masses are classically seen, which often involve the posterior tracheal wall. (35256089) However, diffuse submucosal infiltration may also be the only manifestation. (ERS handbook 3rd ed.)
- The differential diagnosis of endobronchial nodularity is discussed here: 📖
- Endobronchial biopsy may reveal pathological evidence of amyloid (positive staining with Congo red, and yellow-green birefringence under polarized light). However, amyloidosis tends to bleed, so this does carry a risk of hemorrhage. (Fishman 2023; ERS handbook 3rd ed.)
treatment
- Interventional pulmonology therapies may be helpful to maintain patency of the airway (e.g., argon plasma coagulation, resection, freezing, balloon dilation). Localized amyloid masses may be amenable to excision.
- External beam radiation therapy slows disease progression by suppressing the local plasma cell clone that is causing amyloid development. (ERS handbook 3rd ed.) Radiotherapy is the front-line treatment for patients with extensive or distal disease that can't be managed interventionally. (Murray 2022)
- If tracheobronchomalacia is present, this may be treated with usual approaches. 📖 (25786151)
- Prognosis is guarded, with 45% survival at 6 years. (ERS handbook 3rd ed.) Proximal involvement may carry a worse prognosis. (Rosado-de-Christenson 2022)
basics
- This usually results from localized AL amyloid (without systemic involvement).
- This is usually an asymptomatic finding that is incidentally detected on chest imaging (which may provoke concern regarding the possibility of malignancy).
- Patients usually present with nodules, but diffuse cystic lung disease can also occur. Cyst formation may occur due to a ball-valve effect resulting from amyloid deposition around bronchiolar walls.
epidemiology
- Typically presents around ages ~50-70 years old. (33965158)
- May be associated with an underlying lymphoproliferative disorder and/or Sjogren syndrome. (33965158)
clinical manifestations
- Patients are often asymptomatic.
- However, symptoms can include dyspnea, cough, hemoptysis, wheezing, or recurrent pneumonia. (34366045)
radiology
- Nodules:
- Solitary or multiple pulmonary nodules may occur.
- Nodules are usually peripheral, more often in the lower lobes.
- Size is typically 1-3 cm, but ranges from 0.4-15 cm.
- Edges are usually sharp, with a lobulated contour. (34366045)
- Calcification is seen on a CT scan in a third of the nodules.
- Cavitation may occur. (30732703)
- Cysts:
- Coexisting amyloid pulmonary nodules are usually present. (Fishman 2023)
- Basic cyst characteristics:
- Size is variable.
- There are usually numerous, thin-walled cysts (>10). (34366045)
- Cysts may be lobulated, with internal structures and septations.
- Distribution may be diffuse, or lower-lobe predominant. (Fishman 2023)
- This may look very similar to cysts caused by light chain deposition disease. Differentiating features between the two disorders:
- (1) Multiorgan involvement may favor light chain deposition disease. (33965158)
- (2) Coexistence of nodules favors amyloidosis.


differential diagnosis
- (1) Amyloid deposition may rarely occur within a pulmonary neoplasm. Thus, detecting amyloid on a biopsy doesn't necessarily guarantee the absence of malignancy.
- (2) Rarely, systemic amyloidosis may present with pulmonary nodular amyloidosis. Thus, evaluation is needed to exclude systemic amyloidosis (e.g., investigation of renal function, urine protein, serum and urine protein electrophoresis, liver function, and echocardiography). (Fishman 2023, 30732703)
treatment and prognosis
- The prognosis is generally excellent (assuming that evaluation is negative for systemic amyloidosis). Nodules may show slow growth over years. Thus, initially observing lesions is often reasonable. (30732703)
- Treatment may depend on the underlying etiology:
- (a) Some amyloidomas are surrounded by localized low-grade MALT lymphoma. Treatment of such lesions may also involve the treatment of the associated MALT lymphoma.
- (b) Amyloidomas associated with Sjogren syndrome may respond to treatment with steroids and immunosuppression. (30732703)
laryngeal infiltration
- This may cause symptoms including hoarseness, stridor, exertional dyspnea, and occasionally hemoptysis.
- Laryngeal involvement usually reflects localized amyloidosis.
- Treatment may involve laser excision or external beam radiotherapy. (ERS handbook 3rd ed.)
mediastinal and hilar lymphadenopathy
- Lymphadenopathy may be massive, mimicking sarcoidosis. Progression is slow, often with calcification. Lymphadenopathy may occasionally cause superior vena cava syndrome or tracheal compression. (ERS handbook 3rd ed.)
- Lymphadenopathy usually results from a systemic etiology of amyloidosis (e.g., low-grade B-cell lymphoma).
other pulmonary manifestations
- Sleep apnea due to macroglossia (as a result of amyloid infiltration of the tongue).
- Pulmonary hypertension may occur due to vascular wall involvement.
- Diaphragm involvement may cause ventilatory failure.
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References
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- 25786151 Mohning MP, Janssen WJ, Groshong SD, Canham EM. Anchored to asthma. Ann Am Thorac Soc. 2015 Mar;12(3):448-50. doi: 10.1513/AnnalsATS.201410-456CC [PubMed]
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- 28483133 Scelsi CL, Khasnavis T, Patel NG, Keshavamurthy JH, Davis WB. Persistent Lobar Atelectasis in a Patient With Chronic Hoarseness. Chest. 2017 May;151(5):e107-e113. doi: 10.1016/j.chest.2017.01.029 [PubMed]
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- 33965158 Chopra M, Patel B, Puthalapattu S, Nguyen T. An Unusual Case of Chronic Hemoptysis. Chest. 2021 May;159(5):e331-e335. doi: 10.1016/j.chest.2020.12.031 [PubMed]
- 34366045 Avdeev SN, Merzhoeva ZM, Samsonova MV, Makarova MA, Cherniaev AL. A 61-Year-Old Woman With Insidious Dyspnea and Diffuse Cystic Lung Disease. Chest. 2021 Aug;160(2):e199-e203. doi: 10.1016/j.chest.2021.02.044 [PubMed]
- 35256089 Hoan L, Hang LM, Linh LT, My TT, Minh TN, Manh PT, Cuong NN. A 32-Year-Old Man With Dyspnea and Stridor. Chest. 2022 Mar;161(3):e153-e157. doi: 10.1016/j.chest.2021.09.028 [PubMed]
- 35680318 Kumar A, Epps SM, Jeffus S, Caceres JD, Meena NK, Killam J, Venkata AN. A 34-Year-Old Man With Lightheadedness and Dyspnea. Chest. 2022 Jun;161(6):e371-e376. doi: 10.1016/j.chest.2022.01.005 [PubMed]
Books:
- Shah, P. L., Herth, F. J., Lee, G., & Criner, G. J. (2018). Essentials of Clinical pulmonology. In CRC Press eBooks. https://doi.org/10.1201/9781315113807
- Shepard, JO. (2019). Thoracic Imaging The Requisites (Requisites in Radiology) (3rd ed.). Elsevier.
- Walker C & Chung JH (2019). Muller’s Imaging of the Chest: Expert Radiology Series. Elsevier.
- Palange, P., & Rohde, G. (2019). ERS Handbook of Respiratory Medicine. European Respiratory Society.
- Rosado-De-Christenson, M. L., Facr, M. L. R. M., & Martínez-Jiménez, S. (2021). Diagnostic imaging: chest. Elsevier.
- Murray & Nadel: Broaddus, V. C., Ernst, J. D., MD, King, T. E., Jr, Lazarus, S. C., Sarmiento, K. F., Schnapp, L. M., Stapleton, R. D., & Gotway, M. B. (2021). Murray & Nadel’s Textbook of Respiratory Medicine, 2-Volume set. Elsevier.
- Fishman's: Grippi, M., Antin-Ozerkis, D. E., Cruz, C. D. S., Kotloff, R., Kotton, C. N., & Pack, A. (2023). Fishman’s Pulmonary Diseases and Disorders, Sixth Edition (6th ed.). McGraw Hill / Medical.