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Key findings
• Pulmonary amyloidosis most commonly presented as nodular disease and was frequently identified incidentally.
• Incomplete amyloid subtyping and heterogeneous management approaches were common.
What is known and what is new?
• Pulmonary amyloidosis is a rare condition with variable clinical and radiologic presentation.
• This study highlights real-world diagnostic challenges, including frequent incomplete amyloid typing.
• A diverse patient population and broader clinical spectrum were observed compared to prior reports.
What is the implication, and what should change now?
• Systematic amyloid subtyping should be prioritized to guide appropriate management.
• Standardized diagnostic and management pathways are needed to improve patient outcomes.
Introduction
Amyloidosis describes a heterogeneous group of rare and underdiagnosed protein misfolding disorders characterized by extracellular deposition of insoluble amyloid fibrils—aberrant protein aggregates that disrupt normal tissue architecture and organ function ( 1 ). To date, 31 amyloid fibril proteins have been identified in humans, and amyloid disorders are classified according to the specific precursor protein involved. The most common forms include immunoglobulin light-chain amyloidosis (AL), associated with plasma cell dyscrasias; serum amyloid A-derived (AA) amyloidosis, typically occurring in the setting of chronic inflammatory or infectious diseases; and transthyretin-related amyloidosis (ATTR). ATTR amyloidosis exists as two major subtypes: wild-type ATTR (ATTRwt), an age-related form frequently associated with cardiac involvement, and hereditary or mutant ATTR (ATTRm), caused by pathogenic variants in the transthyretin gene and associated with variable cardiac and neurologic manifestations. Additional clinically relevant forms include β2-microglobulin amyloidosis, which occurs predominantly in patients receiving long-term dialysis ( 2 - 4 ). While systemic amyloidosis incidence in Western populations is estimated at ~5–13 per million person-years, the incidence of pulmonary amyloidosis remains poorly defined and is largely described through case series and reviews ( 5 , 6 ). Autopsy-based analyses have further identified clinically unrecognized pulmonary amyloid deposition, suggesting that the true prevalence of pulmonary involvement is likely underestimated ( 7 ).
Pulmonary amyloidosis was first described by Lesser in 1877 ( 8 ) and subsequent clinicopathologic observations have demonstrated that amyloid deposition within the lung can occur in several distinct anatomic patterns. Accordingly, pulmonary amyloidosis is classically categorized into three major forms based on distribution: nodular pulmonary amyloidosis, tracheobronchial amyloidosis (TBA), and diffuse alveolar-septal amyloidosis ( 9 ). Across these patterns, AL (λ > κ) represents the most frequently reported underlying subtype, followed by AA amyloidosis, whereas ATTR involvement of the lung is uncommon and typically occurs in the setting of systemic disease ( 5 ).
Primary pulmonary amyloidosis is more common than secondary amyloid pulmonary ( 10 ). Pulmonary amyloidosis presents with nonspecific symptoms such as cough, hemoptysis, and dyspnea, often mimicking more common respiratory disorders and delaying diagnosis ( 9 ). Diagnosis relies on clinical assessment, imaging, and Congo red-confirmed biopsy, with immunohistochemistry or mass spectrometry for amyloid subtyping. Computed tomography (CT) and magnetic resonance imaging (MRI) help evaluate pulmonary extent and systemic involvement ( 2 ). Management depends on amyloid subtype and organ involvement and may include chemotherapy, stem cell transplantation, organ transplantation, or targeted medical therapy ( 1 ). Owing to its rarity, diagnostic complexity, and absence of standardized treatment guidelines, care remains individualized and challenging ( 11 ). Therefore, we conducted a detailed case series to provide a comprehensive description of patients with confirmed pulmonary amyloidosis, highlighting the key presenting symptoms, diagnostic strategies, radiologic findings, and treatment approaches, as well as patient survival. We present this article in accordance with the AME Case Series reporting checklist (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2730/rc ).
Methods
Study design and ethics
This study was a retrospective, non-consecutive case series conducted at a single tertiary academic medical center in Detroit, Michigan. The study included patients diagnosed with pulmonary amyloidosis between January 2020 and December 2024.
This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was reviewed and approved by the Henry Ford Health Institutional Review Board (No. 17895-01). Given the retrospective design and use of de-identified data, the requirement for informed consent was waived.
Registration
Clinical trial registration was not applicable, as this study was a retrospective case series and did not involve prospective enrollment or interventional assignment.
Setting
Patients were managed at a tertiary academic medical center providing subspecialty pulmonary, hematologic, oncologic, and pathologic services. Data collection, diagnostic evaluation, and follow-up occurred during routine clinical care.
Participants
Patients were eligible for inclusion if they had histopathologic confirmation of pulmonary amyloidosis, defined by Congo red-positive amyloid deposition with apple-green birefringence under polarized light on lung or tracheobronchial tissue specimens.
Patients without tissue confirmation of pulmonary amyloidosis were excluded.
Data collection
Clinical data were extracted from the electronic medical record and included:
❖ Demographics (age, sex, race, smoking history);
❖ Clinical presentation (symptomatic vs. incidental diagnosis);
❖ Respiratory symptoms (cough, dyspnea, wheezing, hemoptysis);
❖ Comorbidities [e.g., end stage renal disease (ESRD), autoimmune disease, malignancy];
❖ Family history;
❖ Imaging findings (chest radiograph and CT);
❖ Pulmonary function test (PFT) results when available;
❖ Histopathologic findings and amyloid typing when performed;
❖ Treatment strategies and clinical outcomes.
Three investigators independently reviewed and abstracted data to ensure accuracy and consistency.
Histopathologic evaluation
All biopsy specimens underwent hematoxylin and eosin (H&E) staining and Congo red staining. Amyloid typing was pursued using immunohistochemistry and/or mass spectrometry when clinically indicated and feasible.
Interventions and management
Management strategies varied depending on clinical presentation, extent of disease, and presence of systemic involvement. Interventions included systemic medical therapy, surgical resection with surveillance, supportive or palliative care, or observation alone. Management strategies evolved as diagnostic clarity improved, particularly following amyloid subtyping and hematologic evaluation.
Follow-up and outcomes
Follow-up and vital status were determined through longitudinal chart review; when follow-up was not documented, vital status could not be confirmed.
Statistical analysis
Descriptive statistics were used to summarize demographic, clinical, radiologic, pathologic, and outcome data. Continuous variables are reported as medians and ranges, and categorical variables as counts and percentages. No comparative or inferential statistical analyses were performed due to the descriptive nature of the case series.
Results
Clinical overview of 12 patients with pulmonary amyloidosis
Patient 1
An 81-year-old non-smoking woman with Parkinson’s disease presented with dyspnea. Imaging showed multiple bilateral pulmonary nodules with calcifications. Biopsy confirmed nodular pulmonary amyloidosis. Labs suggested Sjögren syndrome, but no monoclonal proteins were detected. She declined further workup and treatment, opting for supportive care. At data collection, she was receiving palliative care.
Patient 2
A 73-year-old former smoker presented with a persistent cough unresponsive to steroids and antibiotics. Chest CT revealed spiculated lung masses, and positron emission tomography (PET) showed hypermetabolic activity. Biopsy confirmed TBA, with mass spectrometry identifying ATTR-type amyloid. A 99m Tc-pyrophosphate (PYP) scan indicated concurrent cardiac involvement. Diagnosed with pulmonary and cardiac ATTR amyloidosis, he was treated with diflunisal due to the high cost of tafamidis. He remained alive at the time of data collection.
Patient 3
A 65-year-old former smoker with monoclonal gammopathy of undetermined significance and ESRD was undergoing evaluation for kidney transplantation when a left upper lobe lung nodule was discovered. Biopsy revealed adenocarcinoma with amyloid deposition. Imaging showed bone involvement and a mediastinal mass. Monoclonal proteins were detected, but before further evaluation could be completed, the patient developed septic shock and respiratory failure and died after a prolonged hospitalization.
Patient 4
A 67-year-old man with ESRD, atrial myxoma, and prior kidney and liver transplants was incidentally found to have a mediastinal mass and bilateral lung nodules during a stroke workup. Wedge resection of the right upper lobe confirmed nodular pulmonary amyloidosis. Monoclonal proteins were absent, PYP scan was negative for transthyretin (ATTR) involvement, and mass spectrometry was not performed for unclear reasons. In the absence of systemic disease, he was managed with clinical surveillance and remained alive at the time of data collection.
Patient 5
A 74-year-old smoker with ulcerative colitis (UC) and ductal carcinoma in situ was incidentally found to have lung nodules on screening CT. Biopsy confirmed nodular pulmonary amyloidosis with AL-type amyloid. Serum studies revealed an IgG lambda M protein, and bone marrow biopsy confirmed systemic AL amyloidosis. She was treated with daratumumab, cyclophosphamide, bortezomib, and dexamethasone, and remained alive at the time of data analysis.
Patient 6
A 79-year-old former smoker presented with weakness and fatigue. CT showed a 22 mm left lung nodule and multiple smaller nodules. Biopsy confirmed nodular pulmonary amyloidosis. She was initially lost to follow-up but re-established care two years later. At data collection, she was alive and undergoing further evaluation.
Patient 7
A 76-year-old man with neuromyelitis optica and monoclonal B-cell lymphocytosis presented with dyspnea. Imaging revealed nodular and interstitial lung changes. Biopsy confirmed nodular pulmonary amyloidosis with suspected marginal zone lymphoma, though scant tissue limited diagnosis. Mass spectrometry confirmed AL-type amyloid. Monoclonal protein studies and bone marrow biopsy were negative. He was treated with Dara-CyBorD and remained stable at data analysis.
Patient 8
An 85-year-old non-smoking woman with no significant medical history presented with a 2-week history of cough and dyspnea. CT revealed a right upper lobe nodule, and biopsy confirmed nodular pulmonary amyloidosis. She remained stable and was undergoing further evaluation at the time of data collection.
Patient 9
A 76-year-old non-smoker with ESRD and Parkinson’s disease was incidentally found to have a lung mass during anemia workup. Biopsy confirmed nodular pulmonary amyloidosis. He had no further follow-up documented in our system. The patient passed away approximately 2 years later; the specific cause of death was not determined.
Patient 10
A 76-year-old former smoker with a history of adrenal and colonic adenomas was found to have an enlarging right lung base nodule on screening CT. Biopsy confirmed nodular pulmonary amyloidosis. No further workup or treatment was pursued following diagnosis for unclear reasons. She remained alive and clinically stable at the time of data collection.
Patient 11
A 73-year-old man with chronic obstructive pulmonary disease (COPD), Parkinson’s disease, and a smoking history was incidentally found to have lung nodules and mediastinal lymphadenopathy during a stroke workup. Biopsy confirmed nodular pulmonary amyloidosis with atypical lymphoplasmacytic infiltrate suggestive of lymphoma or plasma cell neoplasm, but limited tissue precluded definitive diagnosis. Monoclonal antibodies were detected. He declined further workup due to poor functional status, and no subsequent follow-up was documented.
Patient 12
An 82-year-old non-smoking woman with congestive heart failure (CHF) presented with a 1-month history of cough and dyspnea. CT showed a 4 cm pleural-based mass; biopsy confirmed nodular pulmonary amyloidosis and a plasma cell neoplasm. She was alive and undergoing further evaluation at the time of data collection.
Composite analysis of 12 patients with pulmonary amyloidosis
Demographic features
In our cohort (n=12), the median age was 76 years (range, 65–85 years). Gender distribution was equal: 50% male (n=6) and 50% female (n=6). Ethnicities included 50% White (n=6), 42% Black (n=5), and 8% (n=1) identifying with another ethnic category. Most patients were former smokers (67%, n=8), while the remaining 33% (n=4) had never smoked ( Figure 1 ).
Clinical presentation
Among the 12 patients evaluated, 42% (n=5) presented with symptoms attributable to pulmonary amyloidosis. Of these, 17% (n=2) reported isolated shortness of breath, 8% (n=1) had a persistent cough, and 17% (n=2) experienced both symptoms. One patient (n=1, 8%) presented with generalized weakness. The remaining 50% (n=6) were asymptomatic and diagnosed incidentally, representing half of the cohort ( Figure 2 ).
Comorbidities
Comorbidities were common in our cohort: 42% (n=5) had more than three, 17% (n=2) had two, 25% (n=3) had one, and 16% (n=2) had none. Reported conditions included UC, lymphoma, arthritis, atrial myxoma, cirrhosis, ESRD, Parkinson’s disease, COPD, and CHF. Notably, 25% had ESRD and 17% had Parkinson’s disease. A family history of cancer was present in 58% (n=7) of patients.
Imaging findings
Chest radiography and CT were performed in all patients (n=12), revealing nodules ranging from 11 mm to 4 cm. Bilateral nodules were present in 75% (n=9), mediastinal masses or lymphadenopathy in 50% (n=6), and calcified nodules in 25% (n=3). Airspace abnormalities included consolidation in 42% (n=5) and patchy opacities in 33% (n=4). Pleural effusions were observed in 33% (n=4) ( Figure 3 ).
PFT results
Among 12 patients, PFTs were unavailable in 42% (n=5). The remaining 58% (n=7) showed the following: normal function (8%, n=1); moderate obstruction with low diffusing capacity of the lung for carbon monoxide (DLCO) (8%, n=1); moderate obstruction with normal DLCO (8%, n=1); mild obstruction with normal DLCO (8%, n=1); mild obstruction with moderate DLCO reduction (8%, n=1); severe obstruction with normal DLCO (8%, n=1); isolated reduced DLCO (8%, n=1; Figure 4 ).
Histopathologic findings
Histologic examination revealed deposits of amorphous eosinophilic material in the lung and bronchial mucosa. Congo red staining was performed in all cases (n=12) as part of the diagnostic workup and demonstrated apple-green birefringence under polarized light. These findings are consistent with a diagnosis of pulmonary amyloidosis ( Figure 5 ).
Type of pulmonary involvement and amyloid typing
All but one of the 12 patients (92%, n=11) were diagnosed with nodular pulmonary amyloidosis, while one patient (8%, n=1) had TBA. Amyloid typing was completed in 25% of patients (n=3), including AL-type in two patients (Patients 5 and 7) and ATTR-type in one patient (Patient 2). Typing was pending in 25% (n=3; Patients 6, 8, and 12) at the time of analysis. One patient (8%; Patient 11) declined further evaluation due to poor functional status, and no subsequent follow-up was documented. Amyloid typing was not performed for unclear reasons in two patients (17%; Patients 4 and 10). Typing could not be completed in one patient who died before evaluation (8%; Patient 3). One patient (8%; Patient 9) had no further follow-up documented after diagnosis and was later reported deceased, with cause of death unclear ( Figure 6 ).
Treatment and survival
Among the 12 patients, 25% (n=3) received systemic medical therapy, 8% (n=1) received palliative care, 8% (n=1) underwent surgical resection with surveillance, and 25% (n=3) were undergoing further diagnostic evaluation at last follow-up. Thirty-three percent (n=4) did not receive treatment or complete further workup: 1 patient (8%) died before treatment initiation, 1 (8%) had no additional workup or treatment documented after diagnosis for unclear reasons, 1 (8%) declined further evaluation due to poor functional status with no subsequent follow-up documented, and 1 (8%) was lost to follow-up and was later reported deceased.
At the time of analysis, 75% (n=9) were alive. Two patients died (17%). One patient (8%) had no documented follow-up after declining further evaluation, and therefore, vital status could not be confirmed ( Figures 7,8 ).
Discussion
In this case series of 12 patients with pulmonary amyloidosis, we observed several noteworthy clinical and demographic trends that expand upon existing literature.
Consistent with recent descriptions of nodular pulmonary amyloidosis, our findings demonstrate typical radiographic features, including well-defined solid pulmonary nodules with occasional calcification, cavitation, or associated cystic lung disease on CT imaging. In contrast to prior series in which most patients are asymptomatic, 42% of patients in our cohort were symptomatic at presentation. Additionally, our cases illustrate a broader disease spectrum, encompassing localized pulmonary amyloidosis as well as pulmonary involvement in systemic AL and ATTR amyloidosis and in association with lymphoproliferative disorders, underscoring the importance of comprehensive hematologic evaluation and longitudinal follow-up ( 12 ). Although multiple pulmonary amyloidosis subtypes have been described, the predominant subtype in our series was nodular pulmonary amyloidosis, with only one case of tracheobronchial involvement. This nodular subtype is typically indolent, often asymptomatic, and associated with an excellent prognosis; it rarely impairs pulmonary function or survival and can be managed with surveillance, while surgical excision may be curative in selected cases ( 5 ). Unlike nodular disease, diffuse alveolar-septal amyloidosis is typically associated with both pulmonary and systemic involvement ( 13 ). Notably, this pattern was absent in our cohort, possibly reflecting the rarity of this subtype or selection bias inherent in our referral population.
Most patients were older adults, with the majority aged ≥65 years, and a substantial proportion had a history of smoking—findings consistent with other series reporting high smoking prevalence across pulmonary amyloidosis subtypes, including diffuse alveolar-septal, tracheobronchial, and cystic forms ( 14 ). Sex distribution in our cohort diverged from previously reported patterns. Whereas prior studies suggest a male predominance, our series demonstrated a near-equal distribution of male and female patients ( 3 ).
Although pulmonary amyloidosis has been described in various clinical settings, racial representation remains poorly characterized. Most case series either omit racial data or report predominantly White patients. A review of 41 amyloidosis studies found that over 95% failed to report race or ethnicity, underscoring a significant gap in demographic representation ( 15 ). In a study of 2,416 patients with systemic AL amyloidosis, only 14% were from minority backgrounds, with non-Hispanic Black patients comprising just 8%, despite being more likely to present with advanced disease ( 16 ). In contrast, our cohort demonstrated notable ethnic diversity, with Black patients comprising 42% of cases, suggesting that racial patterns in pulmonary amyloidosis may be underrecognized and highlighting the need for more inclusive research.
Several patients in our study had underlying medical conditions associated with amyloidosis. Notably, one patient had Parkinson’s disease, which has emerging links to amyloid deposition. Amyloid PET imaging research has revealed that β-amyloid plaques and other amyloid forms are present in non-Alzheimer’s neurodegenerative conditions, including Parkinson’s disease—signaling potential systemic or multi-organ involvement beyond the central nervous system ( 17 ). We also identified one patient with undifferentiated arthritis, and chronic inflammatory arthritis is a well-known risk factor for AA amyloidosis due to persistent inflammation and serum amyloid A overproduction ( 18 ). Other notable comorbidities included ESRD, lung adenocarcinoma, solid organ transplant, and UC—conditions linked to amyloid through chronic inflammation, tissue remodeling, or altered protein metabolism ( 19 - 22 ). One patient in our cohort had serologic findings suggestive of Sjögren’s syndrome, paralleling a recently reported case of secondary pulmonary amyloidosis associated with Sjögren’s syndrome, with both cases demonstrating bilateral calcified pulmonary nodules on imaging ( 23 ). Although our patient with pulmonary ATTR was symptomatic, recent studies suggest that pulmonary transthyretin amyloid deposition is frequently subclinical in older adults ( 24 ); moreover, the absence of a documented family history does not exclude hereditary ATTR amyloidosis, given its variable penetrance ( 22 ). Interestingly, two-thirds of our patients also had a family history of cancer, suggesting potential shared genetic or environmental risk factors, though the clinical significance remains unclear.
Beyond classic nodular patterns, CT imaging in our cohort also demonstrated heterogeneous thoracic manifestations, including mediastinal masses, lymphadenopathy, consolidation, and pleural effusions, highlighting the wide radiographic spectrum of pulmonary amyloidosis reported in prior literature ( 24 , 25 ). Given the variability in clinical symptoms and imaging, tissue biopsy with Congo red staining remains the gold standard for diagnosis, and subsequent amyloid protein typing (preferably by mass spectrometry-based proteomic analysis) is crucial to guide prognosis and treatment ( 26 , 27 ). In our study, amyloid protein typing was completed in only 25% of patients. Among those typed, AL-type was the most identified, with one ATTR case; others remained untyped due to delays, refusal, or loss to follow-up.
Interestingly, nodular pulmonary amyloidosis has been associated with indolent B-cell lymphoproliferative disorders, likely due to localized light chain deposition. In a study by Grogg et al. , 21% of patients had low-grade B-cell lymphoma, including mucosa-associated lymphoid tissue (MALT) type ( 28 ). Similarly, we observed underlying hematologic pathology in three patients—two with low-grade B-cell lymphoma and one with plasma cell dyscrasia—underscoring the importance of systemic hematologic evaluation, even when imaging suggests localized disease.
PFTs in our cohort ranged from normal to varying degrees of obstructive defects and were overall nonspecific and nondiagnostic, consistent with prior studies. Published literature indicates that nodular pulmonary amyloidosis is frequently associated with preserved spirometry, although DLCO may decrease when the nodular burden is substantial ( 29 ). TBA, particularly in its early stages, may present with normal pulmonary function, but can progress to fixed airflow obstruction and characteristic flow-volume loop flattening as airway wall thickening becomes more pronounced ( 30 ). In contrast, diffuse alveolar-septal disease causes a restrictive defect with markedly reduced DLCO and exertional hypoxemia, reflecting extensive alveolar–capillary amyloid deposition ( 31 ).
Turning to treatment, management of pulmonary amyloidosis is largely guided by expert opinion in the absence of evidence-based guidelines or randomized controlled trials. Data on treatment efficacy remain limited due to small, heterogeneous cohorts, limited follow-up, and noncomparative study designs ( 32 ). We observed a wide spectrum of management in our cohort—ranging from monitoring to systemic therapy and, in one case, palliative care—mirroring patterns described in the literature. Nodular pulmonary amyloidosis often requires no intervention, as lesions are typically slow-growing and asymptomatic—making periodic monitoring sufficient in most cases. For symptomatic patients, options include surgical resection, bronchoscopic removal, or laser therapies which generally yield favorable outcomes ( 14 ).
Management of TBA is highly individualized, depending on airway involvement. For significant obstruction, rigid bronchoscopy with laser or forceps debulking can restore patency ( 31 ), while Dumon stents may provide lasting relief and help avoid tracheostomy ( 33 ). In progressive or diffuse cases of tracheobronchial and particularly alveolar-septal amyloidosis, systemic therapy is warranted. Initial treatments were modeled after multiple myeloma, but AL patients are more fragile with higher early mortality ( 8 ).
Early regimens included melphalan and dexamethasone, followed by bortezomib—a proteasome inhibitor—though side effects, including cytopenia, neuropathy, and cardiac toxicity, were significant ( 33 ). This led to the development of the CyBorD (dara-VCD; daratumumab, cyclophosphamide, bortezomib, and dexamethasone) regimen, which is now recommended as first-line therapy ( 34 ). If inadequate, patients may be considered for autologous stem cell transplant (ASCT), though eligibility depends on functional status and comorbidities ( 35 ). For patients with ATTR, tafamidis acts as a transthyretin stabilizer, preventing tetramer dissociation and subsequent amyloid fibril formation, and represents a disease-modifying therapy that may slow progression ( 36 ). In advanced disease or poor functional status, palliative care—including steroids, pulmonary rehabilitation, and symptom relief with opioids—may be more appropriate ( 35 ).
Overall, our findings reinforce that pulmonary amyloidosis remains a diagnostically challenging and therapeutically heterogeneous condition. In the absence of standardized treatment or surveillance guidelines, management is individualized and guided by amyloid subtype, anatomic pattern, and the presence of systemic disease ( 5 , 8 , 9 , 32 ). Consistent with prior literature, prognosis appears to be driven more by amyloid subtype and extra-cardiopulmonary involvement than by pulmonary deposition alone ( 1 , 4 , 5 ). In our cohort, the predominance of nodular disease—often asymptomatic and indolent—further supports the generally favorable course of localized pulmonary involvement described in previous series ( 9 , 14 , 29 ).
Strengths and limitations
This study has several limitations inherent to its retrospective, single-center design and small sample size, which limit generalizability and preclude inferential statistical analysis. Incomplete amyloid subtyping, loss to follow-up, and early mortality in some patients further restricted comprehensive outcome assessment. However, strengths of this case series include detailed clinicopathologic characterization, racial diversity within the cohort, and inclusion of real-world diagnostic and management challenges encountered in pulmonary amyloidosis.
Rationale for conclusions
The conclusions are supported by consistent clinicopathologic patterns across cases, including predominant nodular disease, frequent incidental detection, and heterogeneous diagnostic and management pathways. Despite limited sample size and incomplete follow-up, these recurring findings justify the conclusions regarding diagnostic challenges and the need for standardized evaluation.
Conclusions
Pulmonary amyloidosis remains a rare and underrecognized manifestation of a heterogeneous systemic disorder, frequently identified incidentally and often presenting with nonspecific respiratory findings that complicate timely diagnosis. The absence of standardized diagnostic algorithms and evidence-based treatment guidelines creates significant challenges for pulmonologists, particularly when pulmonary involvement represents the initial manifestation of systemic or lymphoproliferative disease. Management is inherently individualized and guided by amyloid subtype, extent of organ involvement, and patient-specific factors.
Our experience underscores persistent gaps in diagnostic completion—particularly in amyloid subtyping—and highlights the variability in therapeutic decision-making that results from limited high-quality evidence. Given the rarity of this condition and the predominance of small case series in the literature, larger multicenter studies and prospective registries are urgently needed to better define optimal diagnostic workflows, risk stratification, and treatment strategies. Ultimately, improved standardization and collaborative research efforts will be essential to advance care for patients with pulmonary amyloidosis.
Supplementary
The article’s supplementary files as
Acknowledgments
None.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was reviewed and approved by the Henry Ford Health Institutional Review Board (No. 17895-01). Given the retrospective design and use of de-identified data, the requirement for informed consent was waived.
Footnotes
Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2730/rc
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2730/coif ). The authors have no conflicts of interest to declare.
Data Sharing Statement
Available at https://jtd.amegroups.com/article/view/10.21037/jtd-2025-1-2730/dss
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