Diffuse Alveolar Septal Amyloidosis Research Articles

A descriptive analysis of 21 patients with pulmonary amyloidosis: An observational study.

Pulmonary amyloidosis is an extremely rare disease, often detected incidentally because of its asymptomatic nature and potential to result in fatal outcomes. In this study, we aimed to present the clinical and radiological features of patients diagnosed with pulmonary amyloidosis by biopsy. This descriptive study included 21 patients with pathologically diagnosed pulmonary amyloidosis. Pulmonary amyloidosis was classified as diffuse alveolar-septal amyloidosis (DASA), cystic amyloidosis (CPA), tracheobronchial amyloidosis (TBA), nodular amyloidosis (NPA), and extraparenchymal pulmonary amyloidosis (pleural and mediastinal lymph node). Clinical, bronchoscopic, and radiological specific characteristics were presented in detail to be used for differential diagnosis. The median age of the patients was 63 (40-83) years, and 14 (66.7%) were male. Twenty patients (95.2%) presented with at least 1 comorbidity. All patients diagnosed with tracheobronchial amyloidosis were symptomatic at presentation, whereas those diagnosed with NPA/extraparenchymal amyloidosis were often asymptomatic. The patients included 1 case of DASA, 1 case of CPA, 10 cases of NPA, 6 cases of TBA, and 3 cases of extraparenchymal amyloidosis involving the mediastinal lymph node and pleura. Sixteen patients (76.2%) were classified as localized amyloidosis, while 5 patients (23.8%) were classified as systemic amyloidosis following the diagnosis of multiple myeloma, monoclonal gammopathy of undetermined significance, systemic lupus erythematosus, Sjogren's syndrome, and B-cell lymphoma. Bronchoscopic biopsies were sufficient for diagnosis, and notably, even transbronchial needle aspiration could be a useful diagnostic method. During the follow-up, we observed that the disease remained stable without progression. However, it is important to note that patients with concurrent malignancies experience fatal outcomes. In conclusion, it is crucial to distinguish pulmonary amyloidosis from other pulmonary diseases such as malignancies, infectious diseases, and interstitial lung diseases, which may have similar clinical and radiological findings. Bronchoscopic diagnostic methods are usually sufficient for the diagnosis. Although patients with pulmonary involvement mostly remain stable during long-term follow-up without progression, it is important to consider the risk of malignancy.

A DUAL DIAGNOSIS: CYCLOPHOSPHAMIDE TOXICITY AND DIFFUSE ALVEOLAR-SEPTAL AMYLOIDOSIS CAUSING HYPOXEMIA

TOPIC: Diffuse Lung Disease TYPE: Fellow Case Reports INTRODUCTION: Patients with cardiac amyloidosis have multiple possible causes of hypoxia including pulmonary edema, infection, drug toxicity, and pulmonary involvement of amyloidosis. Treatment varies significantly for these different etiologies. This broad differential can make diagnosis challenging and bronchoscopy is often needed to establish a definitive diagnosis. CASE PRESENTATION: A 72 yo male with cardiac AL amyloidosis presented with fever and hypoxic respiratory failure. He completed 4 cycles of cyclophosphamide, bortezomib, and dexamethasone 2 weeks prior to presentation. Right heart catheterization (RHC) demonstrated normal pressures. CT chest showed diffuse ground glass opacities (GGO) and basilar predominant interlobular septal thickening. He was diuresed but continued to require supplemental oxygen. Bronchoscopy with BAL and transbronchial biopsy was performed. BAL WBC was 121 with 48% lymphocytes and 48% macrophages. Infectious evaluation returned negative. Transbronchial biopsy returned with lambda-predominant plasma cell infiltrate and amyloid deposition. He was started on prednisone with improvement in symptoms and liberation from supplemental oxygen after 3 weeks of therapy. PFTs obtained at follow-up showed mild obstruction and moderately reduced DLCO. DISCUSSION: Pulmonary toxicity is a known complication of cyclophosphamide therapy that results in pneumonitis, typically occurring weeks after administration. CT imaging shows scattered or diffuse GGOs. Pathology demonstrates diffuse alveolar damage. Case series have shown improvement with drug cessation and steroids. Diffuse alveolar-septal amyloidosis (DASA) is 1 of several patterns of pulmonary amyloidosis. DASA is associated with AL amyloidosis. DASA is a common pathologic finding but is rarely symptomatic unless severe enough to impair gas exchange. CT imaging shows interlobular septal thickening, reticular opacities, and GGOs. Pathology reveals amyloid deposition within the alveolar septum and vessel walls and a plasma cell infiltrate. Treatment is systemic therapy for amyloidosis. This patient with cardiac amyloidosis and cyclophosphamide use was a diagnostic challenge. Given his fever, normal RHC, and failure to improve with diuresis, there was concern for infection vs cyclophosphamide toxicity. Infectious evaluation with BAL was negative and he was started on steroids with improvement in symptoms. However, pathology returned with findings consistent with DASA.His clinical presentation and rapid improvement with prednisone indicate a component of cyclophosphamide toxicity causing hypoxemia. His pathology findings and persistent reduction in DLCO suggest DASA also contributed to his hypoxemia. CONCLUSIONS: DASA and cyclophosphamide toxicity are uncommon causes of respiratory failure and have nonspecific findings on CT imaging. Distinguishing these etiologies can be challenging without bronchoscopy and histological samples. REFERENCE #1: Khoor A, Colby TV. Amyloidosis of the Lung. Arch Pathol Lab Med. 2017 Feb;141(2):247-254. doi: 10.5858/arpa.2016-0102-RA. PMID: 28134587. REFERENCE #2: Malik SW, Myers JL, DeRemee RA, Specks U. Lung toxicity associated with cyclophosphamide use. Two distinct patterns. Am J Respir Crit Care Med. 1996 Dec;154(6 Pt 1):1851-6. doi: 10.1164/ajrccm.154.6.8970380. PMID: 8970380. REFERENCE #3: Rossi SE, Erasmus JJ, McAdams HP, Sporn TA, Goodman PC. Pulmonary drug toxicity: radiologic and pathologic manifestations. Radiographics. 2000 Sep-Oct;20(5):1245-59. doi: 10.1148/radiographics.20.5.g00se081245. PMID: 10992015. DISCLOSURES: No relevant relationships by David Dennis, source=Web Response No relevant relationships by David Zaas, source=Web Response

SYSTEMIC AL AMYLOIDOSIS PRESENTING WITH DIFFUSE ALVEOLAR SEPTAL INVOLVEMENT AND RESPIRATORY FAILURE: A CASE REPORT AND REVIEW OF THE LITERATURE

Amyloidosis is the extracellular deposition of amyloid fibril protein in any tissue or organ. The clinical manifestations of pulmonary amyloidosis are variable and without specific symptoms. We report a rare case of diffuse alveolar septal amyloidosis which is an extremely rare pattern of involvement, with a very poor prognosis, to improve our understanding of the disease. A 27-year-old man complained of shortness of breath and cyanosis. High-resolution computed tomography revealed diffuse ground-glass opacifications with interlobular septal thickening in both lungs. The immune-histochemistry showed monoclonal lambda light chains. This case also showed nephrotic syndrome and cardiac arrhythmia, suggesting an involvement of the kidney and the heart. Diagnosis: The diagnosis was finally established by tru-cut transthoracic sonar guided lung biopsy (TSLB), and histological examination revealed Congo red-positive amorphous eosinophilic deposits in the alveolar sept. Interventions: The patient was admitted to a respiratory intensive care unit and put on non-invasive ventilation, then discharged on domiciliary oxygen therapy, and started treatment with chemotherapy melphalan 2 mg daily plus prednisone 60 mg daily immediately after the result of histopathology. Outcomes: Three months after treatment, dyspnea and hypoxemia improved, and he continued treatment. The patient was in a good clinical condition after 10 months of follow-up, but he died suddenly. As it is difficult to distinguish diffuse alveolar septal amyloidosis from other interstitial and granulomatous lung diseases because of their similar symptoms and imaging findings, thus, transthoracic sonar guided lung biopsy and histological examination is very important in the diagnosis of diffuse alveolar septal amyloidosis.

Systemic AL amyloidosis presenting with diffuse alveolar septal involvement and respiratory failure: a case report and review of the literature

BackgroundAmyloidosis is the extracellular deposition of amyloid fibril protein in any tissue or organ. The clinical manifestations of pulmonary amyloidosis are variable and without specific symptoms. We report a rare case of diffuse alveolar septal amyloidosis which is an extremely rare pattern of involvement, with a very poor prognosis, to improve our understanding of the disease.Case presentationA 27-year-old man complained of shortness of breath and cyanosis. High-resolution computed tomography revealed diffuse ground-glass opacifications with interlobular septal thickening in both lungs. The immune-histochemistry showed monoclonal lambda light chains. This case also showed nephrotic syndrome and cardiac arrhythmia, suggesting an involvement of the kidney and the heart. Diagnosis: The diagnosis was finally established by tru-cut transthoracic sonar guided lung biopsy (TSLB), and histological examination revealed Congo red-positive amorphous eosinophilic deposits in the alveolar sept. Interventions: The patient was admitted to a respiratory intensive care unit and put on non-invasive ventilation, then discharged on domiciliary oxygen therapy, and started treatment with chemotherapy melphalan 2 mg daily plus prednisone 60 mg daily immediately after the result of histopathology. Outcomes: Three months after treatment, dyspnea and hypoxemia improved, and he continued treatment. The patient was in a good clinical condition after 10 months of follow-up, but he died suddenly.ConclusionAs it is difficult to distinguish diffuse alveolar septal amyloidosis from other interstitial and granulomatous lung diseases because of their similar symptoms and imaging findings, thus, transthoracic sonar guided lung biopsy and histological examination is very important in the diagnosis of diffuse alveolar septal amyloidosis.

Amyloidosis of the respiratory system: 16 patients with amyloidosis initially diagnosedante mortemby pulmonologists

BackgroundAnte mortem diagnosis of amyloidosis of the respiratory system is rare. Few data are available regarding clinical presentation, precursor proteins, diagnostic procedures, comorbidities, complications, and outcome. We assessed clinical features of a series of patients with amyloidosis of the respiratory system in two Japanese centres.MethodsMedical records of 16 patients with amyloidosis of the respiratory system were retrospectively analysed. Amyloid was diagnosed by polarisation microscopy using Congo red-stained tissue specimens and classified immunohistochemically.ResultsMedian patient age was 71 years, and median follow-up period was 5 years. Immunoglobulin light-chain (AL)-λ amyloidosis was found in eight and AL-κ in five patients. Two patients harboured wild-type transthyretin and one harboured serum amyloid A-derived amyloid. Five different forms of amyloidosis of the respiratory system were observed: nodular pulmonary amyloidosis (seven patients), diffuse alveolar-septal amyloidosis (five), mediastinal lymph node amyloidosis (three), tracheobronchial amyloidosis (one), and pleural amyloidosis (one). One patient had diffuse alveolar-septal amyloidosis and mediastinal lymph node amyloidosis. Three of five patients with diffuse alveolar-septal amyloidosis were diagnosed by transbronchial lung biopsy as having concurrent diffuse alveolar haemorrhage or pneumocystis pneumonia. Two of three patients with mediastinal lymph node amyloidosis were diagnosed by endobronchial ultrasound-guided transbronchial needle aspiration.ConclusionsNot only nodular pulmonary amyloidosis, diffuse alveolar-septal amyloidosis, and tracheobronchial amyloidosis but also mediastinal lymph node amyloidosis and pleural amyloidosis should be considered in the differential diagnosis of amyloidosis of the respiratory system. Useful diagnostic methods include transbronchial lung biopsy for diffuse alveolar-septal amyloidosis and endobronchial ultrasound-guided transbronchial needle aspiration for mediastinal lymph node amyloidosis.

Coital Hemoptysis Due to Cardiac AL Amyloidosis

A 48-year-old woman presented with recurrent hemoptysis during intercourse. The computed tomography (CT) pulmonary angiogram demonstrated bilateral patchy ground glass opacities and no pulmonary embolism and a small pulmonary cyst (Figure A, arrow). She was treated with azithromycin, and follow-up chest CT 12 days later demonstrated complete resolution (Figure D). Stress echocardiogram suggested multivessel coronary artery disease (CAD), but coronary angiogram demonstrated only mild CAD. An exercise right-heart catheterization showed exercise-induced pulmonary arterial hypertension and elevated filling pressures. Cardiac magnetic resonance imaging showed delayed subendocardial enhancement, left ventricular hypertrophy, and biatrial enlargement (Supplemental Figure: 3-chamber and 4-chamber views, available online at http://www.mayoclinicproceedings.org). Subsequent right ventricular biopsy at 200× magnification showed a pericellular pattern of amyloid deposition (Figure B, arrow) on Congo red stain with characteristic apple-green birefringence (Figure C, arrow) under polarized light diagnostic of AL (lambda) cardiac amyloidosis. Coital hemoptysis is infrequently described and typically due to cardiac etiology such as heart failure, mitral valve disease, or CAD.1Fuks L. Shitrit D. Amital A. Fox B.D. Kramer M.R. Postcoital hemoptysis: our experience and review of the literature.Respir Med. 2009; 103: 1828-1831Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar Amyloidosis is an uncommon cause of hemoptysis, but more often due to pulmonary parenchymal disease and pulmonary vascular fragility rather than cardiac disease.2Road J.D. Jacques J. Sparling J.R. Diffuse alveolar septal amyloidosis presenting with recurrent hemoptysis and medial dissection of pulmonary arteries.Am Rev Respir Dis. 1985; 132: 1368-1370PubMed Google Scholar We hypothesize that when imposed on a noncompliant, amyloid-infiltrated heart, increased cardiac workload and systemic arterial pressures during intercourse caused a dramatic elevation in left ventricular filling pressures leading to flash pulmonary edema. The cystic pulmonary lesion may indicate pulmonary involvement, with possible increased pulmonary microvascular involvement and a predisposition to hemoptysis. If present, pulmonary microvascular involvement may have predisposed to hemoptysis in the setting of rapidly increased cardiac filling pressures. After a positive serum protein electrophoresis, a bone marrow biopsy revealed multiple myeloma for which the patient underwent autologous stem cell transplant and is doing well. We thank Omar F. AbouEzzeddine, MDCM, MS, and Mandeep Singh, MD, MPH, for their mentorship and assistance in manuscript preparation. Supplemental material can be found online at http://www.mayoclinicproceedings.org. Supplemental material attached to journal articles has not been edited, and the authors take responsibility for the accuracy of all data.

The lung in amyloidosis.

Amyloidosis is a disorder caused by misfolding of autologous protein and its extracellular deposition as fibrils, resulting in vital organ dysfunction and eventually death. Pulmonary amyloidosis may be localised or part of systemic amyloidosis.Pulmonary interstitial amyloidosis is symptomatic only if the amyloid deposits severely affect gas exchange alveolar structure, thus resulting in serious respiratory impairment. Localised parenchymal involvement may be present as nodular amyloidosis or as amyloid deposits associated with localised lymphomas. Finally, tracheobronchial amyloidosis, which is usually not associated with evident clonal proliferation, may result in airway stenosis.Because the treatment options for amyloidosis are dependent on the fibril protein type, the workup of all new cases should include accurate determination of the amyloid protein. Most cases are asymptomatic and need only a careful follow-up. Diffuse alveolar-septal amyloidosis is treated according to the underlying systemic amyloidosis. Nodular pulmonary amyloidosis is usually localised, conservative excision is usually curative and the long-term prognosis is excellent. Tracheobronchial amyloidosis is usually treated with bronchoscopic interventions or external beam radiation therapy.

Amyloidosis of the Lung.

-Amyloidosis is a heterogeneous group of diseases characterized by the deposition of congophilic amyloid fibrils in the extracellular matrix of tissues and organs. To date, 31 fibril proteins have been identified in humans, and it is now recommended that amyloidoses be named after these fibril proteins. Based on this classification scheme, the most common forms of amyloidosis include systemic AL (formerly primary), systemic AA (formerly secondary), systemic wild-type ATTR (formerly age-related or senile systemic), and systemic hereditary ATTR amyloidosis (formerly familial amyloid polyneuropathy). Three different clinicopathologic forms of amyloidosis can be seen in the lungs: diffuse alveolar-septal amyloidosis, nodular pulmonary amyloidosis, and tracheobronchial amyloidosis. -To clarify the relationship between the fibril protein-based amyloidosis classification system and the clinicopathologic forms of pulmonary amyloidosis and to provide a useful guide for diagnosing these entities for the practicing pathologist. -This is a narrative review based on PubMed searches and the authors' own experiences. -Diffuse alveolar-septal amyloidosis is usually caused by systemic AL amyloidosis, whereas nodular pulmonary amyloidosis and tracheobronchial amyloidosis usually represent localized AL amyloidosis. However, these generalized scenarios cannot always be applied to individual cases. Because the treatment options for amyloidosis are dependent on the fibril protein-based classifications and whether the process is systemic or localized, the workup of new clinically relevant cases should include amyloid subtyping (preferably with mass spectrometry-based proteomic analysis) and further clinical investigation.

Pulmonary Diffuse Alveolar Septal Amyloidosis -Diagnosed by Transbronchial Lung Biopsy-

Diffuse alveolar septal involvement is a rare form of pulmonary amyloidosis. Ante-mortem diagnosis is unusual, and most of the reported cases were diagnosed at autopsy. It has recently been reported that transbronchial lung biopsy via a flexible fiberoptic bronchoscope was a relatively safe method to confirm diffuse alveolar septal amyloidosis.We report a case of pulmonary diffuse alveolar septal amyloidosis confirmed by transbronchial lung biopsy. The patient’s chief complaints were dyspnea on exertion and epigastric pain aggravated over a one-year period, while a chest roentgenogram showed bilateral diffuse interstitial infiltration. This case also showed nephrotic syndrome, cardiac arrhythmia, congestive heart failure, a tingling sensation in both hands and multiple nodules in the gastrointestinal tracts, suggesting involvement of the kidney, heart, peripheral nerves and gastrointestinal tracts.We propose that when diffuse interstitial lung disease is present with systemic signs such as nephrotic syndrome or cardiac arrhythmia, amyloidosis should be considered as a possible diagnosis. Also, transbronchial lung biopsy may be a useful confirmative diagnostic tool.