Systemic amyloidosis is underdiagnosed in light-chain amyloidosis (AL), as is plasma cell dyscrasias (PCD). Early detection and accurate evaluation of organ involvement in systemic amyloidosis remain critical challenges. We aimed to assess the utility of [18F]florbetapir (FBP) and [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) for the early detection and evaluation of organ involvement in systemic amyloidosis.

We included 66 participants and performed biochemical assays in serum and urine and whole-body PET/computed tomography using [18F]FBP and [18F]FDG, followed by visual, maximum standardized uptake value (SUVmax), and target-to-background ratio (TBR) analyses. The clinical evaluation of organ involvement was based on the histological analysis of tissue biopsies obtained from suspected organs in AL and PCD cases.

[18F]FBP SUVmax and TBR analyses revealed comparable uptake in AL patients and significantly greater uptake than in PCD patients. Distinct regional distributions of [18F]FBP and [18F]FDG were observed between the PCD and AL groups. The [18F]FBP SUVmax and visual analysis provided comparable measures of organ involvement and demonstrated high sensitivity, outperforming [18F]FDG in detecting organ amyloidosis in both PCD and AL patients. More organ involvement was detected by [18F]FBP PET (SUVmax or visual) than by biopsies based evaluation.

[18F]FBP PET, through both visual and SUVmax analysis, is more sensitive than [18F]FDG PET and biopsy-based analysis for detecting organ amyloidosis in PCD and AL patients. It serves as a valuable noninvasive method for the early and accurate detection of systemic amyloidosis, with the potential to improve diagnostic precision and facilitate timely intervention in systemic amyloidosis patients.

Amyloidosis, a polymeric deposition disease classified according to protein subtype, may have varied pulmonary manifestations. Its anatomic-radiologic phenotypes include nodular, cystic, alveolar-septal, and tracheobronchial forms. Clinical presentation may range from asymptomatic parenchymal nodules to respiratory failure from diffuse parenchymal infiltration or diaphragmatic deposition.

In this review, we systematically describe the molecular subtypes of amyloidosis and their clinical and radiologic findings in the lungs as well as key extrapulmonary organ systems. We detail novel treatment approaches to systemic amyloidosis. We also discuss prognostic elements for each subtype. We identify key clinical scenarios where reaching a precise diagnosis can be complicated, and we offer insights on the varied presentations of pulmonary amyloidosis.

Pulmonary amyloidosis is often difficult to diagnose as it may mimic other conditions, including fibrotic interstitial lung diseases and neoplasms, or can co-exist with certain connective tissue diseases. Despite some early artificial intelligence screening tools, improved familiarity among clinicians can aid in the more accurate and timely diagnosis of this multidimensional clinical entity. We additionally believe that multidisciplinary clinical pathwaysto diagnose and/or treat pulmonary amyloidosis have the potential to improve awareness, decrease diagnostic delay, and further elucidate knowledge on this multifaceted disease.

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.

The assessment of pulmonary nodules is a common and often challenging clinical scenario. This evaluation becomes even more complex in patients with connective tissue diseases (CTDs), as a range of disease-related factors must also be taken into account. These diseases are characterized by immune-mediated chronic inflammation, leading to tissue damage, collagen deposition, and subsequent organ dysfunction. A thorough examination of nodule features in these patients is required, incorporating anatomic and functional information, along with patient demographics, clinical factors, and disease-specific knowledge. This integrated approach is vital for effective risk stratification and precise diagnosis. This review article addresses specific CTD-related factors that should be taken into account when evaluating pulmonary nodules in this patient group.

Pulmonary amyloidosis is characterized by extracellular deposition of fibrous protein called amyloid in the lungs and has three subtypes: nodular, diffuse, and tracheobronchial amyloidosis. Pulmonary nodular amyloidosis can mimic other lung diseases including infectious diseases, metastatic lung tumors, sarcoidosis, and pulmonary hyalinizing granuloma. A biopsy of the lesion is essential for a definitive diagnosis. Herein, we report the case of a 66-year-old man who presented for shortness of breath on exertion and was diagnosed with nodular pulmonary amyloidosis on ultrasound-guided percutaneous needle biopsy. A chest X-ray and computed tomography (CT) revealed bilateral slowly growing multiple calcified pulmonary nodules and cavities. Malignancy was suspected based on 18F-fluoro-deoxyglucose (18F-FDG) positron emission tomography/CT (PET/CT) images. An ultrasound-guided percutaneous needle biopsy was performed, and histopathologic examination of the lesion confirmed nodular pulmonary amyloidosis. This case highlights the importance of considering nodular pulmonary amyloidosis in the differential diagnosis of pulmonary nodules with increased uptake of 18F-FDG on PET/CT and the utility of ultrasound-guided needle biopsy in the definitive diagnosis.

Amyloidosis is a disease caused by misfolded proteins that deposit in the extracellular matrix as fibrils, resulting in the dysfunction of the involved organ. The lung is a common target of Amyloidosis, but pulmonary amyloidosis is uncommonly diagnosed since it is rarely symptomatic. Diagnosis of pulmonary amyloidosis is usually made in the setting of systemic amyloidosis, however in cases of localized pulmonary disease, surgical or transbronchial tissue biopsy might be indicated. Pulmonary amyloidosis can be present in a variety of discrete entities. Diffuse Alveolar septal amyloidosis is the most common type and is usually associated with systemic AL amyloidosis. Depending on the degree of the interstitial involvement, it may affect alveolar gas exchange and cause respiratory symptoms. Localized pulmonary Amyloidosis can present as Nodular, Cystic or Tracheobronchial Amyloidosis which may cause symptoms of airway obstruction and large airway stenosis. Pleural effusions, mediastinal lymphadenopathy and pulmonary hypertension has also been reported. Treatment of all types of pulmonary amyloidosis depends on the type of precursor protein, organ involvement and distribution of the disease. Most of the cases are asymptomatic and require only close monitoring. Diffuse alveolar septal amyloidosis treatment follows the treatment of underlying systemic amyloidosis. Tracheobronchial amyloidosis is usually treated with bronchoscopic interventions including debulking and stenting or with external beam radiation. Long-term prognosis of pulmonary amyloidosis usually depends on the type of lung involvement and other organ function.

A 61-year-old woman, an ex-smoker with a 10 pack year smoking history, was referred to our clinic for the evaluation of insidious dyspnea and diffuse, bilateral infiltrates on a chest radiograph. She reported that she had been experiencing dyspnea on exertion and dry cough for the past 1.5 years. She denied fevers, chills, hemoptysis, or weight loss. Aside from a smoking history, there were no comorbidities or environmental exposures. She had no family history of lung diseases or other disorders. She worked as a school teacher and had no occupational exposures. There were no pets in the home and no prior occupational exposures.

Localized gastric amyloidosis (LGA) is a rare disease characterized by abnormal extracellular deposition of amyloid protein restricted to the stomach and it is confirmed by positive results of Congo red staining. Over decades, only a few cases have been reported and studies or research focusing on it are few. Although LGA has a low incidence, patients may suffer a lot from it and require proper diagnosis and management. However, the pathology of LGA remains unknown and no overall review of LGA from its presentations to its prognosis has been published. Patients with LGA are often asymptomatic or manifest atypical symptoms, making it difficult to differentiate from other gastrointestinal diseases. Here, we report the case of a 70-year-old woman with LGA and provide an overview of case reports of LGA available to us. Based on that, we conclude current concepts of clinical manifestations, diagnosis, treatment, and prognosis of LGA, aiming at providing a detailed diagnostic procedure for clinicians and promoting the guidelines of LGA. In addition, a few advanced technologies applied in amyloidosis are also discussed in this review, aiming at providing clinicians with a reference of diagnostic process. With this review, we hope to raise awareness of LGA among the public and clinicians.

Primary Sjögren's Syndrome (pSS) is characterized by an immune-mediated lymphoplasmacytic infiltration of the salivary and lacrimal glands. Pulmonary nodules are not uncommonly encountered in these patients.

We conducted a retrospective computer-assisted search for patients with pSS who were encountered at our institution between 1999 and 2018 and had histologically characterized pulmonary nodule(s)/mass (es) (PNs).

Of 41 patients with pSS and PNs, median age was 67 years (IQR, 56-74), 94% were women, and 39% had a smoking history. The PNs proved to be non-Hodgkin lymphoma (NHL) in 16 patients (39%), lung carcinoma in 11 patients (27%), other malignancies in 2 patients (5%), and benign diseases in remaining 12 patients (29%), including 7 with amyloidomas. Patients with NHL were younger (p = 0.006) while smoking exposure was more prevalent in patients with lung carcinoma (p = 0.022). Patients with NHL had a higher number of PNs and more often manifested random distribution, cysts, ground-glass changes and consolidations. Upper and/or mid-lung location, spiculated borders, solitary nodule, increasing size, and higher SUV_mean on FDG-PET scan were associated with lung carcinoma. At the end of follow-up (median 5.9 years), 8 patients (20%) had died and included 5 patients with lung carcinoma; no deaths were observed in the NHL group.

The majority of biopsied PNs in patients with pSS were malignant, most commonly lymphomas. Smoking exposure, solitary nodule, and high FDG avidity were more frequently associated with lung carcinoma. The clinical context, CT and ¹⁸FDG-PET are complementary in the evaluation and management of PNs in patients with pSS.

Amyloidosis is an uncommon heterogeneous and multi-systemic disease characterized by extracellular amyloid deposition. The size of proteins varies and forms a part of local disease or systemic process. Light chain amyloidosis (AL) is the most prevalent form of systemic amyloidosis which may also be seen in localized disease. Isolated tracheobronchial amyloidosis (TBA) is rather unusual with local amyloid deposition which may pose a diagnostic dilemma with subsequent therapeutic challenge. Awareness of such a presentation is crucial in the diagnosis of this rare disease. We describe three cases who presented with haemoptysis, which on further evaluation were diagnosed as isolated TBA, and a review of literature.

Systemic amyloidosis is a heterogeneous group of disorders where misfolded proteins deposit in the various organs as nonbranching fibrils with a β-pleated-sheet structure called amyloid. Extensive extracellular deposition of these amyloid fibrils eventually leads to organ dysfunction. Involvement of the heart, termed as cardiac amyloidosis, leads to heart failure if left untreated and carries high morbidity and mortality. Current interest in cardiac amyloidosis is growing rapidly thanks to the recent development of effective targeted treatment options, driving the need for better and earlier detection of the condition, which is largely underdiagnosed and far commoner than recognized. Timely diagnosis of cardiac amyloidosis is challenging, but is poised to improve with emergence of newer noninvasive imaging techniques, potentially obviating the need for endomyocardial biopsy in some patients and providing prognostic information. With recent advances in the therapeutic options for cardiac amyloidosis, an area of immense interest is the adoption of imaging as biomarkers for longitudinal assessment of disease progression and treatment response. In this article, we provide an overview of cardiac amyloidosis, discuss the role of imaging modalities in cardiac amyloidosis, and explore future directions for imaging in cardiac amyloidosis.

The clinical diagnosis of pulmonary involvement in individuals with systemic AL amyloidosis remains challenging. [18F]florbetapir imaging has previously identified AL amyloid deposits in the heart and extra-cardiac organs. The aim of this study is to determine quantitative [18F]florbetapir pulmonary kinetics to identify pulmonary involvement in individuals with systemic AL amyloidosis.

We prospectively enrolled 58 subjects with biopsy-proven AL amyloidosis and 9 control subjects (5 without amyloidosis and 4 with ATTR cardiac amyloidosis). Pulmonary [18F]florbetapir uptake was evaluated visually and quantified as distribution volume of specific binding (Vs) derived from compartmental analysis and simpler semiquantitative metrics of maximum standardized uptake values (SUVmax), retention index (RI), and target-to-blood ratio (TBR).

On visual analysis, pulmonary tracer uptake was absent in most AL subjects (40/58, 69%); 12% (7/58) of AL subjects demonstrated intense bilateral homogeneous tracer uptake. In this group, compared to the control group, Vs (median Vs 30-fold higher, 9.79 vs. 0.26, p < 0.001), TBR (median TBR 12.0 vs. 1.71, p < 0.001), and RI (median RI 0.310 vs. 0.033, p < 0.001) were substantially higher. Notably, the AL group without visually apparent pulmonary [18F]florbetapir uptake also demonstrated a > 3-fold higher Vs compared to the control group (median 0.99 vs. 0.26, p < 0.001). Vs was independently related to left ventricular SUVmax, a marker of cardiac AL deposition, but not to ejection fraction, a marker of cardiac dysfunction. Also, intense [18F]florbetapir lung uptake was not related to [11C]acetate lung uptake, suggesting that intense [18F]florbetapir lung uptake represents AL amyloidosis rather than heart failure.

[18F]florbetapir PET/CT offers the potential to noninvasively identify pulmonary AL amyloidosis, and its clinical relevance warrants further study.

Light chain deposition disease (LCDD) rarely involves the lungs. We report clinical and radiologic findings of pulmonary LCDD.

We retrospectively identified patients with biopsy-proven pulmonary LCDD seen at Mayo Clinic (Rochester, Minnesota) from January 1997 through December 2018. Demographic, clinical, and imaging features were analyzed.

We identified 10 patients with pulmonary LCDD (median age at diagnosis, 55 years; range, 39-77 years). Eight patients were women and 7 were never-smokers. Dyspnea (n = 3) and chest pain (n = 3) were the most common respiratory symptoms. Associated conditions included Sjögren syndrome (n = 6), sarcoidosis (n = 1), and limited scleroderma (n = 1). Eight patients had mucosa-associated lymphoid tissue (MALT) lymphoma. Among the 9 patients with chest computed tomography (CT) images, 8 (89%) had cysts. Cysts were predominantly distributed in the lower lung and were round or oval. All patients had multiple cysts (5 patients had 1-5 cysts, 3 had >20 cysts). The median diameter of the largest cyst was 18 mm (range, 5-68 mm). All 9 patients had solid nodules (3 had >10 nodules). Five patients had subsolid nodules. The median diameter of the largest solid nodules was 13 mm (range, 6-26 mm). Positron emission tomography-CT images were available for 8 patients. The median maximum standardized uptake value of the most avid pulmonary nodule was 2.2 (range, 1.9-6.0). Two patients died during a median follow-up of 2.3 years (range, 0.5-9.9 years).

Pulmonary LCDD is characterized by cysts and nodules. The disease is associated with MALT lymphoma, especially in the setting of Sjögren syndrome.

Although pathological confirmation is the gold standard for diagnosis of amyloidosis, there is a need for a relevant imaging modality to identify involved organs and evaluate disease extent. Thus, we prospectively investigated imaging findings of Tc-DPD scintigraphy in AL and ATTR amyloidosis.A total of 21 subjects with pathologically confirmed AL or ATTR amyloidosis were included. Pretreatment whole body Tc-DPD planar scanning and regional SPECT/CT were performed in all subjects. For allegedly involved organs, Tc-DPD uptake was visually and semi-quantitatively evaluated on a 4-point scale (grade 0: no uptake, 1: uptake less than spine, 2: uptake similar to spine, and 3: uptake greater than spine).There were 29 organs involved in AL and 12 in ATTR. Significant Tc-DPD uptake was found in 24 organs (sensitivity = 82.8%) in AL and 9 organs (sensitivity = 75.0%) in ATTR. Additional SPECT/CT was helpful to ensure abnormal DPD uptake in the involved organs, which was uncertain by attenuation in planar imaging. Degree of Tc-DPD uptake was significantly higher in ATTR compared with AL amyloidosis (P = .017). Diffuse soft tissue uptake with photon defects in the liver area was found only in ATTR amyloidosis.This study showed that Tc-DPD scintigraphy might have capacity to differentiate between AL and ATTR subtypes with good sensitivity in various organs involving primary systemic AL and ATTR amyloidosis. Additional SPECT/CT significantly improved the diagnostic efficacy of Tc-DPD scintigraphy.

Pulmonary amyloidosis is a rare disease that incorporates deposition of amyloid microfibril material in the lung parenchyma. The condition generally presents as an indolent subacute-to-chronic pulmonary disease and requires tissue biopsy to establish the diagnosis. Nodular pulmonary amyloidosis, a subtype of pulmonary amyloidosis, is characterised by special radiographic and pathological features. While the disease can be associated with inflammatory conditions; its association with mucosal-associated lymphoid tissue (MALT lymphoma) is unusual and carries management challenges. Herein, we illustrate a case study of nodular pulmonary amyloidosis associated with underlying MALT lymphoma in a patient with known systemic lupus erythematosus. The aim of this article is to share the management experience of this complex condition with the medical community and to conduct an up-to-date literature review on nodular pulmonary amyloidosis.

We present a case of a 70-year-old man with enlarged mediastinal and cervical lymph nodes that provided interesting radiologic and pathologic observations. The 70-year-old black man was found to have enlarged mediastinal lymph nodes. He had symptoms of atypical chest pain and generalized weakness for 2 weeks prior to the diagnosis. He denied shortness of breath, fever, chills, or night sweats. He was treated for hypertension and onychomycosis. Basic laboratory findings were within normal limits. Pulmonary function tests at the time of presentation showed FEV1, FVC, and FEV1/FVC ratio of 123% predicted, 133% predicted, and 0.7, respectively. Meanwhile, total lung capacity and carbon monoxide diffusing capacity were 103% and 107% predicted, respectively. Two weeks before he presented to our institution, the patient underwent bronchoscopy with transbronchial biopsies of the right lower lobe and endobronchial ultrasound-guided transbronchial needle aspiration of the right hilar lymph nodes.

Although several case reports and case series have described (18)F-FDG PET/CT in amyloidosis, the value of (18)F-FDG PET/CT for diagnosing amyloidosis has not been clarified. We investigated the imaging findings of (18)F-FDG PET/CT in patients with primary systemic AL amyloidosis.

Subjects were 15 patients (M:F = 12:3; age, 61.5 ± 7.4 years) with histologically confirmed primary systemic AL amyloidosis who underwent pretreatment (18)F-FDG PET/CT to rule out the possibility of malignancy or for initial workup of alleged cancer. For involved organs, visual and semiquantitative analyses were performed on (18)F-FDG PET/CT images. In total, 22 organs (10 hearts, 5 kidneys, 2 stomachs, 2 colons, 1 ileum, 1 pancreas, and 1 liver) were histologically confirmed to have primary systemic AL amyloidosis.

F-FDG uptake was significantly increased in 15 of the 22 organs (68.2 %; 10 hearts, 2 kidneys, 1 colon, 1 ileum, and 1 liver; SUVmax = 7.0 ± 3.2, range 2.1-14.1). However, in 11 of 15 PET-positive organs (78.6 %; 10 hearts and the ileum), it was difficult to differentiate pathological uptake from physiological uptake. Definitely abnormal (18)F-FDG uptake was found in only 4 of the 22 organs (18.2 %; 2 kidneys, 1 colon, and the liver). (18)F-FDG uptake was negative for pancreas and gastric lesions.

Although (18)F-FDG PET/CT showed high uptake in two-thirds of the organs involving primary systemic AL amyloidosis, its sensitivity appeared to be low to make differentiation of pathological uptake from physiological uptake. However, due to the small number of cases, further study for the role of (18)F-FDG PET/CT in amyloidosis will be warranted.

We herein examined the biological effects of cells treated with (18)F labeled drugs for positron emission tomography (PET). The relationship between the intracellular distribution of (18)F and levels of damaged DNA has yet to be clarified in detail. We used culture cells (Chinese Hamster Ovary cells) treated with two types of (18)F labeled drugs, fluorodeoxyglucose (FDG) and fluorine ion (HF). FDG efficiently accumulated in cells, whereas HF did not. To examine the induction of DNA double strand breaks (DSB), we measured the number of foci for 53BP1 that formed at the site of DNA DSB. The results revealed that although radioactivity levels were the same, the induction of 53BP1 foci was stronger in cells treated with (18)F-FDG than in those treated with (18)F-HF. The clonogenic survival of cells was significantly lower with (18)F-FDG than with (18)F-HF. We concluded that the efficient accumulation of (18)F in cells led to stronger biological effects due to more severe cellular lethality via the induction of DNA DSB.