Deposition Of Amyloid Protein Research Articles

Tracheobronchial amyloidosis following COVID-19 infection.

Deposition of amyloid proteins in extracellular space can occur due to uncontrolled inflammatory processes. Tracheobronchial amyloidosis (TBA) is a rare form of such disease. A 68-year-old woman was evaluated for chronic cough following a COVID-19 infection. Although post-viral sequelae were suspected, further investigation revealed TBA. This condition involves amyloid deposits within the airways. The temporal association with COVID-19 raises a potential etiological link, suggesting viral-induced inflammatory or immune-mediated processes may play a role. This case underlines the need to consider rare etiologies like TBA in patients with unresolved respiratory symptoms post-COVID-19.

Costal Amyloidosis: First Case in Literature

Amyloidosis is a heterogeneous group of diseases characterized by the extracellular deposition of amyloid proteins in various tissues and organs, which leads to significant morbidity and mortality. The most commonly affected organs include the kidneys, liver, spleen, heart, and nervous system, where the deposition of amyloid proteins disrupts normal function and causes a wide range of clinical manifestations. Involvement of osseous structures, particularly the ribs, is exceedingly rare and has not been extensively documented in the medical literature, making it a subject of significant clinical interest. This study aims to present a rare and fortuitously discovered case of costal amyloidosis in a patient who initially presented with a chest wall mass. The patient’s presentation, diagnostic workup, and subsequent management are detailed to provide a comprehensive overview of this unusual manifestation of amyloidosis. Clinical evaluation revealed a firm, non-tender mass on the chest wall, prompting further investigation. Biological analyses included a series of laboratory tests to rule out common differential diagnoses and identify potential systemic involvement. Radiological evaluation comprised of advanced imaging techniques, including chest X-ray, computed tomography (CT), and magnetic resonance imaging (MRI), which highlighted the nature and extent of the osseous involvement. A biopsy of the mass was performed, and histopathological examination confirmed the diagnosis of amyloidosis through the identification of amyloid deposits using specific staining techniques. The case also examines the evolutionary aspects of the disease, discussing the progression and changes observed over time through regular follow-ups. Therapeutic strategies were implemented based on the latest guidelines and tailored to the patient's specific condition, including both pharmacological and surgical interventions. The short-term and long-term outcomes of these interventions are analyzed, highlighting the challenges and successes encountered during the treatment process. By presenting this case, we aim to shed light on the rare occurrence of costal amyloidosis, its diagnostic challenges, and therapeutic considerations. This case underscores the importance of considering amyloidosis in the differential diagnosis of chest wall masses and contributes to the broader understanding of the disease's clinical spectrum. Additionally, it emphasizes the necessity of a multidisciplinary approach in managing such rare and complex cases, ensuring comprehensive care and improved patient outcomes.

Investigating the Impact of IL-6 and CXCL8 on Neurodegeneration and Cognitive Decline in Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder primarily affecting the elderly, characterized by severe cognitive impairment and memory loss. Emerging evidence suggests that neuroinflammation plays a significant role in AD pathogenesis, with cytokines like interleukin-6 (IL-6) and C-X-C motif chemokine ligand 8 (CXCL8) contributing to the disease progression. We utilized GEO datasets to identify IL-6 and CXCL8 as pivotal inflammatory markers in AD. In vitro experiments were conducted using SK-N-BE(2)-M17 and THP-1 cell lines treated with IL-6 and CXCL8 to model AD. Additionally, in vivo tests on Amyloid Precursor Protein/Presenilin 1 (APP/PS1) AD mouse models were performed to assess the impact of these cytokines on cognitive functions and brain pathology. The results indicated a significant decrease in cell viability, increased apoptosis, and elevated inflammatory factor secretion following IL-6 and CXCL8 treatment in vitro. In vivo, AD mouse models treated with these cytokines exhibited exacerbated emotional distress, decreased social interaction, impaired cognitive functions, and increased amyloid protein deposition in neural tissues. The study highlights the detrimental effects of IL-6 and CXCL8 on neuronal health and cognitive functions in AD. These findings suggest that targeting these cytokines could offer potential therapeutic interventions for improving patient outcomes in Alzheimer's disease.

Challenges in the approach to a patient with aortic stenosis and cardiac amyloidosis with ATTR mutation associated with negative scintigraphy - A case report

IntroductionCardiac amyloidosis (CA) poses significant diagnostic and therapeutic challenges. In this case report, we detail a patient with CA due to a rare transthyretin (CA-TTR) mutation, manifesting with negative myocardial scintigraphy and requiring genetic testing for diagnosis. The patient also had severe aortic stenosis (AS), necessitating discussion with a heart team to determine the optimal treatment strategy. Case reportA 70-year-old male with a family history of sudden death was previously diagnosed with third-degree atrioventricular block and treated with a pacemaker. He presented with worsening exertional dyspnoea, and examination revealed a third heart sound, a systolic murmur indicative of AS and bilateral muscular atrophy in the thenar region. Transthoracic echocardiography indicated severe AS and moderate left ventricular dysfunction, with images suggesting infiltrative disease. Pyrophosphate scintigraphy revealed no abnormal cardiac tracer uptake. Cardiac magnetic resonance imaging (MRI) revealed extensive, heterogeneous, subendocardial late gadolinium enhancement in both the atria and ventricles, which was consistent with CA. Genetic testing identified the Phe84Leu mutation in the TTR gene. Following heart team discussions, the patient underwent successful transcatheter aortic valve implantation (TAVI) and remained asymptomatic in follow-up, being monitored at an outpatient clinic specializing in CA and using tafamidis. DiscussionCA-TTR can be an autosomal dominant disease with variable penetrance involving abnormal amyloid protein deposition in tissues and can often be diagnosed noninvasively via myocardial scintigraphy. However, some TTR mutations do not affect scintigraphy results, necessitating genetic testing when clinical suspicion is high, potentially avoiding endomyocardial biopsy. Moreover, AS occurs in up to 16 % of TTR amyloidosis patients, with the conditions mutually exacerbating each other. Recent consensus suggests that TAVI reduces mortality in patients with severe AS and amyloidosis. ConclusionsVarious diagnostic algorithms emphasize the use of myocardial scintigraphy for suspected CA-TTR. Genetic testing is crucial when scintigraphy results are negative, but clinical suspicion remains high, potentially circumventing invasive procedures. Compared with medical management alone, TAVI has been shown to improve quality of life and survival in patients with concurrent severe AS and CA.

Anticoagulation in Atrial Fibrillation Associated With Cardiac Amyloidosis: A Narrative Review.

Cardiac amyloidosis (CA) involves the abnormal deposition and accumulation of amyloid proteins in the heart muscle. A hallmark of disease progression is declining heart function, which can lead to structural irregularities, arrhythmias, and ultimately heart failure. Atrial fibrillation (AF) is the most common arrhythmia that presents in CA patients, and this arrhythmia is significant because it can moderately increase the risk of patients developing intracardiac thrombi, thereby putting them at risk for thromboembolic events. The management of this complication entails the use of anticoagulants like vitamin K antagonists and direct oral anticoagulants to reduce the risk of thrombus formation. This article seeks to review AF in CA and the use of anticoagulation therapy for the management and reduction of thromboembolic risk. The major conclusions of this review are centered around the need for safe administration of anticoagulant therapy to CA patients, regardless of their CHA2DS2-VASc risk score. This review highlights the importance of taking a multidisciplinary or collaborative approach to CA treatment to ensure that all aspects of this multifaceted disease can be properly managed while minimizing adverse events like bleeding risk and drug-drug interactions.

Advancing Renal Amyloidosis Care: The Role of Modern Diagnostic Techniques with the Potential of Enhancing Patient Outcomes.

Renal amyloidosis is a set of complex disorders characterized by the deposition of amyloid proteins in the kidneys, which causes gradual organ damage and potential kidney failure. Recent developments in diagnostic methods, particularly mass spectrometry and proteome profiling, have greatly improved the accuracy of amyloid typing, which is critical for disease management. These technologies provide extensive insights into the specific proteins involved, allowing for more targeted treatment approaches and better patient results. Despite these advances, problems remain, owing to the heterogeneous composition of amyloid proteins and the varying efficacy of treatments based on amyloid type. Access to sophisticated diagnostics and therapy varies greatly, highlighting the global difference in renal amyloidosis management. Future research is needed to investigate next-generation sequencing and gene-editing technologies, like clustered regularly interspaced short palindromic repeats (CRISPR), which promise more profound insights into the genetic basis of amyloidosis.

Amyloid goiter with diffuse thyrolipomatosis: a rare entity

Diffuse thyroid lipomatosis with amyloid deposition is a rare entity. We report a case of a 42-year-old lady who presented with progressive enlargement of the thyroid gland with compressive symptoms. Her thyroid hormone levels were within normal limits. Imaging revealed enlarged thyroid gland with multiple fat density lesions. She underwent total thyroidectomy, and histopathology revealed diffuse infiltration of thyroid stroma by mature adipose tissue and an associated amyloid deposition. A diagnosis of amyloid goiter with diffuse lipomatosis of the thyroid gland was rendered. Only a few cases of diffuse lipomatosis with concurrent deposition of amyloid protein have been reported in the literature.

Raman microspectroscopy for label‐free diagnosis of amyloid light‐chain amyloidosis in various organs

AbstractSystemic amyloidosis is a group of diseases in which misfolded proteins aggregate as fibrous amyloid proteins with a β‐sheet structure and deposit in organs, resulting in organ failure. Most types of amyloidosis have a poor prognosis, and prompt diagnosis is essential for treatment. Systemic immunoglobulin light‐chain (AL) amyloidosis is a type of amyloidosis that occurs when abnormal immunoglobulin light‐chain proteins are deposited in various organs and tissues. The deposition of amyloid proteins in tissues has traditionally been confirmed using Congo red staining and polarised light microscopy, which show apple‐green birefringence. In this study, we aimed to verify whether amyloid deposition in the heart, kidney, rectum, duodenum and skin can be detected using Raman microspectroscopy. Serial sections were prepared from formalin‐fixed paraffin‐embedded tissue biopsy samples obtained from patients with systemic amyloidosis. One of the serial sections was stained with Congo red to confirm the deposition of amyloid proteins using polarised light microscopy, whereas the other was left unstained for Raman microspectroscopy. A characteristic peak at Raman shift of 1665–1680 cm−1, which may represent a β‐sheet structure of amyloid proteins, was recorded in the area where the amyloid deposition had been confirmed by Congo red staining. Based on the peak at 1640–1680 cm−1, a colour map was obtained to detect amyloid protein‐positive regions. Thus, amyloid protein detection using Raman microspectroscopy may be useful for rapid diagnosis of amyloidosis.

Efficacy of topical gabapentin in women with primary macular amyloidosis: A side-by-side triple-blinded randomized clinical trial.

Primary cutaneous macular amyloidosis (PCMA) is a chronic pruritic cutaneous disease characterized by heterogeneous extracellular deposition of amyloid protein in the skin. This study aimed to evaluate the efficacy of topical 6% gabapentin cream for the treatment of patients with PCMA. In this triple-blind clinical trial, a total of 34 patients, who were diagnosed with PCMA, treated using two different strategies of topical gabapentin as the active group and vehicle cream as the control group. Pruritus score reduction in both groups was statistically significant compared with the baseline value (p < 0.001). There was a significant pigmentation score reduction in intervention group compared with control group after 1 month of the study (p < 0.001). The differences of pigmentation score changes between the groups were not significant at month 2 (p = 0.52) and month 3 (p = 0.22). The results of this study suggest that topical gabapentin cream may be effective as a topical agent in the treatment of pruritus associated with PCMA without any significant adverse effects. It is recommended to perform similar studies with a larger sample size and longer duration in both sexes.

A case of bilateral amyloidosis localized to extraocular muscles mimicking thyroid eye disease

BackgroundAmyloidosis is a rare condition characterized by the abnormal deposition of amyloid proteins in various tissues and organs. While systemic amyloidosis has been well-documented, amyloid deposition in extraocular muscles is an exceptionally rare occurrence, with only 35 reported cases. This case report sheds light on the importance of considering amyloidosis in the differential diagnosis of patients presenting with proptosis and diplopia, which are often associated with thyroid eye disease.Case presentationA woman in her twenties sought medical attention due to a complaint of diplopia. Her ocular examination revealed almost normal findings except for exotropia and proptosis. Orbital magnetic resonance imaging displayed fusiform enlargement of nearly all eye muscles, a presentation typically observed in thyroid eye disease. However, despite corticosteroid therapy, her symptoms showed no improvement. Given the unusual lack of response to conventional treatment, and inhomogeneous enhancement of the muscle, an extraocular muscle biopsy was conducted. This biopsy yielded a unique finding—amyloid deposition within the muscle tissue. This discovery was particularly intriguing due to the extreme rarity of amyloidosis affecting extraocular muscles, with fewer than three dozen documented cases worldwide.ConclusionThis unique case underscores the critical need for a comprehensive approach to diagnosing patients with proptosis and diplopia. While these symptoms are commonly attributed to thyroid eye disease, it is essential to consider alternative diagnoses such as amyloidosis, especially when standard treatments fail to yield results. The discovery of amyloid deposition in the extraocular muscles, although exceedingly rare, emphasizes the significance of a thorough differential diagnosis. In conclusion, this case report highlights the importance of vigilance in clinical practice, encouraging ophthalmologists to explore less common diagnostic possibilities when faced with challenging cases. Further research and clinical investigation are warranted to better understand the mechanisms and potential treatments for amyloidosis affecting the extraocular muscles.

Optimizing cardiac amyloidosis assessment: utility of 1-h and 3-h 99mTc-PYP imaging

BackgroundTransthyretin amyloid cardiomyopathy (ATTR-CM), characterized by the extracellular deposition of an insoluble amyloid protein in the heart, is one of the main causes of heart failure in elderly patients. In this study, our primary objective was to explore the diverse applications and temporal significance of 1-h and 3-h imaging using 99mTc-PYP in the context of ATTR-CM. Additionally, we compared tracer kinetics in the heart and bone to comprehensively assess the diagnostic advantages and time-related considerations associated with these two incubation periods.MethodsTwenty-seven patients at Nagasaki University Hospital who underwent 99mTc-PYP planar, and SPECT cardiac imaging were classified into two groups (ATTR-CM-positive and -negative groups) based on the American Heart Association statement. Cardiac retention was assessed with both a semiquantitative visual score and a quantitative analysis. To assess bone accumulation, a ROI with an equal volume was drawn on the sternum and calculated as the bone-to-contralateral ratio (B/CL). We also evaluated correlation between heart-to-contralateral lung (H/CL) ratio and left ventricular wall thickness.ResultsAmong patients who underwent 99mTc-PYP imaging, the H/CL ratio was significantly higher at 1 h than at 3 h regardless of the group (from 2.20 ± 0.36 to 1.99 ± 0.35, p < 0.01 in the positive group and from 1.35 ± 0.12 to 1.19 ± 0.21, p = 0.01 in the negative group). The gap of H/CL between highest H/CL of negative case and lowest H/CL of positive case was narrower in 3 h. On the other hand, correlation between H/CL and left ventricular posterior wall thickness tends to be clearer in 3 h (p = 0.12, r = 0.30 for 1 h, p = 0.04, r = 0.39 at 3 h).ConclusionOur study suggests that both 1-h and 3-h incubation times for 99mTc-PYP imaging have different benefits for ATTR cardiac amyloidosis. A one-hour incubation may be preferable for differential diagnostic purposes, while a three-hour incubation may provide greater utility in evaluating disease severity.

A multiclass extreme gradient boosting model for evaluation of transcriptomic biomarkers in Alzheimer’s disease prediction

BackgroundPatients with young-onset Alzheimer's disease (AD) (before the age of 50 years old) often lack obvious imaging changes and amyloid protein deposition, which can lead to misdiagnosis with other cognitive impairments. Considering the association between immunological dysfunction and progression of neurodegenerative disease, recent research has focused on identifying blood transcriptomic signatures for precise prediction of AD. MethodsIn this study, we extracted blood biomarkers from large-scale transcriptomics to construct multiclass eXtreme Gradient Boosting models (XGBoost), and evaluated their performance in distinguishing AD from cognitive normal (CN) and mild cognitive impairment (MCI). ResultsIndependent testing with external dataset revealed that the combination of blood transcriptomic signatures achieved an area under the receiver operating characteristic curve (AUC of ROC) of 0.81 for multiclass classification (sensitivity = 0.81; specificity = 0.63), 0.83 for classification of AD vs. CN (sensitivity = 0.72; specificity = 0.73), and 0.85 for classification of AD vs. MCI (sensitivity = 0.77; specificity = 0.73). These candidate signatures were significantly enriched in 62 chromosome regions, such as Chr.19p12-19p13.3, Chr.1p22.1-1p31.1, and Chr.1q21.2-1p23.1 (adjusted p < 0.05), and significantly overrepresented by 26 transcription factors, including E2F2, FOXO3, and GATA1 (adjusted p < 0.05). Biological analysis of these signatures pointed to systemic dysregulation of immune responses, hematopoiesis, exocytosis, and neuronal support in neurodegenerative disease (adjusted p < 0.05). ConclusionsBlood transcriptomic biomarkers hold great promise in clinical use for the accurate assessment and prediction of AD.

Unveiling Alarming Trends: Worsening All Cause Mortality in US Adults over 25 with Amyloid 1999-2020 Analysis

Introduction: Amyloidosis is a collective term for conditions with an abnormal extracellular deposition of amyloid protein. Amyloidosis can be classified based on the location of deposition (localized vs systemic) and by the different subtypes of proteins which are created as a result of a variety of diseases (plasma cell dyscrasias, chronic inflammation, nephrotic syndrome, genetic). Depending on the affected organs, amyloidosis can present with, not limited to, hepatomegaly, renal impairment, nerve conduction impairment, cardiac conduction abnormalities, restrictive cardiomyopathy, and multiorgan failure. In the last century there has been an increase in innovations leading to a better understanding of the pathology, diagnostic tests, staging, and treatment options for amyloidosis. Our study aims to compare all cause mortality trends in adults over 25 years old diagnosed with amyloidosis in the United States. Methods: The national mortality trends from 1999 to 2020 for all subtypes of amyloid were analyzed from the CDC WONDER database. The data was extracted using ICD codes E85 (Amyloidosis) with subgroups E85.0 (Non-neuropathic heredofamilial amyloidosis), E85.3 (Secondary systemic amyloidosis), E85.4 (Organ-limited amyloidosis), E85.8 (Other amyloidosis), and E85.9 (Amyloidosis, unspecified. Data was stratified for age groups above 25 years old. Age-adjusted mortality rates (AAMRs) were calculated per 100,000 people and death certificate data was stratified by reported sex, race/ethnicity, and US census region. Results: Between 1999 and 2020 there were 40,015 deaths from amyloid. Our analysis revealed that all-cause AAMR per 100,000 people with amyloid showed an increasing trend between 1999 to 2020 (Figure 1). Subgroup analysis on race/ethnicity revealed the AAMR for the Black population has been consistently higher to other groups (Table 1). On average, from 1999 to 2020, the Black population had the highest AAMR (1.52 AAMR) followed by the White population (0.78 AAMR), Hispanic (0.55 AAMR), and Asian (0.5 AAMR). Further subgroup analysis revealed men have a higher AAMR (1.9 AAMR, 2020) compared to women (0.8 AAMR, 2020). Overall there are similar census region trends of all mortality in Amyloid: North (1.5 AAMR, 2020), Midwest (1.5 AAMR, 2020), South (1.0, AAMR, 2020) and West (1.3 AAMR, 2020). Conclusion: Due to advancement in technology, amyloid diseases are becoming more widely recognized and increasingly diagnosed. Unfortunately, treatment of amyloidosis remains limited to early diagnosis and treatment of the underlying condition. This includes modalities such as chemotherapy and stem cell transplantation for plasma cell dysplasias and TTR stabilizers for hereditary amyloidosis. These trends in increase in AAMR likely reflect the increased awareness/diagnostics of amyloid disease and complications. The African American population may have higher AAMR due to socioeconomic and environmental factors, health disparities, and research bias. We also suspect men have a higher ATTR than women as it has been reported that ATTR and AL Amyloidosis tends to occur more frequently in men than women and is associated with more severe disease (Kroi et al., 2020, Desport et al., 2012). Further research is necessary to expand on the disparities seen with the ultimate goal of providing targeted therapies to reverse this downward trend.

SAT499 Amyloid Goiter: A Case Series

Abstract Disclosure: J. Paz-Ibarra: None. M. Concepción-Zavaleta: None. A.P. Solis Pazmino: None. J. Somocurcio Peralta: None. Background: Amyloid goiter (AG) is a rare presentation of thyroid swelling, characterized by the presence of deposits of amyloid protein in the thyroid tissue, accompanied by fat deposition or thyrolipomatosis. It may occur in 50% and up to 80% of patients with primary and secondary amyloidosis, respectively. Currently, the treatment is surgical resection of the thyroid gland. The present study reports a case series of primary thyroidal nodular amyloid goiter diagnosed by fine-needle cytology (FNC). Clinical cases:There were 2 female and 1 male patient from Peru. All three patients had comorbidities prior to AG diagnosis. F1: 65 years old, history of Rheumatoid Arthritis, Sjogren’s disease nephron Angio sclerosis, and polycystic kidney disease. F2: 67 years old, history of rheumatoid arthritis, end-stage renal disease (ESRD), arterial hypertension. M1: 28-year-old man with a history of pulmonary tuberculosis, bronchiectasis, and ESRD on HD due to renal amyloidosis of 9 years' evolution. They reported dyspnea, dysphagia, and dysphonia. On their physical examination, they had a bilateral, firm, and diffusely enlarged thyroid gland. Her serum T3, T4, and TSH levels were all normal. The PAAF reported a colloid goiter (Bethesda II). A total thyroidectomy was performed, with no complications. An alcohol-fixed smear was stained with Congo red: the amyloid material appeared cherry red and it also showed apple-green birefringence when observed with a polarizing microscope. Conclusions: Secondary amyloidosis generally has a neoplastic origin or is secondary to chronic inflammatory diseases. The development of a giant goiter with compressive symptoms is the most common form of presentation and represents amyloid infiltration of the gland. Total thyroidectomy is the method of choice for both diagnosis and treatment of amyloid goiter. Histological evaluation of the resected thyroid gland is crucial to make a definitive diagnosis. Presentation Date: Saturday, June 17, 2023

EXPLORING MACULAR AMYLOIDOSIS IN PHOTOEXPOSED AREAS: CLINICAL AND HISTOLOGICAL INSIGHTS

Macular amyloidosis is a dermatological condition characterized by the deposition of amyloid proteins in the skin, particularly in photoexposed areas. This study offers clinical and histological insights into macular amyloidosis, focusing on its presentation, diagnosis, and histopathological features. A comprehensive review of clinical cases and histological specimens was conducted, highlighting common clinical manifestations and characteristic histological findings associated with macular amyloidosis. The study sheds light on the pathogenesis and etiology of the condition, exploring the role of chronic sun exposure and genetic predisposition. Additionally, diagnostic challenges and therapeutic options for macular amyloidosis are discussed, emphasizing the importance of accurate diagnosis and multidisciplinary management approaches.

DP25 Widespread subcutaneous nodular kappa light chain amyloidosis

Abstract A 69-year-old woman was referred to the dermatology department for evaluation of multiple widespread subcutaneous lesions involving the neck, torso and limbs. These lesions, initially diagnosed in the community as lipomas, had been slowly progressing in size and number for 3 years. She had remained systemically well. Her only medical history was essential thrombocythaemia. She took no regular medication. On examination, there were multiple subcutaneous lesions appreciated on palpation with no overlying epidermal change. The patient was experiencing pain in a sciatic distribution. Magnetic resonance imaging of the femur showed a 12-cm enhancing area of subcutaneous nodularity encasing the sciatic nerve. Computed tomography of the chest, abdomen and pelvis showed multiple subcutaneous, ill-defined, soft tissue lesions of the anterior abdominal wall with no lymphadenopathy or organ abnormality. Deep incisional biopsies from two separate locations were completed. There was an unremarkable epidermis and dermis. In the subcutaneous fat, the septae appeared thickened alongside thickened elastic fibres and a prominent multifocal granulomatous reaction with a high degree of elastophagocytosis. There were multifocal aggregates of plasma cells that displayed no cytological atypia. In situ hybridization showed strong kappa light chain restriction. Plasma protein electrophoresis was completed and confirmed a paraprotein band in the gamma region of IgM kappa. Full blood count revealed a high platelet count (585 × 109 cells L–1) but was otherwise unremarkable alongside normal renal and liver function, bone profile, lactate dehydrogenase, B2 microglobulin, Bence–Jones proteins and infection screen. A Congo red stain was performed on the original histological samples. This showed apple green birefringence under polarized light-confirming amyloid. Haematology completed a bone marrow biopsy, which was normal. Referral to the National Amyloid Centre was made. Serum amyloid P scan showed no visceral involvement. A diagnosis of subcutaneous amyloid kappa light chain subtype (AL) was made. The patient has since commenced rituximab, bortezomib (Velcade®), cyclophosphamide and dexamethasone (R-VCD) chemotherapy at 4-weekly intervals over a 4-month period. Primary localized cutaneous amyloidosis is characterized by extracellular deposition of amyloid protein in the skin without evidence of systemic involvement and is often subtyped into macular, papular and nodular. Amyloidoma (tumoral amyloidosis) is rare and defined as a solitary localized deposit of amyloid. There are only four case reports in the literature of multiple subcutaneous amyloid deposits, and only one of these cases was of AL (light chain) vs. amyloid A (AA) subtype. This case showed nodules restricted to the neck (Nguyen TU, Oghalai JS, McGregor DK et al. Subcutaneous nodular amyloidosis: a case report and review of the literature. Hum Pathol 2001; 32:346–8). To our knowledge, this is the first case of widespread kappa light chain subcutaneous amyloidosis.

Clinical Application of 99mTc-Pyrophosphate Scintigraphy for Diagnosis of Cardiac Amyloidosis: A Case Series.

Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy resulting from deposition of insoluble amyloid protein in the myocardial interstitium. The accumulation of amyloid protein causes the myocardium to thicken and stiffen, leading to diastolic dysfunction and, eventually, heart failure. Two primary types of amyloidosis-transthyretin and immunoglobulin light chain-account for nearly 95% of all CA diagnoses. Three case studies are presented. The first demonstrates a patient positive for transthyretin amyloidosis, the second demonstrates a patient positive for light-chain CA, and the third demonstrates a patient showing blood-pool uptake on the [99mTc]Tc-pyrophosphate scan but negative for CA.

A rare presentation of amyloid goiter with renal amyloidosis in a young female

Amyloidosis is a rare systemic disorder caused by abnormal folding of normal soluble proteins leading to fibril formation in one or more body organs, systems or soft tissues. Amyloid goiter is characterized by deposits of amyloid protein in the thyroid tissue. Amyloid infiltration of thyroid gland with development of secondary goiter is rare. Here we report a case of 36-year-old female presented with progressive painless swelling over neck. Thyroid profile was normal. Ultrasound neck showed enlarged bilateral thyroid gland and isthmus. Fine needle aspiration cytology suggestive of subacute thyroiditis (granulomatous thyroiditis). Total thyroidectomy was done and biopsy sample revealed amyloid goiter.

Machine Learning Approaches in Diagnosis, Prognosis and Treatment Selection of Cardiac Amyloidosis

Cardiac amyloidosis is an uncommon restrictive cardiomyopathy featuring an unregulated amyloid protein deposition that impairs organic function. Early cardiac amyloidosis diagnosis is generally delayed by indistinguishable clinical findings of more frequent hypertrophic diseases. Furthermore, amyloidosis is divided into various groups, according to a generally accepted taxonomy, based on the proteins that make up the amyloid deposits; a careful differentiation between the various forms of amyloidosis is necessary to undertake an adequate therapeutic treatment. Thus, cardiac amyloidosis is thought to be underdiagnosed, which delays necessary therapeutic procedures, diminishing quality of life and impairing clinical prognosis. The diagnostic work-up for cardiac amyloidosis begins with the identification of clinical features, electrocardiographic and imaging findings suggestive or compatible with cardiac amyloidosis, and often requires the histological demonstration of amyloid deposition. One approach to overcome the difficulty of an early diagnosis is the use of automated diagnostic algorithms. Machine learning enables the automatic extraction of salient information from "raw data" without the need for pre-processing methods based on the a priori knowledge of the human operator. This review attempts to assess the various diagnostic approaches and artificial intelligence computational techniques in the detection of cardiac amyloidosis.

Diagnostic Challenges and Solutions in Systemic Amyloidosis

Amyloidosis refers to a clinically heterogeneous group of disorders characterized by the extracellular deposition of amyloid proteins in various tissues of the body. To date, 42 different amyloid proteins that originate from normal precursor proteins and are associated with distinct clinical forms of amyloidosis have been described. Identification of the amyloid type is essential in clinical practice, since prognosis and treatment regimens both vary according to the particular amyloid disease. However, typing of amyloid protein is often challenging, especially in the two most common forms of amyloidosis, i.e., the immunoglobulin light chain amyloidosis and transthyretin amyloidosis. Diagnostic methodology is based on tissue examinations as well as on noninvasive techniques including serological and imaging studies. Tissue examinations vary depending on the tissue preparation mode, i.e., whether it is fresh-frozen or fixed, and they can be carried out by ample methodologies including immunohistochemistry, immunofluorescence, immunoelectron microscopy, Western blotting, and proteomic analysis. In this review, we summarize current methodological approaches used for the diagnosis of amyloidosis and discusses their utility, advantages, and limitations. Special attention is paid to the simplicity of the procedures and their availability in clinical diagnostic laboratories. Finally, we describe new methods recently developed by our team to overcome limitations existing in the standard assays used in common practice.