M307 AMYLOID LIGHT CHAIN (AL) AMYLOIDOSIS PRESENTING AS PRURITUS AND DYSPNEA

Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.

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A case of isolated amyloid light-chain amyloidosis of the radial nerve

Journal of Neurosurgery ◽

10.3171/2015.10.jns151095 ◽

2016 ◽

Vol 125 (3) ◽

pp. 598-602 ◽

Cited By ~ 4

Author(s):

Ron Ron Cheng ◽

Ramin Eskandari ◽

Cynthia T. Welsh ◽

Abhay K. Varma

Keyword(s):

Peripheral Nerve ◽

Light Chain ◽

Radial Nerve ◽

Systemic Disease ◽

Mass Spectrometry Analysis ◽

Al Amyloidosis ◽

Electrodiagnostic Testing ◽

Nerve Involvement ◽

Peripheral Nerve Involvement ◽

Amyloid Light Chain

Peripheral nerve involvement may be the first sign of systemic amyloid light-chain (AL) amyloidosis, a rare disease. Physical examination and electrodiagnostic testing are the mainstays of peripheral neuropathy evaluation at presentation. Sural nerve biopsy is performed in conjunction with serum and urine protein evaluation to differentiate between focal and systemic disease. Systemic disease is treated with a combination of chemotherapy, steroids, and stem cell transplantation. Isolated peripheral nerve disease is extremely rare. The authors here report the case of an 80-year-old woman who presented with progressive right upper-extremity weakness due to right radial neuropathy discovered upon electrodiagnostic testing. Magnetic resonance neurography (MRN) revealed a focal lesion within the right radial nerve. She underwent radial nerve exploration and excision of an intraneural mass consisting of amyloid on histopathology, with mass spectrometry analysis diagnostic for AL amyloidosis. Noninvasive testing and clinical history did not suggest systemic involvement. This unique case of isolated peripheral nerve AL amyloidosis in the absence of signs and symptoms of systemic disease is described, and the literature demonstrating peripheral nerve involvement in AL amyloidosis is reviewed.

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Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: incidence, bleeding manifestations, and response to high-dose chemotherapy

Blood ◽

10.1182/blood.v97.6.1885 ◽

2001 ◽

Vol 97 (6) ◽

pp. 1885-1887 ◽

Cited By ~ 122

Author(s):

Elie B. Choufani ◽

Vaishali Sanchorawala ◽

Timothy Ernst ◽

Karen Quillen ◽

Martha Skinner ◽

...

Keyword(s):

Light Chain ◽

Medical Center ◽

Bleeding Complications ◽

Plasma Cell Dyscrasia ◽

High Dose ◽

Al Amyloidosis ◽

Related Factor ◽

Factor X ◽

Factor X Deficiency ◽

Amyloid Light Chain

Acquired deficiency of factor X occurs in patients with systemic amyloid light-chain (AL) amyloidosis, presumably due to adsorption of factor X to amyloid fibrils. Of 368 consecutive patients with systemic AL amyloidosis evaluated at Boston Medical Center, 32 patients (8.7%) had factor X levels below 50% of normal. Eighteen of these patients (56%) had bleeding complications, which were more frequent and severe in the 12 patients below 25% of normal; 2 episodes were fatal. Ten factor X–deficient patients received high-dose melphalan chemotherapy followed by autologous stem cell transplantation. Of 7 patients alive 1 year after treatment, 4 had a complete hematologic response, and all 4 experienced improvement in their factor X levels. One of 2 additional patients with partial hematologic responses had improvement in factor X. Thus, aggressive treatment of the underlying plasma cell dyscrasia in AL amyloidosis can lead to the amelioration of amyloid-related factor X deficiency.

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A comparison of immunohistochemistry and mass spectrometry for determining light chain amyloid ﬁbril protein from formalin-ﬁxed renal biopsy tissue in a single Chinese center

10.21203/rs.2.13027/v1 ◽

2019 ◽

Author(s):

Ying Sun ◽

Jian Sun ◽

Wei Sun ◽

Junyi Pang ◽

Yubing Wen ◽

...

Keyword(s):

Mass Spectrometry ◽

Renal Biopsy ◽

Light Chain ◽

Protein Identification ◽

Amyloid Fibrils ◽

Al Amyloidosis ◽

Precise Diagnosis ◽

Ffpe Tissues ◽

Amyloid Light Chain ◽

Formalin Fixed

Abstract Background Amyloidosis, a disease caused by abnormal protein deposition in tissues, is classiﬁed according to the protein precursor that form amyloid ﬁbrils. Diagnosis of amyloidosis is type-specific as the identification of amyloid protein determines the following treatment. However, around a quarter of amyloidosis cases cannot be accurately subtyped by most commonly used immunohistochemistry (IHC). In order to obtain precise diagnosis, our study is focusing on another protein identification methods, laser microdissection and mass spectrometry (LDMS). Methods 20 cases of Amyloid Light-chain (AL) amyloidosis without further subtype were included. IHC and LDMS were used to detect light chains on formalin-ﬁxed parafﬁn-embedded (FFPE) tissues from renal biopsy. Results 100% consistence between positive IHC and LDMS results were observed, however, chances of subtyping using LDMS is increased to 94% compared to IHC which is only 76%. Conclusion LDMS is a valuable tool in regard to subtyping amyloidosis.

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Dissecting the Molecular Features of Systemic Light Chain (AL) Amyloidosis: Contributions from Proteomics

Medicina ◽

10.3390/medicina57090916 ◽

2021 ◽

Vol 57 (9) ◽

pp. 916

Author(s):

Paola Rognoni ◽

Giulia Mazzini ◽

Serena Caminito ◽

Giovanni Palladini ◽

Francesca Lavatelli

Keyword(s):

Light Chain ◽

Amyloid Fibrils ◽

Cell Clone ◽

Experimental Models ◽

Critical Discussion ◽

Al Amyloidosis ◽

Primary Role ◽

Molecular Features ◽

Amyloid Light Chain ◽

Models Of Disease

Amyloidoses are characterized by aggregation of proteins into highly ordered amyloid fibrils, which deposit in the extracellular space of tissues, leading to organ dysfunction. In AL (amyloid light chain) amyloidosis, the most common form in Western countries, the amyloidogenic precursor is a misfolding-prone immunoglobulin light chain (LC), which, in the systemic form, is produced in excess by a plasma cell clone and transported to target organs though blood. Due to the primary role that proteins play in the pathogenesis of amyloidoses, mass spectrometry (MS)-based proteomic studies have gained an established position in the clinical management and research of these diseases. In AL amyloidosis, in particular, proteomics has provided important contributions for characterizing the precursor light chain, the composition of the amyloid deposits and the mechanisms of proteotoxicity in target organ cells and experimental models of disease. This review will provide an overview of the major achievements of proteomic studies in AL amyloidosis, with a presentation of the most recent acquisitions and a critical discussion of open issues and ongoing trends.

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Multiorgan involvement by amyloid light chain amyloidosis

Journal of International Medical Research ◽

10.1177/0300060518814337 ◽

2019 ◽

Vol 47 (4) ◽

pp. 1778-1786 ◽

Cited By ~ 3

Author(s):

Guoliang Li ◽

Dan Han ◽

Suhua Wei ◽

Huaiyu Wang ◽

Limei Chen

Keyword(s):

Light Chain ◽

Amyloid Fibrils ◽

Normal Structure ◽

Al Amyloidosis ◽

Initial Symptom ◽

Close Monitoring ◽

Clinical Complexity ◽

Amyloid Light Chain ◽

Low Incidence ◽

Chemotherapy Strategy

Amyloid light chain (AL) amyloidosis is a protein conformational disease. AL amyloidosis results from aggregation of misfolded proteins that are deposited in tissues as amyloid fibrils. Diagnosis of AL amyloidosis can be challenging due to its low incidence and clinical complexity. Therapy requires a risk-adapted approach involving dose reductions and schedule modifications of chemotherapy regimens along with close monitoring of hematologic and organ responses. We herein describe a patient whose condition was diagnosed as systemic AL amyloidosis and presented with splenic rupture as the initial symptom. Congo red staining of the kidney biopsy was positive. The normal structure of the liver and spleen had been replaced by amyloid deposition. The chemotherapy strategy involved a combination of bortezomib, cyclophosphamide, thalidomide, and dexamethasone.

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Pathology and Proteomics-Based Diagnosis of Localized Light-Chain Amyloidosis in Dogs and Cats

Veterinary Pathology ◽

10.1177/0300985820934113 ◽

2020 ◽

Vol 57 (5) ◽

pp. 658-665

Author(s):

Ayumi Kadota ◽

Susumu Iwaide ◽

Shinya Miyazaki ◽

Ikki Mitsui ◽

Noboru Machida ◽

...

Keyword(s):

Potassium Permanganate ◽

Light Chain ◽

Congo Red ◽

Light Chains ◽

Al Amyloidosis ◽

Specificity And Sensitivity ◽

Amyloid Deposits ◽

Liquid Chromatography Tandem Mass ◽

Congo Red Staining ◽

Amyloid Light Chain

Amyloidosis is classified according to the amyloid precursor protein, and accurate diagnosis of the amyloidosis type may guide appropriate treatment. Immunohistochemistry and Congo red staining are the most frequently used methods used to distinguish types of amyloidosis, but problems with specificity and sensitivity indicate the need for an alternative diagnostic method. In this study, we evaluated laser microdissection-liquid chromatography-tandem mass spectrometry (LMD-LC-MS/MS) for the diagnosis of amyloid light-chain (AL) amyloidosis in animals. Plasmacytomas with amyloid deposits from 15 dogs and 2 cats were subjected to Congo red staining with or without potassium permanganate pretreatment, immunohistochemistry for kappa and lambda light chains, and LMD-LC-MS/MS. Congo red staining was diagnostic in 12 of 17 cases based on resistance to potassium permanganate pretreatment, but in 5 of 17 cases the pretreatment unexpectedly reduced Congo red staining or abrogated the birefringence and a definitive diagnosis could not be reached. Immunohistochemistry detected kappa or lambda light chains in 6 of 17 cases. With LMD-LC-MS/MS, immunoglobulin lambda light chain was detected in all 17 cases. The amyloid signature proteins ApoA-I, ApoA-IV, and ApoE were detected in 9, 1, and 3 of the 15 canine cases by LMD-LC-MS/MS, but not in the feline cases. In conclusion, LMD-LC-MS/MS consistently determined the amyloid type in all examined specimens, while Congo red staining after potassium permanganate treatment and immunohistochemistry were less sensitive tests.

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Incidentally Detected Amyloid Light-Chain Amyloidosis Caused by Monoclonal Gammopathy of Undetermined Significance: Possible Time-Dependent Change in Colonic Findings

Case Reports in Gastroenterology ◽

10.1159/000494919 ◽

2018 ◽

Vol 12 (3) ◽

pp. 737-746

Author(s):

Toshiro Fukui ◽

Yuji Tanimura ◽

Yasushi Matsumoto ◽

Shunsuke Horitani ◽

Takashi Tomiyama ◽

...

Keyword(s):

Plasma Cell ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Amyloid Deposition ◽

Fecal Occult Blood ◽

Al Amyloidosis ◽

Plasma Cell Disorder ◽

Amyloid Light Chain ◽

Cell Disorder ◽

Undetermined Significance

Amyloid light-chain (AL) amyloidosis is associated with plasma cell disorder and monoclonal light chains. This type of amyloidosis is the prominent type involving the gastrointestinal tract. Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder and a known precursor of more serious diseases. A 72-year-old male was treated for high blood pressure, diabetes, and gout at the clinic of a private physician. Due to a positive fecal occult blood test discovered during colon cancer screening, he underwent colonoscopy and was diagnosed with adenomatous polyps by biopsies. Two months later, he was referred to our hospital for endoscopic resection of the polyps. Although the polyps were successfully removed, a colonoscopy revealed two types of ulcerative lesions. Immunohistopathological evaluations obtained from these lesions and polyps confirmed amyloid deposition. Although esophagogastroduodenoscopy results were normal, a biopsy specimen from the patient’s stomach showed the same type of amyloid deposition. Immunoelectrophoresis showed M-proteins for anti-IgG-λ in the serum and λ type Bence-Jones protein in the urine. His blood, bone marrow, and urine test results led to a diagnosis of MGUS. A coronary angiography revealed multivessel stenosis, and the patient’s cardiac function improved after coronary artery stenting. Hereafter, a combination therapy with bortezomib, lenalidomide, and dexamethasone is planned. This is a case report of systemic AL amyloidosis caused by MGUS, which was incidentally detected by colonoscopy.

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