Amyloidosis of the breast: predominantly AL type and over half have concurrent breast hematologic disorders

Said, Samar M.; Reynolds, Carol; Jimenez, Rafael E.; Chen, Beiyun; Vrana, Julie A.; Theis, Jason D.; Doğan, Ahmet; Shah, Sejal

doi:10.1038/modpathol.2012.167

Cited by 57 publications

(64 citation statements)

References 19 publications

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“…9 The assay has been used extensively for typing amyloidosis at the Mayo Clinic, and nationally through the reference laboratory services of Mayo Medical Laboratories. [10][11][12][13][14][15][16][17][18][19] We and others have shown the possibility of applying proteomic approaches including MS-based proteomics for typing amyloidosis in SFA specimens in a research setting. [20][21][22][23][24][25] In this study, we show the clinical validation and implementation of an MS-based proteomic assay for the diagnosis and typing of amyloidosis in SFA specimens in a 1988 Clinical Laboratory Improvement Amendments (CLIA) accredited laboratory setting.…”

Section: Introductionmentioning

confidence: 99%

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Vrana¹,

Theis²,

Dasari³

et al. 2014

Haematologica

152

111

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Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. Here we describe the development and implementation of a clinical assay using mass spectrometry-based proteomics to type amyloidosis in subcutaneous fat aspirates. First, we validated the assay comparing amyloid-positive (n=43) and -negative (n=26) subcutaneous fat aspirates. The assay classified amyloidosis with 88% sensitivity and 96% specificity. We then implemented the assay as a clinical test, and analyzed 366 amyloid-positive subcutaneous fat aspirates in a 4-year period as part of routine clinical care. The assay had a sensitivity of 90%, and diverse amyloid types, including immunoglobulin light chain (74%), transthyretin (13%), serum amyloid A (%1), gelsolin (1%), and lysozyme (1%), were identified. Using bioinformatics, we identified a universal amyloid proteome signature, which has high sensitivity and specificity for amyloidosis similar to that of Congo red staining. We curated proteome databases which included variant proteins associated with systemic amyloidosis, and identified clonotypic immunoglobulin variable gene usage in immunoglobulin light chain amyloidosis, and the variant peptides in hereditary transthyretin amyloidosis. In conclusion, mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for the diagnosis and typing of systemic amyloidosis. The assay reveals the underlying pathogenesis by identifying variable gene usage in immunoglobulin light chains and the variant peptides in hereditary amyloidosis.Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics ABSTRACT Subcutaneous fat aspiration for diagnosis of systemic amyloidosisSpecimens were obtained, stained with Congo red and interpreted according to previously established protocols described elsewhere.5 For the validation cohort one half of each specimen was used to make a smear and stained with Congo red. The other half, irrespective of whether the smear was positive for amyloid by Congo red, was processed for MS-based proteomic analysis. For the clinical cohort, one half of each specimen was used to make a smear and stained with Congo red. The other half was processed for MS-based proteomic analysis only if the first half stained positive for amyloidosis, as required by the established clinical practice and test validation criteria. Mass spectrometry-based proteomic analysis of subcutaneous fat aspiratesThe SFA specimens were processed for MS analysis using a modification of a previously established protocol.26 Briefly, the aspirate was solubilized and digested in trypsin and used for protein identification by nano-flow liquid chromatography electrospray tandem MS.9 Peptide spectra present in the raw data files were matched against a composite protein sequence database using three different search engines (Sequest Measurement of serum immunoglobulin free light chainsSerum immunoglobulin ...

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Section: Introductionmentioning

confidence: 99%

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Vrana¹,

Theis²,

Dasari³

et al. 2014

Haematologica

152

111

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“…Although LCMS/MS can detect amyloid protein and is superior as compared to classical pathological technique, its accuracy is less than 100% [7,[23][24][25]. This is thought to be related to several limitations that are associated with LCMS/ MS.…”

Section: Discussionmentioning

confidence: 99%

Optimal conditions and the advantages of using laser microdissection and liquid chromatography tandem mass spectrometry for diagnosing renal amyloidosis

et al. 2018

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Background Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has recently been utilized to accurately detect the amyloid proteins of renal amyloidosis. The present study investigated the optimal procedures for analyzing samples by LCMS/MS, and the advantage of using this technique to diagnosis renal amyloidosis. Methods To detect amyloid proteins, laser microdissected glomeruli from AL (n = 13) or AA (n = 10) renal amyloidosis patients were digested and analyzed by LCMS/MS. To determine the best procedures for analyzing samples by LCMS/MS, we examined the suitability of tissue samples, frozen or formalin-fixed paraffin-embedded (FFPE), the number of dissected glomeruli required for analysis (2, 10, or 50 glomeruli), and the amount of trypsin with or without dithiothreitol (DTT). We additionally compared the detection of amyloid proteins between immunostaining and LCMS/MS. Results Examining 10 dissected glomeruli from FFPE sections digested with trypsin 3 µL (0.1 mg/mL) without DDT made it possible to detect amyloid protein in all 10 AA and in 10 out of 12 AL amyloidosis cases. All AA amyloidosis cases were diagnosed using immunohistochemistry for amyloid A. With immunostaining, however, there were several inconclusive immunoglobulin and/or their light chain staining noted in the AA or AL amyloidosis cases. Even so, LCMS/MS was able to accurately detect amyloid protein in renal amyloidosis. Conclusion The use of 10 laser microdissected glomeruli (170,000-220,000 µm 2 ) with amyloid deposition from FFPE sections digested with trypsin 3 µL (0.1 mg/mL) allowed the accurate detection of amyloid protein in AA and AL amyloidosis.

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“…B-cell or plasma cell proliferation for AL, chronic inflammatory diseases for AA as previously explained). [1] Breast amyloidosis treatment options include conservative excision of the nodules or, in rare and diffuse cases such as the one presented, mastectomy can be considered.…”

Section: Discussionmentioning

confidence: 99%

“…AL, caused by immunoglobulin light-chains [amyloid heavy chain (AH) is more rare and caused by heavy chains], is secondary to plasma cell dyscrasia (clonal plasma cell disorder secreting fibril-forming monoclonal immunoglobulin), while AA is reactive amyloidosis associated with chronic inflammatory disease (rheumatoid arthritis, Reiter syndrome, etc.). [1] The precise aetiology and pathogenesis of amyloidosis are unknown. AL amyloidosis can be systemic, affect more than one organ or tissue (commonly involving heart, gastrointestinal tract and tongue), or less commonly localized, affecting individual organs.…”

Section: Introductionmentioning

confidence: 99%

Breast amyloidosis: a case report

Boscaini¹,

Pignatti²,

Tazzioli³

et al. 2016

PAR

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Amyloidosis is an uncommon disorder characterized by extracellular deposition of abnormal proteins. Breast involvement has rarely been reported and can clinically be misdiagnosed as breast cancer. A 60-year-old woman presented with a 3-mm diameter mass in the right breast close to a silicon implant positioned 20 years before. A core biopsy, performed to rule out breast cancer, showed amyloid deposit. Further exams confirmed a systemic amyloid light chain amyloidosis. After few months the mass increased causing breast volume and shape distortion. Since breast cancer may be the cause of amyloid deposits or be hidden by it, the patient underwent a bilateral skin sparing mastectomy and expander and fat grafting breast reconstruction. The resection specimens showed amyloid deposits only, no evidence of cancer. At 2 years follow-up, no breast amyloidosis recurrence was shown. Breast amyloidosis is rare but can occur in a plastic surgeon's practice. It is mandatory to rule out a comitant breast cancer or systemic amyloidosis.

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Amyloidosis of the breast: predominantly AL type and over half have concurrent breast hematologic disorders

Cited by 57 publications

References 19 publications

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Clinical diagnosis and typing of systemic amyloidosis in subcutaneous fat aspirates by mass spectrometry-based proteomics

Optimal conditions and the advantages of using laser microdissection and liquid chromatography tandem mass spectrometry for diagnosing renal amyloidosis

Breast amyloidosis: a case report

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