Jason D Theis

Mayo Clinic - Rochester, Rochester, Minnesota, United States

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Publications (42)268.95 Total impact

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    ABSTRACT: To determine the impact of amyloid on the prognosis of patients with hypertrophic cardiomyopathy (HC), we reviewed outcomes of patients who underwent septal myectomy for HC from March 7, 1996, to October 9, 2012, with amyloid deposits identified in operative specimens. Amyloid subtypes were differentiated by mass spectrometry-based proteomics. The survival rate was compared with that of an age-matched population (2:1) without amyloid who underwent septal myectomy for HC. Sixteen patients (mean age ± SD 71 ± 8 years; 12 men) met study criteria. All 16 had intraventricular peak systolic gradients reduced intraoperatively from 105 ± 53 mm Hg to 3 ± 7 mm Hg (p <0.001). Amyloid deposits in specimens ranged from minimal to mild. Nine patients had senile (transthyretin-type) amyloidosis, 4 had immunoglobulin-associated amyloidosis, 2 had apolipoprotein A4 amyloidosis type, and 1 had serum amyloid A type. There were no deaths before 30 days. Twelve patients had New York Heart Association class III or IV function preoperatively, and at last follow-up (median 3 years), class I or II. Only 1 patient received postoperative amyloidosis treatment. The postoperative survival rate at 2 and 4 years was 100% (n = 11 at risk) and 91% (n = 6 at risk), respectively, similar to that of the age-matched population with HC without amyloid who underwent myectomy (p = 0.13). Patients undergoing septal myectomy for HC who have histologic evidence of mild amyloidosis have early outcomes and midterm survival similar to those of patients with HC without amyloidosis who undergo myectomy. In conclusion, although longer follow-up is necessary, small amounts of amyloid, regardless of subtype, do not confer a poor prognosis on patients with HC who undergo septal myectomy.
    The American Journal of Cardiology 08/2014; · 3.21 Impact Factor
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    ABSTRACT: Examination of abdominal subcutaneous fat aspirates is a practical, sensitive and specific method for the diagnosis of systemic amyloidosis. In this study, we describe 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 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%), 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. Mass spectrometry-based proteomic analysis of subcutaneous fat aspirates offers a powerful tool for clinical diagnosis and typing of systemic amyloidosis. The assay reveals underlying pathogenesis by identifying variable gene usage in immunoglobulin light chain and the variant peptides in hereditary amyloidosis.
    Haematologica 04/2014; · 5.94 Impact Factor
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    ABSTRACT: Shotgun proteomics of hereditary amyloid deposits generates all the information necessary to identify pathogenic mutant peptides and proteins. However, these mutant peptides are invisible to traditional database search strategies. We developed a two-pronged informatics workflow for detecting both known and novel amyloidogenic mutations from clinical proteomics data sets. We implemented the workflow in a CAP/CLIA certified clinical laboratory dedicated for proteomic subtyping of amyloid deposits extracted from formalin-fixed paraffin-embedded specimens. Performance of the workflow was characterized on a validation cohort of 49 hereditary amyloid samples, with confirmed mutations, and 85 controls. The sensitivity, specificity, positive predictive value and negative predictive value of the known mutation detection workflow were determined to be 92%, 100%, 100% and 96%, respectively. For novel mutation detection workflow, these performance parameters were 82%, 99%, 99%and 90%, respectively. Validated workflow was applied to detect amyloidogenic mutations from a clinical cohort of 150 amyloid samples. The known mutation detection workflow detected rare frame shift mutations in apolipoprotein A1 and fibrinogen alpha amyloid deposits. The novel mutation detection workflow uncovered unanticipated mutations (W22G and C71Y) of the serum amyloid A4 protein present in patient amyloid deposits. In summary, clinical amyloid proteomics data sets contain mutant peptides of clinical significance that are recoverable with improved bioinformatics.
    Journal of Proteome Research 03/2014; · 5.06 Impact Factor
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    ABSTRACT: Multiple myeloma is a disease characterized by a clonal expansion of plasma cells that secrete a monoclonal immunoglobulin also referred to as an M-protein. In the clinical laboratory, protein electrophoresis (PEL), immunofixation electrophoresis (IFE), and free light chain nephelometry (FLC) are used to monitor and quantify an M-protein. Here we present an alternative method based on monitoring a clonotypic (i.e. clone specific) peptide from the M-protein heavy chain variable region using LC-MS/MS. Tryptic digests were performed on IgG purified serum from 10 patients with a known IgG M-protein. Digests were analyzed by shot-gun LC-MS/MS and the results were searched against a protein database with the patient specific heavy chain variable region sequence found by gene sequencing added to the database. In all 10 cases, the protein database search matched multiple clonotypic peptides from each patient's heavy chain variable region. The clonotypic peptides were then used to quantitate the amount of M-protein in patient serum samples using selected reaction monitoring (SRM) on a triple quadrupole mass spectrometer. The response for the clonotypic peptide observed by SRM correlated with the response of the M-protein observed by PEL. In addition, the clonotypic peptide was clearly observed by SRM in samples that were negative by IFE and FLC. Monitoring clonotypic peptides using SRM has the capacity to redefine clinical residual disease due to its superior sensitivity and specificity compared to current analytical methods.
    Journal of Proteome Research 02/2014; · 5.06 Impact Factor
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    ABSTRACT: Abstract Protein and peptide drugs administered subcutaneously, such as insulin can be amyloidogenic and result in localized amyloid deposits at the sites of medication injections. These iatrogenic amyloidoses typically present as a localized subcutaneous nodule or skin reaction at the site of administration, and often pose diagnostic challenges. We have analyzed the amyloid proteome in 52 cases of insulin and enfuvirtide associated amyloidosis using laser microdissection/tandem mass spectrometry. We show that the deposits are composed of the drug, as well as other amyloid precursor proteins such as apolipoproteins A-I, A-IV, E and serum amyloid protein. Mass spectrometry-based amyloid sub-typing allows for accurate amyloid diagnosis with resultant therapeutic and prognostic implications. This insight into the amyloid proteome in drug-induced amyloidosis may help further understand pathogenesis of amyloid fibril formation.
    Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 01/2014; · 2.51 Impact Factor
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    ABSTRACT: Amyloidosis derived from leukocyte chemotactic factor 2 (ALECT2) is a recently described disease. Here, we report the characteristics and outcome of 72 patients with renal ALECT2, which included 19 who had another kidney disease on biopsy. Ninety-two percent of patients were Hispanics and over half were elderly. Three had other organ, but not cardiac, amyloidosis involvement. All patients without concurrent disease, except three, presented with chronic renal insufficiency. Proteinuria was variable and absent in a third, whereas nephrotic syndrome and hematuria were rare. After a median follow-up of 26 months, one-third developed end-stage renal disease (ESRD). The median renal survival was 62 months. Independent predictors of renal survival were serum creatinine at diagnosis, with a value of 2.0 mg/dl being the best cutoff for predicting ESRD, percentage global glomerulosclerosis, and presence of diabetes. Only four patients died and four had received chemotherapy for an erroneous diagnosis of immunoglobulin light chain-derived amyloidosis. Five patients underwent kidney transplantation; none had graft loss but one had disease recurrence. Patient survival is superior to renal immunoglobulin light chain-derived amyloidosis and reactive amyloidosis largely due to the absence of cardiac involvement. Thus, renal ALECT2 mainly affects elderly Hispanics who typically present with chronic renal insufficiency and bland urine sediment, with or without proteinuria.Kidney International advance online publication, 22 January 2014; doi:10.1038/ki.2013.558.
    Kidney International 01/2014; · 8.52 Impact Factor
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    ABSTRACT: Using laser microdissection and mass spectrometry-based proteomics (MS) we subtyped amyloid deposits from 130 cases of hepatic amyloidosis. Although we confirmed that immunoglobulin light chain amyloidosis (AL) was the most frequent cause of hepatic amyloidosis, leukocyte cell-derived chemotaxin 2 (LECT2) amyloidosis (ALect2) accounted for 25% of cases. This novel finding was associated with Hispanic ancestry, incidental discovery of amyloid in liver specimens sampled for other unrelated conditions and a characteristic pattern of hepatic amyloid deposition. Although ALect2 patients had a common LECT2 polymorphism, pathogenic mutations were not discovered, suggesting that constitutive or compensatory LECT2 overexpression led to ALect2 deposition. These findings indicate that ALect2 is common cause of hepatic amyloidosis in the United States population, and subtyping hepatic amyloid deposits by an accurate analytic method such as MS is required for optimal clinical management of hepatic amyloidosis patients and to avoid incorrect and unnecessarily toxic therapies.
    Blood 01/2014; · 9.78 Impact Factor
  • 01/2014; 106(2):1a–2a.
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    ABSTRACT: Monoclonal gammopathy is increasingly recognized as a common cause of membranoproliferative glomerulonephritis (MPGN); however, establishing this diagnosis can be challenging. We report the case of a 58-year-old asymptomatic woman who presented with proteinuria with protein excretion of 5,000mg/d, microscopic hematuria, and normal kidney function. Kidney biopsy was consistent with MPGN pattern of injury. Immunofluorescence studies were positive for nonspecific segmental immunoglobulin M (IgM) and C3 staining. Electron microscopy showed subendothelial, subepithelial, and mesangial electron-dense deposits. The workup excluded an infectious or autoimmune disease, but IgG κ monoclonal protein was detected in serum at a concentration of 0.4mg/dL. Because there was a mismatch between the serum monoclonal protein (IgG κ) and immunofluorescence staining pattern (nonspecific IgM, no light chain restriction), laser microdissection and mass spectrometry were performed on the kidney biopsy tissue. This identified the deposits as monoclonal IgG κ, thereby leading to the diagnosis of monoclonal gammopathy-associated MPGN. Our case emphasizes the importance of searching for an underlying cause of MPGN, reviews the technique of laser microdissection-mass spectrometry, and highlights its application as a pathology tool for the evaluation of monoclonal gammopathy-related glomerulonephritis.
    American Journal of Kidney Diseases 10/2013; · 5.29 Impact Factor
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    ABSTRACT: Shotgun proteomics technology has matured in the research laboratories and is poised to enter clinical laboratories. However, the road to this transition is sprinkled with major technical unknowns such as long-term stability of the platform, reproducibility of the technology and clinical utility over traditional antibody-based platforms. Further, regulatory bodies that oversee the clinical laboratory operations are unfamiliar with this new technology. As a result, diagnostic laboratories have avoided using shotgun proteomics for routine diagnostics. In this perspectives article, we describe the clinical implementation of a shotgun proteomics assay for amyloid subtyping, with a special emphasis on standardizing the platform for better quality control and earning clinical acceptance. This assay is the first shotgun proteomics assay to receive regulatory approval for patient diagnosis. The blueprint of this assay can be utilized to develop novel proteomics assays for detecting numerous other disease pathologies. Copyright © 2013 John Wiley & Sons, Ltd.
    Biological Mass Spectrometry 10/2013; 48(10):1067-1077. · 3.41 Impact Factor
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    ABSTRACT: The field of proteomics has long promised to deliver tools that positively impact patient care and clinical outcomes. Shotgun proteomics, in particular, with its capability for characterizing thousands of proteins in complex clinical samples has been a leading tool in the search for biomarkers and proteomic-based diagnostic tests. In the Special Feature, Jason Theis and co-workers at Mayo Clinic in Rochester, MN provide a first-hand perspective of challenges encountered to develop and implement a shotgun proteomics-based diagnostic assay for sub-typing forms of amyloidoisis. Using shotgun proteomics to identify amyloid proteins from microdissected biopsy tissue the diagnostic is able to characterize more than 20 subtypes of amyloidosis. Developing the assay is only one step to clinical acceptance and the authors and discuss how they have been able to make this key transition.
    Biological Mass Spectrometry 10/2013; 48(10):i. · 3.41 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES: The kidney is the organ most commonly involved in systemic amyloidosis. This study reports the largest clinicopathologic series of renal amyloidosis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This study provides characteristics of 474 renal amyloidosis cases evaluated at the Mayo Clinic Renal Pathology Laboratory from 2007 to 2011, including age, sex, serum creatinine, proteinuria, type of amyloid, and tissue distribution according to type. RESULTS: The type of amyloid was Ig amyloidosis in 407 patients (85.9%), AA amyloidosis in 33 (7.0%), leukocyte chemotactic factor 2 amyloidosis in 13 (2.7%), fibrinogen A α chain amyloidosis in 6 (1.3%), Apo AI, Apo AII, or Apo AIV amyloidosis in 3 (0.6%), combined AA amyloidosis/Ig heavy and light chain amyloidosis in 1 (0.2%), and unclassified in 11 (2.3%). Laser microdissection/mass spectrometry, performed in 147 cases, was needed to determine the origin of amyloid in 74 of the 474 cases (16%), whereas immunofluorescence failed to diagnose 28 of 384 light chain amyloidosis cases (7.3%). Leukocyte chemotactic factor 2 amyloidosis and Apo AI, Apo AII, or Apo AIV amyloidosis were characterized by diffuse interstitial deposition, whereas fibrinogen A α chain amyloidosis showed obliterative glomerular involvement. Compared with other types, Ig amyloidosis was associated with lower serum creatinine, higher degree of proteinuria, and amyloid spicules. CONCLUSIONS: In the authors' experience, the vast majority of renal amyloidosis cases are Ig derived. The newly identified leukocyte chemotactic factor 2 amyloidosis form was the most common of the rarer causes of renal amyloidosis. With the advent of laser microdissection/mass spectrometry for amyloid typing, the origin of renal amyloidosis can be determined in >97% of cases.
    Clinical Journal of the American Society of Nephrology 05/2013; · 5.07 Impact Factor
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    ABSTRACT: We report a 12-year-old boy with nephrotic syndrome due to renal AA amyloidosis. The AA amyloidosis was associated with a 3-year history of systemic-onset juvenile idiopathic arthritis. The presence of serum amyloid A protein was confirmed by laser microdissection of Congo Red-positive glomeruli and vessels followed by liquid chromatography and tandem mass spectrometry; this analysis excluded hereditary and familial amyloidosis. Aggressive management of the systemic-onset juvenile idiopathic arthritis resulted in improvement in clinical and laboratory parameters. The case represents an unusual cause of nephrotic syndrome in children. Early diagnosis of renal amyloidosis and management of systemic-onset juvenile idiopathic arthritis is paramount to preventing progression of kidney disease.
    American Journal of Kidney Diseases 05/2013; · 5.29 Impact Factor
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    ABSTRACT: Amyloidosis affecting lymph nodes (LN) may occur in the setting of systemic amyloidosis or as an entity localized to the site of production (peritumoral). Why some LN amyloid remains peritumoral is unknown. We speculated that the composition of amyloid in these two presentations differs. We analyzed the amyloid proteome in LN amyloid samples to identify differences between the systemic and peritumoral subtypes. In immunoglobulin-derived LN amyloidosis (N=26), 70% had heavy chain amyloid (AH or mixed AH/AL). True localized lymph node amyloidosis was rare, with only 2 patients without a monoclonal protein component. Nineteen patients (73%) had typical amyloid syndromes (100% of AL vs 67% of AH/AL, p 0.02). A trend to improved survival for the AH/AL group in comparison to AL (median 5-year survival 48 vs 19 months, p 0.06) was seen. Mass spectrometric amyloid analysis is a powerful tool for characterizing amyloid and may provide additional prognostic information.
    American Journal of Hematology 04/2013; · 4.00 Impact Factor
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    ABSTRACT: PURPOSE OF REVIEW: Laser microdissection (LMD) and mass spectrometry (MS) is a new technique that consists of dissection of glomeruli, tryptic digestion of dissected material, analysis by MS and generation of a protein profile using different algorithms. The review focuses on the use of this methodology as an ancillary technique in a clinical laboratory for the diagnosis of kidney diseases. RECENT FINDINGS: LMD/MS is used in the diagnosis and typing of kidney diseases with organized deposits such as amyloidosis. Uncommon and familial forms of renal amyloidosis are diagnosed and typed on the basis of the presence of specific amyloidogenic proteins. LMD/MS is used to confirm and identify immunoglobulins and complement factors in immune complex mediated and complement-mediated proliferative glomerulonephritis, respectively. In particular, LMD/MS can detect monoclonal immunoglobulins in cases of equivocal immunofluorescence studies in monoclonal immunoglobulins-associated glomerulonephritis. LMD/MS can detect specific complement factors of the alternative pathway and terminal pathway in complement-mediated glomerulonephritis. SUMMARY: LMD/MS is currently used for diagnosis and typing of amyloidosis. In addition, LMD/MS is useful in determining the type of immunoglobulins and complement factors in immune complex and complement-mediated glomerulonephritis, respectively.
    Current opinion in nephrology and hypertension 03/2013; · 3.96 Impact Factor
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    ABSTRACT: BACKGROUND AND OBJECTIVES: Organized deposits are present in amyloidosis, fibrillary GN, and immunotactoid glomerulopathy. However, the constituents of the deposits are not known. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Laser microdissection of glomeruli followed by mass spectrometry was performed to determine the composition of the deposits. The results were compared with cryoglobulinemic GN. RESULTS: The results are divided into four major groups: amyloidogenic proteins, structural/other proteins, complement proteins, and Igs. With regards to amyloidogenic proteins, large spectra numbers of apolipoprotein E are noted in amyloidosis (41.8±20.9) compared with fibrillary (15.6±12.5) and immunotactoid (12.3±12) glomerulopathy. Apolipoprotein E was absent in cryoglobulinemic GN. Serum amyloid P component is present in large spectra numbers in amyloidosis (14.1±6.7) and small spectra numbers in immunotactoid glomerulopathy, but it is absent in fibrillary and cryoglobulinemic GN. However, large spectra numbers of Ig γ-1 chain C region are present in immunotactoid glomerulopathy (47.3±34.6) compared with fibrillary (16.25±19.7) and cryoglobulinemic (13.3±4.9) GN. All cases of Ig light chain-associated amyloidosis showed spectra for the respective Ig light-chain C region (mean=10±1.7). CONCLUSIONS: Based on the spectra numbers, the study shows that the relative amount of apolipoprotein E to Ig light-chain C region/amyloidogenic proteins or Ig γ-1 chain C region is associated with the organization of the deposits in amyloidosis, fibrillary GN, and immunotactoid glomerulopathy. However, the absence of apolipoprotein E correlates with the lack of fibrillar deposits in cryoglobulinemic GN.
    Clinical Journal of the American Society of Nephrology 02/2013; · 5.07 Impact Factor
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    ABSTRACT: Little is known about the rare entities of heavy- and light-chain amyloidosis (AHL) and heavy-chain amyloidosis (AH). Here, we report the renal and hematological characteristics, pathology, and outcome of 16 patients with renal AH/AHL (5 with AH and 11 with AHL) and compare them with 202 patients with renal light-chain amyloidosis (AL) diagnosed during the same time period. All cases were diagnosed by kidney biopsy that showed Congo red-positive deposits. Amyloid typing was done by laser microdissection and mass spectrometry (LMD/MS) on 12 patients or by immunofluorescence on four patients. All patients with renal AH/AHL were Caucasians, with a male/female ratio of 2.2 and a median age at biopsy of 63 years. Compared with patients with renal AL, those with renal AH/AHL had less frequent concurrent cardiac involvement, higher likelihood of having circulating complete monoclonal immunoglobulin, lower sensitivity of fat pad biopsy and bone marrow biopsy for detecting amyloid, higher incidence of hematuria, and better patient survival. The hematological response to chemotherapy was comparable with renal AL. In 42% of patients, AH/AHL could not have been diagnosed without LMD/MS. Thus, renal AH/AHL is an uncommon and underrecognized form of amyloidosis, and its diagnosis is greatly enhanced by the use of LMD/MS for amyloid typing. The accurate histological diagnosis of renal AH/AHL and distinction from AL may have important clinical and prognostic implications.Kidney International advance online publication, 9 January 2013; doi:10.1038/ki.2012.414.
    Kidney International 01/2013; · 8.52 Impact Factor
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    ABSTRACT: The human germinal centre-associated lymphoma gene is specifically expressed in germinal centre B-lymphocytes and germinal centre-derived B-cell lymphomas, but its function is largely unknown. Here we demonstrate that human germinal centre-associated lymphoma directly binds to Syk in B cells, increases its kinase activity on B-cell receptor stimulation and leads to enhanced activation of Syk downstream effectors. To further investigate these findings in vivo, human germinal centre-associated lymphoma transgenic mice were generated. Starting from 12 months of age these mice developed polyclonal B-cell lymphoid hyperplasia, hypergammaglobulinemia and systemic reactive amyloid A (AA) amyloidosis, leading to shortened survival. The lymphoid hyperplasia in the human germinal centre-associated lymphoma transgenic mice are likely attributable to enhanced B-cell receptor signalling as shown by increased Syk phosphorylation, ex vivo B-cell proliferation and increased RhoA activation. Overall, our study shows for the first time that the germinal centre protein human germinal centre-associated lymphoma regulates B-cell receptor signalling in B-lymphocytes which, without appropriate control, may lead to B-cell lymphoproliferation.
    Nature Communications 01/2013; 4:1338. · 10.74 Impact Factor
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    ABSTRACT: Nodular pulmonary amyloidosis, a rare localized form of amyloidosis, has been associated with immunoglobulin light chains (AL type) and variably with low-grade lymphoma. The clinicopathologic features of 18 cases were investigated; 5 of 14 had autoimmune disease. In 14 cases monotypic plasma cells could be demonstrated by immunohistochemistry. By mass spectrometry analysis of the amyloid deposits, all 18 cases showed a peptide profile with an abundance of immunoglobulin light chains (12 κ, 4 λ, and 2 mixed κ and λ), with 13 also showing significant codeposition of heavy chains (10 γ, 2 α, 1 δ). Of 14 patients with follow-up, 3 developed recurrent pulmonary amyloidoma, 2 had pulmonary recurrence plus cutaneous extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type with and without amyloid, and 1 had a history of parotid gland MALT lymphoma. This study highlights the unique features of this localized form of amyloidosis. AL κ type is more frequent than AL λ type, with a ratio of 3:1, in contrast to the AL λ predominance that characterizes systemic AL amyloidosis. In addition, the majority of nodular pulmonary amyloid is of mixed AL/AH type, a rare finding in systemic amyloidosis. The association of nodular pulmonary amyloidoma with autoimmune disease and lymphoma indicate the majority of these lesions relate to an underlying lymphoplasmacytic neoplasm in the spectrum of MALT lymphoma.
    The American journal of surgical pathology 12/2012; · 4.06 Impact Factor
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    ABSTRACT: Introduction: In rare instances, amyloidosis presents as a focal, macroscopic lesion involving peripheral neural tissues (amyloidoma). In all known reported cases, peripheral nerve amyloidomas have had immunoglobulin light-chain fibril composition and occurred in the context of paraproteinemia. Methods: A 46-year-old man presented with progressive insidious-onset right lumbosacral radiculoplexus neuropathy without paraproteinemia. MRI-targeted fascicular nerve biopsy was performed on an enlarged sciatic nerve after earlier distal fibular nerve biopsy was nondiagnostic. Laser dissected mass spectroscopy of the discovered amyloid protein was performed after immunohistochemistry failed to identify the specific amyloid protein. Complete gene sequencing of apolipoprotein A1 (ApoA1) was performed. Results: Only wild-type ApoA1 amyloid was found in the congophilic component in the nerve. Conclusions: This case highlights the utility of MRI-guided fascicular nerve biopsy combined with laser-dissected mass spectrometric analysis. Importantly, the case expands the known causes of amyloidomas to include wild-type ApoA1. Muscle Nerve 46: 817-822, 2012.
    Muscle & Nerve 11/2012; 46(5):817-22. · 2.31 Impact Factor

Publication Stats

454 Citations
268.95 Total Impact Points

Institutions

  • 2008–2014
    • Mayo Clinic - Rochester
      • Department of Laboratory Medicine & Pathology
      Rochester, Minnesota, United States
  • 2013
    • Drexel University College of Medicine
      Philadelphia, Pennsylvania, United States
    • Columbia University
      New York City, New York, United States
  • 2008–2012
    • Mayo Foundation for Medical Education and Research
      • • Division of Nephrology and Hypertension
      • • Division of Hematology
      Rochester, Michigan, United States