Amyloidosis and Light Chain Plasmocytoma

1976 ◽  
Vol 62 (2) ◽  
pp. 219-226 ◽  
Author(s):  
Giovanna Tosato ◽  
Enzo Fagiolo
Keyword(s):  
Bone Marrow ◽  
Light Chain ◽  
Light Chains ◽  
Primary Amyloidosis ◽  
Intercellular Substance ◽  
Osteolytic Lesions ◽  
Small Areas ◽  
Type K ◽  
Amyloid Deposits ◽  
Initial Symptoms

Nine cases of light chain plasmocytomas, 6 type λ and 3 type k, have been studied in reference to amyloid presence and localisation. Bone marrow plasmocytosis, light chains in serum and/or in the urine, and osteolytic lesions were demonstrated in all the patients. Initial symptoms, i.e., macroglossia and lymphadenopathy, were secondary to amyloid deposits in two patients; the absence of overt evidence of plasmocytoma had previously led to the diagnosis of « primary » amyloidosis in one case. Amyloidosis may therefore be associated with concealed plasmocytomas, evident only after a certain period of time. Amyloidosis was not detected in the sites where it was clinically suspected in two cases. However, on bone marrow aspirates, amyloid was present in seven patients where thioflavine T appeared as homogeneous, amorphous, intercellular substance localised in small areas.

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

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.

A patient with AL amyloidosis with negative free light chain results

2016 ◽  
Vol 54 (6) ◽  
Author(s):  
Paolo Milani ◽  
Veronica Valentini ◽  
Giovanni Ferraro ◽  
Marco Basset ◽  
Francesca Russo ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Light Chain ◽  
Left Ventricular ◽  
Free Light Chain ◽  
Response To Treatment ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Light Chain Restriction ◽  
Serum And Urine

AbstractThe detection and quantification of amyloidogenic monoclonal light chains are necessary for the diagnosis and evaluation of response to treatment in AL amyloidosis. However, the amyloid clone is often small and difficult to detect. We report the case of a 68-year-old man who was referred to our Center in April 2013 after syncope and the identification of left ventricular hypertrophy at echocardiography, suspected for amyloidosis. A commercial agarose gel electrophoresis immunofixation (IFE) did not reveal monoclonal components in serum and urine. The κ serum free light chain (FLC) concentration was 21.5 mg/L, λ 33 mg/L (κ/λ ratio 0.65), NT-proBNP 9074 ng/L (u.r.l. <332 ng/L) and an echocardiogram confirmed characteristic features of amyloidosis. The abdominal fat aspiration was positive and the amyloid typing by immune-electron microscopy revealed λ light chains deposits. A high-resolution (hr) IFE of serum and urine showed a faint monoclonal λ component in the urine. A bone marrow biopsy showed 8% plasma cells (BMPC) and a kappa/lambda light-chain restriction with λ light chain on immunofluorescence. The diagnosis of AL (λ) amyloidosis with cardiac involvement was made. In May 2013, patient was started on cyclophosphamide, bortezomib and dexamethasone. After six cycles, serum and urine hr-IFE were negative, the bone marrow biopsy showed 3% BMPC without light chain restriction by immunofluorescence, and a decrease of NT-proBNP was observed (5802 ng/L).Thus, treatment was discontinued. In this patient the amyloid clone could be detected only by in house hr-IFE of urine and bone marrow examination. The detection of the small dangerous amyloidogenic clone should be pursued with a combination of high-sensitivity techniques, including assessment of BMPC clonality. Studies of novel tools, such as mass spectrometry on serum and next-generation flow cytometry analysis of the bone marrow, for detecting plasma cell clones in AL amyloidosis and other monoclonal light chain-related disorders are warranted.

scholarly journals Primary Amyloidosis Presenting with Nephrotic Syndrome and Atypical Intrahepatic Cholestasis: Report of 2 Cases

2015 ◽  
Vol 13 (2) ◽  
pp. 90-94
Author(s):  
Ufuk Ilgen ◽  
Zeynep Kendi Celebi ◽  
Gulsah Kaygusuz ◽  
Sim Kutlay ◽  
Gokhan Nergizoglu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Nephrotic Syndrome ◽  
Liver Failure ◽  
Light Chain ◽  
Intrahepatic Cholestasis ◽  
Relevant Literature ◽  
Primary Amyloidosis ◽  
Lambda Light Chain ◽  
Hepatic Amyloidosis ◽  
Kidney Liver

Abstract Liver is one of the most commonly involved organs in both primary and secondary systemic amyloidoses, but hepatic amyloidosis, manifested as mild to moderate enlargement, is usually not symptomatic nor it is clinically problematic. Rarely, massive hepatomegaly, severe cholestatic hepatitis or liver failure may be encountered in patients with systemic amyloidosis. Two cases with lambda light-chain amyloidosis presenting with nephrotic syndrome and atypical intrahepatic cholestasis are discussed with clinical features, laboratory and kidney, liver and bone marrow biopsy findings in view of the relevant literature.

Analysis of Vλ-Jλ expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r(λIII) as a new amyloid-associated germline gene segment

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 948-953 ◽  
Author(s):  
Vittorio Perfetti ◽  
Simona Casarini ◽  
Giovanni Palladini ◽  
Maurizio Colli Vignarelli ◽  
Catherine Klersy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Light Chain ◽  
Amyloid Fibrils ◽  
Plasma Cells ◽  
Strong Association ◽  
Gene Segment ◽  
Variable Region ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Primary Amyloidosis

Abstract Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by extracellular deposition of monoclonal light-chain variable region (V) fragments in the form of amyloid fibrils. Light-chain amyloid is rare, and it is not fully understood why it occurs in only a fraction of patients with a circulating monoclonal component and why it typically associates with λ isotype and λVI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal Vλ regions from 55 consecutive unselected cases of primary amyloidosis and the results were compared with the light-chain expression profile of polyclonal marrow plasma cells from 3 healthy donors (a total of 264 sequences). We demonstrated that: (1) the λIII family is the most frequently used both in amyloidosis (47%) and in polyclonality (43%); (2) both conditions are characterized by gene restriction; (3) a very skewed repertoire is a feature of amyloidosis, because just 2 germline genes belonging to the λIII and λVI families, namely 3r (22% of cases, λIII) and 6a (20%, λVI), contributed equally to encode 42% of amyloid Vλ regions; (4) these same 2 gene segments have a strong association with amyloidosis if their prevalences are compared with those in polyclonal conditions (3r, 8.3%,P = .024; 6a, 2.3%, P = .0008, χ2 test); (5) the Jλ2/3 segment, encoding the fourth framework region, appears to be slightly overrepresented in AL (83% versus 67%, P = .03), and this might be related to preferential Jλ2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that Vλ-Jλ expression is more restricted in plasma cells from amyloidosis than from polyclonal bone marrow and identify 3r as a new disease-associated gene segment. Overusage of just 2 gene segments,3r and 6a, can thus account for the λ light-chain overrepresentation typical of this disorder.

Correlation of Serum Free Light Chains and Bone Marrow Plasma Cell Infiltration in Multiple Myeloma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4865-4865
Author(s):  
Graham P. Mead ◽  
Steven D. Reid ◽  
Bradley M. Augustson ◽  
Mark T. Drayson ◽  
Arthur R. Bradwell ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Cell Infiltration ◽  
Light Chains ◽  
Normal Bone Marrow ◽  
Free Light Chains ◽  
Serum Free ◽  
Normal Bone

Abstract Diagnostic criteria for multiple myeloma include abnormal plasma cell infiltration of the bone marrow plus the presence of monoclonal immunoglobulin in the serum and/or monoclonal free light chains in the urine. However, recent studies have indicated that measurement of free light chains in the serum (sFLC) is more sensitive than urine assays. Also, because of the slow clearance of IgG from serum (half-life ~20 days compared with 2–6 hours for sFLC) intact immunoglobulin assays can be slow to reflect the full extent of response to treatment. The aim of this study was to compare the relative sensitivity and specificity of serum free light chain (sFLC) measurement, urine free light chain measurement (uFLC) and serum immunofixation (sIFE) with bone marrow analysis for assessment of myeloma. All 45 patients studied were enrolled in the UK MRC Myeloma VII trial and 75 serum samples were selected for sFLC measurement and sIFE. The sera had been collected at various times before, during and after treatment but all within 4 days of a bone marrow assessment and uFLC measurement (by radial immunodiffusion assay). sFLC results were classified as abnormal if the kappa/lambda ratio was outside the normal range and for uFLC, if there was &gt;40mg/L. The bone marrow assessment was called abnormal if 5% or greater plasma cell infiltration was recorded in aspirate or trephine, in accordance with the EBMT criteria. The results of the comparisons are summarised in the table. Summary of paraprotein assays Bone Marrow Normal Abnormal Serum Free Light Chains Normal 19 4 Abnormal 5 47 Urine Free Light Chains Normal 21 21 Abnormal 3 30 Serum Immunofixation Normal 10 5 Abnormal 14 46 Of the three paraprotein assays, sFLC had the highest concordance with bone marrow biopsy. Compared with the bone marrow assessment, the relative sensitivity and specificity of the sFLC assays was 92% and 79% respectively. For uFLC the values were 59% and 88%, respectively and for sIFE, 90% and 42% respectively. Of the 5 sera abnormal by the sFLC assays but with concurrent normal bone marrow results, all were abnormal by sIFE. Of the 4 patients with normal sFLC results but abnormal marrows, 3 were sIFE positive and of the 5 with negative sIFE results but abnormal marrows, 4 had abnormal sFLC ratios. Only 1 patient had an abnormal marrow with normal sFLC and sIFE results. In this comparison sFLC measurement showed a good degree of correlation with bone marrow assessments of myeloma, while uFLC assays were considerably less sensitive. Both sFLC and sIFE assays appeared to identify disease in 5 patients who had normal bone marrow assessments. This was presumably because the serum assays sample monoclonal protein produced throughout the body while distribution of the disease in the bone marrow is occasionally “patchy”. The sIFE results were positive in a much higher number (14) of bone marrow-negative patients. The 9 “extra” positives, which had normal bone marrow results and free light chain ratios, might result from a greater sensitivity for detecting tumours producing intact immunoglobulin with low levels of free light chains. Some of the 9 subsequently became sIFE negative so the slow clearance of monoclonal intact immunoglobulin is an alternative explanation for the discordant results. This could not be proven, however, as all patients had some form of treatment in the intervening period.

Comparaison of Serum Free Light Chain Measurement with Classical Methods for the Evaluation of Patients with Immunoproliferative Diseases under Treatment.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5123-5123
Author(s):  
Florence Cattan ◽  
Richard Delarue ◽  
Fadi Fakhouri ◽  
Aicha Abbas ◽  
Bertrand Arnulf ◽  
...  
Keyword(s):  
Light Chain ◽  
Free Light Chain ◽  
Routine Activity ◽  
Light Chains ◽  
Primary Amyloidosis ◽  
Moderate Increase ◽  
Light Chain Deposition Disease ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Bence Jones Proteinuria

Abstract Background: Therapeutic evaluation of immunoproliferative diseases requires precise quantification of the monoclonal (M) component. It currently relies on standardized methods such as serum electrophoresis or measurement of Bence-Jones proteinuria. In some cases, absence or very low level of serum and/or urinary M component hinders precise evaluation by conventional techniques. Serum quantification of free light chains (FLC) by nephelemetry, developed by Dr A. Bradwell and colleagues, has been shown to be relevant in such situations. Our study was designed to assess the usefulness of this method in the routine activity of a single institution. Patients and methods: forty-eight consecutive patients referred to the hematology and/or nephrology department of our institution were evaluated. These patients presented with immunoproliferative diseases including multiple myeloma (n = 38) among which 20 light chain myelomas, primary amyloidosis (n = 8) and light chain deposition disease (LCDD) (n = 2). Standard electrophoresis, measurement of Bence-Jones proteinuria and serum FLC measurement (FreeliteTM, The Binding Site, Birmingham, UK) were performed in all patients with a minimum of three consecutive evaluation during treatment. The three methods were compared to determine their respective clinical benefits for clinicians. Results: Nine patients with light chain myeloma and all patients with amyloidosis and LCDD presented with proteinuria under 0.5 g/d. In addition, 4 patients with myeloma had a serum M component below 5 g/L. Thus, difficult evaluation may be expected in 48 % of patients. Two patients failed to be evaluated by the FLC method because of normal concentrations of kappa and lambda light chains and normal kappa to lambda ratio. Thirty five percent of patients (17/48) were easily evaluated by the classical methods and no substantial additional information was obtained using serum free light chain measurement. In 21/48 (44%) of patients, for whom classical method failed to recognize any M component in serum or urine, serum FLC measurement proved very useful. For the remaining 8 patients with proteinuria < 0.5 g/d or serum M component < 5 g/l in whom evaluation with classical methods is difficult, determination of serum FLC demonstrated higher sensitivity to variations during treatment. Results were not influenced by the type of treatment. A cost-effective study shown a moderate increase in cost with FreeliteTM compared to classical methods. Conclusion: We studied the interest of a new serum FLC measurement method in the management of patients with immunoproliferative diseases. As expected, it appears very high in patients in whom classical methods are not suitable, a common feature in patients with light chain myeloma, amyloidosis and LCDD. By contrast, patients assessable with classical techniques do not benefit from this new method. We conclude that this method can be very useful, albeit only in a minority of patients with hardly assessable immunoproliferative diseases. It is our belief that serum FLC quantification should be restricted to this subgroup of patients.

scholarly journals The omega/lambda 5 surrogate immunoglobulin light chain is expressed on the surface of transitional B lymphocytes in murine bone marrow.

1991 ◽  
Vol 173 (1) ◽  
pp. 111-116 ◽  
Author(s):  
B J Cherayil ◽  
S Pillai
Keyword(s):  
Bone Marrow ◽  
Light Chain ◽  
B Lymphocyte ◽  
Light Chains ◽  
Immunoglobulin Light Chain ◽  
Murine Bone Marrow ◽  
Surrogate Light Chain ◽  
Membrane Immunoglobulin ◽  
Kappa Light Chains ◽  
B Lymphoid

The membrane immunoglobulin heavy chain (micron) plays a feedback role during the pre-B stage of B lymphocyte differentiation. In pre-B cell lines, micron associates with two surrogate light chain proteins. The omega chain is disulfide linked to mu and was predicted to be the product of the lambda 5 gene. The iota chain is noncovalently associated with micron. We demonstrate that the omega protein is indeed the product of the lambda 5 gene and that mu, omega, and iota are coassociated in the same complex. Antibodies against the omega/lambda 5 protein demonstrate the existence of a subpopulation of "transitional" bone marrow B cells that express micron and omega on the cell surface. The majority of these cells also express surface kappa light chains, indicating that in B lymphoid ontogeny the lambda 5 gene is inactivated after the onset of kappa light chain expression.

scholarly journals Identification of Amyloidogenic Light Chains Requires the Combination of Serum-Free Light Chain Assay with Immunofixation of Serum and Urine

2009 ◽  
Vol 55 (3) ◽  
pp. 499-504 ◽  
Author(s):  
Giovanni Palladini ◽  
Paola Russo ◽  
Tiziana Bosoni ◽  
Laura Verga ◽  
Gabriele Sarais ◽  
...  
Keyword(s):  
Light Chain ◽  
Gel Electrophoresis ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Agarose Gel ◽  
Agarose Gel Electrophoresis ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Amyloid Deposits ◽  
Serum And Urine

Abstract Background: The diagnosis of systemic immunoglobulin light-chain (AL) amyloidosis requires demonstration of amyloid deposits in a tissue biopsy and amyloidogenic monoclonal light chains. The optimal strategy to identify the amyloidogenic clone has not been established. We prospectively assessed the diagnostic sensitivity of the serum free light chain (FLC) κ/λ ratio, a commercial serum and urine agarose gel electrophoresis immunofixation (IFE), and the high-resolution agarose gel electrophoresis immunofixation (HR-IFE) developed at our referral center in patients with AL amyloidosis, in whom the amyloidogenic light chain was unequivocally identified in the amyloid deposits. Methods: The amyloidogenic light chain was identified in 121 consecutive patients with AL amyloidosis by immunoelectron microscopy analysis of abdominal fat aspirates and/or organ biopsies. We characterized the monoclonal light chain by using IFE and HR-IFE in serum and urine and the FLC κ/λ ratio in serum. We then compared the diagnostic sensitivities of the 3 assays. Results: The HR-IFE of serum and urine identified the amyloidogenic light chain in all 115 patients with a monoclonal gammopathy. Six patients with a biclonal gammopathy were omitted from the statistical analysis. The diagnostic sensitivity of commercial serum and urine IFE was greater than that of the FLC κ/λ ratio (96% vs 76%). The combination of serum IFE and the FLC assay detected the amyloidogenic light chain in 96% of patients. The combination of IFE of both serum and urine with the FLC κ/λ ratio had a 100% sensitivity. Conclusions: The identification of amyloidogenic light chains cannot rely on a single test and requires the combination of a commercially available FLC assay with immunofixation of both serum and urine.

Amyloid Deposits in Bone Marrow Aspirates in Primary Amyloidosis

2009 ◽  
Vol 208 (1-6) ◽  
pp. 111-113 ◽  
Author(s):  
Per Stavem ◽  
Ingegerd Frøyshov Larsen ◽  
Bernt Ly ◽  
Tore O. Rørvik
Keyword(s):  
Bone Marrow ◽  
Primary Amyloidosis ◽  
Amyloid Deposits
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