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Serum protein electrophoresis (SPE) in combination with immunotyping (IMT) is the diagnostic standard for detecting monoclonal proteins (M-proteins). However, interpretation of SPE and IMT is weakly standardized, time consuming and investigator dependent. Here, we present five machine learning (ML) approaches for automated detection of M-proteins on SPE on an unprecedented large and well-curated data set and compare the performance with that of laboratory experts. SPE and IMT were performed in serum samples from 69,722 individuals from Norway. IMT results were used to label the samples as M-protein present (positive, n=4,273) or absent (negative n=65,449). Four feature-based ML algorithms and one convolutional neural network (CNN) were trained on 68,722 randomly selected SPE patterns to detect M-proteins. Algorithm performance was compared to that of an expert group of clinical pathologists and laboratory technicians (n=10) on a test set of 1,000 samples. The random forest classifier showed the best performance (F1-Score 93.2 %, accuracy 99.1 %, sensitivity 89.9 %, specificity 99.8 %, positive predictive value 96.9 %, negative predictive value 99.3 %) and outperformed the experts (F1-Score 61.2 ± 16.0 %, accuracy 89.2 ± 10.2 %, sensitivity 94.3 ± 2.8 %, specificity 88.9 ± 10.9 %, positive predictive value 47.3 ± 16.2 %, negative predictive value 99.5 ± 0.2 %) on the test set. Interestingly the performance of the RFC saturated, the CNN performance increased steadily within our training set (n=68,722). Feature-based ML systems are capable of automated detection of M-proteins on SPE beyond expert-level and show potential for use in the clinical laboratory. [ABSTRACT FROM AUTHOR]

Oligoclonal bands (OCB) analysis is the reference standard for detecting an intrathecal IgG synthesis. Alongside OCB, free light chains kappa (FLCκ) are considered an additional sensitive biomarker for determining patterns 2 or 3, indicating intrathecal Ig synthesis. However, kFLC IF is not suitable for detecting a monoclonal pattern 5. The primary aim of this study was to evaluate the impact of incorporating FLCκ analysis into routine cerebrospinal fluid (CSF) diagnostics instead of OCB testing on the rate of missed monoclonal IgG detection. A two-center retrospective biomarker study was conducted. OCB were identified using isoelectric focusing in polyacrylamide gels followed by silver staining or in agarose gels followed by immunofixation. FLCκ were quantified using nephelometry and FLCκ assay (Siemens). Out of a combined total of 17,755 OCB analyses conducted between 2011 and 2021, a subset of 269 cases (1.5 %) exhibited pattern 5. 98 samples (36 %), which included 18 samples with intrathecal inflammation as determined by additional OCB pattern 2 were included in the FLCκ analysis. Of those, 16 (89 %) had intrathecal FLCκ synthesis. While FLCκ offers a promising avenue for detecting an intrathecal inflammation, the pattern 5, though rare, remains a valuable additional finding of OCB analysis. A combined approach of FLCκ and OCB analysis is recommended for a comprehensive assessment of the humoral intrathecal immune response. [ABSTRACT FROM AUTHOR]

This document discusses the use of the lipemia index (L-index) as a potential tool for identifying patients with monoclonal gammopathy. The study found that the L-index had good specificity but low sensitivity for detecting M-proteins in serum and plasma samples. The accuracy of the L-index varied depending on the type of M-protein, and there was a low concordance between plasma and serum L-index values. The article suggests that the L-index test could be useful for identifying IgM plasma cell disorders, but further research is needed to improve its diagnostic performance. [Extracted from the article]

Serum free light chain (sFLC) measurements have inherent analytical limitations impacting sFLC clinical interpretation. We evaluated analytical and diagnostic performance of three polyclonal sFLC assays on four analytical platforms. sFLC concentration was measured using Diazyme FLC assays (Diazyme) on cobas c501/c503 analyzer (Roche); Freelite assays (The Binding Site) on Optilite analyzer (The Binding Site) and cobas c501 analyzer and Sebia FLC ELISA assays (Sebia) on AP22 ELITE analyzer (DAS). Imprecision, linearity, method comparison vs. Freelite/Optilite, antigen excess detection and reference value verification were assessed. Diagnostic performance was compared on 120 serum samples and on follow-up samples of five patients with κ and λ monoclonal gammopathy. Method comparison showed excellent correlation with Freelite/Optilite method for all assays. A large proportional negative bias was shown for both Sebia κ and λ ELISA and a significant positive proportional bias for λ in the low (<10 mg/L) Freelite/cobas c501 method. Clinically relevant underestimation of κ sFLC levels due to antigen excess was shown for 7% of each Diazyme/cobas application and for 11 and 32.1% of λ sFLC assay of respectively Diazyme/cobas and Sebia/AP22. sFLC reference values revealed application specific. Cohen's κ values were (very) good for κ sFLC but only moderate to good for λ sFLC. In 4/10 follow-up patients, significant differences in clinical interpretation between sFLC assays were noticed. Important analytical limitations remain for all sFLC applications. Differences in reference values and diagnostic performance hamper interchangeability of sFLC assays. Assay specific sFLC decision guidelines are warranted. [ABSTRACT FROM AUTHOR]

All of the 25 tested healthy control sera had an abnormal high FLC-ratio which was caused by consistently high FLC kappa results combined with consistently low FLC lambda results. Concordance analysis FLC-ratio For the concordance analysis, the FLC-ratios ( I i / I i ) are classified according to the kit-insert into three groups: below (low), above (high) or within the reference range (normal) (Figure 2). Development of a rapid and quantitative lateral flow assay for the simultaneous measurement of serum and immunoglobulin free light chains (FLC): inception of a new near-patient FLC screening tool. As a consequence, the FLC-ratio test-result of individual patients may be normal or abnormal depending on the FLC assay that is used. [Extracted from the article]

Objectives: Laboratory testing has an extensive role in the diagnosis of monoclonal gammopathies. Since the last updates of the International Myeloma Working Group (IMWG) guidelines for the diagnosis of monoclonal gammopathies, debate has arisen as to whether urine analysis remains relevant for the diagnosis of these entities., Methods: We carried out a retrospective study with data from 132 patients with a newly diagnosed serum M-protein. Patients were divided into two groups depending on the presence of M-protein in urine and different variables were recorded and statistically compared between groups., Results: The aim of the study was to find a serum M-protein cut-off value under which urine analysis could be avoided in the first laboratory diagnosis. The results show that when the concentration of serum M-protein is ≤3.5 g/L and eGFR is >30 mL/min/1.73 m 2 (sensitivity (S): 100 %, specificity (Sp): 49 %, negative-predictive value (NPV): 100 %) the probability of finding M-protein in urine is negligible. Patients with alpha heavy chain have a higher probability of having M-protein in urine. Thus, when the heavy chain of the M-protein is gamma or mu, serum cut-off value can be raised up to ≤4.9 g/L (S: 97 %, Sp: 52 %, NPV: 98 %)., Conclusions: Settling these two cut-off values when a new M-protein is discovered could avoid a significant number of urine analyses, optimizing laboratory and healthcare resources., Competing Interests: Competing interests: The authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Studies that investigate the accuracy and precision of M-protein quantification are scarce. These studies are prone to give a biased view, since they are exclusively performed by institutions with international top-expertise on M-protein diagnostics. To obtain a realistic impression of the accuracy and precision of M-protein quantification, we studied results of 73 laboratories participating in the Dutch External Quality Assessment (EQA) program for M-protein diagnostics. To measure accuracy, healthy serum was spiked with respectively 1 and 5 g/L human IgG-kappa monoclonal antibody daratumumab. To measure precision, five sera were selected to be repeatedly send to all blinded EQA-participants. The reported concentrations for the EQA-sample spiked with 5 g/L daratumumab ranged from 2.6 to 8.0 g/L (mean 4.9 g/L, between-laboratory CV = 23%). 98% of the participants detected and correctly characterized the 1 g/L daratumumab band. Both the accuracy (mean 1.7 g/L) and precision (between-laboratory CV = 46%) of this 1 g/L M-protein was poor. In the five EQA-samples that were repeatedly send to the same 73 participating laboratories, between-laboratory precision (mean CV = 25%) was significantly different than the within-laboratory precision (mean CV = 12%). Relatively poor precision was observed in sera with small M-proteins. The EQA-data reveal a large variation in reported M-protein concentrations between different laboratories. In contrast, a satisfactory within-laboratory precision was observed when the same sample was repeatedly analyzed. The M-protein concentration is correlated with both accuracy and precision. These data indicate that M-protein quantification to monitor patients is appropriate, when subsequent testing is performed within the same laboratory. [ABSTRACT FROM AUTHOR]

Background: Serum free light chain (sFLC) measurements are increasingly important in the context of screening for monoclonal gammopathies, prognostic stratification and monitoring of therapy responses. In this study we have performed a method comparison of four sFLC assays that are currently available for routine clinical use. Methods: In a retrospective study, sFLC analyses were performed on a cohort that included 139 patients with various monoclonal gammopathies and 54 control sera without an M-protein. Method comparisons of the following four FLC assays were performed: Freelite (Binding Site), N-Latex FLC (Siemens), Seralite (Abingdon Health) and Sebia FLC (Sebia). Results: Bland-Altman agreement analysis showed biases varying between −0.1 and 16.2 mg/L for κFLC, −6.0 and 6.8 mg/L for λFLC and −0.04 and 0.38 for the ratio of the involved to uninvolved FLC. Strong agreements were observed for FLC-concentrations below 100 mg/L. The clinical concordance of the κ/λFLC-ratio of the four methods varied between 86% and 92%. Significant quantitative differences were observed between the different methods, mainly in sera with high FLC concentrations. Most assays consistently overestimated FLC concentrations compared to SPE. Conclusions: Good overall clinical concordances were observed between the four sFLC assays that were compared in this study. Although good agreements were observed between the FLC assays, significant absolute differences in FLC concentrations in individual patients can be seen, particularly at higher FLC concentrations. Because of inequivalent absolute sFLC values between the methods in individual patients, none of the four sFLC assays can be used interchangeably. [ABSTRACT FROM AUTHOR]

Nevertheless, in the remaining four samples (summarized in Table 1) the -FLC band was still present shifted to a new migration point (indicated by a black arrow) that was different from the intact IgM- immunoglobulin band location, on the sIF gel (Figure 1, lanes 7-12). In order to further evaluate this phenomenon we performed additional specific sIF tests on previously typed as IgM- positive routine samples (with total IgM 1.46-49.33 g/L, M. protein<30.8 g/L, -FLC 9.25-1145 mg/L), using a FLC antisera. The quantitative -FLC values determined were far below the minimal detection limit of the immunofixation gel (120 mg/L for the Electrophoresis protein - (ELP) lane and 50 mg/L for the -free lane) [[3]], thus the -FLC band was supposed not to be visible on the sIF. [Extracted from the article]

Background: The heavy/light chain (HLC) immunoassay quantifies the different heavy chain/light chain combinations of each immunoglobulin (Ig) class. This makes the HLC assay suited to quantify monoclonal immunoglobulins (M-protein) and for monitoring of patients with monoclonal gammopathies. This method is particularly advantageous for those samples in which electrophoretic quantification of the M-protein is not possible. Methods: In this study we tested the analytical performance of the HLC assay in 166 routine clinical samples and in 27 samples derived from the Dutch external quality assessment (EQA) for M-protein diagnostics (74 participating laboratories). Analytical accuracy was assessed by verification that the sum of the HLC-pairs equaled total Ig concentration. Sensitivity of the HLC assay was determined in a direct method comparison with immunofixation electrophoresis (IFE). Results: Comparison of HLC data with routine Ig diagnostics in 27 EQA samples showed very good correlation for both the quantification of polyclonal and monoclonal IgG, IgA and IgM (Pearson correlations [r] were 0.94, 0.99 and 0.99, respectively; slopes were 0.94, 1.07 and 0.98, respectively). The overall concordance between IFE and the HLC ratio was high (93%) with a Cohen κ coefficient of 0.84. Discrepancies between both assays were mainly caused by the higher sensitivity of IFE to detect monoclonality. Conclusions: We conclude that the HLC assay is an accurate method to quantify M-proteins that can improve monitoring of M-proteins in the beta fraction that cannot be quantified using electrophoretic techniques. e [ABSTRACT FROM AUTHOR]

Background: Serum free light chain (sFLC) measurements are increasingly important in the context of screening for monoclonal gammopathies, prognostic stratification, and monitoring of therapy responses. At the same time, analytical limitations have been reported with the currently available nephelometric and turbidimetric sFLC assays. We have evaluated a new quantitative sFLC ELISA for its suitability in routine clinical use. Methods: Reference ranges of the Sebia FLC assay were calculated from 208 controls. Assay interference, reproducibility, lot-to-lot variability, and linearity were assessed. Method comparison to the Freelite assay (Binding Site) was conducted by retrospective analysis of 501 patient sera. Results: Reference ranges of the Sebia κ/λFLC-ratio were 0.37-1.44. We observed good sensitivity (1.5 mg/L) and linearity in both polyclonal and monoclonal sFLC samples and never experienced antigen excess. Sebia FLC reproducibility varied between 6.7% and 8.1% with good lot-tolot consistency. Method comparison with Freelite showed the following correlations: κFLC R = 0.94, λFLC R = 0.92 and κ/λFLC-ratio R = 0.96. The clinical concordance of the κ/λFLC-ratio of both methods was 94%. Significant quantitative differences were observed between both methods, mainly in sera with high FLC concentrations. The Sebia monoclonal FLC concentrations were coherent with those obtained by serum protein electrophoresis (SPE). Freelite monoclonal FLC concentrations were consistently higher, with a mean 12-fold overestimation compared to SPE. Conclusions: The Sebia FLC assay provides a novel platform for sensitive and accurate sFLC measurements. The Sebia FLC showed good clinical concordance with Freelite. Further studies are warranted to confirm the clinical value of this assay. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 76-year-old White Spanish woman for a study of the multiple myeloma (MM) detected in an analytical control. Topics discussed include medical history of arthrosis and osteoporosis with hypertension and bone pain, laboratory tests performed on patient like blood analysis, magnetic resonance imaging (MRI) and bone marrow aspiration (BMA), and detection of immunoglobulin E (IgE) MM with serum proteinogram.

The article presents a study on the prozone effect observed for heavy chain alpha in the serum immunofixation electrophoresis of a patient with monoclonal IgA-lambda gammopathy. Topics discussed include information on the Antigen-antibody interaction; discussions on the serum protein electrophoresis on agarose gel; and the information on the performing the complete blood count on an hematology analyser.

Background: Monoclonal (M) components can interfere with the direct bilirubin (D-Bil) assay on the AU Beckman Coulter instrumentation and produce spurious results, such as D-Bil values greater than total bilirubin (T-Bil) or very low/negative D-Bil values. If properly detected, this interference may uncover undiagnosed patients with monoclonal gammopathy (MG). Methods: We investigated the interference rate on the D-Bil AU assay in serum samples known to contain M proteins along with their isotype and described the protocol set up in our laboratory to help with the diagnosis of MG based on D-Bil spurious results as first indication. Results: During a period of 4 years, 15.4% (345 of 2235) of serum samples containing M immunoglobulins produced erroneous D-Bil results, although no clear relationship between the magnitude or isotype of the M component and interference could be found. In total 22 new patients were diagnosed with MG based on the analytical artefact with the D-Bil as first indication. Conclusions: The D-Bil interference from MG on the Beckman AU analysers needs to be made known to laboratories in order to prevent clinical confusion and/or additional workup to explain the origin of anomalous results. Although this information may not add to the management of existing patients with serum paraproteins, it can benefit patients that have not been diagnosed with MG by triggering follow up testing to determine if M components are present. [ABSTRACT FROM AUTHOR]

Recently, monoclonal gammopathy of renal significance (MGRS) reclassified all monoclonal (M) gammopathies that are associated with the development of a kidney disease but do not meet the definition of symptomatic multiple myeloma (MM) or malignant lymphoma. The purpose was to distinguish the M gammopathy as the nephrotoxic agent independent from the clonal mass. The diagnosis of MGRS obviously depends on the detection of the M-protein. More importantly, the success of treatment is correlated with the reduction of the M-protein. Therefore, familiarity with the M-protein tests is a must. Protein electrophoresis performed in serum or urine is inexpensive and rapid due to automation. However, poor sensitivity especially with the urine is an issue particularly with the low-level M gammopathy often encountered with MGRS. Immunofixation adds to the sensitivity and specificity but also the cost. Serum free light chain (sFLC) assays have significantly increased the sensitivity of M-protein detection and is relatively inexpensive. It is important to recognize that there is more than one assay on the market and their results are not interchangeable. In addition, in certain diseases, immunofixation is more sensitive than sFLC. Finally, novel techniques with promising results are adding to the ability to identify M-proteins. Using the time of flight method, the use of mass spectrometry of serum samples has been shown to dramatically increase the sensitivity of M-protein detection. In another technique, oligomeric LCs are identified on urinary exosomes amplifying the specificity for the nephrotoxic M-protein. [ABSTRACT FROM AUTHOR]

Background: POEMS syndrome is defined by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. The vascular endothelial growth factor (VEGF) appears to play a key role in the pathogenesis of the syndrome, and its concentrations are deemed to correlate to disease activity. The aim of the present study was to verify whether other biochemical markers including serum free light chains (FLC) and heavy/light chains (HLC) would be of value in monitoring POEMS patients. Methods: Fifty-three serum samples were collected from seven POEMS patients at diagnosis and during a follow-up period (range 14-56 months). VEGF was measured using an ELISA method, while FLC and HLC concentrations were measured using Binding Site reagents on a BNII (Siemens) nephelometer. Results: At diagnosis all patients presented high VEGF concentrations, while the κ/λFLC ratio (FLCr) was within the reference range. Four patients had abnormal HLC, HLCκ/HLCλ (HLCr) and FLC values. The relationship between the trend of VEGF and both HLC and FLC during the follow-up was analysed by means of Cohen's κ coefficient. VEGF and HLC values displayed a significant k-Cohen (0.537, p = 0.002) in all chemotherapy-responder patients while in non-responders it did not. Conversely, in both responders and non-responders, VEGF and FLC values did not attain a significance on k-Cohen analysis. In three out of four responders HLCr values increased, thus reflecting an improved clinical condition. Conclusions: The findings made in the present study indicate that HLC, either as intact immunoglobulin or as HLCr, may provide useful information, particularly in identifying responders and confirm that the role of FLC is unreliable in monitoring patients with POEMS syndrome. [ABSTRACT FROM AUTHOR]

The serum free light chain (FLC) assay has proven to be an important complementary test in the management of patients with monoclonal gammopathies. The serum FLC assay has value for patients with plasma cell disorders in the context of screening and diagnosis, prognostic stratification, and quantitative monitoring. Nonetheless, serum FLC measurements have analytical limitations which give rise to differences in FLC reporting depending on which FLC assay and analytical platform is used. As the FLC measurements are incorporated in the International Myeloma Working Group guidelines for the evaluation and management of plasma cell dyscrasias, this may directly affect clinical decisions. As new certified methods for serum FLC assays emerge, the need to harmonise patient FLC results becomes increasingly important. In this opinion paper we provide an overview of the current lack of accuracy and harmonisation in serum FLC measurements. The clinical consequence of non-harmonized FLC measurements is that an individual patient may or may not meet certain diagnostic, prognostic, or response criteria, depending on which FLC assay and platform is used. We further discuss whether standardisation of serum FLC measurements is feasible and provide an overview of the steps needed to be taken towards harmonisation of FLC measurements. [ABSTRACT FROM AUTHOR]

In the present study we describe a patient who has interference due to paraproteinemia in her labaratory results. In a patient with a total protein concentration of 10.8 g/dL, a direct bilirubin result higher than total was detected. She also had discordant results in her whole blood count parameters. Further investigation was performed on this patient. Presence of any cold agglutinin and cryoglobulin was tested and excluded first. After 2-mercaptoethanol (2-ME) treatment, patient was idendified as Ig-M Kappa monoclonal gammapathy on immunofixation electrophoresis (IFE). Direct bilirubin interference disappeared after removal of the paraprotein by polyethylene glycol (PEG) precipitation. Laboratory specialist should know paraprotein interference and be able to manage it. [ABSTRACT FROM AUTHOR]

The article offers information on the free light chain ratio in patients with chronic kidney disease. It mentions the guidelines for diagnosis and management of all monoclonal gammopathies. It also mentions the issues relating to the renal impairment along with the medical care of patients with monoclonal gammopathies.

The article presents a study that describes the condition of a patient with immunoglobulin (Ig) multiple myeloma (MM) with extensive excretion of free light chains (FLC). It describes the method of the study that observes a 58-year-old white man who was admitted to hospital due to fatigue and weight loss. It outlines the result which indicates that IgD MM may be associated with an extensive production of FLC and misdiagnosed as a light-chain MM.

A letter to the editor is presented in response to the article "Identification of 5-fluorocytosine as a new interfering compound in serum capillary zone electrophoresis" by Hélène Caillon and colleagues in the previous issue.

The article presents an observational prospective study which determines the frequency of improper serum separation on gel tubes and its relationship with monoclonal gammopathy. Findings reveal that out of 42,080 patients who underwent the two-year study, 23 of them demonstrated improper serum separation. It concludes that the occurrence of incomplete serum separation on the gel tubes is an uncommon phenomenon.

Hematological neoplasms associated with systemic mast cell disease are most frequently of myeloid origin. There are a few reports, however, of systemic mastocytosis (SM) cases associated with lymphoid or plasma cell neoplasms as well. In this report, the authors present a case of SM (with D816V mutation in the c-KIT gene) associated with JAK2 V617F mutation negative essential thrombocythemia. The leading symptom of the 78-year-old female was recurring hydrothorax that responded only to interferon alpha therapy. During the first year of therapy, the patient developed insulin-dependent diabetes and hypothyroidism. The hematological workup also revealed IgG kappa monoclonal gammopathy that was non-progressive in the following next three years. Low levels of complements without known clinical significance accompanied the entire picture. [ABSTRACT FROM AUTHOR]

Background: New monoclonal antibody-based assays for serum-free light chains (FLC) have become available. Methods: In a clinical study with 541 patients, the new N Latex FLC assays were compared with the Freelite™ FLC assays and immunofixation electrophoresis (IF). Results: Comparison of the different FLC kappa (κ) assays showed a slope of 0.99 with a deviation of 5.0%, rs=0.92, for FLC lambda (λ) a slope of 1.22, deviation 13.8%, rs=0.90 and for the κ/λ ratio a slope of 0.72, deviation -4.6%, rs=0.72. The concordance for the FLC κ assays was 91%, for FLC λ 85% and κ/λ ratio 95%. The clinical sensitivity and specificity of the κ/λ ratios in the study were comparable: 60% and 99% for the N Latex FLC assay and 61% and 97% for the Freelite™ assay. In IF-FLC positive samples, the N Latex FLC κ/λ ratio scored 20/23 (87%) samples outside the reference range and Freelite™ 21/23 (91%). For IF-FLC negative samples, N Latex FLC assay κ/λ ratio scored 338/350 (97%) within the reference range and Freelite™ scored 332/350 (95%). Conclusions: The concordance scores and the clinical sensitivity and specificity of the new N Latex FLC assays and Freelite™ assays appeared comparable, but there are some differences in measurement of concentrations between the methods. [ABSTRACT FROM AUTHOR]

Skeletal-extraskeletal angiomatosis is defined as a benign vascular proliferation affecting the medullar cavity of the bone and at least one other type of tissue, including skin, subcutaneous tissue, viscera, muscle, or synovium, and which does not spread to avascular tissue such as cartilage. Primary hemangiomas/cavernous hemangiomas (cavernomas) are exceedingly rare in the skull, accounting for 0.2% of all osseous neoplasms and are usually located in frontal and parietal bones. The authors present the case of a 66-year-old man who was admitted with right-side hemiparesis. MRI revealed a destructive bone lesion of the left frontal bone. Digital subtraction angiography of the brain did not reveal pathological vascularization, but a minor submucous hemangioma was seen in the nasal airway. Urine test for Bence-Jones proteins was positive for IgG λ light chain. Bone marrow aspiration and CSF analysis revealed no evidence of systemic myelomatosis suggesting a monoclonal gammopathy of undetermined significance. A highly vascular tumor was surgically removed. The histopathology verified cavernous hemangioma of the skull and the nasal submucous hemangioma. We discuss the diagnostic procedure, possible pathophysiological mechanisms and treatment implementation. It is possible that immunoglobulins from monoclonal gammopathies have an etiologic role in the development of the bone and skin changes in older patients, as an acquired condition, by producing a vascular injury that could lead to the multiple hemangiomas in skeletal-extraskeletal angiomatosis. To prevent misdiagnosis with lesions of other origins, multiple lesions of the head must be resected and histopathologically verified. In conclusion, to the best of our knowledge, this is the first case of giant cavernous hemangioma of the skull associated with paraproteinemia and skeletalextraskeletal angiomatosis limited to the head. [ABSTRACT FROM AUTHOR]

Background: Serum free light chain (FLC) analysis is used in the prognostic assessment and monitoring of patients with monoclonal gammopathies (MG). Its use in detection of MG is less widespread despite good sensitivity for diseases poorly detected by serum protein electrophoresis (SPE), e.g., FLC disease and AL amyloidosis. FLC analysis may facilitate earlier diagnosis in these diseases. However, if replacing urine protein electrophoresis (UPE) in an initial screening algorithm, this must be balanced against any loss of detection of Bence Jones proteinuria (BJP). Methods: We assessed the effect of replacing UPE with FLC. Sensitivity of FLC for BJP was assessed in 126 clinical cases where UPE and FLC analyses were performed. Impact on disease detection was assessed from 753 patient sera tested by SPE and FLC and 128 patients matched associated urine samples. Results: Sensitivity of FLC for BJP was 98%. Use of FLC in routine testing increased the number of MG detected by 7%. Conclusions: Using FLC alongside or in place of UPE can give clinical benefit through earlier diagnosis and hence treatment earlier in the patients' disease. [ABSTRACT FROM AUTHOR]

Background: Quantification of monoclonal immunoglobulin free light chains (FLCs) in serum is used increasingly in clinical practice for the diagnosis, prognostic assessment, and treatment monitoring of monoclonal gammopathies. It is used as an adjunct to standard serum protein electrophoresis and immunofixation. However, methods for FLC quantification need further standardization and validation. Methods: The Czech Myeloma Group and the Czech Society of Clinical Biochemistry have initiated an interlaboratory study where six laboratories collaborating with the primary myeloma treatment centres measured FLC concentrations in 12 serum samples from patients with monoclonal gammopathies. Results: Repeatability of the measurements in five laboratories was calculated based on differences between the results of duplicate measurements. We found that repeatability depended more on the laboratory than on the device used for measurement. Conclusions: The study revealed several weak points in the methodology, including the need for a uniform sample dilution procedure. Interlaboratory reproducibility was comparable with values achieved in the NEQAS programme. Because the κ/λ ratio cannot be measured with high precision, κ and λ FLC concentrations should be used where possible. Due to its impact on the clinical management of patients with gammopathy, FLC quantification needs to become a part of the regular quality control cycle in myeloma centres. [ABSTRACT FROM AUTHOR]

Background: The Freelite™ system for nephelometric or turbidimetric measurement of serum free light chains (FLCs) has been available since 2001. It has been valuable for the management of patients with oligosecretory myeloma, light chain myeloma and AL amyloidosis. However, there are several limitations of the method. The goal of this study was to evaluate the analytical performance of the FLC assay. Methods: Titrated controls and clinical serum specimens were used to determine precision and post-dilution recovery. Results: As reported elsewhere, we found that the assay had several limitations, including poor post-dilution linearity and overestimation by nephelometry. Conclusions: These data demonstrate that the results of the FLC assay must be interpreted jointly by the clinician and the biologist, taking into account the individual patient's clinical and biological characteristics. Clin Chem Lab Med 2010;48:73–9. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to evaluate the efficiency of free light chain (FLC) analysis in comparison to serum protein electrophoresis (SPE) for detecting M-proteinemia. Methods: A total of 553 consecutive patients for whom evaluation of M-proteinemia was requested were included in this study. For all patients, serum FLC analysis and SPE followed by pentavalent immunofixation analysis was performed. Identification of monoclonal bands was performed using specific antisera. FLC analysis was performed using the Modular P analyzer in accordance with the manufacturer's recommendations. Local reference ranges for FLCs on this platform were established based on samples from patients with a normal electrophoretic pattern [no monoclonal bands, no hypo- or hypergammaglobulinemia, no acute phase pattern and normal kidney function, i.e., estimated glomerular filtration rate (eGFR) >60 mL/min]. Results: Local reference ranges (95%) were established (n=243): κ: 8.01–28.26 mg/L; λ: 8.07–23.58 mg/L and κ/λ ratio: 0.74–1.66. Negative and positive predictive values were 98.6% and 49.5%, respectively, for screening for M-proteinemia by SPE alone, 94.3% and 21.7% for FLC concentration and 95.1% and 21.4% for FLC with the κ/λ-ratio included. Combining protein electrophoresis and FLCs resulted in a negative predictive value of 99.0% and a positive predictive value of 23.4%. Conclusions: Serum FLC analysis alone is not suitable for screening for M-proteinemia. Clin Chem Lab Med 2009;47:1507–11. [ABSTRACT FROM AUTHOR]

The article presents a study of the sensitivity of various biochemical methods and their combinations for the analysis of serum and urine to determine the presence of monoclonal proteins in malignant monoclonal gammopathy. Serum and urine samples from patients with malignant monoclonal gammopathy were examined using protein electrophoresis, serum immunofixation and urine immunofixation. Combining free light chain (FLC) assessment with serum electrophoresis and immunofixation is recommended.

Background: Protein and immunofixation electrophoresis of serum and urine are established as diagnostic aids for identifying monoclonal gammopathies. However, many patient sera sent to laboratories are not accompanied by urine samples and recent reports suggest the use of serum free light chain (sFLC) analysis in combination with serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) could eliminate the need for urinalysis. The aim of the study was to assess the utility of sFLC measurement in addition to serum protein electrophoresis in the identification of patients with B-cell malignancies. Methods: A total of 952 serum samples were analysed by serum protein electrophoresis and those with abnormal bands were analysed by immunofixation. sFLCs were measured in a retrospective manner by automated assay. Results: In our study of 952 patient sera, it was found that FLC analysis identified 23 additional cases of B-cell malignancies which were missed by SPE. Conclusions: The additional malignancies identified by sFLC analysis add support for its inclusion in the routine screening protocol for B-cell malignancies. Clin Chem Lab Med 2009;47:302–4. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to an article on monoclonal gammopathy (MG) associated with bone marrow (BM) plasma cell separation.