Search

This document provides a summary of a study on proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID), a kidney disease characterized by the presence of a monoclonal immunoglobulin. The study analyzed 15 patients with PGNMID in Belgium and The Netherlands and provided detailed information on patient demographics, kidney function, biopsy findings, and treatment regimens. The study found that patients who received clone-directed therapy had a better renal response compared to those who did not. Recurrence of PGNMID after kidney transplantation was common, and the study calls for further research to improve diagnostic and therapeutic strategies for this disease. [Extracted from the article]

Serum electrophoresis (SPEP) is a method used to analyze the distribution of the most important proteins in the blood. The major clinical question is the presence of monoclonal fraction(s) of antibodies (M-protein/paraprotein), which is essential for the diagnosis and follow-up of hematological diseases, such as multiple myeloma. Recent studies have shown that machine learning can be used to assess protein electrophoresis by, for example, examining protein glycan patterns to follow up tumor surgery. In this study we compared 26 different decision tree algorithms to identify the presence of M-proteins in human serum by using numerical data from serum protein capillary electrophoresis. For the automated detection and clustering of data, we used an anonymized data set consisting of 67,073 samples. We found five methods with superior ability to detect M-proteins: Extra Trees (ET), Random Forest (RF), Histogram Grading Boosting Regressor (HGBR), Light Gradient Boosting Method (LGBM), and Extreme Gradient Boosting (XGB). Additionally, we implemented a game theoretic approach to disclose which features in the data set that were indicative of the resulting M-protein diagnosis. The results verified the gamma globulin fraction and part of the beta globulin fraction as the most important features of the electrophoresis analysis, thereby further strengthening the reliability of our approach. Finally, we tested the algorithms for classifying the M-protein isotypes, where ET and XGB showed the best performance out of the five algorithms tested. Our results show that serum capillary electrophoresis combined with decision tree algorithms have great potential in the application of rapid and accurate identification of M-proteins. Moreover, these methods would be applicable for a variety of blood analyses, such as hemoglobinopathies, indicating a wide-range diagnostic use. However, for M-protein isotype classification, combining machine learning solutions for numerical data from capillary electrophoresis with gel electrophoresis image data would be most advantageous. [ABSTRACT FROM AUTHOR]

Free light chain (FLC) assays and the ratio of κ/λ are recommended for diagnosis, prognosis and monitoring of plasma cell dyscrasias (PCD). Limited data exists on FLC clinical specificity in patients diagnosed with other conditions. We assessed the κ, λ, and κ/λ FLC ratio using the FreeLite assay and the Sebia FLC ELISA assay in 176 patients with clinical presentations of fatigue, anemia, polyclonal hypergammaglobulinemia, joint disorders, kidney disease and non PCD-cancers with no monoclonal protein observed on serum protein electrophoresis or MASS-FIX immunoglobulin isotyping. Manufacturer defined reference intervals (RI) and glomerular filtration rate (GFR) specific RI (renal RI) were utilized. For the κ/λ ratio, 68.7 % (121/176) of specimens on the FreeLite and 87.5 % (154/176) of specimens on the Sebia assay were within RI. For κ, 68.2 % (120/176) and 72.2 % (127/176) of results were outside RI for FreeLite and Sebia respectively. For λ, 37.5 % (66/176) and 84.1 % (148/176) of FreeLite and Sebia results were outside RI. With FreeLite and Sebia, patients with kidney disease (n=25) had the highest κ/λ ratios. 44 patients (25.0 %) had GFR <60 mL/min/BSA. When renal RI were applied, 13.6 % had a FLCr outside the renal RI with FreeLite, and 4.5 % with Sebia. In a cohort of patients with signs and symptoms suggestive of PCDs, but ultimately diagnosed with other conditions, Sebia FLC had improved clinical specificity relative to FreeLite, if one was using an abnormal κ/λ ratio as a surrogate for monoclonality. [ABSTRACT FROM AUTHOR]

Objective: Rare disease. Background: Non-IgM lymphoplasmacytic lymphoma (LPL) is a rare subtype of LPL, constituting less than 5% of the cases, and is often associated with IgG, IgA, or light chain paraproteins and is rarely a non-secretor. Non-IgM LPL remains poorly studied, and the differential diagnosis from other small B-cell lymphomas with plasmacytic differentiation and plasma cell neoplasm is challenging. Case Report: A 67-year-old woman presented with weight loss, persistent anemia, and borderline leukopenia. Serum protein electrophoresis and immunofixation demonstrated a faint IgG and kappa band against a dense polyclonal background. Bone marrow biopsy revealed hypercellular marrow with involvement by abnormal B cells with undetectable surface and cytoplasmic immunoglobulin light chains. Interestingly, these B cells showed no expression of light chains or production of IgG and IgM; however, they showed production of intracytoplasmic IgA. The concomitant neoplastic plasma cells also displayed no definitive light chain expression. Both IgH and IgK gene rearrangements were positive for clonal process. Molecular studies showed positive MYD88 L265P mutation and CXCR4 mutation (c.1013C>G). The overall findings confirmed marrow involvement by non-IgM LPL. The patient received 6 cycles of rituximab and bendamustine treatment, and no residual marrow involvement was found on the follow-up bone marrow biopsy. Conclusions: We report a non-IgM LPL case featuring no light chain production and no heavy chain secretion, which we believe is the first reported case of this kind in the literature. [ABSTRACT FROM AUTHOR]

Simple Summary: Outcomes for high-risk myeloma patients are still poor, despite many advances in treatment. In addition, scarce data exist on double maintenance in transplant-eligible high-risk newly diagnosed multiple myeloma (NDMM) patients. We present the results of a prospective study on 120 transplant-eligible NDMM patients with prolonged cytogenetic risk-based all-oral maintenance with lenalidomide + ixazomib (IR) for high-risk patients and lenalidomide (R) alone for non-high-risk patients after ixazomib–lenalidomide–dexamethasone (IRD) induction plus autologous stem cell transplantation followed by IRD consolidation. We found that high-risk cytogenetics had no impact on the proportion of patients achieving sustained undetectable minimal residual disease or on the rate of progression-free survival with IR maintenance. Our data suggest that prolonged use of all-oral double maintenance with IR with reasonable adverse effects would be a potential option for high-risk myeloma patients. Scarce data exist on double maintenance in transplant-eligible high-risk (HR) newly diagnosed multiple myeloma (NDMM) patients. This prospective phase 2 study enrolled 120 transplant-eligible NDMM patients. The treatment consisted of four cycles of ixazomib–lenalidomide–dexamethasone (IRD) induction plus autologous stem cell transplantation followed by IRD consolidation and cytogenetic risk-based maintenance therapy with lenalidomide + ixazomib (IR) for HR patients and lenalidomide (R) alone for NHR patients. The main endpoint of the study was undetectable minimal residual disease (MRD) with sensitivity of <10−5 by flow cytometry at any time, and other endpoints were progression-free survival (PFS) and overall survival (OS). We present the preplanned analysis after the last patient has been two years on maintenance. At any time during protocol treatment, 28% (34/120) had MRD < 10−5 at least once. At two years on maintenance, 66% of the patients in the HR group and 76% in the NHR group were progression-free (p = 0.395) and 36% (43/120) were CR or better, of which 42% (18/43) had undetectable flow MRD <10−5. Altogether 95% of the patients with sustained MRD <10−5, 82% of the patients who turned MRD-positive, and 61% of those with positive MRD had no disease progression at two years on maintenance (p < 0.001). To conclude, prolonged maintenance with all-oral ixazomib plus lenalidomide might improve PFS in HR patients. [ABSTRACT FROM AUTHOR]

Predictors of arthritis development in patients with anti-citrullinated protein antibodies (ACPAs) and musculoskeletal symptoms are needed for risk stratification and to improve clinical outcomes. The aim of this study was to assess the relationship between serum protein electrophoresis (SPE) constituents and the development of clinical arthritis in ACPA-positive patients with musculoskeletal pain. We prospectively followed 82 ACPA-positive patients with musculoskeletal pain but no baseline arthritis during a median of 72 months (interquartile range 57–81 months). The primary outcome was arthritis development, as judged by clinical examination. SPE constituents were evaluated in baseline sera by immunoturbidimetric methods. Serum levels of the analysed proteins (albumin, orosomucoid, α1-anti-trypsin, haptoglobin, and immunoglobulins IgA, IgG, and IgM) were related to arthritis development by Cox regression analyses. During the follow-up period, 39/82 patients (48%) progressed to arthritis. Median baseline levels of orosomucoid and α1-anti-trypsin were higher in patients who developed arthritis than in those who did not (p = 0.04), while median albumin levels were significantly lower (p = 0.03). Immunoglobulin levels did not differ between the groups. Univariable analysis demonstrated a significantly increased risk of arthritis with elevated baseline haptoglobin [hazard ratio (HR) 2.53, 95% confidence interval (CI) 1.32–4.85, p = 0.005] and orosomucoid levels (HR 2.63, 95% CI 1.09–6.31, p = 0.03). However, neither remained significant in multivariable analysis adjusting for elevated C-reactive protein (CRP) levels. SPE does not add prognostic value for arthritis development in ACPA-positive patients with musculoskeletal pain. [ABSTRACT FROM AUTHOR]

Introduction: Canine leishmaniosis (CanL) is a systemic disease that affects dogs. When multiplication of the parasite cannot be controlled, dogs consistently show high levels of antigen and IgG antibodies, which lead to the formation of circulating immune complexes (CIC). Timely intervention to reduce the parasite load and CIC levels is crucial for preventing irreversible organ damage. However, a diagnostic test to quantify CIC levels is currently lacking. Methods: In this real-world study, we aimed to examine the performance of a new ELISA to measure CIC levels in dogs naturally infected with Leishmania infantum. Thirty-four dogs were treated according to their clinical condition and followed for 360 days. Before (day 0) and after treatment (days 30, 90, 180, 270, and 360), all dogs underwent a physical examination, and blood samples were obtained for CBC, biochemical profile, serum protein electrophoresis and IFAT. Serum PEG-precipitated CIC were determined by ELISA. Results: Our results indicate higher CIC levels in dogs in advanced disease stages showing higher antibody titres (p < 0.0001, r = 0.735), anemia (p < 0.0001), dysproteinemia (p < 0.0001), and proteinuria (p = 0.004). Importantly, dogs responding well to treatment exhibited declining CIC levels (p < 0.0001), while in poor responders and those experiencing relapses, CIC were consistently elevated. CIC emerged as a robust discriminator of relapse, with an area under the curve (AUC) of 0.808. The optimal cut-off to accurately identify relapse was an optical density of 1.539. Discussion: Our findings suggest that declining CIC levels should be expected in dogs showing a favorable treatment response. Conversely, in dogs displaying a poor response and recurrent clinical relapses, CIC levels will be high, emphasizing the need for vigilant monitoring. These findings suggest that CIC could serve as a valuable biomarker for disease progression, treatment efficacy, and relapse detection in CanL. Our study contributes to enhancing diagnostic approaches for CanL and underscores the potential of CIC as a complementary tool in veterinary practice. As we move forward, larger studies will be essential to confirm these findings and establish definitive cut-offs for clinical application. [ABSTRACT FROM AUTHOR]

Canine heartworm disease by Dirofilaria immitis and canine leishmaniosis by Leishmania infantum (CanL) are both vector-borne diseases with frequently overlapping endemicity and able to trigger the acute phase response, being characterized by variations in acute phase proteins (APP). Recently, erythrocyte sedimentation rate (ESR), an indicator of inflammation, has gained attention in veterinary medicine, proving useful in several conditions that include CanL active forms in dogs. This study aims to evaluate ESR in heartworm-infected dogs, compare levels with heartworm-infected and L. infantum seropositive dogs as well as clinically healthy dogs, and assess correlations with other laboratory parameters. From October 2022 to January 2023, a prospective observational study was conducted enrolling heartworm-infected (Dirofilaria group) and heartworm-infected L. infantum seropositive (Dirofilaria/Leishmania group) animals subgrouped according to the CanL clinical form (Dirofilaria/Leishmania active and non-active groups). A group of clinically healthy dogs (control group) was also included. For each dog enrolled physical examination and laboratory tests (complete blood count, biochemical panel including APP, serum protein electrophoresis) were performed. Dirofilaria and Dirofilaria/Leishmania groups presented a significantly higher ESR level compared to healthy dogs. Dirofilaria/Leishmania active group had the highest ESR level among the groups considered. Dirofilaria/Leishmania non-active group had an ESR similar to the Dirofilaria group, but significantly higher and lower compared to the control and the Dirofilaria/Leishmania active group, respectively. A significant positive correlation between ESR and C-Reactive Protein has been found in all groups except for the Dirofilaria/Leishmania non-active group. In Dirofilaria/Leishmania active group a strong positive correlation between ESR and gamma globulins percentage as well as a strong negative correlation between ESR and albumin, albumin/globulins ratio were found. Overall, the ESR was confirmed to be an inflammation marker as well as a helpful disease index, being notably increased in heartworm-infected dogs affected by an active form of CanL. [ABSTRACT FROM AUTHOR]

The presented case study focuses on the complexities and challenges in diagnosing one of the forms of amyloidosis, where abnormal protein (amyloid) deposits in various organs and tissues lead to affection of many organs, especially the heart, kidneys, liver, spleen, and occasionally the central nervous system. Its aetiology remains largely unknown, making diagnosis and treatment particularly challenging. This report details the case of an 88-year-old patient, disabled for months (with a modified Rankin Scale score of 4), who presented to the Neurology Department with sudden right limb paresis and speech disorders. Initial assessments indicated suggested ischemic stroke, and patients received thrombolysis. Further laboratory tests and imaging, including serum protein electrophoresis and computer tomograph (CT) scans, suggested transthyretin amyloidosis (ATTR), which was later confirmed through genetic testing. This case underscores the rapid, multi-organ progression of amyloidosis and its devastating impact, highlighting the necessity for early diagnosis and a multidisciplinary treatment approach. Despite ongoing research, the pathogenesis of amyloidosis remains elusive, and current treatment options are primarily symptomatic. This study aims to shed light on the diagnostic difficulties and the urgent need for timely intervention in amyloidosis cases. [ABSTRACT FROM AUTHOR]

Background: Examination of urine by immunofixation electrophoresis (UIFE) is one of the tests recommended for screening and monitoring of monoclonal gammopathies, especially multiple myeloma. Unlike the serum free light chain measurement, a positive result on urine immunofixation is diagnostic for monoclonal immunoglobulin light chains. Urine is usually concentrated, generally by membrane filtration, prior to electrophoresis. Methods: Alternative methods to membrane filtration for urine concentration were examined. Residual urine specimens submitted for urine protein electrophoresis were concentrated by precipitation of the proteins by ammonium sulfate salt precipitation, precipitation with ethanol and acetonitrile, and by desiccation. The concentrated specimens were subjected to immunofixation electrophoresis using antisera to free light chains (FLC). The results were compared with those from conventional immunofixation electrophoresis using specimens concentrated by membrane filtration. Results: Ammonium sulfate, ethanol, and acetonitrile precipitation results were less than satisfactory. Concentration by desiccation provided results comparable, if not better than, those by membrane filtration and conventional UIFE. The cost of desiccation is minimal compared to more than $5.00/specimen cost of concentration by membrane filtration. The differences in the results with conventional UIFE and the method described here are likely due to (a) variability in the reactivity of different antisera to free monoclonal light chains, and (b) obscuration of monoclonal free light chains by co-migration with intact immunoglobulin monoclonal proteins. Conclusions: Concentrating urine by desiccation for immunofixation electrophoresis is technically simple, inexpensive, and provides results comparable to concentrating by membrane filtration. Using FLC provides a more sensitive assay than using conventional antisera. [ABSTRACT FROM AUTHOR]

This study aimed to assess the effect of exercise on serum electrophoretic protein pattern, C-reactive protein (CRP) and platelet aggregation in horses subjected to a jumping exercise. The possible relationship between acute-phase reactions and platelet reactivity in the context of exercise was investigated. Blood samples were collected from 10 jumper horses at rest (TREST), within 5 min from the end of exercise (TPE5), and 30 min (TPE30) and 60 min after exercise (TPE60). The serum values of total proteins; CRP; albumin; α1-, α-2, β1-, β2- and γ-globulins; and the maximum degree of aggregation and the initial velocity of aggregation (slope) were evaluated. According to one-way analysis of variance, CRP and α1-, α-2, β1- and β2-globulins increased after exercise compared with rest condition (p < 0.001), whereas albumin and platelet aggregation showed lower values after exercise than at rest (p < 0.001). CRP and α1-globulin values were negatively correlated with both platelet aggregation indices at TPE5, whereas no significant correlation among these parameters was found at TREST, TPE30 and TPE60. This study provides evidence that an acute-phase response occurred in horses after the jumping exercise and suggests a linkage between the inflammatory status and the platelet responsiveness in horses during exercise. [ABSTRACT FROM AUTHOR]

Tongue extramedullary plasmacytoma (EMP) with regional lymph node metastases is a very rare pathology. Despite being a rare entity, extramedullary plasmacytoma should be considered a differential diagnosis in cases of a mass or ulcer in the tongue. A 60-year-old lady presents with an ulcerative lesion over the right lateral border of the tongue with dimensions 3.5 × 2 cm for one year. Initially, on histopathological examination, a possibility of plasma cell neoplasm was suspected; on further IHC, serum protein electrophoresis, and radiological investigations, a definite diagnosis of solitary EMP of the right lateral border of the tongue with regional nodal metastases was confirmed. The patient received radiotherapy for the primary disease along with the involved neck nodal sites. [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]

This document discusses the use of serum protein electrophoresis (SPE) in clinical applications, particularly in the detection and quantification of monoclonal proteins (M-proteins). The International Myeloma Working Group (IMWG) has developed guidelines for the study of monoclonal gammopathies, but these guidelines do not specify how to quantify M-proteins. Two main methods, perpendicular drop (PD) and tangent skimming (TS), are used to quantify M-proteins, with PD tending to overestimate and TS tending to underestimate the quantification. The choice of method depends on the patient's specific electrophoretic pattern. The document emphasizes the need for standardized guidelines and ongoing discussions among different working groups to ensure accurate quantification of M-proteins. [Extracted from the article]

Background: To improve the early detection rate of multiple myeloma (MM), the M-protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based monoclonal immunoglobulin (M-protein) screening integrated into the blood biochemistry panel. This study updated 7-year follow-up findings of MM patients diagnosed by screening-driven and symptom-driven approaches. Methods: The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening-driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma-related end-organ damage were categorized into the symptom-driven group. Results: There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening-driven group, while 545 were to the symptom-driven group. Compared to the symptom-driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease-related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression-free survival (PFS) than the symptom-driven group (62.2 vs. 24.9months, p<0.001, HR: 2.12, 95% CIs: 1.69–2.65), with median follow-ups of 32.6 and 27.4months. Furthermore, the median overall survival (OS) was significantly longer in patients of the screening group (not reached vs. 62.3months, p<0.001, HR: 2.49, 95% CIs: 1.81–3.41). After being adjusted for well-acknowledged myeloma prognostic factors, the screeningdriven diagnostic pattern remained an independent prognostic factor indicating improved PFS and OS in MM patients. Conclusion: Routine M-protein screening for MM in the hospital population results in an earlier diagnosis and better patient outcomes. [ABSTRACT FROM AUTHOR]

The diagnosis of Multiple Myeloma (MM) is made by demonstration clonal plasma cells in Bone Marrow (BM) aspiration/biopsy, in addition to assessing serum biochemical parameters, conducting radiological examinations, and considering the clinical presentation. In most cases, predominantly mature plasma cells are observed, along with scattered immature forms in the BM. Several morphological variants of plasma cells have been reported, including Auer rod-like inclusions, small lymphocyte-like cells, hairy cell-like cells, anaplastic variants, promonocyte-like cells, crystal-storing histiocytes, Burkitt-like cells, and blastoid cells. In this series of five cases, most showed a typical clinical presentation and laboratory findings suggestive of plasma cell dyscrasia. However, the morphology of each case exhibited unusual morphological variants, posing diagnostic challenges. These variants included Auer rod-like inclusions, small lymphocytes/lymph-plasmacytoid cells, hairy-like cells, multilobulated nuclei, and anaplastic variants mimicking dysplastic megakaryocytes, leading to various differential diagnoses. The age range of these cases was 57-76 years. Most of the cases presented with generalised dull aching body pain. Imaging studies revealed lytic lesions involving various parts of the bone, including the skull, ribs, vertebrae, and femur. Biochemical assays suggested the possibility of plasma cell dyscrasia. Two of the cases had primary Plasma Cell Leukaemia (PCL), which is a rare and highly aggressive plasma cell neoplasm. The anaplastic variant is associated with a poor prognosis, aiding in predicting treatment responses. However, due to the unusual morphological presentation, the diagnosis of MM or PCL was made after conducting ancillary studies such as Serum Protein Electrophoresis (SPEP), serum free light chain assay, Immunofixation Electrophoresis (IFE), and immunophenotyping through Immunohistochemistry (IHC) or flow cytometry. [ABSTRACT FROM AUTHOR]

Multiple Myeloma (MM) is the most common malignant neoplasm of bone and can manifest with different clinical features in oral cavity. MM lesions in skull and jaws have characteristic punched out lesions but are often confused with meningioma when they occur in skull as solitary lesions. We report a case of MM that reported in oral cavity for which prompt diagnosis was done, but there were symptoms that persisted for years and a skull lesion that was diagnosed and treated as meningioma before MM was diagnosed from the oral lesions. This is the first case where the patient has been actually treated for meningioma, and then diagnosed with MM after months. In that case, SBP or MM should be included in the differential diagnosis of a dural mass, particularly when a patient is complaining of neurological deficits. Also, the role of oral physician in the diagnosis of MM should be stressed in diagnosis and multidisciplinary management, thus facilitating better clinical outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic kidney disease (CKD) is a major cause of morbidity and mortality in cats. Despite the increasing worldwide interest in feline CKD, the specific role of systemic inflammation in these patients remains poorly defined. The aim of the present prospective study was to assess serum amyloid A (SAA) and erythrocyte sedimentation rate (ESR) levels as markers of inflammation in cats diagnosed with CKD at IRIS stages 2–4. The results indicate a systemic inflammatory state associated with feline CKD, as both markers showed significantly higher levels in affected animals than in healthy ones. Compared to SAA, the rise in ESR appears to be more closely linked to advanced stages of the disease and could, therefore, correlate with the uremic condition. This prospective study aimed to evaluate inflammatory status in cats affected by chronic kidney disease (CKD) at IRIS stages 2–4, using serum amyloid A (SAA) and the erythrocyte sedimentation rate (ESR) as inflammatory markers. Thirty-two cats with CKD and ten clinically healthy cats (i.e., control group) were enrolled. The recording of signalment data, complete physical examinations, and abdominal ultrasonography were performed for each animal. Additionally, ESR levels, complete blood count, clinical chemistry (including SAA determination), serum protein electrophoresis, and complete urinalysis were executed. This study's results showed that mean ESR and SAA concentrations in cats with CKD were statistically higher compared to those of the control group (p = 0.0005 and p = 0.007, respectively). The SAA concentration was significantly increased at IRIS stages 2, 3, and 4 compared to the control group. Meanwhile, the ESR was significantly higher in cats at IRIS stages 3 and 4 (p = 0.0003 and p = 0.0007, respectively), but not at IRIS stage 2, compared to the control group. These results provide evidence that feline CKD is associated with a systemic inflammatory status. Moreover, the rise in ESR appears to be more linked to advanced stages of the disease and could, therefore, correlate with the uremic condition. [ABSTRACT FROM AUTHOR]

Background: Serum Protein Electrophoresis (SPE) is crucial for the diagnosis and follow-up of monoclonal gammopathy (MG), as it helps to separate and identify these paraproteins. Currently, Pakistan lacks standardized guidelines for SPE reporting and analytical performance. This survey aims to analyze reporting variations from Consultant Chemical Pathologists in Pakistani laboratories. Methods: This cross-sectional survey was conducted by the section of Chemical Pathology, Department of Pathology and Laboratory Medicine, at Aga Khan University Hospital, Karachi. A previously validated and published tool was used with some modifications to assess analytical techniques, reporting patterns, and interpretations provided with SPE by different laboratories. Frequency and percentages were calculated for each response and descriptive results were also evaluated. Differences between laboratories were also assessed qualitatively. Results: Out of the eight laboratories contacted, seven participated in the survey, yielding a response rate of 87.5%. Immunofixation Electrophoresis (IFE) was used by all labs for serum immunotyping. All labs reported a new small abnormal band in patients with no known monoclonal gammopathy or with a known M-protein. Variations were found in terminologies used to label paraprotein, terminologies used to report normal and pathological SPE patterns, electrophoretic technique, methods for quantifying paraprotein in the gamma region on SPE and for albumin quantification. Similarly, the number of decimal places reported, reporting of multiple monoclonal proteins and small paraprotein in the beta region or monoclonal proteins less than 1 g/L, approach for screening, number of fractions reported in gamma region and reporting of interferences were also not standardized and variations were noticed. Conclusions: Our survey highlighted variations in practices of SPE reporting. These differences in laboratory practices could result in inconsistent test results, which could adversely affect patient care. [ABSTRACT FROM AUTHOR]

Background: We report through this case, the exceptional occurrence of Waldenström's macroglobulinemia in a renal transplant. Methods: A 65-year-old diabetic man, who had a kidney transplant in 2008, presented to the hospital in 2020 for ketoacid decompensation. The blood ionogram showed hyperproteinemia at 102 g/L. Electrophoresis and immunofixation of serum proteins revealed a monoclonal immunoglobulin of IgM Kappa isotype numbered at 46 g/L. Confirmation of Waldenström's disease was made by myelogram and immunophenotyping of tumor cells. Results: The diagnosis adopted for our case is Waldenström's disease which occurred 12 years after the kidney transplantation. Conclusions: Post-transplant lymphoproliferative syndromes are secondary to immunosuppressive therapy, the main concern in this case is the involvement of the graft with the risk of losing its function, hence the interest of monitoring and identifying any hyperproteinemia. [ABSTRACT FROM AUTHOR]

Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 °C and dissolve upon reheating. They can induce small-vessel vasculitis with renal involvement. Cryoglobulinemic glomerulonephritis is a rare manifestation that occurs in patients with monoclonal gammopathy, specifically Waldenström's macroglobulinemia. We present the case of a 52-year-old patient with a history of cutaneous vasculitis and hypothyroidism, who presented with generalized edema, moderate anemia, hypercholesterolemia, nephrotic range proteinuria of 12.69 g/day, microhematuria, arterial hypertension, and hypocomplementemia via the classical pathway, without acute kidney injury and with negative serological studies and positive cryoglobulins in the second determination. Serum and urine protein electrophoresis and immunofixation studies showed a monoclonal band of IgM and kappa light chain. Renal biopsy was consistent with cryoglobulinemic glomerulonephritis. In the context of dysproteinemia and cryoglobulinemic glomerulonephritis, bone-marrow aspiration and biopsy were performed, leading to the diagnosis of Waldenström's macroglobulinemia. Monoclonal gammopathies have been described in association with type I cryoglobulinemias. This described association is uncommon, which is why we present this case, along with a review of the literature. [ABSTRACT FROM AUTHOR]

This letter reports a case of a 63-year-old woman who had an increase in C-reactive protein (CRP) levels, a marker of inflammation, despite not having any signs of infection or inflammation. After months of investigation, it was determined that the high CRP levels were due to an analytical interference caused by the presence of human anti-animal antibodies in the patient's blood. This interference led to unnecessary surgeries, investigations, and antibiotic treatments. The study highlights the importance of considering analytical interferences when interpreting laboratory results. [Extracted from the article]

This article discusses a case report of a fifty-eight-year-old woman with primary systemic amyloidosis, a rare condition characterized by the accumulation of amyloid protein in various organs. The patient presented with multiple skin lesions, including papules on the eyelids, nose, and ears, as well as alterations in the tongue and fingers. Dermoscopic examination and histopathological analysis confirmed the diagnosis of primary systemic amyloidosis. Further investigations revealed additional symptoms, such as anemia, renal disease, cardiac involvement, and motor neuropathy. The patient was managed symptomatically and is under regular follow-up. The article emphasizes the importance of thoroughly investigating cases of systemic amyloidosis to determine the extent of organ involvement and predict the disease's course and outcome. [Extracted from the article]

Purpose: This study aimed to investigate the correlation between calculated globulin (CG, total protein level minus albumin level) and the gamma globulin fraction (Gamma), obtained from serum protein electrophoresis with serum IgG levels in adults (≥ 18 years). Methods: Using linear regression models, analyses of CG and Gamma levels correlation with IgG levels in adults were performed. Receiver-operator curves were created to determine cutoff values and the respective sensitivity and specificity measures. Results: A total of 886 samples were analyzed. CG and Gamma were positively and statistically correlated with IgG levels (r2 = 0.4628 for CG, and = 0.7941 for Gamma, p < 0.0001 for both analyses). For the detection of hypogammaglobulinemia, i.e., IgG level below the reference value (6 g/L), a CG cutoff value of 24 g/L showed a sensitivity of 86.2% (95% CI 69.4–94.5) and a specificity of 92% (90.0–93.6). A Gamma cutoff value of 7.15 g/L yielded a sensitivity of 100% (88.3–100) and a specificity of 96.8 (95.3–97.8). Conclusion: Both CG and Gamma levels determined by protein electrophoresis analysis may be used to screen for antibody deficiencies in adults, enabling earlier diagnosis of antibody deficiencies in a routine clinical setting. [ABSTRACT FROM AUTHOR]

Alterations in the serum protein pattern may be associated with many diseases, including neoplastic processes. In veterinary medicine, these changes are poorly understood. Therefore, this study was aimed at the analysis of the distribution of blood serum protein fractions separated by agarose gel electrophoresis, and at the determination of the concentrations of main acute phase proteins in bitches with mammary gland neoplasia. The evaluation was conducted on twelve female dogs with palpable single or multiple nodules in the parenchyma of the mammary gland and on ten tumor-free clinically healthy bitches to compare the possible differences in the obtained results. Blood serum was used to perform agarose gel electrophoresis of the main blood serum protein fractions and to analyze the concentrations of total serum proteins and the following canine acute phase proteins: serum amyloid A, haptoglobin, C-reactive protein and α1-acid glycoprotein. The concentrations of total serum proteins were slightly higher in bitches with mammary gland tumors. Serum protein electrophoresis showed lower mean concentrations of albumin and α1-globulins in the affected dogs, while the concentrations of α2-and β1-globulins were significantly higher (P=0.0032 and P=0.0021, respectively) compared to dogs without mammary gland tumors. In the concentrations of acute phase proteins, significantly higher mean concentrations of C-reactive protein and haptoglobin were obtained in dogs with mammary tumors (P=0.0025 and P=0.0002, respectively). The values of α1-acid glycoprotein did not vary markedly between the bitches with and without mammary tumors. Presented data suggest that neoplastic processes in the mammary gland may also alter the electrophoretic pattern of blood serum proteins and induce changes in the production of some inflammatory proteins. [ABSTRACT FROM AUTHOR]

Primary plasma cell leukaemia (pPCL) is a rare and lethal form of plasma cell dyscrasia that can occur either de novo (primary) or as a leukemic transformation of refractory or relapsed multiple myeloma. We report a case of pPCL with lambda light chain disease and multiple chromosomal abnormalities in a 75-year-old female who presented with generalized weakness. Her peripheral blood smear showed hyperleukocytosis with 78% circulating plasma cells. Serum protein electrophoresis (SPE) does not reveal the M band and serum immunofixation (SI) light chain analysis in serum showed an elevated lambda light chain. Skeletal radiography and PET-CT (positron emission tomography--computerized tomography) did not reveal any lytic lesions. Immunophenotypic studies reveal a CD38-positive population with negativity for T cells, B cells, myeloid markers, and a negative CD45. Fluorescent in situ hybridization (FISH) analysis results disclosed the deletion of 13q14.3 and t(11; 14). This case highlighted the usefulness of the peripheral smear findings and high fluorescent lymphocyte activity, which directed the pathologist to initiate workup for pPCL, and comprehensive laboratory biochemical and radiological evaluation further helps to confirm and differentiate pPCL from multiple myeloma. [ABSTRACT FROM AUTHOR]

Background: Early detection of breast cancer (BC) is extremely important as late diagnosis has been associated with a high rate of mortality. Immunogenic proteins and autoantibodies have been considered as favorable targets for early detection and targeted therapy in cancer. Accordingly, the present study aimed to identify the immunogenic antigens in both early and advanced stages of BC via a serologic proteome analysis (SERPA) approach. Method: This is a case-control study wherein we separated the proteins from BC tissues in the early stages (n = 10) and advanced stages (n = 10) utilizing two-dimensional electrophoresis (2DE) and then transferred them onto a Polyvinylidene Difluoride (PVDF) membrane. To explore the tumor antigens reacting with antibodies, two-dimensional (2D) blots of tumor tissues in the early and advanced stages were separately probed with the sera from the same patients. Afterwards, we identified antibody-reactive proteins via liquid chromatography with tandem mass spectrometry (LC-MS/MS). Results: Fibrinogen beta chain (FGB), protein deglycase DJ-1(PARK7), and peroxiredoxin-2 (PRDX2) were the highly reactive antigens identified in the earlystage patients. In addition, RuvB-like1 (RUVBL1) and triose phosphate isomerase (TPI) were recognized as the immune reactive proteins in the late-stage patients. Conclusion: The results herein revealed that the immune-proteome pattern of BC patients changes along with tumor progression from primary to advanced stages. Moreover, immunogenic proteins seemed to stimulate the humoral immune system to produce autoantibodies in the initiation phase of BC; these autoantibodies could be employed as complementary factors for early detection of BC. The findings are however preliminary, and further studies with a larger sample size are required for verification and validation of previous findings. [ABSTRACT FROM AUTHOR]

Background: A deficiency in alpha-1 antitrypsin (AAT1) is a rare disorder that represents a significant health threat and early diagnostic priority issue. We investigated the usefulness of the serum protein electrophoresis (SPE) as an opportunistic screening tool for AAT1 deficiency. Methods: For 6 months, all SPE carried out for any reasons were evaluated in our center. In those with less than 3% of alpha-1 globulins, AAT1 concentrations were studied. The SERPINA1 gene was subsequently sequenced in those patients displaying concentrations below 100 mg/dL. Results: Out of the total, 14 patients (0.3%) were identified with low AAT1 concentrations, with 11 of them agreeing to enter the study. Of those, mutations in the SERPINA1 gene were discovered in 10 patients (91%). Heterozygous mutations were detected in seven patients; three had the c.1096G>A mutation (p.Glu366Lys; Pi*Z), two had the c.863A>T mutation (p.Glu288Val; Pi*S), one had the c.221_223delTCT mutation (p.Phe76del; Pi*Malton), and the last one had the c.1066G>A (p.Ala356Thr) mutation, which was not previously described. Finally, one patient had the c.863A>T mutation in homozygosis, whereas two double heterozygous patients c.863A>T/c.1096G>A were detected. Conclusions: An altered result in the concentration of AAT1 anticipates a mutation in the SERPINA1 gene in a manner close to 91%. The relationship between a decrease in the alpha-1 globulin band of the SPE and an alteration in the AAT1 concentration is direct in basal states of health. The SPE is presented as a highly sensitive test for opportunistic screening of AAT1 deficiency. [ABSTRACT FROM AUTHOR]

TEMPI syndrome is a new and poorly understood disease that is currently considered a type of plasma cell neoplasm with paraneoplastic manifestations. The TEMPI acronym defines the hallmarks of the syndrome: T for telangiectasia; E for erythrocytosis with elevated erythropoietin; M, monoclonal gammopathy; P, perinephric collections; and I, intrapulmonary shunting. Due to the marked erythrocytosis as the most common presenting feature, TEMPI is often misdiagnosed as polycythemia vera. However, unlike polycythemia vera, TEMPI is not associated with a JAK2 mutation. The pathogenesis of TEMPI syndrome is unknown, although a few hypothetical disease mechanisms have been previously discussed. Here we present a new case of TEMPI syndrome, discuss results of a next-generation sequencing (NGS) panel covering 1,425 known cancer-related genes, and review the current literature with focus on an update of the genetics of TEMPI syndrome. This is the first report of TEMPI that includes results of comprehensive NGS testing. [ABSTRACT FROM AUTHOR]

Background Immunoglobulin monoclonal light chains (MLCs) in serum and urine are markers for monoclonal gammopathy and could serve as markers of minimal residual disease (MRD) in multiple myeloma (MM). Excretion of MLCs in urine is known to result in renal damage and shorter survival in patients with LC-predominant MM. Methods Retrospective review of urine immunofixation in 1738 specimens at 3 medical centers was conducted to assess the utility of urinalysis for diagnosis and monitoring of monoclonal gammopathy. We tested 228 stored urine specimens via the modified urine immunofixation method, using antisera to assay free LCs (FLCs). Results Our review of urine immunofixation results and medical records validated the theory that the only meaningful value-added finding was detection of monoclonal free light chains. Examination of 228 urine specimens using our novel method revealed 18.4% additional positive results. The rate of incremental findings for lambda LCs was nearly 3-fold higher than for kappa LCs. Conclusions The new method of urine immunofixation is significantly more sensitive and more efficient than the conventional method for detecting MLCs in urine. The new assay appears to be sensitive enough to prove that MLCs serve as a marker of MRD in MM. [ABSTRACT FROM AUTHOR]

Background: Several studies have demonstrated the analytical sensitivity of MALDI-TOF mass spectrometry (MALDI-TOF MS) by immunoenrichment for M-protein analysis. We report the results of a novel, low-cost, reagent-based extraction process using acetonitrile (ACN) precipitation to enrich for κ and λ light chains which can be analysed by MALDI-TOF MS. Methods: Institutional Ethics committee approval was obtained. Serum samples from patients with monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), plasmacytoma, AL amyloidosis and Waldenström macroglobulinemia (WM) underwent ACN precipitation. The images obtained were overlaid on apparently healthy donor serum samples to confirm the presence of M-protein. A sample was considered positive for M-protein if there was a sharp or broad peak within the κ or λ mass/charge (m/z) range: m/z- [M + 2H]2+: 11,550–12,300 Da and λ m/z - [M + 2H]2+: 11,100–11,500 Da. Images were acquired at a m/z range of 10,000–29,000 Da. Corresponding serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (IFE) and serum free light chain (sFLC) assay by nephelometry were performed for all the samples. Results: Two-hundred-and-two serum samples were included in the study: MM- 184 (91%); AL amyloidosis- 2 (1%); plasmacytoma- 8 (4%); MGUS- 6 (3%) and WM- 2 (1%). All the SPEP positive samples were identified by MALDI-TOF MS. Out of 179 samples positive for M-protein by IFE, MALDI-TOF MS was positive in 176 samples (98%). Compared to IFE, the sensitivity and specificity of M-protein identification by MALDI-TOF MS were 98.3% and 52.2%, respectively. Conclusions: This study demonstrates the feasibility of qualitatively identifying M-protein without the need for antibody-based immunoenrichment, making the technique cost-effective. [ABSTRACT FROM AUTHOR]

Serum protein electrophoresis (SPE) is an important laboratory technique in the diagnosis of multiple myeloma. Analytical interference affects SPE as well as many other laboratory methods. Here, we have presented the fibrinogen interference that mimics the monoclonal band in the SPE in the sample sent in the gel biochemistry tube. A female patient presented to the emergency department with abdominal pain, nausea, and decreased urine output. In patients with high serum creatinine and blood urea nitrogen levels, a complete blood count has been found to be compatible with the presence of pancytopenia. Although an abnormal band similar to the M-spike protein was observed in the β/γ-region on the SPE evaluation, no monoclonal immunoglobulin was found in immunofixation electrophoresis. It was assured that the sample sent for SPE was collected in the correct tube (gel biochemistry tube). It was noted that the patient was receiving hemodialysis treatment while the sample was sent for SPE. It was considered that the specimen of the patient was contaminated with heparin. To test this theory, we added 1 ml of heparin to 5 ml of blood taken from a healthy subject in a gel biochemistry tube. Similarly, we observed that a band formed between the beta-gamma region in the SPE. Interferences are one of the most important causes of laboratory errors. Because they can have clinically important consequences such as misdiagnosis and treatment, laboratory specialists need to recognize these interferences and inform clinicians about them. [ABSTRACT FROM AUTHOR]

Extramedullary solitary plasmacytoma (EMP) is a plasma cell neoplasm involving the soft tissues without the involvement of the bone marrow. In this case report, we present an isolated soft tissue growth on the lingual gingiva of the left mandibular canine-premolar region diagnosed as EMP based on clinical, histological, and laboratory results. Orthopantomogram and occlusal radiographs showed no osteolytic lesions. Hematoxylin and Eosin staining showed sheets of inflammatory cells, predominantly atypical plasma cells with varying degrees of differentiation showing features of pleomorphism, and multinucleated giant cells with intervening collagen fibers. Positive immunoreactivity for CD56, CD138, and kappa light chain restriction were observed. Serum protein electrophoresis demonstrated an increase in IgA levels and immunofixation electrophoresis confirmed the presence of the M band in the IgG and kappa lanes, indicating monoclonal gammopathies. Based on the above findings, the case was diagnosed as EMP; the consultant pathologist, however, recommended excluding multiple myeloma. [ABSTRACT FROM AUTHOR]

Background: The extramedullary disease usually occurs in the advanced stages of multiple myeloma and predicts poor survival. Commonly involved extramedullary sites in multiple myeloma include the nasal cavity, lymph nodes, lung, central nervous system, liver, spleen, skin, and orbit. Pleural effusion in multiple myeloma is unusual and rarely due to multiple myeloma itself. Myelomatous pleural effusions occur in less than 1% of cases of multiple myeloma. Material and methods: Eight patients were diagnosed with myelomatous pleural effusion in the Department of Medical Oncology at a tertiary cancer care center in India, during the 7-year period (2012 to 2018). Clinical presentation, diagnosis, treatment, and survival details were abstracted from medical records. Results: We report eight patients with myelomatous pleural effusion, constituting 0.45 % of all multiple myeloma cases treated during the study period. Five out of the eight patients were females with a median age of 58 years. Three patients had myelomatous pleural effusion at the time of initial diagnosis and five developed pleural effusion at disease progression. IgG was the common immunoglobulin subtype. The International staging system stage was stage I in one patient and stage III in seven patients. After the diagnosis of multiple myeloma, all patients developed myelomatous pleural effusion at a median of 7 months and all patients died within 2 weeks. Conclusion: Pleural effusions in multiple myeloma should be investigated to rule out myelomatous pleural effusion. Myelomatous pleural effusion is rare, having a poor prognostic outlook and an aggressive natural course. [ABSTRACT FROM AUTHOR]

Background Serum protein electrophoresis (SPEP) is an easy test separating serum proteins based on their physical and chemical properties. Although it is frequently used in the differential diagnosis of multiple myeloma and various chronic inflammatory diseases, its value in the etiologic classification of glomerular diseases has yet to be studied. Material and Methods We retrospectively reviewed the medical records of patients who underwent renal biopsy from 2008 to 2016 at our institution. We excluded patients who can not be classified as primary (PGn) or secondary glomerulonephritis (SGn). Univariate and multivariate logistic regression analyses were performed for the prediction of SGn. Results Four hundred thirty-two patients were included in the study. Of those, 57.9% had PGn. Rheumatological diseases, malignancies, and infections were the most common etiologic causes of SGn, accounting for nearly 75%. Univariate analysis revealed that alpha-1 (α1), gamma (Ɣ), and albumin fractions significantly differ between PGn and SGn groups. ROC curve analysis determined the cut-off value of (α1*Ɣ)/albumin ratio as 1.48. Multivariate analysis revealed that total serum protein and (α1*Ɣ)/albumin ratio were significantly independent predictors for SGn (p = 0.020 and p < 0.001, respectively). Conclusions A ratio generated by multiplying α1 and Ɣ and dividing by albumin from SPEP, an easy, reliable, and cheap test, may help clinicians differentiate between PGn and SGn after validation in more extensive prospective studies. [ABSTRACT FROM AUTHOR]

Myeloma‐related disorders, including multiple myeloma, extramedullary plasmacytoma, and solid osseous plasmacytoma, are rare in horses. Clinical complaints for myeloma‐related disorders are nonspecific, and when present, M‐protein location is more variable on protein electrophoresis in horses relative to dogs and cats. Here, we describe a case of a 15‐year‐old Thoroughbred mare who presented with recurrent blepharitis. Marked hyperglobulinemia was an incidental finding on routine hematologic and biochemical testing. Bone marrow aspiration consisted of >30% plasma cells, and serum protein electrophoresis demonstrated a monoclonal gammopathy in the alpha 2 fraction leading to a diagnosis of multiple myeloma. Immunofixation and radial immunodiffusion confirmed the presence of an IgG M‐protein. Based on a restricted peak in the alpha 2 location, the specific M‐protein is suspected to be IgG(T), an IgG isotype unique to horses. M‐protein migration in horses is variable relative to dogs and cats, yet immunofixation can still be used to identify equine IgG M‐protein isotypes. The unique clinical presentation in this case also serves as a reminder to consider neoplasia in horses with unusual or nonspecific clinical signs. [ABSTRACT FROM AUTHOR]

Cation exchange high-performance liquid chromatography (HPLC) is one of the techniques available for determining glycated hemoglobin (HbA1c) and also the method of choice for structural hemoglobinopathies screening. The objective of this case is to show how in a routine HbA1c test it is possible to incidentally find a hemoglobinopathy. In a routine blood analysis, an abnormal value for the hemoglobin A2 (HbA2) was obtained during the study of HbA1c with HPLC on the ADAMS™ A1c HA-8180T. After suspecting it could be due to the presence of a hemoglobinopathy, the study of possible variants was expanded using electrophoresis and HPLC on the Hydrasys and Variant II analysers, respectively. Since it could not be identified by these conventional methods, a genetic study was also carried out using Sanger sequencing. The patient presented a low HbA2 (1.3 %) and a 24.9 % variant with a retention time of 1.95 min, compatible with alpha-globin chain variant. In the genetic study, the pathogenic variant c.138C>G was detected in the HbA2 gene in heterozygosis, which resulted in the expression of the structural hemoglobinopathy known as hemoglobin Bari. The initial screening for structural hemoglobinopathies allows its identification or suspicion especially when it was performed with HbA1c analysis, requiring subsequent confirmation and diagnosis by other techniques. [ABSTRACT FROM AUTHOR]

A 64-year-old male with a history of osteoarthritis, gastroesophageal disease, and psoriatic arthritis presented with dysphagia and weight loss. Initial tests did not reveal any abnormalities, but further examination showed the presence of anterior bridging calcified osteophytes in the neck, which were causing esophageal obstruction. The patient was not a candidate for surgery, so conservative management was recommended. The article discusses the differential diagnosis for vertebral bony growth and highlights the importance of considering various factors in diagnosing and managing esophageal obstruction. [Extracted from the article]

This article discusses a case of bullous pemphigoid (BP), a skin disorder characterized by blistering and erosions. The standard diagnostic method for BP involves the detection of IgG autoantibodies and/or C3 complement fraction at the dermo-epidermal junction (DEJ). However, this particular case presented with linear deposits of IgM at the DEJ, along with non-classical clinical features. The significance of IgM in cutaneous immunopathology is not well understood, and the existence of IgM-mediated BP has been a topic of debate. The patient was treated with oral corticosteroids and eventually achieved complete clinical remission. [Extracted from the article]

This article discusses a rare case of scleromyxedema, a type of cutaneous mucinosis characterized by abnormal mucin deposition in the skin. The patient, a 50-year-old Indian male, presented with erythematous papules and thickening of the skin primarily on the face. Dermoscopic examination revealed yellowish-brown and yellowish-white roundish areas with linear irregular vessels and accentuated pigmentary network. The patient did not show any signs or symptoms of systemic involvement at the time of diagnosis, but long-term follow-up is still necessary. Scleromyxedema is a chronic disease associated with monoclonal gammopathy and can have severe systemic implications. [Extracted from the article]

Objective: Challenging differential diagnosis. Background: The differential diagnosis for a parotid mass is broad, including infectious, autoimmune, and neoplastic etiologies. In people with HIV, regardless of viral suppression or immune status, neoplastic causes are more common. This report describes the evaluation of a woman with a large parotid mass, with an ultimate diagnosis of multiple myeloma with extramedullary plasmacytoma. Case Report: A 51-year-old woman with HIV infection presented with headache, weight loss, and right facial mass that was present for 5 years but more rapidly enlarging in the prior year. CD4 count was 234 cells/mL, and HIV RNA was 10 810 copies/mL. Physical examination was significant for a large deforming right-sided facial mass, decreased sensation in the V1 and V2 distributions, and right-sided ophthalmoplegia and ptosis. MRI and PET/CT scan confirmed a metabolically active large parotid mass with extension into the cavernous sinus. An IgG kappa monoclonal spike was present on serum protein electrophoresis. Incisional biopsy of the facial mass showed atypical lymphoid cells with plasmablastic and plasmacytic morphology with a high mitotic rate and proliferation index. She was diagnosed with R-ISS stage II IgG kappa multiple myeloma with extramedullary plasmacytoma, and initiated on chemotherapy, radiation, and antiretroviral therapy. Conclusions: A rapidly enlarging parotid mass should prompt timely evaluation and biopsy for definitive diagnosis, particularly in immunocompromised patients, including people with HIV. Extramedullary plasmacytomas have a more aggressive disease process in people with HIV and are associated with high-risk multiple myeloma and progression, as seen in this patient. [ABSTRACT FROM AUTHOR]

CPD questions Learning objective To identify the classic histological features of scleromyxoedema as well as the potentially life-threatening complications of scleromyxoedema. Histologically, scleromyxoedema is typically characterized by increased fibroblast proliferation, fibrosis and interstitial mucinosis. In recent years, an atypical variant of scleromyxoedema with interstitial granulomatous-like features has been described.[5],[6] In addition to the classic histopathological features of scleromyxoedema, biopsies from these patients can show a dermal CD68 SP + sp histiocytic infiltrate mimicking granuloma annulare. [Extracted from the article]

Lymphoplasmacytic lymphoma (LPL) is a neoplasm of small B lymphocytes, plasmacytoid lymphocytes and plasma cells usually involving the bone marrow (BM). A subset of LPL which is associated with IgM monoclonal gammopathy is called Waldenstrom's macroglobulinaemia (WM), and usually requires therapeutic intervention when a patient becomes symptomatic (Bone Marrow failure characterised by cytopenia or hyperviscosity syndrome). Here, we report the case of an 80-year-old female with clinically unsuspected WM who initially presented to the Emergency Department (ED) with nausea and vomiting. The patients' gastrointestinal symptoms subsequently settled and was awaiting discharge. Non-specific, borderline size significant lymph nodes on CT chest was the only substantial past medical history. The diagnosis of WM was made after the Biochemistry Biomedical Scientist (BMS) detected the presence of a Type I monoclonal cryoglobulin. A potential cryoprecipitate was suspected when repeated 'clotting' error flags occurred during routine laboratory analyses; the sample aspiration difficulties being attributed to the viscous nature of the sample. The investigation of inaccessible low volume lymphadenopathy in the elderly should include serum protein electrophoresis and immunoglobulins as this may have established an earlier diagnosis in this case. The application of good scientific principles informed the laboratory investigation and resulted in the identification of a large IgM monoclonal cryoglobulin that prompted further appropriate investigations resulting in the diagnosis of WM. This case also highlights the importance of good communication between the laboratory and clinical staff. [ABSTRACT FROM AUTHOR]

Simple Summary: Serum protein electrophoresis (SPE) is a widely used method to determine the concentration of a serum protein fraction in human and veterinary medicine. Serum protein electrophoresis allows the separation of serum proteins into several categories based on their ability to migrate in an electrical field on different supports. Typical migration patterns could be identified in the course of different disorders such as inflammation or neoplasia. However, to be clinically useful, the interpretation of SPE data had to be performed in light of an appropriate method—and species-specific reference intervals (RIs) and for all species, including marine mammals, attention should also be given to the different living environments. In this work, we established the RIs for serum protein fractions evaluated using agarose gel electrophoresis in bottlenose dolphins (Tursiops truncatus) under human care. These data are a new tool for health assessment in dolphins, thus, they may be useful for clinicians to better interpret laboratory data. Serum protein electrophoresis (SPE) is the most used and reliable method to determine the percentage of serum protein subfractions. The interpretation of the kinetics of total proteins and albumin and globulin fractions is receiving increased attention in wild animals, as well as in domestic animals, due to the possibility of identifying typical pathologic patterns. However, the interpretation of these data had to be performed in light of an appropriate method—and species- specific reference intervals (RIs). In marine mammals, as well as other non-domestic species, specific attention should also be given to the different environment (free ranging vs. human managed) and the associated different exposure to environmental stimuli. The aim of this report was to establish RIs for the serum protein fractions evaluated using agarose gel electrophoresis (AGE) in bottlenose dolphins under human care. Peripheral blood samples were collected from 40 bottlenose dolphins during standard veterinary procedures to evaluate their health status. Total protein concentration was determined using the biuret method while AGE was performed using an automated system. A pooled dolphin's serum sample was used to determine the intra-assay and inter-assay imprecision of AGE. The RIs were calculated using an Excel spreadsheet with the Reference Value Advisor set of macroinstructions. The intra and inter-assay imprecisions were 1.2% and 2.5%, respectively, for albumin; 2.9% and 5.7%, respectively, for α-globulins; 3.8% and 4.0%, respectively, for β-globulins; and 3.4% and 4.8%, respectively, for γ-globulins. The total protein, albumin, α-globulin, β-globulin, and γ-globulin concentrations were 65.5 ± 5.4 g/L, 45.5 ± 4.9 g/L, 8.0 ± 1.0 g/L, 5.0 ± 2.0 g/L, and 7.0 ± 2.0 g/L, respectively. We established the RIs for the total protein and serum protein fractions using AGE in bottlenose dolphins under human care. [ABSTRACT FROM AUTHOR]

Free light chain (FLC) is used for the diagnosis and prediction with regard to the progression risk of plasma cell disorders and Freelite reagent using the SPAplus analyzer (The Binding Site) has been one of the widely used option. However, N Latex FLC reagent with the Atellica CH 930 analyzer (Siemens Healthineers) has shown the advantages of automation and high throughput. We aimed to evaluated clinical implication by differential analytical performances of two assays. A total of 322 serum samples were collected from 193 patients requested for FLC analysis including 131 multiple myeloma patients. The precision, linearity, dilution recovery of N Latex FLC assay was evaluated. We compared the two assays and analyzed the monomer-dimer pattern for discrepant results. The precision, linearity, and dilution recovery performance was appropriate for the routine use in clinical laboratories. Despite the good correlation within normal range, proportional bias up-to 170% was observed in samples with high concentrations especially for lambda. The higher value samples with N Latex FLC assay contained more monomer forms than controls. All opposite changes of FLC burden by the N Latex FLC assay proved to present concordant dynamic changes when assessed by serum protein electrophoresis. Clinical laboratories should be aware of the inter-assay variability of FLC quantitative measurements using different platforms, especially for high concentrations of both kappa and lambda measurements, possibly due to monomer/dimer ratio diversity. Clinical interpretations for multiple myeloma disease status might not be dramatically affected only when the same assay is utilized during follow-up periods. [ABSTRACT FROM AUTHOR]

BACKGROUND: Thromboembolic (TE) disorders are among the most common complications of beta-thalassemia. We designed this cross-sectional study to investigate the state of hypercoagulability and platelet activation in patients with beta-thalassemia. PATIENTS AND METHODS: Seventy-five patients diagnosed with beta-thalassemia by hemoglobin electrophoresis were divided into three groups of 25 patients each: Group I (thalassemia trait), Group II (thalassemia intermedia [TI]), and Group III (thalassemia major). In addition, 50 healthy individuals were included as controls. Both patients and control groups were subjected to clinical and laboratory assessment, which included measurement of protein C, anti-thrombin III, D-dimer, CD41, CD42, CD61, and CD62P, and detection of beta-chain mutations. RESULTS: Levels of the platelet activation marker CD62P were significantly higher in beta-thalassemia patients (26.28 ± 18.01%) than in controls (4.78 ± 2.27%) (P < 0.001). The D-dimer level was significantly higher in beta-thalassemia patients (348.41 ± 571.01 ng/mL) than in controls (71.6 ± 39.61 ng/mL) (P < 0.001). Protein-C and AT-III levels were significantly lower in beta-thalassemia patients (71.45 ± 13.26%, 78.38 ± 15.32%) in comparison with controls (94.9 ± 13.03%, 96.52 ± 11.01%) (P < 0.001 and P < 0.001, respectively). TE disorders were found in 7/25 (9%) beta-thalassemia patients, especially in older and postsplenectomy patients. TE was most commonly found in beta-TI. Beta-chain mutations were found in all patients with TE disorders, especially compound heterozygous intervening sequence (IVS) (IVS1.6 [T > C]/IVS1.110 [G > A]). CONCLUSION: Postsplenectomy teenagers and adults with beta-thalassemia with lower levels of natural anticoagulant in the blood, an increased level of D-dimer, and platelet activator factor had a significantly higher risk for TE than those with childhood beta-thalassemia and the control group. In comparison with other beta-thalassemia patients, TI with beta-chain mutations is more likely to develop TE. [ABSTRACT FROM AUTHOR]

Background: Multiple laboratory tests are employed for detection of monoclonal proteins in patients and include serum protein electrophoresis (SPEP), immunofixation electrophoresis, free light chain (FLC) immunoassay, and mass spectrometry (Mass-Fix). Recently, reports on a drift in FLC quantitation results have been brought to light. Methods: We studied a cohort of 16 887 patients whose sera were tested for a monoclonal protein by a FLC assay, serum protein electrophoresis, and Mass-Fix. This is a retrospective study designed to assess the impact of a drift on the performance of FLC ratio (rFLC) in groups of patients with and without detectable plasma cell disorders (PCDs). Results: The results demonstrated that 63% of patients with monoclonal protein equal or higher than 2 g/L (by SPEP) had an abnormal rFLC (reference range 0.26–1.65). Conversely, 16% of patients with undetectable monoclonal protein by other methods (i.e., SPEP and Mass-Fix) who also had no record of treated PCD had an abnormal rFLC. In these cases, there was an imbalance in the number of kappa high rFLCs to lambda low rFLCs of 201 to 1. Conclusions: The results of this study suggest decreased specificity of rFLC for a monoclonal kappa FLC in the 1.65 to 3.0 range. [ABSTRACT FROM AUTHOR]

Background: Dual hematological malignancies, asynchronous or synchronous, are underrecognized entities and are usually suspected when clinical, hematological, or biochemical features cannot be explained by the primary malignancy alone. We present a case of synchronous dual hematological malignancies (SDHMs), where the patient was diagnosed with symptomatic multiple myeloma (MM) and essential thrombocythemia (ET), when excessive thrombocytosis occurred following initiation of MPV (melphalan-prednisone-bortezomib) antimyeloma therapy. Case description: An 86-year-old woman presented to the emergency in May 2016 with confusion, hypercalcemia, and acute kidney injury. She was diagnosed with free light chain (FLC) lambda and Immunoglobulin G (IgG) lambda MM and startedMPV (standard of care at that time) treatment with darbopoietin support. At diagnosis, she had normal platelet count since the ET was likely masked by bone marrow suppression due to active MM. After she reached stringent complete remission with no MP detected on serum protein electrophoresis or immunofixation, we noticed that her platelet counts increased to 1,518,000 × 109/L. She was tested positive for mutation in exon 9 of calreticulin (CALR). We concluded that she had concomitant CALR-positive ET. After bone marrow recovery from MM, the ET became clinically apparent. We started hydroxyurea for ET. Treatment for MM with MPV did not affect the course of ET. Presence of concomitant ET did not decrease the efficacy of sequential antimyeloma therapies in our elderly and frail patient. Conclusion: The possible mechanism underlying the occurrence of SDHMs is unclear but is likely due to stem cell differentiation defects. SDHMs can be challenging to treat and warrant several considerations. In the absence of clear guidelines on how to manage SDHMs, management decisions depend on several factors including disease aggressiveness, age, frailty, and comorbidities. [ABSTRACT FROM AUTHOR]