Search

Background: Lupus anticoagulant (LA) is an in vitro phenomenon with prolongation of a phospholipid-dependent coagulation test which is not due to an inhibitor specific to a coagulation factor. Occasionally, addition of normal pooled plasma to patient plasma with lupus anticoagulant potentiates the inhibitory effect of lupus anticoagulant in the mixture, resulting in a paradoxical prolongation instead of shortening of clotting time. The phenomenon has been termed the "lupus cofactor effect". Lupus anticoagulant are known to be associated with lymphoma and immunoglobulin M (IgM) paraproteinaemia. Cases of lymphoplasmacytic lymphoma with concomitant IgM paraproteinaemia and lupus anticoagulant demonstrating lupus cofactor phenomenon on activated partial thromboplastin time (APTT) assay has been reported previously. However, to our best knowledge, there were no reported cases of low grade B-cell lymphoma with positive LA results and lupus cofactor effect demonstrated on dilute Russell's viper venom time (DRVVT) and/or silica clotting time (SCT) assays in the literature. Case presentation: We report two cases of low grade B-cell lymphoma associated with monoclonal IgM paraprotein, high levels of anti-cardiolipin IgM antibody and presence of lupus anticoagulant with lupus cofactor phenomenon on DRVVT and/or SCT assay. Conclusions: Our cases demonstrate a possible novel association between low grade B-cell lymphoma, IgM paraproteinaemia, high levels of anti-cardiolipin IgM antibody and the presence of lupus cofactor effect on DRVVT and SCT assays. The DRVVT assay in the first patient and SCT assay in second patient were falsely negative in the neat sample or less diluted sample, and the lupus anticoagulant activities were only revealed on dilution of samples with normal pooled plasma. This highlights the potential importance of dilution of samples with normal pooled plasma while evaluating the LA status of low grade B-cell lymphoma patients with a markedly prolonged APTT and/or prolonged PT by DRVVT and SCT assays, especially if there is concomitant IgM paraproteinaemia and a high level of anti-cardiolipin IgM antibody. [ABSTRACT FROM AUTHOR]

AbstractIsolated hypogammaglobulinemia (IH) is an electrophoretic pattern that can be encountered on serum protein electrophoresis (SPEP) and is defined as a decreased but morphologically normal γ-globulin fraction with normal α- and β-globulin fractions. SPEP is mainly used to detect monoclonal proteins which are usually observed as additional peaks in the electropherogram. However, they may also be more discretely present in a significant proportion of patients presenting with IH. Therefore, we aimed to evaluate i) via both retrospective and prospective analysis to what extent paraproteins as identified by immunofixation are present in patients demonstrating IH on SPEP and ii) whether other parameters may predict their presence in IH-patients. For this purpose, we first reviewed historic SPEP- and immunofixation results in our tertiary hospital and determined paraprotein prevalence in this retrospective cohort. This analysis showed immunofixation was requested in only 519/3938 (13.2%) historic IH-results with 52/519 (10%) patients demonstrating paraproteins. Next, various laboratory parameters were compared between paraprotein-positive and -negative patients and subjected to logistic regression models but regrettably, no parameter could be retained as promising predictor of paraproteins. Lastly, to confirm paraprotein prevalence seen in the historical query, we conducted a six-month prospective analysis during which immunofixation was requested more frequently in IH-cases during routine diagnostics and which showed paraproteins to be present in 20/83 (24.1%) of IH-patients. Hence, as up to 24% of patients with IH may harbour paraproteins, one should consider performing follow-up analyses (e.g. immunofixation, urine electrophoresis and/or free light chain analysis) for all IH-cases identified via SPEP. [ABSTRACT FROM AUTHOR]

Background Interferences on chemistry and immunoassay results due to paraproteinemia may lead to erroneous diagnoses and treatment. Such interferences are difficult to recognize and even more difficult to deal with. This report describes 1 such case where multiple measurands were affected and how the interferant was overcome. Case Report Paraproteins present in an immunoglobulin (Ig)G-lambda multiple myeloma specimen interfered with results of total bilirubin, direct bilirubin, inorganic phosphate, iron, ferritin, and total thyroxine measured on 3 platforms: AU5800, Alinity ci, and cobas pure. Repeat testing upon dilution with normal saline or deproteinization by polyethylene glycol precipitation gave unsatisfactory results on some or all the affected measurands. Repeat testing after dilution of the interferant serum with a healthy serum corrected the anomalous results for all the affected measurands. Conclusion Dilution of paraproteinemic serum with a healthy serum of known concentrations appears to be the most suitable method to negate the effects of paraproteinemic interferences. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinemia (WM) is a rare lymphoproliferative malignancy presenting with paraproteinemia. The symptoms are attributable to both lymphoproliferation and IgM flare. Gastrointestinal manifestations are not uncommon. It is an indolent disease with good response to chemoimmunotherapy but with possible persistence of asymptomatic paraproteinemia. Resurgence of gastrointestinal symptoms in a patient of WM maintaining reasonable response warrant a thorough search for alternate pathology. Herein we describe a rare case of sequential occurrence of WM with Eosinophilic Gastrointestinal Disease posing a diagnostic and therapeutic challenge. [ABSTRACT FROM AUTHOR]

Peripheral neuropathy is a prevalent complication in plasma cell disorders, posing significant diagnostic and therapeutic challenges. This study presents three cases initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Despite initial symptom regression post-immunomodulatory treatment, the patients exhibited progressive neurological deficits. Advanced laboratory evaluation confirmed monoclonal protein presence, yet traditional diagnostic methods, including bone marrow biopsy and flow cytometry, yielded normal results. Utilizing 18F-FDG PET/CT, we identified multiple hypermetabolic vertebral lesions, which upon biopsy, confirmed the diagnosis of plasmacytoma. Our findings underscore the utility of PET/CT as a reliable diagnostic tool for monoclonal gammopathy associated neuropathy, advocating for its consideration in cases with equivocal diagnosis. When the diagnosis is in doubt, biopsy of a lesion may facilitate early and accurate diagnosis, potentially influencing treatment strategies and patient outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: The purpose of the study is to evaluate the prediction of vertebral fractures in patients with plasma cell dyscrasias using dual-layer CT. The study retrospectively enrolled 81 patients diagnosed with plasma cell dyscrasia who underwent whole-body DLCT at diagnosis and follow-up. In the baseline CT, conventional CT image data (CI), calcium-suppressed image data (CaSupp25 and CaSupp100), and virtual calcium-only (VCa) image data were quantitatively analyzed in the lumbar vertebral bodies and in fractured vertebral bodies. New vertebral fractures occurred in 24 patients during follow-up. Lower CT numbers in CI and VCa, and higher CT numbers in CaSupp25, at baseline were significantly associated with a higher risk of new fractures. Logistic regression analysis revealed that CT numbers in CaSupp25 and VCa might be better predictors of fractures than CI. Cut-off values were suggested: CI at 103 HU and VCa at 129 HU. In conclusion, quantitative assessment with CaSupp and calculation of VCa can predict vertebral fracture risk in multiple myeloma patients, indicating that DLCT may be useful in detecting imminent fractures. Purpose: To evaluate the prediction of vertebral fractures in plasma cell dyscrasias using dual-layer CT (DLCT) with quantitative assessment of conventional CT image data (CI), calcium suppressed image data (CaSupp), and calculation of virtual calcium-only (VCa) image data. Material and Methods: Patients (n = 81) with the diagnosis of a plasma cell dyscrasia and whole-body DLCT at the time of diagnosis and follow-up were retrospectively enrolled. CI, CaSupp25, and CaSupp100 were quantitatively analyzed using regions of interest in the lumbar vertebral bodies and fractured vertebral bodies on baseline or follow-up imaging. VCa were calculated by subtraction (CaSupp100-CaSupp25), delineating bone only. Logistic regression analyses were performed to assess the possibility of imminent spine fractures. Results: In 24 patients, new vertebral fractures were observed in the follow-up imaging. The possibility of new vertebral fractures was significant for baseline assessment of CT numbers in CI, CaSupp25, and VCa (p = 0.01, respectively), with a higher risk for new fractures in the case of lower CT numbers in CI (Odds ratio = [0.969; 0.994]) and VCa (Odds ratio = [0.978; 0.995]) and in the case of higher CT numbers in CaSupp 25 (Odds ratio 1.015 [1.006; 1.026]). Direct model comparisons implied that CT numbers in CaSupp 25 and VCa might show better fracture prediction than those in CI (R2 = 0.18 both vs. 0.15; AICc = 91.95, 91.79 vs. 93.62), suggesting cut-off values for CI at 103 HU (sensitivity: 54.2%; specificity: 82.5; AUC: 0.69), for VCa at 129 HU (sensitivity: 41.7%; specificity: 94.7; AUC: 0.72). Conclusions: Quantitative assessment with CaSupp and calculation of VCa is feasible to predict the vertebral fracture risk in MM patients. DLCT may prove useful in detecting imminent fractures. [ABSTRACT FROM AUTHOR]

The diagnosis of multiple myeloma requires detection of paraproteinemia and confirmation of monoclonal bone marrow infiltration, along with signs of end-organ damage. Despite the increasing prevalence, serum paraproteinemia is not routinely measured. We examined the relationship between alterations in routine hematological parameters and the development of paraproteinemia in a case-control study. Data was retrieved from a laboratory database in the capital region of Denmark between 01/01/2012 and 31/12/2022. Patients were included if they had a test for paraproteinemia (n = 134,740) and at least one prior hematological parameter (white blood cells, hemoglobin and platelet count) with a minimum follow-up of 1 year. Between 96,999 and 103,590 patients were included in each of the three hematological groups. We found white blood cell count and the presence of paraproteinemia followed an inverse J-shaped curve, with the highest presence below 3 × 109/L and above > 9 × 109/L. The adjusted OR below and above the nadir of 4 × 109/L was 1.61 (95% CI 1.25; 2.08, p < 0.0001) and 1.03 (95% CI 1.03; 1.04, p < 0.0001). Hemoglobin levels were inversely associated the presence of paraproteinemia, with the highest association below 6 mmol/L with an OR of 1.30 (95% CI 1.28; 1.32, p < 0.0001) adjusted for age and gender. Platelet count followed a U-shaped curve with the highest association at < 100 × 109/L. The adjusted OR below and above the nadir of 250 × 109/L was 1.13 (95% CI 1.10; 1.17, p < 0.0001) and 1.10 (95% CI 1.08; 1.12, p < 0.0001) respectively. In conclusion, all three parameters showed significant association with later paraproteinemia. [ABSTRACT FROM AUTHOR]

Abstract Background Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy. Case presentation a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity. Conclusions Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease.

Abstract Multiple myeloma (MM) is a disease, that at times poses diagnostic and monitoring challenges. Over the last decades laboratory methods have been expanded with serum free light chain (FLC) analysis. Alerted by two index cases with clinical impact due to failure of the FLC analysis to indicate a disease progression, we aimed to identify any clinical consequences due to known differences between FLC analysis methods. We applied two FLC analysis methods (Freelite Binding Site [FBS] and N‐Latex Siemens [NLS]) on all patients with MM and monoclonal gammopathy of uncertain significance diagnosed/followed up at Södra Älvsborg Hematology Unit, from April to December 2022. From a total of 123 patients with malignant plasma cell disorder, we identified five cases (4.1%) where solely the FBS method, as opposed to NLS, urine and serum electrophoresis, could support diagnosis or detect progression. The consequences of this discrepancy included not only change of diagnosis or delayed therapy but also change of treatment. Our findings indicate that a stronger awareness of the potential weaknesses of different FLC methods is needed, which calls for a closer collaboration between clinical chemists and hematologists.

Background: Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy. Case presentation: a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity. Conclusions: Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy‐related peripheral neuropathies encompass a spectrum of clinical presentations in which the monoclonal protein directly damages the tissues, including the peripheral nervous system. Given the prevalence of both peripheral neuropathy and monoclonal gammopathy in the general population, these conditions may overlap in clinical practice, posing a challenge for clinicians in determining causality. Therefore, a comprehensive understanding of primary clinical syndromes and their neurophysiological patterns is of great importance for accurate differential diagnoses and effective treatment strategies. In this article, we examine the main forms of monoclonal gammopathies that affect the peripheral nerve. We explore the clinical and electrophysiological aspects and their correlation with each syndrome's corresponding monoclonal protein type. This knowledge is essential for healthcare professionals to diagnose better and manage patients presenting with monoclonal gammopathy‐related peripheral nervous system involvement. [ABSTRACT FROM AUTHOR]

Background: Upon infection activated plasma cells produce large quantities of antibodies which can lead to the emergence of a monoclonal component (MC), detectable by serum protein electrophoresis (SPEP). This study aims to investigate any correlation between SARS‐CoV‐2 infection and MC development and, if identified, whether it persists during follow‐up. Methods: SPEPs of 786 patients admitted to hospitals between March 01 2020 and March 31 2022 were evaluated. Positive (SARS‐CoV‐2+) and negative (SARS‐CoV‐2−) patients to nasopharyngeal swab for SARS‐CoV‐2 by RT‐PCR were included. The persistence/new occurrence of MC was investigated for all patients during follow‐up. Patient groups were compared by chi‐square analysis. Results: MC was identified in 12% of all patients admitted to hospital, of which 28.7% were SARS‐CoV‐2+. The most common immunoglobulin isotype in both groups was IgG‐k. There was no correlation between MC development and SARS‐CoV‐2 infection (p = 0.173). Furthermore, the risk of MC persistence in SARS‐CoV‐2‐negative patients was revealed to be higher than in the SARS‐CoV‐2+ at follow‐up (HR = 0.591, p = 0.05). Conclusions: Our study suggests that the detection of MC during SARS‐CoV‐2 infection is most likely due to the hyperstimulation of the humoral immune system, as also occurs in other viral infections. [ABSTRACT FROM AUTHOR]

Sinonasal system malignancies are rare, constituting only 1% of all malignancies and less than 5% of head and neck malignancies. The common form of plasma cell dyscrasias is called multiple myeloma (MM), and the localized forms are called solitary bone plasmacytoma and extramedullary plasmacytoma (EMP). EMP constitutes 3-4% of malignant plasma cell dyscrasias and 1% of all head and neck tumors. 90% of EMP cases occur in the head and neck region, because the nasal and paranasal sinus regions are rich in plasma cells at around 75%. This study aims to present two different cases of plasma cell tumors presenting in the paranasal region. Based on the imaging studies, the first case is seen to have been diagnosed as MM due to bone marrow involvement and to have received systemic chemotherapy treatment, whereas the second case is seen to have undergone endoscopic total excision of the lesion due to the absence of systemic involvement. In the first case, MM was considered to have gone into remission in the sixth month after chemotherapy; however, the patient died one year after diagnosis. In the second case, no recurrence was detected during the fifth year postoperative follow-up. As a result, patients who show sinonasal symptoms should be examined in detail. [ABSTRACT FROM AUTHOR]

Serum protein electrophoresis (SPEP) is a valuable laboratory test that separates proteins from the blood based on their electrical charge and size. the test can detect and analyze various protein abnormalities, and the interpretation of graphic SPEP features plays a crucial role in the diagnosis and monitoring of conditions, such as myeloma. Furthermore, the advancement of artificial intelligence (AI) technology presents an opportunity to enhance the organization and optimization of analytical procedures by streamlining the process and reducing the potential for human error in SPeP analysis, thereby making the process more efficient and reliable. For instance, AI can assist in the identification of protein peaks, the calculation of their relative proportions, and the detection of abnormalities or inconsistencies. this review explores the characteristics and limitations of AI in SPEP, and the role of standardization in improving its clinical utility. It also offers guidance on the rational ordering and interpreting of SPeP results in conjunction with AI. Such integration can effectively reduce the time and resources required for manual analysis while improving the accuracy and consistency of the results. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy (MG) is a spectrum of diseases ranging from the benign asymptomatic monoclonal gammopathy of undetermined significance to the malignant multiple myeloma. Clinical guidelines and laboratory recommendations have been developed to inform best practices in the diagnosis, monitoring, and management of MG. In this review, the pathophysiology, relevant laboratory testing recommended in clinical practice guidelines and laboratory recommendations related to MG testing and reporting are examined. The clinical guidelines recommend serum protein electrophoresis, serum immunofixation and serum free light chain measurement as initial screening. The laboratory recommendations omit serum immunofixation as it offers limited additional diagnostic value. The laboratory recommendations offer guidance on reporting findings beyond monoclonal protein, which was not required by the clinical guidelines. The clinical guidelines suggested monitoring total IgA concentration by turbidimetry or nephelometry method if the monoclonal protein migrates in the non-gamma region, whereas the laboratory recommendations make allowance for involved IgM and IgG. Additionally, several external quality assurance programs for MG protein electrophoresis and free light chain testing are also appraised. The external quality assurance programs show varied assessment criteria for protein electrophoresis reporting and unit of measurement. There is also significant disparity in reported monoclonal protein concentrations with wide inter-method analytical variation noted for both monoclonal protein quantification and serum free light chain measurement, however this variation appears smaller when the same method was used. Greater harmonization among laboratory recommendations and reporting format may improve clinical interpretation of MG testing. [ABSTRACT FROM AUTHOR]

Background: M’ proteins or paraproteins refer to immunoglobulins that are produced by clonal plasma cells and are a characteristic feature of monoclonal gammopathies. Routine electrophoresis on agarose gel and immunofixation can be used to detect immunoglobulin paraprotein (M-protein). We aimed to evaluate the performance of agarose gel electrophoresis alone and in combination with immunofixation for detecting serum M-proteins. Methods: One hundred and twenty-three patients suspected of paraproteinemia were evaluated. Routine serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) protocols were performed. Data from SPE, and SPE-IFE (gel images and electrophoretograms) were collected and reviewed. Results: 21% cases were confirmed using the SPE-IFE combination, and among them, 33% had positive light chain (λ) only on IFE. Similarly, nine cases with biclonal gammopathy on SPE were characterized by IFE. Conclusion: IFE can be a confirmatory test in cases where SPE results are not reliable and it can be a complementary test when characterization of the M protein detected on SPE is required. [ABSTRACT FROM AUTHOR]

Context.--Monoclonal gammopathy of renal significance (MGRS) is a relatively new concept for patients with renal monoclonal protein deposition (RMPD) (except monoclonal cast nephropathy) and has been used as a reason for nephrologists to obtain a bone marrow biopsy (BMB). It takes a team of pathologists and clinicians to determine when RMPD at our institution can be defined as MGRS. Objective.--To identify the proportion of various subtypes of tentative MGRS diagnosed by renal biopsy that can be confirmed as final MGRS after BMB. Design.--One hundred thirty kidney biopsies with variants of RMPD were identified during the past 10 years. Biopsy cases with known myeloma, B-cell lymphoma, or monoclonal cast nephropathy were separated as a heavy-burden group. The remaining biopsies with RMPD were considered tentative MGRS. Their BMB and clinical indices were further analyzed to determine the final percentage of MGRS diagnoses. Results.--Among the 130 renal paraprotein deposition cases, 44 (33.8%) were categorized as the heavy-burden group. In the remaining 86 cases, 33 (38.4%) with subsequent identification of myeloma (.10% of monoclonal plasma cells) or lymphoma in BMB were further considered as heavy-burden cases. Eighteen cases (18 of 86; 20.9%) did not receive follow-up BMB; thus, no further analysis was performed. BMBs diagnosed as either nonmalignant (no plasma cells; 8 of 86 cases; 9.3%) or premalignant (,10% plasma cells; 27 of 86 cases; 31.4%) were confirmed to be final MGRS (35 of 86; 40.7%). Conclusions.--The data indicate that BMB is an important element in the confirmation of MGRS. [ABSTRACT FROM AUTHOR]

Approximately half of the calcium in the blood circulates in the ionized, free form; which is critical for cellular function. As a result, its levels are tightly regulated by homeostatic mechanisms dependent on hormones such as PTH, vitamin D, and fibroblast growth factor-23. The other half of the total calcium is in a complex with anions, predominantly albumin. Clinically, the levels of albumin are known to influence the relationship of total calcium to free calcium. However, the relevance of changes in other serum proteins on calcium homeostasis is less appreciated. We present the case of a 70-year-old woman who was followed over 5 years with persistently elevated total calcium levels but with normal ionized calcium levels. Her evaluation was notable for IgA paraprotein, which paralleled her history of elevated total serum calcium. Extensive clinical investigations did not reveal hyperparathyroidism or cancer-mediated hypercalcemia. Additional in vitro analyses comparing the plasma containing the IgA paraprotein against a healthy control revealed that a high-molecular-weight IgA paraprotein in the patient has increased capacity to reduce the amount of free calcium in solution, thus providing a direct mechanistic explanation for the clinical findings. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy of renal significance (MGRS) has gained importance because identifying the monoclonal deposit and addressing it, rather than treating renal dysfunction as the primary pathology, has salvaged the patients from progressing into end-stage renal disease. Since it affects elderly population, there could be a propensity to misdiagnose them with cardiorenal syndrome. We present four patients of MGRS diagnosed from our center. They presented with proteinuria or unexplained renal dysfunction. Three of the patients were diagnosed to have amyloidosis, of which two had lambda-type and one had kappa amyloidosis. The fourth patient had fibrillary glomerulonephritis with kappa restriction, further evaluation of which led to diagnosis of chronic lymphocytic leukemia. Absence of "M" band in protein electrophoresis and a normal bone marrow study should not stop physicians from further evaluation. Quantitative serum immunofixation electrophoresis and electron microscopic examination of renal biopsy have become a comprehensive diagnostic tool in such patients. [ABSTRACT FROM AUTHOR]

Copyright of Revista Médica de Rosario is the property of Circulo Medico de Rosario and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Waldenstroms macroglobulinemia (WM) or Lymphoplasmacytic lymphoma is a rare B cell lymphoproliferative malignancy characterized by serum monoclonal immunoglobulin M (IgM) protein and lymphoplasmacytic infiltration in the bone marrow. Patients usually present in their seventh decade with symptoms related to the infiltration of the marrow or the effects of monoclonal IgM in the blood. Objective: Was to study the clinical characteristics and treatment outcome of patients diagnosed with WM. Materials and methods: This is a retrospective analysis of 26 cases of WM treated at a tertiary cancer centre. Results: WM constituted 0.68% of our nonHodgkin's lymphoma. The median age at presentation was 67 years with a male to female ratio of 2:1. Four patients had lymphadenopathy, six had splenomegaly and four patients had evidence of hyper viscosity. All patients had IgM paraproteinemia, the M band was IgM-kappa in 19 patients and IgM-lambda in seven patients. All patients had a histopathological confirmation. According to IPSS-WM, 12 patients each were in the intermediate and high risk group and 2 in the low risk group. Among the 26 patients, 20 patients received upfront treatment and four patients were kept under observation. The indications for treatment were cytopenia in ten patients, constitutional symptoms in five, hyper viscosity in four and symptomatic lymphadenopathy in one patient. Sixteen patients received rituximab-based chemotherapy. Four patients with features with hyper viscosity underwent plasmapheresis. The three year progression free survival and overall survival were 69.4% and 78 % respectively. Conclusions: WM is a low grade B cell lymphoproliferative disorder having an indolent course and do not require treatment for prolonged period. Diagnosis is challenging due to lack of distinct diagnostic features. Rituximab containing regimens are the standard of care. Newer targeted treatment options may improve the outcome of this incurable disease. [ABSTRACT FROM AUTHOR]

A 45-year-old man presented with an isolated sciatic mononeuropathy, which then evolved into a lumbosacral radiculoplexus neuropathy. His initial symptoms included lower limb pain, sensory disturbance and later weakness, without autonomic dysfunction. Neurophysiology suggested a postganglionic neuropathy. MR and ultrasound scans of the thighs showed right sciatic nerve thickening, and CSF analysis showed albuminocytological dissociation. Fluorodeoxyglucose positron emission tomography (FDG PET) was unremarkable. He then developed orthostatic symptoms and urinary disturbance, and was found to have an IgM paraprotein. Fat aspirate, cardiac and wholebody imaging found no amyloid deposition, and genetic testing for transthyretin amyloidosis was negative. A bone marrow biopsy was unremarkable. However, neuropathology review of a proximal, fascicular nerve biopsy identified a lambda chain-restricted plasma cell population with positive Congo red staining, leading to a diagnosis of peripheral nerve restricted amyloid light amyloidosis. We discuss the diagnostic approach to this case from the perspectives of neurology, neurophysiology, radiology and neuropathology. [ABSTRACT FROM AUTHOR]

Aim: Multiple myeloma is a malignancy of clonal plasmacytes. Osteolytic lesions represent a criterion for symptomatic myeloma and are associated with bone loss, pathological fractures, and osteoporosis. Skeletal surveys with other sophisticated techniques and dual-energy x-ray absorptiometry (DEXA) are used to screen lytic lesions, and bone mineral loss, respectively. Here, we aimed to investigate the rates of detection regarding osteolytic lesions and bone mineral loss by several imaging techniques. Materials and Methods: The study was carried out in Aydın Adnan Menderes University Hospital/Turkey, between the years 2004-2020. Three-hundred and ten symptomatic myeloma patients were screened retrospectively. The results of radiological techniques were recorded. The detection rate of osteolytic lesions, fractures, and plasmacytomas by imaging techniques, as well as the detection rate of bone mineral loss with DEXA were recorded. Also, the relationship between the detected lytic lesions and gender, myeloma type, and the sensitivity and specificity of DEXA to detect osteoporosis in cases with lytic lesions were investigated. Results: Skeletal survey and PET-CT detected lytic lesions in 71.3% and 81.2% of patients, respectively. PET-CT had a sensitivity of 96.1% and specificity of 90.6% to detect lytic lesions. MRI was only used for patients with suspicious fractures and detected them for all patients who underwent MRI. The osteoporosis rate was 83.1% for 113 patients who underwent DEXA. No association was detected between lytic lesions and gender/myeloma type. The sensitivity and specificity of BMD-DEXA to detect osteoporosis among patients who have lytic lesions were 85.3% and 23.5%, respectively. Conclusion: Our study demonstrated that osteolytic lesions are not correlated with gender or myeloma type. PET-CT is a sensitive and specific method for detecting osteolytic lesions. Although DEXA is sensitive, its specificity is limited in patients with lytic lesions. Giriş: Multipl myelom, klonal plazma hücrelerinin bir malignitesidir. Osteolitik lezyon varlığı, semptomatik myelom için bir tanı kriteri olarak kabul edilmektedir. Ayrıca, kemik kaybı, patolojik kırıklar ve osteoporoz ile ilişkilidir. Litik lezyon varlığı ve kemik mineral kaybını saptamak için çeşitli görüntüleme yöntemleri ve çift enerjili x-ışını absorbsiyometrisi (DEXA) kullanılır. Bu çalışmada görüntüleme yöntemleri ve DEXA ile osteolitik lezyonların ve kemik mineral kaybının saptanma oranlarının araştırılması amaçlanmıştır. Gereç ve Yöntem: Bu çalışma 2004-2020 yılları arasında Aydın Adnan Menderes Üniversitesi Hastanesi/Türkiye'de gerçekleştirildi. Üç yüz on semptomatik myelom hastası retrospektif olarak incelendi. Osteolitik lezyon, fraktür ve plazmasitomların görüntüleme yöntemleriyle tespit oranı ve ayrıca DEXA ile kemik mineral kaybı saptama oranı kaydedildi. Ayrıca tespit edilen litik lezyonlar ile cinsiyet, myelom tipi arasındaki ilişki ve litik lezyon saptanan olgularda DEXA'nın osteoporozu saptama duyarlılığı ve özgüllüğü araştırıldı. Bulgular: Litik lezyonlar, direkt grafi ve PET-BT ile hastaların sırasıyla %71,3'ünde ve %81,2'sinde saptadı. PET-BT'nin litik lezyonları saptamada duyarlılığı %96,1 ve özgüllüğü %90,6 idi. MR görüntülemesine, sadece fraktür şüphesi olan hastalarda başvuruldu ve MR çekilen tüm hastalarda fraktür tespit edildi. DEXA çekilen 113 hastada osteoporoz oranı %83,1 idi. Litik lezyon varlığı ile cinsiyet/myelom tipi arasında herhangi bir ilişki saptanmadı. Osteolitik lezyon saptanan olgularda DEXA' nın osteoporozu saptamadaki duyarlılığı %83,3, özgüllüğü %23,5 olarak bulundu. Sonuç: Çalışmamız, osteolitik lezyonların cinsiyet veya myelom tipi ile korele olmadığını göstermiştir. PET-BT, osteolitik lezyonları saptamak için hassas ve spesifik bir yöntemdir. DEXA, osteoporozu saptamada duyarlı bir yöntem olmasına ragmen; özgüllüğü, litik lezyonları olan hastalarda sınırlı bir değere sahiptir. [ABSTRACT FROM AUTHOR]

Introduction: Plasma cell disorders (PCD) are a group of conditions characterized by disproportionate proliferation of a single clone of B lymphocytes. Multiple myeloma (MM) is a malignant type of plasma cell disorders. Improvements in MM survival have led patients and physicians to pursue strategies to improve quality of life for those living longer with this disease. Bone disease and instability associated with MM have made physicians reluctant to recommend physical activity (PA) to this patient population. The goal of this study was to examine the relationship between PA and physical and psychosocial patient-reported outcomes in patients withMMand precursor conditions. Methods: We used a cross-sectional study design. Questionnaires on PA, demographics, fatigue, distress, and other aspects of quality of life were posted on the HealthTree® Cure Hub website, a patient portal through which individuals withMMand related disorders obtain support, track laboratories and other information about their diseases, and participate in research. Results: A total of 794 individuals, including 664 with MM, are included in the current analysis. We observed potential inverse associations between PA and poor quality of life, including problems with sleep, fatigue, neuropathy, distress, and several psychosocial states. On average, patients reported that their PA levels have declined since diagnosis and that theywould like to be evenmore active in the future than theywere before their diagnosis. Conclusions: In our cross-sectional study, regular PA was associated with multiple quality-of-life indicators and other patient-reported outcomes, including better sleep and less fatigue, neuropathy, and distress. The findings of this study can help guide the design of prospective studies of the role of PA in MM survivorship. [ABSTRACT FROM AUTHOR]

Objective The acid/molybdate assay performed on the Beckman Coulter AU5821 could be subject to paraprotein interference, which potentially results in spurious hyperphosphatemia. We attempted to find a reliable solution to eliminate paraprotein interference in laboratory test results and discuss the causes of paraprotein interference. Methods We observed 50 multiple myeloma patients with serum paraproteins. We used the trichloroacetic acid (TCA) deproteinizing method to confirm that paraproteins indeed interfered with phosphate detection in the serum acid/molybdate assay. Furthermore, we used the dry chemical method (Vitros 5.1 FS, Johnson) and deionized water (H2O), normal saline (NS), and healthy human serum as alternative diluents. We assessed the clinical acceptability of the 4 methods by evaluating a bias percentage (bias%) lower than 10% under the premise of TCA treatment as a serum phosphate reference method. Results In total, comparing the results of the TCA treatment on the Beckman Coulter AU5821, 3/50 (6%) multiple myeloma patients exhibited phosphate pseudo-elevation (bias% >10%). Additionally, we found pseudo-hypophosphate only in immunoglobulin (Ig)G-kappa paraprotein samples, and all were above 50 g/L. The bias% between TCA and dry chemical method for the 3 patients was below 10%. The maximum acceptable dilutions for patient 22 were 8-fold H2O, 4-fold H2O , and 2-fold serum; those for patient 45 were 16-fold H2O, 16-fold H2O, and 2-fold serum. However, the bias% of patient 40 was beyond the acceptable range in all 3 dilution groups. Conclusion High concentrations of IgG kappa–type paraproteins are more likely to interfere with serum phosphorous detection. Both the TCA and dry chemical method can effectively eliminate paraprotein interference. [ABSTRACT FROM AUTHOR]

Background: Multiple myeloma is characterized by the uncontrolled proliferation of monoclonal plasma cells in the bone marrow, leading to the production of non-functional intact immunoglobulin chains. This retrospective study aimed to investigate the correlation between plasma cell percentage (below 60% and above 60%) in different types of monoclonal gammapathies (IgA, IgG) and various biochemical parameters. Methods: This analysis was conducted at the Division of Biochemistry in the Malabar Cancer Centre, a tertiary care cancer center in Kerala, India. A total of 89 patient case reports were reviewed, and complete treatment data were available for 60 patients. The study aimed to evaluate the relationship between plasma cell percentage (below 60% and above 60%) in different types of monoclonal gammapathies (IgA, IgG) and various biochemical parameters. Results: The majority of the patients enrolled in the study were above 60 years of age, and more men were included than women. Among the parameters studied, a significant increase in plasma protein level was observed in the group with a plasma cell percentage below 60% and IgG type monoclonal gammapathy (P value = 0.014, p < 0.05). Additionally, there was a significant elevation in WBC count in patients with plasma cell percentage below 60% and IgG type MM when compared to IgA type MM patients (p = 0.023, p < 0.05). However, no significant changes were observed in plasma protein level, liver enzyme activity, renal function, serum electrolytes, CBC, and calcium level between patients with plasma cell percentages above and below 60% in multiple myeloma. Conclusion: This study found that only a few biochemical and hematological parameters showed significant deviations between plasma cell percentages above and below 60% in different types of monoclonal gammapathies in multiple myeloma patients. [ABSTRACT FROM AUTHOR]

High-dose melphalan-based autologous stem cell transplant (ASCT) remains a standard of care for plasma cell disorders (PCDs). Currently, there is variability in the literature surrounding the timing of melphalan administration to avoid potential cytotoxic effects, although the administration has been safely proposed when given at least 8 hours prior to stem cell infusion. The objectives of this study were to assess differences in safety and efficacy outcomes between day -1 and day -2 single-dose melphalan administration in patients undergoing ASCT for PCDs. A retrospective chart review was performed at our institution comparing patients receiving melphalan on day -1 to an equal number of patients receiving melphalan on day -2. The primary endpoint was time to neutrophil engraftment from stem cell infusion. Univariate analyses were performed. Mean time to neutrophil engraftment from stem cell infusion was identical at 10.7 days for both cohorts (p = 0.88). Mean time to platelet engraftment from stem cell infusion was shorter with day -1 administration (17.4 vs. 18.6 days, p = 0.06). Mean time to neutrophil and platelet engraftment from melphalan infusion were significantly shorter with day -1 administration. Similar outcomes were observed for length of hospitalization, infection- and mucositis-related toxicities, hematologic response, transplant-related mortality, and overall survival. Our findings show no difference in time to neutrophil engraftment from stem cell infusion and a trend toward shorter time to platelet engraftment with day -1 administration. Based on our study, day -1 melphalan administration is an acceptable and safe practice. [ABSTRACT FROM AUTHOR]

Introduction: The incidence of acute interstitial nephritis (AIN) has been increasing in recent years. The causes and outcomes of AIN have been changing with time and vary widely based on geographical region. Methods: A retrospective observational study was conducted in a tertiary care center. All (n = 6234) native kidney biopsies were reviewed from January 2016 to December 2021. All biopsy-proven AIN cases were included in the study. AIN associated with systemic diseases (such as SLE, Sjogren's, sarcoidosis, plasma cell dyscrasias), proliferative glomerulonephritis, and allograft biopsies were excluded. Results: Among 6234 biopsies analyzed, there were 156 biopsy-proven AIN cases. The majority were in the 6th decade of life (24.4%) and males (80.8%). 50% of the patients had a history of drug intake, the most common being tenofovir (12.3%) followed by alternate forms of medications (10.3%). The majority (96.2%) presented with acute kidney injury (AKI). At the end of six months, 79.5% recovered completely, 19.2% progressed to chronic kidney disease. The presence of nephrotic range proteinuria at presentation was associated with progression to chronic kidney disease Conclusion: AIN is an important cause of AKI, especially in the elderly population. Drugs are the most common cause, especially HAART follwed by alternate forms of medication. The presence of nephrotic range proteinuria was associated with increased risk of progression to chronic kidney disease. [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]

Objective Biclonal gammopathies (BGs) are rare situations characterized by the production of 2 monoclonal proteins. There are no available data on BGs in North Africa. We aimed to estimate the prevalence of BGs in our population and describe their clinical and laboratory features. Methods We conducted a 31-year retrospective study including patients with persistent double monoclonal bands based on the results of immunofixation/immunoelectrophoresis. Results A total of 35 patients with available clinical data (sex ratio, M/F = 1.53; mean age, 70 ± 10.87 years [range, 45–90 years]) were included. The main associated conditions were multiple myeloma (MM) (40%), BG of undetermined significance (BGUS) (34%), and lymphoproliferative diseases (23%). Only one-third of the patients had 2 monoclonal spikes on serum protein electrophoresis. The most common paraprotein combinations were immunoglobulin (Ig)G-IgG (25%) and IgG-IgA (23%) with different light chains in one-half of the cases. The mean follow-up was 25.6 months (median, 12 months). No BGUS evolved into a malignant disease. Conclusion BGs are rare in clinical laboratory routine but must be accurately identified by the pathologist. Our cohort is characterized by a high prevalence of BGUS compared with MM. [ABSTRACT FROM AUTHOR]

Simple Summary: Waldenström Macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with bone marrow involvement and IgM monoclonal gammopathy. Detection of MYD88 L265P mutation (MYD88mut) has a crucial contribution to the diagnosis, since >90% of WM cases harbor this mutation. No studies have focused specifically on peripheral blood (PB) involvement in this entity. We evaluate the incidence of leukemic involvement in WM by multiparametric flow cytometry (MFC) and molecular techniques (IGH rearrangement and MYD88mut) at diagnosis. Overall, 80/100 (80%) of the patients presented PB involvement by any technique. The presence of PB involvement by MFC in 50% of the patients supports the role of PB immunophenotyping as an objective tool in the evaluation of patients presenting with IgM monoclonal gammopathy and would reinforce the value of this approach in clinical practice, avoiding morbidity especially in cases of indolent clinical behavior and in frail patients. Waldenström Macroglobulinemia (WM) is a lymphoplasmacytic lymphoma with bone marrow (BM) involvement and IgM monoclonal gammopathy. To date, no studies have focused specifically on peripheral blood (PB) involvement. In this study, 100 patients diagnosed with WM according to the World Health Organization (WHO) criteria were included based on the demonstration of MYD88mut in BM and the availability of PB multiparametric flow cytometry (MFC) analysis. Leukemic involvement by MFC was detected in 50/100 patients. A low percentage of mature small lymphocytes in PB smears was observed in only 15 cases. MYD88mut by AS-qPCR was detected in PB in 65/100 cases. In cases with leukemic expression by MFC, MYD88mut was detected in all cases, and IGH was rearranged in 44/49 cases. In 21/50 patients without PB involvement by MFC, molecular data were consistent with circulating disease (MYD88mut by AS-qPCR 3/50, IGH rearranged 6/50, both 12/50). Therefore, PB involvement by standard techniques was detected in 71/100 patients. MYD88mut was detected in PB by dPCR in 9/29 triple negative cases. Overall, 80% of the patients presented PB involvement by any technique. Our findings support the role of PB MFC in the evaluation of patients with IgM monoclonal gammopathy and provide reliable information on correlation with molecular features. The development of a feasible MFC assay may stand as an objective tool in the classification of mature B cell neoplasms presenting with IgM monoclonal gammopathy. [ABSTRACT FROM AUTHOR]

• Of the 16 analytes investigated, the most promising early indicator of Multiple Myeloma was an increased Calculated Globulin. • The median Calculated Globulin was 78.6% higher in the active Multiple Myeloma group than in the Control group. • The Median Calculated Globulin was 35.7% higher in the smouldering Multiple Myeloma group than in the control group. • Calculated Globulin was not a particularly useful indicator of free light chain Multiple Myelomas. • Calculated Globulin is easily implemented as it is derived from the routinely requested total protein and albumin analytes. Multiple Myeloma (MM) is a haematological malignancy with increasing global incidence. Diagnosis of MM should be initiated at the primary care level to achieve the best patient outcome. However, this can be delayed due to nonspecific presenting symptoms, such as back pain and fatigue. The aim of this study was to investigate if commonly requested blood tests could indicate MM in primary care and potentially lead to earlier diagnosis. This retrospective observational study involved an audit of clinical and laboratory data from 109 MM patients, including patients with Active MM (N = 53), Smouldering MM (N = 33), and Free light chain MM (N = 23). Of the 16 potential biomarkers investigated, the most promising indicator for early detection of active MM and Smouldering MM was an increased Calculated Globulin (CG). The median CG for patients with active MM (50 g/L) was 78.6% higher than the healthy control group (28 g/L). Smouldering MM patients had a median CG value (38 g/L), which was 35.7% higher than the control group. Of interest, the median CG result was only 16.7% higher in the control group than in the free light chain MM group, suggesting CG would not be as effective at detecting this subtype. CG is derived from Total Protein and Albumin data, which are commonly measured in routine liver function profiles, thus there is no additional test or cost requirement. Based on these data, CG has potential as a clinical biomarker to support early detection of MM at the primary care level and allow for appropriate targeted investigations. [ABSTRACT FROM AUTHOR]

The term monoclonal gammopathies of renal significance (MGRS) encompasses a group of renal histopathological lesions fulfilling two criteria: (a) they are caused by nephrotoxic monoclonal immunoglobulins and (b) the monoclonal immunoglobulins are produced by small B-cell or plasma cell clones which do not meet the criteria for multiple myeloma or malignant lymphoma. Here, we provide a review of the MGRS definition and related terminology and elaborate on the diagnostic approach and treatment principles from the general physician perspective. [ABSTRACT FROM AUTHOR]

Simple Summary: Waldenström's macroglobulinemia is a lymphoproliferative disorder rarely described in veterinary medicine. According to the human classification of hematopoietic tumors, this disease is defined as a subtype of lymphoplasmacytic lymphoma with bone marrow involvement and monoclonal gammopathy of IgM type. Cytopathology is a convenient and accurate diagnostic procedure to diagnose lymphoma in dogs. However, ancillary techniques, such as PCR for antigen receptor rearrangement, flow cytometry, immunohistochemistry, and histology, are usually required to fully characterize the grade and phenotype, especially in ambiguous cases. Immunosecretory lymphoproliferative disorders result from malignant clonal expansion of B-cells and are usually characterized by hyperglobulinemia, although normoglobulinemia can also occur, hypoglobulinemia being rarer. Monoclonal gammopathy can be suspected on serum protein electrophoresis as it usually migrates as a narrow peak in the γ or β fractions, but immunofixation is required for confirmation and characterization. This case report describes clinicopathologic features, diagnosis, treatment, and the outcome of Waldenström's macroglobulinemia in a 2-year-old neutered female Small Munsterlander dog with atypical bimorphic plasmacytoid differentiation and unusual M-protein migration on serum protein electrophoresis. A 2-year-old neutered female Small Munsterlander dog was presented for an insect bite. Physical examination revealed a poor body condition, a peripheral lymphadenomegaly, and suspected splenomegaly. A complete blood count (Sysmex XN-V) revealed marked leukocytosis with lymphocytosis and abnormal dot plots. An abnormal monomorphic lymphoid population and marked rouleaux formation were noted on the blood smear. Lymph node aspirates contained an atypical bimorphic population of lymphocytes, either with a plasmacytoid or a blastic appearance. This double population was also found in the spleen, liver, bone marrow, tonsils, and other tissues. Peripheral blood and lymph node clonality assays revealed clonal BCR gene rearrangement. Flow cytometry revealed a mixed population of small-sized B-cells (CD79a+ CD21+ MHCII+) and medium-sized B-cells (CD79a+ CD21− MHCII−) in lymph nodes and a dominant population of small-sized mature B-cells (CD21+ MHCII+) in peripheral blood. Though normoproteinemic, serum protein electrophoresis revealed an increased α2-globulin fraction with an atypical restricted peak, identified as monoclonal IgM by immunofixation. Urine protein immunofixation revealed a Bence-Jones proteinuria. A diagnosis of Waldenström's macroglobulinemia was made. Chemotherapy was initiated, but the dog was euthanized 12 months after the initial presentation due to marked clinical degradation. [ABSTRACT FROM AUTHOR]

Serum κ and λ free light chains can be markedly elevated in monoclonal gammopathies; consequently, serum free light chain (sFLC) immunoassays are susceptible to inaccuracies caused by antigen excess. As a result, diagnostics manufacturers have attempted to automate antigen excess detection. A 75-year-old African-American woman had laboratory findings consistent with severe anemia, acute kidney injury, and moderate hypercalcemia. Serum and urine protein electrophoresis and sFLC testing were ordered. The sFLC results initially showed mildly elevated free λ light chains and normal free κ. The pathologist noted that sFLC results were discrepant with the bone marrow biopsy, electrophoresis, and immunofixation results. After manual dilution of the serum, repeat sFLC testing revealed significantly higher λ sFLC results. Antigen excess causing falsely low sFLC quantitation may not be detected by immunoassay instruments as intended. Correlation with clinical history, serum and urine protein electrophoresis results, and other laboratory findings is essential when interpreting sFLC results. [ABSTRACT FROM AUTHOR]

This letter, published in the Annals of Clinical Biochemistry, discusses the potential interference of paraproteins in Roche c702 assays. The authors encountered negative interference in the Roche enzymatic creatinine assay due to a paraprotein in a patient with Waldenstrom's macroglobulinaemia. They also reviewed the literature and found that other Roche assays, such as total bilirubin, HDL cholesterol, and phosphate, can be affected by paraprotein interference. However, their investigation of 102 samples with significant paraproteinemia did not detect any spurious results in the nine assays tested on the Roche c702. The authors emphasize the importance of further investigation when results do not align with previous results or the clinical picture. [Extracted from the article]