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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]

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 The concentration of monoclonal immunoglobulins (Igs) in neoplastic monoclonal gammopathic manifestations is generally measured by densitometric scanning of the monoclonal peaks on gel or by measuring absorbance at 210 nm in capillary electrophoresis (CE). For monoclonal Igs migrating in the beta region, measurement is complicated by the major beta-region proteins, namely, transferrin and C3. Methods C3 interference in densitometry was eliminated by heat treatment of serum, and monoclonal Igs were quantified by densitometry of the residual band. The immunochemical measurement of transferrin was converted to its equivalent densitometric quantity. For monoclonal Ig migrating with transferrin, the contribution of the latter was removed by subtracting the converted transferrin concentration from the combined densitometric quantification of the band. With CE, monoclonal Ig was measured by using immunosubtraction (ISUB) to guide demarcation. Results The results obtained using the C3 depletion and transferrin subtraction method were lower and yet comparable to the results derived from using CE measurement guided by ISUB. As we expected, the results from both methods were lower than those derived from a perpendicular drop measurement of the peak or via nephelometric assay of the involved isotype. Discussion Accurate measurement of monoclonal Igs is important for the diagnosis and monitoring of monoclonal gammopathic manifestations. Determination of serum free light chain concentration per gram of monoclonal Ig is an essential measure for the diagnosis of light chain–predominant multiple myeloma. The method described herein improves accuracy of measurements for monoclonal Igs migrating in the beta region, without the need for special reagents or equipment. [ABSTRACT FROM AUTHOR]

Sera from patients with multiple myeloma usually display a single monoclonal immunoglobulin band on serum protein immunofixation electrophoresis. Multiple bands may be seen if the myeloma is bi- or triclonal or if the monoclonal immunoglobulin has rheumatoid factor activity. We describe a patient with light chain–predominant IgA lambda myeloma; the patient's serum displayed 2 spatially distinct bands reacting for alpha heavy and lambda light chains. The methods used to establish monoclonality are addressed. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinemia (WM) is a form of lymphoplasmacytic lymphoma that can cause hyperviscosity syndrome due to unchecked monoclonal antibody production. Some patients are also found to have associated cryoglobulinemia, which can cause systemic complications including vasculitis, renal disease, and pulmonary complications. Cryoglobulins can also serve as a source of interference with various laboratory assays. Therapeutic plasma exchange (TPE) is one of the recommended treatment modalities to manage hyperviscosity. Herein, we present the case of an 84-year-old female patient with Waldenström macroglobulinemia who presented with hyperviscosity syndrome and discrepant laboratory findings, and who then developed transfusion-related acute lung injury (TRALI) during TPE. This case is one of many in the emerging possible linkages observed between cryoglobulinemia and TRALI. [ABSTRACT FROM AUTHOR]

Background Concentration of serum free light chains has been promoted as an assay in the evaluation of monoclonal gammopathic manifestations. A high false-positive rate in patients without monoclonal gammopathic manifestations and a high false-negative rate in patients with those manifestations have been reported. The false-negative rate for lambda chain–associated lesions is higher than that for kappa chain–associated lesions. Objective To assess the serum free light chains in light-chain myelomas. Methods Concentrations of involved and uninvolved serum free light chains were retrospectively reviewed in patients with light-chain myelomas. Results The highest recorded levels of involved light chains in kappa-chain myelomas and lambda-chain myelomas were comparable. The levels of uninvolved light chains were higher, although not statistically significantly, in lambda-chain lesions. Conclusions The results of serum free light chains in light-chain myelomas support the clinical usefulness of the assay in monitoring patients with light chain myeloma. [ABSTRACT FROM AUTHOR]

Patient: 44-year-old white woman. Chief Complaints: Cramping, nausea, shortness of breath, visual disturbances ("seeing yellow dots"). Medical History: Status asthmticus, tobacco use, hypertension, migraines. Principle Laboratory Findings: Tables 1-7, Figures 1-4. [ABSTRACT FROM AUTHOR]

In the detection of monoclonal proteins using capillary electrophoresis (CE), several problems have been described, especially for small amounts of paraprotein, light chain (LC) disease, and cases associated with contrast interference. In this report, we describe 3 unusual cases that showed false-positive peaks due to radiologic contrast interference and the escape of monoclonal LC in CE. In these cases questionable for monoclonal components, conventional gel tests and free LC assays could be helpful to confirm monoclonal gammopathy. Therefore, multiple methodological modalities should be combined for diagnosing and monitoring plasma cell neoplasms and related disorders. [ABSTRACT FROM AUTHOR]

Waldenstrom macroglobulinemia (WM) is a rare B-cell lymphoproliferative disorder with clinical features of lymphoplasmacytic infiltration of the bone marrow, progressive anemia, and immunoglobulin M (IgM) monoclonal gammopathy. It can be distinguished from other B-cell lymphoproliferative disorders by molecular, cytogenetic and immunophenotyping. Despite advancements in therapy, WM is incurable and remains a challenging disease to diagnose and manage in patients with familial predisposition and second cancers. This report provides a review of the current clinical presentations, laboratory findings, and treatment of WM. [ABSTRACT FROM AUTHOR]