Nonsecretory Myeloma Research Articles

A rare case of non-secretory multiple myeloma without bone marrow involvement

A rare case of non-secretory multiple myeloma without bone marrow involvement

Atypical imaging feature of Non-secretory multiple myeloma

Non-secretory multiple myeloma (NSMM) is a rare variant of the classic form of multiple myeloma in which no monoclonal gammopathy can be demonstrated in the serum or urine. We describe a rare case of non-secretory multiple myeloma in a 23 year old female presenting with bilateral limb weakness of two years duration. Clinically she was diagnosed to have Pott's spine and was treated with category 1 anti tubercular drugs. Hematological investigations showed plasmacytosis and radiography showed osteolytic lesions. No monoclonal gammopathy was found in the serum or urine. MRI showed multiple compressions with sclerosis within vertebral bodies suggestive of osteomalacia/ diffuse infiltrative disorder. The free light chain (FLC) assay revealed increment in the free kappa light chain and an abnormal κ/λ ratio. Free Light Chain assay (FLC) when used in complement with Protein Electrophoresis (PEP) and Immunofixation Electrophoresis (IFE) were pivotal in diagnosis of non secretory multiple myeloma or light chain myelomas. FLC is a useful monitoring tool because it reflects therapy results due to short serum half life.

Polymyositis associated with non-secretory myeloma – a case report

Idiopathic inflammatory myopathies, a heterogeneous group of disorders characterised by weakness and inflammation of skeletal muscle, are often associated with malignancies. This association has been infrequently reported in Asian countries. We report a case of an Indian patient who presented with polymyositis in conjunction with non-secretory myeloma, hypercalcaemia and renal failure.

Phase II randomized trial of bevacizumab versus bevacizumab and thalidomide for relapsed/refractory multiple myeloma: a California Cancer Consortium trial

Vascular endothelial growth factor (VEGF) is upregulated in multiple myeloma (MM), and circulating VEGF levels may correlate with response to therapy (Hideshima, et al 2005, Pittini, et al 2002). Thalidomide has been part of the standard treatment for MM and is thought to inhibit VEGF-associated angiogenesis (Du, et al 2004). Bevacizumab, a monoclonal antibody directed against VEGF-A, inhibits VEGF (Jenab-Wolcott and Giantonio 2009). Accordingly, we set out to test the efficacy and safety of bevacizumab alone and in combination with thalidomide in MM patients.

Non-Secretory Myeloma or Light Chain-Producing Multiple Myeloma: A Case Report

Nonsecretory multiple myeloma (NSMM) is a rare variant of the classic form of MM that has a similar clinical and radiologic presentation except for the absence of the M-protein in serum and/or urine. Depending on the author, NSMM may have or not detectable monoclonal free light chain in urine/serum. We describe here a case of a 51-year-old woman who presented with back pain and multiple osteolytic bone lesions. This woman had no other symptoms and her serum basic analyses were normal. She had normal serum and urine protein electrophoresis, but a monoclonal kappa light chain band in plasmatic and urinary immunofixation was found. A CT guide biopsy from the D4 vertebra showed 9% plasmocytes in the bone marrow, 100% of them with an abnormal phenotype, all being CD38+ and CD138+, confirming the diagnosis of light chain myeloma, initially presenting as NSMM. A high index of suspicion is needed to diagnose cases like this, as the biology of NSMM is not completely understood. The potential value of more sensitive quantitative diagnostic techniques for this disease is being studied. doi:10.4021/jmc156w

Myelomagenesis: Capturing Early Microenvironment Changes

Plasma cell neoplasms result from the clonal expansion of terminally differentiated, immunoglobulin heavy-chain class switched B cells that typically secrete a monoclonal immunoglobulin. The 2008 World Health Organization (WHO) classification of plasma cell neoplasms encompasses a broad spectrum of disorders, from the precursor disorder monoclonal gammopathy of undetermined significance (MGUS) to plasma cell leukemia. The classification includes, in addition to precursor lesion MGUS, plasma cell myeloma, plasmacytoma, immunoglobulin deposition diseases, and osteosclerotic myeloma. Plasma cell myeloma is further divided into symptomatic plasma cell myeloma or multiple myeloma (MM), asymptomatic smoldering myeloma (SMM), non-secretory myeloma, and plasma cell leukemia. Although histopathologic cut-off criteria are incorporated into the classification schema, distinction between MGUS, SMM, and MM depends primarily on the presence or absence of end-organ damage, as defined by "CRAB" criteria (hypercalcemia, renal insufficiency, anemia, lytic bone lesions, or a combination of these). Systematic evaluation of pathogenetic differences between MGUS and MM should offer invaluable insights into early myelomagenesis. Given the complex, intertwined nature of the malignant plasma cell and its surroundings, multiple pathogenetic mechanisms play a critical role in interactions between neoplastic cells and their microenvironment. Understanding the events leading to end-organ damage, like anemia and bone remodeling, is a critical part of investigating early myelomagenesis and should provide us with better tools for early identification and treatment of these patients.

A Case of Non-secretory Myeloma with Crystal-storing Histiocytosis

Crystal-storing histiocytosis (CSH) is a rare event observed in association with lymphoproliferative diseases, and mainly occur in plasma cell dyscrasias. It is presumed to be an intra-lysosomal accumulation of the secreted paraproteins. Crystal formation can be seen inside histiocyte-like cells with phagocytosed crystalline inclusions in the bone marrow and extramedullary sites. CSH is a rare morphological entity with poor prognostic implications and may be confused with Gaucher or pseudo-Gaucher cells. Herein we report a case of non-secretory myeloma associated with CSH showing a poor clinical course. A 79-yr-old male presenting with dizziness was evaluated in hematology department for anemia. Laboratory tests revealed Hb of 4.9 g/dL and β2-microglobulin of 21,000 ng/mL (reference range, 0-370). Presence of monoclonal protein was not detected on protein electrophoresis and immunofixation in serum and urine. However, serum free light chain assay showed an increased kappa-light chain level of 126 mg/L (reference range, 3.3-19.4) resulting in an increased kappa/lambda ratio. The bone marrow touch print showed numerous plasma cells and crystal-laden histiocytes and immunohistochemical stainings on bone marrow biopsy revealed positivity for CD38, CD56 and kappa in the plasma cells and CD68 and kappa in crystal-laden histiocytes.

Professor Emeritus Maxime Seligmann (1927-2010)

European Journal of ImmunologyVolume 40, Issue 12 p. 3301-3301 News and EFISFree Access Professor Emeritus Maxime Seligmann (1927–2010) First published: 25 November 2010 https://doi.org/10.1002/eji.201090066AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Maxime Seligmann passed away on April, 26, 2010. He was an outstanding French physician-scientist who has influenced the development of modern immunology over the past fifty years and was President of the French Society for Immunology from 1984 to 1988. Born in 1927, he completed his medical education at the Faculty of Medicine at Paris University, becoming a pediatrician and hematologist. His scientific career and interest in immunology began at the Pasteur Institute in Dr. Grabar's laboratory before moving in 1957 to work at the Saint-Louis hospital in Paris; there Maxime Seligmann headed both a clinical immunology department and a research laboratory supported by INSERM, Paris 7 University and CNRS. More recently, he contributed to the fight against the HIV epidemic at the Assistance Publique – Hôpitaux de Paris and ANRS. During the later stages of his career, he was a member of the French National Ethics committee. As a physician-scientist, Maxime Seligmann was insightful and brillant, always starting from clinical observations to understand fundamental immunology. His first groundbreaking work was the identification of antibodies to DNA in lupus patients in 1957 1. This was a provocative finding that raised countless issues and investigations over the years. Thereafter, his work dealt with a breath of immuno-hematological issues, with numerous contributions to the fields of monoclonal immunoglobulins and lymphoproliferative diseases. The list of innovative findings include the idiotypic nature and antibody activity of monoclonal immunoglobulins 2-5, the genetic susceptibility to Waldenstrom's macroglobulinemia (a seminal observation in 1967) 6, the monoclonal nature of lymphoid malignancies, the pathophysiology of non-secretory and light chain myelomas, and the first description of T-cell malignancies 7-9. The discovery of α heavy chain disease 10 remained a central focus of Maxime Seligmann's work. Beyond the description of the clinical, cellular and molecular characteristics of the disease, he emphazised its unique epidemiological features, pointing to the potential triggering role of intestinal micro-organisms; in fact, antibiotics turned out to be of therapeutic value. More broadly, his research interests extended to several aspects of autoimmunity and immunodeficiencies, areas for which he was a WHO expert. These achievements were shared with many colleagues around the world; Maxime Seligmann was an invaluable discussant at internationl conferences with exchanges of thoughts, material and elaboration regarding theoretical models for B and T lymphocyte homeostasis. Maxime Seligmann was also a superb teacher, running many medical and scientific courses. Indeed he remains an inspiring model for several generations of physician-scientists. He was dedicated to his faculty duties and one personnal achievement was the recognition of immunology, both medical and biological, as a medical specialty. In the early 1980s Maxime Seligmann became a French-government adviser proposing changes to the medical course in part to facilitate the development of clinical investigation, which he thought to be an endangered science. Maxime Seligmann also served as an Executive Committee member of the European Journal of Immunology for 17 years (1975–1991). This task was, as usual, accomplished with integrity and thoughtfulness. We shall all miss him. Jean-Claude Brouet Department of Immunology, Saint-Louis Hospital, Paris References 1Seligmann, M., Vox Sang. 1957. 2: 270– 282. 2Seligmann, M. et al., Nature 1968. 220: 711– 712. 3Hurez, D. et al., J. Immunol. 1968. 100: 69– 79. 4Seligmann, M. et al., Science 1966. 154: 790– 791. 5Preud'homme, J. L. and Seligmann, M., Proc. Natl. Acad. Sci. USA 1972. 69: 2132– 2135. 6Seligmann, M. et al., Am. J. Med. 1967. 43: 66– 83. 7Brouet, J. C. et al., New Engl. J. Med. 1973. 289: 341– 344. 8Salmon, S. E. and Seligmann, M., Lancet 1974. ii: 1230– 1233. 9Seligmann, M., Neoplasias and B cell precursors. Nature 1979. 279: 578. 10Seligmann, M. et al., Science 1968. 162: 1396– 1397. Volume40, Issue12December 2010Pages 3301-3301 ReferencesRelatedInformation

Assessment of the Performance of Serum Heavy Chains Immunoassay to Monitor Response to Treatment and Its Correlation with Other Tumor Measurements In Serial Samples From Patients with Newly Diagnosed MM

AbstractAbstract 2986Currently available methods for the measurement of tumor load in multiple myeloma include the measurement of monoclonal proteins by electrophoresis, the percentage of myeloma cells in the bone marrow, and the more recently described serum free light chain (FLC) assay. The recent development of antibodies which bind to conformational epitopes spanning the junctional regions between the bound or light chains and their respective heavy chains has now allowed for the specific measurement of serum IgGκ, IgGλ, IgAκ and IgAλ concentrations (HLC). How this novel test may fit in with the other tumor measuring methods has not been fully established. We evaluated the correlation of serum HLC assays with FLC assays, serum monoclonal protein measurement by electrophoresis (M spike), and total immunoglobulin G or A, in serial samples of patients with newly diagnosed MM undergoing a lenalidomide containing induction regimen. Methods:Total immunoglobulins were quantitated by immunonephelometry. HLC and FLC concentrations were quantitated with standard reagents (The Binding Site, Ltd). M spike was evaluated by electrophoresis. Pearson's regression was used to determine correlations among the above tests. Result:Serum samples at baseline, 3 months and 6 months after therapy from 16 patients were assayed. Ig subtypes are as follows: 7 IgGκ, 1 IgGλ, 3 IgAκ, 3 IgAλ, 1 light chain and 1 nonsecretory myeloma. The FLC of the involved chain was abnormal in all but one case, including cases of light chain and nonsecretory MM. The HLC of the involved chain was abnormal in all cases, except the patient with non-secretory MM, in which case, the IgG and were both suppressed. HLC did not correlate well with FLC (r=0.08). Similarly, the HLC k/l ratio did not correlate well with FLC k/l ratio (r=0.33). The HLC moderately correlated with M spike (r= 0.49). The HLC of the involved chain correlate strongly to total immunoglobulin (r=0.9).At 3 months post treatment, HLC and FLC of the involved chains decreased dramatically from baseline levels and plateaud in most cases. HLC kinetics seemed to be slower than FLC as, in 4 cases, FLC normalized before HLC. Interestingly, in these 4 cases, the continual decline in HLC correlated better to the change in the M spike. We also observed a recovery of the previously suppressed uninvolved HLC in 6 cases, leading to the continual improvement in the HLC κ/λ ratio even after the HLC normalization. Conclusion:HLC kinetics showed differences compared to FLC and correlated better with the monoclonal spike. FLC normalized faster but, once normalized, seemed to correlate less well than HLC with M spike and ongoing clinical response. Increased HLC of the uninvolved chain was observed in a subset of patients, after therapy. The HLC κ/λ ratio, which takes into account the changes of the uninvolved chain, is an appealing tool for disease monitoring once HLC of the involved chain normalized. HLC is complimentary to other tumor assessment tools and needs to be further explored in a larger patient cohort. Disclosures:No relevant conflicts of interest to declare.

Evaluation of Serum Free Light Chains In Chinese Multiple Myeloma Patients

AbstractAbstract 5011 Purpose:Serum Free-Light Chain (sFLC) Assay is a sensitive tool recently used for diagnosis and response assessment of plasma cell disorders, especially in light chain multiple myeloma, nonsecretory multiple myeloma and primary amyloidosis. According to assemble analysis of multiple large-scale clinical research results, guideline of sFLC analysis was introduced by IMWG in 2008. But sFLC assay has not been routinely used in China and the clinical significance of the item has been explored in this study. Patients and Methods:Serum specimens from 36 cases of MM patients identified by IFE were analyzed. The median age was 56.2(36-74). 24(66.7%) patients were male. The M protein type was IgG in 50%, IgA in 22%, IgD in 3%, light chain in 25%. According to D-S staging, 11% pts was inIIA, 58% in IIIA, 31% in IIIB. 8% patients was in±of ISS staging, 17% inII and 75% in III. Normal range for FLC measurements is as follows: κ3.3–13.1 mg/L, λ5.7–26.3 mg/L, and κ/λ ratio of 0.26–1.65. Results:Abnormal rFLCs were detected 100% in 14 newly-diagnosed patients. 86% patients had measurable disease. In κ-MM patients, levels of sFLC-κ were (553.1±471) mg/L; sFLC-λ were (14.2±4) mg/L; the median of rFLC was 32.62. In λ-MM patients, levels of sFLC-κ were (5.3±2.67) mg/L; sFLC-λ were (2503±1043) mg/L; the median of rFLC was 0.002.22 MM patients were detected during the follow up after treatment. Abnormal clonal rFLC could be found 100% in 3 PD patients, 66.7% in 12 PR/SD patients and 0 in 7 ≥VGPR patients. There was no statistical significance between sFLC and sTLC (p≥0.05). The value of iFLC in ≥VGPR group was statistical different from other response assessment groups (p<0.05). In 24 patients with measurable disease (9 with κ-MM,15 with λ-MM), an elevated level of iFLC was associated with increased myeloma cells in bone marrow and β2-microglobulin, but not with ALB, LDH. Conclusions:sFLC assay is a highly sensitive diagnostic and response monitoring tool for multiple myeloma. An elevated level of iFLC was associated with increased myeloma cells in bone marrow and β2-microglobulin, but not with ALB, LDH in measurable disease. More patients and longer follow-up are needed to further evaluate the diagnostic and prognostic significance of this judgment parameter. Disclosures:No relevant conflicts of interest to declare.

Nonsecretory myeloma in a child

Nonsecretory myeloma in a child

Efficacy and outcome of autologous transplantation in rare myelomas

As rare myelomas, i.e. the IgD, IgE, IgM and non-secretory forms, constitute only a small proportion of any study, relatively little is known about their prognosis in the era of peripheral stem cell transplantation. We used the European Group for Blood and Marrow Transplantation Myeloma Database to compare the outcome following autologous transplantation of over 20,000 patients with common myelomas (IgG, IgA and light chain myeloma) with the outcome of patients with rare myelomas: 379 IgD, 13 IgE, 72 IgM and 976 non-secretory cases. The study confirms the multiple adverse prognostic factors seen in IgD myeloma. Somewhat surprisingly, patients with IgD and non-secretory myeloma both had higher complete remission rates before and after transplantation than patients with common myelomas. However, while the overall survival of patients with non-secretory myeloma was similar to that of the patients with common myelomas, the survival of patients with IgD myeloma was significantly worse (although better than survival rates reported for non-transplanted patients); this was due to higher transplant-related mortality and relapse/progression rates. The post-transplantation survival of patients with IgE or IgM myeloma appears to be very poor. This study provides data on the biological features of rare myelomas. The overall survival of patients with IgD, IgE or IgM myeloma is poor following autologous transplantation but substantially better than that reported for patients who were not transplanted.

Nonsecretory multiple myeloma, how to make a diagnosis?

Nonsecretory multiple myeloma, how to make a diagnosis?

Prediction of Response and Progression in Multiple Myeloma With Serum Free Light Chains Assay: Corroboration of the Serum Free Light Chain Response Definitions

The International Myeloma Working Group (IMWG) proposed response and progression criteria using serum free light chain (sFLC) testing for patients with nonsecretory multiple myeloma (MM). We attempt to validate these criteria by comparing paraprotein responses with sFLC responses in patients with secretory myeloma. Prospectively entered data for 89 patients with MM enrolled on various clinical trials at the Cleveland Clinic between April 2004 and December 2006 were reviewed. By standard paraprotein criteria, 4 patients had complete remission (CR), 22 had partial remission (PR), 34 had stable disease (SD), 26 had progressive disease (PD), and 3 were inevaluable. Only 43 patients (48%) had an involved sFLC > or = 10 mg/dL (which is considered evaluable by the IMWG), of which 14 had PR, 8 had SD, 18 had PD, and 3 were inevaluable. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for sFLC in predicting response were 81%, 83%, 64%, and 92% respectively. The sensitivity, specificity, PPV, and NPV for sFLC in predicting progression were 93%, 80%, 72%, and 95% respectively. sFLC reliably predicts response and progression in MM. However, half of the patients had inevaluable disease by sFLC, thus limiting the utility of sFLC testing in patients with nonmeasurable disease by electrophoretic methods.

Recommendations for Use of Free Light Chain Assay in Monoclonal Gammopathies

Recommendations for Use of Free Light Chain Assay in Monoclonal GammopathiesThe serum immunoglobulin free light chain assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the free light chain assay in the evaluation and management of multiple myeloma and related plasma cell disorders. In the context of screening, the serum free light chain assay in combination with serum protein electrophoresis and immunofixation yields high sensitivity, and negates the need for 24-hour urine studies for diagnoses other than light chain amyloidosis. Second, the baseline free light chains measurement is of major prognostic value in virtually every plasma cell disorder. Third, the free light chain assay allows for quantitative monitoring of patients with oligosecretory plasma cell disorders, including AL, oligosecretory myeloma, and nearly twothirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial free light chains measurements outperform protein electrophoresis and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial free light chains measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using free light chain assay in place of 24-hour urine electrophoresis for monitoring or for serial measurements in plasma cell disorders with measurable disease by serum or urine electrophoresis.

Sternum osteolysis on coronary computed tomography in a patient with non-secretory multiple myeloma

Sternum osteolysis on coronary computed tomography in a patient with non-secretory multiple myeloma

A Case of Non Secretory Type Multiple Myeloma Associated with Systemic Lupus Erythematosus

The development of malignant tumors is a more frequent finding in lupus patients than the general population. However, the incidence of multiple myeloma associated with systemic lupus erythematosus (SLE) is a rare manifestation. SLE is an autoimmune disease characterized by B cell hyperactivity, formation of autoantibodies, and multi-clonal hypergammaglobulinemia. Serum immunoglobulin increases, with a specific increase in IgG, which is due to an increase in autoantibody formation related to extrinsic and intrinsic antigens. We report on a patient with SLE combined with IgG, lambda type nonsecretory multiple myeloma, which was diagnosed with refractory anemia and hypergammaglobulinemia.

A Rare Masquerader of Lung Cancer: Nonsecretory Multiple Myeloma with Plasmacytoma of Bone Presenting as Acute Kidney Injury

Multiple myeloma (MM) is a neoplasm of B cell lineage characterized by excessive proliferation of abnormal plasma cells which produce immunglobulins. If a monoclonal spike is not found in serum or urine but the patient has clinical findings and bone marrow plasma cell infiltration suggestive of MM, then the patient may have a rare subtype known as nonsecretory multiple myeloma (NSMM). Here, we describe a rare case of NSMM with plasmacytoma of bone who presented with severe hypercalcemia, acute kidney injury and a large thoracal mass on chest X-ray masquerading as lung cancer.

Serum free light-chain assay for nonsecretory multiple myeloma with light chain cast nephropathy and light chain deposition disease

Serum free light-chain assay for nonsecretory multiple myeloma with light chain cast nephropathy and light chain deposition disease

Exoftalmos unilateral como debut de mieloma múltiple no secretor

A 56 year-old male presented blurred vision and diplopia for 2 months, left unilateral exophthalmos, restricted ocular motility and papilledema. The imaging proofs showed osteolytic lesions in the left sphenoid bone, fourth rib and fourth dorsal vertebral body with associated masses of soft tissues. Biopsy was performed and the diagnosis of plasma cell neoplasm was established. The diagnosis of non-secretory multiple myeloma was made by analytical criteria and bone marrow biopsy. Local radiotherapy and polychemotherapy was prescribed. The ophthalmologist can play an important role in the diagnosis of systemic neoplasms that require the intervention of a multidisciplinary team.