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Annals of Internal Medicine Dec 2022Monoclonal gammopathy of undetermined significance (MGUS) is of considerable clinical importance to primary care physicians given its high prevalence in the general... (Review)
Review
Monoclonal gammopathy of undetermined significance (MGUS) is of considerable clinical importance to primary care physicians given its high prevalence in the general population. MGUS has a variable but lifelong risk for progression to hematologic cancer, such as multiple myeloma, Waldenström macroglobulinemia, or light-chain amyloidosis. In addition, MGUS has been associated with several nonmalignant yet symptomatic disorders that require therapy directed toward eliminating the monoclonal gammopathy. Thus, it is important not only to understand the essentials of diagnosing and monitoring patients with MGUS but also to recognize when to refer patients with MGUS to a specialist.
Topics: Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Multiple Myeloma; Waldenstrom Macroglobulinemia; Disease Progression
PubMed: 36508741
DOI: 10.7326/AITC202212200 -
The New England Journal of Medicine May 2021
Review
Topics: Humans; Kidney; Kidney Diseases; Paraproteinemias
PubMed: 34010532
DOI: 10.1056/NEJMra1810907 -
Nature Reviews. Nephrology Jan 2019The term monoclonal gammopathy of renal significance (MGRS) was introduced by the International Kidney and Monoclonal Gammopathy Research Group (IKMG) in 2012. The IKMG...
The term monoclonal gammopathy of renal significance (MGRS) was introduced by the International Kidney and Monoclonal Gammopathy Research Group (IKMG) in 2012. The IKMG met in April 2017 to refine the definition of MGRS and to update the diagnostic criteria for MGRS-related diseases. Accordingly, in this Expert Consensus Document, the IKMG redefines MGRS as a clonal proliferative disorder that produces a nephrotoxic monoclonal immunoglobulin and does not meet previously defined haematological criteria for treatment of a specific malignancy. The diagnosis of MGRS-related disease is established by kidney biopsy and immunofluorescence studies to identify the monotypic immunoglobulin deposits (although these deposits are minimal in patients with either C3 glomerulopathy or thrombotic microangiopathy). Accordingly, the IKMG recommends a kidney biopsy in patients suspected of having MGRS to maximize the chance of correct diagnosis. Serum and urine protein electrophoresis and immunofixation, as well as analyses of serum free light chains, should also be performed to identify the monoclonal immunoglobulin, which helps to establish the diagnosis of MGRS and might also be useful for assessing responses to treatment. Finally, bone marrow aspiration and biopsy should be conducted to identify the lymphoproliferative clone. Flow cytometry can be helpful in identifying small clones. Additional genetic tests and fluorescent in situ hybridization studies are helpful for clonal identification and for generating treatment recommendations. Treatment of MGRS was not addressed at the 2017 IKMG meeting; consequently, this Expert Consensus Document does not include any recommendations for the treatment of patients with MGRS.
Topics: Biomarkers; Biopsy; Genetic Testing; Humans; Kidney Diseases; Paraproteinemias
PubMed: 30510265
DOI: 10.1038/s41581-018-0077-4 -
Haematologica Sep 2022IgM monoclonal gammopathy of undetermined significance is a pre-malignant condition for Waldenström macroglobulinemia and other B-cell malignancies, defined by... (Review)
Review
IgM monoclonal gammopathy of undetermined significance is a pre-malignant condition for Waldenström macroglobulinemia and other B-cell malignancies, defined by asymptomatic circulating IgM monoclonal protein below 30 g/L with a lymphoplasmacytic bone marrow infiltration of less than 10%. A significant proportion, however, develop unique immunological and biochemical manifestations related to the monoclonal protein itself in the absence of overt malignancy and are termed IgM-related disorders or, more recently, monoclonal gammopathy of clinical significance. The indication for treatment in affected patients is dictated by the pathological characteristics of the circulating IgM rather than the tumor itself. The clinical workup and treatment options vary widely and differ from those for Waldenström macroglobulinemia. The aim of this review is to alert clinicians to IgM monoclonal gammopathy of clinical significance and to provide practical guidance on when to screen for these phenotypes. We discuss clinical characteristics, the underlying clonal profile, diagnostic workup and treatment considerations for five important subtypes: cold agglutinin disease, type I and II cryoglobulinemia, IgM-associated peripheral neuropathy, Schnitzler syndrome and IgM-associated AL amyloidosis. The inhibition of the pathogenic effects of the IgM has led to great success in cold agglutinin disease and Schnitzler syndrome, whereas the other treatments are centered on eradicating the underlying clone. Treatment approaches in cryoglobulinemia and IgM-associated peripheral neuropathy are the least well developed. A multidisciplinary approach is required, particularly for IgM-related neuropathies and Schnitzler syndrome. Future work exploring novel, clone-directed agents and pathogenic IgM-directed therapies is welcomed.
Topics: Anemia, Hemolytic, Autoimmune; Cryoglobulinemia; Humans; Immunoglobulin M; Lymphoma, B-Cell; Paraproteinemias; Schnitzler Syndrome; Waldenstrom Macroglobulinemia
PubMed: 35770530
DOI: 10.3324/haematol.2022.280953 -
Journal of Neurology Jan 2019POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder,... (Review)
Review
POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is a rare paraneoplastic syndrome, caused by a plasma cell proliferative disorder, which is most commonly lambda restricted. The neurological hallmark, which forms one of the mandatory criteria for diagnosis, is a subacute onset demyelinating neuropathy, which can be rapidly disabling and painful. A number of multi-system features are also characteristic of this disorder, and certainly not restricted to those included in its acronym, which though limited, remains a useful and memorable name, helping distinguish POEMS syndrome from other paraproteinaemic neuropathies. The discovery of vascular endothelial growth factor (VEGF) in association with POEMS syndrome has been extremely useful in aiding clinical diagnosis, and monitoring response to treatment, as well as helping understand the underlying mechanism of disease. Interestingly, however, treatment targeting VEGF has been disappointing, suggesting other disease mechanisms or inflammatory processes are also important. Current understanding of the pathogenesis of POEMS syndrome is outlined in detail in the accompanying article by Cerri et al. Here, we review the clinical features of POEMS syndrome, differential diagnosis and available treatment options, based on current literature.
Topics: Humans; POEMS Syndrome
PubMed: 30498913
DOI: 10.1007/s00415-018-9110-6 -
American Society of Clinical Oncology... Apr 2022Our knowledge of monoclonal gammopathies is continuously evolving. Once accepted as a possible precursor condition to multiple myeloma, monoclonal gammopathies as an... (Review)
Review
Our knowledge of monoclonal gammopathies is continuously evolving. Once accepted as a possible precursor condition to multiple myeloma, monoclonal gammopathies as an entity are now associated with many renal, neurologic, and dermatologic disorders of clinical significance. This change has created a challenge for patients and clinicians, as a monoclonal gammopathy may be a harbinger not of multiple myeloma but of other lymphoproliferative disorders such as light-chain amyloidosis and Waldenström macroglobulinemia. Early recognition of monoclonal gammopathies along with a careful workup are essential in determining the next steps in the care of a given patient. Recognition has become all the more important as we understand how to triage the 4% to 9% of patients with monoclonal gammopathies depending on age, with the goal of limiting overdiagnosis and misdiagnosis. In this review, we focus on treatment strategies for patients with monoclonal gammopathies that are not multiple myeloma, including smoldering multiple myeloma, light-chain amyloidosis, and Waldenström macroglobulinemia.
Topics: Amyloidosis; Humans; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias; Waldenstrom Macroglobulinemia
PubMed: 35394823
DOI: 10.1200/EDBK_349643 -
The Lancet. Oncology Jun 2019Recent advances in the treatment of multiple myeloma have increased the need for accurate diagnosis of the disease. The detection of bone and bone marrow lesions is... (Review)
Review
Recent advances in the treatment of multiple myeloma have increased the need for accurate diagnosis of the disease. The detection of bone and bone marrow lesions is crucial in the investigation of multiple myeloma and often dictates the decision to start treatment. Furthermore, detection of minimal residual disease is important for prognosis determination and treatment planning, and it has underscored an unmet need for sensitive imaging methods that accurately assess patient response to multiple myeloma treatment. Low-dose whole-body CT has increased sensitivity compared with conventional skeletal survey in the detection of bone disease, which can reveal information leading to changes in therapy and disease management that could prevent or delay the onset of clinically significant morbidity and mortality as a result of skeletal-related events. Given the multiple options available for the detection of bone and bone marrow lesions, ranging from conventional skeletal survey to whole-body CT, PET/CT, and MRI, the International Myeloma Working Group decided to establish guidelines on optimal use of imaging methods at different disease stages. These recommendations on imaging within and outside of clinical trials will help standardise imaging for monoclonal plasma cell disorders worldwide to allow the comparison of results and the unification of treatment approaches for multiple myeloma.
Topics: Consensus; Diagnostic Imaging; Humans; International Agencies; Multimodal Imaging; Multiple Myeloma; Paraproteinemias; Plasma Cells; Practice Guidelines as Topic
PubMed: 31162104
DOI: 10.1016/S1470-2045(19)30309-2 -
Blood Cancer Journal Apr 2022Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and... (Review)
Review
Monoclonal gammopathy associated with dermatological manifestations are a well-recognized complication. These skin disorders can be associated with infiltration and proliferation of a malignant plasma cells or by a deposition of the monoclonal immunoglobulin in a nonmalignant monoclonal gammopathy. These disorders include POEMS syndrome, light chain amyloidosis, Schnitzler syndrome, scleromyxedema and TEMPI syndrome. This article provides a review of clinical manifestations, diagnostics criteria, natural evolution, pathogenesis, and treatment of these cutaneous manifestations.
Topics: Amyloidosis; Humans; Monoclonal Gammopathy of Undetermined Significance; Paraproteinemias; Plasma Cells; Skin Diseases
PubMed: 35411042
DOI: 10.1038/s41408-022-00661-1 -
Blood Jun 2019Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of... (Review)
Review
Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant plasma cell dyscrasia that consistently precedes multiple myeloma (MM) with a 1% risk of progression per year. Recent advances have improved understanding of the complex genetic and immunologic factors that permit progression from the aberrant plasma cell clone to MGUS and overt MM. Additional evidence supports bidirectional interaction of MGUS cells with surrounding cells in the bone marrow niche that regulates malignant transformation. However, there are no robust prognostic biomarkers. Herein we review the current body of literature on the biology of MGUS and provide a rationale for the improved identification of high-risk MGUS patients who may be appropriate for novel clinical interventions to prevent progression or eradicate premalignant clones prior to the development of overt MM.
Topics: Humans; Paraproteinemias
PubMed: 31010848
DOI: 10.1182/blood.2019846782 -
Journal of Nippon Medical School =... 2019Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the... (Review)
Review
Abnormal proliferation of plasma cells and some monoclonal B cells frequently cause the secretion of monoclonal immunoglobulins or immunoglobulin fragments into the serum, causing monoclonal gammopathy, which leads to various diseases including renal diseases. Therefore, monoclonal gammopathy is frequently associated with kidney diseases, including glomerular and tubulointerstitial diseases. Glomerular disease, with the deposition of monoclonal immunoglobulins or their components, includes monoclonal immunoglobulin deposition disease (MIDD), AL or AH amyloidosis, type I cryoglobulinemia, proliferative glomerulonephritis with monoclonal IgG deposits (PGNMID), immunotactoid glomerulopathy, and fibrillary glomerulonephritis. In addition, tubulointerstitial diseases with the deposition of monoclonal immunoglobulins or their components are constituted by light chain (myeloma) cast nephropathy, light chain associated Fanconi's syndrome (light chain proximal [crystal] tubulopathy), and crystal-storing histiocytosis. In the present review article, we demonstrate the clinicopathological characteristics of MIDD, which is one of the representative diseases of plasma cell dyscrasias, and discuss various renal diseases with the deposition of monoclonal immunoglobulins or their components in glomeruli and the tubulointerstitium. We recommend that these renal diseases are arranged as one disease category, "renal diseases with deposition of monoclonal immunoglobulins or their components", in order to simplify the understanding of complicated diseases in plasma cell dysplasia.
Topics: Antibodies, Monoclonal; Cryoglobulinemia; Fanconi Syndrome; Glomerulonephritis; Histiocytosis; Humans; Immunoglobulin G; Kidney Diseases; Kidney Glomerulus; Kidney Tubules; Paraproteinemias
PubMed: 30918151
DOI: 10.1272/jnms.JNMS.2019_86-1