scholarly journals Differential diagnosis of monoclonal gammopathy of undetermined significance

Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 595-603 ◽  
Author(s):  
Giampaolo Merlini ◽  
Giovanni Palladini
Keyword(s):  
Differential Diagnosis ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Cell Clone ◽  
Organ Damage ◽  
Organ Injury ◽  
Al Amyloidosis ◽  
Monoclonal Protein ◽  
Undetermined Significance

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder occurring in 4.2% of adults > 50 years of age, which can progress into symptomatic diseases either through proliferation of the plasma cell clone, giving rise to multiple myeloma and other lymphoplasmacellular neoplasms, or through organ damage caused by the monoclonal protein, as seen in light-chain amyloidosis and related conditions. Differential diagnosis of asymptomatic and symptomatic monoclonal gammopathies is the determinant for starting therapy. The criteria for determining end-organ damage should include markers of organ injury caused by the monoclonal protein. Patient assessment and optimal follow-up are now performed using risk stratification models that should also take into account the risk of developing AL amyloidosis. Patients with low-risk MGUS (approximately 40% of all MGUS patients) need limited assessment and very infrequent follow-up. The ongoing development of novel molecular biomarkers and advanced imaging techniques will improve the identification of high-risk patients who may benefit from early therapeutic intervention through innovative clinical trials.

scholarly journals Follow-up Care of Monoclonal Gammopathy of Undetermined Significance: A Guide for Primary Care Physicians

2021 ◽  
Vol 8 (5) ◽  
Author(s):  
Hammad Z ◽  
◽  
Hernandez E ◽  
Tate S ◽  
◽  
...  
Keyword(s):  
Plasma Cell ◽  
Primary Care Physicians ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Organ Damage ◽  
M Protein ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
End Organ Damage ◽  
Undetermined Significance

Monoclonal Gammopathy of Undetermined Significance (MGUS) is a condition in which M protein, an abnormal monoclonal immunoglobulin, is present in the blood at a nonmalignant level. Specifically, it is defined by: blood serum M protein concentration <3 g/dL (<30 g/L), <10% plasma cells in the bone marrow, and no evidence of end organ damage [1,2]. Evidence of end organ damage includes hypercalcemia, renal insufficiency, anemia, and bone lesions. These are indicative of MGUS progression and which can be attributed to the monoclonal plasma cell proliferative process [3]. MGUS occurs in 3% of the general population older than 50 years. Incidence increases with age and varies with sex with higher rates observered in males than females [1,4]. MGUS is the most common plasma cell disorder, with 60% of patients that present to the Mayo Clinic with a monoclonal gammopathy being diagnosed with MGUS [3]. While it is typically an asymptomatic condition, it is premalignant disorder to other monoclonal gammopathies. Multiple Myeloma (MM) is almost always preceded by MGUS and the majority of patients will have detectable levels of M protein for at least 5 years prior to MM diagnosis [5,6]. MGUS also precedes immunoglobulin light chain (AL) amyloidosis and Waldenstrom Macroglobulinemia (WM) and tends to progress to disorders at a fixed but unrelenting rate of 1% per year [4].

scholarly journals Monoclonal Gammopathy of Renal Significance—A Rare Renal Presentation: A Review of Cases Reported

2020 ◽  
Vol 8 ◽  
pp. 232470962094050
Author(s):  
Asim Kichloo ◽  
Najma Nawaz ◽  
Jagmeet Singh ◽  
Michael Aljadah ◽  
Michael Stanley Albosta ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Renal Disease ◽  
Monoclonal Gammopathy ◽  
Organ Damage ◽  
Direct Effects ◽  
Monoclonal Protein ◽  
Renal Manifestation ◽  
Plasma Cell Disorder ◽  
Cell Disorder ◽  
Undetermined Significance

Monoclonal gammopathy of undetermined significance is a precursor to multiple myeloma characterized by monoclonal gammopathy without evidence of end organ damage. Some patients with clonal plasma cell disorder that do not meet the requirements for multiple myeloma have been seen to develop pathologic renal disease due to direct effects from deposition of monoclonal protein, referred to as monoclonal gammopathy of renal significance. In this article, we present a rare renal manifestation of monoclonal gammopathy of renal significance as focal segmental glomerulosclerosis.

scholarly journals Incidentally Detected Amyloid Light-Chain Amyloidosis Caused by Monoclonal Gammopathy of Undetermined Significance: Possible Time-Dependent Change in Colonic Findings

2018 ◽  
Vol 12 (3) ◽  
pp. 737-746
Author(s):  
Toshiro Fukui ◽  
Yuji Tanimura ◽  
Yasushi Matsumoto ◽  
Shunsuke Horitani ◽  
Takashi Tomiyama ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Amyloid Deposition ◽  
Fecal Occult Blood ◽  
Al Amyloidosis ◽  
Plasma Cell Disorder ◽  
Amyloid Light Chain ◽  
Cell Disorder ◽  
Undetermined Significance

Amyloid light-chain (AL) amyloidosis is associated with plasma cell disorder and monoclonal light chains. This type of amyloidosis is the prominent type involving the gastrointestinal tract. Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder and a known precursor of more serious diseases. A 72-year-old male was treated for high blood pressure, diabetes, and gout at the clinic of a private physician. Due to a positive fecal occult blood test discovered during colon cancer screening, he underwent colonoscopy and was diagnosed with adenomatous polyps by biopsies. Two months later, he was referred to our hospital for endoscopic resection of the polyps. Although the polyps were successfully removed, a colonoscopy revealed two types of ulcerative lesions. Immunohistopathological evaluations obtained from these lesions and polyps confirmed amyloid deposition. Although esophagogastroduodenoscopy results were normal, a biopsy specimen from the patient’s stomach showed the same type of amyloid deposition. Immunoelectrophoresis showed M-proteins for anti-IgG-λ in the serum and λ type Bence-Jones protein in the urine. His blood, bone marrow, and urine test results led to a diagnosis of MGUS. A coronary angiography revealed multivessel stenosis, and the patient’s cardiac function improved after coronary artery stenting. Hereafter, a combination therapy with bortezomib, lenalidomide, and dexamethasone is planned. This is a case report of systemic AL amyloidosis caused by MGUS, which was incidentally detected by colonoscopy.

Evaluation of Prognostic Factors for Malignant Transformation of Monoclonal Gammopathy of Undetermined Significance

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5123-5123
Author(s):  
Federico Sackmann ◽  
Claudia Corrado ◽  
Isolda Fernandez ◽  
Miguel A Pavlovsky ◽  
Pablo Mountford ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Malignant Transformation ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Bone Lesions ◽  
Monoclonal Protein ◽  
Lytic Bone Lesions ◽  
Beta 2 ◽  
Beta 2 Microglobulin ◽  
Undetermined Significance

Abstract Background: monoclonal gammopathy of undetermined significance (MGUS) has a prevalence of 1 to 3%. Although it has an indolent evolution, some patients (pts) will develop a malignant transformation. Thus, prognostic factors that may identify pts who will progress are important. We update our experience published before. Methods: we performed a retrospective analysis of 387 pts with MGUS diagnosed between 1982 and 2008 in our institution to identify simple haematological variables associated with progression. Actuarial progression free survival (PFS) and overall survival (OS) were also calculated. MGUS was diagnosed when monoclonal component (MC) was present at a concentration of 3 gr per decilitre or less, no or only moderate amounts of monoclonal light chains in the urine, absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to monoclonal protein; and if performed a proportion of plasma cells of 10 percent or less. MC was detected by agarose gel and/or cellulose acetate electrophoresis in serum and/or urine. The identification of the MC was performed by immunoelectrophoresis or immunofixation and the quantification of immunoglobulins, by radial immunodifussion. Progression to myeloma was defined by: MC &gt; 3 gr/dl, plasma cell infiltration &gt; 10%, or associated lytic bone lesions. Progression to another B-cell neoplasm was considered when there was histologic evidence of the disease. The identification of prognostic factors was made using Cox models. PFS and OS were calculated using the Kaplan Meier method and the curves were compared with the log-rank test. Results: The median (md) age at diagnosis was 62 years (range 24–89 years) and 18% of the pts were younger than 50. Anemia not related to the monoclonal protein was present in 18% of the pts. Albumin, beta 2 microglobulin and erythrocyte sedimentation rate (ESR) were normal in 88%, 50% and 41% of the pts, respectively. MC was 0.6 gr/dl (range 0.1–2.9). In 70% of the cases it was IgG, 15% IgA, 13% IgM and 2% biclonal. The light chain was Kappa in 65% of the pts. Bence Jones was detected in only 9%. Uninvolved immunoglobulins (UI) were reduced in 21% of the pts. Bone marrow analysis were performed in 79 pts (20%) and md plasma cell infiltration was 3 (range 0 – 10). The 387 pts were followed for 2340 person-years (md 4.75 years, range 0 – 31) during which 31 pts (8%) evolved to a malignancy (23 multiple myeloma, 7 NHL, and 1 amyloidosis) and 17 (4.6%) died (3 related to progressive disease, 6 related to non hematological malignancy, 2 associated to cardiovascular disorders, 2 secondary to infection and 4 of unknown cause). PFS and OS at 10 years were 89% and 91%, respectively. The overall risk of progression was 1.3% per year. Among all the variables analysed (age, gender, hemoglobin, albumin, beta 2 microglobulin, ESR, type and concentration of MC, Bence Jones and reduction of UI), only MC concentration (HR 4.81, CI 2.2 – 10.32, p = 0.00007) and ESR (HR 3.67, CI 1.7 – 7.88, p = 0.001) had prognostic value for progression. Conclusions: MC concentration and ESR at diagnosis identified a subgroup of pts with higher risk of transformation in our experience.

scholarly journals Monoclonal gammopathy of undetermined significance

Blood ◽  
2019 ◽  
Vol 133 (23) ◽  
pp. 2484-2494 ◽  
Author(s):  
Tarek H. Mouhieddine ◽  
Lachelle D. Weeks ◽  
Irene M. Ghobrial
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Cell Clone ◽  
Plasma Cell Dyscrasia ◽  
Bone Marrow Niche ◽  
Immunologic Factors ◽  
Risk Of Progression ◽  
Undetermined Significance

Abstract 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.

Nonchemotherapy Treatment of Immunoglobulin Light Chain Amyloidosis

2020 ◽  
Vol 143 (4) ◽  
pp. 373-380
Author(s):  
Layla Van Doren ◽  
Suzanne Lentzsch
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Cell Clone ◽  
Standard Of Care ◽  
Organ Damage ◽  
Current Therapy ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare, life-threatening disease characterized by the deposition of misfolded proteins in vital organs such as the heart, the lungs, the kidneys, the peripheral nervous system, and the gastrointestinal tract. This causes a direct toxic effect, eventually leading to organ failure. The underlying B-cell lymphoproliferative disorder is almost always a clonal plasma cell disorder, most often a small plasma cell clone of <10%. Current therapy is directed toward elimination of the plasma cell clone with the goal of preventing further organ damage and reversal of the existing organ damage. Autologous stem cell transplantation has been shown to be a very effective treatment in patients with AL amyloidosis, although it cannot be widely applied as patients are often frail at presentation, making them ineligible for transplantation. Treatment with cyclophosphamide, bortezomib, and dexamethasone has emerged as the standard of care for the treatment of AL amyloidosis. Novel anti-plasma cell therapies, such as second generation proteasome inhibitors, immunomodulators, monoclonal antibodies targeting a surface protein on the plasma cell (daratumumab, elotuzumab), and the small molecular inhibitor venetoclax, have continued to emerge and are being evaluated in combination with the standard of care. However, there is still a need for therapies that directly target the amyloid fibrils and reverse organ damage. In this review, we will discuss current and emerging nonchemotherapy treatments of AL amyloidosis, including antifibril directed therapies under current investigation.

scholarly journals Monoclonal gammopathy of renal significance

2021 ◽  
Author(s):  
Thomas Reiter ◽  
Maja Nackenhorst
Keyword(s):  
B Cell ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Cell Clone ◽  
Wide Spectrum ◽  
Organ Damage ◽  
Early Recurrence ◽  
Close Cooperation ◽  
Underlying Disorder ◽  
The Right

SummaryMonoclonal gammopathy of renal significance (MGRS) encompasses a group of kidney disorders in which a monoclonal immunoglobulin secreted by a B cell or plasma cell clone causes renal damage, without meeting hematological criteria for malignancy. The underlying disorder in patients with MGRS is generally consistent with monoclonal gammopathy of undetermined significance (MGUS). Because of the wide spectrum of MGRS-associated diseases, defined through the location and mechanism of renal injury, it is often challenging to establish the right diagnosis. Kidney biopsy must be considered early; hence, close cooperation between hematologist and nephrologists is crucial in diagnosis and treatment from the beginning to prevent irreversible organ damage. Anti B‑cell or plasma-cell clone directed therapy with cytostatic or immunomodulatory agents can save and ameliorate renal function significantly. This is underlined by the fact that, untreated, MGRS-associated disease shows early recurrence in patients after kidney transplantation.

scholarly journals Learning from Patients: The Interplay between Clinical and Laboratory Research in AL Amyloidosis

Hemato ◽  
2021 ◽  
Vol 3 (1) ◽  
pp. 3-16
Author(s):  
Moshe E. Gatt ◽  
Marjorie Pick
Keyword(s):  
Patient Care ◽  
Plasma Cell ◽  
Light Chain ◽  
Cell Clone ◽  
Organ Injury ◽  
Laboratory Research ◽  
Al Amyloidosis ◽  
Related Factors ◽  
Amyloid Light Chain

Primary systemic light chain amyloidosis (AL) is a rare monoclonal plasma cell disorder. Much research has been performed to determine the factors that underly amyloidogenicity. However, there is increasing evidence that the primary clone, and also patient-related factors, influence the mechanism and rate of the process. The lessons learnt from patient care definitely imply that this is not solely due to the deposition of material in the tissues that cause organ injury but amyloid light chain precursors are likely to mediate cellular toxicity. The disease rarity, combined with the lack of in vitro tools, and that multi-organ failure has a wide clinical spectrum, result in investigative challenges and treatment limitations (due to AL patient frailty). All these characteristics make the disease difficult to diagnose and indicate the need to further study its origins and treatments. This review will focus on the various aspects of the amyloidogenic plasma cell clone, as learnt from the patient care and clinics, and its implications on basic as well as clinical trials of AL research. Details regarding the etiology of the plasma cell clone, understanding the diagnosis of AL, and improvement of patient care with specific consideration of the future perspectives of individualized patient therapy will be described.

Differential Diagnosis of Monoclonal Gammopathies

1999 ◽  
Vol 123 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Raymond Alexanian ◽  
Donna Weber ◽  
Frank Liu
Keyword(s):  
Multiple Myeloma ◽  
Differential Diagnosis ◽  
Clinical Features ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Monoclonal Immunoglobulin ◽  
Monoclonal Gammopathies ◽  
Plasma Cell Dyscrasias ◽  
Waldenström's Macroglobulinemia ◽  
Undetermined Significance

Abstract Several disorders are associated with a monoclonal immunoglobulin detected by serum or urine electrophoresis, the most common being a monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenström’s macroglobulinemia, and amyloidosis. The clinical features of these conditions, as well as other similar entities, are described in this review. The objective is to demonstrate the importance of electrophoretic studies in the differential diagnosis of plasma cell dyscrasias and in guiding the decision for rational therapies.

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