Monoclonal Gammopathy of Undetermined Significance, Waldenström Macroglobulinemia, AL Amyloidosis, and Related Plasma Cell Disorders: Diagnosis and Treatment

2006 ◽  
Vol 81 (5) ◽  
pp. 693-703 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Angela Dispenzieri ◽  
Robert A. Kyle
Keyword(s):  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Diagnosis And Treatment ◽  
Al Amyloidosis ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Plasma Cell Disorders ◽  
Undetermined Significance

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.

Hyperphosphorylated paratarg-7: a new molecularly defined risk factor for monoclonal gammopathy of undetermined significance of the IgM type and Waldenström macroglobulinemia

Blood ◽  
2011 ◽  
Vol 117 (10) ◽  
pp. 2918-2923 ◽  
Author(s):  
Sandra Grass ◽  
Klaus-Dieter Preuss ◽  
Alexandra Wikowicz ◽  
Evangelos Terpos ◽  
Marita Ziepert ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Monoclonal Gammopathy ◽  
Immunoglobulin A ◽  
Cell Receptor ◽  
Carrier State ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Phosphatase Treatment ◽  
Increased Risk ◽  
Undetermined Significance

Abstract We recently described paratarg-7 (P-7), a protein of unknown function, as the target of 15% of immunoglobulin A (IgA) and IgG paraproteins in monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma. To determine the frequency of P-7 as a paraprotein target in IgM-MGUS and Waldenström macroglobulinemia (WM), sera from patients with IgM-MGUS/WM were tested for reactivity with recombinant P-7 by enzyme-linked immunoabsorbent assay. The specificity of the paraprotein-mediated reaction was shown by absorption studies and cloning of the respective B-cell receptor. The paraproteins of 18 (9 WM and 9 IgM-MGUS) of 161 patients (11%) reacted with P-7. Isoelectric focusing and phosphatase treatment showed that P-7 was hyperphosphorylated (pP-7) in all patients with an anti–P-7-specific IgM paraprotein tested. Because only 4 of 200 healthy controls (2%) were carriers of pP-7, pP-7 carrier state is associated with a significantly increased risk (odds ratio = 6.2; P = .001) for developing IgM-MGUS/MW. Family analyses showed that the pP-7 carrier state is inherited as a dominant trait. After IgA/IgG-MGUS and multiple myeloma, IgM-MGUS/WM is the second neoplasia associated with pP-7 carrier state. The dominant inheritance of pP-7 explains cases of familial IgM-MGUS/WM and enables the identification of family members at increased risk.

scholarly journals Pattern of somatic mutations in patients with Waldenström macroglobulinemia or IgM monoclonal gammopathy of undetermined significance

Haematologica ◽  
2017 ◽  
Vol 102 (12) ◽  
pp. 2077-2085 ◽  
Author(s):  
Marzia Varettoni ◽  
Silvia Zibellini ◽  
Irene Defrancesco ◽  
Virginia Valeria Ferretti ◽  
Ettore Rizzo ◽  
...  
Keyword(s):  
Monoclonal Gammopathy ◽  
Somatic Mutations ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Undetermined Significance

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 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.

scholarly journals Immunoglobulin M Monoclonal Gammopathy of Undetermined Significance and Smoldering Waldenström Macroglobulinemia

2013 ◽  
Vol 13 (2) ◽  
pp. 184-186 ◽  
Author(s):  
Robert A. Kyle ◽  
Terry M. Therneau ◽  
Angela Dispenzieri ◽  
Shaji Kumar ◽  
Joanne T. Benson ◽  
...  
Keyword(s):  
Monoclonal Gammopathy ◽  
Immunoglobulin M ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Undetermined Significance

Evaluation of the Cytogenetic Aberration Pattern in AL Amyloidosis Compared to Monoclonal Gammopathies Not Requiring Treatment: Translocation t(11;14) Is More Frequent in AL Amyloidosis.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2500-2500 ◽  
Author(s):  
Tilmann Bochtler ◽  
Stefan O. Schonland ◽  
Anna Jauch ◽  
Christiane Heiss ◽  
Axel Benner ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Control Group ◽  
Al Amyloidosis ◽  
Fish Analysis ◽  
Cell Content ◽  
Cytogenetic Aberration ◽  
Cytogenetic Aberrations ◽  
Plasma Cell Disorders ◽  
Unknown Significance

Abstract Introduction: Cytogenetic aberrations (CA) have emerged as important pathogenetic and prognostic factors in plasma cell disorders. However, in AL amyloidosis (AL) only a few reports with small numbers of patients have been published. Methods: Using interphase FISH analysis in CD138+ cells, we evaluated the role of CA in a series of 85 AL patients as compared to 146 patients with a monoclonal gammopathy without treatment requirement in a prospective manner. Our panel included IgH translocations t(11;14), t(4;14), t(14;16) and translocation of 14q32 with an unidentified partner, gains of 1q21, 11q23 and 19q13 as well as deletions of 8p21, 13q14 and 17p13. Using these probes we could detect at least one of these aberrations in 95% of AL and in 88% of the control group. Age, gender and plasma cell content were statistically equally distributed among both groups. Results: The most frequent aberration in AL was t(11;14), which was detected in 45% of AL patients as compared to 26% of the control group (p=0,056). It was strongly associated with the lack of an intact immunoglobulin (p&lt;0,001), thus accounting for the frequent light chain only subtype in AL. Markedly, t(11;14) was more frequently found in combination with gain 11q23 in AL than in the control group (20% versus 6%, p = 0.005). Other frequent aberrations in AL included deletion 13q14 (32%) and gain 1q21 (21%), which were observed in the control group at comparable frequencies (34% and 20%). The overlapping character of the underlying plasma cell disorder in both disease entities was also emphasized by the similarities of branching patterns of the five major CA in cluster analysis applied in 169 patients (figure 1). The relation of clinical parameters and chromosomal aberrations was also evaluated. The analyzed CA had no impact on the organ involvement pattern in AL patients. Conclusions: We observed a high frequency for t(11;14) in AL. Apart from this finding, the cytogenetic patterns known in monoclonal gammopathy of unknown significance and multiple myeloma were widely shared by AL amyloidosis. Figure Figure

Sign in / Sign up

Export Citation Format

Share Document