scholarly journals Recommendations for use of Tumor Markers in Monoclonal Gammopathies

2007 ◽  
Vol 26 (2) ◽  
pp. 165-172
Author(s):  
Marijana Dajak
Keyword(s):  
Tumor Markers ◽  
Monoclonal Gammopathy ◽  
Clinical Biochemistry ◽  
M Protein ◽  
Monoclonal Gammopathies ◽  
Undetermined Significance

Preporuke za Primenu Tumorskih Markera Kod Monoklonskih GamapatijaMonoklonske gamapatije čine grupu poremećaja koji se karakterišu klonskom proliferacijom plazma ćelija. M protein je tumorski marker specifičan za monoklonske gamapatije jer odražava klonsku produkciju imunoglobulina. Monoklonske gamapatije uključuju: multipli mijelom,Waldenström-ovu makroglobulinemiju (WM), nesekretorni mijelom, prikriveni (smoldering) multipli mijelom, monoklonsku gamapatiju od neodređenog značaja (MGUS,Monoclonal gammopathy of undetermined significance), primarnu sistemsku amiloidozu i bolest teških lanaca. Dijagnoza multiplog mijeloma je zasnovana na detekciji M proteina u serumu i/ili urinu, infiltraciji plazma ćelija u koštanoj srži i litičkim koštanim lezijama na radiografiji skeleta. Prema NACB (National Academy of Clinical Biochemistry) preporukama, tumorski markeri za dijagnozu,screening, identifikaciju klonaliteta, praćenje bolesti i prognostičku evaluaciju kod monoklonskih gamapatija su: elektroforeza proteina u serumu i/ili urinu, imunofiksacija u serumu i/ili urinu, slobodni laki lanci (SLL) u serumu i/ili urinu, viskoznost seruma i β2-mikroglobulin. Imunofiksacija se koristi za identifikaciju klonaliteta (tipa) M proteina primećenog na elektroforezi i kada postoji sumnja bez obzira na normalan proteinski elektroforetogram. Posebno je korisna za prepoznavanje i razlikovanje biklonskih ili triklonskih gamapatija. Viskoznost seruma trebalo bi određivati ako pacijent ima znake i simptome sindroma hiperviskoznosti. WM je najčeŠći uzrok hiperviskoznosti, ali se takođe može pojaviti i kod pacijenata sa velikim nivoima monoklonskog IgA ili IgG. Automatizovana imunoodređivanja SLL u serumu su osetljivija od tradicionalne elektroforetske metode i imunofiksacije za detekciju mijeloma monoklonskih lakih lanaca, nesekretornog mijeloma i AL amiloidoze. Osim toga, odnos SLL u serumu je nezavisan faktor rizika za nastanak maligne progresije kod pacijenata sa MGUS. Određivanje SLL u serumu i elektroforeze proteina seruma kao testova prve linije za razmatranje prisustva mogućih poremećaja B ćelija daje dodatnu dijagnostičku informaciju.

scholarly journals Prevalence of Monoclonal Gammopathy of Undetermined Significance in a Large Population with Annual Physical Examination in Beijing, China

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5519-5519
Author(s):  
Jinuo Wang ◽  
Jian-Hua Han ◽  
Yue-lun Zhang ◽  
Xin-xin Cao ◽  
Dao-Bin Zhou ◽  
...  
Keyword(s):  
Physical Examination ◽  
Light Chain ◽  
Chinese Population ◽  
Monoclonal Gammopathy ◽  
Conflicts Of Interest ◽  
Large Population ◽  
M Protein ◽  
Monoclonal Protein ◽  
Significant Difference ◽  
Undetermined Significance

Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant plasma cell disorder. Previous studies in Western countries have described the prevalence of MGUS in Caucasians. However, data is limited in Chinese population. We therefore performed this study to ascertain the prevalence and characteristics of MGUS among Chinese population. Methods A total of 154597 consecutive healthy participants from Beijing who underwent annual physical examination between December 2013 and April 2019 at Peking Union Medical College Hospital were enrolled. Serum M protein was evaluated by capillary electrophoresis. Patients with a positive or suspicious serum M protein were suggested to be referred to the hematological clinic for immunofixation electrophoresis (IFE) and free light chain (FLC) assays. MGUS was defined in accordance with previous definitions. We calculated age-specific and sex-specific prevalence and described laboratory characteristics of patients with MGUS among those participants. Results MGUS were diagnosed in 843 patients (0.55%, 95%CI 0.51% to 0.59%). The median age at presentation was 58 years, with a range of 25-96 years. The overall prevalence of MGUS was 1.14% among participants aged 50 years or older and 2.6% among those aged 70 years or older. In both sexes, the prevalence increased with age: 0.1% (<40 years), 0.36% (40-49 years), 0.78% (50-59 years), 1.28% (60-69 years), 2.19% (70-79 years), and 3.77% (≥80 years) separately (Figure 1). The prevalence among men were higher than that among women (0.67% vs. 0.40%, OR =1.719, 95% CI 1.490 to 1.983, P<0.001) (Figure 1). The median concentration of serum Monoclonal protein was 1.4 g/L (0.1 -27.8 g/L). M protein level was less than 0.5g/L in 220 patients (26.1%), less than 5 g/L in 81.1% and more than 15 g/L in only 1.9% of 843 persons. There was no significant difference in the concentration of the monoclonal protein among the age groups. Of the 519 patients who were tested for IFE, the isotype of the monoclonal immunoglobulin was IgG in 344 (66.3%), IgA 112 (21.6%), IgM in 48 (9.2%), IgD in 2 (0.4%), light-chain in 3 (0.6%) and biclonal in 10 (1.9%). The serum light-chain type was kappa in 260 (50.1%), lambda in 255 (49.1%) patients, while 4 patients (0.8%) with biclonal M protein have both kappa and lambda light-chain. Of the 180 people who were tested for FLC, 42 (23.3%) had an abnormal FLC ratio. IgG isotype, M protein <15 g/L and normal FLC ratio were found in 102 patients (56.7%) and the remaining 78 people (43.4%) had 1(30.6%) or 2(12.8%) abnormal factors. Conclusions MGUS was found in 1.14% of persons 50 years of age or older and 2.6% among those 70 years of age or older among healthy Chinese population. The prevalence of MGUS increases with age. Males have a higher frequency of MGUS than Females. These observations offer the overall situation of MGUS epidemiology in a large Chinese population. Disclosures No relevant conflicts of interest to declare.

scholarly journals Monoclonal gammopathies of clinical significance

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 380-388
Author(s):  
Angela Dispenzieri
Keyword(s):  
Differential Diagnosis ◽  
Clinical Significance ◽  
Monoclonal Gammopathy ◽  
Monoclonal Gammopathies ◽  
Skin Biopsies ◽  
Unexplained Symptoms ◽  
Symptoms And Signs ◽  
Important Disease ◽  
Iv Immunoglobulin ◽  
Undetermined Significance

Abstract “Monoclonal gammopathy of clinical significance” (MGCS) is the term used to describe nonmalignant monoclonal gammopathies causing important disease. MGCS is the differential diagnosis for any patient presenting with what appears to be a monoclonal gammopathy of undetermined significance but is also experiencing other unexplained symptoms. Broadly, these conditions can be separated into symptoms and signs referable to the nerves, the kidneys, and the skin. The first step in making these diagnoses is to consider them. With a particular condition in mind, the next step is to order those tests that can help confirm or dismiss a particular diagnosis. Nearly all of the renal and dermatologic conditions are diagnosed by renal and skin biopsies, respectively. The importance of a highly competent renal pathologist and dermatopathologist cannot be underestimated. Biopsy is less specific for the neuropathic conditions. Because several of the MGCSs are syndromes, recognizing other manifestations is also key. Treatment recommendations for many of these conditions are anecdotal because of their rarity, but for several of the conditions, IV immunoglobulin, rituximab, and plasma cell–directed therapy are the best options.

The predictive power of serum κ/λ ratios for discrimination between monoclonal gammopathy of undetermined significance and multiple myeloma

2005 ◽  
Vol 43 (1) ◽  
Author(s):  
Enrique Bergón ◽  
Elena Miravalles ◽  
Elena Bergón ◽  
Isabel Miranda ◽  
Marta Bergón
Keyword(s):  
Multiple Myeloma ◽  
Predictive Value ◽  
Monoclonal Gammopathy ◽  
Predictive Power ◽  
Protein Detection ◽  
M Protein ◽  
Likelihood Ratios ◽  
Geographic Population ◽  
Significant Difference ◽  
Undetermined Significance

AbstractThe predictive power of serum κ/λ ratios on initial presentation of immunoglobulin G (IgG) or IgA monoclonal component was studied to differentiate between monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma (MM) patients. The retrospective study involved 145 patients clinically diagnosed with monoclonal gammopathy of undetermined significance or multiple myeloma, who had serum M-protein IgG <35g/L or IgA <20g/L at M-protein detection. Serum light chains κ and λ were measured by fixed-time nephelometry. Test performance indices, predictive values and likelihood ratios were calculated according to the Weissler recommendation. MM patients were considered as diseased and MGUS patients as non-diseased in order to estimate the performance characteristics of serum κ/λ ratios. There was a statistically significant difference in κ/λ ratios distribution between both groups of patients, in both M-protein κ-type (Mann-Whitney U=168, p<0.001) and in M-protein λ-type (Mann-Whitney U=143, p<0.001). Negative likelihood ratios at threshold levels of 0.6 and 4.2 were 2.17- and 3.32-fold greater, respectively, than positive likelihood ratios, so that the predictive power of a serum κ/λ ratio within these limits is better in ruling out (negative predictive power) than ruling in disease (positive predictive power). The post-test characteristics of a serum κ/λ ratio interval between 0.6 and 4.2 in discriminating MGUS from MM in our geographic population were: sensitivity 0.96 (0.93–0.99 95%CI); specificity 0.70 (0.63–0.77); positive predictive value 0.68 (0.64–0.73); negative predictive value 0.96 (0.94–0.99); likelihood ratios (+)LR 3.23 (2.68–4.04); and (−)LR 17.16 (11.00–63.00). Thus, serum M-protein with a κ/λ ratio between 0.6 and 4.2 increases the posterior probability of MGUS from 0.60 to 0.96 in asymptomatic patients, for whom only monitoring may be suggested when the serum κ/λ ratio is within these limits.

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 Clinical Presentation and Renal Histopathological Findings in Patients with Monoclonal Gammopathy and Kidney Disease

2020 ◽  
Author(s):  
Gaetano Alfano ◽  
Alice Delrio ◽  
Francesco Fontana ◽  
Annachiara Ferrari ◽  
Giacomo Mori ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Monoclonal Gammopathy ◽  
Renal Involvement ◽  
Lymphoproliferative Disorders ◽  
M Protein ◽  
Al Amyloidosis ◽  
Light Chain Deposition Disease ◽  
Monoclonal Gammopathies ◽  
Increased Risk ◽  
Kidney Involvement

AbstractMonoclonal gammopathies have been widely associated with renal lesions. Nephrotoxicity of the secreted monoclonal (M)-protein relies on a complex interplay between biological characteristics and serum concentration. Little is known about the prevalence and renal manifestations of the different types of monoclonal gammopathies in patients with kidney disease.We reviewed all renal biopsies in our Center during a 12-year period to characterize patients diagnosed with monoclonal gammopathy. Data about demographics, laboratory examinations, renal manifestations and histological lesions were collected retrospectively. Results were correlated with the different lymphoproliferative disorders to evaluate the relationship between renal involvement and monoclonal gammopathies.Monoclonal gammopathy was detected in 179 (13.4%) patients. The circulating M-protein was secreted by monoclonal gammopathy of undetermined significate (MGUS) (51.9%), myeloma multiple (MM) (25.7%), primary amyloidosis (AL) (8.9%), smoldering MM (5 %), non-Hodgkin lymphoma (NHL) (6.7%) and HL (1.7%). Documented renal involvement in benign disorders such as MGUS and SMM accounted for 7.5% and 11.1%, respectively. MM was associated with an increased risk of kidney involvement (adjusted odds ratio=36.4; P=<0.001) and manifested with higher serum creatinine compared to other disorders. AL amyloidosis was principally secondary to MGUS (75%) and presented with nephrotic proteinuria. NHL and HL patients had heterogeneous renal manifestations. MGRS manifested both with light chain deposition disease and membranoproliferative glomerulonephritis. Compared to the other lymphoproliferative disorders, MM and AL amyloidosis showed higher creatinine blood levels and proteinuria, respectively. MM was significantly associated with kidney disease in our cohort of patients.Monoclonal gammopathy is a frequent diagnosis in patients with kidney disease. An accurate diagnostic process including lab tests and kidney biopsy is necessary to identify if the secreted M-protein is associated with renal involvement.

scholarly journals Clinical Presentation, Renal Histopathological Findings, and Outcome in Patients with Monoclonal Gammopathy and Kidney Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Gaetano Alfano ◽  
Alice Delrio ◽  
Francesco Fontana ◽  
Giacomo Mori ◽  
Silvia Cazzato ◽  
...  
Keyword(s):  
Kidney Disease ◽  
End Stage Renal Disease ◽  
Monoclonal Gammopathy ◽  
Kidney Biopsy ◽  
Clinical Manifestations ◽  
Kidney Injury ◽  
M Protein ◽  
Monoclonal Gammopathies ◽  
Stage Renal Disease ◽  
End Stage

Monoclonal gammopathies are associated with acute and chronic kidney injury. Nephrotoxicity of the secreted monoclonal (M)-protein is related to its biological properties and blood concentration. Little is known about epidemiology, clinical manifestations, and outcome of monoclonal gammopathies in patients with kidney disease. We retrospectively collected data about demographics, clinical manifestations, and renal histological lesions of all patients (n = 1334) who underwent kidney biopsy between January 2000 and March 2017. Monoclonal gammopathy was detected in 174 (13%) patients with a mean age of 66.4 ± 13.1 years. The spectrum of monoclonal gammopathies comprised monoclonal gammopathy of undetermined significate (MGUS) (52.8%), multiple myeloma (MM) (25.2%), primary amyloidosis (AL) (9.1%), smoldering MM (SMM) (4%), non-Hodgkin lymphoma (NHL) (6.8%), and Hodgkin lymphoma (HL) (1.7%). Monoclonal gammopathy of renal significance (MGRS) accounted for 6.5% in patients with MGUS and 14.2% in patients with SMM. Evaluation of kidney biopsy revealed that M-protein was directly involved in causing kidney injury in MM (93.1%). MM was the only gammopathy significantly associated with an increased risk of kidney injury (odds ratio [OR] = 47.5, CI 95%, 13.7–164.9; P ≤ 0.001 ). While there were no significant differences in the progression toward end-stage renal disease or dialysis P = 0.776 , monoclonal gammopathies were associated with a different risk of death P = 0.047 at the end of the follow-up. In conclusion, monoclonal gammopathy was a frequent finding (13%) in patients who underwent kidney biopsy. M-protein was secreted by both premalignant (56.8%) and malignant (43.2%) lymphoproliferative clones. Kidney biopsy had a key role in identifying MGRS in patients with MGUS (6.5%) and SMM (14.2%). Among monoclonal gammopathies, only MM was significantly associated with biopsy-proven kidney injury. The rate of end-stage renal disease or dialysis was similar among monoclonal gammopathies, whereas NHL, MM, and SMM showed a higher rate of deaths.

scholarly journals Monoclonal gammopathy of undetermined significance and risk of lymphoid and myeloid malignancies: 728 cases followed up to 30 years in Sweden

Blood ◽  
2014 ◽  
Vol 123 (3) ◽  
pp. 338-345 ◽  
Author(s):  
Ingemar Turesson ◽  
Stephanie A. Kovalchik ◽  
Ruth M. Pfeiffer ◽  
Sigurdur Y. Kristinsson ◽  
Lynn R. Goldin ◽  
...  
Keyword(s):  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Protein Concentration ◽  
Free Light Chain ◽  
M Protein ◽  
Myeloid Malignancies ◽  
Lymphoid Malignancies ◽  
Key Points ◽  
Undetermined Significance

Key Points Free light chain ratio, M-protein concentration, and immunosuppression predict progression of MGUS to lymphoid malignancies.

scholarly journals Activated idiotype-reactive cells in suppressor/cytotoxic subpopulations of monoclonal gammopathies: correlation with diagnosis and disease status

Blood ◽  
1988 ◽  
Vol 72 (3) ◽  
pp. 1064-1068 ◽  
Author(s):  
U Dianzani ◽  
A Pileri ◽  
M Boccadoro ◽  
A Palumbo ◽  
P Pioppo ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Peripheral Blood ◽  
Gene Rearrangement ◽  
Clinical Status ◽  
Disease Status ◽  
M Protein ◽  
Cytotoxic Cells ◽  
Monoclonal Gammopathies ◽  
Beta Gene ◽  
Undetermined Significance

The phenotypic pattern of peripheral blood T (PBT) lymphocytes was correlated with diagnosis and clinical status in 63 patients with monoclonal gammopathies (MGs). The numbers of lymphocytes expressing activation and CD11 determinants were significantly increased in suppressor/cytotoxic and helper/inducer subpopulations of patients with multiple myeloma (MM) and MG of undetermined significance (MGUS). The number of activated suppressor/cytotoxic cells was closely correlated with diagnosis and disease status. These cells were significantly higher in MM at diagnosis (160 +/- 88) than MGUS patients (61 +/- 79; P less than .01). Their number decreased to MGUS levels in MM in stable remission (58 +/- 53), but not in MM with tumor progression (172 +/- 102; P less than .001). In individual patients, part of these cells specifically adhered to dishes precoated with the related M-protein. No monoclonal T-beta gene rearrangement was detected in PBT and cytotoxic/suppressor subpopulations from two patients with a large proportion of activated cells.

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