scholarly journals Paraprotein-associated diseases: a complex relationship between monoclonal gammopathy of unknown significance and severe organ damage

2021 ◽  
Vol 14 (1) ◽  
pp. 9-10
Author(s):  
Hermine Agis
2018 ◽  
Vol 5 (1) ◽  
pp. 19
Author(s):  
Li Liu ◽  
Lydia C Contis ◽  
Octavia Melvina Palmer

Background: Acquired hemophagocytic lymphohistiocytosis (HLH) is an aggressive hyperinflammatory syndrome. Without prompt diagnosis and proper treatment, it can be life-threatening. HLH is commonly present in the setting of other autoimmune disorders, infection, organ transplantation, and malignancy.  However, to our knowledge, HLH associated with monoclonal gammopathy of undetermined significance (MGUS) has not been reported.Case presentation: A 67-year-old woman with an extensive history of MGUS and renal transplant presented with progressive fatigue, weight loss, intermittent fevers, splenomegaly, and pancytopenia. Serum protein electrophoresis with immunofixation identified a new monoclonal protein IgG lambda and a rapidly increasing pre-existing free kappa light chain. A bone marrow biopsy revealed focal clusters of kappa restricted plasma cells which comprised less than 10\% of marrow cellularity. Skeletal survey was negative for osteolytic lesions. She was also free of any end-organ damage.  Histological examination showed a prominent increase in histiocytes and macrophages, many of which show erythrophagocytosis and lymphophagocytosis. Together with her clinical presentation along with a hyperferritinemia, a diagnosis of HLH was confirmed utilizing the criteria of the Histiocyte Society. The patient underwent a splenectomy. Prompt treatment with etoposide and high dose dexamethasone eventually stabilized the patient and resulted in a full recovery, which coincided with the disappearance of the serum monoclonal IgG lambda.Conclusions: This report reveals a novel association of HLH with the progression of MGUS. Familiarity with this syndrome and its association with other conditions is indicated to ensure prompt diagnosis and appropriate patient treatment.


2015 ◽  
Vol 81 (2) ◽  
pp. 213 ◽  
Author(s):  
SarveshS Thatte ◽  
AtulM Dongre ◽  
SiddhiB Chikhalkar ◽  
UdayS Khopkar

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Marja Kovala ◽  
Minna Seppala ◽  
Kati Kaartinen ◽  
Seppo Meri ◽  
Eero Olavi Honkanen ◽  
...  

Abstract Background and Aims Monoclonal gammopathy is an entity where a B-cell or plasma cell clone produces monoclonal immunoglobulin. When paraproteinemia and a kidney disease is discovered without criteria for treatment of haematological malignangy, the entity is called monoclonal gammopathy of unknown significance (MGUS) or of renal significance (MGRS). It can cause variable histology, among which membranoproliferative glomerulonephritis (MPGN) has been described. Direct entrapment of paraprotein in glomeruli/tubules can be observed by immunofluorescence (IF), but IF can also be negative as paraprotein can cause complement-associated disease by acting as an activator of the classical pathway or as a dysregulator of the alternative pathway. Electron microscopy (EM) is needed to differentiate possible organized deposits. Method We investigated the prevalence, clinical parameters, histology, and the type of monoclonal gammopathy in biopsy-proven MPGN between 2006-2017. A total of 15 adult patients with a detected urine and/or serum paraprotein with concurrent biopsy-proven diagnosis were discovered among 60 patients (Figure 1). Two diagnostic biopsies were from transplants. Results MGUS was diagnosed in 15/60 (25%) of patients. Clinical variables are summarized in Table 1. The mean age at presentation was 59 years (37-79), 47-% were males. Smoldering myeloma was diagnosed in 2 (13%) patients and overt malignancy in 3 (20%) patients. Histological features are summarized in Table 2. There were 7 (47%) with dominant staining for C3 (6 with C3 glomerulonephritis, 1 Dense Deposition Disease) and 8 (53%) with dominant staining for Ig, of which 4 (31%) had mesangioproliferative, 4 (31%) membranoproliferative, 3 (23%) minimal change, 2 (15%) crescentic and 1 (8%) exudative pattern in light microscopy (LM). Seven (47%) biopsies, which did not stain for kappa or lambda light chains. The most common EM deposit location was subendothelial (69%). Conclusion MPGN was associated with a significant risk of underlying monoclonal gammopathy, as many (25%) patients were diagnosed with concurrent MGUS. When MPGN is observed, it should prompt investigations of the possible underlying monoclonal gammopathy and possibly, hematological neoplasm.


Author(s):  
Salomon Manier ◽  
Karma Z. Salem ◽  
David Liu ◽  
Irene M. Ghobrial

Multiple myeloma (MM) is an incurable disease that progresses from a premalignant stage termed monoclonal gammopathy of undetermined significance (MGUS) and an intermediate stage of smoldering multiple myeloma (SMM). Recent major advances in therapy with more effective and less toxic treatments have brought reconsideration of early therapeutic intervention in management of SMM, with the goal of reducing progression of the disease before the occurrence of end-organ damage to MM and improving survival. Key to this effort is accurate identification of patients at high risk of progression who would truly benefit from early intervention. In this review, we discuss the current definitions, risk factors, risk stratification, prognosis, and management of MGUS and SMM, as well as new emerging therapeutic options under active investigation.


2017 ◽  
Vol 1 (1) ◽  
pp. 18-23 ◽  
Author(s):  
Nelson Leung

Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant condition signifying the presence of a B-cell lymphoproliferative disorder. By connotation, it should not meet the definition of multiple myeloma, Waldenström macroglobulinemia, or lymphoma. In addition, it cannot be responsible for any end-organ damage. Similar to polyclonal immunoglobulins (Ig), monoclonal gammopathy has been increasingly recognized as an important cause of kidney disease. The recent introduction of the term “monoclonal gammopathy of renal significance” (MGRS) highlights this importance. MGRS is similar to MGUS in which the B-cell lymphoproliferative disorder has not reached a state considered to be malignant, but differentiates itself by the presence of a monoclonal gammopathy related kidney disease. This distinction is important since it separates MGRS, which is not benign, from the MGUS condition, which is benign. It also allows for a better classification of kidney diseases caused by monoclonal gammopathies. There are many renal diseases and lesions that have been identified to be secondary to MGRS. In addition, MGRS-associated renal diseases can mimic polyclonal Ig mediated kidney diseases. Kidney biopsy with immunofluorescence is the key for diagnosing MGRS-related kidney diseases. Once the diagnosis is made, a specific evaluation is needed for the diagnosis and treatment of MGRS-related kidney diseases that differs from the polyclonal Ig counterparts.


Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 595-603 ◽  
Author(s):  
Giampaolo Merlini ◽  
Giovanni Palladini

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.


2013 ◽  
Vol 6 (4) ◽  
pp. 445-446
Author(s):  
Marsela Resuli ◽  
Finn Thomsen Nielsen ◽  
Peter Gimsing ◽  
Claus B. Andersen ◽  
Martin Egfjord

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4755-4755
Author(s):  
Lucie Kovarova ◽  
Ivana Buresova ◽  
Ludek Pour ◽  
Renata Suska ◽  
Zdenek Adam ◽  
...  

Abstract Introduction: Multiple myeloma (MM) is a B-cell neoplasia caused by the proliferation of clonal plasma cells (PCs). MM and benign monoclonal gammopathy of unknown significance (MGUS) are routinely distinguished on the basis of paraprotein concentration, level of PCs infiltration and the presence or absence of other clinical features. Flowcytometric detection of PCs according to the expression of CD38 and CD138 has limitation in discrimination between normal and abnormal PCs, but this is possible in multicolor phenotypic analysis. The aim of this study is to compare the numbers of normal and abnormal PCs in MGUS and MM subjects and to find some parameter useful for evaluation PCs distribution. Materials and methods: 51 newly diagnosed untreated MM patients (63,9±10,0 years old) and 31 non-treated MGUS subjects (64,2±13,8 years old) were analysed. Lysed whole bone marrows were analysed by flowcytometric immunophenotyping and PCs were indentified by expression of CD38, CD138, CD45 and also CD56 and CD19. Results: Discrimination between normal CD19+ PCs and abnormal CD56+ PCs was done on CD38+CD138+ population. Ratio of normal PCs count and abnormal PCs counts (normal/abnormal=N/A) was used to describe a distribution of PCs. Subjects with MGUS had 0,97±1,65% (average±SD) of CD38+CD138+ cells (median 0,45; range 0,03–7,47%) with average N/A ratio 2,91±3,94 (median 1,36; range 0,01–18,44). Newly diagnosed MM patients had 4,96±9,94% of CD38+CD138+ cells (median 0,85; range 0,02–41,80%) with average N/A ratio 1,70±3,03 (median 0,13; range 0–11,5). In 9,7% MGUS subjects evaluation of distibution of PCs showed transformation of MGUS into MM. In some newly diagnosed MM patients (31,4%) CD38+CD138+ plasma cells were positive for CD19 although they were aberrant and these PCs were mostly CD45+. In some patients (9,7% of MGUS; 17,6% of MM) PC did express neither CD19 nor CD56 and this fact may complicate further evaluation of PCs. Conclusions: Results confirmed that in MGUS subjects we can find lower numbers of PCs which are mostly CD45+CD19+. A majority of plasma cells in newly diagnosed MM patients are abnormal CD56+ PCs and these plasma cells are usually CD45−. Further follow-up of patients can confirm the N/A ratio as a predictive factor for transformation of MGUS into MM and its value for evidence of relapse or progression to active myeloma.


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