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Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disorder, characterized by chronic urticarial rash and immunoglobulin M (IgM) monoclonal gammopathy. Anti-interleukin-1 (IL-1) therapies have been shown to be more effective in managing the clinical symptoms of SchS compared to anti-IL-6 therapies. In this case report, we present a male patient with urticarial rash, fever, and arthralgia. Laboratory tests identified the presence of IgMκ monoclonal protein, and the absence of IL-1β in serum. Whole exome sequencing (WES) did not reveal any pathological variants associated with monogenic autoinflammatory diseases or the MYD88 L265P mutation. He met the diagnostic criteria for SchS and was treated with bortezomib, leading to a significant improvement in clinical symptoms and a decline in IgMκ monoclonal protein levels. The patient tolerated the treatment well. This case suggests that bortezomib may be considered as a potential treatment option for SchS, in addition to anti-IL-1 therapies and bruton tyrosine kinase (BTK) inhibitors. [ABSTRACT FROM AUTHOR]

Schnitzler syndrome (SchS) is a rare acquired systemic autoinflammatory disorder, characterized by chronic urticarial rash and immunoglobulin M (IgM) monoclonal gammopathy. Anti-interleukin-1 (IL-1) therapies have been shown to be more effective in managing the clinical symptoms of SchS compared to anti-IL-6 therapies. In this case report, we present a male patient with urticarial rash, fever, and arthralgia. Laboratory tests identified the presence of IgMκ monoclonal protein, and the absence of IL-1β in serum. Whole exome sequencing (WES) did not reveal any pathological variants associated with monogenic autoinflammatory diseases or the MYD88 L265P mutation. He met the diagnostic criteria for SchS and was treated with bortezomib, leading to a significant improvement in clinical symptoms and a decline in IgMκ monoclonal protein levels. The patient tolerated the treatment well. This case suggests that bortezomib may be considered as a potential treatment option for SchS, in addition to anti-IL-1 therapies and bruton tyrosine kinase (BTK) inhibitors.

Purpose of Review: Waldenström macroglobulinemia is a rare non-Hodgkin lymphoma (NHL) characterized by lymphoplasmacytic bone marrow infiltration associated with an immunoglobulin M (IgM) monoclonal gammopathy. Over the past two decades, a number of important novel therapies have emerged for the treatment of relapsed and refractory (R/R) WM. The purpose of this review is to discuss these novel agents. Recent Findings: Chemoimmunotherapy which formed the basis treatment for R/R WM is slowly being replaced by novel targeted agents. These therapies, including Bruton's tyrosine kinase inhibitors, proteasome inhibitors, and B-cell lymphoma 2 inhibitors, have widened the landscape of management. Emerging therapies currently under investigation, such as bispecific T-cell engagers, chimeric antigen T-cell receptor therapy, and novel small molecule inhibitors, have additionally shown the potential to improve response and survival. Summary: The treatment of R/R WM has greatly evolved, in large part due to a greater understanding of the biology of WM, and the evaluation of novel targeted agents in the basket trials of NHL, showing early activity in the small WM cohorts. Combination regimens with these established and emerging novel therapies have the potential to further improve disease control and induce higher rates of deep responses. Strategies aimed at altering the disease trajectory would require randomized controlled trials to provide relevant data on optimal integration and sequencing of more effective and tolerable regimens earlier in the disease course. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinaemia (WM) is a unique, cluster of differentiation (CD) 20+ B‐cell malignancy, with a characteristic immunoglobulin M‐secreting lymphoplasmacytic bone marrow infiltrate that is bolstered by a highly supportive microenvironment, including upregulated programmed death 1 expression. However, the impact of checkpoint inhibition in WM is unclear. Commentary on: Kothari et al. PembroWM: A phase II trial to investigate the safety and efficacy of rituximab and pembrolizumab in relapsed/refractory Waldenström's macroglobulinaemia. Br J Haematol 2024; 205:2273‐2281. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinemia (WM) is a rare, non-Hodgkin lymphoma that remains incurable. Rituximab, an anti-CD20 monoclonal antibody has been the cornerstone of treatment against WM, and its combination with an alkylator, bendamustine, achieves durable remission in treatment-naive patients with symptomatic WM. However, novel “druggable” targets that have been identified within the clonal lymphoplasmacytic cells in WM have resulted in a rapid development of targeted therapies in both the frontline and relapsed and refractory (R/R) settings. Several agents directed against the known targets have shown promising efficacy, with mostly manageable toxicities. The class of Bruton’s tyrosine kinase (BTK) inhibitors has transformed the therapeutic landscape for patients with WM, given their convenient oral dosing and strong efficacy, with high rates of attainment of very good partial response (VGPR). The tolerability of the next-generation BTK inhibitors appears to be superior to that of the first-in-class agent, ibrutinib. Targeted therapies from other classes have also demonstrated efficacy in both single-agent and combination regimens. Inhibitors of proteasome BCL-2, mTOR and PI-3 kinase have demonstrated efficacy in WM. Emerging therapies under investigation will continue to further shape the management paradigm, especially in the R/R setting. These include bispecific antibodies, radiotherapeutic agents and chimeric antigen receptor T-cell (CART) cell therapies. This review outlines the current literature and future direction of targeted therapies in WM.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic disorder characterized by an IgM paraprotein. The clinical presentation of WM varies and can include common manifestations such as anemia and hyperviscosity, in addition to less common features such as cryoglobulinemia, IgM-related neuropathy, and immunoglobulin light chain (AL) amyloidosis. Amyloidosis is a protein-folding disorder in which vital organ damage occurs due to the accumulation of misfolded protein aggregates. The most common type of amyloidosis in patients with an IgM paraprotein is AL amyloidosis, although other types of amyloidosis may occur. IgM-related amyloidosis has distinct clinical features when compared with other subtypes of AL amyloidosis. This review highlights the diagnostic criteria of IgM-related AL amyloidosis, as well as the clinical characteristics and treatment options for this disorder.

Waldenström macroglobulinemia (WM) is a rare, non-Hodgkin lymphoma that remains incurable. Rituximab, an anti-CD20 monoclonal antibody has been the cornerstone of treatment against WM, and its combination with an alkylator, bendamustine, achieves durable remission in treatment-naive patients with symptomatic WM. However, novel "druggable" targets that have been identified within the clonal lymphoplasmacytic cells in WM have resulted in a rapid development of targeted therapies in both the frontline and relapsed and refractory (R/R) settings. Several agents directed against the known targets have shown promising efficacy, with mostly manageable toxicities. The class of Bruton's tyrosine kinase (BTK) inhibitors has transformed the therapeutic landscape for patients with WM, given their convenient oral dosing and strong efficacy, with high rates of attainment of very good partial response (VGPR). The tolerability of the next-generation BTK inhibitors appears to be superior to that of the first-in-class agent, ibrutinib. Targeted therapies from other classes have also demonstrated efficacy in both single-agent and combination regimens. Inhibitors of proteasome BCL-2, mTOR and PI-3 kinase have demonstrated efficacy in WM. Emerging therapies under investigation will continue to further shape the management paradigm, especially in the R/R setting. These include bispecific antibodies, radiotherapeutic agents and chimeric antigen receptor T-cell (CART) cell therapies. This review outlines the current literature and future direction of targeted therapies in WM. [ABSTRACT FROM AUTHOR]

• Amyloid-like IgM deposition neuropathy can present with multiple mononeuropathies and autonomic dysfunction. • IgM deposition can result in pathologic findings of non-congophilic IgM kappa deposits and nerve microvasculitis. • Early treatment of amyloid-like IgM deposition neuropathy may result in motor improvement. Amyloid-like IgM deposition neuropathy is a distinct entity in the setting of IgM monoclonal gammopathy in which endoneurial perivascular entire IgM-particle accumulation leads to a painful sensory followed by motor peripheral neuropathy. We report a 77-year-old man presenting with progressive multiple mononeuropathies starting with painless right foot drop. Electrodiagnostic studies showed severe axonal sensory-motor neuropathy superimposed by multiple mononeuropathies. Laboratory investigations were remarkable for biclonal gammopathy of IgM kappa, IgA lambda and severe sudomotor and mild cardiovagal autonomic dysfunction. A right sural nerve biopsy showed multifocal axonal neuropathy, prominent microvasculitis, and prominent large endoneurial deposits of Congo-red negative amorphous material. Laser dissected mass spectrometry-based proteomics identified IgM kappa deposit without serum amyloid-P protein. This case has several distinctive features, including motor preceding sensory involvement, prominent IgM-kappa proteinaceous deposits replacing most of the endoneurium, a prominent inflammatory component, and improvement of motor strength after immunotherapy. [ABSTRACT FROM AUTHOR]

Introduction: Schnitzler syndrome (SchS), first described in 1972, is a rare autoinflammatory condition characterized by chronic urticaria and monoclonal gammopathy of IgM or, exceptionally, IgG profile. Additional features include recurrent fever, evidence of abnormal bone remodeling, a neutrophilic dermal infiltrate on skin biopsy, leukocytosis or elevated C-reactive protein, according to the Strasbourg criteria.

Waldenström macroglobulinemia (WM) is a rare lymphoplasmacytic disorder characterized by an IgM paraprotein. The clinical presentation of WM varies and can include common manifestations such as anemia and hyperviscosity, in addition to less common features such as cryoglobulinemia, IgM-related neuropathy, and immunoglobulin light chain (AL) amyloidosis. Amyloidosis is a protein-folding disorder in which vital organ damage occurs due to the accumulation of misfolded protein aggregates. The most common type of amyloidosis in patients with an IgM paraprotein is AL amyloidosis, although other types of amyloidosis may occur. IgM-related amyloidosis has distinct clinical features when compared with other subtypes of AL amyloidosis. This review highlights the diagnostic criteria of IgM-related AL amyloidosis, as well as the clinical characteristics and treatment options for this disorder. [ABSTRACT FROM AUTHOR]

Summary: Patients with asymptomatic/smouldering Waldenström macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow‐up of 9·5 [8·1–11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and β2‐microglobulin (β2M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time‐to‐progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88WT) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7–8·7) vs. 4·7 (2·4–7·7) years for the MYD88L265P cohort, n = 42; P = 0·11]. The presence of C‐X‐C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4WT vs. 5·6 years for CXCR4MUT, P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age‐, sex‐ and calendar year‐matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and β2M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre‐emptive intervention in this patient population. [ABSTRACT FROM AUTHOR]

Waldenstrom macroglobulinemia (WM) is a lymphoplasmacytic lymphoma that presents with symptomatic anemia, thrombocytopenia, constitutional symptoms, extramedullary disease and rarely hyperviscosity syndrome. The presence of both IgM monoclonal protein and ≥10% monoclonal lymphoplasmacytic cells is required for the diagnosis. MyD88 is present in 67-90% of patients but is not pathognomonic for WM. Many patients who fulfill the criteria of WM are asymptomatic and do not require treatment. Recent advances in the understanding of the biology of WM have paved the way for new treatment options. The use of novel agents with or without rituximab enables the use of effective chemotherapy-free regiments upfront and in the relapsed setting. New targeted treatments such as venetoclax and CXCR4 antagonists are being investigated. [ABSTRACT FROM AUTHOR]

Introduction: We assessed the specific sonographic pattern of structural nerve abnormalities in immunoglobulin M (IgM) neuropathy and disease controls.Methods: We enrolled 106 incident patients-32 patients with IgM neuropathy, 42 treatment-naive patients with chronic inflammatory demyelinating polyneuropathy, and 32 patients with axonal neuropathies. All patients underwent standardized ancillary testing in addition to standardized sonography of the brachial plexus and the large arm and leg nerves bilaterally.Results: We found widespread nerve enlargement in IgM neuropathy and chronic inflammatory demyelinating polyneuropathy (CIDP), with specific enlargement of brachial plexus and proximal segments of median nerve but not in axonal disease controls (P < .001). Sonographic nerve hypertrophy in IgM neuropathy was not associated with nerve conduction, clinical, or laboratory characteristics.Discussion: Immunoglobulin M neuropathy is characterized by widespread nerve enlargement indistinguishable from CIDP. Our data provide evidence to confirm that the disease process is not confined to the more distal parts of nerves in either classical demyelinating or axonal variants of neuropathy with associated IgM. [ABSTRACT FROM AUTHOR]

The finding of an IgM monoclonal gammopathy often represents a diagnostic challenge. In fact, there are many pathological disorders associated with this condition, each of which has distinctive characteristics and requires specific clinical, instrumental, and laboratory assessments to set the appropriate treatment. This review has two aims. Firstly, to provide a framework of the broad spectrum of IgM-associated disorders: (1) monoclonal gammopathy of undetermined significance (MGUS); (2) Waldenström macroglobulinemia (WM); (3) IgM-related disorders (among which hyperviscosity syndrome, light chain amyloidosis, cold agglutinin disease, cryoglobulinaemia, IgM neuropathy, Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome, Castleman disease); (4) IgM-secreting multiple myeloma (IgM-MM); and (5) other lymphoproliferative disorders which may be associated with IgM (such as chronic lymphocytic leukemia, small lymphocytic lymphoma, and B-cell non Hodgkin lymphoma). Secondly, to give a detailed insight regarding diagnosis and treatment of WM. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinemia (WM) is a unique CD20+, B-cell non-Hodgkin lymphoma, characterized by lymphoplasmacytic infiltration of the bone marrow and circulating monoclonal immunoglobulin M. The clinical manifestations and outcomes of patients are highly variable. High-level evidence supports integration of monoclonal anti-CD20 antibody, rituximab, to the chemotherapy backbone to treat WM. However, its contemporary management has become more nuanced, with deeper understanding of the pathophysiology and incorporation of Bruton's tyrosine kinase (BTK) inhibitors to the treatment paradigm. Prior knowledge of the patients' MYD88 L265P and CXCR4 mutation status may aid in the treatment decision-making. Currently, the two frequently utilized approaches include fixed-duration chemoimmunotherapy and BTK inhibitor-based continuous treatment until progression. Randomized trials comparing these two vastly divergent approaches are lacking. Recent studies demonstrating efficacy of B cell lymphoma-2 (BCL2) inhibitors and non-covalent BTK inhibitors in patients, previously exposed to a covalent BTK inhibitor, are a testament to the rapidly expanding options against WM. [ABSTRACT FROM AUTHOR]

The management of Waldenström macroglobulinaemia ( WM) relies predominantly on small trials, one of which has demonstrated activity of dexamethasone, rituximab and cyclophosphamide ( DRC) in the frontline setting. We report on the efficacy of DRC, focusing on relapsed/refractory (R/R) patients. Ibrutinib, a recently approved agent in WM demonstrated limited activity in patients with MYD88 WT genotype. Herein, we additionally report on the activity of DRC based on the MYD88L265P mutation status. Of 100 WM patients evaluated between January 2007 and December 2014 who received DRC, 50 had R/R WM. The overall response rate ( ORR) was 87%. The median progression-free survival ( PFS) and time-to-next-therapy ( TTNT) were 32 (95% confidence interval [ CI]: 15-51) and 50 (95% CI: 35-60) months, respectively. In the previously untreated cohort ( n = 50), the ORR was 96%, and the median PFS and TTNT were 34 months (95% CI: 23-not reached [ NR]) and NR (95% CI: 37- NR), respectively. Twenty-five (86%) of 29 genotyped patients harbored MYD88L265P. The response rates and outcomes were independent of MYD88 mutation status. Grade ≥3 adverse effects included neutropenia (20%), thrombocytopenia (7%) and infections (3%). Similar to the frontline setting, DRC is an effective and well-tolerated salvage regimen for WM. In contrast to ibrutinib, DRC offers a less expensive, fixed-duration option, with preliminary data suggesting efficacy independent of the patients' MYD88 status. [ABSTRACT FROM AUTHOR]

Background: The management of IgM monoclonal gammopathies undetermined significance (IgM-MGUS) and Waldenstrom's macroglobulinemia (WM) may be challenging. Modern immunoassays that quantify specific monoclonal heavy and light chain immunoglobulins are promising for their use in these applications. Methods: Ninety consecutive patients (39 IgM-MGUS, 32 indolent WM [iWM], and 19 WM) seen between January 2007 and March 2014 were analyzed. Heavy/light chain (HLC) and serum free light chains assays (FLC) were determined at diagnosis to study their utility as biomarkers in IgM monoclonal gammopathies. Results: The HLC involved to uninvolved IgM ratios (iHLC/uHLC) showed a progressive increase when going from IgM-MGUS, to iWM and to WM (p = 0.002). Furthermore, an iHLC/uHLC > 62 identified a group of iWM patients with a shorter time-to-progression (TTP) (108 vs. 133 months, p = 0.033). Separate analysis of the involved and uninvolved components showed that only the suppression of the uninvolvedimmunoglobulin was predictive of shorter TTP (HR = 3.04, p = 0.03) suggesting that it could be the majorcontributor to the prognostic value of the Hevylite assay. Additionally, a multivariate analysis showed that immunosuppression (either classical immunoparesis or Hevylite immunosuppression) was an independent prognostic factor (p = 0.016) reinforcing its relevance in the disease mechanism. Finally, monoclonal sFLC levels were highest in WM patients, with 83% presenting values > 60 mg/L. Conclusions: The results suggest that the levels of immunosuppression and/or the iHLC/uHLC ratio of IgM immunoglobulins measured by Hevylite are associated with greater disease activity which significantly impacts in the outcome of WM patients and may also help in the differentiation of IgMMGUS from iWM. [ABSTRACT FROM AUTHOR]

Its antecedent condition, monoclonal gammopathy of undetermined significance (MGUS) of the IgM class, comprising approximately 15% of MGUS, afflicts a much larger population that is at risk of progression to WM or a similar lymphoproliferative disorder (Kyle I et al i , [6]). The major recurrent hot-spot mutation, L265P, in the I MYD88 i gene, although not pathognomonic of IgM monoclonal gammopathies, is a salient contributor to enhanced cell growth and survival, and is encountered in even a higher proportion (upto 95%) of patients with WM (Poulain I et al i , [10]). [Extracted from the article]

Objectives We retrospectively evaluated the clinical features, serum levels of IgM, and prevalence of IgM related diseases in patients with serum immunofixation electrophoresis (sIFE) confirmed IgM monoclonal gammopathy at our center. Methods We included patients with sIFE confirmed IgM monoclonal gammopathy between January 2008 and December 2014 in this retrospective study. We evaluated clinical data, sIFE, serum IgM levels, and diagnosis. Results In total, 7107 patients had sIFE confirmed monoclonal gammopathy, with 377 (5.3%) patients having the IgM type. The median age was 62 years (range, 19–105 years). The median level of serum IgM is 8.3 g/L (range, 0.24–150 g/L). The diagnosis included monoclonal gammopathy of undetermined significance (MGUS, 157 patients, 41.6%), Waldenstrom macroglobulinemia (WM, 105 patients, 27.9%), B cell non-Hodgkin’s lymphoma (69 patients, 18.3%), primary cold agglutinin disease (pCAD, 16 patients, 4.2%), primary amyloidosis (14 patients, 3.7%), cryoglobulinaemia (six patients, 1.6%), IgM MGUS associated neuropathy (five patients, 1.3%), multiple myeloma (three patients, 0.8%), and POEMS syndrome (two patients, 0.5%). Levels of serum IgM > 15.5 g/L were 80.6% sensitive and 89.2% specific for the diagnosis of WM. Kappa type light chain indicated the diagnosis of WM, pCAD, IgM MGUS associated neuropathy and cryoglobulinaemia, while lambda type light chain indicated POEMS and amyloidosis. There were 41/157 (26.1%) MGUS patients diagnosed with complications due to IgM-unrelated autoimmune diseases. Conclusion IgM monoclonal gammopathy contains a broad spectrum of diseases. Levels of serum IgM and the type of light chain can be used to help with differential diagnosis. The association between MGUS and some autoimmune diseases requires further investigation. [ABSTRACT FROM AUTHOR]

Waldenström's Macroglobulinemia (WM) is characterized by the presence of an IgM monoclonal protein regardless of its size, 10% or more bone marrow infiltration by small lymphocytes with a plasmacytoid or plasma cell differentiation. These cells usually have the following markers: IgM+, CD5 − , CD10 − , CD19 + , CD20 + and CD23 − . Chronic lymphocytic leukemia as well as other lymphoproliferative disorders such as mantle cell, marginal zone and mucosa-associated lymphoid tissue (MALT) lymphoma must be excluded. Weakness or fatigue from anemia, fever, night sweats, or weight loss represent the most common symptoms. Hepatosplenomegaly may be a major feature. Anemia, thrombocytopenia, hyperviscosity or peripheral neuropathy may be prominent features. Systemic amyloidosis, renal insufficiency and cryoglobulinemia may also be seen. WM must be differentiated from smoldering Waldenström's Macroglobulinemia (SWM) which is an intermediate disease state characterized by an IgM protein ≥3 g/dL and/or a bone marrow containing ≥10% bone marrow lymphoplasmacytic infiltration but no end-organ damage such as symptomatic anemia, constitutional symptoms, hyperviscosity, symptomatic hepatosplenomegaly or lymphadenopathy. [ABSTRACT FROM AUTHOR]

Background: Fibrillary glomerulonephritis (FGN) is a rare primary glomerular disease that seldom coexists with other diseases. Membranoproliferative glomerulonephritis is a pathologic finding of renal lesions associated with IgM-secreting monoclonal proliferations. We present a case study of a patient with unusual simultaneous FGN and IgM-related renal disorder in nonmalignant monoclonal IgM gammopathy.Case Presentation: A 63-year-old male presented with nephrotic syndrome and elevated serum creatinine levels. Laboratory examination revealed elevated levels of serum IgM and low C3 levels. Serum and urine immunofixation electrophoresis showed a monoclonal IgM with a kappa light chain. A bone marrow biopsy revealed less than 5 % bone marrow infiltration by lymphoplasmacytic lymphoma, and a renal biopsy revealed mesangiocapillary glomerulonephritis on light microscopy. Immunofluorescent and immunohistochemical staining indicated granular deposits of immunoglobulin G in the mesangium and granular deposits of immunoglobulin M and κ light chains along the capillary wall. Electron microscopy revealed randomly arranged nonbranching fibrils of approximately 15 nm in diameter in the glomerular mesangium and subendothelial electron-dense deposits. According to these results, we confirmed FGN and membranoproliferative glomerulonephritis, which were attributed to monoclonal IgM deposits.Conclusion: To the best of our knowledge, this is the first report of simultaneous FGN and membranoproliferative glomerulonephritis in nonmalignant IgM monoclonal gammopathy. [ABSTRACT FROM AUTHOR]

Waldenström macroglobulinemia (WM) is a distinct hematologic malignancy characterized by a lymphoplasmacytic bone marrow infiltration and the presence of immunoglobulin (Ig)M monoclonal protein. Patients typically present at an advanced age, and a substantial proportion are asymptomatic at diagnosis. A unifying diagnosis of WM may be missed by an unsuspecting hematologist, as symptomatic patients present with a multitude of non-specific manifestations. Although constitutional and neuropathy-related symptoms predominate, concomitant IgM-induced hyperviscosity-associated features can provide useful diagnostic clues. There are specific indications for initiation of therapy. This review focuses on the most up-to-date management strategies of WM, in addition to highlighting the recent discoveries of MYD88 and CXCR4 mutations that have shed unprecedented light on the complex signaling pathways, and opened avenues for novel therapeutic targeting. Although WM remains incurable, with the rapid emergence and integration of effective novel therapies, its clinical course appears poised to improve in the foreseeable future. [ABSTRACT FROM AUTHOR]

The article discusses a study which examined the prevalence of MYD88 L265P somatic mutation in patients with immunoglobulin M (IgM) monoclonal gammopathy of undetermined significance (MGUS) and smouldering Waldenstrom macroglobulinemia (WM). Topics discussed include the use of polymerase chain reaction (PCR) technology to analyze mutation from DNA collected from bone marrow slides, the overall survival of the patients, and the high prevalence of MYD88 L265P mutation in WM and SWM patients.

Polyneuropathy associated with anti-Myelin-Associated Glycoprotein (MAG) antibody is a well-defined immune-mediated disease that develops in individuals with IgM monoclonal gammopathy. Factors related to response to rituximab treatment in anti-MAG neuropathy have not been clarified so far. We prospectively evaluated the clinical status, immunological changes, and electrophysiological parameters before and 12 months after rituximab treatment in 7 patients with anti-MAG neuropathy. Pathological indices of sural nerve biopsy specimens before rituximab treatment were investigated. Overall, 4 patients improved by more than 5% either clinical scale, expressed according to the Medical Research Council (MRC) sum score or sensory sum score (SSS) 12 months after rituximab treatment. The modified Rankin Scale (mRS) scores improved in 2 patients. With respect to the relationship between the response to rituximab treatment and the clinicopathological findings, short disease duration and preservation of nerve fiber density were significantly related. The immunohistochemical assessment suggested that low-intensity binding of anti-IgM antibody to the myelin sheath may contribute to the degree of response to rituximab treatment. The degree of axonal loss and the deposition of pathogenic autoantibodies in myelinated fibers may determine the therapeutic response to rituximab treatment in anti-MAG neuropathy. [ABSTRACT FROM AUTHOR]

Abstract: Monoclonal IgM anti-MAG associated peripheral neuropathies are part of demyelinating dysimmune peripheral neuropathies. The hematological disease probably does not influence the outcome of the neuropathy. Neuropathies associated with IgM anti-MAG antibodies are predominantly sensory and distal polyneuropathies associated with ataxia, unsteadiness and tremor. The neurophysiological features include a symmetric sensorimotor demyelinating neuropathy with more slowing of conduction in the distal than in the proximal nerve segments, a length-dependence, and a variable degree of denervation. High titers of IgM anti-MAG antibodies confirm the diagnosis. The natural history is mostly slow with mild to moderate functional impairment. However, some patients have a faster evolution associated with a more severe handicap. Immunotherapies studies have failed to demonstrate significant efficacy of these treatments. Furthermore, severe adverse effects are not uncommon with any of these therapies. Thus, the risk of possible severe adverse effects must be balanced against any possible benefits. More research is needed to improve the management of anti-MAG neuropathies: research on treatment, on prognostic factors, and development of specific assessment scales adapted to the particularities of anti-MAG neuropathies. [Copyright &y& Elsevier]

A single nodular lesion can be observed in various pulmonary diseases, including cancer, tuberculosis, and fungal infection. Waldenström's macroglobulinemia (WM) usually occurs in older adults and involves the lymph nodes, bone marrow, and spleen. Respiratory tract involvement is very rare. We reported a case of WM-associated renal amyloidosis. The patient was admitted with the initial presentation as a single mass in the lung and progression to renal involvement. [ABSTRACT FROM AUTHOR]