Search

Abstract Antiphospholipid syndrome (APS), cryoglobulinemia, and monoclonal gammopathies are variably accompanied by thrombotic complications. We describe a patient with recurrent skin microvascular thrombosis, APS, cryoglobulinemia, marginal zone lymphoma, and IgMκ monoclonal gammopathy, responsive to chemoimmunotherapy. The cryoglobulin fraction contained the IgMκ paraprotein, while antiphospholipid antibodies (aPL) were predominantly in the cryosupernatant. A retrospective analysis of aPL‐positive patients in our institution showed that 8.1% co‐expressed monoclonal gammopathy. These overlap patients had thrombotic complications and most had recurrences. Patients with multiple gammopathies of thrombotic significance may have several autoantibodies and constitute a high‐risk group.

Abstract Background Paraproteinemic keratopathy is a rare disorder characterized by the bilateral accumulation of polychromatic deposits diffusely in all corneal layers together or not with diffuse or patchy pseudo lipid deposits. We present an atypical case of paraproteinemic keratopathy which lead to an initial misdiagnosis of infectious crystalline keratopathy. Case presentation a 69-year-old woman with an asymptomatic keratopathy detected during a cataract intervention. Slit-lamp examination revealed several hyper refringent subepithelial foci with fern-shaped branches, resembling crystalline keratopathy, in her left eye. Anterior segment optical coherence tomography revealed exclusively subepithelial hyperreflective lesions limited to the anterior stroma. The progressive bilateralization and progression of the condition prompted us to include other entities with crystalline corneal deposits in our differential diagnosis. Hematological analysis showed a high number of free Kappa light chains. Despite the typical clinical appearance of crystalline keratopathy, the atypical evolution and test results led us to consider that monoclonal gammopathy could be the cause of this entity. Conclusions Paraproteinemic keratopathy may present in its early stages as a unilateral subepithelial crystalline keratopathy. Thus, it must always be taken into account in the differential diagnosis of any crystalline keratopathy, particularly when there are no predisposing factors for an infectious crystalline keratopathy. Early recognition of this rare entity is important to address the associated potentially serious systemic disease.

Abstract Multiple myeloma (MM) is a disease, that at times poses diagnostic and monitoring challenges. Over the last decades laboratory methods have been expanded with serum free light chain (FLC) analysis. Alerted by two index cases with clinical impact due to failure of the FLC analysis to indicate a disease progression, we aimed to identify any clinical consequences due to known differences between FLC analysis methods. We applied two FLC analysis methods (Freelite Binding Site [FBS] and N‐Latex Siemens [NLS]) on all patients with MM and monoclonal gammopathy of uncertain significance diagnosed/followed up at Södra Älvsborg Hematology Unit, from April to December 2022. From a total of 123 patients with malignant plasma cell disorder, we identified five cases (4.1%) where solely the FBS method, as opposed to NLS, urine and serum electrophoresis, could support diagnosis or detect progression. The consequences of this discrepancy included not only change of diagnosis or delayed therapy but also change of treatment. Our findings indicate that a stronger awareness of the potential weaknesses of different FLC methods is needed, which calls for a closer collaboration between clinical chemists and hematologists.

Abstract Background Myeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac amyloidosis (CA) but occasionally with wild-type transthyretin (ATTR) CA. In recent years, ATTR amyloidosis has attracted necessity for its reliable diagnosis with the addition of new treatments. Usually, both wild-type ATTR CA and AL-type CA present with marked cardiac hypertrophy, but renal dysfunction is milder in wild-type ATTR amyloidosis than in AL-type amyloidosis. Peripheral neurologic and autonomic symptoms such as numbness and dysesthesia are moderately present in AL-type amyloidosis, but less so in wild-type ATTR amyloidosis. Furthermore, the prognosis of ATTR-type amyloidosis is better than that of AL-type amyloidosis. Case presentation A 72-year-old man with cardiac hypertrophy presented with New York Heart Association functional class III dyspnea and leg edema. He had no history of carpal tunnel syndrome. An electrocardiogram showed atrial fibrillation and low voltage. The N-terminal pro-B-type natriuretic peptide level was 3310 pg/mL, and troponin T was elevated to 0.073 ng/mL. However, the glomerular filtration rate was only slightly decreased at 69.0 mL/min/1.73 m2. The serum free light-chain assay revealed a significant increase in the kappa chain, with positive results in Bence Jones proteins and serum immunoelectrophoresis. Bone marrow examination confirmed the diagnosis of monoclonal gammopathy of undetermined significance (MGUS). AL-type amyloidosis associated with a myeloproliferative disorder was suspected, and the prognosis was initially predicted to be poor, classified as Mayo stage IV. Contrary to this prognosis, the patient showed a slow progression of heart failure. Further imaging modalities and cardiac tissue findings confirmed the diagnosis as transthyretin type amyloidosis, and a favorable prognosis was established with the use of tafamidis. Conclusions MGUS occasionally coexists with wild-type ATTR CA. Scant autonomic symptoms, mild renal dysfunction, and slow progression of heart failure might be clues that the CA associated with the myeloproliferative disease is wild-type ATTR amyloidosis.

Multiple myeloma (MM) is the second most common hematological malignancy, characterized by unregulated monoclonal proliferation in the bone marrow. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are premalignant conditions that can progress to MM. Identifying etiological risk factors for MM and its precursor diseases is crucial for prevention. Obesity, diet, vitamin D levels, and gut microbiota alterations have been identified as lifestyle factors affecting MM and MGUS risk. Upon disease onset, treatment strategies aim to reduce disease burden, enhance prognosis, and optimize patients’ quality of life. Nutrition and body weight have been shown to affect disease progression and treatment outcomes. MM patients often present with vitamin D, vitamin B12, and folate deficiencies, which worsen disease prognosis. High body mass index is linked to increased death rates among MM patients and an increased risk of MGUS transformation to MM. Gut microbiota has also been associated with disease progression and response to treatment. This literature review aims to summarize the available evidence regarding the impact of nutrition and nutritional status on MM patients beyond prevention, highlighting the significance of gut microbiome and dysbiosis in MM progression.

Fever of unknown origin (FUO), despite the wide diagnostic potential of modern medicine, remains a difficult problem for clinicians. Often, making a correct diagnosis requires a comprehensive examination of the patient, as well as the joint work of doctors from different specialties.A 57-year-old male patient was hospitalized due to an episode of loss of consciousness, unmotivated weight loss and daily evening temperature rises to 38-39о C, accompanied by chills and increased sweating. Previously, he was examined by a general practitioner, a cardiologist, and repeatedly by a hematologist. There was no evidence of an infectious disease, arrhythmias, multiple myeloma, lymphoproliferative disorders. Monoclonal gammopathy of undetermined significance (MGUS) was diagnosed. Blood tests revealed neutrophilia (9800 cells/ μl) and moderate anemia. The patient was hospitalized to determine the FUO cause. Heart auscultation revealed a systolic murmur in the mitral valve, which was previously absent. Echocardiography revealed a mobile masses on the mitral valve, severe mitral regurgitation, and therefore infective endocarditis was diagnosed. Empirical antibiotic therapy with ceftriaxone and levofloxacin was administered. Further blood culture revealed growth of a HACEK representative Aggregatibacter actinomycetemcomitans, sensitive to both drugs. Examination established the odontogenic nature of endocarditis. During treatment, stable normothermia and significant blood count improvement were achieved. However, fluoroquinolone therapy led to tendinopathy. Due to persistent grade 3 mitral regurgitation, the patient underwent routine mitral valve replacement. Further follow-up revealed satisfactory condition of the patient.A feature of this case is the atypical course of infective endocarditis, occurring under a hematological mask, which made its diagnosis difficult. When examining a FUO patient, infective endocarditis should be included in the range of possible causes, taking into account not only the typical clinical picture, but also the numerous masks of this disease.

Background and Objectives: Protein abnormalities include monoclonal gammopathies of undetermined significance (MGUS) and malignant lymphoplasmacytic tumors such as multiple myeloma (MM), Waldenström macroglobulinemia, and amyloid light-chain amyloidosis. MGUS prevalence increases with age, especially in individuals over 50. MGUS progresses to various lymphoplasmacytic diseases, including smoldering MM and MM. Almost all blood donors (BDs) are asymptomatic but some of them could present protein abnormalities. Our objective was to assess the prevalence and impact of protein abnormalities and monoclonal gammopathies (MGs) on transfusion safety among BDs in Morocco. Methods: Two hundred eighty-one serum samples were collected from BDs aged over 40 years old. Total serum protein measurement and protein electrophoresis were performed using the Architect ci8200 and Capillarys-2-Piercing automated systems, respectively. Immunofixation was conducted using hydrates. Results: Protein levels ranged between 59 and 87 g/L (average = 71.69 ± 4.96 g/L). Our results showed 195 (69.39%) normal profiles, 6 (2.13%) MGs, 14 (4.98%) heterogeneous restriction of γ-globulins, and 66 other abnormalities (23.48%) regarding the levels of albumin and proteins from alpha and beta fractions. Conclusion: Our preliminary results appeal to blood transfusion professionals regarding ethical considerations and transfusion safety. BDs with abnormal protein levels should benefit systematically from diagnostic tests and therapies.

Background Data on the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in China are very limited. Our aim was to determine the prevalence and clinical characteristics of MGUS in a large Chinese population.Methods This study included 49,220 healthy people who received serum immunofixation electrophoresis (sIFE) and serum protein electrophoresis (SPE) tests. Serum free light chain ratio, immunoglobulin quantification, and other clinically correlates of MGUS were performed for all patients with M-protein.Results A total of 576 MGUS patients were identified by sIFE, with a median age of 58 years and an overall prevalence of 1.17% (95% CI, 1.08–1.27). Among those aged 50 years and older, the prevalence of MGUS was 2.26% (95% CI, 2.04–2.50). The prevalence of MGUS was significantly higher in males than in females (P

Peripheral neuropathy is a prevalent complication in plasma cell disorders, posing significant diagnostic and therapeutic challenges. This study presents three cases initially diagnosed with chronic inflammatory demyelinating polyneuropathy (CIDP). Despite initial symptom regression post-immunomodulatory treatment, the patients exhibited progressive neurological deficits. Advanced laboratory evaluation confirmed monoclonal protein presence, yet traditional diagnostic methods, including bone marrow biopsy and flow cytometry, yielded normal results. Utilizing 18F-FDG PET/CT, we identified multiple hypermetabolic vertebral lesions, which upon biopsy, confirmed the diagnosis of plasmacytoma. Our findings underscore the utility of PET/CT as a reliable diagnostic tool for monoclonal gammopathy associated neuropathy, advocating for its consideration in cases with equivocal diagnosis. When the diagnosis is in doubt, biopsy of a lesion may facilitate early and accurate diagnosis, potentially influencing treatment strategies and patient outcomes.

Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic premalignant plasma cell disorder that is characterized by the presence of serum M-protein less than 30 g/L or 3 g/dL, bone marrow (BM) clonal plasma cells less than 10%, absence of plasma cell myeloma (PCM) related end-organ damage (CRAB symptoms: hypercalcemia, renal insufficiency, anemia and, bone lesions) and absence of B-cell lymphoma or other disease known to produce an M-protein. MGUS is generally considered a preneoplastic disorder that does not always progress to overt malignancy (1, 2). Diverse endocrinopathies occur in patients with plasma cell disorders (3-6). One possible scenario is the rather rare POEMS syndrome, which is a paraneoplastic syndrome with key manifestations of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (7). We present a case study which emphasizes the importance of multidisciplinary evaluation of MGUS.

Monoclonal antibodies (MoAbs) targeting several cellular receptors have significantly improved the prognosis of multiple myeloma (MM). Their high effectiveness and safety raise the question of whether earlier therapeutic intervention in monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) influences the natural course of the disease. MM is preceded by clinically recognized conditions such as MGUS and SMM. Numerous studies are investigating the disease biology and immune profile of SMM and MGUS to unravel the intricate relationship between immunosurveillance and disease progression. The standard approach to MGUS and SMM remains close observation. Early studies indicate benefits in terms of progression or even survival for promptly treating high-risk SMM patients. Ongoing debates are focused on which patients with SMM and MGUS to treat, as well as on determining the optimal therapeutic approach. The first approach aims to cure by attempting to eliminate the pathological clone, while the second approach is preventive, aiming to manage disease progression to active MM and restore the immune system. In this review, we focus on the available and emerging data on early treatment, particularly with MoAbs alone or in combination with other therapies, in SMM and MGUS patients.

Abstract Multiple myeloma (MM) is a hematological malignancy characterized by unregulated and clonal proliferation of plasma cells in the bone marrow; these cells produce and secrete an anomalous monoclonal immunoglobulin, or a fragment of this, called M protein. The clinical manifestations of MM result from the proliferation of these plasmocytes, the excessive production of monoclonal immunoglobulin and the suppression of normal humoral immunity, leading to hypercalcemia, bone destruction, renal failure, suppression of hematopoiesis and humoral immunity, increasing the risk for the development of infections. The increase in life expectancy of the world population led to a concomitant increase in the prevalence of MM, a pathology that usually affects the elderly population. The aim of this review is to update the reader on epidemiology, diagnostic criteria, differential diagnosis with other monoclonal gam-mopathies, systemic treatment and prognosis of MM.

Key Clinical Message Light chain proximal tubulopathy (LCPT) is a rare type of monoclonal gammopathy of renal significance. Clinicians should consider LCPT in the differential diagnosis of patients with renal or proximal tubular dysfunction with monoclonal gammopathy. They should confirm diagnosis by renal biopsy and initiate chemotherapy before disease progression.

Multiple myeloma (MM) is an incurable hematologic malignancy characterized by a multistep evolutionary pathway, with an initial phase called monoclonal gammopathy of undetermined significance (MGUS), potentially evolving into the symptomatic disease, often preceded by an intermediate phase called “smoldering” MM (sMM). From a biological point of view, genomic alterations (translocations/deletions/mutations) are already present at the MGUS phase, thus rendering their role in disease evolution questionable. On the other hand, we currently know that changes in the bone marrow microenvironment (TME) could play a key role in MM evolution through a progressive shift towards a pro-inflammatory and immunosuppressive shape, which may drive cancer progression as well as clonal plasma cells migration, proliferation, survival, and drug resistance. Along this line, the major advancement in MM patients’ survival has been achieved by the introduction of microenvironment-oriented drugs (including immunomodulatory drugs and monoclonal antibodies). In this review, we summarized the role of the different components of the TME in MM evolution from MGUS as well as potential novel therapeutic targets/opportunities.

Objective: Multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS), the precursor of MM, are plasma cell neoplasms. The evolution of the treatment of MM in recent years has dramatically improved the outcome for these patients. Currently, multidisciplinary studies are being conducted to elucidate the etiopathogenesis of the disease and develop specific treatment agents and prognostic markers. The present study investigates the relationships between immunoexpression of CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 and disease progression in cases of MM and MGUS. Materials and Methods: Immunohistochemical staining for CD138, Pan-Ras, CCL-3, DKK-1, and MUM-1 were performed on bone marrow biopsy samples from 94 MM and 20 MGUS patients diagnosed between 2011 and 2018. Immunohistochemical results were examined semiquantitatively, and the associations between the immunohistochemical, clinical, and biochemical markers utilized for MM and MGUS patient staging were analyzed. Results: Pan-Ras, DKK-1, and MUM-1 staining results were significantly higher in MM compared to MGUS (p=0.005, 0.001, and 0.001, respectively). The mean CCL-3 expression in patients with MGUS was 23.15%, while it was 18.68% in cases of MM (p=0.413). CCL-3 expression was significantly higher in high-risk MGUS cases compared to other risk groups according to the Mayo Clinic Risk Stratification for MGUS. According to the International Staging System and the Revised International Staging System, CD138 expression was higher among stage II and stage III patients than stage I patients. Conclusion: Differences in Pan-Ras, MUM-1, DKK-1, and CCL-3 expressions between MM and MGUS suggest that these molecules may play a role in the progression of MGUS to MM. CCL-3, an immunohistochemical marker, may be predictive of MGUS progression, while CD138 is associated with more advanced stages of MM.

Background. The group of plasma cell neoplasms includes benign and malignant diseases. Sometimes there are difficulties in making a diagnosis. The study of the diagnostic and prognostic significance of immunohistochemical (IHC) markers is of current interest.Aim. To study the significance of IHC markers and histological features of the bone marrow in primary diagnosis in patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).Materials and methods. The study included 287 patients with plasma cell neoplasms: MGUS (n = 148), MM (n = 139). The observation period was 50 months. All patients have performed an aspiration biopsy and histological examination of the bone marrow with IHC analysis of CD138+, CD56+, CD34+, κ- and λ-chains expression.Results. During the observation period the progression of MGUS to MM was recorded in 8.8 % (n = 13) of cases, the progression of MM was determined in 38.1 % (n = 53) of cases.In patients with MGUS and MM the determined percentage of plasma cells at aspiration biopsy was somewhat lower than at histological examination (p >0.001). Statistically significant differences were determined between the groups MGUS and MM by the type of infiltration (р 50 %), in our study interstitial and diffuse type of lesion with large accumulations was more common compared to the nodular type (p = 0.001).The CD138+ expression (IHC) more than 10 % was associated with a decrease of progression-free survival in patients with MGUS.In MM patients with an interstitial type of bone marrow infiltration and CD138+ over 10 % osteodestructive syndrome was detected by X-ray methods in 82.9 % of cases.Determination of CD56+ and immunoglobulin light chains expression in patients with MM and MGUS indicated an unfavorable prognosis.Resistance to chemotherapy or disease progression in MM patients most often occurred with a combination of IgG and immunoglobulin light chains secretion, with CD138+ plasma cells more than 50 % according to IHC, with a diffuse type of bone marrow lesion with accumulations of plasma cells. MGUS patients progressed more frequently with more than 20 % CD138+ plasma cells according to IHC, interstitial type and diffuse plasma cells accumulation type of bone marrow lesion, secretion of IgG or two immunoglobulins.Conclusion. The significance of the IHC study in the diagnosis of plasma cell neoplasms was confirmed. Markers associated with the disease progression and chemotherapy resistance in patients with MGUS and MM were identified.

Abstract Background Monoclonal gammopathy of undetermined significance (MGUS) precedes multiple myeloma (MM). Use of electronic health records may facilitate large‐scale epidemiologic research to elucidate risk factors for the progression of MGUS to MM or other lymphoid malignancies. Aims We evaluated the accuracy of an electronic health records‐based approach for identifying clinically diagnosed MGUS cases for inclusion in studies of patient outcomes/ progression risk. Methods and Results Data were retrieved from Kaiser Permanente Southern California's comprehensive electronic health records, which contain documentation of all outpatient and inpatient visits, laboratory tests, diagnosis codes and a cancer registry. We ascertained potential MGUS cases diagnosed between 2008 and 2014 using the presence of an MGUS ICD‐9 diagnosis code (273.1). We initially excluded those diagnosed with MM within 6 months after MGUS diagnosis, then subsequently those with any lymphoid malignancy diagnosis from 2007 to 2014. We reviewed medical charts for 100 randomly selected potential cases for evidence of a physician diagnosis of MGUS, which served as our gold standard for case confirmation. To assess sensitivity, we also investigated the presence of the ICD‐9 code in the records of 40 randomly selected and chart review‐confirmed MGUS cases among patients with a laboratory report of elevated circulating monoclonal (M‐) protein (a key test for MGUS diagnosis) and no subsequent lymphoid malignancy (as described above). The positive predictive value (PPV) for the ICD‐9 code was 98%. All MGUS cases confirmed by chart review also had confirmatory laboratory test results. Of the confirmed cases first identified via M‐protein test results, 88% also had the ICD‐9 diagnosis code. Conclusion The diagnosis code‐based approach has excellent PPV and likely high sensitivity for detecting clinically diagnosed MGUS. The generalizability of this approach outside an integrated healthcare system warrants further evaluation.

Monoclonal gammopathy of undetermined significance (MGUS) is associated with several autoimmune conditions, including central nervous system (CNS) vasculitis. Epstein-Barr virus (EBV) is a pathogen capable of triggering a systemic immune response and is involved in the occurrence of a wide range of B-cell lymphoproliferative disorders. In systemic autoimmune diseases, EBV infection is suspected to play a central role in pathogenesis. Here, we present a case that was thought to be a systemic autoimmune disease and CNS vasculitis that developed after EBV infection, demonstrating that rituximab is effective for the treatment.

The coexistence of dual hematological neoplasms is an unusual and challenging presentation due to the different combination of etiopathology. The presentation of synchronous dual hematological malignancies can be one of the 3 types: myeloid + lymphoid or dual lymphoid or dual myeloid. Here, we are reporting a case of a 53-year-old male with simultaneous presence of JAK2 V617F-positive myeloproliferative neoplasm with features favoring prefibrotic phase of primary myelofibrosis (pre-PMF) in combination with monoclonal gammopathy of undetermined significance (MGUS). In such cases of simultaneous existence of dual hematological neoplasm management, it is recommended to treat the more aggressive one. Currently, our management plan is focusing on treating the pre-PMF and observation of MGUS with regular monitoring for transformation to MM.

Multiple myeloma is a tumor of plasma cells, one of the most common malignant blood diseases. It is preceded by a stage called monoclonal gammopathy of undetermined significance, from which true multiple myeloma develops in only a small percentage of cases. It was assumed that this process is associated with the accumulation of genetic mutations, but in recent years there is increasing evidence that the bone marrow microenvironment plays a key role in progression and that it can become a target for therapy that prevents the myeloma development. The review considers the role of mesenchymal stem cells, immune system cells, endotheliocytes, fibroblasts, adipocytes, osteoclasts and osteoblasts in multiple myeloma progression, as well as the impact of the sympathetic nervous system and microbiome composition.

Monoclonal gammopathy of clinical significance (MGCS) represents a new clinical entity referring to a myriad of pathological conditions associated with the monoclonal gammopathy of undetermined significance (MGUS). The establishment of MGCS expands our current understanding of the pathophysiology of a range of diseases, in which the M protein is often found. Aside from the kidney, the three main organ systems most affected by monoclonal gammopathy include the peripheral nervous system, skin, and eye. The optimal management of these MGUS-related conditions is not known yet due to the paucity of clinical data, the rarity of some syndromes, and limited awareness among healthcare professionals. Currently, two main treatment approaches exist. The first one resembles the now-established therapeutic strategy for monoclonal gammopathy of renal significance (MGRS), in which chemotherapy with anti-myeloma agents is used to target clonal lesion that is thought to be the culprit of the complex clinical presentation. The second approach includes various systemic immunomodulatory or immunosuppressive options, including intravenous immunoglobulins, corticosteroids, or biological agents. Although some conditions of the MGCS spectrum can be effectively managed with therapies aiming at the etiology or pathogenesis of the disease, evidence regarding other pathologies is severely limited to individual patient data from case reports or series. Future research should pursue filling the gap in knowledge and finding the optimal treatment for this novel clinical category.

Multiple myeloma (MM) is still an incurable disease, despite considerable improvements in treatment strategies, as resistance to most currently available agents is not uncommon. In this study, data on drug resistance in MM were analyzed and led to the following conclusions: resistance occurs via intrinsic and extrinsic mechanisms, including intraclonal heterogeneity, drug efflux pumps, alterations of drug targets, the inhibition of apoptosis, increased DNA repair and interactions with the bone marrow (BM) microenvironment, cell adhesion, and the release of soluble factors. Since MM involves the BM, interactions in the MM-BM microenvironment were examined as well, with a focus on the cross-talk between BM stromal cells (BMSCs), adipocytes, osteoclasts, osteoblasts, endothelial cells, and immune cells. Given the complex mechanisms that drive MM, next-generation treatment strategies that avoid drug resistance must target both the neoplastic clone and its non-malignant environment. Possible approaches based on recent evidence include: (i) proteasome and histone deacetylases inhibitors that not only target MM but also act on BMSCs and osteoclasts; (ii) novel peptide drug conjugates that target both the MM malignant clone and angiogenesis to unleash an effective anti-MM immune response. Finally, the role of cancer stem cells in MM is unknown but given their roles in the development of solid and hematological malignancies, cancer relapse, and drug resistance, their identification and description are of paramount importance for MM management.

BackgroundDue to the various clinical and pathological manifestations of kidney involvement in lymphoproliferative disorder (LPD), the whole spectrum of kidney disease in LPD is still unclear, and data on kidney prognosis is scarce.MethodsWe retrospectively reviewed the renal pathology profiles from January 2010 to December 2021, and 28 patients with B-cell LPD combined with intact renal biopsy data were included.ResultsThere were 20 men and eight women aging 41 to 79 years at the time of renal biopsy (median age 62 years). According to hematological diagnosis, patients were classified into four groups: chronic lymphocytic leukemia (CLL) (group1, n=7), Waldenström macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) (group 2, n=8; WM, n=6; LPL, n=2), Other non-Hodgkin’s lymphomas (NHL) (group3, n=7; diffuse large B-cell lymphoma (DLBCL), n=2; mucosa-associated lymphoid tissue (MALT) lymphoma, n=4; Low grade B-cell lymphoma, n=1), and monoclonal gammopathy of undetermined significance/monoclonal gammopathy of renal significance (MGUS/MGRS) (group 4, n=6). Median serum creatinine (Scr) level was 129 (range,59-956) umol/L. Eight patients (29%) were presented with acute kidney injury (AKI), and five patients (18%) required hemodialysis upon admission. Twenty-three patients (82%) presented with proteinuria (median protein excretion, 2.14 g/d), 11(39%) of whom had the nephrotic syndrome. Interstitial malignant infiltration was the most frequent renal lesion (n=6). Eight patients underwent immunohistochemistry of renal tissues, of which three patients (CLL, n=1; LPL, n=1; WM, n=1) had confirmed lymphoma infiltrates, and the infiltrating cells in the remaining five patients (CLL, n=1; MALT lymphoma, n=2; MGUS, n=2) were considered unrelated to lymphoma. The most common glomerular diseases were renal amyloidosis (n=4) and membranous nephropathy (n=4). Only 20 patients were treated, 13 of whom were treated with rituximab separately or in combination. The median follow-up time was 11 months. Of these, six had achieved hematological response, complete response in five cases. Eight had achieved renal response. At the end-of-study visit, four patients died and two progressed to end stage kidney disease (ESKD).ConclusionIn conclusion, the clinicopathological spectrum of renal involvement in BLPD is diverse. Renal biopsy and immunohistochemistry are required for early diagnosis and prognostic assessment.

Abstract Background This study aimed to analyze the clinicopathological characteristics of patients with paraproteinemia and renal damage. Methods Ninety-six patients from 2014 to 2018 with paraproteinemia and renal damage were enrolled and the clinical data, renal pathology, treatment and prognosis data were collected. Results A total of 96 patients (54 male and 42 female), accounting for 2.7% of all renal biopsies, were enrolled in this study. Among them, 42 were monoclonal gammopathy of renal significance (MGRS), 21 were renal monotypic immunoglobulin alone (renal monoIg), and 19 were monoclonal gammopathy of undetermined significance (MGUS). Individuals with multiple myeloma (MM) accounted for the fewest number of patients (n = 14). In the MGRS group, the main diseases were amyloidosis (n = 25) and cryoglobulinemic glomerulonephritis (n = 7), while in the MM group, the main diseases were cast nephropathy (n = 9) and light chain deposit disease (n = 3). In the MGUS group, it was mainly IgA nephropathy (IgAN, n = 10) and idiopathic membranous nephropathy (n = 5); while in the renal monoIg group, most of the cases were IgAN (n = 19). Chemotherapy was mainly administered to patients in the MM group, while immunosuppression therapy was mostly administered to patients in the renal monoIg group. Most patients with renal monoIg exhibited a major response, followed by the patients with MGUS and MGRS, while most of the patients with MM had a partial response but none had a major response. Approximately more than half (57.1%) of the patients with MM progressed to end-stage renal disease (ESRD), followed by MGRS (33.3%); however, the mortality rate was low in both the MGRS and MM groups. The survival analysis reviewed that serum creatinine, hemoglobin levels, and the serum κ/λ ratio were independent risk factors for ESRD in patients with MGRS. Conclusions The clinicopathological changes in patients with MGRS were between those in patients with MM and MGUS. The treatment for MGRS and MM was more intensive, and the overall mortality rate was low. Both MGUS and renal monoIg alone exhibited slighter clinicopathological features than MGRS and MM, and the treatment was focused mostly on primary renal diseases.

Co-occurrence of myelodysplastic syndrome (MDS) and plasma cell neoplasm in patients with no history of chemo and/or radiotherapy is rarely reported. Herein, we report a case of a female in her seventieth decade of life who was referred to the hospital for pancytopenia. The patient was asymptomatic and was doing well overall. Serum protein electrophoresis was remarkable for a lambda-restricted monoclonal protein (IgG) estimated at 1.8g/dL. Immunoglobulin G serum level was also elevated, and serum Kappa/Lambda free light chain ratio was decreased. At that time, a bone marrow biopsy showed myelodysplastic syndrome with excess blasts-2 (MDS-EB2) and a monoclonal plasma cell proliferation. Some studies have shown that patients with plasma cell neoplasm could be associated with an increased risk of developing MDS compared to the general population. Based on reviewing the literature, to our knowledge, the pathological mechanism of the co-occurrence of both diseases is not yet clear.

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is a rare, heterogeneous, but treatable autoimmune-mediated peripheral neuropathy characterized by demyelination. CIDP can occur independently or simultaneously with a variety of diseases such as diabetes, monoclonal gammopathy of undetermined significance (MGUS), connective tissue disease, and HIV. It is important to identify CIDP and specific peripheral neuropathies caused by these diseases; this review aims to summarize the CIDP literatures related to diabetes, MGUS, SLE, and HIV, and to be helpful for the management of such patients.

Immunoglobulin M monoclonal gammopathy of undetermined significance (MGUS) comprises 15-20% of all cases of MGUS. IgM MGUS is distinct from other forms of MGUS in that the typical primary progression events include Waldenstrom macroglobulinaemia and light chain amyloidosis. Owing to its large pentameric structure, IgM molecules have high intrinsic viscosity and precipitate more readily than other immunoglobulin subtypes. They are also more commonly associated with autoimmune phenomena, resulting in unique clinical manifestations. Organ damage attributable to the paraprotein, not fulfilling criteria for a lymphoid or plasma cell malignancy has recently been termed monoclonal gammopathy of clinical significance (MGCS) and encompasses an important family of disorders for which diagnostic and treatment algorithms are evolving. IgM related MGCS include unique entities such as cold haemagglutinin disease, IgM related neuropathies, renal manifestations and Schnitzler’s syndrome. The diagnostic approach to, and management of these disorders differs significantly from other categories of MGCS. We describe a practical approach to the evaluation of these patients and our approach to their treatment. We will also elaborate on the key unmet needs in IgM MGCS and highlight potential areas for future research.

Abstract Background Lately, monoclonal gammopathy of renal significance (MGRS) has been defined as a group of renal disorders that are strongly associated with monoclonal protein, including amyloid immunoglobulin light chain (AL) amyloidosis. Amyloid myopathy is rare (1.5% of all patients with amyloidosis) and the prognosis is poor. Furthermore, only approximately 20% of patients with amyloid myopathy are reported to have renal involvement, indicating a lack of data in the literature. Case presentation Here, we report a rare case of MGRS-related AL amyloidosis complicated by amyloid myopathy that presented with muscle weakness in the upper and lower limbs, neck and fingers, and nephrotic syndrome. Blood, urine, and bone marrow examination revealed monoclonal gammopathy of undetermined significance (MGUS) (Bence Jones protein-lambda). Muscle biopsy of the vastus lateralis muscle demonstrated amyloid proteins in the sarcolemma and in the blood vessel walls on Congo red staining, suggesting amyloid myopathy, and tiny inclusions in fibers on modified Gomori trichrome stain. Although we thought they were reminiscent of nemaline bodies, we could not confirm the nature of this structure. Renal biopsy demonstrated amyloid proteins in the mesangial region, part of the capillary walls, and the blood vessel walls on direct fast scarlet staining. As these amyloid proteins were positive for p-component staining and negative for amyloid A staining, β2-microglobulin, and pre-albumin, and as lambda light chains were positive in the mesangial region, we diagnosed the patient with MGRS-related AL amyloidosis. Although he was treated with melphalan and dexamethasone, his symptoms did not improve. Conclusions AL amyloidosis involving the kidneys and muscles has a poor prognosis, and a delayed diagnosis of amyloid myopathy is common because of its rarity and frequent misdiagnosis, which increases organ function deterioration. Therefore, early detection, therapeutic intervention, and careful follow-up are crucial.

Abstract Background Acquired von Willebrand syndrome (AVWS) has been associated with monoclonal gammopathy of undetermined significance (MGUS), with limited data on its management. Methods We conducted a systematic literature search in Medline (Ovid), Embase, and Scopus up to September 11, 2019, for studies reporting on the management of AVWS associated with MGUS (AVWS‐MGUS). Data on patient characteristics, laboratory parameters at presentation, and clinical and laboratory outcomes were extracted. Objectives To describe the clinical presentation and outcomes of different therapeutic approaches. Results Seventy‐five studies were included in the final review, for a total of 137 patients. Most patients had von Willebrand factor ristocetin cofactor activity

Various epidemiological studies, including case reports and -series in addition to larger, population-based studies, have reported an increased prevalence of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma in individuals with a prior history of immune-related conditions. This is believed to support the role of chronic antigen stimulation in the pathogenesis of these conditions. In this short review, we summarize some of the largest population-based studies researching autoimmune diseases, infections, and the subsequent risk of MGUS, and discuss our understanding on its etiology and pathogenesis. Furthermore, we highlight important methodological limitations of previous studies in the field, but almost all studies on MGUS have been based on clinical, possibly biased, cohorts. Finally, we discuss future directions in researching the associations of MGUS and other disorders, including immune-related conditions, where screening studies play an important role.

The human microbiota is a unique set of microorganisms colonizing the human body and evolving within it from the very beginning. Acting as an insider, the microbiota provides nutrients, and mutualistically interacts with the host’s immune system, thus contributing to the generation of barriers against pathogens. While a strong link has been documented between intestinal dysbiosis (i.e., disruption to the microbiota homeostasis) and diseases, the mechanisms by which commensal bacteria impact a wide spectrum of mucosal and extramucosal human disorders have only partially been deciphered. This is particularly puzzling for multiple myeloma (MM), a treatable but incurable neoplasia of plasma cells that accumulate in the bone marrow and lead to end-organ damage. Here we revise the most recent literature on data from both the bench and the bedside that show how the gut microbiota modulates cancer immunity, potentially impacting the progression of asymptomatic monoclonal gammopathy of undetermined significance (MGUS) and smoldering MM (SMM) to full blown MM. We also explore the effect of the gut microbiome on hematopoietic stem cell transplantation, chemotherapy, immunomodulating therapy and cancer immunotherapy in MM patients. Additionally, we identify the most cogent area of investigation that have the highest chance to delineate microbiota-related and pathobiology-based parameters for patient risk stratification. Lastly, we highlight microbiota-modulating strategies (i.e., diet, prebiotics, probiotics, fecal microbiota transplantation and postbiotics) that may reduce treatment-related toxicity in patients affected by MM as well as the rates of undertreatment of SMM patients.

Cryoglobulins are immunoglobulins that undergo reversible precipitation at cold temperatures. Monoclonal type-I cryoglobulinaemia is the least frequent and is associated to hematological diseases such as multiple myeloma, Waldenström’s macroglobulinaemia, chronic lymphocytic leukaemia and lymphoma. We describe the case of a 60-year-old female patient, who suffered from burning pain in her feet for ten months before her admission. The patient presented intermittent distal cyanosis that progressed to digital ischaemia. She also reported paresthesia in her hands, difficulty in writing, and a 26-kg-weight loss. At the physical examination, it was identified livedo reticularis, palpable purpura, and painful ecchymotic lesions in her calves and feet. Moreover, peripheral pulses were palpable and symmetrical. It was observed an atrophy of the right first dorsal interosseous and both extensor digitorum brevis, as well as a distal bilateral apalesthesia and allodynia. Both Achilles reflexes were absent. Laboratory tests revealed anemia, high erythrosedimentation rate and C-reactive protein. Serum protein electrophoresis showed a monoclonal IgG-Kappa gammopathy. The results also evidenced the presence of Bence-Jones proteinuria. The bone marrow biopsy revealed less than 10% of plasma cells, and skin biopsy informed leukocytoclastic vasculitis. The patient was treated with high-dose intravenous steroids and cyclophosphamide. The treatment showed that the skin lesions had improved, pain disappeared and motor deficit stopped its progression.

Monoclonal gammopathy of renal significance (MGRS) is a new nosology in modern nephrology and oncohematology. MGRS is defined as kidney injury due to nephrotoxic monoclonal immunoglobulin produced by the B-cell line clone which does not reach the hematological criteria for specific treatment initiation. Monoclonal proteins pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: 1) limited knowledge about the MGRS among hematologists and nephrologists; 2) lack of necessary diagnostic resources in most health-care facilities; 3) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. Consensus document comprises the opinion of experts leading nephrologists and hematologists of Russian Federation on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy, 1516 of March 2019, Pavlov First Saint Petersburg State Medical University. The present Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses.

A 52-year-old African-American woman with a prior history of monoclonal gammopathy of undetermined significance (MGUS) developed infiltrating ductal carcinoma of the left breast. Following a mastectomy, she underwent reconstruction with a silicone gel breast implant. Three years later, her MGUS had progressed to active multiple myeloma (MM). She had a minimal response after two different regimens of bortezomib-based treatments and monthly zoledronic acid, and was placed on maintenance therapy with bortezomib, intravenous dexamethasone, and oral methylprednisolone, as well as ongoing monthly zoledronic acid. After 1 year of this maintenance therapy, during which her myeloma markers remained unchanged, she had her silicone implant replaced with saline. Despite no change in her myeloma treatment, her laboratory values began to steadily improve following removal of the silicone implant. Her M-protein decreased from 2.14 to 0.83 g/dL and her IgG levels from 3,330 to 1,210 mg/dL following replacement of her silicone implant with saline. To our knowledge, this is the first report in which removal of silicone implants improved the clinical status of a patient with MM following a year of maintenance therapy during which the patient’s myeloma laboratory values remained unchanged. Further studies are warranted to determine if silicone breast implant removal can, in fact, improve MM patients’ disease status.

Pleural effusion is a rare presentation of plasma cell myeloma, occurring in around 6% of patients during the course of their disease, most commonly as a consequence of a concurrent disease process like heart failure secondary to amyloid deposition. Direct infiltration of the pleural fluid by malignant cells leading to myelomatous pleural effusion is a rare mechanism occurring in less than 1% of patients with plasma cell myeloma, and it is associated with a worse prognosis. There are few case reports of myelomatous pleural effusion as an initial presentation of multiple myeloma. Pleural fluid infiltration by monoclonal plasma cells in the absence of an underlying plasma cell myeloma was not reported before in the literature. Tuberculosis is a known cause of polyclonal gammaglobulinemia, however few case reports described the coexistence of monoclonal gammopathy of undetermined significance and tuberculosis. Here we present an interesting case of pleural fluid infiltration by an abnormal looking clonal plasma cells associated with active pulmonary tuberculosis and parapneumonic effusion in a patient with a background of acute myeloid leukemia. Interestingly, the clonal plasma cell proliferation was confined to the pleural fluid without any evidence of an underlying plasma cell neoplasms (including monoclonal gammopathy of undetermined significance and plasmacytomas). Since our patient had an underlying meyloid neoplasm, we though about the possibility of secondary malignancy. However, in almost all patients with coexisting myeloid and plasma cell neoplasms, myeloid neoplasms developed following chemotherapeutic treatment of plasma cell neoplasms not the other way around. Given that, one must conclude localized extramedullary (pleural) plasma cell proliferation probably represents a transient reactive process to pulmonary tuberculosis which is an extremely rare phenomenon and not described before.

The pathogenetic relationship of kidney damage and an aberrant clone of the B-cell line producing nephrotoxic monoclonal immunoglobulin underlies the concept of “monoclonal gammopathy of renal significance” (MGRS). Herein the aberrant clone does not reach the criteria necessary for initiating antitumor therapy according to oncohematological indications. MGRS is a new nosology in modern nephrology and oncohematology. Monoclonal protein’s pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: i) limited knowledge about the MGRS among hematologists and nephrologists; ii) lack of necessary diagnostic resources in most health-care facilities; iii) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. In order to overcome these limitations, leading oncohematologists and nephrologists of the Russian Federation on behalf of professional communities at the end of 2019 published a conciliation document: “Monoclonal gammopathy of renal significance: Consensus of hematologists and nephrologists of Russia on the establishment of nosology, diagnostic approach and rationale for clone specific treatment”. Consensus document comprises the opinion of experts – leading nephrologists and hematologists of Russian Federation – on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia “Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy”, 15–16 of March 2019, Pavlov First Saint Petersburg State Medical University, Saint Petersburg, Russia. Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses which we present here.

Indra Ramasamy Department of Blood Sciences, Worcester Royal Hospital, Worcester WR5 1DD, Worcestershire, UKCorrespondence: Indra RamasamyDepartment of Blood Sciences, Worcester Royal Hospital, Charles Hastings Way, Worcester WR5 1DD, Worcestershire, UKEmail indrar@ozemail.com.auBackground: We determined the detection rate of monoclonal gammopathy of undetermined significance (MGUS) and follow-up of MGUS patients in a center that uses reflex testing at globulin levels outside the reference range as part of its routine service to detect monoclonal protein (M-protein). We recorded the natural history and follow-up of these patients. This is one of the first reports on the diagnosis and follow-up of MGUS patients within the UK.Patients and Methods: A total of 163 patients diagnosed in 2006 and 393 patients with M-protein on long-term follow-up in 2006 were followed over a period of 10 years (y) by community physicians with laboratory support.Results: In 2006, newly diagnosed patients with an M-protein and total number of patients as a percentage of the Worcestershire population were, respectively, 0.025%, 0.045% (at 45– 49y); 0.1%, 0.25% (at 60– 64y); and 0.26%, 1.12% (at 75– 79y). Patients with M-protein had a survival of 35.5% at 10 y and 43.5% at > 10y follow-up. Kaplan–Meier analysis of patients with an M-protein showed that lymphoplasma-cell proliferative disorders (LPD)-free survival was 91% for both 10y and > 10y follow-up. LPD-free survival decreased to approximately 73% when competing causes (death due to unrelated causes, transient M-protein, loss to follow-up) were censored. Progression to LPD occurred at initial M-protein values of 3g/L at diagnosis. During follow-up, 38.3% died without evidence of LPD, 12% were diagnosed with transient M-protein, 8.7% developed LPD, 10.9% had stable M-protein, 4.9% showed increasing M-protein, and 25.2% were lost to follow-up. Survival curves showed that M-protein isotype contributed to LPD-free survival in the order IgG=IgM>IgA>biclonal M-protein.Conclusion: Geographical variations in the diagnosis and follow-up of MGUS patients in the UK need investigation. From public health viewpoint, it is essential to determine MGUS follow-up to improve clinical care and individualise risk-based follow-up of patients.Keywords: MGUS, monoclonal gammopathy of undetermined significance, MGUS progression, MGUS follow-up, community physician

Abstract Background Monoclonal gammopathy of undetermined significance (MGUS) is a plasma cell dyscrasia and precursor to multiple myeloma. It has known ocular manifestations, but has not previously been shown to have an association with autoimmune retinopathy. Case presentation A 57 year-old female presented with 1 year of progressive, bilateral, peripheral vision loss, photopsias, and nyctalopia. Her fundus examination and extensive ancillary testing were concerning for hereditary versus autoimmune retinopathy. The patient was found to have anti-retinal antibodies against carbonic anhydrase II and enolase proteins with a negative genetic retinal dystrophy panel. Malignancy work-up was negative, but the patient was diagnosed with MGUS, a premalignant condition. The patient was treated with immunosuppressive therapies, with rituximab demonstrating the most robust therapeutic response with respect to patient symptoms and ophthalmic testing. Conclusions MGUS should be considered as a potential etiology of autoimmune retinopathy in patients without other autoimmune or malignant disease processes. Immunosuppressive therapy may be helpful in limiting disease progression, with rituximab showing efficacy in retinopathy refractory to other agents.

Monoclonal gammopathy of renal significance (MGRS) is a new nosology in modern nephrology and oncohematology. MGRS is defined as kidney injury due to nephrotoxic monoclonal immunoglobulin produced by the B-cell line clone which does not reach the hematological criteria for specific treatment initiation. Monoclonal protein’s pathological effects on kidney parenchyma result in irreversible decline of kidney function till the end stage renal disease that in line with the position of International Consensus of hematologists and nephrologists determinates critical necessity for clone specific treatment in patients with MGRS despite the absence of hematological indications for treatment initiation. Main challenge of MGRS in Russian Federation is an inaccessibility of an in-time diagnostic and appropriate treatment for the great majority of patients due to the following reasons: i) limited knowledge about the MGRS among hematologists and nephrologists; ii) lack of necessary diagnostic resources in most healthcare facilities; iii) lack of approved clinical recommendations and medical economic standards for treatment of this pathological entity. Consensus document comprises the opinion of experts — leading nephrologists and hematologists of Russian Federation — on the problem of MGRS including the incoherence in nosology classification, diagnostics approach and rationale for clone specific treatment. Consensus document is based on conclusions and agreements reached during the conference of leading nephrologists and hematologists of Russia which was held in the framework of symposia «Plasma cell dyscrasias and lymphoproliferative diseases: modern approaches to therapy», 15-16 of March 2019, Pavlov First St-Petersburg State Medical University, St-Petersburg, Russia. The present Consensus is intended to define the principal practical steps to resolve the problem of MGRS in Russian Federation that are summarized as final clauses.

Abstract Background Although most cases of tubulointerstitial nephritis in paraproteinemia are monoclonal light chain deposition-mediated, interstitial nephritis as neoplastic interstitial cell infiltration has rarely been described. On the other hand, lympho-plasma-cell-rich tubulointerstitial nephritis, in which the infiltrative cells are usually polytypic, is often evident in primary Sjögren’s syndrome (pSS). Herein we present a rare case of pSS in a patient who had been diagnosed as having IgA kappa-type monoclonal gammopathy of undetermined significance (MGUS) and developed tubulointerstitial nephritis with monotypic (IgA kappa) lympho-plasmacytic infiltrates. Case presentation A 74-year-old Japanese woman with pSS who had been diagnosed as having IgA kappa-type MGUS developed progressive renal dysfunction. Renal biopsy revealed tubulointerstitial nephritis with abundant plasma cell-rich mononuclear cell infiltrates without atypia. Immunohistochemical staining for immunoglobulins and light chains showed that most infiltrates were positive for IgA and kappa. Most of the infiltrative cells were positive for CD38 and CD138, and cells positive for CD 19 and CD 45 were also widely evident. Electron microscopy and immunofluorescence studies revealed no apparent immunological deposits in the glomeruli and tubules. Bone marrow and whole-body radiological examinations revealed no findings suggestive of multiple myeloma or lymphoma. Renal function improved rapidly with prednisolone 40 mg daily and has been maintained at the same level on low-dose prednisolone and azathioprine for 18 months. Conclusion Tubulointerstitial nephritis with monotypic cell infiltrates, without immunological deposits, is a quite rare histological picture in MGUS, and might be a unique renal manifestation in patients with pSS.

Abstract Monoclonal gammopathy of undetermined significance (MGUS) may be associated with pathologies with severe neuromuscular manifestations such as sporadic late‐onset nemaline myopathy (SLONM). We describe a difficult to diagnose case of SLNOM with marked clinical improvement after achieving gammopathy complete hematologic response.

The objective of this paper was to report on a case of steroid-responsive chorea in a patient with κ light-chain monoclonal gammopathy. In addition to subacute-onset generalized chorea, evidence of peripheral neuropathy in this elderly gentleman led us to investigate for paraproteinemia. We treated the patient with intravenous steroids in view of elevated κ light-chain assay and bone marrow biopsy, suggestive of monoclonal gammopathy of undetermined significance. There was a remarkable improvement of paresthesias and chorea at 6 months follow-up with no evidence of evolution to malignancy at 1 year. Autoimmune chorea is a treatable condition if identified and treated timely.

Marcin Pasiarski,1,2 Barbara Sosnowska-Pasiarska,3 Ewelina Grywalska,4,5 Agnieszka Stelmach-Gołdyś,1 Artur Kowalik,6 Stanisław Góźdź,2,7 Jacek Roliński4,5 1Department of Hematology, Holycross Cancer Center, Kielce, Poland; 2Department of Immunology, Faculty of Health Sciences, Jan Kochanowski University, Kielce, Poland; 3Department of Oncocardiology, Holycross Cancer Center, Kielce, Poland; 4Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Lublin, Poland; 5Clinical Immunology Department, St. John’s Cancer Center, Lublin, Poland; 6Department of Molecular Diagnostics, Holycross Cancer Center, Kielce, Poland; 7Department of Oncology, Holycross Cancer Center, Kielce, PolandCorrespondence: Ewelina GrywalskaDepartment of Clinical Immunology and Immunotherapy, Medical University of Lublin, Chodzki 4a, Lublin 20-093, PolandTel +48 81 448 6420Fax +48 81 448 6421Email ewelina.grywalska@gmail.comPurpose: Patients with monoclonal gammopathy of undetermined significance (MGUS) have an increased risk of developing infections. Streptococcus pneumoniae vaccinations are recommended for immunocompromised patients, including patients with lymphoproliferative disorders such as MGUS. The objective of the study was to assess the immune response to the 13-valent pneumococcal conjugate vaccine (PCV13) in treatment-naive MGUS patients versus healthy subjects. All study groups were evaluated for the levels of specific pneumococcal antibodies, the levels of IgG and IgG subclasses, and selected peripheral blood lymphocyte subpopulations, including the proportion of plasmablasts before and after immunization.Patients and methods: A total of 22 previously untreated patients with MGUS and 15 healthy age- and sex-matched volunteers were included in the study. All participants were immunized with PCV13 Prevenar13 (Pfizer). The following parameters were assessed: 1) serum-specific pneumococcal antibody titers before and 30 days after vaccination, 2) percentage of plasmablasts, defined as CD19+/IgD−/CD27++, before and 7 days after vaccination, 3) serum total IgG and IgG1, IgG2, IgG3, IgG4 levels before and 30 days after vaccination.Results and conclusion: PCV13 vaccination in MGUS patients is safe and effectively protects against S. pneumoniae infection. In unvaccinated individuals, vaccination should be carried out as soon as possible after diagnosis. It can protect patients against serious infectious complications, which can contribute to extending the time to progression and transformation into more aggressive diseases. PCV13 vaccination is more effective in MGUS patients with a lower concentration of M protein. Serum M protein concentration in patients diagnosed with MGUS may be a useful predictor of the effectiveness of vaccination.Keywords: 13-valent pneumococcal conjugate vaccine, immune response, monoclonal gammopathy of undetermined significance, M protein, plasmablasts, pneumococcal antibodies

Sneddon-Wilkinson disease (SWD) or subcorneal pustular dermatosis is considered a rare pustular skin disease with chronic relapsing course. An association between SWD and other chronic conditions, such as IgA or IgG monoclonal gammopathy of undetermined significance (MGUS), IgA myeloma, pyoderma gangrenosum, thyroid gland disorders, and neoplastic diseases other than MGUS/myeloma, is known. We describe the case of a 92-year-old male patient with SWD and a concurrent IgG MGUS who had been treated with systemic betamethasone, topical mometasone furoate, and methylprednisolone aceponate, with a complete and durable resolution of symptoms and skin lesions without side effects. Systemic and topical steroids were very effective and well tolerated in our patient. This is the second case reported in the literature on the efficacy of a corticosteroid regimen in SWD in a fragile patient. This therapeutic approach (instead of dapsone therapy) has been used due to its relatively good safety profile.

Scleromyxoedema is a rare generalized cutaneous mucinosis, which in absence of thyroid disease, occurs almost invariably in patients with monoclonal gammopathies. A 54-year-old female patient presented with complaint of tightening of skin on the extremities, abdomen, forehead, gradually progressive since 1 year, episodes of generalized tonic–clonic convulsions, and acute psychosis since 5 days. Cutaneous examination revealed nonpitting edema over the face and sclerodermoid changes over extremities. Laboratory investigations showed presence of M-band on serum-protein electrophoresis and monoclonal spike of IgG lambda component on immunofixation. Magnetic resonance imaging of the brain showed periventricular subcortical lacunar infarcts. Skin biopsy with mucin staining was suggestive of scleromyxoedema. All other investigations were normal. Bone marrow biopsy showed a mild focal increase in plasma cells. The cutaneous, serological, and electrophoretic findings as well as the clinical profile of the patient were consistent with the diagnosis of monoclonal gammopathy of undetermined significance associated with scleromyxoedema. This case is presented because of its rare occurrence.