Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance : A Cohort Study Nested in a Clinical Trial.

BACKGROUND: Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) are asymptomatic precursor conditions to multiple myeloma and related disorders. Smoldering multiple myeloma is distinguished from MGUS by 10% or greater bone marrow plasma cells (BMPC) on sampling, has a higher risk for progression, and requires specialist management. OBJECTIVE: To develop a multivariable prediction model that predicts the probability that a person with presumed MGUS has 10% or greater BMPC (SMM or worse by bone marrow criteria) to inform the decision to obtain a bone marrow sample and compare its performance to the Mayo Clinic risk stratification model. DESIGN: iStopMM (Iceland Screens, Treats or Prevents Multiple Myeloma), a prospective population-based screening study of MGUS. (ClinicalTrials.gov: NCT03327597). SETTING: Icelandic population of adults aged 40 years or older. PATIENTS: 1043 persons with IgG, IgA, light-chain, and biclonal MGUS detected by screening and an interpretable bone marrow sample. MEASUREMENTS: Monoclonal gammopathy of undetermined significance isotype; monoclonal protein concentration; free light-chain ratio; and total IgG, IgM, and IgA concentrations were used as predictors. Bone marrow plasma cells were categorized as 0% to 4%, 5% to 9%, 10% to 14%, or 15% or greater. RESULTS: The c-statistic for SMM or worse was 0.85 (95% CI, 0.82 to 0.88), and calibration was excellent (intercept, -0.07; slope, 0.95). At a threshold of 10% predicted risk for SMM or worse, sensitivity was 86%, specificity was 67%, positive predictive value was 32%, and negative predictive value was 96%. Compared with the Mayo Clinic model, the net benefit for the decision to refer for sampling was between 0.13 and 0.30 higher over a range of plausible low-risk thresholds. LIMITATION: The prediction model will require external validation. CONCLUSION: This accurate prediction model for SMM or worse was developed in a population-based cohort of persons with presumed MGUS and may be used to defer bone marrow sampling and referral to hematology. PRIMARY FUNDING SOURCE: International Myeloma Foundation and the European Research Council.

Clinicopathological characteristics and prognosis in patients with monoclonal gammopathy and renal damage in central China: a multicenter retrospective cohort study.

Renal involvement is common in monoclonal gammopathy (MG); however, the same patient may have both MG and non-paraprotein-associated renal damage. Accordingly, distinguishing the cause of renal damage is necessary because of the different clinical characteristics and associated treatments. In this multicenter retrospective cohort study, we described the clinicopathological characteristics and prognosis of 703 patients with MG and renal damage in central China. Patients were classified as having MG of renal significance (MGRS), MG of undetermined significance (MGUS), or hematological malignancy. 260 (36.98%), 259 (36.84%), and 184 (26.17%) had MGRS, MGUS, and hematological malignancies, respectively. Amyloidosis was the leading pattern of MGRS (74.23%), followed by thrombotic microangiopathy (8.85%) and monoclonal immunoglobulin deposition disease (8.46%). Membranous nephropathy was the leading diagnosis of MGUS (39.38%). Renal pathological findings of patients with hematological malignancies included paraprotein-associated lesions (84.78%) and non-paraprotein-associated lesions (15.22%). The presence of nephrotic syndrome and an abnormal free light chain (FLC) ratio were independently associated with MGRS. The overall survival was better in patients with MGUS than in those with MGRS or hematological malignancies.

Smouldering multiple myeloma: To seek or not to seek? To treat or not to treat. That is the question.

In this issue, the British Society for Haematology presents guidelines for the diagnosis and management of patients with smouldering multiple myeloma (SMM). The authors provide a practical, evidence-based approach to managing these patients. Key questions remain yet unsolved. Commentary on: Hughes et al. Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper. Br J Haematol 2024;204:1193-1206.

A Brazilian Rare-Disease Center's Experience with Glucosylsphingosine (lyso-Gb1) in Patients with Gaucher Disease: Exploring a Novel Correlation with IgG Levels in Plasma and a Biomarker Measurement in CSF.

Gaucher disease (GD, OMIM 230800) is one of the most common lysosomal disorders, being caused by the deficient activity of the enzyme acid ß-glucocerebrosidase (Gcase). Three clinical forms of Gaucher's disease (GD) are classified based on neurological involvement. Type 1 (GD1) is non-neuronopathic, while types 2 (GD2) and 3 (GD3) are neuronopathic forms. Gcase catalyzes the conversion of glucosylceramide (GlcCer) into ceramide and glucose. As GlcCer accumulates in lysosomal macrophages, it undergoes deacylation to become glycosylsphingosine (lyso-Gb1), which has shown to be a useful and reliable biomarker for the diagnosis and monitoring of treated and untreated patients with GD. Multiple myeloma (MM) is one of the leading causes of cancer-related death among patients with GD and monoclonal gammopathy of undetermined significance (MGUS) is a non-neoplastic condition that can be a telltale sign of a B clonal proliferation caused by the chronic activation of B cells. This study aimed to quantify Lyso-Gb1 levels in dried blood spots (DBS) and cerebrospinal fluid (CSF) as biomarkers for Gaucher disease (GD) and discuss the association of this biomarker with other clinical parameters. This is a mixed-methods study incorporating both cross-sectional and longitudinal elements within a cohort design with a convenience-sampling strategy. Data collection took place from January 2012 to March 2023. Lyso-Gb1 extraction from DBS involved the use of a methanol-acetonitrile-water mixture, followed by incubation and centrifugation. Analysis was performed using UPLC-MS/MS with MassLynx software version 4.2 and the control group for the DBS measurements included general newborns. CSF Lyso-Gb1 was extracted using ethyl acetate, analyzed by UPLC-MS/MS with a calibration curve, and expressed in pmol/L. Lysosomal activity in CSF was assessed by measuring chitotriosidase (Cht), and other lysosomal enzyme activities were assessed as previously described in the literature. Patients with metachromatic leukodystrophy (MLD) were used as controls. Thirty-two treated patients (twenty-nine GD1 and three GD3, all on ERT except for one GD type on SRT with eliglustat) and three untreated patients (one GD1, one GD2, and one GD3) were included. When analyzing only the treated GD1 group, a significant correlation was found between lyso-Gb1 and age (rho = -0.447, p = 0.001), ChT, and IgG levels (rho = 0.73, p < 0.001; and rho = 0.36, p = 0.03, respectively). Five GD1 patients (three females, mean age 40 years) also had their CSF collected and analyzed. The average measurement of lyso-Gb1 in CSF was 94 pmol/L (range: 57.1-157.9 pmol/L) versus <6.2 pmol/L in the control group (MLD). This is the first time, to the best of our knowledge, that lyso-Gb1 has been associated with IgG levels. While this finding reflects a risk for MGUS or MM and not only chronic plasma B-cell activation, it still requires further studies. Moreover, the analysis of CSF lyso-Gb1 levels in GD1 patients was demonstrated to be significantly higher than the control group. This raises the hypothesis that CSF lyso-Gb1 may serve as a valuable indicator for neurological involvement in GD, providing insights into the potential implications for neurological manifestations in GD, including GD1. The correlation between lyso-Gb1 and ChT levels in treated GD1 patients further underscores the interconnectedness of lysosomal markers and their relevance in monitoring.

Regression of Intermediate-High Risk Monoclonal Gammopathy of Undetermined Significance (MGUS) With Long-term Use of Curcumin: A Case Report.

Patients with intermediate-high risk MGUS are not offered therapeutic options to date and standard of care remains observation with re-evaluations of the patient every 3 to 6 months. Given the persistent risk of progression as well as potential complications experienced by some, and anxiety experienced by most patients, early intervention with non-toxic curcumin, aimed at potentially slowing down or stopping disease progression might be therapeutic. We present here an intermediate-high risk MGUS patient who has been taking curcumin for 16 years and has shown a decrease in disease markers and an increase in uninvolved immunoglobulins, adding to the body of evidence of benefit of curcumin to MGUS patients.

RAB22A as a predictor of exosome secretion in the progression and relapse of multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is an incurable malignant plasma cell disease. We explored the role of RAB22A in exosome secretion, epithelial-mesenchymal transition (EMT) and immune regulation. METHODS: We obtained MM samples from Gene Expression Omnibus (GEO) data sets. We downloaded the "IOBR" package, and used the "PCA" and "ssGSEA" algorithms to calculate the EMT scores and exosome scores. The "CIBERSORT" package was used to analyze the infiltration of immune cells. We extracted the exosomes of mesenchymal stem cell (MSC) to verify the biological function of RAB22A. RESULTS: The expression level of RAB22A in smoldering multiple myeloma (SMM) and MM patients was significantly higher than that in normal people and monoclonal gammopathy of undetermined significance (MGUS) patients, and the expression level of RAB22A in relapse MM patients was significantly higher than that in newly diagnosed patients. The EMT scores and exosome scores of high RAB22A group were significantly higher than those of low RAB22A group, and the exosome scores of MSC in recurrent patients were significantly higher than those of newly diagnosed patients. In addition, the infiltration levels of monocyte, NK cells resting, eosinophils, T cells regulatory and T cells CD4 memory activated were positively correlated with RAB22A. After down-regulating the expression of RAB22A in MM-MSC, the secretion of exosomes decreased. Compared with the exosomes of MSC in si-RAB22A group, the exosomes in control group significantly promoted the proliferation of MM. CONCLUSIONS: RAB22A is a potential therapeutic target to improve the prognosis of MM, which is closely related to exosome secretion, EMT and immune cell infiltration.

The effects of short-term, progressive exercise training on disease activity in smouldering multiple myeloma and monoclonal gammopathy of undetermined significance: a single-arm pilot study.

BACKGROUND: High levels of physical activity are associated with reduced risk of the blood cancer multiple myeloma (MM). MM is preceded by the asymptomatic stages of monoclonal gammopathy of undetermined significance (MGUS) and smouldering multiple myeloma (SMM) which are clinically managed by watchful waiting. A case study (N = 1) of a former elite athlete aged 44 years previously indicated that a multi-modal exercise programme reversed SMM disease activity. To build from this prior case study, the present pilot study firstly examined if short-term exercise training was feasible and safe for a group of MGUS and SMM patients, and secondly investigated the effects on MGUS/SMM disease activity. METHODS: In this single-arm pilot study, N = 20 participants diagnosed with MGUS or SMM were allocated to receive a 16-week progressive exercise programme. Primary outcome measures were feasibility and safety. Secondary outcomes were pre- to post-exercise training changes to blood biomarkers of MGUS and SMM disease activity- monoclonal (M)-protein and free light chains (FLC)- plus cardiorespiratory and functional fitness, body composition, quality of life, blood immunophenotype, and blood biomarkers of inflammation. RESULTS: Fifteen (3 MGUS and 12 SMM) participants completed the exercise programme. Adherence was 91 ± 11%. Compliance was 75 ± 25% overall, with a notable decline in compliance at intensities > 70% V̇O2PEAK. There were no serious adverse events. There were no changes to M-protein (0.0 ± 1.0 g/L, P =.903), involved FLC (+ 1.8 ± 16.8 mg/L, P =.839), or FLC difference (+ 0.2 ± 15.6 mg/L, P =.946) from pre- to post-exercise training. There were pre- to post-exercise training improvements to diastolic blood pressure (- 3 ± 5 mmHg, P =.033), sit-to-stand test performance (+ 5 ± 5 repetitions, P =.002), and energy/fatigue scores (+ 10 ± 15%, P =.026). Other secondary outcomes were unchanged. CONCLUSIONS: A 16-week progressive exercise programme was feasible and safe, but did not reverse MGUS/SMM disease activity, contrasting a prior case study showing that five years of exercise training reversed SMM in a 44-year-old former athlete. Longer exercise interventions should be explored in a group of MGUS/SMM patients, with measurements of disease biomarkers, along with rates of disease progression (i.e., MGUS/SMM to MM). REGISTRATION: https://www.isrctn.com/ISRCTN65527208 (14/05/2018).

Diagnosis and management of smouldering myeloma: A British Society for Haematology Good Practice Paper.

Multiple myeloma is a bone marrow-based plasma cell tumour that develops from asymptomatic pre-cursor conditions smouldering myeloma and monoclonal gammopathy of uncertain significance and all are characterised by the presence of a monoclonal protein in the blood. Diagnosis and distinction between these conditions is based on blood tests, the bone marrow biopsy and cross sectional imaging. There are various risk stratification models that group patients with smouldering myeloma into risk groups based on risk of progression to symptomatic disease. Management is mainly observational for patients with smouldering myeloma although clinical trials for high-risk disease may be available. Restaging is required if evidence for progression.

Retinopathy in a Patient With IgM MGUS: Causal Association or an Epiphenomenon?

BACKGROUND/AIM: The presence of a monoclonal gammopathy of undetermined significance (MGUS) even in small amounts may trigger tissue damage through immunological or other mechanisms, irrespective of the potential for malignant transformation. The aim of the study was to present a case of monoclonal gammopathy of clinical significance with ocular manifestations and discuss relevant literature. CASE REPORT: In our case, a patient presented with vision disturbances that was eventually attributed to the underlying IgM MGUS after extensive workup to exclude other potential etiologies. The patient showed a clinical response with the fixed-duration DRC (dexamethasone, rituximab, cyclophosphamide) regimen that persisted for at least 1.5 years. Herein, we present, in detail, the patient management and discuss the underlying pathophysiology of this rare entity with few available published data in this field. CONCLUSION: A high level of clinical suspicion is necessary in order to detect the association between MGUS and a clinical sign or symptom that cannot be attributed elsewhere.

Single monoclonal spike characterized as double monoclonal gammopathy in a patient with multiple myeloma: A rare finding.

Multiple myeloma (MM) is associated with the secretion of a unique monoclonal protein (M-protein) due to overproduction of immunoglobulin (Ig) by a clone of abnormally proliferating plasma cells. However, in 4% of the cases more than one M-protein can be found. This category of gammopathies is called "double monoclonal gammopathies." Here, we present a rare case of MM with double monoclonal gammopathy, where the presence of both M-proteins was observed in the single sharp peak on capillary zone electrophoresis (CZE). Further the interference of Hook effect is also discussed. Double monoclonal gammopathies need to be identified to increase diagnostic accuracy and reliability, and to get a better understanding of the disease pathogenesis and progression.

Sjögren's disease activity associates with cardiovascular disease and monoclonal gammopathy: a university cohort study of disease activity and comorbidities.

BACKGROUND: We used the University of Wisconsin cohort to determine the extent to which the EULAR Sjögren's syndrome disease activity index (ESSDAI) was associated with comorbidities that contribute to mortality. METHODS: Our University of Wisconsin, Madison cohort had 111 patients with Sjögren's Disease (SjD) by 2016 ACR/EULAR criteria and 194 control patients with sicca. Our study was performed from March 1st, 2020 through April 1st, 2023. We collected data using a standardized collection tool, including components of the Charlson Comorbidity Index (CCI). Stratifying our SjD patients by ESSDAI < 5 and ESSDAI ≥ 5, we assessed differences in comorbidities associated with mortality. RESULTS: At time of SjD diagnosis, the ESSDAI ≥ 5 group had increased odds of peripheral vascular disease compared to controls (OR 10.17; 95% CI 1.18-87.87). Patients with a current ESSDAI ≥ 5 were more likely to have a myocardial infarction compared to controls (OR 9.87; 95% CI 1.17-83.49). SjD patients had increased prevalence of monoclonal gammopathy compared to controls (9.3% vs 0.5%, p < 0.001). SjD patients with high ESSDAI at diagnosis had greater prevalence of monoclonal gammopathy compared to the SjD patients with a low ESSDAI (16% vs 5%, p = .04). As reported elsewhere, the ESSDAI ≥ 5 group had increased odds of chronic pulmonary disease (OR 4.37; 95% CI 1.59-11.97). CONCLUSION: We found high ESSDAI scores were associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. Furthermore, monoclonal gammopathy was more frequent in SjD patients compared to sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario. Key Points • High ESSDAI scores are associated with worse cardiovascular outcomes, specifically peripheral vascular disease and myocardial infarction. • Monoclonal gammopathy is more frequent in SjD patients than sicca controls, supporting screening for monoclonal gammopathy in the appropriate clinical scenario.

Establishing Monoclonal Gammopathy of Undetermined Significance as an Independent Pre-Disease State of Multiple Myeloma Using Raman Spectroscopy, Dynamical Network Biomarker Theory, and Energy Landscape Analysis.

Multiple myeloma (MM) is a cancer of plasma cells. Normal (NL) cells are considered to pass through a precancerous state, such as monoclonal gammopathy of undetermined significance (MGUS), before transitioning to MM. In the present study, we acquired Raman spectra at three stages-834 NL, 711 MGUS, and 970 MM spectra-and applied the dynamical network biomarker (DNB) theory to these spectra. The DNB analysis identified MGUS as the unstable pre-disease state of MM and extracted Raman shifts at 1149 and 1527-1530 cm-1 as DNB variables. The distribution of DNB scores for each patient showed a significant difference between the mean values for MGUS and MM patients. Furthermore, an energy landscape (EL) analysis showed that the NL and MM stages were likely to become stable states. Raman spectroscopy, the DNB theory, and, complementarily, the EL analysis will be applicable to the identification of the pre-disease state in clinical samples.

[Clinical Significance of Serum Free Light Chain in Monoclonal Gammopathy].

OBJECTIVE: To investigate the expression and clinical significance of serum free light chain (sFLC) in patients with monoclonal gammopathy (MG). METHODS: The peripheral blood of 98 patients with MG and 30 healthy volunteers were collected. The level of sFLC was detected by immunoturbidimetry, and the value of sFLC in diagnosis, disease severity, and efficacy evaluation was analyzed. RESULTS: Among 98 MG patients, there were 58 males and 40 females, 45 cases of monoclonal gammopathy of renal significance (MGRS), 33 cases of monoclonal gammopathy of undetermined significance (MGUS), 20 cases of hematological malignancy (HM), 58 cases of IgG type, 26 cases of IgA type, 7 cases of IgM type, 5 cases of light chain type, 2 cases of non-secreting type, 35 cases of κ type, 63 cases of λ type, 53 cases of renal insufficiency, 45 cases of normal renal function. The expression levels of sFLC-κ and sFLC-λ in MG patients were significantly higher than those of the control group (P <0.01). The expression levels of sFLC-κ and sFLC-λ in HM patients were significantly higher than MGRS and MGUS patients, and in MGRS patients were also significantly higher than MGUS patients (P <0.05). Patients with abnormal renal function had higher expression levels of sFLC-κ and sFLC-λ than patients with normal renal function (P <0.01). sFLC-κ and sFLC-λ were positively correlated with the expression level of globulin (r =0.392, r =0.435) and ß2-MG (r =0.403, r =0.468) in MG patients, as well as serum creatinine in patients with abnormal renal function (r =0.586, r =0.631), while no significant correlation was found with age, sex, albumin, lactate dehydrogenase, and serum calcium. After treatment, the levels of sFLC-κ and sFLC-λ were significantly decreased (P <0.01). CONCLUSION: sFLC is significantly elevated in MG patients and can be quickly detected with high sensitivity, which is helpful for the diagnosis of disease type, judgment of disease severity, and evaluation of therapy.

Laboratory reflex testing strategy for the early identification of primary care patients with multiple myeloma.

OBJECTIVES: Our objective was to shorten the screen for multiple myeloma (MM), through reflex testing. DESIGN AND METHODS: The clinical laboratory in the public University Hospital of San Juan (Alicante, Spain), serves 234,551 inhabitants. Through an intervention agreed with general practitioners, the Laboratory Information System (LIS) automatically registered serum immunoglobulins (Ig) when serum total proteins (STP) > 80 g/L for the first time in primary care patients. When concomitantly one Ig presented a value above and one below its reference interval, the LIS automatically registered a serum protein electrophoresis (SPEP). When a monoclonal peak in SPEP, immunofixation electrophoresis (IFE) for the typification of monoclonal bands (MB) was performed. If MB were present, a comment in the report explained the intervention. The number of additionally registered Ig, SPEP, IFE, and new diagnosis of MM were counted. The number of days elapsed from the report of elevated STP result to the final MM diagnosis was also counted as median and interquartile range (IQR), and compared to a pre intervention period. RESULTS: 2071 cases of hyperproteinemia were identified, and had 91 a monoclonal peak, confirmed by IFE. In 35 patients it was a new finding, and 9 were diagnosed with MM, 3 Waldestrom macroglobulinemia, 2 lymphoplasmacytic lymphoma and 21 monoclonal gammopathy of undetermined significance. The number of days elapsed from hyperproteinemia to diagnosis was lower in the intervention period (21.5 vs 119.4) (P < 0.01). As our results show, in addition to shortening the time to diagnosis, an increased rate of detection of plasma cell disorders was observed when using our algorithm. CONCLUSIONS: The above laboratory interventions agreed with clinicians, making use of laboratory technology resulted in early identification of MM.

Development and validation of a diagnostic nomogram model for predicting monoclonal gammopathy of renal significance.

In patients with kidney disease, the presence of monoclonal gammopathy necessitates the exploration of potential causal relationships. Therefore, in this study, we aimed to address this concern by developing a nomogram model for the early diagnosis of monoclonal gammopathy of renal significance (MGRS). Univariate and multivariate logistic regression analyses were employed to identify risk factors for MGRS. Verification and evaluation of the nomogram model's differentiation, calibration, and clinical value were conducted using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis. The study encompassed 347 patients who underwent kidney biopsy, among whom 116 patients (33.4%) were diagnosed with MGRS and 231 (66.6%) with monoclonal gammopathy of undetermined significance. Monoclonal Ig-related amyloidosis (n = 86) and membranous nephropathy (n = 86) was the most common renal pathological type in each group. Notably, older age, abnormal serum-free light chain ratio, and the absence of microscopic hematuria were identified as independent prognostic factors for MGRS. The areas under the ROC curves for the training and verification sets were 0.848 and 0.880, respectively. In conclusion, the nomogram model demonstrated high accuracy and clinical applicability for diagnosing MGRS, potentially serving as a valuable tool for noninvasive early MGRS diagnosis.

Early detection of multiple myeloma: A first step towards a screening programme.

Novel therapies for multiple myeloma have substantially improved the prognosis, but before patients are able to benefit from treatment, a diagnosis must have been made. The Myeloma UK laboratory working group has developed a three-part tool box to help primary care physicians to suspect myeloma despite mostly vague symptoms, to do the right tests and to derive the proper conclusions from the results. Commentary on: Drayson et al. Laboratory practice is central to earlier myeloma diagnosis; utilising a primary care diagnostic tool and laboratory guidelines integrated into haematology services. Br J Haematol 2024;204:476-486.

Immune-Pathogenesis of Myeloma.

This research indicates that monoclonal gammopathy of undetermined significance (MGUS) and myeloma may stem from chronic immune activation and inflammation, causing immune dysfunction and spatial immune exclusion. As the conditions progress, a shift toward myeloma involves ongoing immune impairment, affecting both innate and adaptive immunity. Intriguingly, even in advanced myeloma stages, susceptibility to immune effector cells persists. This insight highlights the intricate interplay between immune responses and the development of these conditions, paving the way for potential therapeutic interventions targeting immune modulation in the management of MGUS and myeloma.

Molecular Pathogenesis of Multiple Myeloma: Clinical Implications.

Multiple myeloma is a malignancy of bone-marrow-localized, isotype-switched plasma cells that secrete a monoclonal immunoglobulin and cause hyperCalcemia, Anemia, Renal failure, and lytic Bone disease. It is preceded, often for decades, by a relatively stable monoclonal gammopathy lacking these clinical and malignant features. Both conditions are characterized by the presence of types of immunoglobulin heavy gene translocations that dysregulate a cyclin D family gene on 11q13 (CCND1), 6p21 (CCND3), or 12q11 (CCND2), a maf family gene on 16q23 (MAF), 20q11 (MAFB), or 8q24 (MAFA), or NSD2/FGFR3 on 4p16, or the presence of hyperdiploidy. Subsequent loss of function of tumor suppressor genes and mutations activating MYC, RAS, NFkB, and cell cycle pathways are associated with the progression to malignant disease.

Surgical Approach for Monoclonal Gammopathy of Undetermined Significance-Related Ocular Copper Deposition.

PURPOSE: The aim of this study was to present the surgical management of a patient with ocular copper deposition associated with monoclonal gammopathy of undetermined significance (MGUS). METHODS: This is a case report of a 44-year-old man with MGUS who presented to us with bilateral diffuse deposition of copper in the cornea and lens. RESULTS: Despite initiating systemic therapy for MGUS, no corneal clearing was observed. A decision was made to proceed with cataract extraction in the left eye given worsening vision. Despite trypan blue staining and a central descemetorhexis, visualization remained too poor to complete phacoemulsification. Pars plana lensectomy and vitrectomy to remove the residual lens material and placement of a posterior chamber intraocular lens in the sulcus with endoillumination was subsequently performed. As vision in the left eye steadily improved postoperatively, cataract surgery was then performed in the right eye. With use of trypan blue, creation of a 6-mm central descemetorhexis, and a retinal light pipe for endoillumination anteriorly to augment visualization, capsulorhexis, phacoemulsification, and insertion of intraocular lens in the bag were completed without difficulty. The patient's vision improved at subsequent follow-ups, reaching a final best-corrected visual acuity of 20/20-1 in the right eye and 20/25-1 in the left eye. CONCLUSIONS: Ocular copper deposition is a rare manifestation of MGUS. Cataract extraction is challenging, often requiring advanced techniques. Endoillumination is useful to improve visualization through the dense corneal copper deposition.