Bence-Jones Research Articles

Heimdall, an alternative protein issued from a ncRNA related to kappa light chain variable region of immunoglobulins from astrocytes: a new player in neural proteome

The dogma “One gene, one protein” is clearly obsolete since cells use alternative splicing and generate multiple transcripts which are translated into protein isoforms, but also use alternative translation initiation sites (TISs) and termination sites on a given transcript. Alternative open reading frames for individual transcripts give proteins originate from the 5′- and 3′-UTR mRNA regions, frameshifts of mRNA ORFs or from non-coding RNAs. Longtime considered as non-coding, recent in-silico translation prediction methods enriched the protein databases allowing the identification of new target structures that have not been identified previously. To gain insight into the role of these newly identified alternative proteins in the regulation of cellular functions, it is crucial to assess their dynamic modulation within a framework of altered physiological modifications such as experimental spinal cord injury (SCI). Here, we carried out a longitudinal proteomic study on rat SCI from 12 h to 10 days. Based on the alternative protein predictions, it was possible to identify a plethora of newly predicted protein hits. Among these proteins, some presented a special interest due to high homology with variable chain regions of immunoglobulins. We focus our interest on the one related to Kappa variable light chains which is similarly highly produced by B cells in the Bence jones disease, but here expressed in astrocytes. This protein, name Heimdall is an Intrinsically disordered protein which is secreted under inflammatory conditions. Immunoprecipitation experiments showed that the Heimdall interactome contained proteins related to astrocyte fate keepers such as “NOTCH1, EPHA3, IPO13” as well as membrane receptor protein including “CHRNA9; TGFBR, EPHB6, and TRAM”. However, when Heimdall protein was neutralized utilizing a specific antibody or its gene knocked out by CRISPR-Cas9, sprouting elongations were observed in the corresponding astrocytes. Interestingly, depolarization assays and intracellular calcium measurements in Heimdall KO, established a depolarization effect on astrocyte membranes KO cells were more likely that the one found in neuroprogenitors. Proteomic analyses performed under injury conditions or under lipopolysaccharides (LPS) stimulation, revealed the expression of neuronal factors, stem cell proteins, proliferation, and neurogenesis of astrocyte convertor factors such as EPHA4, NOTCH2, SLIT3, SEMA3F, suggesting a role of Heimdall could regulate astrocytic fate. Taken together, Heimdall could be a novel member of the gatekeeping astrocyte-to-neuroprogenitor conversion factors.

Discordance of light chain isotypes between serum and glomerular deposits in proliferative glomerulonephritis with monoclonal IgG deposits: a case report and review of the literature

BackgroundProliferative glomerulonephritis with monoclonal immunoglobulin G (IgG) deposits (PGNMID) is a disease entity with nonorganized granular glomerular deposition with monoclonal proteins of both heavy and light chains. Dysproteinemia was observed in only 30% of the patients with PGNMID. We herein report a case of PGNMID with discrepancy between serum and glomerular deposits.Case presentationThe patient was a 50-year-old man who had been followed at a local clinic due to hypertension, type 2 diabetes, hyperlipidemia, hyperuricemia, fatty liver, and obesity. Proteinuria had been noted five years previously, and he had been referred to a hematology department due to hyperproteinemia, high gamma globulin, and κ Bence-Jones protein (BJP) positivity one year previously. Bone marrow aspiration showed 5% plasma cells, and he was referred to the nephrology department to evaluate persistent proteinuria. He was hypertensive, and his estimated glomerular filtration rate was 54.2 ml/min/1.73 m2. His urinary protein level was 0.84 g/g⋅Cr. Urine and serum immunofixation showed BJP-κ type and IgG-κ type, respectively. Kidney biopsy showed an increase in mesangial cells and matrix without nodular lesions under a light microscope. Immunofluorescence microscopy showed granular deposits of IgG and C3 on the capillary wall and weak positivity for C1q. IgG3 was predominant among the IgG subclasses, and intraglomerular κ and λ staining was negative for κ and positive for λ. Direct fast scarlet staining was negative. Electron microscopy showed lumpy deposits without a fibrillar structure in the subepithelial area. Based on the above findings, a diagnosis of membranous nephropathy-type PGNMID was made. Since proteinuria increased gradually after three years of treatment with valsartan (40 mg, daily), oral prednisolone (30 mg, daily) was initiated, which led to decreased proteinuria. The dose of oral prednisolone was gradually tapered to 10 mg per day. At that time, proteinuria was 0.88 g/g⋅Cr. We found 204 cases in 81 articles in the PubMed database, among which 8 showed discrepancy in the heavy and/or light chains between serum and kidney.ConclusionsWe experienced a case of membranous nephropathy-type PGNMID with discrepancy in light chains between serum and kidney that was successfully treated with oral prednisolone.

Diagnostic and Prognostic Value of PACAP in Multiple Myeloma

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a multifunctional neuropeptide with well-known anti-inflammatory, antioxidant, antitumor, and immunomodulatory effects. PACAP regulates the production of various proinflammatory factors and may influence the complex cytokine network of the bone marrow microenvironment altered by plasma cells, affecting the progression of multiple myeloma (MM) and the development of end-organ damage. The aim of our study was to investigate the changes in PACAP-38 levels in patients with MM to explore its value as a potential biomarker in this disease. We compared the plasma PACAP-38 levels of MM patients with healthy individuals by ELISA method and examined its relationship with various MM-related clinical and laboratory parameters. Lower PACAP-38 levels were measured in MM patients compared with the healthy controls, however, this difference vanished if the patient achieved any response better than partial response. In addition, lower peptide levels were found in elderly patients. Significantly higher PACAP-38 levels were seen in patients with lower stage, lower plasma cell infiltration in bone marrow, lower markers of tumor burden in serum, lower total urinary and Bence-Jones protein levels, and in patients after lenalidomide therapy. Higher PACAP-38 levels in newly diagnosed MM patients predicted longer survival and a higher probability of complete response to treatment. Our findings confirm the hypothesis that PACAP plays an important role in the pathomechanism of MM. Furthermore, our results suggest that PACAP might be used as a valuable, non-invasive, complementary biomarker in diagnosis, and may be utilized for prognosis prediction and response monitoring.

DP25 Widespread subcutaneous nodular kappa light chain amyloidosis

Abstract A 69-year-old woman was referred to the dermatology department for evaluation of multiple widespread subcutaneous lesions involving the neck, torso and limbs. These lesions, initially diagnosed in the community as lipomas, had been slowly progressing in size and number for 3 years. She had remained systemically well. Her only medical history was essential thrombocythaemia. She took no regular medication. On examination, there were multiple subcutaneous lesions appreciated on palpation with no overlying epidermal change. The patient was experiencing pain in a sciatic distribution. Magnetic resonance imaging of the femur showed a 12-cm enhancing area of subcutaneous nodularity encasing the sciatic nerve. Computed tomography of the chest, abdomen and pelvis showed multiple subcutaneous, ill-defined, soft tissue lesions of the anterior abdominal wall with no lymphadenopathy or organ abnormality. Deep incisional biopsies from two separate locations were completed. There was an unremarkable epidermis and dermis. In the subcutaneous fat, the septae appeared thickened alongside thickened elastic fibres and a prominent multifocal granulomatous reaction with a high degree of elastophagocytosis. There were multifocal aggregates of plasma cells that displayed no cytological atypia. In situ hybridization showed strong kappa light chain restriction. Plasma protein electrophoresis was completed and confirmed a paraprotein band in the gamma region of IgM kappa. Full blood count revealed a high platelet count (585 × 109 cells L–1) but was otherwise unremarkable alongside normal renal and liver function, bone profile, lactate dehydrogenase, B2 microglobulin, Bence–Jones proteins and infection screen. A Congo red stain was performed on the original histological samples. This showed apple green birefringence under polarized light-confirming amyloid. Haematology completed a bone marrow biopsy, which was normal. Referral to the National Amyloid Centre was made. Serum amyloid P scan showed no visceral involvement. A diagnosis of subcutaneous amyloid kappa light chain subtype (AL) was made. The patient has since commenced rituximab, bortezomib (Velcade®), cyclophosphamide and dexamethasone (R-VCD) chemotherapy at 4-weekly intervals over a 4-month period. Primary localized cutaneous amyloidosis is characterized by extracellular deposition of amyloid protein in the skin without evidence of systemic involvement and is often subtyped into macular, papular and nodular. Amyloidoma (tumoral amyloidosis) is rare and defined as a solitary localized deposit of amyloid. There are only four case reports in the literature of multiple subcutaneous amyloid deposits, and only one of these cases was of AL (light chain) vs. amyloid A (AA) subtype. This case showed nodules restricted to the neck (Nguyen TU, Oghalai JS, McGregor DK et al. Subcutaneous nodular amyloidosis: a case report and review of the literature. Hum Pathol 2001; 32:346–8). To our knowledge, this is the first case of widespread kappa light chain subcutaneous amyloidosis.

Isolated bone marrow amyloid light chain amyloidosis coexisting with multiple myeloma.

A 62-year-old woman was diagnosed with Bence-Jones protein multiple myeloma in another hospital. She referred sternum pain and a clavicle fracture. Nuclear magnetic resonance showed multiple lytic lesions in clavicle, rib, vertebra, humerus and sternum. She was referred to our hospital because of an inadequate response to treatment. Complete blood count, kidney function, calcium, lactate dehydrogenase and beta-2-microglobulin did not show abnormalities. Monoclonal immunoglobulins in serum were not detected. Immunofixation in serum and urine was positive for kappa light chain. A bone marrow aspirate was performed in the sternum. The sternal aspirate showed a patchy infiltration by plasma cells (CD19–, CD56+, CD117+) of variable size, some of them binucleated with a cytoplasm with a flammig appearance. Nebulous amorphous basophilic protein material suggestive of amyloid was also observed (Figure 1a). Congo red stain was positive, and the microscope fluorescence showed apple-green birefringence under polarized light and confirmed the suspicion (Figure 1b). Fluorescence in situ hybridisation (FISH) showed the t (11;14) (q13;q32); the TP53 was normal. The study in the fat tissue did not show amyloid and the renal and heart functions were normal. The patient was diagnosed of amyloid light chain amyloidosis associated with multiple myeloma and started treatment with bortezomib, lenalidomide and dexamethasone. The response was suboptimal, and daratumumab was added to the treatment. This case demonstrates the importance of recognizing the presence of amyloid in bone marrow aspiration. This diagnosis is relevant for the prognostic and therapeutic implication. All authors have contributed equally to the manuscript. None The authors declare they have no conflicts of interest. The authors received no specific funding for this work. A written informed consent was obtained from the patient.

Parathyroid Carcinoma Mimicking Multiple Myeloma: A Tale of Refractory Hypercalcemia

Primary hyperparathyroidism yields various symptoms, including hypercalcemia, pathological fracture, and renal impairment. Parathyroid carcinoma is the rarest cause of primary hyperparathyroidism, accounting for <1% of the cases. We reported a case of a 46-year-old male with closed fractures at the humerus and femur. Further findings revealed severe refractory hypercalcemia, renal impairment, anemia, and bone lytic lesion (CRAB). No palpable cervical mass was identified. Surprisingly, the serum protein electrophoresis was normal, and urinary Bence-Jones protein was negative along with normal bone marrow aspiration. Hence, multiple myeloma was unlikely. The intact parathyroid hormone level was very high, along with a suspicious nodule on the left thyroid lobe (TIRADS 4). Total thyroidectomy and total parathyroidectomy were performed. The post-surgical pathological examination confirmed the diagnosis of parathyroid carcinoma. After the surgery, the patient was in stable condition with normal intact parathyroid hormone and serum calcium levels. In this case, primary hyperparathyroidism was caused by parathyroid carcinoma with “CRAB” symptoms, mimicking multiple myeloma. Primary hyperparathyroidism should be considered in the patient with refractory hypercalcemia.

Biochemical profile of Bence-Jones type multiple myeloma.

Multiple myeloma (MM) is a malignant tumor occurring from plasma cells that produce an abnormal monoclonal immunoglobulin - a paraprotein. A distinctive feature of Bence-Jones myeloma is the excretion of monoclonal free light chains of immunoglobulins with 24h urine, and the absence of monoclonal intact immunoglobulins secretion. Comprehensive analysis of biochemical parameters in blood serum and 24h urine in patients with Bence-Jones multiple myeloma using electrophoretic and immunoturbidimetric methods to assess their sensitivity as biomarkers. 50 patients with a morphologically confirmed diagnosis of MM of the Bence-Jones immunochemical type were examined. 28 people without oncological diseases were examinedas a control. Detection of monoclonal secretion in blood serum and daily urine was performed by immunofixation electrophoresis on the Hydrasys 2 electrophoretic system (Sebia). The determination of free light chains of immunoglobulins (FLC) was performed by the immunoturbidimetric method (Binding Site) on an Advia 1800 analyzer (Siemens). Analysis of IgG, IgA, IgM, β2-microglobulin and C-reactive protein was performed on Cobas 6000 analyzer (Roche). The median excretion of Bence-Jones protein in 24h urine of MM patients was 0.49 g/24h (0.06-2.45 g/24h). In the blood serum, in 86% of cases, the presence of paraproteinemia, represented by κ and λ type light chains of immunogloublins was detected. At the same time, the frequency of detection of monoclonal secretion in blood serum in Bence-Jones type λ myeloma was 95.7%, which was statistically significantly higher than the frequency of detection of monoclonal secretion of type κ - 77.8%. In patients with identified paraproteinemia, Bence-Jones protein excretion in daily urine (median 0.82 g/day) was statistically significantly higher than in patients without a monoclonal component detected in blood serum (median 0.04 g/24h). The levels of FLC in blood serum obtained by immunoturbidimetry in Bence-Jones myeloma of the corresponding type were higher than the reference levels in 100% of cases. The median level of κ-FLC reached 4358 mg/l, λ-FLC - 2225 mg/l, which was statistically significantly higher than the control levels. The median concentrations of IgG, IgA and IgM in patients with Bence-Jones myeloma were statistically significantly lower than in the control group, while the medians of β2-microglobulin and C-reactive protein were significantly higher than in the control. Our investigation showed high diagnostic efficiency of electrophoretic and immunoturbidimetric analysis of monoclonal secretion in patients with Bence-Jones MM, while FLC analysis demonstrated maximum sensitivity. Bence-Jones MM revealed biochemical signs of secondary immunodeficiency and general inflammatory syndrome.

Diet and Proteinuria: State of Art.

Proteinuria is a broad term used to describe the pathological presence of proteins, including albumin, globulin, Bence-Jones protein, and mucoprotein in the urine. When persistent, proteinuria is a marker of kidney damage and represents a reliable predictor of the risk of progression of renal failure. Medical nutrition therapy is imperative for patients with proteinuria because it may slow the progression of renal disease. The aim of this review is to explore different nutritional approaches in the management of proteinuria and their influence on pathophysiological processes. As such, protein restriction is the main dietary intervention. Indeed, other management approaches are frequently used to reduce it regarding micro and macronutrients, but also the dietary style. Among these, the nutritional approach represents one of the most used and controversial interventions and the studies rarely take the form of randomized and controlled trials. With this work we aspire to analyze current clinical knowledge of how nutrition could influence proteinuria, potentially representing a useful tool in the management of proteinuric nephropathy.

Multiple Myeloma with Skin and Renal Involvement and Anaplasma Phagocytophilum Co-Infection in a Dog

Abstract An 11-year-old male Cocker Spaniel was presented with acute onset of apathy, polyuria and polydipsia. Blood examination showed hypoalbuminemia and hyperglobulinemia, while electrophoresis revealed monoclonal gammopathy. Subsequent tests showed glycosuria, proteinuria, a positive serology test for Anaplasma spp. and ultrasonographical changes of the liver and spleen. Urine electrophoresis confirmed the presence of Bence-Jones protein. The dog’s condition deteriorated, and the dog had developed skin lesions on the neck and body. The owner decided to euthanize the dog and agreed to bone marrow and skin biopsy. Bone marrow cytology revealed an increased number of plasma cells and several cellular atypia. Histopathology of the skin lesions showed a round cell tumor of lymphoid or plasmacytoid origin. Subsequent immunohistology supported the diagnosis of multiple myeloma cutaneous involvement. This case report describes unusual features observed in a dog with multiple myeloma.

Chromosomal Aberrations and Bence-Jones Proteins as a Significant Biomarkers in Multiple Myeloma

Multiple Myeloma (MM) is a hematological malignity associated with the proliferation and accumulation of bone marrow terminally differentiated plasma cells. The outcomes of patients with MM have dramatically improved over the past decade with the establishment of novel agents. Nonetheless, the disease presents considerable heterogeneity in clinical course, presentation, and survival. Molecular and chromosomal analyses were performed on 46 patients with MM. The survival time of patients with MM concerning molecular and chromosome stratification showed that 20% of them were with high risk [hypodiploid (gain1q, loss1p) Del17p, Del13q, t(11;14) t(4;14) and multiple mutations] who survived 60 months and the median survival time in these patients was 20.8 months. In patients with MM who had a standard risk, death outcome was not registered during the observation period. Taking into account, all MM patients included in our study, Bence Jones proteins in the urine wеre present in 35.8% of ММ patients, while in 64.2%, their presence was not observed. The percentage difference is statistically significant The utilization of these crucial biomarkers in the clinical background for this disease in the future can only be achieved through thorough evaluation and validation in clinical trials.

Biochemical profile of multiple myeloma about 50 cases

Multiple myeloma (MM) is a clonal proliferation of plasma cells invading the bone marrow and secreting monoclonal immunoglobulin. In order to study the epidemiological and biological and biochemical characteristics of MM, we carried out a retrospective work on a cohort of 50 cases collected at the Avicenna Military Hospital in Marrakesh, during a period of 5 years (from January 2013 to December 2017). Our study included 32 men (64%) and 18 women (36%), with an average age of 60.6 years, with extremes at 44 and 87 years. The circumstances of discovery were dominated by bone pain and alteration in general condition, which are revealing in more than 65% of cases. Biologically: the sedimentation rate was accelerated in 86% of cases, a monoclonal peak appearance was revealed on serum proteins electrophoresis in 88%of cases, most often located in the γ zone (64%), a predominance of the Ig G isotype (64%), and kappa light chains in 60% of cases, Bence Jones protein (BJP) was found in 7 patients, i.e. 14% of cases, and plasmacytosis over 10% was found on the myelograms in 90 % of cases.

B2 Microglobulin and Bence Jones Proteinuria Guide the Diagnosis of Idiopathic AA Amyloidosis: A Journal to Diagnosis

Amyloidosis is a disease caused by the extracellular deposition of pathological insoluble fibrillary protein in multiple tissues and may result in severe organ dysfunction. There are two major forms of amyloidosis: AL amyloid and AA amyloidosis, which complicates any chronic inflammatory condition, including rheumatologic, chronic infections, and certain neoplasms. In small but increasing numbers, the chronic inflammatory state underlying AA amyloidosis remains obscure, despite extensive investigations, which are known as idiopathic. In the current case, the first extensive evaluation to determine the inflammatory disease was negative. The patient had B2 microglobulin elevation and Bence jones proteinuria, which are non-specific findings, but are not conclusive, for malignancies. The diagnosis of Idiopathic AA amyloidosis was guided by understanding the pathophysiology of B2 microglobulin and Bence jones proteinuria along with excluding all other etiologies. Unfortunately, the development of restrictive cardiomyopathy and ESRD within 3 months indicates a rapid progression and poor prognosis in this patient. Clinicians may not be familiar that B2 microglobulin and Bence jones proteinuria are also found in amyloidosis, which may delay the diagnosis. Inflammatory process and kidney injury due to AA amyloidosis caused previous markers positivity in our patient. It is plausible that delays in diagnosis may be multi-faceted and heavily influenced by the average age of the patient, the complexity and the rareness of the disease. Also, non-disease-specific symptoms may reduce the likelihood of a prompt diagnosis. Therefore, establishing the diagnosis is difficult, and early diagnosis requires high clinical suspicion.

Effect of MAGE-C1 Gene Expression on Prognosis and Effectiveness of Bortezomib-Containing Courses in Multiple Myeloma

Introduction. The group of genes, encoding cancer-testis antigens is actively studied as a new markers of refractory in some diseases, including multiple myeloma (MM). It is suggested that the MAGE-C1 gene in MM may be considered as an additional marker predicting the effectiveness of therapy.Purpose. Determine of MAGE-C1 gene expression by quantitative real-time polymerase chain reaction (qRT-PCR) in MM patients and assess the correlation of expression with some laboratory parameters and response on bortezomib-containing therapy.Patients and methods. A prospective study from February 2019 to July 2021 included 76 MM patients (43 men and 33 women) aged 35 to 82 years (median 58). The level of MAGE-C1 gene expression by qPCR-PCR in bone marrow samples, enriched with CD138+ cells, was determined for all patients. Quantity of MAGE-C1 expression was calculated with 2ΔCt method relative to housekeeping gene expression. Plasma cell content ranged from 1 to 89% (median 26%), monoclonal paraprotein secretion vary from 2.1 to 82.1 g/l, Bence-Jones protein in urine (from trace values to 12.54 g/day) was determined in 50 patients. High - risk cytogenetic [t(4; 14)(p16; q32), del17p] was documented in 22 patients, bone plasmocytomas - in 36 patients, myeloma nephropathy - in 17. All patients recieved induction with bortezomib - containing courses. Median follow-up duration: 14 months (1-22 months). As a control, similar bone marrow cells of 7 healthy donors were investigated.Results. The average value of MAGE-C1 expression in donors was 0.01 ± 0.007, a range of values vary from 0.0003 to 0.06. Gene expression MAGE-C1 index > 0.06 is accepted as increased expression. High serum lactate dehydrogenase (LDH) level (higher than the upper limit of reference values) was observed in patients with high MAGE-C1 gene expression [median - 0.35], normal LDH-level (≤ 260 U/L) was observed in patients with lower MAGE-C1 gene expression [median - 0.04]; p < 0.0001 (Figure 1). Negative correlation was found between the content of hemoglobin (Hb) and level of MAGE-C1 expression: Hb ≥ 12.0 g/dl was observed in patients with increased MAGE-C1 expression [median - 0.27], and Hb 5.5-11.8 g/dl - in patients with lower expression indices [median 0.1]; p=0,034.Antitumor response was evaluated after induction therapy in 51 patients. In 100% of patients with MAGE-C1 expression of ≤ 0.06 ≥ partial response (PR) was achieved, while in patients with MAGE-C1 expression of 0.07-1.0 ≥ PR was achieved in 84.6% of cases, and in patients with MAGE-C1 expression of > 1.0 - in 58%; p > 0.05. Besides, patients with ≥ PR had a level of MAGE-C1 expression lower than patients with a refractory to bortezomib [median 0.17 vs 1.14]; p = 0.04 (Figure 2).Conclusions. High MAGE-C1 gene expression in MM patients is associated with an increase in LDH, which corresponds to stage III by R-ISS. Probability of achievement of the antitumor response ≥ PR on the bortezomib-containing induction is reliable above at patients with low MAGE-C1 expression while the hyperexpression of this gene is followed by a refractory to a bortezomib therapy. Further study of MAGE-C1 gene expression may promote a personalized approach in the choice of antitumor therapy. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

An Unexplained Hyperphosphatemia in an Hispanic Woman , a Diagnosis Challenge

IntroductionHyperphosphatemia could be a finding in renal failure, tumor lysis syndrome, hypoparathyroidism, and ingestion of exogenous phosphate. We present the case of a woman with hyperphosphatemia in which we finally diagnosed multiple myeloma, serum phosphate level achieved normal range after chemotherapy started. Although hyperphosphatemia in multiple myeloma is a very rare finding, there are some reports. The proposed mechanisms include a large amount of paraproteins that interferes with phosphorus level determination showing a false increased level. When samples have been deproteinated before analysis, serum phosphorus level can decrease obtaining a true level. This case reminds clinicians the importance of seeking additional causes for abnormal phosphorus levels before starting treatments that could lead to hypophosphatemia.Case reportAn hispanic woman at the 7th decade of life that only suffered from controlled hypothyroidism, who assisted with complaints of axial pain mainly in thoracic and lumbar segments. She denied neurological and B symptoms. She had a CT scan performed and was referred to the hematology service.On clinical examination we didn't find any neurological signs, no megalies and no palpable nodes. The patient brought a CT spine scan showing thoracic images suggestive of mets with collapse of 50% in T12-L1 and a mass in S2.With these findings we decided to start intrahospitalary studies for excluding malignancy.Her relevant laboratories were: creatinine 0,7, BUN 25, Hemoglobin 9 gr/dl VCM 102 WBC 3330 Granulocytes 55% Platelet 222.000, UN 10,7, albumin 2.8, Lactate dehydrogenase 425. A series of labs seeking secondary causes of malignancy was made including plasmatic cell neoplasie.The hepatic function was normal but an unusually high Phosphorus level was detected (19,6) with normal calcemia (8.98), the tumoral biomarkers were in normal range (CEA, CA 19-9, Ca 125, AFP) and an elevated B2 microglobulin (8) was found. Additional labs included bence jones protein and PTH, both in normal range. A new Thoracic CT described mosaic infiltrates and an extensive bone involvement suggestive of lytic metastatic changes. The abdomen CT showed multiple lytic lesions in lumbo-sacral spine and pelvis, The skull radiography had lytic lesions too. The nephrology service was required by the Hyperphosphatemia and they asked about external intake of phosphorus finding that she was taking “hydrolyzed collagen”, so they started iv fluid and chelators (aluminium hydroxide and no calcium chelators).Because of unresponsive hyperphosphatemia, nephrology started hemodialysis.Hematology found high IgG levels (5500) concluding the need for bone marrow studies . Finally a the bone marrow study was performed and prescribed steroids on suspicion of Multiple myeloma. Until this day the Phosphorus level still remained in high levels (17,7) despite hemodialysis sessions. The bone marrow study revealed a plasmatic cell population of 28,9% with big and abundant cytoplasm, some of them with binucleations suggestive of infiltration by plasmatic cell neoplasie. The seric electrophoresis revealed a paraprotein (seric protein of 9,3 with a monoclonal peak of gamma region of 3,4 gr/dl), the seric immunofixation was positive for a monoclonal IgG lambda component. With this report we began chemotherapy treatment for Myeloma with CyBorD regimen (Cyclophosphamide, Bortezomib, dexamethasone). After treatment was initiated, phosphorus level began to lower and achieved normal range (4.28) in the first two weeks. Then she was discharged to continue outpatient management. Nowadays she is receiving her 3rd chemotherapy cycle without complications, her phosphorus level still remains within normality.ConclusionsSpurious hyperphosphatemia in patients with paraproteinemias like multiple myeloma can occur. The IgG monoclonal can interfere with the phosphomolybdate principle used in the assay of serum phosphate on most automated chemistry analysers. For labs which do not have a multilayered film technology based system, a serial dilution analysis of the suspected analyte could be performed. DisclosuresNo relevant conflicts of interest to declare.

Primary Laryngeal Amyloidosis and CO2 Laser as the Treatment Modality

Introduction Amyloidosis is brought about by intracellular and/or extracellular accumulation of insoluble abnormal amyloid fibrils that alters the normal function of the tissues. Localized laryngeal amyloidosis is a rare disease which lacks long-term follow-up studies. It is prone to recurrence; hence meticulous excision is required. We are doing this study to analyse clinical features of primary laryngeal amyloidosis, the subsites commonly found in, and the effectiveness of CO2 laser as treatment modality. Materials and Methods It is a retrospective study of 13 patients diagnosed as Primary Laryngeal Amyloidosis in between 2005 to 2018, where clinical features, histologic and immuno-histochemical patterns of the patients were evaluated. Systemic amyloidosis was ruled out by the non-appearance of Bence-Jones proteins in urine and serum electrophoresis examination. Systemic workups were pursued during the follow-up. The patients were followed up 3 monthly for the first year, then 6 monthly after that, for 3 years. The last patient who underwent the surgery was in the 2018 and had just finished his 2nd follow up, while the rest have been followed up for 3 years. Results Hoarseness was the most common complaint in all the patients. The subsites most common for amyloid deposition were seen in the true vocal cords followed by supraglottis, anterior commissure, ventricle and the subglottis. Microscopically, the amyloid was deposited within the submucosa surrounded by lymphoplamocytic infiltration. All cases were treated with microlaryngoscopic CO2 Laser excision. With the exception of one patient, the rest had no recurrence. Conclusion Primary Laryngeal Amyloidosis is an uncommon benign disease that has a predisposition for recurrence. With use of CO2 laser as the primary treatment modality, the percentage of recurrence has drastically reduced. Systemic involvement should be ruled out. A frequent follow-up of the patients is desirable for early detection of recurrences. Laser is a novel treatment of laryngeal amyloidosis.

Comparison of 24-hour versus random urine samples for determination and quantification of Bence Jones protein in a South African population

BackgroundThe International Myeloma Working Group and College of American Pathologists recommend a 24-h urine collection to determine the Bence Jones protein (BJP) excretion level for monitoring treatment response in patients with multiple myeloma (MM). There are several issues related to sample collection and the method is prone to inaccuracy.ObjectiveThis study compared measured 24-h to random urine collections for the quantitation of BJP in a South African population.MethodsSixty-six patients with MM submitted random urine samples with their routine 24-h urine collection from April 2016 – March 2018. Measured 24-h urine BJP was compared to two estimated 24-h BJP excretions calculated as follows: Estimation 1 (E1): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 10. Estimation 2 (E2): Estimated 24-h BJP (mg/24 h) = Urine BJP/Creatinine ratio (mg/mmol) × 15 mg/kg for women or × 20 mg/kg for men.ResultsCorrelation of estimation equations E1 and E2 to the measured 24-h urine BJP was 0.893. Patients showed no difference in classification of treatment response using either the E1 or E2 estimation equations when compared to the measured 24-h urine BJP results.ConclusionThis study demonstrates that the estimated 24-h BJP shows a high degree of correlation with the measured 24-h BJP and can likely be used to monitor treatment response in South African patients with MM.

Role of adjunct plasma exchange or high cut-off hemodialysis in the management of myeloma cast nephropathy: A systematic review.

e20032 Background: Renal impairment by cast nephropathy is a common complication in multiple myeloma. Tubulointerstitial injury results from precipitation of filtered free light chains (FLC) with Uromodulin in the distal convoluted tubules. Rapid reduction in serum FLC levels has shown to improve renal function in modeling studies. Extracorporeal light chain removal techniques such as plasma exchange (PEX) and high cut-off hemodialysis (HCO-HD) have been explored as potential adjunct treatment options for cast nephropathy in various clinical trials. Methods: PubMed, Cochrane library, and Clinicaltrials.gov were searched systematically for the use of plasma exchange and/or hemodialysis with chemotherapy in the treatment of myeloma cast nephropathy using their MeSH words and keywords. PRISMA guidelines were followed for screening and 5 out of 866 studies were finalized (N = 342). Results: Zucchelli et al. 1988 (n = 29) reported a dramatic reduction in Bence Jones protein (BJP) levels of 0.81 ± 0.46 g/day (P value &lt; 0.01) and 1-year survival rate of 66% in the PEX group and decrease in BJP of 3.25 +/- 0.21 g/day (P-value &lt; 0.05) with a survival rate of 28% in the control group. Clark et al. 2005 (n = 104) reported a primary composite response (patient alive at 6 months + dialysis independence + serum creatinine improvement of 50% at 6 months) in 57.9% of patients in the PEX group and 69.2% in the control group [95% CI, -8.3% to 29.1%]; P = 0.36. Johnson et al. 1990 (n = 21) reported a mean change of 880 μmol /L ± 260(SD) in serum creatinine in the PEX group and 570 μmol /L +/-240 in the control group. HD independence at 3 months was reported as 41.3% (n = 19) in the HCO-HD group and 33.3% (n = 16) in the conventional HD group (95% CI -12%–27.9%; P = 0.42) in the MYRE trial 2017 (n = 98). The EuLITE trial 2019 (n = 90) compared the efficacy of the high cut-off vs high flux hemodialysis (HF-HD) technique and concluded that there was no clinical benefit of one over the other. Independence from HD was achieved in 56% (n = 24) in the HCO-HD cohort vs 51% (n = 24) in HF-HD cohort (relative risk [RR] 1.09, 95% CI 0.74–1.61; P = 0.81). Conclusions: The use of high cut-off hemodialysis and plasma exchange as adjunct therapy did not show any significant survival benefit or improvement in clinical outcome. The role of routine use of PEX/HCO-HD in the management of cast nephropathy is still unclear and the decision to use these modalities should be made on an individual basis.

Systemic Mastocytosis Associated with "Smoldering" Multiple Myeloma.

A 79-year-old woman presented with a long history of peripheral eosinophilia. Previous right hemicolectomy for colonic polyposis was reported. Laboratory tests were notable for mild macrocitic anaemia and eosinophilia. β2 microglobulin and serum tryptase levels were elevated. Serum immunofixation revealed IgA/kappa monoclonal protein. Bence-Jones protein was positive. Bone marrow (BM) biopsy revealed the coexistence of two neoplastic components. Cohesive clusters of bland-looking, spindle-shaped mast cells, representing 20% of marrow cellularity, were close to aggregates of mature plasma cells occupying 40% of marrow cellularity. Molecular analysis on marrow aspirate demonstrated KIT D816V mutation, TET2 mutation, monoallelic deletion of TP53/17p13 and trisomy of ATM/11q23. A bone density study revealed mild osteoporosis. Full skeletal X-rays and magnetic resonance imaging (MRI) of spine and hips showed multiple, small rarefaction areas and an old L1-L2 fracture, both ascribed to osteoporosis. The association of systemic mastocytosis (SM) and multiple myeloma (MM) is very uncommon. The coexistence of SM with MM placed our patient in the SM with associated clonal haematological non-mast-cell lineage disease (SM-AHN) subtype. Midostaurin therapy was started.

Multiple Myeloma Presenting as Chest Wall Lesion: A Case Report

Multiple myeloma is defined by &gt;10% of clonal plasma cells in bone marrow or biopsy-proven extramedullary plasmacytoma and by the evidence of end-organ damage including bone lesions and renal insufficiency. It usually occurs in the age group of 50-70 years with higher incidence in males. Swelling on the chest wall is an uncommon presentation of multiple myeloma. In this case of 85-year-old male patient, two soft tissue density lesions on the posterolateral and anterior chest wall, multiple punched-out lesions in the skull, diffuse osteopenia and multiple lytic lesions were noted in ribs, sternum and thoracic spine, with evidence of myeloma cells in the bone marrow and bence jones protein in urine. Radiologic imaging plays an important role in providing a provisional diagnosis and thus, helping the clinician in such cases.

(F)utility of urine Bence Jones proteins for "routine" screening for plasma cell dyscrasia.

Testing urine for Bence Jones Protein (BJP) had been a time old procedure used for screening and monitoring of monoclonal disorders since its description. However, has poor sensitivity and despite advances in diagnostic methods of monoclonal disorders it is being continued to be requested in individuals for evaluation of myeloma or plasma cell disorders. Effective utilization and minimizing untimely or unnecessary investigations is important in the evaluation and management of any medical condition. Though, we are hard-wired during our education with some "trigger" or "peculiar" words that make us jump to actions too quickly, without comprehending the actual problem. Supporting evidence is presented to avoid reflexive use of multiple tests and utilize tests that improve utilization, reduce waste, and uphold the Choosing Wisely principles in providing optimal care to the patients.