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Monoclonal Gammopathy of Undetermined Significance (MGUS) is a clonal plasma cell disorder that is considered preneoplastic, asymptomatic, and only requiring observation. However, MGUS may result in cutaneous complications, which are poorly understood, causing treatment delays and patient suffering. We present 30 patients with cutaneous findings associated with MGUS, characterizing clinical presentations, isoforms, treatments, and outcomes. These included: MGUS-associated 'rashes' (pruritic eczematous rashes), reactive and mucin-depositional conditions (pyoderma gangrenosum, scleromyxedema), M-protein-related deposition disorders (POEMS syndrome, Waldenstrom macroglobulinemia), and cutaneous lymphomas. Twelve of 30 (40%) patients received multiple myeloma drugs (MMDs). Eleven (92%) patients improved, and those not receiving MMDs rarely improved, suggesting that MMDs have efficacy for cutaneous manifestations of MGUS. Therefore, trialing MMDs may be warranted for patients with MGUS not responding to other therapies. Moreover, evaluation for monoclonal gammopathy in elderly patients with intractable pruritus or other chronic skin conditions that are non-responsive to skin-directed therapies should be considered. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a plasma cell malignancy characterized by a monoclonal expansion of plasma cells that secrete a characteristic M-protein. This M-protein is crucial for diagnosis and monitoring of MM in the blood of patients. Recent evidence has emerged suggesting that N-glycosylation of the M-protein variable (Fab) region contributes to M-protein pathogenicity, and that it is a risk factor for disease progression of plasma cell disorders. Current methodologies lack the specificity to provide a site-specific glycoprofile of the Fab regions of M-proteins. Here, we introduce a novel glycoproteogenomics method that allows detailed M-protein glycoprofiling by integrating patient specific Fab region sequences (genomics) with glycoprofiling by glycoproteomics. Glycoproteogenomics was used for the detailed analysis of de novo N-glycosylation sites of M-proteins. First, Genomic analysis of the M-protein variable region was used to identify de novo N-glycosylation sites. Subsequently glycopeptide analysis with LC-MS/MS was used for detailed analysis of the M-protein glycan sites. Genomic analysis uncovered a more than two-fold increase in the Fab Light Chain N-glycosylation of M-proteins of patients with Multiple Myeloma compared to Fab Light Chain N-glycosylation of polyclonal antibodies from healthy individuals. Subsequent glycoproteogenomics analysis of 41 patients enrolled in the IFM 2009 clinical trial revealed that the majority of the Fab N-glycosylation sites were fully occupied with complex type glycans, distinguishable from Fc region glycans due to high levels of sialylation, fucosylation and bisecting structures. Together, glycoproteogenomics is a powerful tool to study de novo Fab N-glycosylation in plasma cell dyscrasias. [ABSTRACT FROM AUTHOR]

Multiple myeloma and monoclonal gammopathy of undetermined significance are plasma cell dyscrasias characterized by monoclonal proliferation of pathological plasma cells with uncontrolled production of immunoglobulins. Autoimmune pathologies are conditions in which T and B lymphocytes develop a tendency to activate towards self-antigens in the absence of exogenous triggers. The aim of our review is to show the possible correlations between the two pathological aspects. Molecular studies have shown how different cytokines that either cause inflammation or control the immune system play a part in the growth of immunotolerance conditions that make it easier for the development of neoplastic malignancies. Uncontrolled immune activation resulting in chronic inflammation is also known to be at the basis of the evolution toward neoplastic pathologies, as well as multiple myeloma. Another point is the impact that myeloma-specific therapies have on the course of concomitant autoimmune diseases. Indeed, cases have been observed of patients suffering from multiple myeloma treated with daratumumab and bortezomib who also benefited from their autoimmune condition or patients under treatment with immunomodulators in which there has been an arising or worsening of autoimmunity conditions. The role of bone marrow transplantation in the course of concomitant autoimmune diseases remains under analysis. [ABSTRACT FROM AUTHOR]

TAFRO syndrome (TS) is a recently recognized and heterogenous systemic disease characterized by a confluence of symptoms: thrombocytopenia (T), anasarca (A), fever (F), reticulin myelofibrosis (R), and organomegaly (O). First described in Japan in 2010, the pathogenesis remains unclear and includes various clinical conditions such as malignancies, rheumatologic disorders, infections, and "Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, and Skin changes" (POEMS) syndrome. Due to its heterogeneous presentation and potential life-threatening delays in diagnosis, accurate diagnosis is crucial. According to the literature, no specific imaging modality has been recommended for the work-up of patients with suspected TS. Here, we report a case of TS and its management using 18F-FDG-PET/CT imaging as an attractive complementary diagnostic tool. [ABSTRACT FROM AUTHOR]

This document is a collection of abstracts from the Australasian Journal of Dermatology. The articles cover a range of topics, including the diagnosis of bacterial skin infections, the economic viability of genotyping in epilepsy patients, and the diagnosis of fungal infections. Other articles discuss the complications of certain skin conditions, such as Stevens-Johnson Syndrome and toxic epidermal necrolysis, and the potential association between a COVID-19 vaccine and toxic epidermal necrolysis. The document also includes case studies and discussions on the treatment of different dermatological conditions, such as morphoea and lymphomatoid papulosis. Additionally, there are articles on the impact of bariatric surgery on dermatology drugs, the treatment of livedoid vasculopathy, and the role of interleukin-17 in pyoderma gangrenosum. The document provides valuable information for researchers and library patrons interested in dermatology. [Extracted from the article]

The given text provides concise summaries of various medical case reports and studies, covering a wide range of topics. These summaries offer valuable insights into rare medical conditions and their management, emphasizing the importance of early diagnosis and treatment. The text is culturally sensitive and respectful of diverse perspectives, allowing library patrons to quickly determine if they want to explore the underlying text further. [Extracted from the article]

This document provides information on the diagnosis and management of transthyretin cardiac amyloidosis (ATTR), a commonly overlooked cause of heart failure in older patients. It explains that the misfolding of a protein called transthyretin leads to the accumulation of insoluble fibrils in various organs, including the heart. The article emphasizes the importance of distinguishing between different types of amyloidosis for accurate diagnosis and management. It highlights the use of a 12-lead ECG and technetium 99m bone scintigraphy in detecting and confirming the diagnosis of ATTR. The article also discusses the development of novel therapies for ATTR and the importance of early diagnosis and referral to specialized clinics for appropriate management. [Extracted from the article]

Summary: Systemic light chain (AL) amyloidosis is a relapsing plasma cell disorder. Therapy is limited, particularly for triple‐class refractory disease. We report the use of belantamab mafodotin, a BCMA‐directed drug–antibody conjugate, for relapsed AL amyloidosis, including patients traditionally excluded from clinical trials. Thirty‐one patients were reviewed, with a median of three prior lines of therapy. The median follow‐up was 12 months (95% CI 4–19), and a median of five doses were delivered. The best haematological overall response rate was 71%, and the complete/very good partial response was 58%. Sixty‐eight percent had keratopathy and improved in all. Belantamab mafodotin has high efficacy and good tolerability in patients with relapsed AL amyloidosis. [ABSTRACT FROM AUTHOR]

Light chain amyloidosis is a plasma–cell disorder with a poor prognosis. It is a progressive condition, causing worsening pain, disability, and life-limiting complications involving multiple organ systems. The medical regimen can be complex, including chemotherapy or immunotherapy for the disease itself, as well as treatment for pain, gastrointestinal and cardiorespiratory symptoms, and various secondary symptoms. Patients and their families must have a realistic awareness of the illness and of the goals and limitations of treatments in making informed decisions about medical therapy, supportive management, and end-of-life planning. Palliative care services can thus improve patients' quality of life and may even reduce overall treatment costs. Light chain (AL) amyloidosis is a clonal plasma cell disorder characterized by the excessive secretion of light chains by an indolent plasma cell clone that gradually accumulates in vital organs as amyloid fibrils and leads to end-organ damage. With progressive disease, most patients develop diverse clinical symptoms and complications that negatively impact quality of life and increase mortality. Complications include cardiac problems including heart failure, hypotension, pleural effusions, renal involvement including nephrotic syndrome with peripheral edema, gastrointestinal symptoms leading to anorexia and cachexia, complex pain syndromes, and mood disorders. The prognosis of patients with advanced AL amyloidosis is dismal. With such a complex presentation, and high morbidity and mortality rates, there is a critical need for the establishment of a palliative care program in clinical management. This paper provides an evidence-based overview of the integration of palliative care in the clinical management of AL amyloidosis as a means of reducing ER visits, rehospitalizations, and in-hospital mortality. We also discuss potential future collaborative directions in various aspects of clinical care related to AL amyloidosis. [ABSTRACT FROM AUTHOR]

This article provides information on the diagnosis and management of smouldering myeloma, a precursor condition to multiple myeloma. It discusses various diagnostic tests and imaging techniques used to identify smouldering myeloma and emphasizes the importance of restaging if there is evidence of progression. The article also provides recommendations for screening and initial investigations for suspected myeloma. Additionally, it discusses risk stratification models and treatment options for smouldering myeloma, including the use of lenalidomide. The article concludes by highlighting ongoing clinical trials and the need for further research in the treatment of smouldering myeloma. [Extracted from the article]

Free light chain (FLC) assays and the ratio of κ/λ are recommended for diagnosis, prognosis and monitoring of plasma cell dyscrasias (PCD). Limited data exists on FLC clinical specificity in patients diagnosed with other conditions. We assessed the κ, λ, and κ/λ FLC ratio using the FreeLite assay and the Sebia FLC ELISA assay in 176 patients with clinical presentations of fatigue, anemia, polyclonal hypergammaglobulinemia, joint disorders, kidney disease and non PCD-cancers with no monoclonal protein observed on serum protein electrophoresis or MASS-FIX immunoglobulin isotyping. Manufacturer defined reference intervals (RI) and glomerular filtration rate (GFR) specific RI (renal RI) were utilized. For the κ/λ ratio, 68.7 % (121/176) of specimens on the FreeLite and 87.5 % (154/176) of specimens on the Sebia assay were within RI. For κ, 68.2 % (120/176) and 72.2 % (127/176) of results were outside RI for FreeLite and Sebia respectively. For λ, 37.5 % (66/176) and 84.1 % (148/176) of FreeLite and Sebia results were outside RI. With FreeLite and Sebia, patients with kidney disease (n=25) had the highest κ/λ ratios. 44 patients (25.0 %) had GFR <60 mL/min/BSA. When renal RI were applied, 13.6 % had a FLCr outside the renal RI with FreeLite, and 4.5 % with Sebia. In a cohort of patients with signs and symptoms suggestive of PCDs, but ultimately diagnosed with other conditions, Sebia FLC had improved clinical specificity relative to FreeLite, if one was using an abnormal κ/λ ratio as a surrogate for monoclonality. [ABSTRACT FROM AUTHOR]

Light chain measurements form an essential component of the testing strategy for the detection and monitoring of patients with suspected and/or proven plasma cell disorders. Urine-based electrophoretic assays remain at the centre of the international guidelines for response assessment but the supplementary role of serum-free light chain (FLC) assays in response assessment and the detection of disease progression due to their increased sensitivity has been increasingly recognised since their introduction in 2001. Serum FLC assays have also been shown to be prognostic across the spectrum of plasma cell disorders and are now incorporated into risk stratification scores for patients with monoclonal gammopathy of undetermined significance (MGUS), smouldering multiple myeloma, and light chain amyloidosis (AL amyloidosis), as well as being incorporated into the criteria for defining symptomatic multiple myeloma. There are now multiple different commercially available serum FLC assays available with differing performance characteristics, which are discussed in this review, along with the implications of these for patient monitoring. Finally, newer methodologies for the identification and characterisation of monoclonal FLC, including modifications to electrophoretic techniques, mass spectrometry-based assays and Amylite, are also described along with the relevant published data available regarding the performance of each assay. [ABSTRACT FROM AUTHOR]

This document is a list of articles published in the journal Seminars in Thrombosis and Hemostasis. The articles cover a wide range of topics related to platelets, coagulation, and thrombosis. Some of the topics include the role of platelets in cancer, the measurement of microparticles, risk factors for venous thromboembolism, and the use of statins in COVID-19 patients. The articles provide valuable information for researchers and healthcare professionals interested in these areas of study. [Extracted from the article]

Serum kappa, lambda, the K/λ light chain concentrations are used for screening, diagnosis, and monitoring of patients with multiple myeloma and other plasma cell disorders. Biological variation studies conducted on healthy subjects showed that free light chains have a low within and high between-individual variation. We determined if this variation were genetically linked. We obtained a single serum sample from 16 pairs of identical twins, 8 neonate twins, and 19 presumed directly-related siblings children, measured Κ and λ light chains and computed the Κ/λ ratio. As expected, Κ/λ results from each twin neonate were near identical (reflecting maternal/placental transfer). For older children and adult twins, the Κ/λ ratio form a cluster of results that were a subset of the reference range. There was one outlier, a female with a high, different from her twin sister. She likely had a monoclonal gammopathy (no followup was possible). Excluding this pair, results from neonate twins (14.4% ±10.3%) and non-neonate twins (18.0 ± 15.3%) were not significantly different. Results between non-twin siblings were more scattered (53.2%±53.4%) and different from neonate and non-neonate twin adult and children. We suggest that the Κ/λ free light chains may be genetically linked. Measurement of serum free kappa (K) and lambda light (l) chains and the K/L ratio are used to diagnose multiple myeloma and monitoring the disease following treatment. In health, the K/L ratio are consistent and occupy a small fraction of the reference range. By studying twins, we determined that this ratio is likely genetically determined. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a clonal plasma cell disorder that commonly presents with anemia, renal failure, hypercalcemia, and lytic bone lesions. MM is also frequently associated with thrombotic complications; however, it may rarely present with bleeding diathesis. We report a case of a 42-year-old gentleman with relapsed immunoglobulin G lambda MM who presented with epistaxis, gingival bleeding, and oozing at the venepuncture site. Routine tests of coagulation revealed a prolonged prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time. The PT and aPTT failed to correct with pooled normal plasma and the patient was thus diagnosed to have an acquired heparin-like anticoagulant (HLAC). The source of this HLAC has long been debated, but recent data have demonstrated that this HLAC may be the paraproteins produced by the malignant plasma cells. The patient was treated with intravenous protamine sulfate, repeated cycles of plasma exchange, and a daratumumab-based quadruplet regimen but eventually succumbed to an intracranial hemorrhage. HLAC is a rare but potentially fatal complication of MM that must be considered when patients with MM present with bleeding diathesis. [ABSTRACT FROM AUTHOR]

This article discusses a case of a patient with VEXAS syndrome, a rare autoinflammatory systemic disease with various manifestations. The patient presented with a recurrent rash and physical examination revealed erythematous edematous papules, plaques, and nodules on the head, neck, trunk, and extremities. Biopsies showed neutrophilic eccrine hidradenitis, a previously undescribed finding in VEXAS syndrome. The patient also had persistent leukopenia, lymphopenia, and macrocytic anemia, as well as other hematologic abnormalities. Treatment with various medications was not effective, but the patient showed improvement with adalimumab. The article highlights the importance of recognizing skin manifestations and histopathological findings associated with VEXAS syndrome for early diagnosis and treatment. [Extracted from the article]

Plasma cell dyscrasias can have a heterogenous onset and, also, kidney involvement, associated with various clinical presentations. This mandates always considering plasma cell dyscrasias as a possible diagnosis when faced with a case with unusual progression. We report the case of a 44-year-old male with a sellar mass that was diagnosed first as an atypical pituitary adenoma, who later developed kidney involvement manifested as renal insufficiency and proteinuria, with a pathology report suggesting focal and segmental glomerulosclerosis. Within a year, he was diagnosed with multiple myeloma, prompting pathological reevaluation of the sellar mass and the change of diagnosis to solitary sellar plasmacytoma. [ABSTRACT FROM AUTHOR]

Background: To improve the early detection rate of multiple myeloma (MM), the M-protein screening system has been performed in the hospital population at Zhongshan Hospital Fudan University since 2014, with electrophoretic-based monoclonal immunoglobulin (M-protein) screening integrated into the blood biochemistry panel. This study updated 7-year follow-up findings of MM patients diagnosed by screening-driven and symptom-driven approaches. Methods: The retrospective study compared the characteristics and outcomes of patients diagnosed through two patterns by reviewing the plasma cell disease database from January 2014 to October 2021. The screening-driven group included patients diagnosed through the screening system during workups of unrelated medical conditions or routine checkups. In contrast, patients who visited or were referred to the hematological department due to myeloma-related end-organ damage were categorized into the symptom-driven group. Results: There were 3,110,218 serum protein electrophoresis (SPEP) tests performed during 7 years, with 1.95% (60,609) patients yielding positive SPEP results. Of 911 confirmed MM cases (excluding concurrent amyloidosis), 366 were assigned to the screening-driven group, while 545 were to the symptom-driven group. Compared to the symptom-driven group, the screening group had more IgG subtypes, earlier International Stage System stages, fewer disease-related symptoms, lower ECOG scores, less extramedullary disease, a lower percentage of bone marrow plasma cells, and a lower level of lactate dehydrogenase. Frontline response results of two groups were similar. Patients detected through screening had a significantly improved median progression-free survival (PFS) than the symptom-driven group (62.2 vs. 24.9months, p<0.001, HR: 2.12, 95% CIs: 1.69–2.65), with median follow-ups of 32.6 and 27.4months. Furthermore, the median overall survival (OS) was significantly longer in patients of the screening group (not reached vs. 62.3months, p<0.001, HR: 2.49, 95% CIs: 1.81–3.41). After being adjusted for well-acknowledged myeloma prognostic factors, the screeningdriven diagnostic pattern remained an independent prognostic factor indicating improved PFS and OS in MM patients. Conclusion: Routine M-protein screening for MM in the hospital population results in an earlier diagnosis and better patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Castleman disease, also known as giant lymph node hyperplasia or angiofollicular lymph node hyperplasia, is a highly heterogeneous clinicopathological entity that belongs to the family lymphoproliferative disorders. Castleman disease accompanied by bronchiolitis obliterans is uncommon and often poses a great diagnostic challenge, which is easily confused with respiratory diseases and impeding the correct diagnosis and treatment. The main aim in presenting such rare case studies is to raise awareness and expand the diagnostic horizon of clinicians for appropriate management. Case presentation: Here, we present a 69-year-old Chinese male who was admitted to our hospital due to right chest pain for 6 months, accompanied by cough, expectoration, and fever. Laboratory examinations revealed elevated immunoglobulin G and C-reactive protein, and normal serum levels of tumor markers and interleukin-6. Computed tomography scan detected diffuse bronchial wall thickening and patchy area of air trapping consistent with small airway disease. Pulmonary function test showed mild small airway obstructive ventilation dysfunction and moderate decrease in diffusion capacity. The pathological result of the right axillary lymph node was consistent with the plasma cell type Castleman disease. According to the above examinations, the patient was finally diagnosed with the plasma cell type Castleman disease accompanied with bronchiolitis obliterans. He received immunosuppressive medication after surgery and has been followed up for 11 months. Now the patient is currently in stable condition without recurrence. Conclusion: Castleman disease is a rare lymphoproliferative disorder with a variety of symptoms. At present, the treatment of Castleman disease accompanied with bronchiolitis obliterans is mostly based on experiences or previous case reports, and there is no standard treatment. Here, we report an uncommon case of Castleman disease accompanied with bronchiolitis obliterans in which the patient received immunosuppressive medication after surgery and has been followed up for 11 months without experiencing a recurrence, which may deepen and extend our understanding of this disease. [ABSTRACT FROM AUTHOR]

Monoclonal gammopathy of undetermined significance (MGUS) is a pre-malignant plasma cell disorder with an etiology that is incompletely understood. Modifiable risk factors and genetic predispositions likely interact to increase MGUS risk in specific individuals and populations. Identifying geographic prevalence patterns and modifiable risk factors is critical for understanding the etiology of MGUS. The aim of this review was to outline original research on MGUS prevalence across geographic locations and modifiable risk factors. We conducted a systematic review of 39 eligible studies from PubMed®, Embase®, and Web of Science® written in English and published by February 2023. Our protocol was registered in accordance with PROSPERO guidelines. Studies were synthesized using Research Electronic Data Capture and appraised using the National Heart, Lung, and Blood Institute study quality assessment tools. The prevalence of MGUS ranged from 0.24% to 9% across geographic locations. Modifiable risk factors for MGUS include infections, autoimmune diseases, chronic inflammatory conditions, lifestyle factors, environmental exposures, and ionizing radiation. Therefore, the development of MGUS may be related to chronic antigenic stimulation and genetic aberrations that promote clonal proliferation of plasma cells. Prospective studies assessing gene–environment interactions are needed to further define risk factors for MGUS and inform screening and preventative strategies. [ABSTRACT FROM AUTHOR]

Plasma cell leukemia (PCL) is a rare and aggressive plasma cell disorder, exhibiting a more unfavorable prognosis than multiple myeloma. PCL is classified into pPCL and sPCL. Recently, the IMWG has recommended new PCL definition criteria, which require the presence of ≥5% circulating plasma cells in peripheral blood smears. Due to its low incidence, research on pPCL and sPCL is limited. We conducted a retrospective study and analyzed clinical and cytogenetic data of pPCL and sPCL patients. Overall survival (OS) and progression-free survival (PFS) were assessed by the Kaplan-Meier method, and survival distributions were compared using the log-rank test. This is a small cohort comprising 23 pPCL and 9 sPCL patients. Notably, sPCL patients showed a higher incidence of extramedullary infiltration and a higher percentage of bone marrow plasma cells (p = 0.015 and 0.025, respectively). Although no significant difference was found between the two groups in OS and PFS, a trend emerged suggesting a superior survival outcome for pPCL patients, with a higher cumulative 1-year PFS rate (38.3% vs. 13.3%) and a lower early mortality rate (mortality rate at 3 months: 15% vs. 33%). We also suggested that pPCL patients carrying t(11;14) may have a longer median survival time than individuals with other cytogenetic abnormalities, but this was not confirmed due to the small sample size. Our study revealed clinical and cytogenetic features of pPCL and sPCL patients according to the new diagnostic criteria. The findings suggested a generally better prognosis for pPCL than sPCL and the likelihood of t(11;14) translocation acting as a favorable prognostic factor in pPCL. It is important to note that our study had a limited sample size, which may lead to bias. We hope well-designed studies can be conducted to provide more results. [ABSTRACT FROM AUTHOR]

Multiple myeloma (MM) is a plasma cell disorder and the second most common blood cancer. While it is still considered incurable, significant progress has been made in understanding its pathophysiological mechanisms, leading to the development of successful therapeutics such as proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, CAR-T cells, and bispecific antibodies. This special issue aims to highlight recent developments in understanding the molecular complexity of MM, identifying new therapeutic targets, and predictive biomarkers to guide treatment decisions. The articles cover topics such as clinical proteomics, ERBB2 as a predictor of poor survival outcomes, miRNA expression patterns, platelets' role in bleeding and thrombosis, genetic abnormalities in extramedullary MM, machine learning approaches for personalized treatments, autophagy-related gene polymorphisms, and the interaction between macrophages and the urokinase plasminogen activator receptor system in MM. [Extracted from the article]

This article discusses the case of a 63-year-old woman who presented with a rugged surface on her left parietal scalp. Imaging tests revealed a mass that had infiltrated the parietal bone, leading to a suspected diagnosis of en plaque meningioma. However, histopathological examination revealed a plasma cell neoplasm, specifically a plasmacytoma. This case highlights the importance of considering rare conditions and the need for appropriate interventions, such as biopsies, when radiological suspicions arise. The patient underwent tumor resection and radiotherapy and remained stable during the follow-up period. [Extracted from the article]

This article, published in the journal Cytopathology, discusses the diagnosis of myelomatous meningitis through cerebrospinal fluid cytology examination. Myelomatous meningitis is a rare complication of multiple myeloma, a neoplastic plasma cell disorder. The article presents a case study of a 72-year-old woman with a history of IgA-lambda multiple myeloma who developed symptoms of headache, disequilibrium, and neurological deficits. Cerebrospinal fluid analysis, combined with immunocytochemistry, confirmed the presence of myeloma cells in the central nervous system, leading to a diagnosis of myelomatous meningitis. The article emphasizes the importance of prompt diagnosis and multidisciplinary approaches in managing this condition. [Extracted from the article]

This document discusses a case study of a patient with primary cold agglutinin disease (CAD), a rare autoimmune hemolytic anemia. The patient did not respond to traditional B-cell directed treatments, but showed a favorable response to a daratumumab-based regimen. The authors suggest that daratumumab may be a promising treatment option for CAD, particularly in cases that are refractory or relapsed. They also note that further research, including case series and small prospective trials, is needed to investigate the efficacy of daratumumab in CAD. [Extracted from the article]

This article discusses a rare case of cutaneous amyloid lesions as a presenting symptom of multiple myeloma. The patient, a 56-year-old woman with a history of various health conditions, presented with painless lesions on her ears that had been growing for several months. Skin biopsy confirmed the presence of amyloid deposits, and further tests revealed systemic AL amyloidosis and kappa light-chain multiple myeloma. This case is unique and highlights the importance of early diagnosis and treatment. [Extracted from the article]

Chronic neutrophilic leukemia (CNL) is a rare type of blood cancer characterized by the overproduction of mature neutrophils. Most CNL patients have a mutation in the CSF3R gene, which is considered a key diagnostic indicator. This article presents a case study of an 82-year-old man with CNL who also had monoclonal gammopathy of undetermined significance (MGUS) and developed severe ascites due to neutrophil infiltration in the liver. The patient's condition deteriorated, leading to emaciation and aspiration pneumonia. The article highlights the need for early intervention and treatment to prevent severe organ damage in CNL patients. [Extracted from the article]

The wave of coronavirus disease 2019 (COVID-19) with Omicron variant reached its first peak in Beijing, China in December 2022. We delineated characteristics and factors associated with adverse outcome of patients with plasma cell dyscrasias (PCDs) and COVID-19 during the first month of the wave. A total of 104 patients with a median age of 65 years were included in the study, with multiple myeloma (74%, n=77) and primary Immunoglobulin light chain amyloidosis (16.3%, n=17) being the two most common disease. Overall, severe or critical COVID-19 was developed in 18 (17.3%) patients, with a total all-cause mortality rate of 4.8% (n=5). The vaccination coverage was 41% and 48.1%, before and during the upsurge of Omicron, respectively, calling for the improvement of vaccination in PCD patients. Multivariable analysis revealed that age was the only independent risk factors (OR=1.14, 95% CI: 1.06–1.26, p = 0.002) associated with the development of severe or critical disease. Among patients with severe or critical group, low levels of albumin (HR=18.29; 95% CI: 1.82–183.44, p = 0.013) and high levels of lactic dehydrogenase (LDH) (HR=0.08; 95% CI: 0.01–0.65, p = 0.018) were associated with longer time to negative conversion of COVID-19. [ABSTRACT FROM AUTHOR]

Plasma cell dyscrasias are a heterogeneous group of neoplasms characterized by abnormal proliferation of plasma cells with or without over production of monoclonal immunoglobulins. Chromosomal abnormalities are acquired either early in the course of the disease or during disease progression. Plasma cell dyscrasias are categorized into multiple cytogenetic subtypes that form an integral component of risk-stratified treatment protocols. The primary genetic events are IgH gene translocations and non-random gains of chromosomes 3/5/7/9/11/15/19 and or 21. The secondary genetic events consist of chromosome 1 abnormalities (1p deletion and 1q gain or amplification), deletion 17p/TP53, deletion 13q, and MYC gene rearrangements. Plasma cells being at the end of differentiation spectrum of B cells, have low proliferative potential precluding the use of karyotyping in identification of chromosomal abnormalities. Analysis of enriched plasma cells using interphase fluorescent in situ hybridization (FISH) is the technique of choice for identifying these abnormalities. It is essential to enrich plasma cells before the FISH analysis, and numerous plasma cell enrichment techniques have been described. In the paper, we review the cytogenetic approach to identify clinically significant genetic aberrations including the effective use of FISH panels and plasma cell enrichment techniques. [ABSTRACT FROM AUTHOR]

Primary plasma cell leukaemia is a rare and aggressive plasma cell disorder with a poor prognosis. The aim of the EMN12/HOVON-129 study was to improve the outcomes of patients with primary plasma cell leukaemia by incorporating carfilzomib and lenalidomide in induction, consolidation, and maintenance therapy. The EMN12/HOVON-129 study is a non-randomised, phase 2, multicentre study conducted at 19 academic centres and hospitals in seven European countries (Belgium, Czech Republic, Denmark, Italy, Norway, The Netherlands, and the UK) for previously untreated patients with primary plasma cell leukaemia aged 18 years or older. Inclusion criteria were newly diagnosed primary plasma cell leukaemia (defined as >2 ×109 cells per L circulating monoclonal plasma cells or plasmacytosis >20% of the differential white cell count) and WHO performance status 0–3. Patients aged 18–65 years (younger patients) and 66 years or older (older patients) were treated in age-specific cohorts and were analysed separately. Younger patients were treated with four 28-day cycles of carfilzomib (36 mg/m2 intravenously on days 1, 2, 8, 9, 15, and 16), lenalidomide (25 mg orally on days 1–21), and dexamethasone (20 mg orally on days 1, 2, 8, 9, 15, 16, 22, and 23). Carfilzomib–lenalidomide–dexamethasone (KRd) induction was followed by double autologous haematopoietic stem-cell transplantation (HSCT), four cycles of KRd consolidation, and then maintenance with carfilzomib (27 mg/m2 intravenously on days 1, 2, 15, and 16 for the first 12 28-day cycles, and then 56 mg/m2 on days 1 and 15 in all subsequent cycles) and lenalidomide (10 mg orally on days 1–21) until progression. Patients who were eligible for allogeneic HSCT, could also receive a single autologous HSCT followed by reduced-intensity conditioning allogeneic HSCT and then carfilzomib–lenalidomide maintenance. Older patients received eight cycles of KRd induction followed by maintenance therapy with carfilzomib and lenalidomide until progression. The primary endpoint was progression-free survival. The primary analysis population was the intention-to-treat population, irrespective of the actual treatment received. Data from all participants who received any study drug were included in the safety analyses. The trial was registered at www.trialregister.nl (until June 2022) and https://trialsearch.who.int/ as NTR5350; recruitment is complete and this is the final analysis. Between Oct 23, 2015, and Aug 5, 2021, 61 patients were enrolled and received KRd induction treatment (36 patients aged 18–65 years [20 (56%) were male and 16 (44%) female], and 25 aged ≥66 years [12 (48%) were male and 13 (52%) female]). With a median follow-up of 43·5 months (IQR 27·7–67·8), the median progression-free survival was 15·5 months (95% CI 9·4–38·4) for younger patients. For older patients, median follow-up was 32·0 months (IQR 24·7–34·6), and median progression-free survival was 13·8 months (95% CI 9·2–35·5). Adverse events were most frequently observed directly after treatment initiation, with infections (two of 36 (6%) younger patients and eight of 25 (32%) older patients) and respiratory events (two of 36 [6%] younger patients and four of 25 [16%] older patients) being the most common grade 3 or greater events during the first four KRd cycles. Treatment-related serious adverse events were reported in 26 (72%) of 36 younger patients and in 19 (76%) of 25 older patients, with infections being the most common. Treatment-related deaths were reported in none of the younger patients and three (12%) of the older patients (two infections and one unknown cause of death). Carfilzomib and lenalidomide-based therapy provides improved progression-free survival compared with previously published data. However, results remain inferior in primary plasma cell leukaemia compared with multiple myeloma, highlighting the need for new studies incorporating novel immunotherapies. Dutch Cancer Society, Celgene (a BMS company), and AMGEN. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 34-year-old woman with a history of liver transplantation who developed abdominal distention and acute kidney injury. It is reported that complications following transplantation, including clostridioides difficile infection, led to her hospitalization. It further highlights the complexities in managing post-transplant patients and the need for comprehensive diagnostic evaluation.

Acquired isolated factor VII (FVII) deficiency is a rare but important discovery in patients with plasma cell disorders with significant therapeutic and prognostic implications. The present analysis and review of cases reported in the literature is intended to highlight disease-related characteristics associated with this rare clotting defect, clinical manifestations and outcome, and potential underlying mechanisms, and to provide guidance on how to manage these patients in terms of prophylactic and therapeutic measures. The discovery of acquired FVII deficiency in a patient with multiple myeloma (MM) or monoclonal gammopathy of uncertain significance (MGUS) should prompt an evaluation for AL amyloidosis, particularly for amyloid hepatosplenic involvement, whenever not previously documented. Acquired FVII deficiency in patients with MM and AL amyloidosis is frequently associated with severe bleeding diathesis, also related to a number of concomitant predisposing factors, adversely affecting the outcome. The prompt institution of a rapidly acting therapy is crucial to prevent severe bleeding complications and positively impact outcome. Recombinant activated factor VII (rVIIa) may represent a useful supportive care measure, both in treating active bleeding and in the peri-procedural setting. However, further clinical experience is needed to optimize the therapeutic management of this rare disorder. [ABSTRACT FROM AUTHOR]

Background: The cluster of differentiation 200 (CD200) is a recently introduced marker, used to differentiate various lymphoproliferative disorders (LPDs) and is a potential target for chemotherapy. Objective: The objective is to study the utility of CD200 expression by flow cytometry (FC) in various LPDs and plasma cell disorders. Materials and Methods: This is a retrospective study done over a period of 2 years. The study group included 52 cases with a clinical suspicion of LPD (n = 40) or plasma cell disorder (n = 12). Clinical data, morphological data on peripheral blood, and/or bone marrow examination were analyzed and correlated with the final results on FC. Results: Out of 40 LPDs, chronic lymphocytic leukemia (CLL) accounted for a majority of the cases accounting for 57.5% (23 cases). Plasma cell myelomas (PCM) were the most common plasma cell disorders accounting for 75% (nine cases). All cases of CLL showed CD200 expression and the two cases of mantle cell lymphoma (MCL) were CD200 negative. Splenic marginal zone lymphomas (MZL) involving marrow showed dim CD200 expression. Bright CD200 expression was also observed in all cases of hairy cell leukemia (HCL) and 67% of cases diagnosed as PCM. Conclusion: CD200 is a very useful marker in the diagnosis of various LPDs especially CLL, HCL, and PCMs. It can be used as an additional marker particularly in distinguishing CLL/small lymphocytic lymphoma (SLL) from MCL and atypical CLL from other CD5+ B-cell neoplasms and extranodal MZL. [ABSTRACT FROM AUTHOR]

Plasma cell dyscrasias (PCDs) are characterized by a bone marrow plasma cell clone producing a monoclonal component (MC). This heterogeneous group comprehends malignant diseases as multiple myeloma (MM), conditions requiring only observation, like monoclonal gammopathy of undetermined significance (MGUS), and rarer entities where the MC causes organ dysfunction in absence of malignant PCD [(i.e. monoclonal gammopathy of clinical significance (MGCS)]. The evaluation of urine proteins has a key role in the management of PCDs, particularly quantification of proteinuria and albuminuria in the diagnostic workflow and clinical management of MGCS with renal involvement. In immunoglobulin light chain (AL) amyloidosis, proteinuria (cut-off: 0.5 g/24h) and urine albumin/creatinine ratio (UACR; cut-off: 300 mg/g) are used for diagnosis of renal involvement. These biomarkers are also included in staging systems that stratify the severity of renal involvement (proteinuria cut-off: 5 g/24h; UACR cut-off: 3 600 mg/g) and in renal response criteria (decrease of proteinuria/UACR >30% from baseline). In light chain deposition disease (LCDD), relatively low grade proteinuria (cut-off: 2 g/24h) results in higher risk of end-stage renal failure and its reduction after treatment (>50% from baseline) associates with better outcome. Finally, the presence of a MC and tubular proteinuria raises suspicion of light chain proximal tubulopathy (LCPT) with acquired Fanconi syndrome, especially in presence of other abnormalities at the urine examination (e.g. glycosuria, phosphaturia, uricosuria). The clinical laboratory, with the determination of biomarkers in urine provides crucial data in PCD management: for the diagnostic workflow, assessment of severity of the disease and evaluation of treatment effectiveness. [ABSTRACT FROM AUTHOR]

Patients with hematological malignancy (HM) are at higher risk of infection with SARS-CoV-2 and potentially severe outcomes. The rate was 15.2% (12/79) in patients without prior history of COVID-19 infection and 17.7% (11/62) in patients who did not receive a vaccine during the follow-up period. Within the last 12 months, 35/93 (37.6%) participants had received anti-CD20 therapy, 7/93 (7.5%) bispecific antibody therapy, and 6/93 (6.5%) Bruton tyrosine kinase inhibitor therapy (Table 1). [Extracted from the article]

.83 ht 1 Abbreviations: IgG, immunoglobulin G; IgRT, immunoglobulin replacement therapy; IQR, interquartile range. We demonstrate that, in previously stable patients, IgRT dose reductions lead to a reduction in trough IgG, which is associated with an increased frequency of infections requiring outpatient antibiotic use. [Extracted from the article]

Adenopathy and extensive skin patch overlying a plasmacytoma (AESOP) syndrome is a rare plasma cell neoplasm with a paraneoplastic syndrome. This case report describes the 28th case of AESOP syndrome, which was associated with multiple myeloma. The patient presented with a dark red plaque on the right hypochondriac region and underwent various tests, including a PET-CT scan and biopsies, to confirm the diagnosis. The study also provides a summary of previously reported cases of AESOP syndrome, highlighting the clinical features and outcomes. AESOP syndrome is often associated with other plasma cell disorders, and the prognosis is generally favorable with appropriate treatment. [Extracted from the article]

Background: Plasma cell neoplasm is a group of disorders involving mature B-cells that results in excessive production of specific monoclonal heavy-chain immunoglobulins. Plasma cell neoplasm can present in different clinical forms. Case Presentation: An elderly female presented with long-standing nasal congestion and was diagnosed with nasal plasmacytoma. After a complete checkup, including 2-[18F] fluorodeoxyglucose (FDG) positron emission tomography (PET)/ computed tomography (CT), a diagnosis of extramedullary nasal plasmacytoma with synchronous multiple myeloma was concluded. Herein, we report a single case of a patient with extramedullary nasal plasmacytoma and synchronous multiple myeloma, including its clinical and imaging findings. Conclusion: Multiple myeloma shows generally poor prognosis. Conversely, the prognosis of extramedullary plasmacytoma is good, and recurrence, metastasis, and transformation into multiple myeloma are rare. It is important to distinguish solitary plasmacytoma from other plasma cell diseases to choose the best treatment. A systemic understanding of the clinical and imaging features of extramedullary plasmacytoma and multiple myeloma are may help clinical and imaging doctors correctly diagnose the disease. [ABSTRACT FROM AUTHOR]

The corresponding evolving technology and imaging techniques have the potential to revolutionize the practice of skeletal radiology, enabling more accurate diagnoses, personalized treatment approaches, and improved patient outcomes. Further research is required to explore the potential of novel imaging techniques, including advanced MRI sequences and functional imaging modalities, in providing valuable insights into skeletal pathologies. In their study on lumbar spine computed tomography to magnetic resonance imaging (CT to MRI) synthesis, the researchers employed a generative adversarial network (GAN) model to generate synthesized images. Musculoskeletal (MSK) disorders are among the top five contributors to disability-adjusted life years (DALYs) worldwide [[1]]. [Extracted from the article]

Keywords: daratumumab; plasma cell; refractory; thrombotic thrombocytopenic purpura (TTP) EN daratumumab plasma cell refractory thrombotic thrombocytopenic purpura (TTP) 429 433 5 07/14/23 20230715 NES 230715 INTRODUCTION Immune-mediated thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition usually associated with IgG antibody-mediated destruction of the disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13) enzyme. ADAMTS13 activity was typically performed within 24 h of sample collection, whereas ADAMTS13 antigen and anti-ADAMTS13 IgG antibody titres were analysed in batches, delaying incorporation of the results into the clinical management. ADAMTS13 activity B ( b TECHNOZYM® ADAMTS13 Activity ELISA Kit), ADAMTS13 antigen (TECHNOZYM® ADAMTS13 Antigen ELISA Kit) and anti-ADAMTS13 IgG antibody titres (TECHNOZYM® ADAMTS13 INH ELISA Kit) were determined by ELISA method. Both had a reduction in anti-ADAMTS13 IgG antibody titres after daratumumab and had negative anti-ADAMTS13 IgG antibody titres by 90 days. [Extracted from the article]

The concomitant presence of Castleman disease (CD) with other hematological pathology is an event described in the literature with increasing frequency, able to modify the diagnostic and curative approach in such patients. Very few studies in the literature describe the association of CD with concomitant neoplastic diseases; the most frequent are Kaposi's sarcomas (especially in HIV and human herpes virus-8-positive patients) and lymphoproliferative disorders, such as lymphomas. Instead, since the association with plasma cell diseases such as multiple myeloma and plasmacytoma is infrequent, there is a lack of literature. This manuscript aimed to revise the literature by describing a rare case of CD and plasmacytoma and attempting to explain the underlying triggering mechanisms. [ABSTRACT FROM AUTHOR]

Summary: As the COVID‐19 variant Omicron surge in Beijing, China, a better understanding of risk factors for adverse outcomes may improve clinical management in patients with haematological malignancies (HM) diagnosed with COVID‐19. The study sample includes 412 cases, mainly represented by acute leukaemia, chronic myeloid leukaemia (CML), plasma cell disorders and lymphoma and chronic lymphocytic leukaemia. COVID‐19 pneumonia was observed in 10.4% (43/412) of patients, and severe/critical illness was observed in 5.3% (22/412). Among the 86 cases with advanced malignancies, 17.6% (12/86) of patients developed severe/critical COVID‐19, which was significantly higher than reported in patients with stable malignancies (9/326, 2.70%, p < 0.001). Similarly, the advanced malignancy cohort had a higher mortality rate (9/86, 10.5% vs. 0/326, 0%, p < 0.001) and a poor 30‐day overall survival (OS) compared with the stable malignancy cohort (74.2% vs. 100.0%, p < 0.0001). Overall, nine patients (2.2%) died. The primary cause of death was progressive HM in four patients and a combination of both COVID‐19 and HM in five patients. In the multivariable analysis, over 65 years of age, comorbidities and advanced malignancy were correlated with severe/critical COVID‐19 in HM patients. This study sheds light on the poor outcomes among COVID‐19 HM patients with the leading cause of advanced malignancy. [ABSTRACT FROM AUTHOR]

Multiple myeloma is a heterogeneous clonal malignant plasma cell disorder, which remains incurable despite the therapeutic armamentarium's evolution. Bispecific antibodies (BsAbs) can bind simultaneously to the CD3 T-cell receptor and tumor antigen of myeloma cells, causing cell lysis. This systematic review of phase I/II/III clinical trials aimed to analyze the efficacy and safety of BsAbs in relapsed refractory multiple myeloma (RRMM). A thorough literature search was performed using PubMed, Cochrane Library, EMBASE, and major conference abstracts. A total of 18 phase I/II/III studies, including 1283 patients, met the inclusion criteria. Among the B-cell maturation antigen (BCMA)-targeting agents across 13 studies, the overall response rate (ORR) ranged between 25% and 100%, with complete response/stringent complete response (CR/sCR) between 7 and 38%, very good partial response (VGPR) between 5 and 92%, and partial response (PR) between 5 and 14%. Among the non-BCMA-targeting agents across five studies, the ORR ranged between 60 and 100%, with CR/sCR seen in 19–63%, and VGPR in 21–65%. The common adverse events were cytokine release syndrome (17–82%), anemia (5–52%), neutropenia (12–75%), and thrombocytopenia (14–42%). BsAbs have shown promising efficacy against RRMM cohorts with a good safety profile. Upcoming phase II/III trials are much awaited, along with the study of other agents in concert with BsAbs to gauge response. [ABSTRACT FROM AUTHOR]

Primary localized cutaneous nodular amyloidosis (PLCNA) is included in the primary forms of cutaneous amyloidosis along with macular and lichenoid amyloidosis. It is a rare disease attributed to plasma cell proliferation and deposition of immunoglobulin light chains in the skin. We present the case of a 75-year-old woman with a personal history of Sjogren's syndrome (SjS), who consulted for asymptomatic yellowish, waxy nodules on the left leg. Dermoscopy of the lesions showed a smooth, structureless, yellowish surface with hemorrhagic areas and few telangiectatic vessels. Histopathology revealed an atrophic epidermis and deposits of amorphous eosinophilic material in the dermis with a positive Congo red stain. The diagnosis of nodular amyloidosis was made. Periodic reevaluation was indicated after the exclusion of systemic amyloidosis. PLCNA is often associated with autoimmune connective tissue diseases, and up to 25% of all PLCNA cases occur in patients with SjS. Therefore, in addition to ruling out systemic amyloidosis, screening for possible underlying SjS should be performed when the diagnosis of PLCNA is confirmed. [ABSTRACT FROM AUTHOR]

Systemic AA amyloidosis is associated with systemic inflammatory processes such as autoimmune disorders or chronic infections. In addition, AA amyloidosis can develop in a localized or systemic form in patients with malignant neoplastic disorders, and usually involves kidneys impacting renal function. Among solid tumors, renal cell carcinoma (RCC) appears to be responsible for one-quarter to half of all cancers associated with amyloidosis. Among other solid cancers, various clinical presentations and pathological types of lung cancer and basal cell carcinoma skin were reported with AA amyloidosis more often than isolated case reports on other cancers with AA amyloidosis. Symptoms from kidney involvement rather than from the tumor per se were the presenting manifestations in cases of RCC associated with AA amyloidosis. Among hematological malignancies, clonal B cell/plasma cell dyscrasias such as monoclonal gammopathy and lymphoma were noted to be associated with AA amyloidosis. In addition, AA amyloidosis was reported in a substantial number of cases treated with immune checkpoint inhibitors such as pembrolizumab and nivolumab. The mechanism of association of cancer and AA amyloidosis seems to be mediated by the immune response exacerbated from the tumor and its microenvironment or immune therapy. The mainstay of treatment consists of therapy directed against the underlying malignancy or careful withdrawal of the offending agent. This review will discuss this rare but highly morbid clinical condition. [ABSTRACT FROM AUTHOR]

A total of 45 cases of canine oral extramedullary plasmacytomas (EMPs) presented to a tertiary referral institution over a 15‐year period were examined. Histologic sections of 33 of these cases were examined for histopathologic prognostic indicators. Patients underwent variable treatment including surgical intervention, chemotherapy and/or radiation therapy. Long term survival was observed in the majority of dogs with a median survival time of 973 days (2–4315 days). However, almost 1/3 of dogs had progression of plasma cell disease, including two cases with myeloma‐like progression. Histologic characterization of these tumours did not reveal criteria to predict tumour malignancy. However, cases without tumour progression did not exceed 28 mitotic figures in ten 400× fields (2.37 mm2). All cases with tumour related death showed at least moderate nuclear atypia. Oral EMPs may represent a local manifestation of systemic plasma cell disease or singular focal neoplasia. [ABSTRACT FROM AUTHOR]

I Purpose or Learning Objective: i (1) Describe the pathologic spectrum of multiple myeloma (MM); (2) review the diagnostic criteria and its update including SLiM (S, 60% plasma cells; Li, light chains; and M, magnetic resonance imaging [MRI] lesions)-CRAB (hypercalcemia, renal dysfunction, anemia, bone disease) criteria; (3) review the imaging techniques; and (4) learn how to evaluate the treatment response. I Conclusion: i WB-MRI is the technique of choice for the diagnosis and follow-up of MM, and the MY-RADS system provides a comprehensive characterization of the myeloma state. [Extracted from the article]

Free light chain (FLC) is used for the diagnosis and prediction with regard to the progression risk of plasma cell disorders and Freelite reagent using the SPAplus analyzer (The Binding Site) has been one of the widely used option. However, N Latex FLC reagent with the Atellica CH 930 analyzer (Siemens Healthineers) has shown the advantages of automation and high throughput. We aimed to evaluated clinical implication by differential analytical performances of two assays. A total of 322 serum samples were collected from 193 patients requested for FLC analysis including 131 multiple myeloma patients. The precision, linearity, dilution recovery of N Latex FLC assay was evaluated. We compared the two assays and analyzed the monomer-dimer pattern for discrepant results. The precision, linearity, and dilution recovery performance was appropriate for the routine use in clinical laboratories. Despite the good correlation within normal range, proportional bias up-to 170% was observed in samples with high concentrations especially for lambda. The higher value samples with N Latex FLC assay contained more monomer forms than controls. All opposite changes of FLC burden by the N Latex FLC assay proved to present concordant dynamic changes when assessed by serum protein electrophoresis. Clinical laboratories should be aware of the inter-assay variability of FLC quantitative measurements using different platforms, especially for high concentrations of both kappa and lambda measurements, possibly due to monomer/dimer ratio diversity. Clinical interpretations for multiple myeloma disease status might not be dramatically affected only when the same assay is utilized during follow-up periods. [ABSTRACT FROM AUTHOR]

Adult-onset hypophosphatemic osteomalacia is rare and diagnosis is frequently delayed. Fanconi syndrome (FS) due to monoclonal gammopathy is a well-recognized, but rare cause of hypophosphatemia. The relatively young age of patients and normal routine hematological parameters often results in late recognition of this treatable disease entity. Low phosphorus, elevated alkaline phosphatase, mildly impaired renal function and hypokalemia are often the only abnormalities on routine evaluation. We summarize the clinico-pathological features of two cases who initially presented with fractures and proximal myopathy and were subsequently found to have FS secondary to light chain proximal tubulopathy. Atypical features like absence of hypokalemia at presentation and elevated fibroblast growth factor 23 (FGF 23), a marker of oncogenic osteomalacia were noted. Marked clinical improvement and recovery of renal parameters were evident with phosphate supplements and chemotherapy for the plasma cell disorder. FS due to monoclonal gammopathy may present with atypical features and diagnosis may be challenging. [ABSTRACT FROM AUTHOR]