Plasmacytoma Research Articles

Triple monoclonal protein-related kidney lesions in a patient with plasma cell dyscrasia: a case report

A toxic monoclonal protein typically results in a single kidney pathology due to the specific biophysical characteristics of monoclonal proteins. Multiple monoclonal protein lesions are rarely reported and often portend a poor prognosis. We present a 57-year-old male who developed rapidly progressive glomerulonephritis after concealed ruptured diverticulitis. A kidney biopsy showed light chain cast nephropathy, light chain proximal tubulopathy, and thrombotic microangiopathy. Laboratories showed IgG kappa with an M-spike of 0.2 g/dl and a kappa light chain of 16 mg/dl. A bone marrow biopsy showed 3% kappa-restricted plasma cells. The dramatic renal presentation despite the minimal hematological burden is suggestive of a highly toxic light chain, which is consistent with monoclonal gammopathy of renal significance (MGRS). Clone-directed therapy and a complement blockade were initiated. The patient remained dialysis-dependent despite a hematological response. This case highlights the importance of considering the toxic properties of monoclonal proteins in causing kidney diseases. Our case is the first report of an MGRS patient with three distinct kidney lesions. Triple monoclonal protein-related kidney lesions are very rare and are usually associated with multiple myeloma. Light chain cast nephropathy (LCCN) is a myeloma-defining event but his light chain (LC) (<50 mg/dl) and plasma cell (<10%) burdens were low which makes this case very unusual. Sepsis-induced low-flow stage and the toxic properties of LC may induce LCCN in this patient. Aggressive therapy is likely needed to eradicate the clone in order to achieve an organ response.

Demonstration of T-Cell Monotypia Using Anti-TCRbeta1/2 (TRBC1/2) Immunostaining as a Rapid and Cost-Effective Alternative to PCR-Based Clonality Studies for the Diagnosis of T-Cell Lymphoma

Background/Objectives: T-cell lymphomas are often histologically indistinguishable from benign T-cell infiltrates, and diagnosis typically relies on slow, complex, and expensive multiplexed PCR reactions, requiring significant training and experience to interpret them. We aimed to raise highly specific antibodies against the two alternatively used and very similar T-cell receptor beta constant regions, TCRbeta1 and TCRbeta2, encoded by the TRBC1 and TRBC2 gene segments, respectively. We sought to demonstrate the feasibility of detecting TCRbeta1 and TCRbeta2 immunohistochemically in routine clinical (formalin-fixed, paraffin-embedded (FFPE)) tissue sections as a novel diagnostic strategy for T-cell lymphomas. Methods: Recombinant rabbit antibodies were validated using Western blotting and FFPE immunostaining of T-cell leukemia lines. The immunostaining of FFPE tissue containing benign and lymphomatous T-cell populations was undertaken, with corroboration by BaseScopeTM high-sensitivity in situ hybridization and quantitative real-time PCR (Q-PCR). An additional Q-PCR literature review and analysis of publicly available RNAseq data was used to determine the TCRbeta2/TCRbeta1 ratio cut-off to separate benign and malignant T-cell populations. Results: Our TCRbeta1/TCRbeta2 antibody pair gave highly specific FFPE tissue staining. All benign samples analyzed (immunohistochemically, by BaseScopeTM, by Q-PCR, and by RNAseq data analysis) had TCRbeta1/TCRbeta2 or TRBC1/TRBC2 ranges well within the previously published flow cytometric benign range (TCRbeta2/TCRbeta1 = 0.18:1–5.7:1), while samples of T-cell lymphoma did not. One out of thirteen (7.7%) lymphoma samples showed some detectable TCRbeta1/TCRbeta2 protein co-expression, and 4 out of 13 (30.8%) T-cell lymphomas showed a TRBC1/TRBC2 transcript co-expression using BaseScopeTM. Conclusions: Analyzing T-cell monotypia immunohistochemically, analogous to B-cell monotypia (kappa: lambda ratio for B-cell and plasma cell neoplasms), could make the diagnosis of T-cell lymphomas cheaper, quicker, and more accurate. Larger studies are needed to validate our antibodies for clinical use.

Common laboratory results-based artificial intelligence analysis achieves accurate classification of plasma cell dyscrasias

Background Plasma cell dyscrasias encompass a diverse set of disorders, where early and precise diagnosis is essential for optimizing patient outcomes. Despite advancements, current diagnostic methodologies remain underutilized in applying artificial intelligence (AI) to routine laboratory data. This study seeks to construct an AI-driven model leveraging standard laboratory parameters to enhance diagnostic accuracy and classification efficiency in plasma cell dyscrasias. Methods Data from 1,188 participants (609 with plasma cell dyscrasias and 579 controls) collected between 2018 and 2023 were analyzed. Initial variable selection employed Kruskal-Wallis and Wilcoxon tests, followed by dimensionality reduction and variable prioritization using the Shapley Additive Explanations (SHAP) approach. Nine pivotal variables were identified, including hemoglobin (HGB), serum creatinine, and β2-microglobulin. Utilizing these, four machine learning models (gradient boosting decision tree (GBDT), support vector machine (SVM), deep neural network (DNN), and decision tree (DT) were developed and evaluated, with performance metrics such as accuracy, recall, and area under the curve (AUC) assessed through 5-fold cross-validation. A subtype classification model was also developed, analyzing data from 380 cases to classify disorders such as multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS). Results 1. Variable selection: The SHAP method pinpointed nine critical variables, including hemoglobin (HGB), serum creatinine, erythrocyte sedimentation rate (ESR), and β2-microglobulin. 2. Diagnostic model performance: The GBDT model exhibited superior diagnostic performance for plasma cell dyscrasias, achieving 93.5% accuracy, 98.1% recall, and an AUC of 0.987. External validation reinforced its robustness, with 100% accuracy and an F1 score of 98.5%. 3. Subtype Classification: The DNN model excelled in classifying multiple myeloma, MGUS, and light-chain myeloma, demonstrating sensitivity and specificity above 90% across all subtypes. Conclusions AI models based on routine laboratory results significantly enhance the precision of diagnosing and classifying plasma cell dyscrasias, presenting a promising avenue for early detection and individualized treatment strategies.

Oncolytic viruses: a potential breakthrough immunotherapy for multiple myeloma patients

Oncolytic virotherapy represents an innovative and promising approach for the treatment of cancer, including multiple myeloma (MM), a currently incurable plasma cell (PC) neoplasm. Despite the advances that new therapies, particularly immunotherapy, have been made, relapses still occur in MM patients, highlighting the medical need for new treatment options. Oncolytic viruses (OVs) preferentially infect and destroy cancer cells, exerting a direct and/or indirect cytopathic effect, combined with a modulation of the tumor microenvironment leading to an activation of the immune system. Both naturally occurring and genetically modified viruses have demonstrated significant preclinical effects against MM cells. Currently, the OVs genetically modified measles virus strains, reovirus, and vesicular stomatitis virus are employed in clinical trials for MM. Nevertheless, significant challenges remain, including the efficiency of the virus delivery to the tumor, overcoming antiviral immune responses, and the specificity of the virus for MM cells. Different strategies are being explored to optimize OV therapy, including combining it with standard treatments and targeted therapies to enhance efficacy. This review will provide a comprehensive analysis of the mechanism of action of the different OVs, and preclinical and clinical evidence, focusing on the role of oncolytic virotherapy as a new possible immunotherapeutic approach also in combination with the current therapeutic armamentarium and underlying the future directions in the context of MM treatments.

Secondary Cutaneous Plasmacytoma Occurring in a Knee Arthrotomy Scar: A Case Report

Secondary Cutaneous Plasmacytoma Occurring in a Knee Arthrotomy Scar: A Case Report

Insights into cardiac amyloidosis screening in TAVI from a Greek/Cypriot Cohort: the GRECA-TAVI registry

Abstract Background Transthyretin amyloid cardiomyopathy (ATTR-CM) is a disease with a poor prognosis and an unknown prevalence in the general population. Specific patient subgroups are at higher risk, such as patients with severe aortic stenosis (AS). Purpose To investigate the prevalence of ATTR-CM in Greek and Cypriot patients with severe AS that undergo Transcatheter Aortic Valve Implantation (TAVI). Methods A total of eight (n=8) tertiary hospital centers from Greece and Cyprus formed part of the GRECA-TAVI registry to evaluate the prevalence of ATTR-CM in patients undergoing TAVI. The inclusion criteria were diagnosis of severe AS in the presence of left ventricular hypertrophy (i.e. ≥12mm). Patients were referred for ATTR-CM screening by Tc99m-DPD or Tc99m-PYP bone scintigraphy. A complete hematologic workup was performed in all patients to rule out plasma cell dyscrasias. Cases with equivocal bone scintigraphy findings were not included in analysis. Results A total number of n=303 AS patients were screened from January 2023 until February 2024. Screening for CA with Tc99m-DPD/PYP bone scintigraphy and hematological tests was complete for all the patients included in the study. A positive bone scan (i.e. Perugini scale 2 or 3) was found in n=31 or 10.2% of the patients. The mean age of patients was not significantly different between AS patients with and without ATTR-CM (82,25 ±1,8 vs. 81,21 ±0,44 respectively, p=0.478). A male predominance was found in the ATTR-CM subgroup, although this was not statistically significant compared to non-ATTR-CM patients (%male: 64.5% vs. 49.3%, respectively, p=0.13). ATTR-CM patients had a lower LVEF compared to non-ATTR-CM patients (47.5% ±2.13 vs. 55% ±0.75, p=0.046). Conclusions The prevalence of ATTR-CM in this cohort of patients with severe AS undergoing TAVI was ~10%. These findings call for the implementation of national screening strategies for ATTR-CM which still remains significantly underdiagnosed in many geographic parts of the globe.

Outcomes in patients with light chain cardiac amyloidosis undergoing heart transplantation: a single centre UK study

Abstract Background Light chain cardiac amyloidosis (AL-CA) results in restrictive cardiomyopathy associated with progressive heart failure and poor survival. Traditionally, outcomes following heart transplantation in patients with AL-CA have been worse than in other heart failure cohorts and consequently, many centres do not offer this population transplantation. Purpose and Methods This was a retrospective observational study of 18 patients with AL-CA (age 52.7years +/- 8.3, male 66%) referred to our centre in the UK for assessment for heart transplantation from 2008 to 2023. Seven patients (39%) were listed for transplant, and all received orthotopic heart transplantation (OHT). This study compared pre-transplantation characteristics in those offered cardiac transplantation with those not transplanted. We also examined post-transplantation outcomes in this group (n=7) compared with the overall heart transplantation population (n=95) at our centre. Results Patients with AL-CA who were not offered transplantation (n=11) were older (mean age 54.3 vs 50.3 years), were more likely male (72% vs 57%) but had similar baseline renal function to those transplanted (median eGFR 60.4 vs 54.2ml/min). Reasons against offering OHT included extensive multisystem or renal amyloid deposition (n=4), insufficient haematological response (n=2), heart failure not advanced enough for OHT (n=1) and malignancy (n=1). Pre-transplant right heart catheterisation of patients undergoing OHT demonstrated a mean transpulmonary gradient of 7.8mmHg (+/- 1.9) and cardiac output of 2.94/min (+/- 0.3). Five patients (71%) had a complete and two (29%) a partial haematological response to clonally directed chemotherapy. Three patients were bridged to transplant with biventricular assist devices for 9, 10 and 51 days, respectively. Five patients developed episodes of histologically confirmed rejection of grade 2R that resolved with medical management. One patient experienced first degree atrioventricular block and had a pulseless electrical activity arrest 19 days after transplantation before being fitted with a permanent pacemaker. Two patients went on to receive autologous stem cell transplantation. Patients with AL-CA undergoing OHT had a lower mortality rate compared with non-transplanted patients over a median follow up of 9 months (HR 0.3, 95%CI 0.07-1.3, p = 0.10). Two patients with AL-CA died at 42 days and 7.7 years after OHT. Five patients (71%) are alive under follow up at 4, 7.5, 9, 10 months and 7.7 years post OHT. There was no difference in survival between patients who underwent heart transplantation for AL-CA and patients who underwent heart transplantation for all other indications (HR 1.94, 95%CI 0.3 – 12, p=0.45). Conclusions In selected patients with AL-CA, OHT offers favourable outcomes. After clonally directed therapy to control the underlying plasma cell dyscrasia, heart transplantation should be considered in the absence of widespread systemic disease.

Acquired Bortezomib Resistance in Multiple Myeloma:From Mechanisms to Strategy.

Multiple myeloma (MM) is a heterogeneous plasma cell tumor with a survival period of several months to over ten years. Despite the development of various new drugs, MM is still incurable and recurs repeatedly. Bortezomib, a landmark event in the history of MM treatment, has dramatically improved the prognosis of patients with MM. Although proteasome inhibitors (PIs) represented by bortezomib, have greatly prolonged MM survival, unfortunately, almost all MM will develop bortezomib resistance, leading to relapse with a shorter survival. It has been reported that both the tumor microenvironment and myeloma cells drive bortezomib resistance. Multiple treatment methods have been attempted to overcome bortezomib resistance, but unfortunately, there has been no breakthrough. It is believed that the key resistance mechanism has not yet been discovered. A deeper understanding of the mechanism of bortezomib resistance and strategies to overcome it can help identify key resistance mechanisms and further improve the prognosis of MM.

Comparative Study of Metabolic Tumor Volume in Multiple Myeloma and Related Plasma Cell Dyscrasias: 11C-Acetate PET vs. 18F-FDG PET.

Introduction Accurate diagnosis of multiple myeloma (MM) and related disorders depends on imaging studies for lesion detection, which is crucial for treatment planning. The 18F-fluorodeoxyglucose (FDG) PET imaging system is well-established, with high sensitivity and specificity in identifying myeloma lesions. Additionally, 11C-acetate serves as an effective radiotracer for detecting MM lesions. Metabolic tumor volume (MTV) measured with 18F-FDG PET has been suggested as a prognostic factor in MM patients. This study aimed to compare the feasibility of measuring MTV in patients with myeloma-related diseases using 11C-acetate or 18F-FDG PET/CT. Methods We retrospectively reviewed six patients with MM - three with symptomatic MM and three with smoldering MM - and one patient with a myeloma-related disorder, all of whom underwent both 11C-acetate and 18F-FDG PET/CT scans. Using a dedicated workstation (PET-STAT; AdIn Research, Inc., Tokyo, Japan) equipped with a standardized uptake value (SUV)-based automated contouring program, we calculated the SUV for MTV. Bone areas with an SUV above thresholds of 2.0 or 2.5 were grouped accordingly. Results MTV detection in the whole body was significantly higher with 11C-acetate compared to 18F-FDG at both thresholds. For the 2.5 threshold, MTV was 129 ± 109 mL versus 3.93 ± 9.38 mL (p = 0.016), and for the 2.0 threshold, it was 316 ± 221 mL versus 12.1 ± 23.7 mL (p = 0.016). Conclusions MTV measurements were significantly higher in PET/CT using 11C-acetate compared to 18F-FDG. This finding highlights the potential superiority of 11C-acetate over 18F-FDG for assessing the MTV of lesions in patients with MM.

PLASMA CELL NEOPLASM IN BREAST: A RARE CASE REPORT

Abstract Introduction/Objective Breast carcinoma continues to be the most common malignancy in women however plasma cell neoplasms are rare in breast tissue. Most of these recorded cases are from patients with Multiple myeloma (1). We present a rare case of a new breast lesion in a 69 year female incidentally found on imaging. She had a history of adenocarcinoma of lung with brain metastasis undergoing treatment. Methods/Case Report The patient’s breast lesion presentation was unusual without any pain or associated symptoms, but a new right breast mass was incidentally discovered on CT-Chest Abdomen-Pelvis. Mammogram revealed a 1.4 cm circumscribed mass in lower, outer breast with scattered calcifications. With the suspicion for a primary breast malignancy or metastatic disease from her lung cancer the patient’s breast lesion was biopsied. On histology, abnormal proliferation of cells with ovoid nuclei, vesicular chromatin and variable cytoplasm was noted with a background of mature adipose tissue. Immunohistochemistry showed neoplastic cells positive for plasma cell associated markers including CD38 (patchy), CD56, CD138, and MUM1 with a kappa restriction on ISH. The Ki67 showed 20% proliferation index. EBER was negative and SMARC4 and INI were preserved. Other immunohistochemical stains were performed to rule out differentials and were all negative. The morphology and IHCs were consistent with the diagnosis of Plasma cell neoplasm with kappa-restriction. Subsequently this patient developed a shoulder lesion which on biopsy showed a plasma cell neoplasm expressing plasma cell markers and kappa light chain overexpression. Results (if a Case Study enter NA) NA Conclusion It is critical to distinguish a breast plasma cell neoplasm from other primary and metastatic breast lesions in order to avoid unnecessary surgery and cytotoxic chemotherapy. Rarely, plasma cell neoplasm can manifests as a breast lesion, which in this case turned out to be the early manifestation of multiple myeloma.

Co-existence of Myelodysplastic Disorders and Plasma Cell Neoplasms: Case Series

Abstract Introduction/Objective The development of myelodysplastic syndrome (MDS) in patients with plasma cell neoplasm (PCN) receiving treatment is well reported. However, co-occurrence of both, without any chemotherapy history, is sparsely documented in the literature. We aim to highlight the possible association between both. Methods/Case Report Database search was done using Epic Slicer-Dicer for cases with biopsy proven co-existing MDS and PCN (from 2010-2022). The patients’ charts were reviewed to collect and analyze the clinical features. Results (if a Case Study enter NA) We identified 3 patients, all in their seventies on presentation: First patient: man, presented with unexplained chronic anemia. Serum protein electrophoresis (SPEP) showed elevated levels of monoclonal IgG kappa (4.2 g/dl). Evaluation of the BM biopsy revealed MDS with low blasts (WHO-5) with IgG plasma cell myeloma (56% Kappa-restricted plasma cells). Chromosome analysis revealed normal karyotype. Molecular studies were not done. Second patient: man, with Rheumatoid Arthritis and anemia. SPEP revealed biclonal IgG lambda (2.0 g/dl). BM biopsy indicated 5-8% lambda-restricted plasma cell proliferation. Anemia was managed with darbopoetin, but without improvement. The patient did not get chemotherapy. Follow-up BM biopsy was done, showing MDS with low blasts and ringed sideroblasts (WHO-5) alongside the PCN. FISH showed two abnormal IGH rearrangement populations. Chromosome analysis revealed normal karyotype. Molecular studies were not done. Third patient: woman, with pancytopenia. SPEP indicated monoclonal protein IgG lambda (1.8 g/dl). BM biopsy revealed 10% lambda-restricted plasma cell proliferation, coexisting with MDS with increased blasts grade 2 (WHO-5). Molecular studies showed: 2-FLT3 L601_K602insNFREYEYDL and ASXL1 E635fs*15. Chromosome analysis revealed normal karyotype. No in common clinical findings found during chart reviewing the cases. Conclusion Further investigating the underlying pathology, bone marrow microenvironment, and molecular and cytogenetics abnormalities in a larger number of patients with co-existing MDS and PCN is important. Also, if there was an association, it is important to study the sequence of occurrence between them.

Plasma Cell Leukemia with atypical CCND1/IGH fusion and Monocytoid morphology; A Rare Case Finding

Abstract Introduction/Objective Plasma cell leukemia (PCL) is a rare and aggressive form of plasma cell dyscrasia, often presenting as a variant of multiple myeloma (MM). It is characterized by the presence of ≥5% circulating plasma cells in peripheral blood, either as a primary or secondary manifestation of MM. Methods/Case Report Our case is of a 77-year-old male who presented with epigastric tenderness and bi-basilar crackles. Laboratory results showed severe hypercalcemia, elevated creatinine, leukocytosis, and elevated absolute neutrophil and lymphocyte counts. Imaging revealed widespread lytic lesions in the ribs, scapulae, thoracolumbar spine, and bony pelvis. Peripheral blood smear showed significant macrocytic anemia with rare polychromatophilic cells, numerous immature plasmacytoid cells (>20% of total cell count) and monocytoid morphology. Flow cytometry confirmed a population of monotypic plasma cells (28% of total cells). Bone marrow biopsy revealed a hypercellular plasma cell infiltrate with complex clonal karyotypic abnormalities, including the t(11;14)(q13;q32), rearrangements of 1p, and gain of 1q. FISH analysis showed an atypical CCND1/IGH fusion in 57% of cells, with one fusion, two orange (CCND1), and two green (IGH) signals. The case presented demonstrates a rare instance of an atypical CCND1/IGH fusion in plasma cell leukemia with monocytoid morphology, which poses diagnostic challenges. Prompt and accurate diagnosis is essential for managing the condition, given its consistently poor prognosis despite advancements in therapy over the past decade. Results (if a Case Study enter NA) NA Conclusion Our case highlights the importance of recognizing rare molecular abnormalities in PCL and suggests that further research into the molecular pathways involved in the disease is needed to improve diagnosis, treatment options and clinical outcomes.

Understanding renal tubular acidosis.

Renal tubular acidosis is a group of disorders characterised by metabolic acidosis, hyperchloraemia, normal anion gap, and potassium imbalance. Genetic mutations, drugs or acquired disorders disrupt the function of various transport proteins and enzymes in the renal tubules, causing diminished bicarbonate reabsorption or inability to excrete hydrogen ions, leading to proximal (type 2) and distal (type 1) renal tubular acidosis, respectively. These conditions are typically associated with hypokalaemia, which, if severe, can cause muscle paralysis and dangerous cardiac arrhythmias. A rare mixed variant (type 3), including features of both type 1 and type 2 renal tubular acidosis, has also been described. On the other hand, aldosterone deficiency or resistance leads to the hyperkalaemic form of renal tubular acidosis (type 4). If untreated, renal tubular acidosis can lead to long-term severe complications such as growth retardation, osteoporosis, rickets, osteomalacia, and renal calculi. Moreover, renal tubular acidosis might be the initial presentation of a more severe underlying pathology, such as autoimmune disease or plasma cell dyscrasias. A better understanding of the condition can help physicians diagnose and treat it early and prevent adverse outcomes.

Daratumumab-Based Therapeutic Approaches and Clinical Outcomes in Multiple Myeloma and other Plasma Cell Dyscrasias: Insights from a Nationwide Real-World Chart Review Study.

Singapore leads Southeast Asia in the routine use of daratumumab for multiple myeloma and other plasma cell dyscrasias. This retrospective review analyzed 112 patients who received daratumumab between 2012 and 2020. Tolerability, and efficacy based on prior lines (PL) of therapy, cytogenetic risk group, and the presence of renal impairment were presented. Infusion-related reactions occurred in 26.8% of patients. Grades 1 and 2 hematological and non-hematological adverse events were observed in 14.3% and 33.9% of patients, respectively. After a median follow-up of 16.9 months, there was no significant difference in overall response rates (ORR) (86% versus 76.3%, p = 0.082) or depth of response (≥ complete response (CR), 35.1% versus 28.9%, p = 0.469) between myeloma patients with and without renal dysfunction. Newly diagnosed and relapsed/refractory patients had an ORR of 92% and 76.3%, and a ≥ VGPR (very good partial response) rate of 80% and 55.3%, respectively. Median progression-free survival (PFS) was better for patients with 0/1 PL compared to ≥ 2 PLs (19.8 versus 6.2 months, p < 0.001), with a deeper response (≥ CR, 38.5% versus 16.7%, p = 0.033). Forty-six and a half percentage of patients had high-risk FISH abnormalities, and those with 0/1 PL had a significantly better ORR than those with ≥ 2 PLs (83.3% vsersus 47.1%, p = 0.022), achieving an ORR similar to that of the general cohort (80.2%, p = 0.905). In conclusion, positioning daratumumab in earlier lines of therapy leads to better outcomes and may mitigate the impact of high-risk FISH abnormalities.

Kidney function in newly diagnosed myeloma patients: factors associated with kidney impairment and recovery

Kidney disease is a common complication of multiple myeloma (MM) and a risk factor for increased morbimortality. In this retrospective cohort study based on medical records, we analyzed the kidney function of patients with renal disease related to MM during the first year of treatment. All patients included were consecutively admitted to the outpatient services of two hospitals between January 2009 and January 2019 and met the diagnostic criteria for MM regardless of the reason for seeking medical help. We excluded patients who had kidney disease or who were on dialysis before MM diagnosis. We investigated the factors associated with renal function recovery using multivariate analysis. We evaluated 167 patients (median age of 66 ± 11.49 years). Almost half of the patients had arterial hypertension (76; 45.5%). The majority had International Staging System (ISS) grades 3 (73; 43.7%) or 2 (60; 35.9%). Seventy-four (44%) patients had an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m² at the time of MM diagnosis. Fifty-two patients (31%) underwent hematopoietic stem cell transplantation (HSCT). After 12 months, 4 (2.3%) patients needed dialysis, and 18 (10.7%) died. The factors associated with an eGFR < 60 ml/min/1.73 m² were anemia, hyperuricemia, 24-hour proteinuria > 1.0 g, and extramedullary plasmacytoma. However, only baseline renal function (eGFR > 60 ml/min/1.73 m2) and HSCT were associated with greater recovery of renal function at 12 months of follow-up.

Clonality Determination by Detecting Unmodified Monoclonal Serum Free Light Chains Using On-Probe Extraction Coupled with Liquid Chromatography-High-Resolution Mass Spectrometry.

Serum free light chains (FLCs) are an essential clinical biomarker for the diagnosis and monitoring of patients with plasma cell neoplasms. The current widely used immunoassay methods quantify total serum FLCs, which include monoclonal FLCs as well as FLCs in the polyclonal background. Patients with chronic diseases, inflammatory disorders, or renal dysfunction can have elevated total FLCs that lead to ambiguous results. These patients may benefit from a direct measurement of monoclonal FLCs. The purpose of this study was to develop a method that couples on-probe extraction (OPEX) with liquid chromatography-high-resolution mass spectrometry (LC-HR-MS), abbreviated to OPEX-MS, to directly determine the clonality of FLCs. OPEX immunocapture was performed using microprobes loaded with anti-kappa or anti-lambda light chain antibodies. Captured proteins were separated by reversed-phase LC and analyzed by HR-MS. Four cohorts of samples from unique patients were tested based on immunoassay FLC results. The LC-HR-MS analysis in the OPEX-MS method provides both a unique retention time along with deconvoluted masses of FLC monomers and dimers for each clone. The study found that 16 out of 49 (33%) kappa FLC elevated samples as well as 83 out of 100 (83%) dual kappa and lambda FLC elevated samples did not have monoclonal FLCs, which is consistent with the knowledge that there is often no clonal population in samples with mildly elevated FLC immunoassay results. The OPEX-MS method can serve as a complementary approach to directly determine clonality in patients with difficult-to-interpret FLC immunoassay results.

Extramedullary plasmacytoma of the liver: report of a case

Extramedullary plasmacytoma of the liver: report of a case

8062 Uncommon Presentation of Multiple Myeloma as a Rapidly Growing Thyroid Goiter Initially Thought to be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

8062 Uncommon Presentation Of Multiple Myeloma As A Rapidly Growing Thyroid Goiter Initially Thought To Be Hashimoto's Thyroiditis

Abstract Disclosure: M.S. Shah: None. S. Humayon: None. K.P. Sanu: None. C. Peñaherrera: None. We present a unique case of an 85-year-old female with rapidly growing anterior neck swelling and subclinical hyperthyroidism, initially suggestive of Hashimoto's thyroiditis. The goiter initially responded well to steroids but rebounded back in size despite two courses of prednisone. This prompted further diagnostic workup which revealed unexpected findings, ultimately leading to the diagnosis of multiple myeloma involving the thyroid parenchyma and lymph nodes. The patient had no history of thyroid disorders or recent upper respiratory tract infections. She exhibited sudden neck swelling, mild subclinical hyperthyroidism, and positive TPO antibodies. Initial fine needle aspiration suggested lymphoid tissue with Hurthle cell differentiation, raising suspicion of Hashimoto's thyroiditis. Flow cytometry supported this diagnosis, but the potential for a Hurthle cell neoplasm persisted. Prednisone temporarily reduced thyroid size, but disease recurrence necessitated surgical excisional and incisional biopsies. Subsequent biopsies revealed plasma cell neoplasms consistent with multiple myeloma. The pathologic report confirmed MYC rearrangement, indicative of multiple myeloma involvement in lymph nodes and thyroid tissue. Protein electrophoresis revealed two restricted bands migrating in the gamma globin region. The patient experienced subclinical hyperthyroidism that evolved into euthyroidism over a month. Incidental findings included non-invasive, low grade papillary urothelial carcinoma. Disease progression was evident in a follow-up PET/CT, prompting oncology consultation. The patient initiated Revlimid with chemotherapy. Levothyroxine was prescribed for postoperative hypothyroidism, with adjustments based on thyroid panel results. This case report illustrates the intricate diagnostic challenges posed by multiple myeloma masquerading as a thyroid disorder. The unexpected evolution of the disease, marked by MYC rearrangement and metastatic spread, emphasizes the need for heightened vigilance in managing such cases. Clinicians should consider alternative diagnoses when treatment efforts fail to provide adequate response. This will ensure timely and appropriate management in clinical practice. This report contributes valuable insights into the diagnostic complexities and multidisciplinary considerations for addressing similar presentations in endocrine and oncology settings. Presentation: 6/1/2024

Comparison of 2 Free Light Chain Assays: Performance of the Free Light Chain Ratio as a Risk Factor for MGUS Progression.

New immunoglobulin free light chain (FLC) assays are available. Despite analytical differences, it seems possible to use free light chain ratios (FLCr) generated by different assays and apply similar cut-points for the diagnosis of multiple myeloma. It is still unknown if we can use different assays for risk stratification of patients with monoclonal gammopathy of undetermined significance (MGUS). Patients diagnosed with MGUS (N = 923) had FLC tested using a nephelometric FreeLite (Binding Site) assay on BNII instruments (Siemens) and a Sebia FLC assay (Sebia) on a DS2 ELISA analyzer (Dynex). Patients were followed up for progression to any plasma cell dyscrasia (PCD) for several decades. The Mayo MGUS risk stratification model for progression was assessed with both assays (M-spike >1.5 g/dL; non-IgG isotype and abnormal FLCr), using package insert reference intervals (RI) and a new metric called principal component 2 (PC2). There were 94 events of progression to PCD in the cohort during a median of 38 years of follow-up. Freelite and Sebia FLC showed similar hazard ratios in the risk models for elevated FLCr. An alternative clinical decision point lower than the package insert RI was evaluated for the Sebia assay, which improved risk stratification for patients with a low FLCr. The PC2 metric showed similar performance to the FLCr in models, without superior benefit. The Sebia ELISA-based FLC assay can be employed in an MGUS risk stratification model with similar performance to the original 2005 risk stratification model using the FreeLite assay.