Plasma Cell Proliferative Disorder Research Articles

POEMS-associated Multicentric Castleman Disease: A diagnostic and Therapeutic Conundrum

Abstract Introduction/Objective A rare multisystemic, paraneoplastic hematologic disorder, POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is associated with an overproduction of pro-inflammatory cytokines caused by a plasma cell proliferative disorder. Castleman disease is a rare clinical entity described as a polyclonal lymphoid proliferation, that leads to generalized lymphadenopathy. It is rarely presented in association with POEMS Syndrome. Methods/Case Report A 55-year-old hispanic male, when being evaluated for liver mass, revealed bile duct thickening and a pancreatic head mass. Endoscopic fine needle aspiration biopsies were negative; however, the cross sectional imaging identified enlarged left axillary lymph nodes. His excisional lymph node biopsy showed human herpese virus-8 (HHV-8) negative multicentric Castleman disease (MCD). Several features of POEMS syndrome were noted. The axillary lymph node biopsy demonstrated florid follicular hyperplasia, scattered regressed germinal centers and concentric rings of mantle zone lymphocytes. CD138, kappa-ISH, and lambda-ISH highlight scattered polytypic plasma cells. Our case fulfills the mandatory criteria of POEMS syndrome with the presence of neuropathy and a constellation of other major and minor criterion including, axillary Castleman, splenomegaly, hepatomegaly, skin changes, ascites and bilateral renal cortical lesions. Furthermore the patient also has a history of cerebrovascular accident and chronic cough favoring POEMS syndrome. Results (if a Case Study enter NA) NA Conclusion The complexity and multi-organ involvement, leads to frequent misdiagnosis of POEMS disease. In addition significant overlap of symptoms of POEMS syndrome makes it difficult to differentiate from other plasma cell disorders associated with MCD. Our study includes a brief review of the literature delineating the characteristics and overlap between POEMS syndrome and other diseases.

The Journey to Diagnosis of Light Chain Amyloidosis: A Real-World Experience from a Single Center in Latin America

Light chain (AL) amyloidosis is a form of systemic amyloidosis, causing organ dysfunction; mainly affecting heart and kidneys. Due to the non-specific clinical manifestations, diagnosis is challenging and patients experience a long journey and treatment delay. Consequently, AL amyloidosis patients have extensive organ involvement at the time of diagnosis which implies a poor prognosis. Early diagnosis of AL amyloidosis is of paramount importance. There is limited real-world data from Latin America regarding the time from initial patient reported symptom onset to diagnosis. This retrospective cohort study aimed to assess clinical and laboratory characteristics, diagnostic journey, and outcomes of patients with AL amyloidosis treated in a medical care program in Argentina. AL amyloidosis patients were identified using a 12-year follow-up data (January 1, 2010 to December 31, 2022) from the institutional registry of amyloidosis (IRA).The IRA is registered in ClinicalTrials.gov (NCT01347047) and is approved by the IRB (CEPI 1635). Diagnosis of AL amyloidosis was confirmed by tissue biopsy staining positive with Congo red in addition to the demonstration of a monoclonal plasma cell proliferative disorder and the presence of amyloid-related systemic syndrome.The symptoms and signs related to amyloidosis were selected based on previously reported data in the literature. The number of medical consultations and health care resource utilization was collected from electronic medical records of patients in the medical care program. fThe statistical analyses were performed with Stata version 13.0. The continuous variables were presented as mean and standard deviation (SD) or median and interquartile range (IQR), and the categorical variables were presented as absolute frequencies and percentages. The survival rate was estimated by Kaplan-Meier. From 181807 community patients included in the comprehensive health care program, 28 patients were diagnosed with AL amyloidosis and included in the study. The median age at diagnosis was 73 (IQR, 66.5-80.5) years old and 64% (n=18) were female (Table 1).Heart and kidney were the most frequently affected organs. The median time from the first sign and/or symptom related to AL amyloidosis to diagnosis was 15.9 months (IQR, 8.8-38.2). Only 4 patients (14%) were diagnosed within the first six months since the onset of symptoms. Prior to diagnosis, the median number of symptoms and/or signs presented by the patients was 4 (IQR, 3.5-7). The median number of medical consultations prior to diagnosis was 3 (IQR, 1-5). The most consulted medical specialties were internal medicine (n=24, 86%), cardiology (n=14, 50%) and nephrology (n=10, 36%). Twelve patients (43%) were hospitalized at least once before diagnosis and 4 (14%) were hospitalized at least 3 times. Ten (36%) patients were diagnosed during a hospitalization. Involvement of more than three organs was present in 25% (n=7) of the patients. Fifty-seven percent (n=16) had cardiac involvement, mostly in advanced stages. Out of 23 patients that underwent treatment, 22 patients were treated with bortezomib based regimens in first line; 3 in combination with anti CD38. The median overall survival was 21 months (IQR, 4.6-49.8). The one-year overall survival rate after diagnosis was 55% (95% CI 34-71). The one-year overall survival rate for patients diagnosed within the first 12 months from the onset of symptoms was 70% (95% CI 32-89), while for those diagnosed after 12 months from the onset of symptoms, it was 45% (95% CI 20-67). This study provides real-world evidence about the diagnostic journey of AL amyloidosis patients in Latin America. AL amyloidosis is a complex disease with diverse manifestations, leading to diagnostic challenges even with growing awareness among the medical community. Patients often underwent a diagnostic odyssey involving multiple specialists and hospitalizations before the definitive diagnosis is reached.

Socioeconomic factors associated with a late-stage multiple myeloma diagnosis: An analysis of the National Cancer Database.

e20036 Background: Multiple myeloma is an aggressive monoclonal plasma cell proliferative disorder that is the second most common hematologic malignancy. On a global scale, multiple myeloma led to an estimated 106,000 deaths in 2018 alone. The exact cause of multiple myeloma is not well understood. Later stage of diagnosis is correlated with worse outcomes; thus, it is critical to assess the socioeconomic factors associated with diagnosis at early versus late stages. Methods: Using the National Cancer Database, we aimed to identify associations between socioeconomic factors of patients that present with Revised International Staging System (R-ISS) stage I multiple myeloma in comparison to R-ISS stage III at diagnosis. In this study, 5,512 patients from the National Cancer Database who were diagnosed with R-ISS stage I and stage III multiple myeloma were analyzed based on age, ethnicity, race, education, insurance type, income, education, geographic location, facility type, sex, Charlson-Deyo score, and urban or rural setting. Demographic factors of patients that presented with stage I and stage III disease were analyzed using chi square, ANOVA, and multivariate analyses. All patients included in the study were diagnosed with multiple myeloma between 2004 and 2020. Results: We identified significant (P < 0.05) associations between insurance type, median income, education, rural setting, and Charlson-Deyo score with diagnosis of R-ISS stage III multiple myeloma. For insurance type, private insurance, other government insurance, and Medicaid had lower percentages of R-ISS stage III diagnosis than patients without insurance (P < 0.001). Medicaid and over government insurance were up to 70% less likely to present with stage III MM than patients without insurance (P < 0.001). Regarding income and education, patients from a zip-code associated with an income of < $38,000 and zip-codes with lower levels of high school diploma had higher rates of stage III multiple myeloma diagnosis (P < 0.001). Patients from completely rural or less than 2,500 urban population adjacent to a metro area (P < 0.005) and not adjacent to a metro area (P < 0.025) showed significant increase in later stage multiple myeloma diagnosis than those from a metro setting with population above one million. Patients with Stage III at presentation were older than patients with stage I on average (P < 0.001). There were no significant differences seen based on race, sex, ethnicity, or region in the United States. Conclusions: Factors associated with increased likelihood of later stages of diagnosis of multiple myeloma include insurance type, median income, education, and rural location. Future analysis should further investigate the specific barriers to early patient diagnosis and treatment due to insurance type, education level, and rural setting.

Systemic AL amyloidosis: current approach and future direction

Systemic Light chain (AL) amyloidosis is a monoclonal plasma cell proliferative disorder characterized by deposition of amyloidogenic monoclonal light chain fragments causing organ dysfunction. It is a fatal disease and if not diagnosed and treated early can lead to organ failure and potentially death. The renal system along with the cardiovascular system are the most common organs involved but other organs such as gut and liver can be involved as well. The initial evaluation of patients requires confirming the diagnosis with tissue biopsy and staining with Congo red followed by confirmatory typing with mass spectrometry of the Congo red positive tissue. Then establishing the extent of the organs involvement by various staging and biomarkers testing. The treatment options and the tolerability of therapy depend on the disease staging, frailty, and co-morbidities. The autologous hematopoietic cell transplantation (HCT) after high dose melphalan therapy is an effective strategy which is usually done after initial bortezomib induction therapy. Unfortunately, most systemic AL amyloidosis patients are not candidate for HCT due to frailty, old age, multi-organ involvement, renal and heart failure at the time of diagnosis. While it is widely accepted that the patients need to be treated until they achieve complete hematologic response, the maintenance therapy after HCT is not well established in AL amyloidosis. In this review, we report the literature on the latest treatment updates of AL amyloidosis and the ongoing clinical trials highlighting the future treatments.

POEMS syndrome associated with vitiligo (P13-8.007)

<h3>Objective:</h3> To report a case of POEMS syndrome with vitiligo. This is the second case to be reported and the first in an Afro-American patient. <h3>Background:</h3> POEMS syndrome is a rare plasma-cell disorder with multisystem involvement, characterized by the acronym composing its name: Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein (M-protein), and Skin changes. Major criteria include mandatory polyneuropathy and monoclonal plasma cell proliferative disorder in addition to Castleman’s disease, sclerotic bone lesions, or elevated vascular endothelial growth factor (VEGF). Minor criteria, still helpful for diagnosis, include organomegaly, endocrinopathy, papilledema, thrombosis, and skin changes, the most common being hyperpigmentation. <h3>Design/Methods:</h3> Case Presentation <h3>Results:</h3> A 50-year-old Afro-American male presented with 3 years of ascending stocking-glove pattern numbness and skin discoloration in his feet. Other positive history included anhidrosis, heat intolerance and erectile dysfunction suggestive of dysautonomia. Medical history included hypoparathyroidism and idiopathic cirrhosis. He did not have history of alcohol overuse, diabetes, or glucose intolerance. Examination revealed confluent hypopigmented macules in feet, vibratory sensation impairments up to knees, absent temperature sensation in feet, and abnormal Romberg test and tandem gait. Remainder of the neurological examination was normal. Laboratory tests were significant for elevated free kappa and lambda light chains, plasma VEGF levels twice over normal range, and an IgA monoclonal band on serum protein electrophoresis. Other relevant laboratory findings included PTH-independent hypercalcemia and alkaline phosphatase elevation. Radiographs of hands, elbows, shoulders, and knees disclosed non-sclerotic lytic lesions. Nerve conduction studies were consistent with a sensorimotor axonal polyneuropathy. The patient met diagnostic criteria for POEMS syndrome. Autologous stem cell transplantation was recommended but the patient declined. His vitiligo, neuropathy, and monoclonal gammopathy remain stable under surveillance at 4 years without pharmacotherapy. <h3>Conclusions:</h3> POEMS syndrome should be suspected in any patient with new onset of vitiligo in the presence of an underlying polyneuropathy and a monoclonal plasma cell proliferative disorder. <b>Disclosure:</b> Dr. Landman has nothing to disclose. Dr. Escobar-Montealegre has nothing to disclose. Dr. Singh has nothing to disclose. Dr. Morales has nothing to disclose. Dr. Rossi has nothing to disclose.

Epidemiology of monoclonal gammopathy in Morocco – A hospital‐based study

Monoclonal gammopathies are a group of disorders associated with clonal proliferation of plasma cells that produces a monoclonal protein. The main objective of this study was to describe the epidemiological and immunochemical characteristics of monoclonal gammopathies diagnosed during 19 years in a Moroccan teaching hospital. This retrospective study enrolled 443 Moroccan patients with monoclonal gammopathy, patients meeting the inclusion and exclusion criteria in at the biochemistry department of Military Hospital in Rabat, the capital of Morocco, from January 2000 to August 2019. Of the 443 enrolled patients, 320 (72.23%) were men and 123 (27.77%) were women. All patients were of Caucasian origin, from 12 Moroccan regions. The patient's samples were collected and subjected to serum protein electrophoresis and serum immunofixation electrophoresis to further characterize the monoclonal protein. The mean ± SD age of the 443 participants was 62.24 ± 13.14 years. Reasons for being admitted to the hospital were as follows, bone pain (41.60%), renal failure (19.08%), alteration of the general condition (12.21%), and anemia (10.69). Plasma cell proliferative disorders in our study were as follows, multiple myeloma (MM) (45.65%), Monoclonal gammopathies of undetermined significance (MGUS) (39.05%), Waldenstrom's macroglobulinemia (5.58%), Lymphoma (2.27% + 1.2%), Chronic Lymphocytic Leukemia (2.48%), Plasma cell leukemia (1.86%), Plasmacytoma (0.62%), POEMS syndrome (0.41%), and Amyloidosis (0.84%). The most frequent isotypes in MM were the IgGκ (62) 36.5%, IgGλ (52) 30.6%, IgAκ (27) 15.9%, and the IgAλ (19) 11.2%. It is also worth noting that Free light chain MM represents 20% of all cases of MM. We found that monoclonal gammopathies are age-related and affects men more than women, also the results of this study point to the delayed diagnosis of monoclonal gammopathies, since most of our patients were diagnosed at the MM stage. The most frequent isotypes were the IgGκ and IgGλ in MM and MGUS, in Waldenström macroglobulinemia were IgMκ and IgMλ and the oligoclonal profile represented only 3.70%.

Disparity in the detection of chromosome 15 centromere in patients of African ancestry with a plasma cell neoplasm

PurposeFluorescence in situ hybridization (FISH) is the current gold standard assay that provides information related to risk stratification and therapeutic selection for individuals with plasma cell neoplasms. The differential hybridization of FISH probe sets in association with individuals’ genetic ancestry has not been previously reported. MethodsThis retrospective study included 1224 bone marrow samples from individuals who had an abnormal plasma cell proliferative disorder FISH result and a concurrent conventional G-banded chromosome study. DNA from bone marrow samples obtained from the G-banded chromosome study was genotyped, and a biogeographical ancestry prediction was carried out. ResultsUsing a cohort of individuals with a plasma cell neoplasm, we identified reduced hybridization of a chromosome 15 centromere FISH probe (D15Z4). Metaphase FISH studies of cells with 2 copies of chromosome 15 demonstrated a failure of the D15Z4 FISH probe to hybridize to one chromosome 15 centromere, revealing a false-positive monosomy 15 FISH result in some individuals. Surprisingly, individuals with a monosomy 15 FISH result had a median African ancestry of 77.2% (95% CI 74.1%-80.3%), compared with a median African ancestry of 2.2% (95% CI 2.0%-2.5%) in the non–monosomy 15 cohort (P value = 9.4 × 10−10). Thus, individuals with African ancestry had an 8.02-fold (95% CI 3.73-17.25) increased probability of having a false-positive monosomy 15 result (P value = 9.92 × 10−8). ConclusionThis study emphasizes a concern regarding the reliability of diagnostic genomic tools and their application in interpreting genetic testing results in diverse patient populations. We discuss alternative methodologies to better represent different ancestry groups in clinical diagnostic testing.

Family History of Hematologic Malignancies and Risk of Multiple Myeloma in Black Americans

Introduction: Multiple Myeloma (MM) is the most common hematologic malignancy in Black Americans. Standardized incidence rates are increasing, consistent with an aging population, and are 2- to 3- fold higher among Black Americans compared to White Americans for reasons that remain unclear. Methods: Using participants enrolled in the Integrative Molecular And Genetic Epidemiology (IMAGE) study of myeloma (955 MM cases; 1,316 sex-, race-, age-, geography- matched controls), we investigated the risk of MM associated with family history of cancer and differences by race. We estimated risk using odds ratios and corresponding 95% confidence intervals adjusted for confounders calculated from logistic regression. Results: Overall, MM risk in cases with a first degree relative affected with any hematologic malignancy was significantly elevated compared to controls (OR=1.36, 95% CI 1.02-1.82; P=0.038). Myeloma risk associated with a family history of MM was higher than the risk associated with any hematologic malignancy (OR=2.13, 95% CI 1.20-3.79; P=0.001), and the magnitude of this effect was greater for Black Americans (OR=4.88, 95% CI 1.90-12.51; P=0.001) than White Americans (OR=1.03, 95% CI 0.45-2.32; P=0.951) with similar relationships observed among first degree relatives with any plasma cell proliferative disorder (ORBlack=5.34, 95% CI 2.11-13.54; P=0.0004 and ORWhite=1.18, 95% CI 0.59-2.37;P=0.642) and with increasing numbers of affected relatives (P-trend=0.001). Conclusions: Findings confirm our previous report that the excess risk of MM observed in Black Americans may be attributed to shared germline and environmental susceptibility. Studies, which include family history of plasma cell proliferative disorders, to determine screening effectiveness in high-risk populations are warranted.

Evidence Supporting Light Chain Cast Nephropathy As a Myeloma Defining Event

BACKGROUND In 2014, the International Myeloma Working Group (IMWG) revised the Renal involvement of the CRAB (hyperCalcemia, Renal, Anemia, Bone lesions) criteria for the diagnosis of multiple myeloma (MM) as an acute decline in kidney function represented by either a serum creatinine (Scr) > 2 mg/dl or an estimated glomerular filtration rate of < 40 ml/min/1.73 m2 secondary to light chain cast nephropathy (LCCN) biopsy proven or suspected. Since LCCN occurs only in patients with high serum free light chain (FLC) levels, a high tumor burden is presumed but how often it occurs with other myeloma defining events (MDE) is unknown. METHODS Patients were selected from 2 cohorts. The first cohort came from a multicenter study on LCCN who were all diagnosed with MM between 2000 and 2018. Only newly diagnosed patients were included in this study. A second cohort was identified from the Mayo Clinic Kidney Biopsy database from 2003 to 2013. Inclusion criteria of this cohort were: the LCCN must be the dominate pathology on the kidney biopsy and it is secondary to a plasma cell proliferative disorder. Laboratory and radiologic data were collected to assess for CRAB criteria. Bone lesions were assessed by standard skeletal X-ray, MRI or CT/PET. Most had skeletal X-ray. The new SLiM CRAB criteria which have the addition 3 biomarkers: (S) >60% bone marrow plasma cells, (Li) an involved to uninvolved free light chain (FLC) ratio > 100 and (M) >1 bone lesion on MRI were also assessed. RESULTS From the multicenter study, 28 patients were excluded for having relapsed MM and 27 were from Mayo who were included in the second cohort leaving 123 patients. In the Mayo cohort, 52 patients were identified who met criteria. Both cohorts were comparable in age, sex, bone marrow plasma cells and hemoglobin at diagnosis (Table 1). Interestingly, 3.3% of the multicenter cohort and 3.9% of the Mayo cohort did not meet the R criterion due to a presenting creatinine of ≤ 2.0 mg/dl. In the multicenter cohort 2/99 (2.0%) and 4/52 (7.7%) of the Mayo cohort had < 10% bone marrow plasma cells. The presenting involved FLC was higher in the multicenter group (p = 0.001). In the multicenter cohort, 99.1% met at least one of the SLiM criteria and 84.7% met one the C,A,B criteria. In the Mayo cohort, fewer patients met at least one of the SLiM criteria (86.5%, p < 0.001) but more patients met one or more of the C,A,B criteria (98.1%, p = 0.01). All but 1 patient from the multicenter cohort met one or more of the SliM C,A,B criteria. The most common SLiM criteria met in the multicenter cohort was Li while it was M in the Mayo cohort. The most common C,A,B criteria in the multicenter cohort was A while it was B in the Mayo cohort. DISCUSSION This study provides the first evidence that nearly all patients who present with biopsy proven LCCN have at least one other MDE. Bone marrow burden was met in 98.0% of the multicenter cohort where all patients were diagnosed with MM, 92.3% of the Mayo cohort where the diagnosis of MM was not a prerequisite. More importantly, 84.7% and 98.1% of patients from the 2 cohorts respectively had another MDE besides LCCN confirming that LCCN is associated with high tumor burden. All but 1 patient would have been diagnosed with MM based on the SLiM CRAB criteria. In comparison to patients with other kidney lesions associated with monoclonal immunoglobulin, generally only 20-30% met the CRAB criteria for MM. This is why it is more appropriate to classify those patients as having monoclonal gammopathy of renal significance while patients with LCCN should be diagnosed with MM. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Recent developments on the application of molecular probes in multiple myeloma: Beyond [18F]FDG.

Multiple myeloma (MM) is a neoplastic plasma cell proliferative disorder characterized by various osteolytic bone destruction as a radiological morphological marker. Functional imaging, particularly nuclear medicine imaging, is a promising method to visualize disease processes before the appearance of structural changes by targeting specific biomarkers related to metabolism ability, tumor microenvironment as well as neoplastic receptors. In addition, by targeting particular antigens with therapeutic antibodies, immuno-PET imaging can support the development of personalized theranostics. At present, various imaging agents have been prepared and evaluated in MM at preclinical and clinical levels. A summary overview of molecular functional imaging in MM is provided, and commonly used radiotracers are characterized.

Plasma cell dyscrasias with complete loss of immunoglobulin heavy chain expression: A rare case

Background: We are presenting a cases of the monoclonal plasma cell proliferative disorders with complete loss of immunoglobulin heavy chain (HC) expression, which is not LC-MGUS. Method: Many literatures and text books were being reviewd regarding the classification, presentation and annual progression rate of Light chain myeloma and other dyscrasias expressing only light chain.Result: Literature data is very scarce. Most of the literatures are batting around LC-MGUS, but not beyond that. Conclusions: More light should be thrown on this darker area of light chain expressing plasma cell dyscrasias for better management.

Correlation of changes in subclonal architecture with progression in the MMRF CoMMpass study

Multiple myeloma (MM) is a heterogeneous plasma cell proliferative disorder that arises from its premalignant precursor stages through a complex cascade of interactions between clonal mutations and co-evolving microenvironment. The temporo-spatial evolutionary trajectories of MM are established early during myelomatogenesis in precursor stages and retained in MM. Such molecular events impact subsequent disease progression and clinical outcomes. Identification of clonal sweeps of actionable gene targets in MM could reveal potential vulnerabilities that may exist in early stages and thus potentiate prognostication and customization of early therapeutic interventions. We have evaluated clonal evolution at multiple time points in 76 MM patients enrolled in the MMRF CoMMpass study. The major findings of this study are (a) MM progresses predominantly through branching evolution, (b) there is a heterogeneous spectrum of mutational landscapes that include unique actionable gene targets at diagnosis compared to progression, (c) unique clonal gains/ losses of mutant driver genes can be identified in patients with different cytogenetic aberrations, (d) there is a significant correlation between co-occurring oncogenic mutations/ co-occurring subclones e.g., with mutated TP53+SYNE1, NRAS+MAGI3, and anticorrelative dependencies between FAT3+FCGBP gene pairs. Such co-trajectories may synchronize molecular events of drug response, myelomatogenesis and warrant future studies to explore their potential for early prognostication and development of risk stratified personalized therapies in MM.

Effect of the sequence of pull of bone marrow aspirates on plasma cell quantification in plasma cell proliferative disorders.

The evaluation of plasma cell (PC) compartment is influenced by the quality of bone marrow aspirate (BMA). Herein, we evaluated the impact of sequence of pull on quality of clinical assessment in plasma cell proliferative disorders (PCPDs). Histomorphology along with smears from first pull and second pull BMA and flow cytometric immunophenotyping (FCMI) data from second pull aspirate were evaluated for cellularity and PC%. Of the 484 samples, BMA smears were adequate in 87.4% of first pull (median PC=7%; IQR=2-25%) and 51.2% of second pull samples (median PC=2%; IQR=0.5-12%; p < 0.001). Recovery of PC was least on FCMI (median PC=0.59%; IQR=0.14-3.07%), however, sample adequacy was met in 42.6% of samples with acquisition of ≥3 million events. Second pull smears under-reported PC% in 34% of newly diagnosed multiple myeloma (NDMM) (<10% PC) and 46% of MM on therapy (<5% PC), resulting in suboptimal assessment. Bone marrow biopsy (BMBx) was evaluated in a total of 309 cases (median PC=10.0%; IQR 4.0-40.0%) with significantly higher numbers of BMPC% on BMBx compared with first pull smears (Mean ± 2SD: 25.9% ± 30.54 vs. 20.77% ± 20.20; p=0.001). First pull BMA smears were of superior quality but inadequate in one-tenth of samples. Second pull smears underreported PC% and recovery of PC compartment was poorest on FCMI. Concurrent bone marrow biopsy and use of the first pull sample for FCMI along with acquisition of a higher number of cells on FCMI may enhance the quality of assessment in PCPDs.

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

Hyperphosphatemia: A Clue to Diagnosis

Serum phosphate level reference range in adults is 2.5 mg/dL to 4.5 mg/dL and in children is 3 mg/dL to 6 mg/dL. The causes of hyperphosphatemia fall into four categories. These are decreased renal excretion of phosphorus, exogenous phosphorus administration, redistribution of phosphorus, and pseudohyperphosphatemia. We report a 69-year-old gentleman presented with the history of swelling of feet and facial puffiness of 1 month duration. He had renal failure with normal sized kidneys. Serum phosphorus was high. Advanced investigations revealed plasma cell proliferative disorder (clonal bone marrow plasma cells &gt;10%) on bone marrow examination, presence of M band at the junction of beta-2 and gamma region, and elevated serum IgG and serum beta-2 microglobulin. Hyperphosphatemia in multiple myeloma may be true, or pseudohyperphosphatemia. Diligent history, examination, and investigations have yielded the possibility of pseudohyperphosphatemia owing to multiple myeloma in our patient. The interference with the phosphomolybdate ultraviolet assay for serum phosphorus estimation is one of the reasons of pseudohyperphosphatemia in multiple myeloma. The other mechanism of pseudohyperphosphatemia could be the direct binding of paraprotein to phosphorus.

Gastrointestinal amyloidosis in a patient with smoldering multiple myeloma: A case report

BACKGROUNDSmoldering multiple myeloma (SMM) is an asymptomatic plasma cell proliferative disorder that can progress to multiple myeloma (MM). Amyloidosis (light chain) (AL) is the most common form of systemic amyloidosis. There are few reports of SMM coexisting with AL involving the digestive tract. CASE SUMMARYA 63-year-old woman presented with lower limb edema, abdominal distension, abdominal pain, and hematochezia. Gastroscopy showed gastric retention, gastric angler mucosal coarseness, hyperemia, and mild oozing of blood. Colonoscopy showed hyperemic and edematous mucosa of the distal ascending colon and sigmoid colon with the presence of multiple round and irregular ulcers, submucosal ecchymosis, and hematoma. Gastric and colonic tissue biopsy confirmed the diagnosis of AL by positive Congo red staining. MM was confirmed by bone marrow biopsy and immunohistochemistry. The patient had no hypercalcemia, renal dysfunction, anemia, bone lesions or biomarkers of malignancy defined as plasma cells > 60% in bone marrow. Additionally, no elevated serum free light chain ratio, or presence of bone marrow lesions by magnetic resonance imaging (SLiM criteria) were detected. The patient was finally diagnosed with SMM coexisting with AL. She received chemotherapy and was discharged when the symptoms were relieved. She is doing well at nearly five years of follow up.CONCLUSIONThis case highlights that high index of suspicion is required to diagnose gastrointestinal AL. It should be suspected in elderly patients with endoscopic findings of granular-appearing mucosa, ecchymosis, and submucosal hematoma. Timely diagnosis and appropriate therapy can help to improve the prognosis of these patients.

Flow cytometric immunophenotyping of plasma cells across the spectrum of plasma cell proliferative disorders: A fresh insight with pattern-based recognition.

The expression pattern of common antigens including cytoplasmic kappa/lambda ratio (cyKLR) was evaluated by flow cytometric immunophenotyping (FCMI) to explore their relevance in discriminating normal and aberrant plasma cells (NPC and APC, respectively) across spectrum of plasma cell proliferative disorders (PCPD). In this prospective analysis, 791 samples from PCPD (treatment naive=455; partially treated=336) were evaluated for expression of CD38, CD138, CD45, CD19, CD56, CD27, CD81, CD117, Cy-kappa, and Cy-lambda using FCMI. Amongst the entire cohort, 20.7% (n=164) samples displayed only APC, 21% (n=165) only NPC and 58% (n=462) showed coexistence of NPC and APC. Using pattern-based recognition (PBR) for three common patterns (CD19 vs. CD56; CD27 vs. CD56 and CD19 vs. CD27), APC was separable from NPC in 93% samples. In 6.5% samples, the gating markers contributed in APC-NPC differentiation and in the remaining 0.5% CD117 and CD81 proved useful. Clonality assessment was found to be crucial to label plasma cell compartment as completely normal or aberrant in 42% cases with either all NPC or all APC. Sixty one out of 462 cases (13%) revealed cyKLR within normal reference range and in these cases; abnormal cyKLR was demonstrable only after gating APC separately based on PBR. Fair discrimination between NPC and APC is achievable in all PCPD samples using eight markers (Gating: CD38, CD138, CD45; PBR:CD19, CD56, CD27; clonality: Cy-kappa and Cy-lambda). Thus, combined assessment of clonality and immunophenotypic aberrancies is required for accurate, reliable and precise assessment of NPC and APC compartments in PCPD.

POEMS Syndrome: A Case Report and Literature Review

POEMS syndrome is a rare paraneoplasic syndrome associated to a plasma cell proliferative disorder, which is characterized by the presence of peripheral neuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal gammopathy (M) and skin change (S). Because of the rarity of this disease, the small number of cases described in the literature and the polymorphism of the clinical manifestations, the diagnosis of POEMS syndrome remains difficult. The prognosis of the disease is related to the early onset of specific treatment. We hereby present a clinical case of POEMS syndrome in a 41-year-old woman revealed by a polyneuropathy, in order to highlight the diagnostic problems and to raise awareness of this syndrome.

A Case of POEMS Syndrome Previously Diagnosed with Extramedullary Plasmacytoma

POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes) syndrome is a rare multisystem disorder associated with osteosclerotic myeloma. It is characterized by peripheral polyneuropathy, presence of monoclonal plasma cell proliferative disorder, and one or more of the following features – sclerotic bone lesions, Castleman disease, elevated levels of vascular endothelial growth factor, organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, and thrombocytosis. Extramedullary plasmacytoma (EMP) is a rare plasma cell neoplasm that arises in isolated tissues without bone marrow involvement or systemic characteristics of multiple myeloma. Herein, we report a male patient who was previously diagnosed with EMP and later developed POEMS.

An Analysis of M-protein in Plasma cell Dyscrasia Patients Identifies that IgG Lambda Subtype is More Commonly Associated with Normal Serum Free Light Chain (SFLC) Ratio.

The determination of monoclonal protein (M-protein) by SPE, IFE and SFLC assay is fundamental in the diagnosis of Plasma cell proliferative disorder (PCPD). In the present study, we seek to assess the diagnostic performance and concordance of these three techniques in un-treated PCPD patients. All new patients with dysproteinemia and/or suspected PCPD were included in this retrospective observational study. The baseline parameters were retrieved from electronic medical records. SPE was performed on gel electrophoresis system; monoclonal component was identified by IFE. SFLC assays were performed by nephelometry using a latex-enhanced immunoassay. Total 402 patients of PCPD were included (10.9% of MGUS/SMM and 89.1% of multiple myeloma). The combination of SPE + rSFLC (ratio of kappa/lambda light chain) and SPE + IFE + rSFLC was able to detect M-protein across all subgroups of patients. In 61 patients, rSFLC values were within normal range (54.5% of MGUS/SMM and 10.3% of MM) and was more commonly seen with IgG lambda M-protein (57.4% vs. all-others). The median dFLC value, among these patients, was higher for MM than MGUS/SMM patients (23.8 vs. 14.4mg/L, respectively). The combination of SPE and rSFLC can be reliably used to detect M-protein in PCPD patients. In a small subgroup of MM patients, despite the presence of an intact immunoglobulin (M-protein), the rSFLC is not abnormal. Historically, these patients should respond better to treatment. However, a further follow-up analysis with more number of such patients would be advantageous for better understanding.