Primary Amyloidosis

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S83-S83 ◽  
Author(s):  
R Bhuyan ◽  
T T Tran ◽  
L Mc Phaul ◽  
Y Liu
Keyword(s):  
Bone Marrow ◽  
Renal Failure ◽  
Physical Examination ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Amyloid Deposition ◽  
Primary Amyloidosis ◽  
Plasma Cell Neoplasm ◽  
Cell Neoplasm

Abstract Introduction/Objective Amyloid light chain (AL) results from the deposition of immunoglobulin light chain fragments, and can lead to dysfunction in multiple organs. Our patient was being investigated for unknown malignancy with high differential for plasma cell neoplasm for severe amyloidosis leading to renal failure, uncontrolled ascites and thickening of the skin. The patient died of progressive liver and renal failure. Our autopsy findings show severe amyloidosis deposition in spleen, heart, kidney and liver with no significant plasma cells in the bone marrow, the findings correlate with a rare condition of primary AL amyloidosis. Methods 63 years old man with no past medical history presenting with progressive leg swelling with 15 pounds weight loss. He was admitted to another hospital a month ago. Patient was a smoker with a pack in 2-3 days for 38 years, occasional alcohol intake with no history of heavy alcohol use and no drug use. The patient worked as a chef and lived with his wife. Physical examination shows temporal wasting with cachecxia, had difficulty in staying upright and wanting to sleep when presented to the emergency department. Physical examination was significant for decreased breath sound bilaterally, more on left side, central weakness noted given difficultly sitting upright from laying down flat. Also, there were some lymphadenopathy in the jugular digastric region. Laboratory showed an increase elevation in alkaline phosphatase to the 1000s along with elevated LDL to 300s, nephrotic range proteinuria. Chest X-ray showed left pleural effusion and CT chest and abdomen showed slight hepatosplenomegaly with hypoattenuation and focal calcification. Autopsy finding indicated heavy spleen (260 grams) with a stiff and hard texture. Liver weighs in upper limit of normal (1660 grams) with a yellow firm surface. There is significant amyloid deposition in spleen. Also, moderate amyloid deposition was seen in all the organs including liver, kidney, heart and, also in the skin. No definite lesion was seen in the gross, nor cancer cells found in the microscopy examination. Bone marrow examination did not reveal plasma cells, ruling out the possibility of multiple myeloma or plasma cell dyscrasia. Conclusion This is a rare case of AL primary amyloidosis with aggressive progression and poor prognosis not associated with plasma cell neoplasm.

Del20q and Gain/Loss of Sex Chromosomes in Patients with Plasma Cell Neoplasm

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S12-S12
Author(s):  
Benjamin Lee ◽  
Shiyong Li
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Sex Chromosomes ◽  
Plasma Cells ◽  
Sex Chromosome ◽  
Plasma Cell Neoplasm ◽  
Clonal Proliferation ◽  
Age Related ◽  
Cell Neoplasm ◽  
Gain Loss

Abstract Aim Plasma cell neoplasm (PCN) is a clonal proliferation of plasma cells involving bone marrow and extramedullary anatomic sites. The purpose of this study is to investigate the prevalence and clinical significance of del20q and gain/loss of sex chromosomes in patients with PCN. Materials and Methods Routine karyotype analysis was performed on bone marrow aspirate specimens from patient with plasma cell neoplasm in the cytogenetics laboratory using the G-banding technology. Results from January 1, 2012 to June 21, 2019 were retrieved for analysis. Results Among the 8,665 karyotype results, 1,116 were abnormal and 593 demonstrated del20q and/or gain/loss of sex chromosomes. 33% (113/347) have bone marrow PCN when del20q and gain/loss of sex chromosomes occur in isolation, while 94% (256/250) have bone marrow PCN when 1 or more other autosomal abnormalities are also present. In those with isolated del20q or gain/loss of sex chromosomes, the frequency of bone marrow PCN ranges from 29–50%. Del20 occurs 1–6 years after therapy and in some patients is transient. Gain/loss of sex chromosome is generally present during the follow-up period. Conclusion Del20q and gain/loss of sex chromosomes do not appear to correlate with bone marrow PCN. Isolated Del20q likely represents transient treatment-related abnormality, while isolated gain/loss of sex chromosomes is probably age-related.

An Interphase Chromosome Profiling Assay to Determine the Need for CD 138 Enrichment in the Genetic Workup of Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4211-4211
Author(s):  
Ramesh Babu ◽  
Prasad Koduru
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Unknown Origin ◽  
Normal Result ◽  
Interphase Chromosome ◽  
Marker Chromosomes ◽  
Plasma Cell Neoplasm ◽  
Cell Neoplasm ◽  
Clonal Abnormalities

Abstract Plasma cell neoplasm, a B-cell malignancy is very common in elderly population and is currently incurable despite multiple treatment strategies. Genetic characterization, especially karyotype plays an important role in the diagnosis, prognosis as well as in the follow-up during treatment. In general, plasma cells are non-dividing and don't cooperate in tissue culture and as a result, over 90% of all standard cytogenetic studies end up having a "normal" karyotype. FISH testing using several probes has proven very useful in detecting the clonal abnormalities. It has been suggested and some laboratories do use CD138 antibodies to enrich the plasma cells in an effort to increase the detection rate of clonal abnormalities. However this additional step adds cost to the overall testing and the efficacy of this enrichment and the clinical utility is somewhat controversial. Many institutions don't enrich the plasma cells and still can detect the clonal abnormalities using FISH probes. It would be of interest if the need for enrichment is clarified and if the results from un-enriched studies are comparable to those of enriched, then the cost savings will be obvious. FISH testing, while extremely useful in increasing the detection of clonal abnormalities on the "normal" cytogenetic samples, has limitations in the sense that it can only detect the common changes targeted in the panels. Approximately 25% of all abnormal cases do have complex karyotypes harboring changes both numerical as well as structural that are beyond the scope of detection utilizing the current FISH panel of probes. These additional clonal changes have prognostic significance and it is well established that the greater the complexity of the karyotype, the worse is the prognosis. Therefore, it is imperative, from a clinical management standpoint that the testing laboratories use technologies that will detect all chromosomal abnormalities given the dismal culture success rate of traditional cytogenetic methods in detecting the abnormal clones. We have recently developed and validated a novel technology termed "Interphase Chromosome Profiling" (ICP) (Cytogenet Genome Res 2014;142:226, Abstract #22) which detects all chromosome abnormalities including the characterization of marker chromosomes and material of unknown origin i.e., add, in karyotypes. We utilized this technology on 10 unenriched samples from patients clinically suspected of multiple myeloma/plasma cell neoplasm. Each case had the traditional karyotype and FISH studies, in addition to ICP. Seven of the ten had a normal result with cytogenetics and FISH. ICP also produced a normal result in these cases. Three cases had an abnormal result by Cytogenetics and FISH. One of them had only one cell with abnormalities in the cytogenetic study. All three had complex karyotypes harboring the classic numerical abnormalities characteristic of multiple myeloma such as trisomy for chromosomes 3, 5, 7, 9, 11 etc. as well as multiple structural abnormalities including marker chromosomes and extra material of unknown origin (add). FISH failed to identify many of these structural changes which is an inherent limitation of the current design of panel of probes in clinical use. ICP on the other hand, detected not only all the abnormalities identified by both cytogenetics and FISH, but clarified and/or characterized the marker chromosomes and "add"s in these complex karyotypes. Interestingly, ICP identified a NOVEL duplication of the long arm of chromosome X, dup(X)(q21.3qter) in two of the three abnormal cases. Review of the literature indicates that this duplication on X chromosome is found in 20% of cases and harbors Cancer/Testis Antigens (CTAs) belonging to the MAGE family (CTA-X-MAGE) (Clin Dev Immunol. 2012;2012:257695. doi: 10.1155/2012/257695. Epub 2012 Mar 11) and is a potential target for novel immunotherapies. Yet classical cytogenetic approaches including FISH on enriched or unenriched samples will fail to identify this very important and common abnormality for which there is a potential therapy. Our results strongly indicate that ICP is very sensitive technique and can identify all chromosome abnormalities in interphase nuclei regardless of enrichment procedures for samples from multiple myeloma patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Plasma cell neoplasm with varied morphology: A report of two cases

2019 ◽  
Vol 11 (03) ◽  
pp. 281-283
Author(s):  
Gautam Kumar Vasnik ◽  
S. Venkatesan ◽  
Sanjeevan Sharma ◽  
Ajay Malik
Keyword(s):  
Bone Marrow ◽  
Differential Diagnosis ◽  
Plasma Cell ◽  
Final Diagnosis ◽  
Plasma Cell Neoplasm ◽  
Clonal Proliferation ◽  
Cytoplasmic Vacuoles ◽  
Cell Neoplasm ◽  
Morphological Diagnosis ◽  
Morphological Variants

AbstractPlasma cell (PC) neoplasm (PCN) with varied morphology has been described in the literature. The majority of clonal proliferation of PCs is composed of easily recognizable morphology in the bone marrow (BM). However, few cases may cause diagnostic complexity, as they exhibit varied cytological and architectural heterogeneity which may pose problem in morphological diagnosis and require the use of ancillary techniques like immunohistochemistry (IHC). We illustrate here two such cases of PCN with varied morphology in BM aspirate, in the form of clustering/rosetting and multiple clear cytoplasmic vacuoles, respectively, leading to varied differential diagnosis. However, later, the histopathological features on BM biopsy findings were relatively characteristic and IHC confirmed the final diagnosis. The morphological variants documented in both these cases are exceptional and representative of the various forms of atypical PCs.

The Natural History of Smoldering (Asymptomatic) Multiple Myeloma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3396-3396 ◽  
Author(s):  
Robert Kyle ◽  
Ellen Remstein ◽  
Terry Therneau ◽  
Angela Dispenzieri ◽  
Paul Kurtin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
M Protein ◽  
Cell Content ◽  
Bone Marrow Plasma ◽  
M Spike

Abstract Smoldering multiple myeloma (SMM) is characterized by a serum M protein ≥ 3g/dL and/or 10% or more of plasma cells in the bone marrow. However, the definition is not standardized, and it is not known whether both serum M protein levels and bone marrow plasma cell counts are necessary for diagnosis or if one parameter is sufficient. We reviewed the medical records and bone marrows of all patients from Mayo Clinic seen within 30 days of recognition of an IgG or IgA M protein ≥ 3g/dL or a bone marrow containing ≥ 10% plasma cells from 1970 to 1995. This allows for a minimum potential follow-up of 10 years. Patients with end-organ damage at baseline from plasma cell proliferation, including active multiple myeloma (MM) and primary amyloidosis (AL) and those who had received chemotherapy were excluded. A differential of the bone marrow aspirate coupled with the bone marrow biopsy morphology and immunohistochemistry using antibodies directed against CD138, MUM-1 and Cyclin D1 were evaluated in every case in order to estimate the plasma cell content. In all, 301 patients fulfilled either of the criteria for SMM. Their median age was 64 years and only 3% were less than 40 years of age; 60% were male. The median hemoglobin value was 12.9 g/dL; 7% were less than 10 g/dL, but the anemia was unrelated to plasma cell proliferation. IgG accounted for 75%, IgA 22%, and biclonal proteins were found in 3%. The serum light-chain was κ in 67% and λ in 33%. The median serum M spike was 2.9 g/dL; 11% were at least 4.0 g/dL. Uninvolved serum immunoglobulins were reduced in 81%; only 1 immunoglobulin was reduced in 31% and both were decreased in 50%. The urine contained a monoclonal κ protein in 36% and λ in 18% and 46% were negative. The median size of the urine M spike was 0.04 g/24h; only 5 (3%) were > 1 g/24h. The median bone marrow plasma cell content was 15 – 19%; 10% had less than 10% plasma cells, while 10% had at least 50% plasma cells in the bone marrow. Cyclin D-1 was expressed in 17%. Patients were categorized into 3 groups: Group 1, serum M protein ≥ 3g/dL and bone marrow containing ≥ 10% plasma cells (n= 113, 38%); Group 2, bone marrow plasma cells ≥ 10% but serum M protein < 3g/dL (n= 158, 52%); Group 3, serum M protein ≥ 3g/dL but bone marrow plasma cells < 10% (n= 30, 10%). During 2,204 cumulative years of follow-up 85% died (median follow-up of those still living 10.8 years), 155 (51%) developed MM, while 7 (2%) developed AL. The overall rate of progression at 10 years was 62%; median time to progression was 5.5 yrs. The median time to progression was 2.4, 9.2, and 19 years in groups 1, 2, and 3 respectively; correspondingly at 10 years, progression occurred in 76%, 59%, and 32% respectively. Significant risk factors for progression with univariate analysis were serum M spike ≥ 4g/dL (p < 0.001), presence of IgA (p = 0.003), presence of urine light chain (p = 0.006), presence of λ urinary light chain (p = 0.002), bone marrow plasma cells ≥ 20% (p < 0.001) and reduction of uninvolved immunoglobulins (p < 0.001). The hemoglobin value, gender, serum albumin, and expression of cyclin D-1 were not of prognostic importance. On multivariate analysis, the percentage of bone marrow plasma cells was the only significant factor predicting progression to MM or AL.

Bone Marrow Biopsy May Be Required During the Initial Evaluation of Individuals with Asymptomatic Monoclonal Gammopathy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5067-5067
Author(s):  
Meletios Athanasios Dimopoulos ◽  
Evangelos Terpos ◽  
Maria Gkotzamanidou ◽  
Evangelos Eleutherakis-Papaiakovou ◽  
Magdalini Migkou ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Bone Marrow Biopsy ◽  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Incidental Finding ◽  
M Protein ◽  
Monoclonal Protein

Abstract Abstract 5067 The incidental finding of a monoclonal gammopathy during workup for various conditions or in the context of a routine check-up is increasingly common. Several “patients” are then referred for diagnostic evaluation of their monoclonal gammopathy and additional workup is needed. It has been proposed that a bone marrow (BM) aspirate and biopsy is indicated when the monoclonal protein (M-protein) is ≥1.5 g/dL, when abnormalities are noted in the complete blood cell count, serum creatinine level, serum calcium level, or radiographic bone survey, in individuals with non-IgG monoclonal gammopathy and in those with an abnormal serum free light chain (FLC) ratio. The aim of this study was to identify factors that could aid in the evaluation of individuals presenting with asymptomatic monoclonal gammopathy and in whom invasive diagnostic testing with a bone marrow biopsy is considered. Thus, we analyzed our database and identified patients who were referred to the Department of Clinical Therapeutics of the University of Athens, Greece, for evaluation of asymptomatic monoclonal gammopathy and in whom a BM trephine biopsy, a serum and urine protein electrophoresis (SPEP) with immunofixation and quantitative immunoglobulins were performed. SPEPs were scanned and M-protein was measured using imaging analysis software. Patients with a monoclonal M-protein ≥ 3 g/dl (30 g/L), i.e. those diagnosed with asymptomatic/smoldering myeloma (SMM) or Waldenstrom's macorglobulinemia based on the standard criteria, were not included in the analysis. Clonality of BM plasma cells or lymphoplasmacytes was assessed by immunohistochemistry. Patients who eventually were diagnosed with plasma cell related conditions (i.e. amyloidosis, peripheral neuropathy, dermatoses, etc.) were also excluded from the analysis. Our analysis included 161 patients: 53% were females, median age was 64 year (range 33–89 years), 53% had a monoclonal IgG protein, 15.5% had a monoclonal IgA protein, 24% a monoclonal IgM protein and 2.5% had only a monoclonal light chain, while 4% had a biclonal protein. In 64% of patients the monoclonal light chain was kappa and in 37% was lambda. The median serum M-protein was 0.948 g/dl (range 0.1–2.99 g/dl); 52% of patients had an M-protein of <1 g/dl and 79% of <2 g/dl. Immunoparesis of at least one of the uninvolved immunoglobulins was present in 38% of cases and of both of the uninvolved immunoglobulins in 6%. Median BM infiltration by monoclonal plasma cells or lymphoplasmacytes was 15%. In 66.5% of individuals there was a BM infiltration of ≥10% by monoclonal plasma cells or lymphoplasmacytes, while in 10% of the studied cases the BM infiltration was ≥50%. A significant correlation of the size of M-protein and of the infiltration of the BM was found (R=0.592, p<0.001). However, 27% of patients with M-protein <0.5 g/dl had ≥10% clonal plasma cells or lymphoplasmacytes in their BM biopsies. The respective rates were 46% for those with M-protein <1 g/dl, 54% for those with M-protein 1.5 g/dl and 58% for those with M-protein <2 g/dl. Ninety per cent of those who had immunoparesis of at least one of the uninvolved immunoglobulins had ≥10% clonal plasma cells or lymphoplasmacytes. A BM infiltration of ≥10% was more frequent in individuals with a monoclonal IgG or IgA protein (72% and 80%, respectively) vs. 45% of those with a monoclonal IgM protein (p=0.015). Light chain isotype, age and gender were not predictive of the degree of BM plasma cell infiltration. In multivariate analysis, immunoparesis of at least one of the uninvolved immunoglobulins (OR: 6.45, 95% CI: 2.32–18, p<0.001), an IgG or IgA monoclonal protein (OR: 2.67, 95% CI: 1.1–6.4, p=0.028) and an M-protein of ≥1 g/dl (OR: 5.4, 95% CI: 2.23–13) were independently associated with the presence of ≥10% of clonal infiltration in BM biopsy. By combining the above risk factors we found that in those who had all three, 97% had ≥10% clonal cells in the BM biopsy, while in those with 0–1 of the above factors the probability to find ≥10% clonal cells was 43%. These findings indicate that even patients with low risk for BM infiltration by clonal plasma cells, may be diagnosed as SMM when a BM biopsy is performed. In conclusion, our data on a large number of individuals with asymptomatic monoclonal gammopathy who underwent a BM biopsy may indicate that the latter exam may provide useful information and could be included in the standard initial workup of these individuals. Disclosures: No relevant conflicts of interest to declare.

Comparison Of Hevylite™ Assay and Plasma Cell Immunophenotyping For Response Evaluation and Residual Disease Characterisation In IgA Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5319-5319
Author(s):  
Daniela Lakomy ◽  
Stephanie Lemaire-Ewing ◽  
Cedric Rossi ◽  
Jessica Borgeot ◽  
Jean-Noël Bastie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Binding Site ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Conflicts Of Interest ◽  
Residual Disease ◽  
Response To Treatment ◽  
Response Evaluation ◽  
Bone Marrow Plasma

Abstract Introduction The evaluation of multiple myeloma response to treatment as defined by international guidelines is currently based on morphologic examination of bone marrow plasma cells, serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and serum free light chain assay. For several years new tools are available as bone marrow plasma cell immunophenotyping and the HevyliteTM assay. HevyliteTM IgA assay provides an automated evaluation of serum heavy/light chain ratio (HLC) of the involved and uninvolved immunoglobulin (Ig) (i.e. IgAΚ/IgAλ). This is particularly interesting in IgA myeloma where the use of SPEP is limited due to a frequent comigration of monoclonal IgA with other proteins. We therefore compared the IgA quantification by Hevylite™ assay and the bone marrow plasma cell immunophenotyping for response evaluation and residual disease characterisation in IgA myeloma. Methods Hevylite™ assay, SPEP, IFE were performed in eleven IgA myeloma patients at different times: after induction chemotherapy, after the consolidation phase and after autologous stem-cell transplantation (ASCT). In the same time, minimal residual disease (MRD) assessment was performed on bone marrrow by multiparameter flow cytometry (MFC). Hevylite™ assay was performed on a Binding Site SPAplus analyser (Hevylite, Binding Site, Birmingham, UK) following the manufacturer recommendations. SPE and IFE were realized on Sebia Hydrasys analyser (Sebia, Evry, France) and results were read by two experienced biologists. Results 1. We found a perfect agreement between the IFE and immunophenotyping results at each time of evaluation, for positive results as for negative results. 2. The SPEP was contributive only in two patients and in these cases it was less sensitive than IFE. In the other patients, the monoclonal IgA migrated in beta region and/or as multiple bands, making the quantitative estimation difficult. 3. In all patients, when MRD by MFC was undetectable and IFE was negative, the HLC ratio was normal. 4. In 3 patients, HLC ratio was consistent with the IFE and MRD by MFC at each time of evaluation. Nevertheless, in 8 patients out of 11, while HLC ratio became normal, MRD by MFC and IFE were still positive. In all cases, the normalization of HLC ratio was followed, at the next step of evaluation, by the normalization of MFC and IFE. 5. In 5 patients, the normalization of HLC ratio occurred before ASCT, while IFE and MRD by MFC were still positive. Nevertheless, after ASCT, IFE and MRD by MFC became also negative, in accordance with the HLC ratio (Table 1). Conclusions During the evaluation of response to treatment of IgA myeloma, we observed a normalization of HLC ratio (Hevylite™ IgA assay) preceding the normalization of MRD by MFC and IFE. This could be explained by the fact that IFE and immunophenotyping provide very sensitive information but only on the monoclonal component. HLC ratio reflects the balance between the monoclonal and polyclonal Igs of involved and uninvolved isotype. A normalization of HLC ratio can be interpreted as an increasing polyclonal Ig proportion parallel with a decreasing monoclonal Ig proportion and may reflect the reconstitution of polyclonal plasma cells. If confirmed by other studies and long term follow-up, HLC ratio could be a non-invasive predictive marker of a good response in IgA myeloma. Disclosures: No relevant conflicts of interest to declare.

Metastatic CD138+ Lobular Breast Carcinoma Mimicking a Plasma Cell Neoplasm

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S107-S107
Author(s):  
Margaux Canevari ◽  
Justin Wells ◽  
Eric Pryor
Keyword(s):  
Bone Marrow ◽  
Breast Carcinoma ◽  
Bone Marrow Biopsy ◽  
Plasma Cell ◽  
Cytokeratin 20 ◽  
Serous Adenocarcinoma ◽  
Plasma Cell Neoplasm ◽  
Eosinophilic Cytoplasm ◽  
Cell Neoplasm ◽  
Lobular Breast Carcinoma

Abstract We present a case of an 85-year-old female who received a bone marrow biopsy for concern over myelodysplastic symptoms and was subsequently diagnosed with a CD138-positive metastatic lobular breast carcinoma that mimicked a plasma cell neoplasm. Her medical history included endometrial serous adenocarcinoma (pT1a N0), severe mitral regurgitation, and atrial fibrillation. She presented with a 3-month history of thrombocytopenia (60,000/mcL) and a down-trending macrocytic anemia (nidus hemoglobin: 6-7 g/dL) that prompted a bone marrow biopsy. The aspirate smears were aparticulate and hemodiluted, while the touch preparations revealed a homogeneous population of large, plasmacytoid cells. These were again seen filling the medullary cavity on the bone marrow biopsy with eccentrically placed nuclei containing nucleoli and abundant eosinophilic cytoplasm. The cells were CD138, cytokeratin 7 and 8/18, mammoglobulin, and GATA-3 positive. They were cytokeratin 20, TTF-1/Napsin, PAX-8, and uroplakin negative. Further testing revealed the cells to be estrogen receptor positive (strong, 90%+), progesterone negative, HER2 negative, p120 positive (strong cytoplasmic), and E-cadherin negative. The patient’s prior serous adenocarcinoma histomorphology was not consistent with the plasmacytoid cells. Prior literature revealed a case report on a metastatic lobular carcinoma to bone marrow and discussion on the morphologic similarities, but the case was CD138 negative. This case highlights that CD138 can be positive in certain carcinomas, some of which can have a plasmacytoid morphology. Suspicion should be raised in an elderly female population.

scholarly journals Daratumumab Interferes with Flow Cytometric Evaluation of Multiple Myeloma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5630-5630 ◽  
Author(s):  
Sudhir Perincheri ◽  
Richard Torres ◽  
Christopher A Tormey ◽  
Brian R Smith ◽  
Henry M Rinder ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Flow Cytometry ◽  
Cell Population ◽  
Plasma Cell ◽  
Light Chain ◽  
Plasma Cells ◽  
Kappa Light Chain ◽  
Positive Events ◽  
History Of

Abstract The diagnosis of multiple myeloma (MM) requires the demonstration of clonal plasma cells at ≥10% marrow cellularity or a biopsy-proven bony or extra-medullary plasmacytoma, plus one or more myeloma-defining events. Clinical laboratories use multi-parameter flow cytometry (MFC) evaluation of cytoplasmic light chain expression in CD38-bright, CD45-dim or CD138-positive, CD45dim cells to establish plasma cell clonality with a high-degree of sensitivity and specificity. Daratumumab, a humanized IgG1 kappa monoclonal antibody targeting CD38, has been shown to significantly improve outcomes in refractory MM, and daratumumab was granted breakthrough status in 2013. Daratumumab is currently approved for treatment of MM patients who have failed first-line therapies. It has been noted that daratumumab can interfere in blood bank assays for antibody screening, as well as serum protein electrophoresis (SPEP). We describe for the first time daratumumab interference in the assessment of plasma cell neoplasms by MFC; daratumumab interfered with both CD38- and CD138-based gating strategies in three MM patients. Patient A is a 68 year old man with a 10 year history of MM who had failed multiple therapies. He had then been treated with daratumumab for two months, stopping therapy 25 days prior to bone marrow assessment. Patient B is a 53 year old man with a 3 year history MM who had failed numerous treatments. He had been receiving daratumumab monotherapy for two months at the time of his bone marrow studies. On multiple marrow aspirates at times of relapse prior to receiving daratumumab, both patients had demonstrated CD38-bright positive CD45dim/negative plasma cells expressing aberrant CD56, as well as kappa light chain restriction; mature B cells were polyclonal in both. Patient C is a 65 year old man with a four-year history of MM status post autologous stem cell transplantation, who had been receiving carfilzomib and pomalidomide following relapse and continues to have rising lambda light chains and rib pain. He now has abnormal plasma cells in blood worrisome for plasma cell leukemia. Bone marrow aspirates from patients A and B, and blood from patient C demonstrated near absence of CD38-bright events as detected by MFC (Figure 1). Hypothesizing that these results were due to blocking of the CD38 antigen by daratumumab, gating on CD138-positive events was assessed; surprisingly, virtually no CD138-positive events were detected by MFC. All 3 samples demonstrated a CD56-positive CD45dim population; when light chain studies were employed using specific gating on the CD56-positive population, light chain restriction was demonstrated in all patients (Figure 1). Aspirate morphology confirmed numerous abnormal, nucleolated plasma cells (Figure 2A), thus excluding a sampling error. CD138 and CD38 expression was also tested on the marrow biopsy cores from both patients. In contrast to MFC, immunohistochemistry (IHC) showed positive labeling of plasma cells with both CD138 (Figure 2B) and CD38 (Figure 2C). The reason for the labeling discrepancy between MFC and IHC is unknown. The different antibodies in the assays may target different epitopes; alternatively, tissue fixation/decalcification may dissociate the anti-CD38 therapeutic monoclonal from its target. Detection of clonal plasma cell populations is important for assessing response to therapy. Laboratories relying primarily on MFC to assess marrow aspirates without a concomitant biopsy may falsely diagnose remission or significant disease amelioration in daratumumab-treated patients. MFC is generally highly sensitive for monitoring minimal residual disease (MRD) in MM, but daratumumab-treated patients should have their biopsy evaluated to confirm the MRD assessment by MFC. We were able to detect large numbers of plasma cells and also demonstrate clonality in our patients based on an alternative MFC marker, aberrant CD56 expression, an approach that may not be possible in all cases. Figure 1 Flow cytometry showing near-absence of CD38-bright elements in the marrow of patient A (top panels). Gating on CD56-positive cells in the same sample reveals a kappa light chain-restricted plasma cell population (bottom panels). Figure 1. Flow cytometry showing near-absence of CD38-bright elements in the marrow of patient A (top panels). Gating on CD56-positive cells in the same sample reveals a kappa light chain-restricted plasma cell population (bottom panels). Figure 1 The marrow aspirate from Fig. 1 shows abnormal plasma cells (A). Immunohistochemistry on the concomitant biopsy shows the presence of numerous CD138-positive (B) and CD38-positive (C) plasma cells. Figure 1. The marrow aspirate from Fig. 1 shows abnormal plasma cells (A). Immunohistochemistry on the concomitant biopsy shows the presence of numerous CD138-positive (B) and CD38-positive (C) plasma cells. Disclosures No relevant conflicts of interest to declare.

Analysis of Vλ-Jλ expression in plasma cells from primary (AL) amyloidosis and normal bone marrow identifies 3r(λIII) as a new amyloid-associated germline gene segment

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 948-953 ◽  
Author(s):  
Vittorio Perfetti ◽  
Simona Casarini ◽  
Giovanni Palladini ◽  
Maurizio Colli Vignarelli ◽  
Catherine Klersy ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Light Chain ◽  
Amyloid Fibrils ◽  
Plasma Cells ◽  
Strong Association ◽  
Gene Segment ◽  
Variable Region ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Primary Amyloidosis

Abstract Primary (AL) amyloidosis is a plasma cell dyscrasia characterized by extracellular deposition of monoclonal light-chain variable region (V) fragments in the form of amyloid fibrils. Light-chain amyloid is rare, and it is not fully understood why it occurs in only a fraction of patients with a circulating monoclonal component and why it typically associates with λ isotype and λVI family light-chain proteins. To provide insights into these issues, we obtained complete nucleotide sequences of monoclonal Vλ regions from 55 consecutive unselected cases of primary amyloidosis and the results were compared with the light-chain expression profile of polyclonal marrow plasma cells from 3 healthy donors (a total of 264 sequences). We demonstrated that: (1) the λIII family is the most frequently used both in amyloidosis (47%) and in polyclonality (43%); (2) both conditions are characterized by gene restriction; (3) a very skewed repertoire is a feature of amyloidosis, because just 2 germline genes belonging to the λIII and λVI families, namely 3r (22% of cases, λIII) and 6a (20%, λVI), contributed equally to encode 42% of amyloid Vλ regions; (4) these same 2 gene segments have a strong association with amyloidosis if their prevalences are compared with those in polyclonal conditions (3r, 8.3%,P = .024; 6a, 2.3%, P = .0008, χ2 test); (5) the Jλ2/3 segment, encoding the fourth framework region, appears to be slightly overrepresented in AL (83% versus 67%, P = .03), and this might be related to preferential Jλ2/3 rearrangement in amyloid (11 of 12 cases) versus polyclonal 3r light chains (13 of 22 cases). These findings demonstrate that Vλ-Jλ expression is more restricted in plasma cells from amyloidosis than from polyclonal bone marrow and identify 3r as a new disease-associated gene segment. Overusage of just 2 gene segments,3r and 6a, can thus account for the λ light-chain overrepresentation typical of this disorder.

A rare case of plasmacytoma of mandible revealing plasma cell myeloma

2021 ◽  
Vol 2 (5) ◽  
Author(s):  
Hari Ram ◽  
◽  
Sneha Gupta ◽  
Praveen Kumar Singh ◽  
Shivani Sharma ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Rare Case ◽  
Plasma Cells ◽  
Solitary Plasmacytoma ◽  
Bence Jones Protein ◽  
Jaw Bones ◽  
Plasma Cell Neoplasm ◽  
Cell Neoplasm ◽  
Single Bone

Multiple myeloma (MM) is a malignant proliferation of plasma cells with multiple foci. Plasmacytoma is a solitary plasma cell neoplasm involving a single bone. The most commonly involved bone is vertebra. Jaw bones are rarely involved as a first bone as they have lesser hematopoietic marrow. A solitary plasmacytoma may progress to multiple myeloma within few months to year. We present a case of a swelling of mandible that on further investigations confirmed the diagnosis of multiple myeloma. We have discussed the course of treatment given and its prognosis. Keywords: multiple myeloma; plasmacytoma of jaw; bence jones Protein; abnormal plasma cells; CD138.

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