scholarly journals Bone marrow histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid, and myeloid findings in 87 patients

Blood ◽  
2011 ◽  
Vol 117 (24) ◽  
pp. 6438-6444 ◽  
Author(s):  
Linda N. Dao ◽  
Curtis A. Hanson ◽  
Angela Dispenzieri ◽  
William G. Morice ◽  
Paul J. Kurtin ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Poems Syndrome ◽  
Skin Changes ◽  
Bone Marrow Histopathology ◽  
Blood Smears ◽  
Peripheral Blood Smears ◽  
Lymphoid Aggregates

Abstract POEMS is an uncommon syndromic disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. There are few descriptions of the bone marrow pathology of POEMS; therefore, peripheral blood smears and bone marrow aspirates and biopsies from 87 patients (143 total, 67 pretreatment, 76 posttreatment cases) with POEMS were studied. Plasma cell clonality was analyzed by flow cytometry, immunohistochemistry, and/or in situ hybridization. Monotypic plasma cells were detected in 44 pretreatment cases (66%); the majority of plasma cells expressed λ light chain (91%). The monotypic plasma cells typically were present in a background of increased polytypic plasma cells. Lymphoid aggregates were found in 33 (49%) pretreatment cases and in most cases were rimmed by plasma cells (97%). Megakaryocyte hyperplasia (36 cases) and clusters (62 cases) were frequent; however, none of the 43 cases tested had the JAK2V617F mutation. In summary, we have identified a novel constellation of features that should strongly suggest POEMS syndrome as part of the differential diagnosis. The constellation of λ-restricted monoclonal gammopathy, plasma cell rimming around lymphoid aggregates, and megakaryocytic hyperplasia in a bone marrow is highly suggestive of this diagnosis, especially in the context of a peripheral neuropathy.

scholarly journals Utility of Flow Cytometry and Fluorescence in Situ Hybridization in Follow-up Monitoring of Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1880-1880
Author(s):  
Saurav Chopra ◽  
Timothy Dunham ◽  
Benjamin Darbro ◽  
Carol J Holman
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Residual Disease ◽  
Initial Diagnosis ◽  
Detection Rates ◽  
Cell Counts ◽  
Ancillary Studies

Introduction Diagnosis and follow-up monitoring of Multiple Myeloma (MM) requires documentation of (clonal) plasma cells using morphological bone marrow assessment and other ancillary studies including CD138 immunohistochemistry (IHC), flow cytometry (FC), and myeloma-specific fluorescence in situ hybridization (FISH). While IHC and FC have traditionally been shown to be the more sensitive methods for the assessment of residual disease, the detection rates of FISH have markedly increased with the recent use of magnetic cell sorting for CD138 cell enrichment. We, therefore, aimed to revisit the clinical utility of these ancillary studies in the diagnosis and follow-up of MM. Methods We retrospectively reviewed the reports of bone marrow biopsy specimens received for the initial diagnosis or follow-up assessment of MM from October 2015 to January 2019. All cases that had both FC and FISH performed were included in the analysis. Patient demographics, treatment history and the results of bone marrow evaluation were recorded. Results During the study period, we evaluated a total of 1,712 biopsy specimens from 464 MM patients (mean±SD age: 64.0±9.4 years; females 41.4%). Of these, 87 cases were submitted for initial diagnosis and 1,625 cases had already established MM and were being evaluated for post-treatment residual disease. For both initial diagnosis and follow-up cases, CD138+ IHC demonstrated highest plasma cell burden (mean: 49.1% and 4.6%, respectively) followed by morphological aspirate count (mean: 29.6% and 2.3%, respectively) and FC (mean: 10.9% and 1.8%, respectively). Both FC and FISH had comparable detection rates at the time of initial diagnosis (95.4% versus 97.7%, respectively) and for follow-up cases (28.6% versus 28.2%, respectively). The FC and FISH results were concordant in 97.7% of the initial diagnosis cases and 89.7% of follow-up cases. Discordant cases with positive FISH results and negative FC results included 2 (2.3%) initial diagnosis cases and 81 (5.0%) follow-up cases whereas those with negative FISH and positive FC results included 87 (5.3%) follow-up cases. In comparison with all concordant cases, the FISH positive, FC negative discordant cases were older in age, more likely to have received treatment with Daratumumab, and less likely to have received stem cell transplantation (p <0.05) (Table 1). When compared to the FC and FISH positive concordant cases; both discordant groups had significantly lower plasma cell counts detected by the aspirate smear and CD138+ IHC (Figure 1). Among all FC positive cases, the discordant cases had lower FC detected plasma cell counts and were less likely to have aberrant CD56 expression as compared to the concordant cases (p <0.05) (Table 2). Finally, among all FISH positive cases, the discordant cases were less likely to have 13q lesion and aneuploidy of chromosomes 5, 9, and 15 (p <0.05) as compared to the concordant cases. Also, between these groups, the percentage of plasma cells with individual FISH aberrations was significantly lower among the discordant cases (Table 3). Conclusion Overall, FISH (with magnetic cell sorting) and FC have comparable detection rates at the initial diagnosis and follow-up assessment. Approximately 10% of the follow-up cases have discordant FISH and FC results where residual disease is detected by only one of these modalities. Also, the discordant cases have significantly lower plasma cell counts as compared to the FC and FISH positive concordant cases. Therefore, this study suggests that both FC and FISH are useful for the follow-up monitoring of MM, especially in the cases with low plasma cell burden. Finally, the higher frequency of Daratumumab treatment in FISH positive, FC negative discordant cases might suggest Daratumumab's potential interference with the residual disease detection by FC. Disclosures No relevant conflicts of interest to declare.

APRIL Provides Springtime for Antibody-Producing Plasma-Cell Lifetime

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 2568-2568
Author(s):  
Bertrand Huard ◽  
Elodie Belnoue ◽  
Thomas Mc Kee ◽  
Thomas Matthes ◽  
Claire-Anne Siegrist ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Constitutive Expression ◽  
Lymphoid Tissues ◽  
Tnf Superfamily ◽  
Unique Source

Abstract Antibody-producing plasma cells depend on their environment for survival, but the molecules involved in this process are still not well defined. Plasma cells are fully equipped to respond to a proliferation inducing ligand (APRIL) from the tumor necrosis factor (TNF) superfamily, by virtue of their constitutive expression of the B-cell maturation antigen (BCMA), as canonical receptor from the TNF receptor superfamily, and the heparan sulfate proteoglycan (HSPG), CD138, as co-receptor. Here, we report that APRIL promoted the in vitro survival of plasma cells by upregulating expression of several anti-apoptotic molecules, such as bcl-2, bcl-xL and mcl-1. We further observed an in situ localization for APRIL consistent with this pro-survival role, both in mucosa-associated lymphoid tissues (MALT) and the bone marrow. In upper MALT, the tonsillar epithelium produced APRIL. Upon infection, APRIL production increased considerably when APRIL-secreting neutrophils, recruited from the blood, infiltrated the crypt epithelium. HSPG retained secreted APRIL in the sub-epithelium of the infected zone to create APRIL-rich niches, wherein IgG-producing plasma cells accumulated. In lower MALT, neutrophils were the unique source of APRIL giving rise to similar niches for IgA-producing plasmocytes in villi of lamina propria. The requirement on an inflammatory reaction in niche establishment implies that plasma-cell survival in mucosa is associated to pathogen presence, and must be short as a consequence. We observed also APRIL in the bone marrow. In this latter organ, maturating granulocytes produced constitutively APRIL. Such constitutive expression of a plasma cell pro-survival explains, at least in part, why plasma-cell longevity in the bone marrow can be so long lasting. These in situ human observations were confirmed in vivo with APRIL-deficient mice.

A Paracrine Circuit Regulates Vascular Endothelial Growth Factor Production By Bone Marrow Plasma Cells in Patients with POEMS Syndrome

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1757-1757
Author(s):  
Chen Wang ◽  
Qian-qian Cai ◽  
Xin-xin Cao ◽  
Dao-bin Zhou ◽  
Jian Li
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Serum Levels ◽  
Poems Syndrome ◽  
Newly Diagnosed ◽  
Bone Marrow Biopsies ◽  
Fluorescent Intensity ◽  
Bone Marrow Plasma ◽  
Endothelial Growth Factor

Abstract Background : POEMS syndrome is a rare paraneoplastic disorder, characterized by polyneuropathy, organomegaly, osteosclerosis and extravascular volume overload, due to an underlying plasma cell dyscrasia. Vascular endothelial growth factor (VEGF), a potent angiogenic cytokine that can increase vascular permeability, plays a critical role in its pathogenesis. Despite extensive VEGF studies concerning its role in disease diagnosis, monitoring and response assessment, little is known about its cellular source and mechanisms governing the production of VEGF in POEMS patients. Methods and Materials : Patients with POEMS syndrome, 62 newly diagnosed and 46 of them after lenalidomide-dexamethasone (LenDex) treatment, admitted to Peking Union Medical College Hospital between February 2014 and April 2015, were included in the current study. Clinical information, serum and bone marrow samples were collected with the Institutional approval. Serum levels of VEGF were measured by ELISA. VEGF levels in bone marrow plasma cells were quantified via real-time quantitative PCR and multiparameter flow cytometry, respectively. In addition, the phenotype, clonality and intracellular interleukin-6 (IL-6) expression of bone marrow plasma cells were also analyzed by flow cytometry. Furthermore, immunohistochemical staining was performed to study the plasma cell distribution, clonality and expression of VEGF, IL-6 and hypoxia-inducible factor-1α (HIF-1α) in bone marrow biopsies. Statistical analyses were conducted using SPSS 22, and a p < 0.05 was considered as significant. Results : Serum levels of VEGF were dramatically elevated in patients with newly diagnosed POEMS syndrome (median 5958 pg/mL), significantly higher than both disease and healthy controls (p < 0.001), and can be used as a diagnostic marker (area under curve 0.988, p < 0.001). A cut-off value of 2000 pg/mL had a specificity of 97.7% with a sensitivity of 91.9% in support of the diagnosis. After treatment, VEGF levels decreased gradually (6-cycle after LenDex, median 1184 pg/mL, p < 0.001; 12-cycle after LenDex, median 832 pg/mL, p < 0.001). Bone marrow plasma cells showed remarkable VEGF expression, validated in both mRNA and protein levels, which also decreased in response to LenDex therapy. More importantly, a statistically linear correlation was observed between serum and bone marrow plasma cell VEGF levels (newly diagnosed patients, rho = 0.33, p = 0.01; post-therapeutic patients, rho = 0.53, p < 0.001), supporting that bone marrow plasma cells were the source of circulating VEGF. Intriguingly, immunophenotying revealed that bone marrow plasma cells were polyclonal in most newly diagnosed cases. Monoclonal population, co-existing with polyclonal plasma cells, was observed only in 11 patients (18%). Further analyses showed that the relative amounts of these two populations were similar (41% vs. 59%) and they also had comparable intracellular VEGF expression (mean fluorescent intensity, 2009 vs. 2367, p = 0.594). However, monoclonal plasma cells had significantly higher intracellular IL-6 expression (mean fluorescent intensity, 1635 vs. 865, p = 0.006). In 46 newly diagnosed cases with bone marrow biopsies available, immunohistochemical staining was performed, and plasma cells were typically distributed in a scattered manner, with focal aggregates observed in 21 cases (46%). Intracellular κ and λ light chain staining demonstrated that the background scattered plasma cells were polyclonal, while both monoclonal and polyclonal fractions were observed in the focal area, which showed similar nuclear and intracellular staining of HIF-1α and VEGF, respectively. In contrast, IL-6 was mainly expressed in λ-restricted plasma cells. Conclusion : Bone marrow plasma cells are the potential source of VEGF production in patients with POEMS syndrome. Monoclonal plasma cells, aggregates focally in the bone marrow, may secret IL-6 to stimulate polyclonal plasma cells proliferation, and consequent VEGF production in a paracrine circuit. Disclosures Off Label Use: Lenalidomide for POEMS syndrome.

Fluorescent in Situ Hybridization Analysis at Bone Marrow Biopsy Section in Multiple Myeloma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4898-4898
Author(s):  
Eun Hae Cho ◽  
Sang-Mi Lee ◽  
Hyeon-Seok Eom ◽  
In-Suk Kim ◽  
Gyeong-Won Lee ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
In Situ Hybridization ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Cytogenetic Study ◽  
Fish Analysis ◽  
Molecular Cytogenetic ◽  
Plasma Cell Neoplasms

Abstract Abstract 4898 Introduction The technique of fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms has recently been introduced to detect molecular cytogenetic abnormalities in plasma cell myeloma of bone marrow (BM) aspirate. However, in case of sub-optimal BM aspirate or the focal distribution of myeloma in the BM, the plasma cells are significantly lower in the BM aspirate than those of biopsy section. Therefore, we have developed a sensitive fluorescence in situ hybridization (FISH) technique which is combined with immunochemistry and is applicable to BM biopsy section for molecular cytogenetic study of plasma cell neoplasms. Patients and Methods Conventional cytogenetic analysis and FISH results of BM samples of 35 multiple myeloma (MM) patients at the time of diagnosis have been evaluated. The probe for IgH rearrangement has been used for hybridization with myeloma cells coupled with CD138 immunostain at BM biopsy section. Results Nineteen patients (54.3%) had abnormal FISH IgH results in biopsy section, whereas seven (20%) cases had abnormal findings in BM aspirate. FISH IgH analysis at biopsy section revealed various signal patterns and proportions (range 6-87%) of cells with atypical signals out of CD138 positive cells. Among five cases with <10% of plasma cells at BM aspirate, four (80%) had abnormal FISH results at biopsy section, whereas one (20%) had abnormal signals at aspirate. There is no correlation between the proportions of cells with atypical signal corrected by the plasma cell count at BM aspirate and the proportions of cells with atypical signal at biopsy section. Conclusions FISH analysis combined with immunostain which is applied at biopsy section is a highly sensitive and convenient technique to detect and quantify monoclonal plasma cells. It could be used for molecular cytogenetic study in plasma cell neoplasms even though there are less than 10% of plasma cells at BM aspirate and the monitoring of residual disease. Disclosures Kong: National cancer center, Korea: Research Funding.

Validation of Immuno-Magnetic Chromatography As a Novel Method for the in Situ enrichment of Plasma Cells in Bone Marrow.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2930-2930
Author(s):  
Eric Crawford ◽  
Victoria Golembiewski-Ruiz ◽  
Mingya Liu ◽  
Robert D MacPhee
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Fish Analysis ◽  
Microscope Slide ◽  
Novel Method ◽  
Standard Risk ◽  
Supernatant Solution

Abstract Abstract 2930 Background: Multiple myeloma (MM) is characterized by the clonal proliferation of terminally differentiated plasma cells. These dyscrasias range from the phenotypically benign monoclonal gammopathy of unknown significance (MGUS), to the clinically significant form, multiple myeloma (MM). Molecular cytogenetic abnormalities are one of the measures that has been used to stratify patients. As the clinical cut-off values for individual fluorescence in situ hybridization (FISH) probes can exceed the total percentage of abnormal plasma cells within a specimen, the International Myeloma Workshop Consensus Panel recommends analysis for genetic abnormalities by FISH, preferably after plasma cell sorting, as one means to stratify patients into standard risk or high risk categories. Purpose: We present a novel method for plasma cell isolation in which antibody coated para-magnetic immunobeads are used in a two-step separation process that deposits an enriched population of CD138+ plasma cells directly onto a predefined area of a microscope slide in a manner suitable for subsequent staining and FISH analyses. Materials and Methods: The clinical materials utilized were appropriately anonymized extraneous volumes of bone marrow aspirates obtained after all routine clinical testing requests had been fulfilled. Briefly, 100ml of bone marrow is incubated with a blocking buffer and paramagnetic immunobeads covalently conjugated to anti-CD138 antibody (WaveSense, Irvine, CA) for 45 minutes at room temperature with gentle agitation. Primary enrichment is achieved when the tube is placed in a magnetic dock for 15 minutes allowing the paramagnetic immunobead-plasma cell-complexes to sediment on the side of the reaction tube. Unbound cells remain in the supernatant solution which is gently removed. The cells from the supernatant are still suitable for additional analysis for hematologic disorders not involving a CD138+ lineage. The residual CD138+ cell population is resuspended in blocking buffer. This enriched cell suspension is pipetted into an EpiSep® (WaveSense, Irvine, CA) chambered slide. As the solution diffuses through the unit, the suspended plasma cell-paramagnetic bead complexes are immobilized at the slide's surface as they pass close to a fixed magnet in the slide dock while the residual supernatant solution is eluted into adjacent chambers containing compact absorbent pads. A small volume of Carnoy's fixative is introduced through the EpiSep port to affect an initial fixation of the captured plasma cells deposited on the microscope slide's surface. The unit is then manually separated from the microscope slide. Samples were analyzed with a panel of FISH probes to assess copy number changes for chromosomes 5, 7, 13, 1p/1q, 17p and t(4;14), t(11;14) and t(14;16). Results: Bone marrow from 32 patients with indications of possible or known plasma cell disorders were enriched for CD138+ plasma cells. Conventional non-enriched FISH analysis detected reportable abnormalities in 11 (34%) of patients. With enrichment, abnormalities were detected in 21 (66%) of patients. When compared to abnormalities detected by FISH on non-enriched marrow, new abnormalities were detected in 14 (44%) of cases. Of the14 cases, 5 (36%) cases had abnormalities that shifted the prognosis from standard risk to high. An additional 3 cases (21%) had patterns consistent with an uncharacterized IGH rearrangement which may also hold a higher risk. The increased rate of abnormal cells ranged from 1.2x to 44.0x with an average increase of 9.7x. Cut-off values for the FISH analysis with this enrichment method were comparable to other methods of plasma cell enrichment. Discussion and Conclusions: We evaluated the use of a novel method to isolate and present only the target cell lineage. Deposition of a sorted plasma cell suspension via a slide chamber limits loss of plasma cells and confines these cells to a defined area for analysis. This method preserves cell morphology and avoids loss of cells that can occur with manual slide dropping methods. We found this strategy significantly increased both the sensitivity of detection levels and accuracy for determinations of these low-level, clinically prognostic genetic alterations while reducing the amount of bone marrow required for complete FISH analysis. Disclosures: MacPhee: WaveSense: Consultancy.

Should CD138 Immunohistochemistry be Standard Recommended Practice for Bone Marrow Evaluation of Plasma Cell Neoplasms?

2020 ◽  
Vol 154 (Supplement_1) ◽  
pp. S110-S110
Author(s):  
A Vijayanarayanan ◽  
K Inamdar ◽  
M Menon ◽  
P Kuriakose
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Linear Correlation ◽  
Plasma Cells ◽  
Pearson Correlation ◽  
Protein Electrophoresis ◽  
Pearson Correlation Coefficient ◽  
Cell Percentage ◽  
Significant Linear Correlation ◽  
Plasma Cell Neoplasms

Abstract Introduction/Objective Myeloma diagnosis by a pathologist requires 10% plasma cells (PC) or a biopsy proven plasmacytoma in addition to myeloma defining events. PC% &gt; 60% is a biomarker of malignancy under this definition. WHO allows for assesment of plasma cell percentage either by aspirate count or by CD138 immunohistochemistry (IHC). There is lack of consensus on aspirate smear adequacy for PC% estimation. Uneven distribution of plasma cells, hemodilution and/or patchy infiltration can lead to gross underestimation. We compared PC% by aspirate count and CD138 IHC and established corelation with serum protein electrophoresis (SPEP) values. Methods 67 myeloma cases were included after excluding cases with suboptimal or inadequate aspirate smears. Two hematopathologists evaluated the diagnostic marrow (therapy naive) for PC% by aspirate count and CD138 IHC on biopsy/clot section. Corresponding SPEP and Free light chain (FLC) values were obtained. Correlation coefficent was calculated using Pearson correlation coefficient (GraphPad Prism). Results The Ig subtypes included IgG (41/67) and IgA (17/67). 12 cases had available FLC values. Both average and median PC% by CD138 IHC was considerably higher (50%, 52%) compared to aspirate count (29%, 21%). However, PC% by aspirate smear count and CD138 IHC demonstrated a significant linear correlation (r=0.71, p60% by CD138 (and not by aspirate count). Conclusion CD138 IHC based PC% is consistently higher, nevertheless, statistically significant linear corelation is observed between aspirate count PC% and CD138 IHC. A significant linear correlation is observed between CD138 IHC and SPEP (IgG and IgA), however, no such correlation is observed with aspirate count. More cases were diagnosed as myeloma (11%) and higher propotion of cases (35%) had biomarker of malignancy i.e. PC% &gt;60% by CD138 IHC. Based on these findings, we propose estimation of PC% by CD138 immunostain be a recommended standard practice for better clinicopathologic and biologic correlation.

scholarly journals An Unprecedented Case of p190 BCR-ABL Chronic Myeloid Leukemia Diagnosed during Treatment for Multiple Myeloma: A Case Report and Review of the Literature

2018 ◽  
Vol 2018 ◽  
pp. 1-5
Author(s):  
Kosuke Miki ◽  
Naoshi Obara ◽  
Kenichi Makishima ◽  
Tatsuhiro Sakamoto ◽  
Manabu Kusakabe ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Chronic Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Plasma Cells ◽  
Bone Marrow Examination ◽  
Bone Lesions ◽  
Dexamethasone Treatment ◽  
Lytic Bone Lesions

We report the case of a 76-year-old man who was diagnosed as having chronic myeloid leukemia (CML) with p190 BCR-ABL while receiving treatment for symptomatic multiple myeloma (MM). The diagnosis of MM was based on the presence of serum M-protein, abnormal plasma cells in the bone marrow, and lytic bone lesions. The patient achieved a partial response to lenalidomide and dexamethasone treatment. However, 2 years after the diagnosis of MM, the patient developed leukocytosis with granulocytosis, anemia, and thrombocytopenia. Bone marrow examination revealed Philadelphia chromosomes and chimeric p190 BCR-ABL mRNA. Fluorescence in situ hybridization also revealed BCR-ABL-positive neutrophils in the peripheral blood, which suggested the emergence of CML with p190 BCR-ABL. The codevelopment of MM and CML is very rare, and this is the first report describing p190 BCR-ABL-type CML coexisting with MM. Moreover, we have reviewed the literature regarding the coexistence of these diseases.

scholarly journals Multiple myeloma: circulating lymphocytes that express plasma cell antigens

Blood ◽  
1984 ◽  
Vol 64 (2) ◽  
pp. 352-356
Author(s):  
GJ Ruiz-Arguelles ◽  
JA Katzmann ◽  
PR Greipp ◽  
NJ Gonchoroff ◽  
JP Garton ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Plasma Cell ◽  
Peripheral Blood ◽  
Plasma Cells ◽  
Peripheral Blood Lymphocytes ◽  
Tumor Burden ◽  
B Cell Differentiation ◽  
Blood Lymphocytes ◽  
Bone Marrow Plasma

The bone marrow and peripheral blood of 14 patients with multiple myeloma were studied with murine monoclonal antibodies that identify antigens on plasma cells (R1–3 and OKT10). Peripheral blood lymphocytes expressing plasma cell antigens were found in six cases. Five of these cases expressed the same antigens that were present on the plasma cells in the bone marrow. Patients that showed such peripheral blood involvement were found to have a larger tumor burden and higher bone marrow plasma cell proliferative activity. In some patients, antigens normally found at earlier stages of B cell differentiation (B1, B2, and J5) were expressed by peripheral blood lymphocytes and/or bone marrow plasma cells.

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