Classic Hodgkin Lymphoma With Intrasinusoidal Pattern of Infiltration and Concurrent Plasma Cell Variant of Castleman Disease

2019 ◽  
Vol 152 (Supplement_1) ◽  
pp. S113-S113
Author(s):  
Sean Barrett ◽  
Katsiaryna Laziuk ◽  
Richard Hammer
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Hodgkin Lymphoma ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Large Cell ◽  
Castleman Disease ◽  
Neoplastic Cells ◽  
Classic Hodgkin Lymphoma ◽  
Cell Variant

Abstract The relationship between Hodgkin lymphoma and plasma cell variant of Castleman disease is uncommon but has been previously described. Most reported cases were diagnosed concurrently. However, sinusoidal involvement by Hodgkin lymphoma is very rare and morphologically can mimic anaplastic large cell lymphoma. Here we present a case of classic Hodgkin lymphoma with a sinusoidal pattern of infiltration coexisting with the plasma cell variant of Castleman disease. A 16-year-old male presented to clinic with shortness of breath and a worsening cough with yearlong duration. Medical history revealed no autoimmune disease, but there was a prolonged allergy history with chronic sinusitis. Imaging showed a right sided mediastinal mass, supraclavicular lymphadenopathy, and pleural effusion. CBC demonstrated anemia, neutrophilia, lymphopenia, and thrombocytosis. Excision of a supraclavicular lymph node revealed effaced architecture with marked plasmacytosis in the interfollicular areas and permeation of sinusoidal spaces by neoplastic cells with morphological features of classic Reed-Sternberg/Hodgkin cells; histiocytes, neutrophils, and residual follicles with regressed germinal centers were seen in the background. Immunohistochemistry revealed strong positivity for CD30 and CD15 by the neoplastic cells as well as positivity for PAX5, MUM1, and CD200 and faint membrane positivity for CD20. The neoplastic cells were negative for CD79a, CD45, EMA, ALK1, and associated T-cell markers. CD138 highlighted increased plasma cells that were negative for CD56, CD200 and polytypic for kappa and lambda. Concurrent bone marrow biopsy revealed a normocellular bone marrow with mild plasmacytosis and no evidence of involvement by lymphoma. Both lymph node and bone marrow were negative for HHV-8. Flow cytometry of the lymph node revealed no monotypic B-cell population and T cells showed predominance of CD4-positive cells with no aberrant antigen expression. The unusual morphologic pattern of classic Hodgkin lymphoma made the diagnosis challenging, and demonstration of proper immunophenotype is required for diagnosis.

scholarly journals A Coordinated Change in Chemokine Responsiveness Guides Plasma Cell Movements

2001 ◽  
Vol 194 (1) ◽  
pp. 45-56 ◽  
Author(s):  
Diana C. Hargreaves ◽  
Paul L. Hyman ◽  
Theresa T. Lu ◽  
Vu N. Ngo ◽  
Afshin Bidgol ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Lymph Node ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Fetal Liver ◽  
B Cell Precursors ◽  
Secondary Lymphoid Organs ◽  
Splenic Red Pulp ◽  
Medullary Cords ◽  
Red Pulp

Antibody-secreting plasma cells are nonrecirculatory and lodge in splenic red pulp, lymph node medullary cords, and bone marrow. The factors that regulate plasma cell localization are poorly defined. Here we demonstrate that, compared with their B cell precursors, plasma cells exhibit increased chemotactic sensitivity to the CXCR4 ligand CXCL12. At the same time, they downregulate CXCR5 and CCR7 and have reduced responsiveness to the B and T zone chemokines CXCL13, CCL19, and CCL21. We demonstrate that CXCL12 is expressed within splenic red pulp and lymph node medullary cords as well as in bone marrow. In chimeric mice reconstituted with CXCR4-deficient fetal liver cells, plasma cells are mislocalized in the spleen, found in elevated numbers in blood, and fail to accumulate normally in the bone marrow. Our findings indicate that as B cells differentiate into plasma cells they undergo a coordinated change in chemokine responsiveness that regulates their movements in secondary lymphoid organs and promotes lodgment within the bone marrow.

Unicentric plasma cell variant of castleman disease in the mesenteric lymph node: a rare and unusual case

Pathology ◽  
2012 ◽  
Vol 44 ◽  
pp. S85
Author(s):  
Jennifer Kim ◽  
Tamazin Leecy ◽  
Annabelle Mahar ◽  
Rooshdiya Karim ◽  
Christina Brown ◽  
...  
Keyword(s):  
Lymph Node ◽  
Plasma Cell ◽  
Mesenteric Lymph Node ◽  
Unusual Case ◽  
Castleman Disease ◽  
Mesenteric Lymph ◽  
Cell Variant

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% > 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% >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 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.

scholarly journals Production of interleukin-1 by bone marrow myeloma cells

Blood ◽  
1989 ◽  
Vol 74 (1) ◽  
pp. 380-387 ◽  
Author(s):  
F Cozzolino ◽  
M Torcia ◽  
D Aldinucci ◽  
A Rubartelli ◽  
A Miliani ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Plasma Cell ◽  
Plasma Cells ◽  
Interleukin 1 ◽  
Long Bone ◽  
Bone Lesions ◽  
Normal Donor ◽  
Biologic Activity ◽  
Culture Supernatants

Plasma cells isolated from bone marrow (BM) aspirates of 12 patients with multiple myeloma (MM) and nine patients with monoclonal gammopathy of undetermined significance (MGUS) were analyzed for production of cytokines with bone-resorbing activity, such as interleukin-1 (IL-1), tumor necrosis factor (TNF), and lymphotoxin (LT). Culture supernatants of plasma cells from MM, but not from MGUS or normal donor, invariably contained high amounts of IL-1-beta and lower amounts of IL-1-alpha. With a single exception, TNF/LT biologic activity was not detected in the same supernatants. IL-6 was present in two of five supernatants tested. Normal B lymphocytes released both IL-1 and TNF/LT activities for four days after activation in vitro; however, production of these cytokines ceased at the final stage of plasma cell. Unexpectedly, the mRNA extracted from MM plasma cell hybridized with TNF- and LT- specific, as well as IL-1-specific probes, although the culture supernatants did not contain detectable TNF/LT biologic activity. When tested in the fetal rat long bone assay, MM plasma cell supernatants displayed a strong osteoclast-activating factor (OAF) activity, which was greatly reduced but not completely abolished by neutralizing anti- IL-1 antibodies. Anti-TNF or anti-LT antibodies were ineffective in the same test. We conclude that the IL-1 released in vivo by malignant plasma cells has a major role in pathogenesis of lytic bone lesions of human MM.

scholarly journals Myeloma Cell Associated Therapeutic Protein Discovery Using Single Cell RNA-Seq Data

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-5
Author(s):  
Lijun Yao ◽  
Reyka G Jayasinghe ◽  
Tianjiao Wang ◽  
Julie O'Neal ◽  
Ruiyang Liu ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Cell Surface ◽  
B Cell ◽  
Tumor Cells ◽  
Plasma Cell ◽  
Tissue Specificity ◽  
Plasma Cells ◽  
Expression Data ◽  
Intracellular Proteins

Multiple myeloma (MM) is a hematological cancer of the antibody-secreting plasma cells. Despite therapeutic advancements, MM remains incurable due to high incidence of drug-resistant relapse. In recent years, targeted immunotherapies, which take advantage of the immune system's cytotoxic defenses to specifically eliminate tumor cells expressing certain cell surface and intracellular proteins have shown promise in combating this and other B cell hematologic malignancies. A major limitation in the development of these therapies lies in the discovery of optimal candidate targets, which require both high expression in tumor cells as well as stringent tissue specificity. In an effort to identify potential myeloma-specific target antigens, we performed an unbiased search for genes with specific expression in plasma and/or B cells using single-cell RNA-sequencing (scRNAseq) of 53 bone marrow samples taken from 42 patients. By comparing >40K plasma cells to >97K immune cells across our cohort, we were able to identify a total of 181 plasma cell-associated genes, including 65 that encode cell-surface proteins and 116 encoding intracellular proteins. Of particular interest is that the plasma cells from each patient were shown to be transcriptionally distinct with unique sets of genes expressed defining each patient's malignant plasma cells. Using pathway enrichment analysis, we found significant overrepresentation of cellular processes related to B-Cell receptor (BCR) signaling, protein transport, and endoplasmic reticulum (ER) stress, involving genes such as DERL3, HERPUD1, PDIA4, PDIA6, RRBP1, SSR3, SSR4, TXNDC5, and UBE2J1. To note, our strategy successfully captured several of the most promising MM therapeutic targets currently under pre-clinical and clinical trials, including TNFRSF17(BCMA), SLAMF7, and SDC1 (CD138). Among these, TNFRSF17 showed very high plasma cell expression, with concomitant sharp exclusion of other immune cell types. To ascertain tissue specificity of candidate genes outside of the bone marrow, we analyzed gene and protein expression data from the Genotype-Tissue Expression (GTEx) portal and Human Protein Atlas (HPA). We found further support for several candidates (incl. TNFRSF17,SLAMF7, TNFRSF13B (TACI), and TNFRSF13C) as being both exclusively and highly expressed in lymphoid tissues. While several surface candidates were not found to be lymphocyte-restricted at the protein level, they remain relevant considerations as secondary targets for bi-specific immunotherapy approaches currently under development. To further investigate potential combinatorial targeting, we examine sample-level patterns of candidate co-expression and mutually-exclusive expression using correlation analysis. As the majority of our detected plasma cell-specific genes encode intracellular proteins, we investigated the potential utility of these epitopes as therapeutic targets via MHC presentation. Highly expressed candidates include MZB1, SEC11C, HLA-DOB, POU2AF1, and EAF2. We analyzed protein sequences using NetMHC and NETMHCII to predict high-affinity peptides for common class-I and class-II HLA alleles. To correlate MHC allelic preference with candidate expression in our cohort, we performed HLA-typing for 29 samples using Optitype. To support our scRNAseq-driven findings, we cross-referenced gene expression data with 907 bulk RNA-sequencing samples, including 15 from internal studies and 892 from the Multiple Myeloma Research Foundation (MMRF), as well as bulk global proteomics data from 4 MM cell lines (TIB.U266, RPMI8226, OPM2, MM1ST) and 4 patients. We see consistent trends across both cohorts, with high positive correlation (Pearson R ranging between 0.60 and 0.99) for a majority of genes when comparing scRNA and bulk RNA expression in the same samples. Our experimental design and analysis strategies enabled the efficient discovery of myeloma-associated therapeutic target candidates. In conclusion, this study identified a set of promising myeloma CAR-T targets, providing novel treatment options for myeloma patients. Disclosures Goldsmith: Wugen Inc.: Consultancy. DiPersio:Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees.

Composite Prolymphocytoid and Hodgkin Transformation of Chronic Lymphocytic Leukemia

2000 ◽  
Vol 124 (6) ◽  
pp. 907-909 ◽  
Author(s):  
Maureen J. O'Sullivan ◽  
Zahid Kaleem ◽  
Michael J. Bolger ◽  
Paul E. Swanson ◽  
Mary M. Zutter
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Hodgkin Lymphoma ◽  
Progressive Disease ◽  
Plasma Cells ◽  
Single Agent ◽  
Malignant Neoplasm ◽  
Lymphocytic Leukemia ◽  
Richter Syndrome ◽  
Classic Hodgkin Lymphoma ◽  
Single Agent Chemotherapy

Abstract The indolent course of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is occasionally altered by transformation to a histologically distinct, rapidly progressive, and clinically unresponsive hematologic malignant neoplasm. We report a case of CLL that, after 3 years of slowly progressive disease and treatment with single-agent chemotherapy (fludarabine phosphate), underwent a composite prolymphocytoid and classic Hodgkin lymphoma transformation. The diagnosis of classic Hodgkin lymphoma was based on the presence of Reed-Sternberg cells with typical morphologic structure and immunophenotype (CD15+, CD30+, CD45−, CD20−) associated with the characteristic polymorphous inflammatory background consisting of numerous eosinophils, plasma cells, and reactive T lymphocytes. The remainder of the lymph node and the peripheral blood showed increased numbers of prolymphocytes admixed with typical small CLL cells. Recognition of such a transformation is of the utmost importance, since histologically similar Reed-Sternberg–like cells may be seen in Richter transformation. In contrast to prolymphocytoid transformation of CLL, Richter syndrome is rapidly fatal, with a median survival of 4 to 5 months. The patient pursued a clinical course similar to pure prolymphocytoid transformation and died with disease after 30 months following treatment with combination chemotherapy.

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