Lower number of 5-hydroxymethylcytosine-expressing cells in plasma cell myeloma than in reactive plasma cell hyperplasia: a useful immunohistochemical approach for identification of neoplastic plasma cells

Plasma cell myeloma is a bone marrow disorder characterized by neoplastic proliferation of plasma cells within the bone marrow replacing normal cells. We present a case report of a 25-year-old female with bilateral lower and upper limb pains. She had been seen in various health facilities for the past 2 years with progressively worsening disability. Skeletal survey revealed multiple osteolytic lesions in the appendicular skeleton resembling vanishing bone syndrome. Ultrasound-guided biopsy was done with histological diagnosis of plasma cell myeloma. This case is unique because of the young age at presentation, HIV seropositive status and atypical appearance of the lesions.

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Increased circulating plasma cells detected by flow cytometry predicts poor prognosis in patients with plasma cell myeloma

Cytometry Part B Clinical Cytometry ◽

10.1002/cyto.b.21606 ◽

2017 ◽

Vol 94 (3) ◽

pp. 493-499 ◽

Cited By ~ 7

Author(s):

Mi Hyun Bae ◽

Chan-Jeoung Park ◽

Bo Hyun Kim ◽

Young-Uk Cho ◽

Seongsoo Jang ◽

...

Keyword(s):

Flow Cytometry ◽

Plasma Cell ◽

Poor Prognosis ◽

Plasma Cells ◽

Plasma Cell Myeloma

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Immunohistological diagnosis of plasma cell myeloma based on cytoplasmic kappa/lambda ratio of CD138-positive plasma cells

Leukemia & Lymphoma ◽

10.3109/10428194.2012.685734 ◽

2012 ◽

Vol 53 (11) ◽

pp. 2205-2209 ◽

Cited By ~ 1

Author(s):

Shoko Nakayama-Ichiyama ◽

Taiji Yokote ◽

Yuji Hirata ◽

Kazuki Iwaki ◽

Toshikazu Akioka ◽

...

Keyword(s):

Plasma Cell ◽

Plasma Cells ◽

Plasma Cell Myeloma

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Biclonal IgD and IgM Plasma Cell Myeloma: A Report of Two Cases and a Literature Review

Case Reports in Hematology ◽

10.1155/2013/293150 ◽

2013 ◽

Vol 2013 ◽

pp. 1-5 ◽

Cited By ~ 2

Author(s):

Zhongchuan W. Chen ◽

Ioanna Kotsikogianni ◽

Jay S. Raval ◽

Christine G. Roth ◽

Marian A. Rollins-Raval

Keyword(s):

Bone Marrow ◽

Plasma Cell ◽

Plasma Cells ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Protein Electrophoresis ◽

Plasma Cell Myeloma ◽

Clinical Behavior ◽

Therapeutic Implications ◽

Immunohistochemical Studies

Biclonal plasma cell myelomas producing two different isotypes of immunoglobulins are extremely rare entities; to date, the combination of IgD and IgM secretion by a biclonal plasma cell myeloma has not been reported. Bone marrow biopsy immunohistochemical studies in two cases revealed neoplastic plasma cells coexpressing IgD and IgM, but serum protein electrophoresis identified only the IgM monoclonal paraprotein in both cases. Biclonal plasma cell myelomas, while currently not well characterized in terms of their clinical behavior, should be distinguished from B-cell lymphoma with plasmacytic differentiation, given the different therapeutic implications. Both cases reported herein demonstrated chemotherapy-resistant clinical courses.

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The Cytologic Reaction of the Spleen in Experimental Amyloidosis in Mice

Blood ◽

10.1182/blood.v16.4.1491.1491 ◽

1960 ◽

Vol 16 (4) ◽

pp. 1491-1498

Author(s):

AVINOAM ZLOTNICK ◽

CHLOE TAL

Keyword(s):

Plasma Cell ◽

Plasma Cells ◽

Methyl Violet ◽

Globulin Fraction ◽

Cell Hyperplasia ◽

Experimental Amyloidosis ◽

The Subject ◽

The Relationship ◽

Normal Controls

Abstract Seventy W.-H. Swiss line mice were injected with adjuvant, TAB vaccine and TAB vaccine plus adjuvant. The 61 mice which survived form the subject of this study. Spleen smears and histologic sections taken after completing immunization revealed a marked deposition of amyloid in 48 of the animals. Varying degrees of plasma cell hyperplasia were observed in 46 animals, and increased granulopoiesis in 37. In 28 of the amyloid-bearing animals some of the plasma cells were transformed into "flame cells" which stained faintly positively with PAS and metachromatically with methyl violet. Electrophoresis of the pooled sera of animals receiving adjuvant alone, TAB plus adjuvant or TAB alone, compared to normal controls, showed decrease in albumine and an increase in the globulin fraction. Animals receiving adjuvant alone showed an increase in the beta globulins, while animals receiving TAB plus adjuvant or TAB alone showed an increase in the gamma globulins. The relationship between the production of amyloid, plasma cell hyperplasia and the appearance of "flame cells" is discussed.

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Cyclin D1 Immunohistochemistry Identifies a Subset of Plasma Cell Myeloma with Superior Overall Survival.

Blood ◽

10.1182/blood.v104.11.4854.4854 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4854-4854

Author(s):

James R. Cook ◽

Eric D. Hsi ◽

Raymond R. Tubbs ◽

Sarah Worley ◽

Mohamad A. Hussein

Keyword(s):

Bone Marrow ◽

Overall Survival ◽

Cyclin D1 ◽

Plasma Cell ◽

Plasma Cells ◽

D1 Protein ◽

Progression Free Survival ◽

Plasma Cell Myeloma ◽

Free Survival ◽

Cyclin D1 Protein

Abstract The expression of Cyclin D1 is dysregulated in approximately half of cases of plasma cell myeloma due to translocations, aneusomy, or other abnormalities. Recent studies using quantitative mRNA analysis have suggested that increased Cyclin D1 mRNA expression is associated with a favorable prognosis. Previous attempts to examine the significance of cyclin D1 protein expression by immunohistochemistry have been hampered by the use of antibodies with weak staining and high background. In this study, we employ a newly available, commercial antibody that gives superior staining in B5 fixed tissues. We performed immunohistochemistry for Cyclin D1 on bone marrow core biopsies from a series of 44 newly diagnosed plasma cell myeloma patients who were uniformly treated on a Phase II study of rituxan, melphalan and prednisone. 22 patients (50%) were positive for Cyclin D1, defined as any plasma cells with positive nuclear staining. Cyclin D1 positive and negative cases displayed no significant differences in the initial levels of β2m (3.6±0.5 mg/L vs. 3.5±0.5 mg/L, p=0.860), number of bone marrow plasma cells (63±5.5% vs. 47±6.2%, p=0.063), or proportion of cases classified as SWOG stage 3-4 (2 of 22 (9%) vs. 5 of 22 (23%), p=0.412). The cyclin D1 positive cases displayed a superior overall survival with an estimated 3-year survival of 95% for Cyclin D1 positive cases versus 56% for Cyclin D1 negative cases (p=0.032). The cyclin D1 positive cases also displayed a trend towards better progression-free survival (median progression free survival of 15.7 months for Cyclin D1 positive versus 12.8 months for Cyclin D1 negative, p=0.13). In a Cox proportional hazards regression model, used to compare the effect of Cyclin D1 protein expression on overall survival time while adjusting for stage, the Cyclin D1 positive patients continued to show a strong trend to better overall survival (p=0.062). This study demonstrates that cyclin D1 immunohistochemistry, which could be readily performed in most pathology laboratories, is capable of identifying a subset of plasma cell myeloma with a favorable survival. Additional studies are ongoing to determine if these results can be generalized to other forms of therapy. If confirmed, routine cyclin D1 immunohistochemistry at the time of diagnosis may offer important prognostic information that could identify lower risk patients for whom less intensive therapies might be appropriate.

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Evaluation of a 5-Color Flow Cytometric Technique for Immunophenotyping and Quantitation of Plasma Cell Myeloma in Post-Therapy Bone Marrows.

Blood ◽

10.1182/blood.v108.11.5036.5036 ◽

2006 ◽

Vol 108 (11) ◽

pp. 5036-5036

Author(s):

Tove Isaacson ◽

Andrzej Jakubowiak ◽

Lloyd Stoolman ◽

Usha Kota ◽

William Finn ◽

...

Keyword(s):

Bone Marrow ◽

Flow Cytometry ◽

Minimal Residual Disease ◽

Plasma Cell ◽

Plasma Cells ◽

Residual Disease ◽

Plasma Cell Myeloma ◽

Color Flow ◽

Flow Cytometric ◽

Minimal Residual

Abstract Multiparameter flow cytometry is a useful tool for comprehensive immunophenotyping of plasma cell myeloma, and has been proposed as a sensitive method for the evaluation of minimal residual disease in patients following treatment. This study aimed to assess the value of flow cytometry in quantitation of residual disease, in comparison to routine morphologic examination of first-pull bone marrow aspirate smears, in myeloma patients post-therapy. Heparinized bone marrow aspirates were obtained from 27 treated patients with plasma cell myeloma. Cells were prepared for 5-color flow cytometric analysis within 24-hours of specimen draw. Surface membrane staining with anti-CD19, CD20, CD38, CD45, CD56, and CD138 was followed by ammonium chloride lysis of red cells. Fixed and permeabilized cells were analyzed for cytoplasmic light chains to confirm clonality. Data were acquired using an FC500 flow cytometer (Beckman-Coulter), analyzed with CXP software with plasma cells isolated based on bright CD38+ or CD138+ expression. A median of 97,639 cellular events (range 14,279 to 262,508) were collected per analysis. Flow cytometric enumeration of plasma cells was compared to 500-cell differential counts of Wright-Giemsa-stained first-pull aspirate smears from the same cases. The median plasma cell count as determined by flow cytometry was 0.5% (range 0–7.9%). The median plasma cell count estimated by morphologic review was 8.0% (range 0–84.4%). Flow cytometry underestimated the plasma cell content in all but one case. Clonal plasma cells expressed CD38 and CD138 in all cases; 87.5% (21/24) coexpressed CD56, 25% (6/24) coexpressed CD45, and 4.2% (1/24) coexpressed CD19. None was positive for CD20. Although detection of minimal residual disease after therapy for acute leukemia is routinely achieved by flow cytometric analysis, successful quantitation of minimal residual disease in treated myeloma patients using flow cytometry remains limited as it usually underestimates the plasma cell content of bone marrow samples compared to routine morphology of first-pull aspirates. We have observed that this holds true for both pre-treatment and post-treatment specimens. Causes for the discrepancy may include hemodilution of second-pull aspirates used for flow cytometry, fragility and loss of plasma cells during preparation for flow cytometry, and incomplete disaggregation of plasma cells from bone marrow spicules. With improved outcome of treatments, better and more reliable methods of detection of minimal residual disease are needed for optimal prognostic stratification. We are currently validating alternative methods, which may offer more sensitivity while at the same time allow more objectivity, for assessing the amount of minimal residual disease in myeloma patients.

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Increased Circulating Plasma Cells Predicts Poor Overall Survival in Symptomatic Plasma Cell Myeloma Patients

Blood ◽

10.1182/blood.v126.23.4205.4205 ◽

2015 ◽

Vol 126 (23) ◽

pp. 4205-4205

Author(s):

Mi Hyun Bae ◽

Sang Hyuk Park ◽

Chan-Jeoung Park ◽

Bo Hyun Kim ◽

Young-Uk Cho ◽

...

Keyword(s):

Flow Cytometry ◽

Overall Survival ◽

Plasma Cell ◽

Peripheral Blood ◽

Plasma Cells ◽

Survival Curve ◽

Plasma Cell Myeloma ◽

Newly Diagnosed ◽

Kaplan Meier ◽

Meier Survival Curve

Abstract Backgrounds Flow cytometry can rapidly determine immunophenotypes of neoplastic plasma cells (PCs) and quantify PCs in patients with plasma cell myeloma. Flow cytometric immunophenotyping and quantification of neoplastic plasma cells is sensitive and reliable tool for diagnosis and disease monitoring in patients with monoclonal gammopathy. Circulating PCs (cPCs) in peripheral blood (PB) after autologous hematopoietic stem cell transplantation is a marker of high-risk disease in patients with plasma cell myeloma. We assessed the utility of quantification of cPCs using flow cytometry for risk stratification in newly diagnosed plasma cell myeloma patients in the era of novel agents. Methods PB and bone marrow (BM) aspirates of 85 newly diagnosed patients with symptomatic plasma cell myeloma from August 2013 to July 2014 were analyzed by five-color flow cytometry using monoclonal antibodies against CD45, CD19, CD56, CD38, and CD138. The gating strategy employed first used the expression of CD38 and CD138 to identify plasma cells among 100,000 to 200,000 events. cPCs in PB was determined according to the patient's specific immunophenotype of neoplastic PCs in BM. Results The median age of the patient population was 68 years (45~87) and 58% were female. Median follow-up duration was 19.2 months. Six out of 85 patients (7%) did not show cPCs. Among 79 patient (93%) who had detectable cPCs, the median cPCs was 0.09% (0.006~3.612%). Patients without cPCs or cPCs under 0.05% were assigned to low cPCs group (n=32, 38%) and others to high cPCs group (n=53, 62%) according to receiver operating characteristics analysis. High cPCs group showed higher level of BM neoplastic PCs detected by both methodologys of morphology and flow cytometry (P=0.002, 0.033, respectively), higher BM cellularity (P=0.011), higher serum M protein level (P=0.013), lower hemoglobin (P=0.008), and lower platelet level (P=0.034) than low cPCs group. High cPCs group was associated with adverse cytogenetics such as t(4;14) and monosomy 13 (P=0.008), and CD45 negative immunophenotype (P=0.007). In survival analysis, high cPCs presented shorter overall survival (OS) than low cPCs group (P=0.013) (Fig. 1). It was independent with patient age and cytogenetic risks (P =0.011). Conclusion By flow cytometry cPCs was detected in most symptomatic plasma cell myeloma patients. Increased cPCs ≥0.05% among PB leukocytes could be an independent prognostic factor showing adverse effect in overall survival in symptomatic plasma cell myeloma patients. Figure 1. Kaplan-Meier survival curve of patients with plasma cell myeloma who showed 0.05% or more circulating plasma cells in peripheral blood and patients with circulating plasma cells less than 0.05%. Figure 1. Kaplan-Meier survival curve of patients with plasma cell myeloma who showed 0.05% or more circulating plasma cells in peripheral blood and patients with circulating plasma cells less than 0.05%. Disclosures No relevant conflicts of interest to declare.

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