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PubMed1975

Virus-bearing plasma cells in peripheral blood of a patient with 'hairy cell' leukemia.

Electron-microscopic examination of peripheral blood from a patient with 'hairy cell' leukemia revealed classical 'hairy cells', atypical lymphoid cells and numerous pathological plasma cells. Osmiophilic granular material coated the cell surface of 'hairy cells' and lymphoid cells but not the plasmalemma of the plasma cells. The most important features of the plasma cells were cytoplasmic protrusions and masses of oncogenic virus A particles in their endoplasmic reticular cisternae.

Cytoplasm↗
PubMed1995

Interleukin-6 and interleukin-1 beta production in a pediatric plasma cell granuloma of the lung.

Plasma cell granuloma (PCG) is a pseudotumor of unknown origin. It is frequently accompanied by acute-phase clinical and biological signs that resume after complete surgical removal, suggesting production of soluble mediators. We therefore investigated the role of cytokines in a previously healthy 10-year-old boy with a PCG of the lung and systemic symptoms. In this case, very high serum levels of interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) were found before tumor excision, associated with inflammatory signs including major hyper-gamma-globulinemia. Pathologic analysis of the tumor showed an accumulation of fibroblasts and plasma cells producing immunoglobulins. Local production of IL-1 beta and IL-6 could be demonstrated at the messenger RNA (mRNA) level by the reverse transcriptase polymerase chain reaction and could be attributed to inflammatory cells by in situ hybridization and immunohistochemistry, whereas plasma cells exhibited membrane expression of the IL-6 receptor. Postsurgery follow-up showed rapid normalization of serum IL-1 beta and IL-6, whereas inflammatory protein levels decreased. This confirms the local production of cytokine within the PCG and raises the question of whether a dysregulation of cytokine production initiates the disease.

Base Sequence↗
PubMed1994

Fluorescence image analysis of plasma cells in monoclonal gammopathies.

The DNA content of plasma cells was estimated by fluorescence image analysis in monoclonal gammopathies. Image analysis provides the possibility of measuring the bone marrow plasma cell population separately from the other myeloid cells. Plasma cells were labeled, identified and then relocated for propidium iodide intensity measurements. Patients with DNA malignancy grade > 0.20 or with DNA index > 1.15 had a poorer survival rate than did patients with a low DNA malignancy grade or DNA index. DNA malignancy grade is based on the variance of DNA values around the normal diploid peak, as proposed by Böcking. Of all the biologic and clinical parameters investigated, the serum beta 2 microglobulin level was the most important prognostic factor for survival in the multivariate regression analysis, and the DNA entropy index provided the most significant additional information.

Aged↗
PubMed2006

Four-color flow cytometric analysis of myeloma plasma cells.

We monitored the behavior of residual myeloma plasma cells in patients with multiple myeloma after high-dose therapy and autologous or allogeneic transplantation using 3 methods of a flow cytometric technique using 4-color staining, immunofixation, and polymerase chain reaction approaches. We analyzed 17 cases by a relatively simple flow cytometric technique using CD38/CD45/CD19/CD56. Detectable myeloma plasma cells were found in 5 patients at diagnosis and 9 patients after treatment. Of 14 cases, 9 (64%) had CD19-CD56+ myeloma plasma cells, and 5 (36%) of 14 had CD19-CD56- myeloma plasma cells. When 37 bone marrow samples that had less than 5% myeloma plasma cells were assessed, myeloma plasma cells were detected in all 20 immunofixation-positive cases and 3 of 17 immunofixation-negative cases (P = .002). All 4 polymerase chain reaction-negative samples characterized as immunofixation-negative contained no detectable myeloma plasma cells. Flow cytometry can provide effective information to detect low levels of myeloma plasma cells.

Adult↗
PubMed1992

Plasma cell granuloma of the lung.

Plasma cell granuloma is an uncommon, nonneoplastic pulmonary lesion. An 11-year retrospective review of resected pulmonary tumors yielded six patients with plasma cell granulomas. Fine needle aspiration biopsy results were falsely positive for carcinoma in one patient. Adherence or invasion of the mediastinum was present in three patients. Granuloma in one patient, who underwent two operative procedures, was deemed unresectable at the initial thoracotomy. For both diagnostic and therapeutic reasons, early surgical excision is recommended for plasma cell granulomas of the lung.

Adult↗
PubMed2003

Identification of mature plasma cells in early rat yolk sac. A possible origin from the endodermal cell layer: immunohistochemistry and immunoelectron microscopic study.

Plasma cells play a pivotal role in the immune system and are responsible for the synthesis and release of immunoglobulins. Numerous in vitro culture experiments on the yolk sac demonstrated the generation of mature cells of the myeloid and lymphoid lineages under appropriate culture conditions. However, there are no reports describing the development of mature lymphoid cells in the yolk sac so far. For this reason, we undertook this study to investigate the development of antibody-containing plasma cells during early yolk sac haematopoiesis. Immunohistochemistry and immunoelectron microscopy were employed in the study. Results of this work demonstrated very weak immune staining for the intracytoplasmic IgA, IgG, and IgM at days 10 and 11 of embryonic life, while dark staining was obtained at 12 days. Positive staining was localized to the endodermal cell layer. Electron microscopic examinations revealed the existence of cells with the typical characteristics of plasma cells inside the endodermal cell layer, which may suggest their endodermal origin. To further verify the nature of these cells, intracytoplasmic immunoglobulins were demonstrated by immunoelectron microscopy. The present study demonstrated emergence of mature functioning plasma cells in early rat yolk sac. In a previous work we hypothesized the possibility of endodermal origin of yolk sac macrophages. This study adds additional evidence to support that hypothesis. The possible role of plasma cells in the yolk sac is discussed.

Animals↗
PubMed1973

In vitro induction of tumor-specific immunity. I. Parameters of activation and cytotoxic reactivity of mouse lymphoid cells immunized in vitro against syngeneic and allogeneic plasma cell tumors.

Induction of tumor-specific immunity in vitro was accomplished by cocultivation of cortisone-resistant murine thymocytes or spleen cells with irradiated syngeneic plasma cell tumors (PCT). The cytotoxic activity generated could be detected in a short-term (51)Cr-release assay. Optimal cytotoxic activity against PCT-associated transplantation antigens (TATA) was generated after 7 days in culture. Unlike cytotoxic responses to tumor allografts in which the cytotoxic activity was directed against allogeneic transplantation antigens, the cytotoxic activity obtained in the syngeneic tumor system was specific to the immunizing syngeneic PCT. Similar parameters of induction of cytotoxic responses in in vitro tumor allograft responses and in the syngeneic tumor system suggested that both reactions are cell-mediated cytotoxic immune responses. With regard to the magnitude of cytotoxic responses obtained, allogeneic transplantation antigens induced about a 30-fold higher cytotoxic immune response than plasma cell TATA. The results are consistent with the concept that in vitro tumor allograft responses and in vitro responses against TATA of PCT are similar in quality, but differ in the magnitude of the cytotoxic response provoked.

Animals↗
PubMed1995

Plasma cell dyscrasias: classification, clinical and laboratory characteristics, and differential diagnosis.

Plasma cell dyscrasias form a heterogeneous group of diseases characterized by the expansion of the number of monoclonal bone marrow plasma cells that produce monoclonal immunoglobulins. Sensitive electrophoretic methods have shown that the incidence of these diseases is as high as 5% in adult individuals. Thus, the majority of cases should be considered to be a normal phenomenon. A few transform into neoplastic diseases, plasma cells becoming responsible for lytic bone lesions, the hallmark of MM. The distinction of benign and malignant forms is frequently difficult at presentation. We can easily recognize solitary myeloma, overt myeloma and plasma cell leukaemia, which require immediate chemotherapy. Therapy could be safely withheld in all the remaining forms, which require only follow-up. Thus, we suggest that plasma cell dyscrasias should be classified simply into two main groups according to the need of immediate chemotherapy. The appearance of new bone lesions and the increase of the M-component level remain the only two criteria that define malignant transformation. Several clinical and laboratory prognostic parameters indicate the risk of transformation, and hence how close the follow-up of the patient should be. Parameters related to the expansion of the plasma cell clone (percentage of bone marrow plasma cells, M-component level, lytic bone lesions and beta 2-microglobulin) are not always very low and very high in the benign and malignant forms, respectively, and frequently overlap in patients with intermediate plasma cell expansions. On the contrary, all parameters related to the intrinsic malignancy of the plasma cells (plasma cell LI, Karyotypic abnormalities and molecular alterations) have, by definition, to be normal in the benign forms. MRI is a new tool that may, early on, reveal lytic bone lesions undetectable by conventional radiography.

Clinical Laboratory Techniques↗
PubMed1992

Circulating peripheral blood plasma cells in multiple myeloma.

These studies indicate that monoclonal plasma cells can be detected in the peripheral blood of patients with active myeloma even when they are not detectable by routine WBC differentials performed on Wright-stained blood smears. These cells are usually not present in patients with MGUS and true SMM. They are detected in approximately 60% of patients with new, active MM and over 90% of patients with relapsed or refractory MM. If treatment is effective, they tend to decrease or disappear from the blood. When immunological, molecular, or cytogenetic studies are performed on peripheral blood cells from patients with MM, it must be realized that monoclonal plasma cells may be present and that they can influence the results of these tests. Although monoclonal plasma cells can circulate in the peripheral blood, it is not yet clear whether this cell represents the myeloma stem cell. It is possible that there are precursor cells that do not have plasma cell morphology in the blood or marrow that then differentiate into plasma cells. This question can only be answered by first depleting the plasma cells and then examining the remaining B-cells with appropriate immunological and molecular techniques.

Blood Cell Count↗
PubMed1978

Distribution of IgA 1 and IgA 2 plasma cells in various normal human tissues and in the jejunum of plasma IgA-deficient patients.

The distribution of IgA 1 and IgA 2 plasma cells was studied in normal human tissues. IgA 2 is a minor constituent in peripheral lymph nodes as well as in serum and in bone marrow plasma cells. An increased proportion of IgA 2 plasma cells was observed in gastric and intestinal mucosa, as well as in bronchial mucosa and salivary and mammary glands. Tonsils and mesenteric lymph nodes exhibit values intermediate between those of central and peripheral lymphoid systems. In patients with plasma IgA-deficiency, IgA 2 is the predominant intestinal IgA plasma cells. This may explain the frequent association of an asymptomatic condition and plasma IgA deficiency.

Adolescent↗
PubMed1995

Plasma cell myeloma associated with eosinophilia.

The association of plasma cell myeloma and eosinophilia is rare. The authors describe a 49-year-old man with plasma cell myeloma and marked absolute peripheral blood eosinophilia, 109.7 x 10(9)/L. Analysis of his bone marrow revealed cytologically atypical plasma cells that expressed monotypic IgG lambda and marked eosinophilia with normal maturation. A combination of steroids and chemotherapy resulted in a significant and sustained decrease in his absolute eosinophil count and bone marrow plasma cells. Analysis of the patient's pre-therapy serum revealed immunoreactive interleukin-3 (IL-3), but not IL-5 or granulocyte/macrophage colony stimulating factor (GM-CSF). The post-therapy serum sample was negative. Immunohistochemical analysis of the plasma cells for IL-3 and IL-5 was negative. This review of the literature has revealed five cases of plasma cell myeloma associated with eosinophilia described previously. In two patients, the eosinophilia was attributed to drug therapy. In the remaining cases, the pathogenesis of the eosinophilia was unexplained. In this case, IL-3 secreted either by the neoplastic cells at a level below detection by immunohistochemistry or by other cells in response to the presence of plasma cell myeloma may have played a role in causing the eosinophilia.

Bone Marrow↗
PubMed2003

Evaluation of intensive chemotherapy in AL amyloidosis: usefulness of flow cytometric analysis of plasma cells in bone marrow.

To investigate whether monoclonal plasma cells in the bone marrow are useful as a therapeutic marker in AL amyloidosis, serial flow cytometry was performed in five patients with this disorder before and after chemotherapy. Four patients were treated with 2 or 3 courses of VAD (vincristine, doxorubicin and dexamethazone) and subsequently with high-dose melphalan followed by auto-PBSCT. The remaining one patient was treated with two courses of VAD alone. Before treatment all patients exhibited a CD19- CD56+ subpopulation, which indicated monoclonal plasma cells, in varying degrees. After treatment all patients showed a decrease in monoclonal plasma cells in accordance with the disappearance of M-protein in serum and/or urine. In two patients treated with VAD followed by auto-PBSCT, polyclonal (CD19+ CD56-) and total plasma cells gradually increased in the follow-up study, while monoclonal plasma cells stayed at less than 0.3% nine months after treatment. No apparent correlation was found between altered maturation of plasma cells and disappearance of M-protein. With respect to easy detection of monoclonal plasma cells producing amyloidogenic M-protein, flow cytometry of bone marrow aspirates is useful and reliable in the follow-up of patients with AL amyloidosis and in the evaluation of the effects of chemotherapy.

Aged↗
PubMed1986

Binucleated form of plasma cells in oral lesions--their "vital statistics".

Plasma cells are currently held to represent the end-stage differentiation of B-lymphocytes and hence do not undergo division. However, binucleated and occasionally multi-nucleated forms of plasma cells have often been recorded in histological materials containing plasma cell infiltrates. It was decided that a study be conducted to provide more information on the microscopic features of these binucleated cells. Of the fifty surgical specimens from different oral lesions examined by light microscopy, binucleated plasma cells were found in thirty-three specimens. The mean maximum diameter, surface area and volume were 26.87 microns, 534.61 microns 2 and 9466.28 microns 3 respectively. Morphologically, they resembled the mononucleated or single nucleated plasma cells. Their cytoplasm contain abundant basophilic cytoplasm and a prominent perinuclear golgi image. The two nuclei exhibit a clock-face or cartwheel appearance.

Cell Nucleus↗
PubMed2001

Systemic capillary leak syndrome preceding plasma cell leukaemia.

We report a patient with plasma cell leukaemia with systemic capillary leak syndrome, a rare disorder often associated with monoclonal gammopathy. In this patient, the manifestation of capillary leak syndrome antedated the diagnosis of plasma cell leukaemia by 5-6 months. During that time, he was repeatedly admitted to the hospital with weight gain, congestive cardiac failure, cough and anasarca in the presence of normal renal function, liver function and normal echocardiography. On presentation, a serum protein electrophoresis showed monoclonal IgG; the blood smear showed 60% plasma cells with a total count of 4.4 x 10(9)/l. A bone marrow aspirate showed replacement of the normal marrow by sheets of immature plasma cells. His systemic capillary leak syndrome initially responded to decongestive therapy with terbutaline and aminophylline but later on he became refractory to them and responded to vincristine, doxorubicin and dexamethasone (VAD) combination therapy only transiently. Danocrine and pentoxifylline, added during VAD chemotherapy, did not produce a durable response in capillary leak syndrome, which finally responded to autologous peripheral blood stem cell transplantation (PBSCT). After PBSCT, he remained free of capillary leak for 10 months without terbutaline, pentoxifylline corticosteroids, aminophylline or danocrine. His disease relapsed without recurrence of the capillary leak. He died 15 months after PBSCT and 20 months after the diagnosis of plasma cell leukaemia.

Adult↗
PubMed1989

Serum levels of interleukin 6, a potent myeloma cell growth factor, as a reflect of disease severity in plasma cell dyscrasias.

Using a specific and very sensitive (1 pg = 1 U) bioassay, we investigated the presence of IL-6, a potent myeloma cell growth factor, in the sera of 131 subjects with plasma cell dyscrasias. 22 had monoclonal gammopathy of undetermined significance (MGUS), 13 had smoldering myeloma (SMM), 85 had overt multiple myeloma (MM), and 11 had plasma cell leukemia (PCL). Significant serum IL-6 levels were detected in only 3% of the MGUS/SMM group, but in 35% of the overt MM group and 100% of the PCL group. During overt MM, IL-6 was detected in 37% of the patients at diagnosis, 13% of those with stable MM, and 60% of those with fulminating disease. These data demonstrate that serum levels of IL-6, a potent myeloma cell growth factor in vitro, correlate with disease severity in plasma cell dyscrasias. Serial studies performed in 3 patients and correlative studies with labeling index in vivo in 25 patients have confirmed this concept. Taken together, this suggests that this cytokine is probably involved in vivo during the progressive phase of MM. Thus, anti-IL-6 or anti-IL-6 receptor antibodies could be useful as therapeutic agents at this stage of the disease.

Humans↗
PubMed2000

Radiotherapy in the management of plasma cell tumors.

Most patients with plasma cell tumors receive radiation therapy at some time during the course of their disease. Plasma cell tumors are radio-responsive, but the systemic nature of the disease in most patients limits the application of localized irradiation. In patients with solitary plasmacytomas (osseous and non-osseous), radiation therapy is the primary treatment modality. It provides excellent local control that may translate into a long remission and even cure. Adequate dose and careful anatomic planning are essential. In patients with multiple myeloma, effective palliation of pain can be achieved with relatively small fields and low doses of radiation. Hemibody irradiation has been shown to provide cost-effective palliation but is associated with toxicity and has failed to contribute to a more definitive therapeutic approach. Hemibody irradiation is rarely used today. Total-body irradiation is often employed in conditioning regimens prior to autologous or allogeneic stem-cell transplantation for multiple myeloma. However, the magnitude of its contribution to the efficacy of high-dose programs in multiple myeloma remains to be studied. This article explores the rationale for and various aspects of providing effective radiotherapy in patients with plasma cell tumors.

Humans↗
PubMed1998

A high frequency of circulating B cells share clonotypic Ig heavy-chain VDJ rearrangements with autologous bone marrow plasma cells in multiple myeloma, as measured by single-cell and in situ reverse transcriptase-polymerase chain reaction.

In multiple myeloma (MM), the VDJ rearrangement of the immunoglobulin heavy chain expressed by MM plasma cells provides a unique clonotypic marker. Although clonotypic MM cells have been found in the circulation, their number has been controversial. Our objective was to provide direct evidence, using single-cell assays, for the frequency of clonotypic cells in blood of 18 MM patients, and to confirm their identity as B cells. The clonotypic Ig heavy-chain (IgH) VDJ was determined from single plasma cells using consensus reverse transcriptase-polymerase chain reaction (RT-PCR), subcloning, and sequencing. For all patients, using patient-specific primers, clonotypic transcripts were amplified from 10 or more individual plasma cells. Using in situ RT-PCR, for all patients greater than 80% of plasma cells were found to be clonotypic. Three separate methods, RT-PCR, single-cell RT-PCR, and in situ RT-PCR, were used to analyze clonotypic cells in peripheral blood mononuclear cells (PBMC) from MM patients. Sequencing of the IgH transcripts expressed by individual cells obtained by limiting dilution of freshly isolated PBMC from a MM patient showed that all B cells expressed an identical CDR3. This intraclonal homogeneity indicates an escape from antigenic-selection, characteristic of malignant B cells. For this patient, the frequency of clonotypic PBMC, about 25%, was comparable to the number of PBMC B cells (34%). Because the PBMC included less than 1% plasma cells, virtually all clonotypic PBMC must be B cells. Using single-cell RT-PCR, clonotypic IgH transcripts were identified in individual sorted B cells from blood. To accurately quantify the number of clonotypic B cells, sorted B cells derived from 18 MM patients (36 samples) and 18 healthy donors (53 samples) were analyzed using in situ RT-PCR with patient-specific primers. Clonotypic transcripts were not detectable among normal B cells. For the 18 MM patients, a mean of 66% +/- 4% (SE) of blood B cells were clonotypic (range, 9% to 95%), with mean absolute number of 0.15 +/- .02 x 10(9)/L blood. Over time in individual patients, conventional chemotherapy transiently decreased circulating clonotypic B cells. Their numbers were increased in granulocyte colony-stimulating factor (G-CSF)- mobilized blood of one patient. However, clonotypic B cells of a one patient became undetectable after allogeneic transplant, correlating with complete remission. Although contributions to MM spread and progression is likely, their malignant status and impact has yet to be clarified. Their high frequency in the blood, and their resistence to conventional chemotherapy suggests that the number of circulating clonotypic cells should be clinically monitored, and that therapeutic targeting of these B cells may benefit myeloma patients.

B-Lymphocyte Subsets↗