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PubMed2003

The diagnostic difficulties of meningeal and intracerebral plasma cell granulomas--presentation of three cases.

Meningeal and intracerebral plasma cell granulomas are uncommon inflammatory lesions of unknown etiology. In this paper the diagnostic difficulties in two patients with meningeal plasma cell granuloma and one patient with intracerebral plasma cell granuloma are described. The first patient had an intracranial extra-axial lesion, which was first diagnosed as a meningioma. One and a half years later she underwent a second resection for recurrent tumor growth and the diagnosis of a meningeal plasma cell granuloma was made. The second patient was treated for a central nervous system B-cell lymphoma but proved to have an intracerebral plasma cell granuloma in retrospect 11 years later. In the third patient tuberculous meningitis was considered to be the most likely diagnosis because infratentorial contrast-enhanced thickened meninges (pachymeningitis) were found together with a high protein level in the cerebrospinal fluid and a positive Mantoux test. However, pathological examination of an extra-axial, cervical lesion that was operated upon revealed a meningeal plasma cell granuloma. These cases show the importance of diagnosing a meningeal or intracerebral plasma cell granuloma correctly, since it has both therapeutical and prognostic implications.

Adult↗
PubMed1991

Expression of cytoadhesion molecules (CD56, CD54, CD18 and CD29) by myeloma plasma cells.

Recently we reported the expression of the human natural killer cell associated antigen CD56 (Leu 19/NKH1) in plasma cells of a majority of multiple myeloma (MM) patients. CD56 is known to be an isoform of the human neural adhesion molecule N-CAM which is involved in homotypic adhesive interactions. By immunophenotyping using four CD56 specific monoclonal antibodies and immunoprecipitation analysis we here confirm that the Leu 19 antigen expressed by myeloma plasma cells is identical to N-CAM and corresponds to the 145 kDa isoform. Because of the possible biological role of adhesion molecules on myeloma cells, we compared the expression of N-CAM with the intercellular adhesion molecule 1 (ICAM-1) and the beta 1 and beta 2 integrins. By immunogold-silver staining of cytospin preparations of mononuclear cell suspensions, bone marrow plasma cells of 17 MM patients were analysed. Plasma cells expressed N-CAM (CD56) in 14 patients. ICAM-1 (CD54) in 16 patients, and beta 2 integrins (CD18) in eight patients. beta 1 integrins (CD29) were expressed in all patients. The expression of beta 2 integrins was always very weak while N-CAM, ICAM-1 and the beta 1 integrins showed a moderate to strong positivity. The plasma cells of five haematological normal individuals lacked significant N-CAM expression but were positive for ICAM-1 and both integrin subgroups. One plasma cell leukaemia patient and two out of four end-stage MM patients showed no expression of N-CAM or beta 2 integrins on their circulating plasma cells. Among 11 previously established myeloma cell lines, surface expression of ICAM-1 and the integrins was detected in most cases, while N-CAM was present in only four lines. Most cell lines showed coexpression of the fibronectin receptors (VLA-4 and VLA-5) and the laminin receptor (VLA-6). The collagen receptor (VLA-2) was not expressed. The N-CAM negative cell lines included four cell lines that were derived from plasma cell leukaemia patients. These results indicate that the expression of adhesion molecules is an intrinsic part of the biology of multiple myeloma.

Antigens, CD↗
PubMed1975

The bone marrow in multiple myeloma: correlation of plasma cell ultrastructure and clinical state.

The bone marrow plasma cells of 52 patients with various kinds of monoclonal gammopathies were studied by electron microscopy, and compared to the bone marrow plasma cells of 22 patients with reactive plasmacytosis. Virtually every marrow from patients with myeloma and macroglobulinemia contained plasma cells with disparity between the nuclear maturation and cytoplasmic differentiation. This asynchronous development was not present in plasma cells of reactive marrows nor in plasma cells from patients with megaloblastic anemias. The degree of asynchrony observed in myeloma and macroglobulinemia was proportional to the extent of disease as judged by clinical criteria. For the most part plasma cells of patients with non-myelomatous monoclonal gammopathy failed to exhibit significant asynchrony. These observations are consistent with the view that multiple myeloma is a neoplastic disorder with a definably malignant-appearing cellular proliferation.

Adult↗
PubMed2005

Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles.

Plasmablastic lymphoma is an aggressive neoplasm that shares many cytomorphologic and immunophenotypic features with plasmablastic plasma cell myeloma. However, plasmablastic lymphoma is listed in the World Health Organization (WHO) classification as a variant of diffuse large B-cell lymphoma. To characterize the relationship between plasmablastic lymphoma and plasmablastic plasma cell myeloma, we performed immunohistochemistry using a large panel of B-cell and plasma cell markers on nine cases of plasmablastic lymphoma and seven cases of plasmablastic plasma cell myeloma with and without HIV/AIDS. The expression profiles of the tumor suppressor genes p53, p16, and p27, and the presence of Epstein-Barr virus (EBV) and human herpes virus type 8 (HHV-8) were also analyzed. All cases of plasmablastic lymphoma and plasmablastic plasma cell myeloma were positive for MUM1/IRF4, CD138, and CD38, and negative for CD20, corresponding to a plasma cell immunophenotype. PAX-5 and BCL-6 were weakly positive in 2/9 and 1/5 plasmablastic lymphomas, and negative in all plasmablastic plasma cell myelomas. Three markers that are often aberrantly expressed in cases of plasma cell myelomas, CD56, CD4 and CD10, were positive in 5/9, 2/5, and 6/9 plasmablastic lymphomas, and in 3/7, 1/5, and 2/7 plasmablastic plasma cell myelomas. A high Ki-67 proliferation index, overexpression of p53, and loss of expression of p16 and p27 were present in both tumors. No evidence of HHV-8 infection was detected in either neoplasm. The only significant difference between plasmablastic lymphoma and plasma cell myeloma was the presence of EBV-encoded RNA, which was positive in all plasmablastic lymphoma cases tested and negative in all plasma cell myelomas. In conclusion, most cases of AIDS-related plasmablastic lymphoma have an immunophenotype and tumor suppressor gene expression profile virtually identical to plasmablastic plasma cell myeloma, and unlike diffuse large B-cell lymphoma. These results do not support the suggestion in the WHO classification that plasmablastic lymphoma is a variant of diffuse large B-cell lymphoma.

Adult↗
PubMed1983

IgE myeloma associated with plasma cell leukaemia.

A patient presented with plasma cell leukaemia and was found to have an IgE secreting multiple myeloma. IgE myeloma is very rare with only 18 cases recorded. However, this case is the fifth recorded of IgE myeloma associated with plasma cell leukaemia. Since plasma cell leukaemia only occurs in 1.6% of all cases of myeloma, it seems certain that this is a significant association.

Aged↗
PubMed1977

Growth kinetics of plasma cell myeloma.

The plasma cell labeling index(ex) (LI) of 128 patients with multiple myeloma at various stages of disease was compared as a function of tumor mass load and length of treatment. No significant differences in LI were noted for patients with various degrees of tumor reduction. Patients observed during the first 3 months of treatment had significantly higher LI than did untreated patients and those studied after longer intervals. In vivo cell-cycle analysis of myeloma cells by the halving time of the grain-count method failed to establish the length of the cell cycle but defined the length of S+G2 phases as being longer than 60 hours. Similar studies conducted in vitro defined a shorter combined length of S+G2 phase. In 2 patients in whom continuous infusion with [3H] thymidine was performed, the generation time was established as 8 days. Both patients had similar initial LI (5.7 and 6.6) but different growth fractions (19 and 47%). The measured tumor mass doubling time was much longer than the calculated one, suggesting the presence of considerable intrinsic cell loss (83 and 47%). These observations were summarized by a hypothetical two-compartment model for the growth kinetics of multiple myeloma.

Bone Marrow↗
PubMed2003

Skeletal trauma preceding the development of plasma cell dyscrasia: eight case reports and review of the literature.

Plasma cell dyscrasias are clonal proliferations and accumulations of plasma cells. The etiology of monoclonal neoplasms still remains elusive. A direct correlation between a history of trauma and the development of plasma cell dyscrasias has not been established. Two recent case reports have described plasmacytomas that were diagnosed in patients who suffered injury at the site of plasma cell neoplasms. We report a series of eight patients who stated a history of trauma to the site where plasma cell neoplasms were later diagnosed. The duration from the date of injury to diagnosis ranged from 2 mo to 20 yr. The M:F ratio was 6:2. The median age was 52 (28-75). Multiple myeloma was confirmed in six patients and plasmacytoma without systemic disease in the other two patients. All eight patients had a kappa monoclonal plasma cell population, and all but one had a detectable peripheral kappa light chain. All patients presented with persistent discomfort at the site where they had experienced trauma. Even though this article does not establish a relationship between trauma, and the development of plasma cell dyscrasia, persistent discomfort at a previous trauma site warrants a complete evaluation and consideration for possible plasma cell dyscrasias.

Adult↗
PubMed1976

Cytoplasmic fibrils in plasma cell leukemia.

In a patient with plasma cell leukemia, associated with pleural effusion, ultrastructural studies of the peripheral blood plasma cells showed an abundance of cytoplasmic fibrils. The nature of fibrils was not clarified, but they were not amyloid fibrils. This finding, coupled with a liaterature review, suggests that the cytoplasmic fibrils in plasma cells may be an additional cytological feature of this rare form of leukemia.

Cytoplasm↗
PubMed2004

Endogenous lithium and boron red cell-plasma ratios: normal subjects versus bipolar patients not on lithium therapy.

This study was undertaken to compare endogenous lithium concentrations in human blood and its components from normal donors versus bipolar patients. The patients were not on lithium therapy at the time that the blood samples were donated and had not received any lithium therapy for at least 2 yr. Blood components were separated by centrifugation. The analytical method for lithium as developed in this laboratory consists of thermal-neutron activation of freeze-dried samples. 3H is produced via the reaction 6Li + n = 3H + 4He, and high-sensitivity rare gas mass spectrometry is used to measure 3He formed from beta-decay of 3H. Boron measurements are made concurrently using 4He from the reaction 10B + n = 4He + 7Li. Seven normal donors and seven patients with a diagnosis of bipolar disorder participated in this study. Measurements of lithium and boron were made in whole blood, plasma, and red cells. Red cell-plasma ratios R(Li) and R(B) were calculated after corrections were made for trapped plasma in the red cells. The results show that bipolar patients may have higher concentrations of lithium in blood, plasma, and red cells (p = 0.08, 0.02, and 0.02, respectively) and may have higher R(Li) values than normal donors (p = 0.01). No evidence was found for bipolar-normal differences in these four parameters for boron. Although our sample size is admittedly very small, the results clearly show that the endogenous red cell ratio R(Li) and plasma or red cell lithium concentrations may become useful diagnostic indicators for bipolar illness if the analytical methods are further developed.

Adult↗
PubMed1987

Intestinal plasma cell alterations in acquired immunodeficiency syndrome.

Immunofluorescence studies of plasma cells were performed on small intestinal and colonic biopsies obtained from a series of patients with acquired immunodeficiency syndrome or the "AIDS related complex" plus homosexual male and heterosexual controls. The AIDS group was significantly depleted of IgA plasma cells compared to the control groups. In contrast, the numbers of IgM plasma cells were increased in the AIDS and homosexual control groups compared to the heterosexuals. Plasma cell fluorescence intensities for IgA and IgM were decreased in the AIDS patients, implying less cytoplasmic immunoglobulin per cell. The frequency of IgA plasma cell depletion did not differ in men and women, patients with opportunistic infections or Kaposi's sarcoma, or in patients with and without gastrointestinal symptoms. The extent of IgA plasma cell depletion did not correlate with serum IgA concentrations. IgA plasma cell numbers also did not correlate with selected parameters of nutritional status and intestinal absorption. Studies of salivary IgA output demonstrated decreased secretion of soluble IgA in AIDS patients, and an increased secretion of IgA in particulate form. These results suggest that abnormalities in IgA secretion occur in AIDS and might influence its clinical manifestations.

AIDS-Related Complex↗
PubMed1993

The bone marrow of multiple myeloma patients contains B cell populations at different stages of differentiation that are clonally related to the malignant plasma cell.

One of the distinguishing features of multiple myeloma (MM) is the proliferation of a clonal plasma cell population in the bone marrow (BM). It is of particular interest that the tumor plasma cells appear to be restricted to the microenvironment of the BM and are rarely detected in the peripheral system, yet the disease is found widely disseminated throughout the axial skeleton. Furthermore, isolation of MM tumor cell lines has proven to be quite problematic due to their slow growth rate. These observations have instigated the search for earlier cells in the B cell lineage that are clonally related to the plasma cell tumor and that may represent the growth fraction of the tumor. We used allele-specific oligonucleotides (ASO) derived from the third complementarity determining region of the rearranged tumor immunoglobulin heavy chain gene to detect isotypes clonally related to the plasma cell tumor. By reverse transcribing RNA from the BM with a panel of CH primers (mu, delta, alpha, and gamma), followed by ASO-polymerase chain reaction amplification, we demonstrate the existence of preswitch isotype species that are clonally related to the myeloma tumor. Furthermore, we show that separation of the BM cells into CD45+ and CD38+ cell populations results in a lineage-specific expression of the clonally related RNA molecules, with the C mu and C delta in the CD45+, and C gamma in the CD38+ population. Interestingly, clonally related C alpha transcripts are also derived from the CD45+ fraction. These results confirm the presence of B cell populations clonally related to the plasma cell tumor and are consistent with models that propose the existence of myeloma precursors.

ADP-ribosyl Cyclase↗
PubMed2003

Fine-needle aspiration cytology of a para-aortical solitary plasma-cell tumor.

Extramedullary plasma-cell tumor (EMP) is a very rare disease and mainly arises in the head and neck area. An EMP arising in the paraaortical space was diagnosed by fine needle aspiration cytology and immunocytochemistry, in a 48-year-old male. Smears were cellular and showed dissociated monomorphic plasma cells. Immunocytochemistry demonstrated monoclonal expression of kappa-light immunoglobulin chain and CD38 positivity. Cytomorphology and immunocytochemical profile allowed a definitive diagnosis of plasmacytoma.

Aorta↗
PubMed2003

Presence of a bone marrow stromal cell line with myoid differentiation in reactive plasmacytosis and plasma cell myeloma.

The presence of myoid cells (MCs) - stromal cells with myogenic differentiation - in human bone marrow (BM) has been observed during hematopoiesis in embryonic life, whereas during adult life, it is strictly related to various pathologic conditions. The aim of this study was to examine the presence, distribution and quantitation of cells in the stroma of the BM expressing alpha-smooth muscle actin (alpha-SMA) in reactive BM plasmacytosis and plasma cell myeloma. For this reason, a series of 10 trephine BM biopsies from patients with plasma cell myeloma and 10 specimens from healthy controls with reactive plasmacytosis were examined for the presence of stromal cells with myoid differentiation, using a monoclonal antibody recognizing alpha-SMA. Our results suggest that the incidence of MCs and subsequent fibrosis rises in plasma cell myeloma and in a lesser degree in the BM stroma of individuals with reactive plasmacytosis.

Actins↗
PubMed1989

Meningeal infiltration by non-myelomatous IgD-secreting plasma cell dyscrasias.

Two cases of meningeal invasion by non-myelomatous plasma cell dyscrasias--a plasma cell leukaemia and an extramedullary plasmacytoma--are described. Both were secretors of IgD paraprotein and both were diagnosed in life, characteristics which we have not found in any other published case of plasma cell leptomeningitis. Analysis of our patients and of another 25 cases suggests as predisposing factors of meningeal invasion the male sex, presentation in the form of plasma cell leukaemia, presence of the IgD paraprotein and tumoral involvement of pleura, lung, pericardium and testicles. Aggressive treatment of this neurological complication controlled the meningeal disorder in some cases. However, the majority died of disseminated disease in spite of systemic chemotherapy. Until an effective treatment can be found, able to maintain remission or cure the systemic disease, prophylaxis of the central nervous system in plasma cell dyscrasias does not appear to be advisable.

Adult↗
PubMed1972

Immune and natural antibodies to syngeneic murine plasma cell tumors.

Cytotoxic antibody to a plasma cell tumor antigen was produced in syngeneic BALB mice by immunization with viable or inactivated plasma cell tumors. Antibody with the same specificity was found in the sera of normal BALB and other strains of mice. This natural antibody reacted with an antigen with characteristics indistinguishable from the previously described alloantigen, PC.1, and with viral envelope antigen, chiVEA. The incidence of cytotoxic reactivity and the antibody titers reached a peak in normal BALB mice at 3-4 months of age, and were lower in 9-12-month old mice. The sera of germfree mice had lower reactivity; but when the mice were transferred to conventional conditions, their sera soon became as active as those of conventional mice. A virus common to all plasma cell tumors, which is present in latent form in some normal tissues of BALB and other PC.1 positive strains, is suggested as the cause for the PC.1 antigen and for the appearance of natural antibody to it. The considerable evidence for the close association of a virus with plasma cell tumors is presented.

Animals↗
PubMed2005

Blimp-1 is required for maintenance of long-lived plasma cells in the bone marrow.

Long-lived plasma cells, residing primarily in the bone marrow, continuously secrete antibody and provide an important component of humoral memory. However, when such cells secrete autoantibodies or become transformed, they can be pathogenic. We have shown recently that the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) is required for the formation of plasma cells. To determine what role Blimp-1 might play in maintenance of plasma cells, we generated mice in which the gene encoding Blimp-1 could be deleted in an inducible manner. Deletion of Blimp-1 either in vitro or in vivo leads to loss of previously formed B220(LO)CD138(HI) plasma cells. Using BrdU incorporation, we confirmed that Blimp-1 is required for the maintenance of nondividing, long-lived plasma cells in the bone marrow. Blimp-1 is also required for long-term maintenance of antigen-specific immunoglobulin in serum. Thus Blimp-1 is required not only for the formation but also for the maintenance of long-lived plasma cells. This finding provides the possibility of new drug design strategies for autoimmunity and multiple myeloma focused on blocking Blimp-1 expression or activity.

Animals↗
PubMed1996

Distribution of plasma cell markers and intracellular IgE in cell line U266.

The IgE-producing plasma cell line U266 was used to study intracellular IgE and the distribution of the plasma cell markers CD38 and PCA-1. We found two separate clusters of U266 based on the differences in their light scatter properties in the flow cytometer. One cluster displayed high scatter signals (high SS), whereas the other showed low scatter signals (low SS). Most (75%) of the cells in the low SS cluster were positive for intracellular IgE. In contrast, high SS cells had a higher expression of surface IgE and a considerably lower proportion of these cells expressed intracellular IgE. Different patterns of expression of the plasma cell antigens CD38 and PCA-1 were observed. While the low SS cluster displayed a high (76%) expression of PCA-1 and a low (5%) CD38 expression, the high SS cluster expressed 21 and 42%, respectively. About 2/3 of the cells in the low SS cluster appeared to be in the G1 phase of the cell cycle while 1/3 were in the S/G2 phase. In the high SS cluster the opposite distribution (2/3 in S/G2) was observed. Taken together our results indicate an association between cell cycle stages, expression of intracellular IgE and plasma cell markers.

ADP-ribosyl Cyclase↗