Reactive Plasmacytosis Research Articles

A simple and sensitive method for determining plasma cell isotype and monoclonality in bone marrow using flowcytometry.

In this paper we describe a new, rapid and sensitive method to determine plasma cell isotype and clonality in bone marrow using flowcytometry. With the use of a new fixation and permeabilization reagent (Permeafix), which preserves cell structure and morphology, and a monoclonal antibody (Mab) specific for plasma cells (B-B4), it has become possible to specifically select plasma cells and to determine the cytoplasmatic immunoglobulins by flowcytometry. Thirty successive bone marrow aspirates from multiple myeloma patients and patients with MGUS were studied as well as 10 bone marrow samples from patients with reactive plasmacytosis. Each sample was analysed both by immunofluorescence on cytospin smears and FACS analysis. There were no discrepancies between plasma cell isotype as determined by FACS and cytospin. Moreover, FACS analysis was shown to allow detection of very low numbers of plasma cells and to determine whether these plasma cells are mono- or polyclonal. Possible applications are discussed.

Reactive plasmacytosis and plasmacytic skin infiltration in a patient

European Journal of HaematologyVolume 55, Issue 2 p. 131-132 Reactive plasmacytosis and plasmacytic skin infiltration in a patient Sevgi Yetgin, Corresponding Author Sevgi YetginDepartment of Pediatric Hematology, Hacettepe University, Institute of Child Health, Ihsan Doǧramaci Children's Hospital, 06100 Ankara, TurkeySearch for more papers by this authorAliye Uç, Corresponding Author Aliye UçDepartment of Pediatric Hematology, Hacettepe University, Institute of Child Health, Ihsan Doǧramaci Children's Hospital, 06100 Ankara, TurkeySearch for more papers by this authorNamik özbek, Corresponding Author Namik özbekDepartment of Pediatric Hematology, Hacettepe University, Institute of Child Health, Ihsan Doǧramaci Children's Hospital, 06100 Ankara, TurkeySearch for more papers by this authorGönül Hiçsönmez, Corresponding Author Gönül HiçsönmezDepartment of Pediatric Hematology, Hacettepe University, Institute of Child Health, Ihsan Doǧramaci Children's Hospital, 06100 Ankara, TurkeySearch for more papers by this author Sevgi Yetgin, Corresponding Author Sevgi YetginDepartment of Pediatric Hematology, Hacettepe University, Institute of Child Health, Ihsan Doǧramaci Children's Hospital, 06100 Ankara, TurkeySearch for more papers by this authorAliye Uç, Corresponding Author Aliye UçDepartment of Pediatric Hematology, Hacettepe University, Institute of Child Health, Ihsan Doǧramaci Children's Hospital, 06100 Ankara, TurkeySearch for more papers by this authorNamik özbek, Corresponding Author Namik özbekDepartment of Pediatric Hematology, Hacettepe University, Institute of Child Health, Ihsan Doǧramaci Children's Hospital, 06100 Ankara, TurkeySearch for more papers by this authorGönül Hiçsönmez, Corresponding Author Gönül HiçsönmezDepartment of Pediatric Hematology, Hacettepe University, Institute of Child Health, Ihsan Doǧramaci Children's Hospital, 06100 Ankara, TurkeySearch for more papers by this author First published: August 1995 https://doi.org/10.1111/j.1600-0609.1995.tb01823.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume55, Issue2August 1995Pages 131-132 RelatedInformation

The Expression of Lysozyme in Multiple Myeloma

Lysozyme, a hitherto myelomonocytic marker, has been previously reported as being raised in the sera of some myeloma patients. This fact, and the sporadical observation of a positive immunohistochemical lysozyme staining seen in some myelomas, prompted us to systematically search for an expression of lysozyme in both neoplastic and reactive plasma cells. A total of 74 paraffin-embedded, formalin-fixed, EDTA-decalcified core biopsies of newly diagnosed cases of plasmacytoma were immunohistochemically investigated for lysozyme expression by a modified avidin-biotin immunoperoxidase technique. The myelomas were subclassified according to their nuclear maturity into poorly differentiated plasmacytoma (PDP) (30 cases), moderately differentiated plasmacytoma (MDP) (24 cases), and well differentiated plasmacytoma (WDP) (20 cases). An unexpected lysozyme positivity was seen in 16/74 cases, and was most prevalent in 10/30 cases of PDP. No correlation has been detected between either lysozyme and kappa or lambda light chain expression, or an abnormal activity of chloroacetate esterase sometimes seen in myeloma. Since lysozyme has not been found in normal plasma cells or reactive plasmacytosis, the expression of this antigen in myeloma represents another example of so-called lineage infidelity, and parallels the previously reported abnormal expression of other myelomonocytic markers in some myelomas and a myeloma cell line. Apart from the unsettled prognostic impact, a facultative lysozyme expression in myeloma must be always considered when applying algorhythmic immunohistological strategies in delineating the histogenesis of haematopoietic or lymphatic malignancies.

Diagnostic and Prognostic Value of the MB2 Monoclonal Antibody in Paraffin-Em bedded Bone Marrow Sections of Patients with Multiple Myeloma and Monoclonal Gammopathy of Undetermined Significance

Routinely processed bone marrow biopsies of 59 patients with untreated multiple myeloma (MM) and of 41 patients with monoclonal gammopathies of undetermined significance (MGUS) were immunocytochemically studied with the MB2 monoclonal antibody. In 54 of 59 biopsies of patients with MM, most neoplastic plasma cells showed strong cytoplasmic positivity to MB2. In contrast, only three biopsies of patients with MGUS contained highly MB2-positive plasma cells, whereas the plasma cells in the remaining biopsies were either negative (18 of 41) or revealed a weak dot-like staining of the cytoplasm (20 of 41). Plasma cells in tonsillar tissue, gastric and duodenal mucosae, and bone marrow with reactive plasmacytosis were not stained with MB2. These findings suggest that MB2 helps to distinguish between MM and MGUS. Because the five MB2-negative patients with MM were all in stage III and had very short survival time, neoplastic plasma cell staining with MB2 could also have a prognostic significance.

Polyclonal Bence Jones Proteinuria Associated with Reactive Plasmacytosis.

A 43 year old black male patient presented with progressive respiratory symptoms, fever and malaise of short duration accompanied by mild epistaxis. Physical examination revealed generalised lymphadenopathy and hepatosplenomegaly. Peripheral blood examination showed a striking plasmacytosis. Further investigation revealed Bence Jones proteinuria consisting of both kappa and lambda light chains. There was no monoclonal peak on serum electrophoresis and cytoplasmic immunoglobulin and gene rearrangement studies on the peripheral blood plasma cells demonstrated polyclonality. The possible role of Epstein-Barr virus in stimulating B cell proliferation in this case is discussed.

Histology and immunohistology of bone marrow biopsy in multiple myeloma.

B5-fixed/paraffin-embedded Jamshidi needle biopsies from 125 multiple myeloma patients were reviewed according to both morphological and immunohistological criteria. At microscopic examination, the following parameters were evaluated: i) grade of malignancy (low = 56; intermediate = 50; high = 19); ii) growth pattern (interstitial +/- sheets/nodules = 90; nodular = 13; packed marrow = 18; sarcomatous = 4); III) histological stage (I = 64; II = 35; III = 26). Comparison of the findings in trephine biopsies and aspirates showed that in 30% of the cases the latter led to an underestimation of the tumor burden. Immunohistochemical determination of Ig easily allowed: i) differential diagnosis from exuberant reactive plasmacytosis; ii) recognition and counting of neoplastic plasma cells; iii) detection of minimal residual disease after treatment. Immunohistochemistry also confirmed phenotypic aberration of neoplastic plasma cells, showing positivity for CD45, EMA, and cytokeratins in 14%, 59%, and 25% of the cases, respectively. Furthermore, it displayed expression of the P-glycoprotein in 4/8 resistant cases. These findings underline that routinely processed Jamshidi needle biopsies can be of great value in the study of patients with multiple myeloma.

Differentiation of plasma cell infiltrates in the bone marrow. A clinicopathological study on 80 patients including immunohistochemistry and morphometry.

In 80 patients immunohistochemical, morphometrical and clinical studies were performed on routinely referred trephine biopsies of the bone marrow showing an abnormal increase in plasma cells. From the approximately determined density of plasma cell infiltrates two main groups were distinguished, the first with an involvement exceeding 20% and the second with less than 10% of the total marrow area involved. The first group (n = 30; 324 +/- 130 plasma cells per square millimeter bone marrow) consisted of patients with frank malignant myeloma (MM) by clinical and histomorphological diagnosis. The second group (n = 50; 132 +/- 54 plasma cells per square millimeter bone marrow) with plasmacytic differentiation of infiltrates, had to be further divided into one component with evidence for initial or residual MM following chemotherapy (n = 27), another with obviously monoclonal gammopathy of undetermined significance--benign monoclonal gammopathy (BMG, n = 6), and a final set of cases with a reactive plasmacytosis mostly associated with an inflammatory condition (n = 17). There was an excellent agreement between the intracellular immunoglobulin staining as defined by the immunoperoxidase technique and the serum or urinary M-component detected by immunoelectrophoresis. In MM significant correlations were found between osteoclastic activity (number of osteoclasts specifically stained by acid phosphatase) per trabecular bone area, presence of lytic bone defects and the density of plasma cell infiltrates in the marrow. This latter feature corresponded well with the titer of secreted serum M-components measured by quantitative immunoelectrophoresis. Using morphological data alone, BMG cases could not be discriminated with any certainty from initial or residual plasmacytic MM. They consequently need a prolonged clinical follow up to clarify the nature of the lesions.

Reactive Plasmacytosis Complicated with Drug-induced Pancytopenia

Reactive Plasmacytosis Complicated with Drug-induced Pancytopenia

Frequency distribution of plasma cells in the medullary cords of tumour-draining axillary and paracolic lymph nodes.

Five hundred and ninety-seven axillary lymph nodes draining 104 invasive ductal breast cancers, and 94 paracolic lymph nodes draining 30 invasive adenocarcinomas of the large bowel were investigated immunohistologically to determine the frequency distribution of plasma cells (PC) in the medullary cords (MC). The degree of plasmacytic infiltration was calculated semiquantitatively using the 3-grade scale (0/+, + +, + + +) of Cottier et al. (1973). Statistical analysis yielded the following results: While a marked reactive plasmacytosis (+ + +) was seen in 28.7% of the paracolic lymph nodes, only 1.5% of the axillary lymph nodes exhibited a comparable degree of plasmacytic infiltration (p less than 0.0001). Conversely, low PC counts (0/+) were encountered in 51.1% of the paracolic lymph nodes, but in 83.9% of the axillary lymph nodes. A comparison of axillary lymph nodes with and without nodal metastasation revealed no significant differences (nodal-negative cases: 0/+: 83.6%, + +: 14.3%, + + +: 2.1%; nodal-positive cases: 0/+: 84.3%, + +: 14.9%, + + +: 0.8%). However, significantly more (p less tha 0.001) paracolic lymph nodes of the nodal-negative group revealed a marked plasmacytosis, whereas in the nodal-positive group lymph nodes with low PC counts were more frequent (nodal-negative cases: 0/+: 27.7%, + +: 29.7%, + + +: 42.6%; nodal-positive cases: 0/+ 74.5%, + +: 10.6%, + + +: 14.9%). The degree of plasmacytic reactions in the tumour-regional lymph nodes was not related to the stage of the primary tumour. Moreover, no correlation exists between the PC content of the MC and the amount of PC in metastatic deposits of the same lymph nodes. Altogether, these results do not support the concept that the plasmacytic reactions in the MC of tumour-draining lymph nodes are chiefly determined by effects (stimulating or suppressing) of the primary carcinomas. The topography of the lymph nodes, however, seems to be the main determinant influencing the PC content of MC.

Plasma cell acid phosphatase score in multiple myeloma and related disorders.

A detailed classification of plasma cells stained for acid phosphatase activity is introduced. With this method, patients with multiple myeloma, non-myeloma gammopathies, reactive plasmacytosis and other diseases in which plasma cells are involved, were investigated. The results show that our method can discriminate between multiple myeloma and reactive plasmacytosis. The overlap between multiple myeloma and other monoclonal gammopathies is much smaller than observed in other studies. Surprisingly low levels of acid phosphatase activity were found in the cells from patients with lymphoplasmacytoid immunocytoma. It is concluded that the acid phosphatase score can be of value for studying disorders in which plasma cells are involved.

Bone marrow histology in myeloma: its importance in diagnosis, prognosis, classification and staging

Summary.A study has been made of 420 bone marrow biopsies from patients with multiple myeloma (220), idiopathic monoclonal gammapathy (50), reactive plasmacytosis (42) and solitary plasmacytoma (22). Histology and immunohistological parameters were more reliable than cytology in distinguishing a reactive from a neoplastic plasmacytosis. Histological variables were correlated with the clinical features of the patients to determine the factors which were of value in predicting prognosis. Plasma cell maturity and the extent of infiltration in the biopsy by myeloma cells proved to be highly significant in predicting the duration of survival. On the basis of these criteria multiple myeloma was classified into two types: plasmacytic of low‐grade malignancy and plasmablastic of high‐grade malignancy; and into three stages which accurately reflected the progression of the disease. We conclude that a bone biopsy provides useful information for the diagnosis, classification and staging of patients with multiple myeloma.

Bone marrow histology in myeloma: its importance in diagnosis, prognosis, classification and staging.

A study has been made of 420 bone marrow biopsies from patients with multiple myeloma (220), idiopathic monoclonal gammapathy (50), reactive plasmacytosis (42) and solitary plasmacytoma (22). Histology and immunohistological parameters were more reliable than cytology in distinguishing a reactive from a neoplastic plasmacytosis. Histological variables were correlated with the clinical features of the patients to determine the factors which were of value in predicting prognosis. Plasma cell maturity and the extent of infiltration in the biopsy by myeloma cells proved to be highly significant in predicting the duration of survival. On the basis of these criteria multiple myeloma was classified into two types: plasmacytic of low-grade malignancy and plasmablastic of high-grade malignancy; and into three stages which accurately reflected the progression of the disease. We conclude that a bone biopsy provides useful information for the diagnosis, classification and staging of patients with multiple myeloma.

Immunoperoxidase staining of bone marrow sections.

Paraffin-embedded sections of bone marrow from 131 patients were studied. The specificity of the immunoperoxidase technique for detecting intracellular kappa and lambda light chains of immunoglobulin was first evaluated in 34 cases of typical multiple myeloma or macroglobulinemia. The monoclonal light chain detected in the bone marrow myeloma was identical to the result of immunoelectrophoresis of serum or urine. By use of the same method, 97 cases in which the diagnosis was difficult were examined; cases included those of bone marrow plasmacytosis, lymphocytosis, and morphologically unusual cells. All marrow cells with monoclonal immunoglobulin detected by immunoperoxidase stain eventually proved to be a B-cell neoplastic or potentially neoplastic process. This study confirms the specificity of the immunoperoxidase stain and demonstrates its value in solving clinical diagnostic problems, that is, the diagnosis of nonsecretory myeloma and unusual morphology, differentiating the monoclonal plasmaproliferative disorders from reactive plasmacytosis or lymphoma from lymphocytosis.

Enzymecytochemistry and immunohistochemistry in monoclonal gammopathy and reactive plasmacytosis.

Peripheral blood smears and bone-marrow smears from 29 patients with malignant M-components (25 with multiple myeloma and 4 with malignant lymphoma), 13 patients with benign monoclonal gammopathy (BMG), and 20 patients with polyclonal reactive plasmacytosis were examined by leucocyte alkaline phosphatase score (LAP-score) and by acid phosphatase score in plasma cells from bone-marrow smears. Furthermore, tissue sections from marrow biopsies from all patients were examined by the three-layer unlabelled immunoperoxidase technique to detect cytoplasmic immunoglobulin. The LAP-score was significantly higher in patients with malignant M-components than in patients with BMG and also higher in IgA and IgG myeloma than in IgA and IgG BMG, but the latter difference was not significant. Furthermore, a significant positive correlation between paraprotein concentration and LAP-score was found in multiple myeloma. Acid phosphatase score in plasma cells showed no clear distinction between multiple myeloma and BMG. Immunohistochemical examination showed a distinct monoclonal pattern in both multiple myeloma and BMG, allowing identification of the M-component which in all cases corresponded to the M-component detected by serum examination. Cells producing immunoglobulin classes not matching the M-component were more rare in multiple myeloma than in BMG, but the difference between the two conditions was quantitative and allowed no clear distinction.

A diffuse plasma-cell disease in a golden hamster (Cricitus auratus).

A 3 1/2 year-old male hamster with neurologic disturbances hud a systemic plasms-cell disease. The most prominent feature was widespread plasmacytic infiltration of the meninges with secondary degeneration of the brain. It is uncertain whether the disease should He considered a plasma-cell neoplasm or a florid reactive plasmacytosis.

Bone marrow findings of reactive plasmacytosis.

Bone marrow findings of reactive plasmacytosis.

PERIPHERAL PLASMACYTOSIS IN SERUM SICKNESS.

Case Studies1 October 1963Peripheral Plasmacytosis in Serum SicknessJOHN J. SCHMIDT, M.D., HAROLD J. ROBINSON, M.D., CHARLES S. PENNYPACKER, M.D., F.A.C.P.JOHN J. SCHMIDT, M.D.Search for more papers by this author, HAROLD J. ROBINSON, M.D.Search for more papers by this author, CHARLES S. PENNYPACKER, M.D., F.A.C.P.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-59-4-542 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptThe appearance of plasma cells in the peripheral blood in appreciable numbers is an uncommon event. More seriously, this occurrence is a sign of proliferative disease of the plasma cell system. Peripheral plasmacytosis may also occur in certain viral diseases (1-4). A third situation so characterized is serum sickness (5). With the widespread use of active immunization and the introduction of antibiotics, the incidence of true serum sickness has waned. Therefore, it is deemed important to report a case of severe, explosive, accelerated serum sickness that was accompanied by a reactive peripheral plasmacytosis. Coincident with this, there was a demonstration...

Relation of Bone Marrow Findings to Serum Protein Changes in Lymphosarcoma, Chronic Lymphocytic Leukemia and Hodgkin's Disease

Abstract In order to correlate the electrophoretic alterations in the serum proteins and the findings in the bone marrow, with particular reference to atypical lymphocytic forms and plasma cells, 14 cases of lymphosarcoma, six of chronic lymphocytic leukemia and six of Hodgkin’s disease were studied. No numerical relationship could be found between the degree of lymphoid atypia and the changes in serum globulin. A correlation, however, was apparent between the plasma cell concentration in the bone marrow and the changes in the serum gamma globulin, inasmuch as pronounced hypergammaglobulinemia occurred in all four cases of malignant lymphoma associated with bone marrow plasmacytosis (ranging from 2.8 to 12.8 per cent) and hypogammaglobulinemia of moderate to marked degree was present in five of the six cases of malignant lymphoma in which plasma cells were virtually absent in the bone marrow. When the findings of the fixed sections of the marrow are included, plasmacytosis was demonstrated in bone marrow in eight of 10 cases in which serum gamma globulins were elevated. In two cases, serum globulins were qualitatively abnormal. In one, a case (case 15) of Hodgkin’s disease, a small fraction of electrophoretically homogeneous globulin was noted. In the other, case 5, in which the histologic diagnosis was lymphocytic lymphosarcoma, macroglobulins constituted 40 per cent of the serum proteins, and Bence Jones proteinuria was associated. Predominantly mature plasmacytosis of 12.8 per cent was present in the bone marrow. This case may be regarded as illustrative of the interrelationship between myeloma and lymphosarcoma and supports the view21 that, clinically and morphologically, transitional forms occur between lymphatic tumors and plasmacytomas. On the basis of this material, it is suggested that in cases of lymphosarcoma, Hodgkin’s disease and chronic lymphocytic leukemia, alterations in the plasma content of the bone marrow, either as reactive plasmacytosis or as virtual absence of plasma cells, appear to be a major pathogenetic factor in the occurrence of hypergammaglobulinemia and hypogammaglobulinemia, respectively. Hypogammaglobulinemia was observed in three of six cases of chronic lymphocytic leukemia; two of 14 cases of lymphosarcoma; and one of six classified as Hodgkin’s disease. Conversely, quantitative increases in the gamma globulin level occurred in none of the six cases of chronic lymphocytic leukemia; in six of 14 cases of lymphosarcoma (including two of three classified as lymphosarcoma, reticular cell type), and in three of the six cases of Hodgkin’s disease.

Agranulocytosis with reactive bone marrow plasmacytosis; report of a case.

Agranulocytosis with reactive bone marrow plasmacytosis; report of a case.