Lymphoplasmacytoid Immunocytoma Research Articles

Combined polymerase chain reaction approach for clonality detection in lymphoid neoplasms.

The present study analyzes the efficiency of a combination of four immunoglobulin heavy chain (IgH) gene polymerase chain reaction (PCR) primer systems and a multiplex T-cell receptor gamma chain (TRG) gene PCR for detection of clonality in 409 samples (234 paraffin sections, 175 bone marrow aspirates) of different lymphomas. Using the four IgH PCR systems together, clonality was detected in all samples of B-cell chronic lymphocytic leukemias, hairy cell leukemias, common acute lymphoblastic leukemias, and Burkitt-like B-cell lymphomas. Clonality was detected in all bone marrow aspirates with lymphoplasmacytoid immunocytoma, mantle cell lymphoma, marginal zone B-cell lymphoma, and unclassifiable low-grade B-cell lymphomas. The combined IgH gene PCR approach allowed clonality detection in 78.2% of myelomas, 75% of Burkitt lymphomas, 74.4% of diffuse large B-cell lymphomas, 68.7% of follicular center lymphomas, 50% of posttransplant lymphomas, 28.6% of anaplastic large cell lymphomas, 29% of T-cell lymphomas, and 18.8% of Hodgkin diseases. The combination of the four IgH gene primer systems with the multiplex TRG gene PCR allowed detection of clonality in 84.2% of B-cell neoplasms, 92.1% of T-cell non-Hodgkin lymphomas, and 18.8% of Hodgkin diseases, which was much more efficient than single PCR protocols.

Scanning and transmission electron microscopy of clonal peripheral blood lymphocytes in low grade non-Hodgkin's B-cell lymphomas with predominant splenomegaly.

Peripheral blood mononuclear cells (PBLs) from 14 patients with low grade non-Hodgkin's B-cell lymphomas with predominant splenomegaly were studied by means of scanning (SEM) and transmission electron microscopy (TEM). All patients had peripheral blood and bone marrow involvement, the absence of lymphoadenopathy, and, except in one case, immunophenotypic features of a malignant proliferation of mature spleen B-cells arising from outside the germinal center, but not consistent with CLL or HCL. Several distinctive cytological features were observed in PBLs of the different subgroups. The SEM surface features of PBLs in patients with intermediate differentiation lymphocytic lymphoma (IDL) (five cases), lymphoplasmacytoid immunocytoma (LP-IC) (two cases), and mixed small and large cells malignant lymphoma (one case) were characterized by the presence of numerous well-developed microvilli. Some distinctive TEM ultrastructural features were also seen in the different cases. In the two cases of splenic lymphoma with villous lymphocytes (SLVL), SEM revealed large and elongated surface microvilli generally arising from two or three poles of the cells. This surface morphology, confirmed by TEM analysis, may be pathognomonic of this disease. Four additional cases, tentatively classified as small lymphocytic lymphoma on the basis of immunophenotypic data, were extremely heterogeneous at both SEM and TEM analysis. The ultrastructural features revealed by SEM and TEM may be useful for the more precise characterization of this heterogeneous group of diseases, which is generally difficult to define even when immunophenotypic and molecular approaches are used.

Gene rearrangement of bcl‐1 and bcl‐2 is confined to distinct subgroups of high‐grade malignant B‐cell lymphomas

The occurrence of bcl-1 and bcl-2 gene rearrangements was investigated in 37 cases of high-grade B-cell lymphomas. Bcl-2 rearrangement was detectable only in single cases of primary centroblastic lymphoma with a follicular growth pattern, whereas secondary centroblastic lymphomas evolving from a centroblastic-centrocytic lymphoma were positive in up to 60 per cent of the cases analysed. Bcl-1 rearrangement was found only in one case of immunoblastic B-cell lymphoma with a history of pre-existing lymphoplasmacytoid immunocytoma. It is concluded that there may be a subgroup of centroblastic lymphomas with a biology similar to that of centroblastic-centrocytic lymphomas. The detection of bcl-1 rearrangement in high-grade lymphomas may indicate a secondary high-grade lymphoma.

Histopathology and Immunocytochemistry of Lymph Node Biopsies in Chronic Lymphocytic Leukemia and Immunocytoma.

When lymph node biopsies of lymphocytic neoplasms are studied with subtle morphological and immunohistochemical methods meaningful information is obtained, that is not only of theoretical value, but which also relates to the clinical behavior ("leukemia," paraproteinemia, prognosis). Such an analysis allows us to differentiate three subtypes of chronic lymphocytic leukemia (diffuse, pseudofollicular and tumor forming) and to recognize two subtypes of immunocytoma (lympho plasmacytoid and lympho plasmacytic). The plasmacytoid-plasmacytic differentiation is usually not recognizable in blood smears. CLL cells show only IgM + IgD on their surfaces, whereas in immunocytoma monotypic cytoplasmic immunoglobulins are evident, and they are not only of the IgM type. The CD5 negative lymphoplasmacytic subtype differs clearly from chronic lymphocytic leukemia and from the majority of cases of lymphoplasmacytoid immunocytoma, which are CD5 positive.

Chlorambucil/Prednisone versus CHOP in Symptomatic Chronic Lymphocytic Leukemias of B-Cell type. A Randomized Trial

The therapeutic efficacy of intensive chemotherapy (CHOP) versus palliative low-dose therapy (chlorambucil/prednisone, ChP) was studied in a randomized trial including 258 previously untreated patients with asymptomatic low-grade non-Hodgkin lymphomas stage III and IV. The patients were stratified according to histological subgroup (the Kiel classification). 113 patients with chronic lymphocytic leukemia (CLL), including B-CLL and leukemic lymphoplasmacytoid immunocytoma (1C), were evaluated separately and presented here. The therapeutic goal was to achieve an asymptomatic state in the ChP group, while in patients allocated to CHOP the intention was to reach complete remission. Thus, in the CHOP group a higher response rate was noted than in the ChP group but no statistically significant difference in overall survival was seen. The results do not support the use of intensive chemotherapy as first line therapy in symptomatic CLL.

Reticulin fibre content of bone marrow infiltrates of malignant non-Hodgkin's lymphomas (B-cell type, low malignancy) — a morphometric evaluation before and after therapy

A morphometric study was performed on bone marrow infiltrates of non-Hodgkin's lymphomas (B-cell type, low malignancy) to evaluate the content of argyrophilic (reticulin) fibres in the various subtypes before and after therapy. In congruence with the corresponding lymph node lesions, subtypes consisted of lymphocytic lymphoma--chronic lymphocytic leukaemia (CLL, n = 39), centroblastic-centrocytic lymphoma (CB-CC, n = 35), lymphoplasmacytoid immunocytoma (LPI, n = 22) and finally hairy cell leukaemia (HCL, n = 21). In comparison with control specimens, morphometric measurements on trephine biopsies (initial staging procedure) disclosed a borderline or minimal increase in reticulin in CLL and moderate fibrosis in CB-CC and LPI, whereas HCL had the greatest increase in fibres. The marrow surrounding focal or patchy lymphoma infiltrates of CLL and CB-CC displayed no relevant changes in fibre density with respect to the control samples. Following chemotherapy, repeated trephine biopsies (restaging procedure) were obtainable from 38 patients. There was no significant decrease in the fibre content of CLL, CB-CC and LPI infiltrates. In HCL an incomplete reduction was recorded after interferon treatment. So-called benign lymphoid lesions may be distinguished from focal-patchy infiltrates of CB-CC and LPI not only by showing a central localization, but also by the absence of significant amounts of reticulin. However, considering the density of the reticulin fibres, a clear-cut discrimination of these lymphoid aggregates from an early nodal-central growth pattern of CLL is not feasible in many cases.

Morphological and immunohistochemical investigation of non‐Hodgkin's lymphoma combined with Hodgkin's disease

Twenty cases with a morphological picture highly suspicious for a combination of non-Hodgkin's lymphoma and Hodgkin's disease were investigated. The infiltrates of Hodgkin's disease differed from those of non-Hodgkin's lymphoma in their cellular component of Hodgkin and Sternberg-Reed cells and the irregularity in the fibre pattern. Based upon histological and immunohistochemical criteria the 20 cases were divided into three groups. Group 1 (n = 10) contained seven chronic lymphocytic leukaemias of B type, one lymphoplasmacytoid immunocytoma, and two centroblastic/centrocytic lymphomas. The non-Hodgkin's lymphoma components showed a monotypic immunoglobulin distribution pattern and/or leukaemic blood picture. Adjacent to the non-Hodgkin's lymphoma was typical Hodgkin's disease in which Hodgkin and Sternberg-Reed cells were positive for both immunoglobulin light chains and IgG and reacted with anti-CD15. Group 2 (n = 5) consisted exclusively of centroblastic/centrocytic lymphoma in combination with Hodgkin's disease in which the few Hodgkin and Sternberg-Reed cells were negative with anti-CD15 monoclonal antibody. Group 3 (n = 5) consisted of four chronic lymphocytic leukaemias of B type and one lymphoplasmacytoid immunocytoma. In these cases no combination with Hodgkin's disease could be diagnosed apart from the presence of partially CD15 positive Hodgkin and Sternberg-Reed cells. The following conclusions were drawn: anti-CD15 (LeuM1 and 3C4/C3D-1) can neither confirm nor exclude Hodgkin's disease since, while they do not detect Hodgkin and Sternberg-Reed cells in all cases of Hodgkin's disease, they do recognize Hodgkin and Sternberg-Reed cells in some B-cell lymphomas; anti-CD30 (Ber-H2) reacted with Hodgkin and Sternberg-Reed cells in all cases of Hodgkin's disease and also detected these cells in cases of non-Hodgkin's lymphoma.

Lupus anticoagulant associated syndrome in benign and malignant systemic disease--analysis of ten observations.

The clinical and laboratory findings in seven female patients with primary autoimmune diseases, one female patient with lymphoplasmacytoid (LP) immunocytoma and IgM paraproteinemia, and two male patients with multiple myeloma are described. The common denominator in all patients was a lupus anticoagulant or a closely related coagulation disorder. Recurrent thrombosis was observed in six patients with autoimmune diseases and in two patients with malignant monoclonal gammopathies. Other clinical manifestations included cerebral disorders (four patients with autoimmune disease/two patients with monoclonal gammopathy), repeated obstetric complications (6/1), asymptomatic valvular heart disease (6/1), renal dysfunction (6/2), hepatic involvement (2/2), and arthropathy (2/0). Laboratory investigations revealed a biologic false-positive serological test for syphilis in six patients with autoimmune disease and one with monoclonal gammopathy, antinuclear antibodies (4/0), antibodies against DNA (4/1), and a positive direct Coombs test (3/1) which was accompanied by hemolytic anemia in two patients (1/1). Additionally slight leukocytopenia (2/1) and thrombocytopenia (6/2) were observed; abnormal bleeding was only seen in one patient with severe thrombocytopenia. Other complications characteristic of LP immunocytoma or multiple myeloma were missing. The obvious similarities between the patients with autoimmune diseases and the patients with malignant monoclonal gammopathies suggest analogous pathogenetic mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)

Primary non-Hodgkin's lymphomas of the CNS.

This paper reports on 10 patients (4 male, 6 female) with primary non-Hodgkin's lymphomas of the brain (CNS-NHL--mean age 46.8 years, mean postdiagnostic survival 10 months). Pathological CSF (cerebrospinal fluid) was found in all 8 patients examined (positive cytology in 7/8 cases). Solitary tumors, diffuse periventricular infiltration or diffuse cerebral infiltration were demonstrated in cerebral computer-assisted tomography (CAT). Angiographical findings were unspecific. The histologic subtypes were lymphoplasmacytoid immunocytoma (4), unclassified low grade (1), centroblastic (1), B-immunoblastic (1), T-immunoblastic (1), lymphoblastic convoluted T-cell type (1), unclassified high grade (1) NHL. Patients who had received radiotherapy (+/- surgery) in this group had a mean survival of 15.66 months (sigma = 7.63). In addition, an overview of 83 well-documented, cases of the literature tries to characterize main histological and topographical distributions, histology-, patient's age-, and therapy-related survival. Patients with primary CNS-NHL have a 5-year survival expectancy of 30% compared with 2.3% in secondary CNS-manifestations of systemic non-Hodgkin's lymphomas. In this report, the beneficial effect of radiotherapy (mean survival 30.3 months) compared to surgery or symptomatic treatment (3.6 or 3.3 months) could be confirmed. It is concluded that primary CNS-NHL frequently present with atypical neuropsychiatric syndromes; diagnosis should be established preferentially with CAT and CSF-examinations or stereotactic biopsies, whereas open surgery should be avoided. An approach to exact classification should be attempted, as survival is clearly related to histological subtypes.

Relation between enzymatic activities and the degree of malignancy of human lymphomas

The relationship between the intracellular levels of DNA polymerase alpha (DP-alpha), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) and the degree of malignancy of human lymphomas was investigated. Twelve non-neoplastic lymph nodes and 88 malignant lymphomas were examined. For non-Hodgkin's lymphomas (NHL) the low or high grade of malignancy was established according to three classifications: the Rappaport, the Kiel and the Working Formulation for Clinical Usage, with the latter also recognizing an intermediate grade group. Non-neoplastic lymph nodes had significantly lower levels of all the three enzymes than those found in high-grade malignant NHL (the P value ranged from < 0.02 to < 0.001). Hodgkin's disease, a slowly evolving neoplasia, showed lower levels of DP-alpha ( P < 0.001) and ADA ( P < 0.001), but not of LDH, than high-grade NHL. Among NHL, whatever classification was used, the low-grade malignant lymphomas had significantly lower levels than the high-grade ones for all the three enzymes ( P < 0.005 or P < 0.001). The intermediate-grade group of the Working Formulation different from the high-grade group for DP-alpha ( P < 0.01) and ADA ( P < 0.02) but not for LDH. It differed from the low-grade group only for ADA ( P < 0.005). Lymphoblastic and Burkitt's lymphomas were the groups with the highest levels of the three enzymes. Among low-grade lymphomas very low values were found in the histological entities defined as DLWD in the Rappaport classification, CLL and lymphoplasmacytoid immunocytoma in the Kiel classification and small lymphocytic (group A) in the WF. The levels of all enzymes in these histotypes were always significantly different from the other low-grade histotypes, and from the intermediate-grade ones of the WF. In the Kiel classification polymorphous lymphoplasmacytoid lymphoma, recently recognized as a group with a quite aggressive clinical course, was characterized by high levels of all three enzymes. Moreover, among centroblastic-centrocytic (Cb-Cc) lymphomas those associated with a better prognosis (Cb-Cc follicular, with small centrocytes) had lower levels of DP-alpha ( P < 0.05) than those with a mixed cellular population. Taken together, these data suggest that intracellular enzyme values may have a role in better defining the prognosis of NHL.

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.

Characterization of B-cell non-Hodgkin's lymphomas. A study using a panel of monoclonal and heterologous antibodies.

A panel of monoclonal and heterologous antibodies directed against clearly defined antigens was used to characterize the cellular composition of 57 non-Hodgkin's lymphomas, classified according to the Kiel classification, with a slight modification. The antisera were directed against T-lymphocytes and their subsets (Leu1, Leu2a, Leu3a, TA1), B-lymphocytes and their subsets (BA1, BA2, HLA-DR, CR1, sIg), macrophages (TA1, OKM1, anti-human monocyte 1, HLA-DR, CR1), dendritic reticulum cells (CR1, BA2, HLA-DR), interdigitating reticulum cells (HLA-DR, BA1) and Langerhans cells (OKT6, NA1/34). On the basis of the staining pattern of the neoplastic cells with the antibodies used and the nature and number of admixed cells, in particular T-cell subsets, dendritic reticulum cells and macrophages, the NHL could be divided into groups which correspond to the different diagnostic categories of the Kiel classification. Furthermore, the results underlined the existence of intermediate lymphocytic lymphoma as a separate diagnostic category. Histogenetically, the marker pattern of the neoplastic cells and the number and arrangement of the admixed cells are consistent with the view that at least two different lines of B-cell lymphomas can be recognized. One is related to the germinal centre cell reaction (to which B-lymphoblastic (Burkitt type), centroblastic, centroblastic/centrocytic, centrocytic, and intermediate lymphocytic lymphoma, and polymorphic immunocytoma belong) and the other is related to the plasma cell reaction (including chronic lymphocytic leucaemia and lymphoplasmacytoid immunocytoma), whereas B-immunoblastic lymphoma can originate from either line. Thus, polymorphic immunocytoma is a follicle centre cell lymphoma with differentiation into plasma cells rather than a lymphoplasmacytoid immunocytoma with blastic cells.

Primary malignant lymphomas of the central nervous system in man.

Sixty-eight primary malignant lymphomas of the CNS exclusively confined to the brain and its leptomeninges from a series of about 8000 intracranial neoplasms (incidence 0.85%) were examined and classified according to current histopathologic criteria. Average age at onset of symptoms was 55 years, mean duration of illness to time of diagnosis was 3 months. Survival averaged 1,8 months with supportive care, but 17,2 months with surgery, radiation and/or chemotherapy. CSF cytology was useful and reliable tool for clinical diagnosis. The cerebral hemispheres were affected in about 50%, the basal ganglia in 18%, posterior fossa in 10%, while multifocal lesions amounted to 22%. All CNS tumors were of the diffuse type of non-Hodgkin's lymphomas; no follicular (germinal center) lymphomas were observed. Three histological patterns comparable to extraneural lymphomas were distinguished: Immunoblastoma (reticulosarcoma) occurred most frequently (58.8%), lympho-plasmacytoid immunocytoma constituted 28 percent, while lymphoblastic lymphoma occurred least frequently (13.2%). There were no significant differences with regard to onset, location, growth pattern or clinical course except for a much poorer prognosis of lymphoblastic lymphoma. Although there are no definite cytological differences between malignant lymphomas arising in extraneural sites or as primary lesions in the CNS, the latter showed a much greater proportion of phagocyting histiocytes (and microglia) and a frequent occurrence of plasmacytes and their precursors which apparently exceded pure host reaction. The prognostic value of modern classification schemes for CNS lymphomas needs further critical evaluation.