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  • Hodgkin's disease  (9)
  • Autoimmunoblastic lymphadenopathy  (2)
  • germinal center  (2)
  • 2-CdA  (1)
  • 1
    ISSN: 1569-8041
    Keywords: germinal center ; Hodgkin's disease ; Ig gene rearrangement ; micromanipulation ; Reed–Sternberg cell ; single-cell PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During their development, B lymphocytes are repeatedly selected for the expression of an appropriate surface receptor: the pre-B-cell receptor at the pre-B-cell stage and surface immunoglobulin (Ig) at the transition from a pre-B cell to a mature B cell. Furthermore, stringent selection for B cells expressing high affinity antibodies operates when antigen-activated B cells proliferate within germinal centers (GC). Here, somatic point mutations are introduced into rearranged V region genes at a high rate, and B cells acquiring favorable mutations are selected to differentiate into memory B cells or plasma cells. In the frame of this developmental scheme, extending a recent analysis, we investigated 10 primary cases of Hodgkin's disease (HD) for B-lineage origin and clonality [1]. Single Hodgkin and Reed–Sternberg (H-RS) cells were micro manipulated from frozen tissue sections and analyzed by PCR for rearranged V genes. Clonal VH and/orV_κ/V_λ gene rearrangements were obtained from 9 of the cases. This shows that H-RS cells represent a clonal, B-lineage-derived population of tumor cells. Somatic mutations were found in all clonal VH gene rearrangements. Interestingly, mutations leading to stop codons in in-frame V gene rearrangements were detected in four cases. Since GC B cells acquiring such crippling mutations are usually efficiently eliminated within the GC, the finding of those mutations indicates that H-RS cells are derived from precursors within the GC that escaped apoptosis by a transforming event.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1569-8041
    Keywords: germinal center ; Hodgkin's disease ; Ig gene rearrangement ; micromanipulation ; Reed–Sternberg cell ; single-cell PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract During their development, B lymphocytes are repeatedly selected for theexpression of an appropriate surface receptor: the pre-B-cell receptor atthe pre-B-cell stage and surface immunoglobulin (Ig) at the transition froma pre-B cell to a mature B cell. Furthermore, stringent selection for Bcells expressing high affinity antibodies operates when antigen-activated Bcells proliferate within germinal centers (GC). Here, somatic pointmutations are introduced into rearranged V region genes at a high rate, andB cells acquiring favorable mutations are selected to differentiate intomemory B cells or plasma cells. In the frame of this developmental scheme, extending a recent analysis, weinvestigated 10 primary cases of Hodgkin's disease (HD) for B-lineage originand clonality [1]. Single Hodgkin and Reed–Sternberg (H-RS) cells weremicromanipulated from frozen tissue sections and analyzed by PCR forrearranged V genes. Clonal VH and/orV_κ/V_λ gene rearrangements wereobtained from 9 of the cases. This shows that H-RS cells represent a clonal,B-lineage-derived population of tumor cells. Somatic mutations were found inall clonal VH gene rearrangements. Interestingly, mutationsleading to stop codons in in-frame V gene rearrangements were detected in fourcases. Since GC B cells acquiring such crippling mutations are usuallyefficiently eliminated within the GC, the finding of those mutations indicatesthat H-RS cells are derived from precursors within the GC that escapedapoptosis by a transforming event.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1569-8041
    Keywords: cladribine ; 2-CdA ; mantle-cell lymphoma ; treatment
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Purpose: Cladribine (2-chlorodeoxyadenosine, 2-CdA) has been reported to be effective in the treatment of low-grade lymphomas. The objective of this multicenter study was to evaluate the activity of cladribine in mantle-cell lymphomas as first-line therapy or in first relapse using an intermittent two-hour infusion of cladribine. Patients and methods: A total of 47 courses, or an average of four courses per patient, were administered to 12 patients (seven untreated, five relapsed) with 5 mg/m2 cladribine given as an intermittent two-hour infusion over five consecutive days for a maximum of six cycles every four weeks. Results: Cladribine showed activity in patients with mantle-cell lymphomas, achieving a response rate of 58% (95% confidence interval (95% CI): 28%–85%). Myelosuppression was the major toxicity with 17% of grade 3 and 4 neutropenia. Thrombocytopenia was rare with only 2% of grade 3 and 4. Conclusion: These results demonstrate single-agent activity of cladribine in mantle-cell lymphomas using the intermittent two-hour infusion dosage regimen. To further improve treatment results, cladribine should be combined with other agents active in mantle-cell lymphomas.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 424 (1994), S. 321-326 
    ISSN: 1432-2307
    Keywords: Hodgkin's disease ; Monocytoid B-cells ; Monocytoid B-cell reaction ; B-zone activation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In contrast with various forms of lymphadenitis, the presence of reactive monocytoid B-cells (MBCs) has only rarely been reported in Hodgkin's disease (HD). In order to analyse their occurrence in HD, we reviewed 120 cases before or after treatment. MBCs were identified morphologically and immunohistochemically in 8 cases (nodular paragranuloma, n=2; nodular sclerosis, n=2; and interfollicular mixed cellularity HD, n=4). Acute toxoplasmic, cytomegalovirus, or Epstein-Barr virus (EBV) infections were excluded by serological tests and immunohistochemistry. MBCs were negative by immunostaining for EBV encoded latent membrane protein, while Sternberg-Reed and Hodgkin's cells expressed positivity in 50% of cases. MBCs were only identified in cases with partial or incomplete lymph node infiltration by HD together with an activated B-zone of residual non-infiltrated tissue. The relation of MBCs and HD infiltrates followed three distinct patterns: large HD infiltrates without any connection to MBC foci; small areas containing various numbers of Sternberg-Reed and Hodgkin's cells at the border between MBC foci and surrounding lymphoid tissue; and HD infiltrates within at least some MBC clusters. The data obtained suggest that MBCs occurring in HD represent a transient phenomenon associated with a B-zone activation irrespective of treatment and that they are usually not histogenetically related to HD.
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  • 5
    ISSN: 1432-2307
    Keywords: Autoimmunoblastic lymphadenopathy ; T-cell receptor γ ; Immunoglobulin heavy chain ; Clonality ; Polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The morphological classification of angioimmunoblastic lymphadenopathy (AILD) or T-cell lymphoma of AILD-type (AILD-TCL) is still a subject of considerable difficulty and controversy. The aim of the current study was to examine the value of clinical, morphological, immunohistochemical variables in paraffin-embedded tissues in predicting the clonality of the respective lesion. Fifteen lymph node biopsies derived from 13 patients from Chengdu, China, were diagnosed as AILD or AILD-TCL and included in this study. The specimes were examined using a panel of monoclonal antibodies and a scoring system of morphological features. Clonality of the paraffin-embedded material was investigated using a novel polymerase chain reaction-technique to amplify rearranged T-cell receptor (TCR)-γ sequences. Additional experiments were carried out to investigate the presence of clonal rearrangements of the immunoglobulin heavy chain (IgH) locus. We found clonal rearrangements of the TCR-γ locus in 9 out of 15 lymph node biopsies. In 3 patients, the predominant cell clones carried clonal IgH and TCR-γ rearrangements whereas 1 patient with polyclonal TCR-γ pattern displayed IgH-monoclonality. The statistical evaluation of morphological and immunohistochemical data indicated that no single variable was able significantly to predict the clonality of the lesion. Furthermore, demonstrable clonality for the TCR-γ or the IgH loci of a lesion did not correlate with a bad clinical course. Our data correlate with findings of other studies investigating AILD-TCL in Caucasian populations.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-2307
    Keywords: Autoimmunoblastic lymphadenopathy ; T-cell receptor γ ; Immunoglobulin heavy chain ; Clonality ; Polymerase chain reaction
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The morphological classification of angioimmunoblastic lymphadenopathy (AILD) or T-cell lymphoma of AILD-type (AILD-TCL) is still a subject of considerable difficulty and controversy. The aim of the current study was to examine the value of clinical, morphological, immunohistochemical variables in paraffin-embedded tissues in predicting the clonality of the respective lesion. Fifteen lymph node biopsies derived from 13 patients from Chengdu, China, were diagnosed as AILD or AILD-TCL and included in this study. The specimes were examined using a panel of monoclonal antibodies and a scoring system of morphological features. Clonality of the paraffin-embedded material was investigated using a novel polymerase chain reaction-technique to amplify rearranged T-cell receptor (TCR)-γ sequences. Additional experiments were carried out to investigate the presence of clonal rearrangements of the immunoglobulin heavy chain (IgH) locus. We found clonal rearrangements of the TCR-γ locus in 9 out of 15 lymph node biopsies. In 3 patients, the predominant cell clones carried clonal IgH and TCR-γ rearrangements whereas 1 patient with polyclonal TCR-γ pattern displayed IgH-monoclonality. The statistical evaluation of morphological and immunohistochemical data indicated that no single variable was able significantly to predict the clonality of the lesion. Furthermore, demonstrable clonality for the TCR-γ or the IgH loci of a lesion did not correlate with a bad clinical course. Our data correlate with findings of other studies investigating AILD-TCL in Caucasian populations.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 110 (1985), S. 238-243 
    ISSN: 1432-1335
    Keywords: Hodgkin's disease ; Radiotherapy ; Chemotherapy ; Malignant schwannoma ; Malignant fibrous histiocytoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Two cases of soft tissue sarcoma following treatment of nodular sclerosing Hodgkin's disease are described. One patient developed a malignant schwannoma after radiotherapy, the other was diagnosed as having a malignant fibrous histiocytoma after treatment with radiation and chemotherapy. Both secondary malignancies arose within the irradiated field after a latent period rangig from 9.5 years in the first to 21 years in the second case. A review of the pertinent literature is given and previous reports of malignant tumors and leukemias following therapy for Hodgkin's disease are summarized.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 114 (1988), S. 405-410 
    ISSN: 1432-1335
    Keywords: B cells ; Leu7 cells ; Hodgkin's disease ; Subtype ; stage
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Cases of lymphocyte predominance type Hodgkin's disease were investigated using immunohistochemical methods and compared for morphological subtype and clinical stage. Cases of nodular paragranuloma showed a high, diffuse paragranuloma a moderate, and the mixed type a low, content of B cells. There was no significant correlation between B cell content and clinical stage. The number of Leu7+ cells was significantly increased in stage I of nodular paragranuloma. Hodgkin cells did not react with the CD15 antibody in most cases of paragranuloma but showed reactivity in the mixed type.
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 16 (1995), S. 208-216 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Apoptose ; bcl-2 ; In-situ-Endmarkierung ; M. Hodgkin ; Key words Apoptosis ; bcl-2 ; In situ end-labelling ; Hodgkin's disease
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Previous studies have concentrated on the proliferative behaviour of the neoplastic cell compartment in Hodgkin's disease (HD). The aim of the current investigation was to analyse the frequency of programmed cell deaths in Hodgkin and Reed-Sternberg (HRS) cells in the different subtypes of HD and to correlate this phenomenon with the expression of the bcl-2 oncogene. For this purpose, we investigated paraffin-embedded material from 63 cases of HD. Oncogene expression was determined by immunohistochemistry with the monoclonal antibody bcl-2-124. The detection of apoptotic cells was facilitated by application of the in situ end-labelling (ISEL) technique. Our results confirmed that bcl-2 expression is low in the lymphocyte-predominant subtype of HD. Apoptotic cells were found in all subtypes to a variable extent and were not significantly associated with any particular subtype. Interestingly, there was no correlation of bcl-2 expression and the presence or absence of apoptotic HRS cells. Hence, other factors must be operative in the regulation of programmed cell death in HD. Such mechanisms have been described for lymphocytes under various conditions, such as negative selection in germinal centres and within the thymus, DNA damage due to irradiation, and cellular cytotoxicity.
    Notes: Zusammenfassung Das Auftreten apoptotischer Zellveränderungen beim M. Hodgkin stellt ein seit langem beschriebenes, wenn auch wenig beachtetes Phänomen dar. Betrachtet man das Wachstum maligner Lymphome als Bilanzproblem, so ist es naheliegend, sich neben Untersuchungen zum Proliferationsverhalten auch mit dem Absterben der Tumorzellen zu befassen. Ziel der vorgestellten Untersuchung war, das Auftreten von Apoptosen in den verschiedenen Subtypen des M. Hodgkin zu analysieren und mit der Expression des bcl-2 Onkoproteines zu korrelieren. Hierzu wurde in Paraffin eingebettetes Material von insgesamt 63 Fällen herangezogen und histologisch klassifiziert. Der Nachweis einer Onkogenexpression erfolgte mit Hilfe der Immunhistochemie unter Verwendung eines monoklonalen Antikörpers. Das Auffinden apoptotischer Zellen wurde durch den Einsatz der In-situ-Endmarkierungsmethode („in-situ end-labelling“, ISEL) wesentlich erleichtert. Die statistische Auswertung der Ergebnisse bestätigte die signifikant geringere Expression des bcl-2-Onkogens in Fällen des lymphozytenreichen Subtyps. Apoptosen konnten in den verschiedenen Subtypen in unterschiedlicher Ausprägung beobachtet werden. Eine signifikante Häufung derselben in einem bestimmten Subtyp ließ sich nicht belegen. Interessanterweise ergaben sich in den untersuchten Fällen auch keine signifikanten Zusammenhänge zwischen der Expression des bcl-2 und der Apoptoserate. Demnach müssen andere Faktoren in der Regulation des programmierten Zelltods beim M. Hodgkin eine gegenüber dem bcl-2 dominante Rolle spielen. Die Existenz solcher Regelmechanismen ist für Lymphozyten während der negativen Selektion im Keimzentrum oder im Thymus, unter Strahleneinfluß und während der zellulären Zytotoxizität belegt.
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Journal of cancer research and clinical oncology 101 (1981), S. 135-148 
    ISSN: 1432-1335
    Keywords: Hodgkin's disease ; Ultrastructure ; Reticulum cells ; Hodgkin's cells ; Sternberg-Reed cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Lymph nodes from patients with Hodgkin's disease of the nodular sclerosis or mixed cellularity type were examined by electron microscopy to classify all the cells that occur in these types of lymphoma. Most of the cells showed morphological features that were the same, or nearly the same as those of cells of normal lymphoid tissue. These included typical interdigitating reticulum cells (IDC), histiocytic reticulum cells, so-called dark reticulum cells, and sinus macrophages. There were also small and medium-sized lymphocytes, immunoblasts, plasma cells, and plasma cell precursors resembling those seen in non-specific lymphadenitis. Germinal center cells, on the other hand, were present in negligible numbers. Special attention was paid to Hodgkin's (H) and Sternberg-Reed (SR) cells. This group of cells proved to be heterogeneous. The only common features were a large cell size, large nuclei, and a prominent nucleolus. Some of the H and SR cells resembled immunoblasts of normal lymphoid tissue. The cytoplasm of these cells contained numerous polyribosomes, and their heterochromatin was coarsely condensed at the nuclear membrane. Other H and SR cells were more similar to histiocytic cells or reticulum cells because of the large number of cell organelles (e.g., lysosome-like granules) and diffuse heterochromatin. Finally, cases of the nodular sclerosis type of Hodgkin's disease showed another cell type with some resemblance to IDC. The cells of this type are called lacunar cells because of their special light-microscopic appearance.
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