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Thomas Rüdiger

Publications and source records attributed to Thomas Rüdiger.

At least 19 recordsLinked to original sources
PubMed2006

Chromosomal breakpoints affecting immunoglobulin loci are recurrent in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma.

Chromosomal breakpoints affecting immunoglobulin (IG) loci are recurrent in many subtypes of B-cell lymphomas. However, despite the predominant B-cell origin of the Hodgkin and Reed-Sternberg (HRS) cells in classical Hodgkin lymphoma (cHL), the presence of chromosomal translocations in IG loci has not yet been systematically explored. Therefore, we have investigated a series of cHL for chromosomal breakpoints in the IGH (n = 230), IGL (n = 139), and IGK (n = 138) loci by interphase cytogenetics. Breakpoints in the IGH, IGL, or IGK locus were observed in the HRS cells of 26 of 149 (17%), 2 of 70, and 1 of 77 evaluable cHLs, respectively. The IG partners could be identified in eight cHLs and involved chromosomal bands 2p16 (REL), 3q27 (BCL6, two cases), 8q24.1 (MYC), 14q24.3, 16p13.1, 17q12, and 19q13.2 (BCL3/RELB). In 65 of 85 (76%) cHLs evaluable for an IGH triple-color probe, the HRS cells showed evidence for a (partial) deletion of the IGH constant region, suggesting the presence of class switch recombination (CSR). Furthermore, analyses with this probe in cases with IGH breakpoints indicated that at least part of them seem to be derived from CSR defects. Our results show that chromosomal breakpoints affecting the IG loci are recurrent in cHL.

Adolescent↗
PubMed2006

'Normal counterparts' of nodal peripheral T-cell lymphoma.

Peripheral T-cell lymphomas (PTCL) have been difficult to classify. A homogeneous principle of classification is still lacking, partly because lymph node compartments containing functionally distinct T-cell subsets have not been identified. A correlation to differentiated T-cell subsets, as CD4(+) or CD8(+) cells as well as cytotoxic populations has not revealed clinically meaningful entities. Upon antigen encounter, mature T-cells pass through distinct stages characterized by their surface molecule expression. Naïve T-cells are CD45RA(+)/CD45R0(-)/CD27(+)/CCR7(+), however, after antigen contact CD45RA expression is replaced by CD45R0. They differentiate to central memory cells, which retain CD27 and CCR7, or to effector-memory cells, which loose expression of both molecules depending on the strength of the antigen interaction. Immunohistological analysis of PTCL showed an effector or effector-memory cell phenotype (CD45RA(-)/CD45R0(+)/CD27(-)) for both angioimmunoblastic T-cell lymphoma (AILT) and anaplastic large cell lymphoma (ALCL), but different cytotoxic and activation markers expressed by these tumours. A subset of CD4(+) PTCL-not otherwise specified (PTCL-NOS) may correspond to a central memory cell phenotype (CD45RA(-)/CD45R0(+)/CD27(+)). Thus, a correlation of PTCL to stages of differentiation, rather than to the direction of differentiation, may reveal homogeneous categories. A comparison between the lymphomas and their normal counterparts may contribute to the understanding of the underlying transformation mechanisms.

Antigens, Differentiation, T-Lymphocyte↗
PubMed2006

Hodgkin disease-like posttransplantation lymphoproliferative disorder of donor origin in a renal allograft recipient.

Posttransplantation lymphoproliferative disorder (PTLD) develops in 1.6% of renal allograft recipients. More than 90% are of recipient origin. There are only a few reports of Hodgkin disease-like PTLD in allograft patients. We report the case of a Hodgkin disease-like PTLD of donor origin in a 16-year-old renal allograft recipient. Fourteen months after transplantation, an increasing inhomogeneous structure in the hilar region of the transplanted kidney became apparent and was excised. Histological examination showed Hodgkin- and Sternberg-Reed-like cells. Immunostaining showed CD20-positive and CD15-negative cells and Epstein-Barr virus (EBV) involvement (EBV-encoded small nonpolyadenylated RNA and EBV-determined nuclear antigen 2). DNA fingerprinting analysis proved the lymphoma to be of donor origin. Treatment consisted of nephrectomy, discontinuation of immunosuppression therapy, and local radiation. Three years after lymphoma removal, the patient was still without relapse and underwent retransplantation with stable function of the second allograft for more than 2 years now.

Adolescent↗
PubMed2006

The role of high-dose therapy in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) represent a heterogeneous group of non-Hodgkin's lymphomas. With few exceptions (eg, anaplastic large-cell lymphoma expressing the anaplastic lymphoma kinase), PTCLs have generally been reported to have a worse prognosis compared with B-cell lymphomas. Despite the poor outcome after conventional therapy, the impact of high-dose therapy with autologous or allogeneic stem cell transplantation (SCT) in these rare diseases is poorly defined mainly because of the lack of prospective PTCL-restricted studies. Most data exist for high-dose therapy with autologous SCT in relapsing or refractory disease. Because most studies showed similar results for PTCL compared with aggressive B-cell lymphomas in which high-dose therapy with autologous SCT is accepted as standard therapy, this approach seems appropriate in relapsing or refractory PTCL. Results for high-dose therapy with autologous SCT as first-line therapy mainly rely on studies on aggressive lymphomas that also included lymphomas of the T-cell phenotype. Our own recently published PTCL-restricted prospective study confirmed the feasibility with only moderate toxicity and a good response rate. Overall, patients with a good remission status after induction therapy exhibited a high complete response rate after transplantation, and at least a subgroup of patients remained in long-term remission. The greatest uncertainty exists for the impact of allogeneic SCT after high-dose therapy. In refractory or relapsing PTCL, this approach might improve the outcome for eligible patients, especially when using reduced-intensity conditioning. Overall, because data on high-dose therapy for PTCL are limited, larger and randomized studies are necessary to definitely confirm the preliminary results.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

Transmembrane adaptor molecules: a new category of lymphoid-cell markers.

Transmembrane adaptor proteins (of which 7 have been identified so far) are involved in receptor signaling in immune cells. They have only a short extracellular region, with most of the molecule comprising a substantial intracytoplasmic region carrying multiple tyrosine residues that can be phosphorylated by Src- or Syk-family kinases. In this paper, we report an immunohistologic study of 6 of these molecules in normal and neoplastic human tissue sections and show that they are restricted to subpopulations of lymphoid cells, being present in either T cells (LAT, LIME, and TRIM), B cells (NTAL), or subsets of both cell types (PAG and SIT). Their expression in neoplastic lymphoid cells broadly reflects that of normal lymphoid tissue, including the positivity of plasma cells and myeloma/plasmacytoma for LIME, NTAL, PAG, and SIT. However, this study also revealed some reactions that may be of diagnostic/prognostic value. For example, lymphocytic lymphoma and mantle-cell lymphoma showed similar profiles but differed clearly from follicle-center lymphoma, whereas PAG tended to be selectively expressed in germinal center-derived subsets of diffuse large B-cell lymphoma. These molecules represent a potentially important addition to the panel of immunophenotypic markers detectable in routine biopsies that can be used in hematopathologic studies.

Adaptor Proteins, Signal Transducing↗
PubMed2005

Medical history and risk for lymphoma: results of a population-based case-control study in Germany.

Since lymphomas are malignancies of cells of the immune system, associations with disorders characterised by impaired immune functions can be assumed. We investigated the relationship between a history of selected medical conditions and the risk for lymphoma including specified subentities within our population-based case-control study of lymphoma among adults conducted in Germany between 1999 and 2002. Overall, we found decreased risks for a history of repeated diarrhoea, warts, arthrosis, allergies, and appendectomy (at a younger age). Elevated risks for lymphoma correlated with tonsillectomy (at a younger age), whereas null results were found for selected auto-immune disorders in adulthood. Although the numbers are small, most of the results for the subentities corresponded with these findings. These results are compatible with the notion that persistent immunological alterations contribute to the aetiology of lymphoma, but partially inconsistent with the Th1/Th2-shift paradigm.

Adolescent↗
PubMed2005

Identification of the tumor cells in peripheral T-cell lymphomas by combined polymerase chain reaction-based T-cell receptor beta spectrotyping and immunohistological detection with T-cell receptor beta chain variable region segment-specific antibodies.

Most nodal peripheral T-cell lymphomas (PTCL) originate from alphabeta-T cells, and they often contain reactive T cells that may hamper immunophenotyping. To specifically identify the neoplastic population in immunohistochemically stained slides, we assessed the heterogeneity of the T-cell receptor beta chain variable region (TCRVbeta). This region contains 65 gene segments, of which only one is expressed after rearrangement. To investigate PTCL, we developed a polymerase chain reaction assay to define the clonally rearranged TCRVbeta segment. Detecting the corresponding epitope with segment-specific antibodies enabled identification of tumor cells among the T cells. The TCRVbeta segment of the tumor cells was defined in 13 of 13 PTCL not otherwise specified and 11 of 13 angioimmunoblastic T-cell lymphomas. Antibodies corresponding to the respective TCRVbeta segment of the tumor were available for seven cases from each group. After applying these antibodies in combination with antibodies against CD3, CD5, CD4, CD8, and cytotoxic molecules, double stains were evaluated by confocal laser scanning microscopy. In 9 of 14 cases, less than 50% of T cells expressed the clonally rearranged TCRVbeta segment. Phenotypes defined in double stains differed from those obtained by conventional immunohistochemistry in 11 of 14 cases. The combination of TCRVbeta polymerase chain reaction and immunohistochemistry may facilitate more reliable detection and characterization of tumor cells in PTCL.

Antibodies↗
PubMed2005

Noninvasive imaging of angiogenesis inhibition following nitric oxide synthase blockade in the ischemic rat heart in vivo.

OBJECTIVE: Nitric oxide synthase inhibition has anti-angiogenic properties. Magnetic resonance (MR) imaging was used to image the functional significance of these microvascular changes in a rat model of chronic ischemic myocardium in vivo. METHODS: The authors quantitatively determined myocardial perfusion and regional blood volume, left ventricular geometry, and function using MR imaging. Animals received either L-NAME + hydralazine or no treatment and were investigated 1 and 2 weeks after induction of coronary artery stenosis or sham operation at rest and during vasodilatation. Double-labeling immunohistochemistry was used to visualize angiogenesis and to compare with data obtained by MR imaging. RESULTS: Left ventricular mass and end-diastolic volumes were comparable in both groups 2 weeks after treatment. However, basal and maximum perfusion in animals with L-NAME + hydralazine treatment were reduced compared to animals not treated (p < .05). Basal regional blood volume remained constant in all groups, whereas maximum regional blood volume was reduced by L-NAME + hydralazine (p < .05). Endothelial cell proliferation, a direct marker for angiogenesis, was reduced by L-NAME + hydralazine (p < .01). CONCLUSIONS: MR imaging allows noninvasive quantification of functional microcirculation and angiogenesis in the rat heart in vivo. Nitric oxide synthase blockade results in changes in functional microcirculation and in an inhibition of angiogenesis in both ischemic and nonischemic myocardial tissue.

Animals↗
PubMed2004

Anaplastic large cell lymphomas lack the expression of T-cell receptor molecules or molecules of proximal T-cell receptor signaling.

Anaplastic large cell lymphoma (ALCL) designates a heterogeneous group of CD30(+) (systemic or primary cutaneous) peripheral T-cell lymphomas (PTCLs). A subgroup of systemic ALCL is transformed by anaplastic lymphoma kinase (ALK). We compared 24 ALK(+), 15 ALK(-) systemic, and 7 cutaneous ALCLs with 29 nonanaplastic PTCLs in terms of T-cell receptor (TCR) rearrangements, expression of TCRs and TCR-associated molecules (CD3, ZAP-70 [zeta-associated protein 70]). Despite their frequent clonal rearrangement for TCRbeta, only 2 (4%) of 47 ALCLs expressed TCRbeta protein, whereas TCRs were detected on 27 of 29 nonanaplastic PTCLs. Moreover, both TCRbeta(+) ALCLs lacked CD3 and ZAP-70 (ie, molecules indispensable for the transduction of cognate TCR signals). Defective expression of TCRs is a common characteristic of all types of ALCL, which may contribute to the dysregulation of intracellular signaling pathways controlling T-cell activation and survival. This molecular hallmark of ALCL is analogous to defective immunoglobulin expression distinguishing Hodgkin lymphoma from other B-cell lymphomas.

Anaplastic Lymphoma Kinase↗
PubMed2004

Nodal peripheral T-cell lymphomas and, in particular, their lymphoepithelioid (Lennert's) variant are often derived from CD8(+) cytotoxic T-cells.

Nodal peripheral T-cell lymphomas are not well understood, and most of them are classified in the "not otherwise specified group" (PTCL-NOS). Data on their normal cellular derivation are ambiguous. Most peripheral T-cell lymphomas are composed of tumor cells and a (sometimes dominant) reactive background, which also includes resting and activated T-lymphocytes. We defined the phenotype of the tumor cells in 101 PTCL-NOS based on their cytological atypia and using immunohistochemical double stains on paraffin sections with CD4/Ki67 and CD8/Ki67. The results were correlated to clinical presentation and outcome. Lineage could be defined in 98 cases (97%). Tumor cells were CD4(+) in 43 cases and CD8(+) in 38. These presented at a younger age but a higher clinical stage compared with the CD4(+) lymphomas. In 15 cases, the atypical cells were CD4(-)CD8(-); two cases were CD4(+)CD8(+). Of 17 lymphoepithelioid (Lennert's) lymphomas, 15 expressed CD8, one each was CD4(+) and CD4(-)CD8(-).

Adult↗
PubMed2004

EphA3 is induced by CD28 and IGF-1 and regulates cell adhesion.

Stimulation of CD28 alone has been shown to regulate cytokine gene transcription and expression of the type 1 insulin-like growth factor receptor (IGF-1R) in lymphocytes. In this study, the ephrin receptor tyrosine kinase ephA3, was identified as a new CD28-responsive gene in Jurkat cells by using a human cytokine/receptor array. EphA3 was not detected in normal peripheral T cells, in any subset of thymus-derived developing T cells, or in Hodgkin's lymphoma. However, contrary to previous findings, EphA3 was detected in a panel of T-cell lymphomas. Stimulation of Jurkat cells with ephrin-A5 resulted in loss of cell adhesion to fibronectin and recruitment of the adapter protein CrkII to EphA3. Interestingly, EphA3 expression in CD28-stimulated Jurkat cells was enhanced by IGF-1 or by overexpression of the IGF-1R, and was suppressed by anti-IGF-1R blocking antibodies. The data suggest that CD28- and IGF-1-regulated expression of EphA3 is associated with adherence and that it may be involved in the motility of malignant T cells.

Antibodies↗
PubMed2004

Genomic profiling of peripheral T-cell lymphoma, unspecified, and anaplastic large T-cell lymphoma delineates novel recurrent chromosomal alterations.

To characterize genetic alterations in peripheral T-cell lymphoma, not otherwise specified (PTCL NOS), and anaplastic large T-cell lymphoma (ALCL), 42 PTCL NOS and 37 ALCL [17 anaplastic large cell kinase (ALK)-negative ALCL, 9 ALK-positive ALCL, 11 cutaneous ALCL] were analyzed by comparative genomic hybridization. Among 36 de novo PTCL NOS, recurrent chromosomal losses were found on chromosomes 13q (minimally overlapping region 13q21, 36% of cases), 6q and 9p (6q21 and 9p21-pter, in 31% of cases each), 10q and 12q (10q23-24 and 12q21-q22, in 28% of cases each), and 5q (5q21, 25% of cases). Recurrent gains were found on chromosome 7q22-qter (31% of cases). In 11 PTCL NOS, high-level amplifications were observed, among them 3 cases with amplification of 12p13 that was restricted to cytotoxic PTCL NOS. Whereas cutaneous ALCL and ALK-positive ALCL showed few recurrent chromosomal imbalances, ALK-negative ALCL displayed recurrent chromosomal gains of 1q (1q41-qter, 46%), and losses of 6q (6q21, 31%) and 13q (13q21-q22, 23%). Losses of chromosomes 5q, 10q, and 12q characterized a group of noncytotoxic nodal CD5+ peripheral T-cell lymphomas. The genetics of PTCL NOS and ALK-negative ALCL differ from other T-NHLs characterized genetically so far, among them enteropathy-type T-cell lymphoma, T-cell prolymphocytic leukemia, and adult T-cell lymphoma/leukemia.

Adolescent↗
PubMed2004

Myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation as first-line therapy in peripheral T-cell lymphomas: first results of a prospective multicenter study.

Peripheral T-cell lymphomas (PTCL) show a poor outcome following conventional chemotherapy. However, the role of high-dose therapy is still unclear. We initiated a prospective multicenter phase II study to evaluate the feasibility and the efficacy of myeloablative radiochemotherapy followed by autologous peripheral blood stem cell transplantation (APBSCT) as first-line treatment in PTCL. After 4-6 courses CHOP (cyclophosphamide, doxorubicine, vincristine, and prednisone) chemotherapy, an induction therapy with either the DexaBEAM (dexamethasone, carmustine, melphalan, etoposide, and cytarabine) or the ESHAP (etoposide, methylprednisolone, cytarabine, and cisplatin) protocol was administered. If a complete (CR) or a partial remission (PR) was achieved, myeloablative radiochemotherapy (hyperfractionated total body irradiation and high-dose cyclophosphamide) with APBSCT was performed. From June 2000 to November 2002, 30 patients (pts) were enrolled into the study. The two main PTCL subgroups included were PTCL not specified and angioimmunoblastic T-cell lymphoma (each n=12). In all, 21 of the 30 pts (70%) were transplanted. The main toxicities were myelosuppression and infections. The overall response rate after myeloablative therapy was 100% (20 CR, one PR). In total, 16 of 21 transplanted pts (76%) remained in CR at a median follow-up of 15 months (range, 6-32 months) from treatment start. Nine pts received no APBSCT mainly due to progressive disease. In conclusion, this first prospective PTCL-restricted study of frontline myeloablative radiochemotherapy with APBSCT shows feasibility and high efficacy. Our data suggest a substantial impact on outcome, however, longer follow-up is necessary to confirm survival benefit.

Adult↗
PubMed2003

Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) and T-cell/histiocyte-rich B-cell lymphoma (T/HRBCL) are distinct tumors and are treated differently. They are linked by a morphologic and probably a biologic continuum, which renders the differential diagnosis difficult. To develop criteria to distinguish the entities along the morphologic continuum, we correlated the lymph node architecture and immunophenotype of both tumor cells and reactive components of 235 neoplasms in the spectrum of NLPHL and T/HRBCL with clinical data. Two hundred and eighteen cases fitted the World Health Organization (WHO) criteria of NLPHL (139) or T/HRBCL (79). While tumor cells in both entities were immunophenotypically similar, background composition differed: in NLPHL small B cells and CD3+CD4+CD57+ T cells were common, whereas in T/HRBCL, CD8+ cytotoxic T cells and histiocytes dominated. Follicular dendritic cells (FDCs) formed expanded meshworks in NLPHL, whereas they were absent in T/HRBCL. Seventeen cases represented a gray zone: within FDC meshworks, neoplastic B cells resided in a background depleted of small B cells but rich in T cells and histiocytes. Tumor cells either were loosely scattered or formed clusters, thus resembling areas of either T/HRBCL or inflammatory diffuse large BCL (DLBCL) within the nodules. Patients with these NLPHLs with T-cell/histiocyte-rich nodules presented at a high stage and with B symptoms, as in T/HRBCL, but had an excellent survival, as in NLPHL. This morphologic pattern suggests a biologic continuum between NLPHL and T/HRBCL.

Adult↗
PubMed2003

Angioimmunoblastic T cell lymphoma is derived from mature T-helper cells with varying expression and loss of detectable CD4.

Angioimmunoblastic T cell lymphoma (AILT) is a rare lymphoma that is regarded as a clinicopathologic entity but shows considerable histomorphologic diversity, variable immunophenotypes and inconsistent T cell receptor (TCR) gene rearrangement. One hundred four paraffin blocks of AILT were investigated defining tumor cell lineage by triple immunostains with a confocal laser scanning microscope and correlating morphology, immunophenotype and TCRgamma gene rearrangement to clinical outcome. Ninety-nine cases were CD4(+), some of them showing a mixture of CD4(+) and CD4(-) tumor cells. The remaining 5 specimens were CD3(+)/CD4(-)/CD8(-). A considerable number of T cells of different subtypes could always be found, but even in 13 cases predominated by CD8(+) cells, proliferation could be attributed to atypical CD4(+) cells. TCRgamma gene rearrangement was monoclonal in 48 cases (69%) among 70 tested. In 29 of these semi-quantitative gene scan analysis resulted in a median proportion of monoclonal peak of 35% of PCR-products. Clinical outcome was identical grouping patients by clonality of TCRgamma, absence or presence of clear cell clusters and international prognostic index. We conclude that AILT is mainly derived from CD2(+)CD3(+)CD4(+)CD5(+)CD7(-) mature T-helper cells with varying expression and partial loss of detectable CD4. A significant number of non-neoplastic T cells (resting CD4(+) T cells and activated small or medium-sized CD8(+) lymphocytes) may coexist with a minor neoplastic T cell population. Clinicopathologic correlation suggests AILT to be a well defined homogeneous entity with poor prognosis. Currently no prognostic factors can be derived.

Adult↗
PubMed2002

Primary gastric follicular lymphoma with parafollicular monocytoid B-cells and lymphoepithelial lesions, mimicking extranodal marginal zone lymphoma of MALT.

The incidence of B-cell non-Hodgkin lymphomas (B-NHL) at nodal and extranodal sites is fairly different. Follicular lymphomas (FL) occur predominantly at nodal sites and rarely in the gastrointestinal tract, while marginal zone lymphomas (MZL) of the mucosa-associated lymphatic tissue (MALT) type predominate in the digestive organs and especially in the stomach. We report a 72-year-old female patient admitted for gastroscopy because of epigastric pain. The antral biopsies showed dense lymphocytic infiltrates, partially forming follicles with widened marginal zones and monocytoid cells. Multiple lymphoepithelial lesions (LEL) were also observed. A MZL of the MALT type was suspected morphologically. Immunohistochemical analysis revealed the lymphatic infiltrates to be CD20, bcl-2, bcl-6 and CD10 positive, and negative for CD43, CD5 and cyclin D1. PCR-based analysis showed a JH/bcl-2 rearrangement, corresponding to the translocation t(14;18). An extranodal FL mimicking MZL was diagnosed. The present case is remarkable, as it demonstrates that the detection of LEL and monocytoid B-cells, although suggestive for MZL, is not entirely specific and can also be observed in FL. Pathologists should be aware of this diagnostic pitfall in classifying gastric B-NHL. In equivocal cases, a careful morphological examination, supported by specific immunohistochemical and molecular findings, should lead to the correct diagnosis.

Aged↗
PubMed2002

Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas.

Myasthenia gravis (MG) is the leading paraneoplastic manifestation of thymomas and is probably related to the capacity of thymomas to mature and export potentially autoreactive T cells. Why some thymomas are MG associated (MG+) and others are not (MG-) has been unclear. We addressed this question by comparing the percentages of intratumorous naive mature CD45RA+ thymocytes in 9 MG(+) and in 13 MG(-) thymomas by fluorescence-activated cell sorting analysis. Our results show that intratumorous naive CD4 T cells were present in all MG(+) thymomas and in one MG(-) thymoma with the development of MG only 2 months after surgery. By contrast, the percentage of naive CD4(+) T cells was significantly reduced in all 13 MG(-) thymomas (P <.0001). Alterations in intratumorous thymopoiesis were reflected by corresponding alterations of naive T-cell subset composition in the blood, in that only MG(-) patients had significantly decreased levels (P =.02) of naive CD4(+) T cells compared with age- and sex-matched control persons. We conclude that paraneoplastic MG is highly associated with the efficiency of thymomas to produce and export naive CD4(+) T cells. The acquisition of the CD45RA(+) phenotype on CD4(+) T cells during terminal intratumorous thymopoiesis is associated with the presence of MG in most thymoma patients.

Adult↗