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Einleitung: Das lymphoepitheliale Karzinom ist das häufigste Karzinom des Nasopharynx. Es macht mindestens 30 % aller Malignome des Nasenrachens aus. Als undifferenziertes Karzinom des Nasopharynx, auch Schmincke-Tumor genannt, zeigt es eine besondere Häufung in der Afrikanischen und Chinesischen Bevölkerung. Die Peakinzidenz liegt zwischen dem 20. und 30. sowie nach dem 60. Lebensjahr. Beim Nasopharynxkarzinom ist die zelluläre Immunität durch eine gestörte T-Zellfunktion deutlich herabgesetzt. Hierbei spielt die Infektion mit dem onkogenem Epstein-Barr-Virus eine Rolle. Die Lokalisation außerhalb des Nasopharynx stellt eine Rarität dar, es liegen lediglich Fallberichte vor.Fallbericht: Wir berichten über eine 73-jährige Patientin mit einem Zungengrundkarzinom, in dessen Histologie sich ein niedriggradig differenziertes Plattenepithelkarzinom vom Typ eines lymphoepithelialen Karzinoms zeigte. Die Patientin wurde nach Diagnosestellung einer primären Radiotherapie zugeführt.Schlussfolgerung: Trotz ihres seltenen Auftretens ausserhalb des Nasopharynx muss bei einer Raumforderung im Oropharynx an ein undifferenziertes Karzinom mit lymphozytären Stroma gedacht werden. Insbesondere aufgrund ihrer bekannten frühen Metastasierung, ist die Halslymphknotenschwellung, auch beidseitig, als mögliches Frühsymptom zu erkennen. Die Therapie der Wahl ist eine primäre Strahlentherapie der Primärregion und der Lymphabflusswege. Chemotherapeutika, wie Cisplatin und 5-Fluoruracil können ergänzend eingesetzt werden. Eine Neck-Dissection bei zervikaler Metastasierung verringert die Wahrscheinlichkeit regionärer Rezidive.Schlüsselwörter: Schmincke-Tumor, Oropharynx, Zungengrund

To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma Udgivelsesdato: 2008/2/8

To study the differential expression of cell membrane-bound receptors and their potential role in growth and/or survival of the tumor cells, highly purified follicular lymphoma cells were analyzed, using gene expression analysis, and compared to non-malignant B cell populations. Filtering the genome for overexpressed genes coding for cell membrane-bound proteins/receptors resulted in a hit list of 27 identified genes. Among these, we have focused on the aberrant over expression of CX3CR1, in different types of B cell lymphoma, as compared to non-malignant B cells. We show that CX3CR1, which normally is not expressed on B cells, is expressed both at the mRNA and protein level in several subtypes of lymphoma. CX3CR1 has also shown to be involved in the homing to specific tissues that express the ligand, CX3CL1, in breast and prostate cancer and may thus be involved in dissemination of lymphoma Udgivelsesdato: 2008/2/8

The redshifted 21-cm line of distant neutral H atoms provides a probe of the cosmic “dark ages” and the epoch of reionization (“EOR”) which ended them, within the first billion years of cosmic time. The radio continuum produced by this redshifted line can be seen in absorption or emission against the cosmic microwave background (“CMB”) at meterwaves, yielding information about the thermal and ionization history of the universe and the primordial density perturbation spectrum that led to galaxy and large-scale structure formation. Observing this 21-cm background is a great challenge, as it is necessary to detect a diffuse signal at a brightness temperature that differs from that of the CMB at millikelvin levels and distinguish this from foreground continuum sources. A new generation of low-frequency radio arrays is currently under development to search for this background. Accurate theoretical predictions of the spectrum and anisotropy of this background, necessary to guide and interpret future observations, are also quite challenging. Toward this end, it is necessary to model the inhomogeneous reionization of the intergalactic medium and determine the spin temperature of the 21-cm transition and its variations in time and space as it decouples from the temperature of the CMB. In my talk, I summarized some of the theoretical progress in this area. Here, I will focus on just a few of the predictions for the 21-cm background from the EOR, based on our newest, large-scale simulations of patchy reionization. These simulations are the first with enough N-body particles (from 5 to 29 billion) and radiative transfer rays to resolve the formation of and trace the ionizing radiation from each of the millions of dwarf galaxies believed responsible for reionization, down to 108 M[sun], in a cubic volume large enough (90 and 163 comoving Mpc on a side) to make meaningful statistical predictions of the fluctuating 21-cm background.

Mantle cell lymphoma (MCL) is an aggressive lymphoid malignancy for which better treatment strategies are needed. To identify potential diagnostic and therapeutic targets, a signature consisting of MCL-associated genes was selected based on a comprehensive gene expression analysis of malignant and normal B cells. The corresponding protein epitope signature tags were identified and used to raise monospecific, polyclonal antibodies, which were subsequently analyzed on paraffin-embedded sections of malignant and normal tissue. In this study, we demonstrate that the initial selection strategy of MCL-associated genes successfully allows identification of protein antigens either uniquely expressed or overexpressed in MCL compared with normal lymphoid tissues. We propose that genome-based, affinity proteomics, using protein epitope signature tag-induced antibodies, is an efficient way to rapidly identify a number of disease-associated protein candidates of both previously known and unknown identities., QC 20141128

Contains fulltext : 47723.pdf (publisher's version ) (Closed access), Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological characteristics. Cytomorphological subtypes, growth pattern and markers of proliferation (mitotic and Ki-67 indices) were analysed. In addition to the known cytological subtypes, classical (87.5%), small cell (3.6%), pleomorphic (5.9%) and blastic (2.6%), we identified new pleomorphic subgroups with mixtures of cells (classical + pleomorphic type; 1.6%) or transitions (classical/pleomorphic type; 1.6%), which, however, did not differ significantly in overall survival time. Exactly 80.5% of cases displayed a diffuse growth pattern, whereas 19.5% of cases had a nodular growth pattern, which was associated with a slightly more favourable prognosis. A high proliferation rate (mitotic or Ki-67 indices) was associated with shorter overall survival. Cut-off levels were defined that allowed three subgroups with different proliferation rates to be discriminated, which showed significantly different clinical outcomes (P < 0.0001). Based on this large clinicopathological study of prospective clinical trials, multivariate analysis confirmed the central prognostic role of cell proliferation and its superiority to all other histomorphological and clinical criteria.

Contains fulltext : 47723.pdf (publisher's version ) (Closed access), Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological characteristics. Cytomorphological subtypes, growth pattern and markers of proliferation (mitotic and Ki-67 indices) were analysed. In addition to the known cytological subtypes, classical (87.5%), small cell (3.6%), pleomorphic (5.9%) and blastic (2.6%), we identified new pleomorphic subgroups with mixtures of cells (classical + pleomorphic type; 1.6%) or transitions (classical/pleomorphic type; 1.6%), which, however, did not differ significantly in overall survival time. Exactly 80.5% of cases displayed a diffuse growth pattern, whereas 19.5% of cases had a nodular growth pattern, which was associated with a slightly more favourable prognosis. A high proliferation rate (mitotic or Ki-67 indices) was associated with shorter overall survival. Cut-off levels were defined that allowed three subgroups with different proliferation rates to be discriminated, which showed significantly different clinical outcomes (P < 0.0001). Based on this large clinicopathological study of prospective clinical trials, multivariate analysis confirmed the central prognostic role of cell proliferation and its superiority to all other histomorphological and clinical criteria.

Contains fulltext : 47723.pdf (publisher's version ) (Closed access), Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological characteristics. Cytomorphological subtypes, growth pattern and markers of proliferation (mitotic and Ki-67 indices) were analysed. In addition to the known cytological subtypes, classical (87.5%), small cell (3.6%), pleomorphic (5.9%) and blastic (2.6%), we identified new pleomorphic subgroups with mixtures of cells (classical + pleomorphic type; 1.6%) or transitions (classical/pleomorphic type; 1.6%), which, however, did not differ significantly in overall survival time. Exactly 80.5% of cases displayed a diffuse growth pattern, whereas 19.5% of cases had a nodular growth pattern, which was associated with a slightly more favourable prognosis. A high proliferation rate (mitotic or Ki-67 indices) was associated with shorter overall survival. Cut-off levels were defined that allowed three subgroups with different proliferation rates to be discriminated, which showed significantly different clinical outcomes (P < 0.0001). Based on this large clinicopathological study of prospective clinical trials, multivariate analysis confirmed the central prognostic role of cell proliferation and its superiority to all other histomorphological and clinical criteria.

Contains fulltext : 47723.pdf (publisher's version ) (Closed access), Mantle cell lymphoma (MCL) is a distinct lymphoma subtype with a particularly poor clinical outcome. The clinical relevance of the morphological characteristics of these tumours remains uncertain. The European MCL Network reviewed 304 cases of MCL to determine the prognostic significance of histopathological characteristics. Cytomorphological subtypes, growth pattern and markers of proliferation (mitotic and Ki-67 indices) were analysed. In addition to the known cytological subtypes, classical (87.5%), small cell (3.6%), pleomorphic (5.9%) and blastic (2.6%), we identified new pleomorphic subgroups with mixtures of cells (classical + pleomorphic type; 1.6%) or transitions (classical/pleomorphic type; 1.6%), which, however, did not differ significantly in overall survival time. Exactly 80.5% of cases displayed a diffuse growth pattern, whereas 19.5% of cases had a nodular growth pattern, which was associated with a slightly more favourable prognosis. A high proliferation rate (mitotic or Ki-67 indices) was associated with shorter overall survival. Cut-off levels were defined that allowed three subgroups with different proliferation rates to be discriminated, which showed significantly different clinical outcomes (P < 0.0001). Based on this large clinicopathological study of prospective clinical trials, multivariate analysis confirmed the central prognostic role of cell proliferation and its superiority to all other histomorphological and clinical criteria.

Pyothorax-associated lymphoma (PAL) is a rare haematological malignancy often associated with artificial pneumothorax due to the treatment of pulmonary tuberculosis. A 76 year old man with chronic tube-drained pyothorax and a history of artificial pneumothorax for pulmonary tuberculosis was admitted to our hospital because of progressive right thoracic pain, weight loss, and pyrexia. After clinical examination and imaging processes a chest wall tumour anterior on the right side was diagnosed as well as a persisting pyothorax. Surgery was performed to resect the tumour and drain the pleural cavity. A diagnosis of a high grade B-cell lymphoma was established after histological examination of the surgical biopsy. Epstein-Barr virus (EBV) was identified in the tumour by immunocytochemical and molecular methods. Additional gastric involvement of B-cell lymphoma could be diagnosed by gastroscopy because of postoperative gastrointestinal bleeding. The patient received chemotherapy with 2 courses of cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP). The response was favourable initially, but 2 months later the patient died because of lymphoma progression.Most cases of PAL have been described by Japanese investigators and only a few cases are reported in Western countries. To the best of our knowledge this case of PAL is the first to be documented in Germany.Awareness of this rare entity, together with diligent histological examination, in patients with chronic pyothorax are essential for a correct diagnosis and correct early treatment., Das Pyothorax-assoziierte Lymphom (PAL) stellt eine seltene maligne Erkrankung dar, die sich häufig auf der Basis einer Pneumothoraxbehandlung nach Tuberkulose entwickelt. Ein 76 jähriger Mann mit einem chronischen Pleuraempyem auf der Basis einer artifiziellen Pneumothoraxtherapie nach stattgehabter Tuberkulose wurde mit zunehmenden rechts-thorakalen Schmerzen, Gewichtsabnahme und Fieber stationär aufgenommen. Nach klinischer Untersuchung und bildgebenden Verfahren wurde die Diagnose eines Tumors der rechten Thoraxwand bei weiterhin bestehendem Pyothorax gestellt. Nach chirurgischer Resektion des Tumors und Debridement des Pyothorax ergab sich die Diagnose eines hoch malignen Epstein-Barr-Virus (EBV) positiven B-Zell-Lymphoms. Zusätzlich gelang der gastroskopische Nachweis des B-Zell-Lymphoms im Magen bei postoperativ aufgetretener oberer gastrointestinaler Blutung. Der Patient erhielt postoperativ 2 Zyklen Chemotherapie nach dem CHOP-Schema (Cyclophosphamid, Doxorubicin, Vincristin und Prednisolon). Nach primärem Erfolg der Chemotherapie starb der Patient 2 Monate später an einer Progression des Tumorleidens.PAL stellt eine vor allem von japanischen Autoren berichtete Entität dar. Nur wenige europäische Fälle sind bisher beschrieben worden. Nach unserem Kenntnisstand ist dies der erste in Deutschland dokumentierte Fall. Die Differentialdiagnose des PAL verbunden mit einer genauen histologischen Untersuchung sollte bei Patienten mit chronischem Pyothorax immer in Erwägung gezogen werden, um durch eine frühzeitige Diagnosestellung die Patienten der adäquaten Therapie zuführen zu können.

We report on the analysis of a murine anaplastic lymphoid cell line TS1G6, established recently by interleukin (IL)-9 transfection. TS1G6 revealed a highly characteristic pattern of large anaplastic cells with mononuclear, binuclear, or multinuclear cells resembling Hodgkin (H) or Sternberg-Reed (SR) cells. This cell line is tumorigenous after injection of as few as 10(4) lymphoma cells into nude or immunocompetent C57Bl/6 mice and leads to death from progressive disease of all treated animals within a few weeks. The histological analysis of these tumors revealed a diffuse large cell malignant lymphoma that is morphologically almost identical to human anaplastic large cell lymphoma (ALCL). The lymphoma cells did not show overexpression of the anaplastic lymphoma kinase (ALK) gene, which is found in about 50% of the cases of human ALCL. Thus, this model may be an animal model for an important subset of human ALCL. The cytokine profile, which is of the T helper 2 type, showed strong parallels to the human lymphoma counterpart. Mice suffering from such lymphomas could not be cured with a regimen using high dose cyclophosphamide similar to many ALCL patients. Such an animal model for ALCL has not yet been recognized, but may provide the basis for investigating new antitumor immunotherapies in a fully immunocompetent host.

Nosological classification of sinus histiocytosis with massive lymphadenopathy (SHML; Rosai-Dorfman disease) is difficult, and the normal cellular counterpart of Rosai-Dorfman (RD) cells is uncharacterised. The peculiar S-100+ phenotype of RD cells suggests a relationship with the dendritic cell family. Recent investigations have revealed cathepsin E to be selectively concentrated in antigen-presenting cells, whereas cathepsin D was found to be expressed in cells of macrophage lineage. Cathepsin D and E distribution was investigated by immunohistochemistry in a series of SHML biopsies and in two types of dendritic cell proliferative lesions: dermatopathic lymphadenitis (DL) and Langerhans' cell histiocytosis (LCH). In SHML biopsies, RD cells and monocyte-related elements of the sinuses and pulp coexpressed cathepsin D and E. LCH cells also stained for both these aspartic proteinases. Conversely, in DL cathepsin E and D were localised to separate cells that resembled Langerhans' cells (LC) or macrophages, respectively, in morphology and distribution. Our data outline the peculiar immunophenotype of RD and LCH cells and suggest that caution should be exercised in the identification of their normal cellular counterpart. The common expression of cathepsin D and E and of S-100 protein suggests some phenotypic overlap between SHML and LCH cells, despite their striking morphological divergence

As a consequence of the disastrous accident in Lapua (Finland) in 1976, where an explosion in a cartridge loading facility killed 40 and injured more than 70 persons, efforts were undertaken to examine and improve the safety of such installations. An ammunition factory in Switzerland considered the replacement of the manual supply of propellant hoppers by a new pneumatic supply system. This would reduce the maximum quantity of propellant in the hoppers to a level, where an accidental ignition would no longer lead to a detonation, and this would drastically limit the effects on persons. A quantitative risk assessment of the present and the planned supply system demonstrated that, in this particular case, the pneumatic supply system would not reduce the risk enough to justify the related costs. In addition, it could be shown that the safety of the existing system can be improved more effectively by other safety measures at considerably lower costs. Based on this practical example, the paper demonstrates the advantages of a strictly quantitative risk assessment for the safety planning in explosives factories. The methodological background of a risk assessment and the steps involved in the analysis are summarized. In addition, problems of quantification are discussed. (Author), This article is from 'Minutes of the Explosives Safety Seminar (21st) Held at Houston, Texas on 28-30 August 1984. Volume 2,' AD-A152 150, p1485-1505.