255 research outputs found

    Differential Diagnoses of Systemic Mastocytosis in Routinely Processed Bone Marrow Biopsy Specimens: A Review

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    Diagnosis of systemic mastocytosis (SM) is mainly based on the morphological demonstration of compact mast cell infiltrates in various tissue sites. In almost all patients such infiltrates are detected in the bone marrow. Reliable immunohistochemical markers for the diagnosis and grading of SM have been established, but various differential diagnoses including myeloproliferative neoplasms, basophilic and eosinophilic leukemias may be very difficult to delineate. Even more challenging is the recognition of hematological neoplasms with signs of mast cell differentiation but not fulfilling diagnostic criteria for SM, especially the rare myelomastocytic leukemia. It is also important to separate the reactive state of mast cell hyperplasia from indolent variants of SM, especially those with a very low degree of bone marrow infiltration and absence of compact mast cell infiltrates. When the lymphocytic component of the SM infiltrate is very prominent, SM may be confused with an indolent lymphoma, especially lymphoplasmacytic lymphoma which almost always shows a marked reactive increase in mast cells. In aggressive and leukemic variants of SM, mast cells may be very atypical and devoid of metachromatic granules. This hypogranulation can be regarded as cellular atypia and may lead to the misdiagnosis aspect of monocytic leukemia or histiocytic neoplasm. Regarding immunohistochemical anomalies, mast cells in aggressive and leukemic SM have been found to express CD30 (Ki1-antigen). Thus, anaplastic large cell lymphoma or Hodgkin's disease may first be considered rather than SM. There is increasing evidence that most patients with long-standing adult-type urticaria pigmentosalike skin lesions have in fact indolent SM. Therefore, such skin lesions are an important clue to the correct diagnosis in these patients. However, in aggressive or leukemic SM skin lesions are usually absent and then the correct diagnosis relies on an appropriate investigation of bone marrow biopsy specimens using both SM-related immunohistochemical markers (tryptase, KIT, CD25, CD30) but also markers excluding potential differential diagnoses. Investigation for presence of the activating KIT point mutation D816V is very helpful to establish a correct diagnosis of SM in all the difficult cases exhibiting a low degree of bone marrow infiltration or puzzling morphological findings. Copyright (C) 2010 S. Karger AG, Base

    KITD816V+ systemic mastocytosis associated with KITD816V+ acute erythroid leukaemia: first case report with molecular evidence for same progenitor cell derivation

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    Toll-like receptor (TLR)-9 recognizes CpG motifs in microbial DNA. TLR9 signalling stimulates innate antimicrobial immunity and modulates adaptive immune responses including autoimmunity against chromatin, e.g., in systemic lupus erythematosus (SLE). This review summarizes the available data for a role of TLR9 signalling in lupus and discusses the following questions that arise from these observations: 1) Is CpG-DNA/TLR9 interaction involved in infection-induced disease activity of lupus? 2) What are the risks of CpG motifs in vaccine adjuvants for lupus patients? 3) Is TLR9 signalling involved in the pathogenesis of lupus by recognizing self DNA

    Histological investigations on the thyroid glands of marine mammals (Phoca vitulina, Phocoena phocoena) and the possible implications of marine pollution

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    In 1988 and 1989, thousands of harbor seals (Phoca vitulina) died in the North Sea from phocine distemper infection. The morphology of thyroid glands from 40 harbor seals found dead on the North Sea coastlines of Schleswig-Holstein, Federal Republic of Germany, during an epizootic of phocine distemper, was compared with the morphology of thyroid glands from five healthy harbor seals collected in Iceland. Thyroid glands from seven harbor porpoises (Phocoena phocoena) found dead in 1990 on the North Sea coastlines also were evaluated. Colloid depletion and fibrosis were found in the thyroid glands of harbor seals which died during the epizootic, but not in animals from Iceland. Thyroid glands of the porpoises showed similar lesions, but to a lesser degree, than those observed in the North Sea seals

    Evaluation of Mast Cell Activation Syndromes: Impact of Pathology and Immunohistology

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    Mast cell activation syndromes (MCAS) are clinically defined disease states with a largely unknown morphological background. Since mastocytosis may be associated with MCAS, it is crucial in every patient to document or exclude mastocytosis by appropriate histological, molecular, and serological investigations of tissues/organs that are commonly involved in mastocytosis like skin, mucosa of the gastrointestinal tract and bone marrow. Accordingly, histopathological investigation including immunohistological stains is crucial to reach the final diagnosis in such patients and to classify MCAS into primary MCAS, which can present with or without evidence of overt mastocytosis, or secondary MCAS, where an underlying disease with or without tissue inflammation is detected. Cases without evidence of mastocytosis, monoclonal mast cells, or any underlying disease should be termed idiopathic MCAS. When the activating point mutant KIT D816V is detectable but criteria for diagnosis of mastocytosis are not completely met, a so-called (mono)clonal MCAS as a subvariant of primary MCAS should be diagnosed. Copyright (C) 2012 S. Karger AG, Base

    Transport, magnetic, thermodynamic and optical properties in Ti-doped Sr_2RuO_4

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    We report on electrical resistivity, magnetic susceptibility and magnetization, on heat capacity and optical experiments in single crystals of Sr_2Ru_(1-x)Ti_xO_4. Samples with x=0.1 and 0.2 reveal purely semiconducting resistivity behavior along c and the charge transport is close to localization within the ab-plane. A strong anisotropy in the magnetic susceptibility appears at temperatures below 100 K. Moreover magnetic ordering in c-direction with a moment of order 0.01 mu_B/f.u. occurs at low temperatures. On doping the low-temperature linear term of the heat capacity becomes reduced significantly and probably is dominated by spin fluctuations. Finally, the optical conductivity reveals the anisotropic character of the dc resistance, with the in-plane conductance roughly following a Drude-type behavior and an insulating response along c

    Splenomegaly, elevated alkaline phosphatase and mutations in the SRSF2/ASXL1/RUNX1 gene panel are strong adverse prognostic markers in patients with systemic mastocytosis

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    We evaluated the impact of clinical and molecular characteristics on overall survival (OS) in 108 patients with indolent (n=41) and advanced SM (advSM, n=67). Organomegaly was measured by magnetic resonance imaging (MRI)-based volumetry of liver and spleen. In multivariate analysis of all patients, an increased spleen volume greater than or equal to450?ml (hazard ratio [HR], 5.2; 95% confidence interval [CI], [2.1–13.0]; P=0.003) and an elevated alkaline phosphatase (AP; HR 5.0 [1.1–22.2]; P=0.02) were associated with adverse OS. The 3-year OS was 100, 77, and 39%, respectively (P<0.0001), for patients with 0 (low-risk, n=37), 1 (intermediate-risk, n=32) or 2 (high-risk, n=39) parameters. For advSM patients with fully available clinical and molecular data (n=60), univariate analysis identified splenomegaly greater than or equal to1200?ml, elevated AP and mutations in the SRSF2/ASXL1/RUNX1 (S/A/R) gene panel as significant prognostic markers. In multivariate analysis, mutations in S/A/R (HR, 3.2 [1.1–9.6]; P=0.01) and elevated AP (HR 2.6 [1.0–7.1]; P=0.03) remained predictive adverse prognostic markers for OS. The 3-year OS was 76% and 38%, respectively (P=0.0003), for patients with 0-1 (intermediate-risk, n=28) or 2 (high-risk, n=32) parameters. We conclude that splenomegaly, elevated AP and mutations in the S/A/R gene panel are independent of the WHO classification and provide the most relevant prognostic information in SM patient

    Definitions, Criteria and Global Classification of Mast Cell Disorders with Special Reference to Mast Cell Activation Syndromes: A Consensus Proposal

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    Activation of tissue mast cells (MCs) and their abnormal growth and accumulation in various organs are typically found in primary MC disorders also referred to as mastocytosis. However, increasing numbers of patients are now being informed that their clinical findings are due to MC activation (MCA) that is neither associated with mastocytosis nor with a defined allergic or inflammatory reaction. In other patients with MCA, MCs appear to be clonal cells, but criteria for diagnosing mastocytosis are not met. A working conference was organized in 2010 with the aim to define criteria for diagnosing MCA and related disorders, and to propose a global unifying classification of all MC disorders and pathologic MC reactions. This classification includes three types of `MCA syndromes' (MCASs), namely primary MCAS, secondary MCAS and idiopathic MCAS. MCA is now defined by robust and generally applicable criteria, including (1) typical clinical symptoms, (2) a substantial transient increase in serum total tryptase level or an increase in other MC-derived mediators, such as histamine or prostaglandin D 2, or their urinary metabolites, and (3) a response of clinical symptoms to agents that attenuate the production or activities of MC mediators. These criteria should assist in the identification and diagnosis of patients with MCAS, and in avoiding misdiagnoses or overinterpretation of clinical symptoms in daily practice. Moreover, the MCAS concept should stimulate research in order to identify and exploit new molecular mechanisms and therapeutic targets. Copyright (C) 2011 S. Karger AG, Base

    Experimental investigation of the effect of ionization on the 51V(p,n)51Cr reaction

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    The investigation of the effects of average atomic ionization on nuclear reactions is of prime importance for nuclear astrophysics. No direct experimental measurement using a plasma target has been done yet. In this regard, we measured for the first time the neutron production of a (p,n) reaction in different states of ionization. The studied nuclear reaction was 51V(p,n)51Cr. We measured a significantly lower neutron production than expected when the target was ionized, even when taking into account existing electron screening theory or the effect of the stopping power in the target on the injected proton beam. This experiment is a first step in the process to characterize the influence of ionization at astrophysically relevant energies.Comment: 20 pages, 10 figures, submitted to EP

    Microscopic examination of bone marrow aspirates in malignant disorders of haematopoiesis—a comparison of two slide preparation techniques

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    It is mandatory to perform microscopic examinations of bone marrow aspirates during the diagnosis of many neoplastic haematopoiesis disorders. In 2008, The International Committee for Standardization in Hematology recommended the use of two types of slides for the microscopic evaluation of bone marrow: wedge-spread film and crush film slides. Because these techniques have not yet been compared, we performed such a comparison. Routine bone marrow samples from 250 patients diagnosed due to different neoplastic haematological disorders were evaluated. The major differences between the two compared techniques were identified in 13 patients with non-Hodgkin’s lymphoma, seven patients with systemic mastocytosis and 11 patients with acute leukaemias or myelodysplastic syndromes or chronic myelomonocytic leukaemia. Differences were noted also in many patients with multiple myeloma, but the clinical significance of these discrepancies was rather modest. The major causes of the differences observed seemed to be the dilution of marrow with blood cells and the focal growth of many neoplastic cells. We believe that the crush technique is more advantageous compared to the wedge-spread films. Therefore, we recommend the use of crush films as the primary method for establishing a diagnosis or for making therapeutic decisions based on the microscopic examination of bone marrow

    Proposed Diagnostic Criteria and Classification of Canine Mast Cell Neoplasms: A Consensus Proposal

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    Mast cell neoplasms are one of the most frequently diagnosed malignancies in dogs. The clinical picture, course, and prognosis vary substantially among patients, depending on the anatomic site, grade and stage of the disease. The most frequently involved organ is the skin, followed by hematopoietic organs (lymph nodes, spleen, liver, and bone marrow) and mucosal sites of the oral cavity and the gastrointestinal tract. In cutaneous mast cell tumors, several grading and staging systems have been introduced. However, no comprehensive classification and no widely accepted diagnostic criteria have been proposed to date. To address these open issues and points we organized a Working Conference on canine mast cell neoplasms in Vienna in 2019. The outcomes of this meeting are summarized in this article. The proposed classification includes cutaneous mast cell tumors and their sub-variants defined by grading- and staging results, mucosal mast cell tumors, extracutaneous/extramucosal mast cell tumors without skin involvement, and mast cell leukemia (MCL). For each of these entities, diagnostic criteria are proposed. Moreover, we have refined grading and staging criteria for mast cell neoplasms in dogs based on consensus discussion. The criteria and classification proposed in this article should greatly facilitate diagnostic evaluation and prognostication in dogs with mast cell neoplasms and should thereby support management of these patients in daily practice and the conduct of clinical trials
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