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  • Megakaryocytes  (6)
  • Bone marrow biopsies  (5)
  • Differential diagnosis  (4)
  • 1
    ISSN: 1432-2307
    Keywords: Key words Macrophages ; Pseudo-Gaucher cells ; Chronic myeloid leukaemia ; Bone marrow transplantation ; Bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  A morphometric and immunohistochemical study was performed on 354 bone marrow trephine biopsies derived from 126 patients with chronic myeloid leukaemia (CML) before and after allogeneic bone marrow transplantation (BMT). The purpose of this investigation was to evaluate the macrophage population, including several subsets and their dynamics in the posttransplant period. In addition to the total CD68+ resident (mature) macrophages the so-called activated fraction identified by its capacity to express α-d-galactosyl residues, the pseudo-Gaucher cells (PGCs) and the iron-laden histiocytic reticular cells were also considered. Following immuno- and lectin-histochemical staining morphometric analysis was carried out on sequential postgraft bone marrow specimens at standardized intervals. Compared to the normal bone marrow and calculated per haematopoiesis (cellularity) an overall decrease of about 40–50% in the quantity of CD68+ macrophages and the BSA-I+ subpopulation was detectable in the early posttransplant period (9–45 days after BMT). Noteworthy was the temporal recurrence of PGCs in the engrafted bone marrow, which was not associated with a clonally transformed cell population or leukaemic relapse. Reappearance of postgraft PGCs was most prominent in the first 2 months after BMT. This conspicuous feature was presumed to be functionally associated with a pronounced degradation of cell debris following pretransplant myelo-ablative therapy (scavenger macrophages). Evidence for an activation of the BSA-I+ macrophage subset was derived from the identical carbohydrate-binding capacity shown by the PGCs. In the regenerating haematopoiesis shortly after BMT a significant correlation between the number of BSA-I+ macrophages and erythroid precursor cells was determinable. This result implicates a close functional relationship between postgraft reconstitution of erythropoietic islets and centrally localized activated macrophages. In conclusion, findings emerging from this study included the reappearance of PCGs in the engrafted bone marrow independently of a leukaemic relapse and the significant association of the activated BSA-I+ macrophage subset with the recovery of erythropoiesis.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Pediatric surgery international 15 (1999), S. 437-439 
    ISSN: 1437-9813
    Keywords: Key words Joint chondromatosis ; Recurrence ; Differential diagnosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A case of chondromatosis of the upper ankle joint in childhood is described. It is a monoarticular disease with a good prognosis, frequently without known prior trauma or inflammation, although often free fragments of cartilage are seen in the joint cavities. It originates from the synovium of the joint, and is known in the literature as Reichel syndrome.
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 370 (1976), S. 273-289 
    ISSN: 1432-2307
    Keywords: Bone marrow biopsy ; Hairy cell leukemia ; Differential diagnosis ; Myelofibrosis ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 24 patients with hairy cell leukemia, histological and fine structural findings from biopsies of the bone marrow are reported and their validity is compared with other diagnostic procedures available. Diagnosis by light microscopy of anterior iliac crest biopsies obtained by the method of myelotomy is possible with a high degree of accuracy. The differentiation of hairy cell leukemia from other myelo- or lymphoproliferative disorders based on cytomorphology as well as patterns of growth is emphasized. Morphological differences between fibrosis in this entity and other lesions such as malignant lymphomas, Hodgkin's disease, osteomyelofibrosis and -sclerosis are emphasized. Electron microscopy of the bone marrow shows single fibroblastic cells with numerous slender cytoplasmic processes randomly dispersed among the hairy cells. These fibroblasts are probably responsible for the synthesis of the reticulin and collagen fibres in their surroundings. Moreover fine structure of the hairy cells demonstrates pinocytic activity but no apparent phagocytosis in contrast to the phagocytic reticulum cells (histiocytes, macrophages). In the bone marrow the precursor cells and the many immature forms of hairy cells exhibit an overall lymphocytoid appearance during their maturation, suggesting a lymphocytic origin.
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  • 4
    ISSN: 1432-2307
    Keywords: Chronic myeloproliferative disorders ; Thrombocytosis ; Primary Thrombocythaemia ; Granulo ; Erythrocytopoiesis ; Reticulin Fibers ; Circular Deviation ; Histomorphometry ; Bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A histomorphometric analysis was performed on trephine biopsies of the bone marrow in 55 patients with chronic myeloproliferative disorders (CMPDs) and marked thrombocytosis (platelet count exceeding 600 × 109/l). This study aimed at discriminating primary (essential) thrombocythaemia (PTH) from the various other subtypes of CMPDs presenting with thrombocytosis. Following the diagnostic requirements postulated by the Polycythemia-vera-Study-Group for PTH and polycythaemia vera rubra (P.vera) and the generally accepted criteria for the establishment of chronic myeloid leukaemia (CML) and agnogenic myeloid metaplasia (AMM), our cohort of 55 patients was divided into the following subgroups: CML (16 cases), P.vera (11 cases), AMM (13 cases) and finally PTH (15 cases). Histomorphometric measurements revealed that PTH was distinguishable from the other subtypes of CMPDs with respect to several histological variables: patients with PTH had a normal amount of neutrophilic granulo- and erythrocytopoiesis as well as a non-increased content of reticulin (argyrophilic) fibers in contrast to the findings in CML, P.vera and of course AMM. Moreover, sizes of megakaryocytes and their nuclei were significantly greater in PTH and internalization of haematopoietic cells (emperipolesis) was more frequently encountered in comparison with the other subtypes of CMPDs. Deviation of the circular perimeter of megakaryocyte shape was most prominently expressed in CML and AMM, and consequently generated an increased number of a-nuclear cytoplasmic fragments. In contrast to this feature aberration of the nuclei from a circular outline occurred in a less pronounced way in CML, but was excessive in P.vera, AMM and PTH. Our morphometric evaluation demonstrates that certain histological features may serve as a valuable aid in discriminating PTH from the other occasionally thrombocythaemic subtypes of CMPDs.
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  • 5
    ISSN: 1432-2307
    Keywords: Megakaryocytes ; Sinus wall ; Transmural migration ; 3D-reconstruction ; Double-immunostaining
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Using sequential double-immunostaining and a newly-developed three-dimensional (3D-) reconstruction technique on serially cut sections from bone marrow trephines, we studied the transmural passage of megakaryocytes through the sinus wall. Biopsies derived from patients with primary (idiopathic) osteomyelofibrosis were exposed to monoclonal antibody against type IV collagen to delineate the sinus walls and also the frequently thickened basement membrane. Staining with the primary antibody was followed by Y2/51 (CD61) to identify all elements of megakaryopoiesis. In most instances serial sectioning and 3D-reconstruction revealed an amoeboid shape of megakaryocytes and a tandem-like arrangement in close spatial contact with the abluminal surface of the sinus wall. Preceded by formation of cytoplasmic processes, straight penetration of entire megakaryocytes through gaps in the sinus walls into the lumen was seen. Where collagen deposits apparently presented a barrier, a mole-like tunnelling through the basement membrane material (type IV collagen) was recognizable. Our findings are in keeping with the assumption that megakaryocyte locomotion is an essential requirement for normal thrombocytogenesis.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1432-0584
    Keywords: Key words CML ; Myelofibrosis ; Dynamics ; Megakaryocytes ; Morphometry ; Interferon ; Busulfan ; Sequential bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph1+-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.
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  • 7
    ISSN: 1432-0584
    Keywords: Key words Chronic myeloproliferative disorders ; Erythroid precursors ; Neutrophil granulopoiesis ; Megakaryocytes ; Macrophages ; Myelofibrosis ; Enzyme-immunohistochemistry ; Morphometry ; Bone marrow biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  The aim of this review is to evaluate morphological characteristics of the different subtypes of chronic myeloproliferative disorders (MPDs) derived by applying immunohistochemical and morphometric techniques to bone marrow biopsies and to combine these results with relevant clinical parameters. In comparison to control specimens, a significant decrease in erythroid precursors is determinable in chronic myeloid leukemia (CML), while this cell lineage is most prominent in polycythemia vera (PV) and moderately to markedly reduced in idiopathic myelofibrosis (IMF). On the other hand, neutrophilic granulopoiesis shows a predominance in CML and a relevant increase in PV, but no conspicuous changes are detectable in essential thrombocythemia (ET). CML is characterized by a prevalent growth of dwarflike micromegakaryocytes, occurring in particular in the so-called megakaryocyte-rich subtypes (about 30%). This finding differs significantly from the pleomorphous aspect, i.e., clusters of small to giant-sized megakaryocytes in PV and the grossly abnormal (dysplastic) appearance of this cell lineage in patients with IMF. Similar cytological abnormalities of megakaryopoiesis consistent with maturation defects are never encountered in ET. The incidence of mature (resident) macrophages (phagocytic reticular cells) is significantly enhanced in IMF in comparison to the other MPDs and controls. Moreover, there is a striking difference in the density of reticulin-collagen fibers, ranging from normal (ET) to extreme values (IMF). In IMF more than 80% of the patients present with some degree of myelofibrosis-osteosclerosis at diagnosis, while the rest show an initial prefibrotic, hypercellular stage. This feature deserves special attention since, when accompanied by thrombocythemia, it may simulate ET. Sequential bone marrow biopsies in patients with IMF disclose that evolution of myelofibrosis is progressive, but occurs at a variable and unpredictable speed. A synoptical approach regarding clinical diagnosis and histological subtyping of MPDs is explicitly recommended and demonstrated by sets of diagnostic criteria. This rationale requires equal consideration of laboratory data and morphology by clinicians to include well-defined subtypes of MPDs into prospective management studies. Furthermore, it may even warrant follow-up studies and repeated bone marrow examinations in initially unclassifiable cases.
    Type of Medium: Electronic Resource
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  • 8
    ISSN: 1432-0584
    Keywords: CML ; Myelofibrosis ; Dynamics ; Megakaryocytes ; Morphometry ; Interferon ; Busulfan ; Sequential bone marrow biopsies
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To evaluate treatment-related changes of the reticulin stain-measured fibrosis in Ph1+-CML, a clinicopathological study was performed on sequential trephine biopsies of the bone marrow following either interferon (IFN) or busulfan (BU) monotherapy. Using the monoclonal antibody CD61 for the identification of megakaryopoiesis and Gomori's silver impregnation method, number of megakaryocytes and density of argyrophilic (reticulin and collagen) fibers were determined by morphometry. We studied specimens from 26 patients with IFN-alpha 2b (including nine patients with additional IFN gamma) therapy and from 23 patients who had received BU. In both groups, repeated bone marrow biopsies (total 125) revealed a significant increase in the fiber content, as well as in the number of megakaryocytes during treatment. To assess the dynamics of myelofibrosis more precisely, computation of differences in the degree of fiber density between the first and last examination was carried out. Regarding the considerable variations in the biopsy intervals, a so-called myelofibrosis progression index (MPI) was calculated. Following this rationale, we were able to demonstrate that, in comparison to the BU-group, speed of progression of bone marrow fibrosis was significantly increased in CML patients treated with IFN. Preliminary statistical analysis indicated a relationship between myelofibrosis on admission, which was always associated with increased growth of megakaryocytes, and the MPI with survival. Even when these parameters were regarded, prognosis was significantly more favorable in the IFN-treated patients. The failure of IFN and BU to inhibit the evolution of myelofibrosis may be related to several conversely acting pathomechanisms. Among others, the inability of both therapeutic agents to reduce the number of megakaryocytes more effectively should be taken into consideration.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 16 (1995), S. 106-119 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Maligne Lymphome ; Fokale reaktive lymphoide Hyperplasie ; Knochenmark ; Differentialdiagnose ; Histotopographie ; Fasergehalt ; Immunhistochemie ; Key words Malignant lymphomas ; Reactive lymphoid hyperplasia ; Bone marrow ; Differential diagnosis ; Histotopography ; Fiber content ; Immunohistochemistry
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The purpose of this study was to provide criteria for the differentiation of reactive lymphoid hyperplasia (RLH) and focal involvement of the bone marrow by malignant lymphoma (ML). Using trephine bone-marrow biopsy specimens embedded in paraffin wax and unequivocally established samples with ML for comparison, all patients with questionable lymphoid or lymphohistiocytic marrow aggregates were re-examined, together with obviously reactive lesions. Following this procedure, a number of characteristics were found that differed in validity with regard to diagnosis. In addition to cytology, which is preferably assessed in Giemsa-stained specimens and evaluated by the Kiel classification, histotopography, fiber content, and immunohistochemical reactions are the most valuable tools for differential diagnosis. RLH is consistent with a central-perivascular localization, a distinctive border and the presence of germinal centers, no or only minimal reticulin fibrosis and a polyclonal reaction pattern with a mixed population of B- and T-lymphocytes, following staining with appropriate antibodies. In uncertain cases (i. e., extensive lymphoproliferations in HIV-myelopathy) the results of immunohistochemical staining are of definite importance for the diagnostic evaluation of these lesions.
    Notes: Zusammenfassung Die vorliegende Studie verfolgt das Ziel, Kriterien für die differentialdiagnostische Abgrenzung zwischen fokaler reaktiver lymphatischer Hyperplasie (RLH) und nodulären Infiltraten von malignen Lymphomen (ML) im Knochenmark festzulegen. Im Vergleich zu klinisch und histologisch gesicherten Fällen von ML und offensichtlich reaktiven Veränderungen wurden alle in ihrer diagnostischen Zuordnung fraglichen lymphoiden bzw. lymphohistiozytären Läsionen anhand von Beckenkammbiopsien nach Paraffineinbettung noch einmal untersucht. Als wesentliches Ergebnis konnte eine Reihe von diagnostischen Merkmalen herausgearbeitet werden, die allerdings von sehr unterschiedlicher Wertigkeit waren. Neben der Zytologie, welche besonders gut in nach Giemsa gefärbten Präparaten auswertbar ist und sich problemlos nach den entsprechenden Maßgaben der Kiel-Klassifikation zuordnen läßt, sind Histotopographie, Fasergehalt und Immunhistochemie von besonderer nosologischer Bedeutung. Für eine RLH sprechen eine zentral-perivaskuläre Lokalisation mit scharfer Abgrenzung sowie Keimzentren, keine oder allenfalls eine minimale Retikulinfibrose sowie schließlich nach Anwendung immunhistochemischer Verfahren ein polyklonales Reaktionsmuster mit einer Mischpopulation aus B- und T-Lymphozyten. Im Zweifelsfall (z. B. bei ausgedehnter Lymphoproliferation im Rahmen einer HIV-Myelopathie) ist alleine die Immunhistochemie in der Lage, diagnostisch wegweisende Anhaltspunkte zu geben.
    Type of Medium: Electronic Resource
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  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Der Pathologe 16 (1995), S. 128-138 
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Dreidimensionale Rekonstruktion ; Lichtmikroskopie ; Serienschnitte ; Megakaryozyten ; Primäre Osteomyelofibrose ; Knochenmark ; Key words Three-dimensional reconstruction ; Light microscopy ; Serial sections ; Megakaryocytes ; Primary osteomyelofibrosis ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Computer-based three-dimensional reconstruction of serially cut light microscopic sections is being increasingly used in medical and biological research. Compared with conventional two-dimensional evaluation of histological sections, complex histotopographical relationships and structural details are easy to assess and could be imposingly visualized on the graphics screen. Because of the rapid progress in modern computer hardware, uncomplicated and fast reconstruction systems are available on standard personal computers. Therefore, 3D reconstruction is applicable for a wide range of investigations that warrant 3D exploration. Own results are presented and the principles of 3D reconstruction, as well as the problems and difficulties in this new technique, are discussed. The complex ameboid morphology of megakaryocytes in bone marrow of primary (idiopathic) osteomyelofibrosis is examined with this new method in combination with selective immunohistochemical staining procedures. 3D reconstruction can visualize the complexity of cytoplasmic and nuclear formation impressively. Moreover, the models generated permit exact quantitative measurements of cell morphology. The technique presented is a powerful tool for anatomical-morphological investigations and can furthermore increase our comprehension of complex histomorphological objects.
    Notes: Zusammenfassung Computergestützte dreidimensionale Rekonstruktionsverfahren von lichtmikroskopischen Serienschnitten haben sich in den letzten Jahren in allen Bereichen der medizinisch-biologischen Forschung etablie-ren können. Im Vergleich zur konventionellen zweidimensionalen Schnittbetrachtung lassen sich komplexe histotopographische Beziehungen sowie Strukturcharakteristika besser erfassen und auch eindrucksvoll darstellen. Aufgrund der schnell fortschreitenden Entwicklung im Bereich der Computertechnik sind heutzutage Rekonstruktionssysteme auch auf preisgünstigen Rechnersystemen verfügbar, so daß sich dieser neuen Methode ein zunehmendes Anwendungsgebiet erschließt. Anhand von eigenen Befunden werden die Grundlagen der 3 D-Rekonstruktion besprochen sowie Schwierigkeiten und Probleme dieser neuen Technik diskutiert. In Kombination mit kontrastreichen und selektiven immunhistochemischen Färbungen wird beispielhaft die komplexe amöbenartige Morphologie der Megakaryozyten bei der primären (idiopathischen) Osteomyelofibrose durch lichtmikroskopische Serienschnitte aus dem Knochenmark vorgestellt. Die erzeugten 3 D-Modelle vermitteln einen plastischen Eindruck von der Komplexität der Zell- und Kernstrukturen dieser Zellen und stellen die Basis für exakte quantitative Analysen der Zellmorphologie dar. Die vorgestellte Technik beinhaltet ein ergänzendes Werkzeug für anatomisch-morphologische Analysen und ist in der Lage, entscheidende Erkenntnisse bei der Untersuchung vielschichtiger histomorphologischer Objekte zu liefern.
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