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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 307-324 
    ISSN: 1432-2307
    Keywords: Polycythemia vera ; Secondary polycythemia ; Histopathology ; Ultrastructure ; Cytogenetics ; Bone marrow biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Clinical and morphological studies including light microscopy, electron microscopy and karyotyping of the bone marrow, were performed on a total of 164 patients with polycythemic conditions. A final diagnosis was obtained from clinical findings and histopathology of plastic embedded core biopsies of the bone marrow including sequential examinations. 51 patients revealed a secondary polycythemia whereas 113 displayed polycythemia vera (P. vera). In this last group 83 cases have persisting P. vera. 30 showed a transgression towards chronic myeloid leukemia with or without accompanying myelofibrosis — osteomyelosclerosis (so called chronic megakaryocytic-granulocytic myelosis — CMGM). The histopathology of the bone marrow in P. vera revealed consistent alterations which are useful in distinguishing this disorder from secondary polycythemia (SP) and CMGM: depletion of iron storage, increased neutrophilic granulopoiesis but no gross atypia in maturation, polymorphism of megakaryocytes with conspicuous giant forms and dilatation and increased branchings of venous sinusoids. Electron microscopic findings were in agreement and showed further abnormalities of cytological maturation in the erythrocytic and granulocytic lineage. Cytogenetic studies in 27 non-treated patients with P. vera revealed the Philadelphia chromosomes in 2 cases, whereas in SP only minor chromosomal anomalies have been encountered in a few patients. It is concluded that histopathology of trephine biopsies of the bone marrow is an invaluable aid to establish a correct diagnosis, differentiating P. vera from the other potentially polycythemic disorders and helping to detect a possible progression towards leukemia at an early stage. Cytogenetic investigations may show early structural and numerical abnormalities of the karyotype and possibly precede a presumptive transgression towards myeloid leukemia (CMGM). A simultaneously performed histological and chromosomal examination of bone marrow samples is therefore desirable in each case of a polycythemic condition.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 325-341 
    ISSN: 1432-2307
    Keywords: Polycythemia vera ; Myeloid leukemia ; Histopathology ; Ultrastructure ; Cytogenetics ; Survival
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Of 113 Patients with polycythemia vera (P. vera) who had been followed for the last 8 years, 30 cases (27%) developed myeloid leukemia with fibrosis of the bone marrow. Core biopsies of the bone marrow including sequential examinations in several cases revealed neoplastic proliferation of neutrophil granulopoiesis and an atypical megakaryopoiesis with accompanying fibrosis of varying degrees. These alterations were consistent with a subtype of chronic myeloid leukemia — the so called chronic megakaryocytic-granulocytic myelosis (CMGM) — and correspond to (agnogenic) myeloid metaplasia with osteomyelofibrosis/-sclerosis. 5 of those 30 patients showed spontaneous transgression into myeloid leukemia, none of them had received any ionizing radiation or cytostatic therapy. A blast crisis or so called acute leukemia in P. vera was seen only in one patient who was treated by an overdose of radioactive phosphorus and later evolved into osteomyelosclerosis with blastic transformation. These findings of a chronic leukemia or CMGM arising from P. vera was further confirmed by atypia of ultrastructure and particularly by our cytogenetic evaluation. Chromosomal studies showed a Ph′-chromosome to be present in 5 of 8 patients with CMGM and myelofibrosis. Clinical and statistical evaluation of survival times showed a median survival expectation of all P. vera patients of 15 years. Life expectancy of the patients who still displayed P. vera was more favorable than those cases with transformation into CMGM, disregarding any therapy. Transformation of P. vera into CMGM occurred about 8 years after the onset of disease and following transgression into leukemia, half of these patients were dead after 2.5 years. Our results demonstrate that P. vera represents a “panmyelosis” with an inherent malignant nature, or a neoplastic proliferation of all three cell lines. This concept is supported by several facts: atypia of cytological differentiation as observed by light- and electron microscopy of the bone marrow, chromosomal anomalies with aneuploidy and an infrequent Ph'-marker, spontaneous transgression into chronic myeloid leukemia or its subtype CMGM without relevant therapy and a clonal evolution as shown by enzymatic studies reported in the literature.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-1440
    Keywords: Parathyroid gland ; secondary hyperparathyroidism ; activated chief cell ; secretory cycle ; electron microscopy ; Nebenschilddrüse ; sekundärer Hyperparathyreoidismus ; stimulierte Hauptzelle ; sekretorischer Cyclus ; Elektronenmikroskopie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Bei zwei klinisch stark unterschiedlich ausgeprägten Formen des sekundären, renal bedingten Hyperparathyreoidismus (Hyperpara) wird die Feinstruktur der hyperplastischen Epithelkörper (EK) miteinander verglichen. Die Beobachtungen lassen dabei ein cyclisches Geschehen im Sekretionsablauf der stimulierten Hauptzelle erkennen, wie es bisher nur bei Tieren beobachtet wurde. Bei dem Patienten mit dem endokrin hochaktiven Hyperpara ist einmal die rein numerische Vermehrung der EK-Zellen (Gesamtgewicht der EK) entscheidend für die Ausprägung des klinischen Krankheitsbildes, zum anderen ist aber auch eine Änderung in der Funktionswertigkeit eingetreten, in dem Sinne, daß sich weitaus mehr Zellgruppen auf dem Höhepunkt der Sekretionsphase des funktionellen Cyclus befinden.
    Notes: Summary The fine structure of parathyroid gland hyperplasia is compared in two cases of secondary (renal) hyperparathyroidism of extremely different clinical course. The results suggest the presence of a secretory cycle in the activated chief cell until now only seen in animals. In the patient with the hyperparathyroidism of high endocrine activity two facts are decisive for the severe clinical course: first the increase in absolute number of parathyroid cells (the total weight of the parathyroid glands), second an alteration of the functional state that means, an increased number of cell groups according to their fine structure are at the peak of the secretory phase of their functional cycle.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Journal of molecular medicine 52 (1974), S. 1063-1069 
    ISSN: 1432-1440
    Keywords: Parathyroid gland ; primary water-clear hyperplasia ; acute hyperparathyroidism ; clinical findings ; electron microscopy ; Nebenschilddrüse ; primäre wasserhelle Zellenhyperplasie ; akuter Hyperparathyreoidismus ; klinische Symptomatik ; Elektronenmikroskopie
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung Klinische und morphologische Befunde wurden bei einer Patientin mit akutem Hyperparathyreoidismus bei primaärer wasserheller Zellenhyperplasie vorgestellt und miteinander verglichen. Von klinischer Sicht aus ist insbesondere die lange bestehende Anamnese, der Befund eines primären Hyperparathyreoidismus hoher Aktivität und das plötzliche Auftreten der letal endenden Krise bemerkenswert. Die klinische Symptomatik sowie die Differentialdiagnose dieser seltenen, jedoch lebensbedrohlichen Komplikation wird eingehend erörtert und zusammen mit den wenigen Literaturangaben dazu besprochen. Die elektronenmikroskopischen Untersuchungen an den wasserhellen Zellen kann fließende übergänge zwischen Hauptzellen-ähnlichen Zellgruppen und typischen Zellen mit weitgehender vakuoliger Degeneration des Cytoplasmas aufzeigen, ebenso wie vakuolig entartete oxyphile Zellen. Die Hauptzellen-ähnlichen, organellenreichen Formen werden als eigentlichen Parathormon produzierende Zellen angesehen und die nur sehr wenigen vorhandenen Sekretgranula auf die plötzliche Ausschüttung in der hyperparathyreoten Krise zurückgeführt. In den Vakuolen werden kristallgitterartige Strukturen neben amorphen Anteilen und Lipide gesehen. Folglich könnte die primäre wasserhelle Zellenhyperplasie als Sonderform der primären Hauptzellenhyperplasie angesprochen werden, bei der ein möglicher Synthesedefekt wohl im Bereiche des Golgiapparates vorliegt, der das Cytoplasma von Hauptzellen und oxyphilen Zellen mit vakuolig entarteten Sekretprodukten anfüllt.
    Notes: Summary Clinical and morphological findings are presented in a patient with acute hyperparathyroidism in primary water-clear cell hyperplasia and compared with each other. The long lasting clinical history, the symptoms of primary hyperparathyroidism of high activity, and the very sudden onset of a crisis with a lethal outcome were thought to be remarkable. Discussion of the symptoms and differential diagnosis of this rarely occuring but fatal complication is followed by a review of the pertinent literature. Electron microscopy shows the water-clear cells to exhibit transitional forms between chief cells and typical completely vacuolated cells besides oxyphils with vacuoles. The more chief cell like form is considered to display the really parathormone producing cell. An only very small amount of secretory granules is in consequence to the sudden exocytosis in hyperparathyroid crisis. The vacuoles contain crystal lattice structures, amorphous material and lipids. The primary water-clear cell hyperplasia could be a special form of the primary chief cell hyperplasia with a certain defect in the Golgi apparatus leading to a continuous filling of the cytoplasma of chief cells and oxyphil cells by vacuolated secretory products.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 39 (1979), S. 177-190 
    ISSN: 1432-0584
    Keywords: Chronische myelo-monozytäre Leukämie ; Seeblaue Histiozyten ; Knochenmarksbiopsie ; Elektronenmikroskopie ; Chronic myelomonocytic leukemia ; Sea-blue histiocytes ; Bone marrow biopsy ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Clinical data and light and electron microscopic findings are presented in a patient with chronic myelomonocytic leukemia of about 5 years' duration and no need for specific therapy. Cytogenetic studies failed to demonstrate a Philadelphia-chromosome. The leading clinical symptoms were anemia, moderate hepatomegaly, and leukocytosis with monocytes in the peripheral blood count. Light microscopy of bone marrow cores showed hypercellularity of neutrophil granulocytic and monocytic cell lines including some precursor forms. Electron microscopy confirmed the existence of a biphasic myelomonocytic cell proliferation with predominance of mature forms in both lineages; there were no gross cellular abnormalities and no “hiatus leukaemicus”. Conspicuous were cells of an undeterminated origin apparently neither belonging to the neutrophil granulocytic nor monocytic series and large histiocytic cells, possibly corresponding to the so-called sea-blue histiocytes of light microscopy. The high degree of maturation of both cell lines in the bone marrow is in accordance with the relatively benign and prolongated course of this rare type of leukemia.
    Notes: Zusammenfassung Von einem Patienten mit einer chronischen myelo-monozytären Leukämie von etwa 5 Jahren Dauer und ohne spezifische Therapie werden klinische sowie licht- und elektronenmikroskopische Befunde vorgestellt. Zytogenetische Untersuchungen ließen ein Philadelphia-Chromosom nicht erkennen. Die führenden Symptome waren eine geringe Anämie, eine mäßige Lebervergrößerung und Leukozytose mit Monozyten im peripheren Blutausstrich. Lichtmikroskopische Untersuchungen des Knochenmarkes zeigten eine Zellvermehrung der neutrophilen granulozytären und der monozytären Zellreihen einschließlich einiger Frühformen. Die Elektronenmikroskopie bestätigte das Vorhandensein einer biphasischen myelo-monozytären Zellproliferation mit Vorwiegen der reifen Formen in beiden Zellinien. Es bestanden keine bemerkenswerten zellulären Anomalien und kein „hiatus leucaemicus“. Auffallend waren Zellen unbestimmbarer Herkunft, die weder der neutrophilgranulozytären oder monozytären Reihe sicher zuzuordnen waren, und große histiozytäre Zellen, die wahrscheinlich den sogenannten „seeblauen Histiozyten“ der Lichtmikroskopie entsprechen. Der hohe Grad der Ausreifung in beiden Zellinien im Knochenmark steht in Übereinstimmung mit dem relativ gutartigen und langen Verlauf dieses seltenen Types einer Leukämie.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 38 (1979), S. 407-420 
    ISSN: 1432-0584
    Keywords: Polycythämia vera ; Ultrastruktur des Knochenmarkes ; Kernspalten ; Mikromegakaryozyten ; myeloproliferative Erkrankungen ; Polycythemia vera ; Bone marrow ultrastructure ; Nuclear clefts ; Micromegakaryocytes ; Myeloproliferative disorders
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Electron microscopy (thin sections and freeze-fracture replicas) was performed on the bone marrow of ten patients with Polycythemia vera prior to any treatment. In addition to a hyperplasia of all three cell lineages and the sinuses, atypias were observed in the maturing erythroblasts. These aberrations of normal development consisted mainly of deep invaginations of the nuclear envelope in proerythroblasts and conspicuous nuclear clefts in erythro- and normoblasts. In comparison with similar changes in dyserythropoietic and aplastic anemia as well as leukemia these alterations are discussed in connection with disturbances of DNA synthesis. Further atypias involved megakaryopoiesis which displayed microforms probably as an evidence for maturation arrest. These ultrastructural abnormalities with their morphological features of a neoplastic proliferation of all three cell lineages in Polycythemia vera are in good agreement with the new concept of a transformation of a pluripotent stem cell with clonal character.
    Notes: Zusammenfassung Elektronenmikroskopische Untersuchungen (Dünnschnitte und Gefrierbrechungen) wurden am Knochenmark von zehn Patienten mit Polycythämia vera vor der Behandlung durchgeführt. Au\er der Hyperplasie aller drei Zellreihen und der Sinus wurden vor allem Atypien der reifenden Erythroblasten gesehen. Diese Abweichungen der normalen Entwicklung bestanden hauptsächlich aus tiefen Einstülpungen der Kernhülle im Proerythroblasten und in auffallenden Kernspalten in Erythro- und Normoblasten. Im Vergleich zu ähnlichen Veränderungen bei dyserythropoetischen und aplastischen Anämien ebenso wie bei Leukämien werden diese Anomalien im Zusammenhang mit Störungen der DNA-Synthese diskutiert. Weitere Atypien betrafen die granulocytäre Reihe mit abnormen Kernschleifen und die Megakaryopoese, die Mikroformen aufwies, was wohl als ein Ausdruck der Reifungshemmung zu werten ist. Diese ultrastrukturellen Anomalien mit ihren morphologischen Kriterien der neoplastischen Proliferation aller drei Zellreihen bei der Polycythämia vera passen gut in das neue Konzept der Transformation einer pluripotenten Stammzelle mit klonalem Charakter.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1432-0584
    Keywords: Key words Apoptosis ; PCNA-labeling ; Idiopathic thrombocytopenia ; Polyglobuly ; Reactive thrombocytosis ; Primary thrombocythemia ; Polycythemia vera ; AML ; Hematopoietic turnover index ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In order to determine the dynamics of hematopoietic cell turnover, proliferative activity and incidence of apoptosis (programmed cell death) were evaluated in bone marrow trephine biopsies. Selection of patients (20 in each group) included in addition to a control group, idiopathic thrombocytopenia (ITP), reactive thrombocytosis (TH), secondary polycythemia-smokers' polyglobuly (PG), primary (essential-hemorrhagic) thrombocythemia (PTH), polycythemia vera (PV), and finally acute myeloid leukemia (AML). Apoptosis was demonstrated by the in situ end-labeling technique (ISEL) and proliferative activity by applying the monoclonal antibody PC10 raised against proliferating cell nuclear antigen (PCNA). To assess dynamic features of hematopoiesis, an index was calculated consisting of the ratio between PCNA-positive nuclei and the apoptotic cell fraction. This factor was termed the hematopoietic turnover index (HTI). Morphometric analysis revealed that the HTI was significantly increased in AML and PV. According to cell culture studies both disorders are characterized by either a prevalent proliferation of the myeloid or erythroid cell mass. On the other hand, PG, PTH, and TH showed no relevant enhancement of this index in comparison to the control specimen. In vitro experiment results are in keeping with the finding that PG and PTH are not associated with a significant expansion of the erythroid lineage (CFU-E). Similar to ITP and TH, in PTH megakaryocyte proliferation (CFU-MEG) is the predominant feature of cell turnover. Differences between PTH and TH are in line with the reduced in vitro formation of CFU-MEG in the latter disorder. In conclusion, our in situ study on turnover rates of the bone marrow in various neoplastic and reactive lesions extends previous experimental data on hematopoietic cell kinetics.
    Type of Medium: Electronic Resource
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