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  • 1
    Electronic Resource
    Electronic Resource
    Polycythemia vera (1980)
    Springer
    Virchows Archiv 389 (1980), S. 307-324 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00430657
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  • 2
    Electronic Resource
    Electronic Resource
    Polycythemia vera (1980)
    Springer
    Virchows Archiv 389 (1980), S. 325-341 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00430658
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  • 3
    Electronic Resource
    Electronic Resource
    Polycythemia vera: Electron microscopy of the bone marrow in 10 non-treated patients (1979)
    Springer
    Annals of hematology 38 (1979), S. 407-420 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01007902
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  • 4
    Electronic Resource
    Electronic Resource
    Hematopoietic turnover index in reactive and neoplastic bone marrow lesions: quantification by apoptosis and PCNA labeling (1997)
    Springer
    Annals of hematology 75 (1997), S. 33-39 
    Details
    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
    URL: http://dx.doi.org/10.1007/s002770050309
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