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  • 1
    ISSN: 1432-2307
    Keywords: Myelodysplastic syndrome ; Myelofibrosis ; Cytogenetics ; Histopathology ; Bone marrow biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Chromosome analyses of bone marrow and peripheral blood cells were performed in a total of 51 patients with myelodysplastic syndromes (MDS) simultaneously with histopathological examination of resinembedded bone marrow biopsies. Diagnosis of MDS was established by histopathology according to the French-American-British (FAB) classification, and reassessed by haematological data and clinical course. Clonal karyotypic changes were found in 30 of the 51 patients (59%): in 15 of 19 (79%) patients with refractory anaemia, 7 of 11 (64%) with refractory anaemia and excess of blasts (RAEB), 6 of 10 (60%) with RAEB in transformation, and 2 of 11 (18%) with chronic myelomonocytic leukaemia. The following three features of the histopathology revealed positive correlations with karyotype abnormalities: all cases of myelofibrosis in MDS (7/51) were accompanied by chromosome aberrations, microforms of megakaryocytes with reduced nuclear lobulation were observed in 18 of 30 cases with karyotype changes, and hypocellularity of haematopoiesis was associated with aberrations of chromosome 7 in 2 of 4 cases. No positive correlations were revealed between abnormal karyotypes and the transformation to acute leukaemia. The survival times were significantly decreased in patients with complex (3 and more) karyotype changes, when compared with patients with single (1–2) chromosome aberrations or normal karyotype, independently of the FAB classification.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-2307
    Keywords: Megakaryocytes ; Chronic myeloproliferative disorders ; Morphometry ; Histology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A morphometric evaluation of number and grouping of megakaryocytes (MK) in five different groups of chronic myeloproliferative disorders (CMPD) was performed by counting 60 high power fields equaling approximately 14.28 mm2 of haematopoiesis in each case. Twenty-one up to 29 cases were evaluated for each of five categories of CMPD and one control group; a total of 132 cases of CMPD and 33 control cases were used. The mean number of MK per square millimetre was 15.54±1.53 in chronic myeloid leukaemia of common or granulocytic type (CML.CT), 69.91±5.85 in CML with megakaryocytic increase (CML.MI), 59.59 ±3.27 in polycythaemia vera (P. vera), 59.85±4.59 in primary thrombocythaemia (PTH), 67.58±4.11 in chronic megakaryocytic granulocytic myelosis (CMGM), and 19.7±3.07 in controls. The distinction between free or isolated MK, and between clustered or grouped MK corresponds to the total cell counts of MK in the various groups of CMPD. Clustering of MK was significantly higher in CMGM and PTH compared to other groups, but the difference between them was not statistically significant. Significant differences in the mean number of MK were obtained between controls and CML.CT on the one hand and all other groups of CMPD on the other. The results further support the histological sub-classification of CMPD according to the primary disorders of the Hannover classification (not advanced by sclerosis, fibrosis or excess of blasts, respectively).
    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.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 287-305 
    ISSN: 1432-2307
    Keywords: Myeloproliferative disease ; Osteomyelofibrosis ; Bone marrow biopsy ; Blast crisis ; Ultrastructure ; Basophilic leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The clinical and morphological findings are presented in two patients suffering from myelofibrosis and osteomyelosclerosis which terminated in an acute blastic crisis. Clinical follow-up data and light microscopy of the bone marrow however, revealed a chronic megakaryocytic-granulocytic myelosis (CMGM) with progression into myelofibrosis during the course of disease. In one patient the blastic transformation involved predominantly basophils, and in the other, neutrophils, with an accompanying abnormal proliferation of megakaryocytes in both cases. Electron microscopy of this cell population demonstrated remarkable atypicalities of the neutrophilic, basophilic and megakaryocytic cell lines. These abnormalities consisted of a nuclear-cytoplasmic asynchrony and a partial arrest of maturation, sometimes resulting in bizarre cell forms. Our investigations support the hypothesis of a mixed cellularity type of myelosis with a gradual and insiduous progression into osteomyelofibrosis/-sclerosis and a potential blastic crisis. In the evolution of blastic crisis all cell lines may be transformed, but with predominance of one population — basophils and neutrophils in our two cases — in addition to atypicalities of megakaryocytes.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 389 (1980), S. 269-286 
    ISSN: 1432-2307
    Keywords: Myelofibrosis ; Osteomyelosclerosis ; Histopathology ; Cytogenetics ; Bone marrow biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A combined histological and cytogenetic study was performed on the bone marrow in 33 patients with overt osteomyelofibrosis/-sclerosis (MF/OMS) and so called agnogenic myeloid metaplasia including blast crisis. Histopathology of the plastic embedded samples of bone marrow showed an abnormal proliferation of megakaryopoiesis with conspicuous atypias of growth and maturation in addition to a neoplastic neutrophilic granulopoiesis, particularly in the early stages of MF. Thus a biphasic population of neoplastic hematopoiesis is postulated and this lesion is called chronic megakaryocytic-granulocytic myelosis (CMGM) with myelofibrosis — CMGM stage III — or with osteomyelosclerosis — CMGM stage IV. Initiation of fibrillogenesis, the most striking alteration of this disorder, is partially attributed to disorganization of megakaryopoiesis with abnormal proliferation and clustering around the sinuses and intraluminal growth, with subsequent obliteration of the vascular compartment. Cytogenetic evaluation demonstrated the Philadelphia chromosome (Ph'-chromosome) in 93% of CGL and in 67% of MF/OMS, including cases with blast crisis. Unlike CGL and MF/OMS where a Ph'-chromosome is common, myelofibrosis of non-neoplastic origin and AML displayed no Ph'-chromosome. Further aberrations such as aneuploidy involved the C/D group chromosomes predominantly and were especially prominent in blast crisis (about 50%) with no significant differences in CGL and MF/OMS or in AML. Our results of chromosomal analysis, evaluated in close context with histopathology, show no fundamental differences between CGL and myeloproliferative disorders of mixed cellularity, i.e., chronic megakaryocytic-granulocytic myelosis (CMGM). For this reason the terminal stages of fibrotic and osteosclerotic lesions belong into these categories of CMGM or CGL respectively. In conclusion MF/OMS are final stages or subtypes of CML, carrying the same chromosomal marker and demonstrating remarkable atypias of the hematopoietic tissue suggestive of malignancy. The fibrotic/ osteosclerotic alteration itself is thought to represent a secondary nonneoplastic feature.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 373 (1977), S. 191-211 
    ISSN: 1432-2307
    Keywords: Myeloproliferative disorder ; Thrombocytes ; Megakaryocytic-granulocytic myelosis ; Bone marrow biopsy ; Megakaryocyte lineage ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary The fine structure of the bone marrow in chronic megakaryocytic-granulocytic myelosis (CMGM) was studied in 5 nontreated patients to investigate possible malignant proliferation of megakaryocytes and the role of megakaryopoiesis in fibrillogenesis, terminating in osteomyelofibrosis. In comparison with normal megakaryopoiesis there is an enormous increase of the megakaryocytic cell line and many immature and atypical forms are seen. Most conspicuous are microforms, nuclear-cytoplasmic disorganization and nuclear inclusions. Asynchrony of maturation causes abnormal thrombocytogenesis with premature detachment of platelets resulting in immature and peculiar giant forms of thrombocytes. Besides megakaryocytes appearing superficially normal the maturation anarchy of many cells is so severe that by analogy with observations in other leukaemic cells these abnormalities are thought to be representative of a malignant growth. Moreover, there is a striking accumulation of microfibrils and single collagen fibres around megakaryoblasts. Since these cells contain all those organelles commonly associated with fibre production the initial step for fibrillogenesis may therefore arise from the megakaryoblasts prior to platelet release, or any fibroblast proliferation.
    Type of Medium: Electronic Resource
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  • 7
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 420 (1992), S. 473-478 
    ISSN: 1432-2307
    Keywords: Histopathology ; Bone marrow ; Megakaryocytes ; Myeloid leukaemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary A histological study on sequential bone marrow biopsies in patients with chronic myeloid leukaemia (CML) was performed. We wished to answer the question as to whether a different content of megakaryopoiesis in the bone marrow of CML patients has a prognostic significance for the development of myelofibrosis during the course of disease. In addition, the significance of possible changes in the quantity of megakaryopoiesis in this process was assessed. In 186 patients who had no fibre increase at first diagnosis, the rate of subsequent myelofibrosis varied from 19% for the common or granulocytic subtype (CML.CT) to 40% for patients with features of megakaryocytic increase (CML.MI). No significant differences were found either in the rapidity of progression to fibrosis or in the final rate of osteomyelosclerosis. Whereas in CML.MI most patients (75%) showed an increase of fibres only, this was accompanied by an additional increase of megakaryocytes in CML.CT, changing the histological pattern from CML.CT to MI or MP, respectively. The data therefore revealed a correlation between fibre increase and subtyping of CML as suggested by the Hannover classification of chronic myeloproliferative diseases. Subtypes of CML with megakaryocytic increase could be shown to present a “pre-myelofibrotic” stage of disease and may therefore be conceived as a particular pathway of acceleration.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Annals of hematology 70 (1995), S. 301-308 
    ISSN: 1432-0584
    Keywords: Key words Myelodysplastic syndromes (MDS) ; Prognosis ; Histopathology ; Scoring system ; Bone marrow biopsy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  To compare the prognostic value of scoring systems in primary myelodysplastic syndromes (pMDS), four clinicohematological systems (Rennes, Bournemouth, Düsseldorf, Pavia) and the histopathological Hannover Scoring System were applied to 415 MDS patients from the Bone Marrow Registry of Hannover Medical School. According to the FAB classification, 180 patients (43%) were diagnosed as RA, 33 (8%) as RARS, 99 (24%) as RAEB, 36 (9%) as RAEBt, and 48 (12%) as CMMOL; 19 patients (4%) were not further classified (MDS.UC). All scoring systems revealed three or four groups of patients with significantly different survival times. The ranges and standard deviations in these groups were similar but high in all scoring systems. A good differentiation between short-term survivors (〈1 year survival time) and intermediate-term survivors (1–4 years) was possible with all tested scoring systems, but the differentiation between intermediate- and long-term survivors (〉4 years) was not distinctive enough. The problem of risk assessment in the single patient is furthermore elucidated by the values of specificity and sensitivity, which were relatively low in all scoring systems tested. Best results were yielded by the Bournemouth Score for long-term survivors and the Düsseldorf and Hannover Score for intermediate- and short-term survivors. Multivariate analysis of all parameters used in the scoring systems showed the highest negative impact on survival for increase of myeloblasts, anemia, myelofibrosis, high age of the patient, and abnormal localization of immature precursors (ALIPs). Therefore, the histopathological Hannover Scoring System is not only equal to clinicohematological risk assessment in pMDS, but also includes important independent prognostic parameters. Risk assessment for the individual low-risk MDS patient using only initial parameters may be rendered impossible due to the biological nature of pMDS. Therefore, sequential analysis is needed to elucidate random events which alter the prognosis.
    Type of Medium: Electronic Resource
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  • 9
    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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  • 10
    ISSN: 1432-0584
    Keywords: Myeloproliferative disorders ; Megakaryopoiesis ; Histopathology ; Bone marrow
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Histologic diagnoses from bone marrow biopsies were analyzed in a total of 1165 patients presenting with thrombocythemic platelet counts at initial examination. Two cut-off points suggested by the Polycythemia Vera Study Group to define thrombocythemia by platelet counts were compared: the former limiting value of 1000×109/l platelets versus the recently proposed value of 600×109/l. The percentage of all nonproliferative disorders was 41% under the lower, dropping to 11% under the high cut-off point. The respective figures for myeloproliferative disorders increased from 49% under the lower to 74% under the high limiting value. Primary thrombocythemia was included in 72% by the lower, and in only 40% by the high limiting value when classified by its histologic pattern in bone marrow biopsy. A striking decrease of platelet counts occurs, related to fiber increase, among each of three main groups of myeloproliferative disorders: in CML with megakaryocytic predominance from 40% down to 25%, in megakaryocytic-granulocytic myelosis (primary, i.e., agnogenic myelofibrosis) from 36.6% to 10%, and in primary thrombocythemia from 72.6% to 28.6% in cases with reticulin sclerosis.
    Type of Medium: Electronic Resource
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