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  • 1
    Electronic Resource
    Electronic Resource
    Macrophages and their subpopulations following allogeneic bone marrow transplantation for chronic myeloid leukaemia (2000)
    Springer
    Virchows Archiv 437 (2000), S. 160-166 
    Details
    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
    URL: http://dx.doi.org/10.1007/s004280000224
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  • 2
    Electronic Resource
    Electronic Resource
    Hairy cell leukemia (1976)
    Springer
    Virchows Archiv 370 (1976), S. 273-289 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00445773
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  • 3
    Electronic Resource
    Electronic Resource
    Ultrastructure of blastic crisis in osteomyelofibrosis (1980)
    Springer
    Virchows Archiv 389 (1980), S. 287-305 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00430656
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  • 4
    Electronic Resource
    Electronic Resource
    Osteomyelofibrosis/-sclerosis: A histological and cytogenetic study on core biopsies of the bone marrow (1980)
    Springer
    Virchows Archiv 389 (1980), S. 269-286 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00430655
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  • 5
    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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  • 6
    Electronic Resource
    Electronic Resource
    Myeloid dysplasia (MD): a hematological disorder preceding acute and chronic myeloid leukemia (1980)
    Springer
    Virchows Archiv 389 (1980), S. 343-367 
    Details
    ISSN: 1432-2307
    Keywords: Preleukemia ; Myeloid dysplasia ; Bone marrow biopsy ; Chronic myeloid leukemia ; Acute non-lymphocytic leukemia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary Light- and electron microscopic appearances of core biopsies of the bone marrow in 27 selected patients out of about 195 cases with a clinically suspected preleukemic syndrome. The correct diagnosis of “ preleukemia” was established retrospectively by sequential biopsies of the iliac crest or autopsy in those patients who developed overt leukemia in periods ranging from 2 to 36 months. As a final diagnosis chronic myelogenous leukemia (CML) was established in 10, with accompanying blast crisis in 6 and acute non-lymphocytic leukemia (ANLL) in 11 cases. Histomorphology of the resin embedded cores of bone marrow showed hypercellularity in 21 specimens, a hypocellular marrow in 5 and a normal bone marrow in 1 case. There was also a conspicuous macrocytic or megaloblastoid maturation of erythropoiesis with frequent sideroblasts. Ultrastructural abnormalities included atypical nuclear clefts, dense iron deposits in the mitochondrial matrix and an increase of ferritin uptake. Neutrophilic granulopoiesis showed a shift to the left and often a remarkable aberration of nuclear segmentation consistent with a pseudo-Pelger-Huët anomaly. Electron microscopy displayed atypias of granulogenesis in comparison with maturation and segmentation of the nuclei, abnormal nuclear loops and blebs and very conspicuous nuclear fibrillar appendages (so called Nebenkerne). There was also an increase in eosinophilic granulocytes, monocytic elements, edema and a remarkable perivascular plasmacytosis of the myeloid stroma. Our results suggest that characteristic morphological features of the bone marrow exist before onset of overt, acute and chronic leukemia. These alterations are identical in CML and ANLL and are the morphological substrate of a maturation defect of hematopoiesis which precedes the establishment of the leukemic clone. The clinical term preleukemia should be replaced by myeloid dysplasia (MD), thus indicating transformation into overt leukemia in only a certain proportion of patients (only 27 of 195 clinically suspected patients who displayed an identical histopathology of MD in the bone marrow in 93 cases to date) and has to include ANLL as well as CML.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00430659
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  • 7
    Electronic Resource
    Electronic Resource
    Chronic megakaryocytic-granulocytic myelosis — An electron microscopic study (1977)
    Springer
    Virchows Archiv 373 (1977), S. 191-211 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF00432237
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  • 8
    Electronic Resource
    Electronic Resource
    Chronic megakaryocytic-granulocytic myelosis — An electron microscopic study including freeze-fracture (1977)
    Springer
    Virchows Archiv 375 (1977), S. 129-146 
    Details
    ISSN: 1432-2307
    Keywords: Myeloproliferative disorder ; Megakaryocytic-granulocytic myelosis ; Granulocyte lineage ; Bone marrow biopsy ; Freeze-fracture ; Electron microscopy
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 5 patients with chronic megakaryocytic-granulocytic myelosis (CMGM) bone marrow specimens were studied by electron microscopy to investigate possible abnormalities of the granulocytic cell lineage. Thin sections were compared with freeze-fracture replicas to elucidate further aspects of leucocyte cytology. The atypia exhibited in these cells (eosinophils, basophils and neutrophil granulocytes) consisted mostly of a disorganization of granulopoiesis with hyper- and hypogranulation, a pathological increase in the number of nuclear blebs and a maturation asynchrony sometimes leading to Pelger-like cell forms. Moreover, a presumptive stem cell was demonstrated in the erythopoietic and granulocytic cell lines resembling CFU cells. In conclusion, granulopoiesis in CMGM exhibited abnormalities as generally observed in chronic myelogenous leukaemia. When considered with our previous finding of malignancy in megakaryopoiesis, CMGM has to be classified as a myelosis of mixed cellularity.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00428101
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  • 9
    Electronic Resource
    Electronic Resource
    Histomorphometry of bone marrow biopsies in chronic myeloproliferative disorders with associated thrombocytosis - features of significance for the diagnosis of primary (essential) thrombocythaemia (1988)
    Springer
    Virchows Archiv 413 (1988), S. 407-417 
    Details
    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.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00716989
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  • 10
    Electronic Resource
    Electronic Resource
    Differentiation of plasma cell infiltrates in the bone marrow (1988)
    Springer
    Virchows Archiv 412 (1988), S. 553-562 
    Details
    ISSN: 1432-2307
    Keywords: Plasma cell infiltrates ; Bone marrow biopsies ; Malignant myeloma ; Reactive plasmacytosis ; Benign monoclonal gammopathy ; Immunohistochemistry ; Osteoclastic activity
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary In 80 patients immunohistochemical, morphometrical and clinical studies were performed on routinely referred trephine biopsies of the bone marrow showing an abnormal increase in plasma cells. From the approximately determined density of plasma cell infiltrates two main groups were distinguished, the first with an involvement exceeding 20% and the second with less than 10% of the total marrow area involved. The first group (n=30; 324±130 plasma cells per square millimeter bone marrow) consisted of patients with frank malignant myeloma (MM) by clinical and histomorphological diagnosis. The second group (n=50; 132±54 plasma cells per square millimeter bone marrow) with plasmacytic differentiation of infiltrates, had to be further divided into one component with evidence for initial or residual MM following chemotherapy (n=27), another with obviously monoclonal gammopathy of undetermined significance - benign monoclonal gammopathy (BMG,n=6), and a final set of cases with a reactive plasmacytosis mostly associated with an inflammatory condition (n=17). There was an excellent agreement between the intracellular immunoglobulin staining as defined by the immunoperoxidase technique and the serum or urinary M-component detected by immunoelectrophoresis. In MM significant correlations were found between osteoclastic activity (number of osteoclasts specifically stained by acid phosphatase) per trabecular bone area, presence of lytic bone defects and the density of plasma cell infiltrates in the marrow. This latter feature corresponded well with the titer of secreted serum M-components measured by quantitative immunoelectrophoresis. Using morphological data alone, BMG cases could not be discriminated with any certainty from initial or residual plasmacytic MM. They consequently need a prolonged clinical follow up to clarify the nature of the lesions.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00844291
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