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  • 1
    Electronic Resource
    Electronic Resource
    Chromosome analyses in patients with myelodysplastic syndromes: Correlation with bone marrow histopathology and prognostic significance (1992)
    Springer
    Virchows Archiv 421 (1992), S. 47-52 
    Details
    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
    URL: http://dx.doi.org/10.1007/BF01607138
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  • 2
    Electronic Resource
    Electronic Resource
    Trisomy 1 and 8 occur frequently in hepatocellular carcinoma but not in liver cell adenoma and focal nodular hyperplasia. A fluorescence in situ hybridization study (1995)
    Springer
    Virchows Archiv 427 (1995), S. 373-378 
    Details
    ISSN: 1432-2307
    Keywords: Hepatocellular carcinoma ; Cholangiocellular carcinoma ; Cytogenetics ; Chromosome 1 ; Fluorescence in situ hybridization (FISH)
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Conventional cytogenetic studies revealed gains and structural aberrations of chromosome 1 to be the most consistent chromosomal aberrations in hepatocellular carcinoma (HCC). We investigated touch preparations of eight HCC, five cholangiocellular carcinomas (CCC), five liver cell adenomas (LCA), four focal nodular hyperplasias (FNH) as well as nine specimens of normal liver tissue using fluorescence in situ hybridization (FISH) with centromere specific probes for chromosomes 1 and 8. Polysomies of chromosome 1, especially trisomy 1, were found in five of eight HCC and four of five CCC but in no normal liver tissue or benign tumour. Only three of seven cases of HCC revealed trisomy 8 whereas the five benign liver tumours and all normal liver tissues examined had disomy 8. Our results confirm conventional cytogenetic findings in terms of chromosome 1 aberrations in HCC although they are not specific for these types of malignant liver tumours. Since α-satellite probes were used in our study, only gains or losses including the centromeric regions of the chromosomes 1 and 8 could be detected. Nevertheless, our findings suggest that FISH may help in the differential diagnosis of malignant versus benign neoplasms of the liver.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF00199385
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  • 3
    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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  • 4
    Electronic Resource
    Electronic Resource
    Zytogenetik als Ergänzung zur Histopathologie am Beispiel des myelodysplastischen Syndroms (1994)
    Springer
    Der Pathologe 15 (1994), S. 286-291 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Myelodysplastisches Syndrom ; Knochenmark ; Zytogenetik ; Histopathologie ; Prognose ; Key words Myelodysplastic syndrome ; Bone marrow ; Cytogenetics ; Histopathology ; Prognosis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The value of cytogenetics performed simultaneously with histopathology was evaluated in patients with myelodysplastic syndrome (MDS). Clonal karyotype changes of the bone marrow cells supporting the histological diagnosis were found in 38/69 cases (55 %). The chromosome aberrations, especially complex changes, were significantly correlated to distinct histopathological findings such as atypias of the haematopoietic cell lines and myelosclerosis. Complex karyotype changes were further associated with short survival of the MDS patients. Our results demonstrate that cytogenetic analyses are helpful in supplementing the histopathological diagnoses. Recent developments in molecular cytogenetics even allow the detection of chromosomal aberrations in non-dividing cells from cytological preparations or tissue sections which may become available for routine diagnosis.
    Notes: Zusammenfassung Die Bedeutung simultaner zytogenetischer und histologischer Untersuchungen wurde bei Patienten mit myelodysplastischem Syndrom (MDS) überprüft. Die Ergebnisse zeigen, daß klonale Karyotypveränderungen der Knochenmarkzellen bei 38 der 69 (55 %) analysierten Patienten auftraten und damit häufig eine Absicherung der histologischen Diagnose erlaubten. Die Chromosomenanomalien, insbesondere komplexe Karyotypveränderungen, korrelierten signifikant mit einer Reihe histopathologischer Befunde, darunter Atypien der einzelnen hämatologischen Zellreihen und Myelosklerose. Durch den Nachweis komplexer Karyotypveränderungen war eine unabhängige prognostische Aussage möglich. Damit zeigen unsere Ergebnisse am Beispiel des MDS, daß zytogenetische Analysen eine sinnvolle Ergänzung der histologischen Untersuchung sein können. Darüber hinaus ist durch den Einsatz der molekularen Zytogenetik die Bestimmung von Chromosomenanomalien in zytologischen Ausstrichpräparaten oder Gewebeschnitten möglich, wodurch sich solche Befunde auch für die tägliche Diagnostik verwenden lassen.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050056
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  • 5
    Electronic Resource
    Electronic Resource
    Zytogenetik und molekulare Untersuchungen sichern die histopathologischen Diagnosen von chronischen myelopro-liferativen Erkrankungen ab (1995)
    Springer
    Der Pathologe 16 (1995), S. 41-45 
    Details
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Chronische myeloproliferative Erkrankungen ; Philadelphia-Translokation ; Zytogenetik ; Molekulargenetik ; Fluoreszenz-in-situ-Hybridisierung ; Histopathologie ; Key words Chronic myeloproliferative disorders ; Philadelphia-translocation ; Cytogenetics ; Molecular genetics ; Fluorescence in situ hybridization ; Histopathology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary The histopathological classification of chronic myeloproliferative disorders can be supported by applying cytogenetics and molecular genetics to the analysis of bone marrow or blood cells, as demonstrated in 253 cases evaluated. The Philadelphia translocation (9;22) is the most important genetic parameter, being specific for chronic myeloid leukemia. Conventional methods for the detection of the t(9;22) are karyotyping and Southern blot analysis of the bcr gene. The newly established technique of fluorescence in situ hybridization (FISH) allows visualization of bcr-abl fusion even in non dividing cells. Molecular cytogenetics for t(9;22) yield results that are rapid and reliable as well as easily quantifiable.
    Notes: Zusammenfassung Zytogenetische und molekulargenetische Untersuchungen von Knochenmark- oder Blutzellen sind für die histopathologische Klassifikation der chronischen myeloproliferativen Erkrankungen hilfreich, was durch die simultane Auswertung von 253 Fällen gezeigt wird. Insbesondere die Analyse der Philadelphia-Translokation (9;22) ist dabei für die Bestätigung oder den Ausschluß einer chronischen myeloischen Leukämie wichtig. Für den Nachweis der t(9;22) stehen die konventionelle Karyotypisierung mit Bestimmung des Philadelphia-Chromosoms und das Southernblotverfahren zur Analyse einer Umlagerung des bcr-Gens zur Verfügung. Durch die neuere Methode der Fluoreszenz-in-situ-Hybridisierung (FISH) kann auch eine bcr-abl-Fusion an Interphasekernen dargestellt werden. Diese molekulare Zytogenetik ist ein rasches und zuverlässiges Verfahren zum Nachweis der Philadelphia-Translokation, das zudem leicht quantifizierbare Ergebnisse liefert.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002920050074
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  • 6
    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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  • 7
    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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