Atypical micromegakaryocytes, promegakaryoblasts and megakaryoblasts: a critical evaluation by immunohistochemistry, cytochemistry and morphometry of bone marrow trephines in chronic myeloid leukemia and myelodysplastic syndromes

Thiele, Jürgen; Titius, B. R.; Kopsidis, Christoph; Fischer, R.

doi:10.1007/bf02899693

Cited by 19 publications

(11 citation statements)

References 22 publications

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“…Morphometry of CD61+ megakaryopoiesis in the control group of 14 patients following monotherapy with STI571 and classification into different subgroups in accordance with previous studies36 …”

supporting

confidence: 86%

“…Regression of the fibre content in the majority, but not all patients, 19,22 accompanied by a normalization of megakaryopoiesis could be related to a direct anti-PDGF receptor effect of this agent. 41 According to our findings derived from morphometry after CD61 immunostaining, there is a significant decline in the quantity of atypical small micromegakaryocytes (size £ 150 lm) characteristic of CML 36,46,47 and the return of a large, normally appearing cell fraction. It should be emphasized that, according to morphometry, not only size and shape (form factor) of megakaryocytes and their nuclei returned to normal features, but the nuclear-cytoplasmic ratio did so also.…”

Section: Discussionmentioning

confidence: 86%

“…Morphometric analysis of CD61 megakaryopoiesis was carried out in a selected cohort of 14 patients with STI571 as monotherapy. We performed planimetric measurements of megakaryocytes and evaluations of proliferation and apoptosis in the total series by two planimeters (MOP‐A‐MO1‐Kontron and VIDAS‐Zeiss‐Kontron) with a standard programme set 36 on large (18.4 × 3.9 mm 2 ) trephine biopsies with an artefact‐free BM area of 8.2 ± 2.7 mm 2 .…”

Section: Bone Marrow Biopsiesmentioning

confidence: 99%

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Bone marrow changes in chronic myelogenous leukaemia after long‐term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients

Thiele¹,

Kvasnicka²,

Schmitt‐Graeff³

et al. 2005

Histopathology

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supporting

confidence: 86%

Section: Discussionmentioning

confidence: 86%

Section: Bone Marrow Biopsiesmentioning

confidence: 99%

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Bone marrow changes in chronic myelogenous leukaemia after long‐term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients

Thiele¹,

Kvasnicka²,

Schmitt‐Graeff³

et al. 2005

Histopathology

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“…lA), PAS-reactivity was restricted to the more mature, glycogen-containing forms. According to a previously conducted study [39], this difference in staining reactivity reflected the number of very small immature and atypical precursors (pro-and megakaryoblasts). Islets of erythro-and normoblasts were small and dispersed and included relatively few erythroid elements (Fig.…”

Section: Clinical and Histomorphometrical Findingsmentioning

confidence: 88%

Clinical and histological features retain their prognostic impact under interferon therapy of CML: A pilot study

Thiele¹,

Kvasnicka²,

Niederle³

et al. 1995

American J Hematol

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In 55 patients with Ph1+ CML under interferon (IFN) monotherapy, an immunohistochemical and morphometric study on pretreatment bone marrow biopsies was performed to evaluate the prognostic impact of clinical as well as histological disease features. For identification of megakaryocytes we used the PAS stain and CD61 to calculate the subfraction of precursors (pro- and megakaryoblasts). Demonstration of macrophages and their different subsets was carried out by PG-M1 (CD68) and the GSA-1 lectin. The erythroid precursors were stained by Ret40f (anti-glycophorin C). Density of argyrophilic (reticulin plus collagen) fibers was determined by applying Gomori's silver impregnation method. Clinical variables like state of hematological response to IFN administration, age, spleen and liver size, myeloblasts plus promyelocytes, basophils as well as basophils and eosinophils exerted a predictive capacity by univariate statistical analysis. However, when entering these factors into previously published risk models, i.e., the so-called Sokal score and its modifications, to assess subgroups with different survival patterns or relative risk groups, a clear-cut discrimination was not feasible. Bone marrow features of prognostic value consisted of megakaryocytes and their precursors, fibers, and pro- and erythroblasts. Only when including histological variables into a formerly reported Cox model, could a significant separation of patients into the different categories or relative risk groups be computated. In conclusion, the present data emphasize the prognostic impact of histological parameters to be considered in all clinical trials on CML.

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“…In these cases it is absolutely mandatory to restrict the diagnosis of a MDS/CMPD to initial blood and BM examinations at first presentation and any therapy should be explicitly excluded [29,66] . Furthermore, it is important that in BM specimens maturation defects should be recognized in at least two lineages [82] , especially erythropoiesis and megakaryocytes (atypical micromegakaryocytes, abnormal nuclear lobulation, compact nuclei) [83] . Finally, although in the past decade many groups were engaged in the study of risk stratification and prognosis of CIMF patients, a comparison of these data reveals an extreme heterogeneity [84,85] .…”

Section: Chronic Idiopathic Myelofibrosismentioning

confidence: 99%

Classification of Ph-Negative Chronic Myeloproliferative Disorders – Morphology as the Yardstick of Classification

Kvasnicka

Thiele

2007

Pathobiology

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Objective: Histopathology of bone marrow (BM) biopsies plays a crucial role in the interdisciplinary approach to diagnosis and classification of Ph-negative chronic myeloproliferative disorders. Based on careful clinicopathologic studies, BM features are critical determinants that help to predict overall prognosis, to detect complications such as progression to myelofibrosis and blast crisis, and to assess therapy-related changes. Methods and Results: A systematic evaluation of BM histopathology allows an objective identification of cases of (true) essential thrombocythemia and their separation from early prefibrotic stages of chronic idiopathic myelofibrosis. By follow-up examinations that include BM biopsies, the progression of the disease process is unveiled, which is especially important for patients with initial polycythemia vera and prefibrotic chronic idiopathic myelofibrosis that may require a different therapeutic approach than the full-blown stages. Conclusion: BM biopsy should be considered as major diagnostic tool for evaluation and follow-up of patients enrolled in prospective studies.

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Atypical micromegakaryocytes, promegakaryoblasts and megakaryoblasts: a critical evaluation by immunohistochemistry, cytochemistry and morphometry of bone marrow trephines in chronic myeloid leukemia and myelodysplastic syndromes

Cited by 19 publications

References 22 publications

Bone marrow changes in chronic myelogenous leukaemia after long‐term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients

Bone marrow changes in chronic myelogenous leukaemia after long‐term treatment with the tyrosine kinase inhibitor STI571: an immunohistochemical study on 75 patients

Clinical and histological features retain their prognostic impact under interferon therapy of CML: A pilot study

Classification of Ph-Negative Chronic Myeloproliferative Disorders – Morphology as the Yardstick of Classification

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