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  • Title: Histopathology in the diagnosis and classification of acute myeloid leukemia, myelodysplastic syndromes, and myelodysplastic/myeloproliferative diseases.
    Author: Orazi A.
    Journal: Pathobiology; 2007; 74(2):97-114. PubMed ID: 17587881.
    Abstract:
    In spite of the impressive advances in the area of molecular pathology, bone marrow morphology remains the diagnosis cornerstone to identify the various subtypes of myeloid neoplasms. Morphological examination of the bone marrow requires both bone marrow aspirate and bone marrow trephine biopsy. Immunohistochemistry of bone marrow biopsy with markers reactive in paraffin-embedded tissues represents a powerful diagnostic tool; its results can be easily correlated with those obtained by other techniques such as flow cytometry and genetic analysis, and above all, the clinical findings. The role of the bone marrow biopsy will be particularly stressed in this review article. Particular emphasis is being given to the correct identification of cases of myeloid neoplasms associated with myelofibrosis and for which the bone marrow biopsy represents the only available diagnostic mean. Moreover, the often low cellular yield of the bone marrow aspirate in these cases may also be insufficient to obtain adequate cytogenetic information. Such cases include two subtypes of acute myeloid leukemia which typically cause diagnostic difficulties: acute megakaryoblastic leukemia and acute panmyelosis with myelofibrosis (acute myelosclerosis). Acute myeloid leukemia with multilineage dysplasia, therapy-related myelodysplastic syndrome/therapy-related acute myeloid leukemia and de novo myelodysplastic syndromes (MDS) will also be discussed. The value of bone marrow biopsy in this group of disorders is generally well established. In MDS, in particular, bone marrow biopsy may help in confirming a suspected diagnosis by excluding reactive conditions in which dyshematopoietic changes may also be observed. It can increase the diagnostic accuracy and helps in refining the IPPS risk evaluation system. Among the alterations detected by bone marrow biopsy, a prognostically important finding is the presence of aggregates or clusters of immature myeloid precursor cells (myeloblasts and promyelocytes). These can also be identified by immunohistochemistry with CD34, an antigen expressed in progenitor and early precursor marrow cells, which can be used to demonstrate pathological accumulations of blasts in aggressive subtypes of myeloid neoplasms. Immunohistologic analysis is especially helpful in cases of MDS with fibrosis and cases with hypocellular marrows (hypoplastic MDS). In both of these variants, the presence of reticulin fibrosis or fatty changes in the bone marrow can make accurate disease characterization very difficult or impossible using bone marrow aspirates. Finally, the important group of the myelodysplastic/myeloproliferative disorders can only be accurately categorized by a careful multiparametric approach in which the bone marrow biopsy exerts a pivotal role.
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