Nukhet N Tuzuner and John M Bennett

commonly associated with acute megakaryoblastic leukemia. The second example is hypocellullar (hypoplastic) acute leukemia in which bone marrow aspirations from several sites and biopsy from one site are necessary for diagnosis.3 The third example is that of an uncommon localized extramedullary mass of cells of the granulocytic-monocytic series (granulocytic sarcomas).4 These tumors can be seen in an established diagnosis of acute myeloblastic leukemia (AML), either at presentation or as the first manifestation of relapse. In all three instances, although touch preparation smears may be helpful, well-prepared hematoxylin and eosin (H & E) stains and cell lineage specific antibodies (MPO, CD68, factor VIII, CD79a, CD3, CD1a, CD20) that can be applied to paraffin-embedded material that identify cell surface or cytoplasmic antigens5-7 can often establish the diagnosis.

The acute leukemias are a heterogeneous group of neoplasms affecting uncommitted or partially committed hematopoietic stem cells. The origin of the malignant neoplasm is almost invariably within the marrow. Replacement of the marrow pulp or the repression of normal hematopoietic cells results in variable degrees of anemia, neutropenia, and thrombocytopenia.

Historically, the term "acute" implied not only a poorly differentiated blast population, but also a clinical syndrome that led to a rapidly fatal outcome. Since it is apparent that, with modern chemotherapy, including bone marrow transplantation (BMT), patients with acute leukemia of several morphological types can enjoy complete remission (CR), and indeed cure, the term acute should be maintained only for nosological reasons.

Traditionally, morphology and cytochemistry identified the different involved lineages. During the past 15 years, major advances in our knowledge of the nature of acute leukemia consequent to the application of the techniques of immunology, cytogenetics, and molecular genetics have taken place. The demonstration of membrane and cytoplasmic antigens or enzymes by immunological or immunocytochemical methods and detection of the recurring chromosomal abnormalities either by conventional cytogenetic or molecular methods provide supplementary arguments for accurate classification.

Identification of subclasses of acute leukemia is important for three reasons. First, some leukemias have clinical features that influence the therapeutic approaches. Second, differences in response rate and survival are observed in the treatment of acute leukemias. Third, classification greatly facilitates communication and cooperation around the world, and comparisons of results are possible only through reproducible definitions of acute leukemias.

Examination of both peripheral blood and bone marrow smears is necessary for the diagnosis and classification of the acute leukemias. If the peripheral blast count is 20 percent or more peripheral blood samples may be adequate for morphological and immunological diagnosis. However, bone marrow aspirates will be needed to determine the leukemia cell karyotype.1

There are three instances in which the diagnosis of acute leukemia can be made on the basis of histological material. The first occurs when there is an abundance of reticulin in the bone marrow, resulting in a so-called dry-tap.2 Although bone marrow fibrosis can be present in any of the acute leukemias it is most

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