A review of diagnosis of
acute promyelocytic leukemia (APL) is presented. There are still many patients with progressive disease with
leukocytosis at presentation. These are at greater risk of early death due to
bleeding (often intracranial), or, less frequently, due to thrombotic complications. In Czechia, we have, in some instances, noted an unacceptably long time from the first symptoms to diagnosis and to administration of the highly specific differentiation
therapy with
tretinoin (ATRA) along with
anthracycline chemotherapy. This combination is highly efficient--cures are seen in some 70% of patients. Therefore, we present a diagnostic minimum for each and every internist, and even better for every general practician, to get acquainted with. All cases of
pancytopenia and
consumption coagulopathy should be suspected of APL and referred to a specialized hematologist without any delay. In the following more detailed review of diagnostic measures, much attention is given to APL morphology, which is the first clue leading to diagnosis. The finding of the typical hypergranular FAB M3 morphology and of cells with bundles of Auer rods ("faggot cells"), along with the
HLA-DR, CD33+ immunophenotype, is highly (but not absolutely) specific for APL. In cases of the micro-/hypo-granular variant FAB M3v Form, and whenever APL cannot be ruled out with certainty, a test to prove the presence of the
PML/RARalpha fusion gene is indicated, using either RT-PCR or, eventually, immunological demonstration of the specific distribution of the PML
protein in the cell nucleus. Given that morphology of APL cases, as defined according to WHO criteria (95% of which carry the
PML/RARalpha fusion gene), admits extremely divergent morphological pictures ofthe variant forms, we recommend these investigations to be performed in every case of de novo
acute myeloid leukemia. A review of the less frequent morphological, as well as genetic variants is given, and the principles of immunophenotypic, cytogenetic and molecular diagnostics are also reviewed.