Abstract
A 73-year-old woman presented with a short history of spontaneous bruising, petechiae and rectal bleeding. Full blood count showed haemoglobin of 92 g/l, white cell count of 148 · 10/l and platelet count of 27 · 10/l. Coagulation studies showed prothrombin time 16 s, activated partial thromboplastin time 25 s, thrombin time 13AE1 s, fibrinogen 2AE81 g/l and D-dimer 61 608 ng/ml fibrinogen equivalent units. The blood film showed numerous granular myeloblasts with large nuclear indentations and invaginations – cup-like blasts (figures). Bone marrow examination showed similar blasts accounting for >90% of nucleated cells, with minimal maturation. Immunophenotyping confirmed acute myeloid leukaemia (CD117, CD13, CD33 and myeloperoxidase positive) but surprisingly the blasts were negative for CD34 and HLA-DR, a finding that is more characteristic of acute promyelocytic leukaemia [M3 acute myeloid leukaemia (AML)]. Cytogenetics studies showed a normal karyotype. Screening for FLT3 internal tandem duplication (ITD) and NPM1 mutations were both positive. Acute myeloid leukaemia with cup-like blasts is defined by characteristic cup-like indentations of the nuclei in myeloid blasts. This feature appears more prominent in peripheral blood than bone marrow smears. On electron microscopy, the nuclear invagination has been shown to be filled with cytoplasmic organelles. These blasts are typically negative for CD34 and HLA-DR on immunophenotyping, which in the presence of bleeding and laboratory evidence of disseminated intravascular coagulation may cause confusion with acute promyelocytic leukaemia. However, the karyotype associated with AML with cup-like blasts is usually normal but with molecular studies showing mutations in FLT3 and NPM1, either alone or in combination. AML with cup-like blasts may be a distinct biological entity. Its characteristic morphology and immunophenotype may be a clue to the associated FLT3 ITD and NPM1 mutation profile in normal karyotype AML.
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