The morphological recognition of acute promyelocytic leukemia is of critical importance because of the need for early specific treatment. However cytological features are quite variable and in patients in whom the cells have scanty hyperbasophilic cytoplasm, or in whom granules are so densely packed that it is difficult to distinguish cytoplasm from nucleus, recognition of the key features can be difficult. We should like to highlight the value of examination of crushed leukemic cells in blood and bone marrow films from patients with acute promyelocytic leukemia. We present here two patients, both with confirmed PML-RARA fusion in whom the detection of multiple Auer rods surrounding the nuclei of crushed cells facilitated a morphological diagnosis that was otherwise difficult.
The first patient was a 40-year-old woman who presented with bruising and nose bleeds. Her blood count showed: hemoglobin concentration (Hb) 87 g/l, white cell count (WBC) 8.2 × 109/l, neutrophils 0.9 × 109/l, primitive myeloid cells 6.4 × 109/l, and platelet count 10 × 109/l. Coagulation screen including fibrinogen concentration was normal. Both the blood film and bone marrow aspirate showed some crushed cells with multiple Auer rods surrounding the nuclei. This bone marrow image (top) shows four promyelocytes, one crushed with Auer rods and the others intact with hyperbasophilic blebbed cytoplasm; one cell has a bilobed nucleus and another has several Auer rods. The final diagnosis was of classical acute promyelocytic leukemia. The second patient was a 25-year old woman who presented with tiredness, menorrhagia, and bruising. Her blood count showed Hb 96 g/l, WBC 2.9 × 109/l, and platelet count 16 × 109/l. A coagulation screen shows a prolonged prothrombin time, reduced fibrinogen (0.6 g/l), and raised D-dimer. A blood film showed primitive cells with scanty hyperbasophilic, blebbed cytoplasm (bottom right) but with some crushed cells revealing the presence of multiple Auer rods (bottom left). The final diagnosis was of the hyperbasophilic variant of acute promyelocytic leukemia .
Facilitation of a cytomorphological diagnosis by detection of crushed cells with multiple Auer rods was of particular importance in indicating the diagnosis in these two patients for different reasons. In the first patient, there was no coagulation abnormality and no t(15;17) was present, cytogenetic analysis showing only 46,XX,del(7)(q22q36)/46,XX; FISH analysis, however, showed a fusion signal on chromosome 15 in 17 of 20 metaphases, indicating a cryptic insertion of RARA into PML. In the second patient, although cytogenetic and molecular genetic features were typical, cytological diagnosis was otherwise difficult because of the cytoplasmic features of the leukemic promyelocytes.