An uncommon morphological variant of acute promyelocytic leukemia

Abstract

The two most frequently observed morphological variants of acute promyelocytic leukemia are the classic hypergranular form and the hypogranular or microgranular variant. The former is characterized by abundant brightly staining granules (sometimes including giant granules) plus Auer rods, usually in bundles. The latter variant has a characteristic bilobed nucleus with finer, apparently scanty granules, many of the granules being below the level of resolution of the light microscope; Auer rods are often present and may be in bundles. We report here another morphological variant of acute promyelocytic leukaemia. A 29-year-old woman was referred urgently from the antenatal clinic at 28-weeks gestation when a routine full blood count showed a white cell count of 1.3 × 109/l, hemoglobin concentration of 68 g/l, platelet count of 16 × 109/l and neutrophil count of 0.3 × 109/l. A coagulation screen showed a marginally short prothrombin time of 10.8 s (normal range 11.1-13.5), normal activated partial thromboplastin time and fibrinogen concentration of 3.1 g/l (a slightly lower concentration than expected at this period of gestation). A bone marrow aspirate was performed with difficulty and the single film obtained showed hyperbasophilic blast cells with prominent cytoplasmic blebs (Image). Plentiful small granules were present but no Auer rods were detected. The significance of the cytological features was not initially appreciated but when immunophenotyping showed no expression of CD34 or HLA-DR the slide was further reviewed. Occasional characteristic bilobed nuclei were detected (centre cell, left image). Acute promyelocytic leukemia was suspected and urgent confirmatory investigations and treatment were arranged. The diagnosis was confirmed by demonstration of a microparticulate distribution of PML protein and by cytogenetic analysis, which showed 46,XX,t(15;17)(q24;q21)[9]/46,XX[1]. The cytological features in this patient are close to those of the hyperbasophilic variant of acute promyelocytic leukemia, first described by McKenna and colleagues in 1982 [1] with the difference that in the three previously reported patients the small hyperbasophilic promyelocytes had sparse or no visible granules and were considered to resemble micromegakaryocytes. In our current patient and a previous patient reported by one of us [2] the cells were cytologically similar to megakaryoblasts except for the presence of granules. In the previous case also it was the immunophenotype that first raised the suspicion of acute promyelocytic leukemia. The rapid accurate identification of acute promyelocytic leukemia is important because of the need for urgent specific treatment to avert the risk of life-threatening hemorrhage. It is therefore important to recognize morphological variants that may resemble the French–American–British (FAB) M2 or M7 categories of acute myeloid leukemia. In the absence of bundles of Auer rods, hyperbasophilic blebbed cytoplasm and bilobed nuclei may offer a clue to the diagnosis.