Acute megakaryoblastic leukaemia with erythrophagocytosis

Abstract

A 42-year-old man with Down syndrome presented with fever and facial ecchymosis. A full blood count showed: white blood cells 21.0 × 109/l, haemoglobin concentration 89 g/l and platelets 14 × 109/l. The blood film showed 30% small to medium sized blast cells with scant cytoplasm and anisopoikilocytosis with dacrocytes. A bone marrow aspiration was performed. The bone marrow was hypercellular, with the presence of 40% of heterogeneous blast cells. Most blast cells were similar to those in the peripheral blood, being small with round to slightly irregular nuclei and scant agranular cytoplasm, but medium to large blast cells with irregular nuclei and cytoplasmic blebs were also present. Moreover, a small proportion of blasts were very large, either multinucleated or with polylobulated nuclei with a moderate amount of cytoplasm with blebs and, sometimes, coarse myeloperoxidase (MPO)-negative granules (all images, ×100 objective). Dysplasia was present in 12% of erythroid cells. Abundant examples of erythrophagocytosis by leukaemic blast cells were present (top images). Multiple mitosis were observed with some mitotic figures indicating that the cells were hyperdiploid (bottom left image). The blasts were positive for cluster of differentiation (CD)117, CD33, CD34, CD41 and CD61, and negative for MPO, CD71 and CD14 by flow cytometry. There was a complex karyotype with monosomy of 7 and 16, a marker chromosome and the known germline trisomy of 21. GATA-binding protein 1 (GATA1) Sanger sequencing showed no mutations. A diagnosis of myeloid leukaemia associated with Down syndrome (acute megakaryoblastic leukaemia) was made. However, the age of the patient and the absence of a GATA1 mutation suggest that this case differs from the cases usually reported in the first 5 years of life. The patient received induction treatment with ‘3+7’ (idarubicin and cytarabine) and FLAG-IDA (fludarabine, cytarabine and idarubicin) regimens; however, the disease was refractory to treatment and the patient died at 4 months after diagnosis. Erythrophagocytosis by leukaemic blasts is a rare finding in acute myeloid leukaemia. It has been reported in leukaemias with monocytic or megakaryocytic morphology and the presence of t(8;16)(p11.21;13.3), inv(8)(p11.21q13.3) or tetraploidy.