Acute differentiated dendritic cell leukemia: a variant form of pediatric acute myeloid leukemia with MLL translocation

Dendritic cells (DCs) are the primary antigen-presenting cells (APCs) for eliciting T-cell response.1 The immunophenotype and function of DCs are heterogeneous in vivo.1 DCs can be generated in vitro from cord blood or bone marrow CD34+ progenitors,1 and from peripheral blood or cord blood monocytes in the presence of tumor necrosis factor (TNF) and IL-4.1, 2, 3 Induction of DC differentiation in vitro from acute or chronic leukemia cells has been described using a combination of cytokines.2, 3 Primitive DC neoplasms are rare and remain unclassified according to the French–American–British (FAB) system.4 The recent World Health Organization (WHO) classification of hematological malignancies introduced a distinct category among the DC neoplasm but not in myeloid neoplasms.5 In the present study, we identified three pediatric cases of acute myeloid leukemia (AML) with features of well-differentiated DCs. We performed a morphological, immunological and molecular characterization of these cases using well-established methodologies. Detailed information regarding Materials and methods are reported in Supplementary Materials and methods. Demographic and clinical features of all three patients are listed in Table 1. They were admitted in three different children's hospitals in Italy (Catania for case 1; Padova for case 2; Catanzaro for case 3). They presented with fever, pallor, abdominal and joint pain, cervical adenopathy and mild hepatosplenomegaly. In all three cases, the white blood cell count was normal. There was no involvement of the central nervous system. Morphologic evaluation of the bone marrow aspirates was similar in the three cases. The marrows were completely replaced with large blasts in a percentage of 85, 80 and 85% for cases 1, 2 and 3, respectively. The blasts were characterized by irregular nuclei, slightly basophilic cytoplasm and prominent cytoplasmic projections. There were no cytoplasmatic granules and no evidence of phagocytosis (Figure 1a–c). Myeloperoxidase (MPO) and alpha naphthyl acetate esterase (NAE) reactions were negative (Figure 1d). Additional morphological features are shown in Supplementary Figure 1A (for case 1), 1B (case 2) and 1C (case 3). We provided several images of blasts in order to demonstrate the DC nature of this form of leukemia.