Down syndrome-associated transient abnormal myelopoiesis with placental involvement

[摘要] A 2-day-old Down syndrome (DS) neonate born at 35 weeks 5 dayspresented with leukocytosis and blasts showing cytoplasmic blebs(Panel1×600). By flow-cytometry, blasts were positive for CD34, CD61and CD71 consistent with megakaryoblasts. Based on fetoplacentalcirculation (Figure), blasts lodged in the umbilical cord, chorionic plate,villi and membranes (Panels 2–5, H&E×100). Megakaryoblasts weregenerally confined to vascular lumina, but they infiltrated their walls(Panel 2 right, H&E×100). Immunohistochemically, blasts expressedCD61 (Panels 2,4,5×100 objective). Leukocytosis and increased blastsresolved within two weeks. These findings are consistent with DSassociated transient abnormal myelopoiesis (TAM) with placentalinvolvement. Somatic mutations of GATA1 are involved in the pathogenesis of DSTAM. GATA1 gene is necessary for the developmentof megakaryocytic lineages. Trisomy 21 perturbs fetal hematopoiesis,providing the context for: transformation of these fetal hematopoieticcells by acquired mutations in the GATA1 gene to produce DSTAM.Eighty percent of DSTAM cases resolve spontaneously within threemonths, coinciding with the transition of hematopoiesis from fetal liverto bone marrow. Fetal and maternal malignancies can cross and metastasize to the placenta. In fetal metastasis, tumor cells stay confinedto the fetal vessels, while, in maternal malignancies, cells infiltrate theperi-villous(maternal) space (Panel 6*). Patient’s parental verbal andwritten consent was received.

[关键词] down syndrome;GATA-1;MYELOID LEUKAEMIA