Autopsy case of a stillbirth with transient abnormal myelopoiesis associated with Down syndrome: Immunohistochemical demonstration of GATA1 mutation in placental tissues.

Abstract

Transient abnormal myelopoiesis (TAM) in neonates with Down syndrome (DS) exhibits hematological features that are indistinguishable from those of acute megakaryoblastic leukemia. However, TAM typically resolves spontaneously within several months postnatally. Some patients with TAM, however, develop severe clinical manifestations, which can lead to an unfavorable prognosis. TAM originates in utero through the acquisition of somatic GATA1 mutations, resulting in the loss of the full-length GATA1 protein and excessive production of the N-terminal truncated short isoform of the GATA1 protein (GATA1s). Herein, we report the pathological findings from an autopsy of a female stillbirth with TAM and DS, including an examination of her placental tissues. Immunohistochemical analysis revealed the expression of GATA1s, but not full-length GATA1, in CD42b-positive atypical immature megakaryocytes and blasts in the placental blood vessels. This confirms the diagnosis of TAM and suggests the utility of placental tissue for histological diagnosis. Additional unique findings from the autopsy specimens are discussed.