Donor-derived MDS/AML with germline GATA2 mutation in recipient from Family 1, and MDS/AML in matched related donor from Family 2. (A) Donor-derived MDS/AML after HSCT in patient with germline GATA2 mutation transplanted with healthy parent harboring same mutation. Upper panel shows pre-HSCT bone marrow of 21-year-old man diagnosed with AML (patient 1). The bone marrow is hypocellular for age with numerous blasts (upper left image of core biopsy; original magnification ×500; hematoxylin and eosin [H&E] stain) that are positive for CD34 by immunohistochemistry (IHC; brown stained cells, upper middle image; original magnification ×500). The blasts are large with a high nuclear to cytoplasmic ratio and fine chromatin shown on the marrow aspirate (upper right image; original magnification ×1000; Wright-Giemsa stain). Cytogenetic analysis revealed an abnormal karyotype involving monosomy 7 and trisomy 13. Lower panel shows bone marrow 3 years after HSCT when the patient peripheral blood counts were falling. Abnormal dysplastic megakaryocytes are seen (lower left image; original magnification ×500; H&E core biopsy) in a hypocellular marrow for age. CD34-positive blasts are increased (5% to 9%) by IHC (red stained cells in lower middle image; original magnification ×500). Aspirate smear shows dysplastic megakaryocytes, multinucleated erythroid precursors, and abnormal dysplastic cells (composite lower right image; original magnification ×1000). Cytogenetic analysis revealed presence of monosomy 7 in all of the female donor cells, consistent with donor-derived MDS/AML. Germline GATA2 mutation was identified in both the mother donor and the recipient son after HSCT. (B) MDS/AML with germline GATA2 mutation in identical twin MRD. Images of the bone marrow of the identical twin MRD for patient 2. At the time of HSCT, the donor was healthy with normal peripheral blood counts. Patient 2 died several months after HSCT of AML, and MDS developed in the identical twin donor 17 years later. Images of bone marrow show dysplastic megakaryocytes (upper left image of core biopsy; original magnification ×500; H&E stain) and increased CD34-positive blasts (red cells, IHC for CD34, upper middle image; original magnification ×500). IHC for CD61 highlights presence of micromegakaryocytes (small red cell, lower middle image; original magnification ×500). Aspirate shows scattered blasts and dysplastic binucleated precursor (inset) (lower left image of aspirate; original magnification ×1000; Wright-Giemsa stain). Flow cytometry analysis of the bone marrow of the patient in comparison with normal control marrow (right panels) revealed underlying immunodeficiency characterized by severe decrease to absence of monocytes, natural killer cells, precursor B cells, and mature B cells in the bone marrow. EB-1, excess blasts 1.