* A newborn with a karyotype of 47, XY, +21 presented at birth with a white blood cell count of 27 700/(mu)L of which 61 % were blast cells. The blast cell morphologic structure was initially not characteristic of any particular lineage, although the cytoplasm contained fine granules and occasional small vacuoles. Routine cytochemical stains were negative, except one for nonspecific esterase that was faintly positive in most of the blast cells. Flow cytometric analyses showed that the blast cells expressed glycophorin A with a subset dimly coexpressing CD45 and were negative for CD34, CD71, myeloid, lymphoid, and platelet-associated antigens. These immunophenotypic findings were consistent with an abnormal erythroid phenotype. A few days postpartum, markedly dysplastic erythroid precursor cells appeared in the peripheral blood and increased in number as the early blast cells decreased. After a period of subdued blast cell production, a second wave of increase in the number of blast cells and dysplastic erythroblasts followed and ended with the disappearance of circulating abnormal cells. The child is now 5 years old and no major illness has been reported since the remission of this disorder. This case most likely belongs to the category of transient myeloproliferative disorders, although the erythroid-like phenotype of blast cells and the evidence of single-lineage maturation to circulating dysplastic erythroid precursors allow the suggestion that this process could represent a special form of a self-limited hematologic disorder in Down syndrome.
(Arch Pathol Lab Med. 2002;126:474-477)
The transient myeloproliferative disorder (TMD) of Down syndrome, also known as transient abnormal myelopoiesis, characteristically manifests in the first few days of life, with numerous circulating blast cells exceeding the number of blast cells in the bone marrow and spontaneous resolution within a few weeks.’ Because of close resemblance to hematologic malignancy, some authors choose to designate this self-limited entity as acute myeloid leukemia with spontaneous remission.2 The blast phenotype in TMD is variable, but the immature cells have usually been positive for platelet-specific antigens CD41, CD42b, and CD61, for panmyeloid antigens in some cases, frequently for the stem cell marker CD34, and often coexpressed CD7.2-4 Molecular studies have demonstrated an expression of erythroid-specific genes in blast cells of TMD.5 Based on immunophenotypic analysis and recent molecular studies, the cell of origin is believed to be committed to the megakaryocytic lineage or is derived from a putative common precursor with a potential of differentiation along both megakaryocytic and erythroid pathways.5
Despite the accumulated evidence of dual megakaryocytic and erythroid differentiation, a TMD with an exclusive commitment to erythroid lineage has not been documented. The condition described herein was initially diagnosed as consistent with TMD, pending anticipated spontaneous resolution. Immunophenotypic analysis, however, showed a striking deviation from the hitherto described patterns with an almost exclusive bright expression of glycophorin A. The appearance of a large number of markedly dysplastic erythroid forms in the peripheral blood suggested the possibility of a rare form of TMD with erythroid differentiation.
REPORT OF A CASE
A male neonate with typical stigmata of Down syndrome was born full term after an uncomplicated pregnancy. The liver was slightly palpable at birth but the spleen and lymph nodes were not palpable. Karyotyping performed from a peripheral blood specimen revealed 47, XY, trisomy 21. On the first day postpartum, the patient’s hemoglobin was 11.7 g/dL with a red blood cell count of 2.9 X 10^sup 6^/mL. His white blood cell count was 27700/(mu)L with 61% blast cells, 10% myelocytes, 2% metamyelocytes, 5% band neutrophils, 9% segmented neutrophils, 10% lymphocytes, and 3% monocytes. The platelet count of 17000/(mu)L triggered an order for platelet transfusion to prevent any hemorrhagic event in his condition. A tentative diagnosis of a TMD was rendered. To monitor the further development of the patient’s disorder, a complete automated blood cell count and a differential cell count were performed almost every day until disappearance of blast cells and other atypical cells. On days 4 and 5 postpartum, hematopathologic evaluation of the circulating blast cells, consisting of cytochemical studies and flow cytometric analysis, respectively, was performed on a peripheral blood sample. Daily monitoring of the peripheral blood picture revealed 2 waves of abnormal cell production. Already during the first wave, markedly dysplastic erythroid precursors in different stages of maturation started to appear and their numbers gradually increased as the blast cells decreased in number. A similar dynamic was observed during the second wave that ended on postpartum day 35 by virtual disappearance of circulating abnormal cells. The results obtained by special studies led to the reevaluation of the original diagnosis as an erythroblastic disorder of undetermined prognostic significance. The patient received no antileukemic treatment, and bone marrow examination was not performed for lack of parental consent. He has received, however, a total of 8 platelet transfusions until the platelet counts stabilized above 30000/(mu)L around the time of spontaneous resolution. Since the onset of remission in the neonatal period, the child has reportedly not experienced any major illness and is well 5 years after diagnosis.