Transient Myeloproliferative Disorder With a CD7+ and CD56+ Myeloid/Natural Killer Cell Precursor Phenotype in a Newborn M. Svaldi, M.D., W. Moroder, M.D., H. Messner, M.D., L. Battisti, M.D., R. Venturi, Ph.D., P. Coser, M.D., and M. Mitterer, M.D. Abstract: A newborn with a transient myeloproliferative disorder and a myeloid/natural killer cell leukemia phenotype is described. The blasts expressed CD7, CD33, CD34, CD56, and CD117 but did not react with cytoplasmic myeloperoxidase and were negative for cy CD22, HLA-DR, and CD90 expression. No megakaryoblas- tic surface markers were identified. The blast population disap- peared from the peripheral blood and bone marrow within 2 months, but hepatomegaly and recurrent respiratory insufficiency persisted. The patient died of unilateral pneumonia in the third month of life. Neither extramedullary infiltration nor other hema- tologic signs of disease progression were found. Key Words: Acute congenital leukemia—Immunophenotype— Transient myeloproliferative disorder. CASE REPORT During a routine ultrasound in the seventh month of pregnancy, it was discovered that the male fetus had hepa- tosplenomegaly. A cordocentesis was carried out and the umbilical cord blood was analyzed. The fetus had a leuko- cyte count greater than 42,000/L, a normochromic anemia (8 g/dL), and a moderate thrombocytopenia (120,000/L). Eighty percent of the leukocytes were ungranulated blasts. According to the French-American-British Cooperative group classification, the blasts were morphologically and immunocytochemically undifferentiated (negative for my- eloperoxidase, alpha-naphthyl esterase, AS-D chloroacetate esterase, and periodic acid-Schiff). Immunophenotype analysis showed a blast population of the myeloid/natural killer cell type (Table 1), with the simultaneous expression of CD34, CD33, and CD56 antigens on the blast surface. Further, the blasts were strongly positive for CD7 and the c-kit ligand receptor (CD117). Thy 1 (CD90), cytoplasmic myeloperoxidase, and the HLA-DR antigens CD10 and CD19, in contrast, were negative. Megakaryocytic markers were not identified. Chromosome analysis revealed a tri- somy 21 (47 XY) in the blast population, which was also the germ line karyotype. No other chromosomal abnormalities were detected. An MLL gene rearrangement, known to be frequently involved in childhood acute leukemia (1), was not present, as shown by interphase fluorescence in situ hybridization analysis. A search for tandem duplications of the MLL gene, however, was not performed. Chromosomal translocations BCR-ABL (p190 and p210), AML1-ETO, and CBF–MYH11 (inv 16) were excluded by polymerase chain reaction analysis. Cesarean section was carried out in the 34th week of pregnancy. A prominent hepatosplenomegaly was present at birth. The white blood cell count was 39,000/L, the plate- let count was 121,000/L, and hemoglobin was 8 g/dL. Seventy-seven percent of the cells in the peripheral blood were blasts; in the bone marrow, the percentage was lower, with 35%. These blasts had the same immunophenotype as those in the periphery. Respiratory insufficiency was the main clinical sign in the first few days after delivery, which made intensive care necessary. Skin lesions of the “blue- berry muffin” type were observed, but they dissolved within 1 week. Six weeks later, blasts were no longer identifiable in the peripheral blood, and the bone marrow aspirate showed a blast infiltration of less than 5%. Dysmyelopoietic signs such as hypogranulated neutrophils and pseudopelger forms were continuously present in the peripheral blood. Splenomegaly disappeared, but hepatomegaly remained. The patient’s clinical condition deteriorated in the third month of life because of persistent diarrhea and fever, and the patient was fed by parenteral nutrition. Routine sero- logic and culture analyses for viral and bacterial agents were repeatedly negative. The liver increased in size daily, but blasts were not observed either in the peripheral blood or in the bone marrow. The patient died on day 96 of respiratory insufficiency caused by unilateral pneumonia. No necro- scopy was performed, but two postmortem liver biopsies were carried out. Twelve portal fields showed a nonspecific, inflammatory infiltrate, a normal centrolobular structure, and a diffuse periportal iron deposition, but there were no signs of either hepatic leukemic infiltration or fibrosis. DISCUSSION Transient myeloproliferative disorder (TMD) is a rare clonal disease (2) that usually disappears within the first months of life (3). It is frequently present in children with Down syndrome (4,5) but also occurs in phenotypically normal newborns (6). There is only one report of a patient Submitted for publication February 8, 2001; accepted April 30, 2001. From the Departments of Hematology (M.S., P.C.), Pediatrics (H.M., L.B.), and Gynecology (W.M.) and the Laboratory of Cytogenetics (V.R.), Regional Hospital Bozen, Bozen, Italy; and the Department of Transfusion Medicine, Franz Tappeiner Hospital, Meran, Italy (M.M.). Address correspondence and reprint requests to Dr. Manfred Mitterer, Department of Transfusion Medicine, Franz Tappeiner Hospital, Rossinis- trasse 5, I-39012 Meran, Italy; e-mail: mitman@dnet.it. Journal of Pediatric Hematology/Oncology, Vol. 24, No. 5, June/July 2002 © 2002 Lippincott Williams & Wilkins, Inc. 394