Submitting Author: Nakashima, Megan Okumoto, MD
Institution: Cleveland Clinic Foundation
Additional authors:Claudiu V. Cotta, M.D., Ph.D.
Session: Erythroleukemia and megakaryoblastic AML and mimics

The patient is a newborn male infant, born at term (39.2 wks) via vacuum-assisted vaginal delivery to a healthy 31 year-old mother. He showed no outward signs of distress, however peripheral blood examination was significant for neutrophilic leukocytosis (18.46 k/uL; nl 8.04-15.40) and thrombocytopenia (86 k/uL; nl 150-450).

Peripheral blood smears showed 17% circulating blasts and no leukoerythroblastic changes. The peripheral blast count peaked at 25% on day of life (DOL) 15. It subsequently decreased to 2% on DOL 22 and no blasts were present on DOL 27. Platelet count steadily increased from birth and reached normal range at DOL 15 [Figure 1].

Throughout this time the patient appeared healthy, with no signs of disease. Detailed physical exam showed no phenotypic evidence of Down syndrome or palpable organomegaly. Thyroid function tests were normal and there was no echocardiographic or electrocardiographic evidence of a congenital heart defect. Five months later, the patient is well, developing normally, with normal blood counts.

Bone marrow biopsy was not performed. Peripheral blood smears showed medium to large blasts with fine chromatin, prominent nucleoli and scant to moderate lightly basophilic cytoplasm with occasional cytoplasmic blebs [Figures 2-5].

Flow cytometry, peripheral blood, DOL 2 [Figures 6-7]

Positive: CD4 (dim), CD7 (dim subset), CD16 (dim), CD33, CD38 (dim), CD41, CD42b, CD45 (dim), CD61, CD123 (dim).

Negative: cCD3, sCD3, CD10, CD14, CD19, CD34, CD64, CD117, HLA-DR, TdT, myeloperoxidase

Interphase FISH, peripheral blood, DOL 2, examination focusing on blasts:

No evidence of translocation or extra copies of chromosome 21 using an AML1 (21q22) probe [Figures 8-9].

Negative for MLL (11q23) translocation (dual-color break-apart probe).

Conventional cytogenetics, synchronized and unsynchronized PHA-stimulated peripheral blood, DOL 10: 46,XY[100]

Conventional cytogenetics, GM-CSF supplemented and unstimulated peripheral blood, DOL 23 [Figure 10]: 46,XY[9] (suboptimal growth)

Comparative genomic hybridization (CGH) NimbleGen CGX array, peripheral blood, DOL 30 [Figure 11]: Arr(1-22)x2,(XY)x1 (normal male).

GATA1 mutation studies were negative

This is a case of congenital expansion of blasts in the peripheral blood, mimicking congenital acute myeloid leukemia or transient abnormal myelopoiesis (TAM) related to Down syndrome. Although the blast count was initially high (up to 25%) it soon decreased and blasts were undetectable within a month. By flow cytometry the blasts had a megakaryocytic immunophenotype. Throughout the entire time, the patient had no signs or symptoms of leukemia or organomegaly. Currently he has normal blood counts and no developmental abnormalities.

The transience, morphology and immunophenotype of this blast population is reminiscent of TAM seen in infants with trisomy 21, but multiple techniques (FISH, cytogenetics and CGH) showed no evidence of abnormalities involving parts of chromosome 21. Rare cases of TAM have been reported in the absence of phenotypic Down syndrome, usually in patients with either mosaic or partial trisomy 21. Even fewer cases have been reported with trisomy 21 restricted to the blast cells. In our case examination of the blasts by FISH showed no evidence of an abnormality selectively involving the blasts.

To our knowledge this is the first reported case of transient myeloproliferative disorder with no evidence of extra material from chromosome 21 in either the germ-line or blast cells.

We are unable to submit slides in addition to the photographs, as the volume of the peripheral blood specimen was limited (the patient was a newborn) and most of it was used for flow cytometric analysis. Bone marrow biopsy was not performed due to the lack of clinical signs or symptoms of leukemia. Due to the transient nature of the findings, obtaining additional specimens with significant blast counts at later examinations failed.

Transient abnormal myelopoiesis of newborn, not associated with Down syndrome.

Transient abnormal myelopoiesis of newborn, not associated with Down syndrome

Case 49