Table of Contents
Definition / general | Clinical features | Case reports | Treatment | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics descriptionCite this page: Mihova D. Transient abnormal myelopoiesis associated with Down syndrome. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/leukemiaTAM.html. Accessed March 2nd, 2021.
Definition / general
- Myeloid proliferations related to Down syndrome (trisomy 21) include transient abnormal myelopoiesis (TAM) and Myeloid leukemia associated with Down syndrome; separate categories in WHO 2008
- TAM occurs in 10% of Down syndrome newborns, clinical and morphologic findings indistinguishable from AML
- Blasts morphologically and immunophenotypically are similar to megakaryocytic lineage
- Down syndrome patients have increased risk for AML, usually AMKL (AML M7)
- TAM usually resolves in 2 - 14 weeks in neonates, but 20 - 30% progress to AMKL within 3 years
- TAM: early death in 17%, associated with high white blood cells at diagnosis, increased bilirubin and liver enzymes and failure to normalize white blood cells (Blood 2006;107:4606)
- TAM rarely occurs without Down syndrome (Arch Dis Child Fetal Neonatal Ed 1998;79:F215)
Clinical features
- 10% of newborns with Down syndrome but uncommon in neonates with trisomy 21 mosaicism
- Thrombocytopenia, marked leucocytosis, %blasts in peripheral blood may exceed %blasts in bone marrow; also hepatosplenomegaly, cardiopulmonary failure, hyperviscosity, splenic necrosis and progressive hepatic fibrosis
Case reports
- Stillborn male fetus, gestational age 28 weeks, with severe disease (Nat Clin Pract Oncol 2007;4:433)
- Newborn with transient myeloproliferative disease (Hum Pathol 2000;31:396)
Treatment
- Less intensive chemotherapy may be effective (J Clin Oncol 2007;25:5442)
Microscopic (histologic) description
- Blasts have moderate basophilic cytoplasm with cytoplasmic blebs, coarse azurophilic granules resembling those in basophils, round to slightly irregular nuclei
- Also promegakaryocytes, micromegakaryocytes and dyserythropoiesis
- Peripheral blood: White blood cells up to 100K with 30 - 50% blasts, nucleated red blood cells and micromegakaryocytes
Microscopic (histologic) images
Images hosted on other servers:
abnormal myelopoiesis
of Down syndrome
Positive stains
Negative stains
- CD11b, CD13, CD14, CD15, glycophorin A, myeloperoxidase and Sudan Black B
Molecular / cytogenetics description
- Trisomy 21 and acquired mutations in GATA1 gene in almost all cases (versus 4% of all Down syndrome infants, Blood 2007;110:2128), specific mutations may differ in TAM and subsequent AMKL (Int J Hematol 2007;86:250)
- Loss of GATA1 impairs maturation of megakaryocyte erythroid progenitors (Blood 2006;107:87)
- JAK3 mutations in 50% (Br J Haematol 2007;137:337)
