[1446] Morphology of Myeloid Leukemia of Down Syndrome

Kelley Mast, Jeffrey W Taub, Claudio Mosse, Prasad Mathew, Johann Hitzler, Todd Alonzo, Heath Jones, Alan S Gamis, David Head. Vanderbilt University, Nashville, TN; Indiana University, Indianapolis, IN; Wayne State University, Detroit, MI; Children's Mercy Hospitals and Clinics, Kansas City, MO; Children's Oncology Group, Arcadia, CA; University of New Mexico, Albuquerque, NM; Hospital for Sick Children, Toronto, ON, Canada

Background: Down syndrome (DS) has a 46X increased incidence of acute myeloid leukemia (AML) with reported megakaryocytic (MK) differentiation and frequently preceding myelodysplastic syndrome (MDS). Associated mutations of GATA-1, a transcription factor involved in erythroid (E) and MK differentiation, are often seen. Due to the lack of clinical difference in MDS and AML-MK in DS, the WHO combines these entities as AML-DS, but subtypes differ cytologically.
Design: Bone marrows from 162 patients on COG protocol AAML0431 (Treatment of DS Children with AML and MDS) were evaluated for blasts, dysplasia, fibrosis, and immunophenotype. Cases were classified using modified WHO criteria as MDS-DS, AML-MK, AML-E, mixed AML-MK/E, and AML NOS (non-MK or -E).
Results: Of cases reviewed, 57 had MDS and 105 had AML.

Results Summary
DiagnosisCasesBlasts*Dysplasia*Ring Megakaryocytes*Fibrosis*
* = % based on informative cases for each finding

While AML-MK was the most frequent subtype, E or MK/E lineage was seen in some cases. Most AML and MDS cases had MK and E dysplasia, with minimal myeloid (MY) dysplasia. E dysplasia consisted mainly of megaloblastoid change. MK dysplasia varied, but had unique morphology: peripherally displaced nuclei (ring megakaryocytes resembling Touton giant cells) often with a large central eosinophilic inclusion.

Conclusions: Cases of AML-DS have been described as MDS or AML-MK. In this study, while AML-MK was most frequent, we also observed AML-E and AML-MK/E cases. MDS cases differed from MDS in other settings. Both AML and MDS cases had MK and E, with little MY, dysplasia. We noted frequent, previously undescribed MK morphology with unique ringed nuclei. These findings may facilitate early diagnosis of this disease in DS patients and are concordant with observed GATA-1 mutations, which block E and MK differentiation.
Category: Hematopathology

Monday, March 4, 2013 9:30 AM

Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 221, Monday Morning


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