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Pathologic Features of Down Syndrome Myelodysplastic Syndrome and Acute Myeloid Leukemia: A Report From the
Kelley J Mast1, Jeffrey W Taub1, Todd A Alonzo1
1From the Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee (Drs Mast, Mosse, Jones, and Head); the Division of Hematology/Oncology, Children's Hospital of Michigan, Wayne State University, Detroit (Dr Taub); the Department of Biostatistics, University of Southern California, Monrovia (Dr Alonzo and Mr Wang); the Division of Hematology/Oncology/Bone Marrow Transplantation, Children's Mercy Hospital, Kansas City, Missouri (Dr Gamis); the Pathology and Laboratory Medicine Service, VA Tennessee Valley Healthcare System, Nashville (Dr Mosse); the Department of Pediatrics, University of New Mexico, Albuquerque (Dr Mathew); the Division of Hematology-Oncology, IWK Health Centre, Halifax, Nova Scotia, Canada (Dr Berman); the Departments of Oncology (Dr Campana and Ms Coustan-Smith) and Pathology (Dr Raimondi), St. Jude Children's Research Hospital, Memphis, Tennessee; the Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, The National University Cancer Institute, NUH Medical Centre, Singapore (Dr Campana and Ms Coustan-Smith); the Department of Laboratory Medicine and Pathology, University of Minnesota Medical School, Minneapolis (Dr Hirsch); the Department of Pediatrics, University of Toronto, Toronto, Ontario, Canada (Dr Hitzler); and the Division of Hematology/Oncology, The Hospital for Sick Children Developmental and Stem Cell Biology, The Hospital for Sick Children Research Institute, Toronto, Ontario, Canada (Dr Hitzler). Dr Mast now has a joint appointment at the Pathology and Laboratory Medicine Service, VA Tennessee Valley Healthcare System, Nashville. Dr Mathew is currently at the Department of Pediatrics, Presbyterian Health Services, Albuquerque, New Mexico. Dr Berman is currently at the Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada. Dr Jones is currently at Pathgroup Labs, Nashville, Tennessee. Dr Campana is no longer at the Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee. Ms Coustan-Smith is no longer at the Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee.
Context.—:
Detailed diagnostic features of acute myeloid leukemia in Down syndrome are lacking, leading to potential misdiagnoses as standard acute myeloid leukemia occurring in patients with Down syndrome.
Objective.—:
To evaluate diagnostic features of acute myeloid leukemia and myelodysplastic syndrome in patients with Down syndrome.
Design.—:
Diagnostic bone marrow samples from 163 patients enrolled in the Children's Oncology Group study AAML0431 were evaluated by using central morphologic review and institutional immunophenotyping. Results were compared to overall survival, event-free survival, GATA1 mutation status, cytogenetics, and minimal residual disease results.
Results.—:
Sixty myelodysplastic syndrome and 103 acute myeloid leukemia samples were reviewed. Both had distinctive features compared to those of patients without Down syndrome. They showed megakaryocytic and erythroid but little myeloid dysplasia, and marked megakaryocytic hyperplasia with unusual megakaryocyte morphology. In acute myeloid leukemia cases, megakaryoblastic differentiation of blasts was most common (54 of 103, 52%); other cases showed erythroblastic (11 of 103, 11%), mixed erythroid/megakaryoblastic (20 of 103, 19%), or no differentiation (10 of 103, 10%). Myelodysplastic syndrome and acute myeloid leukemia cases had similar event-free survival and overall survival. Leukemic subgroups showed interesting, but not statistically significant, trends for survival and minimal residual disease. Cases with institutional diagnoses of French American British M1-5 morphology showed typical features of Down syndrome disease, with survival approaching that of other cases.
Conclusions.—:
Myelodysplastic syndrome and acute myeloid leukemia in Down syndrome display features that allow discrimination from standard cases of disease. These distinctions are important for treatment decisions, and for understanding disease pathogenesis. We propose specific diagnostic criteria for Down syndrome-related subtypes of acute myeloid leukemia and myelodysplastic syndrome.