| Session: Ph- chronic myeloproliferative disease |
| Case number: 122 |
Submitter(s): Maria A. Proytcheva.
Clinical history
One day-old female with a prenatal diagnosis of Down syndrome (DS), presented with hyperleukocytosis and thrombocytopenia.
CBC: WBC 99.91 K/uL, Hb 16.2 g/dL, Hematocrit 48.2%, MCV 117.9 fL, RDW 15.9, Platelet count 57 K/uL.
Peripheral blood differential (500 cells): Blast (NOS) 69%, Lymph. 4.6%, Monocytes 3.2%, Neutrophils 11.2%, Bands 4.2%, Metamyelocytes 5%, Myelocytes 2.6%, Eosinophils 0.2%. NRBCs: 16 per 100 WBC.
Details of gross/microscopic pathology:
PB: There is hyperleukocytosis with moderate to severe thrombocytopenia, but there is no anemia. A significant population of morphologically heterogeneous blasts is present. The blasts have variable size, finely speckled to clumped chromatin, 1 to 3 conspicuous nucleoli, and a variable amount of cytoplasm, from scant to abundant. Some blasts have cytoplasmic blebs. Micromegakaryocyts are present. A small number of granulocytes at any stage of maturation is present as well. The platelets show variability in the size and granulation with many giant forms are present. No significant red cell abnormalities are present. There is prominent polychromasia along with numerous nucleated red blood cells.
Immunophenotype (flow cytometry/immunohistochemistry):
A significant number of CD33, CD34, CD41a, CD61 positive megakaryoblasts with a dim aberrant expression of CD19 (B-cell) and CD7 (T-cell marker) is identified in the peripheral blood by flow cytometry. While most of the cells are immature and express CD34, there is a continuum of expression of this marker as well as CD41a and CD61, platelet associated antigens, thus indicating a degree of megakatyocytic maturation. HLA-DR, TdT, and MPO are negative as are CD13, CD20, CD2, CD3, CD5, CD7, CD4 and CD8.
Cytogenetics:
47,XX,+21[20].
Molecular analysis:
None.
Interesting feature(s) of submitted case:
The case is a nice example of transient leukemia (transient myeloproliferative disorder) arising in the settings of Down syndrome. The interesting features of the case are the extreme white blood cells count (99.91 K/mL), very high peripheral blood blast count (69%), the characteristic morphologic heterogeneity and immunophenotype of these blasts, the identification of megakaryocytic lineage, and the flow cytometric evidence of maturation. Finally, this case is instructive in making a distinction between congenital leukemia and transient leukemia in an individual with a constitutional or mosaic trisomy 21 and brings awareness of the disorder to the general hematopathology audience.
The case also brings into discussion whether this disorder is non-neoplastic as it used to be considered in the past, or whether, based on the clonal nature of the process, it should be regarded instead as leukemia with a high incidence of spontaneous remission. Although the GATA-1 mutation status was not examined in the case, the role of this transcription factor in the myeloid leukemogenesis in DS also deserves discussion.
Proposed diagnosis:
Transient leukemia (transient myeloproliferative disorder) of Down syndrome.
Panel diagnosis:
agree with proposed diagnosis
Comments:
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