| Session: Chronic myelogenous leukemia |
| Case number: 095 |
Submitter(s): Dahua Zhang, Catherine Leith.
Clinical history
This 40-year-old man, living in Asia, presented with a one year history of fatigue and dyspnea on exertion. He was profoundly anemic, requiring transfusion, and was transferred emergently to the US. At diagnosis, the patient had splenomegaly. Laboratory studies showed WBC of 4.6 x 109/L (34% neutrophils, 36% lymphocytes, 5% monocytes, <1% eosinophils, 2% basophils, 3% metamyelocytes and myelocytes, and 19% blasts), hemoglobin 7g/dL, hematocrit 20%, and platelet count of 292 x 109/L. The patient was treated with Gleevec, with resolution of his splenomegaly resolved. He remains transfusion independent with stable counts, and no circulating blasts 5 months later.
Details of gross/microscopic pathology:
Peripheral blood smear reveals normocytic, normochromic anemia with red cell anisocytosis, few nucleated red cells and rare tear drops. Circulating blasts and micromegakaryocytes are noted. The blasts have high N:C ratio, some with pseudopod formation and vacuolated cytoplasm. Platelets include some hypogranular forms. Basophilia or eosinophilia is not appreciated. There is only a modest left shift. The bone marrow aspirate was a dry tap. Touch imprint of the core biopsy shows blasts with similar morphology to the peripheral blood. The bone marrow biopsy was fixed with Z-5 solution. The marrow is essentially replaced by large clusters of atypical megakaryocytes (>50/hpf), mononuclear cells and immature myelocytes. There is marked background fibrosis, highlighted by reticulin stain, and prominent osteosclerosis.
Immunophenotype (flow cytometry/immunohistochemistry):
Immunohistochemical stains were performed on the bone marrow biopsy. CD61 highlights megakaryocytes, including some small mononuclear cells, not distinguishable as megakaryocytes on H&E. CD34 shows an increase in CD34+ cells with small clusters but no large aggregates. Myeloperoxidase stains most small mononuclear cells.
Cytogenetics:
46, XY, t(9;22)(q34;q11.2)[17]/46, XY[1]
nuc ish (ABLx3),(BCRx3);(ABL con BCLx2)[104/200].
Molecular analysis:
Not done.
Interesting feature(s) of submitted case:
This case of chronic myeloid leukemia is remarkable for the very significant degree of marrow fibrosis, with accompanying megakaryocyte hyperplasia, and osteosclerosis. While fibrosis is described at diagnosis in CML, this degree of fibrosis, with the osteosclerosis, is more reminiscent of chronic idiopathic myelofibrosis. Additionally, the patient presented in blast phase, rather than with stable disease. The increased blast count led to consideration of acute myelofibrosis/acute megakaryoblastic leukemia. The preservation of some normal hematopoiesis (neutrophil and platelet count maintained), splenomegaly, and the identification of the t(9;22) led us to favor CML in blast phase. The patient has had an excellent response to Gleevec, supporting this diagnosis.
Proposed diagnosis:
Chronic myelogenous leukemia with myelofibrosis presenting in myeloid blast phase.
Panel diagnosis:
agree with proposed diagnosis
Comments:
Additional flow cytometric histograms from the submitter: The CD45 dim CD34 positive blasts (green) express weak CD33 and are partially positive for CD61, suggesting megakaryocytic differentiation. Normal lymphocytes (red) express bright CD45 and are negative for all other markers. CD45 negative events (blue) are small in size and partially positive for CD61, likely representing platelet admixed with nucleated red cells.
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