| Session: Chronic myelogenous leukemia |
| Case number: 222 |
Submitter(s): Karl S. Theil.
Clinical history
A 63 year old man was referred to a hematologist for evaluation of leukocytosis and left-shifted differential discovered during an episode of acute gout. The past medical history included a cardiac transplant 14 years previously for congenital heart disease. Current medications included prednisone and allopurinol for gout, and mycophenolate mofetil and cyclosporine for immunosuppression. There was no palpable hepatosplenomegaly. A CBC showed WBC 69,000/uL; Hgb 7.0 g/dL; MCV 91 fL; and platelets 104,000/uL. There were 7% blasts, 2% promyelocytes, 5% myelocytes, 8% metamyelocytes, 71% neutrophils, 0% lymphocytes, 5% monocytes, 1% eosinophils, and 1% basophils with 5 NRBC/100 WBC.
Details of gross/microscopic pathology:
Peripheral blood smear [Figure 1], [Figure2] showed a leukocytosis with circulating blasts, a left shift in myeloid maturation, and absolute eosinophilia, basophilia, and monocytosis. There were occasional teardrop cells and giant platelets. The marrow aspirate [Figure 3] was hemodilute, but cellular with increased myeloid elements, 2% blasts, and slight dyserythropoiesis. Stainable iron was decreased. The majority of the marrow biopsy was characterized by well-developed marrow fibrosis [Figure 4] with entrapped small dysplastic megakaryocytes as shown in H&E, [Figure 5], [Figure 6] reticulin [Figure 7] and trichrome [Figure 8], [Figure 9] stains. Focal areas of hyperplastic hematopoiesis represented less than 20% of the area of the biopsy. [Figure 10] There was focal osteosclerosis.[Figure 8]
Immunophenotype (flow cytometry/immunohistochemistry):
Not performed.
Cytogenetics:
Cytogenetic analysis of the bone marrow aspirate demonstrated a 46,XY,t(9;22)(q34;q11.2)[4]/46,idem,add(20)(p13)[16] karyotype. The presence of clonal evolution favored accelerated phase disease.
Molecular analysis:
Interphase FISH using dual-color, dual-fusion probes for BCR and ABL1 genes (Abbott Molecular, Inc., Des Plaines, IL) demonstrated an abnormal signal pattern, with 94% of nuclei showing BCR-ABL fusion: nuc ish (ABL1 x 3),(BCR x 3), (ABL1 con BCR x 2).
Interesting feature(s) of submitted case:
The distinction between chronic myelogenous leukemia (CML) and chronic idiopathic myelofibrosis can be problematic when there is significant marrow fibrosis. Marrow fibrosis may be encountered in chronic and accelerated phase (AP) of CML, and, while extensive marrow fibrosis is suggestive of CML-AP, the independent significance of this in defining CML-AP remains to be determined. This case also demonstrates the value in pursuing cytogenetic and molecular analysis to rule out the Philadelphia chromosome and clonal evolution when a chronic myeloproliferative disorder is a diagnostic possibility.
Proposed diagnosis:
Chronic myelogenous leukemia, accelerated phase, with extensive marrow fibrosis.
Panel diagnosis:
agree with proposed diagnosis
Comments:
PowerPoint:
Presentation Link
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