| Session: Chronic myelogenous leukemia |
| Case number: 166 |
Submitter(s): Richard L. McMasters, Michele Hibbard, Rebecca Fleck, Daniel Mackey, Wayne Chen, Shi-Ping Jiang, Jess Savala, Dennis P. O'Malley.
Clinical history
The patient is a 79 year old man who presented with a two week history of shortness of breath and mild splenomegaly. Routine CBC: WBC 105.2 x 106/L (25 segs, 25 bands, 9 metas, 17 myelos, 7 promyelos, 1 blast, 5 lymphs, 7 monos, 4 eos, 0 basos); RBC 3.9 x 1012/L; hemoglobin 13.2 g/dL; hematocrit 36.0%; MCV 92.3 fL; MCH 33.8 pg; MCHC 36.7 g/dL; RDW 16.7%; platelets 321 x 106/L. He had no history of hematological disease and CBC ten months prior had been normal. Clinical workup did not identify an infectious or inflammatory process. Hydroxyurea was started and the WBC count returned to baseline within two weeks. The oncologist has prescribed imatinib mesylate but approval from the third party payer has been delayed.
Details of gross/microscopic pathology:
The peripheral smear showed neutrophilia with a left shift to the blast stage. However, eosinophilia was relatively mild and basophilia was absent. The aspirate smears showed myeloid hyperplasia with an M:E ratio of 8:1. There was no increase in blasts. The bone marrow trephine biopsy was markedly hypercellular (> 95%). Many of the megakaryocytes were unusually small.
Immunophenotype (flow cytometry/immunohistochemistry):
Flow cytometry showed myeloid predominance (97% of total gated events); there was no increase in blasts.
Cytogenetics:
Karyotype: 46,XY,t(4;22)(q12;q11.2)[20].
FISH analysis used a three color, dual fusion probe set with an aqua probe for the region 5' of ABL, an orange probe for ABL and a green probe for BCR. There was no evidence of BCR/ABL fusion; however, there was a split signal in one of the BCR loci in 78% of nuclei scored: nuc ish 9q34(5'ABLx2,ABLx2),22q11(BCRx3)[78].
Molecular analysis:
Interesting feature(s) of submitted case:
Five cases of chronic myeloproliferative disease with t(4;22)(q12;q11.2) have been reported (Reddy KS, Sulcova V, Cancer Genet Cytogent 2000; 118: 121-31 / Baxter EJ, et al., Hum Mol Genet 2002; 11: 1391-97 [2 cases] / Trempat P, et al, Oncogene 2003; 22: 5702-6 / Safley AM, et al., Genes Chromosomes Cancer 2004; 40: 44-50). The first case was not studied at the molecular level. In the other four cases, PCR testing proved that the t(4;22)(q12;q11.2) created a fusion gene with BCR at the 5' end and PDGFRA at the 3' end. Although this disease (by definition) is not CML, it has similar clinical and morphologic features. Three patients had a "blast phase" at some point in the clinical course. Two patients were treated with imatinib mesylate and had a complete hematological response. Interestingly, we are aware of one case of chronic eosinophilic leukemia in which t(4;22)(q12;q11.2) by routine cytogenetics was not associated with a breakpoint in the BCR gene (submitted by Dr. Changjun Yue).
Proposed diagnosis:
Chronic myeloproliferative disease with t(4;22)(q12;q11.2) and presumptive BCR-PDGFRA fusion gene.
Panel diagnosis:
agree with proposed diagnosis
Comments:
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