| Session: Chronic myelogenous leukemia |
| Case number: 149 |
Submitter(s): Lawrence Tsao, Joseph Pierce, Mohammad A. Vasef, Kaaren K. Reichard.
Clinical history
The patient is a 79 year old male with no significant past medical history presenting with coagulopathy and marked leukocytosis.
CBC w/ differential:
WBC: 84 x10E3/mm3
RBC: 2.54 x10E6/mm3
Hgb: 8.5 gm/dL
HCT: 23 %
MCV: 90 fL
MCHC: 37.5 gm/dL
RDW: 15.7 %
Plt: 59 x10E3/mm3
Neut: 94 %
Meta: 2 %
Lymph: 0 %
Myelo: 2 %
Mono: 1 %
Promy: 1 %
Blast: 0 %.
Details of gross/microscopic pathology:
Microscopic examination of the peripheral blood shows a marked leukocytosis with left-shift of the granulocytic lineage, but a predominance of neutrophils without circulating blasts. No basophilia or monocytosis is identified. Anemia and thrombocytopenia are present.[figure1][figure2]Microscopic examination of the bone marrow aspirate shows predominance of granulocytic lineage due to marked granulocytic hyperplasia with decreased erythroid and megakaryocytic lineages. The granulocytic lineage is left-shifted, but show numerous mature granulocytes and no significant increase in blasts is present. Many granulocytic precursors contain coarse azurophilic granules, but an increase in basophilic precursors is not present. Scattered sea-blue histiocytes are identified. The bone marrow core biopsy shows a markedly hypercellular bone marrow with >90% cellularity and osteopenia. Megakaryocytes are decreased, and small, hypolobated forms are not present.[figure3][figure4][figure5]
Immunophenotype (flow cytometry/immunohistochemistry):
Flow cytometry preformed on a bone marrow aspirate shows predominance of mature and maturing granulocytic elements. No blasts are identified by CD34.[figure6]
Cytogenetics:
Cytogenetic karyotyping shows the classic Philadelphia chromosome in all metaphases examined:
46,XY,t(9;22)(q34;q11)[20]
FISH using BCR-ABL dual fusion probe system demonstrates the typical abnormal fusion pattern of 2F1G1R in 175 of 200 cells exained.[figure7][figure8]
Molecular analysis:
High levels of BCR-ABL transcripts involving the M-BCR breakpoint are detected by quantitative RT-PCR. In addition, low levels of BCR-ABL transcripts involving the m-BCR breakpoint are detected, presumably due to alternative splicing.[figure9]
Interesting feature(s) of submitted case:
This case demonstrates the morphologic heterogeneity of chronic myelogenous leukemia (CML) and the importance of molecular assays in the workup of CML. Morphologically, the case shows many atypical features including: a prominent degree of granulocytic maturation, absence of basophilia, lack of the typical megakaryocytic features, and marked erythroid and megakaryocytic hypoplasia without increased blasts. Some of these features are suggestive of the neutrophilic variant of chronic myelogenous leukemia (N-CML), commonly associated with BCR-ABL transcripts involving the mu-BCR breakpoint,. However, although morphologically resembling N-CML, the BCR-ABL transcript detected in this case involves the M-BCR breakpoint, stressing the importance of molecular assays.
Proposed diagnosis:
Chronic myelogenous leukemia, chronic phase.
Panel diagnosis:
agree with proposed diagnosis
Comments:
PowerPoint:
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