| Session: Chronic myelogenous leukemia |
| Case number: 175 |
Submitter(s): David Viswanatha.
Clinical history
A 66 year old male initially presented in 2002 with Ph+ chronic myeloid leukemia (CML) in accelerated phase (WBC 119 X 109/L with 17% circulating blasts). He was managed with imatinib mesylate and hydroxyurea. Despite difficulty maintining an optimal imatinib dose, he was in complete hematologic (HR) and cytogenetic remission (CR) by 2005, although fluorescence in situ hybridization (FISH) analysis for the BCR-ABL abnormality revealed 1.5% dual fusion positive signals. In early 2006, he remained in HR, but a bone marrow revealed 3/20 metaphases with the t(9;22) and FISH analysis demonstrated 3.3% positive signals. By 04/2006, the patient was experiencing difficulties tolerating imatinib with increasing debility due to fluid retention. Despite dose reduction, imatinib was stopped in 09/2006. He continued to feel unwell and was reassessed in 12/2006. At presentation, the patient's CBC data included: Hgb 12.7 g/dL, MCV 83.7 fL, WBC 6.8 X 109/L, platelets 440 X 109/L. A bone marrow biopsy was obtained.
Details of gross/microscopic pathology:
The WBC differential and peripheral blood smear were remarkable for basophilia (22%), but no substantial left shift or circulating blasts. The bone marrow aspirate was hypercellular with G:E ratio of 3:1. Morphologic blasts were enumerated at 7% of cells. No dysplastic features were noted, although megakaryocytes were mainly small with monolobated nuclei. A subset of blasts showed unusual cytologic features of erythroid or megakaryocytic character. The B5-fixed marrow biopsy was 90% cellular with some architectural preservation alternating with areas of marked immature cell proliferation. Megakaryocytes were classically small with hypolobate nuclei.
Immunophenotype (flow cytometry/immunohistochemistry):
Immunoperoxiase studies were performed with antibodies directed against hemoglobin, CD34, CD117, CD31 and factor VIII. Hemoglobin showed somewhat disrupted erythroid colonies, as well as mildly increased pronormoblasts. CD34 and CD117 both revealed foci of increased phenotypic myeloblasts, corresponding mainly to the immature cellular regions in the H&E stained biopsy section. Overall, the phenotypic blast percentage was estimated at below 20%. CD31 and factor VIII confirmed an atypical small megakaryocyte population.
Cytogenetics:
Classical cytogenetic studies of the bone marrow aspirate revealed the t(9;22)(q34;q11) in 24 of 25 metaphases. In addition, 6 cells demonstrated a second Ph chromosome, as well as +8.
Molecular analysis:
N/A
Interesting feature(s) of submitted case:
This case demonstrates features of accelerated phase CML (basophilia with a normal WBC and an unusual multi-focal proliferation of myeloblasts detected mainly in the bone marrow biopsy). By morphologic differential and phenotypic assessment, criteria for blast crisis were not met. In addition, the clinical and pathologic changes are supported by recognized karyotypic features of accelerated phase disease.
Proposed diagnosis:
Chronic myeloid leukemia in accelerated phase.
Panel diagnosis:
CML with focal blast phase
Comments:
Stains performed by the panel: Special stains for microorganisms (AFB and GMS) were added to address focal granulomata present on H&E sections. These stains were negative.
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