| Session: Ph- chronic myeloproliferative disease |
| Case number: 196 |
Submitter(s): Dita Gratzinger, Tracy George.
Clinical history
28 year old man presented to his primary care doctor secondary to an enlarging mass in the left upper quadrant, mild fatigue, and night sweats. A CT scan revealed a markedly enlarged spleen, and a CBC showed anemia with hypereosinophilia. Past medical history is limited to bipolar disorder, for which the patient was on Depakote, Zyprexa and Clozaril. Serum tryptase was mildly elevated (16ng/mL, upper limit of normal 11.5ng/mL), and total IgE was normal. After bone marrow biopsy and cytogenetic evaluation, the patient was treated with imatinib mesylate and showed a complete clinical, morphologic, and cytogenetic response following only one week of treatment.
WBC: 10.8K/uL; RBC: 3.25MIL/uL; HGB: 9.1g/dL; HCT: 27.3%; MCV: 84.1fL; PLT: 146K/uL; RDW: 21.6%; Diff: 33% neuts, 12% lymphs, 1% monos, 54% eos (5.8 K/uL).
Details of gross/microscopic pathology:
The peripheral blood smear shows normochromic normocytic anemia with rare circulating nucleated red cells, marked eosinophilia, and rare hypogranular and hypolobated neutrophils.
The bone marrow aspirate shows cellular marrow with increased eosinophils and no increase in mast cells. Adequate iron stores and no ringed sideroblasts are present.
The bone marrow biopsy is markedly hypercellular (nearly 100%) with scattered increased eosinophils. Myeloid and erythroid maturation is normal with a 3:1 M:E ratio and no increase in blasts. Reticulin stain shows 2+ patchy reticulin fibrosis, and a trichrome stain shows focal collagen fibrosis.
Immunophenotype (flow cytometry/immunohistochemistry):
Flow cytometry shows no increase in blasts, aberrant myeloid antigen expression, monoclonal B cell population, or aberrant B or T cell population.
Cytogenetics:
Conventional cytogenetics shows a normal 46X,Y male karyotype.
Fluorescence in situ hybridization (FISH) studies for BCR-ABL are negative.
FISH studies are positive for a deletion involving CHIC2 is positive in 37% of nuclei, consistent with an interstitial deletion on chromosome 4q12 resulting in the FIP11L1-PDGFRa fusion.
Molecular analysis:
PCR for BCR-ABL is negative.
PCR for T cell receptor gamma gene rearrangement is positive both at diagnosis and following complete cytogenetic response with imatinib treatment.
Interesting feature(s) of submitted case:
This young man has hypereosinophilia with a hypercellular marrow, no increase in blasts, and no abnormalities on flow cytometry. Mast cell tryptase is only mildy elevated, and serum IgE is normal. FISH shows an an interstitial deletion on chromosome 4q12 expected to result in the FIP11L1-PDGFRa fusion. The patient has a remarkable clinical, morphologic, and cytogenetic response after only one week of treatment with imatinib. Additionally, despite no morphologic or flow cytometric evidence of an abnormal T cell population, PCR-based T cell clonality studies show a persistent T cell clone both at diagnosis and after treatment.
Proposed diagnosis:
Chronic eosinophilic leukemia with interstitial deletion on chromosome 4q12 resulting in the FIP11L1-PDGFRa fusion.
Panel diagnosis:
agree with proposed diagnosis
Comments:
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