| Session: Mast cell disease |
| Case number: 199 |
Submitter(s): Irina Maric, Weiming Fu, Jennifer Stoddard, Pierre Noel.
Clinical history
Fifty one-year-old male presented with dermatitis, mucosal ulcerations and splenomegaly. CBC data showed: WBC 9.1, Hgb/HCT 12.7/38.3, PLT 193. WBC differential: 41% polys/bands, 15% lys, 4% monos, 40% eos. Absolute eosinophil count 3604. Serum tryptase was 27.8 ng/ml. After detailed clinical investigation and bone marrow biopsy, patient was diagnosed with hypereosinophilic syndrome (HES). Patient was started on imatinib and experienced dramatic improvement in clinical symptoms and decrease in eosinophil counts within one week.
Details of gross/microscopic pathology:
Review of the peripheral blood smear showed marked eosinophilia. Most eosinophils were atypical, with unevenly granular or hypogranular cytoplasm. There was no significant left shift or dysplastic changes in myeloid elements.
Bone marrow biopsy (fixed in B-Plus and decalcified in RapidCal Immuno) revealed mildly hypercellular marrow (45-70%) with interstitial eosinophilia and mild fibrosis. Immunohistochemical staining for tryptase revealed increase in scattered, atypical, spindle-shaped mast cells and one small, non-paratrabecular mast cell aggregate. Findings raised differential diagnosis of systemic mastocytosis (SM). There were no paratrabecular mast cell aggregates, which are characteristically seen in SM patients.
Bone marrow aspirate smear differential: 44% granulocytic precursors, 18% erythroid precursors, 7% lymphocytes, 30% eosinophils and eosinophilic precursors and 1% blasts. Eosinophils were mildly left-shifted. Mast cells were very rare.
Immunophenotype (flow cytometry/immunohistochemistry):
Flow cytometric analysis of bone marrow aspirate showed increase in mast cells (0.05%) positive for CD117 and CD25, but negative for CD2.
Cytogenetics:
N/A.
Molecular analysis:
Nested RT-PCR for FIP1L1-PDGFRa fusion gene was positive. RT-PCR/RFLP analysis for KIT D816V mutation was negative. PCR for T-cell clonal gene rearrangement was negative. RT-PCR for BCR-ABL was negative.
Interesting feature(s) of submitted case:
This patient with marked hypereosinophilia fulfilled 3 out of 4 minor WHO criteria for diagnosis of systemic mastocytosis with eosinophilia (SM-eo). However, major WHO criterion for diagnosis of SM (presence of multifocal mast cell aggregates in bone marrow biopsy) was absent. Clinically, symptoms characteristically associated with SM, such as GI symptoms and UP were absent. Mucosal ulcers and signs of end-organ damage, which are seen in HES patients, were present. In our opinion, this patient should be diagnosed as a primary eosinophilic disorder (HES/CEL), positive for FIP1L1-PDGFRa, since the clinical presentation, clinical course and major pathological findings are associated with the eosinophilic component of the disorder. Please compare this case with the case of KIT D816V-associated SM-eo submitted separately (case # 750167).
Proposed diagnosis:
FIP1L1-PDGFRa-associated HES/CEL.
Panel diagnosis:
agree with proposed diagnosis
Comments:
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