| Session: Mast cell disease |
| Case number: 104 |
Submitter(s): Cordelia E. Sever, Douglas Clark.
Clinical history
This female 61 year old woman presented in 6/2003 with marked splenomegaly, significant weight loss the previous 3-4 months and pancytopenia with WBC 3.0, Hgb/Hct 8.2/25, plt 138,000, 76% neutrophils, 22%lymphs, 1% monos, 1% basophils, 2nRBC/100WBC, numerous teardrops. She had no preexisting medical conditions, significant skin lesions or used any prescription medication. The bone marrow was largely replaced by mast cells. She had no response to 4 months treatment with imatinib followed by hydroxyurea. She underwent splenectomy in 12/2004 with temporary recovery of peripheral blood counts. Repeat deterioration and appearance of skin lesions prompted treatment with Cladribine in 11/2005 and 11/2006, resulting in clearing of skin lesion and improved blood counts with transfusion independence. A CBC on 1/26/2007 demonstrated WBC 10.8, Hgb/Hct 13.9/42, plt 600,000, 80%neutrophils, 11%lymphocytes, 8%monos, 1%basophils.
Details of gross/microscopic pathology:
The bone marrow at diagnosis in 6/2003was 90% replaced by atypical mast cells with slight atypia of residual megakaryocytes.[figure1]Bilateral bone marrow biopsies (acetic acid zinc formalin fixed) in 8/2005 showed complete bone marrow replacement by atypical mast cells with scattered eosinophils.
The splenectomy specimen from 2005 weighed 1,693g and had extensive mast cell infiltrates surrounding the white pulp with concurrent extramedullary hematopoiesis. There was moderate megakaryocyte dyspoiesis without apparent increase of blasts.
The post-treatment blood smear in 1/2007 showed no significant left shift, nRBC/s or tear drops.
Immunophenotype (flow cytometry/immunohistochemistry):
Mast cells in all specimens were strongly positive for CD117 and tryptase.[figure2][figure3]
Cytogenetics:
Insufficent cells from dilute aspirates due to dry taps.
Molecular analysis:
Paraffin embedded tissue from 2003 was sent for c-kit mutation analysis, results are unknown.
Interesting feature(s) of submitted case:
The findings at diagnosis meet criteria for aleukemic mast cell leukemia, a rare variant of systemic mastocytosis. The leukemic variant is usually characterized by rapid disease progression, whereas one aleukemic variant has recently been shown to harbor the c-kit mutation D816V which is mostly associated with imatinib resistant indolent mast cell disorders. This patient's prolonged disease course with continued response to monotherapy would similarly favor kinship to the indolent mast cell disorders. Furthermore, the pattern of splenic involvement with extensive extramedullary hematopoiesis and the post-treatment peripheral blood counts in Jan 2007 with leukocytosis and thrombocytosis are consistent with clonal involvement of all hematopoietic cell lines or an associated clonal hematologic non-mast cell lineage disease.
Proposed diagnosis:
Systemic mastocytosis - aleukemic mast cell leukemia (WHO).
Panel diagnosis:
agree with proposed diagnosis
Comments:
Studies performed by the panel: positive for D816V mutation
PowerPoint:
Presentation Link
Images:
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Figure 1 |
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Figure 2 |
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Figure 3 |
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