| Session: Mast cell disease |
| Case number: 054 |
Submitter(s): Rodney R. Miles, Lauren B. Smith, Cem Akin, Diane Roulston, Charles W. Ross.
Clinical history
28-year-old woman with easy bruising and petechiae; she has hypothyroidism and takes synthroid.
WBC 5000/uL, Hb 7.9 g/dL, Hct 22.2%, Plt 13,000/uL
Differential: 25% lymphocytes, 29% segmented neutrophils and bands, 2% metamyelocytes, 3% myelocytes, 39% blasts, and 2% monocytes.
Details of gross/microscopic pathology:
Peripheral blood smear: 39% blasts. Thrombocytopenia.
Bone marrow aspirate smear: 86% blasts. Occasional atypical hypogranular mast cells (Fig 1-2).
Bone marrow core biopsy (B5 fixation, decalcification) and aspirate clot section: hypercellular bone marrow consisting predominantly of blasts. Findings diagnostic of acute myeloid leukemia with maturation (FAB AML M2) with a recurring cytogenetic abnormality (see below). Subtle infiltrates of atypical mast cells with elongated nuclei around blood vessels and bony trabeculae were not recognized initially (Fig 3-4). Subsequent bone marrow examination showed no morphologic evidence of AML, however mast cell infiltrates were visible on H&E (Fig 5). Atypical mast cells were present on aspirate smears (Fig 6-7), and the original material was re-reviewed.
Immunophenotype (flow cytometry/immunohistochemistry):
At presentation, flow cytometry demonstrated blasts expressing CD33 (dim), CD56, and CD117. CD34 and CD19 were negative. In a subsequent assay, the mast cells expressed bright CD117 with aberrant CD2 and dim CD25 (Fig 8).
Retrospective immunohistochemistry on the original core biopsy revealed multifocal clusters of = or >15 mast cells positive for tryptase (Fig 9) and CD117. In remission, tryptase staining highlighted clusters of atypical spindled mast cells (Fig 10).
Cytogenetics:
46,XX,t(8;21)(q22;q22)[11]/47,idem,+4,i(4)(q10)[9].
Molecular analysis:
C-KIT D816V identified.
Interesting feature(s) of submitted case:
The patient presented with AML showing t(8;21) and trisomy 4. The diagnosis of SM was made in a subsequent bone marrow examination demonstrating complete hematologic and cytogenetic remission of the AML. Retrospectively, mastocytosis was present at initial presentation. In AML, the C-KIT D816V mutation is most common in cases with t(8;21) and trisomy 4. In patients with AML t(8;21), SM, C-KIT mutations, and trisomy 4 have all been associated with worse outcomes, but the incidence and prognostic significance of co-existing C-KIT mutations and mast cell disease has not been reported. AML recurred in this patient approximately 8 months after initial diagnosis, second remission was never achieved, and the patient died 16 months after diagnosis. Detection of mast cell disease requires a high level of suspicion in these cases as the changes in biopsy may not be obvious when high grade infiltration by leukemic cells is present in the biopsy.
Proposed diagnosis:
AML with recurring cytogenetic abnormality t(8;21)(q22;q22) and SM (SM with associated clonal, hematological non-mast cell disease).
Panel diagnosis:
Differential diagnosis includes Tryptase+ AML more likely than MML and SM-AHNMD
Comments:
Studies performed by the panel: no amplification for c-kit, CD25-
PowerPoint:
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