| Session: Mast cell disease |
| Case number: 187 |
Submitter(s): Zhao Ming (David) Dong.
Clinical history
A previously healthy 22-year old man presented in 02/04 with t (8;21) acute myeloid leukemia and concurrent systemic mastocytosis. Although he achieved remission with chemotherapy, he had early relapse of disease with the development of a myeloid sarcoma in brain in 12/04. He underwent an allogeneic sibling stem cell transplant in 02/05 and remained complete remission of AML on the date of last examination (18 months post transplant). Current CBC and differential are within normal range. After successful transplantation, the mature aberrant mast cells can persist in the marrow without adverse consequences for one year, and then significantly decline. By FISH analysis, we demonstrated that the majority of the sorted mast cells had the AML1/ETO gene rearrangement.
Details of gross/microscopic pathology:
Fig. 1. Coexistence of AML and mastocytosis. (A): Myeloblasts with occasional Auer rods in the aspirate at initial diagnostic marrow. (B): Atypical mast cells with hypogranulated cytoplasm in the aspirate at the pre-transplant marrow. (C): Mast cell aggregates in the biopsy. (D) Atypical mast cells with expression of tryptase as demonstrated by immunohistochemical stain.
Fig. 2.Coexistence of myeloid sarcoma and mastocytosis. Brain biopsy demonstrated a highly cellular lesion composed predominately of blast-like cells (A) with strong positivity for myeloperoxidase (B). Interestingly, there were also loosely scattered mast cells with multiple perivascular dense aggregates in the lesion, which were positive for tryptase (C).
Immunophenotype (flow cytometry/immunohistochemistry):
The atypical mast cells express bright CD117 with aberrant expression of CD2 and CD25 (Fig 3).
Cytogenetics:
The complete karotype was 46,XY,t (8;21)(q22;q22)
Molecular analysis:
1. Detection of the AML1/ETO gene rearrangement in the mature aberrant mast cells
Using a cell sorter by gating the population with high side scatter and co-expression of CD117 and CD2 or CD25, we purified mast cells. Then dual color FISH with an AML1/ETO translocation probe was performed on day 28 and 70 post-transplant sorted bone marrow fractions. We demonstrated that the majority (90%) of cells from the CD25+/CD117+ fraction had the typical fusion signal pattern associated with an AML1/ETO gene rearrangement (Fig. 4 A). In contrast, no nuclei of 200 analysed (0%) from the CD25-/CD117- fraction showed the fusion signal (Fig. 4 B).
2. c-Kit D816V point mutation was detected in the CD25+/CD117+ sorted mast cell population but not in the sorted CD33+ control cell fraction.
Interesting feature(s) of submitted case:
1. Myeloid sacroma with mast cell infiltration in brain.
2. A common cytogenetic abnormality existing in both the myeloblasts and the aberrant mature mast cells.
3. Effect of bone marrow transplant on the mature aberrant mast cells.
Proposed diagnosis:
1. Acute myeloid leukemia with t (8;21) and concurrent systemic mastocytosis.
2. Neoplastic mast cells derived from the leukemic clone.
Panel diagnosis:
Consensus not reached. Differential diagnosis includes SM-AHNMD
Comments:
Studies performed by the panel: Bone marrow: non-D816V type of c-kit mutation,CD25+; Brain: CD25+ but tryptase almost negative
Images:
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Figure 1 |
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Figure 2 |
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Figure 3 |
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Figure 4 |
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