| Session: Mast cell disease |
| Case number: 065 |
Submitter(s): Francois M. Cady, Ellen D. Remstein, Ayalew Tefferi.
Clinical history
This 50-year-old gentleman presented with abdominal pain, which was clinically thought secondary to acute appendicitis. The patient is of German heritage, an athlete, and has no significant past medical history. The patient has not had diarrhea or syncope-like episodes, or any other mast cell mediator symptoms. There is no organomegaly. At laparotomy, a tumor involving the small intestine was identified and resected. The tumor was comprised of spindle cells, which expressed CD117 and lacked expression for tryptase, desmin, S-100 protein, and smooth muscle actin. A diagnosis of gastrointestinal stromal tumor (GIST) was rendered. Per history, the GIST was low risk and completely excised. Post-operative imaging studies identified lytic bone lesions involving ribs and the right iliac crest. The latter was biopsied and showed hematopoietic elements with nodules of mast cells. Subsequently, a bone marrow biopsy was performed.
Details of gross/microscopic pathology:
The CBC and peripheral blood smear were normal. The aspirate, clot section, and biopsy all showed erythroid and granulocytic precursors and megakaryocytes to be normal in number (50% cellularity) and cytology. Multifocal, sharply demarcated nodules of spindle and oval-shaped mast cells were present and comprised 10% of the marrow cellularity.
Immunophenotype (flow cytometry/immunohistochemistry):
The mast cells expressed CD117 and tryptase and according to an outside pathology report, also expressed CD25, but lacked expression for CD2 (slides not available for review).
Cytogenetics:
Conventional cytogenetics was performed on the bone marrow aspirate at an outside laboratory, which reported a normal male karyotype, 46, XY[20].
Molecular analysis:
c-kit V560G (exon 11) and D816V (exon 17) mutation analysis by PCR was performed on the paraffin-embedded bone marrow clot (lesional tissue) and GIST. Amplicons were directly sequenced using an ABI 377 Prism DNA sequencer. The GIST showed a V560G (exon 11) mutation, which was not identified in the marrow. Neither tissue sample showed a D816V mutation.
Interesting feature(s) of submitted case:
The patient has two separate c-kit associated tumors. At least two kindreds with familial GIST and mastocytosis have been reported. Both showed germline c-kit mutations, one involving exon 8, affecting the extracellular domain, and the second involving exon 11, the juxtamembrane domain. The current patient showed a V560G (exon 11) mutation in the GIST, which was not identified in the marrow. Neither tissue sample showed a D816V (exon 17) mutation. We speculate this patient has an additional, as yet unidentified, germline c-kit mutation, with development of both systemic mastocytosis and GIST. We also consider the possibility of a false negative assay on the bone marrow lesional tissue.
Proposed diagnosis:
Concurrent GIST and indolent systemic mastocytosis, the relationship of which is unknown.
Panel diagnosis:
agree with proposed diagnosis
Comments:
Studies performed by the panel: no amplification for c-kit, CD25+
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