[1256] Myelomastocytic Leukemia: A Clinical, Pathologic, and Molecular Genetic Study

A McGuire, LR Shier, J Gotlib, B Medeiros, K Wong, C Corless, DA Arber, TI George. Stanford University, Stanford, CA; University of Alberta, Edmonton, AB, Canada; Stanford, Stanford, CA; Oregon State Health Sciences, Portland, OR

Background: Myelomastocytic leukemia (MML) is a rare and recently recognized neoplasm described as involving 2 distinct, but related populations, myeloid and mastocytic. The rare and unusual nature of MML makes diagnosis difficult, with little data to direct its management. This case series is presented to improve diagnosis of this rare leukemia.
Design: We describe 3 cases of MML retrospectively collected from the Pathology Dept at Stanford which did not meet diagnostic criteria for other mast cell disorders. Immunohistochemistry, flow cytometry and cytogenetics were performed using standard techniques. Allele specific PCR was performed for KIT mutations.
Results: Case 1: 64 yo man with AML t(8;21). After induction, a diffuse mast cell infiltrate (20%) was found expressing CD117+, tryptase+, CD25-. PCR found the imatinib sensitive N822K KIT mutation. The patient relapsed with AML 9 mo after complete remission with cytarabine consolidation + imatinib. Case 2: 61 yo woman with pancytopenia. She was refractory to multiple regimens (standard chemotherapy, cladribine, and imatinib + prednisone). Her marrow was diffusely infiltrated by tryptase+, CD117+, CD25- immature mast cells (90%) and bizarre multinucleated mast cells. Karyotype was normal. Initial sample could not be amplified; a second sample 1 mo later was D816V KIT mutation negative. The patient expired 5 mo after diagnosis. Case 3: 35 yo woman with urticaria treated with antihistamines/prednisone, who later presented with pancytopenia. Marrow was diffusely infiltrated by immature mast cells (50%) expressing tryptase+, CD117+, CD25+. A second blast population expressed dim CD117+, MPO+, CD34-. D816V KIT mutation was negative with normal cytogenetics. The patient received cladribine with progressive disease and expired.
Conclusions: All patients showed diffuse marrow infiltrates by immature mast cells lacking the D816V KIT mutation, with an aggressive course refractory to chemotherapy. Findings not previously reported included CD25 expression in mast cells, bizarre multinucleated mast cells, lack of a myeloid neoplasm and the N822K KIT mutation. Previous reports have shown favorable responses to polychemotherapy and marrow transplant suggesting MML should be treated similarly to AML rather than as a systemic mast cell disease. Further study of MML is needed.
Category: Hematopathology

Wednesday, March 11, 2009 1:00 PM

Poster Session VI # 203, Wednesday Afternoon