Systemic Mastocytosis with Associated Clonal Hematological Non-Mast Cell Lineage Disorder (SM-AHNMD) Shows Distinct Hematologic Features and Reveals a Common Clonal Origin of Myeloid and Mast Cells
RN Miranda, G Tang, DM Jones, YO Huh, LJ Medeiros, SA Wang. M.D. Anderson Cancer Center, Houston, TX; University of Massachusetts, Worcester, MA
Background: Systemic mastocytosis (SM) is a clonal proliferation of mast cells with heterogeneous clinical manifestations. Cases of SM can be associated with other myeloid or lymphoid neoplasms (SM-AHNMD). We designed the current study to determine the clinicopathologic characteristics that should raise the suspicion of SM-AHNMD in cases of SM and to analyze clonal relationships between mast cells and myeloid cells in cases of SM-AHNMD.
Design: We reviewed clinicopathologic and hematologic features of cases of SM-AHNMD diagnosed at two large institutions and compared with cases of SM alone (SM). Mast cells and myeloid cells of cases with cytogenetic abnormalities were analyzed by Visual FISH to determine clonal identity. Quantitative pyrosequencing and mutation specific quantitative PCR assay for detection of KIT codon 816 mutation was also compared.
Results: We identified 35 cases of SM-AHMND and 49 cases of SM, during the last 10 years. AHMND were classified as chronic myelomonocytic leukemia (n=9), B cell and plasma cell neoplasms (n=7), myelodysplastic syndrome (n=8), myeloproliferative neoplasm (n=5), acute myeloid leukemia (n=2) and hypereosinophilic leukemia (n=3) and one case of Fanconi's anemia. Karyotypic abnormalities were found in 9 (29%) AHMND cases. Compared with SM, patients with SM-AHMND showed a male predominance (p=0.003), older age (p=.006), lower hemoglobin (p<.0001), lower platelet count (p<.0001), higher serum tryptase level (p<.05), higher levels of mutated KIT (p<.04) and higher frequency of cytogenetic abnormalities (p<.0001). There was no difference in mast cell burden in bone marrow. Visual FISH analysis performed on two cases of SM-AHMND with +8, and one case with del(20)q showed identical cytogenetic abnormalities in mast cells and myeloid cells.
Conclusions: Patients with SM-AHNMD are often older and more often have severe cytopenias; these features should raise the suspicion for SM-AHNMD. Mutated KIT levels are higher in SM-AHNMD compared with SM, indicating that the coexistent hematological malignancy may harbor KIT mutation in addition to mast cells. The FISH results showing identical cytogenetic alterations in mast cells and myeloid cells of SM-AHNMD support a common origin, probably from a pluripotent hematopoietic stem cell.
Tuesday, March 23, 2010 8:30 AM
Platform Session: Section B, Tuesday Morning