A Case of Systemic Mastocytosis Associated with Acute Myeloid Leukemia Terminating as Aleukemic Mast Cell Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation
A 40-yr-old Korean man presented with dyspnea on exertion. In the peripheral blood (PB), the white blood cell (WBC) count was 5×109/L and consisted of 68% myeloblasts and no mast cells. The bone marrow (BM) was hypercellular and included 90.4% typical myeloblasts and no mast cells. The karyotype was 45,X,-Y,t(8;21)(q22;q22). He was diagnosed with AML with t(8;21)(q22;q22) according to the WHO criteria []. He received 1 cycle of combination chemotherapy with idarubicin and cytosine arabinoside and 2 cycles of high-dose chemotherapy with cytosine arabinoside within a period of 5 months. At the end of the first cycle of chemotherapy, complete remission of AML was achieved. The sequential high-dose chemotherapy cycle was complicated with intracranial hemorrhage and severe sepsis, but the patient recovered without any sequelae.\nEight months after the diagnosis, the patient relapsed with clonal evolution. The karyotype was 45,X,-Y,t(8;21)(q22;q22), del(17)(p11.2). In spite of salvage chemotherapy, hematological remission was not achieved. PB showed pancytopenia with WBC count of 1.9×109/L, hemoglobin of 10.6 g/dL, and platelet count of 28×109/L. The differential count showed 16% myeloblasts and 1% circulating immature mast cells. BM aspirate smear showed 31.2% myeloblasts and 5.8% immature mast cells. The myeloblasts showed medium-sized, oval- to irregular-shaped nuclei, prominent nucleoli, and scant basophilic cytoplasm (). Flow cytometric immunophenotyping showed that the leukemic myeloblasts expressed CD34, HLA-DR, CD13, CD33, CD117, CD65, CD15, and CD56, but lacked CD2 (). BM trephine biopsy revealed persistent leukemic myeloblasts and interstitial infiltration of mast cells. Immunohistochemically, these mast cells were positive for tryptase and CD25 (). Reverse transcriptase (RT)-PCR of the BM aspirate showed RUNX1-RUNX1T1 fusion transcript and KIT mutation at codon 816. The patient was diagnosed with SM-AML with t(8;21)(q22;q22).\nHe received HSCT from a HLA-haploidentical donor. The conditioning regimen included busulfan and fludarabine. Twenty-nine days after HSCT, the patient's PB WBC count was 0.8×109/L with 17% metachromatic blasts. BM aspirates also contained metachromatic blasts (62.4%) showing a high nuclear-to-cytoplasmic (N/C) ratio, immature nuclear chromatin, inconspicuous nucleoli, and several metachromatic granules (). Metachromatic blasts infiltrated as interstitial type and focally aggregated in a BM biopsy specimen ().\nOn day 49 after HSCT, pancytopenia worsened, with WBC count of 0.2×109/L, hemoglobin of 8.7 g/dL, and platelet count of 11×109/L; however, myeloblasts or mast cells were not seen in the PB. Instead of them, atypical mast cells (type II) constituted 69.2% of all nucleated cells in a BM aspirate smear () [] and were compactly infiltrated in a BM biopsy sample (). Leukemic myeloblasts were not seen in the BM aspirate smear. On flow cytometric analysis, these atypical mast cells expressed CD13, CD33, CD117, CD25, and CD56, but lacked CD34 and HLA-DR, which were expressed strongly at relapse (). The karyotype was 45,X,-Y,t(8;21)(q22;q22),del (17)(p11.2)[5]//46,XX[15]. FISH using a Vysis RUNX1/RUNX1T1 Dual Color, Dual Fusion Translocation Probe (Abbott Laboratories, Abbott Park, IL, USA) revealed RUNX1-RUNX1T1 rearrangement as nuc ish(RUNX1T1, RUNX1)x3(RUNX1T1 con RUNX1x2)[58/100] (). The atypical mast cells also showed a RUNX1-RUNX1T1 fusion transcript and a KIT 816 mutation on RT-PCR. At this time, the patient was diagnosed with aleukemic mast cell leukemia.\nHe died 4 months after HSCT because of a new intracranial hemorrhage.