De novo Leukemic Variant of Mast Cell Leukemia With KIT D816V

Mast cell leukemia (MCL), a highly aggressive form of systemic mastocytosis, accounts for less than 1% of all cases [1]. It is diagnosed on the basis of the criteria for systemic mastocytosis proposed by the WHO and the presence of at least 20% atypical mast cells of all bone marrow (BM) cells [2]. Here, we present a case of de novo leukemic variant of MCL with KIT D816V; to our knowledge, this is the first report of de novo leukemic variant of MCL in Korea. A 47-yr-old man presented with fever, cough, sputum, diarrhea, and abdominal pain of one-month duration. A complete blood count revealed Hb, 11.4 g/dL; leukocyte count, 3.4×10/L; absolute neutrophil count, 1.2 ×10/L; and platelet count, 44×10/L. Peripheral blood (PB) smear revealed leukoerythroblastosis with 26% abnormal cells, which were found, by immunophenotyping, to have originated from the mast cell lineage. Atypical mast cells displayed various morphological abnormalities (Fig. 1A-F). BM aspirate smears showed ungranulated blasts (12.9%), metachromatic blasts (10.1%), promastocytes (5.9%), and atypical, spindle-shaped mast cells (15.7%) (Fig. 1G). The blasts were negative for myeloperoxidase, periodic acid-Schiff, and α-naphthyl acetate esterase stains. The BM was hypercellular (80%), showing diffuse and interstitial infiltration of spindleshaped cells (Fig. 1H). Immunohistochemistry indicated that immature cells were positive for CD117 (Fig. 1I) and CD68 (Fig. 1J). PB and BM specimens were positive for CD13, CD33, CD117, CD25 (PB), and CD203c (PB), whereas they were negative for CD2 (PB) (Fig. 2A), as determined by flow cytometry immunophenotyping. FISH analysis with BCR/ABL, PML/RARA, RUNX1/RUNX1T1, CBFB-BAF, D7S486/CEP7 probes showed normal findings. Chromosome analysis of BM showed a normal male karyotype. KIT D816V mutation was identified by PCR and direct sequencing of the gene in exons 8, 10, 11, 12, 13, and 17 (Fig. 2B). Based on these results, the patient was diagnosed as having a de novo leukemic variant of MCL. The major challenge lay in determining whether the abnormal cells, including metachromatic atypical cells and granulated or ungranulated blasts, originated from the mast cell lineage cells. Both basophil and mast cell lineages stem from a common progenitor, basophil/mast cell progenitor (BMCP), which expresses ectonucleotide pyrophosphatase/phosphodiesterase-3 (ENPP3; CD203c) [3]. By using flow cytometry immunophenotyping, most abnormal cells were found to simultaneously express CD203c and CD25, indicating that they were neoplastic mast cells. Aberrant expression of CD25 and/or CD2 by mast cells in blood or BM is a criterion for the diagnosis of systemic mastocytosis [4]. The CD25/CD2 immunophenotype shown in this case is a rare occurrence. In a study that reviewed 51 MCL cases, CD25 and CD2 expressions varied, with CD25/CD2