Case Presentation
A 63-year-old man previously diagnosed with MDS/MPN-RS-T 6 years before the presentation was referred to our hospital for rapid progression of leukocytosis and anemia. Physical examination and computed tomography revealed splenomegaly and inguinal lymphadenopathy without skin involvement (Fig. 1 A, B). He did not have fever and had a performance status of 2 according to the Eastern Cooperative Oncology Group score. Blood examination showed the following abnormalities: white blood cell (WBC) count, 44.8 × 109/L with 88% blasts; hemoglobin, 5.5 g/dL; platelet count, 17.0 × 109/L; and serum lactate dehydrogenase (LDH), 300 IU/L. Genetic analyses of his peripheral blood cells detected type 1 CALR mutation without Janus kinase 2 mutation. Severe hypercellular marrow occupied by agranular blasts with small cytoplasm and fine chromatin were detected in the bone marrow aspiration (Fig. 1 C, D), and bone marrow biopsy showed severe myelofibrosis (MF-3) (Fig.1 E). Flow cytometry revealed that blasts expressed CD4, CD7, CD56, and HLA-DR without other myeloid and lymphoid markers. Similar blasts occupied the inguinal lymph node, which suggested lymph node involvement. Based on these results, the patient was suspected to have aggressive NK cell leukemia (ANKL), acute leukemia with ambiguous lineage, or BPDCN.
Due to rapidly increasing WBC count of 106 × 109/L and worsening malaise, the dose-reduced SMILE regimen without methotrexate which contained etoposide 70mg/m2 day1–3, ifosfamide 1050mg/m2 day1–3, dexamethasone 30mg/body day1–3, and L-asparaginase 4000U/m2 day7, 9, 11, 13, 15, 17, 19 was immediately initiated without accurate diagnosis [6]. More than 3 L/day of intravenous hydration and 60 mg/day of febuxostat were administered as prophylaxis for tumor lysis syndrome (TLS). Then, immunohistochemistry demonstrated that blasts were positive for CD123, TCL-1, and CD303, and thus, he was diagnosed with BPDCN (Fig. 2). In addition, blasts were positive for cMyc and Bcl-2 and negative for TdT, with relatively low Ki67 index (Fig. 2). Cytogenetic analysis revealed normal karyotype of blasts. The urine volume after initiating the chemotherapy was 3,000 mL/day, and his condition improved that he could eat a meal the next day. However, his urine volume suddenly decreased, and his condition worsened again on the third day. WBC count immediately decreased; uric acid, potassium, and phosphorus concentrations increased; calcium concentration decreased with rapid increase in serum creatinine concentration, suggesting a clinical TLS (Table 1). Despite the intensive treatment such as aggressive hydration with noradrenaline administration to restore circulation and bicarbonate to correct metabolic acidosis, he finally died of circulatory failure. Autopsy revealed massive ascites and alveolar hemorrhage, whereas majority of malignant cells were not found.