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.