Discussion
In this case report, the patient was diagnosed with BPDCN arising from MDS/MPN-RS-T that progressed into clinical TLS immediately after the initiation of chemotherapy. Majority of patients with MDS/MPN-RS-T have a SF3B1 mutation [7]. Although SF3B1 mutations were not examined in this case, morphologically apparent dysplasia and the presence of ringed sideroblasts strongly supported the diagnosis of MDS/MPN-RS-T. On the other hand, while there is one case report about a patient with MDS/MPN-RS-T that was positive for both CALR andSF3B1 gene mutations [8], BPDCN with CALR mutation has not yet been reported to the best of our knowledge. Therefore, in this case, MDS/MPN-RS-T might already have been accompanied with CALRmutation.
TdT negativity was reportedly associated with inferior survival in BPDCN [9]; however, whether the aggressive clinical course observed in this case was typical for TdT-negative BPDCN remains unknown. Conversely, majority of patients with BPDCN expressing cMyc were reportedly accompanied by 8q24 rearrangement, immunoblastoid morphology, and skin lesions [10]. Although 8q24 rearrangement was not examined in this case, the patient had no skin lesions and his blasts showed classic cytomorphology, which suggested that his clinical features were not typical for MYC-positive BPDCN.
Previous studies showed that BPDCN with leukemic presentation without skin manifestation rarely occurs and tends to present with cytopenia rather than leukocytosis [11]. However, although the patient had leukemia at diagnosis, it was not accompanied with skin lesions and showed very high WBC count, suggesting it to be a very rare case. Moreover, rapid increase in WBC counts and massive splenomegaly indicated a very high tumor burden and rapid tumor growth. The SMILE regimen was selected because it was effective for ANKL [12] and the etoposide contained in SMILE regimen was also effective for BPDCN [13]. Although occurrence of TLS was cautiously considered in spite of low Ki67 index and enough hydration and febuxostat were provided to the patient for the prevention of TLS, he developed fatal TLS. More rigorous management including the early use of rasburicase and induction of hemodialysis is required.
Although the risk prediction of TLS in BPDCN is difficult because of the rarity and heterogeneity of this disease, the evaluation of peripheral blood WBC counts and serum LDH concentration may be useful for risk classification of TLS in BPDCN as in acute leukemia [14].
In conclusion, BPDCN shows clinically heterogeneous characteristics, and patients with clinical symptoms suggesting an aggressive clinical course with high tumor burden, including high WBC count or splenomegaly, should be carefully considered to prevent TLS.
Financial disclosure statement: The authors have nothing to disclose.
Conflict of Interest: There are no conflicts of interest to report.
Author Contribution: KS selected the patient and designed the manuscript. KS, MI, NF, and AK wrote the manuscript. RF performed the immunohistochemistry. All the authors reviewed the paper and agreed with the final version.