Myeloid/NK cell acute leukemia with unique blast morphology: de novo or secondary leukemia?

Abstract

Immature-type natural killer (NK) cell leukemia is rare and heterogeneous, and is variously classified as myeloid/NK cell precursor acute leukemia, myeloid/NK cell acute leukemia, or blastic NK cell lymphoma/leukemia [1–3]. Scott et al. [1] first described 20 cases of adult de novo acute myeloid leukemia showing a CD16/CD33/CD34/ CD56/HLA-DR phenotype. A few additional cases have since been reported, including that presented in this journal [4]. However, Suzuki et al. [2, 3] characterized myeloid/ NK cell precursor acute leukemia as a distinct entity, with a CD7/CD56/CD34/HLA-DR phenotype. Thus, myeloid/NK cell leukemia showing the CD7/CD56/ CD34/HLA-DR phenotype is considered to be more mature than myeloid/NK cell precursor leukemia [3]. Here, we report a case of myeloid/NK cell acute leukemia developing after chemoradiotherapy and with morphologically distinct characteristics. In March 2013, a 63-year-old man presented with poor appetite, lassitude, chest pain, and ophthalmic pain. He had undergone chemoradiotherapy (irradiation with 69.6 Gy/37 Fr and chemotherapy with cumulative doses of 280 mg/body carboplatin and 4,000 mg/body 5FU) for hypopharyngeal squamous cell carcinoma 5 months before referral. His complaints resolved gradually within 1 month; however, he developed anemia (Hb, 7.3 g/dL), thrombocytopenia (platelet count, 36 k/lL), and high lactate dehydrogenase (LDH, 836 IU/ L) in early April 2013. His condition rapidly deteriorated thereafter and he suffered respiratory distress and hepatic/ renal failure. There were no skin lesions, lymphadenopathy, or hepatosplenomegaly. No symptoms suspecting CNS disease were present. Repeat transfusions of red blood cells and platelets were performed. Blood analysis showed the following: white blood cell counts, 3,100/lL (5 % abnormal cells); Hb, 8.7 g/dL; platelet count, 63 K/lL; serum CRP, 2.89 mg/dL; aspartate aminotransferase (AST, 4,169 IU/L); alanine aminotransferase (ALT, 1,191 IU/L); LDH, 6,014 IU/L; total bilirubin, 6.2 mg/dL; direct bilirubin, 4.3 mg/dL; ferritin, 1,036 ng/mL; BUN, 48.2 mg/ dL; creatinine, 3.51 mg/dL; and uric acid, 19.6 mg/dL. The patient then developed coagulopathy, with a plasma D-dimer 2.7 lg/mL (normal \1.0 lg/mL), fibrinogen 140 mg/dL (normal 146–380 mg/dL) and antithrombin-III level of 33 % (normal 80–125 %). The bone marrow smear was cellular and showed 77 % blasts, which possessed round or oval nuclei with prominent nucleoli and a deeply stained cytoplasm with protrusions (mimicking plasmacytoid/megakaryoblastoid cells), some of which (6 %) showed weak staining for myeloperoxidase but stained negative for Periodic Acid-Schiff and iron. There were no azurophilic granules. In addition, we noted very large fishshaped blasts containing numerous nucleoli, large cells with mitotic figures, and unevenly divided binuclear blasts (Fig. 1a–d), Flow cytometry showed that bone marrow blasts were CD33 (80 %)/CD56 (96 %) but CD4 (\5 %)/CD7 (\5 %)/CD13 (\5 %)/CD34 (\5 %)/ CD41 (\5 %)/CD61 (\5 %) and HLA-DR (\5 %). Thus, the diagnosis of myeloid/NK cell leukemia was S. Imashuku (&) N. Kudo Division of Hematology, Takasago-seibu Hospital, 1-10-41 Nakasuji, Takasago 676-0812, Japan e-mail: shinim95@mbox.kyoto-inet.or.jp