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Lee, Y. K.1; Lee, J.1; Kim, M.1; Park, J.-Y.2; Chung, Y.2; Kim, H. J.3; Han, B.3

doi: 10.1097/01.HS9.0000565252.61622.e3
Publication Only: Acute lymphoblastic leukemia - Clinical

1Department of Laboratory Medicine, Hallym University College of Medicine & Hallym University Sacred Heart Hospital, Anyang-si

2Department of Laboratory Medicine, Hallym University College of Medicine, Seoul

3Internal Medicine, Hallym University College of Medicine & Hallym University Sacred Heart Hospital, Anyang-si, Korea, Republic Of

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Natural killer (NK)-lymphoblastic leukemia/lymphoma is a rare hemopoietic neoplasm that was established as an independent entity by the WHO in 2008 and in 2016, it was recategorized as a precursor lymphoid neoplasm. Its identification remains challenging because its features overlap with those of other hematological malignancies, and markers specific to NK-cells such as CD94 and CD161 are not commonly tested. Owing to the disease's rarity, only 3 patients who meet the 2008 WHO criteria have been reported.

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We report the first Korean patient with NK-lymphoblastic leukemia/lymphoma including her NGS-based genetic profile and clinical course.

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A 51-year-old woman was referred to our institution with her WBC count 1.6 × 109/L, hemoglobin 11.9 g/dL, and platelet count 176 × 109/L. Peripheral blood smear showed a few abnormal-looking large lymphocytes, while BM aspirate showed decreased normal hemopoietic precursors and increased blasts (63.0%). The blasts were large and had a high nuclear/cytoplasmic ratio with agranular cytoplasm, nuclei with indentation, and conspicuous nucleoli. All were negative for peroxidase and Sudan Black B but some were positive for acid alpha-naphthyl acetate esterase. BM biopsy showed hypocellularity (10%) but increased immature cells that were positive for CD34 and terminal deoxynucleotidyl transferase (TdT) on immunohistochemistry (IHC). Flow cytometry showed that the majority of blasts were positive for HLA-DR, CD7, CD34, and CD56 but negative for myeloid antigens (CD13, CD33, CD14, CD117, myeloperoxidase), B-cell antigens (CD10, CD19, CD20, CD79a), and other T-cell antigens (CD2, cytoplasmic CD3, surface CD3, CD4, CD5, CD8). The BM karyotype was 46,XX,-7,del(7)(q35),add(11)(q24),-12,+1mar,+2mar[10]/46,XX[10]. Multiplex reverse-transcriptase PCR revealed negativity for all 28 tested leukemia-causing chromosomal translocations. Targeted next-generation sequencing of 54 genes, including BRAF, IKZF1, KRAS, MYD88, NRAS, and TP53, showed no oncogenic mutations; tests for TCRB, IGH, and IGK gene rearrangement showed no dominant clonotypes. Hence, she was diagnosed with NK-lymphoblastic leukemia/lymphoma. Physical and imaging examinations revealed no organomegaly, lymph node enlargement, or skin lesions. The patient underwent 3 cycles of fludarabine and cyclophosphamide for 2 months and has been stable for 6 months since her diagnosis.

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The blasts of our patient was positive for CD34, TdT, HLA-DR, CD7, and CD56 but not for other T-cell, B-cell, or myeloid markers; this ruled out T-acute lymphoblastic leukemia/lymphoma (T-ALL) and mixed-phenotype acute leukemia. The lack of specific TCR and IG clonotypes also ruled out T-ALL. The morphology of blasts and negativity for CD4 ruled out the possibility of blastic plasmacytoid dendritic cell neoplasm (BPDCN). Further analysis for CD4, CD56 and CD123 using IHC will be helpful to verify the differential diagnosis of NK-lymphoblastic leukemia/lymphoma from BPDCN.

Copyright © 2019 The Authors. Published by Wolters Kluwer Health Inc., on behalf of the European Hematology Association.