Rapidly progressed Natural Killer/ T cell Lymphoma with hyperleukocytosis and NOTCH4 mutation but without Epstein-Barr virus infection:A case report

Background: Natural killer/T-cell lymphoma(NKTCL) is a highly aggressive non-Hodgkin's lymphoma that is prevalent in Asia and South America. However, given the high malignancy grade, rapid clinical progress and poor long‐term prognosis of NKTCL, exploring the potential mechanism of NKTCL is of great significance for the development of drugs for NKTCL. Case presentation: We presented a case of a woman who was admitted to hospital with multiple enlarged lymph nodes and high white blood cells,and flow cytometry examination revealed CD56 bright, CD16 dim, surface CD3-, cytoplasmic CD3+, CD2+, CD7-, HLA-DR+, CD57-, TCRβ and TCRγ genes rearrangement. No further pathological diagnosis was made because the patient's condition did not meet the need for biopsy, deteriorated rapidly and died within three days after admission; NKTCL was diagnosed based on clinical manifestations. Whole exome sequencing revealed that the NOTCH4, KMT2D, and S100A16 mutations were closely related to the occurrence and progression of NKTCL. In addition, this patient was EBV-negative. Conclusions: We mainly diagnosed NKTCL by exclusion, and the pathogenesis is complex or not limited to EBV. The discovery of new mutant genes will provide potential impact on clinical diagnosis and research guidance for its pathogenesis, prognosis, drug resistance and targeted therapy.