伴侵袭性临床特征的双表型 NK-大颗粒淋巴细胞白血病：病例报告及文献综述

Natural killer large granular lymphocytic leukemia (NK-LGLL) is a rare and typically indolent lymphoproliferative disorder characterized by clonal expansion of natural killer (NK) cells.

We report a case of a 49-year-old man presented with a four-month history of progressive fatigue that was, initially attributed to anemia who was diagnosed with an atypical manifestation of NK-LGLL with aggressive features including hepatosplenomegaly, hemophagocytic syndrome, and rapid disease progression. Initial clinical and morphological overlaps with aggressive NK-cell leukemia (ANKL) complicated the diagnosis.

However, through molecular profiling and Epstein-Barr virus DNA detection, NK-LGLL has been confirmed, underscoring the importance of genetic testing in resolving diagnostic uncertainties. The report also discusses the therapeutic challenges, as current treatments for NK-LGLL are not standardized, and conventional immunosuppressive therapies carry the risk of infections.

In the present case, treatment with the PI3K inhibitor linperlisib led to transient remission, suggesting its potential as a novel therapeutic approach. The drug was later discontinued due to infections, and the patient subsequently received a thalidomide-based regimen. At last follow-up, the patient remained clinically stable. This case emphasizes the diagnostic complexity of NK cell malignancies and advocates the integration of molecular insights into diagnostic and treatment strategies.

Further research into targeted therapies, including pathway-specific inhibitors, may enhance the management of aggressive NK-LGLL.