Objective: To investigate the clinicopathologic characteristics, diagnosis and therapy of aggressive natural killer cell leukemia (ANKL) patients.
Methods: Clinical manifestations, cellular morphology, immunophenotypic analysis by flow cytometry (FCM), TCR gene rearrangement, pathology and Immunohistochemical analysis of bone marrow (BM) were combined to diagnose the six patients with ANKL.
Results: The median age of the patients were 35.5 years old. All the patients with fever, cytopenia and liver dysfunction. Imageological examination presented hepatosplenomegaly (6/6), and PET/CT presented diffusely increased metabolism in liver, spleen and BM (3/3). BM cytologic examination presented increased hematophagocyte at the early stage and 1%-42% leukemic cell were detected in BM with the progression of diseases. FCM showed the leukemic cells were positive for CD2(6/6), CD56(5/6), CD16(2/6), CD94(3/6), CD38(3/6), cCD3(1/5), CD8(1/6), CD7(2/6), CD57(1/6) and negative for CD3, CD4, TdT, cMPO, TCR α/β, TCR γ/δ. The neoplastic cells were negative for TCR gene rearrangement. Five cases showed increased quantitation of whole blood Epstein-Barr virus (EBV) DNA.
Conclusion: ANKL is a highly aggressive disease. Prompt and repeating BM examination is important to patient with fever, cytopenia and liver dysfunction. The diagnosis of ANKL relies mainly on the integration of clinical, morphologic, immunophenotypic finding and EBV-DNA increasement.
题目: 侵袭性自然杀伤细胞白血病患者的临床病理特点.
目的: 研究侵袭性自然杀伤细胞白血病（aggressive natural killer cell leukemia，ANKL）患者的临床病理特点及诊断、治疗方法.
方法: 联合应用外周血和骨髓细胞形态学、流式细胞学（FCM）、TCR基因重排、骨髓活检病理学和免疫组织化学方法诊断6例ANKL患者.
结果: 6例ANKL患者的中位年龄35.5岁，以发热、血细胞减少和肝功能异常为主要表现。影像学检查示肝脾肿大，3例PET/CT检查发现肝脾和骨髓弥漫性代谢增高。疾病初期的骨髓细胞学检查以噬血细胞增多为特点，随病程进展，骨髓中可检出1%-42%的淋巴瘤细胞，FCM分型结果显示，淋巴瘤细胞CD2+CD56+(5/6)或CD2+CD16+(3/6)，及CD3-CD4-TdT-cMPO-， TCR α/β-, TCR γ/δ-，多重PCR检测TCR基因重排阴性。5例患者外周血EBV-DNA定量均明显升高。疾病进展迅速，患者多在确诊后短期内因原发病进展死亡.
结论: ANKL侵袭性强，疾病进展快，对以发热、血细胞减少和肝功能异常为主要表现的患者，及时并反复行骨髓细胞学及FCM分型检查是主要诊断方法.