以类白血病反应为首发表现的慢性中性粒细胞白血病二例并文献复习

doi:10.16150/j.1671-2870.2020.02.005

摘要/Abstract

摘要：

目的：探讨慢性中性粒细胞白血病（chronic neutrophilic leukemia, CNL）的鉴别诊断及临床特征。方法：回顾性分析2例CNL患者的临床资料、骨髓形态学检查、病理活检及免疫组织化学标志特征,并结合国内外相关文献进行探讨。结果：2例CNL患者均为中老年男性,因白细胞计数升高就诊,外周血以成熟中性粒细胞为主,中性粒细胞碱性磷酸酶（neutrophil alkaline phosphatase, NAP）积分增高;骨髓中有核细胞增生明显活跃,伴中性分叶核粒细胞比例增高;BCR-ABL融合基因及JAK2 V617F基因突变均为阴性。例1患者经多次骨髓检查,且CSF3R T618I突变检测阳性后诊断为CNL,2年半年后其外周血象呈慢性粒-单核细胞白血病样改变,经3个月后因骨痛行胸椎切除术,病理检查提示粒细胞肉瘤,又经1个月后复查骨髓提示急性髓细胞性白血病,予地西他滨联合急性白血病标准方案诱导化疗,骨髓提示未缓解,该患者最终死于脑出血。例2患者经血常规及骨髓检查,考虑为类白血病反应,2年后因脾大加重伴贫血、血清单克隆性IgA-λ增高,复查骨髓提示CNL合并多发性骨髓病（multiple myeloma,MM）,予万珂为主方案化疗后,MM、CNL完全缓解。结论：CNL是一种极其罕见类型的慢性白血病,其可与其他血液肿瘤并存,同时存在向AML转化的高风险。以CSF3R基因突变为特征的分子诊断标准,有助于CNL的诊治。

关键词: 慢性中性粒细胞白血病, 类白血病反应, 急性髓细胞性白血病, 多发性骨髓瘤, 基因突变

Abstract:

Objective: To investigate the clinical characteristics and differential diagnosis of chronic neutrophil leukemia (CNL). Methods: The clinical data, characteristics of cell morphology, pathological and immunohistochemical features of bone marrow biopsy from 2 cases of CNL were retrospectively analyzed, and the relevant literatures were reviewed. Results: Both CNL patients were middle-aged male with leukocytosis as primary complaint. The peripheral blood examination revealed an elevated leukocyte counts with mostly mature neutrophils and increased neutrophil alkaline phosphatase (NAP) score. The proliferation of nucleated cells in bone marrow was significantly increased with higher proportion of neutral lobular granulocytes. Both patients were negative for BCR-ABL fusion gene and JAK2 V617F gene mutations. The case 1 was diagnosed as CNL with detection of CSF3R T618I mutation, and presented a feature of chronic myelomonocytic leukemia in the peripheral blood two and a half years later. The condition progressed rapidly thereafter. The granulocytic sarcoma was identified in thoracic vertebras 3 months later and the disease had transformed into acute myeloid leukemia in the 4^th month. The patient was not responsive to the standard chemotherapy regimen combined with Dicitabine, and eventually died of a cerebral hemorrhage. Case 2 was initially diagnosed as leukemia-like reaction, but suffered from massive splenomegaly, aggravation of anemia and increased serum monoclonal IgA-λ 2 years later. The repea-ted examination of bone marrow then showed CNL accompanied with multiple myeloma (MM). Case 2 achieved completely remission for both MM and CNL after chemotherapy with Vanke as the main regimen. Conclusion: CNL is an extremely rare type of chronic leukemia, with non-specific clinical manifestations and complicated prognosis. CNL may coexist with other hematologic neoplasms, and there is a high risk of conversion to AML. The molecular diagnosis standard characte-rized by CSF3R gene mutation is conductive to the diagnosis and treatment of CNL.

Key words: Chronic neutrophilic leukemia, Leukemia-like reaction, Acute myeloid leukemia, Multiple myeloma, Gene mutation

中图分类号:

R733.7

彭真萍, 项喜喜, 张苏江, 李佳明. 以类白血病反应为首发表现的慢性中性粒细胞白血病二例并文献复习[J]. 诊断学理论与实践, 2020, 19(02): 122-128.

PENG Zhenping, XIANG Xixi, ZHANG Sujiang, LI Jiaming. Chronic neutrophilic leukemia with leukemia-like reaction as the first-onset manifestation: a report of 2 cases and literature review[J]. Journal of Diagnostics Concepts & Practice, 2020, 19(02): 122-128.

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病程	样本类型	CSF3R T618I突变	CSF3R W818X突变	ASXL1 E657fs突变	RUNX1 R204Q突变
CNL初诊时	骨髓穿刺液	83.76%	82.87%	22.71%	3.97%
CNL转化为AML时	骨髓穿刺液	90.81%	83.77%	8%	41.38%
	椎弓组织蜡块	92.91%	92.91%	11.05%	43.49%