Hu Yang, Chen Yan, Wang Li-Hua, Chen Xue, Fang Fang, Liu Shi-Qin, Wu Xue-Qiang, Zhu Ping
Department of Hematology, Peking University First Hospital, Beijing 100034, China.
Institute of Hematology and Oncology, Beijing Aerospace General Hospital, Beijing 100076, China.
Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2014 Apr;22(2):349-56. doi: 10.7534/j.issn.1009-2137.2014.02.016.
The splenic marginal zone lymphoma (SMZL) is a relatively rare chronic B lymphoproliferative disease, which primarily manifest increase of peripheral blood lymphocyte count and/or scale, and splenomegaly, while the peripheral superficial lymph nodes are often not swollen. Therefore, the splenectomy are usually needed to confirm the diagnosis, but the majority of patients could not accept such management, resulting in early difficult diagnosis. This study was purposed to explore the more prior way for diagnosis based flow cytometry (FCM). Six patients with suspected diagnosis of SMZL were used as research objects, 10 healthy bone marrow donors and 10 cases of chronic lymphocytic leukemia (CLL), 3 cases of hairy cell leukemia (HCL), 3 cases of lymphatic plasma cell lymphoma/Waldenströ's macroglobulinemia (LPL/WM) were selected as control. The immunophenotype of bone marrow cells were analyzed and compared by FCM using a panel of antibodies including CD45, CD5, CD10, CD19, CD20, CD22, CD23, CD25, CD103, CD11c, CD123, κ,λ, Cyclin D1, and combined with bone marrow cell morphology. The results indicated that 6 cases of suspected SMZL showed a large increase of lymphocytes and splenomegaly. Because absence of peripheral lymphadenopathy, 6 patients did not suffer from lymph node biopsy, only 1 patient underwent diagnostic splenectomy. The immunophenotypes of bone marrow in patients and controls were analyzed by FCM, as a result, except for the healthy donors, varying degrees of abnormal mature B cell clones were found in bone marrow of all patients, and the further differentiation from other B-cell tumors was performed through CD5, CD10 expression and combination with other B-cell phenotype. All 6 cases of SMZL patients expressed CD19(+) and CD20(+), but CD10 expression was negative, 4 patients expressed CD5(-), 2 patients expressed CD5(+). The expressions of CD23, CD38, ZAP-70, CD11c, CD103, CD123, Cyclin D1 were negative. The morphological examination of bone marrow cells showed velutinous abnormal lymphocytes. Combined with clinical characteristics, 6 patients were diagnosed as SMZL, 1 patient suffered from splenectomy because of concurrent hypersplenism, and this postoperative pathologic examination confirmed the patient with SMZL. Ten cases of CLL mainly expressed CD5, CD23; 3 cases of HCL had more typical morphology of "hair like" in addition to CD11c, CD103 and CD123 positive; 3 cases of LPL/WM had significantly increased light chain restriction expression, IgM, plasmacytoid lymphocytes. It is concluded that the FCM immunophenotype analysis can be used as a powerful tools for clinical diagnosis of SMZL.
脾边缘区淋巴瘤(SMZL)是一种相对罕见的慢性B淋巴细胞增殖性疾病,主要表现为外周血淋巴细胞计数和/或比例增加以及脾肿大,而外周浅表淋巴结通常不肿大。因此,通常需要进行脾切除术来确诊,但大多数患者无法接受这种治疗方式,导致早期诊断困难。本研究旨在探索基于流式细胞术(FCM)的更优先诊断方法。选取6例疑似SMZL患者作为研究对象,选取10名健康骨髓供者以及10例慢性淋巴细胞白血病(CLL)、3例毛细胞白血病(HCL)、3例淋巴浆细胞淋巴瘤/华氏巨球蛋白血症(LPL/WM)患者作为对照。使用包括CD45、CD5、CD10、CD19、CD20、CD22、CD23、CD25、CD103、CD11c、CD123、κ、λ、细胞周期蛋白D1在内的一组抗体,通过FCM分析并比较骨髓细胞的免疫表型,并结合骨髓细胞形态学。结果显示,6例疑似SMZL患者表现为淋巴细胞大量增加和脾肿大。由于无外周淋巴结肿大,6例患者未进行淋巴结活检,仅1例患者接受了诊断性脾切除术。通过FCM分析患者和对照的骨髓免疫表型,结果显示,除健康供者外,所有患者骨髓中均发现不同程度的异常成熟B细胞克隆,并通过CD5、CD10表达以及与其他B细胞表型的组合进一步与其他B细胞肿瘤进行鉴别。6例SMZL患者均表达CD19(+)和CD20(+),但CD10表达为阴性,4例患者表达CD5(-),2例患者表达CD5(+)。CD23、CD38、ZAP-70、CD11c、CD103、CD123、细胞周期蛋白D1的表达均为阴性。骨髓细胞形态学检查显示有绒毛状异常淋巴细胞。结合临床特征,6例患者被诊断为SMZL,1例患者因并发脾功能亢进接受了脾切除术,术后病理检查证实该患者为SMZL。10例CLL主要表达CD5、CD23;3例HCL除CD11c、CD103和CD123阳性外,具有更典型的“毛发样”形态;3例LPL/WM轻链限制性表达、IgM、浆细胞样淋巴细胞明显增加。结论是,FCM免疫表型分析可作为SMZL临床诊断的有力工具。