用流式细胞术从B淋巴增殖性疾病中鉴别脾边缘带淋巴瘤

脾边缘带淋巴瘤（Splenicmarginalzonelymphoma，SMZL）是一种相对少见的原发于脾脏的惰性B淋巴增殖性疾病，表现为外周血淋巴细胞计数和／或比例增高、脾大，而外周浅表淋巴结往往不大，需要应用诊断性脾切除病理检查得以确诊，但患者多数不能接受，早期诊断困难。本研究探索以流式细胞术（flowcytometry，FCM）为主的诊断途径的可行性。选取6例疑诊SMZL患者为研究对象，同时以10名骨髓健康供者及确诊的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）初诊患者为对照。对所有患者及对照组进行骨髓FCM免疫分型，所选抗体组合包括CD45、CD5、CD10、CD19、CD20、CD22、CD23、CD25、CD103、CD11c、CD123、κ、λ、CyclinD1等，同时结合骨髓细胞形态学检查。结果表明：6例疑诊sMzL患者表现为淋巴细胞增高和脾大。因外周淋巴结无肿大6例患者均未行淋巴结活检，仅1例患者行病理诊断性脾切除。经骨髓FCM免疫表型分析，除健康供者外均可发现骨髓中存在不同程度的异常成熟B细胞克隆，并通过CD5、CD10表达与否结合其他表型进一步与其他B细胞肿瘤鉴别。结果6例SMZL患者均CDl9＋、CD20＋，而CD10-，4例患者CD5-，2例CD5＋，而CD23、CD38、ZAP-70、CD11c、CD103、CD123、CyclinD1均不表达。骨髓细胞形态学检查可见有短绒毛的异常淋巴细胞，结合临床特征将6例患者诊断为SMZL。1例患者因合并脾功能亢进需要行脾切除，术后病理证实该病。10例CLL主要表达CD5、CD23之外；在3例HCL除表达CD11c、CD103、CD123，形态学上更有典型的”毛”；3例LPL／WM具有轻链限制性表达、IgM显著升高、浆样淋巴细胞增多的特点。结论：FCM免疫表型分析结合骨髓形态学可作为临床诊断SMZL有力的工具。

Identification of Splenic Marginal Zone Lymphoma from B Lym- phoproliferative Disorders by Flow Cytometry

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 pe- ripheral superficial lymph nodes are often not swollen. Therefore, the splenectomy are usually needed to confirm the di- agnosis, 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 eytometry （FCM）. Six patients with suspected di- agnosis of SMZL were used as research objects, 10 healthy bone marrow donors and 10 cases of chronic lymphocytic leu- kemia （CLL）, 3 eases of hairy cell leukemia （HCL）, 3 cases of lymphatic plasma cell lymphoma/Waldenstrtm＇s mae- roglobulinemia （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, CD11 c,CD123, K, h, Cyclin D1, and combined with bone marrow cell morphology. The results indicated that 6 cases of suspected SMZL showed a large increase of lymphoeytes and splenomegaly. Because absence of peripheral lymphadenop- athy, 6 patients did not suffer from lymph node biopsy, only 1 patient underwent diagnostic spleneetomy. The immuno- phenotypes 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 differentia- tion from other B-cell tumors was performed through CD5, CD10 expression and combination with other B-cell pheno- type. All 6 cases of SMZL patients expressed CD19 ＋ and CD20 ＋ , but CD10 expression was negative, 4 patients expre-sed CD5-, 2 patients expressed CD5 ＋. The expressions of CD23, CD38, ZAP-70, CDllc, 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 ＂ hairlike＂ in addition to CD1 l c, 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.