脑膜淋巴瘤的临床脑脊液细胞学研究

Leptomeningeal lymphoma:cytological study of cerebrospinal fluid

目的探讨脑脊液细胞学、免疫细胞化学和流式细胞分析在脑膜淋巴瘤诊断中的灵敏性和特异性。方法13例诊断为脑膜淋巴瘤的患者，其中原发性中枢神经系统淋巴瘤5例，均为非霍奇金淋巴瘤B细胞型（NHL-B）；继发性8例，包括NHL-B6例，非霍奇金淋巴瘤T细胞型（NHL-T）1例，mantle型1例。神经系统表现为头痛、视乳头水肿、脑脊膜刺激征、脊髓腰骶神经根受累和多脑神经麻痹等。腰穿脑脊液压力升高，细胞计数、蛋白均升高，糖减低。所有患者均采用沉淀池法，免疫细胞化学单克隆抗体CD19、CD20、CD79a、CD34和免疫球蛋白轻链等；其中3例脑脊液进行淋巴细胞亚群流式细胞分析。以4例病毒性脑炎和5例炎性脱髓鞘病患者的脑脊液为对照。结果脑脊液细胞学发现每例患者均有淋巴瘤细胞或异型淋巴细胞。免疫细胞化学发现5例患者多数细胞B细胞标记物阳性；例6多数细胞CD34阳性；例8CD20阳性细胞比例升高；例7CD19、CD20阴性。除例8外，其余脑脊液中细胞呈CD4和CD8阴性或极少数阳性。对照组CD4阳性细胞为主，伴有少量CD8阳性细胞，CD19和CD20阴性或极少数阳性。脑脊液流式细胞分析发现例9和例11的B淋巴细胞占85．9％～97．4％，提示异常的B细胞克隆。对照组以CD4、CD8阳性细胞为主，CD19阳性细胞低于4．0％。结论脑脊液细胞学和免疫细胞化学是诊断脑膜淋巴瘤的重要方法，脑脊液淋巴细胞亚群的流式分析能够对诊断脑膜淋巴瘤有所帮助。

Objective To explore the delicacy and differential of sophisticated scans and routine cytological methods to examine cerebrospinal fluid （CSF） in diagnosis of primary central nervous system lymphoma （PCNSL） with meningeal involvement. Methods We described 13 patients who presented with a neoplastic meningitis of lymphomatous origin, including 5 cases of PCNSL （all NHL-B）; 8 cases of secondary leptomeningeal lymphoma （6 of NHL-B, 1 of NHL-T, 1 of mantle type）. Conventional cytology, immunocytochemistry and flow cytometric immunophenotypic analysis （FCA） of CSF were performed. The relevant literature on the subject was reviewed as welL Results All CSFs of the 13 patients had a number of blast cells or atypical lymphocyte, suspected of lymphoma on conventional cytology. Of the 8 patients performed the immunocytochemical studies of the CSF lymphocytes, 6 showed monoclonal B-lymphocytes with minor T-lymphocytes, consistent with a malignant lymphoprolfferation. On FCA, 4 samples of 2 cases showed a significant increase in the percentage of CD19 positive B cells （85.9%～97.4% of the total lymphocyte population） and a significant decrease in the percentage of T cells, indicating B cell lymphoma when compared with the control, namely CSF of viral meningitis, which showed dominant T cell reaction. Conclusions Cytology, immunocytochemistry and FCA are useful in the diagnosis of leptomeningeal lymphoma. Primary leptomeningeal lymphoma is an unusual form of neurologic lymphoma. The importance of cytological and immunocytochemical studies of the CSF in the cases suspected of CNS lymphoma should bestressed.