13例淋巴瘤合并周围神经病变临床分析

目的 对淋巴瘤合并周围神经病变的临床特点、辅助检查结果进行分析,并探讨其发病机制.方法 回顾分析13例淋巴瘤合并周围神经病变患者诊断、治疗经过,排除继发性带状疱疹病毒感染、相关治疗的不良反应及其他导致周围神经病变的病因.其中T细胞性非霍奇金淋巴瘤(NHL-T)3例,B细胞性非霍奇金淋巴瘤(NHL-B)9例,1例具体病理类型不详.对其周围神经受累的类型和部位、脑脊液细胞学和免疫组织化学、影像学、电生理学以及腓肠神经活体组织病理学检查结果等进行分析.结果 13例中10例周围神经系统症状出现于淋巴瘤明确诊断之前,其中8例以周围神经系统症状首发:11例脑神经受累,8例腰骶神经根受累,6例同时合并听力减退及腰骶神经根受累.脑脊液检查主要呈现蛋白定量(13例)、白细胞计数(8例)以及脑脊液压力(5例)升高,葡萄糖水平降低(7例);细胞学检查可见异型淋巴细胞(9例);免疫组织化学染色及基因重排检测主要表现为B细胞标记抗原(CD19、CD20、CD79α)阳性(3例),CD20阳性细胞数日增加(1例),以及CD4阳性细胞数目增加、T细胞(抗原识别)受体阳性和抗体IgH阴性(1例).肌电图检查显示,周围神经轴索病变或合并髓鞘损害(9例).腓肠神经活体组织病理学检查呈轴索变性和(或)脱髓鞘病变且无淋巴瘤细胞浸润(3例).头部及腰骶部MRI检查显示,双侧听神经及马尾神经根增粗、强化或脑膜强化.13例中9例系由淋巴瘤细胞直接浸润脑脊膜神经根所致,1例为淋巴瘤转移和局部肿大淋巴结压迫引起,其余3例无明确肿瘤细胞浸润证据,结合临床特点和实验室检查结果,考虑副肿瘤综合征可能.结论 淋巴瘤可通过肿瘤细胞直接浸润或副肿瘤综合征导致周围神经病变;周围神经系统症状在淋巴瘤明确诊断前即可出现,临床应对此提高认识.     

系统性淋巴瘤软脑膜转移的脑脊液细胞学分析

目的 探讨CSF细胞学及免疫细胞化学对系统性淋巴瘤软脑膜转移的诊断价值。方法 回顾性分析我院5例系统性淋巴瘤转移至软脑膜的病例,分析其CSF细胞学及免疫细胞化学特点。结果 5例患者中男性3例,女性2例,年龄14～74岁,平均年龄45岁。患者主要临床症状为头痛及恶心呕吐。此外,1例伴有发热,1例伴有脑神经损害,表现为眼肌麻痹。患者MRI扫描显示脑实质内均未发现异常信号,仅2例有脑膜强化。常规CSF细胞学显示5例CSF中均含有大量异型淋巴样细胞。免疫细胞化学显示4例CSF中CD20和/或CD79α阳性的异型细胞比例显著增加,这4例患者之前有脑外B细胞淋巴瘤病史;1例CSF中CD3阳性异型细胞为主。此患者随后发现了乳腺肿瘤,最终诊断为间变性大细胞淋巴瘤。5例CSF中异型细胞均与原发部位肿瘤细胞免疫表型一致,因此系统性淋巴瘤转移至软脑膜诊断明确。结论 CSF细胞学对系统性淋巴瘤的软脑膜转移诊断有重要意义,联合免疫细胞化学检测可进一步明确诊断。少数无系统性淋巴瘤病史的患者需要积极检查寻找原发肿瘤的起源和部位。     

脑膜癌病的脑脊液细胞学特征

目的 探讨脑膜癌病的脑脊液细胞学特征.方法 对4例脑膜癌病患者行腰椎穿刺脑脊液细胞学检查,其中2例行免疫细胞化学检查.脑脊液细胞学检查采用粟氏玻片离心法,MGG染色,免疫细胞化学检查采用酶标聚合物法(LDP法).结果 4例患者经脑脊液细胞学检查均发现肿瘤细胞,细胞成团聚集或散在分布,大小不一,形态各异,胞膜有突起,胞浆深染,核浆比例增大,核仁明显.免疫细胞化学检查示广谱角蛋白(CKpan)阳性1例.结论 脑膜癌病的脑脊液细胞学主要特征为有异常形态的肿瘤细胞,这是脑膜癌病诊断的主要依据,结合免疫细胞化学检查有助于明确肿瘤细胞的性质.     

室管膜型原发性中枢神经系统淋巴瘤四例:临床表现及脑脊液细胞学分析

目的分析室管膜型原发性中枢神经系统淋巴瘤(PCNSL)的临床及影像学特点,探讨脑脊液细胞学检测方法在诊断中的价值。方法回顾4例室管膜型PCNSL患者临床诊断与治疗经过,分析其临床特点、影像学改变、脑脊液细胞学和免疫细胞化学染色结果。结果 4例患者平均发病年龄为44岁,发病至就诊时间13 d～5个月。临床表现为头痛、脑膜刺激征,分别伴有脊神经根征(2例)、多组脑神经麻痹(1例)和偏瘫(1例);病程中有间断低热(3例)。其中2例于发病2和4个月时死于脑疝。腰椎穿刺检查脑脊液压力(2例)、白细胞计数(4例)和蛋白定量(4例)升高,葡萄糖降低(3例)。4例患者脑脊液细胞学检测均发现淋巴瘤细胞或异形淋巴细胞,免疫细胞化学染色大多数细胞呈现B细胞标记物阳性。头部MRI增强扫描第三和第四脑室、侧脑室壁异常强化,合并脑室周围强化病灶(2例)和鞍区病变(1例)。PET扫描和骨髓穿刺检查未发现颅外或脊髓受累证据。结论脑脊液细胞学和免疫细胞化学检测是诊断室管膜型PCNSL的重要方法。室管膜及脑室周围病变应考虑PCNSL的可能,尤其MRI增强扫描发现结节样强化者更应提高警惕。     

脑膜癌病的脑脊液细胞学诊断相关因素研究

目的 探讨影响脑膜癌病脑脊液细胞学诊断的相关因素。方法 回顾性分析46例脑膜癌病患者的临床资料。结果 46例脑膜癌病的脑脊液中，38例发现瘤细胞(约82．6％)；40例腰穿脑脊液中，35例检到瘤细胞；6例脑室穿刺脑脊液中，3例检到瘤细胞；35例腰穿脑脊液检到瘤细胞中，26例为第一次检到瘤细胞，5例第2次检到瘤细胞，3例第3次检到瘤细胞，l例3次以上检到瘤细胞；6例硬脑膜-蛛网膜强化者仅l例脑脊液细胞学检到瘤细胞；4例软脑膜-蛛网膜强化者脑脊液细胞学均检到瘤细胞；38例原发肿瘤中，19例血液系统肿瘤(白血病、淋巴瘤)均检到瘤细胞，7例肺癌检出4例，5例胃癌检出3例，4例乳腺癌检出2例，1例室管膜瘤全部检出，1例脑淋巴瘤全部检出。结论常规脑脊液细胞学检查具有较高的特异性，脑脊液的来源、腰穿检查的次数、脑膜癌病病变的位置、原发肿瘤及组织类型均为影响其敏感性的重要因素。     

室管膜型原发性中枢神经系统淋巴瘤四例：临床表现及脑脊液细胞学分析

目的分析室管膜型原发性中枢神经系统淋巴瘤（PCNSL）的临床及影像学特点,探讨脑脊液细胞学检测方法在诊断中的价值。方法回顾4例室管膜型PCNSL患者临床诊断与治疗经过,分析其临床特点、影像学改变、脑脊液细胞学和免疫细胞化学染色结果。结果4例患者平均发病年龄为44岁,发病至就诊时间13d-5个月。临床表现为头痛、脑膜刺激征,分别伴有脊神经根征（2例）、多组脑神经麻痹（1例）和偏瘫（1例）;病程中有间断低热（3例）。其中2例于发病2和4个月时死于脑疝。腰椎穿刺检查脑脊液压力（2例）、白细胞计数（4例）和蛋白定量（4例）升高,葡萄糖降低（3例）。4例患者脑脊液细胞学检测均发现淋巴瘤细胞或异形淋巴细胞,免疫细胞化学染色大多数细胞呈现B细胞标记物阳性。头部MRI增强扫描第三和第四脑室、侧脑室壁异常强化,合并脑室周围强化病灶（2例）和鞍区病变（1例）。PET扫描和骨髓穿刺检查未发现颅外或脊髓受累证据。结论脑脊液细胞学和免疫细胞化学检测是诊断室管膜型PCNSL的重要方法。室管膜及脑室周围病变应考虑PCNSL的可能,尤其MRI增强扫描发现结节样强化者更应提高警惕。     

脑脊液细胞学检查联合癌胚抗原免疫细胞化学染色在脑膜癌病早期诊断中的应用

目的:探讨脑脊液细胞学检查联合癌胚抗原(CEA)免疫组化染色在脑膜癌病(Meningeal Carcinomatosis,MC)早期诊断中的应用价值。方法:脑脊液细胞学检查采用Shandon Cytospin4离心沉淀仪玻片离心法,CEA免疫细胞化学采用SP法。结果:33例经脑脊液细胞学检查均发现异常细胞,其中首次脑脊液细胞学检查阳性率为87.88%(29/33),22例结合CEA免疫组化染色,阳性率为81.82%(18/22);结论:脑脊液细胞学检查结合免疫细胞化学染色是诊断脑膜癌的重要手段,且两者互为补充。     

脑脊液细胞学检查的特异性发现

目的 回顾本实验室3922例脑脊液(CSF)细胞学检查的特异性发现，探讨其临床意义。方法 1984年4月至2003年4月CSF细胞学检查3922例，CSF标本经自然沉淀法或玻片离心法制片，常规采用迈一格一姬染色，部分标本行．PAS染色或免疫细胞化学染色后观察。结果 CSF细胞学特异性发现包括感染性病原体与恶性肿瘤，共55例，占全部CSF细胞学检查的1．40％。其中感染性病原体包括新型隐球菌5例，镰刀菌1例。恶性肿瘤49例，包括转移性癌26例，转移性淋巴瘤／白血病7例，脑生殖细胞瘤4例，原发性中枢神经系统恶性淋巴瘤(PCNSL)4例，胶质母细胞瘤2例，来源未明的肿瘤6例。PAS染色对新型隐球菌的形态显示良好。转移癌细胞的免疫细胞化学染色上皮膜抗原(EMA)和(或)细胞角蛋白(CK)阳性，淋巴瘤细胞可见LCA，CD20或CD34等标记物阳性。结论CSF细胞学对临床有重要意义，其特异性发现所见的肿瘤细胞以转移癌多见，病原体以新型隐球菌多见。CNS镰刀菌病是罕见的霉菌感染，CSF细胞学可检出镰刀菌。CSF免疫细胞学方法有助于鉴别肿瘤细胞的来源。     

免疫细胞化学检查在诊断脑膜癌病中的应用

目的探讨免疫细胞化学检查在脑膜癌病(MC)诊断中的作用。方法对13例MC患者的脑脊液标本21份分别进行常规脑脊液细胞学和免疫细胞化学检查,比较两种检查方法的阳性率。结果首次脑脊液检查阳性者常规脑脊液细胞学4例,而抗癌胚抗原(CEA)和抗上皮膜抗原(EMA)免疫细胞化学均为10例;总阳性率常规脑脊液细胞学为42.86%(9/21),抗CEA免疫细胞化学为80.95%(17/21),抗EMA免疫细胞化学为85.71%(18/21)。结论免疫细胞化学的敏感性高于常规脑脊液细胞学,可提高MC患者的早期确诊率。     

脑脊液细胞学检查结合免疫组化诊断脑膜癌病的探讨

目的:探讨脑脊液细胞学检查结合免疫组化染色对脑膜癌病(MC)的诊断价值。方法:脑脊液细胞学检查采用侯氏自然沉淀法,免疫组化染色采用链霉素抗生物蛋白-过氧化物酶连结法(SP法)。结果:12例经脑脊液细胞学检查均发现异常细胞。结合免疫组化染色10例,其中5例用常规涂片,异常细胞阳性1例,占20%;另5例用脑脊液细胞学收集法,异常细胞阳性4例,占80%,1例癌胚抗原(CEA)阳性,1例膜上皮抗原(EMA)阳性,2例CEA、EMA均阳性。结论:脑脊液细胞学检查结合细胞免疫组化染色是诊断脑膜癌病的重要手段。     

CSF evaluation in primary CNS lymphoma patients by PCR of the CDR III IgH genes

BACKGROUND: Cytologic evaluation of CSF does not consistently detect malignant cells in patients with primary CNS lymphoma (PCNSL). The potentially more sensitive molecular assessment of monoclonality has not been shown in CSF samples. METHODS: The authors studied nested PCR of the complementary determining region III (CDR III) on 76 CSF specimens of patients with PCNSL. Patients with systemic disseminated B-cell non-Hodgkin's lymphoma (n = 17) and 17 patients with no history of lymphoma were compared. PCR products were evaluated by automated fluorescent fragment analysis (ALF). RESULTS: In 68 patients with PCNSL, the authors analyzed the first obtained CSF sample. Nevertheless, 60 patients were taking corticosteroids. In 16 PCNSL samples, amplifiable DNA was not yielded. Taking into account that at least two independent assays have to be performed, CDR III PCR consistently revealed monoclonal products in eight PCNSL and polyclonal results in 52 PCNSL specimens. CDR III PCR detected no monoclonal PCR products in patients without history of lymphoma. In 10 patients with PCNSL, the PCR result and the CSF cytology were discordant. Concerning therapeutic impact, leptomeningeal tumor spread did not predict tumor response in this group of patients with PCNSL. CONCLUSIONS: This study performed CDR III PCR as a routine diagnostic technique applicable even on CSF samples with low cell counts. These data present low incidence of leptomeningeal involvement in this subset of pretreated PCNSL patients. Because the CSF evaluation did not predict outcome in our patients, further analysis in patients with PCNSL should focus on CSF samples that are obtained very early after diagnosis.     

脑脊液细胞学在脑生殖细胞瘤诊断中的应用及八例报告

目的 通过总结8例脑生殖细胞瘤患者的脑脊液细胞学结果,探讨脑脊液细胞学在脑生殖细胞瘤诊断中的价值.方法 总结2006年1月至2009年6月我院脑脊液细胞学发现肿瘤细胞的8例脑生殖细胞瘤患者,分析其临床特点、影像学和脑脊液细胞学结果.结果 8例患者中男性7例,女性1例.年龄13～25岁,分别以多饮、多尿和少汗等内分泌症状或神经科症状起病.神经科症状包括:头晕、头痛、智能减退、精神行为异常、复视、双下肢无力、尿便障碍等.神经影像学可见鞍上区和(或)松果体区占位、脑室扩张、室管膜和软脑膜强化、神经根增粗强化等.脑脊液绒毛膜促性腺激素3.2～1087.0 mIU/ml.脑脊液细胞学8例均见肿瘤细胞,呈中等大小的圆形,核大,核仁明显,胞质丰富,胞质内可见较多空泡.背景间有小淋巴细胞为主的炎性反应.过碘酸Schiff染色肿瘤细胞胞质中见阳性颗粒.4例行免疫细胞化学染色,其中2例抗胎盘碱性磷酸酶阳性;2例行Ki-67染色,阳性细胞分别占12%和20%.细胞角蛋白和癌胚抗原染色等阴性.结论 脑生殖细胞瘤患者的脑脊液细胞学结果特征明显,结合细胞免疫化学可以明确其类型及脑脊液播散,在诊断脑生殖细胞瘤过程中起着重要作用.

Abstract：

Objective To investigate the value of the cerebrospinal fluid ( CSF ) cytology in diagnosis of intracranial germinomas by reviewing the outcomes of CSF cytology of 8 patients with intracranial germinomas. Methods Eight patients with positive CSF cytology at our clinic from January 2006 to June 2009 were reviewed. Conventional cytology and immunocytochemistry of CSF were performed. The relevant literature on the subject was reviewed. Results The patients, including 7 male and 1 female, developed endocrinological or neurological symptoms at the age of 13 to 25, and the typical neurological presentation included vertigo, headache, mental and behavior disorders, double vision and weakness of legs. The CSF cell count ranged from 0 to 300 leukocytes per cubic and elevated in 7 cases, typically lymphocytic inflammation. CSF level of human chorionic gonadotropin was 3.2-1087.0 mIU/ml, higher than the individual serum level. On CSF cytology studies, typical tumor cells of germinima were found, which had positive particles in cytoplasm on periodic acid Schiff stain. All presents had lymphocyte inflammation ( small lymphocyte predominant ). On immunocytochemical studies of CSF, the tumor cells were positive on placental alkaline phosphatase and Ki-67 stains. Conclusions CSF cytology is clinically useful for diagnosis of primary intracranial germinoma. Further clinical and cytological studies will be necessary for a better understanding of the biology of these tumors.     

Cerebrospinal fluid cytology in meningeal invasion of leukemia and malignant lymphoma. Reliable diagnosis by immunocytochemistry]

Cerebrospinal fluid cytology was performed in 64 patients who were suspected of having a meningeal infiltration of malignant lymphoma or leukemia. Conventional staining with May Grünwald Giemsa revealed a positive result in 51 cases, and a negative result in one case. In 4 cases diagnosis was hampered by blood contamination or a lack of CSF cells. In the remaining 8 cases with doubtful cytologic specimens, additional immunocytochemic staining allowed definite diagnosis. In 5 of these cases malignancy was confirmed, while in the remaining 3 an inflammatory cell pattern was found and later confirmed by follow-up. In summary, immunocytochemistry was essential for definite diagnosis in 12% of CSF cell specimens suspected of leukemia or malignant lymphoma. It may be concluded that immunocytochemistry in CSF cytology is a valuable tool for enhancement of diagnostic reliability.     

脑膜癌病的脑脊液细胞学与临床观察

目的研究脑膜癌病(LC)的脑脊液(CSF、)细胞学、临床及神经影像学特点。方法回顾分析16例LC。结果16例LC患者中，男6例、女10例，年龄29～69岁。亚急性起病，头痛14例，伴恶心、呕吐、眼底视乳头水肿；出现脑膜刺激征12例；双下肢无力5例，排尿困难3例；意识丧失、抽搐7例；视力减退5例，眼肌麻痹4例，听力下降1例，吞咽困难2例，偏瘫1例，多饮多尿1例。消瘦10例，低热5例。7例有癌症病史。CSF压力升高13例，CSF、常规计数白细胞升高10例，蛋白均升高，糖减低9例。CSF细胞学均见癌细胞，4例行免疫组化检查示，肿瘤细胞上皮膜抗原和细胞角蛋白阳性。临床及病理学确定来源肺癌6例、乳腺癌3例、胃癌2例、卵巢癌1例，来源未明4例。结论LC可作为首发症状和主要症状而缺少肿瘤原发灶表现。表现为亚急性脑膜炎，进行性颅内压升高，常合并多脑神经和脊髓神经根损害。CSF细胞学是确诊LC主要方法，结合免疫细胞化学方法对确诊有重要帮助。     

Neoplastic Meningitis with Normal Neurological Findings Magnetic Resonance Imaging Results

Neoplastic meningitis, an unusual complication of systemic cancer, is becoming more common as cancer patients live longer. Although leptomeningeal metastases from solid tumors are usually associated with multifocal neurological signs, the authors report on 4 patients who presented with normal findings on neurological exammation. One man had severe headache and complex partial seizures. Magnetic resonance imaging (MRI) of the bram revealed gadolmium enhancement of multiple cranial nerves. Cerebrospinal fluid (CSF) cytology was positive for melanoma. One woman presented with severe migratory retroorbital headaches. MRIs of the brain with and without gadolinium appeared normal CSF cytology was positive for pulmonary adenocarcinoma. One man presented with morning headache, and a woman presented with back pain. Both had CSF cytologies positive for lymphoma. Neoplastic meningitis can occur without abnormalities on neurological or MRI examinations. Lumbar punctures should be performed on cancer patients with severe, unusual, or prolonged headaches.     

Babinski and the diagnosis of amyotrophic lateral sclerosis

Cytological evaluation of cerebrospinal fluid (CSF) is an important means of following response to intracavitary chemotherapy for leptomeningeal malignancy. We studied the feasibility of quantitative cytological evaluation by retrospective analysis of serial CSF specimens from 7 patients receiving phase I intracavitary chemotherapy for leptomeningeal malignancy who had persistent malignant cytology. Three to 34 CSF specimens per patient obtained over a 3- to 48-week period were reviewed. Significant (five- to 10-fold or greater) reductions in numbers of malignant cells in CSF during treatment could be identified in specimens otherwise diagnosed as positive. Quantitative CSF cytological evaluation is neither overly time consuming nor tedious to perform and may provide useful clinical information.     

Primary brain T-cell lymphoma in an HTLV-1 serologically positive male

Primary central nervous system lymphoma (PCNSL) is a subgroup of extranodal non-Hodgkin lymphoma usually due to B-cells. The incidence of T-cell PCNSL is 1-4% in Western countries. Human T-lymphotropic virus (HTLV-1) causes tropical spastic paraparesis/myelopathy and adult T-cell leukemia/lymphoma. We describe the extremely rare occurrence of T-cell PCNSL in a 29 year old HTLV-1 carrier. Additional unusual features of the case included the patient's young age and normal cerebrospinal fluid cytological findings, without leptomeningeal spread. Given the long latency between HTLV-1 infection and disease manifestation, more such cases may be diagnosed in the future. We recommend that every patient with T-cell PCNSL be screened for HTLV-1.