Chamberlain Marc C, Glantz Michael, Groves Morris D, Wilson Wyndham H
Department of Neurology and Neurological Surgery, Division of Neuro-Oncology, University of Washington, Seattle, WA 98109-1023.
Semin Oncol. 2009 Aug;36(4 Suppl 2):S35-45. doi: 10.1053/j.seminoncol.2009.05.005.
Three methods are routinely used to diagnose neoplastic meningitis (NM): clinical signs and symptoms, cerebrospinal fluid (CSF) cytology, and magnetic resonance imaging (MRI) of the brain and spine. Clinical manifestations are often subtle or may be ascribed to other cancer complications, eg, treatment-related disorders or brain parenchymal metastases. CSF cytology has a high specificity (>95%), but its sensitivity is generally less than 50%. MRI sensitivity and specificity vary with the type of primary cancer; overall, MRI findings consistent with leptomeningeal disease are detected in fewer than 50% of NM patients. While most clinicians evaluate CSF cytology along with MRI and the clinical examination, underdiagnosis is a major problem, since many patients are both cytologically and radiographically negative. Failure to consider NM in the differential diagnosis magnifies the problem of underdiagnosis. CSF flow cytometry is particularly promising for evaluating NM from hematologic cancers, with a diagnostic sensitivity many fold greater than conventional cytology. Research has focused on identifying biochemical markers of tumor cells in the CSF. For example, molecules involved in CNS penetration (eg, matrix metalloproteinases and cathepsins), tumor cell tropism (eg, chemokines CXCL8 and CCL18), and angiogenesis (eg, vascular endothelial growth factor) are elevated in the CSF of patients with NM. Evidence that some tumor types are more likely to infiltrate the CNS also has stimulated research into primary tumor markers predictive of CNS metastases. At present, there is no tumor marker or patient characteristic that reliably predicts the development of NM, and diagnosis still relies on suggestive signs and symptoms, positive CSF cytology, or a consistent MRI-all late manifestations of NM. Until techniques capable of detecting NM early are developed, increased awareness of the disease and standardized evaluation are likely to have the greatest impact on improving diagnosis and implementing earlier treatment.
通常采用三种方法诊断肿瘤性脑膜炎（NM）：临床体征和症状、脑脊液（CSF）细胞学检查以及脑和脊柱的磁共振成像（MRI）。临床表现往往不明显，或可能归因于其他癌症并发症，如治疗相关疾病或脑实质转移。CSF细胞学检查具有较高的特异性（>95%），但其敏感性通常低于50%。MRI的敏感性和特异性因原发性癌症的类型而异；总体而言，在不到50%的NM患者中能检测到与软脑膜疾病相符的MRI表现。虽然大多数临床医生会结合MRI、临床检查来评估CSF细胞学检查结果，但漏诊是一个主要问题，因为许多患者的细胞学和影像学检查结果均为阴性。在鉴别诊断中未考虑NM会使漏诊问题更加严重。CSF流式细胞术在评估血液系统癌症引起的NM方面特别有前景，其诊断敏感性比传统细胞学检查高许多倍。研究集中在识别CSF中肿瘤细胞的生化标志物。例如，参与中枢神经系统穿透的分子（如基质金属蛋白酶和组织蛋白酶）、肿瘤细胞嗜性（如趋化因子CXCL8和CCL18）以及血管生成（如血管内皮生长因子）在NM患者的CSF中升高。一些肿瘤类型更易浸润中枢神经系统的证据也激发了对预测中枢神经系统转移的原发性肿瘤标志物的研究。目前，尚无可靠预测NM发生的肿瘤标志物或患者特征，诊断仍依赖于提示性的体征和症状、CSF细胞学检查阳性或一致的MRI表现——这些都是NM的晚期表现。在能够早期检测NM的技术开发出来之前，提高对该疾病的认识和标准化评估可能对改善诊断和尽早实施治疗产生最大影响。
