Cesk Patol. 2022 Fall;58(3):150-160.
Tumors of the central nervous system (CNS) include primary tumors - itraaxial, growing from brain and spinal cord cells (neuroepithelial tumors) or extraaxial, growing from surrounding structures (brain and spinal cord, nerve sheaths, vascular structures, lymphatic tissue, germ cells, malformations, pituitary glands). Much more often they are located in the intracranial space a solitary or multiple metastatic spread of malignancy originating from another organ (eg lung, breast, malignant melanoma, Grawitzs tumor). The occurrence of metastases of solid tumors is then in the intraaxial or extraaxial region, leptomeningeal or dural. Even morphologically benign tumors with their occurrence in a closed CNS compartment can have malignant behaviour and cause severe slowly developing to acute neurological symptoms, including intracranial hypertension. Primary tumors of the central nervous system present 1-2% of all cancers, with a higher incidence in adults after the age of 60, with a slight predominance in men, with higher mortality in men than in women. About 5% of CNS tumors are hereditary (e.g., Li-Fraumeni syndrome, neurofibromatosis type I, II). The causes of most brain and spinal cord tumors are unclear, the effect of radiation has been definitely demonstrated, there is an increased risk in transplant patients and AIDS (Acquired Immune Deficiency Syndrome) patients, and the potentiating effects of some chemicals and viruses on the development of CNS neoplasms are uncertain. The effectiveness of treatment of brain and spinal cord tumors is influenced by the existence of the so-called hematoencephalic barrier, which protects the brain from the penetration of toxic substances, but at the same time prevents the penetration of most cytostatics to the tumor target. Another obstacle may be the localization of the tumor in areas difficult to access for histological verification (brain stem, optical chiasma) due to the high risk of complications even after stereotactic biopsy. In some cases, in an effort not to cause an irreversible neurological deficit by inconsiderate tissue collection, the sample of histological material can then become inconclusive to tumor cells, i.e., tumor cells are not captured. Last but not least, the radiosensitivity of some brain structures is also limiting, which makes it impossible to apply a higher dose of ionizing radiation to a tumor affecting sensitive tissues or located near of these sensitive tissues. The rapid development of immunohistochemical (IHC) and molecular genetic analysis methods has significantly refined diagnostics and thus theoretically facilitates the choice of the optimal treatment procedure for the individual patient. While advances in modern conformal photon and particle (currently the most frequently proton) radiotherapy, stereotactic radiosurgery has enabled accurately targeted irradiation of the CNS tumor site and at the same time spare the high-risk brain structures, thereby significantly reduce the risk of acute and late neurotoxicity, pharmacotherapy options are still limited. Just molecular-genetic knowledge already provides us with predictive and prognostic information. They should increasingly stratify patients for targeted therapy.
中枢神经系统(CNS)肿瘤包括原发性肿瘤——脑内肿瘤和脊髓肿瘤(神经上皮肿瘤)或脑外肿瘤,源自周围结构(脑和脊髓、神经鞘、血管结构、淋巴组织、生殖细胞、畸形、垂体)。更常见的是,它们位于颅内空间,是源自另一个器官(例如肺、乳腺、恶性黑色素瘤、Grawitz 肿瘤)的恶性肿瘤的单一或多发性转移。然后,实体瘤的转移发生在脑内或脑外区域、软脑膜或硬脑膜。即使是形态学上良性的肿瘤,由于其发生在封闭的 CNS 隔室中,也可能具有恶性行为,并导致严重的缓慢发展到急性神经症状,包括颅内压升高。中枢神经系统原发性肿瘤占所有癌症的 1-2%,60 岁以上成年人的发病率较高,男性略占优势,男性死亡率高于女性。约 5%的 CNS 肿瘤是遗传性的(例如,Li-Fraumeni 综合征、神经纤维瘤病 I 型、II 型)。大多数脑和脊髓肿瘤的病因尚不清楚,辐射的影响已得到明确证实,移植患者和艾滋病(获得性免疫缺陷综合征)患者的风险增加,一些化学物质和病毒对 CNS 肿瘤发展的促进作用尚不确定。血脑屏障的存在影响了脑和脊髓肿瘤的治疗效果,血脑屏障可保护大脑免受有害物质的渗透,但同时也阻止了大多数细胞抑制剂渗透到肿瘤靶标。另一个障碍可能是由于即使在立体定向活检后也存在并发症的高风险,肿瘤位于难以进行组织学验证的区域(脑干、视交叉)。在某些情况下,为了避免因考虑不周的组织采集而导致不可逆转的神经功能缺损,组织学材料样本可能对肿瘤细胞没有结论,即没有捕获到肿瘤细胞。最后但同样重要的是,一些脑结构的放射敏感性也是有限的,这使得无法对影响敏感组织或位于这些敏感组织附近的肿瘤应用更高剂量的电离辐射。免疫组织化学(IHC)和分子遗传学分析方法的快速发展极大地完善了诊断,从而在理论上为每个患者选择最佳治疗方案提供了便利。尽管现代适形光子和粒子(目前最常使用质子)放疗取得了进展,立体定向放射外科能够精确靶向 CNS 肿瘤部位,同时保护高危脑结构,从而显著降低急性和迟发性神经毒性的风险,但药物治疗选择仍然有限。仅仅分子遗传学知识就为我们提供了预测和预后信息。它们应该越来越多地为靶向治疗对患者进行分层。