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原发性中枢神经系统淋巴瘤中的血脑屏障:内皮细胞死亡的超微结构证据

The blood-brain barrier in primary CNS lymphomas: ultrastructural evidence of endothelial cell death.

作者信息

Molnár P P, O'Neill B P, Scheithauer B W, Groothuis D R

机构信息

Department of Neurology, Northwestern University Medical School, Evanston Northwestern Healthcare, Evanston, IL 60201, USA.

出版信息

Neuro Oncol. 1999 Apr;1(2):89-100. doi: 10.1093/neuonc/1.2.89.

DOI:10.1093/neuonc/1.2.89
PMID:11550310
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1920754/
Abstract

The vasculature of 24 primary CNS B-cell lymphomas that were not related to acquired immunodeficiency syndrome was systematically studied by electron microscopy. Seven low-grade astrocytic tumors were included for comparison. Classical electron microscopy features of apoptosis were found in lymphoma cells of 21 of 22 subjects. Capillaries of gliomas and lymphomas showed changes reported previously: variability of endothelial cell (EC)-thickness and number, basal lamina thickness and duplication, and fenestrations. Primary CNS B-cell lymphoma ECs showed two distinctive populations of electron-dense and electron-lucent cells. The electron-dense ECs occurred in 38% of all capillaries, with changes consisting of chromatin condensation in bizarre and contracted nuclei, cytoplasmic shrinkage with markedly increased electron density, and dilatation of the endoplasmic reticulum. We interpreted these changes as indicative of apoptosis. Cell death eventually resulted in complete disintegration of the endothelium with frank discontinuities of the EC component of the blood-tumor barrier in capillaries and postcapillary venules. Another population of ECs had increased cell volume, conspicuous cytoplasmic electron lucency, dispersed organelles, scattered vesicles, and apical stress fibers. We interpreted these changes as indicative of cellular regeneration. Individual apoptotic ECs often lay next to normal or regenerating ECs. Neither type of EC change was observed in gliomas, which also lacked perivascular neoplastic lymphocytic cuffing. We believe that these populations of ECs, which have not been described in other disorders affecting the blood-brain barrier, may be induced by cytokines released from necrotic and/or apoptotic tumor lymphocytes and may explain the unusual imaging characteristics of primary CNS B-cell lymphomas treated with corticosteroids.

摘要

对24例与获得性免疫缺陷综合征无关的原发性中枢神经系统B细胞淋巴瘤的脉管系统进行了电子显微镜系统研究。纳入7例低级别星形细胞瘤作为对照。22例受试者中有21例的淋巴瘤细胞发现了典型的凋亡电子显微镜特征。胶质瘤和淋巴瘤的毛细血管呈现出先前报道的变化:内皮细胞厚度和数量的变异性、基膜厚度和重复以及窗孔。原发性中枢神经系统B细胞淋巴瘤的内皮细胞显示出电子致密和电子透亮两种不同类型的细胞。电子致密内皮细胞出现在所有毛细血管的38%中,其变化包括奇形和收缩核内的染色质凝聚、细胞质收缩伴电子密度明显增加以及内质网扩张。我们将这些变化解释为凋亡的指征。细胞死亡最终导致内皮细胞完全解体,毛细血管和毛细血管后微静脉中的血瘤屏障内皮细胞成分出现明显中断。另一类内皮细胞细胞体积增大,细胞质明显电子透亮,细胞器分散,有散在的小泡和顶端应力纤维。我们将这些变化解释为细胞再生的指征。单个凋亡的内皮细胞常紧邻正常或再生的内皮细胞。在胶质瘤中未观察到这两种类型的内皮细胞变化,胶质瘤也缺乏血管周围肿瘤性淋巴细胞套袖现象。我们认为,这些在影响血脑屏障的其他疾病中未被描述的内皮细胞类型,可能是由坏死和/或凋亡的肿瘤淋巴细胞释放的细胞因子诱导产生的,这可能解释了接受皮质类固醇治疗的原发性中枢神经系统B细胞淋巴瘤的异常影像学特征。