Institut du Cerveau-Paris Brain Institute-ICM, Inserm, Sorbonne Université, CNRS.
Department of Neurology-2, Sorbonne Université, Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Pitié-Salpêtrière-Charles Foix, Paris, France.
Curr Opin Neurol. 2022 Dec 1;35(6):779-786. doi: 10.1097/WCO.0000000000001115. Epub 2022 Oct 21.
Primary central nervous system lymphoma (PCNSL) is a rare subtype of diffuse large B-cell lymphoma (DLBCL) located in the CNS with a less favorable prognosis. Recent information addressing the disease molecular heterogeneity is paving the way for tailored treatment strategies. This article reviews current work on the pathogenesis of the disease, potential biomarkers, and treatments.
Previous molecular classifications of PCNSL, built on DLBCL heterogeneity, did not properly address its intrinsic variability. Recent evidence has shown the existence of four different molecular PCNSL subtypes with associated multiomic characteristics, including prognostic relevance. Several studies have identified the tumor microenvironment (TME) as a driving prognostic factor in PCNSL. Therapy efforts continue mainly into targeting either the NF-κβ (nuclear factor kappa-light-chain enhancer of activated B cells) pathway or modulating the TME through immunomodulatory drugs (lenalidomide) or immunotherapy (antiprogrammed cell death 1/programmed cell death 1 ligand 1).
Despite the increasing understanding of PCNSL pathogenesis with recent studies, future efforts are still needed to yield diagnostic biomarkers to detect either PCNSL or its molecular subtypes and hence ease routine clinical use.
综述目的：原发性中枢神经系统淋巴瘤（PCNSL）是一种罕见的弥漫性大 B 细胞淋巴瘤（DLBCL）亚型，位于中枢神经系统，预后较差。最近关于该疾病分子异质性的信息为制定针对性的治疗策略铺平了道路。本文综述了疾病发病机制、潜在生物标志物和治疗方法的最新研究进展。
最新发现：以前基于 DLBCL 异质性建立的 PCNSL 分子分类并不能很好地解决其内在变异性。最近的证据表明，存在四种不同的分子 PCNSL 亚型，具有相关的多组学特征，包括预后相关性。几项研究已经将肿瘤微环境（TME）确定为 PCNSL 的一个重要预后因素。治疗方法主要集中在靶向 NF-κβ（核因子 kappa-轻链增强子的 B 细胞）通路，或通过免疫调节药物（来那度胺）或免疫疗法（抗程序性细胞死亡 1/程序性细胞死亡配体 1）来调节 TME。
总结：尽管最近的研究对 PCNSL 的发病机制有了更多的了解，但仍需要进一步努力，以产生诊断生物标志物来检测 PCNSL 或其分子亚型，从而便于常规临床应用。
