弥漫大B细胞淋巴瘤（DLBCL）是一种具有侵袭性的B细胞淋巴瘤，在晚期也能够治愈。涉及中枢神经系统（CNS）的DLBCL更难治愈，并且治疗选择较少。原发性CNS淋巴瘤（PCNSL）指的是仅限于CNS的侵袭性淋巴瘤，几乎都属于DLBCL。PCNSL的标准治疗方法是使用高剂量甲氨蝶呤联合治疗作为诱导治疗，年轻患者通常接受剂量密集的巩固治疗。然而，剂量密集治疗并不适用于所有患者，且年长患者的有效治疗选择较少。复发或化疗难治性疾病的患者具有严重的预后。继发性CNS淋巴瘤（SCNSL）指的是侵袭性淋巴瘤首次表现为CNS受累，或在治疗全身DLBCL后CNS复发。独立的CNS复发通常被视为PCNSL进行管理，但同时存在DLBCL侵袭周围部位和CNS的患者则是一个独特的临床挑战。对DLBCL分子回路的了解揭示了不同的遗传亚型，包括具有向CNS侵袭倾向的病例。PCNSL和某些SCNSL的特征是长期激活的B细胞受体和NFKB信号以及免疫逃逸的遗传证据，这些特征可以被治疗性地利用。对支持CNS淋巴瘤的可靶向途径的机制学理解的改善已经导致了许多临床试验，测试有前景的靶向药物联合治疗和免疫疗法。基于生物学合理的策略可能进一步提高CNS淋巴瘤的治愈率，无论是通过克服内在或获得的治疗抗性，还是通过广泛适用于各个年龄段的患者。

Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma curable even in advanced stages. DLBCL involving the central nervous system (CNS) is more difficult to cure and fewer treatment options exist. Primary CNS lymphoma (PCNSL) refers to aggressive lymphomas confined to the CNS, and are almost always DLBCL. Standard approaches for PCNSL use high-dose methotrexate based combinations as induction therapy and younger patients often receive dose-intensive consolidation. However, dose-intensive therapies are not suitable for all patients, and older patients have fewer effective treatment options. Patients with relapsed or chemotherapy-refractory disease have a grave prognosis. Secondary CNS lymphoma (SCNSL) describes aggressive lymphomas involving the CNS at initial presentation or relapses within the CNS after treatment for systemic DLBCL. Isolated CNS relapse is often managed as PCNSL, but patients with synchronous involvement of DLBCL in both the periphery and the CNS pose a unique clinical challenge. Insights into the molecular circuitry of DLBCL have identified distinct genetic subtypes including cases with a predilection for CNS invasion. PCNSL and subsets of SCNSL are characterised by chronically activated B-cell receptor and NFKB signalling along with genetic evidence of immune evasion which may be exploited therapeutically. Improved mechanistic understanding of targetable pathways underpinning CNS lymphomas has led to numerous clinical trials testing targeted agent combinations and immunotherapy approaches with promising early results. Biologically rational strategies may further improve the cure rate of CNS lymphomas either by overcoming intrinsic or acquired treatment resistance and/or by being broadly applicable to patients of all ages.