Bing–Neel syndrome (BNS), a rare complication of Waldenström macroglobulinemia (WM), is caused by the direct infiltration of lymphoplasmacytic cells into the central nervous system (CNS). Since clinical manifestations are heterogeneous and may overlap with IgM-related neuropathies, BNS is often under-recognized and diagnosed late. The incidence of BNS has been reported to be approximately 1% of patients with WM. Because of its extreme rarity, there are no prospective studies on BNS. In 2025, a consensus panel from the 12th international workshop on WM updated the guidelines for BNS, recognizing zanubrutinib as a standard therapy, clarifying imaging and cerebrospinal fluid (CSF) assessments during follow-up, and introducing revised response categories. Although the incidence of BNS is approximately 1% of WM, it decreases overall survival compared to WM alone, and early deaths were reported in historical series. Diagnostic confirmation requires a high index of suspicion and a multimodal approach combining MRI of the brain and spine with gadolinium, CSF cytology and flow cytometry, molecular testing such as MYD88 L265P, and occasionally tissue biopsy. Importantly, MYD88 L265P is also observed in most cases of diffuse large B-cell lymphoma of the CNS and is therefore not disease-specific. Differentiation from IgM-mediated neuropathies is critical because management strategies markedly differ. Historically, high-dose methotrexate- or cytarabine-based chemotherapy, intrathecal therapy, and radiotherapy have been used; however, responses varied, and toxicity was considerable. In contrast, CNS-penetrant Bruton tyrosine kinase (BTK) inhibitors have reshaped therapeutic strategies. Retrospective data support durable responses with ibrutinib, tirabrutinib, and zanubrutinib, while early findings suggest that non-covalent BTK inhibitors expand options for relapsed or refractory cases. Herein, we synthesize current evidence on epidemiology, pathophysiology, and diagnostic work-up. We also outline therapeutic recommendations integrating the genotype, disease pattern, and patient fitness and conclude with unmet needs and future directions.
Bing–Neel综合征（BNS）是华氏巨球蛋白血症（WM）的一种罕见并发症，由淋巴浆细胞直接浸润中枢神经系统（CNS）引起。由于临床表现异质性强，且可能与IgM相关神经病变重叠，BNS常被忽视且诊断延迟。据报道，BNS发病率约占WM患者的1%。因其极为罕见，目前尚无针对BNS的前瞻性研究。2025年，第12届WM国际研讨会专家小组更新了BNS诊疗指南，将泽布替尼确立为标准疗法，明确了随访期间的影像学和脑脊液（CSF）评估标准，并引入了修订后的疗效分类体系。尽管BNS发病率仅占WM患者的1%，但与单纯WM相比，其会降低患者总生存期，历史病例系列中曾有早期死亡报道。确诊需要保持高度警惕，并采用多模态方法：包括钆增强脑脊髓MRI、CSF细胞学与流式细胞术、MYD88 L265P等分子检测，必要时进行组织活检。值得注意的是，MYD88 L265P突变也常见于中枢神经系统弥漫大B细胞淋巴瘤，因此不具备疾病特异性。与IgM介导的神经病变相鉴别至关重要，因两者的治疗策略截然不同。历史上曾采用大剂量甲氨蝶呤或阿糖胞苷化疗、鞘内治疗及放疗，但疗效不一且毒性显著。相比之下，具有CNS渗透性的布鲁顿酪氨酸激酶（BTK）抑制剂重塑了治疗格局。回顾性数据支持伊布替尼、替拉鲁替尼和泽布替尼可产生持续缓解，早期研究提示非共价BTK抑制剂为复发/难治病例提供了新选择。本文综合了当前关于流行病学、病理生理学和诊断评估的证据，结合基因型、疾病模式和患者体能状态提出治疗建议，最后总结未满足的临床需求与未来研究方向。
肿瘤(癌症)患者之家