血管内大B细胞淋巴瘤（IVLBCL）是一种罕见的非淋巴结淋巴瘤，其特征是恶性细胞在血管中的选择性增生，可能是快速进展性痴呆的可治疗病因。由于其多样化的临床和仪器表现，常常被误诊为更常见的快速进展型痴呆病因，例如克雅氏病（CJD）或血管性痴呆。本研究介绍了我们在过去20年中通过尸检诊断的四例IVLBCL病例的临床和组织病理学特征，这些样本来自于我们的朊蛋白病参考中心收到的600多个怀疑为CJD病例的脑组织样本。患者表现出各种不同的临床症状，包括行为异常、失向和警觉度波动。当时进行的诊断测试，包括血液检查、脑脊液分析、脑电图和神经影像学，结果非特异性且有时具有误导性。因此，这些患者曾被多次诊断为CJD、癫痫、血管性痴呆和脑炎。两名患者的储存脑脊液样本在后来进行的研究目的的朊蛋白实时快速震颤引发性转变（RT-QuIC）测试中呈阴性。神经病理学分析揭示了不同脑区的差异性受累，额颞叶新皮质受累程度最高。我们的结果证实了IVLBCL的临床和仪器的明显异质性。神经病理学证据表明额颞叶新皮质的优先受累，有可能相关于临床表型和早期诊断。最后，鉴于其与CJD误诊的治疗意义，我们强调朊蛋白RT-QuIC作为CJD排除性测试在这些患者中的实用性。 © 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.

Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal lymphoma that is characterized by the selective growth of neoplastic cells in blood vessels, representing a potentially treatable cause of rapidly progressive dementia (RPD). Given its diverse clinical and instrumental presentation, it is often misdiagnosed with more common RPD causes, for example, Creutzfeldt-Jakob disease (CJD) or vascular dementia.This study presents the clinical and histopathological characteristics of four IVLBCL cases that we diagnosed post-mortem over 20 years among over 600 brain samples received as suspected CJD cases at our prion disease reference center.Our patients exhibited various presenting symptoms, including behavioral disturbances, disorientation, and alertness fluctuations. The diagnostic tests performed at the time, including blood work, cerebrospinal fluid (CSF) analyses, electroencephalography, and neuroimaging, yielded nonspecific and occasionally misleading results. Consequently, the patients were repeatedly diagnosed as variably having CJD, epilepsy, vascular dementia, and encephalitis. The stored CSF samples of two patients tested negative at prion real-time quaking-induced conversion (RT-QuIC), which we performed afterwards for research purposes. Neuropathological analysis revealed a differential involvement of various brain areas, with frontotemporal neocortices being the most affected.Our results confirm the significant clinical and instrumental heterogeneity of IVLBCL. Neuropathological evidence of the preferential involvement of frontotemporal neocortices, potentially conditioning the clinical phenotype, could be relevant to reach an early diagnosis. Finally, given the therapeutic implications of its misdiagnosis with CJD, we emphasize the utility of prion RT-QuIC as a test for ruling out CJD in these patients.© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.