Rapidly progressive dementia due to intravascular lymphoma: A prion disease reference center experience

Background: 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. Methods: 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. Results: 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. Conclusions: 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.