Primary central nervous system lymphoma (PCNSL) accounts for less than 5% of primary brain tumors [1]. PCNSL is mainly a non-Hodgkin diffuse large B-cell lymphoma that develops in immunocompetent and immunocompromised patients, with a different pathophysiology as PCNSL in immunocompromised patients is known to be linked to Epstein Barr virus (EBV) reactivation, especially in human immunodeficiency virus (HIV)-positive patients and transplant recipients. The prognosis of PCNSL has significantly improved over the past decades as a result of better therapeutic strategies, largely based on systemic chemotherapy and immunotherapy, with or without consolidation treatment [2], [3].

Epileptic seizures are a frequent presenting symptom and a common comorbidity in patients with brain tumors [4], [5], [6], [7]; however, the pathogenesis of tumor-related epilepsy is poorly understood, and different mechanisms are thought to underlie this symptom: tumor location proximal to gray matter, intrinsic tumor epileptogenicity, blood-brain barrier disruption, inflammation and, other peritumoral factors [8]. It is a shared belief among neurologists and neurosurgeons that PCNSL patients are unlikely to develop seizures and it is probably because PCNSL often involves the subcortex relative to cortex, but this neglects the fact that PCNSL, unlike other types of brain tumors, is a highly infiltrative neoplasm that can been characterized as a “whole brain disease” with extensive central nervous system (CNS) involvement that may be significantly underestimated by magnetic resonance imaging [9].

Therefore, we conducted this systematic review of the literature to describe and analyze epileptic seizures in PCNSL. By synthesizing existing evidence, we also aim to identify unanswered questions and future research areas.