Over 2 million people worldwide suffer from multiple sclerosis (MS), a chronic demyelinating inflammatory disorder of the central nervous system (CNS) which can be linked to a progressive deterioration of physical and cognitive functioning (Reich et al., 2018; Walton et al., 2020). Over the years, researchers have dedicated substantial efforts to understanding the intricate interplay between MS and other health conditions, one of which is cancer (Magyari and Sorensen, 2020).

Neuroepithelial tumors arising from CNS glial or supporting cells are collectively referred to as gliomas, which account for 24 % of all primary brain and CNS malignancies, with the majority of them having a fatal prognosis (Davis and Davis, 2018). With a median survival of 15 months following diagnosis, glioblastoma(GBM) is the most common and aggressive form of primary brain tumor in adults (Tamimi and Juweid, 2017).

MS and gliomas co-occurring is a rare but well-reported event. Following Scherer's initial report of a diffuse GBM in a patient with acute demyelinating disease, there have been twenty cases reported, up until 1981, where MS was associated with gliomas (Scherer and La, 1938; Ho and Wolfe, 1981). The exact prevalence of this co-occurrence remains uncertain, largely due to the fact that the majority of evidence stems from individual case reports or small case series. However, two population-based studies did not find any increased risk of gliomas in people with MS (pwMS), but the Swedish retrospective cohort study discovered a decrease in survival among these individuals (Hemminki et al., 2013; Haedenkamp et al., 2020).

While different forms of brain tumors have been associated with MS, it is unclear whether these tumors develop incidentally or as a result of underlying causes. Several theories have been proposed, including the effects of immunomodulatory treatments, the role of chronic inflammation, and the transformation of MS lesions into tumors (Sirko et al., 2020a; Sierra Morales et al., 2017; Acqui et al., 2008a).

Additionally, this phenomenon poses unique diagnostic challenges including symptom overlap, and ambiguities in imaging results that make it difficult to differentiate between the two conditions (Kahovec et al., 2021a). Finally, it is uncertain if the course of MS differs in the presence of brain tumors (Plantone et al., 2015). Given the complex interplay between MS and gliomas, and the reported cases of their co-occurrence, this study aims to conduct a detailed systematic review of current literature, attempting to provide clarity in this area. Our main arguments will revolve around the clinical and diagnostic challenges posed by their co-existence, the potential risks of certain disease-modifying therapies (DMTs) in cancer development, and the exploration of the hypotheses regarding the potential underlying causes for their simultaneous development.