EWSR1::CREB1 fusion is an important characteristic of PPMS; however, it is essential to note that this fusion is not exclusive to PPMS but is also observed in other neoplasms, including angiomatoid fibrous histiocytoma (AFH), clear cell sarcoma, hyalinising clear cell carcinoma of the salivary gland, and clear cell carcinoma of the soft tissue or gastrointestinal tract (Thway and Fisher 2012; Cazzato et al. 2022; Stockman et al. 2012; Rossi et al. 2007). Here, EWSR1 is linked to primary progressive multiple sclerosis.