Radiological and FDG-PET imaging features of Epstein–Barr virus–positive primary central nervous system lymphomas

Background Epstein–Barr virus (EBV)–associated primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin’s lymphoma closely linked to immunodeficiency. Imaging characteristics of EBV-associated are reported to differ from those of typical EBV-negative PCNSL. This study aims to describe the radiological and nuclear medicine imaging features in a large cohort of patients with EBV-associated PCNSL. Methods We conducted a multicenter retrospective descriptive study between 2008 and 2025 on patients with a diagnosis of EBV-associated PCNSL. MRI variables and FDG-PET/CT uptake were assessed. Results Fifty-eight cases of EBV-associated PCNSL were included. All but 1 patient were immunosuppressed. Multiple lesions were present in 71% of cases (41/58). Supratentorial involvement was observed in 90% of cases (52/58). Heterogeneous contrast enhancement was noted in 90% (52/58), with ring-like enhancement in 41% (24/58). Leptomeningeal enhancement occurred in 31% of cases (18/58), and within this group, 50% showed perivascular space enhancement. Lesions showed hypercellularity in 83% (48/58) and intralesional hemorrhage in 81% (47/58). An “eccentric target” sign was present in 26% of cases (15/58), while a “concentric target” sign in 14% (5/35). On FDG-PET, 25/30 patients had hypermetabolic lesions (25/30, 83%). Conclusion Diagnosing EBV-associated PCNSL is challenging due to its rarity and the broad differential diagnosis. Multiple necrotic and hemorrhagic lesions are the most suggestive MRI feature of EBV-associated PCNSL. “Eccentric” and “concentric” target signs, typically associated with CNS toxoplasmosis, can be observed. FDG-PET often reveals hypermetabolic lesions that support a neoplastic diagnosis. Histological confirmation remains essential for confidently treating this tumor entity.