Abstract
Background: The incidence of lymphomatous involvement of the central nervous system (CNS) has been increasing in recent years. However, the rarity of the disease has resulted in a scarcity of available data regarding its clinical presentation, natural history, and prognosis. We aimed to investigate the neurological characteristics of uncommon lymphomatous involvements confined to the CNS and to identify key variables that could serve as predictive biomarkers for treatment outcomes. Methods: We identified patients presenting with neurological symptoms and diagnosed with CNS-restricted lymphomatous involvement between 2005 and 2023. Results: We identified 44 cases, 93% of which were diagnosed with primary central nervous system lymphoma (PCNSL) and 7% with intravascular lymphoma. The median time from symptom onset to diagnosis was 47 days (range: 6-573 days), with no statistically significant difference between patients older and younger than 60 years (p = 0.22). The median follow-up time was 1144 days (range: 27-3501 days). Cognitive deterioration was the most common presenting symptom, occurring in 19 out of 44 patients (43%). Brain MRI revealed that lobar lesions were the most frequent location of lesions, found in 24 out of 44 patients (55%). By the end of the study period, 30 patients (68%) had died, with a median survival of 666 days (range: 17-3291 days). Death was significantly more common in patients who experienced relapses (p = 0.04; 95% CI: 0.99-0.03), with these patients having a four times higher chance of death (HR = 4.1; 95% CI: 1.01-16.09). The time to diagnosis significantly correlated with survival (p = 0.02; 95% CI: 0.005-0.54), as did the Eastern Cooperative Oncology Group (ECOG) performance status at the last follow-up (p = 0.006; 95% CI: 0.0012-0.62). Patients aged over 60 years did not exhibit a higher likelihood of death (p = 0.19; HR = 2.3; 95% CI: 0.63-8.61); however, the threshold age at diagnosis for the maximally predicted mortality was 64 years (ROC = 0.73; p = 0.03). Conclusions: Patients had significant delays in diagnosis, affecting patient outcomes. Cognitive deterioration and lobar lesions were prominent clinical and radiological features. Mortality was notably higher in patients with relapses and those who had a longer time to diagnosis.