Central nervous system involvement in Waldenström macroglobulinemia: a comparative population-based study of Bing-Neel syndrome and histological transformation

Central nervous system (CNS) involvement in Waldenström macroglobulinemia (WM) is a rare complication that can manifest as Bing-Neel syndrome (BNS) or as histological transformation (HT) to diffuse large B-cell lymphoma (DLBCL). We report data from a single-center cohort of 469 patients consecutively diagnosed with WM between 2000 and 2022. BNS was identified in 1.5% (n = 7) and HT with CNS involvement (CNS-HT) in 1.7% (n = 8) of patients. The cumulative incidence of BNS and CNS-HT at 15 years was 2.6% and 2.7%, respectively, with CNS-HT more likely to develop in closer proximity to the initial WM diagnosis. One patient with CNS-HT exhibited a preceding phase of BNS before transformation. In general, patients with BNS and CNS-HT presented with diverse neurological symptoms and clinical features. Parenchymal lesions were uniformly found in all patients with CNS-HT, while neuroimaging findings were less consistent in patients with BNS. Involvement of multiple extramedullary sites was observed in approximately half of the patients with both BNS and CNS-HT. Patients with CNS-HT had poor outcomes, with a median overall survival of 10 months following the onset of CNS involvement, whereas BNS was associated with a more favorable prognosis, particularly in patients treated with ibrutinib. This study is the first to present a comparative analysis of BNS and CNS-HT in WM, providing novel insights into their incidence, clinical features, and outcomes.