Central nervous system involvement by Waldenström macroglobulinaemia (Bing‐Neel syndrome): a multi‐institutional retrospective study

Abstract

Bing-Neel syndrome (BNS) is a rare complication seen in patients with Waldenström macroglobulinaemia (WM), in which lymphoplasmacytic lymphoma (LPL) cells colonize the central nervous system (CNS). In this retrospective multi-centre study, we present the clinicopathological features, imaging findings, therapy, response and outcomes of 34 patients with BNS. The median time from WM diagnosis to BNS diagnosis was 3 years, 15% of patients were diagnosed with BNS at the time of WM diagnosis, and 22% of patients developed BNS when responding to active treatment for WM. Patients with BNS presented with variable clinical features including limb motor deficits, change in mental status and cranial nerve palsies. The diagnosis was made using a combination of cerebrospinal fluid cytology, flow cytometry and detection of the MYD88 L265 mutation, and magnetic resonance imaging. The estimated 3-year overall survival rate was 59%. Of the survivors, 40% have evidence of pathological or radiological persistence of disease. Age older than 65 years, platelet count lower than 100 x 109/l, and treatment for WM prior to BNS diagnosis were associated with worse outcome. Exposure to rituximab for treatment of BNS was associated with a better outcome. Multi-institutional collaboration is warranted to improve treatment and outcomes in patients with BNS.

Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome

“…Using a highly sensitive real time quantitative PCR (qPCR) technique, it has been demonstrated that MYD88 L265P can be detected in the CSF of BNS patients, and the mutation was also present in the CNS biopsy in one patient. 4,18,26 Moreover, disappearance of the MYD88 L265P by AS-PCR correlated with clinical and MRI response. Since the qPCR is a very sensitive technique, caution must be taken to avoid blood contamination of the CSF since MYD88 L265P can also be detected in peripheral blood.…”

“…3 In approximately 15% to 36% of patients, BNS was the presenting symptom with no previous history of WM. 3,4 These patients may have a better prognosis compared to patients with BNS and a previous history of WM. 4 The clinical suspicion of BNS in these patients with neurological symptoms was raised because of the presence of an IgM M-protein in the serum or the detection of a clonal Bcell population by multiparameter flow cytometry (MFC) in the cerebral spinal fluid (CSF).…”

“…6,36 MRI abnormalities can be found in the majority of patients. 3,4 The goal of neuroimaging is not only to find supportive evidence for BNS, but also for the exclusion of differential diagnoses (infectious and others), and to select a possible site for biopsy. MRI should be performed prior to lumbar puncture to exclude focal mass effects and/or obstructive hydrocephalus as well as to avoid non-specific meningeal enhancement that occurs after CSF sampling.…”

“…46 Simon et al In a cohort of 34 patients, Castillo et al estimated the 3 years overall survival rate to be 59% and identified, in univariate analysis, age above 65 years, previous treatment for WM, and platelet count <100 x 10 9 /L as adverse prognostic factors. 4 …”

“…Two recent retrospective surveys added 44 and 34 patients, respectively, to this total. 3,4 A diagnostic work-up and a classification system for BNS were proposed by Hochberg and colleagues in 2009 and 2011. 5,6 However, 80 years following the first publication, no comprehensive guidelines exist for the diagnostic and therapeutic approach or response assessment of BNS.…”