Bing-Neel Syndrome: An Initial Manifestation of Waldenstrom Macroglobulinemia

Waldenstrom macroglobulinemia (WM) is a low-grade B-cell lymphoma characterized by bone marrow infiltration by monoclonal lymphoplasmacytic cells plus an IgM monoclonal gammopathy. Bing-Neel syndrome (BNS) is a rare manifestation of WM where malignant lymphoplasmacytic cells infiltrate the central nervous system (CNS). Though only present in 0.8% of WM cases, it is likely underdiagnosed and may present before or during WM treatment. Here, we present a case of BNS as an initial sign of WM. A 75-year old male presented with confusion, gait instability, and expressive aphasia. MRI demonstrated a 5.5-cm mass in the right frontal lobe, crossing midline. Brain biopsy showed CNS lymphoma and later tested positive for the MYD88L265P mutation suggesting WM (as is a mutation in 90-95% WM patients). Indeed, quantitative serum immunoglobulins showed elevated IgM. Initial treatment for WM was started with rituximab, methylprednisolone, carfilzomib, and ibrutinib. MRI two months after initiation showed good response, and the patient was transitioned to ibrutinib monotherapy. Surveillance MRI one year later showed patchy right frontal lobe enhancement indicating disease progression, and therefore the patient was placed back on his initial treatment regimen. However, ibrutinib later had to be held due to thrombocytopenia. Two months after re-starting chemotherapy, he presented with bizarre behavior, and MRI showed extensive disease progression. He was then transitioned to palliative chemotherapy with high dose methotrexate and rituximab. He has responded well to this regimen, and MRI two years after diagnosis showed no recurrent disease. BNS is a rare but easily missed manifestation of WM. As per the recent National Comprehensive Cancer Network (NCCN) guidelines and the 8th International Workshop on WM (IWWM-8), no standardized diagnostic or management guidelines for BNS is available. Direct brain biopsy is the gold standard for diagnosis. Due to its low incidence, rarity, and limited prospective trial, there is a lack of a clear standard of care therapy. Specific treatment regimen depends on the patient factors and treatment tolerability. IWWM-8 suggests the use of a variety of cytotoxic chemotherapies or ibrutinib. A high-quality meta-analysis of existing reports is critical to characterize the diagnostic features and optimal treatment for BNS. The prognosis of BNS remains unclear, with an estimated three-and five-year survival rate at 59% and 71%, respectively. BNS is an infrequent complication of WM. Clinicians should suspect BNS with persistent, unexplained neurologic symptoms in WM.