Bing-Neel Syndrome Research Articles

A Rare Case of Combined Direct Retinal Involvement and Suspected Bing-Neel Syndrome in a Patient With Waldenstrom’s Macroglobulinemia

A Rare Case of Combined Direct Retinal Involvement and Suspected Bing-Neel Syndrome in a Patient With Waldenstrom’s Macroglobulinemia

Ibrutinib as treatment for Bing–Neel syndrome reclassified as glioblastoma: a case report

BackgroundGlioblastoma is a highly malignant disease with limited treatment options. Ibrutinib, a covalent Bruton tyrosine kinase inhibitor, is an oral agent with manageable side effects used for hematological diseases including Waldenström macroglobulinemia. We present the case of a 69-year-old Caucasian male patient treated with ibrutinib for suspected Bing–Neel syndrome (BNS), which following a biopsy, was reclassified as glioblastoma.Case presentationIn December 2018, a 69-year-old Caucasian male patient was diagnosed with Waldenström macroglobulinemia. As the patient was asymptomatic, without bone marrow failure or high M-component count, watchful waiting was initiated. Due to increasing neurological symptoms, the patient, based on magnetic resonance imaging, was diagnosed with Bing–Neel syndrome in May 2019. The patient received different treatments before starting ibrutinib monotherapy in August 2019 due to disease progression, both on magnetic resonance imaging and clinically. The patient remained clinically stable for 7 months. In March 2020, the patient developed headaches, and both magnetic resonance imaging and a biopsy revealed glioblastoma IDH-wildtype. Treatment was changed in line with the new diagnosis, but the patient died at the end of 2020.ConclusionWe present a case in which a patient with glioblastoma IDH-wildtype remained clinically stable for 7 months when treated with ibrutinib monotherapy, which is similar to what would be expected for the standard treatment for glioblastoma. To our knowledge, this is the first patient receiving ibrutinib for a glioblastoma IDH-wildtype with a meaningful clinical outcome. Our case may therefore support previous nonclinical findings, indicating a therapeutic value of ibrutinib in patients with glioblastoma and support for further investigation of ibrutinib as a possible treatment for glioblastoma.

Waldenström Macroglobulinemia - A State-of-the-Art Review: Part 1: Epidemiology, Pathogenesis, Clinicopathologic Characteristics, Differential Diagnosis, Risk Stratification, and Clinical Problems.

Waldenström macroglobulinemia (WM) is an infrequent variant of lymphoma, classified as a B-cell malignancy identified by the presence of IgM paraprotein, infiltration of clonal, small lymphoplasmacytic B cells in the bone marrow, and the MYD88 L265P mutation, which is observed in over 90% of cases. The direct invasion of the malignant cells into tissues like lymph nodes and spleen, along with the immune response related to IgM, can also lead to various health complications, such as cytopenias, hyperviscosity, peripheral neuropathy, amyloidosis, and Bing-Neel syndrome. Chemoimmunotherapy has historically been considered the preferred treatment for WM, wherein the combination of rituximab and nucleoside analogs, alkylating drugs, or proteasome inhibitors has exhibited notable efficacy in inhibiting tumor growth. Recent studies have provided evidence that Bruton Tyrosine Kinase inhibitors (BTKI), either used independently or in conjunction with other drugs, have been shown to be effective and safe in the treatment of WM. The disease is considered to be non-curable, with a median life expectancy of 10 to 12 years.

Waldenstrom Macroglobulinemia Recurrence with Bing–Neel Syndrome Presentation

Bing–Neel syndrome (BNS) is a rare condition that may occur in patients with Waldenstrom macroglobulinemia (WM) and is caused by lymphoplasmacytic infiltration into the central nervous system. BNS is an extramedullary manifestation of WM which may present with various neurological signs and symptoms that make the diagnosis difficult to achieve. We present a case of BNS in a 60-year-old patient diagnosed 6 years after recovering from Waldenstrom’s macroglobulinemia. We observed the patient for a secondary generalized focal motor seizure. Unenhanced brain CT revealed slight hyperdensity of left parietal subarachnoid spaces. The MRI of the brain and spinal cord showed leptomeningeal enhancement in both parietal lobes. The presence of monoclonal bands (light chain k and IgM) was found in cerebrospinal fluid, leading to the diagnosis of BNS. The patient started treatment with ibrutinib and remains clinically stable during a 1-year follow-up. However, the MRI showed the appearance of a new subcortical left parietal lesion. BNS is an extremely rare presentation of WM that should be recognized and considered early in the presence of unexplained neurological symptoms in patients with a history of WM, even if the patient appears to have recovered.

MYD88 mutation-positive indolent B-cell lymphoma with CNS involvement: Bing-Neel syndrome mimickers.

MYD88 p.L265P mutation occurs in over 90% of Waldenström's macroglobulinemia (WM), which is characterized by lymphoplasmacytic lymphoma (LPL) with monoclonal IgM. WM requires careful diagnosis due to overlapping features with other B-cell malignancies. Bing-Neel syndrome (BNS), a rare complication of WM, involves central nervous system (CNS) invasion. This report describes two cases of morphologically low-grade B-cell lymphoma in the bone marrow accompanied by the presence of a large B-cell lymphoma in the brain and a common MYD88 p.L265P mutation, which were eventually established as BNS mimickers. Although the two components in these cases showed the same identical light-chain restriction, different immunoglobulin heavy-chain rearrangement peaks indicated distinct lymphoma stem cells for CNS and bone marrow lesions. These clinical cases emphasize the challenges in diagnosing BNS. Based on the findings, biopsy is recommended for accurate identification of the clonal relationship and MYD88 mutation status.

Bing–Neel Syndrome: An Unknown GCA Mimicker

Giant cell arteritis (GCA) is a chronic granulomatous vasculitis of medium and large arteries leading to cranial and extracranial manifestations. Temporal artery biopsy is considered the gold standard; however, its sensitivity is low at 47%. We report a unique case of Bing–Neel Syndrome (BNS) presenting as biopsy‐proven GCA. BNS is a rare complication (1%) of Waldenstrom Macroglobulinemia (WM), which results from infiltration of lymph plasmacytoid cells and plasma cells into the central nervous system. A 77‐year‐old female with a past medical history of glaucoma, hypertension, diabetes, and chronic ocular ischemic syndrome in her right eye presented with progressive left eye vision loss for 5 days. Fundoscopic examination was notable for pseudophakic pseudopallor but no optic disc edema. Intraocular pressure was >40 and normalized after acetazolamide. The patient was started on pulse dose steroids by her neuro‐ophthalmologist. She was discharged home on 60 mg of prednisone. At follow up with her neuro‐ophthalmologist, new dot blot hemorrhages in the left eye were noted and she was readmitted for pulse dose of intravenous methylprednisolone. Temporal artery biopsy was consistent with GCA spectrum. Work up revealed paraproteinemia and subsequent bone marrow biopsy demonstrated WM. The patient was treated for her WM and her ophthalmic complications stabilized.

A Case of Bing-Neel Syndrome Presenting Like Giant Cell Arteritis.

A 55-year-old woman presented with new-onset headache, scalp tenderness, shoulder arthralgias, night sweats, and loss of appetite. She was diagnosed with giant cell arteritis by her primary care physician and commenced on oral corticosteroids. However, her headache, scalp tenderness, and night sweats persisted. She then developed right Horner syndrome and trigeminal hypoesthesia. Extensive blood work-up revealed mildly elevated inflammatory markers and a paraproteinemia. Subsequent bone marrow biopsy showed lymphoplasmacytic lymphoma, with 10% of hemopoiesis, and staging led to the diagnosis of Waldenstrom macroglobulinemia without nodal or central nervous system (CNS) lesions. Immunohistochemical staining of a temporal artery biopsy showed perivascular lymphoplasmacytic cells and paraprotein deposits. She was diagnosed with CNS involvement of her macroglobulinemia-Bing-Neel syndrome (BNS). Identification of rare CNS involvement of lymphoma is challenging when a patient is already on steroid immunosuppression. In the absence of clear diagnostic criteria, the rare and heterogenous BNS remains a clinical diagnosis.

Bing–Neel Syndrome and Coexisting Pituitary Macroadenoma in a Patient with Waldenström Macroglobulinemia Revealed by 18F-FDG and 68Ga-Pentixafor PET/CT

A 63-year-old man presenting with peripheral neuropathies was diagnosed of Waldenström's macroglobulinemia, and Bing-Neel syndrome was subsequently confirmed via cerebrospinal fluid examinations. Besides involvement in bone marrow, lymph nodes, as well as the thoracic and sacral nerve root, 68Ga-Pentixafor PET/CT detected active tracer uptake in bilateral choroid plexus, which was negative in 18F-FDG PET/CT, possibly suggesting the involvement of Bing-Neel syndrome. The coexisting pituitary macroadenoma was FDG-avid but negative in 68Ga-Pentixafor PET/CT. After six cycles of chemotherapy, the follow-up PET/CT showed complete remission of the previous disease, including the high uptake of 68Ga-Pentixafor in choroid plexus. However, the hypermetabolic pituitary macroadenoma remained unchanged.

Bing Neel Syndrome: A Rare Contributing Factor of Psychosis and Suicidality.

Suicide rapidly increased in the United States by 30% from 2000 to 2020, accounting for more than 800,000 deaths ( Neurosci Res Program Bull . 1972; 10: 384-8). Studies have shown that there are a multitude of underlying issues, including mental illness, that elevate an individual's risk of dying by suicide ( CDC WONDER: Underlying cause of death, 1999-2019 . Atlanta, GA: US Department of Health and Human Services, CDC; 2020). Presented here is a case of Bing Neel syndrome (BNS) found in a 69-year-old man who died by suicide by jumping off a 135' bridge. His medical history was significant for traumatic brain injury, Waldenstrom macroglobulinemia (WM), major depressive disorder, suicidal ideation, and anxiety. Bing Neel syndrome is a rare central nervous system complication of WM. His wife reported an abrupt mental deterioration starting 5 years before his death, characterized by paranoia, depression, and insomnia. He had been a high-functioning university professor. His decline culminated with the loss of independence in his activities of daily living. At autopsy, it was found that he experienced blunt force injuries related to the fall, causing his death. A neuropathologic examination revealed a brisk and fulminant clonal CD20 + /immunoglobulin M+ lymphocytic infiltrate, involving all sampled regions of his brain, consistent with WM. This workup was critical to obtaining an accurate pathologic diagnosis of BNS and understanding his full clinical status before death. Although BNS was not the proximate cause of death, this diagnosis aided the death investigation as a causal factor in his suicidality and was vital to providing his family closure.

Report of consensus panel 1 from the 11th International Workshop on Waldenstrom's Macroglobulinemia on management of symptomatic, treatment-naïve patients

Consensus Panel 1 (CP1) of the 11th International Workshop on Waldenstrom's Macroglobulinemia (IWWM-11) was tasked with updating guidelines for the management of symptomatic, treatment-naïve patients with WM. The panel reiterated that watchful waiting remains the gold standard for asymptomatic patients without critically elevated IgM or compromised hematopoietic function. For first-line treatment, chemoimmunotherapy (CIT) regimens such as dexamethasone, cyclophosphamide, rituximab (DRC), or bendamustine, rituximab (Benda-R) continue to play a central role in managing WM, as they are effective, of fixed duration, generally well-tolerated, and affordable. Covalent BTK inhibitors (cBTKi) offer a continuous, generally well-tolerated alternative for the primary treatment of WM patients, particularly those unsuitable for CIT. In a Phase III randomized trial updated at IWWM-11, the second-generation cBTKi, zanubrutinib, was less toxic than ibrutinib and induced deeper remissions, thus categorizing zanubrutinib as a suitable treatment option in WM. While the overall findings of a prospective, randomized trial updated at IWWM-11 did not show superiority of fixed duration rituximab maintenance over observation following attainment of a major response to Benda-R induction, a subset analysis showed benefit in patients >65 years and those with a high IPPSWM score. Whenever possible, the mutational status of MYD88 and CXCR4 should be determined before treatment initiation, as alterations in these 2 genes predict sensitivity towards cBTKi activity. Treatment approaches for WM-associated cryoglobulins, cold agglutinins, AL amyloidosis, Bing-Neel syndrome (BNS), peripheral neuropathy, and hyperviscosity syndrome follow the common principle of reducing tumor and abnormal protein burden rapidly and deeply to improve symptoms. In BNS, ibrutinib can be highly active and produce durable responses. In contrast, cBTKi are not recommended for treating AL amyloidosis. The panel emphasized that continuous improvement of treatment options for symptomatic, treatment-naïve WM patients critically depends on the participation of patients in clinical trials, whenever possible.

Diagnosing, Imaging and Successfully Treating a Debilitating Case of Bing-Neel Syndrome: A Multidisciplinary Feat

Waldenstroms Macroglobulinaemia (WM) is a rare B-cell lymphoma representing ~2% of all haematological malignancies. While most neurological complications of WM are secondary to the overproduction of Immunoglobulin M (IgM), Bing-Neel Syndrome (BNS) is an extremely rare direct Central Nervous System (CNS) infiltration by malignant Lymphoplasmocytic Lymphoma (LPL) cells. Limited information on BNS exists in the literature with sparse case reports and case series. Here we present a diagnostically challenging BNS case successfully treated with systemic chemoimmunotherapy and ibrutinib, with remarkable clinical response.

A Case of Waldenström’s Macroglobulinemia Complained of Anorexia

It has been reported that an 82-year-old man had complained of “anorexia with wasting away (weight loss of 35 pounds) over the past six months”. The cause was unknown, and his appetite dropped to only liquid milk and soy milk every day. On further examination, his CA-199 (a tumor marker) was in the normal range, but the serum IgM level was found to be 4 times higher than normal, and lymphoplasmacytic cells in his bone marrow were 2 times higher than normal. His myeloid differentiation factor (MYD88) was detected to be positive in gene mutations, confirming a diagnosis of “Waldenström’s macroglobulinemia” (WM) complicated with “Bing-Neel syndrome” (BNS); as a result, the anorexia was attributed to it, and the symptomatic treatment with Traditional Chinese Medicine (TCM) was proposed to improve his condition.

Unique Presentation of Bing-Neel Syndrome With Co-existing Chronic Lymphocytic Leukemia.

Unique Presentation of Bing-Neel Syndrome With Co-existing Chronic Lymphocytic Leukemia.

Bing–Neel Syndrome: Update on Diagnosis and Treatment

Bing–Neel syndrome (BNS) is a rare neurological complication of Waldenström macroglobulinaemia. We highlight key issues in clinical presentation, diagnosis, and treatment while focusing on new and emerging therapies available for patients diagnosed with BNS. It is anticipated that further development of Bruton Tyrosine Kinase (BTK) inhibitors and less toxic chemoimmunotherapies will improve treatment delivery and response.

Type 1 Cryoglobulinaemia Associated with Waldenström Macroglobulinemia, IgM MGUS or Non-Hodgkin Lymphoma

Introduction: Type 1 cryoglobulinaemia is defined by monoclonal immunoglobulins which precipitate at temperatures <37°C and redissolve on warming. IgM monoclonal protein may be associated with type I cryoglobulinaemia with underlying Waldenström macroglobulinemia (WM), non-Hodgkin lymphoma (NHL) or monoclonal gammopathy of undetermined significance (MGUS). Due to its rarity, the incidence and clinical outcomes are poorly understood, with fewer than 40 patients characterised in the largest series. Clonal characteristics have not previously been described. We analysed the incidence, clinical and clonal characteristics of the largest reported series of IgM-associated type I cryoglobulinaemia. Methods: Data for consecutive adult patients (> 18 years) with IgM-associated type I cryoglobulinaemia identified between 2013-2022 from 2 centres (University College London Hospital [UCLH], UK and AMC, Netherlands) were retrospectively analysed and followed up to June 2022. In order to calculate the incidence of type I cryoglobulinaemia, the total number of requests performed at UCLH was also determined. Results: 423 samples were screened for cryoglobulinaemia between 2013-2022 from all patients with an IgM-associated disorder at the specialist centre, UCLH. 140 (33%) were positive for all-type cryoglobulinaemia; 94 (22%) patients had type I cryoglobulinaemia. Four additional patients were recruited from Amsterdam UMC, without incidence data. In total, 98 patients (58 male, 40 female) were identified with type I cryoglobulinaemia; the majority with underlying WM (defined as >10% bone marrow infiltration) (77; 79%), and remaining IgM MGUS (16; 16%) and NHL (4 marginal zone lymphoma, 1 CLL; 5%). The median age at cryoglobulin diagnosis was 66 years (range 39-90). There was a kappa light-chain predominance in the majority (85%). MYD88L265Pwas present in 44/49 (90%) of WM and 3/8 (38%) MGUS cases. CXCR4 was mutated in 5/13 (38%) WM cases. Coexistent IgM-associated disorders were present in 25: cold agglutinin disease/syndrome (CAD/CAS, 15%), Bing-Neel syndrome (7%), anti-MAG antibodies (5%), Schnitzler syndrome (1%). Those with coexistent CAD/CAS had characteristics of a CAD clone, significantly associated with MGUS (vs WM/NHL, p<0.0001) and MYD88-wild type (p<0.0001). Patients with co-existent anti-MAG antibodies were significantly more likely to have MGUS (p=0.0245). Median M-protein at diagnosis of cryoglobulinaemia was 12g/l (range 0-63) and lowest in the MGUS cohort vs WM vs NHL (4g/l vs 16g/l vs 10g/l, p=0.0003). The majority were diagnosed with cryoglobulinaemia >3 months after diagnosis of the underlying IgM disorder (60/98; 61%), at a median of 46 months (range 4-442) and longer in those with WM compared with MGUS or NHL (51 vs 17 vs 13 months, p=0.023). Forty nine percent were symptomatic at cryoglobulinaemia diagnosis, with a trend towards a greater proportion in those with MGUS/NHL vs WM (75%/60% vs 43%, p=0.0569). The most common symptoms were cutaneous/vasomotor symptoms (28%), neuropathy (21%), hyperviscosity (10%), arthralgia (7%) and renal involvement (2%). No cases had cardiac or pulmonary involvement. At a median follow up of 2.4 years (range 0-9.4), 2-year overall survival (OS) was 89% (95% CI 80-94), 5-year OS was 73% (95% CI 56-84). Age was the only predictor of OS (Hazard ratio [HR] 1.07, 95% CI 1.01-1.12, p=0.006). Fourteen patients required chemoimmunotherapy for cryoglobulinaemia at a median of 1 month (0-7) from diagnosis for cutaneous manifestations (5/14; 36%), cryoglobulinaemic glomerulopathy (2/14; 14%) or hyperviscosity (9/14; 64%). Independent predictors of cryoglobulinaemia-indicated treatment-free survival/death included cutaneous involvement (HR 1.48, 95% CI 1.21-7.7.92, p=0.018) and hyperviscosity (HR 5.21 95% CI 4.21-27.8, p<0.0001) at cryoglobulinaemia diagnosis on multivariate analysis. Conclusions: This is the largest reported series describing the characteristics of IgM-associated type I cryoglobulinaemia. It is common amongst patients with monoclonal IgM disorders and approximately half of patients may be symptomatic. Distinct clonal populations are present in which type I cryoglobulinaemia may develop including an MYD88L265P WM clone and MYD88-wild type CAD/anti-MAG clone. Treatment may be required selectively in those with hyperviscosity, cutaneous or renal involvement, in a short time from diagnosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Bing-Neel Syndrome, a Rare Presentation of Waldenström Macroglobulinemia-A Multicenter Report by the Polish Lymphoma Research Group.

Bing-Neel syndrome (BNS) is a rare presentation of Waldenström macroglobulinemia (WM). BNS is a consequence of the central nervous system (CNS) involvement by lymphoplasmacytic lymphoma (LPL) and, rarely, the peripheral nervous system. The data on BNS are extremely scarce. Therefore, we performed a multicenter retrospective analysis of BNS patients diagnosed and treated in centers aligned with the Polish Lymphoma Research Group. The analysis covers the years 2014–2021. Eleven patients were included, 55% females and the median age at BNS diagnosis was 61 years. The median time from WM to BNS was 3.5 years; 27% of patients did have a diagnosis of WM and BNS made simultaneously or within 30 days from each other. Isolated parenchymal involvement was the least frequent (20%). Patients were treated with different regimens, mostly able to cross the blood-brain barrier, including 18% treated with ibrutinib first line. The cumulative objective response to treatment was 73%. With the median follow-up of 20 months (95% CI, 2–32), the 36-month estimates were: overall survival (OS) 47%, progression-free survival (PFS) 33%, and cumulative incidence of BNS-associated death 41%. The performance status according to ECOG was significant for PFS (HR = 7.79) and the hemoglobin concentration below 11 g/dL was correlated with PFS. To conclude, BNS is a very rare manifestation of WM. It is associated with a poor outcome with most patients succumbing to BNS.

Bing-Neel Syndrome: Real-Life Experience in Personalized Diagnostic Approach and Treatment.

The involvement of the central nervous system (CNS) in Waldenström’s Macroglobulinemia (WM) is a rare extramedullary manifestation of the disease known as Bing-Neel syndrome (BNS). To expand our understanding of this disease manifestation, we conducted a retrospective analysis of the incidence of BNS in 86 consecutive patients with WM [70% male, median age 65 years (range 33-86)] seen in our center during a 30-year period. Six patients (7%) from this group were diagnosed with BNS. The median period of time between WM diagnosis and BNS diagnosis was 6.8 years (range 2.3-15). They demonstrated a range of neurological deficits, including transient expressive aphasia, impaired vision, resting hand tremor, foot drop, and headache. Between the onset of symptoms and the diagnosis of BNS, the median time interval was 12.5 months (range 1-30). The diagnosis was made not on the basis of neurological symptoms or radiological evidence, but on the basis of the presence of WM cells in cerebrospinal fluid (CSF). Intrathecal chemotherapy with methotrexate, cytarabine, and dexamethasone (IT MTX, ARA-C, DEX) was used as front-line treatment, followed by intensive immunochemotherapy with rituximab, high-dose MTX, and ARA-C (R-Hi MTX/ARA-C) in three patients who were fit enough to receive this type of cytotoxic regimen, and rituximab plus bendamustine (R-Benda) in two patients who simultaneously required treatment for WM. Ibrutinib was administered to five patients (three as consolidation and two for initial treatment). All patients responded to front-line treatment, with four (67%) achieving partial response (PR) and two (33%) achieving complete response (CR). This study provides insight into the clinical presentation, diagnostic and treatment options, as well as the outcome of patients who have BNS.

P1112: TREATING BING-NEEL SYNDROME USING A TAILORED APPROACH: EXPERIENCE OF A SPECIALIST NEUROHAEMATOLOGY CLINIC

Background: Bing-Neel syndrome (BNS) is a rare complication of lymphoplasmacytic lymphoma (LPL) comprising LPL infiltration in the central nervous system (CNS). Clinical and radiological features are diverse; the diagnosis is confirmed by cerebrospinal fluid (CSF) analysis using immunological and molecular techniques. Rarely, a tissue biopsy is required. The pattern of presentation including systemic involvement and CSF features inform treatment strategies, which include CNS-penetrating therapies. Aims: To evaluate the diagnostic characteristics of patients with BNS and their influence on therapy. Methods: Data from patients referred between 2011-2021 for management of BNS to our academic neurohaematology centre were retrospectively reviewed. Those with imaging features alone or where it was not possible to distinguish from high-grade transformation were excluded. Results: Thirty-five patients (22 male, 13 female) were identified. Median age at diagnosis of BNS was 65 years (range 48-85). All patients were symptomatic. In 12 patients (34%) BNS was the de novo presentation of the IgM-related disorder, of which 3 (25%) had no detectable bone marrow (BM) infiltration of LPL at diagnosis. Approximately half (17; 49%) had previously received therapy for LPL; median time to BNS diagnosis in these was 49 months (range 3-125). At BNS diagnosis, BM involvement with LPL ranged from 0-95%. More than half (14/26; 54%) had ≤10% infiltrate and almost a fifth (4/26) >60%. All patients had leptomeningeal involvement and 8 (23%) additionally had parenchymal CNS disease. The majority had kappa light-chain predominance: IgMκ (n=26), non-IgMκ (n=5), IgMλ (n=3), one unknown. The BNS diagnosis was made on CSF analysis (n=28; 80%), leptomeningeal tissue biopsy (n=3; 9%) where CSF was non-informative, or by expert opinion based on supportive clinical, radiological and non-definitive CSF features (n=4; 11%). Of those with a diagnosis based on CSF studies, B-cell clonality was confirmed by flow cytometry (27/28; 96%), MYD88L265P mutation (18/28; 64%) and immunoglobulin gene rearrangement (12/28; 43%). In 22 samples with a full dataset, median CSF white cell count was 25/ul (1-233), CSF protein 1.69g/l (0.35-6), CSF IgM 9.49mg/l (1.07-61.5). The majority were treated with intensive regimens (rituximab, methotrexate (MTX), cytarabine (ARA-C) ± thiotepa/idarubicin; n=30) due to the presence of CNS disease bulk and clinical need, and less commonly ibrutinib (n=3), bendamustine-rituximab (BR, n=1); one patient had intrathecal therapy (MTX, ARA-C) at the height of the COVID pandemic. Of those who received 2 cycles of intensive chemotherapy, 3 had ≥4 cycles followed by BCNU/thiotepa autologous stem cell transplant; 10 proceeded to ‘consolidation’ (indefinite) ibrutinib to limit intensive chemotherapy or tackle systemic disease. At a median follow up of 26 months (range 1-121), median survival was not reached; 2-year overall survival was 91% (95% CI 74-97). Three patients died during treatment (1 invasive fungal infection post COVID-19 during ibrutinib consolidation post MTX/ARA-C based therapy) and 2 during MTX-ARA-C based therapy; 7 patients relapsed or progressed and were treated with ibrutinib: 1 relapsed after ibrutinib use, 1 patient was intolerant of ibrutinib and switched to BR. Image:Summary/Conclusion: Our cohort confirms that BNS may present with leptomeningeal disease and/or parenchymal disease, de novo and without systemic disease. Overall outcomes are excellent with intensive regimens, consolidated with or followed by ibrutinib; however, there are treatment-related toxicities emphasising the need for a tailored approach.

Cerebral Localization of Waldenstrom's Macroglobulinemia: Bing Neel Syndrome a Case Report

In Waldenström's disease, direct involvement of the nervous system by tumor infiltration is rare and exceptional, forming Bing-Neel syndrome, which groups together the central neurological damage of this disease. It is associated with neurological manifestations with confusion, temporo-spatial disorientation or motor impairment.The bing and Néel syndrome must be differentiated and discussed in the face of affections of the central nervous system such as multiform glioblastomas or multifocal leukoencephalopathies as well as primary brain lymphoma.

Bing-Neel Syndrome Mimicking Behavioral Variant Frontotemporal Dementia.

An 80-year-old man presented with a 2-year history of cognitive deficits, apathy, and verbal impulsivity, suggestive of behavioral variant frontotemporal dementia. Medical history included idiopathic facial nerve palsy and Waldenstrom macroglobulinemia, a lymphoplasmacytic lymphoma. Brain MRI showed paraventricular, leptomeningeal, and cranial nerve enhancement (Figure) and enlarged ventricles. Immunocytologic analysis of CSF (58 MPt/L, protein 2.69 g/L, immunoglobulin M 173.25 mg/L) revealed neoplastic B cells. Brain biopsy and immunohistology confirmed Bing-Neel syndrome, a rare diffuse or tumorous1 central nervous manifestation of Waldenstrom macroglobulinemia. Clinical features include sensory or motor deficits, behavioral and cognitive changes, as well as facial or oculomotor nerve palsy.2