Waldenström\'s macroglobulinemia (WM) is a B-cell non-Hodgkin\'s lymphoma characterized by clonal IgM-secreting lymphoplasmacytic cell proliferation. Bing-Neel syndrome (BNS) is a rare complication of WM that results in the infiltration of the central nervous system (CNS) with IgM-secreting lymphoplasmacytic cells. This case study presents a 75-year-old Caucasian male with a history of WM and Agent Orange exposure who ultimately was diagnosed with BNS. This patient posed unique diagnostic challenges as the patient experienced clinical symptoms despite the absence of MRI abnormalities and therapeutic challenges.

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.

In Waldenström macroglobulinemia (WM), confirming the presence of Bing-Neel syndrome (BNS) is important because drugs that penetrate the central nervous system (CNS) must be selected. We report the case of a 75-year-old man for whom tirabrutinib, a second-generation Bruton\'s tyrosine kinase inhibitor (BTKi), was useful in treating WM-associated peripheral neuropathy (PN) with BNS. Numbness and muscle weakness in the fingers occurred three years after the initial treatment of WM. WM-associated PN due to demyelinating disease was diagnosed based on the results of a nerve conduction study and magnetic resonance imaging showing bilateral symmetric swelling of the brachial plexus. The cerebrospinal fluid (CSF) cytology results were initially negative; however, the CSF test was repeated because of extremely high protein levels (984 mg/dL) and slightly elevated leukocyte counts (14/µL). The second test revealed abnormal lymphoplasmacytic cells (189/µL), indicating BNS. Rituximab and high-dose methotrexate-containing chemotherapy were administered. Despite the subsequent negative CSF cytology results, his neurological symptoms persisted but subsided soon after the initiation of tirabrutinib. The therapeutic effects of tirabrutinib persisted for 25 months. This case suggested that a careful search for concurrent BNS is important when lesions are close to the CNS or when atypical CSF findings are obtained in patients with WM-associated PN, especially when BTKi options are available.

UNASSIGNED: Bing-Neel syndrome (BNS) is a rare and heterogenous manifestation of Waldenström macroglobulinemia (WM) involving central nervous system (CNS) infiltration by malignant lymphoplasmacytic cells. Efforts to standardize diagnostic criteria have improved in recent years, as have treatment options including the use of the Bruton tyrosine kinase inhibitor (BTKI) ibrutinib.
UNASSIGNED: Here, we present the case of a 70-year-old male with a remote history of WM previously treated with bendamustine and rituximab, who presented to medical attention with several months of left-sided weakness, headache, and ataxia. Brain magnetic resonance imaging revealed numerous enhancing masses in the bilateral cerebral hemispheres, inferior medulla, and upper cervical spine. Laboratory studies showed serum IgM lambda monoclonal gammopathy and elevated free serum kappa and lambda light chains, while cerebrospinal fluid flow cytometry revealed CD19+ B cells. Stereotactic brain biopsy of a right frontal brain lesion was consistent with lymphoplasmacytic lymphoma, confirmed by a positive MYD88 L265P mutation. He received ibrutinib 420 mg orally daily, and this resulted in appreciable clinical and radiologic responses, which have persisted over a 31-month period.
UNASSIGNED: The advent of molecularly targeted agents and novel therapies for WM has provided patients and clinicians with additional therapeutic options. The use of BTK inhibitors with their high-level CNS penetrance, in particular, offers a novel way to treat BNS and improve patient overall survival while maintaining a high level of quality of life. We discuss the importance of MYD88 L265P testing in the context of BNS as well as the expanding role of BTKIs in treating this disease.

UNASSIGNED: This work describes a case of Waldenström macroglobulinemia (WM) relapse presenting with unilateral blurred vision.
UNASSIGNED: A case report is presented.
UNASSIGNED: A 60-year-old woman with a history of WM in remission was referred for suspicious peripheral choroidal lesions and left optic disc swelling. Magnetic resonance imaging revealed optic nerve and cranial nerve infiltration consistent with central nervous system invasion from WM relapse, called Bing-Neel syndrome. Irradiation of the optic nerve and systemic targeted therapy were successful in addressing the ocular features as well as reducing immunoglobulin M paraprotein levels and lymphoproliferative disease burden.
UNASSIGNED: We described the first documented case to our knowledge of intraocular involvement as the earliest sign of relapse of WM. Ophthalmology assessment is warranted in patients with a history of WM who present with new ocular symptoms to aid early detection and treatment of this disease.

A 63-year-old man was diagnosed with Waldenström\'s macroglobulinemia (WM). Six courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) resulted in complete remission, but WM relapsed three years after R-CHOP. After six courses of BR (bendamustine, rituximab), the serum IgM level and CRP normalized. Four years after BR, the patient presented with muscle weakness, sensory disturbance, and myoclonus of lower limbs. T2-weighted magnetic resonance imaging (MRI) showed areas of signal hyperintensity with contrast enhancement in the right temporal and parietal lobes in brain parenchyma, medulla, bilateral basal ganglia, white matter of occipital lobe, and thoracic spinal cord at the Th2-11 levels. Open brain biopsy revealed diffuse proliferation of small lymphocytes and plasmacytoid lymphocytes on the brain surface and around cerebral blood vessels, resulting in a diagnosis of Bing-Neel syndrome (BNS). Two courses of R-MPV (rituximab, methotrexate, procarbazine, and vincristine) resulted in progressive disease, but the neurological symptoms and MRI findings improved following craniospinal irradiation of 30.6 Gy. Three years after craniospinal irradiation, T2-weighted MRI showed recurrence of BNS with progression of myoclonus of lower limbs and IgM elevation. Tirabrutinib was started for the second recurrence of WM and progression of BNS. Two months after the initiation of treatment with tirabrutinib, the myoclonus of lower limbs disappeared and the MRI findings showed improvement. Serum IgM levels decreased and no adverse events were observed. Tirabrutinib shows promise as a therapeutic option for relapsed BNS.

Bing-Neel syndrome (BNS) is a rare disease manifestation of Waldenström\'s macroglobulinemia characterized by abnormal lymphoplasmacytoid cells infiltration of the central nervous system. In September 2019, a 46-year-old man presented to a previous hospital with hand tremors, nausea, and dysuria. Demyelination of cerebral white matter and the spinal cord was discovered using MRI. Steroid pulse therapy was used to treat inflammatory demyelinating disease, and it provided temporary relief, but the symptoms returned when the steroids were stopped. He was referred to our hospital in June 2020, for further evaluation with the possibility of hematological malignancy. BNS was diagnosed based on the presence of abnormal lymphoplasmacytoid cells in the bone marrow and cerebrospinal fluid (CSF), as well as the presence of the MYD88L265P mutation in the CSF specimen. In July 2020, BR (bendamustine, rituximab) therapy was administered, but it was ineffective. Oral administration of tirabrutinib, which was recently approved for WM, began in August 2020. He has achieved long-term remission and steroid withdrawal, with no notable side effects. This is the second report of successful treatment of BNS with tirabrutinib. More research is needed to confirm tirabrutinib\'s efficacy in the treatment of BNS.

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.

A 62-year-old female patient was diagnosed with Waldenstrom\'s macroglobulinemia/lymphoplasmacytic lymphoma (WM/LPL) 8 years ago, which was resolved with rituximab (R) monotherapy. Five years ago, she experienced numbness of the lower limbs, followed by diminished lower limb muscle strength and hearing disturbance. PET-CT scans showed accumulations along the peripheral nerves of the upper and lower limbs together with clonal B lymphocytes in the cerebrospinal fluid, thus a diagnosis of relapse with Bing-Neel syndrome (BNS). After a temporal remission by high-dose cytarabine or bendamustine plus R regimens as salvage treatments, WM/LPL recurred for the third time accompanied by gait disturbances due to muscle weakness and urinary retention. Thus, tirabrultinib was started as a subsequent therapy, which significantly improved the neurological condition together with abnormal findings of magnetic resonance imaging or cerebrospinal fluids. This case is valuable since few relapsed BNS was reported in the literature with successful tirabrutinib 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.