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Table of Contents    
Year : 2021  |  Volume : 69  |  Issue : 5  |  Page : 1459-1460

Meningeal Involvement as Initial Presentation of Waldenström Macroglobulinemia (Bing–Neel Syndrome)

1 Department of Neurology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina
2 Department of Pathology, Italian Hospital of Buenos Aires, Buenos Aires, Argentina

Date of Submission18-Jun-2018
Date of Decision29-Mar-2020
Date of Acceptance15-May-2021
Date of Web Publication30-Oct-2021

Correspondence Address:
Agustin Pappolla
Perón 4190 Street, Postal Address C1199ABB, Buenos Aires
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0028-3886.329587

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How to cite this article:
Pappolla A, Cristina ZM, Rugiero M, Christiansen S, Rivello HG. Meningeal Involvement as Initial Presentation of Waldenström Macroglobulinemia (Bing–Neel Syndrome). Neurol India 2021;69:1459-60

How to cite this URL:
Pappolla A, Cristina ZM, Rugiero M, Christiansen S, Rivello HG. Meningeal Involvement as Initial Presentation of Waldenström Macroglobulinemia (Bing–Neel Syndrome). Neurol India [serial online] 2021 [cited 2022 May 24];69:1459-60. Available from: https://www.neurologyindia.com/text.asp?2021/69/5/1459/329587


A 76-year-old woman with a history of breast cancer in remission complained about a left visual field defect that had started the previous day. She also reported asthenia, night sweats, and severe weight loss in the last 6 months. Her physical examination revealed a right homonymous hemianopsia without other abnormalities. Laboratory tests were performed at admission showing as positive results anemia of chronic disease, C-reactive protein 2.75 mg/dL, erythrosedimentation rate 78 mm/h, and an IgM Kappa monoclonal gammopathy. Serum IgM levels were later determined of 560 mg/mL (normal value: 70–250 mg/mL). CSF examination, including viral serologies, culture, pathology, and flow cytometry was unremarkable. A contrast enhanced CT scan and a brain MRI were performed, showing signs of subcortical vasogenic edema within the left occipital lobe. Additionally, intense dural and leptomeningeal enhancement in the left occipital sulci was observed after contrast administration in both diagnostic procedures. Given her oncological history and the new haematological abnormalities, we decided to perform a whole-body PET scan, observing a marked uptake of the radiotracer at the left occipital lobe [Figure 1]. The rest of the study was negative for oncological disease or organomegalies. A bone marrow aspiration was performed, revealing an IgM-producing lymphoplasmacytic lymphoma. A meningeal biopsy was later performed, confirming the diagnosis with an additional MyD88 gene mutation in the sample [Figure 2]. The patient started treatment with Rituximab and Ibrutinib, achieving to date a marked improvement in her neurological symptoms and imagenological findings.
Figure 1: Brain MRI FLAIR sequence (a) shows subcortical vasogenic edema within the left occipital lobe. T1W brain MRI (b) and CECT scan (c) disclose dural and leptomeningeal enhancement at the left occipital sulci after contrast administration. Whole Body PET-CT scan evidences increased radiotracer uptake (SUV 24) with similar distribution (d)

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Figure 2: Meningeal biopsy shows a dense infiltration of round lymphoid and plasmacytoid cells in hematoxylin and eosin section (a) with positivity for CD20 (b), kappa light chain (c) and IgM (d)

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Waldenstrom's macroglobulinemia (WM) is a lymphoproliferative disease that accounts for 1–2% of non-Hodgkin lymphomas. It is characterized by the abnormal proliferation of lymphoid cells that secrete IgM in the bone marrow, with a peripheral circulating monoclonal paraprotein of the IgM Kappa type. About 20% of the patients develop extramedullary disease in the course of the illness, being the reticuloendothelial system (liver, spleen, and lymph nodes) the most frequent location, followed by CNS involvement in approximately 22% of the cases, also known as Bing–Neel syndrome (BNS).[1],[2]

Approximately, one-third of the patients diagnosed with BNS are simultaneously diagnosed with WM. On the other hand, one-third of the WM diagnosis follow an initial diagnosis of BNS; the rest of the BNS cases are diagnosed in the context of previous WM treatment. The reason why the latter situation might occur is that some common drugs used to treat WM do not penetrate successfully the CNS.[3]

In decreasing order of frequency, the signs and symptoms of BNS are focal deficits, mental status changes, cranial neuropathies (particularly, oculomotor, and facial palsies), headache, and seizures. For this reason, it is highly recommended to perform a brain and/or spinal cord scan with high-field MRI,[3] which may show T2/FLAIR hyperintensities in the brain parenchyma, spinal cord, leptomeninges, or cauda equina with contrast enhancement after gadolinium administration in T1 sequences. Definitive diagnosis can be achieved by CSF pathology and flow cytometry. If negative results are obtained, a directed biopsy associated with immunophenotyping is suggested, including the MyD88 gene mutation.[4]

The agents currently used to treat CNS involvement in WM are Ibrutinib, Bendamustine, Rituximab, and Fludarabine,[5],[6],[7] yielding variable results that mainly depend on the patient's age and the degree of systemic extension of the disease.

This case represented a diagnostic challenge, as the finding of an IgM Kappa paraprotein and constitutional symptoms, both suggesting an underlying oncohematological disease, were present in a patient with a history of breast cancer. In addition, reticuloendothelial involvement was clinically and imagenologically absent and CSF examination was unrevealing. These features directed us toward a bone marrow and meningeal biopsy, leading to the final diagnosis. Knowledge of the clinical presentation, imaging features, and available diagnostic procedures is therefore mainstay for appropriate patient treatment.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Castillo JJ, D'Sa S, Lunn MP, Minnema MC, Tedeschi A, Lansigan F, et al. Central nervous system involvement by Waldenström macroglobulinaemia (Bing-Neel syndrome): A multi-institutional retrospective study. Br J Haematol 2016;172:709-15.  Back to cited text no. 1
García-Sanz R, Montoto S, Torrequebrada A, de Coca AG, Petit J, Sureda A, Rodríguez-García JA, et al. Waldenström macroglobulinaemia: Presenting features and outcome in a series with 217 cases. Br J Haematol 2001;115:575-82.  Back to cited text no. 2
Simon L, Fitsiori A, Lemal R, Dupuis J, Carpentier B, Boudin L, et al. Bing-Neel syndrome, a rare complication of Waldenström macroglobulinemia: analysis of 44 cases and review of the literature. A study on behalf of the French Innovative Leukemia Organization (FILO). Haematologica 2015;100:1587-94.  Back to cited text no. 3
Treon SP, Xu L, Yang G, Zhou Y, Liu X, Cao Y, et al. MYD88 L265P somatic mutation in Waldenström's macroglobulinemia. N Engl J Med 2012;367:826-33.  Back to cited text no. 4
Castillo JJ, Palomba ML, Advani R, Treon SP. Ibrutinib in Waldenström macroglobulinemia: Latest evidence and clinical experience. Ther Adv Hematol 2016;7:179-86.  Back to cited text no. 5
Varettoni M, Marchioni E, Bonfichi M, Picchiecchio A, Arcaini L, Arbasino C, et al. Successful treatment with Rituximab and Bendamustine in a patient with newly diagnosed Waldenstrom's Macroglobulinemia complicated by Bing-Neel syndrome. Am J Hematol 2015;90:152-3.  Back to cited text no. 6
Vos JMI, Kersten M-J, Kraan W, Groeneveld ON, Linn C, Pals ST, et al. Effective treatment of Bing-Neel Syndrome with oral fludarabine: A case series of four consecutive patients. Br J Haematol 2016;172:461-4.  Back to cited text no. 7


  [Figure 1], [Figure 2]


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