BING-NEEL SYNDROME: ILLUSTRATIVE CASES AND COMPREHENSIVE REVIEW OF THE LITERATURE

Main Article Content

Marzia Varettoni
Irene Defrancesco
Luca Diamanti
Enrico Marchioni
Lisa Maria Farina
Anna Pichiecchio

Keywords

Bing-Neel Syndrome, Waldenström’s Macroglobulinemia, Central Nervous System

Abstract

The Bing-Neel syndrome is a rare neurological complication of Waldenström’s Macroglobulinemia which results from a direct involvement of central nervous system by malignant lymphoplasmacytic cells. The clinical suspicion of Bing-Neel syndrome may be difficult because neurologic symptoms are heterogeneous, non specific and sometimes underhand. A definitive diagnosis of Bing-Neel syndrome can be confidently made using brain and spinal cord magnetic resonance imaging as well as histopathology and/or cerebrospinal fluid analysis to confirm the neoplastic infiltration of central nervous system. The detection in the cerebrospinal fluid of patients with Bing-Neel syndrome of the MYD88 (L265P) somatic mutation, which is highly recurrent in Waldenström’s Macroglobulinemia, revealed useful for the diagnosis and monitoring of central nervous system involvement. Despite recommendations recently published, there is still no clear consensus on treatment of Bing-Neel syndrome, which includes systemic immunochemotherapy, intrathecal chemotherapy and brain irradiation as possible options. Ibrutinib, a Bruton kinase inhibitor highly active in patients with Waldenström’s Macroglobulinemia, has been recently added to the therapeutic armamentarium of Bing-Neel syndrome due to its ability to pass the blood-brain barrier. However, prospective clinical trials are eagerly awaited with the aim to define the optimal treatment strategy. 

Here we describe four illustrative cases of Bing-Neel syndrome diagnosed and treated at our Institution and review the literature on this topic. 

 

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References

Owen RG, Treon SP, Al-Katib A, et al. Clinicopathological definition of Waldenstrom’s Macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom’s Macroglobuliemia. Semin Oncol, 2003; 30(2):110-115

Treon SP. How I treat Waldenstrom Macroglobulinemia. Blood 2015; 126: 721-732

Malkani RG, Tallman M, Gottardi-Littel N, et al. Bing Neel syndrome: an illustrative case and a comprehensive review of the published literature. J Neuroncol 2010, 96(3): 301-312

Bing J, von Neel A. Two cases of hyperglobulinaemia with affection of the central nervous system on a toxi-infectious basis. Acta Med Scand 1936; 88: 492-506

Simon L, Fitsiori A, Lemal R et al, Bing-Neel syndrome, a rare complication of Waldenström’s Macroglobulinemia: analysis of 44 cases and review of literature. A study on behalf of the French Innovative Leukemia Organization (FILO). Haematologica 2015; 100 (12): 1587-1594

Castillo JJ, D’Sa S, Lunn MP, et al. Central nervous system involvement by Waldenstrom macroglobulinaemia (Bing-Neel syndrome): a multi-institutional retrospective study. Br J Haematol 2016; 172: 709–715

Minnema MC, Kimby E, D’Sa S et al, Guideline for the diagnosis, treatment and response criteria for Bing-Neel syndrome. Haematologica, 2017; 102(1):43-51

Varettoni M, Marchioni E, Bonfichi M, 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: E152-E153

Cabannes-Hamy A, Lemal R, Goldwirt L, et al. Efficacy of Ibrutinib in the treatment of Bing-Neel syndrome. Am J Hematol, 2016; 91(3): E17-19

Mason C, Savona S, Rini JN, et al. Ibrutinib penetrates the blood brain barrier and shows efficacy in the therapy of Bing Neel syndrome. Br J Haematol, 2016; doi:10.1111/bjh.14218

Stone MJ, Bogen SA. Evidence-based focused review of management of hyperviscosity syndrome. Blood 2012; 119(10): 2205-2208

Stork AC, van der Pol WL, Franssen H, et al. Clinical phenotype of patients with neuropathy associated with monoclonal gammopathy: a comparative study and a review of the literature. J Neurol 2014; 261(7): 1398-1404

Grewal JS, Brar JK, Sahijdak WM et al. Bing Neel syndrome: a case report and systematic review of clinical manifestations, diagnosis and treatment options. Clin Lymphoma Myeloma 2009; 9(6): 462-466

Gupta N, Gupta S, Al Ustwani O, et al. Bing-Neel syndrome in a patient with Waldenstrom's macroglobulinemia: a challenging diagnosis in the face of normal brain imaging. CNS Neurosci Ther 2014;20(10): 945-946

Zetterberg. Patognomonic cerebrospinal fluid findings in Bing-Neel syndrome. J Neurooncol 2011; 104 (2): 615

Hughes MS, Atkins EJ, Cestari DM et al. Isolated optic nerve, chiasm, and tract involvement in Bing Neel syndrome. J Neuroophtalmol 2014; 34(4):340-345

Stacy RC, Jakobiec FA, Hochberg FH, et al. Orbital involvement in Bing Neel syndrome. J Neuroophtalmol, 2010; 30(3): 255-259

Treon SP, Xu L, Yang G et al. MYD88 L265P somatic mutation in Waldenstrom’s macroglobulinemia. N Engl J Med 2012; 367: 826-833

Poulain S, Boyle EM, Roumier C, et al. MYD88 L265P mutation contributes to the diagnosis of Bing Neel syndrome. Br J Haematol 2014; 167: 506-513

Montesinos-Rongen M, Godlewska E, Brunn A, et al. Activating L265P mutations of the MYD88 gene are common in primary central nervous system lymphoma. Acta Neuropathol 2011 Dec; 122(6):791-792

Elliott MA, Letendre L, Li CY, et al. Chronic lymphocytic leukemia with symptomatic diffuse central nervous system infiltration responding to therapy with systemic fludarabine. Br J Haematol 1999; 104: 689-694

Knop S, Herrlinger U, Ernemann U, et al. Fludarabine may induce durable remission in patients with leptomeningeal involvement of chronic lymphocytic leukemia. Leuk Lymphoma 2005; 46: 1593-1598

Vos JM, Kersten MJ, Kraan W et al. Effective treatment of Bing Neel syndrome with oral fludarabine: a case series of four consecutive patients. Br J Haematol 2016; 172 (3): 461-464

Bernard S, Goldwirt L, Amorim S et al. Activity of ibrutinib in mantle cell lymphoma patients with central nervous system relapse. Blood 2015; 126(14):1695-1698

Saad S, Wang TJ. Neurocognitive deficits after radiation therapy for brain malignancies. Am J Clin Oncol 2015; 38(6):634-640

Tallet AV, Azria D, Barlesi F et al. Neurocognitive function impairment after whole brain radiotherapy for brain metastases: actual assessment. Radiat Oncol 2012; 7:77