Abstract
Waldenstrom’s macroglobulinemia (WM) is a chronic lymphoproliferative disorder within the spectrum of lymphoplasmacytic lymphoma characterized by proliferation of plasma cells, small lymphocytes, and plasmacytoid lymphocytes. Central nervous system involvement is very rare (Bing–Neel [BN] syndrome). We present the case of a 62-year-old woman previously diagnosed with WM who presented with Bing–Neel syndrome and review the published literature which consists of only case reports. We performed a Medline search using the terms “Waldenstrom’s macroglobulinemia and central nervous system” and “Bing–Neel” collecting data on presentation, evaluation, treatment, and outcome and summarizing these findings in the largest pooled series to date. Central nervous system manifestations are localization related. Serum laboratory testing reflects systemic disease. Cerebrospinal fluid analysis may show lymphocytic pleocytosis, elevated protein, and IgM kappa or lambda light chain restriction; cytology results are variable. Imaging is frequently abnormal. Biopsy confirms the diagnosis. Treatment data are limited, but responses are seen with radiation and/or chemotherapy. BN syndrome is a very rare complication of WM that should be considered in patients with neurologic symptoms and a history of WM. Treatment should be initiated as responses do occur that may improve quality of life and extend it when limited or no active systemic disease is present.
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References
Swerdlow SH, International Agency for Research on Cancer, World Health Organization (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. International Agency for Research on Cancer, Lyon, France
Waldenstrom J (1944) Incipient myelomatosis or “essential” hyperglobulinemia with fibrogenopenia: a new syndrome? Acta Med Scand 117:216–247
Bing J, Neel A (1936) Two cases of hyperglobulinemia with affection of the central nervous system on a toxi-infection bases. Acta Med Scand 88:492–506
Vula O, Merhaien P (1972) Cerebral reticuloplasmacytosis with hyperglobulinemia. Its relation to the Bing-Neel syndrome. Eur Neurol 7:155–168
Imai F, Fujisawa K, Kiya N, Ninomiya T, Ogura Y, Mizoguchi Y, Sano H, Kanno T (1995) Intracerebral infiltration by monoclonal plasmacytoid cells in Waldenstrom’s macroglobulinemia—case report. Neurol Med Chir (Tokyo) 35:575–579
Logothetis J, Silverstein P, Coe J (1960) Neurologic aspects of Waldenstrom’s macroglobulinemia; report of a case. Arch Neurol 3:564–573
Edgar R, Dutcher TF (1961) Histopathology of the Bing-Neel syndrome. Neurology 11:239–245
Bhatti MT, Yuan C, Winter W, McSwain AS, Okun MS (2005) Bilateral sixth nerve paresis in the Bing-Neel syndrome. Neurology 64:576–577
Torrey JJ, Katakkar SB (1984) Treatable meningeal involvement in Waldenstrom’s macroglobulinemia. Ann Intern Med 101:345–347
Neau JP, Guilhot F, Dumas P, Besson I, Rivasseau-Jonveaux T, Gil R (1991) [Central neurologic forms of Waldenstrom’s disease Bing-Neel syndrome. 3 cases]. Rev Neurol (Paris) 147:56–60
Delgado J, Canales MA, Garcia B, Alvarez-Ferreira J, Garcia-Grande A, Hernandez-Navarro F (2002) Radiation therapy and combination of cladribine, cyclophosphamide, and prednisone as treatment of Bing-Neel syndrome: case report and review of the literature. Am J Hematol 69:127–131
Donix M, Beuthien-Baumann B, von Kummer R, Gahn G, Thomas F, Holthoff V (2007) Nonfluent aphasia in a patient with Waldenstrom’s macroglobulinemia. J Clin Neurosci 14:601–603
Fain O, Wechsler B, Vidailhet M, Raphael M, Schuller E, Godeau P (1992) [Involvement of central nervous system disclosing Waldenstrom’s disease: demonstration of intrathecal secretion of immunoglobulin M]. Rev Med Interne 13:58–60
Garderet L, Baudel JL, Cervera P, Azizi L, Maury E, Guidet B, Gorin NC, Offenstadt G (2006) ‘Indolent’ Waldenstrom’s macroglobulinemia and a cerebrospinal fluid protein level of 16 g/L. Eur J Haematol 77:80–82
Welch D, Whetsell WO Jr, Weil RJ (2002) Pathologic quiz case. A man with long-standing monoclonal gammopathy and new onset of confusion. Central nervous system involvement by Waldenstrom macroglobulinemia-Bing-Neel syndrome. Arch Pathol Lab Med 126:1243–1244
Scheithauer BW, Rubinstein LJ, Herman MM (1984) Leukoencephalopathy in Waldenstrom’s macroglobulinemia. Immunohistochemical and electron microscopic observations. J Neuropathol Exp Neurol 43:408–425
Weiss AH, Smith E, Christoff N, Kochwa S (1965) Cerebrospinal fluid paraproteins in multiple myeloma. J Lab Clin Med 66:280–293
Frantzen E, Hertz H, Matzke J, Videbaek A (1969) Protein studies on cerebrospinal fluid and neurological symptoms in myelomatosis. Acta Neurol Scand 45:1–17
Hansotia P, Gani K, Friedenberg W (1983) Cerebrospinal fluid monoclonal gammopathy in multiple myeloma and Waldenstrom’s macroglobulinemia. Neurology 33:1411–1415
Dimopoulos MA, Kantarjian H, Weber D, O’Brien S, Estey E, Delasalle K, Rose E, Cabanillas F, Keating M, Alexanian R (1994) Primary therapy of Waldenstrom’s macroglobulinemia with 2-chlorodeoxyadenosine. J Clin Oncol 12:2694–2698
Laurencet FM, Zulian GB, Guetty-Alberto M, Iten PA, Betticher DC, Alberto P (1999) Cladribine with cyclophosphamide and prednisone in the management of low-grade lymphoproliferative malignancies. Br J Cancer 79:1215–1219
Richards AI (1995) Response of meningeal Waldenstrom’s macroglobulinemia to 2-chlorodeoxyadenosine. J Clin Oncol 13:2476
Dimopoulos MA, Anagnostopoulos A, Kyrtsonis MC, Zervas K, Tsatalas C, Kokkinis G, Repoussis P, Symeonidis A, Delimpasi S, Katodritou E, Vervessou E, Michali E, Pouli A, Gika D, Vassou A, Terpos E, Anagnostopoulos N, Economopoulos T, Pangalis G (2007) Primary treatment of Waldenstrom macroglobulinemia with dexamethasone, rituximab, and cyclophosphamide. J Clin Oncol 25:3344–3349
Treon SP, Emmanouilides C, Kimby E, Kelliher A, Preffer F, Branagan AR, Anderson KC, Frankel SR (2005) Extended rituximab therapy in Waldenstrom’s macroglobulinemia. Ann Oncol 16:132–138
Weide R, Heymanns J, Koppler H (1999) Induction of complete haematological remission after monotherapy with anti-CD20 monoclonal antibody (RITUXIMAB) in a patient with alkylating agent resistant Waldenstrom’s macroglobulinaemia. Leuk Lymphoma 36:203–206
Weide R, Heymanns J, Koppler H (2000) The polyneuropathy associated with Waldenstrom’s macroglobulinaemia can be treated effectively with chemotherapy and the anti-CD20 monoclonal antibody rituximab. Br J Haematol 109:838–841
Bing J, Fog M, Neel A (1937) Reports of a third case of hyperglobulinemia with affection of the central nervous system on a toxi-infectious basis, and some remarks on the differential diagnosis. Acta Med Scand 91:409–427
Tommasi M, Revol L, Schott B, Lesbros F (1966) [Waldenstrom’s macroglobulinemia. Lesions of the central nervous system]. Ann Anat Pathol (Paris) 11:309–313
Pennacchio L, Orlandini M (1969) [Immunoglobulin diseases. (Basis of modern immunology. Clinical contribution. Bing-Neel syndrome)]. Policlinico Prat 76:401–422
Quilichini R, Benderitter T, Lafeuillade A, Chaffanjon P, Aubert L (1989) [Waldenstrom’s macroglobulinemia with cerebral lymphoproliferative involvement of tumor appearance (Bing and Neel syndrome). An anatomo-clinical case]. Ann Med Interne (Paris) 140:25–29
Jammes T, Mann C, Delhom E, Bertrand P, Berthelemy C, Oweini K, Jonquet O (1990) [Bing-Neel syndrome revealed by normal pressure hydrocephalus. Unusual clinical/course of Waldenstrom disease]. Presse Med 19:1992
Shimizu K, Fujisawa K, Yamamoto H, Mizoguchi Y, Hara K (1993) Importance of central nervous system involvement by neoplastic cells in a patient with Waldenstrom’s macroglobulinemia developing neurologic abnormalities. Acta Haematol 90:206–208
Civit T, Coulbois S, Baylac F, Taillandier L, Auque J (1997) [Waldenstrom’s macroglobulinemia and cerebral lymphoplasmocytic proliferation: Bing and Neel syndrome. Apropos of a new case]. Neurochirurgie 43:245–249
Arias M, Pereiro Zabala I, Requena Caballero I, Sesar Ignacio A, Arias Rivas S, Villamayor Blanco B (2004) [Rapidly progressing dementia as the presenting symptom of Waldenstrom’s macroglobulinemia: findings from magnetic resonance imaging of the brain in Bing Neel syndrome]. Rev Neurol 38:640–642
Kim HD, Shin KC, Cho HS, Kim MK, Lee KH, Hyun MS (2007) Therapeutic experience of Bing-Neel syndrome associated with Waldenstrom’s macroglobulinemia. J Korean Med Sci 22:1079–1081
Drappatz J, Akar S, Fisher DC, Samuels MA, Kesari S (2008) Imaging of Bing-Neel syndrome. Neurology 70:1364
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We thank Dr. Jaun J. Cayaffa for translating the foreign articles.
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Malkani, R.G., Tallman, M., Gottardi-Littell, N. et al. Bing–Neel syndrome: an illustrative case and a comprehensive review of the published literature. J Neurooncol 96, 301–312 (2010). https://doi.org/10.1007/s11060-009-9968-3
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DOI: https://doi.org/10.1007/s11060-009-9968-3