waldenstrom 's macroglobulinemia ( wm ) is the result of a clonal proliferation of lymphocytes that produce monoclonal immunoglobulin m ( igm ) .
it is now considered to correspond to lymphoplasmacytoid lymphoma as defined by the world health organization classification system ( 1 , 2 ) .
many central nervous system ( cns ) complications have been described in wm patients ; the majority have been associated with blood hyperviscosity caused by igm .
the hyperviscosity syndrome is characterized by headache , tinnitus , vertigo , blurred vision , and chronic bleeding from the nose and gums ( 3 ) .
however , cns infiltration by plasmacytoid lymphocytes ( bing - neel syndrome ) has only rarely been reported ( 4 ) .
a 51-yr - old woman was diagnosed with wm three years prior to this presentation .
she received six courses of chlorambucil ( 0.3 mg / kg per day on day one to four orally ) and prednisone ( 45 mg / m per day on day one to four ) .
next , she received fludarabine chemotherapy ( 25 mg / m per day on day one to five intravenously ) with a limited response .
high - dose cyclophosphamide and granulocyte colony - stimulating factor were administered to induce peripheral blood progenitor cell ( pbpcs ) mobilization for autologous stem - cell transplantation ; however , the number of pbpcs collected was not sufficient .
we then decided on a conservative treatment approach , because the patient did not have specific symptoms and the serum igm level was stable ( 3,000 - 3,500 mg / dl ) .
the laboratory values on admission were as follows : white cell count 8,050/l with normal differential counts , hemoglobin 9.6 g / dl , platelets 296,000/l , erythrocyte sedimentation rate 144 mm / hr , total protein 9.44 g / dl , albumin 2.85 g / dl , igg 3144.4 mg / dl , iga 25.4 mg / dl , igm
a brain computed tomography scan revealed multifocal extra - axial tumorous lesions along the dura matter .
a brain magetic resonance imaging showed an extra - axial soft tissue tumor along the left cavernous sinus and tentorium , right frontal convexity and tentorium and falx ; the brain parenchyma appeared to be unremarkable ( fig .
cerebrospinal fluid analysis showed the following : white cell count 43/l with neutrophils 1% , lymphocytes 52% and monocytes 47% , total protein 1.81 g / dl , glucose 104 mg / dl , igm 64.5 mg / dl and a few plasmacytoid lymphocytes on cytology .
stereotactic biopsy of dural tissue at the falx showed a diffuse infiltration with atypical cells , which were identified immunophenotypically as plasmacytoid lymphocyte with expression of lca ( + ) , cd3 ( - ) , cd20 ( + ) , and vs38a ( + ) ( fig .
2 ) . the patient was confirmed to have cns infiltration by atypical plasmacytoid lymphocyte infiltration ( bing - neel syndrome ) .
the paitent received a total dose of 1,980 cgy with irradiation therapy of the whole brain that was administered in 11 fractions , and then her headache subsided , but the igm level was elevated persistently to 3,379.8 mg / dl . following radiation therapy ,
fludarabine chemotherapy was performed ( 25 mg / m per day on 1 to 5 intravenously , two courses ) .
a follow - up brain mri after six months revealed a marked decrease in the size of the mass in the tentorium and falx ( fig .
the patient had no evidence of cns recurrence during the follow - up period of one year
. however , the igm level has been increasing slowly , so further chemotherapy , including rituximab may be considered .
in 1936 bing and neel reported the association of hyperglobulinemia , cns symptoms ( paresthesias , headache , and paralysis ) , and brain infiltration composed of plasma cells and lymphocytes in two patients ( 5 ) . in 1944 , waldenstrom described the syndrome that bears their name ( bing - neel syndrome ) ( 6 ) .
the bing - neel syndrome , originally placed in a " toxic - infectious " category , appears to be the result of involvement of the cns by diffuse neoplasm infiltration .
although they are most often peripheral , they can involve the cns . in wm , the cns may be involved by a variety of mechanisms , including hyperviscosity and direct infiltration by neoplastic cells ( 7 , 8) .
patients with bing - neel syndrome have sometimes presented with a mass containing neoplastic cells , but the masses have been intraparenchymal rather than meningeal ( 8 , 9 ) .
this syndrome can be subdivided into diffuse and tumoral forms . in the diffuse infiltrative form such as this case
, malignant cells are localized mainly in leptomeningeal spaces , periventricular white - matter , pons , and medulla ( 7 , 10 - 12 ) .
radiological findings in this syndrome have been reported , but a typical pattern has not emerged ( 13 - 15 ) . an imaging technique would be the preferable diagnostic test , although histological confirmation is necessary to establish the definitive diagnosis .
intraventricular chemotherapy for bing - neel syndrome was reported to be effective in 1984 ( 15 ) .
however , a review of the literature reveals that the outcome for most patients who underwent chemotherapy was poor , and the patients died within several months ( 10 , 13 , 14 ) .
therefore , patients with bing - neel syndrome may benefit from cranial radiation therapy prior to chemotherapy ( 9 , 12 , 16 ) .
recently , a great deal of interest has been noted by treatments with purine nucleoside analogs ( fludarabine , cladribine , and pentostatin ) because of their remarkable activity in lymphoproliferative disorders .
it has been reported that a patient with bing - neel syndrome ( in its diffuse form ) was successfully treated with cladribine administration ( 17 ) , or radiation therapy and combination of cladribine , cyclophosphamide , and prednisone ( 18 ) . in the present case
further treatment was not possible because of persistant bone marrow suppression . a follow - up brain mri after six months revealed a marked decrease in the size of the mass in the tentorium and falx ; the patient had no evidence of cns recurrence during the follow - up period of one year , but the igm level has been increasing slowly . we think that the major effect of deceased mass size was due to the radiation therapy in the present case .
several retrospective and prospective studies have indicated that rituximab may induce an objective response in approximately 30 - 40% of previous treated patients with wm ( 19 ) .
however , the effect of rituximab treatment on the cerebrospinal fluid b - cell compartment is limited in comparison with the effect on the b cells in the periphery ( 20 ) , and it has not been tried in bing - neel syndrome as yet . therefore , the effect of rituximab on cns involovement of wm need to be validated by of future studies .
 waldenstrom 's macroglobulinemia is an uncommon low - grade b - cell lymphoproliferative disorder in which monoclonal immunoglobulin m is produced . 
 neurological symptoms due to hyperviscosity are frequent manifestations of waldenstrom 's macroglobulinemia . however , central nervous system infiltration by plasmacytoid lymphocytes ( bing - neel syndrome ) has only rarely been reported . 
 we report a case of a 51-yr - old woman suffering from waldenstrom 's macroglobulinemia who complained of persistant headache . 
 brain magnetic resonance imaging revealed an extra - axial soft tissue mass along the left cavernous sinus , left tentorium , right tentorium , and falx cerebri . a stereotactic biopsy of dural tissue from the falx was performed and showed plasmacytoid lymphocyte infiltration . 
 the patient became symptom- free with irradiation of the whole brain followed by chemotherapy with fludarabine . 
INTRODUCTION
CASE REPORT
DISCUSSION