non - secretory myeloma is a rare condition of multiple myeloma ( mm ) that accounts for 1.05.0% of all myeloma patients . , we report on an ige myeloma patient with igg monoclonal gammopathy of undetermined significance with non - secretory ige . a 68-year old woman presented with fever , palpitation and dyspnea . upon physical examination , the patient was diagnosed with anemic conjunctiva . the patient did not present hepatosplenomegaly nor peripheral lym - phadenopathy . g / l ) , cr 7.6 mg / l ( reference ranges 512 mg / l ) , ca 9.4 mg / dl ( reference ranges 810.5 mg / dl ) , and 2-microglobulin 2.2 mg / l ( reference ranges 11.9 mg / l ) . immunoglobulin ( ig ) levels were ige 9.38 iu / ml ( reference ranges 0173 iu / ml ) , igg 4.68 g / l ) , respectively . on wright 's stained smears of bone marrow aspirate , immunohistochemically , plasma cells had positive readings for cd138 , ige and  , but the igg bearing plasma cells were scattered ( figure 1 ) . immunofluorescence staining of igg and ige was performed on a paraffin section of bone marrow using fluorescein ( fitc)-conjugated rabbit anti - human igg antibodies for detecting igg , and using both rabbit anti - human ige polyclonal antibodies and alexa fluor594-labeled goat anti - rabbit igg antibodies for detecting ige . dual staining of ige and igg showed that a part of the ige and igg positive cells was identical ( figure 2 ) . the specificity of the anti - ige antibodies was confirmed by an intensive control study ( data not shown ) . polymerase chain reaction ( pcr ) and capillary immunoelectrophoresis of the pcr products on the paraffin section of bone marrow revealed a rearrangement of the igh gene in the vh ( fr3 ) region . magnetic resonance imaging showed an abnormal signal interpreted as a possible involvement of myeloma in the vertebrae , sacrum and coccyx . immunoelectrophoresis showed an abnormal arc precipitating with anti - igg and anti- sera in the serum and anti- in the urine sample , although the free light chain was not measured ( figure 3 ) . serum immunofixation test identified a faint igg band and clear band of  light chain but not ige ( figure 4 ) . the patient was diagnosed as having non - secretory ige myeloma with igg monoclonal gammopathy of undetermined significance ( mgus ) based on the following findings : i ) serum immunoelectropheresis identified a monoclonal igg and  protein ; ii ) , atypical plasma cells made up 55.5% of the nucleated cells on bone marrow aspirate ; iii ) immunohistochemical staining showed most plasma cells were positive for ige and  , but a few for igg ; iv ) there was no increase in serum ige level ; v ) serum immunofixation did not show any ige monoclonal band . the patient was at stage iii a ( durie and salmon staging system ) or 1 ( international staging system ) . the patient was started on two cycles of road - in chemotherapy : vincristine 1.2 mg / m ( day 1 ) , ranimustine 40 mg / m ( day 1 ) , melphalan 8 mg / m ( days 16 ) , dexamethasone 40 mg ( days 14 , days 912 , days 1720 ) , ifn- 30010 iu sc 3 times / week ( days 2243 , every 6 weeks ) . therapeutic response was judged as a partial response based on international response criteria for multiple myeloma . afterwards , she was treated with eight cycles of mp therapy : melphalan 10 mg / day for 4 days and prednisolon 60 mg / day for 4 days every 6 weeks . two color flow cytometric analyses of bone marrow plasma cells revealed 36.8% cd38 cd49e and 7.8% cd38 cd49e . in june 2008 , the patient was then started on five cycles of btz - dex therapy : bortezomib 1.0 mg / m ( day 1 , day 4 , day 8 , day 11 ) , dexamethasone 20 mg ( days 1 , 2 , days 4 , 5 , days 8 , 9 , days 11 , 12 , every 3 weeks ) followed by three cycles of vad therapy : vincristine 0.4 mg / day ( day 14 ) , doxorubicin 9 mg / m ( days 14 ) , dexamethasone 40 mg / day ( days 14 ) . myeloma cells showed strong positivity for ige and  ( immunostain 60 ) but few cells were positive for igg ( immunostain 80 ) . myeloma cells showed strong positivity for ige and  ( immunostain 60 ) but few cells were positive for igg ( immunostain 80 ) . a ) the bone marrow paraffin section was immunostained with fitc conjugated rabbit anti - human igg antibodies ( green ) ; b ) the same specimen was stained with rabbit anti - human ige antibody and alexa fluor594-labeled goat anti - rabbit igg antibody ( red ) ; c ) dual staining using anti - igg and anti - ige as in a and b ; a part of the cells shows yellow , indicating that they are positive for both igg and ige . 
  immunofluorescence staining . a ) the bone marrow paraffin section was immunostained with fitc conjugated rabbit anti - human igg antibodies ( green ) ; b ) the same specimen was stained with rabbit anti - human ige antibody and alexa fluor594-labeled goat anti - rabbit igg antibody ( red ) ; c ) dual staining using anti - igg and anti - ige as in a and b ; a part of the cells shows yellow , indicating that they are positive for both igg and ige . 
 figure 3immunoelectrophoresis : a ) igg and  monoclonal bands were seen in serum ( arrow ) ; b ) bjp (  ) were seen in urine ( arrow ) . immunoelectrophoresis : a ) igg and  monoclonal bands were seen in serum ( arrow ) ; b ) bjp (  ) were seen in urine ( arrow ) . figure 4serum immunofixation electrophoresis revealed a faint igg band and a clear band of bjp (  ) ( arrow ) . serum immunofixation electrophoresis revealed a faint igg band and a clear band of bjp (  ) ( arrow ) . in contrast to our patient , in most reported cases the ige serum level is extremely high ( 1000200,000-fold increase ) . it is generally accepted that ige myeloma takes a more aggressive clinical course and has a poorer rate of survival ( median 16 months ) . our patient survived for a considerably long time ( 42 months ) compared to the other patients with typical ige myelomas . in the present case , we detected the serum m - components of igg and bjp- but not ige by either immunoelectropheresis or immunofixation . however , cytoplasmic immunoglobulins mainly produced by bone marrow plasma cells ( myeloma cells ) were ige and  light chain , suggesting the non - secretory ige heavy chain with two m - components ( ige , igg ) in our case . only 2 cases with ige as a component of biclonal gammopathy ( iga/+ige/ or igg/+ige/ ) have been reported . due to the low serum m - component of igg and few plasma cells that produce igg , it appears that igg - producing plasma cells are not subjective myeloma clones , suggesting igg mgus . the question is whether myeloma cells produce these two m - components ( igg and ige ) from the same parental clone or two unrelated clones . the dual staining of igg and ige by immunofluoresence revealed that identical myeloma cells produced both ige and igg despite most myeloma cells producing only ige . thus , myeloma cells producing ige or igg m - components may originate from the same parental clone . in fact , bakkus et al . reported that myeloma cells that produce iga/ and ige/ double m - component share a common clonal origin and undergo adifferent class switch , suggesting the possible development of biclonal gammopathy , as in our case . these cells , as predominant populations , do not secrete the ige m - component , indicating non - secretory ige myeloma . non - secretory myeloma is also a rare condition of mm accounting for 1.05.0% in all myeloma patients . to the best of our knowledge , the positivity for both ige and  in most myeloma cells suggests that our case is non - secretory ige heavy chain ( hc ) with bjp- secretion . there are no reports of myeloma cases with non - secretory hc and secretory light chain ( lc ) so far . in general , it is presumed that immunoglobulin hc and lc are synthesized by polyribosome in the endoplasmic reticulum and then folded in the presence of a chaperon protein such as bip . both chains are constructed as a complete immunoglobulin after the formation of intrachain / interchain disulfide bonds . therefore , when the assembly between hc and bip is not achieved , a complete immunoglobulin can not be assembled and both chains are degraded by proteasomes . furthermore , it has been reported that mutations at cys194 and cys214 in lc result in the impairment of intrachain / interchain disulfide bond formation , causing non - secretory myeloma . it is unknown whether the above mechanisms were involved in the non - secretion of ige in the present case . although ige myeloma is thought to be very rare , it could be overlooked because the ige m - protein can not always be detected by standard immunoelectrophoresis , and the ige value is low in some cases of ige myeloma . therefore , it might be important for the diagnosis of ige myeloma to perform not only a serum immunofixation test , but also immunohistochemistry using ige antibodies in the bone marrow .
a 68-year old woman came to our hospital with a severe case of anemia . 
 serum immunoelectropheresis identified a monoclonal immunoglobulin ( ig ) g and  protein . 
 the serum ige level was within the nomal range and the amounts of remaining immunogloblins were low . on bone marrow aspirate , plasma cells made up 55.5% of nucleated cells and the plasma cells showed positive readings for ige  and igg by immunohistochemistry . 
 serum immunofixation did not reveal the ige monoclonal band . 
 she was diagnosed as having non - secretory ige myeloma with igg monoclonal gammopathy of undetermined significance . 
 the nature of this rare myeloma will be discussed .