These cells, as predominant populations, do not secrete the IgE M-component, indicating non-secretory IgE myeloma. urine sample, although the free light chain was not Alvespimycin measured (Physique 3). Serum immunofixation test recognized a faint IgG band and clear band of light chain but not IgE (Physique 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 recognized a monoclonal IgG and protein; ii), atypical plasma cells composed 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/m2 (day 1), Alvespimycin ranimustine 40 mg/m2 (day 1), melphalan 8 mg/m2 (days 1C6), dexamethasone 40 mg (days 1C4, days 9C12, days 17C20), IFN- 300106 IU SC 3 occasions/week (days 22C43, every 6 weeks). Therapeutic response was judged as a partial response based on international response criteria for multiple myeloma.1 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. Regrettably, the patient relapsed in November 2007. She received ROAD-IN chemotherapy again but relapsed after a transient remission. Bone marrow showed the proliferation of myeloma cells with cytoplasmic IgE and chain. Two color circulation 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/m2 (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 1C4), doxorubicin Alvespimycin 9 mg/m2 (days 1C4), dexamethasone 40 mg/day (days 1C4). She died of tumor progression 42 months after the diagnosis. No autopsy was performed (Physique 5). Open in a separate window Physique 1 Bone marrow aspiration. Myeloma cells were detected at 55.5% (Wright-Giemsa stain 100). Myeloma cells showed strong positivity for IgE and (immunostain 60) but few cells were positive for IgG (immunostain 80). Open in a separate window Physique 2 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 TSPAN31 IgG antibody (reddish); 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. Open in a separate window Physique 3 Immunoelectrophoresis: A) IgG and monoclonal bands were seen in serum (arrow); B) BJP () were seen in urine (arrow). Open in a separate window Physique 4 Serum immunofixation electrophoresis revealed a faint IgG band and a clear band of BJP () (arrow). Open in a separate window Physique 5 Patient’s clinical course. Conversation IgE myeloma is the rarest type of multiple myelomas. Forty-six cases have been reported since the first description in 1976.2C9 Clinical manifestations are similar to other types of myeloma.3 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).5 Our patient survived for any 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 Alvespimycin non-secretory IgE heavy chain with two M-components (IgE, IgG) in our case. MM with two M-components, which include an IgE, are rare.10 Only 2 cases with IgE as a component of biclonal gammopathy (IgA/+IgE/ or IgG/+IgE/) have been reported.11,12 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 usually whether myeloma cells produce these two M-components (IgG and IgE).