A case report of biclonal immunoglobulin D lambda/lambda multiple myeloma in patient with liver echinococcosis

Graphical abstract


Introduction
Multiple myeloma (MM) is a disseminated malignant tumor composed of monoclonal plasma cells.It accounts for about 8% of all hematological diseases and mostly occurs in elderly and it is more common in men than women (1.4:1) (1).
Revised International Myeloma Working Group (IMWG) diagnostic criteria for multiple myeloma include clonal bone marrow plasma cell ≥ 10% or biopsy -proven bony or extramedullary plasmacytoma and any one or more of the following myeloma defining events that are presented in the Table 1 (2).
Evidence of end organ damage that can be attributed to the underlying plasma cell proliferative disorder • Hypercalcemia: serum calcium > 0.25 mmol/L higher than the upper limit of normal or > 2.75 mmol/L • Renal insufficiency: creatinine clearance < 40 mL per min or serum creatinine > 177 µmol/L • Anemia: hemoglobin value of > 20 g/L below the lower limit of normal, or a hemoglobin value < 100 g/L • Bone lesions: one or more osteolytic lesions on skeletal radiography, CT or PET-CT Any one or more of the following biomarkers of malignancy: • Clonal bone marrow plasma cell percentage ≥ 60% • Involved: uninvolved serum free light chain ratio ≥ 100 • > 1 focal lesions on MRI studies (2) CT -computerized tomography.PET-CT -positron emision tomography-computerized tomography.MRI -magnetic resonance imaging.
Table 1.Internatinal Myeloma Working Group diagnostic criteria for multiple myeloma; myeloma defining events chains lambda type in a patient with anemia, renal insufficiency and clonal bone marrow plasma cell > 80%.
As a unique myeloma, immunoglobulin D (IgD) was first discovered in 1965.As a rare variant of the disease immunoglobulin D multiple myeloma (IgD MM) represents only 2% of all symptomatic myeloma.There is evidence that IgD MM is associated with high rates of kidney failure, amyloidosis, hypercalcemia and Bence Jones proteinuria (3)(4)(5).
There are two reasons why are just a few reports of IgD MM in literature, the first reason is its low concentration in plasma and the other one is the fact that antiserum for IgD is not used in routine practice.Because of its low concentration it can easily escape electrophoresis detection.Also, IgD MM is often misdiagnosed as light chain myeloma (LC MM) (3).In the case of IgD MM it is characterized by the high preponderance of lambda light chains over kappa light chains (4,6,7).

Case report
A 69 -year-old men with liver echinococcosis was hospitalized in the gastroenterology department.Patient reached out to the doctor in primary practice because of weakened appetite and loss of 10 kilograms in a last month.Serum protein electrophoresis was performed by capillary zone electrophoresis (CZE) method using Capillarys 3 Octa (Sebia, Lisses, France).It revealed a monoclonal peak (M -spike) in the gamma globulin fraction which is showed in the Figure 1.
In order to define the class and type of monoclonal protein, after electrophoresis serum protein immunofixation (s -IFE) was performed.Immunofixation (IF) is the gold standard method to confirm the presence of a monoclonal protein.Immunofixation is a two -step procedure consisting of electrophoresis on agarose and immunoprecipitation.In the first step proteins are separated electrophoretically into sharp bands on the gel and in the second step, a specific antiserum is added to each band for a molecule of individual class and type of immunoglobulin.If there is a monoclonal synthesized immunoglobulin it will make an insoluble complex with antisera which can be stained and proved (1).
Serum immunofixation was performed using agarose Hydragel 2/4 IF gels on Hydrasys 2 Scan (Sebia, Lisses, France).In the first step s-IFE was performed using the anti-IgG, IgA, IgM, total kappa and total lambda antisera.The result of the first s-IFE was the presence of two monoclonal lambda total light chain without corresponding heavy chain.Following the protocol we performed s-IFE using anti-IgD, anti-IgE, total kappa, total lambda, free kappa and free lambda antisera.Serum IFE with anti-IgE antisera, total kappa, total lambda, free kappa and free lambda antisera also showed two monoclonal bands lambda total light chain without corresponding heavy chain but there was also a band on free lambda chain, which has the same electrophoretic mobility as one band in total lambda.Visualization of the agarose gel with anti-IgD antisera showed monoclonal IgD band which has the same mobility in the electric field as one of the lambda bands.The second monoclonal lambda band has the same electrophoretic mobility as free lambda chain.The final result of s-IFE showed IgD lambda and free lambda monoclonal bands (Figure 1).
M spike was measured densimetrically using orthogonally way of measurement and its concentration was 21.60 g/L (Capillarys 3 Octa, Lisses, France).After receiving results from serum protein electrophoresis and s-IFE the bone marrow exami-  5 nation was ordered.The bone marrow examination was performed at pathology department.Result showed hypercellular bone marrow that is extensively diffusely infiltrated with cells that are only partially recognizable as mature and mildly atypical plasma cells and mostly blastoid cells in appearance.
For further diagnostic flow cytometry immunophenotyping is recommended.

Discussion
In this case report we presented patient with IgD lambda MM having anemia, renal failure and > 80 % plasma cells in bone biopsy which meets IMWG criteria for MM diagnosis.Prce As the condition worsened, he had to undergo hemodialysis due to the high concentration of urea and creatinine.
Before development of the new drugs and autologous stem cell transplantation, survival of patients with IgD MM was shorter.With the new drugs and stem cell transplantation outcomes for these patients improved significantly (11,12).Bemelmans et al. in their study described the case of the patient with IgD MM with complete remission of more than eight years (13).Our patient general condi-tion worsened so none of the treatments above has not started.Patient was treated with antibiotics, diuretics, electrolyte solutions and blood transfusions.Due to his previous lung problems, respiratory complications caused his death.
In order to prevent an IgD MM is erroneously diagnosed as a light chain MM it is necessary to follow the protocols and perform s-IFE with anti-IgD and anti-IgE antisera whenever the s-IFE with anti-IgG, IgA, IgM, kappa and lambda antisera shows monoclonal bands kappa or lambda type without monoclonal bands in heavy chain (14).
In conclusion, in this case report we have presented the patient with a similar clinical course as other patients with IgD MM described in literature.We want to point out the importance of following the protocols for accurately identification of monoclonal immunoglobulins.

Figure 1 .
Figure 1.Serum protein electrophoresis and serum protein immunofixation in a patient with IgD multiple myeloma.First immunofixation (3): s-IFE was performed using the anti-IgG, IgA, IgM, total kappa and total lambda antisera.The arrow points two monoclonal bands lambda total light chain.Second immunofixation (4): s-IFE using anti-IgD, total kappa, total lambda, free kappa and free lambda antisera.The arrows points IgD monoclonal band, two monoclonal s-IFE lambda total light chain and monoclonal band free lambda light chain.Third immunofixation (1): s-IFE using anti-IgE, total kappa, total lambda, free kappa and free lambda antisera.The arrows points, two monoclonal s-IFE lambda total light chain and monoclonal band free lambda light chain.s-IFE -serum protein immunofixation.

Table 2 .
Results of laboratory tests of a patient with IgD multiple myeloma The serum concentration of kappa and lambda light chains showed an increase in lambda light chains and a decrease in κ/λ ratio.Laboratory results are presented in Table 2.In our case altered https://doi.org/10.11613/BM.2024.020801Biochem Med (Zagreb) 2024;34(1):020801 3 κ/λ ratio indicate excess production of clonal FLC by the proliferating plasma cell population.A high concentration of β 2 -microglobulin as well as a high erythrocytes sedimentation rate (ESR) was in a favor of multiple myeloma.Quantitative capillary photometry for ESR was performed on iSED (Alcor Scentific, Smithfield, USA) and β2-microglobulin was measured turbidimetrically on Alinity c analyzer (Abbott Laboratories, Chicago, USA).