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E-JCRT CORRESPONDENCE
Year : 2015  |  Volume : 11  |  Issue : 3  |  Page : 660

Immunoglobulin G kappa biclonal gammopathy associated with multiple myeloma, plasmacytoma and cast nephropathy


1 Department of Pathology and Laboratory Medicine, PGIMER, Chandigarh, India
2 Department of Pathology and Laboratory Medicine, MAMC, New Delhi, India
3 Department of Internal Medicine, PGIMER, Chandigarh, India
4 Department of Radiodiagnosis and Imaging, PGIMER, Chandigarh, India

Date of Web Publication9-Oct-2015

Correspondence Address:
Dinesh Pradhan
Department of Pathology and Laboratory Medicine, PGIMER, Sector 12, Chandigarh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.139379

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 > Abstract 

Biclonal gammopathies are characterized by simultaneous appearance of two different monoclonal proteins. Multiclonal gammopathies may be the result of a neoplastic transformation of a cell clone undergoing immunoglobulin (Ig) class switching or due to an independent neoplastic transformation event yielding proliferation of unrelated plasma cell clones. This in turn has implication on the disease manifestation, progression, prognosis and response to therapy. The prevalence of biclonal gammopathy is approximately 1% of all gammopathies and the most common combinations are IgG and IgA (33%), followed by IgM and IgG (24%). Multiple myeloma with biclonal gammopathy is very uncommon. The present case corresponds to an extremely rare occurrence of multiple myeloma with biclonal gammopathy revealing expression of two distinct monoclonal gammaglobulins both of IgG and kappa (κ) subtype in a 56-year-old diabetic man who presented with lower back pain and renal failure. To the best of our knowledge, only one case of IgG κ biclonal gammopathy associated with multiple myeloma have been reported in English literature. This case interestingly also had paraspinal plasmacytoma and cast nephropathy.

Keywords: Biclonal gammopathy, cast nephropathy, multiple myeloma, plasmacytoma


How to cite this article:
Pradhan D, Arora P, Gami A, Kaur N. Immunoglobulin G kappa biclonal gammopathy associated with multiple myeloma, plasmacytoma and cast nephropathy. J Can Res Ther 2015;11:660

How to cite this URL:
Pradhan D, Arora P, Gami A, Kaur N. Immunoglobulin G kappa biclonal gammopathy associated with multiple myeloma, plasmacytoma and cast nephropathy. J Can Res Ther [serial online] 2015 [cited 2019 Nov 14];11:660. Available from: http://www.cancerjournal.net/text.asp?2015/11/3/660/139379


 > Introduction Top


Multiple myeloma is associated with expansion of a single clone of immunoglobulin (Ig) secreting plasma cells that results in the secretion of a unique homogeneous monoclonal protein (M component), however, in 1% of the cases two distinct M-component is present which is referred to as biclonal gammopathy. [1] The presence of two monoclonal proteins may be because of the proliferation of two clones of plasma cells, each producing an unrelated monoclonal Ig, or it may result from the production of two monoclonal proteins by a single clone of plasma cells. [2] Though biclonal gammopathy is a rare plasma cell dyscrasia, the clinical features seem to be similar to monoclonal gammopathy. The most common biclonal pair is IgG + IgA (33%) followed by IgG + IgM (24%). [3] Two cases have been described expressing both cytoplasmic κ and lambda (λ) light chains but secreting only IgG heavy chain, suggesting that it is possible to produce both light chain isotypes. [4]

In our patient, we report IgG kappa (κ) type of biclonal gammopathy detected by appearance of two bands in the gamma region on serum protein electrophoresis whose classes were further confirmed by immunofixation. Although the clinical features of biclonal gammopathy and its response to therapy are similar to those of monoclonal gammopathy, few cases have shown some variations. Further study needs to be carried out on these very rare cases to reach to a conclusion regarding their management and prognosis. We hereby present our data in light of its rarity and unique presentation.


 > Case report Top


This is a case report of a 56-year-old diabetic patient who presented with low back pain, oliguria and swelling at the back with numbness in bilateral lower limbs for 1 month. On examination, there was marked pallor and a localized non-tender bulge in the lower back slightly on the right side of the midline.

Laboratory investigations

Significant laboratory parameters included hemoglobin of 6 g/dl, mild leukocytosis and elevated renal parameters. Blood smear showed normocytic normochromic anemia with rouleaux formation, but no plasma cells were found [Figure 1]a. Bone marrow aspirate revealed a cellular marrow with M:E ratio of 4:1. Plasma cells were 40% of all nucleated cells including some binucleate forms [Figure 1]b.
Figure 1:

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Radiological examination

In X-ray pelvis, an expansile lytic lesion was seen in right superior pubic ramus associated with generalized osteopenia of bones [Figure 2]. Contrast enhanced computed tomography revealed heterogeneously enhancing soft tissue density in paraspinal area along with expansile lytic lesion associated with cortical breech [Figure 3]. Possibilities of plasmacytoma, multiple myeloma and metastasis were considered and histopathological examination was advised for further confirmation.
Figure 2: Radiograph of pelvis (AP view) depicting lytic lesion in superior pubic ramus along with osteopenia of bones

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Figure 3: Contrast enhanced computed tomography scan revealing heterogeneously enhancing soft tissue density in paraspinal area

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Histopathological findings

Trucut biopsy from paravertebral soft tissue mass was taken. Microscopic examination revealed diffuse sheets of plasma cells. Binucleate and immature plasma cells were also seen [Figure 4]. Features were consistent with plasmacytoma. Renal biopsy revealed irregular, angulated fractured cast predominantly in the distal nephron with multinucleated giant cell cuffing the cast, Adjoining interstitium showed focal moderately dense lymphoplasmacytic infiltrate. Glomeruli and vessels were within the normal limits. A diagnosis of cast nephropathy was offered on renal histology.
Figure 4: Photomicrograph of section from paraspinal mass revealing abundant plasma cells with eccentric nucleus and a perinuclear halo (H and E, ×400)

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Biochemical and serological findings

Serum creatinine was 6.6 mg/dl with a creatinine clearance of 21.1 ml/min. Serum calcium was 14.4 mg/dl, β 2 microglobulin 5.26 mg/L, urea 186 mg/dl and alkaline phosphatase 288 U/L. Urinalysis showed moderate proteinuria (2+) with presence of Bence Jones protein (indicative of free κ light chains). Serum protein electrophoresis was performed on agarose gel electrophoresis which revealed two distinct prominent monoclonal band (M bands) in gammaglobulin region [Figure 5], marked with arrows; [Table 1]. Corresponding serum immunofixation electrophoresis revealed the presence of two distinctly separate bands in IgG and κ chain region indicating IgG κ biclonal gammopathy [Figure 6], marked with arrows]. By nephelometry technique, serum IgG was very high 4500 mg/dl, IgA and IgM were not detected. Free light chain assay was also performed by nephelometry, which revealed markedly high levels of κ light chain and κ/λ ratio [Table 2]. Urine protein electrophoresis indicated tubular proteinuria with presence of Bence Jones protein and prominent M bands in the gamma region. Based on the above findings, the diagnosis of multiple myeloma with coexisting plasmacytoma, cast nephropathy and biclonal gammopathy with two distinct IgG and κ components was confirmed. The patient has been hospitalized and chemotherapy started after the confirmation of the diagnosis.
Figure 5: Serum protein electrophoresis on agarose gel (arrow depicts two bands in the gamma region)

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Figure 6: Immunofixation depicting two distinct monoclonal bands of immunoglobulin G and kappa type (arrow)

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Table 1: Serum protein electrophoresis

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Table 2: Free light chain assay

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 > Discussion Top


Biclonal gammopathy instance ranges from 0.14% to 3.2% and is known to occur only in 1% of the cases of multiple myeloma. [5],[6],[7] Literature search elucidates IgG and IgA as the most common biclonal pair seen in >50% of biclonal gammopathies. The occurrence of two IgG monoclonal components corresponds to 10% or less amongst all cases of biclonal gammopathy. [5] Kyle et al. studied 57 cases of biclonal gammopathy, out of which only six had two distinct IgG components. [2]

The present case corresponds to the rare and unique expression of two distinct monoclonal proteins both pertaining to IgG κ class. The existence of true biclonal myeloma must be carefully reviewed. A study done by D'Angelo et al. has hypothesized that a neoplastic clone may undergo a subsequent neoplastic change not closely related to the first and a subclone may evolve with the possibility to rearrange for a light chain different from the first protein. [8]

Therefore, in the present case of multiple myeloma showing two M-components, it could be suggested that the cells which produced the IgG M-component probably have undergone further isotype switching, resulting in the secretion of another IgG M-component by the same cells following an additional mutation of the gene or it might be possible that similar phenotype of M-proteins and similar proliferating sites existed for two clones which may have resulted from two independent transforming events leading to production of similar heavy and light chains exhibiting different isoelectric points. Unfortunately, we could not conduct a fluorescence in situ hybridization analysis or chromosomal study in this case. If these studies had been performed, more information about plasma cell clonality might have been obtained.

In summary, we report an extremely rare case of multiple myeloma associated with paraspinal plasmacytoma, cast nephropathy and biclonal gammopathy having a very infrequent combination of Ig G κ + Ig G κ monoclonal components. In addition to its rarity, this case may elucidate the pathogenesis of plasma cell disorders. The study of molecular events responsible for this exceptional combination may provide an insight into their clonal origin, pathogenesis and may unfold whether they belong to a truly biclonal population or rather a singular neoplastic clone suffering two hits, besides delving on the regulatory interactions between the two clones.

 
 > References Top

1.
Mahto M, Balakrishnan P, Koner BC, Lali P, Mishra TK, Saxena A. Rare case of biclonal gammopathy. Int J Case Rep Images 2011;2:11-4.  Back to cited text no. 1
    
2.
Kyle RA, Robinson RA, Katzmann JA. The clinical aspects of biclonal gammopathies. Review of 57 cases. Am J Med 1981;71:999-1008.  Back to cited text no. 2
[PUBMED]    
3.
Wintrobe MM. Clinical Hematology. 8 th ed. Philadelphia: Lea and Febiger; 1981. p. 1746.  Back to cited text no. 3
    
4.
González D, van der Burg M, García-Sanz R, Fenton JA, Langerak AW, González M, et al. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood 2007;110:3112-21.  Back to cited text no. 4
    
5.
Sakashita C, Saito T, Kurosu T, Yoshinaga H, Kumagai T, Yamamoto K, et al. Two M-components in a single cell lineage in a patient with a dual isotype secretory B-cell tumour. Br J Haematol 1998;102:791-4.  Back to cited text no. 5
    
6.
Wang E, Kulbacki E, Stoecker M. Concomitant Waldenstrom macroglobulinemia and IgA plasmablastic myeloma in a patient with untreated IgM paraproteinemia: Sequential development of biclonal B-cell neoplasms over a 10-year period in a single individual. Hum Pathol 2012;43:1135-41.  Back to cited text no. 6
    
7.
Pizzolato M, Bragantini G, Bresciani P, Pavlovsky S, Chuba J, Vidal R, et al. IgG1-kappa biclonal gammopathy associated with multiple myeloma suggests a regulatory mechanism. Br J Haematol 1998;102:503-8.  Back to cited text no. 7
    
8.
D'Angelo G, Crovetti G, Grizzetti N, Giardini C. Biclonal component in lymphoplasmacytic/lymphoplasmacytoid non-Hodgkin lymphoma. Recenti Prog Med 1994;85:104-7.  Back to cited text no. 8
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
 
 
    Tables

  [Table 1], [Table 2]



 

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