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Year : 2021  |  Volume : 7  |  Issue : 3  |  Page : 265-268

Plasma-Cell Myeloma with Double M-Bands on Serum Protein Electrophoresis: A Diagnostic Conundrum?

Department of Pathology, ABVIMS and Dr RML Hospital, Delhi, India

Date of Submission22-May-2021
Date of Decision04-Aug-2021
Date of Acceptance10-Aug-2021
Date of Web Publication02-Dec-2021

Correspondence Address:
Vijay Kumar
Department of Pathology, ABVIMS and Dr RML Hospital, New Delhi 110001
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/mamcjms.mamcjms_54_21

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Plasma-cell myeloma (PCM) is a monoclonal gammopathy (MGM) characterized by proliferation of abnormal clone of plasma cells infiltrating the bone marrow with consequent end-organ damage. The clonal plasma cells secrete a single clone of immunoglobulins (Igs) leading to presence of M-protein in the serum and/or urine. The M-protein is appreciated as a discrete band on serum protein electrophoresis (SPE) in the gamma globulin region, also called the M-band. Biclonal gammopathy (BGM) occurs due to neoplastic transformation of a plasma-cell clone undergoing Ig class switching or due to an independent neoplastic transformation event yielding proliferation of unrelated plasma-cell clones, therefore resulting in two distinct M-bands on SPE. It is, however, vital to distinguish a true BGM from an apparent one (MGM presenting with two distinct bands on SPE) so as to make an accurate diagnosis. Hereby, we report a case of a 61-year-old man, diagnosed with PCM and presenting with two discrete bands on SPE (simulating a BGM) which turned out to be monoclonal in nature.

Keywords: Biclonal gammopathy, IgG, multiple myeloma, serum protein electrophoresis

How to cite this article:
Misra S, Singh A, Kumar V. Plasma-Cell Myeloma with Double M-Bands on Serum Protein Electrophoresis: A Diagnostic Conundrum?. MAMC J Med Sci 2021;7:265-8

How to cite this URL:
Misra S, Singh A, Kumar V. Plasma-Cell Myeloma with Double M-Bands on Serum Protein Electrophoresis: A Diagnostic Conundrum?. MAMC J Med Sci [serial online] 2021 [cited 2022 Aug 19];7:265-8. Available from: https://www.mamcjms.in/text.asp?2021/7/3/265/331717

  Introduction Top

Monoclonal gammopathy (MGM) is a group of mature B-cell disorders which results in the production of a specific monoclonal immunoglobulin (Ig; M-protein),[1] appearing as a discrete M-band on serum protein electrophoresis (SPE). Plasma-cell myeloma (PCM) is an MGM characterized by proliferation of an abnormal clone of plasma cells infiltrating the bone marrow with associated end-organ damage.[1] Rarely, PCM may present with a biclonal gammopathy (BGM) resulting from a single clone of plasma cells undergoing Ig class switching or two separate clones each producing an unrelated spike on the densitometer tracing/two discrete M-bands on SPE gel.[2] The reported incidence of BGM is 3% to 6% of all gammopathies.[3] True biclonality is characterized by expression of M-proteins which differ in both heavy chain (HC) as well as light chain (LC) isotypes.[4]

We report a case of PCM presenting with two discrete bands on SPE which were monoclonal in nature, mimicking a BGM. We also discuss the diagnostic pitfalls in reporting of BGMs and need to distinguish true biclonality from apparent biclonality resulting from M-protein of monoclonal nature.

  Case Report Top

A 61-year-old male presented to nephrology outpatient department with complaint of generalized weakness since 4 months. Patient was a known case of chronic kidney disease since 6 months presenting with worsening renal function. On examination, pallor was present. Hematologic and biochemical parameters were markedly deranged [Table 1]. On serum-free LC (sFLC) assay, kappa/lambda ratio was 1:408.
Table 1 Laboratory parameters of patient

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Peripheral smear examination revealed normocytic normochromic anemia. Total leukocyte count was within normal limits with few plasmacytoid lymphocytes [Figure 1]a. Platelets were adequately reported. Bone marrow aspirate smears were hemodilute; plasma cells constituted 15% of total nucleated cells [Figure 1]b. Bone marrow biopsy showed cellular marrow spaces with increased plasma cells arranged in sheets as well as singly scattered [Figure 1]c. On immunohistochemistry (IHC), plasma cells were positive for CD 138 [Figure 1]d along with lambda LC restriction [Figure 1]d, inset. Based on the bone marrow findings, deranged laboratory parameters (anemia, renal failure, and hypercalcemia) and sFLC assay (kappa/lambda ratio of 1:408), a diagnosis of PCM was rendered.
Figure 1 (a) Peripheral smear shows normocytic normochromic red blood cell picture with plasmacytoid lymphocytes (black arrows) (Leishman stain, 400×). (b) Bone marrow aspirate smear showing scattered mature and immature plasma cells (black arrows) (Giemsa stain, 400×). (c) Bone marrow trephine biopsy showing interstitial infiltrates of plasma cells (hematoxylin and eosin, 200×). (d) Plasma cells are immunopositive for CD 138 [immunohistochemistry (IHC), 400×] and Kappa light chain (1d, inset) (IHC, 200×).

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The SPE revealed two distinct monoclonal bands (M1 and M2) in gamma region [Figure 2]a, inset which was observed as two unrelated spikes on densitometer tracings [Figure 2]a. A possibility of BGM was considered. For further subtyping of Igs, immunofixation electrophoresis (IFE) was performed which showed IgG to be the M-protein with two discrete bands in lambda region corresponding to early and late gamma (IgG) [Figure 2]b. Thus, the two bands which were reported on SPE turned out to be monoclonal in nature (IgG-lambda) which corroborated with bone marrow biopsy IHC and sFLC assay findings. Based on the IFE, true BGM was ruled out. A final diagnosis of IgG-lambda PCM was made. Clinical response was good after two cycles of conventional chemotherapy for PCM (melphalan, prednisolone, cyclophosphamide, and vincristine) with normalization of SPE, decreasing serum creatinine and serum calcium levels.
Figure 2 (a) Serum protein electrophoresis densitometer tracing shows two unrelated spikes (red arrows) and gel shows two M-bands (dark arrow, 2a, inset), the two peaks are quantified as 7.8% and 5.7% (encircled). (b) Serum immunofixation electrophoresis reveals the M-band to be IgG with two bands in lambda light chain region.

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  Discussion Top

Plasma-cell neoplasms (PCNs) result from expansion of a clone of Ig secreting, HC class switched terminally differentiated B cells that secrete a single monoclonal protein which is observed as M-band on SPE. Of the PCNs, PCM is bone marrow-based, multifocal neoplastic proliferation of plasma cells with associated end-organ damage.[1] Chronic antigenic stimulation giving rise to multiple benign clones followed by mutagenic event initiating malignant transformation has been postulated as the etio-pathogenetic mechanism in PCM.[5] They almost always arise from precursor entity, MGM of undetermined significance.[1]

Rarely, PCM can present with two distinct M-bands on SPE arising due to BGM.[2] BGM can result from either a proliferation of two clones of plasma cells, each producing an unrelated monoclonal spike or from the production of two monoclonal spikes by a single clone of plasma cells. Patients with BGMs can express para-proteins with different HC isotypes, different LC isotypes, or HCs and LCs of different isotypes.[6] The latter situation represents true BGMs, arising from two or more plasma-cell clones.[4],[6] BGMs may also be transitory; observed at presentation or anytime during the course of the disease or, rarely after therapy.[2] This phenomenon is explained by the recovery of normal Ig production from healthy plasma cells.

Sometimes, SPE in PCMs may reveal double bands in gamma globulin region which is not due to true BGM as reported in our case.[7] This may suggest a BGM initially but is resolved on IFE. Such “pseudo-BGM” cases yield a single band in one of the HC lanes (IgG/IgM/IgA) along with two bands in a single LC region. Our case on IFE showed a single band in IgG with two bands in lambda light chain lane. One of the two bands reported in light chain lane is due to the presence of excess free LCs which migrate faster compared to LCs associated with Ig. There may be asynchronous production of components of the Ig molecules, leading to synthesis of both intact monoclonal Ig along with excess monoclonal free LCs.[7] In our case, sFLC assay revealed lambda to be 400 times more than kappa LC, accounting for excess lambda free LC. This led to production of two bands on SPE, one due to intact IgG-lambda and the other due to lambda LCs.

A mimicker of BGM on SPE may be noted in IgA gammopathy as monoclonal IgAs have a tendency to form dimers leading to two distinct bands on SPE. Bora et al.[8] have reported such a case where in resource limited setting, they repeated SPE following pretreatment of serum with beta-mercaptoethanol leading to depolymerization of the dimers and yielding single band on repeat SPE. Pentameric IgM may also break down into different subunits yielding multiple distinct bands on SPE.[7] Sometimes, along with M-band in the gamma region, another band in beta-gamma region may be observed due to the presence of fibrinogen implying insufficient clotting of sample. This can be resolved as fibrinogen band disappears on IFE.[7]

Reporting of BGM is vital as it impacts not only patient treatment and monitoring decisions but is also important to evaluate response synchronicity of the two clones during follow-up. It is equally vital to rule out its mimickers on SPE so as to avoid wrong reporting. This issue can further be resolved by serum IFE as it provides specific isotype of the M-protein.

Authors’ contributions

SM: writing of manuscript; AS: collection of case details; VK: review of manuscript.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Mc Kenna RW, Kyle RA, Kuehl WM, Harris NL, Coupland RW, Fend F. Plasma cell neoplasms. In Swerdlow SH, Campo E, eds. World Health Organization Classification of Tumours. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues. Rev 4th ed. Lyon, France: IARC 2017 p. 241–58.  Back to cited text no. 1
Sharma S, Gupta P, Aggarwal R, Malhotra P, Minz RW, Bansal F. Demystifying biclonal gammopathy: a pathologist’s perspective. Lab Med 2019; 50:357–63.  Back to cited text no. 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. 3
Tschumper RC, Dispenzieri A, Abraham RS, Henderson KJ, Jelinek DF. Molecular analysis of immunoglobulin genes reveals frequent clonal relatedness in double monoclonal gammopathies. Blood Cancer J 2013; 3:e112.  Back to cited text no. 4
Hallek M, Bergsagel PL, Anderson KC. Multiple myeloma: increasing evidence for a multistep transformation process. Blood 1998; 91:3–21.  Back to cited text no. 5
Mahto M, Balakrishnan P, Koner BC, Lali P, Mishra TK, Saxena A. Rare case of biclonal gammopathy. Int J Case Rep Imag 2011; 2:11–4.  Back to cited text no. 6
Srinivasan VK, Bhagat P, Bansal F, Chhabra S. Occurrence of double monoclonal bands on protein electrophoresis: an unusual finding. Indian J Hematol Blood Transfus 2016; 32:184–8.  Back to cited text no. 7
Bora K, Das U, Barman B, Ruram AA. Monoclonal gammopathy with double M-bands: an atypical presentation on serum protein electrophoresis simulating biclonal gammopathy. Indian J Pathol Microbiol 2017; 60:590–2.  Back to cited text no. 8
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