**1. Introduction**

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Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell dyscrasia, present in 3.2% of white people over 50 years of age [1], which converts to multiple myeloma (MM) or related disorders at a rate of just 1% a year [2], an incurable malignancy of plasma cells. While MM is the prototypical monoclonal gammopathy, the most common is MGUS [3].

Monoclonal gammopathies are a heterogeneous group of disorders characterized by the stable or progressive proliferation of an abnormal clone of plasma cells that continue pro‐ ducing antibodies [4]. But because these immunoglobulin proteins are abnormal and mon‐ oclonal (identical copies of each other), these offer no protection against infections and can damage the kidney. This monoclonal immunoglobulin is called M-protein. Each basic unit is a monomeric immunoglobulin consisting of two heavy chains of the same class and subclass and two light chains of the same type. The heavy chain classes are G, A, M, D, E (gamma, alpha, mu, delta, epsilon), while the light chain types are kappa (κ) and lambda (λ).

Monoclonal gammopathies are recognized on serum protein electrophoresis demonstrating a band of migration in the beta or gamma region [5]. When a band is seen on serum protein electrophoresis, immunofixation electrophoresis should be performed. Immunofixation electrophoresis is the gold standard and should be performed to confirm the presence of an M-protein and to distinguish its heavy chain and light chain type [6].

In 1952, Waldeström [7] initially reported finding an M-protein without evidence of malignant disorder, and named the condition "essential hypergammaglobulinemia". For some time, this

© 2013 Cortés et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2013 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

condition was also referred to as "benign monoclonal gammopathy". However, Kyle recog‐ nized that some patients with MGUS could progress to MM, Waldeström macroglobulinemia, light chain amyloidosis, or related disorders. Thus, Kyle coined the term MGUS in 1978 [8]. In 2003, MGUS is defined by serum M-protein concentration less than 3 g/dL, the bone marrow clonal plasma cell less than 10%, with no evidence of other B-cell proliferation disorders [9].

**Site**

**[References]**

Minnesota, USA [10]

Finistere, France [11]

North Carolina, USA [12]

Hospital, Japan [21]

Minnesota, USA [1]

LHNC, Japan [22]

1 hospital, Chile [23]

Bangkok, Thailand [24]

Seongnam, Korean [25]

Germany [26]

142 VA hospitals [15]

Iceland [20] RCS

**Type Study (Length)**

Health CP (1 y)

PB (<1 mo)

PB (NA)

(22 y)

HCS-BS (16 y)

PB (6 y)

RS-IHR (16 y)

RS-BS (15.5 y)

SH (6 mo)

KL (1 y)

RS AGE

PB-HNR SPEP

**Test Identify M-protein**

CAE IE

CAE IE

AGE IFE

CAE AGE

CAE IE

AGE IFE

CAE IE

IFE

HRGE AGE

SPEP IFE

IFE

**SPEP:** Standard serum electrophoresis; **VA:** Veterans Affairs.

**Table 1.** Studies of epidemiology of MGUS

**Nº of Persons Studied (Age, y)**

30,279 (≥30) 17,968 (≥50)

Population Iceland (20-104) **Prevalence % (Age, y); Incidence or Cases**

2.8 % (≥70)

0.2 % (all) 1.7 % (≥50)

8.4/3.8% blacks/whites

11/100,000 (M)

9/100,000 (F)

2.0% (≥70)

3.7/2.9% (M/F)

0.09% blacks 0.04% whites

4.4 % (≥80)

38/46% (M/F)

3.8/2.5% (M/F)

4.4/2.7% (M/F)

NA 11/6 (M/F)

1,200 (≥50) 1.25 % (≥50)

1,732 (≥70) 6.1% total

6,737 (45-85) 0.93%

NA 3,997,815(≥18) 0.05% total;

MGUS: 17 (28-96)

21,463 (≥50) 3.2 % (≥50)

52,781 (≥42) 2.1% (all)

3,260 (50-93) 2.3%

1,118 (65-97) 3.1%

4,702 (45-75) 3.5%

**AGE**: Agarose gel electrophoresis; **CAE**: Cellulose acetate electrophoresis; **CP:** Control prevalence; **HCS-PS:** Hospital cohort study- atomic bomb survivors; **HRGE:** High-resolution gel electrophoresis; **IFE:** Immunofixation; **IE**: Immunoelec‐ trophoresis; **KL:** After scheduled tests for the Korean longitudinal study on health and aging; **LHNC:** Local hospital Nagasaki City**; M/F:** Males/females; **NA:** No available; **PB:** Population based; **PB-HNR:** Population-based Heinz Nixdorf Recall study; **RCS:** Retrospective cohort study; **RS:** Retrospective study; **RS-BS:** Retrospective study of date base of atomic bomb survivors; **RS-IHR:** Retrospective study of inpatient hospitalization records; **SH:** Cross-sectional survey of healthy;

**M-protein IgG % n/MGUS**

Monoclonal Gammopathy of Undetermined Significance

73.3 % 11/15

71.7% 43/60

68.9% NA/694

73.6% NA/1,088

59.0% 10/17

64% 48/75

29% 6/21

59% 97/165 **IgA % n/MGUS**

http://dx.doi.org/10.5772/56138

6.7% 1/15

6.6% 4/60

NA/106 NA/106 NA/106

55.0% 13.0% 32.0%

10.8% NA/694

NA/2,046 NA/2,046 NA/2,046

17.7% NA/1,088

24.0% 4/17

21.3% 16/75

43% 9/21

17% 28/165

55.8% 41.6% -

**IgM % n/MGUS** 113

20.0% 3/15

21.7% 13/60

17.2% NA/694

7.5% NA/1,088

18.0% 3/17


19% 4/21

17% 28/165

The objective of this chapter is to describe new concepts and advances concerning the diag‐ nosis, classification, management of patient, risk factors for malignant transformation and new preventive strategies of progression of MGUS to malignant conditions.
