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Test ID DMOGA Monoclonal Gammopathy, Diagnostic, Serum


Ordering Guidance


To monitor a patient with an established diagnosis of a monoclonal gammopathy, order TMOGA / Monoclonal Gammopathy, Monitoring, Serum.



Specimen Required


Patient Preparation: Fasting (12 hour) preferred but not required

Container/Tube:

Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 2 mL


Forms

If not ordering electronically, complete, print, and send a Renal Diagnostics Test Request (T830) with the specimen.

Useful For

Screening and diagnosis of monoclonal gammopathies including analysis of free light chains

 

Assessing the risk of progression from monoclonal gammopathy of undetermined significance to multiple myeloma

Profile Information

Test ID Reporting Name Available Separately Always Performed
TMAB Therapeutic Antibody Administered? No Yes
TPE Total Protein Yes, (Order TP) Yes
SPE Protein Electrophoresis No Yes
MPTS M-protein Isotype MALDI-TOF MS, S Yes, (Order MALD) Yes
KFLCS Kappa Free Light Chain, S Yes, (Order FLCS) Yes
LFLCS Lambda Free Light Chain, S Yes, (Order FLCS) Yes
KLRS Kappa/Lambda FLC Ratio Yes, (Order FLCS) Yes

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
IFXED Immunofixation Delta and Epsilon, S Yes No

Testing Algorithm

This test includes total protein, serum protein electrophoresis, heavy and light chain typing (kappa and lambda), and quantitation of kappa and lambda free light chains.

 

If a light chain is identified without a corresponding heavy chain during initial testing, immunofixation with IgD and IgE antisera will be performed at an additional charge.

 

See Laboratory Screening Tests for Suspected Multiple Myeloma in Special Instructions.

Method Name

TPE: Colorimetric; Biuret

SPE: Agarose Gel Electrophoresis

MPTS: Matrix-Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS)

KFLCS, LFLCS: Turbidimetry

KLRS: Calculation

IFXED: Immunofixation

Reporting Name

Monoclonal Gammopathy Diagnostic, S

Specimen Type

Serum

Specimen Minimum Volume

1.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Serum Refrigerated (preferred) 14 days
  Frozen  14 days
  Ambient  72 hours

Clinical Information

Monoclonal proteins are markers of plasma cell proliferative disorders. The International Myeloma Working Group guidelines state that to adequately screen for a monoclonal protein, serum protein electrophoresis (SPE), immunofixation electrophoresis, and a serum free light chain (FLC) analysis should all be used. If amyloidosis is suspected, a 24-hour urine monoclonal protein study should be performed.

 

The detection of M-proteins by matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) has shown to be more analytically and clinically sensitive than immunofixation. In addition, the MALDI-TOF method can detect glycosylated light chains that have been demonstrated to be a risk factor for amyloidosis.

 

This expanded monoclonal protein testing panel provides the highest diagnostic sensitivity for the monoclonal light chain diseases such as primary amyloidosis and light chain deposition disease; disorders that often do not have serum monoclonal proteins in high enough concentration to be detected and quantitated by SPE. The FLC assay is specific for free kappa and lambda light chains and does not recognize light chains bound to intact immunoglobulin.

 

Monoclonal gammopathies may be present in a wide spectrum of diseases that include malignancies of plasma cells or B lymphocytes (multiple myeloma: MM, macroglobulinemia, plasmacytoma, B-cell lymphoma), disorders of monoclonal protein structure (primary amyloid, light chain deposition disease, cryoglobulinemia), and apparently benign, premalignant conditions (monoclonal gammopathy of undetermined significance: MGUS, smoldering MM). While the identification of the monoclonal gammopathy is a laboratory diagnosis, the specific clinical diagnosis is dependent on a number of other laboratory and clinical assessments.

 

If a monoclonal protein pattern is detected by MALDI-TOF MS, immunofixation electrophoresis (IFE), or FLC, a diagnosis of a monoclonal gammopathy is established. Once a monoclonal gammopathy has been diagnosed, the size of the clonal abnormality can be monitored by SPE or FLC and, in some instances, by quantitative immunoglobulins. In addition, if the patient is asymptomatic and has a diagnosis of MGUS, the monoclonal gammopathy screen provides the information (size of M-spike, monoclonal protein isotype, FLC kappa/lambda ratio) needed for a MGUS progression risk assessment (see Interpretation).

Reference Values

TOTAL PROTEIN:

≥1 year: 6.3-7.9 g/dL

Reference values have not been established for patients that are <12 months of age.

 

PROTEIN ELECTROPHORESIS

Albumin: 3.4-4.7 g/dL

Alpha-1-globulin: 0.1-0.3 g/dL

Alpha-2-globulin: 0.6-1.0 g/dL

Beta-globulin: 0.7-1.2 g/dL

Gamma-globulin: 0.6-1.6 g/dL

An interpretive comment is provided with the report.

Reference values have not been established for patients that are <16 years of age.

 

M-PROTEIN ISOTYPE MALDI-TOF MS

No monoclonal protein detected

 

M-protein Isotype MALDI-TOF MS Flag

Negative

 

KAPPA-FREE LIGHT CHAIN

0.33-1.94 mg/dL

 

LAMBDA-FREE LIGHT CHAIN

0.57-2.63 mg/dL

 

KAPPA/LAMBDA-FREE LIGHT-CHAIN RATIO

0.26-1.65

Interpretation

Monoclonal Gammopathies:

-A characteristic monoclonal band (M-spike) is often found on serum protein electrophoresis (SPE) in the gamma globulin region and, more rarely, in the beta or alpha-2 regions. The finding of an M-spike, restricted migration, or hypogammaglobulinemic SPE pattern is suggestive of a possible monoclonal protein. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) is performed to identify any immunoglobulin heavy and light chains present.

-A monoclonal IgG or IgA of greater than 3 g/dL is consistent with multiple myeloma (MM).

-A monoclonal IgG or IgA of less than 3 g/dL may be consistent with monoclonal gammopathy of undetermined significance (MGUS), primary systemic amyloidosis, early or treated myeloma, as well as a number of other monoclonal gammopathies.

-A monoclonal IgM of greater than 3 g/dL is consistent with macroglobulinemia.

-An abnormal serum free light chain (FLC) kappa/lambda (K/L) ratio in the presence of a normal MALDI-TOF MS suggests a monoclonal light chain process and should be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine.

-The initial identification of a serum M-spike greater than 1.5 g/dL on SPE should be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine.

-The initial identification of an IgM, IgA, or IgG M-spike greater than 4 g/dL, greater than 5 g/dL, and greater than 6 g/dL, respectively, a VISCS / Viscosity, Serum should be tested to rule out hyperviscosity syndrome.

 

After the initial identification of a monoclonal band, quantitation of the M-spike on follow-up SPE can be used to monitor the monoclonal gammopathy. However, if the monoclonal protein falls within the beta region (most commonly an IgA or an IgM) quantitative immunoglobulin levels may be a more useful tool to follow the monoclonal protein level than SPE. A decrease or increase of the M-spike that is greater than 0.5 g/dL is considered a significant change.

 

Patients with monoclonal light chain diseases who have no serum or urine M-spike may be monitored with the serum FLC value.

 

Patients suspected of having a monoclonal gammopathy may have normal serum SPE patterns. Approximately 11% of patients with MM have a completely normal serum SPE, with the monoclonal protein only identified by MALDI-TOF MS. Approximately 8% of MM patients have hypogammaglobulinemia without a quantifiable M-spike on SPE but identified by MALDI-TOF MS or FLC. Accordingly, a normal serum SPE does not rule out the disease and SPE alone should not be used to screen for the disorder if the clinical suspicion is high.

 

MGUS Prognosis:

-Low-risk MGUS patients are defined as having an M-spike of less than 1.5 g/dL, IgG monoclonal protein, and a normal FLC K/L ratio (0.25-1.65), and these patients have a lifetime risk of progression to MM of less than 5%.

-High-risk MGUS patients (M-spike >1.5, IgA or IgM, abnormal FLC ratio) have a lifetime risk of progression to MM of 60%.

 

Other Abnormal SPE Findings:

-A qualitatively normal but elevated gamma fraction (polyclonal hypergammaglobulinemia) is consistent with infection, liver disease, or autoimmune disease.

-A depressed gamma fraction (hypogammaglobulinemia) is consistent with immune deficiency and can also be associated with primary amyloidosis or nephrotic syndrome.

-A decreased albumin (<2 g/dL), increased alpha-2 fraction (>1.1 g/dL), and decreased gamma fraction (<1 g/dL) is consistent with nephrotic syndrome and, when seen in an adult older than 40 years, should be followed by MPSU / Monoclonal Protein Study, 24 Hour, Urine.

-In the hereditary deficiency of a protein (eg, agammaglobulinemia, alpha-1-antitrypsin [A1AT] deficiency, hypoalbuminemia), the affected fraction is faint or absent.

-An absent alpha-1 fraction is consistent with A1AT deficiency disease and should be followed by a quantitative A1AT assay (AAT / Alpha-1-Antitrypsin, Serum).

Clinical Reference

1. Rajkumar SV, Kyle RA, Therneau TM, et al: Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance. Blood. 2005;106:812-817

2. Katzmann JA, Dispenzieri A, Kyle RA, et al: Elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays. Mayo Clin Proc. 2006;81(12):1575-1578

3. Mills JR, Kohlhagen MC, Dasari S, et al: Comprehensive assessment of M-proteins using nanobody enrichment coupled to MALDI-TOF mass spectrometry. Clin Chem. 2016;62(10):1334-1344

4. Milani P, Murray DL, Barnidge DR, et al: The utility of MASS-FIX to detect and monitor monoclonal proteins in the clinic. Am J Hematol. 2017;92(8):772-779 doi: 10.1002/ajh.24772

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

83520 x2

84155

84165

0077U

86334 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
DMOGA Monoclonal Gammopathy Diagnostic, S In Process

 

Result ID Test Result Name Result LOINC Value
TPE Total Protein 2885-2
602837 Albumin 2862-1
LFLCS Lambda Free Light Chain, S 33944-0
KLRS Kappa/Lambda FLC Ratio 48378-4
TMAB Therapeutic Antibody Administered? In Process
KFLCS Kappa Free Light Chain, S 36916-5
65198 M-protein Isotype MALDI-TOF MS 90990-3
606976 Flag, M-protein Isotype 94400-9
602838 Alpha-1 Globulin 2865-4
602839 Alpha-2 Globulin 2868-8
602840 Beta-Globulin 2871-2
602841 Gamma-Globulin 2874-6
602842 A/G Ratio 44429-9
602843 M spike 51435-6
602844 M spike 35559-4
602836 Impression 49296-7

Day(s) Performed

TPE, SPE, FLCS: Monday through Friday

MPTS, IFXED: Monday through Friday

Report Available

2 to 3 days