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Test ID MPSEX Monoclonal Protein Study, Expanded Panel, Serum

Reporting Name

MPSS Expanded Panel, S

Useful For

Diagnosis of monoclonal gammopathies

 

Eliminating the need for urine monoclonal studies as a part of initial diagnostic studies (ie, rule-out monoclonal gammopathy)

 

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

Profile Information

Test ID Reporting Name Available Separately Always Performed
TPE Total Protein Yes, (order TP) Yes
ELP Protein Electrophoresis Yes, (order PEL) Yes
IMFX Immunofixation Yes, (order IMFXO) Yes
KFLC Kappa Free Light Chain, S Yes, (order FLCP) Yes
LFLC Lambda Free Light Chain, S Yes, (order FLCP) Yes
KLR Kappa/Lambda FLC Ratio Yes, (order FLCP) Yes

Specimen Type

Serum


Specimen Required


Patient Preparation: Fasting preferred but not required

Container/Tube: 

Preferred: Serum gel

Acceptable: Red top

Specimen Volume: 2 mL


Specimen Minimum Volume

1.5 mL

Specimen Stability Information

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

Reference Values

PROTEIN, TOTAL

≥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.

 

IMMUNOFIXATION

No monoclonal protein detected

 

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

Test Classification

This test has been cleared or approved by the U.S. Food and Drug Administration and is used per manufacturer's instructions. Performance characteristics were verified by Mayo Clinic in a manner consistent with CLIA requirements.

CPT Code Information

83883 x 2-Nephelometry, each analyte not elsewhere specified

84155-Protein, total

84165-Protein, electrophoresis

86334-Immunofixation

LOINC Code Information

Result ID Test Result Name Result LOINC Value
81653 Immunofixation 74665-1
KFLC Kappa Free Light Chain, S 36916-5
KLR Kappa/Lambda FLC Ratio 48378-4
LFLC Lambda Free Light Chain, S 33944-0
TPE Total Protein 2885-2
2769 Albumin 2862-1
2770 Alpha-1 Globulin 2865-4
2771 Alpha-2 Globulin 2868-8
2773 Beta-Globulin 2871-2
2774 Gamma-Globulin 2874-6
2785 A/G Ratio 44429-9
22308 M spike 33358-3
22309 M spike 33358-3
15254 Impression 12851-2

Clinical Information

Monoclonal proteins are markers of plasma cell proliferative disorders. It has been recommended that serum and urine protein electrophoresis (PEL) and immunofixation electrophoresis (IFE) be performed as the diagnostic algorithm (eg, MPSS / Monoclonal Protein Study, Serum and MPSU / Monoclonal Protein Study, 24 Hour, Urine): A monoclonal band (M-spike) on serum and/or urine PEL identifies a monoclonal process and quantitates the abnormality. IFE characterizes the type of monoclonal protein (gamma, alpha, mu, delta, or epsilon heavy chain; kappa [K] or lambda [L] light chain). IFE is also more sensitive than PEL for detecting small abnormalities that may be present in diseases such as light chain multiple myeloma, oligosecretory myeloma, and plasmacytomas.

 

With the addition of the serum free light chain (FLC) assay, the expanded monoclonal protein study provides even more diagnostic sensitivity for the monoclonal light chain diseases such as primary amyloid and light chain deposition disease--disorders that often do not have serum monoclonal proteins in high enough concentration to be detected and quantitated by PEL. The FLC assay is specific for free kappa and lambda light chains and does not recognize light chains bound to intact immunoglobulin. Importantly, the addition of the serum FLC assay to serum PEL and IFE makes the serum diagnostic studies sufficiently sensitive so that urine specimens are no longer required as part of initial diagnostic studies.

 

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 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 PEL and/or FLC and in some instances by quantitative immunoglobulins. In addition, if the patient is asymptomatic and has a diagnosis of MGUS, the expanded monoclonal protein study panel provides the information (size of M-spike, monoclonal protein isotype, FLC K/L ratio) needed for a MGUS progression risk assessment (see Interpretation).

Interpretation

Monoclonal Gammopathies:

-A characteristic monoclonal band (M-spike) is often found on protein electrophoresis (PEL) 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 PEL pattern is suggestive of a possible monoclonal protein. Immunofixation electrophoresis (IFE) is performed to identify the immunoglobulin heavy chain and/or light chain.

-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) K/L ratio in the presence of a normal IFE 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 PEL 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, should be followed by VISCS / Viscosity, Serum.

-After the initial identification of a monoclonal band, quantitation of the M-spike on follow-up PEL 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 more a useful tool to follow the monoclonal protein level than PEL. 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 PEL patterns. Approximately 11% of patients with MM have a completely normal serum PEL, with the monoclonal protein only identified by IFE. Approximately 8% of MM patients have hypogammaglobulinemia without a quantifiable M-spike on PEL but identified by IFE and/or FLC. Accordingly, a normal serum PEL does not rule out the disease and PEL 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 PEL 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 (>1.2 g/dL), and decreased gamma fraction (<1 g/dL) is consistent with nephritic 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. Kyle RA, Katzmann JA, Lust JA, Dispenzieri A: Clinical indications and applications of electrophoresis and immunofixation. In Manual of Clinical Laboratory Immunology. Sixth edition. Edited by NR Rose, RG Hamilton, B Detrick. Washington DC. ASM Press, 2002, p 66-70

2. 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

3. 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

Analytic Time

Same day/1 day

Testing Algorithm

Includes total protein, serum protein electrophoresis (SPEP), heavy chain and light chain typing (kappa and lambda).

Method Name

TPE: Biuret

ELP: Agarose Gel Electrophoresis

IMFX: Immunofixation

KFLC, LFLC, KLR: Nephelometry

Forms

If not ordering electronically, complete, print, and send a Hematopathology/Cytogenetics Test Request Form (T726)

(http://www.mayomedicallaboratories.com/it-mmfiles/hematopathology-request-form.pdf)

 

Day(s) and Time(s) Performed

Monday through Saturday; 2 p.m.