Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Plasma Cell Dyscrasias - Multiple Myeloma Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Clinical Background
The spectrum of plasma cell dyscrasias is broad and includes:
Monoclonal Gammopathy of Uncertain Significance (MGUS)
- Prevalence
- Most common plasma cell dyscrasia
- MGUS is found in 3% of individuals aged 50 years, 5% among persons 70 years or older and 7.5% among those 85 year or older
- 1% lifelong risk per year of progression to multiple myeloma or other related disorders
- Clinical Presentation
- Asymptomatic premalignant disorder
- Serum monoclonal (M) protein levels <3g/dL, bone marrow plasma cells <10%
- Absence of end-organ damage - lytic bone lesions, anemia, hypercalcemia or renal failure
- Treatment
- None required
- Follow patient to detect appearance of malignancy
Multiple Myeloma (MM)
- Epidemiology
- Incidence - the annual age-adjusted incidence in the U.S. is 4.3 per 100,000 people, resulting in more than 15,000 new cases every year
- Age - the median age at onset is 66 years
- Sex - M:F; 1.4:1
- Ethnicity - higher incidence in African Americans
- Categories
- Light-chain MM
- Up to 20% of patients with MM lack heavy-chain expression in the M protein
- Nonsecretory MM
- 3% have no detectable M protein in serum or urine
- Clinical Presentation
- Malignant proliferation of plasma cells
- Serum and or urinary M protein levels >3g/dL
- Bone marrow plasma cells >10%
- End-organ damage - lytic bone lesions, anemia, hypercalcemia or renal failure
- Most common presenting symptoms of MM - fatigue, bone pain, recurrent infections, anemia, elevated serum creatinine and hypercalcemia
- Similar to normal heavy chain distribution in serum, approximately 50-75% of monoclonal gammopathies are IgG, 20% are IgA and <1 % are IgD
- IgE gammopathies are rare
- Treatment
- Oral chemotherapy and bone marrow transplantation
Waldenström Macroglobulinemia (WM)
- Clinical Presentation
- Malignant proliferation of lymphoid and plasma cells
- Serum IgM M protein (regardless of the size of the M protein)
- Bone marrow lymphoplasmatic infiltration >10%
- Evidence of end-organ damage - anemia, constitutional symptoms (weakness, fatigue, night sweats, weight loss), hyperviscosity, lymphadenopathy, hepatosplenomegaly
- Most common presenting symptoms - hyperviscosity, anemia and constitutional symptoms
- Treatment
- Oral chemotherapy and plasmapheresis for hyperviscosity
Monoclonal Light-Chain (AL) Amyloidosis
- Clinical Presentation
- Malignant disorder of plasma cells
- Deposit of a fibrillar proteinaceous material (detected by Congo red staining) in various tissues such as liver, kidney, heart, peripheral nerves, tongue and subcutaneous tissue
- Evidence of a monoclonal plasma cell proliferative disorder by serum or urine M protein, or clonal plasma cells in the bone marrow
- The clinical presentation of SA varies
- Depends on the dominant organ involved
- Nephrotic syndrome, restrictive cardiomyopathy and peripheral neuropathy are common presenting syndromes
- Treatment
- Oral chemotherapy and bone marrow transplantation
Solitary Plasmacytoma (SP)
- Clinical Presentation
- Malignant disorder
- Biopsy-proven solitary lesions of bone
- Evidence of local clonal plasma cells, normal bone marrow, normal skeletal survey of spine and pelvis
- Absence of end-organ damage that can be attributed to a plasma cell proliferative disorder
- Patients with SP are at risk of progression to MM
- Most common in medullary sites
- SP can occur in extramedullary sites
- Most frequently localized in the upper respiratory tract (nasal cavity, sinuses and nasopharynx)
- Treatment
- Therapy for SP includes radiation of the involved site
Rare Plasma Cell Dyscrasias
- POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Multiple Myeloma and Skin changes) syndrome
- Immunoglobulin heavy chain disease
See Also
Algorithm(s)
PDF algorithm(s) available at www.arupconsult.com.
Plasma Cell Dyscrasias - Multiple Myeloma Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Adults and Older Children Testing Algorithm
Immunodeficiency Evaluation for Chronic Infections in Infants and Children Testing Algorithm
Tests generally appear in the order most useful for common clinical situations
| Test name: Protein Electrophoresis, Serum
|
| ARUP #: 0050640 |
| Methodology: Capillary Electrophoresis
|
Use: SPEP is the recommended test for patients with suspected plasma cell dyscrasia SPEP can be used to monitor treatment response when plasma cell dyscrasia is known |
| Limitations: SPEP can be normal in patients with oligo-secretory on non-secretory myeloma |
| Follow-up: Order: Immunofixation Electrophoresis (Serum), Quantitation IgA, IgG & IgM (Serum) 0050615 |
| Test name: Immunofixation Electrophoresis Monoclonal Protein Detection Quantitation & Characterization SPE, IFE, IgA, IgG, IgM
|
| ARUP #: 0050615 |
| Methodology: Immunofixation Electrophoresis/Capillary Electrophoresis/Nephelometry
|
Use: Identify and characterize the presence of the M protein or monoclonal free light chain components in patients with abnormal banding patterns from SPEP IFE is more sensitive than SPEP in detecting M proteins Monitor therapy and remission of disease |
| Limitations: IFE can be normal in patients with non-secretory myeloma |
| Follow-up: Order: Bence-Jones Protein Qualitative Free Kappa & Lambda Light Chains (Urine) 0050161, skeletal survey and a bone marrow biopsy to rule out plasma cell dyscrasia if M protein detected as well as calcium and Beta-2 microglobulin concentration |
| Test name: Protein Electrophoresis with Reflex to Immunofixation Electrophoresis Monoclonal Protein Detection, Quantitation & Characterization, IgA, IgG, & IgM, Serum
|
| ARUP #: 0050658 |
| Methodology: Capillary Electrophoresis/Immunofixation Electrophoresis/Nephelometry
|
| Use: Distinguish between proteinuria due to renal disease and monoclonal light chains in serum for patient with renal disease |
| Limitations: SPEP can be normal in patients with oligo-secretory on non-secretory myeloma |
| Follow-up: Order: Bence-Jones Protein Qualitative Free Kappa & Lambda Light Chains (Urine) 0050161, skeletal survey and a bone marrow biopsy to rule out plasma cell dyscrasia if M protein detected |
| Test name: Bence Jones Protein, Qualitative Free Kappa & Lambda Light Chains, Urine
|
| ARUP #: 0050161 |
| Methodology: Immunofixation Electrophoresis/Nephelometry
|
| Use: Diagnosis of Bence-Jones protein and its specificity |
| Limitations: |
| Follow-up:
|
| Test name: Kappa/Lambda Quantitative Free Light Chains with Ratio, Serum
|
| ARUP #: 0055167 |
| Methodology: Nephelometry
|
Use: Quantify kappa and lambda light chains in human serum Diagnosis and monitoring of patients with oligo-secretory or non-secretory myeloma and light-chain amyloidosis |
| Limitations: Low levels of FLC are found in serum of normal individuals due to the over production and secretion of FLC by plasma cells |
| Follow-up:
Order sequential levels for monitoring disease progress to therapy
|
| Test name: Bence Jones Protein, Quantitative Free Kappa & Lambda Light Chains, Urine
|
| ARUP #: 0050618 |
| Methodology: Immunofixation Electrophoresis/Nephelometry
|
| Use: Diagnosis and monitoring the presence of Bence-Jones protein and its specificity |
| Limitations: |
| Follow-up:
Sequential levels for monitoring disease progress
|
| Test name: Lambda Light Chain Immunoglobulin mRNA by in situ Hybridization
|
| ARUP #: 8033744 |
| Methodology: in situ Hybridization
|
| Use: Identification of monoclonal plasma cell populations in tissue and bone marrow biopsies |
| Limitations: |
| Follow-up: Useful in initial diagnosis and follow-up biopsies |
| Test name: Immunofixation Electrophoresis, Immunoglobulin D & Immunoglobulin E, Serum
|
| ARUP #: 0050049 |
| Methodology: Immunofixation Electrophoresis
|
| Use: Identify presence of monoclonal IgD or IgE gammopathy in patients with free kappa or lambda identified by IFE electrophoresis |
| Limitations: |
| Follow-up:
|
| Test name: Bence Jones Protein, Quantitative Free Kappa Light Chains, Urine
|
| ARUP #: 0050689 |
| Methodology: Nephelometry/Immunofixation Electrophoresis
|
| Use: Monitor treatment response when gammopathy is known to be kappa |
| Limitations: |
| Follow-up:
Sequential levels for monitoring disease progress
|
| Test name: Bence Jones Protein, Quantitative Free Lambda Light Chains, Urine
|
| ARUP #: 0050682 |
| Methodology: Nephelometry/Immunofixation Electrophoresis
|
| Use: Monitor treatment response when gammopathy is known to be lambda |
| Limitations: |
| Follow-up:
Sequential levels for monitoring disease progress
|
| Test name: Immunofixation Electrophoresis Gel
|
| ARUP #: 0050272 |
| Methodology: Immunofixation Electrophoresis
|
| Use: Identify and characterize the presence of M protein |
| Limitations: Serum IFE does not provide quantification of M protein |
| Follow-up:
|
| Test name: Beta-2 Microglobulin, Serum or Plasma
|
| ARUP #: 0080053 |
| Methodology: Immunoturbidimetric
|
| Use: Prognostic indicator for multiple myeloma |
| Limitations: |
| Follow-up:
|
| Test name: Chromosome Analysis, Bone Marrow
|
| ARUP #: 0097605 |
| Methodology: Giemsa-Band Analysis
|
| Use:
Detect chromosome abnormalities in bone marrow aspirate consistent with diagnosis of multiple myeloma
Some abnormalities also have prognostic significance |
Limitations: Normal metaphase results are suggestive of a stroma-dependant early myeloma, whereas abnormal metaphase results are suggestive of a stroma-independent later-stage myeloma with an associated poorer prognosis. It is recommended this test be done in conjunction with multiple myeloma FISH panel for increased sensitivity, especially in early stage stroma-dependant myeloma |
| Follow-up:
Repeat testing as clinically indicated to monitor disease progression
|
| Test name: Chromosome Analysis, Multiple Myeloma Panel by FISH
|
| ARUP #: 0092617 |
| Methodology: Fluorescence in situ Hybridization
|
Use: Detect prognostically significant genomic aberrations in IGH/CCNDI, D13S25, IgH and p53 in non-dividing cells from bone marrow aspirate If sufficient sample is available, a sorting method is used to select for plasma cells, increasing the sensitivity of assay |
Limitations: FISH will only detect aberrations specific to probes utilized Test is to be used in conjunction with bone marrow chromosome analysis which may detect additional diagnostically significant chromosome abnormalities |
| Follow-up: Repeat testing as clinically indicated to monitor disease progression |
| Test name: Viscosity, Serum
|
| ARUP #: 0020056 |
| Methodology: Cone-Plate Viscometer
|
| Use: Evaluation of hyperviscosity syndrome associated with plasma cell dyscrasia |
| Limitations: Patients with rheumatoid arthritis, lupus erythematosus or hyperfibrinogenemia occasionally may have increased serum viscosity in serum samples |
| Follow-up: Repeat testing as clinically indicated to monitor disease progression |
| Test name: Viscosity, Whole Blood
|
| ARUP #: 0020054 |
| Methodology: Cone-Plate Viscometer
|
| Use: Evaluation of hyperviscosity syndrome associated with plasma cell dyscrasia |
| Limitations: Patients with rheumatoid arthritis, lupus erythematosus or hyperfibrinogenemia occasionally may have increased blood viscosity in serum samples |
| Follow-up: Repeat testing as clinically indicated to monitor disease progression |
| Test name: Immunohistochemistry Stain Offering
|
| ARUP #: arup005 |
| Methodology: Immunohistochemistry
|
| Use: For fixed tissue samples, consultative cervices as well as immunohistochemical staining for CD52 (Campath), CD79a, CD138 (Syndican-1), IgA, IgD, IgG, IgM, Ki-67 (Mib-1), p53, plasma cell, kappa and lambda are available |
| Follow-up: Useful in initial diagnosis as well as for follow-up of therapy |
Additional Tests Available
| Test name: Protein Electrophoresis, CSF
|
| ARUP #: 0050590 |
| Methodology: Electrophoresis
|
| Comments: |
References
Guidelines
Durie BG, Harousseau JL, Miguel JS, Blade J, Barlogie B, Anderson K, Gertz M, Dimopoulos M, Westin J, Sonneveld P, Ludwig H, Gahrton G, Beksac M, Crowley J, Belch A, Boccadaro M, Turesson I, Joshua D, Vesole D, Kyle R, Alexanian R, Tricot G, Attal M, Merlini G, Powles R, Richardson P, Shimizu K, Tosi P, Morgan G, Rajkumar SV. International uniform response criteria for multiple myeloma. Leukemia.
2006;
20(
9):
1467-1473.
Kyle RA, Treon SP, Alexanian R, Barlogie B, Bjorkholm M, Dhodapkar M, Lister TA, Merlini G, Morel P, Stone M, Branagan AR, Leblond V. Prognostic markers and criteria to initiate therapy in Waldenstrom's macroglobulinemia: consensus panel recommendations from the Second International Workshop on Waldenstrom's Macroglobulinemia. Semin Oncol.
2003;
30(
2):
116-120.
General References
Annibali O, Petrucci MT, Del Bianco P, Gallucci C, Levi A, Foa R, Avvisati G. IgM multiple myeloma: report of four cases and review of the literature. Leuk Lymphoma.
2006;
47(
8):
1565-1569.
Blade J, Rosinol L. Smoldering multiple myeloma and monoclonal gammopathy of undetermined significance. Curr Treat Options Oncol.
2006;
7(
3):
237-245.
Blade J. Clinical practice. Monoclonal gammopathy of undetermined significance. N Engl J Med.
2006;
355(
26):
2765-2770.
Chng WJ, Glebov O, Bergsagel PL, Kuehl WM. Genetic events in the pathogenesis of multiple myeloma. Best Pract Res Clin Haematol.
2007;
20(
4):
571-596.
Comenzo RL. Managing systemic light-chain amyloidosis. J Natl Compr Canc Netw.
2007;
5(
2):
179-187.
Dimopoulos MA, Kastritis E, Anagnostopoulos A. Hematological malignancies: myeloma. Ann Oncol.
2006;
17 Suppl 10:
x137-x143.
Gertz MA. Relevant prognostic features of multiple myeloma and the new International Staging System. Leuk Lymphoma.
2007;
48(
3):
458-468.
Graziani M, Merlini G, Petrini C. Guidelines for the analysis of Bence Jones protein. Clin Chem Lab Med.
2003;
41(
3):
338-346.
Heider U, Fleissner C, Zavrski I, Kaiser M, Hecht M, Jakob C, Sezer O. Bone markers in multiple myeloma. Eur J Cancer.
2006;
42(
11):
1544-1553.
Jaskowski TD, Litwin CM, Hill HR. Detection of kappa and lambda light chain monoclonal proteins in human serum: automated immunoassay versus immunofixation electrophoresis. Clin Vaccine Immunol.
2006;
13(
2):
277-280.
Katzmann JA, Abraham RS, Dispenzieri A, Lust JA, Kyle RA. Diagnostic performance of quantitative kappa and lambda free light chain assays in clinical practice. Clin Chem.
2005;
51(
5):
878-881.
Korbet SM, Schwartz MM. Multiple myeloma. J Am Soc Nephrol.
2006;
17(
9):
2533-2545.
Kumar A, Djulbegovic B. Myeloma (multiple). Clin Evid.
2006;
(
15):
1-29.
Kyle RA, Rajkumar SV. Epidemiology of the plasma-cell disorders. Best Pract Res Clin Haematol.
2007;
20(
4):
637-664.
McMaster ML, Caporaso N. Waldenstrom macroglobulinaemia and IgM monoclonal gammopathy of undetermined significance: emerging understanding of a potential precursor condition. Br J Haematol.
2007;
139(
5):
663-671.
Mead GP, Carr-Smith HD, Drayson MT, Morgan GJ, Child JA, Bradwell AR. Serum free light chains for monitoring multiple myeloma. Br J Haematol.
2004;
126(
3):
348-354.
O'Connell TX, Horita TJ, Kasravi B. Understanding and interpreting serum protein electrophoresis. Am Fam Physician.
2005;
71(
1):
105-112.
Rajkumar SV, Dispenzieri A, Kyle RA. Monoclonal gammopathy of undetermined significance, Waldenstrom macroglobulinemia, AL amyloidosis, and related plasma cell disorders: diagnosis and treatment. Mayo Clin Proc.
2006;
81(
5):
693-703.
Rajkumar SV, Kyle RA. Multiple myeloma: diagnosis and treatment. Mayo Clin Proc.
2005;
80(
10):
1371-1382.
Reece DE. Management of multiple myeloma: the changing landscape. Blood Rev.
2007;
21(
6):
301-314.
San Miguel JF, Gutierrez NC, Mateo G, Orfao A. Conventional diagnostics in multiple myeloma. Eur J Cancer.
2006;
42(
11):
1510-1519.
Sirohi B, Powles R. Epidemiology and outcomes research for MGUS, myeloma and amyloidosis. Eur J Cancer.
2006;
42(
11):
1671-1683.
Veillon DM, Cotelingam JD. Pathologic studies useful for the diagnosis and monitoring of plasma cell dyscrasias. Contrib Nephrol.
2007;
153:
25-43.
Zhan F, Sawyer J, Tricot G. The role of cytogenetics in myeloma. Leukemia.
2006;
20(
9):
1484-1486.
References from the ARUP Institute for Clinical and Experimental Pathology Research®
Chen Z, Issa B, Huang S, Aston E, Xu J, Yu M, Brothman AR, Glenn M. A practical approach to the detection of prognostically significant genomic aberrations in multiple myeloma. J Mol Diagn.
2005;
7(
5):
560-565.
Jaskowski TD, Litwin CM, Hill HR. Detection of kappa and lambda light chain monoclonal proteins in human serum: automated immunoassay versus immunofixation electrophoresis. Clin Vaccine Immunol.
2006;
13(
2):
277-280.
Smock KJ, Perkins SL, Bahler DW. Quantitation of plasma cells in bone marrow aspirates by flow cytometric analysis compared with morphologic assessment. Arch Pathol Lab Med.
2007;
131(
6):
951-955.
Medical Reviewers
Delgado, Julio C., M.D., M.S. Medical Director, Protein Immunology at ARUP Laboratories; Associate Director, Histocompatibility and Immunogenetics Laboratory and Assistant Professor, Clinical Pathology, University of Utah
Frank, Elizabeth L. , Ph.D. Medical Director, Analytic Biochemistry and Calculi at ARUP Laboratories; Associate Professor, Clinical Pathology, University of Utah
Hill, Harry R., M.D. Group Medical Director, Laboratory of Immunology, ARUP Laboratories, and Executive Director of the ARUP Institute for Clinical and Experimental Pathology; Professor and Division Head, Clinical Pathology, University of Utah
Lamb, Allen N., Ph.D. Medical Director, Cytogenetics, ARUP Laboratories; Associate Professor, Department of Pathology, University of Utah
Meikle, A. Wayne, M.D. Medical Director, RIA and Endocrinology at ARUP Laboratories; Professor of Internal Medicine and Pathology, University of Utah
Perkins, Sherrie L. , M.D., Ph.D. Medical Director, Hematopathology at ARUP Laboratories; Professor, Anatomic Pathology, University of Utah
Roberts, William L. , M.D., Ph.D. Medical Director, Automated Core Laboratory at ARUP Laboratories; Professor, Pathology, University of Utah
South, Sarah T. , Ph.D. Medical Director, Cytogenetics at ARUP Laboratories; Assistant Medical Director, CGH Microarray Laboratory, and Assistant Professor, Department of Pediatrics, University of Utah
Comprehensive Review: March 2008
Last Update: March 2008
