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{{Multiple myeloma}}
{{Multiple myeloma}}
{{CMG}}
{{CMG}} {{AE}} {{HMHJ}}; {{HL}}; {{shyam}}


==Overview==
==Overview==
==Laboratory Findings==
Laboratory findings consistent with the [[diagnosis]] of [[multiple myeloma]] include abnormal [[complete blood count]], abnormal [[basic metabolic panel]], elevated monoclonal [[protein]] on serum [[electrophoresis]], elevated [[serum]] free [[Light chain|light chains]], and presence of [[Multiple myeloma|myeloma]]-specific [[protein]] markers by [[immunohistochemistry]] or [[immunophenotyping]]. Some of the laboratory tests are factors that determine the stage of [[Multiple myeloma|multiple myeloma.]]
===Complete blood count===
 
* Blood test: The blood test result of patients with multiple myeloma may show low level of all blood cells.
==Laboratory Tests==
===Quantitative immunoglobulins===
=== Initial Tests ===
* In multiple myeloma, the level of one type may be high while the others are low.
* [[Complete blood counts|Complete blood count]] with differential
* [[Serum albumin]]
* [[Calcium|Serum calcium]]
* [[Serum]] [[Electrolyte|electrolytes]]
* [[Serum creatinine]]
* [[Serum]] [[urea]]
* [[Serum]] [[nitrogen]]
 
=== Confirmatory Tests ===
* 24-hour [[urine]] [[protein]]
* [[Beta-2 microglobulin|β<sub>2</sub>-microglobulin]]
* [[Lactate dehydrogenase]]
* [[Serum]] free [[light chain]] assay
* Serum [[immunofixation]] [[electrophoresis]]
* [[Serum protein electrophoresis]]
* [[Serum]] quantitative [[immunoglobulins]]
* [[Skeletal survey]]
* [[Urine]] [[immunofixation]] [[electrophoresis]]
* [[Urine]] [[protein electrophoresis]]
 
=== Tests Performed by Oncologist ===
* [[Bone marrow aspiration]]
* [[Bone marrow biopsy]]
* [[Cytogenetics]] studies
* [[Flow cytometry]]
* [[Fluorescence in situ hybridization]]
* [[Immunohistochemistry]]


*Blood biochemistry tests: This test may show the high level of calcium in the blood and impairs of renal function.
=== Tests in Special Circumstances ===
* [[Bone]] [[densitometry]]
* [[PET scan|PET/CT]] or whole-body [[MRI]]
* [[Serum]] [[viscosity]]
* [[Tissue]] [[biopsy]] of [[Bone|bony]] or other [[lesion]]


== Laboratory Findings ==
===Complete blood count===
*[[Anemia]]<ref name="canada">Multiple myeloma. Canadian Cancer Society(2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/diagnosis/?region=mb#blood_chem Accessed on September, 20th 2015</ref><ref name="wiki">Multiple myeloma. Wikipedia(2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September 2015</ref>
*[[Thrombocytopenia]]
*[[Leukopenia]]


===Peripheral blood smear===
*[[Rouleaux formation]] of red blood cells: This is defined as the stacking of 4 or more [[red blood cells]]. In healthy individuals, the zeta potential of [[red blood cells]] causes intercellular repulsion. However, in patients with multiple myeloma, there are many positively charged paraproteins, which antagonizes the negative charge on [[red blood cells]] and allows for stacking.<ref name="canada" /><ref name="wiki" />


The presence of unexplained [[anemia]], [[kidney]] dysfunction, a high [[erythrocyte sedimentation rate]] (ESR) and a high serum [[protein]] (especially raised [[immunoglobulin]]) may prompt further testing. A [[medical doctor|doctor]] will request [[protein electrophoresis]] of the blood and urine, which might show the presence of a [[paraprotein]] (monoclonal protein, or M protein) band, with or without reduction of the other (normal) immunoglobulins (known as immune paresis). One type of paraprotein is the [[Bence Jones protein]] which is a urinary paraprotein composed of free light chains (see below).  Quantitative  measurements of the paraprotein are necessary to establish a diagnosis and to monitor the disease. The paraprotein is an abnormal [[immunoglobulin]] produced by the tumor clone. Very rarely, the myeloma is ''nonsecretory'' (not producing immunoglobulins).  
===Basic metabolic panel===
*[[Hypercalcemia]] due to increased [[osteoclasts]] activity: This is one of the defining features of end-organ damage in multiple myeloma.
*Increased [[serum creatinine]] level due to reduced [[renal function]]: This is one of the defining features of end-organ damage in multiple myeloma.
*Abnormal [[blood urea nitrogen]]  
*High [[alkaline phosphatase]] level
*High serum [[protein]] level with normal/decreased albumin level: This creates a high protein gap, which is defined as the difference between the albumin level and the total protein level.
*High lactate dehydrogenase: This occurs in stage III multiple myeloma as defined by the Revised-International Staging System (R-ISS).


In theory, multiple myeloma can produce all classes of immunoglobulin, but IgG paraproteins are most common, followed by IgA and IgM.  IgD and IgE myeloma are very rare. In addition, light and or heavy chains (the building blocks of antibodies) may be secreted in isolation: κ- or λ-light chains or any of the five types of heavy chains (α-, γ-, δ-, ε- or μ-heavy chains).
===Serum protein electrophoresis===
*[[Protein electrophoresis]] is a method that separates proteins in the serum or urine.
*70% of cases have high levels of [[IgG]]
*20% of cases have high levels of [[IgA]]
*5–10% of cases have only [[immunoglobulin light chains]] (Bence Jones proteins)
*Rarely κ- or λ-light chains may be secreted in isolation


Additional findings include: a raised [[calcium]] (when [[osteoclasts]] are breaking down bone, releasing calcium into the bloodstream), raised serum creatinine due to reduced [[renal function]], which may be due to paraprotein deposition in the [[kidney]].
===Urine studies===
*Presence of monoclonal paraprotein on urine protein electrophoresis
*Elevated 24-hour urine protein
*Elevated urine free light chains


[[Immunohistochemistry]] (staining particular cell types using antibodies against surface proteins) can detect plasma cells which express immunoglobulin in the cytoplasm but usually not on the surface; myeloma cells are typically [[CD56]], [[CD38]], [[CD138]] positive and [[CD19]] and [[CD45]] negative. [[Cytogenetics]] may also be performed in myeloma for prognostic purposes.
===Free light chain immunoassay===
*Elevated free kappa light chain
*Elevated free lambda light chain
*Elevated free light chain ratio
*Potentially offers an improvement in monitoring disease progression and response to treatment


Other useful laboratory tests include quantitative measurement of [[IgA]], [[IgG]], [[IgM]] ([[immunoglobulin]]s) to look for immune paresis, and β2-microglobulin which provides prognostic information.  On peripheral blood smear the rouleaux formation of red blood cells is commonly seen.
===Immunofixation===
*Identifies the type of M-protein or immunoglobulin light chain detected by serum or urine electrophoresis


The recent introduction of a commercial immunoassay for measurement of free light chains potentially offers an improvement in monitoring disease progression and response to treatment, particularly where the paraprotein is difficult to measure accurately by electrophoresis (for example in light chain myeloma, or where the paraprotein level is very low). Initial research also suggests that measurement of free light chains may also be used, in conjunction with other markers, for assessment of the risk of progression from [[monoclonal gammopathy of undetermined significance]] (MGUS) to multiple myeloma.
===Quantitative immunoglobulin assay===
*Quantitative measurement of IgA, IgG, IgM immunoglobulins to detect immune paresis
*Monoclonal gammopathy (IgA and/or IgG peak)
*Reverse albumin:globulin ratio (low [[albumin]], high [[globulin]])
*Elevated β2-microglobulin level: β2-microglobulin level is one factor that determines the stage of multiple myeloma.


===Immunophenotyping===
*Multiple myeloma cells are typically [[CD56]], [[CD38]], [[CD138]] positive and [[CD19]] and [[CD45]] negative.
==References==
==References==
{{Reflist|2}}
{{Reflist|2}}
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Latest revision as of 22:47, 29 July 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Hannan Javed, M.D.[2]; Haytham Allaham, M.D. [3]; Shyam Patel [4]

Overview

Laboratory findings consistent with the diagnosis of multiple myeloma include abnormal complete blood count, abnormal basic metabolic panel, elevated monoclonal protein on serum electrophoresis, elevated serum free light chains, and presence of myeloma-specific protein markers by immunohistochemistry or immunophenotyping. Some of the laboratory tests are factors that determine the stage of multiple myeloma.

Laboratory Tests

Initial Tests

Confirmatory Tests

Tests Performed by Oncologist

Tests in Special Circumstances

Laboratory Findings

Complete blood count

Peripheral blood smear

  • Rouleaux formation of red blood cells: This is defined as the stacking of 4 or more red blood cells. In healthy individuals, the zeta potential of red blood cells causes intercellular repulsion. However, in patients with multiple myeloma, there are many positively charged paraproteins, which antagonizes the negative charge on red blood cells and allows for stacking.[1][2]

Basic metabolic panel

  • Hypercalcemia due to increased osteoclasts activity: This is one of the defining features of end-organ damage in multiple myeloma.
  • Increased serum creatinine level due to reduced renal function: This is one of the defining features of end-organ damage in multiple myeloma.
  • Abnormal blood urea nitrogen
  • High alkaline phosphatase level
  • High serum protein level with normal/decreased albumin level: This creates a high protein gap, which is defined as the difference between the albumin level and the total protein level.
  • High lactate dehydrogenase: This occurs in stage III multiple myeloma as defined by the Revised-International Staging System (R-ISS).

Serum protein electrophoresis

  • Protein electrophoresis is a method that separates proteins in the serum or urine.
  • 70% of cases have high levels of IgG
  • 20% of cases have high levels of IgA
  • 5–10% of cases have only immunoglobulin light chains (Bence Jones proteins)
  • Rarely κ- or λ-light chains may be secreted in isolation

Urine studies

  • Presence of monoclonal paraprotein on urine protein electrophoresis
  • Elevated 24-hour urine protein
  • Elevated urine free light chains

Free light chain immunoassay

  • Elevated free kappa light chain
  • Elevated free lambda light chain
  • Elevated free light chain ratio
  • Potentially offers an improvement in monitoring disease progression and response to treatment

Immunofixation

  • Identifies the type of M-protein or immunoglobulin light chain detected by serum or urine electrophoresis

Quantitative immunoglobulin assay

  • Quantitative measurement of IgA, IgG, IgM immunoglobulins to detect immune paresis
  • Monoclonal gammopathy (IgA and/or IgG peak)
  • Reverse albumin:globulin ratio (low albumin, high globulin)
  • Elevated β2-microglobulin level: β2-microglobulin level is one factor that determines the stage of multiple myeloma.

Immunophenotyping

References

  1. ↑ 1.0 1.1 Multiple myeloma. Canadian Cancer Society(2015) http://www.cancer.ca/en/cancer-information/cancer-type/multiple-myeloma/diagnosis/?region=mb#blood_chem Accessed on September, 20th 2015
  2. ↑ 2.0 2.1 Multiple myeloma. Wikipedia(2015)https://en.wikipedia.org/wiki/Multiple_myeloma#Pathophysiology Accessed on September 2015
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