Plasma Cell Dyscrasias

Diagnosis

Indications for Testing

  • Bone pain, recurrent infections, anemia, lytic lesions on plain films

Laboratory Testing

  • Major differential diagnosis is between monoclonal gammopathy of undetermined significance (MGUS), multiple myeloma (MM), and monoclonal light-chain amyloidosis (AL); use of the following tests aids the clinician in determining disease (also refer to Indications for Laboratory Testing)
  • Initial diagnostic workup 
    • CBC with differential
      • Anemia not uncommon – typically normochromic normocytic
      • Thrombocytopenia uncommon – 10-15%
      • Leukocytosis – rare
    • If anemia is out of proportion to disease, consider hemolytic workup – reticulocyte count, haptoglobin, cold agglutinin, direct and indirect Coombs
    • Serum viscosity measurement
      • Order if hyperviscosity symptoms present
      • Serum or whole blood specimen
    • Electrolytes, BUN, calcium, lactate dehydrogenase (LD), protein, albumin
      • LD, calcium, creatinine may be elevated – suggests end-organ damage
    • SPEP or IFE followed by bone marrow biopsy if suspicious of plasma cell dyscrasias
      • SPEP with UPEP (24 hr)
        • Quantifies M protein
        • SPEP can be normal in patients with oligo-secretory (~10-15%) or non-secretory myeloma (~1%)
        • Abnormal patterns of protein fraction values are observed in various conditions
          • Inflammatory and infectious disorders – polyclonal gamma increase
          • Connective tissue disease – polyclonal gamma increase
          • Protein-losing disorders
          • Chronic liver disease –polyclonal gamma increase
          • Chronic renal disease – polyclonal gamma decrease
          • Genetic and metabolic disorders
      • IFE (serum and urine)
        • Serum IFE is more sensitive than urine IFE for M protein detection and characterization (initial diagnosis) 
        • Particularly useful in early identification of minor M proteins or FLC M-components initially identified by abnormal banding patterns seen on SPEP
      • May need to follow with Bence Jones protein (urine) and free kappa and lambda light chains (urine, serum) based on above results
      • In plasma cell dyscrasia, a proteinuria pattern may show a discrete band in the alpha-2, beta, or gamma region
        • Produced by M-components or Bence Jones protein
      • Patients with plasma cell dyscrasias have an abnormal kappa-to-lambda FLC ratio (usually in plasma) due to the clonal secretion of a single FLC by malignant plasma cells
        • FLC ratio is indicated for the diagnosis of patients with oligo-secretory or non-secretory MM and AL
    • Cytogenetics – may be necessary to differentiate WM from IgM MM
      • IgH switch region rearrangements – t(14q32) predominant in MM
      • t(11;14) – high frequency in AL and IgM MM
      • Molecular testing may help to confirm Waldenström macroglobulinemia (WM)/LPL
        • MYD88 L265P mutation found in >90% of WM
        • In individuals with MGUS, MYD88 L256P is marker of risk for disease progression to WM
    • FISH – more sensitive than cytogenetics for abnormalities
      • IGH/CCND1 t(11;14)
      • CKS1B (1q21)
      • IGH (14q32)
      • p53 (17p13.1)
      • 11q13/15q22/9q34 for ploidy analysis
      • If IGH rearrangement detected that does not involve CCND1, additional probes are added
        • IGH/FGFR3 t(4;14)
        • IGH/MAF t(14;16)
  • Expected laboratory findings for specific plasma cell dyscrasias

    Expected Laboratory Findings for Specific Plasma Cell Dyscrasias
    (International Myeloma Working Group Criteria)

    • Monoclonal gammopathy of undetermined significance (MGUS)
      • Serum M protein levels ≤3 g/dL and bone marrow plasma cells ≤10%
      • Absence of the following end-organ damage – lytic bone lesions, hypercalcemia, anemia, or renal failure
    • Multiple myeloma (MM)
      • Symptomatic
        • Serum or urinary M protein levels ≥3 g/dL
        • Bone marrow plasma cells ≥10%
        • Similar to normal heavy chain distribution in serum; ~50-75% of monoclonal gammopathies are IgG, 20% are IgA, and <1% are IgD; IgE gammopathies rare
        • Presence of the following end-organ damage – lytic bone lesions, hypercalcemia, anemia, or renal failure  
          • If no end-organ damage noted, disease referred to as asymptomatic (smoldering) MM
        • Beta-2 macroglobulin – level reflects tumor mass and is considered a standard measure of tumor burden
      • Asymptomatic
        • Above criteria – except no presence of end-organ damage
    • Plasma cell leukemia (PCL)
      • Absolute plasma cell count >2x109/L with plasma cells composing >20% of total leukocytes in peripheral blood
    • Waldenström macroglobulinemia (WM)
      • Serum IgM M protein – regardless of the size of the M protein
      • Bone marrow lymphoplasmacytic infiltration ≥10%
      • Presence of end-organ damage – defined as anemia, hyperviscosity, lymphadenopathy, or hepatosplenomegaly
        • If no end-organ damage noted, disease referred to as indolent or asymptomatic WM
    • Solitary plasmacytoma (SP)
      • Biopsy of proven lesion with evidence of clonal plasma cells
      • Normal bone marrow
      • Normal skeletal survey – except for lesion site
      • Absence of end-organ damage
    • Immunoglobulin deposition diseases
      • Primary monoclonal light-chain amyloidosis (AL)
        • Presence of amyloid-related organ system involvement
          • Evidence of a monoclonal plasma cell proliferative disorder by serum or urine M protein, or by clonal plasma cells in the bone marrow
          • Evidence that amyloid is light chain related – established by immunohistochemistry, direct sequencing
        • 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
        • Presence of end-organ damage
      • Light and heavy chain deposition diseases
    • POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome
      • Presence of monoclonal plasma cell disorder
      • Peripheral neuropathy and at least one of the following

    Dispenzieri, 2009

Histology

  • Bone marrow biopsy
    • Immunophenotyping by flow cytometry – may be useful for initial diagnosis and monitoring response to therapy by identification of clonal plasma cell populations
      • Flow cytometry is not accurate in enumeration of plasma cell numbers
        • Minimum of 100 neoplastic cells necessary for accuracy
      • Flow cytometry may help differentiate MGUS from MM
        • In MGUS – >5% of plasma cells are normal
        • In MM – <5% are normal
      • MM
        • CD38, 56, 19, 45, and 138 are present in ~90% of MM patients 
          • Addition of CD27, 117, and 20 identifies the remainder
        • MM – typically express CD138 (syndecan-1), CD38 (usually dim)
        • Other myeloma markers may include CD56, CD28, CD20, and CD117
        • Myelomas rarely express CD19 (lymphomas typically are CD19, 45, 38+, and CD56-)
      • WM – typically CD25+, CD21+, CD79–, FMC7+, BCL2+,  BCL6–, CD138+
      • Plasma cell leukemia (PCL) – CD38+, CD138+, CD20+; reduced expression of CD117, CD9, CD56
    • Immunohistochemistry staining – kappa or lambda staining should be sufficient for diagnosis unless lymphoma is suspected
      • CD38 or CD138 may help to highlight plasma cells
      • CD56 reaction confirms malignant nature of the infiltrate
      • Ki-67 identifies neoplastic plasma cells – indicates high-grade tumor when present
      • WM – typically sigM+, CD19+, CD20+, CD22+
        • CD5, CD10, or CD23 expressed in ~20% of cases but does not exclude diagnosis of WM

Imaging Studies

  • Skeletal survey x-ray with specific views of affected sites – lytic lesions are frequent in MM and WM
  • MRI/PET/CT – if skeletal survey negative and lesions suspected

Prognosis

  • New proposed molecular cytogenetic classification by IMWG (2009)
  • Further testing for prognostication – FISH, cytogenetics, beta-2 microglobulin
    • Microglobulins
      • Three stages as defined by international staging system with >3.5 g/L being poor prognosis
    • Albumin
      • Decreased level associated with poor prognosis in MM
    • FLC
      • Elevated level associated with poor prognosis in MM, MGUS, SMM, and SP
    • Cytogenetics
      • Presence of hypoploidy and del 13 associated with worse prognosis in MM
    • FISH
    • Prognostic Issues Related to Genetic Markers

      Prognostic Issues Related to Genetic Markers

      Markers

      Survival

      Recurrent Testing

      Established and validated

      14q32 (IGH)

      5 major oncogenes involved in translocation with 14q32 (11q13 [CCND1], 16q23 [C-MAF], 4p16 [FGFR3/MMSET], 6p21 [CCND3], 20q11 [MAFB])

      Presence – 55-70% of MM

      • Depends on translocation partner
        • 6p21, 11q13 – associated with good prognosis
        • 4p16, 16q23, 20q11 – associated with poor prognosis

      Test only once

      t(4;14)

      Detectable only by FISH

      Presence – 15-20% of MM

      • Associated with poor survival with conventional therapy
      • Short remission duration after high-dose chemotherapy with stem-cell support
      • Bortezomib partially abrogates adverse effects

      Test only once

      deletion 17p (p53)

      Presence at diagnosis – <10%

      Presence with advanced disease – much higher

      • More aggressive disease
      • Associated with poorest prognosis
      • Predictive of short duration of response after high-dose chemotherapy
      • Predictive of CNS involvement

      Repeated testing justified

      t(14;16)

      Presence – 5-7%

      • Confers an adverse outcome

      Test only once

      Gains/amplification of 1q21

      Presence at diagnosis – ~30-40%

      Presence at relapse – >70%

      • Associated with increased risk of MM progression
      • May be associated with other high-risk markers such as t(4;14), which worsen prognosis

      Repeated testing justified

      With modest effects

      Hyperdiploidy

      Characterized by odd numbered chromosomes (3, 5, 7, 9, 11, 15, 19, 21)

      Presence – ~45%

      • Weak tendency towards more favorable outcome

      Ploidy characteristics are stable over time – test only once

      t(11;14)

      Presence – 15% of MM

      Light chain amyloidosis – 35-50%

      IgM MM – >90%

      • Weakly associated with improved survival

      Test only once

    • Plasma cell labeling index (PCLI) studies
      • PCLI ≥3% associated with poor prognosis
    • Flow cytometry
      • CD117+ – associated with longer progression, free survival
      • CD28+ – associated with higher risk cytogenetics and more organ involvement

Differential Diagnosis

Screening

  • No recommendation for universal screening
  • Consider screening in the following situations
    • Age-inappropriate bone fractures with no known risk factors
      • Premenopausal females
      • Males <65 years
    • Unexplained proteinuria
    • Elevated total protein (serum)
    • Unexplained peripheral neuropathy

Monitoring

  • MGUS – test at 6 months after initial diagnosis (IMWG, 2010)
    • When stable or if symptoms indicate low-risk MGUS, monitor every 2-3 years  
    • Continue monitoring every 6 months if symptoms indicate intermediate- or high-risk MGUS
  • Smoldering MM (IMWG 2010) – test 2-3 months after initial diagnosis; if stable, test every 4-6 months for a year, then every 6-12 months (IMWG, 2010)
    • FLC – monitor response to therapy in patients with no measurable disease on serum and protein electrophoresis
      • Measurable disease = serum M protein ≥1g/100 ml or urine M protein ≥200 mg/24-hour (requires initial FLC ≥100 mg/L with clonal ratio to be used)
      • Low-risk disease = serum M protein <1.5 gm/dL, IgG subtype, normal FLC ratio (0.26-1.65)
      • Low-intermediate risk disease = any one factor abnormal
      • High-intermediate risk disease = any two factors abnormal
      • High-risk disease = all three factors abnormal
    • SPEP and IFE – monitor response to therapy
  • IMWG Response Criteria for Multiple Myeloma (MM)

    IMWG Response Criteria for Multiple Myeloma (MM)

    Complete response (CR)*

    • Negative immunofixation (serum, urine)
    • Disappearance of soft tissue plasmacytomas
    • <5% plasma cells in bone marrow
    • In patients for whom the only measurable disease is by FLC levels, CR is defined as a normal FLC ratio (0.26-1.65) in addition to the previous criteria

    Stringent CR (sCR)*

    • CR criteria above
    • Normal FLC ratio
    • Absence of clonal cells in bone marrow (by immunohistochemistry or immunofluorescence)

    Very good partial response (VGPR)*

    One of the following criteria

    • Serum and urine M-component detectable by immunofixation but not electrophoresis
    • ≥90% reduction in serum M-component; urine M-component <100 mg/24-hour
      • In patients for whom the only measurable disease is by FLC levels, VGPR is defined as a >90% decrease in difference between involved and uninvolved FLC levels

    Partial response (PR)*

    • ≥50% reduction of serum M protein and reduction in 24-hour urinary M protein by ≥90% or to <200 mg/24-hour
    • If serum and urine M protein are unmeasurable, ≥50% decrease in the difference between involved and uninvolved FLC levels is required
    • If serum and urine M protein are unmeasurable and serum free light assay is also unmeasurable, ≥50% reduction in bone marrow plasma cells is required, provided baseline percentage was ≥30%
    • Additionally (if present at baseline), a ≥50% reduction in size of soft tissue plasmacytomas is also required

    Progressive disease (PD)

    25% increase from lowest response value in one or more of the following

    • Serum M-component (absolute increase must be ≥0.5 g/100 ml)
      • Increases of ≥1 g/100ml are sufficient to define relapse if starting level is ≥5 g/100 ml
    • Urine M-component (absolute increase must be ≥200 mg/24-hour)  
    • In patients without measurable M protein (serum and urine), the difference between involved and uninvolved FLC levels (absolute increase must be >100 mg/l)
    • Bone marrow plasma cell percentage (absolute percentage must be ≥10%)
    • Definite increase in size or definite development of new bone lesions or soft tissue plasmacytomas
    • Development of hypercalcemia (corrected serum calcium >11.5 mg/100ml) attributable solely to the disease

    Stable disease (SD)*

    Does not meet criteria for CR, VGPR, PR, or progressive disease

    *Response categories CR, sCR, VGPR, and PR require two consecutive assessments made at any time before the start of any new therapy

    CR, PR, and SD categories also require no known evidence of progressive or new bone lesions (if radiographic studies performed)

    • Radiographic studies are not required to satisfy response requirements
    • Bone marrow assessments do not need confirmation

Imaging studies

  • Repeat skeletal survey if disease progresses
  • MRI if skeletal survey is negative and disease has progressed
  • PET/MIBI imaging not recommended

Clinical Background

Plasma cell dyscrasias (immunosecretory disorders) are a diverse group of diseases characterized by IgG clones accumulation.

Risk Factors

  • Ionizing radiation
  • Farm and petrochemical industrial exposure

Specific Plasma Cell Dyscrasias

  • Monoclonal gammopathy of undetermined significance (MGUS)

    Incidence

    • Most common plasma cell dyscrasia – 1-2/100 in patients >50 years
      • 50 years – 3% of individuals
      • ≥70 years – 5% of individuals
      • ≥85years – 7.5% of individuals
    • Sex – M>F
    • Ethnicity – African Americans have double the risk of Caucasians; Asians have lowest risk

    Definition

    • Premalignant disorder – risk of MGUS progressing to multiple myeloma (MM) or other related disorder increases 1% per year over lifetime

    Clinical Presentation

    • Asymptomatic in most patients
    • ~20% of MM develops from MGUS
      • Elevated monoclonal (M) protein level, non-IgM MGUS, or abnormal free light chain (FLC) ratio increase risk of MM to 58% over 20 years

    Treatment

    • None required; ongoing trials to evaluate if any treatment prevents progression to MM
    • Follow patient to detect transformation to malignancy
    Multiple myeloma (MM)

    Epidemiology

    • Incidence – 3-9/100,000 in U.S.
    • Age – median onset is 66-70 years; <5% of individuals <40 years (younger patients often have more aggressive disease)
    • Sex – M>F, 1.4:1
    • Ethnicity – twofold increased incidence in African Americans (most common lymphoid malignancy in these patients)

    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
    • Plasma cell leukemia

    Clinical Presentation

    • May be asymptomatic – as many as 1/3 of patients
    • Constitutional – weight loss, fatigue, anorexia, somnolence, malaise
    • Musculoskeletal – bone pain, back pain, pathologic fractures (25-35% of presenting patients)
    • Neurological  – neuropathy (carpal tunnel most common), paresthesias
    • Metabolic – nausea and polydipsia are signs and symptoms of hypercalcemia
    • Recurrent infections – encapsulated organisms most common, especially pneumonia
    • Hematologic – weakness from anemia
    • Complications – pain, hypercalcemia, renal disease, infection
    • End-organ damage – lytic bone lesions, pathologic fracture, cord compression, anemia (Hgb <10 g/dL), hypercalcemia (serum calcium >11.5 mg/dL), renal failure (creatinine >1.95 mg/dL), symptomatic hyperviscosity, or amyloidosis

    Treatment

    • Oral chemotherapy and bone marrow transplant
    Waldenström macroglobulinemia (WM)

    Epidemiology

    • Incidence – 5/1,000,000
    • Age – average onset is 65 years

    Definition

    • Malignant proliferation of lymphoid and plasma cells

    Clinical Presentation

    • Many patients are asymptomatic – disease discovered through routine blood tests
    • Most common presenting symptoms
      • Hyperviscosity – headaches, blurred vision, epistaxis, retinal hemorrhage
      • Anemia
      • Constitutional symptoms – weakness, fatigue, night sweats, weight loss
      • Raynaud phenomenon – acrocyanosis, ulcers, purpura (secondary to cryoglobulinemia)
      • Lymphadenopathy
      • Hepatosplenomegaly, macroglossia (due to amyloid deposition)
      • Peripheral neuropathies, foot drop (secondary to autoantibodies) – myelin-associated glycoprotein (MAG), GM1
      • Bone fractures, severe osteoporosis

    Treatment

    • No cure; disease progress may be slowed with oral chemotherapy and plasmapheresis for hyperviscosity
    Monoclonal light-chain amyloidosis (AL)

    Epidemiology

    • Incidence – 5-13/100,000

    Definition

    • Malignant disorder of plasma cells

    Clinical Presentation

    • Varies – may be asymptomatic; determined by dominant organ involved
    • Nephrotic syndrome, restrictive cardiomyopathy, and peripheral neuropathy are common presenting syndromes

    Treatment

    • Oral chemotherapy and bone marrow transplant
    Solitary plasmacytoma (SP)

    Epidemiology

    • Incidence – rare

    Definition

    • Malignant disorder

    Clinical Presentation

    • Absence of end-organ damage attributable to a plasma cell proliferative disorder
    • Most common in medullary sites but can occur in extramedullary sites
      • 80% localized in the upper respiratory tract (nasal cavity, sinuses, and nasopharynx)
    • Risk of progression to MM

    Treatment

    • Therapy includes radiation of the involved site

Rare Plasma Cell Dyscrasias

  • Plasma cell leukemia (PCL)

    Epidemiology

    • Age – median is 55 years
    • Sex – M>F (minimal)

    Definition

    • Absolute plasma cell count >2x109/L with plasma cells composing >20% of total leukocytes in peripheral blood

    Clinical Presentation

    • Frequent bone involvement
    • Renal failure common
    • High incidence of extramedullary involvement

    Treatment

    • Very poor prognosis
    • Chemotherapy not highly successful
    • Inability to induce remission often precludes bone marrow transplant
    POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome

    Epidemiology

    • Incidence – rare
    • Age – 40s-50s

    Definition

    • Paraneoplastic disorder associated with underlying plasma cell dyscrasias

    Clinical Presentation

    Immunoglobulin heavy-chain disease (includes α chain, γ chain, and μ chain disease)

    Epidemiology

    • Incidence
      • α chain disease – most common heavy-chain disease; seen especially in the Mediterranean
      • γ chain disease – most common in the elderly
      • μ chain disease – least common heavy-chain disease

    Clinical Presentation

    • α chain disease
      • Massive infiltration of lamina propria of intestine and abdominal lymph nodes by lymphocytes, plasma cells, and histiocytes, causing villous atrophy and malabsorption
    • γ chain disease
      • Resembles malignant lymphoma more than multiple myeloma
      • Lymphadenopathy, anemia, fever, and often splenomegaly or hepatomegaly
    • μ chain disease
      • Splenomegaly and hepatomegaly – lymphadenopathy is rare

Indications for Laboratory Testing

  • Tests generally appear in the order most useful for common clinical situations
  • Click on number for test-specific information in the ARUP Laboratory Test Directory
Test Name and Number Recommended Use Limitations Follow Up
CBC with Platelet Count and Automated Differential 0040003
Method: Automated Cell Count/Differential

Initial screen for plasma cell dyscrasias to rule out other disorders

   
Comprehensive Metabolic Panel 0020408
Method: Quantitative Ion-Selective Electrode/Quantitative Enzymatic/Quantitative Spectrophotometry

Initial screen for end-organ damage

   
Lactate Dehydrogenase, Serum or Plasma 0020006
Method: Quantitative Enzymatic

Initial screen for end-organ damage

   
Monoclonal Protein Detection Quantitation and Characterization, SPEP, IFE, IgA, IgG, IgM, Serum 0050615
Method: Qualitative Immunofixation Electrophoresis/Quantitative Capillary Electrophoresis/Quantitative Nephelometry

Identify and characterize the presence of the M protein or monoclonal FLC 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

IFE can be normal in patients with non-secretory MM

If M protein detected, as well as calcium and beta-2 microglobulin concentration, order Kappa and Lambda Free Light Chains (Bence Jones Protein), Qualitative, Urine, skeletal survey, and a bone marrow biopsy to rule out plasma cell dyscrasia

Protein Electrophoresis with Reflex to Immunofixation Electrophoresis Monoclonal Protein Detection, Quantitation & Characterization, IgA, IgG, & IgM, Serum 2002109
Method: Quantitative Capillary Electrophoresis/Qualitative Immunofixation Electrophoresis/Quantitative Nephelometry

Distinguish between proteinuria due to renal disease and monoclonal light chains in serum for patient with renal disease

Components include protein electrophoresis, IgG, IgA, and IgM

If patterns from serum protein electrophoresis are monoclonal or suspicious, immunofixation electrophoresis will be added

SPEP can be normal in patients with oligo-secretory or non-secretory MM

Order Kappa and Lambda Free Light Chains (Bence Jones Protein), Qualitative, Urine, skeletal survey and a bone marrow biopsy to rule out plasma cell dyscrasia if M protein detected

Kappa and Lambda Free Light Chains (Bence Jones Protein), Qualitative, Urine 0050161
Method: Qualitative Immunofixation Electrophoresis/Quantitative Nephelometry

Diagnosis of Bence Jones protein and its specificity

   
Kappa/Lambda Quantitative Free Light Chains with Ratio, Serum 0055167
Method: Quantitative Nephelometry

Quantify kappa and lambda light chains in human serum

Diagnosis and monitoring of patients with oligo-secretory or non-secretory MM and light-chain AL

Low levels of FLC are found in serum of normal individuals due to the overproduction and secretion of FLC by plasma cells

Order sequential levels for monitoring disease progress and response to therapy

Kappa and Lambda Free Light Chains (Bence Jones Protein), Quantitative, Urine 0050618
Method: Qualitative Immunofixation Electrophoresis/Quantitative Nephelometry

Diagnosis and monitoring the presence of Bence Jones protein and its specificity

 

Sequential levels for monitoring disease progress

MYD88 L265P Mutation Detection by PCR, Quantitative 2009318
Method: Real-time Polymerase Chain Reaction

Useful in distinguishing lymphoplasmacytic lymphoma (LPL) from other low-grade B-cell lymphoproliferative disorders which may be in the differential diagnosis

Monitoring of patients with LPL diagnosis and previously identified MYD88 L265P mutation

Analytic sensitivity – 0.5% mutant allele

Does not detect mutations in other regions of the MYD88 gene

Does not detect MYD88 codon 265 mutations other than L265P

Results of this test must be interpreted in the context of morphological and other relevant data

Test should not be used alone to diagnose malignancy

 
Immunofixation Electrophoresis, Immunoglobulin D & Immunoglobulin E, Serum  0050049
Method: Qualitative Immunofixation Electrophoresis

Identify presence of monoclonal IgD or IgE gammopathy in patients with free kappa or lambda identified by IFE electrophoresis

   
Kappa Free Light Chains (Bence Jones Protein), Quantitative, Urine 0050689
Method: Quantitative Nephelometry/Qualitative Immunofixation Electrophoresis

Monitor treatment response when gammopathy is known to be kappa

 

Sequential levels for monitoring disease progress

Lambda Free Light Chains (Bence Jones Protein), Quantitative, Urine 0050682
Method: Quantitative Nephelometry/Qualitative Immunofixation Electrophoresis

Monitor treatment response when gammopathy is known to be lambda

 

Sequential levels for monitoring disease progress

Immunofixation Electrophoresis Gel 0050272
Method: Qualitative Immunofixation Electrophoresis

Identify and characterize the presence of M protein

Serum IFE does not provide quantification of M protein

 
Beta-2 Microglobulin, Serum or Plasma 0080053
Method: Quantitative Immunoturbidimetry

Prognostic indicator for MM

   
Chromosome Analysis, Bone Marrow 2002292
Method: Giemsa Band

Detect chromosome abnormalities in bone marrow aspirate consistent with diagnosis of MM 

Some abnormalities also have prognostic significance

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.

Recommend test be performed in conjunction with MM FISH panel for increased sensitivity, especially in early stage stroma-dependant myeloma

Repeat testing as clinically indicated to monitor disease progression

Multiple Myeloma Panel by FISH 2002294
Method: Fluorescence in situ Hybridization

Detect molecular genetic abnormalities predictive of outcome in individuals with MM; probes include

  • IGH/CCND1 t(11;14)
  • CKS1B (1q21)
  • IGH (14q32)
  • p53 (17p13.1)
  • 11q13/15q22/9q34 for ploidy analysis

If IGH rearrangement detected that does not involve CCND1, additional probes are added

  • IGH/FGFR3 t(4;14)
  • IGH/MAF t(14;16)

FISH will only detect aberrations specific to probes utilized

Use in conjunction with bone marrow chromosome analysis, which may detect additional diagnostically significant chromosome abnormalities

Repeat testing as clinically indicated to monitor disease progression

Chromosome FISH, Multiple Myeloma Panel Process and Hold 2006270
Method: Cell culture/Fluorescence in situ Hybridization

More sensitive than cytogenetics for abnormalities

   
Viscosity, Serum 0020056
Method: Quantitative Viscometry

Evaluation of hyperviscosity syndrome associated with plasma cell dyscrasia

Patients with rheumatoid arthritis, lupus erythematosus, or hyperfibrinogenemia may occasionally have increased serum viscosity in serum samples

Repeat testing as clinically indicated to monitor disease progression

Viscosity, Whole Blood 0020054
Method: Quantitative Viscometry

Evaluation of hyperviscosity syndrome associated with plasma cell dyscrasia

Patients with rheumatoid arthritis, lupus erythematosus, or hyperfibrinogenemia may occasionally have increased blood viscosity in serum samples

Repeat testing as clinically indicated to monitor disease progression

Leukemia/Lymphoma Phenotyping by Flow Cytometry 2008003
Method: Flow Cytometry

Aid in evaluation of hematopoietic neoplasms (ie, leukemia, lymphoma)

Monitor therapy in patients with established diagnosis of hematopoietic neoplasms

Specimens include peripheral blood, bone marrow, and tissue

Markers selected based on clinical history, previous flow studies, and pathologist interpretation

Available markers:

T cell: CD1, CD2, CD3, CD4, CD5, CD7, CD8, TCR alpha-beta, TCR gamma-delta, cytoplasmic CD3

B cell: CD10, CD19, CD20, CD22, CD23, CD103, kappa, lambda, FMC7, cytoplasmic kappa, cytoplasmic lambda

Myelo/Mono: CD11b, CD13, CD14 (Mo2), CD14 (MY4), CD15, CD33, CD64, CD117, myeloperoxidase

Misc: CD11c, CD16, CD25, CD30, CD34, CD38, CD41, CD42b, CD45, CD56, CD57, CD61, HLA-DR, glycophorin, TdT, bcl-2, ALK-1, CD123, CD138, CD200, CD26, CD45

   
Kappa/Lambda Light Chain Panel by in situ Hybridization, Paraffin 2002888
Method: In situ Hybridization

Quantify kappa and lambda light chains in paraffin

   
Chromosome FISH, Interphase 2002298
Method: Fluorescence in situ Hybridization

Help differentiate WM from MM

   
Kappa Light Chains by Immunohistochemistry 2003981
Method: Immunohistochemistry

Aid in histologic diagnosis of plasma cell dyscrasias

Stained and returned to client pathologist for interpretation; consultation available if needed

 

Useful in initial diagnosis and therapy follow up

Lambda Light Chains by Immunohistochemistry 2003984
Method: Immunohistochemistry

Aid in histologic diagnosis of plasma cell dyscrasias

Stained and returned to client pathologist for interpretation; consultation available if needed

   
CD138 (Syndecan-1) by Immunohistochemistry 2003812
Method: Immunohistochemistry

Aid in histologic diagnosis of plasma cell dyscrasias

Stained and returned to client pathologist for interpretation; consultation available if needed

   
CD56 (NCAM) by Immunohistochemistry 2003589
Method: Immunohistochemistry

Aid in histologic diagnosis of plasma cell dyscrasias

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Ki-67 with Interpretation by Immunohistochemistry 2007182
Method: Immunohistochemistry

Aid in histologic diagnosis of plasma cell dyscrasias

Stained and resulted by ARUP

   
CD20, L26 by Immunohistochemistry 2003532
Method: Immunohistochemistry

Aid in histologic diagnosis of plasma cell dyscrasias

Stained and returned to client pathologist for interpretation; consultation available if needed

   
CD19 by Immunohistochemistry 2005114
Method: Immunohistochemistry

Aid in histologic diagnosis of plasma cell dyscrasias

Stained and returned to client pathologist for interpretation; consultation available if needed

   
CD23 by Immunohistochemistry 2003541
Method: Immunohistochemistry

Aid in histologic diagnosis of plasma cell dyscrasias

Stained and returned to client pathologist for interpretation; consultation available if needed

   
Additional Tests Available
 
Click the plus sign to expand the table of additional tests.
Test Name and NumberComments
Protein Electrophoresis, Serum 0050640
Method: Quantitative Capillary Electrophoresis

SPEP can be used to monitor treatment response when plasma cell dyscrasia is known