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)
  • Initial diagnostic workup 
    • CBC with differential
      • Anemia not uncommon – typically normochromic normocytic
        • If anemia is disproportionate to disease, consider hemolytic workup – reticulocyte count, haptoglobin, cold agglutinin, direct and indirect Coombs
      • Platelet disturbances
        • Thrombocytopenia – uncommon
        • Thrombocytosis is rare – consider POEMs (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome evaluation
      • Leukocytosis – rare, except in plasma cell leukemias (PCL)
      • Plasma cells ≥20% on smear confirms PCL
    • Electrolytes, BUN, calcium, lactate dehydrogenase (LD), protein, albumin
      • For evaluation of end-organ damage in determination of MGUS versus MM
    • Viscosity measurement (serum, whole blood)
      • Order if hyperviscosity symptoms present (eg, blurred vision, retinal hemorrhage, stroke)
        • Suggests Waldenström macroglobulinemia (WM)
    • Serum protein electrophoresis (SPEP) with urine protein electrophoresis (UPEP), immunofixation electrophoresis (IFE), and serum free light chain (kappa, lambda) analysis followed by bone marrow biopsy if suspicious for plasma cell dyscrasias
      • SPEP with UPEP
        • Urine test requires 24-hr collection
        • Quantifies M protein
        • SPEP can be normal in patients with oligosecretory or nonsecretory myeloma
          • Oligosecretory – proteins reduced to levels that make detection difficult by standard tests
          • Nonsecretory – no identification of serum or urine proteins or free light chains
      • IFE (serum, urine)
        • Serum IFE is more sensitive than urine IFE for M protein detection and characterization for initial diagnosis
        • Particularly useful in early identification of minor M proteins or free light chain (FLC) M-components initially identified by abnormal banding patterns on SPEP
        • 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
      • Free kappa and lambda light chains testing (urine, serum)
        • Abnormal kappa-to-lambda FLC ratio (usually in plasma) due to the clonal secretion of a single FLC by malignant plasma cells in plasma cell dyscrasias
        • FLC ratio is indicated for the diagnosis of patients with oligosecretory or nonsecretory MM and AL
        • Bence Jones protein measurements may be necessary
  • 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%
        • ~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, renal insufficiency/failure  
          • If no end-organ damage noted, disease referred to as asymptomatic (smoldering) MM as long as <60% plasma cells in bone marrow
        • 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 and plasma cells composing ≥20% of total plasma cells in peripheral blood
    • Waldenström macroglobulinemia (WM) (de Larrea, 2013)
      • Serum IgM gammopathy – 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, smoldering, or asymptomatic WM
      • WHO criteria combine WM and lymphoplasmacytic lymphoma (LL) as a contiguous category of disease
        • LL involves bones with no monoclonal gammopathy present
        • WM is LL plus monoclonal gammopathy
    • 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
    • Systemic amyloidoses
      • 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 (Dispenzieri, 2014)
      • All of the following must be present
        • Monoclonal plasma cell disorder (almost always lambda)
        • Polyneuropathy and at least one of the following (major criteria)
          • Sclerotic bone lesions
          • Castleman disease
          • Elevated vascular endothelial growth factor (VEGF) levels
        • Any one of the following 6 minor criteria
          • Organomegaly
          • Endocrinopathy (excluding diabetes mellitus and thyroid disease)
          • Extravascular volume overload (eg, edema, pleural effusion, ascites)
          • Typical skin changes such as hyperpigmentation, hypertrichosis, acrocyanosis, glomeruloid hemangiomata
          • Papilledema
          • Thrombocytosis/polycythemia

    Dispenzieri, 2014

Histology

  • Morphology
    • >10% clonal plasma cells confirms MM
    • CD138 stains should be used to determine percentage of plasma cells
  • 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 WM/lymphoplasmacytic lymphoma (LPL)
      • MYD88 L265P gene mutation found in >90% of WM
        • Not detected in MGUS or MM
        • May be detected other lymphoproliferative disorders such as marginal zone lymphomas
      • MYD88 L256P is marker of risk for disease progression to WM in patients with WM MGUS
  • 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 gene rearrangement is detected that does not involve the CCND1 gene, additional probes are added
      • IGH/FGFR3 t(4;14)
      • IGH/MAF t(14;16)
  • 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
      • CD19, CD38, CD45, CD56, and CD138 – positive in ~90% of MM patients 
        • Addition of CD20, CD27, and CD117 identifies the remainder
      • Typically express CD138 (syndecan-1), CD38 (usually dim)
      • Other myeloma markers may include CD20, CD28, CD56, and CD117
      • Myelomas rarely express CD19 (lymphomas typically are CD19, CD38+, CD45, and CD56-)
    • WM
      • Typically CD19, CD20, and CD22 – positive 
      • CD5, CD10, and CD23 – may be positive (but not usually)
    • Plasma cell leukemia (PCL) – CD20+, CD38+, CD138+; reduced expression of CD9, CD56, CD117
  • 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
  • AL is a tissue diagnosis
    • Biopsy of an affected site
    • Congo red stain under electron microscope
    • Amyloidosis subtyping
      • AL
      • Mutant apoprotein A-I
      • Mutant fibrinogen A-α
      • Mutant gelsolin
      • Mutant lysozyme
      • Mutant transthyretin
      • Wild-type transthyretin

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 from International Myeloma Working Group (IMWG, 2009)
  • Non-molecular testing for prognostication
    • Microglobulin
      • 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, smoldering multiple myeloma (SMM), and SP
  • Molecular testing
    • Cytogenetics
    • FISH
    • 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
    • Molecular prognostication for MM

      Molecular Prognostication for MM

      Markers

      Survival Relationship

      Testing Recommendations

      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

      Dependent upon translocation partner

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

      Test only in initial prognostication

      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 in initial prognostication

      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 in initial prognostication

      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 in initial prognostication

      t(11;14)

      Presence – 15% of MM: light chain amyloidosis – 35-50; IgM MM – >90%

      Weakly associated with improved survival

      Test only in initial prognostication

Differential Diagnosis

  • Autoimmune disorders (eg, connective tissue diseases)
  • Malignancy
  • Paget disease
  • Infectious disorders
  • Rheumatoid arthritis
  • Protein-losing disorders
  • Chronic diseases
    • Chronic liver disease
    • Chronic renal disease
  • Genetic and metabolic disorders
  • Vitamin D deficiency
  • Polymyalgia rheumatica

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 serum protein
    • Unexplained peripheral neuropathy

Monitoring

  • Monoclonal gammopathy of undetermined significance (MGUS) – test using quantification of serum and urine monoclonal protein (SPEP and IFE) 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 multiple myeloma (SMM) (IMWG, 2010) – test using quantification of serum and urine monoclonal protein 2-3 months after initial diagnosis
    • If stable, test every 4-6 months for a year, then every 6-12 months (IMWG, 2010)
  • Free light chain (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)
    • Nonsecretory MM – marrow assessment and imaging are only reliable means of monitoring (Lonial, 2014)

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 are a diverse group of diseases characterized by clonal protein 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
    • Most MM develops from MGUS
      • Elevated monoclonal (M) protein level, non-IgM MGUS, or abnormal free light chain (FLC) ratio increases risk of MM to 58% over 20 years
    Multiple myeloma (MM)

    Epidemiology

    • Incidence – ~4/100,000 in U.S. (Rajkumar, 2014)
    • Age – median onset is 62 years for men (75% >70 years); 61 years for women (29% >70 years) (NCCN, 2014)
    • 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
      • Classified as primary or secondary

    Clinical Presentation

    • May be asymptomatic – up to 1/3 of patients
    • Constitutional – weight loss, fatigue (secondary to anemia), 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 (secondary to hypercalcemia)
    • Recurrent infections
      • Encapsulated organisms most common
      • Pneumonia frequent
    • Complications – pain, hypercalcemia, end-stage renal disease
    • 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 >2 mg/dL), symptomatic hyperviscosity, or amyloidosis
    Waldenström macroglobulinemia (WM)

    Epidemiology

    • Incidence – ~4-5/1,000,000 (Gertz, 2013)
    • Age – average onset 65 years
    • Sex – M>F; 2:1
    • Ethnicity – Caucasians have double the risk of African Americans

    Definition

    • Malignant proliferation of lymphoid and plasma cells – includes lymphoplasmacytic lymphoma

    Clinical Presentation

    • Many patients are asymptomatic – disease discovered through routine blood tests
    • Most common presenting symptoms
      • Constitutional symptoms – weakness, fatigue (secondary to anemia), night sweats, weight loss
      • Hyperviscosity – headaches, blurred vision, epistaxis, retinal hemorrhage
      • Raynaud phenomenon – acrocyanosis, ulcers, purpura (secondary to cryoglobulinemia)
      • Lymphadenopathy
      • Hepatosplenomegaly, macroglossia (secondary to amyloid deposition)
      • Peripheral neuropathies, foot drop (secondary to autoantibodies-myelin-associated glycoprotein [MAG], GM1)
      • Bone fractures, severe osteoporosis
      • Venous thrombosis, bleeding (secondary to low levels of von Willebrand factor)
    Monoclonal light-chain amyloidosis (AL)

    Epidemiology

    • Incidence – 8-10/million (Gertz, 2013)

    Definition

    • Malignant disorder of plasma cells – production and deposition of aberrant protein

    Clinical Presentation

    • Varies from asymptomatic to organ failure
    • Common presenting symptoms
      • Nephrotic syndrome
      • Restrictive cardiomyopathy
      • Peripheral neuropathy

Rare Plasma Cell Dyscrasias

  • Plasma cell leukemia (PCL)

    Epidemiology

    • Incidence – 0.2-0.3/1,000,000 (Albarracin, 2011)
      • 2-4% of patients with multiple myeloma (MM)
    • Age – median 52-65 years
    • Sex – M>F (minimal)
    • Ethnicity – African Americans have higher prevalence

    Definition

    • Absolute plasma cell count ≥2x109/L and plasma cells composing ≥20% of total plasma cells in peripheral blood (de Larrea, 2013)

    Clinical Presentation

    • More of the cases are primary PCL (de novo and no evidence of previous MM)
      • Secondary PCL is due to transformation of established MM
    • Frequent bone involvement
      • Leads to anemia, thrombocytopenia
      • Incidence of lytic lesions less than in MM
    • Renal insufficiency/failure common
    • High incidence of extramedullary involvement
      • Organomegaly prominent (lymph nodes, liver, spleen)
      • Palpable soft tissue, plasmacytomas
    Solitary plasmacytoma (SP)

    Epidemiology

    • Incidence – rare

    Definition

    • Malignant disorder that does not include the bone marrow
      • Subtypes – osseous and extraosseous

    Clinical Presentation

    • No obvious end-organ damage
    • 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 multiple myeloma (MM)
    POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes) syndrome

    Epidemiology

    • Incidence – <1/100,000 (Dispenzieri, 2014)
    • Age – 40s-50s

    Definition

    • Paraneoplastic disorder associated with underlying plasma cell dyscrasias
    • Also known as Takatsuki syndrome or osteosclerotic myeloma

    Clinical Presentation

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

    Epidemiology

    • Incidence – very rare
      • α chain disease – most common heavy-chain disease
        • Most common in Mediterranean, Middle Eastern, and North African ethnicities
        • Age – 2nd and 3rd decades
        • M>F (slight)
      • γ chain disease
        • Age – most common in elderly, 6th and 7th decade onset
        • M<F
      • μ chain disease – least common heavy-chain disease
        • Age – 6th decade
        • M>F

    Clinical Presentation

    • α chain disease
      • Massive infiltration of lamina propria of intestine and abdominal lymph nodes by lymphocytes, plasma cells, and histiocytes
        • Causies villous atrophy with resultant malabsorption, diarrhea, and weight loss
    • γ chain disease
      • Resembles malignant lymphoma
      • Lymphadenopathy, anemia, fever
      • Splenomegaly/hepatomegaly
      • Often have concomitant autoimmune diseases
    • μ chain disease
      • Splenomegaly and hepatomegaly
      • Lymphadenopathy rare
      • Most patients have neoplasm resembling CLL

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
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 nonsecretory 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

Reflex – if patterns from serum protein electrophoresis are monoclonal or suspicious, immunofixation electrophoresis will be added

SPEP can be normal in patients with oligosecretory or nonsecretory 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), Quantitative, Urine 0050618
Method: Qualitative Immunofixation Electrophoresis/Quantitative Nephelometry

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

Generally preferred over the qualitative test

 

Sequential levels for monitoring disease progress

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

Aids in diagnosis of MM and related disorders

Quantitative kappa/lambda free lights chains test generally preferred

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

Aids in evaluation and management of MM and related plasma cell dyscrasias

Monitor patients with oligosecretory or nonsecretory 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

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 and Immunoglobulin E, Serum 0050049
Method: Qualitative Immunofixation Electrophoresis

Use in initial evaluation of individuals with serum M protein present and negative IgG, IgA and IgM immunofixation studies

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

Quantify and determine clonality of free kappa light chains (Bence Jones protein) in urine

Monitor treatment response if 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

Quantify and determine clonality of free lambda light chains (Bence Jones protein) in urine

 

Sequential levels for monitoring disease progress

Immunofixation Electrophoresis Gel 0050272
Method: Qualitative Immunofixation Electrophoresis

Confirm presence of M protein and classify its heavy- and light-chain type

Aids in detection and management of MM and related disorders

Serum IFE does not provide quantification of M protein

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

Use for risk stratification and staging of MM, WM, and other lymphoproliferative disorders

   
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

Use when the clinical necessity of FISH is uncertain at the time of collection, so that CD138+ sorting on fresh specimen may be attempted and a pellet held for future testing, if desired

   
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, CSF, fluids, and tissues

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

   
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

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

Aids in the prognostication 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
 
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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

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