Plasma Cell Dyscrasias

Plasma cell dyscrasias are characterized by clonal protein accumulation. Symptoms occur due to clonal expansion, but also secondarily due to abnormal protein effects (amyloid deposition, renal failure). There are several types of plasma cell neoplasms, including monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma.

  • Diagnosis
  • Algorithms
  • Screening
  • Monitoring
  • Background
  • Lab Tests
  • References
  • Related Topics

Indications for Testing

  • Unexplained anemia, elevated serum protein, bone pain with lytic lesions on plain films, recurrent infections, renal failure, hypercalcemia, fatigue, or other systemic symptoms indicating malignancy
  • Age-inappropriate bone fractures with no known risk factors
    • Premenopausal females
    • Males <65 years
  • Unexplained proteinuria
  • Unexplained peripheral neuropathy
  • Premalignant condition (eg, monoclonal gammopathy) detected incidentally in asymptomatic patient
  • Solitary plasmacytoma visualized on imaging or with local symptoms

Criteria for Diagnosis

Laboratory Testing

  • 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
        • Thrombocytosis – rare; consider polyneuropathy, organomegaly, endocrinopathy, M protein, and evaluation of POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes)
      • Leukocytosis – rare except in plasma cell leukemia (PCL)
        • Plasma cells ≥20% on smear confirms PCL
    • Serum protein electrophoresis (SPEP)
      • Quantifies M protein
      • Can be normal in patients with oligosecretory or nonsecretory myeloma
        • Oligosecretory – M protein concentration below detection threshold of SPEP
        • Nonsecretory – no identification of M protein in serum or urine
    • Serum immunofixation electrophoresis (IFE)
      • More sensitive than SPEP for M protein detection and characterization
      • Particularly useful in early identification of minor M proteins or monoclonal components initially identified by abnormal banding patters on SPEP
    • Urinary protein electrophoresis (UPEP) with immunofixation (24 hour)
      • In plasma cell dyscrasia, a proteinuria pattern may show a discrete band in the α2, β, or γ region
      • Produced by monoclonal FLC components (Bence Jones protein)
    • Free kappa (κ) and lambda (λ) light-chains testing (serum)
      • Abnormal κ-to-λ FLC ratio due to clonal secretion of a single FLC by malignant plasma cells in plasma cell dyscrasias
      • FLC ratio is indicated for diagnosis of patients with oligosecretory or nonsecretory multiple myeloma (MM) and amyloid light-chain (AL) amyloidosis
    • Calcium (serum)
    • Creatinine (serum)
  • Extended workup for classification and staging
    • Bone marrow aspiration and biopsy
    • Lactate dehydrogenase (LDH)
    • Albumin (serum)
    • Beta-2 microglobulin (serum)
    • Viscosity measurement
      • Consider if signs of hyperviscosity present
        • Blurred vision, retinal hemorrhage, stroke
      • Increased viscosity suggests Waldenström macroglobulinemia (WM)
    • Complete metabolic profile

Histology

  • Bone marrow aspiration and biopsy required for diagnosis
    • Morphology
      • >10% clonal plasma cells confirms MM
      • CD138 stains should be used to determine percentage of plasma cells
    • Flow cytometry
    • Cytogenetics
  • Plasmacytoma – biopsy indicated
  • Amyloidosis suspected – tissue biopsy required
  • Chromosome analysis
  • Fluorescence in situ hybridization (FISH) on plasma cells
    • Performed on plasma cells purified by cell selection (CD138+ isolation) or in combination with cytoplasmic immunoglobulin staining (cIg-FISH)
    • Probes (Palumbo, International Myeloma Working Group [IMWG], 2015)
      • Recommended panel for prognostic assessment – include, at the minimum (National Comprehensive Cancer Network [NCCN], 2017)
        • 1q21 (CKS1B) gain/amplification
        • t(4;14)(p16;q32) (IGH-FGFR3/NSD2) – high risk
        • t(14;16)(q32;q23) (IGH-MAF) – high risk
        • 17p13 (TP53) deletion – high risk
      • Additional probes
        • Common trisomies (+3, +7, +9, +11, and/or 15)
        • 1p (1p32 or 1p21) deletion
        • t(6;14)(p21;q32) (IGH-CCND3)
        • 8q24 (MYC) rearrangement
        • t(11;14)(q13;q32) (IGH-CCND1)
        • 13q- or 13q (RB1/LAMP1) deletion
        • 14q32 (IGH) rearrangement
        • t(14;20)(q32;q12) (IGH-MAFB)
  • Immunophenotyping by flow cytometry
    • May be useful for initial diagnosis, classification, and monitoring response to therapy by identification of clonal plasma cell populations
    • Plasma cell
      • Normally express CD19, CD38 (bright), CD45 (dim to negative), and CD138
      • Clonal plasma cells are mostly CD19 negative
        • May express additional aberrant markers including CD20, CD56, and CD117
        • Cytoplasmic κ or λ light-chain restricted
      • Flow cytometry should not be used to enumerate plasma cells
    • Myelomas rarely express CD19 (lymphomas typically express CD19, CD38, CD45, and are negative for CD56)
  • Immunohistochemistry (IHC) staining
    • CD138 may help to highlight plasma cells
    • Use κ and λ staining for clonality
    • Amyloidosis may be present in plasma cell dyscrasias
      • Diagnosis of plasma cell proliferative disorder is necessary for this diagnosis
      • AL amyloidosis is a tissue diagnosis
      • Biopsy of an affected site using special stains
        • Required to recognize AL amyloidosis – Congo red, thioflavin T, sulfated Alcian blue
        • Gold standard – Congo red avidity with apple-green birefringence under polarized light
      • ​Amyloidosis subtyping is next step after amyloidosis is identified
        • Use direct sequencing, mass spectometry, immunostaining to identify subtype
        • Presence of serum or urine monoclonal protein does not ensure AL amyloidosis diagnosis
        • Other paraproteins can cause amyloidosis – confirmation of subtyping is necessary

Imaging Studies

  • Skeletal survey x-ray with specific views of affected sites
  • CT scan
  • Positron emission tomography (PET)/CT
  • Magnetic resonance imaging (MRI)

Prognosis

  • Risk for MM determined based on traditional criteria
    • Albumin, LDH, and beta-2 microglobulin in combination with cytogenetics

Differential Diagnosis

No recommendation for universal screening

  • Imaging and lab testing are used to evaluate disease response
  • Traditional definitions of multiple myeloma response included
    • Serum protein electrophoresis (SPEP) with immunofixation (IFE)
    • Urinary protein electrophoresis (UPEP) with IFE
    • Serum free light-chain analysis
    • Bone marrow plasma cell quantification
  • Several methods are being studied to detect minimal residual disease (MRD), but there is no current consensus on approach (Kumar, 2016)
    • Multiparametric flow cytometry (MFC)
    • Allele-specific oligonucleotide (ASO)-quantitative polymerase chain reaction (qPCR)  
    • Tandem mass spectometry
    • Next generation sequencing of VDJ sequences
      • International Myeloma Working Group (IMWG) also recommends use of next generation sequencing to evaluate MRD in bone marrow (Kumar, 2016)
  • National Comprehensive Cancer Network (NCCN) (2017) guidelines list specific criteria for categorizing disease as stable, progressive, or clinical relapse following treatment

Risk Factors

  • Ionizing radiation
  • Farm and industrial petrochemical  exposure

Specific Plasma Cell Dyscrasias

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.

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

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

Bence Jones Protein, Quantitation and Characterization, with Reflex to Kappa/Lambda Free Light Chains with Ratio, Urine 2002464
Method: Semi-Quantitative Electrophoresis/Qualitative Immunofixation Electrophoresis/Quantitative Nephelometry

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

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

Limitations 

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

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

Chromosome Analysis, Bone Marrow 2002292
Method: Giemsa Band

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

Limitations 

Only detects aberrations specific to probes utilized

Kappa/Lambda Light Chain Panel by In Situ Hybridization, Stain Only 2013595
Method: In Situ Hybridization

Viscosity, Serum 0020056
Method: Quantitative Viscometry

Viscosity, Whole Blood 0020054
Method: Quantitative Viscometry

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

Guidelines

Berenson JR, Anderson KC, Audell RA, Boccia RV, Coleman M, Dimopoulos MA, Drake MT, Fonseca R, Harousseau J, Joshua D, Lonial S, Niesvizky R, Palumbo A, Roodman D, San-Miguel JF, Singhal S, Weber DM, Zangari M, Wirtschafter E, Yellin O, Kyle RA. Monoclonal gammopathy of undetermined significance: a consensus statement. Br J Haematol. 2010; 150(1): 28-38. PubMed

Chng WJ, Dispenzieri A, Chim C, Fonseca R, Goldschmidt H, Lentzsch S, Munshi N, Palumbo A, Miguel JS, Sonneveld P, Cavo M, Usmani S, Durie BG, Avet-Loiseau H, International Myeloma Working Group. IMWG consensus on risk stratification in multiple myeloma. Leukemia. 2014; 28(2): 269-77. PubMed

Dimopoulos M, Kyle R, Fermand J, Rajkumar V, San Miguel J, Chanan-Khan A, Ludwig H, Joshua D, Mehta J, Gertz M, Avet-Loiseau H, Beksaç M, Anderson KC, Moreau P, Singhal S, Goldschmidt H, Boccadoro M, Kumar S, Giralt S, Munshi NC, Jagannath S, International Myeloma Workshop Consensus Panel 3. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood. 2011; 117(18): 4701-5. PubMed

Dimopoulos M, Terpos E, Comenzo RL, Tosi P, Beksac M, Sezer O, Siegel D, Lokhorst H, Kumar S, Rajkumar SV, Niesvizky R, Moulopoulos LA, Durie BG, IMWG. International myeloma working group consensus statement and guidelines regarding the current role of imaging techniques in the diagnosis and monitoring of multiple Myeloma. Leukemia. 2009; 23(9): 1545-56. PubMed

Dispenzieri A, Buadi F, Kumar SK, Reeder CB, Sher T, Lacy MQ, Kyle RA, Mikhael JR, Roy V, Leung N, Grogan M, Kapoor P, Lust JA, Dingli D, Go RS, Hwa YL, Hayman SR, Fonseca R, Ailawadhi S, Bergsagel L, Chanan-Khan A, Rajkumar V, Russell SJ, Stewart K, Zeldenrust SR, Gertz MA. Treatment of Immunoglobulin Light Chain Amyloidosis: Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement. Mayo Clin Proc. 2015; 90(8): 1054-81. PubMed

Dispenzieri A, Kyle R, Merlini G, Miguel JS, Ludwig H, Hajek R, Palumbo A, Jagannath S, Bladé J, Lonial S, Dimopoulos M, Comenzo R, Einsele H, Barlogie B, Anderson K, Gertz M, Harousseau JL, Attal M, Tosi P, Sonneveld P, Boccadoro M, Morgan G, Richardson P, Sezer O, Mateos MV, Cavo M, Joshua D, Turesson I, Chen W, Shimizu K, Powles R, Rajkumar SV, Durie BG, International Myeloma Working Group. International Myeloma Working Group guidelines for serum-free light chain analysis in multiple myeloma and related disorders. Leukemia. 2009; 23(2): 215-24. PubMed

Durie BG, Harousseau J, Miguel JS, Bladé 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, Cavo 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 Myeloma Working Group. International uniform response criteria for multiple myeloma. Leukemia. 2006; 20(9): 1467-73. PubMed

FernándezdeLarrea C, Kyle RA, Durie BG, Ludwig H, Usmani S, Vesole DH, Hajek R, San Miguel JF, Sezer O, Sonneveld P, Kumar SK, Mahindra A, Comenzo R, Palumbo A, Mazumber A, Anderson KC, Richardson PG, Badros AZ, Caers J, Cavo M, LeLeu X, Dimopoulos MA, Chim CS, Schots R, Noeul A, Fantl D, Mellqvist U, Landgren O, Chanan-Khan A, Moreau P, Fonseca R, Merlini G, Lahuerta JJ, Bladé J, Orlowski RZ, Shah JJ, International Myeloma Working Group. Plasma cell leukemia: consensus statement on diagnostic requirements, response criteria and treatment recommendations by the International Myeloma Working Group. Leukemia. 2013; 27(4): 780-91. PubMed

Fonseca R, Bergsagel PL, Drach J, Shaughnessy J, Gutierrez N, Stewart AK, Morgan G, Van Ness B, Chesi M, Minvielle S, Neri A, Barlogie B, Kuehl WM, Liebisch P, Davies F, Chen-Kiang S, Durie BG, Carrasco R, Sezer O, Reiman T, Pilarski L, Avet-Loiseau H, International Myeloma Working Group. International Myeloma Working Group molecular classification of multiple myeloma: spotlight review. Leukemia. 2009; 23(12): 2210-21. PubMed

Gertz MA. Waldenström macroglobulinemia: 2013 update on diagnosis, risk stratification, and management. Am J Hematol. 2013; 88(8): 703-11. PubMed

Kumar S, Paiva B, Anderson KC, Durie B, Landgren O, Moreau P, Munshi N, Lonial S, Bladé J, Mateos M, Dimopoulos M, Kastritis E, Boccadoro M, Orlowski R, Goldschmidt H, Spencer A, Hou J, Chng WJ, Usmani SZ, Zamagni E, Shimizu K, Jagannath S, Johnsen HE, Terpos E, Reiman A, Kyle RA, Sonneveld P, Richardson PG, McCarthy P, Ludwig H, Chen W, Cavo M, Harousseau J, Lentzsch S, Hillengass J, Palumbo A, Orfao A, Rajkumar V, San Miguel J, Avet-Loiseau H. International Myeloma Working Group consensus criteria for response and minimal residual disease assessment in multiple myeloma. Lancet Oncol. 2016; 17(8): e328-46. PubMed

Kyle RA, Durie BG, Rajkumar SV, Landgren O, Bladé J, Merlini G, Kröger N, Einsele H, Vesole DH, Dimopoulos M, San Miguel J, Avet-Loiseau H, Hajek R, Chen WM, Anderson KC, Ludwig H, Sonneveld P, Pavlovsky S, Palumbo A, Richardson PG, Barlogie B, Greipp P, Vescio R, Turesson I, Westin J, Boccadoro M, International Myeloma Working Group. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering (asymptomatic) multiple myeloma: IMWG consensus perspectives risk factors for progression and guidelines for monitoring and management. Leukemia. 2010; 24(6): 1121-7. PubMed

Mikhael JR, Dingli D, Roy V, Reeder CB, Buadi FK, Hayman SR, Dispenzieri A, Fonseca R, Sher T, Kyle RA, Lin Y, Russell SJ, Kumar S, Bergsagel L, Zeldenrust SR, Leung N, Drake MT, Kapoor P, Ansell SM, Witzig TE, Lust JA, Dalton RJ, Gertz MA, Stewart K, Stewart K, Rajkumar V, Chanan-Khan A, Lacy MQ, Mayo Clinic. Management of newly diagnosed symptomatic multiple myeloma: updated Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) consensus guidelines 2013. Mayo Clin Proc. 2013; 88(4): 360-76. PubMed

Moreau P, San Miguel J, Ludwig H, Schouten H, Mohty M, Dimopoulos M, Dreyling M, ESMO Guidelines Working Group. Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013; 24 Suppl 6: vi133-7. PubMed

Munshi NC, Anderson KC, Bergsagel L, Shaughnessy J, Palumbo A, Durie B, Fonseca R, Stewart K, Harousseau J, Dimopoulos M, Jagannath S, Hajek R, Sezer O, Kyle R, Sonneveld P, Cavo M, Rajkumar V, San Miguel J, Crowley J, Avet-Loiseau H, International Myeloma Workshop Consensus Panel 2. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood. 2011; 117(18): 4696-700. PubMed

NCCN Clinical Practice Guidelines in Oncology, Multiple Myeloma. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: May 2017]

NCCN Clinical Practice Guidelines in Oncology, Systemic Light Chain Amyloidosis. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: May 2017]

NCCN Clinical Practice Guidelines in Oncology, Waldenstrom Macroglobinemia/Lymphoplasmacytic Lymphoma. National Comprehensive Cancer Network. Fort Washington, PA [Accessed: May 2017]

Palumbo A, Avet-Loiseau H, Oliva S, Lokhorst HM, Goldschmidt H, Rosiñol L, Richardson P, Caltagirone S, Lahuerta JJ, Facon T, Bringhen S, Gay F, Attal M, Passera R, Spencer A, Offidani M, Kumar S, Musto P, Lonial S, Petrucci MT, Orlowski RZ, Zamagni E, Morgan G, Dimopoulos MA, Durie BG, Anderson KC, Sonneveld P, San Miguel J, Cavo M, Rajkumar V, Moreau P. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol. 2015; 33(26): 2863-9. PubMed

Protocol for the Examination of Specimens From Patients With Hematopoietic Neoplasms Involving the Bone Marrow. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Jun 2012. College of American Pathologists (CAP). Northfield, IL [Revised: Jun 2012; Accessed: May 2017]

Protocol for the Examination of Specimens From Patients With Non-Hodgkin Lymphoma/Lymphoid Neoplasms. Based on AJCC/UICC TNM, 7th ed. Protocol web posting date: Oct 2013. College of American Pathologists (CAP). Northfield, IL [Revised: Oct 2013; Accessed: May 2017]

Rajkumar V, Dimopoulos MA, Palumbo A, Bladé J, Merlini G, Mateos M, Kumar S, Hillengass J, Kastritis E, Richardson P, Landgren O, Paiva B, Dispenzieri A, Weiss B, LeLeu X, Zweegman S, Lonial S, Rosiñol L, Zamagni E, Jagannath S, Sezer O, Kristinsson SY, Caers J, Usmani SZ, Lahuerta JJ, Johnsen HE, Beksaç M, Cavo M, Goldschmidt H, Terpos E, Kyle RA, Anderson KC, Durie BG, San Miguel JF. International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol. 2014; 15(12): e538-48. PubMed

Swerdlow SH, Campo E, Pileri SA, Harris NL, Stein H, Siebert R, Advani R, Ghielmini M, Salles GA, Zelenetz AD, Jaffe ES. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016; 127(20): 2375-90. PubMed

General References

Albarracin F, Fonseca R. Plasma cell leukemia. Blood Rev. 2011; 25(3): 107-12. PubMed

Bianchi G, Anderson KC, Harris NL, Sohani AR. The heavy chain diseases: clinical and pathologic features. Oncology (Williston Park). 2014; 28(1): 45-53. PubMed

Bladé J, Dimopoulos M, Rosiñol L, Rajkumar V, Kyle RA. Smoldering (asymptomatic) multiple myeloma: current diagnostic criteria, new predictors of outcome, and follow-up recommendations. J Clin Oncol. 2010; 28(4): 690-7. PubMed

Chee CE, Dispenzieri A, Gertz MA. Amyloidosis and POEMS syndrome. Expert Opin Pharmacother. 2010; 11(9): 1501-14. PubMed

Davids MS, Murali MR, Kuter DJ. Serum free light chain analysis. Am J Hematol. 2010; 85(10): 787-90. PubMed

Dispenzieri A, Buadi FK. A review of POEMS syndrome. Oncology (Williston Park). 2013; 27(12): 1242-50. PubMed

Dispenzieri A. POEMS syndrome: 2014 update on diagnosis, risk-stratification, and management. Am J Hematol. 2014; 89(2): 214-23. PubMed

Dispenzieri A. POEMS syndrome: update on diagnosis, risk-stratification, and management. Am J Hematol. 2015; 90(10): 951-62. PubMed

FernándezdeLarrea C, Delforge M, Davies F, Bladé J. Response evaluation and monitoring of multiple myeloma. Expert Rev Hematol. 2014; 7(1): 33-42. PubMed

Hunter ZR, Xu L, Yang G, Zhou Y, Liu X, Cao Y, Manning RJ, Tripsas C, Patterson CJ, Sheehy P, Treon SP. The genomic landscape of Waldenstrom macroglobulinemia is characterized by highly recurring MYD88 and WHIM-like CXCR4 mutations, and small somatic deletions associated with B-cell lymphomagenesis. Blood. 2014; 123(11): 1637-46. PubMed

Kraj M. Immunoglobulin heavy chain/light chain pairs (HLC, Hevylite™) assays for diagnosing and monitoring monoclonal gammopathies. Adv Clin Exp Med. 2014; 23(1): 127-33. PubMed

Landgren O, Tageja N. MYD88 and beyond: novel opportunities for diagnosis, prognosis and treatment in Waldenström's Macroglobulinemia. Leukemia. 2014; 28(9): 1799-803. PubMed

Levinson SS. POEMS syndrome: importance of the clinical laboratory practitioner's role. Clin Chim Acta. 2012; 413(21-22): 1800-7. PubMed

Lonial S, Kaufman JL. Non-secretory myeloma: a clinician's guide. Oncology (Williston Park). 2013; 27(9): 924-8, 930. PubMed

Michels TC, Petersen KE. Multiple Myeloma: Diagnosis and Treatment. Am Fam Physician. 2017; 95(6): 373-383. PubMed

Rajkumar V, Kumar S. Multiple Myeloma: Diagnosis and Treatment. Mayo Clin Proc. 2016; 91(1): 101-19. PubMed

Rajkumar V. Multiple myeloma: 2014 Update on diagnosis, risk-stratification, and management. Am J Hematol. 2014; 89(10): 999-1009. PubMed

Treon SP, Cao Y, Xu L, Yang G, Liu X, Hunter ZR. Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenstrom macroglobulinemia. Blood. 2014; 123(18): 2791-6. PubMed

Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, Argyropoulos KV, Yang G, Cao Y, Xu L, Patterson CJ, Rodig S, Zehnder JL, Aster JC, Harris NL, Kanan S, Ghobrial I, Castillo JJ, Laubach JP, Hunter ZR, Salman Z, Li J, Cheng M, Clow F, Graef T, Palomba L, Advani RH. Ibrutinib in previously treated Waldenström's macroglobulinemia. N Engl J Med. 2015; 372(15): 1430-40. PubMed

References from the ARUP Institute for Clinical and Experimental Pathology®

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): 560-5. PubMed

Chen ZW, Perkins SL, Weiss RL, Bahler DW, Hussong JW, Salama ME. A limited plasma cell flow cytometry panel with reflex CD138 immunohistochemistry is an optimal workflow process for evaluating plasma cell neoplasms in bone marrow specimens Am J Clin Pathol. 2015; 143(1): 78-83. PubMed

Heikal NM, Shetty S. Spindle cell variant of multiple myeloma: immunophenotype and cytogenetics abnormalities. Ann Hematol. 2012; 91(5): 803-4. PubMed

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): 277-80. PubMed

Kelley TW, Baz R, Hussein M, Karafa M, Cook JR. Clinical significance of cyclin D1, fibroblast growth factor receptor 3, and p53 immunohistochemistry in plasma cell myeloma treated with a thalidomide-based regimen. Hum Pathol. 2009; 40(3): 405-12. PubMed

Pandey S, Post SR, Alapat DV, Smock KJ, Post GR. Prolonged prothrombin time correlates with serum monoclonal protein concentration in patients with plasma cell dyscrasia. Int J Lab Hematol. 2013; 35(4): 421-7. PubMed

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Zhou W, Yang Y, Xia J, Wang H, Salama ME, Xiong W, Xu H, Shetty S, Chen T, Zeng Z, Shi L, Zangari M, Miles R, Bearss D, Tricot G, Zhan F. NEK2 induces drug resistance mainly through activation of efflux drug pumps and is associated with poor prognosis in myeloma and other cancers. Cancer Cell. 2013; 23(1): 48-62. PubMed

Medical Reviewers

Content Reviewed: 
June 2017

Last Update: October 2017