Skip to main content

Molecular Diagnostics in Non-Hodgkin Lymphoma

  • Chapter
  • First Online:
Molecular Diagnostics in Cancer Patients

Abstract

Non-Hodgkin Lymphomas (NHLs) are a diverse collection of malignant neoplasms of lymphoid cell origin which include all the malignant lymphomas that are not classified as Hodgkin lymphoma. NHL is the sixth most common type of cancer diagnosed in men and women in the United Kingdom. In the United States of America the past four decades have seen nearly an 80% rise in the incidence of NHL, one of the largest increases observed among any cancer. With improved understanding of biology, data from sequential disease-based clinical trials as well as better supportive care, the outcome of NHL has improved dramatically over the last several decades. Using conventional therapy, depending on subtype and stage, the majority of young adults with NHL can be cured. New insights into the molecular pathogenesis of NHL combined with recent headways in molecular biology and genetics have led to the discovery of several oncogenic pathways involved in lymphomagenesis, which in turn has augmented the diagnostic and therapeutic approaches for NHL patients. This review describes the presentation and evaluation of NHL and summarizes the current concepts about molecular diagnostics of the common subtypes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Steven H, Swerdlow EC, Harris NL, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. Lyon: International Agency for Research on Cancer; 2008. p. 274–88.

    Google Scholar 

  2. Perry AM, Jacques D, Nathwani BN, et al. Classification of non-Hodgkin lymphoma in seven geographic regions around the world: review of 4539 cases from the international non-Hodgkin lymphoma classification Project. Blood. 2015;126:1484.

    Google Scholar 

  3. Smith A, Crouch S, Lax S, et al. Lymphoma incidence, survival and prevalence 2004–2014: sub-type analyses from the UK’s Haematological Malignancy Research Network. Br J Cancer. 2015;112(9):1575–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Naresh K, Srinivas V, Soman C. Distribution of various subtypes of non-Hodgkin’s lymphoma in India: a study of 2773 lymphomas using REAL and WHO Classifications. Ann Oncol. 2000;11(suppl_1):S63–7.

    Article  Google Scholar 

  5. Arora N, Manipadam MT, Nair S. Frequency and distribution of lymphoma types in a tertiary care hospital in South India: analysis of 5115 cases using the World Health Organization 2008 classification and comparison with world literature. Leuk Lymphoma. 2013;54(5):1004–11.

    Article  PubMed  Google Scholar 

  6. Anderson T, Chabner BA, Young RC, et al. Malignant lymphoma I. The histology and staging of 473 patients at the National Cancer Institute. Cancer. 1982;50(12):2699–707.

    Article  CAS  PubMed  Google Scholar 

  7. Economopoulos T, Papageorgiou S, Pappa V, et al. Monoclonal gammopathies in B-cell non-Hodgkin’s lymphomas. Leuk Res. 2003;27(6):505–8.

    Article  CAS  PubMed  Google Scholar 

  8. Jeffers M, Milton J, Herriot R, McKean M. Fine needle aspiration cytology in the investigation on non-Hodgkin’s lymphoma. J Clin Pathol. 1998;51(3):189–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hehn ST, Grogan TM, Miller TP. Utility of fine-needle aspiration as a diagnostic technique in lymphoma. J Clin Oncol. 2004;22(15):3046–52.

    Article  PubMed  Google Scholar 

  10. Dong HY, Harris NL, Preffer FI, Pitman MB. Fine-needle aspiration biopsy in the diagnosis and classification of primary and recurrent lymphoma: a retrospective analysis of the utility of cytomorphology and flow cytometry. Mod Pathol. 2001;14(5):472–81.

    Article  CAS  PubMed  Google Scholar 

  11. Horwitz SM, Zelenetz AD, Gordon LI, et al. NCCN guidelines insights: non-Hodgkin’s lymphomas, version 3.2016. J Natl Compr Cancer Netw. 2016;14(9):1067–79.

    Article  Google Scholar 

  12. Byrne G Jr. Rappaport classification of non-Hodgkin’s lymphoma: histologic features and clinical significance. Cancer Treat Rep. 1977;61(6):935–44.

    PubMed  Google Scholar 

  13. Harris NL, Jaffe ES, Stein H, et al. A revised European-American classification of lymphoid neoplasms: a proposal from the International Lymphoma Study Group. Blood. 1994;84(5):1361–92.

    CAS  PubMed  Google Scholar 

  14. Harris NL, Jaffe ES, Diebold J, et al. World Health Organization classification of neoplastic diseases of the hematopoietic and lymphoid tissues: report of the Clinical Advisory Committee meeting—Airlie House, Virginia, November 1997. J Clin Oncol. 1999;17(12):3835–49.

    Article  CAS  PubMed  Google Scholar 

  15. Cheson BD, Fisher RI, Barrington SF, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32(27):3059–67.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Jaffe E. Classification of natural killer (NK) cell and NK-like T-cell malignancies [editorial; comment]. Blood. 1996;87:1207–10.

    CAS  PubMed  Google Scholar 

  17. Van Dongen J, Langerak A, Brüggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 concerted action BMH4-CT98-3936. Leukemia. 2003;17(12):2257–317.

    Article  PubMed  Google Scholar 

  18. Klein U, Goossens T, Fischer M, et al. Somatic hypermutation in normal and transformed human B cells. Immunol Rev. 1998;162:261–80.

    Article  CAS  PubMed  Google Scholar 

  19. Kuppers R, Rajewsky K, Hansmann ML. Diffuse large cell lymphomas are derived from mature B cells carrying V region genes with a high load of somatic mutation and evidence of selection for antibody expression. Eur J Immunol. 1997;27(6):1398–405.

    Article  CAS  PubMed  Google Scholar 

  20. Kuppers R, Zhao M, Hansmann ML, Rajewsky K. Tracing B cell development in human germinal centres by molecular analysis of single cells picked from histological sections. EMBO J. 1993;12(13):4955–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Shen HM, Peters A, Baron B, Zhu X, Storb U. Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. Science. 1998;280(5370):1750–2.

    Article  CAS  PubMed  Google Scholar 

  22. Lo Coco F, Gaidano G, Louie DC, Offit K, Chaganti RS. Dalla-Favera R. p53 mutations are associated with histologic transformation of follicular lymphoma. Blood. 1993;82(8):2289–95.

    CAS  PubMed  Google Scholar 

  23. Elenitoba-Johnson KS, Gascoyne RD, Lim MS, Chhanabai M, Jaffe ES, Raffeld M. Homozygous deletions at chromosome 9p21 involving p16 and p15 are associated with histologic progression in follicle center lymphoma. Blood. 1998;91(12):4677–85.

    CAS  PubMed  Google Scholar 

  24. Tagawa H, Suguro M, Tsuzuki S, et al. Comparison of genome profiles for identification of distinct subgroups of diffuse large B-cell lymphoma. Blood. 2005;106(5):1770–7.

    Article  CAS  PubMed  Google Scholar 

  25. Huang JZ, Sanger WG, Greiner TC, et al. The t (14; 18) defines a unique subset of diffuse large B-cell lymphoma with a germinal center B-cell gene expression profile. Blood. 2002;99(7):2285–90.

    Article  CAS  PubMed  Google Scholar 

  26. Pasqualucci L, Dalla-Favera R. The genetic landscape of diffuse large B-cell lymphoma. Paper presented at Seminars in Hematology, 2015.

    Google Scholar 

  27. Rosenwald A, Wright G, Chan WC, et al. The use of molecular profiling to predict survival after chemotherapy for diffuse large-B-cell lymphoma. N Engl J Med. 2002;346(25):1937–47.

    Article  PubMed  Google Scholar 

  28. Houldsworth J, Olshen AB, Cattoretti G, et al. Relationship between REL amplification, REL function, and clinical and biologic features in diffuse large B-cell lymphomas. Blood. 2004;103(5):1862–8.

    Article  CAS  PubMed  Google Scholar 

  29. Bea S, Zettl A, Wright G, et al. Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction. Blood. 2005;106(9):3183–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Compagno M, Lim WK, Grunn A, et al. Mutations of multiple genes cause deregulation of NF-κB in diffuse large B-cell lymphoma. Nature. 2009;459(7247):717–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kato M, Sanada M, Kato I, et al. Frequent inactivation of A20 in B-cell lymphomas. Nature. 2009;459(7247):712–6.

    Article  CAS  PubMed  Google Scholar 

  32. Alizadeh AA, Eisen MB, Davis RE, et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature. 2000;403(6769):503–11.

    Article  CAS  PubMed  Google Scholar 

  33. Karube K, Enjuanes A, Dlouhy I, et al. Integrating genomic alterations in diffuse large B-cell lymphoma identifies new relevant pathways and potential therapeutic targets. Leukemia. 2018;32(3):675–84.

    Article  CAS  PubMed  Google Scholar 

  34. Schmitz, Roland, et al. “Genetics and pathogenesis of diffuse large B-cell lymphoma.” New England Journal of Medicine 378.15 (2018): 1396–1407.

    Google Scholar 

  35. Chapuy, Bjoern, et al. “Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes.” Nature medicine 24.5 (2018):679.

    Google Scholar 

  36. Cigudosa JC, Parsa NZ, Louie DC, et al. Cytogenetic analysis of 363 consecutively ascertained diffuse large B-cell lymphomas. Genes Chromosomes Cancer. 1999;25(2):123–33.

    Google Scholar 

  37. Gascoyne RDCE, Jaffe ES, et al. Diffuse large B cell lymphoma NOS. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 291–7.

    Google Scholar 

  38. Kluin PMHN, Stein H, et al. High-grade B cell lymphoma. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 335–40.

    Google Scholar 

  39. Barrans S, Crouch S, Smith A, et al. Rearrangement of MYC is associated with poor prognosis in patients with diffuse large B-cell lymphoma treated in the era of rituximab. J Clin Oncol. 2010;28(20):3360–5.

    Article  CAS  PubMed  Google Scholar 

  40. Rowley JD. Chromosome studies in the non-Hodgkin's lymphomas: the role of the 14;18 translocation. J Clin Oncol. 1988;6(5):919–25.

    Article  CAS  PubMed  Google Scholar 

  41. Bloomfield CD, Arthur DC, Frizzera G, Levine EG, Peterson BA, Gajl-Peczalska KJ. Nonrandom chromosome abnormalities in lymphoma. Cancer Res. 1983;43(6):2975–84.

    CAS  PubMed  Google Scholar 

  42. Leroux D, Monteil M, Sotto J, et al. Variant t (2; 18) translocation in a follicular lymphoma. Br J Haematol. 1990;75(2):290–2.

    Article  CAS  PubMed  Google Scholar 

  43. Lin P, Jetly R, Lennon PA, Abruzzo LV, Prajapati S, Medeiros LJ. Translocation (18; 22)(q21; q11) in B-cell lymphomas: a report of 4 cases and review of the literature. Hum Pathol. 2008;39(11):1664–72.

    Article  CAS  PubMed  Google Scholar 

  44. Johnson NA, Al-Tourah A, Brown C, Connors JM, Gascoyne RD, Horsman DE. Prognostic significance of secondary cytogenetic alterations in follicular lymphomas. Genes Chromosom Cancer. 2008;47(12):1038–48.

    Article  CAS  PubMed  Google Scholar 

  45. Tilly H, Rossi A, Stamatoullas A, et al. Prognostic value of chromosomal abnormalities in follicular lymphoma. Blood. 1994;84(4):1043–9.

    CAS  PubMed  Google Scholar 

  46. Bosga-Bouwer AG, van Imhoff GW, Boonstra R, et al. Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t (14; 18), 3q27, or other translocations: t (14; 18) and 3q27 are mutually exclusive. Blood. 2003;101(3):1149–54.

    Article  CAS  PubMed  Google Scholar 

  47. Morin RD, Mendez-Lago M, Mungall AJ, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature. 2011;476(7360):298–303.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pastore A, Jurinovic V, Kridel R, et al. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015;16(9):1111–22.

    Article  CAS  PubMed  Google Scholar 

  49. Pasqualucci L, Dominguez-Sola D, Chiarenza A, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature. 2011;471(7337):189–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Swerdlow SHCE, Seto M, et al. Mantle cell lymphoma. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. revised 4th ed. Lyon: IARC Press; 2017. p. 285–90.

    Google Scholar 

  51. Musgrove EA, Caldon CE, Barraclough J, Stone A, Sutherland RL. Cyclin D as a therapeutic target in cancer. Nat Rev Cancer. 2011;11(8):558–72.

    Article  CAS  PubMed  Google Scholar 

  52. Espinet B, Salaverria I, Beà S, et al. Incidence and prognostic impact of secondary cytogenetic aberrations in a series of 145 patients with mantle cell lymphoma. Genes Chromosom Cancer. 2010;49(5):439–51.

    CAS  PubMed  Google Scholar 

  53. Eskelund CW, Dahl C, Hansen JW, et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017;130(17):1903–10.

    Article  CAS  PubMed  Google Scholar 

  54. Onaindia A, Medeiros LJ, Patel KP. Clinical utility of recently identified diagnostic, prognostic, and predictive molecular biomarkers in mature B-cell neoplasms. Mod Pathol. 2017;30(10):1338–66.

    Article  CAS  PubMed  Google Scholar 

  55. Du M, Diss TC, Xu C, Peng H, Isaacson PG, Pan L. Ongoing mutation in MALT lymphoma immunoglobulin gene suggests that antigen stimulation plays a role in the clonal expansion. Leukemia. 1996;10(7):1190–7.

    CAS  PubMed  Google Scholar 

  56. Cook JRIP, Chott A, Nakamura S, Muller-Hermelink HK, Harris NL, Swerdlow SH. Extranodal marginal zone lymphoma of mucosa-assoiated lymphoid tissue (MALT lymphoma). In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017.

    Google Scholar 

  57. Zucca E, Bertoni F. The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance. Blood. 2016;127(17):2082–92.

    Article  CAS  PubMed  Google Scholar 

  58. Thieblemont C, Bertoni F, Copie-Bergman C, Ferreri AJ, Ponzoni M. Chronic inflammation and extra-nodal marginal-zone lymphomas of MALT-type. Paper presented at Seminars in Cancer Biology, 2014.

    Google Scholar 

  59. Pyris MAIP, Swerdlow SH, Thieblemont C, Pittaluga S, Rossi D, Harris NL. Splenic marginal zone lymphoma. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 223–5.

    Google Scholar 

  60. Campo EPS, Jaffe ES, Nathwani BN, Stein H, Muller-Hermelink HK. Nodal marginal zone lymphoma. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 263–5.

    Google Scholar 

  61. Dalla-Favera R, Bregni M, Erikson J, Patterson D, Gallo RC, Croce CM. Human c-myc onc gene is located on the region of chromosome 8 that is translocated in Burkitt lymphoma cells. Proc Natl Acad Sci. 1982;79(24):7824–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Capello D, Carbone A, Pastore C, Gloghini A, Saglio G, Gaidano G. Point mutations of the BCL-6 gene in Burkitt's lymphoma. Br J Haematol. 1997;99(1):168–70.

    Article  CAS  PubMed  Google Scholar 

  63. Hamilton-Dutoit SJ, Pallesen G, Franzmann MB, et al. AIDS-related lymphoma. Histopathology, immunophenotype, and association with Epstein-Barr virus as demonstrated by in situ nucleic acid hybridization. Am J Pathol. 1991;138(1):149–63.

    CAS  PubMed  PubMed Central  Google Scholar 

  64. Schmitz R, Ceribelli M, Pittaluga S, Wright G, Staudt LM. Oncogenic mechanisms in Burkitt lymphoma. Cold Spring Harb Perspect Med. 2014;4(2).

    Google Scholar 

  65. Campo EGP, Montserrat E, Harris NL, Muller-Hermelink HK, Stein H, Swerdlow SH. Chronic lymphocytic leukaemia/small lymphocytic lymphoma. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 216–21.

    Google Scholar 

  66. Rai KR, Jain P. Chronic lymphocytic leukemia (CLL)—then and now. Am J Hematol. 2016;91(3):330–40.

    Article  CAS  PubMed  Google Scholar 

  67. Hallek M, Cheson BD, Catovsky D, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on chronic lymphocytic leukemia updating the National Cancer Institute–working group 1996 guidelines. Blood. 2008;111(12):5446–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Marti GE, Rawstron AC, Ghia P, et al. Diagnostic criteria for monoclonal B-cell lymphocytosis. Br J Haematol. 2005;130(3):325–32.

    Article  PubMed  Google Scholar 

  69. Rawstron AC, Bennett FL, O'Connor SJ, et al. Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia. N Engl J Med. 2008;359(6):575–83.

    Article  CAS  PubMed  Google Scholar 

  70. Fazi C, Scarfò L, Pecciarini L, et al. General population low-count CLL-like MBL persists over time without clinical progression, although carrying the same cytogenetic abnormalities of CLL. Blood. 2011;118(25):6618–25.

    Article  CAS  PubMed  Google Scholar 

  71. Hsi ED. Pathologic and molecular genetic features of chronic lymphocytic leukemia. Paper presented at Seminars in Oncology, 2012.

    Google Scholar 

  72. Rodríguez AE, Hernández JÁ, Benito R, et al. Molecular characterization of chronic lymphocytic leukemia patients with a high number of losses in 13q14. PLoS One. 2012;7(11):e48485.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  73. Matutes E, Oscier D, Garcia-Marco J, et al. Trisomy 12 defines a group of CLL with atypical morphology: correlation between cytogenetic, clinical and laboratory features in 544 patients. Br J Haematol. 1996;92(2):382–8.

    Article  CAS  PubMed  Google Scholar 

  74. Puiggros A, Blanco G, Espinet B. Genetic abnormalities in chronic lymphocytic leukemia: where we are and where we go. Biomed Res Int. 2014;2014:1–13.

    Article  CAS  Google Scholar 

  75. Hamblin TJ, Davis Z, Gardiner A, Oscier DG, Stevenson FK. Unmutated Ig V H genes are associated with a more aggressive form of chronic lymphocytic leukemia. Blood. 1999;94(6):1848–54.

    CAS  PubMed  Google Scholar 

  76. Dürig J, Naschar M, Schmücker U, et al. CD38 expression is an important prognostic marker in chronic lymphocytic leukaemia. Leukemia. 2002;16(1):30–5.

    Article  PubMed  Google Scholar 

  77. Wiestner A, Rosenwald A, Barry TS, et al. ZAP-70 expression identifies a chronic lymphocytic leukemia subtype with unmutated immunoglobulin genes, inferior clinical outcome, and distinct gene expression profile. Blood. 2003;101(12):4944–51.

    Article  CAS  PubMed  Google Scholar 

  78. Amaya-Chanaga CI, Rassenti LZ. Biomarkers in chronic lymphocytic leukemia: clinical applications and prognostic markers. Best Pract Res Clin Haematol. 2016;29(1):79–89.

    Article  PubMed  Google Scholar 

  79. Ghia EM, Jain S, Widhopf GF, et al. Use of IGHV3–21 in chronic lymphocytic leukemia is associated with high-risk disease and reflects antigen-driven, post–germinal center leukemogenic selection. Blood. 2008;111(10):5101–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Rossi D, Rasi S, Spina V, et al. Integrated mutational and cytogenetic analysis identifies new prognostic subgroups in chronic lymphocytic leukemia. Blood. 2013;121(8):1403–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Foucar KFB, Stein H. Hairy cell leukaemia. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 226–8.

    Google Scholar 

  82. Bosch F, Campo E, Jares P, et al. Increased expression of the PRAD-1/CCND1 gene in hairy cell leukaemia. Br J Haematol. 1995;91(4):1025–30.

    Article  CAS  PubMed  Google Scholar 

  83. Basso K, Liso A, Tiacci E, et al. Gene expression profiling of hairy cell leukemia reveals a phenotype related to memory B cells with altered expression of chemokine and adhesion receptors. J Exp Med. 2004;199(1):59–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Tiacci E, Trifonov V, Schiavoni G, et al. BRAF mutations in hairy-cell leukemia. N Engl J Med. 2011;364(24):2305–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Tiacci E, Schiavoni G, Forconi F, et al. Simple genetic diagnosis of hairy cell leukemia by sensitive detection of the BRAF-V600E mutation. Blood. 2012;119(1):192–5.

    Article  CAS  PubMed  Google Scholar 

  86. Turakhia S, Lanigan C, Hamadeh F, Swerdlow SH, Tubbs RR, Cook JR. Immunohistochemistry for BRAF V600E in the differential diagnosis of hairy cell leukemia vs other splenic B-cell lymphomas. Am J Clin Pathol. 2015;144(1):87–93.

    Article  CAS  PubMed  Google Scholar 

  87. Andrulis M, Penzel R, Weichert W, von Deimling A, Capper D. Application of a BRAF V600E mutation-specific antibody for the diagnosis of hairy cell leukemia. Am J Surg Pathol. 2012;36(12):1796–800.

    Article  PubMed  Google Scholar 

  88. Swerdlow SHCJ, Sohani AR, Pileri SA, Harris NL, Jaffe ES, Stein H. Lymphoplasmacytic lymphoma. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 232–5.

    Google Scholar 

  89. Morice WG, Chen D, Kurtin PJ, Hanson CA, McPhail ED. Novel immunophenotypic features of marrow lymphoplasmacytic lymphoma and correlation with Waldenström’s macroglobulinemia. Mod Pathol. 2009;22(6):807–16.

    Article  CAS  PubMed  Google Scholar 

  90. Swerdlow SH, Kuzu I, Dogan A, et al. The many faces of small B cell lymphomas with plasmacytic differentiation and the contribution of MYD88 testing. Virchows Arch. 2016;468(3):259–75.

    Article  CAS  PubMed  Google Scholar 

  91. Owen RG, Barrans SL, Richards SJ, et al. Waldenström macroglobulinemia: development of diagnostic criteria and identification of prognostic factors. Am J Clin Pathol. 2001;116(3):420–8.

    Article  CAS  PubMed  Google Scholar 

  92. 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 Waldenström macroglobulinemia. Blood. 2014;123(18):2791–6.

    Article  CAS  PubMed  Google Scholar 

  93. Treon SP, Xu L, Yang G, et al. MYD88 L265P somatic mutation in Waldenström’s macroglobulinemia. N Engl J Med. 2012;367(9):826–33.

    Article  CAS  PubMed  Google Scholar 

  94. Schmidt J, Federmann B, Schindler N, et al. MYD88 L265P and CXCR4 mutations in lymphoplasmacytic lymphoma identify cases with high disease activity. Br J Haematol. 2015;169(6):795–803.

    Article  CAS  PubMed  Google Scholar 

  95. Cao Y, Hunter ZR, Liu X, et al. CXCR4 WHIM-like frameshift and nonsense mutations promote ibrutinib resistance but do not supplant MYD88L265P-directed survival signalling in Waldenström macroglobulinaemia cells. Br J Haematol. 2015;168(5):701–7.

    Article  CAS  PubMed  Google Scholar 

  96. Hunter ZR, Xu L, Yang G, et al. The genomic landscape of Waldenström 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.

    Article  CAS  PubMed  Google Scholar 

  97. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Iqbal J, Wright G, Wang C, et al. Gene expression signatures delineate biological and prognostic subgroups in peripheral T-cell lymphoma. Blood. 2014;123(19):2915–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Harris ME. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26:4124–30.

    Article  Google Scholar 

  100. Falini BL-RL, Campo E, Jaffe ES, Gascoyne RD, Stein H, Muller-Hermelink HL, Kinney MC. Anaplastic large cell lymphoma, ALK-positive. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 413–8.

    Google Scholar 

  101. Foss H-D, Anagnostopoulos I, Araujo I, et al. Anaplastic large-cell lymphomas of T-cell and null-cell phenotype express cytotoxic molecules. Blood. 1996;88(10):4005–11.

    CAS  PubMed  Google Scholar 

  102. van der Krogt J-A, Bempt MV, Ferreiro JF, et al. Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma with the variant RNF213-, ATIC-and TPM3-ALK fusions is characterized by copy number gain of the rearranged ALK gene. Haematologica. 2017;102(9):1605–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  103. Hallberg B, Palmer RH. Mechanistic insight into ALK receptor tyrosine kinase in human cancer biology. Nat Rev Cancer. 2013;13(10):685–700.

    Article  CAS  PubMed  Google Scholar 

  104. Werner MT, Zhao C, Zhang Q, Wasik MA. Nucleophosmin-anaplastic lymphoma kinase: the ultimate oncogene and therapeutic target. Blood. 2017;129(7):823–31.

    Article  CAS  PubMed  Google Scholar 

  105. Lamant L, De Reynies A, Duplantier M-M, et al. Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes. Blood. 2007;109(5):2156–64.

    Article  CAS  PubMed  Google Scholar 

  106. Crescenzo R, Abate F, Lasorsa E. T-cell project: prospective collection of data in patients with peripheral T-cell lymphoma and the AIRC 5xMille consortium “Genetics-Driven Targeted Management of Lymphoid Malignancies”. Convergent mutations and kinase fusions lead to oncogenic STAT3 activation in anaplastic large cell lymphoma. Cancer Cell. 2015;27(5):744.

    Article  CAS  Google Scholar 

  107. Castellar ERP, Jaffe ES, Said JW, et al. ALK-negative anaplastic large cell lymphoma is a genetically heterogeneous disease with widely disparate clinical outcomes. Blood. 2014;124(9):1473–80.

    Article  CAS  Google Scholar 

  108. Zeng Y, Feldman AL. Genetics of anaplastic large cell lymphoma. Leuk Lymphoma. 2016;57(1):21–7.

    Article  CAS  PubMed  Google Scholar 

  109. Pileri SAWD, Sng I, et al. Peripheral T cell lymphoma, NOS. In: Swerdlow S, Campo E, Harris N, et al., editors. WHO classification of tumours of haematopoietic and lymphoid tissues. Revised 4th ed. Lyon: IARC Press; 2017. p. 403–7.

    Google Scholar 

  110. Nelson M, Horsman DE, Weisenburger DD, et al. Cytogenetic abnormalities and clinical correlations in peripheral T-cell lymphoma. Br J Haematol. 2008;141(4):461–9.

    Article  CAS  PubMed  Google Scholar 

  111. Boddicker RL, Razidlo GL, Dasari S, et al. Integrated mate-pair and RNA sequencing identifies novel, targetable gene fusions in peripheral T-cell lymphoma. Blood. 2016;128(9):1234–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Disclosure

The authors certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Suraj Pratap .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Pratap, S., Scordino, T.A. (2019). Molecular Diagnostics in Non-Hodgkin Lymphoma. In: Shukla, K., Sharma, P., Misra, S. (eds) Molecular Diagnostics in Cancer Patients. Springer, Singapore. https://doi.org/10.1007/978-981-13-5877-7_7

Download citation

  • DOI: https://doi.org/10.1007/978-981-13-5877-7_7

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-13-5876-0

  • Online ISBN: 978-981-13-5877-7

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics