Smarter Decisions,
Better Care

UpToDate synthesizes the most recent medical information into evidence-based practical recommendations clinicians trust to make the right point-of-care decisions.

  • Rigorous editorial process: Evidence-based treatment recommendations
  • World-Renowned physician authors: over 5,100 physician authors and editors around the globe
  • Innovative technology: integrates into the workflow; access from EMRs

Choose from the list below to learn more about subscriptions for a:


Subscribers log in here


Related articles

Epidemiology, clinical manifestations, pathologic features, and diagnosis of diffuse large B cell lymphoma

INTRODUCTION

Diffuse large B cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma (NHL) accounting for approximately 25 percent of NHL cases [1,2]. (See "Classification of the hematopoietic neoplasms".)

It is increasingly appreciated that the diagnostic category of "DLBCL" is quite heterogeneous in terms of morphology, genetics, and biologic behavior. A number of clinicopathologic entities are now recognized that are sufficiently distinct to be considered separate diagnostic categories:

T cell histiocyte rich large B cell lymphoma. (See 'T cell histiocyte rich large B cell lymphoma' below.)

Primary DLBCL of the mediastinum, also called primary mediastinal large B cell lymphoma. (See "Primary mediastinal large B cell lymphoma".)

Intravascular lymphoma. (See "Intravascular large cell lymphoma".)

                                

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2014. | This topic last updated: Nov 19, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
  2. Morton LM, Wang SS, Devesa SS, et al. Lymphoma incidence patterns by WHO subtype in the United States, 1992-2001. Blood 2006; 107:265.
  3. van Leeuwen MT, Turner JJ, Joske DJ, et al. Lymphoid neoplasm incidence by WHO subtype in Australia 1982-2006. Int J Cancer 2014; 135:2146.
  4. Smith A, Howell D, Patmore R, et al. Incidence of haematological malignancy by sub-type: a report from the Haematological Malignancy Research Network. Br J Cancer 2011; 105:1684.
  5. Sant M, Allemani C, Tereanu C, et al. Incidence of hematologic malignancies in Europe by morphologic subtype: results of the HAEMACARE project. Blood 2010; 116:3724.
  6. Shirley MH, Sayeed S, Barnes I, et al. Incidence of haematological malignancies by ethnic group in England, 2001-7. Br J Haematol 2013; 163:465.
  7. Møller MB, Pedersen NT, Christensen BE. Diffuse large B-cell lymphoma: clinical implications of extranodal versus nodal presentation--a population-based study of 1575 cases. Br J Haematol 2004; 124:151.
  8. Laurini JA, Perry AM, Boilesen E, et al. Classification of non-Hodgkin lymphoma in Central and South America: a review of 1028 cases. Blood 2012; 120:4795.
  9. Shenoy PJ, Malik N, Nooka A, et al. Racial differences in the presentation and outcomes of diffuse large B-cell lymphoma in the United States. Cancer 2011; 117:2530.
  10. Goldin LR, Landgren O, McMaster ML, et al. Familial aggregation and heterogeneity of non-Hodgkin lymphoma in population-based samples. Cancer Epidemiol Biomarkers Prev 2005; 14:2402.
  11. Goldin LR, Björkholm M, Kristinsson SY, et al. Highly increased familial risks for specific lymphoma subtypes. Br J Haematol 2009; 146:91.
  12. Hui D, Proctor B, Donaldson J, et al. Prognostic implications of extranodal involvement in patients with diffuse large B-cell lymphoma treated with rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone. Leuk Lymphoma 2010; 51:1658.
  13. Armitage JO, Weisenburger DD. New approach to classifying non-Hodgkin's lymphomas: clinical features of the major histologic subtypes. Non-Hodgkin's Lymphoma Classification Project. J Clin Oncol 1998; 16:2780.
  14. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997; 89:3909.
  15. Sehn LH, Scott DW, Chhanabhai M, et al. Impact of concordant and discordant bone marrow involvement on outcome in diffuse large B-cell lymphoma treated with R-CHOP. J Clin Oncol 2011; 29:1452.
  16. Avilés A, Neri N, Huerta-Guzmán J. Large bowel lymphoma: an analysis of prognostic factors and therapy in 53 patients. J Surg Oncol 2002; 80:111.
  17. Daum S, Ullrich R, Heise W, et al. Intestinal non-Hodgkin's lymphoma: a multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin's Lymphoma. J Clin Oncol 2003; 21:2740.
  18. Ferrucci PF, Zucca E. Primary gastric lymphoma pathogenesis and treatment: what has changed over the past 10 years? Br J Haematol 2007; 136:521.
  19. Seymour JF, Solomon B, Wolf MM, et al. Primary large-cell non-Hodgkin's lymphoma of the testis: a retrospective analysis of patterns of failure and prognostic factors. Clin Lymphoma 2001; 2:109.
  20. Vitolo U, Ferreri AJ, Zucca E. Primary testicular lymphoma. Crit Rev Oncol Hematol 2008; 65:183.
  21. Olivier KR, Brown PD, Stafford SL, et al. Efficacy and treatment-related toxicity of radiotherapy for early-stage primary non-Hodgkin lymphoma of the parotid gland. Int J Radiat Oncol Biol Phys 2004; 60:1510.
  22. Laskar S, Bahl G, Muckaden MA, et al. Primary diffuse large B-cell lymphoma of the tonsil: is a higher radiotherapy dose required? Cancer 2007; 110:816.
  23. Grange F, Bekkenk MW, Wechsler J, et al. Prognostic factors in primary cutaneous large B-cell lymphomas: a European multicenter study. J Clin Oncol 2001; 19:3602.
  24. Page RD, Romaguera JE, Osborne B, et al. Primary hepatic lymphoma: favorable outcome after combination chemotherapy. Cancer 2001; 92:2023.
  25. Ribrag V, Bibeau F, El Weshi A, et al. Primary breast lymphoma: a report of 20 cases. Br J Haematol 2001; 115:253.
  26. Domchek SM, Hecht JL, Fleming MD, et al. Lymphomas of the breast: primary and secondary involvement. Cancer 2002; 94:6.
  27. Avilés A, Delgado S, Nambo MJ, et al. Primary breast lymphoma: results of a controlled clinical trial. Oncology 2005; 69:256.
  28. Grigg AP, Connors JM. Primary adrenal lymphoma. Clin Lymphoma 2003; 4:154.
  29. Shikama N, Ikeda H, Nakamura S, et al. Localized aggressive non-Hodgkin's lymphoma of the nasal cavity: a survey by the Japan Lymphoma Radiation Therapy Group. Int J Radiat Oncol Biol Phys 2001; 51:1228.
  30. Proulx GM, Caudra-Garcia I, Ferry J, et al. Lymphoma of the nasal cavity and paranasal sinuses: treatment and outcome of early-stage disease. Am J Clin Oncol 2003; 26:6.
  31. Oprea C, Cainap C, Azoulay R, et al. Primary diffuse large B-cell non-Hodgkin lymphoma of the paranasal sinuses: a report of 14 cases. Br J Haematol 2005; 131:468.
  32. Dursun P, Gultekin M, Bozdag G, et al. Primary cervical lymphoma: report of two cases and review of the literature. Gynecol Oncol 2005; 98:484.
  33. Monnard V, Sun A, Epelbaum R, et al. Primary spinal epidural lymphoma: patients' profile, outcome, and prognostic factors: a multicenter Rare Cancer Network study. Int J Radiat Oncol Biol Phys 2006; 65:817.
  34. Kuo CC, Li WY, Huang CC, et al. Primary renal lymphoma. Br J Haematol 2009; 144:628.
  35. Lu NN, Li YX, Wang WH, et al. Clinical behavior and treatment outcome of primary nasal diffuse large B-cell lymphoma. Cancer 2012; 118:1593.
  36. Guastafierro S, Tedeschi A, Criscuolo C, et al. Primary extranodal non-Hodgkin's lymphoma of the vagina: a case report and a review of the literature. Acta Haematol 2012; 128:33.
  37. de Leval L, Bonnet C, Copie-Bergman C, et al. Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study. Ann Oncol 2012; 23:3143.
  38. Castillo JJ, Winer ES, Olszewski AJ. Sites of extranodal involvement are prognostic in patients with diffuse large B-cell lymphoma in the rituximab era: an analysis of the Surveillance, Epidemiology and End Results database. Am J Hematol 2014; 89:310.
  39. De Paepe P, Achten R, Verhoef G, et al. Large cleaved and immunoblastic lymphoma may represent two distinct clinicopathologic entities within the group of diffuse large B-cell lymphomas. J Clin Oncol 2005; 23:7060.
  40. Ottensmeier CH, Stevenson FK. Isotype switch variants reveal clonally related subpopulations in diffuse large B-cell lymphoma. Blood 2000; 96:2550.
  41. Slack GW, Steidl C, Sehn LH, Gascoyne RD. CD30 expression in de novo diffuse large B-cell lymphoma: a population-based study from British Columbia. Br J Haematol 2014; 167:608.
  42. Stein H, Lennert K, Feller AC, Mason DY. Immunohistological analysis of human lymphoma: correlation of histological and immunological categories. Adv Cancer Res 1984; 42:67.
  43. Doggett RS, Wood GS, Horning S, et al. The immunologic characterization of 95 nodal and extranodal diffuse large cell lymphomas in 89 patients. Am J Pathol 1984; 115:245.
  44. Katzenberger T, Lohr A, Schwarz S, et al. Genetic analysis of de novo CD5+ diffuse large B-cell lymphomas suggests an origin from a somatically mutated CD5+ progenitor B cell. Blood 2003; 101:699.
  45. Hu S, Xu-Monette ZY, Balasubramanyam A, et al. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study. Blood 2013; 121:2715.
  46. Yamaguchi M, Seto M, Okamoto M, et al. De novo CD5+ diffuse large B-cell lymphoma: a clinicopathologic study of 109 patients. Blood 2002; 99:815.
  47. Gascoyne RD, Adomat SA, Krajewski S, et al. Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma. Blood 1997; 90:244.
  48. Kramer MH, Hermans J, Parker J, et al. Clinical significance of bcl2 and p53 protein expression in diffuse large B-cell lymphoma: a population-based study. J Clin Oncol 1996; 14:2131.
  49. Sanchez E, Chacon I, Plaza MM, et al. Clinical outcome in diffuse large B-cell lymphoma is dependent on the relationship between different cell-cycle regulator proteins. J Clin Oncol 1998; 16:1931.
  50. Skinnider BF, Horsman DE, Dupuis B, Gascoyne RD. Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma: correlation with 3q27 and 18q21 chromosomal abnormalities. Hum Pathol 1999; 30:803.
  51. de Leval L, Ferry JA, Falini B, et al. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Pathol 2001; 25:1277.
  52. Colomo L, López-Guillermo A, Perales M, et al. Clinical impact of the differentiation profile assessed by immunophenotyping in patients with diffuse large B-cell lymphoma. Blood 2003; 101:78.
  53. Klein U, Goossens T, Fischer M, et al. Somatic hypermutation in normal and transformed human B cells. Immunol Rev 1998; 162:261.
  54. Küppers 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; 27:1398.
  55. Bastard C, Deweindt C, Kerckaert JP, et al. LAZ3 rearrangements in non-Hodgkin's lymphoma: correlation with histology, immunophenotype, karyotype, and clinical outcome in 217 patients. Blood 1994; 83:2423.
  56. Kramer MH, Hermans J, Wijburg E, et al. Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma. Blood 1998; 92:3152.
  57. Barrans SL, O'Connor SJ, Evans PA, et al. Rearrangement of the BCL6 locus at 3q27 is an independent poor prognostic factor in nodal diffuse large B-cell lymphoma. Br J Haematol 2002; 117:322.
  58. Migliazza A, Martinotti S, Chen W, et al. Frequent somatic hypermutation of the 5' noncoding region of the BCL6 gene in B-cell lymphoma. Proc Natl Acad Sci U S A 1995; 92:12520.
  59. Vitolo U, Gaidano G, Botto B, et al. Rearrangements of bcl-6, bcl-2, c-myc and 6q deletion in B-diffuse large-cell lymphoma: clinical relevance in 71 patients. Ann Oncol 1998; 9:55.
  60. Peng HZ, Du MQ, Koulis A, et al. Nonimmunoglobulin gene hypermutation in germinal center B cells. Blood 1999; 93:2167.
  61. Shen HM, Peters A, Baron B, et al. Mutation of BCL-6 gene in normal B cells by the process of somatic hypermutation of Ig genes. Science 1998; 280:1750.
  62. Küppers 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; 12:4955.
  63. 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; 99:2285.
  64. Barrans SL, Evans PA, O'Connor SJ, et al. The t(14;18) is associated with germinal center-derived diffuse large B-cell lymphoma and is a strong predictor of outcome. Clin Cancer Res 2003; 9:2133.
  65. 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; 106:1770.
  66. Lo Coco F, Gaidano G, Louie DC, et al. p53 mutations are associated with histologic transformation of follicular lymphoma. Blood 1993; 82:2289.
  67. Elenitoba-Johnson KS, Gascoyne RD, Lim MS, et al. Homozygous deletions at chromosome 9p21 involving p16 and p15 are associated with histologic progression in follicle center lymphoma. Blood 1998; 91:4677.
  68. Matolcsy A, Casali P, Warnke RA, Knowles DM. Morphologic transformation of follicular lymphoma is associated with somatic mutation of the translocated Bcl-2 gene. Blood 1996; 88:3937.
  69. Papakonstantinou G, Verbeke C, Hastka J, et al. bcl-2 expression in non-Hodgkin's lymphomas is not associated with bcl-2 gene rearrangements. Br J Haematol 2001; 113:383.
  70. Rao PH, Houldsworth J, Dyomina K, et al. Chromosomal and gene amplification in diffuse large B-cell lymphoma. Blood 1998; 92:234.
  71. Cigudosa JC, Parsa NZ, Louie DC, et al. Cytogenetic analysis of 363 consecutively ascertained diffuse large B-cell lymphomas. Genes Chromosomes Cancer 1999; 25:123.
  72. Pasqualucci L, Trifonov V, Fabbri G, et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat Genet 2011; 43:830.
  73. Yunis JJ, Mayer MG, Arnesen MA, et al. bcl-2 and other genomic alterations in the prognosis of large-cell lymphoma. N Engl J Med 1989; 320:1047.
  74. Johnson NA, Savage KJ, Ludkovski O, et al. Lymphomas with concurrent BCL2 and MYC translocations: the critical factors associated with survival. Blood 2009; 114:2273.
  75. Gascoyne RD, Lamant L, Martin-Subero JI, et al. ALK-positive diffuse large B-cell lymphoma is associated with Clathrin-ALK rearrangements: report of 6 cases. Blood 2003; 102:2568.
  76. De Paepe P, Baens M, van Krieken H, et al. ALK activation by the CLTC-ALK fusion is a recurrent event in large B-cell lymphoma. Blood 2003; 102:2638.
  77. Morris SW. ALK in NHL: To B (cell) or not to B (cell)? Characterization of the entity "ALK+ DLBCL" (editorial). Blood 2003; 102:2316.
  78. Laurent C, Do C, Gascoyne RD, et al. Anaplastic lymphoma kinase-positive diffuse large B-cell lymphoma: a rare clinicopathologic entity with poor prognosis. J Clin Oncol 2009; 27:4211.
  79. Pasqualucci L, Dominguez-Sola D, Chiarenza A, et al. Inactivating mutations of acetyltransferase genes in B-cell lymphoma. Nature 2011; 471:189.
  80. Morin RD, Mendez-Lago M, Mungall AJ, et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 2011; 476:298.
  81. Lohr JG, Stojanov P, Lawrence MS, et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc Natl Acad Sci U S A 2012; 109:3879.
  82. Aukema SM, Siebert R, Schuuring E, et al. Double-hit B-cell lymphomas. Blood 2011; 117:2319.
  83. Hummel M, Bentink S, Berger H, et al. A biologic definition of Burkitt's lymphoma from transcriptional and genomic profiling. N Engl J Med 2006; 354:2419.
  84. Dave SS, Fu K, Wright GW, et al. Molecular diagnosis of Burkitt's lymphoma. N Engl J Med 2006; 354:2431.
  85. Harris NL, Horning SJ. Burkitt's lymphoma--the message from microarrays. N Engl J Med 2006; 354:2495.
  86. Delabie J, Vandenberghe E, Kennes C, et al. Histiocyte-rich B-cell lymphoma. A distinct clinicopathologic entity possibly related to lymphocyte predominant Hodgkin's disease, paragranuloma subtype. Am J Surg Pathol 1992; 16:37.
  87. McBride JA, Rodriguez J, Luthra R, et al. T-cell-rich B large-cell lymphoma simulating lymphocyte-rich Hodgkin's disease. Am J Surg Pathol 1996; 20:193.
  88. Boudová L, Torlakovic E, Delabie J, et al. Nodular lymphocyte-predominant Hodgkin lymphoma with nodules resembling T-cell/histiocyte-rich B-cell lymphoma: differential diagnosis between nodular lymphocyte-predominant Hodgkin lymphoma and T-cell/histiocyte-rich B-cell lymphoma. Blood 2003; 102:3753.
  89. Abramson JS. T-cell/histiocyte-rich B-cell lymphoma: biology, diagnosis, and management. Oncologist 2006; 11:384.
  90. Achten R, Verhoef G, Vanuytsel L, De Wolf-Peeters C. T-cell/histiocyte-rich large B-cell lymphoma: a distinct clinicopathologic entity. J Clin Oncol 2002; 20:1269.
  91. Bouabdallah R, Mounier N, Guettier C, et al. T-cell/histiocyte-rich large B-cell lymphomas and classical diffuse large B-cell lymphomas have similar outcome after chemotherapy: a matched-control analysis. J Clin Oncol 2003; 21:1271.
  92. Williams G, Foyle A, White D, et al. Intravascular T-cell lymphoma with bowel involvement: case report and literature review. Am J Hematol 2005; 78:207.
  93. Colby TV. Current histological diagnosis of lymphomatoid granulomatosis. Mod Pathol 2012; 25 Suppl 1:S39.
  94. Katzenstein AL, Carrington CB, Liebow AA. Lymphomatoid granulomatosis: a clinicopathologic study of 152 cases. Cancer 1979; 43:360.
  95. Castillo JJ, Beltran BE, Miranda RN, et al. Epstein-barr virus-positive diffuse large B-cell lymphoma of the elderly: what we know so far. Oncologist 2011; 16:87.
  96. Dojcinov SD, Venkataraman G, Pittaluga S, et al. Age-related EBV-associated lymphoproliferative disorders in the Western population: a spectrum of reactive lymphoid hyperplasia and lymphoma. Blood 2011; 117:4726.
  97. Adam P, Bonzheim I, Fend F, Quintanilla-Martínez L. Epstein-Barr virus-positive diffuse large B-cell lymphomas of the elderly. Adv Anat Pathol 2011; 18:349.