Diffuse Large B-Cell Lymphoma (DLBCL)

Diffuse large B-cell lymphoma (DLBCL) is the most common histologic subtype of non-Hodgkin lymphoma (NHL), comprising around 30% of all cases. DLBCL is aggressive, and survival is limited to days, weeks, or months if left untreated. 

Over the past 15 years, the management of DLBCL has evolved and improved significantly. This can be attributed in part to a refined classification system of B-cell malignancies, which led to improvements in the clinical investigation of new targeted drugs for the disease. With the advent of targeted therapies, a larger number of patients are getting cured.1

Diffuse Large B-Cell Lymphoma Classification History 

The first type of malignant lymphoma was reported in 1832 by Thomas Hodgkin. Other types of lymphoma were later described in 1845 by Virchow. Many other types of lymphoma were described in the second half of the 19th century and the first half of the 20th century.1

The first attempt at the classification of lymphoma was proposed by Gall and Mallory,2 but the first clinically relevant classification based on differences in morphology, architecture, and cytology was made by H. Rappaport.3,4

Two new classifications were presented at a congress in London in 1973 that were based on the biology of the lymphoid tissue and immunobiology; one was presented by Karl Lennert and his group,5 and another was offered by Lukes and Collins.6

The classification proposed by Lennert and the European Lymphoma Club was updated in 1988. Lennert, with co-author Feller, continued to offer additional modifications in a book they published in 1992.7

In 1991, the International Lymphoma Study Group (ILSG) proposed a new classification called REAL (Revised European American Lymphoma), which was based on the definition of lymphoma entities and distinction according to B- and T-cell origin, as well as precursor and mature cell morphology.8

In 1995, the World Health Organization (WHO) organized an executive committee that invited 10 hematopathologists to chair 10 committees to propose a new classification, which was further discussed with hematologists and oncologists to reach a consensus. Each disease entity was defined on the basis of a combination of morphologic, immunophenotypic, genetic, and clinical features. This new classification presented in the WHO blue books in 2001 and 2008 based its decisions on complex lymphoma features: architectural growth pattern, origin of neoplastic lymphoid cells based on morphology, immunophenotype, and molecular genotype.9,10

The current WHO classification identifies 40 subtypes of lymphoma that allow a more focused and dedicated approach to clinical research and drug development.

Read more about DLBCL types

Diffuse Large B-Cell Lymphoma Management History

When the Rappaport classification system was first used in lymphomas, treatment was mainly palliative and consisted of nitrogen mustard and antimetabolites combined with primitive radiation therapy. The introduction of a new classification based on the clinical course of the disease brought the use of more complex combination therapies. The use of the CHOP (cyclophosphamide, hydroxydaunorubicin [sold as Lipodox® or Doxil®], Oncovin® [vincristine], and prednisone) regimen for the treatment of NHLs prolonged patient survival and provided a better quality of life. 

Read more about DLBCL treatment

And although the CHOP regimen has been used for more than 40 years, DLBCL treatment improved when Rituxan® [rituximab] was approved by the US Food and Drug Administration (FDA) in 2006 for use as a first-line treatment in combination with CHOP. Currently, R-CHOP is the standard treatment for patients with newly diagnosed DLBCL, even though patients with non-germinal center B-cell (non-GCB) subtypes of DLBCL have significantly inferior outcomes compared to their GCB counterparts treated with R-CHOP. Currently, many experimental treatments are in the development pipeline.11,12

Read more about DLBCL experimental therapies


  1. Flodr P, Latalova P, Tichy M, et al. Diffuse large B-cell lymphoma: the history, current view and new perspectives. Neoplasma. 2014;61(5):491-504. doi:10.4149/neo_2014_062
  2. Gall EA, Mallory TB. Malignant lymphoma: a clinico-pathologic survey of 618 cases. Am J Pathol. 1942;18(3):381-429.
  3. Rappaport H, Winter WJ, Hicks EB. Follicular lymphoma: a re-evaluation of its position in the scheme of malignant lymphoma, based on a survey of 253 cases. Cancer. 1956;9(4):792-821. doi:10.1002/1097-0142(195607/08)9:4<792::aid-cncr2820090429>3.0.co;2-b
  4. Garvin AJ, Simon R, Young RC, DeVita VT, Berard CW. The Rappaport classification of non-Hodgkin’s lymphomas: a closer look using other proposed classifications. Semin Oncol. 1980;7(3):234-243.
  5. Lennert K, Mohri N, Stein H, Kaiserling E. The histopathology of malignant lymphoma. Br J Haematol. 1975;31(s1):193-203. doi:10.1111/J.1365-2141.1975.TB00911.X
  6. Lukes RJ, Collins RD. Immunologic characterization of human malignant lymphomas. Cancer. 1974;34(S8):1488-1503. doi:10.1002/1097-0142(197410)34:8+<1488::aid-cncr2820340822>3.0.co;2-c
  7. Lennert K, Feller AC. Histopathology of Non-Hodgkin’s Lymphomas: (Based on the Updated Kiel Classification). 2nd ed. Berlin, Germany: Springer Verlag; 1992. doi:10.1007/978-3-642-97187-7
  8. Chan JK, Banks PM, Cleary ML, et al. A proposal for classification of lymphoid neoplasms (by the International Lymphoma Study Group). Histopathology. 1994;25(6):517-536. doi:10.1111/j.1365-2559.1994.tb01371.x
  9. 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):3835-3849. doi:10.1200/JCO.1999.17.12.3835
  10. Jaffe ES, Barr PM, Smith SM. Understanding the new WHO classification of lymphoid malignancies: why it’s important and how it will affect practice. Am Soc Clin Oncol Educ Book. 2017;37:535-546. doi:10.1200/EDBK_175437
  11. Liberman MJ. A history of diffuse large B cell lymphoma: aiming for better outcomes and higher cure rates. Hematol Transfus Int J. 2015;1(2):31-32. doi:10.15406/HTIJ.2015.01.00008
  12. Wang L, Li LR, Young KH. New agents and regimens for diffuse large B cell lymphoma. J Hematol Oncol. 2020;13(1):175. doi:10.1186/s13045-020-01011-z

Reviewed by Kyle Habet, MD, on 9/1/2022.