Diffuse large B cell lymphoma, DLBCL


A diffuse proliferation of large neoplastic B lymphoid cells, with nuclear size at least twice that of a small lymphocyte (>20 mm5). This is a heterogeneous group of tumours. Some are of follicle centre cell origin. It is unclear which combination of positivity for CD10, bcl-2, bcl-6 and t(14;18) may indicate derivation from a follicle centre cell, either de novo or by transformation11.



Constitutes 30-40% of all adult non-Hodgkin lymphomas2,5. Age range is broad, including children, but with a peak in the 7th decade.

Clinical features

At presentation, 40% of cases are extranodal, most commonly involving the gastrointestinal tract but also lung, skin, central nervous system, salivary gland, Waldeyer's ring, bone, testis, soft tissue, female genital tract, kidney or spleen. Many patients have disseminated disease at presentation.

The majority of cases are primary, but DLBCL may also arise by transformation of B-CLL/SLL, lymphoplasmacytic lymphoma, follicular lymphoma, MALT lymphoma, lymphomatoid granulomatosis or NLPHL5. Immunodeficiency is a risk factor.

Macroscopic appearance

At extranodal sites, DLBCL usually forms a distinct tumour mass.


There is diffuse replacement of the nodal architecture, completely, partially or in an interfollicular or (rarely) sinusoidal pattern. Bands of sclerosis may be seen. The tumour cells are large. Mitotic figures are always numerous5.




10% of cases0, 9/2095, 0/2513



27%2 to 41%1 of cases, 68/2135, 14/3411, 5/2513




positive0, 202/2085, 25/2513






almost all anaplastic cases and some others0, 17/2135



CD44 6v


CD44 9v



usually positive, negative in 30% of anaplastic and immunoblastic variants5


positive0 , 73/1105, 25/2513


minority of cases0

surface Ig

50-75% of cases (IgM > IgG > IgA)0

cytoplasmic Ig

in cases showing plasmacytic differentiation0


20-50% of cases6, 126/2135, 24/3411, 19/2513


20-40% of cases, 95/2125, 29/3411, 24/2513


positive in 50% of extranodal cases5

cyclin D1





minority of cases0, 12/3411


proliferation fraction usually high (>40% and may be >90%)0




DLBCL can be classified as of germinal centre orgin or non-germinal centre type:



germinal centre type

non-germinal centre type









The CD5+ DLBCLs appear to be a subset with a uniform phenotype, CD5+/CD10-/CD19+/CD20+/CD21+/CD23-/cyclinD1-, usually of centroblastic morphology and may be more aggressive5.


Differential diagnosis

†: fresh frozen tissue only


DLBCL accounts for about 40% of all lymphomas and prognosis is very variable. It is generally aggressive but potentially curable. About 40% of adult DLBCL patients respond well to therapy and have prolonged survival, the remainder die of the disease12.

 Adverse prognostic indicators include:



0World Health Organization Classification of Tumours, Tumours of the haematopoietic and lymphoid tissues, IARC Press 2001.

1 Kaufmann, O. Flath, B. Spath-Schwalbe, E. Possinger, K. Dietel, M. Immunohistochemical detection of CD10 with monoclonal antibody 56C6 on paraffin sections. Am J Clin Pathol 1999;111:117-22.

2 de Leval, L., Ferry, J. A., Falini, B., Shipp, M., Harris, N. L. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Path 2001;25:1277-1282.

3 Gascoyne, RD. CD5-positive diffuse large B-cell lymphoma: a distinct entity? Advances in Anatomic Pathology 2002;9:269-270.

4 Large B-cell lymphomas can be stratified and outcome predicted by gene expression profiling. Advances in Anatomic Pathology 2002;9:323-4.

5 Pileri, S.A., Dirnhofer, S., Went, P., Ascani, S., Sabattini, E., Marafioti, T., Tzankov, A., Leoncini, L., Falini, B. and Zinzani, P.L. Diffuse large B-cell lymphoma: one or more entities? Present controversies and possible tools for its subclassification. Histopathology 2002;41:482-509.

6 Cogliatti, S.B., Griesser, H., Peng, H., Du, M.Q., Isaacson, P.G., Zimmermann, D.R., Maibach, R.C. and Schmid, U. Significantly different bcl-2 expression profiles in gastric and non- gastric primary extranodal high-grade B-cell lymphomas. J Pathol 2000;192:470-8.

7 Leoncini, L., Lazzi, S., Bellan, C. and Tosi, P. Cell kinetics and cell cycle regulation in lymphomas. J Clin Pathol 2002;55:648-55.

8 Ohshima, K., C. Kawasaki, et al. (2001). "CD10 and Bcl10 expression in diffuse large B-cell lymphoma: CD10 is a marker of improved prognosis." Histopathology 39(2): 156-62.

9 Uherova, P., C. W. Ross, et al. (2001). "The clinical significance of CD10 antigen expression in diffuse large B-cell lymphoma." Am J Clin Pathol 115(4): 582-8.

10 Xu, Y., R. W. McKenna, et al. (2001). "Clinicopathologic analysis of CD10+ and CD10- diffuse large B-cell lymphoma. Identification of a high-risk subset with coexpression of CD10 and bcl-2." Am J Clin Pathol 116(2): 183-90.

11 McCluggage, W. G., M. Catherwood, et al. (2002). "Immunohistochemical expression of CD10 and t(14;18) chromosomal translocation may be indicators of follicle centre cell origin in nodal diffuse large B-cell lymphoma." Histopathology 41(5): 414-20.

12 Alizadeh, A. A., M. B. Eisen, et al. (2000). "Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling." Nature 403(6769): 503-11.

13 Kusumoto S, Kobayashi Y, Sekiguchi N, et al. Diffuse large B-cell lymphoma with extra Bcl-2 gene signals detected by FISH analysis is associated with a "non-germinal center phenotype". Am J Surg Pathol 2005; 29:1067-73

14 van Galen JC, Muris JJ, Oudejans JJ, et al. Expression of the polycomb-group gene BMI1 is related to an unfavourable prognosis in primary nodal DLBCL. J Clin Pathol 2007; 60:167-72

15 Amen F, Horncastle D, Elderfield K, et al. Absence of cyclin-D2 and Bcl-2 expression within the germinal centre type of diffuse large B-cell lymphoma identifies a very good prognostic subgroup of patients. Histopathology 2007; 51:70-9

This page last revised 10.8.2007.

©SMUHT/PW Bishop