Follicular lymphoma, FL


A neoplasm of follicle centre cells with an, at least partially, follicular pattern.



Constitutes 22-35% of all adult non-Hodgkin lymphomas and 70% of all "low-grade" lymphomas. Median age 59 years, unusual before 40 years and rare before 20 years of age. However, grade 3 disease may sometimes be seen in the head and neck, including tonsils, in boys.

Clinical feature

Sites of involvement are:

Disease is often of advanced stage at the time of presentation and involvement of non-haemopoietic sites is particularly associated with advanced stage disease. Apart from lymphadenopathy, however, patients are often asymptomatic.


Most cases have a predominantly follicular pattern. Neoplastic follicles are usually:
poorly defined
lack mantle zones
lack polarisation
lack tingible body macrophages (starry sky pattern)
closely packed
occupy the entire node

There is also interfollicular infiltration by neoplastic centrocytes.

A follicular growth pattern may be seen in several types of lymphoma which colonise follicles, such as mantle cell lymphoma, marginal zone (MALT) lymphoma and LP Hodgkin disease, as well as in true follicular lymphomas. Focal follicular features have also been reported in tonsillar diffuse large B-cell lymphoma3. This pattern presumably arises from colonisation of non-neoplastic follicles.

The neoplastic cells consist of two types, centrocytes and centroblasts the former usually predominating. 10$ of cases show discrete foci of marginal zone or monocytoid cells. Rarely plasmacytoid or signet ring cell differentiation occurs.

Grading is based on the absolute count of centroblasts across ten representative neoplastic follicles, expressed per x40 high power field of 0.159 mm2. Care must be taken to distinguish large cleaved centrocytes and follicular dndrtitic cells from centroblasts.

Variations in grade between different areas should be noted. Any area of diffuse large B-cell lymphoma indicates transformation.






60-80% of cases1, 95%5












57/2135, 3/106, 15-20%7 



negative, except some grade 3 FL






85% of cases, 201/2095

cutaneous FL is commonly bcl-2 negative





+ (IgM, IgD, IgG or rarely IgA)



average proliferation index 28%( range 5% to 90%)5



†: fresh frozen tissue only

CD21 and CD23 highlight the meshwork of FDCs.



Some cases progress to diffuse large B-cell lymphoma; mutations of p53 have been implicated in this process4.

Differential diagnosis



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

Wotherspoon AC, Hasserjian RP. Immunophenotyping in the differential diagnosis of histologically low grade B cell lymphomas Current Diagnostic Pathology 2000;6:55-63.

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. Positivity seen in 22 of 28 cases.

2 Jones D. Dismantling the germinal center: comparing the processes of transformation, regression and fragmentation of the lymphoid follicle. Advances in Anatomic Pathology 2002;9:129-138.

3 Ree, H.J., Kikuchi, M., Lee, S.S., Ohshima, K., Yang, W.I., Ko, Y.H., Cho, E.Y. and Rhee, J.C. Focal follicular features in tonsillar diffuse large B-cell lymphomas: follicular lymphoma with diffuse areas or follicular colonization. Hum Pathol 2002;33:732-40.

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

5 Thorns C, Kalies K, Fischer U, et al. Significant high expression of CD23 in follicular lymphoma of the inguinal region. Histopathology 2007; 50:716-9

6 Watson P, Wood KM, Lodge A, et al. Monoclonal antibodies recognizing CD5, CD10 and CD23 in formalin-fixed, paraffin-embedded tissue: production and assessment of their value in the diagnosis of small B-cell lymphoma. Histopathology 2000; 36:145-50

7 Calaminici M, Piper K, Lee AM, et al. CD23 expression in mediastinal large B-cell lymphomas. Histopathology 2004; 45:619-24

This page last revised 5.5.2007.

©SMUHT/PW Bishop