Follicular lymphoma is the second most common non-Hodgkin's lymphoma. It is a neoplasm of follicle center B cells that shows a follicular growth pattern due to a chromosomal translocation resulting in overexpression of the bcl-2 gene. This translocation allows the lymphoma cells to evade apoptosis. Follicular lymphoma usually presents as painless lymphadenopathy and involves lymph nodes as well as extranodal sites. Diagnosis involves lymph node biopsy and immunostaining to detect bcl-2 expression. Treatment options include radiation therapy, chemotherapy, and monoclonal antibody therapy.

1. Follicular lymphoma
Yuan Yao

2. Follicular Lymphoma (FL)
• Second most common non-Hodgkin’s lymphoma
• Median age of onset is 60
• A neoplasm of follicle centre B cells
• Neoplastic cells show a follicular growth pattern
• Translocation between chromosome 14 and 18
results in the overexpression of the bcl-2 gene
• It is usually indolent
• Can transform into aggressive diffuse large B-
cell lymphoma

3. Development of Follicular Lymphoma
•For normal B-cells, those cells binding to
antigens in the germinal centres (GC) of
follicules are selected and migrate out as
plasma cells and memory cells. B-cells not
selected die by apoptosis.
•FL cells need to escape the default death
pathways.
•Upregulated expression of the anti-
apoptotic BCL-2 protein via the
chromosomal translocation

4. Normal reactive
lymph node
Follicular
Lymphoma
Morphology
Warnke et al.,1995
Discrete follicles, well sparated Nodularity throughout the node

5. Histopathology
http://www.pathpedia.com
•Small and large follicles next to each other
•Round to oval structure
•Comprised of follicular center B-cells
•No “light” or “dark” zones of normal lymphoid follicle
Centrocytes Centroblasts
Small to large cells Large cells
Irregular nuclei Round to oval nuclei with open
(clear) chromatin
cleaved Non-cleaved
Without nucleoli Small nucleoli
•Consist of two types of neoplastic lymphocytes

6. Follicular Lymphoma Grading
• Proportion of centroblasts
Number of centroblasts in 40X high-power microscopic field (hpf)
grade1: 0-5 centroblasts/ hpf
grade2: 6-15 centroblasts/ hpf
grade3: >15 centroblast/ hpf
grade 3a: > 15 centroblasts/hpf but centrocytes are still
present
grade 3b: centroblasts.

7. Clinical features
• FL predominantly involves lymph nodes,
but also spleen, bone marrow, peripheral
blood.
• Involvement of non-haematopoietic
extranodal sites, such as the
gastrointestinal tract, soft tissue, skin, and
other sites may occur
• Asymptomatic at the time of diagnosis
• Painless lymphadenopathy
• Fever,night sweats, weight lose

8. Diagnosis of the FL
• Lymph node biopsy
-- Histological staining: determine the grade
-- Immunostaining: high levels of bel-2
expression correlate with a worse outcome
• Blood tests
• Chest X-ray
• CT and PET scanning

9. Treatment
Radiation therapy –chemotherapy – nonoclonal antibody therapy

10. References
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subtypes differ by geographic locations." Non-Hodgkin's Lymphoma Classification Project Ann Oncol 9:
717-720.
Leich.E,, et al. (2011). "Pathology, pathogenesis and molecular genetics of follicular NHL." Best Practice
& Research Clinical Haematology 24: 95-109.
Elaine, S. J. (2001). "Pathology and genetics of tumours of haematopoietic and lymphoid tissues." World
Health Organization: 162-167.
Goodlad, J., S. MacPherson, et al. (2004). "Extranodal follicular lymphoma: a clinicopathological and
genetic analysis of 15 cases arising at non-cutaneous extranodal sites." Histopathology 44: 268-276.
Hoffbrand, A., P. Moss, et al., Eds. (2011). Essential Haematology, Blackwell publishing Ltd.
Jong, D. (2005). "Molecular pathogenesis of follicular lymphoma: a cross talk of genetic and immunologic
factors." J.Clinical Oncology 23: 6358-6363.
Bende. RJ,. et al. "Molecular pathoways in follicular lymphoma." Leukemia 21(1): 18-29.
Stevenson, F. and G. Stevenson (2012). "Follicular lymphoma and the immune system: from
pathogenesis to antibody therapy." Blood First edition paper, prepublished online Feb 15.
Warnke, R ., et al. (1995). "Tumors of the lymph nodes and spleen." Atlas of tumor pathology (electronic
fascicle) 14.