|Classification and external resources|
Follicular lymphoma replacing a lymph node
Follicular lymphoma is the most common of the indolent non-Hodgkin's lymphomas, and the second-most-common form of non-Hodgkin's lymphomas overall. It is defined as a lymphoma of follicle center B-cells (centrocytes and centroblasts), which has at least a partially follicular pattern. It is positive for the B-cell markers CD10, CD19, CD20, and CD22 but almost always negative for CD5.
There are several synonymous and obsolete terms for this disease, such as CB/CC lymphoma (Centroblastic and Centrocytic lymphoma), nodular lymphoma and Brill-Symmers Disease.
The tumor is composed of follicles containing a mixture of centrocytes (Kiel nomenclature adopted by WHO experts) or cleaved follicle center cells (older American nomenclature), "small cells", and centroblasts (Kiel nomenclature adopted by WHO experts) or large noncleaved follicle center cells (older American nomenclature), "large cells". These follicles are surrounded by non-malignant cells, mostly T-cells. In the follicles, centrocytes typically predominate; centroblasts are usually in minority.
According to the WHO criteria, the disease is morphologically graded into:
- grade 1 (<5 centroblasts per high-power field (hpf))
- grade 2 (6–15 centroblasts/hpf)
- grade 3 (>15 centroblasts/hpf).
Grade 3 is further subdivided into:
- grade 3A (centrocytes still present)
- grade 3B (the follicles consist almost entirely of centroblasts)
The clinical relevance of this grading system is still being debated; Grades 1, 2, and 3A are considered to be indolent and incurable, whereas grade 3B is considered an aggressive but curable disease similar to diffuse large B-cell lymphoma. Occasional cases may show plasmacytoid differentiation or foci of marginal zone or monocytoid B-cells.
A translocation between chromosome 14 and 18 results in the overexpression of the bcl-2 gene. As the bcl-2 protein is normally involved in preventing apoptosis, cells with an overexpression of this protein are basically immortal. The bcl-2 gene is normally found on chromosome 18, and the translocation moves the gene near to the site of the immunoglobulin heavy chain enhancer element on chromosome 14.
There is no consensus regarding the best treatment protocol. Several considerations should be taken into account including age, stage, and prognostic scores. Patients with advanced disease who are asymptomatic might benefit from a watch and wait approach as early treatment does not provide survival benefit. When patients are symptomatic, specific treatment is required, which might include various combinations of alkylators, nucleoside analogues, anthracycline-containing regimens (e.g., CHOP), monoclonal antibodies (rituximab), radioimmunotherapy, autologous, and allogeneic hematopoietic stem cell transplantation. The disease is regarded as incurable (although allogeneic stem cell transplantation may be curative, the mortality from the procedure is too high to be a first line option). The exception is localized disease, which can be cured by local irradiation.
Personalised idiotype vaccines have shown great promise, but have still to prove their efficacy in randomized clinical trials.
In 2010 Rituximab was approved by the EC for first-line maintenance treatment of follicular lymphoma. Pre-clinical evidence suggests that rituximab could be also used in combination with integrin inhibitors to overcome the resistance to rituximab mediated by stromal cells . 
Trial results released in June 2012 show that bendamustine, a drug first developed in East Germany in the 1960s, more than doubled disease progression-free survival when given along with rituximab. The combination also left patients with fewer side effects than the older treatment (a combination of five drugs -- rituximab, cyclophosphamide (Cytoxan), doxorubicin (Adriamycin), vincristine and prednisone, collectively called R-CHOP). 
There are a large number of recent and current clinical trials for FL.
- Overview at UMDNJ
- Barekman CL, Aguilera NS, Abbondanzo SL (July 2001). "Low-grade B-cell lymphoma with coexpression of both CD5 and CD10. A report of 3 cases". Arch. Pathol. Lab. Med. 125 (7): 951–3. doi:10.1043/0003-9985(2001)125<0951:LGBCLW>2.0.CO;2. PMID 11419985.
- "follicular lymphoma" at Dorland's Medical Dictionary
- "Follicular Lymphomas". Retrieved 2008-07-26.
- Bosga-Bouwer AG, van Imhoff GW, Boonstra R, et al. (February 2003). "Follicular lymphoma grade 3B includes 3 cytogenetically defined subgroups with primary t(14;18), 3q27, or other translocations: t(14;18) and 3q27 are mutually exclusive". Blood 101 (3): 1149–54. doi:10.1182/blood.V101.3.1149. PMID 12529293.
- Bosga-Bouwer AG, Haralambieva E, Booman M, et al. (November 2005). "BCL6 alternative translocation breakpoint cluster region associated with follicular lymphoma grade 3B". Genes Chromosomes Cancer 44 (3): 301–4. doi:10.1002/gcc.20246. PMID 16075463.
- Inoges S, de Cerio AL, Soria E, Villanueva H, Pastor F, Bendandi M (January 2010). "Idiotype vaccines for human B-cell malignancies". Curr. Pharm. Des. 16 (3): 300–7. doi:10.2174/138161210790170111. PMID 20109139.
- "Roche Gets EC Nod for Follicular Lymphoma Maintenance Therapy". October 29, 2010.
- Mraz, M.; Zent, C. S.; Church, A. K.; Jelinek, D. F.; Wu, X.; Pospisilova, S.; Ansell, S. M.; Novak, A. J.; Kay, N. E.; Witzig, T. E.; Nowakowski, G. S. (2011). "Bone marrow stromal cells protect lymphoma B-cells from rituximab-induced apoptosis and targeting integrin α-4-β-1 (VLA-4) with natalizumab can overcome this resistance". British Journal of Haematology 155 (1): 53–64. doi:10.1111/j.1365-2141.2011.08794.x. PMID 21749361.
- "'Rediscovered' Lymphoma Drug Helps Double Survival: Study". June 3, 2012.
- Lymphoma, Follicular at eMedicine
- Turgeon, Mary Louise (2005). Clinical hematology: theory and procedures. Hagerstown, MD: Lippincott Williams & Wilkins. p. 283. ISBN 0-7817-5007-5. "Frequency of lymphoid neoplasms. (Source: Modified from WHO Blue Book on Tumour of Hematopoietic and Lymphoid Tissues. 2001, p. 2001.)"
- An integrative medicine approach
- Resource page for follicular lymphoma
- Information on follicular lymphoma from Lymphoma Information Network