Facts & Figures

• Follicular lymphoma FL accounts for 20–30% of the cases of non-Hodgkin lymphoma NHL in the United States, making this disease the second most common subtype of NHL (Figure).^1,2
  • Approximately 16,000 cases of FL are diagnosed each year.^2,3
  • The overall incidence rate FL increased between 1975 and 2007 and has since been declining.⁴
  • The reason for the decline is unclear, but it may be attributed to changes in the prevalence of risk factors for FL (eg, cigarette smoking, autoimmune conditions, hepatitis C virus infection, and organ transplantation).⁴
  • For the other percentages depicted below, see reference 2.

• The overall 5-year survival rate for FL is approximately 80%.⁴
  • The overall 5-year survival rate has increased from 69% in 1975 to 82% in 2005.⁴
  • Patients with more aggressive disease have a 5-year survival rate of 50%.⁵
• Since FL has a better prognosis than other subtypes of NHL, only 11% of NHL deaths were attributed to underlying FL histology.⁴
  • The tumor typically progresses slowly and responds well to therapy, leading to long survival times.⁶
  • Approximately 45% of patients will develop an aggressive form of the disease by transformation into diffuse large B-cell lymphoma DLBCL at a rate of approximately 3% per year.^7,8
• The median age at diagnosis is 55–65 years.^8,9
• The majority of patients are diagnosed with advanced-stage disease (stages III and IV).¹⁰
  • Patients typically have had asymptomatic lymphadenopathy for several years prior to a diagnosis of FL.⁹
• FL is most common in people with European and African ancestry; rates are substantially lower in people of East Asian ancestry.¹¹

Pathophysiology

• FL is defined as a malignancy of follicle-center B cells originating from the germinal center within a lymph node.^6,9
  • The immunophenotype of FL is CD20+, CD10+, BCL2+, CD23+/–. CD43–, CD5–, CCDN1–, and BCL6+.³
  • Malignant germinal-center B cells are intermixed with nonmalignant cells (eg, T cells, follicular dendritic cells, macrophages) within a lymph node, including cell types involved in a germinal-center reaction.⁶
• Approximately 90% of patients with FL have the t(14;18) translocation, which causes overexpression of the anti-apoptotic protein BCL2.^6,12
  • Other genetic alterations associated with FL include epigenetic regulators, transcription factors, and B-cell signaling proteins, among others.¹²
  • The median number of mutations observed in FL tumors is 5.¹²
• Grading of tumors by the number of centroblasts (ie, active B cells within a germinal center) reflects prognosis and clinical outcome.¹³
  • The Follicular Lymphoma International Prognostic Index FLIPI score assesses the risk of progression by evaluating the number of nodal sites involved, the tumor stage, and other disease parameters.¹³
• FL is generally a slowly progressing disease with a long natural history.
  • Median survival ranges from 8 years to 15 years.¹⁴

References

1. Laurent C, Do C, Gourraud PA, et al. Prevalance of common non-Hodgkin lymphomas and subtypes of Hodgkin lymphoma by nodal site involvement: A systematic retrospective review of 938 cases. Medicine (Baltimore). 2015;94:e987.
2. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma. The Non-Hodgkin’s Lymphoma Classification Project. Blood. 1997;89:3909-3918.
3. American Cancer Society. Cancer Facts & Figures 2016. Atlanta: American Cancer Society; 2016.
4. Howlader N, Morton LM, Feuer EJ, Besson C, Engels EA. Contributions of subtypes of non-Hodgkin lymphoma to mortality trends. Cancer Epidemiol Biomarkers Prev. 2016;25:174-179.
5. Casulo C, Byrtek M, Dawson KL, et al. Early relapse of follicular lymphoma after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone defines patients at high risk for death: an analysis from the National LymphoCare Study. J Clin Oncol. 2015;33:2516-2522.
6. Kridel R, Sehn LH, Gascoyne RD. Pathogenesis of follicular lymphoma. J Clin Invest. 2012;122:3424-3431.
7. Casulo C, Burack WR, Friedberg JW. Transformed follicular non-Hodgkin lymphoma. Blood. 2015;125:40-47.
8. Schatz JH, Oricchio E, Puvvada SD, Wendel HG. Progress against follicular lymphoma. Curr Opin Hematol. 2013;20:320-326.
9. Freedman A. Follicular lymphoma: 2015 update on diagnosis and management. Am J Hematol. 2015;90:1171-1178.
10. Hiddemann W, Cheson BD. How we manage follicular lymphoma. Leukemia. 2014;28:1388-1395.
11. Anderson JR, Armitage JO, Weisenburger DD. Epidemiology of the non-Hodgkin’s lymphomas: distributions of the major subtypes differ by geographic locations. Non-Hodgkin’s Lymphoma Classification Project. Ann Oncol. 1998;9:717-720.
12. Pastore A, Jurinovic V, Kridel R, et al. Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol. 2015;16:1111-1122.
13. Zelenetz AD, Abramson JS, Advani RH, et al. Non-Hodgkin’s lymphomas. J Natl Compr Canc Netw. 2011;9:484-560.
14. Adult Non-Hodgkin Lymphoma Treatment–Health Professional Version (PDQ®). National Cancer Institute. Available at www.cancer.gov/types/lymphoma/hp/adult-nhl-treatment-pdq#link/_552_toc. June 1, 2016.