Follicular Lymphoma

Globally, follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma (NHL),1 and is diagnosed more often in people over the age of 50. It is an indolent and chronic condition named after abnormal B cells that develop in clusters – or follicles – within the lymph nodes. FL is considered an incurable malignancy, however, it carries an excellent prognosis with a 10-year overall survival rate of approximately 80%.2 This has improved significantly since the introduction of rituximab,3 and new research recognizing the clinical heterogeneity of the disease could lead to even more improvements in therapeutic and diagnostic strategies.4 Some FL cases transform into a more aggressive form of NHL – usually diffuse large B cell lymphoma – which is associated with much poorer outcomes.5


The genetic hallmark of FL is the chromosomal translocation t(14;18), which is found in about 85% of patients. This abnormality leads to the overexpression of BCL2 – a member of the protein family that regulates apoptosis – and anti-apoptotic function. Naive B cells carrying t(14;18) have a clear survival advantage when they colonize secondary lymph tissue and undergo the germinal center (GC) reaction.6 This alone isn’t sufficient to induce lymphomagenesis, and other genetic factors – as well as communication between neoplastic B cells and immune and stromal cells in the microenvironment – are thought to support tumor cell growth, cultivate immune privilege, and promote transformation.7

Diagnosis and treatment assessment

Patients with FL can remain asymptomatic for years, and usually present with recurring lymphadenopathy. Diagnosis from a lymph node biopsy will show numerous back-to-back neoplastic follicles, a loss of polarization, and an absence of macrophages.8 The neoplastic cells are a mixture of centrocytes and centroblasts, and clinical aggressiveness increases with the greater proportion of the latter.3 The WHO classification uses a grading system based on the number of centroblasts, with the highest grade clinically and biologically similar to diffuse large B cell lymphoma, and treated in a similar way.3 Bone marrow is also involved in most patients and, in fewer cases, the spleen, peripheral blood, and other intranodal sites, such as the gastrointestinal tract, liver, or testicles.8

Figure 1. Example micrograph of follicular lymphoma.9

Additionally, there are several prognostic tools that can be used alongside histology and immunophenotyping to help stratify a patient’s risk, and potentially guide treatment options. The Follicular Lymphoma International Prognostic Index (FLIPI), for example, uses five factors – age, stage, number of involved nodal areas, serum lactate dehydrogenase, and hemoglobin3 – to help determine a patient’s prognosis.

Cell markers

FL cells are characterized by the expression of CD19, CD20, CD10, and BCL6, and are negative for CD5 and CD23.3

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  1. Dada, R. (2019) Diagnosis and management of follicular lymphoma: A comprehensive review. Eur J Haematol. 103: 152– 163.
  2. Sarkozy C, Maurer MJ et al. (2019) Cause of Death in Follicular Lymphoma in the First Decade of the Rituximab Era: A Pooled Analysis of French and US Cohorts. J Clin Oncol. 37(2):144-152. doi:10.1200/JCO.18.00400
  3. Freedman A, Jacobsen E. (2020) Follicular lymphoma: 2020 update on diagnosis and management. Am J Hematol. 95:316-327.
  4. Magnoli F, Tibiletti MG et al. (2019) Unraveling Tumor Heterogeneity in an Apparently Monolithic Disease: BCL2 and Other Players in the Genetic Landscape of Nodal Follicular Lymphoma. Front Med (Lausanne). 6:44. doi:10.3389/fmed.2019.00044
  5. Wagner-Johnston ND, Link BK et al. (2015) Outcomes of transformed follicular lymphoma in the modern era: a report from the National LymphoCare Study (NLCS). Blood. 126(7):851-857. doi:10.1182/blood-2015-01-621375
  6. Kahl BS, Yang DT. (2016) Follicular lymphoma: evolving therapeutic strategies. Blood. 127(17): 2055-2063. doi:
  7. Kridel R, Sehn LH et al. (2012) Pathogenesis of follicular lymphoma. J Clin Invest. 122(10):3424-3431.
  8. Choi SM, Betz BL et al. (2018) Follicular Lymphoma Diagnostic Caveats and Updates. Arch Pathol Lab Med. 142(11):1330-1340. doi:

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