Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android



Follicular lymphoma (FL) is an indolent lymphoid neoplasm derived from germinal center B cells. It is the most frequent indolent non-Hodgkin lymphoma, accounting for about 20% of all cases. FL is characterized by the t(14;18) (q32;q21) occurring early in the B-cell differentiation process at the pre-B cell stage and leading to the overexpression of the antiapoptotic protein BCL2. However, this translocation, present in circulating B cells at a very low level in up to 70% of healthy individuals, is a weak oncogenic driver, and FL is a multistep disease, requiring additional genomic abnormalities to develop the fully malignant phenotype. The disease is highly “subclonal” at diagnosis, as shown by the variability in allele frequency of the recurrent oncogenic events affecting not only the epigenetic immune escape but also the B-cell receptor, mTOR (mammalian target of rapamycin) and prosurvival pathways. The biological heterogeneity of FL results in a variable clinical presentation and evolution, ranging from a very indolent disease that can be managed for many years with a “watch and wait” approach to an aggressive transformation into diffuse large B-cell lymphoma (DLBCL) and shortened overall survival. When treatment is needed, the use of a monoclonal antibody against CD20 combined with chemotherapy allows a survival of nearly 80% at 10 years. Several prognostic indices based on clinical, biological, and genetic parameters have been developed and validated, but the strongest prognostic factor is the occurrence of an early relapse after treatment initiation (ie, within 24 months). These early events tend to be associated with a histologic transformation (HT) to DLBCL and a very poor outcome. Despite improvements in the genomic characterization of the disease, the accurate prediction of HT at the time of FL diagnosis remains elusive. A better understanding of the interaction between the immune microenvironment and tumor cells may allow the development of targeted therapies and chemotherapy-free options for patients with FL.

Acronyms and Abbreviations

AID, Activation-induced cytidine deaminase; ASCT, Autologous stem cell transplant; B2M, β2 microglobulin; BCR, B-cell receptor;; BNLI, British National Lymphoma Investigation; BR, bendamustine and rituximab; BTLA, B- and T- lymphocyte attenuator; CD, Cluster denomination; CHOP. Cyclophosphamide, hydroxydaunorubicin, vincristine and prednisolone; CI, Confidence interval; CLIITA, Class II transactivator; CR, Complete response; CR30, Complete response rate at 30 months; CNV, Copy number variation; CPC, Common progenitor clone; CT, Computed Tomography; DLBCL, Diffuse large B-cell lymphoma; EFS, Event-free survival; ESMO, European Society for Medical Oncology; FDG, 18FluoroDeoxyGlucose; FL, Follicular Lymphoma; FLIS, FL in situ; FLIPI, follicular lymphoma international prognostic index; FLLC, FL like cells; GC, Germinal Center; GELF, Groupe d’Etude des Lymphomes Folliculaires; GWAS, Genome wide association studies; HBV, Hepatitis B virus; HCV, Hepatitis C virus; HIV1, Human Immunodeficiency Virus 1; HPF, ; HPF, high powered field; HR, Hazard ratio; HT, Histological transformation; IHC, immuno-histochemistry; LDH, Lactate Dehydrogenase; LN, Lymph Node; MALT, Mucosa-associated lymphoid tissue; ME, Micro-environment; MHC, Major histocompatibility complex; NHL, non-Hodgkin lymphoma; OS, Overall survival; PET, Positron Emission Tomography; PFS, Progression-free survival; PI, Prognostic ...

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.