Abstract
Follicular lymphoma (FL) is an indolent disease with a prolonged clinical course, however, a subset of patients with histological transformation (HT) has a poor prognosis. HT affects 10-15% of all follicular lymphoma patients, typically presenting as an early relapse after chemo-immunotherapy (CIT). However, given the diverse clinical presentations, histological confirmation (ideally with metabolic biopsy) is mandatory. The molecular basis of HT is multifaceted, involving genetic and epigenetic alterations, dysregulated signaling pathways, and immune dysregulation. Genetic aberrations, such as mutations in genes like TP53 and MYC, play a pivotal role in driving HT, with recent evidence suggesting baseline differences in the genomic characteristics of FL patients destined to develop HT. Management of HT is a challenge, given the aggressive nature of disease, coupled with paucity of high-quality evidence. Treatment-strategies depend upon patient characteristics, as well as prior therapy directed (or not) at the initial FL. Most patients with HT responding to CIT are consolidated with autologous stem-cell transplantation. Patients with multiply relapsed or refractory disease may be offered cellular therapy (chimeric antigen receptor T cell therapy or allogenic stem-cell transplantation) or bispecific T cell engagers, antibody drug conjugates or immunomodulators like lenalidomide as per fitness and availability. The choice of therapy should be individualized, with a focus on balancing treatment efficacy and toxicity. Elderly/ unfit patients may be offered lenalidomide based therapy. Prognosis remains poor for the vast majority of patients. In this article, we are reporting three cases of follicular lymphoma with HT along with a narrative review of the relevant literature.