Transformed Follicular Lymphoma: Not all fit in one

Follicular Lymphoma (FL) is the second most frequent non-Hodgkin lymphoma accounting for approximately 10-20% of all lymphomas in Western Countries. Histologic transformation (HT) is a frequent event in the clinical course of patients with indolent lymphoma that is often accompanied by a dramatic change in the clinical features of the disease towards a more aggressive course. Although the transformation of Follicular Lymphoma (tFL) was described several decades ago, there is a strong need for a better understanding of both the dynamics of the tumor clonal evolution and the genetic events leading to ()transformation. In addition, the management of patients with tFL is challenged by the heterogeneity of the previous treatments. The present review describes the state of art of tFL, outlining recent advances in the understanding of genetic basis and the evolutionary process governing the initiation and persistence of tumor evolution. It will be also addressed the key questions pending on this incurable disease, such as a lack of a standard therapeutic strategy for tFL patients as well as its outcome in the Rituximab (R) era.