Follicular lymphoma (FL) is the second most common type of non-Hodgkin lymphoma (NHL). It is the most common of the clinically indolent NHLs defined as those lymphomas in which survival of the untreated patient is measured in years. Histologic transformation (HT) refers to the evolution of a clinically indolent NHL (eg, FL) to a clinically aggressive NHL (eg, diffuse large B cell lymphoma, DLBCL) defined as those lymphomas in which survival of the untreated patient is measured in months.
HT of FL occurs at a rate of approximately 1 to 3 percent per year, and is associated with rapid progression of lymphadenopathy, infiltration of extranodal sites, development of systemic symptoms, elevated serum LDH, and often a poor prognosis.
The largest body of information dealing with HT is related to its occurrence in FL, which will be the focus of this review. HT has also been observed in other clinically indolent B cell lymphoproliferative disorders, including marginal zone lymphoma, lymphoplasmacytic lymphoma, and small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL). HT that occurs in patients with SLL/CLL has been termed Richter's transformation. (See "Pathobiology and treatment of Richter's transformation in chronic lymphocytic leukemia/small lymphocytic lymphoma", section on 'Treatment'.)
The epidemiology, diagnosis, and treatment of HT in patients with FL will be discussed here. Richter’s transformation is discussed separately, as is the diagnosis and management of FL that has not undergone HT. (See "Clinical manifestations, pathologic features, diagnosis, and prognosis of follicular lymphoma" and "Initial treatment of limited stage (I/II) follicular lymphoma" and "Initial treatment of advanced stage (III/IV) follicular lymphoma".)
Frequency of transformation — The frequency of histologic transformation (HT) in follicular lymphoma (FL) in the current era is unknown. Data are largely extrapolated from studies performed prior to the general incorporation of rituximab into initial treatment. In these studies, the cumulative incidence of HT in FL varies from 10 to 70 percent and is dependent on the definition of HT, length of follow-up, and whether biopsies or autopsies were performed to document HT [1-7]. In general, however, these risks have been reported to range from 1.4 to 4.4 percent per year, as shown in the following examples: