Follicular lymphoma: a historical overview

Abstract

Lymphoma was first described in 1862 and follicular lymphoma in 1925. Initially considered a benign disorder, and named Brill – Symmers disease after the authors of the original papers, it was rapidly recognized as a malignancy with a variable but often indolent course. Most of its clinical features were described by the early 1940s. Despite discussion about its cell of origin, and in contrast to many other lymphoma subtypes, follicular lymphoma could always be accurately recognized and diagnosed using light microscopy morphological features. B-cell origin was demonstrated in the 1970s and the important role of t(14;18) and bcl-2 gene rearrangement in the pathogenesis of follicular lymphoma was established shortly thereafter. The etiology of follicular lymphoma, the reason for marked geographic variation in its incidence, the role of alternative molecular pathways in its pathogenesis, and the cause for its variable clinical behavior all remain unknown. Several observations suggest an important role for the normal immune response in regulating the clinical behavior of follicular lymphoma. From the earliest descriptions, radiation therapy was shown to be very effective in follicular lymphoma, but not curative. Combination chemotherapy was tested in the 1970s, but despite high rates of response, there was only minimal impact on survival. Interferon combined with anthracycline based chemotherapy was the first treatment to improve survival, but was not widely adopted in the USA. Randomized studies have shown an impact of autologous transplantation on progression free survival. Allogeneic transplantation is a curative therapy, but is too toxic for widespread application. Targeted therapies, particularly rituximab have revolutionized the treatment of follicular lymphoma. A convergence of technological and biological advances will likely lead to further dramatic progress in the next decade. For the first time consistent improvements in survival of follicular lymphoma are reported.

Keywords:

• Follicular lymphoma
• history
• biology
• therapy