Transformed Follicular Lymphoma

Follicular lymphoma has a typically indolent course, but there is a lifelong risk of transformation to an aggressive disease. While the overall risk of transformation appears to be declining in the modern era, transformed follicular lymphoma (TFL) remains a clinical challenge with an abrupt clinical presentation and urgent need for intervention and treatment. The biology of transformation is complex, but there is an emerging picture supporting the critical role of early epigenetic aberrations followed by oncogenic mutations with clonal evolution from a marrow-residing common progenitor cell. The gold standard for diagnosis is with a sufficient biopsy specimen showing transformation to diffuse large B-cell lymphoma or even a higher-grade process. However, a clinical diagnosis of transformation based on imaging and laboratory assessments is often required if lymph nodes are not accessible or in the case of sampling bias, whereby the biopsied site may not capture the more aggressive histologic component. Treatment depends on whether or not the transformation occurs as part of initial presentation or following prior therapy for follicular lymphoma. Historically, consolidative hematopoietic stem cell transplant has been advocated, but there is controversy regarding its role and timing. Targeted and biologic approaches are promising, with emerging prospective data. This chapter will review the key features, biology, and treatment options for transformed follicular lymphoma.