Pathologic Features, Grading, and Variants of Follicular Lymphoma

Abstract

Follicular lymphoma (FL) encompasses a wide spectrum of clinical and pathologic manifestations ranging from a mostly indolent neoplasm to more aggressive types. It was initially described as a nodular lymphoma predominantly composed of B-lymphocytes residing in the germinal center which were morphologically defined as small centrocytes and large centroblasts. The genetic basis of the disease is the presence of the translocation t(14;18)(q32;q21)/IGH-BCL2 that encodes for a fusion protein with potent antiapoptotic characteristic. Although mainly an indolent lymphoma, in a substantial minority of cases, transformation to a more aggressive lymphoma occurs. Multiple variants of follicular lymphoma have been described mainly based on clinical manifestations, patterns of organ involvement, age of patients, and cytogenetic or molecular abnormalities. This has led to the formal recognition of variants of follicular lymphoma such as testicular, primary cutaneous, or duodenal follicular lymphoma. Some of these variants along with high-grade FL may lack t(14;18)(q32;q21)/IGH-BCL2. Similarly, pediatric-type FL (PTFL) affects children and lacks t(14;18)(q32;q21)/IGH-BCL2. A rare variant, diffuse FL, by definition, lacks follicles so it challenges the essential concept that defines follicular lymphoma as a nodular neoplasm. In this chapter, we cover the morphologic spectrum, immunophenotype, cytogenetics, and molecular genetic features as well as the common variants of follicular lymphoma.