Pathobiology of follicular lymphoma
- Jennifer R Brown, MD, PhD
Jennifer R Brown, MD, PhD
- Associate Professor
- Harvard Medical School
- Arnold S Freedman, MD
Arnold S Freedman, MD
- Section Editor — Lymphoproliferative Disorders
- Professor of Medicine
- Harvard Medical School
- Jon C Aster, MD
Jon C Aster, MD
- Professor of Pathology
- Harvard Medical School
Follicular lymphoma (FL) is the second most common subtype of non-Hodgkin lymphomas. It is defined as a lymphoma of follicle center B cells, and virtually always demonstrates a growth pattern that is partially follicular. (See "Classification of the hematopoietic neoplasms".)
The molecular pathogenesis of FL is a complex, multistep process during which a single follicular B cell acquires all of the genetic and epigenetic alterations needed for malignant transformation. The resultant tumor is usually comprised of a mixture of centrocytes (small cleaved follicular center cells) and centroblasts (large noncleaved follicular center cells). Some common steps in this pathway have been elucidated, particularly chromosomal rearrangements involving BCL-2 and certain somatic mutations, some of which are also seen in other non-Hodgkin lymphoma variants. These lesions typically persist and are joined by other acquired lesions in the not uncommon instance in which FL evolves into a more aggressive lymphoma, usually diffuse large B cell lymphoma, an event referred to as histologic transformation. (See "Histologic transformation of follicular lymphoma".)
This review will discuss the pathobiology of FL in adults. In contrast, a different form of FL that mainly develops in children and adolescents appears to have distinctive clinical and pathologic features. The epidemiology, clinical presentation, pathologic features, diagnosis, treatment, and prognosis of FL are discussed separately. General aspects of the pathobiology of non-Hodgkin lymphoma are also discussed separately. (See "Clinical manifestations, pathologic features, diagnosis, and prognosis of follicular lymphoma" and "Initial treatment of limited stage (I/II) follicular lymphoma" and "Treatment of relapsed or refractory follicular lymphoma" and "Overview of the pathobiology of the non-Hodgkin lymphomas".)
CELL OF ORIGIN
FL is a heterogeneous clinicopathologic entity that has as a common feature an origin from germinal center B cells . The tumor is comprised of variable numbers of small, cleaved cells (centrocytes) and larger, blastoid cells (centroblasts) that morphologically resemble cells found in the light and dark zones of normal germinal centers, respectively. The germinal center ancestry of these cells is principally supported by the identification of somatic mutations in the variable region of the immunoglobulin genes (IgVH), which serves as a marker of germinal center transit , the follicular growth pattern of the tumor cells in most cases, and the immunophenotype of the tumor cells, which in most respects closely resembles that of normal follicle center B cells. (See "Overview of the pathobiology of the non-Hodgkin lymphomas", section on 'B cell lymphoma'.)
Overview — The development of the majority of FL tumors in adults is dependent upon the overexpression of B cell leukemia/lymphoma 2 (BCL-2) located on chromosome band 18q21. BCL-2 is an oncogene that blocks programmed cell death (apoptosis). As such, overexpression results in prolonged cell survival. BCL-2 overexpression in itself is not sufficient for FL development and other genetic lesions or host factors are required (figure 1). (See 'Other genetic lesions' below.)
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