Follicular lymphoma (FL) represents 20%–30% of all non-Hodgkin lymphomas (NHL) and is the second most common NHL in Western populations after diffuse large B-cell lymphoma (DLBCL) (1). FL comprises about 80% of the indolent NHLs. The term follicular is derived from the tendency of the neoplastic cells to form microscopic nodules. The cell of origin is the follicular center B cell. Eighty-five to 90% of all cases harbor the characteristic cytogenetic translocation t(14;18), resulting in the placement of the anti-apoptotic bcl-2 gene under the control of the immunoglobulin (Ig) heavy-chain promoter on chromosome 14. Follicular lymphoma is considered incurable without stem-cell transplantation, with the exception of localized disease that may be cured with radiotherapy in a subset of patients. Treatment is therefore based on disease control rather than cure, and eventual relapse after treatment is the usual natural history of FL (2).
The incidence of follicular lymphoma is approximately 2.2–3.2 per 100,000 in the United States and Western Europe (3). Follicular lymphoma is more common in Caucasians than in people of African or Asian descent and typically affects the middle-aged or elderly with an average age at diagnosis of 60 years. The disease occasionally occurs in children or young adults. FL in children is a distinct clinical entity, presenting with localized disease that is often eradicated with initial therapy. In contrast, adults with FL typically present with advanced stage disease and experience recurrence after standard treatment. Although there are no universally accepted risk factors for the development of FL, herbicides and pesticides have been linked with the disease. Familial cases represent a small proportion of total incidence, and there appears to be a slightly increased risk in relatives of patients with FL.
Clinically, patients with FL often present with asymptomatic peripheral lymphadenopathy or have enlarged lymph nodes detected incidentally on imaging studies. Although hilar and mediastinal nodes are frequently involved, large mediastinal masses are uncommon. The spleen and bone marrow are commonly involved by disease, but CNS and organ involvement is uncommon. Infiltration of the bone marrow is present in 60%–80% of patients at time of diagnosis. The majority of patients (70%–80%) will present with advanced stage disease, and up to 25% will have B symptoms or an elevated serum LDH level. Although bone marrow involvement is common and sensitive molecular testing frequently identifies circulating lymphoma cells, cytopenias are uncommon at presentation.
In addition to the classic presentation of FL as described above, there are a few distinct clinical variants. Primary intestinal follicular lymphoma is often found incidentally on endoscopy performed for unrelated indications and most often involves the second portion of the duodenum. Pediatric lymphoma is another variant and has distinct features as noted above. Intrafollicular neoplasia, or in situ FL, refers to follicles with high levels of BCL-2 expression but without other ...