Chapter 62: Follicular Lymphomas

INTRODUCTION

• Follicular lymphoma (FL) is an indolent lymphoid neoplasm that is derived from mutated germinal center B cells and exhibits a nodular or follicular histologic pattern. It is typically composed of a mixture of small, cleaved follicle center cells referred to as centrocytes and large noncleaved follicular center cells referred to as centroblasts. The disease has masqueraded under multiple previous monikers, including "nodular lymphoma" in the Rappaport classification and "follicle center cell lymphoma" in the Working Formulation.

• FL accounts for approximately 20 to 25 percent of adult non-Hodgkin lymphomas (NHL) in the United States, with an annual incidence of approximately 14,000 new cases per year.

• The disease is uncommon in persons younger than age 20 years, and pediatric cases appear to represent a separate disease entity that is typically localized, lacks the translocation 14;18 and BCL-2 expression, and has a very good prognosis.

CLINICAL FEATURES

Symptoms and Signs

• Patients with FL usually present with painless diffuse lymphadenopathy.

• Less frequently, patients may have vague abdominal complaints, including pain, early satiety, and increasing girth, which are caused by a large abdominal mass.

• Approximately 10 percent of patients present with B symptoms (fever, drenching night sweats, or loss of 10% of their body weight).

Staging the Disease

• Evaluation involves performance of a medical history, physical examination (with attention to the lymph nodes in Waldeyer ring and size and involvement of liver and spleen); laboratory testing (including a complete blood count, examination of the blood film and a differential white cell count, lactic acid dehydrogenase [LDH], β₂-microglobulin, comprehensive metabolic panel, serum uric acid level); lymph node biopsy; marrow aspiration and biopsy; flow cytometric analysis of blood, marrow, and lymph node cells; and computed tomography (CT) of the chest, abdomen, and pelvis.

• Excisional lymph node biopsies are strongly preferred for the initial histologic diagnosis, although in cases in which nodal masses are inaccessible, generous needle core biopsies may suffice.

• The diagnosis should not be established solely on the basis of flow cytometry of the blood or marrow, or on cytologic examination of aspiration needle biopsies of lymph node or other tissue.

• In selected circumstances, additional CT scans of the neck, positron emission tomography (PET)/CT imaging, measurement of the cardiac ejection fraction, serum protein electrophoresis, quantitative immunoglobulins, and hepatitis C testing may be useful.

LABORATORY FEATURES

Lymph Node Morphology

• Exhibits a predominantly nodular lymph node pattern; however, the neoplastic follicles are distorted and as the disease progresses, the malignant follicles efface the nodal architecture.

• The World Health Organization has developed a three grade classification system according to the proportion of centroblasts detected microscopically.

• Nearly all authorities now agree, however, that grade 3B FL behaves aggressively and should be treated with anthracycline-containing regimens (e.g., rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone [R-CHOP]) similar to diffuse large B-cell lymphoma.