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CHAPTER 99 small, cleaved follicle center cells (centrocytes) and large noncleaved
follicle center cells (centroblasts). The disease has masqueraded under
FOLLICULAR LYMPHOMA multiple monikers, including “nodular lymphoma” in the Rappa-
port classification, and “follicle center cell lymphoma” in the Working
Formulation. The current World Health Organization (WHO) classi-
1
fication proposes the terms follicular lymphoma, grades 1, 2, and 3, to
Oliver W. Press differentiate cases based on the numbers of centroblasts per high-power
microscopic field (see “Lymph Node Morphology and Lymphocyte
Immunophenotype” below). 2
SUMMARY
EPIDEMIOLOGY
Follicular Lymphoma (FL) is an indolent, neoplastic disorder of germinal FL accounts for approximately 20 to 25 percent of adult non-Hodgkin
center-derived B lymphocytes that afflicts approximately 14,000 people in the lymphomas (NHLs) in the United States, with an annual incidence
United States each year. It typically presents as a disseminated disorder with of approximately 14,000 new cases per year. FL is most common in
3,4
painless, diffuse lymphadenopathy and marrow infiltration, and may be asso- North America and Western Europe, and much less frequent in Eastern
ciated with hepatosplenomegaly and circulating lymphoma cells in the blood. Europe, Asia, Africa, and in Americans of African descent. The median
2
A characteristic translocation, t(14;18), is found in the cells of 85 percent of age at diagnosis is 59 years, and the male-to-female ratio is 1:1.7. The
patients, which deregulates BCL2 protein expression and inhibits apoptosis of disease is rare in persons younger than age 20 years, and pediatric cases
affected B cells. The cells typically express monoclonal surface immunoglob- appear to represent a separate disease entity that is typically localized,
ulin, CD10, CD19, CD20, CD22, CD45, and CD79a on their cell surface, but not lacks the t(14;18) translocation and BCL2 expression, and has a very
5,6
CD5 or CD23. Patients are often asymptomatic at the time of presentation, and good prognosis.
may live for many years in good health without therapy. On the other hand,
most patients eventually develop progressive lymphadenopathy, causing CLINICAL FEATURES
symptoms mandating intervention. Many treatment regimens are effective
at inducing remissions, including single-agent rituximab or chlorambucil; or SYMPTOMS AND SIGNS
several multidrug programs, including bendamustine plus rituximab (BR), Patients with FL usually present with painless diffuse lymphadenopathy.
rituximab, cyclophosphamide, vincristine, and prednisone (R-CVP); rituximab, Less frequently, patients may have vague abdominal complaints, includ-
cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). None ing pain, early satiety, and increasing girth, which may be caused by a
of these therapies, however, is considered curative and most patients eventu- large abdominal mass or hepatosplenomegaly. Approximately 10 per-
ally relapse with recurrent disease. Autologous and allogeneic hematopoietic cent of patients present with B symptoms (fever, drenching night sweats,
cell transplantation (HCT) can induce prolonged remissions in many patients or loss of 10 percent of body weight). The disease usually is widespread
at presentation, with involvement of multiple lymph node–bearing sites,
with relapsed FL, but the role of HCT in this disease is controversial. Histologic liver, and spleen. The marrow is involved in 40 to 70 percent of patients
transformation to aggressive lymphoma occurs in 30 to 40 percent of patients, at diagnosis. FL may occasionally present with primary involvement of
usually leading to death within a few years of transformation. extranodal sites, such as the skin, gastrointestinal tract, ocular adnexa,
and breast, but CNS disease is rare, unless histologic transformation to
diffuse large B-cell lymphoma has occurred. 2
DEFINITION AND HISTORY

Follicular lymphoma (FL) is an indolent lymphoid neoplasm that is LABORATORY FEATURES
derived from mutated germinal center B cells and exhibits a nodular
or follicular histologic pattern. It is typically composed of a mixture of LYMPH NODE MORPHOLOGY AND
LYMPHOCYTE IMMUNOPHENOTYPE
FL exhibits a predominantly nodular lymph node pattern, however, the
neoplastic follicles are distorted and as the disease progresses, the malig-
Acronyms and Abbreviations: ADCC, antibody-dependent cellular cytotoxic- nant follicles efface the nodal architecture (see Chap. 96, Fig. 96–18),
ity; BR, bendamustine and rituximab; CDC, complement-dependent cytotoxicity; commonly resulting in the development of areas of diffuse involve-
CHOP, cyclophosphamide, doxorubicin, vincristine, prednisone; CR, complete response; ment, which may predominate histologically. The WHO has developed
CVP, cyclophosphamide, vincristine, prednisone; FCM, fludarabine, cyclophosphamide, a three-grade system for classifying FL according to the proportion of
mitoxantrone; FDG, fluoro-2-deoxyglucose; FL, follicular lymphoma; FND, fludarabine, centroblasts detected microscopically: grade 1 lymphomas have 0 to
mitoxantrone (Novantrone), dexamethasone; GELF, Groupe d’Etudes des Lymphomes Fol- 5 centroblasts, grade 2 lymphomas have 6 to 15 centroblasts, and grade 3
liculaires; Gy, gray; HLA, histocompatibility locus antigen; IFN, interferon; IPI, international lymphomas have more than 15 centroblasts per high-power micro-
prognostic index; KLH, keyhole limpet hemocyanin; LDH, lactate dehydrogenase; NHL, scopic field (Fig. 99–1). Grade 3 FL is further subdivided into grade 3A,
2
non-Hodgkin lymphoma; ORR, overall response rate; OS, overall survival; PCR, polymerase in which some small centrocytes are present despite the predominance
chain reaction; PET, positron emission tomography; PFS, progression-free survival; PR, of centroblasts, and grade 3B, in which solid sheets of centroblasts are
partial remission; ProMACE/MOPP, prednisone, methotrexate, doxorubicin, cyclophos- exclusively present and centrocytes are entirely absent. Some, but not
2
phamide, etoposide, mechlorethamine, vincristine, procarbazine, prednisone; R-CHOP, all, studies suggest that grades 1 and 2 lymphomas follow a more indo-
rituximab plus CHOP; R-CVP, rituximab plus CVP; RIT, radioimmunotherapy; WHO, World lent course than grade 3 FL, and many authorities suggest that these
7
Health Organization. lower grades should be treated more conservatively than grade 3 FL.
Other studies indicate a similar natural history for grades 1, 2, and 3A.
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