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  • 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.

  • Histologic transformation to diffuse large B-cell lymphoma (DLBCL) occurs at a rate of about 3% per year.


  • FL accounts for approximately 20% of adult non-Hodgkin lymphomas (NHLs) in the Western world, with an annual incidence of approximately 2.7 per 100,000 people per year in the United States.

  • The disease is uncommon in persons younger than age 20 years. Pediatric cases appear to represent a separate disease entity (see below under “Rare Variants of Follicular Lymphoma”).

  • There is a familial predisposition.

    — A genome-wide association study identified variants in the major histocompatibility region and other regions that predispose to FL.

  • There is an increased risk in women with Sjögren syndrome.

  • There is an increased incidence in heavy smokers, particularly in women.

  • Pesticides have been implicated in some studies.


  • 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 lymphomatous mass.

  • Approximately 10% to 20% of patients present with B symptoms (fever, drenching night sweats, or loss of 10% of their body weight).


  • 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.

  • A predominantly nodular lymph node pattern is evident on biopsy; however, the neoplastic follicles are distorted, and as the disease progresses, the malignant follicles efface the nodal architecture (Figure 62–1).

    — The follicular pattern can be highlighted by CD23 staining for follicular dendritic cells.

  • Three grades of FL are recognized based on the proportion of centroblasts (ie, large noncleaved follicular center cells) detected microscopically:

    — Grade 1: 0 to 5 centroblasts per high-power field

    — Grade 2: 6 to 15 centroblasts per high-power field

    — Grade 3: greater than 15 centroblasts per high-power field (3A, with mixture of centrocytes and centroblasts, and 3B, with sheets of centroblasts)

  • Grade 3B FL behaves aggressively and should be treated with anthracycline-containing regimens (eg, rituximab, cyclophosphamide, hydroxydaunorubicin [doxorubicin], vincristine [Oncovin], prednisone [R-CHOP]), similar to DLBCL.

  • FL cells typically express monoclonal surface immunoglobulin (Ig) M (+/– IgD, IgG, and rarely IgA).

  • FL cells usually express the B-cell antigens CD19, CD20, CD22, and CD79a.

  • FL cells usually express the germinal center ...

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