Follicular lymphoma

Overview

•Most common indolent lymphoma; second most common NHL overall (~20-25% of NHL)

•Median age at diagnosis ~60 years; rare under 40

•Arises from germinal centre B-cells; defined by t(14;18)(q32;q21) - brings BCL-2 under immunoglobulin heavy chain promoter → constitutive BCL-2 overexpression → block in apoptosis → accumulation of abnormal follicles

•Immunophenotype: BCL-2+, CD10+, CD20+, CD19+, BCL-6+; CD5- and CD23- (distinguishes from CLL and mantle cell lymphoma)

Presentation

•Painless lymphadenopathy - hallmark; peripheral (cervical, axillary, inguinal); may have waxed and waned over months/years

•B symptoms (fever >38°C, drenching night sweats, weight loss >10% in 6 months) - minority at diagnosis; indicate higher-burden disease

•Splenomegaly - abdominal discomfort, early satiety

•Cytopenias from bone marrow involvement - anaemia, thrombocytopenia, neutropenia

•>80% present at Stage III or IV; bone marrow involved in 50-70%

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Rapidly enlarging nodes, new B symptoms, rising LDH, or new extranodal disease = suspect histological transformation to DLBCL. Requires PET-CT and rebiopsy of most metabolically active site.

Investigations

•Gold standard diagnosis: excisional lymph node biopsy - histology, grade, immunohistochemistry (BCL-2, CD10, CD20, BCL-6)

•FBC - anaemia, thrombocytopenia, lymphocytosis

•LDH and beta-2 microglobulin - prognostic; elevated LDH raises concern for transformation

•CT chest/abdomen/pelvis - staging, assess bulky disease

•PET-CT - staging, identify highest-grade site for biopsy, assess treatment response

•Bone marrow trephine biopsy - assess marrow involvement

•FISH/cytogenetics - confirm t(14;18)

Management

•No GELF criteria met: active watch and wait - early treatment of asymptomatic disease does not improve overall survival

•Stage I-II localised disease (~10-15%): involved-field radiotherapy - potentially curative intent

•Advanced disease meeting GELF criteria: rituximab-based chemoimmunotherapy (e.g. R-CHOP, R-bendamustine)

•Grade 3b follicular lymphoma: managed as DLBCL with curative intent using R-CHOP

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Treatment for low-grade follicular lymphoma is not curative in most advanced cases - goal is disease control and prolonging remission. CD20 positivity underpins rituximab therapy.

Scoring and criteria

•FLIPI score (prognostic): 5 factors - age >60, Stage III/IV, Hb <120 g/L, >4 nodal sites, elevated LDH

•Score 0-1 = low risk (~70% 10-year survival); score 2 = intermediate (~50%); score 3-5 = high risk (~35%)

•GELF criteria (treatment threshold) - treat if ANY ONE present:

•Nodal or extranodal mass >7 cm

•≥3 nodal sites each >3 cm

•Symptomatic splenomegaly

•Pleural effusion or peritoneal ascites

•Cytopenias: Hb <10 g/dL, platelets <100 × 10⁹/L, neutrophils <1.5 × 10⁹/L

•Leukaemic phase (>5 × 10⁹/L circulating lymphoma cells)

•B symptoms or threatened organ function

Complications and prognosis

•Histological transformation to DLBCL - ~2-3% per year (cumulative lifetime risk ~30-40%); significantly worse prognosis post-transformation

•Cytopenias from marrow infiltration; immunosuppression - disease-related (hypogammaglobulinaemia) and treatment-related (rituximab → B-cell depletion, hepatitis B reactivation risk)

•Autoimmune haemolytic anaemia and immune thrombocytopenia may complicate the lymphoma

•Median overall survival >15-20 years with modern rituximab-based therapy; remains incurable in most advanced low-grade cases

•Complete metabolic response on PET-CT after first-line treatment = best long-term outcomes