Definition/General
Introduction:
Follicular lymphoma is the second most common non-Hodgkin lymphoma in Western countries, representing 20-25% of all NHL
It is an indolent B-cell neoplasm characterized by a follicular growth pattern and t(14;18) translocation.
Origin:
Arises from germinal center B-cells
Characterized by blocked apoptosis due to BCL2 overexpression
May transform to diffuse large B-cell lymphoma (30% lifetime risk).
Classification:
WHO Classification grades based on centroblast count: Grade 1-2 (indolent), Grade 3A (indolent), Grade 3B (aggressive)
FLIPI score predicts prognosis.
Epidemiology:
Median age 60 years
Slight female predominance
Higher incidence in Western countries
Rare in Asia and Africa
Environmental factors may play a role.
Clinical Features
Presentation:
Painless lymphadenopathy (80% of cases)
Waxing and waning adenopathy characteristic
Advanced stage at presentation (Stage III-IV in 85%)
Bone marrow involvement common.
Symptoms:
Painless lymph node enlargement
B-symptoms uncommon (20%)
Fatigue (if anemic)
Abdominal distension (splenomegaly)
Usually asymptomatic for years.
Risk Factors:
Environmental exposures (pesticides, solvents)
Occupational factors
Autoimmune disorders
Family history of lymphoma
HCV infection in some regions.
Screening:
No specific screening
Diagnosed by lymph node biopsy
Staging by CT/PET scans
Bone marrow biopsy usually positive
β2-microglobulin elevated.
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Gross Description
Appearance:
Multiple enlarged lymph nodes
Cut surface shows tan to gray nodular pattern
Soft consistency
Pseudofollicular architecture may be visible grossly.
Characteristics:
Node size typically 2-5 cm
Multinodal involvement
Soft, fleshy consistency
Nodular cut surface
Capsule usually intact.
Size Location:
Involves multiple lymph node regions
Cervical, axillary, inguinal, and abdominal nodes common
Extranodal sites: bone marrow, spleen, liver, GI tract.
Multifocality:
Multifocal disease typical at presentation
Bone marrow involvement in 60-70%
Splenic involvement common
CNS involvement rare.
Microscopic Description
Histological Features:
Nodular (follicular) growth pattern with closely packed neoplastic follicles
Absence of mantle zones
Follicles composed of centrocytes and centroblasts.
Cellular Characteristics:
Centrocytes: Small cleaved cells with irregular nuclei
Centroblasts: Large cells with round nuclei and multiple nucleoli
Mixture defines grade.
Architectural Patterns:
Follicular pattern (nodular)
Folliculocentrofollicular pattern
Diffuse areas possible (transformation)
Sclerosis may be present.
Grading Criteria:
Grade 1: 0-5 centroblasts/hpf
Grade 2: 6-15 centroblasts/hpf
Grade 3A: >15 centroblasts/hpf with centrocytes present
Grade 3B: Sheets of centroblasts.
Immunohistochemistry
Positive Markers:
CD20 positive
CD10 positive (85%)
BCL6 positive (90%)
BCL2 positive (85-90%)
CD19 positive
PAX5 positive.
Negative Markers:
CD5 negative
CD23 negative
Cyclin D1 negative
CD3 negative
TdT negative
MUM1 negative (usually).
Diagnostic Utility:
BCL2 positivity in follicular architecture highly suggestive
CD10/BCL6 support germinal center origin
Helps distinguish from reactive hyperplasia.
Molecular Subtypes:
High BCL2 expression correlates with t(14;18)
Ki-67 proliferation index low in Grade 1-2
Flow cytometry shows monoclonal B-cells.
Molecular/Genetic
Genetic Mutations:
t(14;18)(q32;q21) in 80-90% of cases
BCL2 gene rearrangement
KMT2D mutations (80%)
CREBBP mutations (65%)
TP53 mutations (transformation).
Molecular Markers:
BCL2 protein overexpression
IGH-BCL2 fusion transcript
Clonal immunoglobulin gene rearrangements
Chromosomal instability at transformation.
Prognostic Significance:
FLIPI score incorporates age, stage, hemoglobin, LDH, nodal areas
High-risk patients have worse prognosis
Transformation to DLBCL major concern.
Therapeutic Targets:
CD20-targeted therapy (rituximab)
BCL2 inhibitors (venetoclax)
mTOR inhibitors
Radioimmunotherapy
Lenalidomide for relapsed disease.
Differential Diagnosis
Similar Entities:
Reactive follicular hyperplasia
Mantle cell lymphoma
Marginal zone lymphoma
Nodal marginal zone lymphoma
Transformed follicular lymphoma.
Distinguishing Features:
FL: BCL2+, CD10+, t(14;18)+, back-to-back follicles
Reactive: BCL2-, mantle zones present, mixed cell population
MCL: Cyclin D1+, CD5+.
Diagnostic Challenges:
Distinction from reactive hyperplasia in young patients
Recognition of transformation
Grade 3B vs DLBCL
Follicular areas in DLBCL.
Rare Variants:
Primary cutaneous follicle center lymphoma
Pediatric follicular lymphoma
In situ follicular neoplasia
Duodenal follicular lymphoma.
Sample Pathology Report
Template Format
Sample Pathology Report
Complete Report: This is an example of how the final pathology report should be structured for this condition.
Specimen Information
[specimen type], measuring [size] cm
Diagnosis
Follicular Lymphoma, Grade [1/2/3A/3B]
WHO Classification
WHO Classification: Follicular Lymphoma, Grade [X]
Histological Features
Shows follicular (nodular) architecture with [centroblast count] centroblasts per high-power field
Immunohistochemistry
CD20+, CD10+, BCL6+, BCL2+, CD5-, CD23-, Cyclin D1-
Proliferation Index
Ki-67 proliferation index: [X]% (low in Grade 1-2)
Molecular Studies
FISH: t(14;18) [positive/negative], Flow cytometry: [monoclonal B-cell population]
Grading Criteria
Centroblast count: [X] per hpf, Grade [1/2/3A/3B]
Risk Stratification
FLIPI score: [low/intermediate/high] risk
Prognostic Factors
Prognostic factors: [grade, stage, FLIPI score, transformation risk]
Final Diagnosis
Final diagnosis: Follicular Lymphoma, Grade [X], [stage if known]