Haematological Malignancy Diagnostic Service

Follicular Lymphoma

The Concept of the Disease

In normal lymphoid tissues, germinal centres are formed by B-cells responding to antigenic stimuli. Through rapid cellular proliferation, with mutation and rearrangement of immunoglobulin genes, the population of B-cells that can respond to the antigen is expanded and the affinity of the antibodies increases. This is a pivotal step in the normal immune response.

Follicular lymphoma is a tumour of germinal centre cells. The tumour cells share many of the features of B-cells in the normal germinal centre.

How is it Diagnosed?

Lymph Node Biopsy

  • Cells with the morphology of germinal centre cells forming structurally abnormal B-cell follicles and spreading into spaces normally occupied by other cell types
  • Identification of an abnormal germinal centre phenotype by immunocytochemistry or flow cytometry; most importantly, demonstration of abnormal expression of the anti-apoptotic protein BCL2
  • Demonstration of B-cell monoclonality
  • Demonstration of a t(14;18) translocation which deregulates expression of the BCL2 gene
Lymph Node Morphology

Bone Marrow

  • The bone marrow is frequently involved in follicular lymphoma
  • Tumour cells tend to aggregate close to bone
Bone Marrow Trephine Morphology

What is the Clinical Outcome?

The clinical outcome is highly variable; treatment is given primarily on the basis of symptoms and 75% of patients will survive for more than 5 years.

  • Many patients require no immediate treatment or receive local radiotherapy only.
  • Most symptomatic patients have a prolonged period of remission when treated with R-CVP or R-CHOP.
  • A minority of patients have progressive or rapidly relapsing disease. In some cases the tumour undergoes a qualitative change with transformation to diffuse large B-cell lymphoma.

The standard assessment of prognosis is the follicular lymphoma international prognostic index (FLIPI).

Score FLIPI Risk Group
0 – 1 Low
2 Intermediate
≥3 High
Risk Factor Score +0 Score +1
Age (years) ≤60 >60
Stage (Ann Arbor) I or II II or IV
Number of extranodal sites 0 or 1 >1
Performance Status (ECOG) 0 or 1 >1
Serum LDH Normal Raised