Histological and Clinical Prognostic Factors in Follicular Lymphoma: Proposal for a Prognostic Model

Reviewer: Tracy d'Entremont, MD
Last Modified: December 8, 2002

Presenter: Irit Avivi
Presenter's Affiliation: University College London; UK
Type of Session: Scientific


    Follicular lymphoma (FL) is one of the most common types of non-Hodgkin's lymphoma. Despite this, prognostic models to predict patient's survival are less well established than in intermediate/high grade disease. Histological grading according to the WHO classificiation has been shown to be of prognostic value. Other histological parameters such as marginal zone differentiation and the extent of interfollicular infiltrate have been proposed but not tested in a large patient cohort with long follow-up. The aim of this study was to identify independent histological and clinical prognostic factors for predicting overall survival in FL patients.

Materials and Methods

  • 776 patients with FL registered by the British National Lymphoma Investigation between 1975- 1989
  • for 768 patients histology specimens were available
  • Cases were reviewed by two independent, blinded histopathologists for the following parameters:
    histological grade by the new WHO criteria
    exact number of centroblasts/ hi power field
    extent of interfollicular component
    presence or absence of marginal zone differentiation
  • Clinical parameters assessed at diagnosis included: age, sex, Ann Arbor Stage, ESR, lymphocyte count, albumin level, presence or absence of B symptoms, bulky disease, and extranodal disease.


  • ORR was 81% in those receiving therapy
  • With a median follow-up of 16 years,
    5-yr OS = 63%
    10-yr OS = 43%
    15-yr OS = 30%
  • In multivariate analysis, centroblasts/hi power field, age, Ann Arbor stage > 2, ESR, and albumin were shown to be the only independent risk factors (p<0.002 for all)
  • The extent of interfollicular component and the presence of marginal zone differentiation both failed to show any impact on patient's survival.

Author's Conclusions

  • A prognostic index, separating patients into 3 risk groups based on all independent prognostic factors was developed.
  • Patients with low risk disease had a 57% chance of being alive at 15 years
  • Patients with intermediate risk disease had a 35% chance of being alive at 15 years.
  • Patients with poor risk disease had a less than 10% chance of being alivea t 15 years.
  • This prognostic model which incorporates clinical and histological parameters, may predict survival and help to tailor indiviualized management.

Clinical/Scientific Implications

    This study provides us with data that WHO grade is independently associated with overall survival in FL and future prognostic models should incorporate this grading system. However, this study found that WHO grades 1 and 2 tumors had an improved survival compared with WHO grade 3. Previous studies in the literature found that grade 2 tumors had a worse prognosis, more similar to grade 3 tumors. The reason for this discrepancy is unclear and needs further evaluation.

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