Follicular Lymphoma (Non-Hodgkin Lymphoma) Staging 

Updated: Apr 13, 2016
  • Author: Francisco J Hernandez-Ilizaliturri, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP  more...
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Classification and Staging Systems for Follicular Lymphoma

The World Health Organization (WHO)/Revised European-American Lymphoma (REAL) classification and the Cotswolds modified Ann Arbor staging system for follicular lymphoma (non-Hodgkin lymphoma [NHL]) are provided below, [1, 2] as well as the Follicular Lymphoma International Prognostic Index (FLIPI) score. [3]

WHO/REAL classification

Follicular lymphoma (FL) is classified into the following 3 histologic grades [1, 2] :

  • Grade 1: 0-5 centroblasts/high-power field (HPF)

  • Grade 2: 6-15 centroblasts/HPF

  • Grade 3: > 15 centroblasts/HPF

The 2008 WHO classification consolidates cases with few centroblasts as FL grade 1-2 (low-grade). FL grade 3 is divided into 3A and 3B (absence of centrocytes). Diffuse areas in any grade 3 classification should be treated according to diffuse large B-cell lymphoma (DLBCL). [1]

Cotswolds modification of Ann Arbor staging system

The Cotswolds modification maintains the original 4-stage clinical and pathologic staging framework of the Ann Arbor staging system but also adds information regarding the prognostic significance of bulky disease (denoted by an X designation) and regions of lymph node involvement (denoted by an E designation). [4]

The A and B designations denote the absence or presence of symptoms, respectively; the presence of symptoms correlates with treatment response. The importance of imaging modalities, such as computed tomography (CT) scanning, is also underscored. [4]

Table. Cotswolds modification of Ann Arbor staging system (Open Table in a new window)


Area of involvement


Single lymph node group


Multiple lymph node groups on same side of diaphragm


Multiple lymph node groups on both sides of diaphragm


Multiple extranodal sites or lymph nodes and extranodal disease


Bulk > 10 cm


Extranodal extension or single isolated site of extranodal disease


B symptoms: weight loss > 10%, fever, drenching night sweats

FLIPI score

The development and validation of an accurate and easily available prognostic index for FL has facilitated the development of treatment algorithm plans, enabled the cross-talk between investigators, and improved understanding of the results of clinical studies.

Briefly, the FL International Prognostic Index (FLIPI) score was designed by studying clinical characteristics of 1795 newly diagnosed cases of FL between 1985 and 1992 across 27 different cancer centers. Several clinical parameters known to affect the outcome of FL patients were tested in the patient population using a univariate and multivariate analysis. The statistical analysis identified 5 variables that strongly and independently were associated with a poor clinical outcome, as provided below. [3]

Factors (1 point for each variable present) [3] :

  • Age > 60y

  • Ann Arbor Stage III-IV

  • Hemoglobin level < 12 g/dL

  • Lactate dehydrogenase (LDH) level > upper limit of normal (ULN)

  • ≥ 4 nodal sites of disease

Risk category (factors) [3] :

  • Low risk (0 or 1)

  • Intermediate risk (2)

  • High risk (> 3)