What is the WHO/REAL histologic grading system for follicular lymphoma (non-Hodgkin lymphoma)?

Updated: Feb 11, 2020
  • Author: Francisco J Hernandez-Ilizaliturri, MD; Chief Editor: Koyamangalath Krishnan, MD, FRCP, FACP  more...
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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 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]

The 2016 WHO classification of mature B-cell neoplasms includes the following subtypes of follicular lymphoma (FL)1: 

  • In situ follicular neoplasia – Renamed from in situ FL because of the low risk of progression to lymphoma
  • Duodenal-type FL –  Localized process with low risk for dissemination
  • Pediatric-type FL –  Localized clonal proliferation with excellent prognosis; a conservative therapeutic approach (with no treatment beyond excision) may be sufficient; occurs in children and young adults, rarely in older individuals; this is a nodal disease characterized by large, expansile, highly proliferative follicles that often have prominent blastoid follicular center cells rather than classic centroblasts (or centrocytes);  BCL2 rearrangements must not be present, but there may be some BCL2 protein expression;  BCL6 and MYC rearrangements are lacking
  • Predominantly diffuse FL with 1p36 deletion – Accounts for some cases of diffuse FL, lacks BCL2 rearrangement; presents as localized mass, often inguinal

The WHO classification also includes follicular T-cell lymphoma as a provisional entity. To qualify for this designation, the neoplastic cells should express at least 2 or 3 T-follicular helper–related antigens, including CD279/PD1, CD10, BCL6, CXCL13, ICOS, SAP, and CCR5. [1]

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