Follicular lymphoma

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Follicular lymphoma
Diagnosis in short

Follicular lymphoma. H&E stain.

LM Lymph node: abundant abnormally-shaped lymphoid follicles with some of the following: non-polarized mantle zone, non-polarized germinal center, loss of tingible body macrophages, sinuses effaced (lost)
LM DDx diffuse large B-cell lymphoma, other small cell lymphomas, reactive follicular hyperplasia
IHC CD20 +ve, CD10 +ve, BCL-6 +ve, BCL-2 +ve
Molecular t(14;18)(q32;q21) / IGH-BCL2
Gross white lesions +/-subtle fine nodularity (fish flesh-like appearance)
Site lymph node, spleen, bone marrow, others

Prevalence common
Prognosis moderate to good
Clin. DDx other causes of lymphadenopathy - other lymphomas, metastatic carcinoma

Follicular lymphoma, abbreviated FL, is a very common non-Hodgkin lymphoma. It is a small cell lymphoma.


  • A very common type of lymphoma.
  • Moderate prognosis - overall five year survival ~ 66% in one cohort without transformation.[1]
  • May transform to a more aggressive lymphoma, e.g. diffuse large B-cell lymphoma.
    • Prognosis after transformation significantly worse - five year survival ~ 22%.[1]
    • Approximately 2% transform per year, or 10.7% in five years.[1]


  • Lymph node enlargement.
  • Classically white and uniform - usually described as fish flesh-like.
    • May have a vague nodularity.



Features (lymph node):

  • Abundant abnormally-shaped lymphoid follicles - key feature - including some of the following:
    • Non-polarized mantle zone (normal mantle zone is usu. thicker at capsular aspect).
    • Non-polarized germinal center (normal germinal center has dark & light area).
    • Loss of tingible body macrophages.
    • Sinuses effaced (lost).


  • The intrafollicular component of the lymph node is compressed - follicles are often described as "kissing", as they nearly touch.
  • In bone marrow specimens the neoplastic cells classically have a paratrabecular arrangement,[2] i.e. the lymphoma cells are found adjacent to the bone spicules.





  • Grade 1-2: <= 22 centroblasts / HPF; where 1 HPF ~= 0.2376 mm^2 (22 mm eye piece @ 40X objective).
  • Grade 3A: >22 centroblasts / HPF; where 1 HPF ~= 0.2376 mm^2 (22 mm eye piece @ 40X objective).
  • Grade 3B: only centroblasts (within a nodular architecture).


  • Significant interobserver variability.[3]
  • Grade 1 & Grade 2 lumped together.
  • One should evaluate 10 HPFs.
  • Only centroblasts without a nodular architecture is Diffuse large B cell lymphoma (DLBCL).

The usual cut points mentioned by people with HPFitis are:[4]

  • Grade 1: 0-5 centroblasts / HPF.
  • Grade 2: 5-15 centroblasts / HPF.
  • Grade 3: >15 centroblasts / HPF.




  • CD5 -ve.
    • +ve in mantle cell lymphoma.
  • CD23 -ve/+ve.
    • +ve in CLL.
  • CD43 -ve.
    • +ve in mantle cell lymphoma, marginal zone lymphoma.
  • CD11c -ve -- flow cytometry only.
  • CD21 -ve in tumour cells; highlights follicular dendritic cells.
  • BCL2 +ve[5] - like many other small cell lymphomas.
    • Usually negative in benign germinal centres.

A panel to work-up:

  • BCL2, BCL6, CD3, CD5, CD10, CD20, CD23, cyclin D1.




  • t(14;18)(q32;q21)/IGH-BCL2 in 70-95% of cases.[5]
    • Should not be confused with t(14;18)(q32;q21)/IGH-MALT1 seen in MALT lymphomas.[6]

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-Small cells: size ~ mature lymphocytes, quantity - many, angular and round.
-Large cells (intermixed with small cells): size ~1.5-2x mature lymphocyte, 
small nucleoli, moderate quantity of grey/basophilic cytoplasm, moderate 
nuclear pleomorphism.
-Architecture: no gland formation, discohesive, no follicles apparent, no sheets 
of large cells.
-Mitoses are uncommon.

Immunohistochemical stains (tumour cells):
Positive: CD45 (strong, membranous/cytoplasmic), CD20 (strong, membranous/cytoplasmic),
BCL-2 (strong, membranous/cytoplasmic), CD10 (strong, membranous), BCL-6 (moderate,
patchy, nuclear).

Negative: pankeratin, CD3, CD5, CD30, CD21 (follicular dendritic cells not apparent),
CD23 (scattered, rare).

Ki-67: highlights the large cells, primarily -- 5-35% of cells within the core.

The findings favour a follicular lymphoma, based on the cellular morphology and
immunostains; however, they are limited by the type of tissue sampling (core biopsy).
Clinical correlation is suggested.

See also


  1. 1.0 1.1 1.2 Link, BK.; Maurer, MJ.; Nowakowski, GS.; Ansell, SM.; Macon, WR.; Syrbu, SI.; Slager, SL.; Thompson, CA. et al. (Sep 2013). "Rates and outcomes of follicular lymphoma transformation in the immunochemotherapy era: a report from the University of Iowa/MayoClinic Specialized Program of Research Excellence Molecular Epidemiology Resource.". J Clin Oncol 31 (26): 3272-8. doi:10.1200/JCO.2012.48.3990. PMID 23897955.
  2. Iancu, D.; Hao, S.; Lin, P.; Anderson, SK.; Jorgensen, JL.; McLaughlin, P.; Medeiros, LJ. (Feb 2007). "Follicular lymphoma in staging bone marrow specimens: correlation of histologic findings with the results of flow cytometry immunophenotypic analysis.". Arch Pathol Lab Med 131 (2): 282-7. doi:10.1043/1543-2165(2007)131[282:FLISBM]2.0.CO;2. PMID 17284114.
  3. Good, D. 17 August 2010.
  4. Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 813. ISBN 978-0781740517.
  5. 5.0 5.1 5.2 Vitolo U, Ferreri AJ, Montoto S (June 2008). "Follicular lymphomas". Crit. Rev. Oncol. Hematol. 66 (3): 248–61. doi:10.1016/j.critrevonc.2008.01.014. PMID 18359244.
  6. Bacon CM, Du MQ, Dogan A (April 2007). "Mucosa-associated lymphoid tissue (MALT) lymphoma: a practical guide for pathologists". J. Clin. Pathol. 60 (4): 361–72. doi:10.1136/jcp.2005.031146. PMC 2001121. PMID 16950858. //