Difference between revisions of "Follicular lymphoma"

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'''Follicular lymphoma''', abbreviated '''FL''', is a very common non-Hodgkin lymphoma.  It is a [[small cell lymphoma]] and usually has an indolent behaviour.
{{ Infobox diagnosis
| Name      = {{PAGENAME}}
| Image      = Follicular lymphoma -- low mag.jpg
| Width      =
| Caption    = Follicular lymphoma. [[H&E stain]].
| Synonyms  =
| Micro      = 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)
| Subtypes  =
| LMDDx      = [[diffuse large B-cell lymphoma]], other [[small cell lymphomas]], reactive follicular hyperplasia
| Stains    =
| IHC        = CD20 +ve, CD10 +ve, BCL-6 +ve, BCL-2 +ve
| EM        =
| Molecular  = t(14;18)(q32;q21) / IGH-BCL2
| IF        =
| Gross      = white lesions +/-subtle fine nodularity (fish flesh-like appearance)
| Grossing  =
| Site      = [[lymph node]], [[spleen]], [[bone marrow]], others
| Assdx      =
| Syndromes  =
| Clinicalhx =
| Signs      =
| Symptoms  =
| Prevalence = common
| Bloodwork  =
| Rads      =
| Endoscopy  =
| Prognosis  = moderate to good
| Other      =
| ClinDDx    = other causes of lymphadenopathy - other [[lymphoma]]s, metastatic carcinoma
| Tx        =
}}
'''Follicular lymphoma''', abbreviated '''FL''', is a very common [[non-Hodgkin lymphoma]].  It is a [[small cell lymphoma]].


==General==
==General==
*A very common type of lymphoma.
*A very common type of lymphoma.
*Expresses BCL2,<ref name=pmid18359244>{{cite journal |author=Vitolo U, Ferreri AJ, Montoto S |title=Follicular lymphomas |journal=Crit. Rev. Oncol. Hematol. |volume=66 |issue=3 |pages=248–61 |year=2008 |month=June |pmid=18359244 |doi=10.1016/j.critrevonc.2008.01.014 |url=}}</ref> like many other small cell lymphomas.
*Moderate prognosis - overall five year survival ~ 66% in one cohort without transformation.<ref name=pmid23897955>{{Cite journal | last1 = Link | first1 = BK. | last2 = Maurer | first2 = MJ. | last3 = Nowakowski | first3 = GS. | last4 = Ansell | first4 = SM. | last5 = Macon | first5 = WR. | last6 = Syrbu | first6 = SI. | last7 = Slager | first7 = SL. | last8 = Thompson | first8 = CA. | last9 = Inwards | first9 = DJ. | title = 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. | journal = J Clin Oncol | volume = 31 | issue = 26 | pages = 3272-8 | month = Sep | year = 2013 | doi = 10.1200/JCO.2012.48.3990 | PMID = 23897955 }}
</ref>  
*May transform to a more aggressive lymphoma, e.g. [[diffuse large B-cell lymphoma]].
**Prognosis after transformation significantly worse - five year survival ~ 22%.<ref name=pmid23897955/>
**Approximately 2% transform per year, or 10.7% in five years.<ref name=pmid23897955/>
 
==Gross==
*Lymph node enlargement.
*Classically white and uniform - usually described as ''fish flesh-like''.
**May have a vague nodularity.
 
===Images===
<gallery>
Image:Lymphoma_macro.jpg | FL in a lymph node. (WC)
Image:Follicular_lymphoma,_spleen.jpg | FL in the [[spleen]]. (WC)
</gallery>


==Microscopic==
==Microscopic==
Line 22: Line 68:


===Images===
===Images===
<gallery>
Image: Follicular lymphoma -- very low mag.jpg | FL - very low mag.
Image: Follicular lymphoma -- low mag.jpg | FL - low mag.
Image: Follicular lymphoma -- intermed mag.jpg | FL - intermed. mag.
Image: Follicular lymphoma -- high mag.jpg | FL - high mag.
Image: Follicular lymphoma -- very high mag.jpg | FL - very high mag.
</gallery>
<gallery>
Image:Follicular_Lymphoma,_Paratrabecular_Involvement_of_Bone_Marrow_(5691578596).jpg | FL - bone marrow. (WC/euthman)
</gallery>
www:
*[http://www.flickr.com/photos/euthman/3311641845/ Follicular lymphoma - bone marrow (flickr.com)].
*[http://www.flickr.com/photos/euthman/3311641845/ Follicular lymphoma - bone marrow (flickr.com)].
*[http://library.med.utah.edu/WebPath/HEMEHTML/HEME034.html Follicular lymphoma (utah.edu)].
*[http://library.med.utah.edu/WebPath/HEMEHTML/HEME034.html Follicular lymphoma (utah.edu)].
Line 31: Line 88:


Notes:
Notes:
*Significant interobserver variability.<ref>DG. 17 August 2010.</ref>
*Significant interobserver variability.<ref>Good, D. 17 August 2010.</ref>
*Grade 1 & Grade 2 lumped together.
*Grade 1 & Grade 2 lumped together.
*One should evaluate 10 HPFs.
*One should evaluate 10 HPFs.
Line 43: Line 100:
==IHC==
==IHC==
Features:<ref name=pmid18359244/>
Features:<ref name=pmid18359244/>
*CD10 +ve.
*[[CD10]] +ve.
*BCL6 +ve.
*BCL6 +ve.


Line 55: Line 112:
*CD11c -ve -- flow cytometry only.
*CD11c -ve -- flow cytometry only.
*CD21 -ve in tumour cells; highlights follicular dendritic cells.
*CD21 -ve in tumour cells; highlights follicular dendritic cells.
 
*BCL2 +ve<ref name=pmid18359244>{{cite journal |author=Vitolo U, Ferreri AJ, Montoto S |title=Follicular lymphomas |journal=Crit. Rev. Oncol. Hematol. |volume=66 |issue=3 |pages=248–61 |year=2008 |month=June |pmid=18359244 |doi=10.1016/j.critrevonc.2008.01.014 |url=}}</ref> - like many other small cell lymphomas.
Image:
**Usually negative in benign germinal centres.
*[http://www.pathpedia.com/education/eatlas/histopathology/lymph_node/follicular_lymphoma/follicular-lymphoma-%5B16-ln021_cd21%5D.jpeg Follicular lymphoma - CD21 (pathpedia.com)].


A panel to work-up:
A panel to work-up:
*BCL2, BCL6, CD3, CD5, CD10, CD20, CD23, cyclin D1.
*BCL2, BCL6, CD3, CD5, CD10, CD20, CD23, cyclin D1.
===Images===
<gallery>
Image: Follicluar lymphoma - bcl2 -- low mag.jpg | FL - BCL2 - low mag.
Image: Follicular lymphoma - control bcl2 -- low mag.jpg | FL - BCL2 control - low mag.
</gallery>
www:
*[http://www.pathpedia.com/education/eatlas/histopathology/lymph_node/follicular_lymphoma/follicular-lymphoma-%5B16-ln021_cd21%5D.jpeg Follicular lymphoma - CD21 (pathpedia.com)].


==Molecular==
==Molecular==

Latest revision as of 17:34, 20 March 2015

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.

General

  • 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]

Gross

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

Images

  • FL in a lymph node. (WC)

  • FL in the spleen. (WC)

Microscopic

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).

Note:

  • 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.

DDx:

Images

  • FL - very low mag.

  • FL - low mag.

  • FL - intermed. mag.

  • FL - high mag.

  • FL - very high mag.

  • FL - bone marrow. (WC/euthman)

www:

Grading

  • 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).

Notes:

  • 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.

IHC

Features:[5]

Others:

  • 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.

Images

  • FL - BCL2 - low mag.

  • FL - BCL2 control - low mag.

www:

Molecular

  • 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]

Sign out

RETROPERITONEAL MASS, RIGHT, CORE BIOPSIES:
- NON-HODGKIN B-CELL LYMPHOMA, FAVOUR FOLLICULAR LYMPHOMA.

COMMENT:
Morphology:
-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

References

  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. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001121/.
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