Follicular lymphoma

Follicular lymphoma, abbreviated FL, is a very common non-Hodgkin lymphoma. It is a small cell lymphoma and usually has an indolent behaviour.

General

• A very common type of lymphoma.

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, i.e. the lymphoma cells are found adjacent to the bone spicules.

DDx:

• Reactive follicular hyperplasia.
• Diffuse large B-cell lymphoma - esp. for the grade 3B.

Images

• Follicular lymphoma - bone marrow (flickr.com).
• Follicular lymphoma (utah.edu).

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.
• 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:

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

IHC

Features:

• CD10 +ve.
• BCL6 +ve.

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 - like many other small cell lymphomas.
  • Usually negative in germinal centres.

Image:

• Follicular lymphoma - CD21 (pathpedia.com).

A panel to work-up:

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

Molecular

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

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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

• Small cell lymphomas.
• Lymphoma.
• Lymph node pathology.