Surgical Pathology Criteria

Follicular Lymphoma

Differential Diagnosis


Small B Cell Lymphomas

  SLL/CLL Mantle Marginal Zone Lymphoplasmacytic Follicular
CD23 85% 2% 8% 0-30% on immunohistology but up to 60% weak positive on flow 0-25%
CD5 80% 80% 0% 5% 0%
bcl1 2% 85% 0% 0% 0%
CD10 0% 2% 2% 3% 85%
CD43 80% 85% 35% 10-30% 7%
bcl2 95% 95% 65-90% >50% 90%

Reactive Follicular Hyperplasia Follicular Lymphoma
Follicles not densely packed (30/40x field) Follicles densely packed (47/40x field)
Normal architecture retained Obliterates normal architecture
Variable size and shape of follicles Uniform size and shape of follicles
Well defined mantles Poorly defined mantles
Extracapsular follicles infrequent Extracapsular follicles may be seen
Many tingible body macrophages Infrequent tingible body macrophages
Mixed population in follicles Uniform population of atypical cells
Interfollicular cells bland Interfollicular cells may be small, cleaved
bcl2 negative in follicles bcl2 positive in follicles (100% in grade 1)
Light chains mixed (variably demonstrable in paraffin) Light chains monotypic (variably demonstrable in paraffin)
Germ line Ig genes Ig gene rearrangement
Not all cases will demonstrate all of the above architectural and cytologic features


Castleman disease Follicular Lymphoma
Numerous small depleted follicles Cellular follicles
Prominent mantles with concentric layering Mantles generally indistinct
Penetrating hyalinized vessels Penetrating vessels rare
Immunologic and genotypic features as above. A very rare hyaline vascular variant of follicular lymphoma exists.


Progressive Transformation of Germinal Centers Follicular Lymphoma
Small number of large atypical nodules Many atypical small nodules
Surrounding typical reactive follicles Surrounding reactive follicles unusual
Nodules predominantly composed of small non-atypical lymphocytes Nodules composed of atypical lymphocytes
Immunologic and genotypic features as above. Floral variant of follicular lymphoma may mimic PTGC but generally is part of a process that effaces the normal nodal architecture and is usually composed of large atypical cells.


Nodular Lymphocyte Predominant Hodgkin Lymphoma Follicular Lymphoma
Limited number of large nodules Innumerable small nodules
Scattered large cells in background of normal small cells Nearly all cells atypical, small or large
EMA positive large cells (variably) EMA negative
Light chain polytypia or negative Light chain monotypia or negative
CD57+ cells increased, with ringing around large cells No CD57 increase
Both contain follicles composed predominantly of blc2+ B cells.


Follicular Lymphoma Mantle Cell Lymphoma
Distinct nodules composed of cleaved cells Residual germinal centers may simulate nodules
Mantle pattern surrounding germinal center rare Mantle pattern frequent
bcl1 negative bcl1 85%
CD5 negative CD5 80%
CD43 7% CD43 85%
CD10 85% CD10 2%
Follicular dendritic network intact FDC network disrupted or confined to germinal centers
bcl2 92% bcl2 95%
Floral variant of follicular lymphoma surrounds and invades follicles resulting in a lobulated follicle rather than the more even obliteration by mantle cell lymphoma


Extranodal Marginal Zone Lymphoma Follicular Lymphoma
Polymorphous population Uniform population of atypical small lymphocytes
Centers of nodules may contain bcl2 negative residual germinal centers Centers of nodules composed of bcl2 positive small atypical lymphocytes
Plasmacytoid differentiation frequent Plasmacytoid differentiation rare
Lymphoepithelial lesions may be seen No lymphoepitelial lesions
CD10 2% CD10 85%


Follicular Lymphoma SLL/CLL
Distinct nodular pattern Vague proliferation centers
Nodules composed of cleaved cells Nodules composed of prolymphocytes and paraimmunoblasts
Interfollicular cleaved cells common Background sheets of regular small lymphocytes
CD23 0-38% CD23 85%
CD5 negative CD5 80%
CD43 7% CD43 80%
CD10 85% CD10 0%
bcl2 stains over 90% of both

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