CD21

CD21 is a follicular dendritic cells (FDC) marker.  It has a membranous staining pattern, but this is practically difficult to separate from a cytoplasmic pattern in lymphoid tissue.  This stain is most often used as an “architectural” marker or aberrant patterns (nodular lymphocyte predominate Hodgkin lymphoma).  There are some rare tumors of FDC, which will mark with CD21.  CD21 may rarely mark normal B-cells, and strong expression of CD21 in CLL has been associated with a most aggressive disease course (unsure if this is by flow cytometry and/or IHC). 
 
Follicular Lymphoma – It is also helpful to identify the expanded follicular dendritic meshwork in cases of follicular lymphoma (especially helpful in diagnostically challenging cases – i.e. identifying a follicular component in an otherwise diffuse process or in small needle biopsies where architecture may not be visible).
 
Angioimmunoblastic T-cell Lymphoma (AILT) – Extrafollicular dendritic cells in the paracortical region in associated with neoplastic T-cells and high endothelial venules is characteristic of AILT.  CD21 is a helpful marker to highlights the follicular dendritic component in this process.
 
Marginal Zone Lymphoma – CD21 is useful in highlighting follicular colonization by marginal zone cells, which may be obscured by morphology alone.
CD21 Normal Expression Pattern
  • Follicular Dendritic Cells
  • Rare Normal B-cells
  • Rare cases of CLL
  • Generally thought of as a better follicular dendritic marker compared to CD23 (less sensitive)
Photomicrographs
CD21 - Tonsil
CD21 highlighting the follicular dendritic meshwork in benign tonsil tissue.
References
Bone Marrow IHC.  Torlakovic, EE, et. al. American Society for Clinical Pathology Pathology Press © 2009.  pp. 64.
 
MD DY-PW, BacSc F.  A case of t (14; 18)-negative follicular lymphoma with atypical immunophenotype: usefulness of immunoarchitecture of Ki67, CD79a and follicular dendritic cell meshwork in making the diagnosis.  Malaysian Journal of Pathology. 2014. p. 125-129.
 
Harris NL, Swerdlow SH, Jaffe ES, et al. FollicularLymphoma. In: Swerdlow SH, Campo E, Harris NL,Jaffe ES, Pileri SA, Stein H, Thiele J, VardimanJW, editors. WHO classication of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon: IARC Press; 2008. p. 220–6.
 
Troxell ML, Schwartz EJ, van de Rijn M, Ross DT, Warnke RA, Higgins JP, et al. Follicular dendritic cell immunohistochemical markers in angioimmunoblastic T-cell lymphoma. Appl Immunohistochem Mol Morphol. 2005;13: 297–303.
 
Boyd SD, Natkunam Y, Allen JR, Warnke RA. Selective immunophenotyping for diagnosis of B-cell neoplasms: immunohistochemistry and flow cytometry strategies and results. Appl Immunohistochem Mol Morphol. 2013;21: 116–131. doi:10.1097/PAI.0b013e31825d550a