The CD20 antigen is a membrane-embedded, non-glycosylated phosphoprotein, 33-37 kDa. CD20 functions as a Ca2+-permeable cation channel, involved in the regulation of B-cell activation, proliferation and differentiation. CD20 appears on the surface of the pre-B lymphocyte between the time of light chain rearrangement and expression of intact surface immunoglobulin and is lost just before terminal B-cell differentiation into plasma cells. Surface expression of CD20 on activated B cells is approximately 4-fold greater than that found on resting B cells.
CD20 is virtually specific for normal B-cells. A weak expression has been demonstrated in a subpopulation of T-cells, but not in any other cell type.
CD20 is expressed in the large majority of cases of B-cell leukaemia/lymphoma. Early stage precursor B lymphoblastic leukaemia/lymphoma may be negative, and chronic lymphocytic leukaemia/small cell lymphoma may show a weak staining. Plasma cell neoplasms are as a rule CD20 negative. However, a special type of CD20 positive myelomas account for 10-20% of the cases. These myelomas are generally characterized by a more mature plasma cell morphology, chromosomal translocation t(11;14) resulting in cyclin D1 expression, and a better prognosis.
T-cell lymphomas are almost always negative, but CD20 has been demonstrated in few cases of various types of T-cell lymphoma. In Hodgkin lymphoma, the nodular lymphocyte-predominant subtype shows CD20 staining of L&H cells in most cases, while Reed-Sternberg cells in the other subtypes reveal CD20 positivity in about 40, albeit in a minority of neoplastic cells. Acute myeloid leukaemia is CD20 positive in few cases, while blastic transformation in chronic myeloid leukaemia is accompanied by CD20 positivity in about 30%. Thymoma may reveal CD20 positivity in a spindle cell component.
In patients treated with retuximab (a humanized anti-CD20 antibody) for malignant B-cell lymphoma, the CD20 epitopes disappear (both in normal and neoplastic B-cells) as a result of down-modulation of CD20 m-RNA in the cells. This process is potentially reversible. During treatment, the B-cells can be identified with other antibodies, e.g., anti-CD79a.
Together with CD79a, CD20 is one of the most important markers for the identification of B-cell neoplasms as outlined above.
Tonsil and appendix are appropriate controls: The mantle zone B-cells and the germinal centre B-cells must show a very strong staining reaction. No other cells should stain.
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