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.
Selected references
Chang KL, Arber DA, Weiss LM. CD20: A review. Applied Immunohistochemistry 1996; 4:1-15. Jaffe ES, Harris NL, Stein H, Vardiman JW (Eds.) WHO Classification of Tumours. Pathology and Genetics of Tumours of Haematopoietic and Lymphoid Tissues. Lyon, IARC Press 2001. Jilani I, O'Brien S, Manshuri T, Thomas DA, Thomazy VA, Imam M, Naeem S, Verstovsek S, Kantarjian H, Giles F, Keating M, Albitar M. Transient down-modulation of CD20 by rituximab in patients with chronic lymphocytic leukemia. Blood. 2003 Nov 15;102(10):3514-20. Khalidi HS, Brynes RK, Medeiros LJ, Chang KL, Slovak ML, Snyder DS, Arber DA. The immunophenotype of blast transformation of chronic myelogenous leukemia: a high frequency of mixed lineage phenotype in "lymphoid" blasts and A comparison of morphologic, immunophenotypic, and molecular findings. Mod Pathol. 1998 Dec;11(12):1211-21. Mohrmann RL, Arber DA. CD20-Positive peripheral T-cell lymphoma: report of a case after nodular sclerosis Hodgkin's disease and review of the literature. Mod Pathol. 2000 Nov;13(11):1244-52. Zukerberg LR, Collins AB, Ferry JA, Harris NL. Coexpression of CD15 and CD20 by Reed-Sternberg cells in Hodgkin's disease. Am J Pathol. 1991 Sep;139(3):475-83.
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