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CD Markers
CD25
Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 9 March 2013, last major update December 2011
Copyright: (c) 2002-2013, PathologyOutlines.com, Inc.
General
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● Marker for hairy cell leukemia and systemic mastocytosis
Terminology
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● Also called IL2 receptor alpha chain, IL2RA and TAC antigen
Physiology
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● Exists in at least 3 forms: a high affinity dimer, an intermediate affinity monomer (beta subunit), and a low affinity monomer (alpha subunit)
● Considered an activation antigen (also CD30)
● CD4+ CD25+ cells are regulatory T cells (Treg) that (a) suppress the activation of self-reactive T cells and prevent autoimmunity (diagram), (b) may prevent cytotoxic T cells from killing tumor cells (J Hepatol 2006;45:254,
Zhongguo Shi Yan Xue Ye Xue Za Zhi 2006;14:119) and (c) suppress immune cells reactive to host antigens and prevent graft versus host disease
(Semin Cancer Biol 2006;16:150)
● CD4+ CD25+ cells also suppress NK cells (Proc Natl Acad Sci USA 2006;103;5460, J Immunol 2006;176:1582) and may act directly on B cells (Blood 2006;107:3925)
● CD25 shows variability in flow cytometry expression between specimens from same patient (Am J Clin Path 2002;117:615)
Clinical features
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● Coexpression with CD134 on memory T cells is a marker for type 1 diabetes associated T cell immunity (Diabetes 2006;55:50)
● High levels by flow cytometry are associated with advanced stage in esophageal and gastric cancer
(Cancer Immunol Immunother 2005 23;1)
● High CD25 expression is associated with advanced cutaneous T cell lymphoma and with clinical response to denileukin diftitox therapy, a recombinant fusion protein of diphtheria toxin and IL-2, which binds to CD25
(J Invest Dermatol 2006;126:575)
● Anti-CD25 antibody may be useful to treat fulminating ulcerative colitis in children (J Pediatr Gastroenterol Nutr 2006;42:245), for renal or other solid organ transplants to prevent rejection (Transplant Proc 2005;37:3736)
Uses by Pathologists
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● Marker for hairy cell leukemia (present in classic disease, not in variant hairy cell leukemia or other CD103+ lymphoproliferative disorders, Am J Clin Pathol 2009;131:586)
● Diagnose systemic mastocytosis: (a) as part of panel with tryptase and CD117 in suspected cases (Am J Clin Pathol 2009;132:438), (b) if present in GI mucosal mast cells (Am J Surg Pathol 2007;31:1669)
● CD25+ cutaneous mast cells in urticaria pigmentosa may predict subsequent systemic mastocytosis (Am J Surg Pathol 2008;32:139)
● Part of diagnostic criteria for hemophagocytic lymphohistiocytosis is soluble CD25/IL2 receptor >= 2,400 U/ml (Pediatr Blood Cancer 2007;48:124, free full text)
Micro images
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Acquired ocular toxoplasmosis

Adult T cell leukemia/lymphoma (HTLV1+)
Cutaneous T cell lymphoma
Hairy cell leukemia

Hodgkin lymphoma

Mastocytosis
Positive staining - normal
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● Activated B and T cells, macrophages, osteoblasts; some thymocytes, some myeloid precursors and some oligodendocytes; basophils have dim staining by flow cytometry (Arch Pathol Lab Med 2008;132:813)
Positive staining - disease
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● Hairy cell leukemia (most, Am J Clin Path 2006;125:251)
● Anaplastic large cell lymphoma (Am J Clin Path 2003;119:205), most B cell neoplasms, adult T cell leukemia/lymphoma (Am J Clin Pathol 2010;133:592), Reed-Sternberg-like cells in peripheral T cell lymphoma (Am J Surg Pathol 2003;27:1513)
● Most Hodgkin’s lymphomas, some AML
● Often systemic mastocytosis (Am J Surg Pathol 2004;28:1319)
● Acquired ocular toxoplasmosis (Arq Bras Oftalmol 2010;73:443), idiopathic retroperitoneal fibrosis (Am J Surg Pathol 1993;17:482), neuroblastoma
Negative staining
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● Non-neoplastic mast cells (Am J Clin Path 2004;122:560)
● Marginal zone B cell lymphoma (Am J Clin Path 1996;105:277)
● T cell large granular leukemia/lymphoma (Am J Surg Pathol 2005;29:935)
● Often/usually variant hairy cell leukemia (Am J Clin Path 2005;123:132)
Flow cytometry images
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Hairy cell leukemia variant is CD103+ but CD25-
Additional references
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End of CD Markers > CD25
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