CD Markers - CD45

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CD Markers

CD45

Reviewers: Nat Pernick, M.D., (see Reviewers page)
Revised: 8 February 2011, last major update February 2011
Copyright: (c) 2002-2011, PathologyOutlines.com, Inc.

General
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● Commonly used marker of hematopoietic cells except erythrocytes and platelets; plays a major role in immune system

Terminology
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● Also called leukocyte common antigen (LCA), protein tyrosine phosphatase

Physiology
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● CD45 is a high molecular weight transmembrane protein with intrinsic tyrosine phosphatase activity
● CD45 is heavily glycosylated, and expressed at high levels on nucleated hematopoietic cells
● Disruption of the equilibrium between protein tyrosine kinase and phosphatase activity (from CD45 and others) can result in immunodeficiency, autoimmunity or malignancy (Immunol Rev 2009;228:288)
● An essential regulator of T and B cell antigen receptor-mediated activation
● Also required for thymic selection
● Major component of glycocalyx

Clinical features
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Different subsets of hematopoietic cells express different CD45 isoforms due to variable exon splicing, which can change in response to cytokines:
● CD45RA - naive/resting T cells, medullary thymocytes
● CD45RO - memory/activated T cells, cortical thymocytes
● Also CD45RB and CD45RC

● Loss of CD45 mutations cause severe combined immunodeficiency-autosomal recessive, T cell negative, B cell positive, NK cell positive (MIM 608971); patients have a defect in B/T cell development, lymphopenia and deficiency in humoral and cell-mediated immunity
● 77C to G mutation may increase intensity of T cell receptor signaling (J Immunol 2006;176:931), and cause some cases of systemic sclerosis (Genes Immun 2003;4:168), multiple sclerosis (controversial, Nat Genet 2000;26:495) and autoimmune hepatitis (Genes Immun 2003;4:79
● Loss of CD45 activity in lymphocytes of elderly may cause T cell dysfunction (Mech Ageing Dev 2003;124:191)
● Necrotic lymphomas are still CD45+, but occasional necrotic carcinomas may also be CD45+ (Am J Clin Path 1998;110:641)

Uses
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● Confirm presence of inflammatory cells, including intestinal intraepithelial lymphocytes (Arch Pathol Lab Med 2002;126:897)
● Confirm hematopoietic nature of tumors
● May assist in classification of lymphomas and leukemias (Am J Clin Path 1998;110:797)

Micro images
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Normal:

Liver with CD45+ Kupffer cells and lymphocytes

Small intestine with CD45+ intraepithelial lymphocytes

Splenic lymphocytes

Left: thymus; right-tonsil

Lymphoma:

Left: B cell lymphoma-unusual CD45 negative case (fig B); right-CLL

Left: diffuse large B cell lymphoma-urine cytology; middle: diffuse large B cell lymphoma-H&E; right: Hodgkin’s-Reed-Sternberg cells are CD45 negative (fig 3C)

Other:

Histiocytic sarcoma (fig C)

Lymphoepithelioma-like carcinomas-tumor cells are CD45 negative, but infiltrating lymphocytes are CD45+: left-stomach; right-cervix

Left-leukemia cutis; right-myeloid sarcoma of fibula

Leukemic vasculitis in the context of leukemia cutis, in a patient with atypical chronic myeloid leukemia

Flow cytometry images
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Transient myeloproliferative disorder with erythroid differentiation in Down’s syndrome (figure 3C)

Anaplastic large cell lymphoma

Virtual slides
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Diffuse large B cell lymphoma

Positive staining - normal
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● Hematopoietic cells, including basophils, granulocytes, lymphocytes, macrophages / histiocytes, mast cells, monocytes, plasma cells; NOT mature red blood cells and their immediate progenitors, platelets or megakaryocytes
● Dendritic cells, fibrocytes (J Immunol 1998;160:419), medullary thymocytes

Positive staining - disease
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● AML (Am J Clin Pathol 1998;109:211), anaplastic large cell lymphoma (usually, Am J Clin Pathol 2003;119:205, Hum Pathol 1990;21:624), B and T cell lymphomas (most), CD4(+) CD56(+) lineage-negative malignancies (Am J Surg Pathol 2005;29:1274), dendrocytoma (Am J Surg Pathol 1990;14:867)
● Giant cell tumor of tendon sheath (Mod Pathol 1995;8:155), histiocytic sarcoma (Am J Surg Pathol 1998;22:1386), inflammatory pseudotumors (some, Am J Clin Pathol 1996;105:430), interdigitating dendritic cell sarcoma (variable, Am J Clin Pathol 2001;115:589)
● Leukemia cutis, lymphocyte predominant Hodgkin’s lymphoma (Am J Surg Pathol 1994;18:526), myeloid sarcoma (Am J Surg Pathol 1993;17:1011), mycobacterial spindle cell pseudotumor in lymph nodes
● Plasma cell neoplasms (variable, Blood Cells Mol Dis 2004;32:293), post-transplant lymphoproliferative disorders (Am J Clin Pathol 2004;121:246), preB lymphoblastic lymphoma (low, Am J Clin Pathol 2009;132:940), primary effusion lymphoma (Am J Surg Pathol 2004;28:1401)
● Reticulohistiocytoma (variable, Am J Surg Pathol 2006;30:521), transient myeloproliferative disorder of Down's syndrome (Am J Clin Pathol 2001;116:204)
● Candida albicans yeast forms (Am J Clin Pathol 2000;113:59)
● Rarely carcinomas (undifferentiated / neuroendocrine, Mod Pathol 1998;11:1204 or necrotic)

Negative staining
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● Red blood cells and their immediate progenitors, megakaryocytes, osteoblasts, platelets
● Epithelial tumors (although necrotic carcinomas may be CD45+, Am J Clin Pathol 1998;110:641), follicular dendritic cell sarcoma (Am J Clin Pathol 1995;103:90), germ cell tumors, melanoma, mesothelioma, multiple myeloma (CD45+ in 9% by flow cytometry, Am J Clin Pathol 2004;121:482, Am J Clin Pathol 2010;133:265), sarcoma
● Reed-Sternberg cells in classic Hodgkin’s lymphoma (Am J Pathol 1991;139:701)
● Note that infiltrating lymphocytes in any disorder are typically CD45+, and they must be distinguished from tumor cells

Additional references
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● MIM 151460

End of CD Markers > CD45

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