Stains & CD markers
CD5
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: CD5
CD5
Author: Pamela Wirth, Ph.D.
Editorial Board Member: Roberto N. Miranda, M.D.
Last staff update: 18 December 2024 (update in progress)
Copyright: 2002-2024, PathologyOutlines.com, Inc.
PubMed Search: CD5
Table of Contents
Definition / general | Essential features | Terminology | Pathophysiology | Interpretation | Uses by pathologists | Prognostic factors | Microscopic (histologic) images | Positive staining - normal | Positive staining - disease | Negative staining | Flow cytometry description | Flow cytometry images | Molecular / cytogenetics description | Sample pathology report | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Wirth P. CD5. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/cdmarkerscd5.html. Accessed December 22nd, 2024.
Definition / general
- Transmembrane glycoprotein found on the surface of thymocytes, T lymphocytes and some B lymphocytes (B1a)
Essential features
- CD5 is a pan-T cell marker belonging to the scavenger receptor cysteine rich (SRCR) superfamily of receptors (Eur J Immunol 2016;46:1490)
- Used for diagnosis of lymphomas and thymic carcinoma
- Helps differentiate chronic lymphocytic leukemia (CLL) and mantle cell lymphoma from other types of low grade B cell non-Hodgkin lymphomas
Terminology
- Leu1
Pathophysiology
- CD5 is a pan-T cell marker belonging to the SRCR superfamily of receptors
- Regulates the activation and sensitivity of T cells to antigens
- Positive and negative regulator of T cell receptor (TCR) signaling (J Leukoc Biol 2019;105:891)
- Acts as a negative regulator of the T cell receptor by decreasing excessive signaling and thereby preventing overactivation of T cells
- Involved in the differentiation and regulation of a subset of B cells (B1a) (Front Immunol 2018;9:2900)
Interpretation
- Membrane, intracellular
Uses by pathologists
- Used for diagnosis of lymphomas and thymic carcinoma
- Helps differentiate mantle cell lymphomas and CLL from other types of low grade non-Hodgkin lymphomas
- CD5 is typically expressed in chronic lymphocytic leukemia (CLL) and mantle cell lymphoma (MCL), thereby distinguishing these disorders from other small chronic B cell lymphoproliferative disorders (Med Sci Monit 2017;23:2137)
- MCL cells express CD5 and cyclin D1 (CCND1) due to t(11;14) translocation, which is absent in CLL cells (Nat Rev Dis Primers 2017;3:17008)
- CD5+ / SOX11+ / Cyclin D1- large cell lymphoma favors pleomorphic mantle cell lymphoma (Mod Pathol 2024;37:100405, Am J Surg Pathol 2012;36:214)
- CD5 together with CD117 and PAX8 can be used as diagnostic markers for thymic carcinoma (Appl Immunohistochem Mol Morphol 2014;22:372)
- Can distinguish thymic carcinoma from squamous cell carcinoma (SCC) of the lung
- CD5 is positive on neoplastic epithelial cells of most thymic carcinomas and expressed on some atypical thymomas
- CD5 can help distinguish peripheral T cell lymphomas (PTCLs) from other T cell neoplasms, such as angioimmunoblastic T cell lymphoma (which may exhibit partial CD5 expression) and ALK negative anaplastic large cell lymphoma (CD5 negative in most cases) (Leukemia 2020;34:2592, Int J Surg Rep 2023;113:108978)
- CD5 can be incorporated in multiplex immunohistochemistry panels to assess T cell lymphoma spread and behavior (Cancers 2024;16:3430)
Prognostic factors
- Absence of CD5 expression may be associated with superior overall survival and more favorable progression free survival in mantle cell lymphoma (Am J Surg Pathol 2019;43:1052)
- Subset of diffuse large B cell lymphomas (DLBCL) are CD5+ (5 - 22%) and are associated with more aggressive disease (Clin Lymphoma Myeloma Leuk 2020;20:e782)
- CD5+ DLBCL should be tested for cyclin D1 / CCND1 and SOX11 to exclude pleomorphic MCL (Mod Pathol 2024;37:100405)
- Positive expression of CD5 in follicular lymphoma is associated with poor prognosis
- PTCL cases expressing CD5 may correlate with more aggressive disease (Mod Pathol 2013;26:S71)
Microscopic (histologic) images
Contributed by Pamela Wirth, Ph.D. (source: Human Protein Atlas and University of Toronto), Chi Young Ok, M.D., Patricia Tsang, M.D., M.B.A. (Case #499), Nicholas Nowacki, M.D. and Carlos A. Murga-Zamalloa, M.D.
Normal tonsil
Mantle cell lymphoma (MCL), blastoid variant
MCL-leukemic nonnodal
Intestinal T cell lymphoma, NOS
Positive staining - normal
- Expressed on the surface of almost all mature T cells (expression levels increase during T cell development)
- Interfollicular areas of normal tonsil can serve as positive control for CD5 expression
- Found in the thymus, spleen and lymph nodes
- Expressed in a small subset of normal B cells in peripheral blood (adult) and cord blood (Hum Pathol 2012;43:1436)
Positive staining - disease
- Most T cell lymphomas and leukemias
- In ambiguous cases where lymphomas show atypical immunophenotypes, CD5 staining can aid in confirming T cell or B cell origin (Curr Oncol 2021;28:4611)
- Peripheral T cell lymphomas
- Both typical and atypical forms of chronic lymphocytic leukemia (95%) (Leuk Lymphoma 1998;31:209)
- Some studies report lower or varied CD5 positivity rates in atypical forms (Cancers [Basel] 20223;15:4427)
- B cell chronic lymphocytic leukemia (80 - 93%) (Leuk Lymphoma 1998;31:209)
- T cell acute lymphoblastic leukemia (T ALL)
- Mantle cell lymphoma (95%) (Am J Surg Pathol 2019;43:1052)
Negative staining
- Weakly expressed in immature T cells
- Mostly negative in carcinomas (some expression in thymic carcinoma and atypical thymoma)
- Follicular lymphoma (Arch Pathol Lab Med 2014;138:903)
- Thyroid follicular adenoma is typically negative (Pathol Int 2011;61:577)
- Thymic carcinoma (33% positivity) (Mod Pathol 2009;22:1341)
- 16 - 34% of anaplastic large cell lymphoma cases may express CD5 (Am J Clin Pathol 2021;155:479)
- Some expression on spermatogonia (less than 50% by flow cytometry) (Middle East Fertil Soc J 2022;27:3)
- Limited expression in splenic marginal zone B cell lymphoma (SMZL) (20 - 25% expression, weak)
- Limited expression in hairy cell leukemia (HCL) (Curr Oncol 2021;28:4611, Arch Pathol Lab Med 2014;138:903)
- Marginal zone lymphoma of mucosa associated lymphoid tissue (MALT lymphoma) (< 1%) (Hum Pathol 2012;43:1436, Arch Pathol Lab Med 2014;138:903)
- Limited expression of lymphoplasmacytic lymphoma (LPL) (expressed in 20% of cases) (Curr Oncol 2021;28:4611)
- Limited expression in diffuse large B cell lymphoma (5 - 18%) (Leuk Lymphoma 2021;62:3078)
- CD5 expression (partially expressed or absent), along with positive CD3 and CD8 staining, can help identify T cell large granular lymphocytic leukemia (Blood Res 2023;58:S52)
Flow cytometry description
- Flow cytometry analysis can show dim expression of CD5 in lymphomas and can be more sensitive than immunohistochemistry, especially when a strong fluorochrome is used (Haematologica 2010;95:604)
Flow cytometry images
Images hosted on other servers:
Immunophenotype of CD5+ follicular lymphoma
Molecular / cytogenetics description
- Gene location 11q12.2
Sample pathology report
- Bone marrow, core biopsy:
- Chronic lymphocytic leukemia (see comment)
- Comment: 70 year old man presents with fever, fatigue and lymphadenopathy. Flow cytometric analysis of bone marrow demonstrates 65% lymphocytes with CD19+, CD5+, CD23+, CD20+ (dim), CD10- and CD43+ expression.
- Monotypic B lymphocytes in peripheral blood > 5 x 109/L
- Bone marrow biopsy:
- Quality: adequate
- Hypercellularity: 80%, with an interstitial and focally nodular pattern
Board review style question #1
Which of the following immunohistochemical panels is useful in distinguishing thymic carcinoma from squamous cell carcinoma (SCC) of the lung?
- CD5+, FOXN1+, PAX8+, CD117+
- CD10+, BCL2+, CD20+, CD5-
- CD30+, CD15+, PAX5+, CD20-
- CD79a+, SOX11+, CD20+, cyclin D1+
Board review style answer #1
A. CD5+, FOXN1+, PAX8+, CD117+. The positive expression of CD5, FOXN1, PAX8 and CD117 supports a diagnosis of thymic carcinoma and argues against squamous cell carcinoma of the lung (with low to negative expression for these markers in lung SCC). Answer D is incorrect because this panel supports a diagnosis of mantle cell lymphoma. Answer B is incorrect because this panel would support a diagnosis of follicular lymphoma. Answer C is incorrect because this panel supports a diagnosis of Hodgkin lymphoma.
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Board review style question #2
Increased CD5 protein expression is associated with poor survival in which of the following disorders?
- Follicular lymphoma
- Marginal zone lymphoma
- Non-small cell lung cancer
- T cell acute lymphoblastic leukemia
Board review style answer #2
A. Follicular lymphoma. Studies show CD5 positivity is associated with poorer prognosis and decreased overall survival in patients with follicular lymphoma. Answer B is incorrect because CD5 expression does not appear to impact the prognosis of marginal zone lymphoma but may increase the risk of histologic transformation to diffuse large B cell lymphoma. Answer D is incorrect because low (not high) expression of CD5 is associated with poor overall survival in T cell acute lymphoblastic leukemia. Answer C is incorrect because patients with higher CD5 expression in non-small cell lung cancer showed increased overall survival rates.
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