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Lymphoma - B cell neoplasms

Lymph nodes

Normal lymphocyte development - T cells


Reviewer: Nikhil Sangle, M.D., University of Utah and ARUP Laboratories (see Reviewers page)
Revised: 26 March 2011, last major update January 2011
Copyright: (c) 2001-2010, PathologyOutlines.com, Inc.

General
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● Develop from bone marrow, become prothymocytes, then migrate to thymus gland, where self-recognizing T cells are eliminated

Physiology
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● T cell receptors (TCR) are either alpha/beta (95%) or gamma/delta (5%) heterodimers
● T cell progenitors migrate to the thymus and undertake a highly ordered developmental program, regulated by signals derived from microenvironment
● Most immature thymocytes are CD4- CD8- ("double negative" / DN); DN is divided into 4 stages based on CD44 / CD25 expression: DN1 is CD44+, CD25-; DN2 is CD44+, CD25+; DN3 is CD44-, CD25+; DN4 is CD44-, CD25- (Immunol Res 2010;47:45)
● Precursor cell is TdT+, CD34+, HLA-DR+, then drops HLA-DR, then adds CD2, CD5, CD7 (early thymocyte) while undergoing gamma/beta chain rearrangement, then adds CD1 and drops CD34, now a common thymocyte (CD4-, CD8-, "double negative"), then undergoes beta/alpha chain rearrangement (DN3 stage) and adds CD4 and CD8, then splits into helper (CD4) or cytotoxic (CD8) T cell ("single positive") with CD2 and CD3, and without TdT, CD1, CD5 and CD7
● T alpha and delta genes are on 14q11; T beta gene is on 7q34; T gamma gene is on 7p15
Note: T cells and NK cells arise from common progenitor that expresses CD3 epsilon and cannot develop into B cells

Diagrams
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T cell development


T cell biomarker expression during development (AFIP 3rd Series Vol 14)

T cell activation

Clinical features
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● 90% of peripheral T-cell lymphomas have rearrangements of T-alpha, beta and gamma, including all cases of mycosis fungoides and Sezary syndrome
● T cell lymphomas have no distinct marker of clonality, but cells may express an abnormal immunophenotype or TCR gene rearrangement
● As there are only 10 V (variable) regions, a polyclonal population of cells can appear oligoclonal
● T cell clonality is seen in AIDS and congenital immunodeficiency syndromes, but does NOT indicate malignancy
● Rarely a clonal band may comigrate with the germline band; solution - use 2-3 restriction enzymes (HindIII, EcoRI, BamHI)

Positive stains
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● CD2, CD3, CD4 or CD8

Negative stains
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● CD19, CD20

Videos
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T cell development

End of Lymphoma - B cell neoplasms > Lymph nodes > Normal lymphocyte development - T cells


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