Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)== Sara Akhavanfard, M.D., Ph.D. * Ruthann Pfau, Ph.D., FACMG TOC ==Cancer Category/Type== * Angioimmunoblastic T-cell L..."

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Created page with "{{Under Construction}} ==Primary Author(s)*== * Sara Akhavanfard, M.D., Ph.D. * Ruthann Pfau, Ph.D., FACMG __TOC__ ==Cancer Category/Type== * Angioimmunoblastic T-cell L..."

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{{Under Construction}}
==Primary Author(s)*==

* Sara Akhavanfard, M.D., Ph.D.
* Ruthann Pfau, Ph.D., FACMG

__TOC__

==Cancer Category/Type==

* [[Angioimmunoblastic T-cell Lymphoma and Other Nodal Lymphomas of T Follicular Helper Cell Origin]]

==Cancer Sub-Classification / Subtype==

* Angioimmunoblastic T-cell Lymphoma (AITL)

==Definition / Description of Disease<ref>Dogan A, et al., (2017). Angioimmunoblastic T-cell Lymphoma, in World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Revised 4th edition. Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Arber DA, Hasserjian RP, Le Beau MM, Orazi A, and Siebert R, Editors. IARC Press: Lyon, France, p407-411.</ref>==

*A neoplasm of mature T follicular helper (TFH) cells
*Characterized by systemic disease and a polymorphous infiltrate involving lymph nodes
*Have prominent proliferation of high endothelial venules (HEVs) and follicular dendritic cells (FDCs)
*EBV-positive B cells are nearly always present
*Clinically aggressive and seen mainly in older adults

==Synonyms / Terminology==

*Peripheral T-cell Lymphoma
*Angioimmunoblastic Lymphadenopathy with Dysproteinaemia
*Immunoblastic Lymphadenopathy
*Lymphogranulomatosis X

==Epidemiology / Prevalence==

*Occurs in middle-aged and elderly individuals<ref name=":0">{{Cite journal|last=L|first=de Leval|last2=C|first2=Gisselbrecht|last3=P|first3=Gaulard|date=2010|title=Advances in the understanding and management of angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/19961485/|language=en|pmid=19961485}}</ref>
*Males >> Females<ref name=":0" />
*One of the most common specific subtypes of PTCL<ref>{{Cite journal|last=M|first=Vences|last2=Jm|first2=Guayasamin|last3=A|first3=Miralles|last4=I|first4=De la Riva|date=2013|title=To name or not to name: Criteria to promote economy of change in Linnaean classification schemes|url=https://pubmed.ncbi.nlm.nih.gov/26042291/|language=en|pmid=26042291}}</ref><ref>{{Cite journal|last=T|first=Rüdiger|last2=Dd|first2=Weisenburger|last3=Jr|first3=Anderson|last4=Jo|first4=Armitage|last5=J|first5=Diebold|last6=Ka|first6=MacLennan|last7=Bn|first7=Nathwani|last8=F|first8=Ullrich|last9=Hk|first9=Müller-Hermelink|date=2002|title=Peripheral T-cell lymphoma (excluding anaplastic large-cell lymphoma): results from the Non-Hodgkin's Lymphoma Classification Project|url=https://pubmed.ncbi.nlm.nih.gov/11863096/|language=en|pmid=11863096}}</ref><ref>{{Cite journal|last=J|first=Vose|last2=J|first2=Armitage|last3=D|first3=Weisenburger|date=2008|title=International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes|url=https://pubmed.ncbi.nlm.nih.gov/18626005/|language=en|pmid=18626005}}</ref>
**15-30% of non-cutaneous T-cell lymphomas
**1-2% of all non-Hodgkin lymphomas

==Clinical Features<ref>{{Cite journal|last=A|first=Dogan|last2=Ad|first2=Attygalle|last3=C|first3=Kyriakou|date=2003|title=Angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/12780782/|language=en|pmid=12780782}}</ref><ref>{{Cite journal|last=F|first=Lachenal|last2=F|first2=Berger|last3=H|first3=Ghesquières|last4=P|first4=Biron|last5=A|first5=Hot|last6=E|first6=Callet-Bauchu|last7=C|first7=Chassagne|last8=B|first8=Coiffier|last9=I|first9=Durieu|date=2007|title=Angioimmunoblastic T-cell lymphoma: clinical and laboratory features at diagnosis in 77 patients|url=https://pubmed.ncbi.nlm.nih.gov/17873758/|language=en|pmid=17873758}}</ref><ref>{{Cite journal|last=N|first=Mourad|last2=N|first2=Mounier|last3=J|first3=Brière|last4=E|first4=Raffoux|last5=A|first5=Delmer|last6=A|first6=Feller|last7=Cj|first7=Meijer|last8=Jf|first8=Emile|last9=R|first9=Bouabdallah|date=2008|title=Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials|url=https://pubmed.ncbi.nlm.nih.gov/18292286/|language=en|doi=10.1182/blood-2007-08-105759|pmc=PMC2343588|pmid=18292286}}</ref><ref>{{Cite journal|last=W|first=Siegert|last2=C|first2=Nerl|last3=A|first3=Agthe|last4=M|first4=Engelhard|last5=G|first5=Brittinger|last6=M|first6=Tiemann|last7=K|first7=Lennert|last8=D|first8=Huhn|date=1995|title=Angioimmunoblastic lymphadenopathy (AILD)-type T-cell lymphoma: prognostic impact of clinical observations and laboratory findings at presentation. The Kiel Lymphoma Study Group|url=https://pubmed.ncbi.nlm.nih.gov/8664186/|language=en|pmid=8664186}}</ref>==
'''Sign and Symptoms'''

*Advanced-stage disease with systemic symptoms
*Generalized lymphadenopathy
*Hepatosplenomegaly
*Polyclonal hypergammaglobulinemia
*Skin rash, often with pruritus
*Pleural effusion
*Arthritis
*Ascites

'''Laboratory Findings'''

*Circulating Immune Complexes
*Cold agglutinins with haemolytic anemia
*Positive rheumatoid factor
*Positive anti-smooth muscle antibody

==Sites of Involvement==

*Primary site: Lymph node
*Other involved sites: Spleen, Liver, Skin,and Bone marrow<ref>{{Cite journal|last=L|first=de Leval|last2=C|first2=Gisselbrecht|last3=P|first3=Gaulard|date=2010|title=Advances in the understanding and management of angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/19961485/|language=en|pmid=19961485}}</ref><ref>{{Cite journal|last=A|first=Dogan|last2=Ad|first2=Attygalle|last3=C|first3=Kyriakou|date=2003|title=Angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/12780782/|language=en|pmid=12780782}}</ref><ref>{{Cite journal|last=M|first=Federico|last2=T|first2=Rudiger|last3=M|first3=Bellei|last4=Bn|first4=Nathwani|last5=S|first5=Luminari|last6=B|first6=Coiffier|last7=Nl|first7=Harris|last8=Es|first8=Jaffe|last9=Sa|first9=Pileri|date=2013|title=Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project|url=https://pubmed.ncbi.nlm.nih.gov/22869878/|language=en|doi=10.1200/JCO.2011.37.3647|pmc=PMC3532394|pmid=22869878}}</ref><ref>{{Cite journal|last=N|first=Mourad|last2=N|first2=Mounier|last3=J|first3=Brière|last4=E|first4=Raffoux|last5=A|first5=Delmer|last6=A|first6=Feller|last7=Cj|first7=Meijer|last8=Jf|first8=Emile|last9=R|first9=Bouabdallah|date=2008|title=Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials|url=https://pubmed.ncbi.nlm.nih.gov/18292286/|language=en|doi=10.1182/blood-2007-08-105759|pmc=PMC2343588|pmid=18292286}}</ref>

==Morphologic Features<ref>{{Cite journal|last=A|first=Attygalle|last2=R|first2=Al-Jehani|last3=Tc|first3=Diss|last4=P|first4=Munson|last5=H|first5=Liu|last6=Mq|first6=Du|last7=Pg|first7=Isaacson|last8=A|first8=Dogan|date=2002|title=Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10|url=https://pubmed.ncbi.nlm.nih.gov/11781247/|language=en|pmid=11781247}}</ref><ref>{{Cite journal|last=M|first=Rodriguez-Justo|last2=Ad|first2=Attygalle|last3=P|first3=Munson|last4=G|first4=Roncador|last5=T|first5=Marafioti|last6=Ma|first6=Piris|date=2009|title=Angioimmunoblastic T-cell lymphoma with hyperplastic germinal centres: a neoplasia with origin in the outer zone of the germinal centre? Clinicopathological and immunohistochemical study of 10 cases with follicular T-cell markers|url=https://pubmed.ncbi.nlm.nih.gov/19329936/|language=en|pmid=19329936}}</ref>==

'''Pattern-1 (Early involvement)'''

*Bare, hyperplastic follicles, with Well-formed germinal centers, often lacking well-defined mantle cuffs<ref>{{Cite journal|last=Hj|first=Ree|last2=Me|first2=Kadin|last3=M|first3=Kikuchi|last4=Yh|first4=Ko|last5=Jh|first5=Go|last6=J|first6=Suzumiya|last7=Ds|first7=Kim|date=1998|title=Angioimmunoblastic lymphoma (AILD-type T-cell lymphoma) with hyperplastic germinal centers|url=https://pubmed.ncbi.nlm.nih.gov/9630171/|language=en|pmid=9630171}}</ref>
*Paracortical expansion
*Marked Vascular Proliferation, associated with perifollicular or atypical lymphoid cells

'''Pattern-2'''

*Remnant of follicles with regressive changes
*Readily identified neoplastic cells in the expanded paracortex
*Marked perifollicular expansion of clear cells

'''Pattern-3'''

*Totally or sub-totally effacement of normal architecture
*Marked vascular proliferation
*Aggregates of atypical lymphoid cells

==Immunophenotype<ref>{{Cite journal|last=A|first=Attygalle|last2=R|first2=Al-Jehani|last3=Tc|first3=Diss|last4=P|first4=Munson|last5=H|first5=Liu|last6=Mq|first6=Du|last7=Pg|first7=Isaacson|last8=A|first8=Dogan|date=2002|title=Neoplastic T cells in angioimmunoblastic T-cell lymphoma express CD10|url=https://pubmed.ncbi.nlm.nih.gov/11781247/|language=en|pmid=11781247}}</ref><ref>{{Cite journal|last=L|first=de Leval|last2=Ds|first2=Rickman|last3=C|first3=Thielen|last4=Ad|first4=Reynies|last5=Yl|first5=Huang|last6=G|first6=Delsol|last7=L|first7=Lamant|last8=K|first8=Leroy|last9=J|first9=Brière|date=2007|title=The gene expression profile of nodal peripheral T-cell lymphoma demonstrates a molecular link between angioimmunoblastic T-cell lymphoma (AITL) and follicular helper T (TFH) cells|url=https://pubmed.ncbi.nlm.nih.gov/17284527/|language=en|pmid=17284527}}</ref><ref>{{Cite journal|last=Dm|first=Dorfman|last2=Ja|first2=Brown|last3=A|first3=Shahsafaei|last4=Gj|first4=Freeman|date=2006|title=Programmed death-1 (PD-1) is a marker of germinal center-associated T cells and angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/16819321/|language=en|doi=10.1097/01.pas.0000209855.28282.ce|pmc=PMC3137919|pmid=16819321}}</ref><ref>{{Cite journal|last=Kl|first=Grogg|last2=Ad|first2=Attygalle|last3=Wr|first3=Macon|last4=Ed|first4=Remstein|last5=Pj|first5=Kurtin|last6=A|first6=Dogan|date=2005|title=Angioimmunoblastic T-cell lymphoma: a neoplasm of germinal-center T-helper cells?|url=https://pubmed.ncbi.nlm.nih.gov/16079436/|language=en|doi=10.1182/blood-2005-03-1083|pmc=PMC1895208|pmid=16079436}}</ref><ref>{{Cite journal|last=G|first=Roncador|last2=Jf|first2=García Verdes-Montenegro|last3=S|first3=Tedoldi|last4=Jc|first4=Paterson|last5=W|first5=Klapper|last6=E|first6=Ballabio|last7=L|first7=Maestre|last8=S|first8=Pileri|last9=Ml|first9=Hansmann|date=2007|title=Expression of two markers of germinal center T cells (SAP and PD-1) in angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/17640856/|language=en|pmid=17640856}}</ref>==

{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD2, CD3, CD4, CD5, CD10, CXCL13, ICOS, BCL6, PD1(CD279)
|-
|Positive (extrafollicular pattern)||CD21, CD23, CD35
|}

==Chromosomal Rearrangements (Gene Fusions)==

{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Reference
|-
|t(5;9)(q33;q22)||''ITK''/''SYK''||der(5); der(9)||<ref>{{Cite journal|last=B|first=Streubel|last2=U|first2=Vinatzer|last3=M|first3=Willheim|last4=M|first4=Raderer|last5=A|first5=Chott|date=2006|title=Novel t(5;9)(q33;q22) fuses ITK to SYK in unspecified peripheral T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/16341044/|language=en|pmid=16341044}}</ref><ref name=":4">{{Cite journal|last=M|first=Wang|last2=S|first2=Zhang|last3=Ss|first3=Chuang|last4=M|first4=Ashton-Key|last5=E|first5=Ochoa|last6=N|first6=Bolli|last7=G|first7=Vassiliou|last8=Z|first8=Gao|last9=Mq|first9=Du|date=2017|title=Angioimmunoblastic T cell lymphoma: novel molecular insights by mutation profiling|url=https://pubmed.ncbi.nlm.nih.gov/28148900/|language=en|doi=10.18632/oncotarget.14846|pmc=PMC5392284|pmid=28148900}}</ref>
|-
|t(7;14)(q35;q32.1)||''TRB/TCL1A''||der(7); der(14)||<ref>{{Cite journal|last=Mf|first=Cosimi|last2=I|first2=Casagranda|last3=G|first3=Ghiazza|last4=G|first4=Rossi|last5=P|first5=Galvani|date=1990|title=Rearrangements on chromosomes 7 and 14 with breakpoints at 7q35 and 14q11 in angioimmunoblastic lymphadenopathy and IBL-like T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/2284141/|language=en|pmid=2284141}}</ref>
|-
|t(14;14)(q11;q32.1) / inv(14)(q11q32.1)||''TRA-TRD/TCL1A''||der(14)||<ref>{{Cite journal|last=B|first=Schlegelberger|last2=A|first2=Feller|last3=A|first3=Himmler|last4=W|first4=Grote|date=1990|title=Inv(14)(q11q32) in one of four different clones in a case of angioimmunoblastic lymphadenopathy|url=https://pubmed.ncbi.nlm.nih.gov/2293883/|language=en|pmid=2293883}}</ref><ref>{{Cite journal|last=E|first=Leich|last2=E|first2=Haralambieva|last3=A|first3=Zettl|last4=A|first4=Chott|last5=T|first5=Rüdiger|last6=S|first6=Höller|last7=Hk|first7=Müller-Hermelink|last8=G|first8=Ott|last9=A|first9=Rosenwald|date=2007|title=Tissue microarray-based screening for chromosomal breakpoints affecting the T-cell receptor gene loci in mature T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/17582237/|language=en|pmid=17582237}}</ref>
|-
|chr(2)(q33.2)||''CTLA4/CD28''||der(2)||<ref>{{Cite journal|last=Hy|first=Yoo|last2=P|first2=Kim|last3=Ws|first3=Kim|last4=Sh|first4=Lee|last5=S|first5=Kim|last6=Sy|first6=Kang|last7=Hy|first7=Jang|last8=Je|first8=Lee|last9=J|first9=Kim|date=2016|title=Frequent CTLA4-CD28 gene fusion in diverse types of T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26819049/|language=en|doi=10.3324/haematol.2015.139253|pmc=PMC5013939|pmid=26819049}}</ref>
|}

==Characteristic Chromosomal Aberrations / Patterns==

*Clonal rearrangement in T-Cell receptor gene in 75-90% of AITL cases<ref name=":7">{{Cite journal|last=Ad|first=Attygalle|last2=Ss|first2=Chuang|last3=Tc|first3=Diss|last4=Mq|first4=Du|last5=Pg|first5=Isaacson|last6=A|first6=Dogan|date=2007|title=Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics|url=https://pubmed.ncbi.nlm.nih.gov/17448026/|language=en|pmid=17448026}}</ref> <ref>{{Cite journal|last=L|first=de Leval|last2=C|first2=Gisselbrecht|last3=P|first3=Gaulard|date=2010|title=Advances in the understanding and management of angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/19961485/|language=en|pmid=19961485}}</ref><ref name=":8">{{Cite journal|last=Bt|first=Tan|last2=Ra|first2=Warnke|last3=Da|first3=Arber|date=2006|title=The frequency of B- and T-cell gene rearrangements and epstein-barr virus in T-cell lymphomas: a comparison between angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, unspecified with and without associated B-cell proliferations|url=https://pubmed.ncbi.nlm.nih.gov/16931587/|language=en|doi=10.2353/jmoldx.2006.060016|pmc=PMC1867616|pmid=16931587}}</ref>
*Clonal rearrangement in immunoglobulin genes in 25-30% of AITL cases<ref name=":7" /><ref name=":8" />

==Genomic Gain/Loss/LOH==

{| class="wikitable sortable"
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Reference
|-
|3,5,21||Trisomy||<ref name=":1">{{Cite journal|last=B|first=Schlegelberger|last2=Y|first2=Zhang|last3=K|first3=Weber-Matthiesen|last4=W|first4=Grote|date=1994|title=Detection of aberrant clones in nearly all cases of angioimmunoblastic lymphadenopathy with dysproteinemia-type T-cell lymphoma by combined interphase and metaphase cytogenetics|url=https://pubmed.ncbi.nlm.nih.gov/7919378/|language=en|pmid=7919378}}</ref>
|-
|X||Gain||<ref name=":1" />
|-
|6q
|Loss
|<ref name=":1" />
|-
|22q
|Gain
|<ref name=":2">{{Cite journal|last=C|first=Thorns|last2=B|first2=Bastian|last3=D|first3=Pinkel|last4=R|first4=Roydasgupta|last5=J|first5=Fridlyand|last6=H|first6=Merz|last7=M|first7=Krokowski|last8=Hw|first8=Bernd|last9=Ac|first9=Feller|date=2007|title=Chromosomal aberrations in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma unspecified: A matrix-based CGH approach|url=https://pubmed.ncbi.nlm.nih.gov/17044049/|language=en|pmid=17044049}}</ref>
|-
|19
|Gain
|<ref name=":2" />
|-
|11q13
|Gain
|<ref name=":2" />
|-
|13q
|Loss
|<ref name=":2" />
|}

==Gene Mutations (SNV/INDEL)==

{| class="wikitable sortable"
|-
!Gene!!Mutation‡!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism
(LOF/GOF/Other; Driver/Passenger)
!Prevalence
(COSMIC/TCGA/Other)
|-
|''IDH2''||R172S; R172G;R172K||Tumor Suppressor '''ONCOGENE'''||LOF '''GOF'''||20-30%<ref>{{Cite journal|last=Ra|first=Cairns|last2=J|first2=Iqbal|last3=F|first3=Lemonnier|last4=C|first4=Kucuk|last5=L|first5=de Leval|last6=Jp|first6=Jais|last7=M|first7=Parrens|last8=A|first8=Martin|last9=L|first9=Xerri|date=2012|title=IDH2 mutations are frequent in angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/22215888/|language=en|doi=10.1182/blood-2011-11-391748|pmc=PMC3293643|pmid=22215888}}</ref><ref name=":4" /><ref name=":5">{{Cite journal|last=O|first=Odejide|last2=O|first2=Weigert|last3=Aa|first3=Lane|last4=D|first4=Toscano|last5=Ma|first5=Lunning|last6=N|first6=Kopp|last7=S|first7=Kim|last8=D|first8=van Bodegom|last9=S|first9=Bolla|date=2014|title=A targeted mutational landscape of angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24345752/|language=en|doi=10.1182/blood-2013-10-531509|pmc=PMC4260974|pmid=24345752}}</ref><ref name=":11">{{Cite journal|last=C|first=Wang|last2=Tw|first2=McKeithan|last3=Q|first3=Gong|last4=W|first4=Zhang|last5=A|first5=Bouska|last6=A|first6=Rosenwald|last7=Rd|first7=Gascoyne|last8=X|first8=Wu|last9=J|first9=Wang|date=2015|title=IDH2R172 mutations define a unique subgroup of patients with angioimmunoblastic T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26268241/|language=en|doi=10.1182/blood-2015-05-644591|pmc=PMC4600014|pmid=26268241}}</ref>
|-
|''TET2''
|Widely distributed
|Tumor Suppressor
|LOF
|50-80%<ref name=":12">{{Cite journal|last=F|first=Lemonnier|last2=L|first2=Couronné|last3=M|first3=Parrens|last4=Jp|first4=Jaïs|last5=M|first5=Travert|last6=L|first6=Lamant|last7=O|first7=Tournillac|last8=T|first8=Rousset|last9=B|first9=Fabiani|date=2012|title=Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters|url=https://pubmed.ncbi.nlm.nih.gov/22760778/|language=en|pmid=22760778}}</ref><ref name=":5" />
|-
|''DNMT3A''
|W305*
|Tumor Suppressor
|LOF
|20-30%<ref name=":4" /><ref name=":5" />
|-
|''RHOA''
|G17V; G17E; C16R; T19I; D120Y
|Tumor Suppressor '''ONCOGENE'''
|LOF '''GOF'''
|60-70%<ref>{{Cite journal|last=M|first=Sakata-Yanagimoto|last2=T|first2=Enami|last3=K|first3=Yoshida|last4=Y|first4=Shiraishi|last5=R|first5=Ishii|last6=Y|first6=Miyake|last7=H|first7=Muto|last8=N|first8=Tsuyama|last9=A|first9=Sato-Otsubo|date=2014|title=Somatic RHOA mutation in angioimmunoblastic T cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24413737/|language=en|pmid=24413737}}</ref><ref>{{Cite journal|last=Hy|first=Yoo|last2=Mk|first2=Sung|last3=Sh|first3=Lee|last4=S|first4=Kim|last5=H|first5=Lee|last6=S|first6=Park|last7=Sc|first7=Kim|last8=B|first8=Lee|last9=K|first9=Rho|date=2014|title=A recurrent inactivating mutation in RHOA GTPase in angioimmunoblastic T cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/24584070/|language=en|pmid=24584070}}</ref><ref name=":6">{{Cite journal|last=T|first=Palomero|last2=L|first2=Couronné|last3=H|first3=Khiabanian|last4=My|first4=Kim|last5=A|first5=Ambesi-Impiombato|last6=A|first6=Perez-Garcia|last7=Z|first7=Carpenter|last8=F|first8=Abate|last9=M|first9=Allegretta|date=2014|title=Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/24413734/|language=en|doi=10.1038/ng.2873|pmc=PMC3963408|pmid=24413734}}</ref>
|-
|''FYN''
|L174R; R176C; Y531H
|Oncogene
|GOF
|up to 5-10%<ref name=":3">{{Cite journal|last=Sh|first=Lee|last2=Js|first2=Kim|last3=J|first3=Kim|last4=Sj|first4=Kim|last5=Ws|first5=Kim|last6=S|first6=Lee|last7=Yh|first7=Ko|last8=Hy|first8=Yoo|date=2015|title=A highly recurrent novel missense mutation in CD28 among angioimmunoblastic T-cell lymphoma patients|url=https://pubmed.ncbi.nlm.nih.gov/26405154/|language=en|doi=10.3324/haematol.2015.133074|pmc=PMC4666342|pmid=26405154}}</ref><ref name=":6" />
|-
|''PLCG1''
|S345F; G869E
|Oncogene
|GOF
|up to 5-10%<ref name=":3" /><ref name=":4" />
|-
|''CD28''
|D124V; D124E; T195P
|Oncogene
|GOF
|up to 5-10%<ref name=":3" /><ref name=":13">{{Cite journal|last=J|first=Rohr|last2=S|first2=Guo|last3=J|first3=Huo|last4=A|first4=Bouska|last5=C|first5=Lachel|last6=Y|first6=Li|last7=Pd|first7=Simone|last8=W|first8=Zhang|last9=Q|first9=Gong|date=2016|title=Recurrent activating mutations of CD28 in peripheral T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/26719098/|language=en|doi=10.1038/leu.2015.357|pmc=PMC5688878|pmid=26719098}}</ref>
|-
|TNFRSF21
|S428fs*S1
|Tumor Suppressor
|LOF
|<ref name=":4" />
|-
|CCND3
|Q280*
|Tumor Suppressor
|LOF
|<ref name=":4" />
|-
|SAMSN1
|R153*
|Tumor Suppressor
|LOF
|<ref name=":4" />
|}
‡More comprehensive account of specific mutations in these genes can be found in [https://www.cbioportal.org/ cBioPortal] and [https://cancer.sanger.ac.uk/cosmic COSMIC].

==Epigenomics (Methylation)==

*Frequent mutation in epigenetic modifiers like: <ref name=":4" /><ref name=":5" /><ref name=":11" /><ref name=":12" />
**''IDH2'' (20-30%)
**''TET2'' (50-80%)
**''DNMT3A'' (20-30%)

==Genes and Main Pathways Involved==
{| class="wikitable"
|+
!Molecular Features
!Pathway
!Pathophysiologic Outcome
|-
|''FYN'', ''PLCG1'', and ''CD28'' mutations
|T-cell receptor signaling pathway<ref name=":4" /><ref name=":6" /><ref name=":3" /><ref name=":13" />
|Increased proliferation and survival
|-
|''IDH2'', ''TET2'', and ''DNMT3A'' mutations
|Histone modification and chromatin remodeling<ref name=":4" /><ref name=":5" /><ref name=":11" /><ref name=":12" />
|Abnormal gene expression program
|}

*

==Diagnostic Testing Methods==

*Clinical, morphological, and immunophenotypic findings are generally sufficient for diagnosis
*''IDH2'' R172 mutations are specific to AITL
*T-Cell receptor and immunoglobulin genes rearrangement detection by karyotyping and FISH analysis

==Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications)==

*Overall prognosis is poor<ref name=":9">{{Cite journal|last=N|first=Mourad|last2=N|first2=Mounier|last3=J|first3=Brière|last4=E|first4=Raffoux|last5=A|first5=Delmer|last6=A|first6=Feller|last7=Cj|first7=Meijer|last8=Jf|first8=Emile|last9=R|first9=Bouabdallah|date=2008|title=Clinical, biologic, and pathologic features in 157 patients with angioimmunoblastic T-cell lymphoma treated within the Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials|url=https://pubmed.ncbi.nlm.nih.gov/18292286/|language=en|doi=10.1182/blood-2007-08-105759|pmc=PMC2343588|pmid=18292286}}</ref><ref name=":10">{{Cite journal|last=J|first=Vose|last2=J|first2=Armitage|last3=D|first3=Weisenburger|date=2008|title=International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes|url=https://pubmed.ncbi.nlm.nih.gov/18626005/|language=en|pmid=18626005}}</ref>
*Median survival < 3 years, even with aggressive treatment<ref name=":9" /><ref name=":10" />
*Male sex, mediastinal lymphadenopathy, and anemia adversely affect the survival<ref name=":9" />

'''Suggested Treatment Regimens based on NCCN Guideline Version 1.2020 (TCEL-B 3 of 5)'''

Second-line therapy (with intention to transplant) and subsequent therapy:

*Clinical Trial preferred
*Preferred regimens
**Single Agents (alphabetical order)
***Belinostat
***Brentuximab Vedotin for CD30+ AITL
***Romidepsin
**Combination Regimens
***DHAP(Dexamethasone, Cisplatin, Cytarabine)
***ESHAP (Etoposide, Methylprednisolone, Citarabine, Cisplatin)
***GDP (Gemcitabine, Dexamethasone, Cisplatin)
***GemOx (Gemcitabine, Oxaliplatin)
***ICE (Ifosfamide, Carboplatin, Etoposide)
*Other recommended regimens
**Single Agents (alphabetical order)
***Bendamustine
***Gemcitabine
***Lenalidomide
***Pralatrexate

Second-line or initial palliative intent therapy (no intention to transplant) and subsequent therapy:

*Clinical Trial preferred
*Preferred regimens
**Single Agents (alphabetical order)
***Belinostat
***Brentuximab Vedotin for CD30+ AITL
***Romidepsin
*Other recommended regimen (alphabetical order)
**Alemtuzumab
**Bendamustine
**Bertezomib (categort 2B)
**Cyclophosphamide and/or Etoposide (IV or PO)
**Cyclosporine
**Gemcitabine
**Lenalidomide
**Pralatrexate
**Radiation therapy

==Other Information==

N/A

==Links==

[[Angioimmunoblastic T-cell Lymphoma and Other Nodal Lymphomas of T Follicular Helper Cell Origin]]

==References==
(use "Cite" icon at top of page
<references />

HAEM4Backup:Angioimmunoblastic T-cell Lymphoma - Revision history

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)*== * Sara Akhavanfard, M.D., Ph.D. * Ruthann Pfau, Ph.D., FACMG __TOC__ ==Cancer Category/Type== * Angioimmunoblastic T-cell L..."

Bailey.Glen: Created page with "{{Under Construction}} ==Primary Author(s)== Sara Akhavanfard, M.D., Ph.D. * Ruthann Pfau, Ph.D., FACMG TOC ==Cancer Category/Type== * Angioimmunoblastic T-cell L..."