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Created page with "==Primary Author(s)*== *Derick Okwan-Duodu, MD, PhD *Sumire Kitahara, MD __TOC__ ==Cancer Category/Type== *Mature T- and NK-cell Neoplasms ==Cancer Sub-Classification..."

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==Primary Author(s)*==

*Derick Okwan-Duodu, MD, PhD
*Sumire Kitahara, MD
__TOC__

==Cancer Category/Type==

*[[Mature T- and NK-cell Neoplasms]]

==Cancer Sub-Classification / Subtype==

*[[Intestinal T-cell Lymphoma|Intestinal T-cell lymphoma]]

==Definition / Description of Disease==

*Enteropathy-associated T-cell lymphoma (EATL) is an intestinal T-cell neoplasm closely associated with celiac disease<ref name=":5">Arber DA, et al., (2017). Acute myeloid leukaemia with recurrent genetic abnormalities, 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, p372-377.</ref>
*Celiac disease may be diagnosed prior to EATL diagnosis in 20-73% of cases, or both entities may be diagnosed concomitantly in 10-58% of the cases<ref name=":5" />
*Risk factors include homozygosity for HLA-DQ2 and advanced age<ref name=":5" />

==Synonyms / Terminology==

*Historically referred to as enteropathy-associated T-cell lymphoma, type 1, but since "type 2" has been renamed in WHO 2016 as monomorphic epitheliotropic T-cell lymphoma, the word "type" has been dropped from both entities

==Epidemiology / Prevalence==

*0.5-1 in 1 million general population (2-5% in patients with celiac disease, 60-80% in patients with refractory celiac disease type 2)<ref name=":6">{{Cite journal|last=Wh|first=Verbeek|last2=Jm|first2=Van De Water|last3=A|first3=Al-Toma|last4=Jj|first4=Oudejans|last5=Cj|first5=Mulder|last6=Vm|first6=Coupé|date=2008|title=Incidence of enteropathy--associated T-cell lymphoma: a nation-wide study of a population-based registry in The Netherlands|url=https://pubmed.ncbi.nlm.nih.gov/18618372/|language=en|pmid=18618372}}</ref><ref name=":1">{{Cite journal|last=Aj|first=Ferreri|last2=Pl|first2=Zinzani|last3=S|first3=Govi|last4=Sa|first4=Pileri|date=2011|title=Enteropathy-associated T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/20655757/|language=en|pmid=20655757}}</ref><ref name=":2">{{Cite journal|last=J|first=Delabie|last2=H|first2=Holte|last3=Jm|first3=Vose|last4=F|first4=Ullrich|last5=Es|first5=Jaffe|last6=Kj|first6=Savage|last7=Jm|first7=Connors|last8=L|first8=Rimsza|last9=Nl|first9=Harris|date=2011|title=Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project|url=https://pubmed.ncbi.nlm.nih.gov/21566094/|language=en|pmid=21566094}}</ref><ref>{{Cite journal|last=A|first=Rubio-Tapia|last2=Ja|first2=Murray|date=2010|title=Classification and management of refractory coeliac disease|url=https://pubmed.ncbi.nlm.nih.gov/20332526/|language=en|doi=10.1136/gut.2009.195131|pmc=PMC2861306|pmid=20332526}}</ref><ref>{{Cite journal|last=G|first=Malamut|last2=P|first2=Afchain|last3=V|first3=Verkarre|last4=T|first4=Lecomte|last5=A|first5=Amiot|last6=D|first6=Damotte|last7=Y|first7=Bouhnik|last8=Jf|first8=Colombel|last9=Jc|first9=Delchier|date=2009|title=Presentation and long-term follow-up of refractory celiac disease: comparison of type I with type II|url=https://pubmed.ncbi.nlm.nih.gov/19014942/|language=en|pmid=19014942}}</ref>
*> 60% of all cases in intestinal T- cell lymphomas<ref name=":6" /><ref name=":1" /><ref name=":2" />
*M:F 1.04:1 to 2.8:1<ref name=":6" /><ref name=":1" /><ref name=":2" />
*6th-7th decade of life<ref name=":6" /><ref name=":1" /><ref name=":2" />
*Mostly Caucasian (> 90%)<ref name=":6" /><ref name=":1" /><ref name=":2" />
*Uncommon in Asian countries due to low population frequency of celiac HLA risk alleles<ref name=":6" /><ref name=":1" /><ref name=":2" />

==Clinical Features==
Many of the below features are indistiguishable from the presentation of celiac disease, which may delay the diagnosis of EATL. Persistent symptoms following gluten-free diet is highly suggestive of EATL.<ref name=":1" />

'''Signs & Symptoms'''

*Abdominal pain
*Weight loss
*Gluten-insensitive diarrhea/malabsorption
*Bowel obstruction or perforation

'''Laboratory Findings'''

*Anemia
*Hypoalbuminemia
*Hemophagocytosis

If there is no prior diagnosis of celiac disease and lymphoma is the initial presentation, the following findings can point towards celiac disease associated EATL:

*Anti-tissue transglutaminase-2 antibodies or Anti-endomysial antibodies
*Dermatitis herpetiformis

==Sites of Involvement==

*Small intestine (predominantly jejunum and ileum > large intestine and stomach)<ref name=":1" />
*Metastasis involve intra-abdominal node > bone marrow > lung > liver > skin<ref name=":1" />
*CNS (rare)<ref name=":1" />

==Morphologic Features==

*Pleomorphic medium to large neoplastic lymphoid infiltrate<ref name=":2" />
*Neighborhood mucosa characterized by villous atrophy and crypt hyperplasia (non-malignant areas of celiac disease)<ref name=":2" />
*Round or angulated vesicular nuclei<ref name=":2" />
*Prominent nucleoli<ref name=":2" />
*Moderate-abundant pale cytoplasm<ref name=":2" />
*Extensive admixture of inflammatory cells (eosinophils, histiocytes)<ref name=":2" />
*Angiocentric and angioinvasive features with extensive necrosis<ref name=":2" />

==Immunophenotype==

{| class="wikitable sortable"
|-
!Finding<ref name=":7">{{Cite journal|last=P|first=Domizio|last2=Ra|first2=Owen|last3=Na|first3=Shepherd|last4=Ic|first4=Talbot|last5=Aj|first5=Norton|date=1993|title=Primary lymphoma of the small intestine. A clinicopathological study of 119 cases|url=https://pubmed.ncbi.nlm.nih.gov/8470758/|language=en|pmid=8470758}}</ref><ref name=":0">{{Cite journal|last=Deleeuw|first=Ronald J.|last2=Zettl|first2=Andreas|last3=Klinker|first3=Erdwine|last4=Haralambieva|first4=Eugenia|last5=Trottier|first5=Magan|last6=Chari|first6=Raj|last7=Ge|first7=Yong|last8=Gascoyne|first8=Randy D.|last9=Chott|first9=Andreas|date=2007-05|title=Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes|url=https://pubmed.ncbi.nlm.nih.gov/17484883|journal=Gastroenterology|volume=132|issue=5|pages=1902–1911|doi=10.1053/j.gastro.2007.03.036|issn=0016-5085|pmid=17484883}}</ref>!!Marker
|-
|Positive (universal)||CD3, CD7
|-
|Positive (frequent)||CD30 (harbinger of transformation to EATL from RCD2), NKP46 (not seen in IEL of CD or RCD1), CD103,
cytotoxic granule-associated markers (TIA1, granzyme B, perforin)
|-
|Negative (frequent)
|CD4, CD8, CD5, CD56, TCR
|-
|Ki-67
|high
|}

*Immunophenotype of intraepithelial lymphocytes (IEL):<ref name=":7" /><ref name=":0" />
**Varies depending on background type 1 or type 2 refractory celiac disease (RCD).
***Type 1 (RCD1):
****Milder symptoms with high 5-year survival with low risk of EATL development
****Flow cytometry: sCD3+, CD8+, CD5+
***Type 2 (RCD2):
****Severe symptoms with protein-losing enteropathy leads to malnourishment (BMI < 18); low 5-year survival with increased risk of EATL
****Flow cytometry: sCD3_, CD8-, CD5-
****IHC:
*****NKP46: significantly more positive in RCD2 IEL than normal IEL in CD and RCD1; not specific for RCD2 or EATL, can be seen in [[Monomorphic Epitheliotropic Intestinal T-cell Lymphoma|MEITL]]; not seen in [[Indolent T-cell Lymphoproliferative Disorder of the Gastrointestinal Tract|indolent T-cell LPD of GI tract]]
*****CD30+ indicates progression to EATL
****

==Chromosomal Rearrangements (Gene Fusions)==

*No recurrent gene fusions reported

==Characteristic Chromosomal Aberrations / Patterns==

*HLA-DQ2 (HLA-DQA1*0501 and DQB1*02) homozygosity - increased (at least 5-fold) risk for RCD and EATL<ref>{{Cite journal|last=A|first=Al-Toma|last2=Ms|first2=Goerres|last3=Jw|first3=Meijer|last4=As|first4=Peña|last5=Jb|first5=Crusius|last6=Cj|first6=Mulder|date=2006|title=Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/16527694/|language=en|pmid=16527694}}</ref>
*HLA-DQB1*02 genotype correlated with 5q gain <ref name=":0" />

==Genomic Gain/Loss/LOH==

{| class="wikitable"
|-
!Chromosome Number<ref name=":0" /><ref>{{Cite journal|last=Ak|first=Baumgärtner|last2=A|first2=Zettl|last3=A|first3=Chott|last4=G|first4=Ott|last5=Hk|first5=Müller-Hermelink|last6=P|first6=Starostik|date=2003|title=High frequency of genetic aberrations in enteropathy-type T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/14563952/|language=en|pmid=14563952}}</ref><ref name=":3">{{Cite journal|last=A|first=Zettl|last2=G|first2=Ott|last3=A|first3=Makulik|last4=T|first4=Katzenberger|last5=P|first5=Starostik|last6=T|first6=Eichler|last7=B|first7=Puppe|last8=M|first8=Bentz|last9=Hk|first9=Müller-Hermelink|date=2002|title=Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/12414511/|language=en|doi=10.1016/S0002-9440(10)64441-0|pmc=PMC1850794|pmid=12414511}}</ref><ref name=":4">{{Cite journal|last=Ab|first=Moffitt|last2=Sl|first2=Ondrejka|last3=M|first3=McKinney|last4=Re|first4=Rempel|last5=Jr|first5=Goodlad|last6=Ch|first6=Teh|last7=S|first7=Leppa|last8=S|first8=Mannisto|last9=Pe|first9=Kovanen|date=2017|title=Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2|url=https://pubmed.ncbi.nlm.nih.gov/28424246/|language=en|doi=10.1084/jem.20160894|pmc=PMC5413324|pmid=28424246}}</ref><ref>{{Cite journal|last=Tomita|first=Sakura|last2=Kikuti|first2=Yara Y.|last3=Carreras|first3=Joaquim|last4=Kojima|first4=Minoru|last5=Ando|first5=Kiyoshi|last6=Takasaki|first6=Hirotaka|last7=Sakai|first7=Rika|last8=Takata|first8=Katsuyoshi|last9=Yoshino|first9=Tadashi|date=2015-10|title=Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan|url=https://www.nature.com/articles/modpathol201585|journal=Modern Pathology|language=en|volume=28|issue=10|pages=1286–1296|doi=10.1038/modpathol.2015.85|issn=1530-0285}}</ref>!!Gain/Loss/Amp/LOH!!Region
!Genes
!Prevalence
|-
|9q||gain||q22-34
|C-ABL1, NOTCH-1, VAV2, CARD9
|40-71%
|-
|16q
|loss
|12.1
|CLYD
|23%
|-
|1q||gain||q22-44
|CKS1B
|30%
|-
|5q
|gain
|q33.3–34
|UBLCP1, IRGM-1
|17%-30%
|-
|9p
|LOH
|p21
|CDKN2A/B (p16)
|36%; possibly more common in (5 of 9) cases with large cells<ref>{{Cite journal|last=Obermann|first=E. C.|last2=Diss|first2=T. C.|last3=Hamoudi|first3=R. A.|last4=Munson|first4=P.|last5=Wilkins|first5=B. S.|last6=Camozzi|first6=M. L. P.|last7=Isaacson|first7=P. G.|last8=Du|first8=M. Q.|last9=Dogan|first9=A.|date=2004-02|title=Loss of heterozygosity at chromosome 9p21 is a frequent finding in enteropathy-type T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/14743509|journal=The Journal of Pathology|volume=202|issue=2|pages=252–262|doi=10.1002/path.1506|issn=0022-3417|pmid=14743509}}</ref>
|-
|7q
|gain
|q11.21-q36.1
|NSUN5
|24%
|-
|8p
|loss
|p23.3-p11.21
|
|20-30%
|-
|8q
|gain
|q24
|MYC
|25-27%
|-
|13q
|loss
|
|RB
|24%
|-
|17p
|loss
|p12-13.2
|TP53
|23%
|}

*Most copy number alterations are large arm level alterations; no focal gene level alterations reach statistical significance<ref name=":4" />

 
==Gene Mutations (SNV/INDEL)==

{| class="wikitable"
!Gene*<ref name=":4" /><ref>{{Cite journal|last=Sh|first=Swerdlow|last2=Jr|first2=Cook|date=2020|title=As the world turns, evolving lymphoma classifications-past, present and future|url=https://pubmed.ncbi.nlm.nih.gov/31493426/|language=en|pmid=31493426}}</ref>
!Function/Oncogene/Tumor Suppressor Gene
!Frequency<ref name=":4" />
|-
|SETD2
|Tumor suppressor gene
|32%
|-
|YLPM1
|Tumor suppressor gene
|22%
|-
|TET2
|Tumor suppressor gene
|14%
|-
|STAT5B
|Oncogene
|29%
|-
|JAK1
|Oncogene
|23%
|-
|JAK3
|Oncogene
|23%
|-
|STAT3
|Oncogene
|16%
|-
|SOCS1
|Tumor suppressor gene
|7%
|-
|NRAS
|Oncogene
|10%
|-
|KRAS
|Oncogene
|6%
|-
|TP53
|Tumor suppressor gene
|10%
|-
|BCL11B
|Tumor suppressor gene
|13%
|-
|BRIP1
|Tumor suppressor gene
|16%
|-
|TERT
|Oncogene
|17%
|-
|BBX
|Cell cycle transcription factor
|16%
|-
|DAPK3
|Apoptosis
|10%
|-
|PRDM1
|Interferon-related transcription factor
|9%
|}
<nowiki>*</nowiki>The specific mutations in these genes may be found elsewhere ([https://cancer.sanger.ac.uk/cosmic COSMIC], [https://www.cbioportal.org/ cBioPortal])

*''PRDM1'' and ''DAPK3'', followed by ''STAT3'' and ''STAT5B'', are the most common mutually exclusive gene pairs<ref name=":4" />

==Epigenomics (Methylation)==

*SETD2 is a histone H3 lysine 36 methyltransferase (forms H3K37me3)<ref name=":4" />
**Altered (mostly by loss-of-function mutations) in ~32% of EATL
**Results in global H3K36 hypomethylation

==Genes and Main Pathways Involved==

*Chromatin modifying genes: SETD2, TET2, YLPM1; loss of function mutations<ref name=":4" /><ref name=":10">{{Cite journal|last=A|first=Nicolae|last2=L|first2=Xi|last3=Th|first3=Pham|last4=Ta|first4=Pham|last5=W|first5=Navarro|last6=Hg|first6=Meeker|last7=S|first7=Pittaluga|last8=Es|first8=Jaffe|last9=M|first9=Raffeld|date=2016|title=Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas|url=https://pubmed.ncbi.nlm.nih.gov/27389054/|language=en|doi=10.1038/leu.2016.178|pmc=PMC5093023|pmid=27389054}}</ref><ref name=":11">{{Cite journal|last=G|first=Malamut|last2=R|first2=El Machhour|last3=N|first3=Montcuquet|last4=S|first4=Martin-Lannerée|last5=I|first5=Dusanter-Fourt|last6=V|first6=Verkarre|last7=Jj|first7=Mention|last8=G|first8=Rahmi|last9=H|first9=Kiyono|date=2010|title=IL-15 triggers an antiapoptotic pathway in human intraepithelial lymphocytes that is a potential new target in celiac disease-associated inflammation and lymphomagenesis|url=https://pubmed.ncbi.nlm.nih.gov/20440074/|language=en|doi=10.1172/JCI41344|pmc=PMC2877946|pmid=20440074}}</ref><ref name=":12">{{Cite journal|last=Mention|first=Jean-Jacques|last2=Ben Ahmed|first2=Mélika|last3=Bègue|first3=Bernadette|last4=Barbe|first4=Ullah|last5=Verkarre|first5=Virginie|last6=Asnafi|first6=Vahid|last7=Colombel|first7=Jean-Frédéric|last8=Cugnenc|first8=Paul-Henri|last9=Ruemmele|first9=Frank M.|date=2003-09|title=Interleukin 15: a key to disrupted intraepithelial lymphocyte homeostasis and lymphomagenesis in celiac disease|url=https://pubmed.ncbi.nlm.nih.gov/12949719|journal=Gastroenterology|volume=125|issue=3|pages=730–745|doi=10.1016/s0016-5085(03)01047-3|issn=0016-5085|pmid=12949719}}</ref>
*JAK-STAT pathway: JAK1, JAK3, STAT3, STAT5B, SOCS1; mutated drivers in this pathway tended to be mutually exclusive<ref name=":4" /><ref name=":10" /><ref name=":11" /><ref name=":12" />
*RAS/MAPK signaling pathway<ref name=":4" /><ref name=":10" /><ref name=":11" /><ref name=":12" />
*IL-15 deregulation and disruption of intestinal immune homeostasis<ref name=":4" /><ref name=":10" /><ref name=":11" /><ref name=":12" />
*Overexpression of genes involved in Interferon-γ signaling<ref name=":4" />

==Diagnostic Testing Methods==

*No specific recurrent genetic abnormalities that are diagnostic for EATL<ref name=":8">{{Cite journal|last=A|first=Di Sabatino|last2=F|first2=Biagi|last3=Pg|first3=Gobbi|last4=Gr|first4=Corazza|date=2012|title=How I treat enteropathy-associated T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/22271451/|language=en|pmid=22271451}}</ref><ref name=":9">{{Cite journal|last=Sj|first=Van Weyenberg|last2=Mr|first2=Meijerink|last3=Ma|first3=Jacobs|last4=C|first4=van Kuijk|last5=Cj|first5=Mulder|last6=Jh|first6=van Waesberghe|date=2011|title=MR enteroclysis in refractory celiac disease: proposal and validation of a severity scoring system|url=https://pubmed.ncbi.nlm.nih.gov/21330559/|language=en|pmid=21330559}}</ref>
*Clonality can be confirmed by T-cell receptor gene rearrangement studies<ref name=":8" /><ref name=":9" />
**Intraepithelial lymphocytes in type 2 refractory celiac disease show similar gene rearrangement size as EATL<ref name=":8" /><ref name=":9" />
*Chromosomal microarrays may identify genetic abnormalities frequently associated with EATL<ref name=":8" /><ref name=":9" />
*Next generation sequencing may identify genetic abnormalities frequently associated with EATL<ref name=":8" /><ref name=":9" />
*Morphology and immunophenotyping
**Cut-off value of 20% aberrant intraepithelial lymphocytes (cytoplasmic CD3+, surface CD3−, CD7+, CD103+, CD8−, CD4−) to distinguish from refractory celiac disease<ref>{{Cite journal|last=Wh|first=Verbeek|last2=Ms|first2=Goerres|last3=Bm|first3=von Blomberg|last4=Jj|first4=Oudejans|last5=Pe|first5=Scholten|last6=M|first6=Hadithi|last7=A|first7=Al-Toma|last8=Mw|first8=Schreurs|last9=Cj|first9=Mulder|date=2008|title=Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease|url=https://pubmed.ncbi.nlm.nih.gov/18024205/|language=en|pmid=18024205}}</ref>

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

*'''Diagnosis'''
**No specific recurrent genetic abnormality that is diagnostic for EATL
***Gain of 1q and 5q more frequent in EATL, whereas 8q24 (MYC) gain is more frequent in MEITL<ref name=":0" /><ref name=":3" />
***SETD2 mutations are common in both EATL (32%)<ref name=":4" /> and MEITL (91%)<ref>{{Cite journal|last=Roberti|first=Annalisa|last2=Dobay|first2=Maria Pamela|last3=Bisig|first3=Bettina|last4=Vallois|first4=David|last5=Boéchat|first5=Cloé|last6=Lanitis|first6=Evripidis|last7=Bouchindhomme|first7=Brigitte|last8=Parrens|first8=Marie-Cécile|last9=Bossard|first9=Céline|date=09 07, 2016|title=Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations|url=https://pubmed.ncbi.nlm.nih.gov/27600764|journal=Nature Communications|volume=7|pages=12602|doi=10.1038/ncomms12602|issn=2041-1723|pmc=5023950|pmid=27600764}}</ref>
*'''Prognosis'''
**In one study, >3 chromosomal imbalance was associated with worse prognosis<ref name=":3" />
*'''Therapeutic Implications'''
**Recurrent mutations in epigenetic machinery genes - epigenetic modifying drugs may be effective<ref>{{Cite journal|last=Zhang|first=Ping|last2=Zhang|first2=Mingzhi|date=2020-11-07|title=Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma|url=https://doi.org/10.1186/s13148-020-00962-x|journal=Clinical Epigenetics|volume=12|issue=1|pages=169|doi=10.1186/s13148-020-00962-x|issn=1868-7083|pmc=PMC7648940|pmid=33160401}}</ref>
**Mutations involved in JAK-STAT signaling pathway - inhibitors of this pathway may be effective
**Suboptimal response to chemotherapy due to malnutrition, intestinal complications and toxicity and malnutrition
**CD30+ disease may benefit from brentuximab vedotin (adcetris) as second line with or without stem cell transplant<ref>{{Cite journal|last=Sm|first=Horwitz|last2=Rh|first2=Advani|last3=Nl|first3=Bartlett|last4=Ed|first4=Jacobsen|last5=Jp|first5=Sharman|last6=Oa|first6=O'Connor|last7=T|first7=Siddiqi|last8=Da|first8=Kennedy|last9=Y|first9=Oki|date=2014|title=Objective responses in relapsed T-cell lymphomas with single-agent brentuximab vedotin|url=https://pubmed.ncbi.nlm.nih.gov/24652992/|language=en|doi=10.1182/blood-2013-12-542142|pmc=PMC4425442|pmid=24652992}}</ref><ref>{{Cite journal|last=Fanale|first=Michelle A.|last2=Horwitz|first2=Steven M.|last3=Forero-Torres|first3=Andres|last4=Bartlett|first4=Nancy L.|last5=Advani|first5=Ranjana H.|last6=Pro|first6=Barbara|last7=Chen|first7=Robert W.|last8=Davies|first8=Andrew|last9=Illidge|first9=Tim|date=2018-05-10|title=Five-year outcomes for frontline brentuximab vedotin with CHP for CD30-expressing peripheral T-cell lymphomas|url=http://dx.doi.org/10.1182/blood-2017-12-821009|journal=Blood|volume=131|issue=19|pages=2120–2124|doi=10.1182/blood-2017-12-821009|issn=0006-4971|pmc=5946765|pmid=29507077}}</ref>
**No FDA-approved targeted therapies currently available<ref>{{Cite journal|displayauthors=1|last=National Comprehensive Cancer Network|first=|date=January 2021|title=NCCN Clinical Practice Guidelines in Oncology: Peripheral T-cell Lymphomas|url=https://www.nccn.org/professionals/physician_gls/pdf/t-cell.pdf|journal=|volume=|pages=|via=}}</ref>

==Familial Forms==

*While there is a genetic predisposition of those with HLA-DQ2 or HLA-DQ8 to develop celiac disease and EATL is a complication of celiac disease, familial forms of EATL are not described.
**HLA-DQ2 (HLA-DQA1*0501 and DQB1*02) homozygosity - increased (at least 5-fold) risk for RCD and EATL<ref>{{Cite journal|last=A|first=Al-Toma|last2=Ms|first2=Goerres|last3=Jw|first3=Meijer|last4=As|first4=Peña|last5=Jb|first5=Crusius|last6=Cj|first6=Mulder|date=2006|title=Human leukocyte antigen-DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/16527694/|language=en|pmid=16527694}}</ref>
**HLA-DQB1*02 genotype correlated with 5q gain <ref name=":02">{{Cite journal|last=Deleeuw|first=Ronald J.|last2=Zettl|first2=Andreas|last3=Klinker|first3=Erdwine|last4=Haralambieva|first4=Eugenia|last5=Trottier|first5=Magan|last6=Chari|first6=Raj|last7=Ge|first7=Yong|last8=Gascoyne|first8=Randy D.|last9=Chott|first9=Andreas|date=2007-05|title=Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes|url=https://pubmed.ncbi.nlm.nih.gov/17484883|journal=Gastroenterology|volume=132|issue=5|pages=1902–1911|doi=10.1053/j.gastro.2007.03.036|issn=0016-5085|pmid=17484883}}</ref>

==Other Information==

*N/A

==Links==

*[[Intestinal T-cell Lymphoma]]<nowiki/>s
*[[Monomorphic epitheliotropic intestinal T-cell lymphoma|Monomorphic epitheliotropi]]<nowiki/>[[Monomorphic epitheliotropic intestinal T-cell lymphoma|c intestinal T-cell lymphoma]]

==References==

<references />

#

==Notes==
<nowiki>*</nowiki>Primary authors will typically be those that initially create and complete the content of a page. If a subsequent user modifies the content and feels the effort put forth is of high enough significance to warrant listing in the authorship section, please contact the CCGA coordinators (contact information provided on the homepage). Additional global feedback or concerns are also welcome.

HAEM4Backup:Enteropathy-Associated T-cell Lymphoma - Revision history

Bailey.Glen: Created page with "==Primary Author(s)*== *Derick Okwan-Duodu, MD, PhD *Sumire Kitahara, MD __TOC__ ==Cancer Category/Type== *Mature T- and NK-cell Neoplasms ==Cancer Sub-Classification..."

Bailey.Glen: Created page with "==Primary Author(s)== Derick Okwan-Duodu, MD, PhD Sumire Kitahara, MD TOC ==Cancer Category/Type== Mature T- and NK-cell Neoplasms ==Cancer Sub-Classification..."