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

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

Derick Okwan-Duodu MD, PhD; Sumire Kitahara, MD

__TOC__

==Cancer Category/Type==

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

==Cancer Sub-Classification / Subtype==

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

==Definition / Description of Disease==

*Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a primary intestinal T-cell lymphoma derived from intraepithelial lymphocytes that, unlike enteropathy-associated T-cell lymphoma, is not clearly associated with celiac disease

==Synonyms / Terminology==

*Formerly and no longer referred to as type II enteropathy-associated T-cell lymphoma (EATL)

==Epidemiology / Prevalence==

*More prevalent in Asian and Hispanic/indigenous population
*< 1 per 1,000,000

==Clinical Features==

*Abdominal pain
*Weight loss
*Diarrhea
*Long-standing history of malabsorption is atypical

==Sites of Involvement==

*Small Intestine (jejunum > ileum) > large intestine > stomach

==Morphologic Features==

*Monomorphic small- to medium-sized neoplastic cells
*Uniformly round and regular nuclei
*Finely dispersed chromatin
*Inconspicuous nucleoli
*Abundant rim of pale cytoplasm

==Immunophenotype==
'''Postive''': '''CD3, CD8, CD56''', TCR gamma > TCR beta, '''TIA1''', CD20 in 20% of cases, '''MATK''' in >80% of neoplastic cells helps distinguish from EATL, '''SYK''' <ref name=":1" /> (distinguishes from EATL), NKP46

Variably positive between cases: granzyme B, perforin

Negative: CD5, EBV/EBER

'''INCORPORATE INTO TABLE'''

==Chromosomal Rearrangements (Gene Fusions)==

*N/A
*'''No consistent gene fusion reported'''

==Characteristic Chromosomal Aberrations / Patterns==

*No pathognomonic aberrations/patterns described, but multiple genomic gains and losses are frequent

==Genomic Gain/Loss/LOH<ref>{{Cite journal|last=Rj|first=Deleeuw|last2=A|first2=Zettl|last3=E|first3=Klinker|last4=E|first4=Haralambieva|last5=M|first5=Trottier|last6=R|first6=Chari|last7=Y|first7=Ge|last8=Rd|first8=Gascoyne|last9=A|first9=Chott|date=2007|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/|language=en|pmid=17484883}}</ref><ref name=":3">{{Cite journal|last=S|first=Tomita|last2=Yy|first2=Kikuti|last3=J|first3=Carreras|last4=M|first4=Kojima|last5=K|first5=Ando|last6=H|first6=Takasaki|last7=R|first7=Sakai|last8=K|first8=Takata|last9=T|first9=Yoshino|date=2015|title=Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan|url=https://pubmed.ncbi.nlm.nih.gov/26226842/|language=en|pmid=26226842}}</ref>==

In contrast to EATL, gains at 1q32.2-41 and 5q34-35.5 are reported less commonly. However, one study from Japan<ref name=":3" /> described a series a non-celiac associated intestinal T-cell lymphoma with MEITL immunophenotype that demonstrated these gains at a frequency comparable to Western EATL, suggesting more overlap between Western EATL and Asian MEITL than previously thought, requiring additional investigation to further study these observations.

{| class="wikitable sortable"
|-
!Chromosome Number!!Gain/Loss/Amp/LOH!!Region
!Genes
!Prevalence
|-
|8q||gain||q24
|MYC
|25-38%
|-
|9q||gain||q22.31;q33.2; q34.3-13
|PPP6C, ASS1,CARD9
|75%
|-
|1q
|gain
|q32.2-44
|CKS1B
|50%
|-
|5q
|gain
|q34
|
|38%
|-
|8p
|gain
|p11.23
|
|63%
|-
|4p
|gain
|p15.1
|
|63%
|-
|7q
|gain
|q34
|
|63%
|-
|12p
|gain
|p13.31
|ETV6
|
|-
|7p
|loss
|p14.1
|MAFK
|75%
|-
|8p
|loss
|p23.3-p11.21
|
|38%
|-
|16q
|loss
|
|
|50%
|}

==Gene Mutations (SNV/INDEL)<ref name=":0">{{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 name=":2">{{Cite journal|last=A|first=Roberti|last2=Mp|first2=Dobay|last3=B|first3=Bisig|last4=D|first4=Vallois|last5=C|first5=Boéchat|last6=E|first6=Lanitis|last7=B|first7=Bouchindhomme|last8=Mc|first8=Parrens|last9=C|first9=Bossard|date=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/|language=en|doi=10.1038/ncomms12602|pmc=PMC5023950|pmid=27600764}}</ref><ref>{{Cite journal|last=Ml|first=Nairismägi|last2=J|first2=Tan|last3=Jq|first3=Lim|last4=S|first4=Nagarajan|last5=Cc|first5=Ng|last6=V|first6=Rajasegaran|last7=D|first7=Huang|last8=Wk|first8=Lim|last9=Y|first9=Laurensia|date=2016|title=JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/26854024/|language=en|doi=10.1038/leu.2016.13|pmc=PMC4895162|pmid=26854024}}</ref>==

{| class="wikitable sortable"
|-
!Gene*!!Mutation!!Oncogene/Tumor Suppressor/Other!!Presumed Mechanism (LOF/GOF/Other; Driver/Passenger)!!Prevalence (COSMIC/TCGA/Other)
|-
|SETD2||mutation and/or deletion
|Tumor Suppressor||LOF frameshift indels or nonsense mutation||43% -93%
|-
|STAT5B
|
|'''Oncogene'''
|'''GOF'''
|up to 63%
|-
|JAK3
|
|'''Oncogene'''
|'''GOF'''
|46%
|}
'''*Specific mutations in these genes can be found elsewhere ([https://cancer.sanger.ac.uk/cosmic COSMIC], [https://www.cbioportal.org/ cBioPortal])'''

==Epigenomics (Methylation)==

*Defective H3K36 trimethylation<ref name=":2" />

==Genes and Main Pathways Involved<ref name=":0" /><ref>{{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>==

*JAK-STAT (most common)
*RAS
*P53
*TERT
*BBX

'''Include these in the standard table.'''

==Diagnostic Testing Methods==

*Careful clinicopathologic correlation: lack of prior history of celiac disease or histologic features of celiac disease if no prior history known or documented
*Immunohistochemical evaluation (see Immunophenotype above and Clinical Significance below)
**Some immunostains not routinely available at commercial labs (e.g. SYK, MATK)
*

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

*'''Diagnosis'''
**Because of non-specific findings, careful clinical history, along with immunophenotype and morphology, is necessary to arrive at diagnosis

{| class="wikitable sortable mw-collapsible mw-collapsed"
|+
!IHC
!Significance
!Note
|-
|SYK
|Possible role in diagnosis (inclusion)
|Strongly diagnostic<ref name=":1">{{Cite journal|last=G|first=Mutzbauer|last2=K|first2=Maurus|last3=C|first3=Buszello|last4=J|first4=Pischimarov|last5=S|first5=Roth|last6=A|first6=Rosenwald|last7=A|first7=Chott|last8=E|first8=Geissinger|date=2018|title=SYK expression in monomorphic epitheliotropic intestinal T-cell lymphoma|url=https://pubmed.ncbi.nlm.nih.gov/29052597/|language=en|pmid=29052597}}</ref>
|-
|CD56
|Possible role in diagnosis (inclusion)
|Contrasts with majority of EATL
|-
|EBV
|Possible role in diagnosis (exclusion)
|Strongly associated with extranodal NK/T- cell lymphoma, but negative in MEITL
|-
|MATK
|Possible role in diagnosis (inclusion)
|If present in >80% of tumor cells, helps distinguish from EATL
|-
|Gamma delta TCR
|Possible role in diagnosis (inclusion)
|Much more frequent in MEITL compared to EATL (silent or alpha beta TCR)
|}

*'''Prognosis'''
**Poor (median survival of 7 months)
**Resection, chemotherapy combined with autologous stem cell transplantation improves survival <ref>{{Cite journal|last=P|first=Nijeboer|last2=Lr|first2=de Baaij|last3=O|first3=Visser|last4=Bi|first4=Witte|last5=Sa|first5=Cillessen|last6=Cj|first6=Mulder|last7=G|first7=Bouma|date=2015|title=Treatment response in enteropathy associated T-cell lymphoma; survival in a large multicenter cohort|url=https://pubmed.ncbi.nlm.nih.gov/25716069/|language=en|pmid=25716069}}</ref>
*'''Therapeutic Implications'''
**Alemtuzumab and single use of brentuximab and romidepsin in adjuvant setting<ref>{{Cite journal|date=2020-02-07|title=Enteropathy-Associated T-Cell Lymphoma|url=http://dx.doi.org/10.32388/jjq2o0|journal=Definitions|publisher=Qeios}}</ref>
**PEG-asparaginase has been considered as option<ref>{{Cite journal|last=C|first=Gentille|last2=Q|first2=Qin|last3=A|first3=Barbieri|last4=Ps|first4=Ravi|last5=S|first5=Iyer|date=2017|title=Use of PEG-asparaginase in monomorphic epitheliotropic intestinal T-cell lymphoma, a disease with diagnostic and therapeutic challenges|url=https://pubmed.ncbi.nlm.nih.gov/29062389/|language=en|doi=10.3332/ecancer.2017.771|pmc=PMC5636209|pmid=29062389}}</ref>

==Familial Forms==

*Not described

==Other Information==

None

==Links==

[[Intestinal T-cell Lymphoma]]

==References==
(use "Cite" icon at top of page)
<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:Monomorphic Epitheliotropic Intestinal T-cell Lymphoma - Revision history

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

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