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HAEM5:Indolent T-cell lymphoma of the gastrointestinal tract (view source)
Revision as of 14:22, 3 November 2023
, 14:22, 3 November 2023Created page with "{{DISPLAYTITLE:Indolent T-cell lymphoma of the gastrointestinal tract}} Haematolymphoid Tumours (5th ed.) {{Under Construction}} <blockquote clas..."
{{DISPLAYTITLE:Indolent T-cell lymphoma of the gastrointestinal tract}}
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
{{Under Construction}}
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:Indolent T-cell Lymphoproliferative Disorder of the Gastrointestinal Tract]].
}}</blockquote>
==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 Neoplasm]]
==Cancer Sub-Classification / Subtype==
*[[Intestinal T-cell Lymphoma]]
==Definition / Description of Disease==
*Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract (GI TLPD) are rare neoplasms that mimic intestinal T-cell lymphoma and other inflammatory diseases of the GI tract, including Crohn's disease. However, it has distinct cellular derivation, pathobiological features and genomic landscape that remains to be fully elucidated
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1">{{Cite journal|last=E|first=Margolskee|last2=V|first2=Jobanputra|last3=Sk|first3=Lewis|last4=B|first4=Alobeid|last5=Ph|first5=Green|last6=G|first6=Bhagat|date=2013|title=Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features|url=https://pubmed.ncbi.nlm.nih.gov/23861889/|language=en|doi=10.1371/journal.pone.0068343|pmc=PMC3701677|pmid=23861889}}</ref></blockquote>
==Synonyms / Terminology==
*N/A
==Epidemiology / Prevalence==
*Extremely rare
*Etiology not understood, but some have a history of Crohn disease
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":2">{{Cite journal|last=Am|first=Perry|last2=Ra|first2=Warnke|last3=Q|first3=Hu|last4=P|first4=Gaulard|last5=C|first5=Copie-Bergman|last6=S|first6=Alkan|last7=Hy|first7=Wang|last8=Jx|first8=Cheng|last9=Cm|first9=Bacon|date=2013|title=Indolent T-cell lymphoproliferative disease of the gastrointestinal tract|url=https://pubmed.ncbi.nlm.nih.gov/24009234/|language=en|doi=10.1182/blood-2013-07-512830|pmc=PMC3837508|pmid=24009234}}</ref></blockquote>
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats)
EXAMPLE Fatigue
EXAMPLE Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
EXAMPLE Lymphocytosis (low level)
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
*Abdominal pain
*Diarrhea
*Dyspepsia
*Weight loss
*Endoscopic findings:
**Thickened, nodular, hyperemic mucosal surface with superficial erosions
**If presenting as intestinal polyps, may mimic lymphomatous polyposis
*No association with celiac disease
'''ADD REF'''
</blockquote>
==Sites of Involvement==
*Small intestine and colon (predominant)
*Any gastrointestinal mucosa possible
*May present as polypoid lesions in the stomach, duodenum, terminal ileum and colon<ref>{{Cite journal|last=K|first=Hirakawa|last2=T|first2=Fuchigami|last3=S|first3=Nakamura|last4=Y|first4=Daimaru|last5=K|first5=Ohshima|last6=Y|first6=Sakai|last7=T|first7=Ichimaru|date=1996|title=Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis|url=https://pubmed.ncbi.nlm.nih.gov/8780585/|language=en|pmid=8780585}}</ref>
==Morphologic Features==
*Small, monotonous, round, lymphocytes with scant cytoplasm
*Lymphoid infiltrate expands lamina propria and displaces mucosal glands, but does not cause destruction of underlying architecture, and usually does not invade epithelium
*Admixed inflammatory cells are uncommon
'''ADD REF'''
==Immunophenotype==
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD3, CD2, CD5, TIA1 (in CD8+ cases), TCR alpha beta
|-
|Positive (frequent)||CD8 > CD4
|-
|Positive (rare)
|CD4+CD8+ (double positive)
|-
|Negative (universal)||TCR-gamma, EBER, NKp46, CD56
|-
|Negative (frequent)
|Granzyme B, CD103
|-
|Negative (rare)||CD4-CD8- (double negative)
|-
|Ki-67
|< 10%
|}
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":3">{{Cite journal|last=M|first=Cheminant|last2=J|first2=Bruneau|last3=G|first3=Malamut|last4=D|first4=Sibon|last5=N|first5=Guegan|last6=T|first6=van Gils|last7=S|first7=Cording|last8=A|first8=Trinquand|last9=V|first9=Verkarre|date=2019|title=NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: a CELAC study|url=https://pubmed.ncbi.nlm.nih.gov/30448772/|language=en|pmid=30448772}}</ref></blockquote>
==Chromosomal Rearrangements (Gene Fusions)==
Put your text here and fill in the table
{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference)
|Yes
|No
|Yes
|EXAMPLE
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
{| class="wikitable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)
!Features
|-
|t(9;17)(p24.1;q21.2)
|STAT3-JAK2
|Appears to be unique to CD4+ cases (in a series of 10 unselected GI TLPDs, the only cases with JAK-STAT activation were in 4 out of 5 CD4+ cases; none was observed in the CD8+ or CD4+CD8+ double positive cases)
|}
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0">{{Cite journal|last=A|first=Sharma|last2=N|first2=Oishi|last3=Rl|first3=Boddicker|last4=G|first4=Hu|last5=Hk|first5=Benson|last6=Rp|first6=Ketterling|last7=Pt|first7=Greipp|last8=Dl|first8=Knutson|last9=Sm|first9=Kloft-Nelson|date=2018|title=Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract|url=https://pubmed.ncbi.nlm.nih.gov/29592893/|language=en|doi=10.1182/blood-2018-01-830968|pmc=PMC5958657|pmid=29592893}}</ref></blockquote>
</blockquote>
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
*'''Diagnosis'''
**Clinical history, imaging, morphologic and immunophenotypic characterization
**No pathognomonic diagnostic markers (molecular or otherwise)
**Differential diagnosis include extranodal NK/T-cell lymphoma, monomorphic epitheliotropic intestinal lymphoma, peripheral T-cell lymphoma not otherwise specified, inflammatory bowel disease (Crohn's disease, ulcerative colitis), celiac disease
{| class="wikitable"
!Alterations
!Significance
!Note
|-
|'''STAT3-JAK2 fusion'''
|'''Likely role in diagnosis (inclusion)'''
|Likely present in CD4+ GI TLPD and absent in [[Enteropathy-Associated T-cell Lymphoma|EATL]], [[Monomorphic Epitheliotropic Intestinal T-cell Lymphoma|MEITL]], and other T-cell lymphomas<ref name=":0" />
|-
|EBV
|Possible role in diagnosis (exclusion)
|helps distinguishes from T/NK extranodal intestinal lymphoma
|-
|MATK, SYK
|Possible role in diagnosis (exclusion)
|strongly favors monomorphic epithelieotropic intestinal lymphoma<ref>{{Cite journal|last=Sy|first=Tan|last2=Ss|first2=Chuang|last3=T|first3=Tang|last4=L|first4=Tan|last5=Yh|first5=Ko|last6=Kl|first6=Chuah|last7=Sb|first7=Ng|last8=Wj|first8=Chng|last9=K|first9=Gatter|date=2013|title=Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype|url=https://pubmed.ncbi.nlm.nih.gov/23399895/|language=en|pmid=23399895}}</ref><ref>{{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>
|-
|Anti-transglutaminase antibodies
|Possible role in diagnosis (exclusion)
|May help distinguish from enteropathy associated T- cell lymphoma (EATL)
|-
|TCR clonal rearrangement
|Possible role in diagnosis (inclusion)
|May be necessary to distinguish from inflammatory disease (Crohn's disease, celiac for cases with epitheliotropism)
|-
|NKp46
|Possible role in diagnosis (exclusion)
|Positive stain does not favor the diagnosis<ref name=":3" /> but seen in type 2 refractory celiac disease, EATL and MEITL
|}
*'''Prognosis'''<ref name=":2" />
**Indolent, but chronic relapsing clinical course
*'''Therapeutic Implications'''
**Generally unresponsive to therapy<ref name=":1" />
***The potential use of JAK-STAT inhibitors such as tofacinib and AZD1480 has not been formally tested
</blockquote>
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
7
|EXAMPLE Loss
|EXAMPLE
chr7:1- 159,335,973 [hg38]
|EXAMPLE
chr7
|Yes
|Yes
|No
|EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|EXAMPLE
8
|EXAMPLE Gain
|EXAMPLE
chr8:1-145,138,636 [hg38]
|EXAMPLE
chr8
|No
|No
|No
|EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
{| class="wikitable sortable"
!Chromosome Number
!Gain/Loss/Amp/LOH
!Region
!Genes
|-
|1p
|gain
|p32.1; p36
|JUN, NDRG1; PAX7, SDHB
|-
|8q
|gain
|q24.22
|WISP1
|-
|15q
|gain
|q21.2
|PDRM2, STAT3
|-
|17q
|gain
|q21.2q31
|PRDX4, ZFX, ELN
|-
|9q
|gain
|q22-34
|
|-
|7q
|LOH
|11.22q23
|
|-
|Xp
|gain
|p22.11
|
|-
|8p
|loss
|
|
|}
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /></blockquote>
</blockquote>
==Characteristic Chromosomal Patterns==
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
Co-deletion of 1p and 18q
|Yes
|No
|No
|EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
*
</blockquote>
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC / TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE: TP53; Variable LOF mutations
EXAMPLE:
EGFR; Exon 20 mutations
EXAMPLE: BRAF; Activating mutations
|EXAMPLE: TSG
|EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|
|EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
*STAT3
*SOCS1
*TET2
*DNMT3A
*KMT2D
'''INCLUDE THESE IN THE STANDARD TABLE WITH PREVALENCES. WHO BOOK STATES THAT STAT3 IS ABSENT, SO IT WILL BE IMPORTANT TO RECONCILE.'''
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref>{{Cite journal|last=Cr|first=Soderquist|last2=N|first2=Patel|last3=Vv|first3=Murty|last4=S|first4=Betman|last5=N|first5=Aggarwal|last6=Kh|first6=Young|last7=L|first7=Xerri|last8=R|first8=Leeman-Neill|last9=Sk|first9=Lewis|date=2020|title=Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract|url=https://pubmed.ncbi.nlm.nih.gov/31558678/|language=en|doi=10.3324/haematol.2019.230961|pmc=PMC7327650|pmid=31558678}}</ref></blockquote>
</blockquote>
==Epigenomic Alterations==
*Not described
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|EXAMPLE: MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|EXAMPLE: Cell cycle regulation
|EXAMPLE: Unregulated cell division
|-
|EXAMPLE: KMT2C and ARID1A; Inactivating mutations
|EXAMPLE: Histone modification, chromatin remodeling
|EXAMPLE: Abnormal gene expression program
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
*JAK-STAT
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0" /></blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
*No pathognomonic diagnostic markers (molecular or otherwise)
*Imaging (PET/CT)
*Endoscopy
*Morphological and immunophenotypic characterization
*T-cell receptor gene rearrangement studies demonstrate clonality, which can help distinguish from inflammatory disorders of the intestines (Crohn's disease, ulcerative colitis, celiac disease)
*STAT3-JAK2 rearrangement in CD4+ cases may be detected by conventional cytogenetic analysis, FISH may detect JAK2 rearrangement, and NGS may detect rearrangement if available in panel <ref name=":0" />
==Familial Forms==
*Not described
==Additional Information==
*N/A
==Links==
*[[Intestinal T-cell Lymphoma]]
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <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.
<nowiki>*</nowiki>''Citation of this Page'': “Indolent T-cell lymphoma of the gastrointestinal tract”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Indolent_T-cell_lymphoma_of_the_gastrointestinal_tract</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases I]]
[[HAEM5:Table_of_Contents|Haematolymphoid Tumours (5th ed.)]]
{{Under Construction}}
<blockquote class='blockedit'>{{Box-round|title=HAEM5 Conversion Notes|This page was converted to the new template on 2023-11-03. The original page can be found at [[HAEM4:Indolent T-cell Lymphoproliferative Disorder of the Gastrointestinal Tract]].
}}</blockquote>
==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 Neoplasm]]
==Cancer Sub-Classification / Subtype==
*[[Intestinal T-cell Lymphoma]]
==Definition / Description of Disease==
*Indolent T-cell lymphoproliferative disorders of the gastrointestinal tract (GI TLPD) are rare neoplasms that mimic intestinal T-cell lymphoma and other inflammatory diseases of the GI tract, including Crohn's disease. However, it has distinct cellular derivation, pathobiological features and genomic landscape that remains to be fully elucidated
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1">{{Cite journal|last=E|first=Margolskee|last2=V|first2=Jobanputra|last3=Sk|first3=Lewis|last4=B|first4=Alobeid|last5=Ph|first5=Green|last6=G|first6=Bhagat|date=2013|title=Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features|url=https://pubmed.ncbi.nlm.nih.gov/23861889/|language=en|doi=10.1371/journal.pone.0068343|pmc=PMC3701677|pmid=23861889}}</ref></blockquote>
==Synonyms / Terminology==
*N/A
==Epidemiology / Prevalence==
*Extremely rare
*Etiology not understood, but some have a history of Crohn disease
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":2">{{Cite journal|last=Am|first=Perry|last2=Ra|first2=Warnke|last3=Q|first3=Hu|last4=P|first4=Gaulard|last5=C|first5=Copie-Bergman|last6=S|first6=Alkan|last7=Hy|first7=Wang|last8=Jx|first8=Cheng|last9=Cm|first9=Bacon|date=2013|title=Indolent T-cell lymphoproliferative disease of the gastrointestinal tract|url=https://pubmed.ncbi.nlm.nih.gov/24009234/|language=en|doi=10.1182/blood-2013-07-512830|pmc=PMC3837508|pmid=24009234}}</ref></blockquote>
==Clinical Features==
Put your text here and fill in the table <span style="color:#0070C0">(''Instruction: Can include references in the table'') </span>
{| class="wikitable"
|'''Signs and Symptoms'''
|EXAMPLE Asymptomatic (incidental finding on complete blood counts)
EXAMPLE B-symptoms (weight loss, fever, night sweats)
EXAMPLE Fatigue
EXAMPLE Lymphadenopathy (uncommon)
|-
|'''Laboratory Findings'''
|EXAMPLE Cytopenias
EXAMPLE Lymphocytosis (low level)
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Features|The content below was from the old template. Please incorporate above.}}
*Abdominal pain
*Diarrhea
*Dyspepsia
*Weight loss
*Endoscopic findings:
**Thickened, nodular, hyperemic mucosal surface with superficial erosions
**If presenting as intestinal polyps, may mimic lymphomatous polyposis
*No association with celiac disease
'''ADD REF'''
</blockquote>
==Sites of Involvement==
*Small intestine and colon (predominant)
*Any gastrointestinal mucosa possible
*May present as polypoid lesions in the stomach, duodenum, terminal ileum and colon<ref>{{Cite journal|last=K|first=Hirakawa|last2=T|first2=Fuchigami|last3=S|first3=Nakamura|last4=Y|first4=Daimaru|last5=K|first5=Ohshima|last6=Y|first6=Sakai|last7=T|first7=Ichimaru|date=1996|title=Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis|url=https://pubmed.ncbi.nlm.nih.gov/8780585/|language=en|pmid=8780585}}</ref>
==Morphologic Features==
*Small, monotonous, round, lymphocytes with scant cytoplasm
*Lymphoid infiltrate expands lamina propria and displaces mucosal glands, but does not cause destruction of underlying architecture, and usually does not invade epithelium
*Admixed inflammatory cells are uncommon
'''ADD REF'''
==Immunophenotype==
{| class="wikitable sortable"
|-
!Finding!!Marker
|-
|Positive (universal)||CD3, CD2, CD5, TIA1 (in CD8+ cases), TCR alpha beta
|-
|Positive (frequent)||CD8 > CD4
|-
|Positive (rare)
|CD4+CD8+ (double positive)
|-
|Negative (universal)||TCR-gamma, EBER, NKp46, CD56
|-
|Negative (frequent)
|Granzyme B, CD103
|-
|Negative (rare)||CD4-CD8- (double negative)
|-
|Ki-67
|< 10%
|}
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /><ref name=":3">{{Cite journal|last=M|first=Cheminant|last2=J|first2=Bruneau|last3=G|first3=Malamut|last4=D|first4=Sibon|last5=N|first5=Guegan|last6=T|first6=van Gils|last7=S|first7=Cording|last8=A|first8=Trinquand|last9=V|first9=Verkarre|date=2019|title=NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: a CELAC study|url=https://pubmed.ncbi.nlm.nih.gov/30448772/|language=en|pmid=30448772}}</ref></blockquote>
==Chromosomal Rearrangements (Gene Fusions)==
Put your text here and fill in the table
{| class="wikitable sortable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)!!Pathogenic Derivative!!Prevalence
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE t(9;22)(q34;q11.2)||EXAMPLE 3'ABL1 / 5'BCR||EXAMPLE der(22)||EXAMPLE 20% (COSMIC)
EXAMPLE 30% (add reference)
|Yes
|No
|Yes
|EXAMPLE
The t(9;22) is diagnostic of CML in the appropriate morphology and clinical context (add reference). This fusion is responsive to targeted therapy such as Imatinib (Gleevec) (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Chromosomal Rearrangements (Gene Fusions)|The content below was from the old template. Please incorporate above.}}
{| class="wikitable"
|-
!Chromosomal Rearrangement!!Genes in Fusion (5’ or 3’ Segments)
!Features
|-
|t(9;17)(p24.1;q21.2)
|STAT3-JAK2
|Appears to be unique to CD4+ cases (in a series of 10 unselected GI TLPDs, the only cases with JAK-STAT activation were in 4 out of 5 CD4+ cases; none was observed in the CD8+ or CD4+CD8+ double positive cases)
|}
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0">{{Cite journal|last=A|first=Sharma|last2=N|first2=Oishi|last3=Rl|first3=Boddicker|last4=G|first4=Hu|last5=Hk|first5=Benson|last6=Rp|first6=Ketterling|last7=Pt|first7=Greipp|last8=Dl|first8=Knutson|last9=Sm|first9=Kloft-Nelson|date=2018|title=Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract|url=https://pubmed.ncbi.nlm.nih.gov/29592893/|language=en|doi=10.1182/blood-2018-01-830968|pmc=PMC5958657|pmid=29592893}}</ref></blockquote>
</blockquote>
<blockquote class='blockedit'>{{Box-round|title=v4:Clinical Significance (Diagnosis, Prognosis and Therapeutic Implications).|Please incorporate this section into the relevant tables found in:
* Chromosomal Rearrangements (Gene Fusions)
* Individual Region Genomic Gain/Loss/LOH
* Characteristic Chromosomal Patterns
* Gene Mutations (SNV/INDEL)}}
*'''Diagnosis'''
**Clinical history, imaging, morphologic and immunophenotypic characterization
**No pathognomonic diagnostic markers (molecular or otherwise)
**Differential diagnosis include extranodal NK/T-cell lymphoma, monomorphic epitheliotropic intestinal lymphoma, peripheral T-cell lymphoma not otherwise specified, inflammatory bowel disease (Crohn's disease, ulcerative colitis), celiac disease
{| class="wikitable"
!Alterations
!Significance
!Note
|-
|'''STAT3-JAK2 fusion'''
|'''Likely role in diagnosis (inclusion)'''
|Likely present in CD4+ GI TLPD and absent in [[Enteropathy-Associated T-cell Lymphoma|EATL]], [[Monomorphic Epitheliotropic Intestinal T-cell Lymphoma|MEITL]], and other T-cell lymphomas<ref name=":0" />
|-
|EBV
|Possible role in diagnosis (exclusion)
|helps distinguishes from T/NK extranodal intestinal lymphoma
|-
|MATK, SYK
|Possible role in diagnosis (exclusion)
|strongly favors monomorphic epithelieotropic intestinal lymphoma<ref>{{Cite journal|last=Sy|first=Tan|last2=Ss|first2=Chuang|last3=T|first3=Tang|last4=L|first4=Tan|last5=Yh|first5=Ko|last6=Kl|first6=Chuah|last7=Sb|first7=Ng|last8=Wj|first8=Chng|last9=K|first9=Gatter|date=2013|title=Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype|url=https://pubmed.ncbi.nlm.nih.gov/23399895/|language=en|pmid=23399895}}</ref><ref>{{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>
|-
|Anti-transglutaminase antibodies
|Possible role in diagnosis (exclusion)
|May help distinguish from enteropathy associated T- cell lymphoma (EATL)
|-
|TCR clonal rearrangement
|Possible role in diagnosis (inclusion)
|May be necessary to distinguish from inflammatory disease (Crohn's disease, celiac for cases with epitheliotropism)
|-
|NKp46
|Possible role in diagnosis (exclusion)
|Positive stain does not favor the diagnosis<ref name=":3" /> but seen in type 2 refractory celiac disease, EATL and MEITL
|}
*'''Prognosis'''<ref name=":2" />
**Indolent, but chronic relapsing clinical course
*'''Therapeutic Implications'''
**Generally unresponsive to therapy<ref name=":1" />
***The potential use of JAK-STAT inhibitors such as tofacinib and AZD1480 has not been formally tested
</blockquote>
==Individual Region Genomic Gain/Loss/LOH==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Includes aberrations not involving gene fusions. Can include references in the table. Can refer to CGC workgroup tables as linked on the homepage if applicable.'') </span>
{| class="wikitable sortable"
|-
!Chr #!!Gain / Loss / Amp / LOH!!Minimal Region Genomic Coordinates [Genome Build]!!Minimal Region Cytoband
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
7
|EXAMPLE Loss
|EXAMPLE
chr7:1- 159,335,973 [hg38]
|EXAMPLE
chr7
|Yes
|Yes
|No
|EXAMPLE
Presence of monosomy 7 (or 7q deletion) is sufficient for a diagnosis of AML with MDS-related changes when there is ≥20% blasts and no prior therapy (add reference). Monosomy 7/7q deletion is associated with a poor prognosis in AML (add reference).
|-
|EXAMPLE
8
|EXAMPLE Gain
|EXAMPLE
chr8:1-145,138,636 [hg38]
|EXAMPLE
chr8
|No
|No
|No
|EXAMPLE
Common recurrent secondary finding for t(8;21) (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genomic Gain/Loss/LOH|The content below was from the old template. Please incorporate above.}}
{| class="wikitable sortable"
!Chromosome Number
!Gain/Loss/Amp/LOH
!Region
!Genes
|-
|1p
|gain
|p32.1; p36
|JUN, NDRG1; PAX7, SDHB
|-
|8q
|gain
|q24.22
|WISP1
|-
|15q
|gain
|q21.2
|PDRM2, STAT3
|-
|17q
|gain
|q21.2q31
|PRDX4, ZFX, ELN
|-
|9q
|gain
|q22-34
|
|-
|7q
|LOH
|11.22q23
|
|-
|Xp
|gain
|p22.11
|
|-
|8p
|loss
|
|
|}
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":1" /></blockquote>
</blockquote>
==Characteristic Chromosomal Patterns==
Put your text here <span style="color:#0070C0">(''EXAMPLE PATTERNS: hyperdiploid; gain of odd number chromosomes including typically chromosome 1, 3, 5, 7, 11, and 17; co-deletion of 1p and 19q; complex karyotypes without characteristic genetic findings; chromothripsis'')</span>
{| class="wikitable sortable"
|-
!Chromosomal Pattern
!Diagnostic Significance (Yes, No or Unknown)
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE
Co-deletion of 1p and 18q
|Yes
|No
|No
|EXAMPLE:
See chromosomal rearrangements table as this pattern is due to an unbalanced derivative translocation associated with oligodendroglioma (add reference).
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Characteristic Chromosomal Aberrations / Patterns|The content below was from the old template. Please incorporate above.}}
*
</blockquote>
==Gene Mutations (SNV/INDEL)==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well either disease defining and/or clinically significant. Can include references in the table. For clinical significance, denote associations with FDA-approved therapy (not an extensive list of applicable drugs) and NCCN or other national guidelines if applicable; Can also refer to CGC workgroup tables as linked on the homepage if applicable as well as any high impact papers or reviews of gene mutations in this entity.'') </span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!'''Presumed Mechanism (Tumor Suppressor Gene [TSG] / Oncogene / Other)'''!!'''Prevalence (COSMIC / TCGA / Other)'''!!'''Concomitant Mutations'''!!'''Mutually Exclusive Mutations'''
!'''Diagnostic Significance (Yes, No or Unknown)'''
!Prognostic Significance (Yes, No or Unknown)
!Therapeutic Significance (Yes, No or Unknown)
!Notes
|-
|EXAMPLE: TP53; Variable LOF mutations
EXAMPLE:
EGFR; Exon 20 mutations
EXAMPLE: BRAF; Activating mutations
|EXAMPLE: TSG
|EXAMPLE: 20% (COSMIC)
EXAMPLE: 30% (add Reference)
|EXAMPLE: IDH1 R123H
|EXAMPLE: EGFR amplification
|
|
|
|EXAMPLE: Excludes hairy cell leukemia (HCL) (add reference).
<br />
|}
Note: A more extensive list of mutations can be found in cBioportal (https://www.cbioportal.org/), COSMIC (https://cancer.sanger.ac.uk/cosmic), ICGC (https://dcc.icgc.org/) and/or other databases. When applicable, gene-specific pages within the CCGA site directly link to pertinent external content.
<blockquote class='blockedit'>{{Box-round|title=v4:Gene Mutations (SNV/INDEL)|The content below was from the old template. Please incorporate above.}}
*STAT3
*SOCS1
*TET2
*DNMT3A
*KMT2D
'''INCLUDE THESE IN THE STANDARD TABLE WITH PREVALENCES. WHO BOOK STATES THAT STAT3 IS ABSENT, SO IT WILL BE IMPORTANT TO RECONCILE.'''
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref>{{Cite journal|last=Cr|first=Soderquist|last2=N|first2=Patel|last3=Vv|first3=Murty|last4=S|first4=Betman|last5=N|first5=Aggarwal|last6=Kh|first6=Young|last7=L|first7=Xerri|last8=R|first8=Leeman-Neill|last9=Sk|first9=Lewis|date=2020|title=Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract|url=https://pubmed.ncbi.nlm.nih.gov/31558678/|language=en|doi=10.3324/haematol.2019.230961|pmc=PMC7327650|pmid=31558678}}</ref></blockquote>
</blockquote>
==Epigenomic Alterations==
*Not described
==Genes and Main Pathways Involved==
Put your text here and fill in the table <span style="color:#0070C0">(''Instructions: Can include references in the table.'')</span>
{| class="wikitable sortable"
|-
!Gene; Genetic Alteration!!Pathway!!Pathophysiologic Outcome
|-
|EXAMPLE: BRAF and MAP2K1; Activating mutations
|EXAMPLE: MAPK signaling
|EXAMPLE: Increased cell growth and proliferation
|-
|EXAMPLE: CDKN2A; Inactivating mutations
|EXAMPLE: Cell cycle regulation
|EXAMPLE: Unregulated cell division
|-
|EXAMPLE: KMT2C and ARID1A; Inactivating mutations
|EXAMPLE: Histone modification, chromatin remodeling
|EXAMPLE: Abnormal gene expression program
|}
<blockquote class='blockedit'>{{Box-round|title=v4:Genes and Main Pathways Involved|The content below was from the old template. Please incorporate above.}}
*JAK-STAT
<blockquote class='blockedit'>{{Box-round|title=Unassigned References|The following referenees were placed in the header. Please place them into the appropriate locations in the text.}}<ref name=":0" /></blockquote>
</blockquote>
==Genetic Diagnostic Testing Methods==
*No pathognomonic diagnostic markers (molecular or otherwise)
*Imaging (PET/CT)
*Endoscopy
*Morphological and immunophenotypic characterization
*T-cell receptor gene rearrangement studies demonstrate clonality, which can help distinguish from inflammatory disorders of the intestines (Crohn's disease, ulcerative colitis, celiac disease)
*STAT3-JAK2 rearrangement in CD4+ cases may be detected by conventional cytogenetic analysis, FISH may detect JAK2 rearrangement, and NGS may detect rearrangement if available in panel <ref name=":0" />
==Familial Forms==
*Not described
==Additional Information==
*N/A
==Links==
*[[Intestinal T-cell Lymphoma]]
==References==
(use the "Cite" icon at the top of the page) <span style="color:#0070C0">(''Instructions: Add each reference into the text above by clicking on where you want to insert the reference, selecting the “Cite” icon at the top of the page, and using the “Automatic” tab option to search such as by PMID to select the reference to insert. The reference list in this section will be automatically generated and sorted.''</span> <span style="color:#0070C0">''If a PMID is not available, such as for a book, please use the “Cite” icon, select “Manual” and then “Basic Form”, and include the entire reference''</span><span style="color:#0070C0">''.''</span><span style="color:#0070C0">) </span> <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.
<nowiki>*</nowiki>''Citation of this Page'': “Indolent T-cell lymphoma of the gastrointestinal tract”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated {{REVISIONMONTH}}/{{REVISIONDAY}}/{{REVISIONYEAR}}, <nowiki>https://ccga.io/index.php/HAEM5:Indolent_T-cell_lymphoma_of_the_gastrointestinal_tract</nowiki>.
[[Category:HAEM5]][[Category:DISEASE]][[Category:Diseases I]]