Indolent T-cell lymphoma of the gastrointestinal tract

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Haematolymphoid Tumours (5th ed.)

editHAEM5 Conversion Notes
This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Indolent T-cell Lymphoproliferative Disorder of the Gastrointestinal Tract.

Primary Author(s)*

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

Cancer Category / Type

Cancer Sub-Classification / Subtype

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


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[1]

Synonyms / Terminology

  • N/A

Epidemiology / Prevalence

  • Extremely rare
  • Etiology not understood, but some have a history of Crohn disease


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[2]

Clinical Features

Put your text here and fill in the table (Instruction: Can include references in the table)

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)


editv4:Clinical Features
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  • 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

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[3]

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

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%


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[1][4]

Chromosomal Rearrangements (Gene Fusions)

Put your text here and fill in the table

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).


editv4:Chromosomal Rearrangements (Gene Fusions)
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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)
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[5]


editv4: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
Alterations Significance Note
STAT3-JAK2 fusion Likely role in diagnosis (inclusion) Likely present in CD4+ GI TLPD and absent in EATL, MEITL, and other T-cell lymphomas[5]
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[6][7]
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[4] but seen in type 2 refractory celiac disease, EATL and MEITL
  • Prognosis[2]
    • Indolent, but chronic relapsing clinical course
  • Therapeutic Implications
    • Generally unresponsive to therapy[1]
      • The potential use of JAK-STAT inhibitors such as tofacinib and AZD1480 has not been formally tested

Individual Region Genomic Gain / Loss / LOH

Put your text here and fill in the table (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.)

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).

editv4:Genomic Gain/Loss/LOH
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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


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[1]

Characteristic Chromosomal Patterns

Put your text here (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)

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).

editv4:Characteristic Chromosomal Aberrations / Patterns
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Gene Mutations (SNV / INDEL)

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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).


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.


editv4:Gene Mutations (SNV/INDEL)
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  • 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.


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[8]

Epigenomic Alterations

  • Not described

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table.)

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
editv4:Genes and Main Pathways Involved
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  • JAK-STAT


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[5]

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 [5]

Familial Forms

  • Not described

Additional Information

  • N/A

Links

References

(use the "Cite" icon at the top of the page) (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. 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.)

  1. 1.0 1.1 1.2 1.3 E, Margolskee; et al. (2013). "Indolent small intestinal CD4+ T-cell lymphoma is a distinct entity with unique biologic and clinical features". doi:10.1371/journal.pone.0068343. PMC 3701677. PMID 23861889.CS1 maint: PMC format (link)
  2. 2.0 2.1 Am, Perry; et al. (2013). "Indolent T-cell lymphoproliferative disease of the gastrointestinal tract". doi:10.1182/blood-2013-07-512830. PMC 3837508. PMID 24009234.CS1 maint: PMC format (link)
  3. K, Hirakawa; et al. (1996). "Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis". PMID 8780585.
  4. 4.0 4.1 M, Cheminant; et al. (2019). "NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: a CELAC study". PMID 30448772.
  5. 5.0 5.1 5.2 5.3 A, Sharma; et al. (2018). "Recurrent STAT3-JAK2 fusions in indolent T-cell lymphoproliferative disorder of the gastrointestinal tract". doi:10.1182/blood-2018-01-830968. PMC 5958657. PMID 29592893.CS1 maint: PMC format (link)
  6. Sy, Tan; et al. (2013). "Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype". PMID 23399895.
  7. G, Mutzbauer; et al. (2018). "SYK expression in monomorphic epitheliotropic intestinal T-cell lymphoma". PMID 29052597.
  8. Cr, Soderquist; et al. (2020). "Genetic and phenotypic characterization of indolent T-cell lymphoproliferative disorders of the gastrointestinal tract". doi:10.3324/haematol.2019.230961. PMC PMC7327650 Check |pmc= value (help). PMID 31558678.CS1 maint: PMC format (link)

Notes

*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. *Citation of this Page: “Indolent T-cell lymphoma of the gastrointestinal tract”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 12/7/2023, https://ccga.io/index.php/HAEM5:Indolent_T-cell_lymphoma_of_the_gastrointestinal_tract.