Indolent T-cell lymphoma of the gastrointestinal tract
Haematolymphoid Tumours (5th ed.)
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editHAEM5 Conversion NotesThis 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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Synonyms / Terminology
- N/A
Epidemiology / Prevalence
- Extremely rare
- Etiology not understood, but some have a history of Crohn disease
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Clinical Features
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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 FeaturesThe 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
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
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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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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)The content below was from the old template. Please incorporate above.
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) editUnassigned ReferencesThe following referenees were placed in the header. Please place them into the appropriate locations in the text.
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
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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 |
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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/LOHThe content below was from the old template. Please incorporate above.
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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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 / PatternsThe content below was from the old template. Please incorporate above.
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)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.
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Epigenomic Alterations
- Not described
Genes and Main Pathways Involved
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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 InvolvedThe content below was from the old template. Please incorporate above.
- JAK-STAT
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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
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- ↑ 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)
- ↑ 2.0 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)
- ↑ K, Hirakawa; et al. (1996). "Primary gastrointestinal T-cell lymphoma resembling multiple lymphomatous polyposis". PMID 8780585.
- ↑ 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.
- ↑ 5.0 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)
- ↑ 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.
- ↑ G, Mutzbauer; et al. (2018). "SYK expression in monomorphic epitheliotropic intestinal T-cell lymphoma". PMID 29052597.
- ↑ 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.