HAEM4Backup:Monomorphic Epitheliotropic Intestinal T-cell Lymphoma

From Compendium of Cancer Genome Aberrations
Jump to navigation Jump to search

Primary Author(s)*

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

Cancer Category/Type

Cancer Sub-Classification / Subtype

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 [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[2][3]

In contrast to EATL, gains at 1q32.2-41 and 5q34-35.5 are reported less commonly. However, one study from Japan[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.

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)[4][5][6]

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 (COSMIC, cBioPortal)

Epigenomics (Methylation)

  • Defective H3K36 trimethylation[5]

Genes and Main Pathways Involved[4][7]

  • 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
IHC Significance Note
SYK Possible role in diagnosis (inclusion) Strongly diagnostic[1]
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 [8]
  • Therapeutic Implications
    • Alemtuzumab and single use of brentuximab and romidepsin in adjuvant setting[9]
    • PEG-asparaginase has been considered as option[10]

Familial Forms

  • Not described

Other Information

None

Links

Intestinal T-cell Lymphoma

References

(use "Cite" icon at top of page)

  1. ↑ 1.0 1.1 G, Mutzbauer; et al. (2018). "SYK expression in monomorphic epitheliotropic intestinal T-cell lymphoma". PMID 29052597.
  2. ↑ Rj, Deleeuw; et al. (2007). "Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes". PMID 17484883.
  3. ↑ 3.0 3.1 S, Tomita; et al. (2015). "Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan". PMID 26226842.
  4. ↑ 4.0 4.1 Ab, Moffitt; et al. (2017). "Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2". doi:10.1084/jem.20160894. PMC 5413324. PMID 28424246.CS1 maint: PMC format (link)
  5. ↑ 5.0 5.1 A, Roberti; et al. (2016). "Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations". doi:10.1038/ncomms12602. PMC 5023950. PMID 27600764.CS1 maint: PMC format (link)
  6. ↑ Ml, Nairismägi; et al. (2016). "JAK-STAT and G-protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma". doi:10.1038/leu.2016.13. PMC 4895162. PMID 26854024.CS1 maint: PMC format (link)
  7. ↑ A, Nicolae; et al. (2016). "Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas". doi:10.1038/leu.2016.178. PMC 5093023. PMID 27389054.CS1 maint: PMC format (link)
  8. ↑ P, Nijeboer; et al. (2015). "Treatment response in enteropathy associated T-cell lymphoma; survival in a large multicenter cohort". PMID 25716069.
  9. ↑ "Enteropathy-Associated T-Cell Lymphoma". Definitions. Qeios. 2020-02-07.
  10. ↑ C, Gentille; et al. (2017). "Use of PEG-asparaginase in monomorphic epitheliotropic intestinal T-cell lymphoma, a disease with diagnostic and therapeutic challenges". doi:10.3332/ecancer.2017.771. PMC 5636209. PMID 29062389.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.

Retrieved from "https://ccga.io/index.php?title=HAEM4Backup:Monomorphic_Epitheliotropic_Intestinal_T-cell_Lymphoma&oldid=12292"