HAEM4:Monomorphic Epitheliotropic Intestinal T-cell Lymphoma
Revision as of 13:20, 3 November 2023 by Bailey.Glen (talk | contribs) (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...")
 | This page is under construction |
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
Familial Forms
- Not described
Other Information
None
Links
References
(use "Cite" icon at top of page)
- ↑ 1.0 1.1 G, Mutzbauer; et al. (2018). "SYK expression in monomorphic epitheliotropic intestinal T-cell lymphoma". PMID 29052597.
- ↑ Rj, Deleeuw; et al. (2007). "Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes". PMID 17484883.
- ↑ 3.0 3.1 S, Tomita; et al. (2015). "Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan". PMID 26226842.
- ↑ 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)
- ↑ 5.0 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)
- ↑ 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)
- ↑ 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)
- ↑ P, Nijeboer; et al. (2015). "Treatment response in enteropathy associated T-cell lymphoma; survival in a large multicenter cohort". PMID 25716069.
- ↑ "Enteropathy-Associated T-Cell Lymphoma". Definitions. Qeios. 2020-02-07.
- ↑ 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.