Monomorphic epitheliotropic intestinal T-cell lymphoma

Haematolymphoid Tumours (WHO Classification, 5th ed.)

editContent Update To WHO 5th Edition Classification Is In Process; Content Below is Based on WHO 4th Edition Classification

This page was converted to the new template on 2023-12-07. The original page can be found at HAEM4:Monomorphic Epitheliotropic Intestinal T-cell Lymphoma.

(General Instructions – The main focus of these pages is the clinically significant genetic alterations in each disease type. Use HUGO-approved gene names and symbols (italicized when appropriate), HGVS-based nomenclature for variants, as well as generic names of drugs and testing platforms or assays if applicable. Please complete tables whenever possible and do not delete them (add N/A if not applicable in the table and delete the examples); to add (or move) a row or column to a table, click within the table and select the > symbol that appears to be given options. Please do not delete or alter the section headings. The use of bullet points alongside short blocks of text rather than only large paragraphs is encouraged. Additional instructions below in italicized blue text should not be included in the final page content. Please also see Author_Instructions and FAQs as well as contact your Associate Editor or Technical Support)

Primary Author(s)*

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

WHO Classification of Disease

Structure	Disease
Book	Haematolymphoid Tumours (5th ed.)
Category	T-cell and NK-cell lymphoid proliferations and lymphomas
Family	Mature T-cell and NK-cell neoplasms
Type	Intestinal T-cell and NK-cell lymphoid proliferations and lymphomas
Subtype(s)	Monomorphic epitheliotropic intestinal T-cell lymphoma

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

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete 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

The content below was from the old template. Please incorporate above.

• 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

Put your text here and fill in the table (Instruction: Can include references in the table. Do not delete table.)

Finding	Marker
Positive (universal)	EXAMPLE: CD1
Positive (subset)	EXAMPLE: CD2
Negative (universal)	EXAMPLE: CD3
Negative (subset)	EXAMPLE: CD4

editv4:Immunophenotype

The content below was from the old template. Please incorporate above.

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 (distinguishes from EATL), NKP46

Variably positive between cases: granzyme B, perforin

Negative: CD5, EBV/EBER

INCORPORATE INTO TABLE

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.

• N/A
• No consistent gene fusion reported

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
  • 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
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
• Therapeutic Implications
  • Alemtuzumab and single use of brentuximab and romidepsin in adjuvant setting
  • PEG-asparaginase has been considered as option

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. Do not delete table.)

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

The content below was from the old template. Please incorporate above.

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

editUnassigned References

The following referenees were placed in the header. Please place them into the appropriate locations in the text.

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. Do not delete table.)

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

The content below was from the old template. Please incorporate above.

• No pathognomonic aberrations/patterns described, but multiple genomic gains and losses are frequent

Gene Mutations (SNV / INDEL)

Put your text here and fill in the table (Instructions: This table is not meant to be an exhaustive list; please include only genes/alterations that are recurrent and common as well as 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. Do not delete table.)

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.

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)

editUnassigned References

The following referenees were placed in the header. Please place them into the appropriate locations in the text.

Epigenomic Alterations

• Defective H3K36 trimethylation

Genes and Main Pathways Involved

Put your text here and fill in the table (Instructions: Can include references in the table. Do not delete 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

The content below was from the old template. Please incorporate above.

• JAK-STAT (most common)
• RAS
• P53
• TERT
• BBX

Include these in the standard table.

editUnassigned References

The following referenees were placed in the header. Please place them into the appropriate locations in the text.

Genetic 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)

Familial Forms

• Not described

Additional Information

None

Links

HAEM4:Intestinal T-cell Lymphoma

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.)

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: “Monomorphic epitheliotropic intestinal T-cell lymphoma”. Compendium of Cancer Genome Aberrations (CCGA), Cancer Genomics Consortium (CGC), updated 09/6/2024, https://ccga.io/index.php/HAEM5:Monomorphic_epitheliotropic_intestinal_T-cell_lymphoma.