Lymphoma & related disorders

• Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL), previously known as type II enteropathy associated T cell lymphoma, is a primary intestinal mature T cell lymphoma that is considered to arise from intestinal intraepithelial T lymphocytes, is usually positive for CD8 and CD56 and lacks association with celiac disease

• Usually nonspecific clinical symptoms, including a change in bowel habits, chronic abdominal pain (86%), chronic diarrhea (33%), weight loss and complications including intestinal obstruction / perforation (33%) and bleeding (17%); B symptoms are common (48%) (Ann Hematol 2019;98:2541)
• Endoscopically or grossly, the tumor is manifested with mucosal granular forming ulcers, nodules, plaques, diffuse mucosal thickening, strictures or large masses (single or multifocal)
• Patients usually do not manifest with malabsorption or celiac disease

• Diagnosis requires clinicopathological correlation
• In patients without a history of celiac disease presenting with chronic abdominal pain, diarrhea and other related symptoms, abdominal imaging studies are warranted, including abdominal ultrasound, CT with or without contrast, MRI and endoscopy
• Endoscopy usually shows fine mucosal granularity and diffuse thickening of the mucosa with semicircular shallow ulcerations, while abdominal MRI or CT show thickening of bowel wall and mesenteric lymphadenopathy
• Tissue biopsy demonstrates monomorphic neoplastic lymphocytes with aberrant T cell phenotype, positive for CD3, CD8, CD56, TIA1 and T cell receptor gamma or delta

• Important to rule out celiac disease by demonstrating negativity for endomysial antibodies, HLA DQ2 or HLA DQ8

Contributed by Xiaoling Guo, M.D., Ph.D. and Yanhua Wang, M.D.

• 53 year old man with diffuse achy abdominal pain of 2 weeks duration (Cureus 2020;12:e10084)
• 64 year old man with chronic watery diarrhea and weight loss for 5 months (Intest Res 2017;15:546)
• 70 year old woman of Chinese ethnicity with a 4 week history of abdominal pain and persistent vomiting (Hematol Transfus Cell Ther 2020 Jun 6 [Epub ahead of print])
• 70 year old Hispanic woman with a history of diabetes mellitus type 2, presented with intermittent lower abdominal pain, nausea, vomiting and diarrhea for 14 months (Ecancermedicalscience 2017;11:771)
• 83 year old man with fever and diarrhea (J Clin Exp Hematop 2018;58:102)

• Grossly, the findings vary depending the tumor stage, from edematous or granular mucosa, to diffuse thickening of the intestinal wall, to a mass with or without ulceration
• Mass can be sub centimeter to a few centimeters in size

Contributed by Xiaoling Guo, M.D., Ph.D. and Yanhua Wang, M.D.

• Neoplastic lymphocytes are relatively monotonous, intermediate in size, with round or slightly irregular nuclear contours, dispersed chromatin, inconspicuous nucleoli and scant rim of pale cytoplasm
• Prominent epitheliotropism as well as transmural infiltrate are characteristic; only few inflammatory cells are noted in the background, unless associated with mucosal ulceration
• Reference: Cureus 2020;12:e10021

Contributed by Xiaoling Guo, M.D., Ph.D. and Yanhua Wang, M.D.

• CD3, CD8, CD56 and TIA1
• Other cytotoxic markers are variably expressed
• CD20 (approximately 20% of MEITLs aberrantly express CD20; however, other pan B cell markers are negative) (Pathology 2020;52:128)

• CD2, CD4, CD5, PAX5, CD30

Which of the following best describes the features of the small intestine displayed in the above figure?

1. Can be associated with celiac disease
2. Commonly seen in Caucasian population
3. Most common phenotype is CD3+, CD8+, CD56+ and TCRδγ+
4. Monomorphic T cells in lymphoma with indolent clinical outcome
5. Patients usually manifest symptoms of malabsorption

C. Most common phenotype is CD3+, CD8+, CD56+ and TCRδγ+. The figure displays small intestine mucosa with a dense infiltrate of epithelium by monomorphic small to intermediate sized lymphocytes, consistent with monomorphic epitheliotropic T cell lymphoma (MEITL). This is a primary intestinal lymphoma that is distinguished from enteropathy associated T cell lymphoma (EATL) because it is not associated with celiac disease or malabsorption, it is more common in Asian populations and has an aggressive behavior with a poor outcome. Phenotypically, MEITL is usually CD3+, CD8+, CD56+ and TCRδγ+ and aberrantly expresses CD20 in 20% of patients.

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Reference: Monomorphic epitheliotropic intestinal T cell lymphoma

Which of the following is helpful in the diagnosis of monomorphic epitheliotropic intestinal T cell lymphoma (MEITL), rather than enteropathy associated T cell lymphoma (EATL)?

1. Expression of megakaryocyte associated tyrosine kinase (MATK) is downregulated in MEITL and upregulated in EATL
2. Gains in chromosome 8q24 involving MYC are seen in a high proportion of cases of MEITL but not EATL
3. HLA DQ2 or HLA DQ8 alleles are commonly seen in MEITL, not EATL
4. T cell receptor expression in MEITL is usually alpha / beta more than gamma / delta, while in EATL, gamma / delta expression is more than alpha / beta expression
5. T cell receptor expression is relatively the same in MEITL and EATL

B. Gains in chromosome 8q24 involving MYC are seen in a high proportion of cases of MEITL but not EATL. The cytogenetic and molecular features associated with MEITL include gains of 8q24, overexpression of MATK and expression of TCRδγ. In contrast, EATL is characterized by expression of HLA DQ2 or HLA DQ8 alleles as well as the expression of TCRαΒ (Semin Diagn Pathol 2021 [Epub ahead of print]).

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Reference: Monomorphic epitheliotropic intestinal T cell lymphoma