Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Lymphoma

Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype

Leukemia volume 27, pages 1688–1696 (2013)Cite this article

Subjects

Abstract

In this multicentre study, we examined 60 cases of Type II enteropathy-associated T-cell lymphoma (EATL) from the Asia-Pacific region by histological review, immunohistochemistry and molecular techniques. Patients were mostly adult males (median age: 58 years, male:female 2.6:1), presenting with abdominal pain (60%), intestinal perforation (40%) and weight loss (28%). None had a history of coeliac disease and the median survival was only 7 months. Histologically, these tumours could be divided into (i) central tumour zone comprising a monotonous population of neoplastic lymphocytes, (ii) peripheral zone featuring stunted villi and morphologically atypical lymphocytes showing epitheliotropism, and (iii) distant mucosa with normal villous architecture and cytologically normal intra-epithelial lymphocytes (IELs). Characterized by extensive nuclear expression of Megakaryocyte-associated tyrosine kinase (MATK) (87%) and usually a CD8+CD56+ (88%) cytotoxic phenotype, there was frequent aberrant expression of CD20 (24%). T-cell receptor (TCR) expression was silent or not evaluable in 40% but of the remainder, there was predominant expression of TCRαβ over TCRγδ (1.6:1). In keeping with the normal ratio of IEL subsets, CD8+ cases showed predominant CD8αα homodimer expression (77%), regardless of TCR lineage. These tumours constitute a distinct entity from classical EATL, and the pathology may reflect tumour progression from IEL precursors, remnants of which are often seen in the distant mucosa.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Delabie J, Holte H, Vose JM, Ullrich F, Jaffe ES, Savage KJ et al. Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project. Blood 2011; 118: 148–155.

    Article  CAS  PubMed  Google Scholar 

  2. Isaacson PGCA, Ott G, Stein H . Enteropathy-associated T-cell lymphoma. In: Swerdlow SHCE, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW, (eds). WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues 4th edn. IARC: Lyon, France, 2008; pp 289–291.

    Google Scholar 

  3. Chan JK, Chan AC, Cheuk W, Wan SK, Lee WK, Lui YH et al. Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent gammadelta T-cell receptor expression. Am J Surg Pathol 2011; 35: 1557–1569.

    Article  PubMed  Google Scholar 

  4. Sun J, Lu Z, Yang D, Chen J . Primary intestinal T-cell and NK-cell lymphomas: a clinicopathological and molecular study from China focused on type II enteropathy-associated T-cell lymphoma and primary intestinal NK-cell lymphoma. Mod Pathol 2011; 24: 983–992.

    Article  CAS  PubMed  Google Scholar 

  5. Lan Q, Shen M, Garcia-Rossi D, Chanock S, Zheng T, Berndt SI et al. Genotype frequency and F ST analysis of polymorphisms in immunoregulatory genes in Chinese and Caucasian populations. Immunogenetics 2007; 59: 839–852.

    Article  CAS  PubMed  Google Scholar 

  6. Lee KW, Oh DH, Lee C, Yang SY . Allelic and haplotypic diversity of HLA-A, -B, -C, -DRB1, and -DQB1 genes in the Korean population. Tissue Antigens 2005; 65: 437–447.

    Article  CAS  PubMed  Google Scholar 

  7. Liang CK, Chen KH, Hsu WM . Association of HLA type and Mooren’s Ulcer in Chinese in Taiwan. Br J Ophthalmol 2003; 87: 797–798.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Saito S, Ota S, Yamada E, Inoko H, Ota M . Allele frequencies and haplotypic associations defined by allelic DNA typing at HLA class I and class II loci in the Japanese population. Tissue Antigens 2000; 56: 522–529.

    Article  CAS  PubMed  Google Scholar 

  9. Shaw CK, Chen LL, Lee A, Lee TD . Distribution of HLA gene and haplotype frequencies in Taiwan: a comparative study among Min-nan, Hakka, Aborigines and Mainland Chinese. Tissue Antigens 1999; 53: 51–64.

    Article  CAS  PubMed  Google Scholar 

  10. Chim CS, Au WY, Shek TW, Ho J, Choy C, Ma SK et al. Primary CD56 positive lymphomas of the gastrointestinal tract. Cancer 2001; 91: 525–533.

    Article  CAS  PubMed  Google Scholar 

  11. Chuang SS, Chang ST, Chuang WY, Huang WT, Hsieh PP, Tsou MH et al. NK-cell lineage predicts poor survival in primary intestinal NK-cell and T-cell lymphomas. Am J Surg Pathol 2009; 33: 1230–1240.

    Article  PubMed  Google Scholar 

  12. Ko YH, Karnan S, Kim KM, Park CK, Kang ES, Kim YH et al. Enteropathy-associated T-cell lymphoma--a clinicopathologic and array comparative genomic hybridization study. Hum Pathol 2010; 41: 1231–1237.

    Article  CAS  PubMed  Google Scholar 

  13. Ogawa A, Fukushima N, Satoh T, Kishikawa M, Miyazaki K, Tokunaga O . Primary intestinal T-cell lymphoma resembling lymphomatous polyposis: report of a case. Virchows Arch 2000; 437: 450–453.

    Article  CAS  PubMed  Google Scholar 

  14. Tung CL, Hsieh PP, Chang JH, Chen RS, Chen YJ, Wang JS . Intestinal T-cell and natural killer-cell lymphomas in Taiwan with special emphasis on 2 distinct cellular types: natural killer-like cytotoxic T cell and true natural killer cell. Hum Pathol 2008; 39: 1018–1025.

    Article  CAS  PubMed  Google Scholar 

  15. Chott A, Haedicke W, Mosberger I, Fodinger M, Winkler K, Mannhalter C et al. Most CD56+ intestinal lymphomas are CD8+CD5-T-cell lymphomas of monomorphic small to medium size histology. Am J Pathol 1998; 153: 1483–1490.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Takeshita M, Nakamura S, Kikuma K, Nakayama Y, Nimura S, Yao T et al. Pathological and immunohistological findings and genetic aberrations of intestinal enteropathy-associated T cell lymphoma in Japan. Histopathology 2011; 58: 395–407.

    Article  PubMed  Google Scholar 

  17. Chuang SS, Liao YL, Liu H, Lin SH, Hsieh PP, Huang WT et al. The phenotype of intraepithelial lymphocytes in Taiwanese enteropathy-associated T-cell lymphoma is distinct from that of the West. Histopathology 2008; 53: 234–236.

    Article  PubMed  Google Scholar 

  18. Tan SY, Ooi AS, Ang MK, Koh M, Wong JC, Dykema K et al. Nuclear expression of MATK is a novel marker of type II enteropathy-associated T-cell lymphoma. Leukemia 25: 555–557.

    Article  CAS  PubMed  Google Scholar 

  19. Ravikumara M, Nootigattu VK, Sandhu BK . Ninety percent of celiac disease is being missed. J Pediatr Gastroenterol Nutr 2007; 45: 497–499.

    Article  CAS  PubMed  Google Scholar 

  20. DAKO. Histology FISH Accessory Kit. 2010 [cited 15 May 2012]; Working Procedure]. Available from http://www.dako.com/dist/ar42/p234660/prod_products.htm.

  21. McCarthy KP, Sloane JP, Kabarowski JH, Matutes E, Wiedemann LM . A simplified method of detection of clonal rearrangements of the T-cell receptor-gamma chain gene. Diagn Mol Pathol 1992; 1: 173–179.

    CAS  PubMed  Google Scholar 

  22. Akiyama T, Okino T, Konishi H, Wani Y, Notohara K, Tsukayama C et al. CD8+, CD56+ (natural killer-like) T-cell lymphoma involving the small intestine with no evidence of enteropathy: clinicopathology and molecular study of five Japanese patients. Pathol Int 2008; 58: 626–634.

    Article  CAS  PubMed  Google Scholar 

  23. Hayday A, Theodoridis E, Ramsburg E, Shires J . Intraepithelial lymphocytes: exploring the third way in immunology. Nat Immunol 2001; 2: 997–1003.

    Article  CAS  PubMed  Google Scholar 

  24. van Wijk F, Cheroutre H . Intestinal T cells: facing the mucosal immune dilemma with synergy and diversity. Semin Immunol 2009; 21: 130–138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Roitt IM, Delves. PJ . The anatomy of the immune response. In: Roitt’s Essential Immunology 10th edn. Blackwell Science: London, UK, 2001; pp 155–157.

    Google Scholar 

  26. Vose J, Armitage J, Weisenburger D . International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol 2008; 26: 4124–4130.

    Article  PubMed  Google Scholar 

  27. Bagdi E, Diss TC, Munson P, Isaacson PG . Mucosal intra-epithelial lymphocytes in enteropathy-associated T-cell lymphoma, ulcerative jejunitis, and refractory celiac disease constitute a neoplastic population. Blood 1999; 94: 260–264.

    CAS  PubMed  Google Scholar 

  28. Carreras JK, Goldschmidt M, Lamb M, McLear RC, Drobatz KJ, Sørenmo KU . Feline epitheliotropic intestinal malignant lymphoma: 10 cases (1997–2000). J Vet Intern Med 2003; 17: 326–331.

    PubMed  Google Scholar 

  29. Pinkerton ME, Bailey KL, Thomas KK, Goetz TE, Valli VE . Primary epitheliotropic intestinal T-cell lymphoma in a horse. J Vet Diagn Invest 2002; 14: 150–152.

    Article  PubMed  Google Scholar 

  30. Sanz MG, Sellon DC, Potter KA . Primary epitheliotropic intestinal T-cell lymphoma as a cause of diarrhoea in a horse. Can Vet J 2010; 51: 522–524.

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This study was funded by the Programme Project Grant and the CISSP programme (2010/022) from the National Medical Research Council of Singapore, the Singhealth Foundation Project Grant (SHF/FG438P/2010), HSBC Trustee (Singapore) Limited as trustees of the Major John Long Trust Fund and the Chew Woon Poh Trust Fund.

Author information

Authors and Affiliations

  1. Department of Pathology, Singapore General Hospital, Singapore, Singapore

    S-Y Tan & L Tan

  2. Department of Pathology, University Malaya, Kuala Lumpur, Malaysia

    S-Y Tan & P-L Cheah

  3. Singhealth Tissue Repository, Singapore Health Services, Singapore, Singapore

    S-Y Tan & M Koh

  4. Department of Pathology, Chi-Mei Medical Centre, Tainan, Taiwan

    S-S Chuang

  5. Department of Pathology, Taipei Medical University, Taipei, Taiwan

    S-S Chuang

  6. Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan

    S-S Chuang

  7. Department of Medical Oncology, National Cancer Centre, Singapore, Singapore

    T Tang, K Tay & S-T Lim

  8. Department of Pathology, Samsung Medical Center, Sungkyunkwan University, Seoul, Korea

    Y-H Ko

  9. Department of Pathology, Tan Tock Seng Hospital, Singapore, Singapore

    K-L Chuah

  10. Department of Pathology, National University of Singapore, Singapore, Singapore

    S-B Ng

  11. Department of Haematology-Oncology, National University Cancer Institute of Singapore, National University Health System, Singapore, Singapore

    W-J Chng

  12. Cancer Science Institute of Singapore, National University of Singapore, Singapore, Singapore

    W-J Chng

  13. Nuffield Department of Clinical Laboratory Sciences, Oxford University, Oxford, UK

    K Gatter

  14. Department of Pathology, Queen Mary Hospital, Hong Kong SAR, China,

    F Loong

  15. Department of Pathology, First Guangzhou People’s Hospital, Guangzhou, China

    Y-H Liu

  16. Eastern Health Pathology, Melbourne, Victoria, Australia

    P Hosking

  17. NCCS-VARI Translational Research Laboratory, National Cancer Center, Singapore, Singapore

    B-T Teh

  18. Laboratory of Cancer Therapeutics, Duke-NUS Graduate Medical School, Singapore, Singapore

    B-T Teh

  19. Institute of Cell and Molecular Biology, A*STAR, Singapore, Singapore

    S-Y Tan

Authors
  1. S-Y Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. S-S Chuang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. T Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. L Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Y-H Ko
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K-L Chuah
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. S-B Ng
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. W-J Chng
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K Gatter
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. F Loong
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Y-H Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. P Hosking
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. P-L Cheah
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. B-T Teh
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. K Tay
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. M Koh
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. S-T Lim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S-Y Tan.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Additional information

Author Contributions

SYT, LT and STL designed research, performed research, contributed bioresources and data, analysed data and wrote the paper. SSC, TT, YHK, KLC, SBN, WJC, KG, FL, PH, YHL, PLC, BTT, KT and MK performed research, contributed bioresources and research data and analysed data.

Supplementary Information accompanies this paper on the Leukemia website

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tan, SY., Chuang, SS., Tang, T. et al. Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype. Leukemia 27, 1688–1696 (2013). https://doi.org/10.1038/leu.2013.41

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/leu.2013.41

Keywords

This article is cited by

Search

Advanced search

Quick links