Skip to main content

Advertisement

SpringerLink
Log in

Enteropathy-Associated T-Cell Lymphoma

  • T-CELL AND OTHER LYMPHOPROLIFERATIVE MALIGNANCIES (P PORCU, SECTION EDITOR)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Enteropathy-associated T-cell lymphoma is a rare neoplasm with uniformly aggressive features that arises from intestinal T-cells. There is strong evidence supporting its association as a dire complication of celiac disease. The clinical presentation can vary from malabsorption and abdominal pain to an acute abdominal emergency. Originally, it was divided into types I and II in World Health Organization (WHO) classification schemes, reflective of epidemiology and differences in clinicopathologic features. The debate over the degree of separation of the two types is ongoing as new data emerges regarding the pathogenetics. The low incidence and variable patient factors are major barriers in conducting clinical trials and establishing standard treatment regimens. Yet, the collective experience demonstrates favorable outcomes with combination chemotherapy followed by an autologous hematopoietic stem cell transplant in patients who can tolerate such treatment. The prognosis remains dismal; thus, future research studies are warranted to identify effective novel therapies that can improve outcomes in this rare disease entity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  1. Delabie J et al. Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project. Blood. 2011;118:148–55.

    Article  CAS  PubMed  Google Scholar 

  2. Lee M-Y, Tsou M-H, Tan T-D, Lu M-C. Clinicopathological analysis of T-cell lymphoma in Taiwan according to WHO classification: high incidence of enteropathy-type intestinal T-cell lymphoma. Eur J Haematol. 2005;75:221–6.

    Article  PubMed  Google Scholar 

  3. Gale J, Simmonds PD, Mead GM, Sweetenham JW, Wright DH. Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center. J Clin Oncol. 2000;18:795–803.

    CAS  PubMed  Google Scholar 

  4. Tse E et al. Type II enteropathy-associated T-cell lymphoma: a multicenter analysis from the Asia Lymphoma Study Group. Am J Hematol. 2012;87:663–8.

    Article  PubMed  Google Scholar 

  5. Isaacson PG, Chott A, Ott G, Stein H. In World Health Organization classification of tumours of the haematopoietic and lymphoid tissues. In: Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman J, editors. IARC; 2008. p. 289–91.

  6. Sharaiha RZ et al. Increasing incidence of enteropathy-associated T-cell lymphoma in the United States, 1973-2008. Cancer. 2012;118:3786–92.

    Article  PubMed  Google Scholar 

  7. Silano M, Volta U, DeVincenzi A, Dessi M. D. M. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci. 2008;53:972–6.

    Article  CAS  PubMed  Google Scholar 

  8. Lebwohl B, Granath F, Ekbom A, Smedby KE, Murray JA, Neugut AI, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease. Ann Intern Med. 2013;159:169–75.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Chan JKC et al. Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent γδ T-cell receptor expression. Am J Surg Pathol. 2011;35:1557–69.

    Article  PubMed  Google Scholar 

  10. 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;24:983–92.

    Article  CAS  PubMed  Google Scholar 

  11. Tan S-Y et al. Type II EATL (epitheliotropic intestinal T-cell lymphoma): a neoplasm of intra-epithelial T-cells with predominant CD8αα phenotype. Leukemia. 2013;27:1688–96.

    Article  CAS  PubMed  Google Scholar 

  12. Deleeuw RJ et al. Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes. Gastroenterology. 2007;132:1902–11.

    Article  CAS  PubMed  Google Scholar 

  13. Swerdlow SH et al. Cytotoxic T-cell and NK-cell lymphomas: current questions and controversies. Am J Surg Pathol. 2014;38:e60–71.

    Article  PubMed  Google Scholar 

  14. Swerdlow SH et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90.

    Article  PubMed  Google Scholar 

  15. Biagi F, Lorenzini P. C. G. Literature review on the clinical relationship between ulcerative jejunitis, coeliac disease and enteropathy associated T cell lymphoma. Scand J Gastroenterol. 2000;35:785–90.

    Article  CAS  PubMed  Google Scholar 

  16. Sabatino AD, Biagi F, Gobbi PG, C. G. How I treat enteropathy-associated T-cell lymphoma. Blood2. 2012;119:2458–68.

    Article  Google Scholar 

  17. Malamut G, Meresse B, Cellier C, Cerf-Bensussan N. Refractory celiac disease: from bench to bedside. Semin Immunopathol. 2012;34:601–13.

    Article  PubMed  Google Scholar 

  18. Roshan B et al. The incidence and clinical spectrum of refractory celiac disease in a North American referral center. Am J Gastroenterol. 2011;106:923–8.

    Article  PubMed  Google Scholar 

  19. Malamut G, Afchain P, Verkarre V, et al. Presentation and long-term follow-up of refractory celiac disease: comparison of type I with type II. Gastroenterology. 2009;136:81–90.

    Article  PubMed  Google Scholar 

  20. Green PH et al. Risk of malignancy in patients with celiac disease. Am J Med. 2003;115:191–5.

    Article  PubMed  Google Scholar 

  21. Olen O et al. Coeliac disease characteristics, compliance to a gluten free diet and risk of lymphoma by subtype. Dig Liver Dis. 2011;43:862–8.

    Article  PubMed  Google Scholar 

  22. Sieniawski M et al. Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood. 2010;115:3664–70.

    Article  CAS  PubMed  Google Scholar 

  23. Wierdsma NJ et al. Refractory celiac disease and EATL patients show severe malnutrition and malabsorption at diagnosis. Clin Nutr. 2016;35:685–91.

    Article  PubMed  Google Scholar 

  24. Muller-Hermelink H, Delabie J, Ko Y, et al. WHO classification of tumours of the digestive system 112–4 (IARC, 2010).

  25. Ondrejka SL, Moffitt AB, Tse E, Hsi ED, Goodlad JR, au-Yeung R, Kwong Y-L, Srivastava G. Gascoyne R, Rajagopalan D, Love C, Dave S. Whole exome sequencing of type I and type II enteropathy-associated T-cell lymphoma reveals genetic basis of oncogenesis 622 (American Society of Hematology, ASH oral presentation 2015).

  26. Howat AJ, McPhie JL, Smith DA, et al. Cavitation of mesenteric lymph nodes: a rare complication of coeliac disease, associated with a poor outcome. Histopathology1 146, 509–519 (995).

  27. Zettl A, Ott G, Makulik A, Katzenberger T, Starostik P, Eichler T, et al. Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma. Am J Pathol. 2002;161:1635–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Verkarre V, Asnafi V, Lecomte T, et al. Refractory celiac disease is a diffuse gastrointestinal disease. Gut. 2003;52:205–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Zettl A, de Leeuw R, Haralambieva EM-HH. Enteropathy-type T-cell lymphoma. Am J Clin Pathol. 2007;127:701–6.

    Article  PubMed  Google Scholar 

  30. Foukas PG, de Leval L. Recent advances in intestinal lymphomas. Histopathology. 2015;66:112–36.

    Article  PubMed  Google Scholar 

  31. Arps DP, Smith LB. Classic versus type II enteropathy-associated T-cell lymphoma: diagnostic considerations. Arch Pathol Lab Med. 2013;137:1227–31.

    Article  PubMed  Google Scholar 

  32. Malamut G et al. Enteropathy associated T cell lymphoma in celiac disease: a large retrospective study. Dig Liver Dis. 2013;45:377–84.

    Article  CAS  PubMed  Google Scholar 

  33. Tomita S et al. Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. Mod Pathol. 2015;28:1286–96.

    Article  CAS  PubMed  Google Scholar 

  34. Tan SY, Ooi AS, Ang MK, et al. Nuclear expression of MATK is a novel marker of type II enteropathy associated T-cell lymphoma. Leukemia. 2011;25:555–7.

    Article  CAS  PubMed  Google Scholar 

  35. Kikuma K, Yamada K, Nakamura S, Ogami A, et al. Detailed clinicopathologic characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan. Hum Pathol. 2013;45:1274–84.

    Google Scholar 

  36. Küçük C et al. Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells. Nat Commun. 2015;6:6025.

    Article  PubMed  Google Scholar 

  37. Nairismägi M-L et al. JAK-STAT and G protein-coupled receptor signaling pathways are frequently altered in epitheliotropic intestinal T-cell lymphoma. Leukemia. 2016;30:1311–9.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Hapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126:17–25.

    Article  CAS  PubMed  Google Scholar 

  39. Genomic signatures in T-cell lymphoma: How can these improve precision in diagnosis and inform prognosis? - PubMed - NCBI. at <http://www.ncbi.nlm.nih.gov/pubmed/26319391>

  40. Mansoor A et al. NK-cell enteropathy: a benign NK-cell lymphoproliferative disease mimicking intestinal lymphoma: clinicopathologic features and follow-up in a unique case series. Blood. 2011;117:1447–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Leventaki V et al. Indolent peripheral T-cell lymphoma involving the gastrointestinal tract. Hum Pathol. 2014;45(2):421–6.

    Article  CAS  PubMed  Google Scholar 

  42. Takeuchi K et al. Lymphomatoid gastropathy: a distinct clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation. Blood. 2010;116:5631–7.

    Article  CAS  PubMed  Google Scholar 

  43. Daum S et al. Capsule endoscopy in refractory celiac disease. Endoscopy. 2007;39:455–8.

    Article  CAS  PubMed  Google Scholar 

  44. Hadithi M et al. The value of double-balloon enteroscopy in patients with refractory celiac disease. Am J Gastroenterol. 2007;102:987–96.

    Article  PubMed  Google Scholar 

  45. Hadithi M et al. 18F-FDG PET versus CT for the detection of enteropathy-associated T-cell lymphoma in refractory celiac disease. J Nucl Med. 2006;47:1622–7.

    PubMed  Google Scholar 

  46. Hoffmann M et al. 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET) for assessment of enteropathy-type T cell lymphoma. Gut. 2003;52:347–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Van Weyenberg SJB et al. MR enteroclysis in refractory celiac disease: proposal and validation of a severity scoring system. Radiology. 2011;259:151–61.

    Article  PubMed  Google Scholar 

  48. Jantunen E et al. Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT. Blood. 2013;121:2529–32.

    Article  CAS  PubMed  Google Scholar 

  49. d’Amore F et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J Clin Oncol. 2012;30:3093–9.

    Article  PubMed  Google Scholar 

  50. Ellin F, Landström J, Jerkeman M, Relander T. Real-world data on prognostic factors and treatment in peripheral T-cell lymphomas: a study from the Swedish Lymphoma Registry. Blood. 2014;124:1570–7.

    Article  CAS  PubMed  Google Scholar 

  51. Karanam PK, Al-Hamadani M, Go RS. Enteropathy-associated T-cell lymphoma in the US: higher incidence and poorer survival among Asians. Br J Haematol. 2016;172:990–2.

    Article  PubMed  Google Scholar 

  52. Verbeek WHM et al. Aberrant T-lymphocytes in refractory coeliac disease are not strictly confined to a small intestinal intraepithelial localization. Cytometry B Clin Cytom. 2009;76:367–74.

    Article  CAS  PubMed  Google Scholar 

  53. Verbeek WHM et al. The presence of small intestinal intraepithelial gamma/delta T-lymphocytes is inversely correlated with lymphoma development in refractory celiac disease. Am J Gastroenterol. 2008;103:3152–8.

    Article  PubMed  Google Scholar 

  54. Pongpruttipan T et al. Extranodal NK/T-cell lymphoma, nasal type, includes cases of natural killer cell and αβ, γδ, and αβ/γδ T-cell origin: a comprehensive clinicopathologic and phenotypic study. Am J Surg Pathol. 2012;36:481–99.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pathology and Laboratory Medicine Institute, Cleveland Clinic, 9500 Euclid Ave, L-30, Cleveland, OH, 44195, USA

    Sarah Ondrejka

  2. Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic, 9500 Euclid Ave, Cleveland, OH, 44195, USA

    Deepa Jagadeesh

Authors
  1. Sarah Ondrejka
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Deepa Jagadeesh
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Deepa Jagadeesh.

Additional information

This article is part of the Topical Collection on T-Cell and Other Lymphoproliferative Malignancies

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ondrejka, S., Jagadeesh, D. Enteropathy-Associated T-Cell Lymphoma. Curr Hematol Malig Rep 11, 504–513 (2016). https://doi.org/10.1007/s11899-016-0357-7

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11899-016-0357-7

Keywords

Search

Navigation