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Current Hematologic Malignancy Reports

, Volume 11, Issue 6, pp 504–513 | Cite as

Enteropathy-Associated T-Cell Lymphoma

  • Sarah Ondrejka
  • Deepa Jagadeesh
T-CELL AND OTHER LYMPHOPROLIFERATIVE MALIGNANCIES (P PORCU, SECTION EDITOR)
Part of the following topical collections:
  1. Topical Collection on T-Cell and Other Lymphoproliferative Malignancies

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.

Keywords

Intestinal T-cell lymphoma Type I enteropathy-associated T-cell lymphoma Type II enteropathy-associated T-cell lymphoma Monomorphic CD56+ intestinal T-cell lymphoma Celiac disease Refractory celiac disease, monomorphic epitheliotropic intestinal T-cell lymphoma 

References

  1. 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.CrossRefPubMedGoogle Scholar
  2. 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.CrossRefPubMedGoogle Scholar
  3. 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.PubMedGoogle Scholar
  4. 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.CrossRefPubMedGoogle Scholar
  5. 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.Google Scholar
  6. 6.
    Sharaiha RZ et al. Increasing incidence of enteropathy-associated T-cell lymphoma in the United States, 1973-2008. Cancer. 2012;118:3786–92.CrossRefPubMedGoogle Scholar
  7. 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.CrossRefPubMedGoogle Scholar
  8. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 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.CrossRefPubMedGoogle Scholar
  10. 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.CrossRefPubMedGoogle Scholar
  11. 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.CrossRefPubMedGoogle Scholar
  12. 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.CrossRefPubMedGoogle Scholar
  13. 13.
    Swerdlow SH et al. Cytotoxic T-cell and NK-cell lymphomas: current questions and controversies. Am J Surg Pathol. 2014;38:e60–71.CrossRefPubMedGoogle Scholar
  14. 14.
    Swerdlow SH et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127:2375–90.CrossRefPubMedGoogle Scholar
  15. 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.CrossRefPubMedGoogle Scholar
  16. 16.
    Sabatino AD, Biagi F, Gobbi PG, C. G. How I treat enteropathy-associated T-cell lymphoma. Blood2. 2012;119:2458–68.CrossRefGoogle Scholar
  17. 17.
    Malamut G, Meresse B, Cellier C, Cerf-Bensussan N. Refractory celiac disease: from bench to bedside. Semin Immunopathol. 2012;34:601–13.CrossRefPubMedGoogle Scholar
  18. 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.CrossRefPubMedGoogle Scholar
  19. 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.CrossRefPubMedGoogle Scholar
  20. 20.
    Green PH et al. Risk of malignancy in patients with celiac disease. Am J Med. 2003;115:191–5.CrossRefPubMedGoogle Scholar
  21. 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.CrossRefPubMedGoogle Scholar
  22. 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.CrossRefPubMedGoogle Scholar
  23. 23.
    Wierdsma NJ et al. Refractory celiac disease and EATL patients show severe malnutrition and malabsorption at diagnosis. Clin Nutr. 2016;35:685–91.CrossRefPubMedGoogle Scholar
  24. 24.
    Muller-Hermelink H, Delabie J, Ko Y, et al. WHO classification of tumours of the digestive system 112–4 (IARC, 2010).Google Scholar
  25. 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).Google Scholar
  26. 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).Google Scholar
  27. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Verkarre V, Asnafi V, Lecomte T, et al. Refractory celiac disease is a diffuse gastrointestinal disease. Gut. 2003;52:205–11.CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Zettl A, de Leeuw R, Haralambieva EM-HH. Enteropathy-type T-cell lymphoma. Am J Clin Pathol. 2007;127:701–6.CrossRefPubMedGoogle Scholar
  30. 30.
    Foukas PG, de Leval L. Recent advances in intestinal lymphomas. Histopathology. 2015;66:112–36.CrossRefPubMedGoogle Scholar
  31. 31.
    Arps DP, Smith LB. Classic versus type II enteropathy-associated T-cell lymphoma: diagnostic considerations. Arch Pathol Lab Med. 2013;137:1227–31.CrossRefPubMedGoogle Scholar
  32. 32.
    Malamut G et al. Enteropathy associated T cell lymphoma in celiac disease: a large retrospective study. Dig Liver Dis. 2013;45:377–84.CrossRefPubMedGoogle Scholar
  33. 33.
    Tomita S et al. Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. Mod Pathol. 2015;28:1286–96.CrossRefPubMedGoogle Scholar
  34. 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.CrossRefPubMedGoogle Scholar
  35. 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. 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.CrossRefPubMedGoogle Scholar
  37. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Hapgood G, Savage KJ. The biology and management of systemic anaplastic large cell lymphoma. Blood. 2015;126:17–25.CrossRefPubMedGoogle Scholar
  39. 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. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Leventaki V et al. Indolent peripheral T-cell lymphoma involving the gastrointestinal tract. Hum Pathol. 2014;45(2):421–6.CrossRefPubMedGoogle Scholar
  42. 42.
    Takeuchi K et al. Lymphomatoid gastropathy: a distinct clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation. Blood. 2010;116:5631–7.CrossRefPubMedGoogle Scholar
  43. 43.
    Daum S et al. Capsule endoscopy in refractory celiac disease. Endoscopy. 2007;39:455–8.CrossRefPubMedGoogle Scholar
  44. 44.
    Hadithi M et al. The value of double-balloon enteroscopy in patients with refractory celiac disease. Am J Gastroenterol. 2007;102:987–96.CrossRefPubMedGoogle Scholar
  45. 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.PubMedGoogle Scholar
  46. 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.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 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.CrossRefPubMedGoogle Scholar
  48. 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.CrossRefPubMedGoogle Scholar
  49. 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.CrossRefPubMedGoogle Scholar
  50. 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.CrossRefPubMedGoogle Scholar
  51. 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.CrossRefPubMedGoogle Scholar
  52. 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.CrossRefPubMedGoogle Scholar
  53. 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.CrossRefPubMedGoogle Scholar
  54. 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.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  1. 1.Pathology and Laboratory Medicine Institute, Cleveland ClinicClevelandUSA
  2. 2.Department of Hematology and Medical OncologyTaussig Cancer Institute, Cleveland ClinicClevelandUSA

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