Multicenter retrospective analysis of the clinicopathologic features of monomorphic epitheliotropic intestinal T-cell lymphoma

  • Jun Ho Yi
  • Gyeong-Won Lee
  • Young Rok Do
  • Hye Ra Jung
  • Jung Yong Hong
  • Dok Hyun Yoon
  • Cheolwon Suh
  • Yoon Seok Choi
  • Seong Yoon Yi
  • Byeong Seok Sohn
  • Byung-Su Kim
  • Sung Yong Oh
  • Jinny Park
  • Jae-Cheol Jo
  • Seung-Sook Lee
  • Young-Ha Oh
  • Seok Jin Kim
  • Won Seog KimEmail author
Original Article


Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 World Health Organization classifications. To further elucidate the clinicopathologic features of this new disease, we carried out a retrospective, multicenter analysis of 42 patients with MEITL. The median age of the patients was 59 years (range, 20–84 years), and 27 patients (64 %) were male. Thirty-two patients (76 %) were Ann-Arbor stages I–II and 28 (67 %) were Lugano stages I–II1&2. The most frequent site of involvement was the jejunum (N = 21). Most cases expressed CD8 (79 %) and CD56 (95 %) and did not express CD30 (5 %) or EBER (0 %). The median progression-free survival was 6.9 months (95 % CI 4.3–9.6); the median OS was 14.8 months (2.4–27.2). Thirty-two patients (76 %) underwent surgery and 37 (88 %) received chemotherapy. A complete response (CR) rate was 38 %. Sixteen patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 24 cases, most frequently in the primary site (N = 23). Four cases showed central nervous system relapse. Age over 55 years, poor performance scale, advanced Lugano stage (IIE–IV), not achieving CR, and not receiving ASCT were associated with inferior OS. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem essential. As CHOP might be insufficient for achieving CR, more efficient combinations should be investigated. Additionally, considering the frequent local failure and CNS relapse, novel therapeutic approaches are required to improve survival.


Monomorphic epitheliotropic intestinal T-cell lymphoma Mature T-cell neoplasm Prognosis 



  1. 1.
    Koch P, del Valle F, Berdel WE, Willich NA, Reers B, Hiddemann W, Grothaus-Pinke B, Reinartz G, Brockmann J, Temmesfeld A, Schmitz R, Rube C, Probst A, Jaenke G, Bodenstein H, Junker A, Pott C, Schultze J, Heinecke A, Parwaresch R, Tiemann M (2001) Primary gastrointestinal non-Hodgkin’s lymphoma: I. Anatomic and histologic distribution, clinical features, and survival data of 371 patients registered in the German Multicenter Study GIT NHL 01/92. J Clin Oncol 19(18):3861–3873. CrossRefGoogle Scholar
  2. 2.
    Kim SJ, Choi CW, Mun YC, Oh SY, Kang HJ, Lee SI, Won JH, Kim MK, Kwon JH, Kim JS, Kwak JY, Kwon JM, Hwang IG, Kim HJ, Lee JH, Oh S, Park KW, Suh C, Kim WS (2011) Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL). BMC Cancer 11:321. CrossRefGoogle Scholar
  3. 3.
    Chott A, Dragosics B, Radaszkiewicz T (1992) Peripheral T-cell lymphomas of the intestine. Am J Pathol 141(6):1361–1371Google Scholar
  4. 4.
    Swerdlow SH CE, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2008) WHO classification of tumours of haematopoietic and lymphoid tissues. WHO Classification of Tumours, 4th Edition, Volume 2. IARCGoogle Scholar
  5. 5.
    Tan SY, Ooi AS, Ang MK, Koh M, Wong JC, Dykema K, Ngeow J, Loong S, Gatter K, Tan L, Lim LC, Furge K, Tao M, Lim ST, Loong F, Cheah PL, Teh BT (2011) Nuclear expression of MATK is a novel marker of type II enteropathy-associated T-cell lymphoma. Leukemia 25(3):555–557. CrossRefGoogle Scholar
  6. 6.
    Chan JK, Chan AC, Cheuk W, Wan SK, Lee WK, Lui YH, Chan WK (2011) Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent γδ T-cell receptor expression. Am J Surg Pathol 35(10):1557–1569. CrossRefGoogle Scholar
  7. 7.
    Tse E, Gill H, Loong F, Kim SJ, Ng SB, Tang T, Ko YH, Chng WJ, Lim ST, Kim WS, Kwong YL (2012) Type II enteropathy-associated T-cell lymphoma: a multicenter analysis from the Asia Lymphoma Study Group. Am J Hematol 87(7):663–668. CrossRefGoogle Scholar
  8. 8.
    Wilson AL, Swerdlow SH, Przybylski GK, Surti U, Choi JK, Campo E, Trucco MM, Van Oss SB, Felgar RE (2013) Intestinal γδ T-cell lymphomas are most frequently of type II enteropathy-associated T-cell type. Hum Pathol 44(6):1131–1145. CrossRefGoogle Scholar
  9. 9.
    Roberti A, Dobay MP, Bisig B, Vallois D, Boechat C, Lanitis E, Bouchindhomme B, Parrens MC, Bossard C, Quintanilla-Martinez L, Missiaglia E, Gaulard P, de Leval L (2016) Type II enteropathy-associated T-cell lymphoma features a unique genomic profile with highly recurrent SETD2 alterations. Nat Commun 7:12602. CrossRefGoogle Scholar
  10. 10.
    Baumgartner AK, Zettl A, Chott A, Ott G, Muller-Hermelink HK, Starostik P (2003) High frequency of genetic aberrations in enteropathy-type T-cell lymphoma. Lab Invest 83(10):1509–1516CrossRefGoogle Scholar
  11. 11.
    Swerdlow SH CE, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman JW (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. WHO Classification of Tumours, Revised 4th Edition, Volume 2Google Scholar
  12. 12.
    Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, Lister TA (2014) Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol 32(27):3059–3068. CrossRefGoogle Scholar
  13. 13.
    Rohatiner A, d'Amore F, Coiffier B, Crowther D, Gospodarowicz M, Isaacson P, Lister TA, Norton A, Salem P, Shipp M, et al. (1994) Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Annals of oncology : official journal of the European Society for Med Oncol 5 (5):397–400Google Scholar
  14. 14.
    Tomita S, Kikuti YY, Carreras J, Kojima M, Ando K, Takasaki H, Sakai R, Takata K, Yoshino T, Bea S, Campo E, Nakamura N (2015) Genomic and immunohistochemical profiles of enteropathy-associated T-cell lymphoma in Japan. Modern Pathol 28(10):1286–1296. CrossRefGoogle Scholar
  15. 15.
    Kucuk C, Jiang B, Hu X, Zhang W, Chan JK, Xiao W, Lack N, Alkan C, Williams JC, Avery KN, Kavak P, Scuto A, Sen E, Gaulard P, Staudt L, Iqbal J, Zhang W, Cornish A, Gong Q, Yang Q, Sun H, d'Amore F, Leppa S, Liu W, Fu K, de Leval L, McKeithan T, Chan WC (2015) Activating mutations of STAT5B and STAT3 in lymphomas derived from γδ-T or NK cells. Nat Commun 6:6025. CrossRefGoogle Scholar
  16. 16.
    Pfister SX, Markkanen E, Jiang Y, Sarkar S, Woodcock M, Orlando G, Mavrommati I, Pai CC, Zalmas LP, Drobnitzky N, Dianov GL, Verrill C, Macaulay VM, Ying S, La Thangue NB, D'Angiolella V, Ryan AJ, Humphrey TC (2015) Inhibiting WEE1 selectively kills histone H3K36me3-deficient cancers by dNTP starvation. Cancer Cell 28(5):557–568. CrossRefGoogle Scholar
  17. 17.
    Martinelli G, Mancini M, De Benedittis C, Rondoni M, Papayannidis C, Manfrini M, Meggendorfer M, Calogero R, Guadagnuolo V, Fontana MC, Bavaro L, Padella A, Zago E, Pagano L, Zanotti R, Scaffidi L, Specchia G, Albano F, Merante S, Elena C, Savini P, Gangemi D, Tosi P, Ciceri F, Poletti G, Riccioni L, Morigi F, Delledonne M, Haferlach T, Cavo M, Valent P, Soverini S (2018) SETD2 and histone H3 lysine 36 methylation deficiency in advanced systemic mastocytosis. Leukemia 32(1):139–148. CrossRefGoogle Scholar
  18. 18.
    Gale J, Simmonds PD, Mead GM, Sweetenham JW, Wright DH (2000) Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center. J Clin Oncol 18(4):795–803. CrossRefGoogle Scholar
  19. 19.
    Karanam PK, Al-Hamadani M, Go RS (2016) Enteropathy-associated T-cell lymphoma in the US: higher incidence and poorer survival among Asians. Br J Haematol 172(6):990–992. CrossRefGoogle Scholar
  20. 20.
    Sieniawski M, Angamuthu N, Boyd K, Chasty R, Davies J, Forsyth P, Jack F, Lyons S, Mounter P, Revell P, Proctor SJ, Lennard AL (2010) Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood 115(18):3664–3670. CrossRefGoogle Scholar
  21. 21.
    Rongey C, Micallef I, Smyrk T, Murray J (2006) Successful treatment of enteropathy-associated T cell lymphoma with autologous stem cell transplant. Dig Dis Sci 51(6):1082–1086. CrossRefGoogle Scholar
  22. 22.
    Jantunen E, Boumendil A, Finel H, Luan JJ, Johnson P, Rambaldi A, Haynes A, Duchosal MA, Bethge W, Biron P, Carlson K, Craddock C, Rudin C, Finke J, Salles G, Kroschinsky F, Sureda A, Dreger P (2013) Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: a retrospective study by the EBMT. Blood 121(13):2529–2532. CrossRefGoogle Scholar
  23. 23.
    Nijeboer P, de Baaij LR, Visser O, Witte BI, Cillessen SA, Mulder CJ, Bouma G (2015) Treatment response in enteropathy associated T-cell lymphoma; survival in a large multicenter cohort. Am J Hematol 90(6):493–498. CrossRefGoogle Scholar
  24. 24.
    Iqbal J, Weisenburger DD, Chowdhury A, Tsai MY, Srivastava G, Greiner TC, Kucuk C, Deffenbacher K, Vose J, Smith L, Au WY, Nakamura S, Seto M, Delabie J, Berger F, Loong F, Ko YH, Sng I, Liu X, Loughran TP, Armitage J, Chan WC (2011) Natural killer cell lymphoma shares strikingly similar molecular features with a group of non-hepatosplenic γδ T-cell lymphoma and is highly sensitive to a novel aurora kinase A inhibitor in vitro. Leukemia 25(2):348–358. CrossRefGoogle Scholar
  25. 25.
    Raspadori D, Damiani D, Lenoci M, Rondelli D, Testoni N, Nardi G, Sestigiani C, Mariotti C, Birtolo S, Tozzi M, Lauria F (2001) CD56 antigenic expression in acute myeloid leukemia identifies patients with poor clinical prognosis. Leukemia 15(8):1161–1164CrossRefGoogle Scholar
  26. 26.
    Bing Xu XS, Pengcheng Shi, Pengnan Xiao, Zhengshan Yu, Shuyun Zhou (2009) Relationship between CD56 antigen expression and quantification of MDR1 gene expression in patients with de novo acute myeloid leukemia (AML). Paper presented at the Annual Meeting of American Society of Hematology,Google Scholar
  27. 27.
    Schaich M, Koch R, Soucek S, Repp R, Ehninger G, Illmer T (2004) A sensitive model for prediction of relapse in adult acute myeloid leukaemia with t(8;21) using white blood cell count, CD56 and MDR1 gene expression at diagnosis. Br J Haematol 125(4):477–479. CrossRefGoogle Scholar
  28. 28.
    Kassira N, Pedroso FE, Cheung MC, Koniaris LG, Sola JE (2011) Primary gastrointestinal tract lymphoma in the pediatric patient: review of 265 patients from the SEER registry. J Pediatr Surg 46(10):1956–1964. CrossRefGoogle Scholar
  29. 29.
    Aleman BM, Haas RL, van der Maazen RW (2010) Role of radiotherapy in the treatment of lymphomas of the gastrointestinal tract. Best Pract Res Clin Gastroenterol 24(1):27–34. CrossRefGoogle Scholar
  30. 30.
    Ellin F, Landstrom J, Jerkeman M, Relander T (2015) Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study. Blood 126(1):36–41. CrossRefGoogle Scholar
  31. 31.
    Gurion R, Mehta N, Migliacci JC, Zelenetz A, Moskowitz A, Lunning M, Moskowitz C, Hamlin P, Horwitz S (2016) Central nervous system involvement in T-cell lymphoma: a single center experience. Acta Oncologica (Stockholm, Sweden) 55(5):561–566. CrossRefGoogle Scholar
  32. 32.
    Yi JH, Kim JH, Baek KK, Lim T, Lee DJ, Ahn YC, Kim K, Kim SJ, Ko YH, Kim WS (2011) Elevated LDH and paranasal sinus involvement are risk factors for central nervous system involvement in patients with peripheral T-cell lymphoma. Ann Oncol 22(7):1636–1643. CrossRefGoogle Scholar
  33. 33.
    Kikuma K, Yamada K, Nakamura S, Ogami A, Nimura S, Hirahashi M, Yonemasu H, Urabe S, Naito S, Matsuki Y, Sadahira Y, Takeshita M (2014) Detailed clinicopathological characteristics and possible lymphomagenesis of type II intestinal enteropathy-associated T-cell lymphoma in Japan. Hum Pathol 45(6):1276–1284. CrossRefGoogle Scholar
  34. 34.
    Chott A, Haedicke W, Mosberger I, Fodinger M, Winkler K, Mannhalter C, Muller-Hermelink HK (1998) Most CD56+ intestinal lymphomas are CD8+CD5-T-cell lymphomas of monomorphic small to medium size histology. Am J Pathol 153(5):1483–1490. CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Jun Ho Yi
    • 1
  • Gyeong-Won Lee
    • 2
  • Young Rok Do
    • 3
  • Hye Ra Jung
    • 4
  • Jung Yong Hong
    • 5
  • Dok Hyun Yoon
    • 5
  • Cheolwon Suh
    • 5
  • Yoon Seok Choi
    • 6
  • Seong Yoon Yi
    • 7
  • Byeong Seok Sohn
    • 8
  • Byung-Su Kim
    • 9
  • Sung Yong Oh
    • 10
  • Jinny Park
    • 11
  • Jae-Cheol Jo
    • 12
  • Seung-Sook Lee
    • 13
  • Young-Ha Oh
    • 14
  • Seok Jin Kim
    • 15
  • Won Seog Kim
    • 15
    Email author
  1. 1.Division of Hematology-Oncology, Department of MedicineChung-Ang UniversitySeoulSouth Korea
  2. 2.Division of Hematology and Oncology, Department of Internal Medicine, Institute of Health ScienceGyeongsang National University Hospital, Gyeongsang National University College of MedicineJinjuSouth Korea
  3. 3.Division of Hematology-Oncology, Department of Medicine, Dongsan Medical CenterKeimyung University School of MedicineDaeguSouth Korea
  4. 4.Department of Pathology, Dongsan Medical CenterKeimyung University School of MedicineDaeguSouth Korea
  5. 5.Department of Oncology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulSouth Korea
  6. 6.Department of Internal MedicineChungnam National University College of MedicineDaejeonSouth Korea
  7. 7.Department of Internal MedicineInje University Ilsan Paik HospitalGoyangSouth Korea
  8. 8.Department of Internal Medicine, Sanggye Paik HospitalInje University College of MedicineSeoulSouth Korea
  9. 9.Department of Hemato-OncologyHallym University Dongtan Sacred Heart HospitalHwaseongSouth Korea
  10. 10.Department of Internal MedicineDong-A University College of MedicineBusanSouth Korea
  11. 11.Division of Hematology, Department of Internal Medicine, Gil Medical CenterGachon University College of MedicineIncheonSouth Korea
  12. 12.Department of Hematology and OncologyUlsan University Hospital, University of Ulsan College of MedicineUlsanSouth Korea
  13. 13.Department of PathologyKorea Cancer Center HospitalSeoulSouth Korea
  14. 14.Department of PathologyHanyang University Guri HospitalGuri-siSouth Korea
  15. 15.Division of Hematology and Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of MedicineSeoulSouth Korea

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