Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1 + 1946 word(s) 1946 2021-11-23 05:19:27 |
2 update layout and reference Meta information modification 1946 2021-12-06 02:56:29 |

Video Upload Options

Do you have a full video?


Are you sure to Delete?
If you have any further questions, please contact Encyclopedia Editorial Office.
Sato, Y. Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorder. Encyclopedia. Available online: (accessed on 20 June 2024).
Sato Y. Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorder. Encyclopedia. Available at: Accessed June 20, 2024.
Sato, Yasuharu. "Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorder" Encyclopedia, (accessed June 20, 2024).
Sato, Y. (2021, December 04). Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorder. In Encyclopedia.
Sato, Yasuharu. "Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorder." Encyclopedia. Web. 04 December, 2021.
Primary Gastrointestinal T-Cell Lymphoma and Indolent Lymphoproliferative Disorder

Primary gastrointestinal (GI) T-cell neoplasms are extremely rare heterogeneous disease entities with distinct clinicopathologic features. Given the different prognoses of various disease subtypes, clinicians and pathologists must be aware of the key characteristics of these neoplasms, despite their rarity.

primary gastrointestinal T-cell lymphoma enteropathy-associated T-cell lymphoma EATL monomorphic epitheliotropic intestinal T-cell lymphoma MEITL indolent T-cell lymphoproliferative disorder ITLPD-GI NK-cell enteropathy

1. Introduction

The gastrointestinal (GI) tract is a common site for extranodal lymphoma involvement. Primary GI lymphomas are predominately of the B-cell lineage, and T-cell neoplasms are rare, accounting for 13–15% of GI lymphomas [1][2][3]. The majority (>90%) of primary GI T-cell neoplasms exhibit aggressive behavior and are associated with short progression-free survival and overall survival. In contrast, an indolent condition termed indolent T-cell lymphoproliferative disorder of the GI tract (ITLPD-GI) has been identified. GI T-cell lymphoma and lymphoproliferative disorders are heterogeneous entities consisting of various subtypes with distinct clinicopathological features and prognoses. Therefore, both clinicians and pathologists must be aware of the distinct characteristics of these lesions to ensure that appropriate care is provided.
The revised 4th World Health Organization (WHO) classification in 2017 broadly classifies primary GI T-cell lymphoma as enteropathy-associated T-cell lymphoma (EATL) and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). In the 2001 WHO classification, primary GI T-cell lymphoma with digestive symptoms was initially treated as a separate category, termed enteropathy-type T-cell lymphoma (ETL). In 2008, the entity was renamed EATL and further classified into type I and type II. Type I is associated with celiac disease and has a high incidence in Northern Europe. Conversely, Type II is not associated with celiac disease and has a higher incidence in Asian and Hispanic populations [4]. Type I and type II EATLs differ clinically and morphologically, and also exhibit distinct immunological and genetic features. In the revised 4th WHO classification, EATL types I and II have been revised to EATL and MEITL, respectively [5].
In the revised 4th WHO classification, intestinal T-cell lymphoma, not otherwise specified (ITL, NOS) and ITLPD-GI were newly defined. ITL, NOS is defined as T-cell lymphomas arising in the GI tract that are not otherwise specified as EATL, MEITL, anaplastic large cell lymphoma, or extranodal natural killer (NK)/T-cell lymphoma. The clinical course of ITL, NOS is generally aggressive, and this entity may include cases with insufficient immunohistochemical evaluation and cases of secondary involvement of extra-intestinal lymphoma. Currently, ITL, NOS is considered to be a provisional entity [6]. Extranodal NK/T-cell lymphoma of the nasal type (ENKTCL) and anaplastic large cell lymphoma (ALCL) may also occur in the GI tract or involve it secondarily. Furthermore, NK-cell enteropathy has been reported as a pseudomalignant lesion that is often misdiagnosed as lymphoma.

2. Enteropathy-Associated T-Cell Lymphoma

2.1. Definition and Epidemiology

EATL is a rare and aggressive intestinal T-cell lymphoma. The geographic distribution of the incidence of EATL is distinct, with a high incidence in Europe and in individuals of northern European descent. A previous report demonstrated that the proportion of EATL in peripheral T-cell lymphoma was 9.1%, 5.8%, and 1.9% in Europe, North America, and Asia, respectively [7]. EATL typically occurs in older individuals (60–70 years), and large studies have reported either an equal sex distribution or slight male predominance (male: female ratio of 1.04–2.8:1) [7][8][9][10][11].
EATL is a complication of celiac disease [12][13], one of the most common genetic disorders that affects approximately 1% of individuals worldwide [14], with a high prevalence in Europe. Celiac disease is characterized by intolerance to dietary gluten that occurs in individuals with HLA-DQ2 or DQ8, haplotypes of human leukocyte antigen (HLA) class II [14]. The association between celiac disease and EATL was first established in a study demonstrating that the HLA risk alleles (HLADQA1*0501 and DQB1*0201 (HLA-DQ2)) of celiac disease are present in majority of patients with EATL [15]. Moreover, serological evidence of gluten sensitivity in patients with EATL has been reported [12]. Notably, a gluten-free diet reduces the risk of lymphoma in patients with celiac disease [16].

2.2. Pathogenesis

EATL may be preceded by refractory celiac disease (RCD), which is defined as the persistent or recurrent symptoms of malabsorption and mucosal damage despite a strict gluten-free diet for over 12 months. Exclusion of other etiologies, including autoimmune enteropathy, tropical sprue, and lymphoma, is mandatory to diagnose RCD [17]. RCDs are biologically heterogeneous and can be divided into RCD type I (RCD I) and RCD type II (RCD II) based on immunophenotypic and molecular characteristics of intraepithelial lymphocytes (IELs). RCD I is characterized by increased polyclonal intraepithelial IELs of normal immunophenotype (sCD3+, CD8+, and CD103+), whereas RCD II is characterized by monoclonal IELs of aberrant immunophenotype (sCD3, cCD3+, CD8, CD5, and CD103+). IELs in celiac disease and RCD I show downregulated expression of CD5, but they are not entirely CD5-negative, and they may have a mixture of CD5-positive and negative subsets in some cases. Although the vast majority of RCD II show negative CD8, some patients who meet the clinical criteria for RCD and show CD8 positivity have been reported to show consistent monoclonality by PCR analysis of the TCR gene throughout the follow-up [18]. Progression of RCD I to RCD II is considered to be rare [19], and the risk of developing EATL is lower in RCD I (3–14% over 5 years) than in RCD II (33–52%) [20][21][22][23][24] (Table 1).
Table 1. Comparison of celiac disease, RCD I, RCD II, and EATL [5][9][19][20][21][22][23][24][25].
Investigations Celiac Disease RCD I RCD II EATL
Disease type Chronic enteropathy triggered by dietary gluten Persistent autoinflammatory immune response, gluten independent Low-grade
lymphoproliferative disorder
High-grade lymphoma
Immunophenotype sCD3+, cCD3+, CD5−/+, CD8+, CD103+ sCD3+, cCD3+, CD5−/+, CD8+, CD103+ sCD3, cCD3+, CD5, CD8, CD103+, CD30 CD3+, CD8, CD30+, Ki67 LI: high (>50%)
T-cell receptor polyclonal polyclonal monoclonal monoclonal
5-year survival   80–96% [18][20][21] 45–58% [18][20][21] ~20% [5][9][20]
Rate of progression to EATL in 5 years 0.7% [24] 3–14% [19][20][21][22][23] 33–52% [19][20][21][22][23] -
Abbreviations: RCD; refractory celiac disease, EATL; enteropathy-associated T-cell lymphoma, sCD3; surface CD, cCD3; cytoplasmic CD, Ki-67 LI; Ki-67 labeling index.
The NK receptor NKp46 was recently reported to be expressed in larger numbers of IELs in RCD II and EATL, whereas only a few IELs were positive in celiac disease and RCD I, suggesting that NKp46 may be a novel biomarker to clarify diagnosis [26].
Currently, two pathways are recognized for the pathogenesis of lymphoma, which are associated with different clinical presentations and outcomes. EATL secondary to RCD II (54% of all EATLs, according to one study [9]) is associated with severe GI symptoms and higher mortality (5-year survival of 0–8%). In contrast, “de novo” EATL (46%), which occurs in patients with uncomplicated celiac disease or RCD I, has higher survival rates (5-year survival of 59%) [9][21]. Nevertheless, the pathogenesis of de novo EATL remains unclear.

2.3. Cell Origin

Cells that proliferate in RCD and EATL were formerly thought to be thymic-derived conventional intraepithelial T cells, which is T-cell receptor (TCR) αβ+, due to their immunophenotypic similarity to normal intraepithelial T-cells, which account for approximately 80% of IELs [9][27]. Recent molecular and immunophenotypic analyses suggest that lineage-negative innate IELs are the origin of a proportion of RCD II cases [28][29][30][31], and EATL arising from RCD II may have the same origin.

2.4. Histopathology

In EATL, diffuse proliferation of pleomorphic medium to large lymphoma cells is observed. Lymphoma cells have abundant eosinophilic to pale cytoplasm and nuclei that are round or irregular with distinct nucleoli. Infiltration of inflammatory cells, including histiocytes, eosinophils, neutrophils, and plasma cells, is often present in the background [32]. Angiocentric proliferation and vascular invasion are present, and extensive necrosis associated with vascular occlusion is often observed [5][33]. The peripheral intestinal mucosa often exhibits features of celiac disease such as intraepithelial lymphocytosis and villous atrophy.

2.5. Immunophenotype and Genetic Alternations

Neoplastic cells are typically CD3+ (cytoplasmic), CD5, CD4, CD56, and diffusely positive for cytotoxic granule proteins (TIA-1, granzyme B, and perforin) and intraepithelial homing integrin CD103. CD8 tends to be negative but may be expressed in 19–30% cases [4][9][34] and has been reported to be present at a higher frequency in patients without a history of RCD II [9]. CD30 positivity depends on tumor cell morphology but is almost exclusively positive in large cell-based tumors [9]. Neoplastic cells are negative for anaplastic lymphoma kinase (ALK) and Epstein-Barr virus (EBV). Surface TCR expression is typically absent, but intracellular TCRβ (βF1) expression is observed in approximately 25% of cases [9].
Several studies have used microsatellite markers or array-based approaches to detect recurrent copy number gains at chromosomes 9q (the most common in EATL: 46–70%) [35][36][37], 7q, 1q, and 5q; and losses at chromosomes 16q, 8p, 13q, and 9p. Mutually exclusive gains at 9q and losses at 16q are observed in up to 80% of EATL cases [35][37][38][39]. Moreover, recent studies have reported recurrent mutations of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway with frequent activating mutations in STAT5B (26.5–29%), JAK1 (14.7–23%), JAK3 (23–27.3%), and STAT3 (12.1–16%) [36][40].
Targeted next-generation sequencing (NGS) of RCD II cases revealed recurrent activating mutation in JAK1 (75%) and STAT3 (25%) genes [30], which may implicate JAK-STAT pathway mutations to be early events in EATL. Targeted NGS analysis of RCD II also revealed frequent occurrence of deleterious mutations in nuclear factor kappa-light chain-enhancer of activated B-cells (NF-κB) regulators and in several epigenetic regulators [41].

2.6. Clinical Manifestations

Approximately 90% of EATLs occur in the small intestine [7][8]. Multiple lesions occur in 32–54% of cases, and single lesions in the stomach or colon are rare [7][8][9]. Given the close association between EATL and celiac disease, symptoms such as diarrhea, abdominal pain, weight loss, and hypoalbuminemia may precede EATL [7][9][10][42][43][44]. However, the diagnosis of celiac disease is made prior to the diagnosis of EATL in 20–73% of cases [8][9][42]. EATL also causes vomiting due to intestinal obstruction, intestinal bleeding, and intestinal perforation in 25–50% of patients [7][8][9][43][44][45]. Hemophagocytic syndrome is reported in 16–40% of cases [9][46].
EATLs can also spread beyond the GI tract, and the most common sites of involvement are abdominal lymph nodes (35%), followed by bone marrow (3–18%), lung and mediastinal lymph nodes (5–16%), liver (2–8%), and skin (5%) [7][9][10]. Involvement of the central nervous system (CNS) has also been reported [47][48][49]. Endoscopically, EATL can manifest as a large mass, ulceration, or stricture [7][9].

2.7. Prognosis and Treatment Strategies

The prognosis of EATL is very poor. Gale et al. reported 1- and 5- year survival rates of 38.7% and 9.7%, respectively, and 1- and 5-year failure-free survival rates of 19.4% and 3.2%, respectively [8]. Other studies have estimated 5-year survival rates of 11–20% [10][42][43][45][50]. Standard validated treatment strategies for EATL have yet to be established. Surgery and chemotherapy are the treatments of choice, but EATL tends to be refractory to these therapies [50]. CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, and prednisolone) regimen is the most widely implemented approach, but its overall median survival has been reported to be only 7 months [8][42][43][45]. Recently, autologous stem cell transplant (ASCT) following chemotherapy has been reported to significantly enhance survival [9][10][50][51][52]. One study demonstrated that the novel regimen IVE/MTX (ifosfamide, vincristine, etoposide, methotrexate) followed by ASCT improved survival rates compared to anthracycline-based chemotherapy, with a 5-year overall survival rate of 60% [10]. Although surgery is not considered as first-line treatment for lymphoma, tumor reduction surgery has been reported to be an independent prognostic factor of nutritional status [9]. Further, it is estimated that the combination of surgery and chemotherapy will reduce tumor necrosis, peritonitis, and intestinal hemorrhage associated with chemotherapy, underscoring the potential of surgery as a treatment option at the appropriate time.
One case report of a CD30-positive patient with EATL demonstrated that targeted therapy using brentuximab vedotin resulted in complete remission [53]. In another report, a patient with EATL who had multiple relapses following ASCT achieved sustained remission with CD30 chimeric antigen receptor-modified T-cell therapy [54].
For RCD, various immunosuppressive medications such as azathioprine, systemic corticosteroids, or regular budesonide have been used. Although conventional immunosuppressive medications fail in about half of the cases, recent study revealed open-capsule Budesonide has shown clinical and histological improvement in about 90% of the cases, including those in which conventional treatments have failed [55]. Furthermore, in follow-up, 53% of RCDII patients treated with open-capsule budesonide showed absence of the former clonal TCR gene rearrangement and aberrant IEL phenotype. This indicates that open-capsule budesonide may reduce the risk of developing from RCDII to EATL, although longer follow-up is needed [55].


  1. Kohno, S.; Ohshima, K.; Yoneda, S.; Kodama, T.; Shirakusa, T.; Kikuchi, M. Clinicopathological analysis of 143 primary malignant lymphomas in the small and large intestines based on the new WHO classification. Histopathology 2003, 43, 135–143.
  2. Kim, S.J.; Choi, C.W.; Mun, Y.C.; Oh, S.Y.; Kang, H.J.; Lee, S.I.; Won, J.H.; Kim, M.K.; Kwon, J.H.; Kim, J.S.; et al. Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL). BMC Cancer 2011, 11, 321.
  3. Ding, W.; Zhao, S.; Wang, J.; Yang, Q.; Sun, H.; Yan, J.; Gao, L.; Yao, W.; Zhang, W.; Liu, W. Gastrointestinal Lymphoma in Southwest China: Subtype Distribution of 1,010 Cases Using the WHO (2008) Classification in a Single Institution. Acta Haematol. 2016, 135, 21–28.
  4. Chott, A.; Haedicke, W.; Mosberger, I.; Fodinger, M.; Winkler, K.; Mannhalter, C.; Muller-Hermelink, H.K. Most CD56+ intestinal lymphomas are CD8+CD5-T-cell lymphomas of monomorphic small to medium size histology. Am. J. Pathol. 1998, 153, 1483–1490.
  5. Swerdlow, S.H.; Campo, E.; Harris, N.L.; Jaffe, E.S.; Pileri, S.A.; Stein, H.; Thiele, J. WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues, revised 4th ed.; IARC Press: Lyon, France, 2017.
  6. Attygalle, A.D.; Cabecadas, J.; Gaulard, P.; Jaffe, E.S.; de Jong, D.; Ko, Y.H.; Said, J.; Klapper, W. Peripheral T-cell and NK-cell lymphomas and their mimics; taking a step forward—Report on the lymphoma workshop of the XVIth meeting of the European Association for Haematopathology and the Society for Hematopathology. Histopathology 2014, 64, 171–199.
  7. Delabie, J.; Holte, H.; Vose, J.M.; Ullrich, F.; Jaffe, E.S.; Savage, K.J.; Connors, J.M.; Rimsza, L.; Harris, N.L.; Muller-Hermelink, K.; et al. Enteropathy-associated T-cell lymphoma: Clinical and histological findings from the international peripheral T-cell lymphoma project. Blood 2011, 118, 148–155.
  8. Gale, J.; Simmonds, P.D.; Mead, G.M.; Sweetenham, J.W.; Wright, D.H. Enteropathy-type intestinal T-cell lymphoma: Clinical features and treatment of 31 patients in a single center. J. Clin. Oncol. 2000, 18, 795–803.
  9. Malamut, G.; Chandesris, O.; Verkarre, V.; Meresse, B.; Callens, C.; Macintyre, E.; Bouhnik, Y.; Gornet, J.M.; Allez, M.; Jian, R.; et al. Enteropathy associated T cell lymphoma in celiac disease: A large retrospective study. Dig. Liver Dis. 2013, 45, 377–384.
  10. Sieniawski, M.; Angamuthu, N.; Boyd, K.; Chasty, R.; Davies, J.; Forsyth, P.; Jack, F.; Lyons, S.; Mounter, P.; Revell, P.; et al. Evaluation of enteropathy-associated T-cell lymphoma comparing standard therapies with a novel regimen including autologous stem cell transplantation. Blood 2010, 115, 3664–3670.
  11. Verbeek, W.H.; Van De Water, J.M.; Al-Toma, A.; Oudejans, J.J.; Mulder, C.J.; Coupe, V.M. Incidence of enteropathy--associated T-cell lymphoma: A nation-wide study of a population-based registry in The Netherlands. Scand. J. Gastroenterol. 2008, 43, 1322–1328.
  12. O’Farrelly, C.; Feighery, C.; O’Briain, D.S.; Stevens, F.; Connolly, C.E.; McCarthy, C.; Weir, D.G. Humoral response to wheat protein in patients with coeliac disease and enteropathy associated T cell lymphoma. Br. Med. J. Clin. Res. Ed. 1986, 293, 908–910.
  13. Swinson, C.M.; Slavin, G.; Coles, E.C.; Booth, C.C. Coeliac disease and malignancy. Lancet 1983, 1, 111–115.
  14. Green, P.H.; Cellier, C. Celiac disease. N. Engl. J. Med. 2007, 357, 1731–1743.
  15. Howell, W.M.; Leung, S.T.; Jones, D.B.; Nakshabendi, I.; Hall, M.A.; Lanchbury, J.S.; Ciclitira, P.J.; Wright, D.H. HLA-DRB, -DQA, and -DQB polymorphism in celiac disease and enteropathy-associated T-cell lymphoma. Common features and additional risk factors for malignancy. Hum. Immunol. 1995, 43, 29–37.
  16. Silano, M.; Volta, U.; Vincenzi, A.D.; Dessi, M.; Vincenzi, M.D. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig. Dis. Sci. 2008, 53, 972–976.
  17. Ludvigsson, J.F.; Leffler, D.A.; Bai, J.C.; Biagi, F.; Fasano, A.; Green, P.H.; Hadjivassiliou, M.; Kaukinen, K.; Kelly, C.P.; Leonard, J.N.; et al. The Oslo definitions for coeliac disease and related terms. Gut 2013, 62, 43–52.
  18. de Mascarel, A.; Belleannee, G.; Stanislas, S.; Merlio, C.; Parrens, M.; Laharie, D.; Dubus, P.; Merlio, J.P. Mucosal intraepithelial T-lymphocytes in refractory celiac disease: A neoplastic population with a variable CD8 phenotype. Am. J. Surg. Pathol. 2008, 32, 744–751.
  19. Daum, S.; Ipczynski, R.; Schumann, M.; Wahnschaffe, U.; Zeitz, M.; Ullrich, R. High rates of complications and substantial mortality in both types of refractory sprue. Eur. J. Gastroenterol. Hepatol. 2009, 21, 66–70.
  20. Ilus, T.; Kaukinen, K.; Virta, L.J.; Huhtala, H.; Maki, M.; Kurppa, K.; Heikkinen, M.; Heikura, M.; Hirsi, E.; Jantunen, K.; et al. Refractory coeliac disease in a country with a high prevalence of clinically-diagnosed coeliac disease. Aliment. Pharmacol. Ther. 2014, 39, 418–425.
  21. Al-Toma, A.; Verbeek, W.H.; Hadithi, M.; von Blomberg, B.M.; Mulder, C.J. Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: Retrospective evaluation of single-centre experience. Gut 2007, 56, 1373–1378.
  22. Rubio-Tapia, A.; Kelly, D.G.; Lahr, B.D.; Dogan, A.; Wu, T.T.; Murray, J.A. Clinical staging and survival in refractory celiac disease: A single center experience. Gastroenterology 2009, 136, 99–107.
  23. Rishi, A.R.; Rubio-Tapia, A.; Murray, J.A. Refractory celiac disease. Expert Rev. Gastroenterol. Hepatol. 2016, 10, 537–546.
  24. Malamut, G.; Afchain, P.; Verkarre, V.; Lecomte, T.; Amiot, A.; Damotte, D.; Bouhnik, Y.; Colombel, J.F.; Delchier, J.C.; Allez, M.; et al. Presentation and long-term follow-up of refractory celiac disease: Comparison of type I with type II. Gastroenterology 2009, 136, 81–90.
  25. Lebwohl, B.; Granath, F.; Ekbom, A.; Smedby, K.E.; Murray, J.A.; Neugut, A.I.; Green, P.H.; Ludvigsson, J.F. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: A population-based cohort study. Ann. Intern. Med. 2013, 159, 169–175.
  26. Cheminant, M.; Bruneau, J.; Malamut, G.; Sibon, D.; Guegan, N.; van Gils, T.; Cording, S.; Trinquand, A.; Verkarre, V.; Lhermitte, L.; et al. NKp46 is a diagnostic biomarker and may be a therapeutic target in gastrointestinal T-cell lymphoproliferative diseases: A CELAC study. Gut 2019, 68, 1396–1405.
  27. Cellier, C.; Patey, N.; Mauvieux, L.; Jabri, B.; Delabesse, E.; Cervoni, J.P.; Burtin, M.L.; Guy-Grand, D.; Bouhnik, Y.; Modigliani, R.; et al. Abnormal intestinal intraepithelial lymphocytes in refractory sprue. Gastroenterology 1998, 114, 471–481.
  28. Tack, G.J.; van Wanrooij, R.L.; Langerak, A.W.; Tjon, J.M.; von Blomberg, B.M.; Heideman, D.A.; van Bergen, J.; Koning, F.; Bouma, G.; Mulder, C.J.; et al. Origin and immunophenotype of aberrant IEL in RCDII patients. Mol. Immunol. 2012, 50, 262–270.
  29. Schmitz, F.; Tjon, J.M.; Lai, Y.; Thompson, A.; Kooy-Winkelaar, Y.; Lemmers, R.J.; Verspaget, H.W.; Mearin, M.L.; Staal, F.J.; Schreurs, M.W.; et al. Identification of a potential physiological precursor of aberrant cells in refractory coeliac disease type II. Gut 2013, 62, 509–519.
  30. Ettersperger, J.; Montcuquet, N.; Malamut, G.; Guegan, N.; Lopez-Lastra, S.; Gayraud, S.; Reimann, C.; Vidal, E.; Cagnard, N.; Villarese, P.; et al. Interleukin-15-Dependent T-Cell-like Innate Intraepithelial Lymphocytes Develop in the Intestine and Transform into Lymphomas in Celiac Disease. Immunity 2016, 45, 610–625.
  31. Chander, U.; Leeman-Neill, R.J.; Bhagat, G. Pathogenesis of Enteropathy-Associated T Cell Lymphoma. Curr. Hematol. Malig. Rep. 2018, 13, 308–317.
  32. Isaacson, P.; Wright, D.H. Malignant histiocytosis of the intestine. Its relationship to malabsorption and ulcerative jejunitis. Hum. Pathol. 1978, 9, 661–677.
  33. Isaacson, P.G.; Bhagat, G. Enteropathy-associated T-cell lymphoma and other primary intestinal T-cell lymphomas. In Hematopathology, 2nd ed.; Elsevier: Saunders, MO, USA, 2017.
  34. Murray, A.; Cuevas, E.C.; Jones, D.B.; Wright, D.H. Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell lymphoma. Am. J. Pathol. 1995, 146, 509–519.
  35. Zettl, A.; Ott, G.; Makulik, A.; Katzenberger, T.; Starostik, P.; Eichler, T.; Puppe, B.; Bentz, M.; Muller-Hermelink, H.K.; Chott, A. Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma. Am. J. Pathol. 2002, 161, 1635–1645.
  36. Moffitt, A.B.; Ondrejka, S.L.; McKinney, M.; Rempel, R.E.; Goodlad, J.R.; Teh, C.H.; Leppa, S.; Mannisto, S.; Kovanen, P.E.; Tse, E.; et al. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2. J. Exp. Med. 2017, 214, 1371–1386.
  37. Deleeuw, R.J.; Zettl, A.; Klinker, E.; Haralambieva, E.; Trottier, M.; Chari, R.; Ge, Y.; Gascoyne, R.D.; Chott, A.; Muller-Hermelink, H.K.; et al. Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes. Gastroenterology 2007, 132, 1902–1911.
  38. Baumgartner, A.K.; Zettl, A.; Chott, A.; Ott, G.; Muller-Hermelink, H.K.; Starostik, P. High frequency of genetic aberrations in enteropathy-type T-cell lymphoma. Lab. Investig. 2003, 83, 1509–1516.
  39. Cejkova, P.; Zettl, A.; Baumgartner, A.K.; Chott, A.; Ott, G.; Muller-Hermelink, H.K.; Starostik, P. Amplification of NOTCH1 and ABL1 gene loci is a frequent aberration in enteropathy-type T-cell lymphoma. Virchows Arch. 2005, 446, 416–420.
  40. Nicolae, A.; Xi, L.; Pham, T.H.; Pham, T.A.; Navarro, W.; Meeker, H.G.; Pittaluga, S.; Jaffe, E.S.; Raffeld, M. Mutations in the JAK/STAT and RAS signaling pathways are common in intestinal T-cell lymphomas. Leukemia 2016, 30, 2245–2247.
  41. Cording, S.; Lhermitte, L.; Malamut, G.; Berrabah, S.; Trinquand, A.; Guegan, N.; Villarese, P.; Kaltenbach, S.; Meresse, B.; Khater, S.; et al. Oncogenetic landscape of lymphomagenesis in coeliac disease. Gut 2021.
  42. Novakovic, B.J.; Novakovic, S.; Frkovic-Grazio, S. A single-center report on clinical features and treatment response in patients with intestinal T cell non-Hodgkin’s lymphomas. Oncol. Rep. 2006, 16, 191–195.
  43. Daum, S.; Ullrich, R.; Heise, W.; Dederke, B.; Foss, H.D.; Stein, H.; Thiel, E.; Zeitz, M.; Riecken, E.O. Intestinal non-Hodgkin’s lymphoma: A multicenter prospective clinical study from the German Study Group on Intestinal non-Hodgkin’s Lymphoma. J. Clin. Oncol. 2003, 21, 2740–2746.
  44. Cellier, C.; Delabesse, E.; Helmer, C.; Patey, N.; Matuchansky, C.; Jabri, B.; Macintyre, E.; Cerf-Bensussan, N.; Brousse, N. Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group. Lancet 2000, 356, 203–208.
  45. Egan, L.J.; Walsh, S.V.; Stevens, F.M.; Connolly, C.E.; Egan, E.L.; McCarthy, C.F. Celiac-associated lymphoma. A single institution experience of 30 cases in the combination chemotherapy era. J. Clin. Gastroenterol. 1995, 21, 123–129.
  46. Amiot, A.; Allez, M.; Treton, X.; Fieschi, C.; Galicier, L.; Joly, F.; Gornet, J.M.; Oksenhendler, E.; Lemann, M.; Bouhnik, Y. High frequency of fatal haemophagocytic lymphohistiocytosis syndrome in enteropathy-associated T cell lymphoma. Dig. Liver Dis. 2012, 44, 343–349.
  47. Chuah, Y.Y.; Tashi, T.; Lee, Y.Y.; Fu, T.Y.; Shih, C.A. Enteropathy-associated T-cell Lymphoma (EATL) with intracranial metastasis: A rare and dismal condition. Acta Gastroenterol. Belg. 2020, 83, 77–80.
  48. Horvath, L.; Oberhuber, G.; Chott, A.; Effenberger, M.; Tilg, H.; Gunsilius, E.; Wolf, D.; Iglseder, S. Multiple cerebral lesions in a patient with refractory celiac disease: A case report. World J. Gastroenterol. 2020, 26, 7584–7592.
  49. Berman, E.L.; Zauber, N.P.; Rickert, R.R.; Diss, T.C.; Isaacson, P.G. Enteropathy-associated T cell lymphoma with brain involvement. J. Clin. Gastroenterol. 1998, 26, 337–341.
  50. Nijeboer, P.; Malamut, G.; Mulder, C.J.; Cerf-Bensussan, N.; Sibon, D.; Bouma, G.; Cellier, C.; Hermine, O.; Visser, O. Enteropathy-associated T-cell lymphoma: Improving treatment strategies. Dig. Dis. 2015, 33, 231–235.
  51. d’Amore, F.; Relander, T.; Lauritzsen, G.F.; Jantunen, E.; Hagberg, H.; Anderson, H.; Holte, H.; Osterborg, A.; Merup, M.; Brown, P.; et al. Up-front autologous stem-cell transplantation in peripheral T-cell lymphoma: NLG-T-01. J. Clin. Oncol. 2012, 30, 3093–3099.
  52. Jantunen, E.; Boumendil, A.; Finel, H.; Luan, J.J.; Johnson, P.; Rambaldi, A.; Haynes, A.; Duchosal, M.A.; Bethge, W.; Biron, P.; et al. Autologous stem cell transplantation for enteropathy-associated T-cell lymphoma: A retrospective study by the EBMT. Blood 2013, 121, 2529–2532.
  53. Khalaf, W.F.; Caldwell, M.E.; Reddy, N. Brentuximab in the treatment of CD30-positive enteropathy-associated T-cell lymphoma. J. Natl. Compr. Cancer Netw. 2013, 11, 137–140.
  54. Voorhees, T.J.; Ghosh, N.; Grover, N.; Block, J.; Cheng, C.; Morrison, K.; Ivanova, A.; Dotti, G.; Serody, J.; Savoldo, B.; et al. Long-term remission in multiply relapsed enteropathy-associated T-cell lymphoma following CD30 CAR T-cell therapy. Blood Adv. 2020, 4, 5925–5928.
  55. Saurabh, S.; Mukewar, A.S.; Rubio-Tapia, A.; Wu, T.-T.; Jabri, B.; Murray, J.A. Open-Capsule Budesonide for Refractory Celiac Disease. Am. J. Gastroenterol. 2017, 112, 959–967.
Subjects: Gerontology; Hematology
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to :
View Times: 406
Revisions: 2 times (View History)
Update Date: 06 Dec 2021
Video Production Service