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Clinical manifestations, pathologic features, and diagnosis of enteropathy-associated T cell lymphoma

Clinical manifestations, pathologic features, and diagnosis of enteropathy-associated T cell lymphoma
Literature review current through: Jan 2024.
This topic last updated: Jan 25, 2022.

INTRODUCTION — The peripheral T cell lymphomas (PTCLs) are a heterogeneous group of generally aggressive neoplasms that constitute less than 15 percent of all non-Hodgkin lymphomas (NHLs) in adults. (See "Classification of hematopoietic neoplasms".)

Among these, in decreasing frequency of occurrence, are [1,2]:

Peripheral T cell lymphoma, not otherwise specified

Anaplastic large cell lymphoma, primary systemic type

Angioimmunoblastic T cell lymphoma

Extranodal NK/T cell lymphoma, nasal type

Subcutaneous panniculitis-like T cell lymphoma

Enteropathy associated T cell lymphoma

Hepatosplenic T cell lymphoma

Enteropathy associated T cell lymphoma (EATL), also called enteropathy type T cell lymphoma, is a T cell lymphoma that arises in the gastrointestinal tract and is highly associated with celiac disease (gluten-sensitive enteropathy). This entity was originally mistakenly termed "malignant histiocytosis of the intestine," due to the unusual immunophenotype of the tumor cells and initial recognition of a morphologic variant of the disease comprised of large "histiocytic" cells, but it is now clear that these tumors arise from intestinal intraepithelial cytotoxic T cells [3].

The clinical presentation, pathologic features, and diagnosis of EATL will be reviewed here. The treatment of EATL and issues related to other PTCLs are discussed separately. (See "Initial treatment of peripheral T cell lymphoma" and "Initial treatment of peripheral T cell lymphoma", section on 'Outcomes by PTCL subtype'.)

EPIDEMIOLOGY — Enteropathy associated T cell lymphoma (EATL) is a rare tumor that accounts for less than 5 percent of all gastrointestinal lymphomas and less than 1 percent of all non-Hodgkin lymphomas [4]. It is most common in adults from geographic areas with a high incidence of celiac disease, such as the western part of Ireland, Italy, France [5], and Northern Europe. In the Netherlands, for example, the incidence of EATL is approximately 0.10 per 100,000 person years [6]. The mean age at diagnosis is 60 to 65 years and 55 to 65 percent of cases are diagnosed in men [4,7]. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults", section on 'Prevalence'.)

Until recently, EATL was divided into type I disease associated with celiac disease and type II disease, marked by a lack of association with celiac disease. As a result, type II EATL has a broader geographic distribution [8]. The relationship of type II EATL to "classic" type I disease has been controversial, and the 2016 revisions to the World Health Organization classification removed type II disease from the EATL diagnostic category and renamed it monomorphic epitheliotropic intestinal T cell lymphoma [2,9]. (See 'Monomorphic epitheliotropic intestinal T cell lymphoma' below.)

Patients with untreated celiac disease have a substantially increased risk of developing EATL, especially those diagnosed at an older age (ie, over age 33 years) [10]. Management of celiac disease with a gluten-free diet effectively prevents the development of EATL [11,12]. EATL only rarely develops in patients diagnosed with celiac disease early in life (presumably because of effective intervention) and patients with EATL rarely have a long clinical history of celiac disease [13,14]. Similarly, patients with positive celiac disease serology and normal mucosa on biopsy (ie, latent celiac disease) do not appear to have an increased incidence of EATL [15]. The basis for the strong association of EATL with celiac disease is unknown; both antigen-driven T cell proliferation and less specific pro-proliferative effects of chronic inflammation are plausible and non-exclusive possibilities.

CLINICAL FEATURES — Patients typically present with abdominal pain, often associated with intestinal (jejunal) obstruction, perforation, or bleeding. Less common presentations include symptoms of celiac disease or the clinical deterioration of celiac disease despite compliance with a gluten-free diet [5].

An international series of 62 patients with enteropathy associated T cell lymphoma (EATL) reported the following clinical findings at the time of presentation [7]:

Abdominal pain – 88 percent

Systemic B symptoms (fever/chills, weight loss, night sweats) – 63 percent

Fatigue – 38 percent

Infection – 23 percent

Adenopathy – 15 percent

Hepatomegaly – 6 percent

Splenomegaly – 6 percent

Pruritus – 3 percent

The majority presented with stage IV disease (64 percent). Bone marrow involvement (3 percent) was unusual and most patients had normal serum levels of lactate dehydrogenase, calcium, and C-reactive protein.

Many patients are diagnosed with celiac disease at the time of presentation with EATL. A history of childhood onset celiac disease is uncommon. Signs and symptoms of celiac disease include steatorrhea, flatulence, stomach distension, weight loss, iron deficiency anemia, neurologic disorders (particularly peripheral neuropathy), osteopenia, and skin disorders (eg, dermatitis herpetiformis). (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in adults" and "Management of celiac disease in adults", section on 'Non-responders'.)

PATHOLOGY — Enteropathy associated T cell lymphoma (EATL) most commonly involves the proximal jejunum and less frequently involves other parts of the small intestine, the stomach, or the colon [16-19]. Tumor involvement of the liver, spleen, lymph nodes, and viscera such as the gallbladder has been described in a minor subset of cases. Involvement of the lung, skin, or soft tissues is rare.

The international series described above of 62 patients with EATL reported the following sites of involvement at the time of presentation [7]:

Small intestine – 90 percent

Mesenteric/intra-abdominal lymph nodes – 35 percent

Large intestine – 16 percent

Para-aortic/iliac lymph nodes – 11 percent

Stomach – 8 percent

Inguinal/femoral lymph nodes – 6 percent

Other sites – ≤5 percent of cases.

Histology

Tumor — On gross examination of the intestine, multiple circumferentially oriented jejunal ulcers are typically present and are often associated with gut perforation. There may or may not be a mass [20].

The tumor cells invade the intestinal wall and contain a variable admixture of small, medium, and large or anaplastic tumor cells. The cells have a moderate to abundant amount of pale-staining cytoplasm, a round or angulated vesicular nucleus, and prominent nucleoli [1]. Early lesions may show mucosal ulceration with only scattered atypical cells and numerous reactive macrophages, usually without any appreciable mass; these lesions are nonetheless clonal (picture 1 and picture 2) [21].

Adjacent mucosa — The mucosa adjacent to the tumor often contains numerous intraepithelial T cells, macrophages, and eosinophils. Mucosa uninvolved by tumor may or may not show signs of celiac disease including villous atrophy, crypt hyperplasia, an increased number of lymphocytes and plasma cells in the lamina propria, and intraepithelial lymphocytes [22]. Pathologic evidence of celiac disease may depend on the segment analyzed, since in celiac disease villous atrophy is most prominent in the proximal small intestine and may be absent in the distal jejunum or ileum.

Intraepithelial lymphocytes in apparently non-neoplastic mucosa may be clonal, and may represent low-grade precursor lesions to the overt lymphoma [23]. (See "Diagnosis of celiac disease in adults", section on 'Endoscopy with small bowel biopsy' and 'Refractory celiac disease' below.)

Immunophenotype — In the typical case, tumor cells express pan-T antigens (surface CD7+) and the mucosal lymphoid antigen CD103 [23-25]. Although CD3 can be detected intracellularly, these cells lack expression of the T cell receptor/CD3 complex on the cell surface [26]. CD4 (11 percent), CD5 (17 percent), and CD8 (43 percent) are expressed in only a minority of cases, an immunophenotype that is identical to that of the intraepithelial lymphocytes, when present [7]. Many cases express cytotoxic T cell-associated proteins (Granzyme B, TIA-1, perforin) [27,28]. In a significant fraction of cases (37 percent), the large cell component of the tumor is CD30 positive (picture 1). While some cases demonstrate aberrant expression of cytolytic NK cell lineage receptors, these tumors have T cell receptor rearrangements and are clearly of T cell lineage.

Genetic features — The T cell receptor beta and T cell receptor gamma genes are clonally rearranged [3,29]. In addition, many patients have a DQA1*0501 or DQB1*0201 HLA haplotype that is commonly associated with celiac disease [1]. (See "Diagnosis of celiac disease in adults", section on 'Discordant serology and small bowel biopsy'.)

Most cases of EATLs have gene amplifications demonstrated by conventional cytogenetics or fluorescence in situ hybridization (FISH); 50 to 60 percent have complex segmental amplifications of the 9q31.3-qter region [30]. This genetic change is seen in both celiac disease-associated classic EATL and monomorphic epitheliotropic intestinal T cell lymphoma (previously referred to as type II EATL) and is rarely seen in other types of peripheral T cell lymphoma. FISH with probes specific for this region may be helpful in confirming the diagnosis, but the sensitivity and specificity of this genetic abnormality is unknown.

Other recurrent chromosomal gains include 1q32 (26 percent), 5q35 (21 percent), 7q22 (31 percent), and 8q24 (18 percent) [4]. Some tumors demonstrate a deletion in 16q12 [1]. The 1q and 5q abnormalities are more common in classic EATL. While 8q24 gains involving MYC have been reported in a significant minority of EATL, many of these cases represented type II EATL, now referred to as "monomorphic epitheliotropic intestinal T cell lymphoma" and considered a different entity from EATL. (See 'Monomorphic epitheliotropic intestinal T cell lymphoma' below.)

Whole exome DNA sequencing of 69 cases of type I and type II EATL revealed that the most frequently mutated gene was SETD2 (approximately one-third of cases), which encodes a histone methyltransferase involved in epigenetic regulation of gene expression [31]. Mutations were also observed in the components of the JAK/STAT signaling pathway, and small subsets of tumors had mutations in KRAS, TP53, or TERT. Mutations of the JAK/STAT pathway were more common in classic EATL, whereas SETD2 mutations were more frequent in type II EATL (now referred to as monomorphic epitheliotropic intestinal T cell lymphoma; [MEITL]). This analysis also confirmed the presence of 9q gains in both types of tumor and more frequent gains of chromosome 8q24 in MEITL. (See 'Monomorphic epitheliotropic intestinal T cell lymphoma' below.)

DIAGNOSIS — The diagnosis of enteropathy associated T cell lymphoma (EATL) is most commonly made by the pathologic evaluation of a specimen of small bowel resected because of intestinal obstruction or perforation at the time of presentation (table 1). The pathologic diagnosis is based on the combination of characteristic histologic and immunophenotypic findings cited above, often in the context of T cell clonality, and laboratory and clinical evidence of celiac disease.

As described above, in classic EATL, tumor cells of variable size and morphology infiltrate the small intestine while the adjacent "normal" mucosa often demonstrates signs of celiac disease. The tumor cells typically express cytoplasmic CD3 and do not express CD4; most cases are also CD8 negative. Large cells within the tumor infiltrate are frequently CD30 positive, and virtually all cases are also positive for CD103, which is a sensitive (but not specific) marker. CD56 is negative. Clonal rearrangements of the TCR beta and gamma genes are present, and some cases express TCR beta protein; by contrast, immunohistochemical stains for TCR delta are negative.

Since celiac disease is underdiagnosed in certain populations, it has been suggested that patients with a T cell lymphoma and/or a gut primary localization should be tested for underlying celiac disease [32]. Sometimes the underlying celiac disease is only appreciated when villous atrophy is observed in the resected intestine adjacent to the tumor or after the diagnosis of lymphoma, upon detection of serum IgA EMA (endomysial antibodies), serum IgA tTG (anti-tissue transglutaminase), IgG DGP (deaminated gliadin peptide), and/or HLA type (DQA1*0501, DQB1*0201), all of which are associated with celiac disease [20,33]. (See "Diagnosis of celiac disease in adults", section on 'Individuals with high celiac disease probability'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis includes refractory celiac disease and other types of T cell lymphoma that present in the gastrointestinal tract.

Refractory celiac disease — Some cases of enteropathy associated T cell lymphoma (EATL) are preceded by a low-grade precursor lesion that clinically resembles refractory celiac disease (refractory sprue). Refractory celiac disease is clinically defined as the persistence of pathologic changes in the intestine consistent with celiac disease despite a strict gluten-free diet for more than 12 months. These pathologic changes include increased intraepithelial lymphocytes, villous atrophy, and crypt hyperplasia. (See "Diagnosis of celiac disease in adults", section on 'Endoscopy with small bowel biopsy' and "Management of celiac disease in adults", section on 'Refractory sprue'.)

Cases of refractory celiac disease are commonly divided into two types:

Type I refractory celiac disease – These lesions typically show no atypia in the intraepithelial lymphocytes, normal surface T cell receptor, CD3 and CD8 expression by intraepithelial T lymphocytes and a polyclonal pattern on T cell receptor gene rearrangement studies [4].

Type II refractory celiac disease – These lesions also have no atypia in the intraepithelial lymphocytes, but demonstrate a loss of surface T cell receptor, CD3, or CD8 expression and may have a monoclonal T cell receptor gene rearrangement [29,34].

The clinical significance of refractory celiac disease type is incompletely understood. While type I refractory celiac disease is unlikely to progress to EATL, type II may be a precursor lesion to EATL. Imaging with computed tomography, positron emission tomography, and video capsule endoscopy may help to identify cases of refractory celiac disease that have progressed to EATL [35-37].

Monomorphic epitheliotropic intestinal T cell lymphoma — Monomorphic epitheliotropic intestinal T cell lymphoma (MEITL) was previously called "type II EATL" [2]. Unlike EATL, MEITL is not associated with celiac disease nor is it found with an increased incidence in adults from geographic areas with a high incidence of celiac disease. In contrast, MEITL has an increased incidence in Asian and Hispanic populations.

On histology, the tumor cells are monomorphic and small to medium in size, and often infiltrate the intestinal crypt epithelium (picture 2). The adjacent "normal" mucosa demonstrates villous atrophy, crypt hyperplasia, and intraepithelial lymphocytosis. There is no inflammatory background. The tumor cells express CD3 (95 percent), CD8 (63 percent), and CD56 (73 percent) (picture 2), and usually do not express CD4 (5 percent) [1,7].

MEITLs express gamma-delta T cell receptors in up to 80 percent of cases [9]. Frequent mutations in SETD2 and JAK/STAT signaling pathway components, and gains of 8q24 (involving MYC) and 9q may also be seen.

Indolent T cell lymphoproliferative disease — The term "indolent T cell lymphoproliferative disease of the gastrointestinal tract" has been proposed for lesions at any location in the gastrointestinal tract that demonstrate dense, nondestructive infiltrates of clonal small, mature-appearing T cells [2].

In a case series of 10 patients with this proposed entity, symptoms at presentation included abdominal pain, diarrhea, vomiting, food intolerance, and dyspepsia [38]. There were variable findings on endoscopy including polyps, erosions, and erythema. Biopsy demonstrated expansion of the lamina propria with a dense, band-like nondestructive lymphoid infiltrate that sometimes extended into the muscularis mucosae and submucosa with displacement and distortion of mucosal glands. The infiltrate was predominantly comprised of small, monotonous lymphoid cells with slightly irregular nuclei, mature nuclear chromatin, inconspicuous nucleoli, and scant pale cytoplasm. There were occasional eosinophils. On immunophenotypical studies, eight were CD4-/CD8+ and one each was CD4+/CD8- and CD4-/CD8-. Expression of CD30 and CD56 was not seen. Clonality was established in all cases by studies for T cell receptor gamma chain gene rearrangement. Six received chemotherapy with little or no response, and four were followed expectantly; all patients were alive after a median follow-up of 38 months.

This entity can be distinguished pathologically from EATL by the absence of intraepithelial lymphocytes, the monomorphous non-destructive small-cell nature of the infiltrate, and the absence of large CD30+ cells.

Extranodal NK/T cell lymphoma — Extranodal NK/T cell lymphoma is a lymphoma of natural killer (NK) or T cell lineage that most commonly presents with a facial mass. A small percentage of patients may present with gastrointestinal involvement. Because the morphology of the tumor cells is so variable, it is important to consider extranodal NK/T cell lymphoma in all cases of aggressive extranodal lymphoma associated with vascular invasion and necrosis.

The key diagnostic features of NK/T cell lymphoma are the demonstration of NK/T cell markers (CD2, cytoplasmic CD3, CD56, and cytotoxic granule proteins) and Epstein-Barr virus (EBV), which is uniformly present. In contrast, EATL is not associated with EBV infection and infrequently expresses CD56. (See "Clinical manifestations, pathologic features, and diagnosis of extranodal NK/T cell lymphoma, nasal type".)

Gamma-delta T cell lymphoma — Gamma-delta T cell lymphoma most commonly involves the liver and spleen (hepatosplenic gamma-delta T cell lymphoma), but less commonly involves the gastrointestinal tract or the skin; such tumors are sometimes referred to as non-hepatosplenic or mucocutaneous gamma-delta T cell lymphomas. The diagnosis of gamma-delta T cell lymphoma is usually made based upon biopsy specimens demonstrating infiltrating atypical lymphocytes that express CD2, surface CD3, CD7, CD56, and TCRdelta, and do not express CD4, CD5, CD8 or B cell markers (eg, CD20). (See "Clinical manifestations, pathologic features, and diagnosis of hepatosplenic T cell lymphoma".)

Like gamma-delta T cell lymphoma, EATLs express pan-T antigens (surface CD3+ CD7+) and do not express CD4, CD5, or CD8. In contrast to gamma-delta T cell lymphoma, EATLs typically express CD103 [23,24] and have clonal T cell receptor beta rearrangements.

Anaplastic large cell lymphoma — Patients with anaplastic large cell lymphoma (ALCL) typically present with painless lymphadenopathy. On histology, the tumor is composed of large blastic cells with horseshoe-shaped nuclei, prominent nucleoli, with or without a prominent golgi complex (seen as a paranuclear clearing, or hof) in a cohesive growth pattern. On immunohistochemistry there is a homogeneous and strong expression of CD30 in a membrane and golgi pattern. There is also expression of T cell antigens or, in the case of the null cell type, lack of expression of lineage-specific antigens. (See "Clinical manifestations, pathologic features, and diagnosis of systemic anaplastic large cell lymphoma (sALCL)".)

While a subset of patients with EATL may resemble ALCL histologically and express CD30, ALCL is not associated with celiac disease-type symptoms or the presence of the intraepithelial lymphocytic infiltrates in the adjacent "normal" mucosa.

B cell lymphomas — The most common types of lymphoma involving the small intestine are of B cell origin, and include marginal zone B cell lymphoma, diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma, and occasionally, follicular lymphoma. Mantle cell lymphoma and follicular lymphoma often produce multiple polyp-like extensions of the mucosa (lymphomatoid polyposis), a gross appearance that is not seen in EATL. DLBCL and Burkitt lymphoma often produce large masses that may grossly resemble EATL, but are readily distinguishable (like other B cell lymphomas) by their morphologic and immunophenotypic characteristics.

TREATMENT — The treatment of enteropathy associated T cell lymphoma (EATL) is discussed separately. (See "Treatment of relapsed or refractory peripheral T cell lymphoma" and "Initial treatment of peripheral T cell lymphoma", section on 'Outcomes by PTCL subtype'.)

PROGNOSIS — Enteropathy associated T cell lymphoma (EATL) is an aggressive lymphoma with a poor prognosis. In one large series, the disease stage at presentation was IE, IIE, IIIE, and IV in 10, 21, 5, and 64 percent of patients, respectively [7]. While some patients present with limited stage disease, dissemination to the liver, spleen, skin, and other organs is common as the disease progresses [4]. Many patients die from complications of multifocal intestinal perforation due to refractory malignant ulcers. Occasional patients with localized disease are cured after surgical resection and there are reports of long term survival following hematopoietic cell transplantation. (See "Initial treatment of peripheral T cell lymphoma", section on 'Outcomes by PTCL subtype'.)

An international series of 62 patients with EATL with a median follow-up of 10.5 months reported a median overall survival of 10 months and a failure-free survival of six months [7]. Estimated rates of overall and failure-free survival at five years were 20 and 4 percent, respectively. The International Prognostic Index developed for B cell lymphomas was not a good predictor of prognosis in this population. In contrast, the Prognostic Index for PTCL, unspecified (PIT) could be used to divide the patients into four prognostic groups (figure 1). (See "Clinical manifestations, pathologic features, and diagnosis of peripheral T cell lymphoma, not otherwise specified", section on 'Prognosis'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Lymphoma diagnosis and staging".)

SUMMARY

Enteropathy associated T cell lymphoma (EATL) is an uncommon T cell lymphoma that arises in the gastrointestinal tract and is highly associated with celiac disease (gluten-sensitive enteropathy). EATL is most commonly diagnosed in adults from geographic areas with a high incidence of celiac disease, such as the western part of Ireland and Northern Europe. (See 'Epidemiology' above.)

Clinical presentation – Patients typically present with abdominal pain, often associated with intestinal (jejunal) obstruction, perforation, or bleeding. Less common presentations include symptoms of celiac disease or the clinical deterioration of celiac disease despite compliance with a gluten-free diet. (See 'Clinical features' above.)

Diagnosis – EATL is usually diagnosed by the pathologic evaluation of resected small bowel (table 1). On gross examination there are multiple, circumferentially-oriented jejunal ulcers, often associated with gut perforation. The tumor cells that invade the intestinal wall are variable in size and morphology. Most tumor cells express pan-T antigens (surface CD3 and CD7) and CD103. CD4, CD5, and CD8 are usually not expressed. The T cell receptor beta gene is clonally rearranged. Adjacent mucosa may or may not show signs of celiac disease. (See 'Pathology' above and 'Diagnosis' above.)

  1. World Health Organization Classification of Tumours of Haematopoietic and Lymphoid Tissues, Swerdlow SH, Campo E, Harris NL, et al. (Eds), IARC Press, Lyon 2008.
  2. Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood 2016; 127:2375.
  3. Isaacson PG, O'Connor NT, Spencer J, et al. Malignant histiocytosis of the intestine: a T-cell lymphoma. Lancet 1985; 2:688.
  4. Zettl A, deLeeuw R, Haralambieva E, Mueller-Hermelink HK. Enteropathy-type T-cell lymphoma. Am J Clin Pathol 2007; 127:701.
  5. Cellier C, Delabesse E, Helmer C, et al. Refractory sprue, coeliac disease, and enteropathy-associated T-cell lymphoma. French Coeliac Disease Study Group. Lancet 2000; 356:203.
  6. Gonzalez CL, Medeiros LJ, Braziel RM, Jaffe ES. T-cell lymphoma involving subcutaneous tissue. A clinicopathologic entity commonly associated with hemophagocytic syndrome. Am J Surg Pathol 1991; 15:17.
  7. Delabie J, Holte H, Vose JM, et al. Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project. Blood 2011; 118:148.
  8. Deleeuw RJ, Zettl A, Klinker E, et al. Whole-genome analysis and HLA genotyping of enteropathy-type T-cell lymphoma reveals 2 distinct lymphoma subtypes. Gastroenterology 2007; 132:1902.
  9. Chan JK, Chan AC, Cheuk W, 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.
  10. Ekström Smedby K, Vajdic CM, Falster M, et al. Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood 2008; 111:4029.
  11. Silano M, Volta U, Vincenzi AD, et al. Effect of a gluten-free diet on the risk of enteropathy-associated T-cell lymphoma in celiac disease. Dig Dis Sci 2008; 53:972.
  12. Lebwohl B, Granath F, Ekbom A, et al. Mucosal healing and risk for lymphoproliferative malignancy in celiac disease: a population-based cohort study. Ann Intern Med 2013; 159:169.
  13. Collin P, Reunala T, Pukkala E, et al. Coeliac disease--associated disorders and survival. Gut 1994; 35:1215.
  14. Egan LJ, Stevens FM, McCarthy CF. Celiac disease and T-cell lymphoma. N Engl J Med 1996; 335:1611.
  15. Elfström P, Granath F, Ekström Smedby K, et al. Risk of lymphoproliferative malignancy in relation to small intestinal histopathology among patients with celiac disease. J Natl Cancer Inst 2011; 103:436.
  16. Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 15-1996. A 79-year-old woman with anorexia, weight loss, and diarrhea after treatment for celiac disease. N Engl J Med 1996; 334:1316.
  17. Mantovani G, Esu S, Astara G, et al. Primary T cell CD30-positive anaplastic large-cell lymphoma associated with adult-onset celiac disease and presenting with skin lesions. Acta Haematol 1995; 94:48.
  18. Shiboski CH, Greenspan D, Dodd CL, Daniels TE. Oral T-cell lymphoma associated with celiac sprue. A case report. Oral Surg Oral Med Oral Pathol 1993; 76:54.
  19. Tse E, Gill H, Loong F, et al. Type II enteropathy-associated T-cell lymphoma: a multicenter analysis from the Asia Lymphoma Study Group. Am J Hematol 2012; 87:663.
  20. Gale J, Simmonds PD, Mead GM, et al. Enteropathy-type intestinal T-cell lymphoma: clinical features and treatment of 31 patients in a single center. J Clin Oncol 2000; 18:795.
  21. Ashton-Key M, Diss TC, Pan L, et al. Molecular analysis of T-cell clonality in ulcerative jejunitis and enteropathy-associated T-cell lymphoma. Am J Pathol 1997; 151:493.
  22. Chott A, Dragosics B, Radaszkiewicz T. Peripheral T-cell lymphomas of the intestine. Am J Pathol 1992; 141:1361.
  23. Murray A, Cuevas EC, Jones DB, Wright DH. Study of the immunohistochemistry and T cell clonality of enteropathy-associated T cell lymphoma. Am J Pathol 1995; 146:509.
  24. Spencer J, Cerf-Bensussan N, Jarry A, et al. Enteropathy-associated T cell lymphoma (malignant histiocytosis of the intestine) is recognized by a monoclonal antibody (HML-1) that defines a membrane molecule on human mucosal lymphocytes. Am J Pathol 1988; 132:1.
  25. Meresse B, Curran SA, Ciszewski C, et al. Reprogramming of CTLs into natural killer-like cells in celiac disease. J Exp Med 2006; 203:1343.
  26. Tjon JM, Verbeek WH, Kooy-Winkelaar YM, et al. Defective synthesis or association of T-cell receptor chains underlies loss of surface T-cell receptor-CD3 expression in enteropathy-associated T-cell lymphoma. Blood 2008; 112:5103.
  27. Daum S, Foss HD, Anagnostopoulos I, et al. Expression of cytotoxic molecules in intestinal T-cell lymphomas. The German Study Group on Intestinal Non-Hodgkin Lymphoma. J Pathol 1997; 182:311.
  28. de Bruin PC, Connolly CE, Oudejans JJ, et al. Enteropathy-associated T-cell lymphomas have a cytotoxic T-cell phenotype. Histopathology 1997; 31:313.
  29. Verbeek WH, Goerres MS, von Blomberg BM, et al. Flow cytometric determination of aberrant intra-epithelial lymphocytes predicts T-cell lymphoma development more accurately than T-cell clonality analysis in Refractory Celiac Disease. Clin Immunol 2008; 126:48.
  30. Zettl A, Ott G, Makulik A, et al. Chromosomal gains at 9q characterize enteropathy-type T-cell lymphoma. Am J Pathol 2002; 161:1635.
  31. Moffitt AB, Ondrejka SL, McKinney M, et al. Enteropathy-associated T cell lymphoma subtypes are characterized by loss of function of SETD2. J Exp Med 2017; 214:1371.
  32. Catassi C, Fabiani E, Corrao G, et al. Risk of non-Hodgkin lymphoma in celiac disease. JAMA 2002; 287:1413.
  33. Howell WM, Leung ST, Jones DB, et al. 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.
  34. Carbonnel F, Grollet-Bioul L, Brouet JC, et al. Are complicated forms of celiac disease cryptic T-cell lymphomas? Blood 1998; 92:3879.
  35. Hadithi M, Mallant M, Oudejans J, 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.
  36. Mallant M, Hadithi M, Al-Toma AB, et al. Abdominal computed tomography in refractory coeliac disease and enteropathy associated T-cell lymphoma. World J Gastroenterol 2007; 13:1696.
  37. Daum S, Wahnschaffe U, Glasenapp R, et al. Capsule endoscopy in refractory celiac disease. Endoscopy 2007; 39:455.
  38. Perry AM, Warnke RA, Hu Q, et al. Indolent T-cell lymphoproliferative disease of the gastrointestinal tract. Blood 2013; 122:3599.
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References

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