Histopathology of the Complications of Celiac Disease: Enteropathy-Associated T Cell Lymphoma and Ulcerative Jejunitis

Loss of response to a gluten-free diet (refractory sprue) and ulcerative jejunitis are complications of celiac disease that may progress to enteropathy-associated T-cell lymphoma (EATL). Both conditions are characterized by the presence of a nonlymphomatous monoclonal T-cell population in the enteropathic mucosa. In EATL, a similar monoclonal population that shows clonal identity with the lymphoma itself is also present in the enteropathic mucosa. In this study we show that in all three circumstances the monoclonal T-cell population is constituted by cytologically normal, noninvasive intraepithelial T lymphocytes that share an identical aberrant immunophenotype with EATL. Patients with refractory sprue and/or ulcerative jejunitis are, therefore, suffering from a neoplastic T-cell disorder for which hematological treatment strategies need to be devised.

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Serendipity in Refractory Celiac Disease: Full Recovery of Duodenal Villi and Clinical Symptoms after Fecal Microbiota Transfer

Journal of Gastrointestinal and Liver Diseases ◽

10.15403/jgld.2014.1121.253.cel ◽

2016 ◽

Vol 25 (3) ◽

pp. 385-388 ◽

Cited By ~ 15

Author(s):

Yvette H. Van Beurden ◽

Tom Van Gils ◽

Nienke A. Van Gils ◽

Zain Kassam ◽

Chris J.J. Mulder ◽

...

Keyword(s):

Celiac Disease ◽

T Cell ◽

Clostridium Difficile ◽

Clostridium Difficile Infection ◽

Cell Lymphoma ◽

Fecal Microbiota ◽

Disease Type ◽

T Cell Lymphoma ◽

Type Ii ◽

Refractory Celiac Disease

Treatment of refractory celiac disease type II (RCD II) and preventing the development of an enteropathy associated T-cell lymphoma in these patients is still difficult. In this case report, we describe a patient with RCD II who received fecal microbiota transfer as treatment for a recurrent Clostridium difficile infection, and remarkably showed a full recovery of duodenal villi and disappearance of celiac symptoms. This case suggests that altering the gut microbiota may hold promise in improving the clinical and histological consequences of celiac disease and/or RCD II. Abbreviations: CDI: Clostridium difficile infection; EATL : enteropathy associated T-cell lymphoma; FMT: fecal microbiota transfer; IEL: intraepithelial lymphocytes; RCD II: refractory celiac disease type II; TPN: total parenteral nutrition.

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Enteropathy-associated T-cell lymphoma in a patient without a prior diagnosis of celiac disease: A diagnostic conundrum

Indian Journal of Cancer ◽

10.4103/0019-509x.76640 ◽

2011 ◽

Vol 48 (1) ◽

pp. 124

Author(s):

S Jacob ◽

D Mohapatra ◽

ML Nordberg ◽

JD Cotelingam ◽

S Upadhyay ◽

...

Keyword(s):

Celiac Disease ◽

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma

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Are Complicated Forms of Celiac Disease Cryptic T-Cell Lymphomas?

Blood ◽

10.1182/blood.v92.10.3879 ◽

1998 ◽

Vol 92 (10) ◽

pp. 3879-3886 ◽

Cited By ~ 94

Author(s):

Franck Carbonnel ◽

Laurence Grollet-Bioul ◽

Jean Claude Brouet ◽

Marie Françoise Teilhac ◽

Jacques Cosnes ◽

...

Keyword(s):

Bone Marrow ◽

Celiac Disease ◽

T Cell ◽

Cell Lymphoma ◽

Large Cell ◽

Cell Receptor ◽

T Cell Lymphoma ◽

Gluten Free Diet ◽

Gluten Free ◽

Duodenal Biopsies

Abstract We assessed the clonality of duodenal mucosal T cells in patients with celiac disease and controls. Fifteen adult patients were studied. Four patients had a complicated celiac disease, 3 did not respond to a gluten-free diet, and 2 had an ulcerative jejunitis (including 1 patient with nonresponsive celiac disease). Seven patients had an untreated celiac disease responsive to a gluten-free diet. Histological examination of duodenal biopsies of these 11 patients showed benign-appearing celiac disease without evidence of lymphoma. Four patients with nonulcer dyspepsia and normal duodenal biopsies served as controls. TCRγ gene rearrangements were analyzed by multiplex polymerase chain reaction on DNA extracted from duodenal biopsies. Major clonal rearrangements of the T-cell receptor were found in 4 cases, all with complicated celiac disease. Monoclonality was confirmed by DNA sequencing of the junctional region in 3 cases and by hybridization with clone-specific oligoprobes. Patients with celiac disease responsive to gluten-free diet had mainly a polyclonal pattern, with 1 of them having an oligoclonal rearrangement. An oligoclonal pattern was also observed in 2 control patients. Three patients with complicated celiac disease evolved to T-cell lymphoma with liver (n = 2) or bone marrow (n = 1) invasion. Identical clones were found in the enteropathic duodenojejunum and peripheral blood in the patient with large-cell lymphoma with bone marrow invasion. This study suggests that complicated celiac disease is a cryptic T-cell lymphoma.

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Enteropathy-type T-cell Lymphoma that was Pathologically Diagnosed as Celiac Disease

Internal Medicine ◽

10.2169/internalmedicine.46.6377 ◽

2007 ◽

Vol 46 (15) ◽

pp. 1219-1224 ◽

Cited By ~ 9

Author(s):

Hidetoshi Yasuoka ◽

Takashige Masuo ◽

Koshi Hashimoto ◽

Koji Sato ◽

Shuichi Okada ◽

...

Keyword(s):

Celiac Disease ◽

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma

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Enteropathy-associated T cell lymphoma as a complication of longstanding celiac disease

International Journal of Case Reports and Images ◽

10.5348/ijcri-201725-cl-10135 ◽

2017 ◽

Vol 8 (10) ◽

pp. 681

Author(s):

Melika Hosseina ◽

Constantine Soulellis ◽

Alan N. Barkun

Keyword(s):

Celiac Disease ◽

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma

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Are Complicated Forms of Celiac Disease Cryptic T-Cell Lymphomas?

Blood ◽

10.1182/blood.v92.10.3879.422k34_3879_3886 ◽

1998 ◽

Vol 92 (10) ◽

pp. 3879-3886

Author(s):

Franck Carbonnel ◽

Laurence Grollet-Bioul ◽

Jean Claude Brouet ◽

Marie Françoise Teilhac ◽

Jacques Cosnes ◽

...

Keyword(s):

Bone Marrow ◽

Celiac Disease ◽

T Cell ◽

Cell Lymphoma ◽

Large Cell ◽

Cell Receptor ◽

T Cell Lymphoma ◽

Gluten Free Diet ◽

Gluten Free ◽

Duodenal Biopsies

We assessed the clonality of duodenal mucosal T cells in patients with celiac disease and controls. Fifteen adult patients were studied. Four patients had a complicated celiac disease, 3 did not respond to a gluten-free diet, and 2 had an ulcerative jejunitis (including 1 patient with nonresponsive celiac disease). Seven patients had an untreated celiac disease responsive to a gluten-free diet. Histological examination of duodenal biopsies of these 11 patients showed benign-appearing celiac disease without evidence of lymphoma. Four patients with nonulcer dyspepsia and normal duodenal biopsies served as controls. TCRγ gene rearrangements were analyzed by multiplex polymerase chain reaction on DNA extracted from duodenal biopsies. Major clonal rearrangements of the T-cell receptor were found in 4 cases, all with complicated celiac disease. Monoclonality was confirmed by DNA sequencing of the junctional region in 3 cases and by hybridization with clone-specific oligoprobes. Patients with celiac disease responsive to gluten-free diet had mainly a polyclonal pattern, with 1 of them having an oligoclonal rearrangement. An oligoclonal pattern was also observed in 2 control patients. Three patients with complicated celiac disease evolved to T-cell lymphoma with liver (n = 2) or bone marrow (n = 1) invasion. Identical clones were found in the enteropathic duodenojejunum and peripheral blood in the patient with large-cell lymphoma with bone marrow invasion. This study suggests that complicated celiac disease is a cryptic T-cell lymphoma.

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Enteropathy-Type T-cell Lymphoma: Its Relationship to Refractory Celiac Disease

Pathology Case Reviews ◽

10.1097/01.pcr.0000015747.87813.27 ◽

2002 ◽

Vol 7 (3) ◽

pp. 110-116

Author(s):

Dennis P. OʼMalley ◽

Margaret L. Gulley ◽

Peter M. Banks

Keyword(s):

Celiac Disease ◽

T Cell ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Refractory Celiac Disease

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The Intracellular Intensity of CD3 on Aberrant Intraepithelial Lymphocytes Is a Prognostic Factor of the Progression to Overt Lymphoma in Refractory Celiac Disease Type II (Pre-Enteropathy-Associated T Cell Lymphoma)

Digestive Diseases ◽

10.1159/000506305 ◽

2020 ◽

Vol 38 (6) ◽

pp. 490-499 ◽

Cited By ~ 1

Author(s):

Carlota García-Hoz ◽

Laura Crespo ◽

Natalia Lopez ◽

Ana De Andrés ◽

Raquel Ríos León ◽

...

Keyword(s):

Celiac Disease ◽

T Cell ◽

Cell Lymphoma ◽

Intraepithelial Lymphocytes ◽

Disease Type ◽

T Cell Lymphoma ◽

Control Group ◽

Type Ii ◽

Refractory Celiac Disease ◽

Single Center Study

Background: Refractory celiac disease type II (RCD-II) is a very rare yet severe complication of celiac disease (CD) with a 50% rate of progression to Enteropathy-associated T-cell lymphoma (EATL). Timely diagnosis and treatment of RCD-II is of the essence and requires the identification of a population of frequently clonal, phenotypically aberrant intraepithelial lymphocytes (IELs). Flow Cytometry of intestinal IELs is the recommended method to identify the aberrant surface CD3-negative (sCD3–) intracytoplasmic CD3-positive (icCD3ε+) IELs, and a proportion of >20% is diagnostic of RCD-II. There is substantial heterogeneity in the clinical course of RCD-II, and insufficient information on prognostic factors. Aim: To establish flow cytometric predictors of the clinical evolution of RCD-II, to help guide treatment approaches. Patients and Methods: Retrospective single-center study of clinical and immunological features of 6 RCD-II patients and a control group, both identified from a 2,000-patient cohort over 16 years. IEL subset frequencies and the intensity of staining for surface (s) and intracytoplasmic (ic) CD3ε+ on IEL subsets were quantified and correlated with the clinical outcome. Results: Unexpectedly, the frequency of aberrant sCD3– icCD3ε+ cells at diagnosis did not correlate with histological or clinical affection. However, a higher intensity of icCD3ε+ staining in the aberrant IELs relative to expression on normal IELs correlated with monoclonality and with worse clinical outcomes. Conclusion: The ratio of icCD3ε+ on aberrant IELs vs. normal IELs appears to be a useful indicator of prognosis at the time of diagnosis, and may represent a novel tool in the follow-up of RCD-II patients after therapy.

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