Risks for lymphoma and gastrointestinal carcinoma in patients with newly diagnosed adult‐onset celiac disease: Consequences for follow‐up

Gils, Tom van; Nijeboer, Petula; Overbeek, L.I.H.; Hauptmann, Michael; Castelijn, Daan A. R.; Bouma, Gerd; Mulder, Chris J.; Leeuwen, Flora E. van; Jong, Daphne de

doi:10.1177/2050640618800540

Cited by 29 publications

(14 citation statements)

References 19 publications

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“…Along this line, diagnosis of de novo EATL was made in all cases at the same time or shortly after CeD (data not shown). This observation, which is coherent with previous reports, 50 further stresses the role of chronic inflammation in promoting EATL development. Overall, the much more severe prognosis of RCDII-EATL cannot be explained by a distinct mutational profile.…”

Section: Discussionsupporting

confidence: 93%

Oncogenetic landscape of lymphomagenesis in coeliac disease

Cording

Lhermitte

Malamut

et al. 2021

Gut

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ObjectiveEnteropathy-associated T-cell lymphoma (EATL) is a rare but severe complication of coeliac disease (CeD), often preceded by low-grade clonal intraepithelial lymphoproliferation, referred to as type II refractory CeD (RCDII). Knowledge on underlying oncogenic mechanisms remains scarce. Here, we analysed and compared the mutational landscape of RCDII and EATL in order to identify genetic drivers of CeD-associated lymphomagenesis.DesignPure populations of RCDII-cells derived from intestinal biopsies (n=9) or sorted from blood (n=2) were analysed by whole exome sequencing, comparative genomic hybridisation and RNA sequencing. Biopsies from RCDII (n=50), EATL (n=19), type I refractory CeD (n=7) and uncomplicated CeD (n=18) were analysed by targeted next-generation sequencing. Moreover, functional in vitro studies and drug testing were performed in RCDII-derived cell lines.Results80% of RCDII and 90% of EATL displayed somatic gain-of-functions mutations in the JAK1-STAT3 pathway, including a remarkable p.G1097 hotspot mutation in the JAK1 kinase domain in approximately 50% of cases. Other recurrent somatic events were deleterious mutations in nuclear factor kappa-light-chain-enhancer of activated B-cells (NF-κB) regulators TNFAIP3 and TNIP3 and potentially oncogenic mutations in TET2, KMT2D and DDX3X. JAK1 inhibitors, and the proteasome inhibitor bortezomib could block survival and proliferation of malignant RCDII-cell lines.ConclusionMutations activating the JAK1-STAT3 pathway appear to be the main drivers of CeD-associated lymphomagenesis. In concert with mutations in negative regulators of NF-κB, they may favour the clonal emergence of malignant lymphocytes in the cytokine-rich coeliac intestine. The identified mutations are attractive therapeutic targets to treat RCDII and block progression towards EATL.

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Section: Discussionsupporting

confidence: 93%

Oncogenetic landscape of lymphomagenesis in coeliac disease

Cording

Lhermitte

Malamut

et al. 2021

Gut

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“…The role of endoscopic ultrasound in the follow-up of gastric lymphoma is yet to be defined 56. Nor are there guidelines for surveillance of at-risk individuals such as those with disorders associated with an increased risk for lymphoma, such as coeliac disease57 or nodular lymphoid hyperplasia 58 59…”

Section: Discussionmentioning

confidence: 99%

Gastrointestinal lymphoma: the new mimic

Thomas

Schwartz

Quigley

2019

BMJ Open Gastroenterol

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BackgroundGastrointestinal (GI) lymphomas comprise a group of distinct clinicopathological entities of B- or T- cell type, with primary gastrointestinal Hodgkin lymphoma being extremely uncommon. The GI tract is the predominant site of extranodal non-Hodgkin lymphoma accounting for 30–40% of all extranodal lymphomas. In the Western world, the stomach is the most commonly involved site followed by the small bowel. Several chronic inflammatory and immune-mediated disorders which predispose to accelerated cell turnover may lead to the malignant transformation of gut lymphocytes and ultimately manifest as GI lymphoma. The challenge for the clinical gastroenterologist is that these tumors may have varied presentations, ranging from nonspecific symptoms such as dyspepsia or bloating to abdominal pain, nausea, vomiting, GI bleeding, diarrhea, weight loss or bowel obstruction.ObjectiveWe illustrate the range of presentations of GI lymphoma with examples based on consecutive cases evaluated at our institution over a 6-month period. These cases demonstrate how appropriately directed endoscopic evaluation with biopsies has the potential to provide a definitive diagnosis and allow the patient to proceed to definitive therapy.ConclusionsThe GI tract is the most commonly involved site for extranodal lymphoma with the stomach being most frequently involved organ.Chronic Helicobacter pylori infection, celiac disease, inflammatory bowel disease and autoimmune disorders may predispose to GI lymphoma. This heterogenous group of diseases has varied presentations that may mimic several other GI clinico-pathologic entities. GI lymphomas may be diagnosed with appropriately directed endoscopic evaluation coupled with generous tissue sampling and expert pathologic assessment. Management may range from antibiotic therapy, in the case of Helicobacter pylori-associated gastric MALT lymphoma, to chemotherapy with or without radiation and, in rare instances, surgery. There are presently no guidelines to direct endoscopic surveillance of GI lymphomas following treatment.

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“… 9 In addition, there is an association between small intestinal malignancies and CD. 5 However, to date only one study etc. suggested an association between ESC and CD, and our understanding of which patients have CD in the setting of ESC is limited.…”

Section: Discussionmentioning

confidence: 99%

“… 4 It is well-known that there is an imminent relationship between CD and enteropathy-associated T-cell lymphoma (EATL), as well as between CD and small intestinal adenocarcinoma. 5 Squamous cancers etc. are generally determined by the proximal parts of the esophagus.…”

Section: Introductionmentioning

confidence: 99%

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Celiac disease is increased in esophageal squamous cell Carcinoma

Poyrazoglu

Dülger

2021

Pak J Med Sci

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Background and Objective: The intercourse between Esophageal squamous cell carcinoma etc. (ESC) and Celiac disease (CD) is still a complicated subject. The purpose of this research was to define the relationship between CD and ESC, and the factors associated with CD in patients with ESC. Methods: This research was conducted by Van University Medical Center in Turkey from 2012 to 2016. CD was identified by analyzing duodenal biopsy materials from 63 ESC patients via histopathologic examinations. Serum samples from the patients were also serologically tested to identify CD. A control group was selected from among subjects who underwent gastroduodenoscopy due to dyspepsia. Distinctions between case characteristics were evaluated with chi-square tests and t-tests for categorical and continuous factors, respectively. Results: Of the 63 study cases, 6 (9.5%) were both histological and serological positive for CD. Of the 290 control group, 8 (2.8%) had histopathological CD and tested positive for celiac antibodies. The patients with ESC had a significantly higher prevalence of CD compared to the dyspeptic patients (p<0.001). In addition, the mean creatinine levels of ESC patients with histopathological-proven CD were higher than those without CD (p=0.026). Furthermore, ESC patients who tested positive for tTg IgA had significantly higher levels of glucose and AST than those who were negative for tTg IgA (p=0.032) and (p=0.008), respectively. Conclusion: The present study demonstrated a statistically significant positive correlation between ESC and CD. Most remarkably, higher creatinine, glucose, and AST levels may predict CD in patients with ESC. These evidences may lead novel approaches for preventing ESC in patients with CD. doi: https://doi.org/10.12669/pjms.37.5.2757 How to cite this:Poyrazoglu OB, Dulger AC. Celiac disease is increased in esophageal squamous cell Carcinoma. Pak J Med Sci. 2021;37(5):---------. doi: https://doi.org/10.12669/pjms.37.5.2757 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Risks for lymphoma and gastrointestinal carcinoma in patients with newly diagnosed adult‐onset celiac disease: Consequences for follow‐up

Cited by 29 publications

References 19 publications

Oncogenetic landscape of lymphomagenesis in coeliac disease

Oncogenetic landscape of lymphomagenesis in coeliac disease

Gastrointestinal lymphoma: the new mimic

Celiac disease is increased in esophageal squamous cell Carcinoma

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