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Celiac.com 02/19/2024 - A recent study presented at the 2023 annual meeting of the American College of Gastroenterology has raised concerns about the increasing incidence of enteropathy-associated T-cell lymphoma (EATL) – a rare and aggressive form of T-cell, non-Hodgkin lymphoma. This alarming trend has prompted researchers to explore the possible connection between EATL and celiac disease, shedding light on the risks faced by individuals with this autoimmune condition. Lead investigator Dr. Isabel Hujoel, Clinic Director of the Celiac Disease Center at UW Medical Center, Seattle, highlighted the strong association between EATL and celiac disease. While EATL is rare, most cases are observed in patients with celiac disease, suggesting a potential link between the two conditions. The study, utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program database, identified 463 cases of EATL between 2000 and 2020, with an age-adjusted incidence rate of 0.014 per 100,000 people. Alarmingly, the incidence of EATL increased by 2.58% annually over this 20-year period. Despite advancements in medical treatment, the prognosis for EATL remains poor, with a median survival of approximately six months. Findings from the study revealed that most cases were treated with a combination of surgery and chemotherapy. However, survival outcomes did not improve over the study period, underscoring the urgent need for more effective treatment strategies. Dr. Sophia Dar, a gastroenterology fellow at Southern Illinois University School of Medicine, emphasized the importance of early detection and treatment. While chemotherapy showed promising results, the overall mortality rate remained high, highlighting the challenges in managing this aggressive cancer. Researchers emphasized the need for further investigation into the factors contributing to the high mortality rate associated with EATL. Understanding these factors could pave the way for more efficient treatment plans and improved outcomes for patients. Debra Silberg, MD, PhD, Chief Scientific Officer of the nonprofit Beyond Celiac, emphasized the rarity of EATL and the need for targeted screening. Screening for EATL should be considered in cases of refractory celiac disease or when there is suspicion of complications related to celiac disease. The rise in cases of EATL serves as a sobering reminder of the potential complications associated with celiac disease. Heightened awareness, early detection, and improved treatment options are crucial in addressing this rare but deadly cancer among individuals with celiac disease. Read more at gastroendonews.com

Celiac.com 05/27/2023 - Malignancy must be a concern for all of us with celiac disease. The association between increased mortality in celiac disease due to malignant disease has been known since 1962(1) . Subsequent studies have confirmed various types of malignancies occurring in celiac patients with the most frequent being lymphomas, which account for 51-72% of celiac disease-associated malignancy(2, 3) . Both small bowel lymphomas and adenocarcinoma, the most frequent celiac disease-associated malignancies, typically arise in the jejunum but also are found in the duodenum and ileum(2) . Other sites of carcinoma found in greater than expected numbers have been the mouth, pharnyx, lung, breast, and testes2, 3. Celiac disease-associated cancer is found in both child and adult celiacs(2). Enteropathy associated T-cell lymphoma (EATL) of the small bowel is the major lymphoma associated with celiac disease(2, 4). This type of non-Hodgkin lymphoma appears to be primarily associated with celiac disease and is known to increase in people with celiac disease who are 50-70 years of age(4) . There appears to be two forms of EATL, and one of them may originate during refractory celiac disease(2,4). Abnormalities in refractory celiac disease lymphocytes are similar to those of this form of EATL(3) . While the majority of patients with celiac disease have improved symptoms with a strict gluten-free diet, those with refractory celiac disease may be non-responsive because of complications due to the development of EATL(5). The Importance of a Gluten-Free Diet The exact rate of malignancy in celiac disease is unknown since much of the silent or asymptomatic form of the disease remains undiagnosed(5) . Also, the celiac disease status of patients with established lymphoma may never be determined, or may be missed at examination(2, 5). However, European studies have shown an increased mortality rate due to malignancies in celiac disease as high as two to nearly four times that of the non-celiac disease population(2) . Most deaths occurred in the first 3-4 years after diagnosis. Several studies have demonstrated the protective effect of a strict gluten-free diet against malignancy(2, 5) . There appears to be a clear correlation between increased cancer rates (comparing the celiac disease and non-celiac disease populations) and the amount of gluten ingestion. In one of the studies, the excess morbidity of patients on a strict gluten-free diet was only 1.2 compared to 10.7 in patients on a normal (gluten-containing) diet(5). After 5 years or more on a strict gluten-free diet, there appears to be no significant increase in the overall cancer risk compared to the non-celiac disease population. Furthermore, a strict gluten-free diet appears to specifically reduce EATL(6). The Importance of Early Diagnosis Conferring the protective effect of a gluten-free diet with early diagnosis is important in malignancies like lymphoma, which has a poor prognosis(5). The expected five-year survival of advanced small bowel lymphoma is 25-30%; that of intestinal T cell lymphoma is only about 25%7 . Furthermore, gastrointestinal lymphomas often are presented as high grade (i.e., more advanced) malignancy, and are often widespread(5,6). Unfortunately some cases of celiac disease are not diagnosed until presentation of lymphoma. T-cell lymphomas most often arouse the suspicion of undiagnosed celiac disease, but B-cell lymphomas exist in celiac disease as well(8). However, the diagnosis of lymphoma can be difficult to ascertain due to non-specific symptoms or symptoms similar to celiac disease(5,7). Presenting features of gastrointestinal lymphoma are similar to that of uncomplicated celiac disease; "Unexplained deterioration, abdominal pain, weight loss, severe muscle weakness, lymphadenopathy (disorder of the lymph nodes), abdominal mass and pyrexia (fever) should arouse suspicion of lymphoma."(5). Some patients may also have intestinal obstruction, perforation, or bleeding. Furthermore, patients with small bowel tumors (including adenocarcinoma) may present with abdominal pain, anemia, bleeding, weight loss, or obstruction(2, 7). Therefore, Ruskone-Fourmestraux and Rambaud suggest that "the diagnosis of coeliac disease must be made as early as possible and the diet commenced, even in asymptomatic subjects, after detailed and complete patient information."(6). Once diagnosed, therapy for lymphoma or adenocarcinoma may include surgery (such as resection of a portion of the intestine), chemotherapy, and/or radiotherapy(5). Regarding cancer, there is both good and bad news for those of us with celiac disease. While we have an increased risk of cancer, the risk is still very small for most celiacs. The symptoms of gastrointestinal cancers, and especially small bowel cancers, are similar to those of celiac disease itself. It appears, however, that with the exception of refractory celiac disease, a strict gluten-free diet over time may remove the increased chance of cancer due to celiac disease. Undeniably, our vigilant adherence and attitude toward the gluten-free lifestyle must be a mainstay and we must be up to the challenge. References: Gough KR, Read AE, Naish JM. 1962. Intestinal reticulosis as a complication of idiopathic steatorrhea. Gut 3: 232-39. Green PHR, and Jabri B. 2002. Celiac disease and other precursors to small-bowel malignancy. Gastroenterol Clin N Am 31:625-39. Seraphin P, and Mobarhan S. 2002. Mortality in patients with celiac disease. Nutrition Rev 60: 116-8. Catassi C, et al. 2002. Risk of non-Hodgkin lymphoma in celiac disease. JAMA 287:1413-9. Holmes GKT. 2002. Coeliac disease and malignancy. Digest Liver Dis 34:229-37. Ruskone-Fourmestraux A, and Rambaud JC. 2001. Gastrointestinal lymphoma: prevention and treatment of early lesions. Best Practice & Res Clin Gastroenterol 15:337-54. Gill SS, Heuman DM, and Mihas AA. 2001. Small intestinal neoplasm. J Clin Gastroenterol 33: 267-82. Freeman H, Lemoyne M, and Pare P. 2002. Coeliac disease. Best Pract & Res 16:37-49.

Celiac.com 06/15/2017 - Enteropathy-associated T cell lymphoma (EATL) subtypes are characterized by loss of function of SETD2. Although EATL is rare condition, it is deadly. It is also the most common neoplastic complication of celiac disease. A team of researchers recently conducted whole-exome sequencing of 69 EATL tumors, which helped them to define the genetic landscape of EATL. They found that SETD2 was silenced in 32% of EATL patients, making it the most frequently silenced gene in EATL. The research team included AB Moffitt, SL Ondrejka, M McKinney, RE Rempel, JR Goodlad, CH Teh, S Leppa, S Mannisto, PE Kovanen, E Tse, RKH Au-Yeung, YL Kwong, G Srivastava, J Iqbal, J Yu, K Naresh, D Villa, RD Gascoyne, J Said, MB Czader, A Chadburn, KL Richards, D Rajagopalan, NS Davis, EC Smith, BC Palus, TJ Tzeng, JA Healy, PL Lugar, J Datta, C Love, S Levy, DB Dunson, Y Zhuang, ED Hsi, and SS Dave. The team also noted that the JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1, and that the condition causes highly overlapping genetic alterations among the mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma), which indicates shared mechanisms underlying their causes. To model the effects of SETD2 loss in vivo, the team developed a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. The team's data provides the most comprehensive genetic portrait to date of this rare, but deadly disease, and will likely play a key role in future classifications of EATL. Source: J Exp Med. 2017 May 1;214(5):1371-1386. doi: 10.1084/jem.20160894. Epub 2017 Apr 19. The researchers are variously affiliated with the Duke Center for Genomics and Computational Biology, Duke University, Durham, NC, the Duke Cancer Institute, Duke University School of Medicine, Durham, NC, the Pathology and Laboratory Medicine Institute, Cleveland Clinic, Cleveland, OH, the Haematological Malignancy Diagnostic Service, St. James's University Hospital, Leeds LS9 7TF, England, UK, the Haematology Department, Western General Hospital, Edinburgh, Scotland, UK, the Department of Oncology and Research Program Unit, Faculty of Medicine, Helsinki University Hospital Cancer Center and University of Helsinki in Helsinki, Finland, HUSLAB and Medicum, Helsinki University Hospital Cancer Center and University of Helsinki, Helsinki, Finland, the University of Hong Kong, Queen Mary Hospital, Hong Kong, China, the University of Nebraska Medical Center, Omaha, NE, Imperial College London, London, England, UK, the British Columbia Cancer Agency, University of British Columbia, Vancouver, BC, Canada, the University of California, Los Angeles, Los Angeles, CA, Indiana University, Indianapolis, IN, the Presbyterian Hospital, Pathology and Cell Biology, Cornell University, New York, NY, the University of North Carolina at Chapel Hill, Chapel Hill, NC, the Department of Medicine, Duke University School of Medicine, Durham, NC, the Department of Statistical Science, Duke University, Durham, NC, the Hudson Alpha Institute for Biotechnology, Huntsville, AL 35806, and the Department of Immunology, Duke University School of Medicine, Durham, NC.