Top

Journal of Medical Case Reports

Published in:

Open Access 01-12-2022 | Lymphoma | Case report

Malignant complications of celiac disease: a case series and review of the literature

Authors: Barbora Packova, Pavel Kohout, Milan Dastych, Jitka Prokesova, Tomas Grolich, Radek Kroupa

Published in: Journal of Medical Case Reports | Issue 1/2022

Abstract

Background

Celiac disease is an immune-mediated enteropathy triggered by gluten in genetically susceptible individuals. Diagnosis is based on evaluating specific autoantibodies and histopathologic findings of duodenal biopsy specimens. The only therapy for celiac disease is a gluten-free diet. Celiac disease can be complicated by malnutrition, other autoimmune diseases, refractoriness to treatment, and gastrointestinal tumors. This article presents seven cases of malignancies in patients with celiac disease. Its objective is to raise awareness of the malignant complications of celiac disease, leading to earlier diagnosis and improved outcomes.

Case presentation

Seven cases of malignant complications of celiac disease occurred among 190 patients followed at the Department of Internal Medicine and Gastroenterology, University Hospital Brno from 2014 to 2021. We describe these cases and the presentation, diagnostic process, course, management, and outcomes for each, along with proposed potential risk factors of malignant complications. There was one Caucasian man who was 70 years old and six Caucasian women who were 36, 46, 48, 55, 73, and 82 years old in our cohort. Of the seven cases of malignancies in our cohort, four patients were diagnosed with small bowel adenocarcinoma, one with diffuse large B-cell lymphoma, one with carcinoma of the tongue, and one with colorectal carcinoma.

Conclusions

Malignancies occurred in 3.7% of patients followed up for celiac disease. Awareness of the malignant complications of celiac disease, risk factors, presentation, and disease course could lead to earlier diagnosis and improved outcomes.

van Gils T, Nijeboer P, Overbeek LI, et al. Risks for lymphoma and gastrointestinal carcinoma in patients with newly diagnosed adult-onset celiac disease: consequences for follow-up. United Eur Gastroenterol J. 2018;6(10):1485–95. https://doi.org/10.1177/2050640618800540.CrossRef

Catassi C, Fabiani E, Corrao G, et al. Risk of non-Hodgkin lymphoma in celiac disease. JAMA. 2002;287(11):1413–9. https://doi.org/10.1001/jama.287.11.1413.CrossRef

Smedby KE. Malignant lymphomas in coeliac disease: evidence of increased risks for lymphoma types other than enteropathy-type T cell lymphoma. Gut. 2005;54(1):54–9. https://doi.org/10.1136/gut.2003.032094.CrossRef

Halfdanarson TR, Rubio-Tapia A, Ristow KM, Habermann TM, Murray JA, Inwards DJ. Patients with celiac disease and B-cell lymphoma have a better prognosis than those with T-cell lymphoma. Clin Gastroenterol Hepatol. 2010;8(12):1042–7. https://doi.org/10.1016/j.cgh.2010.09.007.CrossRef

Green PHR, Fleischauer AT, Bhagat G, Goyal R, Jabri B, Neugut AI. Risk of malignancy in patients with celiac disease. Am J Med. 2003;115(3):191–5. https://doi.org/10.1016/S0002-9343(03)00302-4.CrossRef

Goldacre MJ, Wotton CJ, Yeates D, Seagroatt V, Jewell D. Cancer in patients with ulcerative colitis, Crohn’s disease and coeliac disease: record linkage study. Eur J Gastroenterol Hepatol. 2008;20(4):297–304. https://doi.org/10.1097/MEG.0b013e3282f2a5e2.CrossRef

Askling J, Linet M, Gridley G, Halstensen TS, Ekström K, Ekbom A. Cancer incidence in a population-based cohort of individuals hospitalized with celiac disease or dermatitis herpetiformis. Gastroenterology. 2002;123(5):1428–35. https://doi.org/10.1053/gast.2002.36585.CrossRef

Elfström P, Granath F, Ye W, Ludvigsson JF. Low risk of gastrointestinal cancer among patients with celiac disease, inflammation, or latent celiac disease. Clin Gastroenterol Hepatol. 2012;10(1):30–6. https://doi.org/10.1016/j.cgh.2011.06.029.CrossRef

Han Y, Chen W, Li P, Ye J. Association between coeliac disease and risk of any malignancy and gastrointestinal malignancy. Medicine (Baltimore). 2015;94(38):e1612. https://doi.org/10.1097/MD.0000000000001612.CrossRef

10.

Poyrazoglu OB, Dulger AC. Celiac disease is increased in esophageal squamous cell Carcinoma. Pak J Med Sci. 2021;37(5):1445–50. https://doi.org/10.12669/pjms.37.5.2757.CrossRef

11.

Koskinen I, Hervonen K, Pukkala E, Reunala T, Kaukinen K, Collin P. Cancer incidence and factors associated with malignancies in coeliac disease during long-term follow-up. GastroHep. 2021;3(2):107–15. https://doi.org/10.1002/ygh2.446.CrossRef

12.

Selby WS, Gallagher ND. Malignancy in a 19-year experience of adult celiac disease. Dig Dis Sci. 1979;24(9):684–8. https://doi.org/10.1007/BF01314465.CrossRef

13.

Cottone M, Termini A, Oliva L, et al. Mortality and causes of death in celiac disease in a Mediterranean area. Dig Dis Sci. 1999;44(12):2538–41. https://doi.org/10.1023/a:1026655609906.CrossRef

14.

Collin P, Reunala T, Pukkala E, Laippala P, Keyriläinen O, Pasternack A. Coeliac disease—associated disorders and survival. Gut. 1994;35(9):1215–8. https://doi.org/10.1136/gut.35.9.1215.CrossRef

15.

Al-Toma A, Goerres MS, Meijer JWR, Peña AS, Crusius JBA, Mulder CJJ. Human leukocyte antigen–DQ2 homozygosity and the development of refractory celiac disease and enteropathy-associated T-Cell lymphoma. Clin Gastroenterol Hepatol. 2006;4(3):315–9. https://doi.org/10.1016/j.cgh.2005.12.011.CrossRef

16.

Malamut G, Cellier C. Complications of coeliac disease. Best Pract Res Clin Gastroenterol. 2015;29(3):451–8. https://doi.org/10.1016/j.bpg.2015.05.005.CrossRef

17.

Goddard CJR, Gillett HR. Complications of coeliac disease: are all patients at risk? Postgrad Med J Lond. 2006;82(973):705–12. https://doi.org/10.1136/pgmj.2006.048876.CrossRef

18.

Sieniawski MK, Lennard AL. Enteropathy-associated T-cell lymphoma: epidemiology, clinical features, and current treatment strategies. Curr Hematol Malig Rep. 2011;6(4):231–40. https://doi.org/10.1007/s11899-011-0097-7.CrossRef

19.

Holmes GK, Dunn GI, Cockel R, Brookes VS. Adenocarcinoma of the upper small bowel complicating coeliac disease. Gut. 1980;21(11):1010–6.CrossRef

20.

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(3):169–75. https://doi.org/10.7326/0003-4819-159-3-201308060-00006.CrossRef

21.

Lebwohl B, Green PHR, Emilsson L, et al. Cancer risk in 47,241 individuals with celiac disease: a nationwide cohort study. Clin Gastroenterol Hepatol. 2022;20(2):e111–31. https://doi.org/10.1016/j.cgh.2021.05.034.CrossRef

22.

Corrao G, Corazza GR, Bagnardi V, et al. Mortality in patients with coeliac disease and their relatives: a cohort study. Lancet. 2001;358(9279):356–61. https://doi.org/10.1016/s0140-6736(01)05554-4.CrossRef

23.

Logan RF, Rifkind EA, Turner ID, Ferguson A. Mortality in celiac disease. Gastroenterology. 1989;97(2):265–71. https://doi.org/10.1016/0016-5085(89)90060-7.CrossRef

24.

Holmes GK, Prior P, Lane MR, Pope D, Allan RN. Malignancy in coeliac disease–effect of a gluten free diet. Gut. 1989;30(3):333–8.CrossRef

25.

Emilsson L, Semrad C, Lebwohl B, Green PHR, Ludvigsson JF. Risk of small bowel adenocarcinoma, adenomas, and carcinoids in a nationwide cohort of individuals with celiac disease. Gastroenterology. 2020;159(5):1686-1694.e2. https://doi.org/10.1053/j.gastro.2020.07.007.CrossRef

26.

Al-Toma A, Volta U, Auricchio R, et al. European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United Eur Gastroenterol J. 2019;7(5):583–613. https://doi.org/10.1177/2050640619844125.CrossRef

27.

Packova B, Kovalcikova P, Pavlovsky Z, et al. Non-invasive prediction of persistent villous atrophy in celiac disease. World J Gastroenterol. 2020;26(26):3780–91. https://doi.org/10.3748/wjg.v26.i26.3780.CrossRef

28.

Neugut AI, Jacobson JS, Suh S, Mukherjee R, Arber N. The epidemiology of cancer of the small bowel. Cancer Epidemiol Biomarkers Prev. 1998;7(3):243–51.

29.

Aparicio T, Zaanan A, Svrcek M, et al. Small bowel adenocarcinoma: epidemiology, risk factors, diagnosis and treatment. Dig Liver Dis. 2014;46(2):97–104. https://doi.org/10.1016/j.dld.2013.04.013.CrossRef

30.

Howdle PD, Jalal PK, Holmes GKT, Houlston RS. Primary small-bowel malignancy in the UK and its association with coeliac disease. QJM. 2003;96(5):345–53. https://doi.org/10.1093/qjmed/hcg058.CrossRef

31.

Zouhairi ME, Venner A, Charabaty A, Pishvaian MJ. Small bowel adenocarcinoma. Curr Treat Options Oncol. 2008;9(4–6):388–99. https://doi.org/10.1007/s11864-009-0098-0.CrossRef

32.

Chang H-K, Yu E, Kim J, et al. Adenocarcinoma of the small intestine: a multi-institutional study of 197 surgically resected cases. Hum Pathol. 2010;41(8):1087–96. https://doi.org/10.1016/j.humpath.2010.01.006.CrossRef

33.

Brousse N, Meijer JWR. Malignant complications of coeliac disease. Best Pract Res Clin Gastroenterol. 2005;19(3):401–12. https://doi.org/10.1016/j.bpg.2005.02.002.CrossRef

34.

Marafini I, Monteleone G, Stolfi C. Association between celiac disease and cancer. Int J Mol Sci. 2020;21(11):4155. https://doi.org/10.3390/ijms21114155.CrossRef

35.

Locher C, Batumona B, Afchain P, et al. Small bowel adenocarcinoma: French intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO). Dig Liver Dis. 2018;50(1):15–9.CrossRef

36.

Giuffrida P, Arpa G, Grillo F, et al. PD-L1 in small bowel adenocarcinoma is associated with etiology and tumor-infiltrating lymphocytes, in addition to microsatellite instability. Mod Pathol. 2020;33(7):1398–409. https://doi.org/10.1038/s41379-020-0497-0.CrossRef

37.

Halfdanarson TR, McWilliams RR, Donohue JH, Quevedo JF. A single-institution experience with 491 cases of small bowel adenocarcinoma. Am J Surg. 2010;199(6):797–803. https://doi.org/10.1016/j.amjsurg.2009.05.037.CrossRef

38.

Vanoli A, Di Sabatino A, Furlan D, et al. Small bowel carcinomas in coeliac or Crohn’s disease: clinico-pathological, molecular, and prognostic features. A study from the small bowel Cancer Italian Consortium. J Crohn’s Colitis. 2017;11(8):942–53. https://doi.org/10.1093/ecco-jcc/jjx031.CrossRef

39.

Potter DD, Murray J, Donohue J, et al. The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease. J Am Coll Surg. 2004;199(3):86. https://doi.org/10.1016/j.jamcollsurg.2004.05.187.CrossRef

40.

Eells AC, Mackintosh C, Marks L, Marino MJ. Gastroesophageal reflux disease and head and neck cancers: a systematic review and meta-analysis. Am J Otolaryngol. 2020;41(6):102653. https://doi.org/10.1016/j.amjoto.2020.102653.CrossRef

41.

Langevin SM, Michaud DS, Marsit CJ, et al. Gastric reflux is an independent risk factor for laryngopharyngeal carcinoma. Cancer Epidemiol Biomarkers Prev. 2013;22(6):1061–8. https://doi.org/10.1158/1055-9965.EPI-13-0183.CrossRef

42.

Lebwohl B, Stavsky E, Neugut AI, Green PHR. Risk of colorectal adenomas in patients with celiac disease. Aliment Pharmacol Ther. 2010;32(8):1037–43. https://doi.org/10.1111/j.1365-2036.2010.04440.x.CrossRef

43.

Pereyra L, Gonzalez R, Mohaidle A, et al. Risk of colorectal neoplasia in patients with celiac disease: a multicenter study. J Crohn’s Colitis. 2013;7(12):e672–7. https://doi.org/10.1016/j.crohns.2013.06.005.CrossRef

44.

Volta U, Vincentini O, Quintarelli F, Felli C, Silano M, Caio G. Collaborating Centres of the Italian Registry of the Complications of Celiac Disease. Low risk of colon cancer in patients with celiac disease. Scand J Gastroenterol. 2014;49:564–8. https://doi.org/10.3109/00365521.2014.893012.CrossRef

45.

DiffuseLargeBCellLymphoma.pdf - DIFFUSE LARGE B-CELL LYMPHOMA Union for International Cancer Control 2014 Review of Cancer Medicines on the WHO List of | Course Hero. https://www.who.int/selection_medicines/committees/expert/20/applications/DiffuseLargeBCellLymphoma.pdf?ua=1&ua=1. Accessed 26 Jan 2022.

46.

Nijeboer P, van Wanrooij R, van Gils T, et al. Lymphoma development and survival in refractory coeliac disease type II: histological response as prognostic factor. United Eur Gastroenterol J. 2017;5(2):208–17. https://doi.org/10.1177/2050640616646529.CrossRef

47.

Mearin M, Catassi C, Brousse N, et al. European multi-centre study on coeliac disease and non-Hodgkin lymphoma. Eur J Gastroenterol Hepatol. 2006;18:187–94. https://doi.org/10.1097/00042737-200602000-00012.CrossRef

48.

Al-Toma A, Verbeek WHM, Hadithi M, von Blomberg BME, Mulder CJJ. Survival in refractory coeliac disease and enteropathy-associated T-cell lymphoma: retrospective evaluation of single-centre experience. Gut. 2007;56(10):1373–8. https://doi.org/10.1136/gut.2006.114512.CrossRef

49.

Di Sabatino A, Biagi F, Gobbi PG, Corazza GR. How I treat enteropathy-associated T-cell lymphoma. Blood. 2012;119(11):2458–68. https://doi.org/10.1182/blood-2011-10-385559.CrossRef

50.

Chan JKC, Chan ACL, 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(10):1557–69. https://doi.org/10.1097/PAS.0b013e318222dfcd.CrossRef

51.

Eigner W, Bashir K, Primas C, et al. Dynamics of occurrence of refractory coeliac disease and associated complications over 25 years. Aliment Pharmacol Ther. 2017;45(2):364–72. https://doi.org/10.1111/apt.13867.CrossRef

52.

Arps DP, Smith LB. Classic versus type II enteropathy-associated T-cell lymphoma: diagnostic considerations. Arch Pathol Lab Med. 2013;137(9):1227–31. https://doi.org/10.5858/arpa.2013-0242-CR.CrossRef

53.

Al-Toma A, Verbeek WHM, Visser OJ, et al. Disappointing outcome of autologous stem cell transplantation for enteropathy-associated T-cell lymphoma. Dig Liver Dis. 2007;39(7):634–41. https://doi.org/10.1016/j.dld.2007.03.009.CrossRef

Title: Malignant complications of celiac disease: a case series and review of the literature
Authors: Barbora Packova
Pavel Kohout
Milan Dastych
Jitka Prokesova
Tomas Grolich
Radek Kroupa
Publication date: 01-12-2022
Publisher: BioMed Central
Keywords: Lymphoma
Celiac Disease
Celiac Disease
Diffuse Large B-Cell Lymphoma
Diffuse Large B-Cell Lymphoma
Published in: Journal of Medical Case Reports / Issue 1/2022
Electronic ISSN: 1752-1947
DOI: https://doi.org/10.1186/s13256-022-03682-3

ACC 2024 Congress

Springer Medicine

Malignant complications of celiac disease: a case series and review of the literature

Abstract

Background

Case presentation

Conclusions

ACC 2024 Congress

Springer Medicine

Abstract

Background

Case presentation

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2022

Streamline-based three-dimensional peak-velocity tracing of transvalvular flow using four-dimensional flow cardiac magnetic resonance imaging for left ventricular diastolic assessment in aortic regurgitation: a case report

Primary biliary cholangitis first demonstrated in pregnancy: a case report

Acute worsening of native lung fibrosis after single lung transplantation for pulmonary fibrosis: two case reports

Atypical dermatologic manifestations in complex regional pain syndrome: a case report

The use of artificial intelligence and machine learning monitoring to safely administer a fluid-restrictive goal-directed treatment protocol to minimize the risk of transfusion during major spine surgery of a Jehovah’s Witness: a case report

A rare cause of abdominal pain managed unconventionally: acute renal infarction caused by atrial fibrillation: a case report