Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease

Background The increased risk of malignancies in coeliac disease is well recognised, but data on incidence and predisposing factors are scarce. Our aim was to determine cancer incidence and its prognostic factors in coeliac disease during a long‐term follow‐up. Methods The study cohort comprised all (n = 1460) coeliac patients diagnosed in Tampere University Hospital catchment area during the period 1960‐2000. Demographic data (age, gender, decade of diagnosis) and coeliac disease characteristics (presenting symptoms, signs of malabsorption, severity of villous atrophy) were obtained from medical records, and patients were stratified into subgroups accordingly. Standardised incidence ratios (SIRs) compared to general population of the same area were calculated for malignancies altogether and according to stratifications. Results The overall risk of malignancy was not increased (SIR 0.97; 95% confidence interval (CI) 0.84‐1.11). The risk of non‐Hodgkin lymphoma was elevated (SIR 3.0; 1.88‐4.54) but less so after ≥15 years of follow‐up (SIR 1.75; 0.70‐3.60). Screen‐detected coeliac disease or malabsorption at diagnosis was not associated with increased risk of non‐Hodgkin lymphoma. The increased risk of gastrointestinal malignancies (SIR 1.42; 95% CI 1.07‐1.85), particularly that of stomach and liver cancers, was associated with females, coeliac disease diagnosis before year 1981 and dermatitis herpetiformis. Conclusions The overall risk of malignancy was not increased in any coeliac disease phenotype. The risk of non‐Hodgkin lymphoma was increased but not in screen‐detected coeliac disease.

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“…This issue requires further studies. Interestingly, opposite to the recent Swedish study, 34 we did not observe any small bowel adenocarcinomas.…”

Section: Discussioncontrasting

confidence: 99%

Cancer incidence and factors associated with malignancies in coeliac disease during long‐term follow‐up

et al. 2021

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“…This is the first investigation of SATB2 expression in celiac disease-associated SBAs, reporting a 25% rate of positive cases. This finding may be of clinical interest because when a cancer of unknown primary is detected in a celiac patient, a SBA should not be excluded a priori even if it proves to be SATB2-positive, considering that celiac disease patients have a significantly higher risk for SBA development in comparison to the general population [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Small Bowel Adenocarcinomas Featuring Special AT-Rich Sequence-Binding Protein 2 (SATB2) Expression and a Colorectal Cancer-Like Immunophenotype: A Potential Diagnostic Pitfall

Neri

Arpa

Guerini

et al. 2020

Cancers

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Special AT-rich sequence-binding protein 2 (SATB2) is a transcription factor expressed by colonic cryptic epithelium and epithelial neoplasms of the lower gastrointestinal (GI) tract, as well as by small bowel adenocarcinomas (SBAs), though at a lower rate. Nevertheless, up to now, only small SBA series, often including a very limited number of Crohn’s disease-associated SBAs (CrD-SBAs) and celiac disease-associated SBAs (CD-SBA), have been investigated for SATB2 expression. We evaluated the expression of SATB2 and other GI phenotypic markers (cytokeratin (CK) 7 and CK20, caudal type homeobox 2 (CDX2) and alpha-methylacyl-CoA racemase (AMACR)), as well as mismatch repair (MMR) proteins, in 100 SBAs, encompassing 34 CrD-SBAs, 28 CD-SBAs and 38 sporadic cases (Spo-SBAs). Any mutual association and correlation with other clinico-pathologic features, including patient prognosis, were searched. Twenty (20%) SATB2-positive SBAs (4 CrD-SBAs, 7 CD-SBAs and 9 Spo-SBAs) were identified. The prevalence of SATB2 positivity was lower in CrD-SBA (12%) in comparison with both CD-SBAs (25%) and Spo-SBAs (24%). Interestingly, six SBAs (two CD-SBAs and four Spo-SBAs) displayed a full colorectal carcinoma (CRC)-like immunoprofile (CK7−/CK20+/CDX2+/AMACR+/SATB2+); none of them was a CrD-SBA. No association between SATB2 expression and MMR status was observed. Although SATB2-positive SBA patients showed a more favorable outcome in comparison with SATB2-negative ones, the difference did not reach statistical significance. When cancers were stratified according to CK7/CK20 expression patterns, we found that CK7−/CK20- SBAs were enriched with MMR-deficient cases (71%) and patients with CK7−/CK20− or CK7−/CK20+ SBAs had a significantly better survival rate compared to those with CK7+/CK20− or CK7+/CK20+ cancers (p = 0.002). To conclude, we identified a small (6%) subset of SBAs featuring a full CRC-like immunoprofile, representing a potential diagnostic pitfall in attempts to identify the site of origin of neoplasms of unknown primary site. In contrast with data on colorectal carcinoma, SATB2 expression is not associated with MMR status in SBAs. CK patterns influence patient survival, as CK7−/CK20− cancers show better prognosis, a behavior possibly due to the high rate of MMR-deficient SBAs within this subgroup.

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“…Further investigations are, however, needed to estimate the actual prevalence of gastric-type duodenal adenomas in hereditary gastrointestinal tumor predisposing syndromes. Interestingly, one case occurred in a patient with celiac disease (CD), an autoimmune condition with a higher risk of developing small intestine adenomas and adenocarcinomas [ 42 ].…”

Section: Sporadic Small Bowel Dysplastic Glandular Lesionsmentioning

confidence: 99%

“…In CD, both raised/adenomatous preinvasive growths and flat dysplastic lesions have been described, always adjacent to carcinoma [ 108 , 109 , 110 ]. It was recently demonstrated that small bowel adenomas are detected much more frequently in CD patients than in non-CD individuals, with a relative risk of 5.73 [ 42 ]. However, in the mucosa adjacent to small bowel carcinoma, flat dysplasia, albeit rare, seems to be more frequent than adenomatous growths [ 110 ].…”

Section: Premalignant Epithelial Lesions In Celiac Disease and Crohn’s Diseasementioning

confidence: 99%

Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations

Vanoli

Grillo

Furlan

et al. 2021

IJMS

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The wider use of gastrointestinal endoscopic procedures has led to an increased detection of small intestinal preneoplastic and neoplastic epithelial lesions, most of which are identified in the duodenum and ampullary region. Like their malignant counterparts, small intestinal glandular precursor lesions, which include adenomas and hamartomas, may arise sporadically or be associated with hereditary tumor syndromes, such as familial adenomatous polyposis, MUTYH-associated polyposis, Lynch syndrome, Peutz-Jeghers syndrome, juvenile polyposis syndrome, and Cowden syndrome. In addition, dysplastic, preinvasive lesions have been observed adjacent to small bowel adenocarcinomas complicating immune-related disorders, such as celiac or Crohn’s disease. Adenomatous lesions may exhibit an intestinal-type, gastric-type, or, very rarely, serrated differentiation, related to different molecular pathogenetic mechanisms. Finally, in the background of multiple endocrine neoplasia 1 syndrome, precursor neuroendocrine growths have been described. In this review we offer a comprehensive description on the histo-molecular features of the main histotypes of small bowel epithelial precursors lesions, including: (i) sporadic adenomas (intestinal-type and gastric-type; non-ampullary and ampullary); (ii) syndromic adenomas; (iii) small bowel dysplasia in celiac and Crohn’s disease; (iv) serrated lesions; (v) hamartomatous lesions; and (vi) neuroendocrine precursor lesions.

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Risk of Small Bowel Adenocarcinoma, Adenomas, and Carcinoids in a Nationwide Cohort of Individuals With Celiac Disease

Cited by 51 publications

References 32 publications

Cancer incidence and factors associated with malignancies in coeliac disease during long‐term follow‐up

Cancer incidence and factors associated with malignancies in coeliac disease during long‐term follow‐up

Small Bowel Adenocarcinomas Featuring Special AT-Rich Sequence-Binding Protein 2 (SATB2) Expression and a Colorectal Cancer-Like Immunophenotype: A Potential Diagnostic Pitfall

Small Bowel Epithelial Precursor Lesions: A Focus on Molecular Alterations

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