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Review
. 2018 Dec 29;11(1):31.
doi: 10.3390/cancers11010031.

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: The Current Knowledge

Paolo Giuffrida  1 , Alessandro Vanoli  2 , Giovanni Arpa  3 , Arturo Bonometti  4 , Ombretta Luinetti  5 , Enrico Solcia  6 , Gino Roberto Corazza  7 , Marco Paulli  8 , Antonio Di Sabatino  9
Affiliations
Review

Small Bowel Carcinomas Associated with Immune-Mediated Intestinal Disorders: The Current Knowledge

Paolo Giuffrida et al. Cancers (Basel). .

Abstract

Small bowel carcinomas (SBC) are uncommon neoplasms, whose predisposing conditions include hereditary syndromes and immune-mediated intestinal disorders including coeliac disease (CD) and Crohn's disease (CrD). Although both CD-associated SBC (CD-SBC) and CrD-associated SBC (CrD-SBC) arise from an inflammatory background, they differ substantially in tumour cell phenotype, frequency of microsatellite instability and nuclear β-catenin expression, as well as in prognosis. For these patients, high tumour-infiltrating lymphocyte density and glandular/medullary histotype represent independent positive prognostic factors. Dysplasia adjacent to SBC is rare and characterized by intestinal phenotype and nuclear β-catenin in CD, while it is frequent and typified by gastro-pancreatobiliary marker expression and preserved membranous β-catenin in CrD. Recent evidence suggests that Epstein-Barr virus-positive dysplasia and SBC, albeit exceptional, do exist and are associated with CrD. In this review, we summarize the novel pathological and molecular insights of clinical and therapeutic interest to guide the care of CD-SBC and CrD-SBC.

Keywords: Crohn’s disease; coeliac disease; dysplasia; histotype; overall survival; tumour-infiltrating lymphocyte.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the pathogenic mechanisms underlying small bowel carcinomas associated with chronic intestinal disorders. In coeliac disease villous atrophy induces crypt hyperplasia, characterised by increased intraepithelial lymphocytes (IEL) similarly to atrophic epithelium. Nuclear Sex-determining Region Y-Box (SOX)-9-positive immature hyperplastic crypts evolve into flat nuclear β-catenin-positive dysplasia, thus leading to coeliac disease-associated carcinoma (CD-SBC). CD-SBC is associated with microsatellite instability (MSI) and high number of tumour-infiltrating lymphocytes (TIL). In Crohn’s disease gastric (MUC5AC+)/pancreatobiliary (CK7+) metaplasia evolves into dysplastic polypoid growth, which lastly becomes Crohn’s disease-associated carcinoma (CrD-SBC). CrD-SBC is almost always microsatellite stable (MSS).
Figure 2
Figure 2
(A,B) Radiologic and histologic images of a coeliac disease-associated small bowel carcinoma. (A) Computed tomography shows a circumferential mass with shouldered borders causing the wall thickening in the duodenum (arrows). (B) Haematoxylin and eosin staining shows a glandular-type carcinoma with a high tumour-infiltrating lymphocyte density. Original magnification: 100×.
See this image and copyright information in PMC

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