Clinicopathological and Molecular Characterisation of Crohn's Disease-associated Small Bowel Adenocarcinomas

Xiaoyan Liao, Guangyuan Li, Russel McBride, Jane Houldsworth, Noam Harpaz, Alexandros D. Polydorides

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background and Aims: Small bowel adenocarcinoma [SBA] is a recognised complication of Crohn's disease [CD], but its low absolute prevalence limits opportunities for clinicopathological characterisation. Methods: We compared the clinical, pathological, and molecular features of 48 SBA from patients with CD [CDSBA] and 29 SBAs from patients without CD [NSBA] who underwent treatment at our tertiary care centre between 2000 and 2018. Results: Patients with CDSBA were younger than those with NSBA [mean age, 56 vs 64; p = 0.02]. Males predominated in both groups. Most CDSBA [69%] occurred in the ileum, whereas most NSBA occurred in the duodenum [38%] and jejunum [31%; p < 0.001]. Stage I tumours were more prevalent in the CDSBA [33% vs 3%; p = 0.002], although the rates of Stage IV disease and disease-specific mortality were similar in both groups. CDSBA were less likely to present a discrete mass [35% vs 93%; p < 0.001] and were more often stricturing or fistulising [75% vs 10%, respectively, p < 0.001] than NSBA. Microscopically, CDSBA were relatively heterogeneous, exhibiting at least three distinct growth patterns in 39% compared with 1% of NSBA [p = 0.01]. Low-grade tubuloglandular adenocarcinoma was the predominant pattern in 19% of CDSBA compared with 0% of NSBA [p = 0.003]. CDSBA were more frequently DNA mismatch repair proficient [90% vs 62%; p = 0.04] and exhibited profiles of frequently mutated genes similar to those of NSBA, except for IDH1 [18%] and SMAD4 [12%] mutations that occurred uniquely in CDSBA. Conclusions: These observations, based on the largest single-centre series described hitherto, establish that CDSBA is a distinct clinical, pathological, and molecular entity.

Original languageEnglish
Pages (from-to)287-294
Number of pages8
JournalJournal of Crohn's and Colitis
Volume14
Issue number3
DOIs
StatePublished - 13 Mar 2020

Keywords

  • Crohn's disease
  • Small bowel adenocarcinoma
  • next-generation sequencing

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