DNA content abnormality frequently develops in the right/proximal colon in patients with primary sclerosing cholangitis and inflammatory bowel disease and is highly predictive of subsequent detection of dysplasia

Histopathology. 2023 Jul;83(1):116-125. doi: 10.1111/his.14913. Epub 2023 Apr 3.

Abstract

Aims: Patients with primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD, termed PSC-IBD) have a higher risk of harbouring nonconventional and/or invisible dysplasias, especially in the right/proximal colon, than those with IBD alone. We postulated that DNA content abnormality may be frequently detected in the right/proximal colon in PSC-IBD patients, even in the absence of dysplasia, and that this may predispose to progression to nonconventional and/or invisible dysplasias that are often associated with increased rates of aneuploidy and advanced neoplasia.

Methods and results: DNA flow cytometry was performed on 96 morphologically benign colon biopsies taken throughout the colon from 25 PSC-IBD patients during the surveillance colonoscopy that preceded the next procedure that detected dysplasia. Thirty (31%) of the 96 benign colon biopsies in this dysplasia group demonstrated abnormal DNA content, with a propensity for the right/proximal colon (70%) (P < 0.001). In contrast, only one (1%) of 87 benign colon biopsies from 20 IBD patients without neoplasia (control group) demonstrated DNA content abnormality, and it was from the left colon. For analysis per patient, 48% (12 of 25) of the patients in the dysplasia group had abnormal DNA content compared with 5% (1 of 20) of the control group (P = 0.002). Of the 12 PSC-IBD patients with DNA content abnormality, invisible dysplasia was detected in 10 (83%) patients on follow-up, nine (75%) of whom had nonconventional dysplasia.

Conclusion: PSC-IBD patients have an increased risk of developing abnormal DNA content in the right/proximal colon, predating the detection of dysplasia.

Keywords: DNA flow cytometry; aneuploidy; colorectal cancer; dysplasia; inflammatory bowel disease; nonconventional; primary sclerosing cholangitis.

MeSH terms

  • Cholangitis, Sclerosing* / complications
  • Cholangitis, Sclerosing* / diagnosis
  • Cholangitis, Sclerosing* / pathology
  • Colonoscopy / adverse effects
  • Colorectal Neoplasms* / pathology
  • Humans
  • Hyperplasia
  • Inflammatory Bowel Diseases* / complications
  • Inflammatory Bowel Diseases* / diagnosis