Serrated Lesions in Inflammatory Bowel Disease: Genotype-Phenotype Correlation

Int J Surg Pathol. 2021 Feb;29(1):46-53. doi: 10.1177/1066896920963798. Epub 2020 Oct 8.

Abstract

Background: Patients with inflammatory bowel disease (IBD) and hyperplastic/serrated polyposis have an increased risk of colorectal cancer. The aim of our study was to elucidate the nature of serrated lesions in IBD patients.

Materials and methods: Sixty-five lesions with serrated morphology were analyzed in 39 adult IBD patients. Lesions were classified according to the WHO 2019 criteria or regarded as reactive, and molecular analysis was performed.

Results: 82.1% of patients had ulcerative colitis, 17.9% had Crohn's disease; 51.3% were female, and the mean age was 54.5 years. The duration of IBD varied significantly (16.7 ± 11.4 years). Endoscopy showed polypoid lesions in 80.3%; the size ranged from 2 to 20 mm. A total of 21.6% of the lesions were located in the right colon. Five lesions were classified as inflammatory pseudopolyps, 28 as hyperplastic polyp, 21 and 2 as sessile serrated lesion without and with dysplasia, respectively, and 9 as traditional serrated adenoma with low-grade dysplasia. Analysis of all true serrated lesions revealed 31 mutations in KRAS and 32 in BRAF gene. No mutations were identified in inflammatory pseudopolyps. In the right colon BRAF mutations were more frequent than KRAS (16 vs 3), while KRAS mutations prevailed on the left side (28 vs 16, P < .001). One patient with traditional serrated adenomas progressed to an adenocarcinoma after 61 months.

Conclusion: The molecular analysis could help discriminate true serrated lesions (IBD-associated or not) from reactive pseudopolyps with serrated/hyperplastic epithelial change. These should help in more accurate classification of serrated lesions.

Keywords: BRAF; KRAS; colorectal carcinoma; histology; molecular analysis; serrated lesions.

MeSH terms

  • Adenoma / diagnosis*
  • Adenoma / genetics
  • Adenoma / immunology
  • Adenoma / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • Colitis, Ulcerative / complications*
  • Colitis, Ulcerative / genetics
  • Colitis, Ulcerative / immunology
  • Colitis, Ulcerative / pathology
  • Colon / diagnostic imaging
  • Colon / pathology
  • Colonic Neoplasms / diagnosis*
  • Colonic Neoplasms / genetics
  • Colonic Neoplasms / pathology
  • Colonic Polyps / diagnosis*
  • Colonic Polyps / genetics
  • Colonic Polyps / immunology
  • Colonic Polyps / pathology
  • Colonoscopy
  • Crohn Disease / complications*
  • Crohn Disease / genetics
  • Crohn Disease / immunology
  • Crohn Disease / pathology
  • DNA Mutational Analysis
  • Diagnosis, Differential
  • Female
  • Genetic Association Studies
  • Humans
  • Immunohistochemistry
  • Intestinal Mucosa / diagnostic imaging
  • Intestinal Mucosa / pathology
  • Male
  • Middle Aged
  • Mutation
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • KRAS protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins p21(ras)