Histologic and molecular diversity and heterogeneity of precancerous lesions associated with inflammatory bowel diseases

Research output: Contribution to journalArticlepeer-review


  • Xianyong Sean Gui
  • Matin Kobel
  • Jose Ferraz
  • Shuhong Liu
  • Young Ou
  • Marco Perrizzolo
  • Robert Winkfein
  • Peter Rambau
  • Douglas Demetrick

Colleges, School and Institutes

External organisations

  • Gastroenterology, University of Calgary, Calgary, AB, Canada.
  • Department of Medicine, University of Washington, Seattle, Washington.


Aims: IBD-associated precancerous lesions may be adenomatous or non-adenomatous with various histomorphologies. We aim to validate the newly proposed classification, to explore the neoplastic nature of the non-adenomatous lesions, and to elucidate the molecular mechanisms underlying the different histomorphologies.

Methods: 44 background precursor lesions identified in 53 cases of surgically resected IBD-associated colorectal and ileal carcinomas were reviewed for the histomorphologic features (classified into adenomatous/type 1, mucinous/type 2, SSA-like/type 3, TSA-like/type 4, differentiated/type 5, eosinophilic/type 6, and serrated NOS/type 7) and analyzed for a key panel of colonic cancer-related molecular markers.

Results: Approximately 60% of the lesions were adenomatous, of which some had mixed serrated, mucinous or eosinophilic changes. The remaining non-adenomatous lesions, including all other types except SSA-like type, mostly showed mixed features and focal adenomatous dysplasia. KRAS mutation and p53 mutant-type expression were found in about half cases across all types, while PIK3CA mutation only in some of adenomatous and eosinophilic lesions, and MLH1/PMS2 loss in a subset of adenomatous, mucinous and eosinophilic but not in differentiated and serrated lesions. SAT-B2 or PTEN loss and IMP3 overexpression were seen in a small subset of lesions. No BRAF, NRAS, or EGFR gene mutation was detected in any type. Certain molecular-morphologic correlations were demonstrated; however, no single or combined molecular alteration(s) was specific to any particular morphologic type.

Conclusions: IBD-associated precancerous lesions are heterogeneous both histologically and molecularly. True colitis-associated adenomatous lesions are unlikely conventional adenomas. Non-adenomatous lesions without frank cytologic dysplasia should also be regarded as neoplastic.


Original languageEnglish
JournalJournal of Clinical Pathology
Publication statusAccepted/In press - 6 Nov 2019


  • inflammatory bowel diseases (IBD), dysplasia, IBD-associated dysplasia, colitis-associated dysplasia (CAD), precancerous lesion, colitis-associated colorectal carcinoma (CACRC)