DNA content analysis of colorectal serrated lesions detects an aneuploid subset of inflammatory bowel disease‐associated serrated epithelial change and traditional serrated adenomas

Aims Serrated lesions ( SL s), including sessile serrated adenoma ( SSA ) and traditional serrated adenoma ( TSA ), are important premalignant lesions for colorectal cancer ( CRC ). Although a small subset of SL s are known to harbour TP 53 mutations and Wnt/β‐catenin pathway activation, suggesting that they may develop dysplasia or CRC via a ‘chromosomal instability ( CIN )‐like’ pathway, it is unclear if aneuploidy (characteristic of conventional adenoma) ever develops in SL s and is associated with development of dysplasia or CRC , in this context. Methods and results DNA flow cytometry was performed on 31 inflammatory bowel disease ( IBD )‐associated SL s without dysplasia [including 10 non‐targeted ‘serrated epithelial change’ ( SEC ), 14 SSA s and seven hyperplastic polyps ( HP s)] as well as 48 dysplastic SSA s and TSA s. One (10%) of 10 SEC cases demonstrated aneuploidy and subsequently developed high‐grade dysplasia ( HGD ) within 4 months, whereas the remaining SEC cases showed normal DNA content without evidence of dysplasia or CRC on follow‐up. One (3.3%) of 30 TSA s without HGD and two (66.7%) of three TSA s with HGD also showed aneuploidy, but no patient developed CRC . By contrast, all SSA s (with or without dysplasia) and HP s showed normal DNA content, but four SSA cases still developed dysplasia or CRC on follow‐up. Conclusions Unlike SSA s and HP s, a small subset of SEC and TSA cases demonstrated aneuploidy, suggesting that they can develop neoplasia via the CIN pathway. DNA content analysis of a larger number of SEC cases, with adequate follow‐up, may allow for a more precise determination of aneuploidy incidence and neoplasia risk.