Dysplasia in sessile serrated lesions: frequency, interobserver variability and added value of immunohistochemistry

Sessile serrated lesions with dysplasia (SSLd) are direct precursors of colorectal carcinomas (CRCs) but pose a diagnostic challenge. We aim to explore contemporary practice leading to recommendations to improve detection of dysplasia.

(i) The frequency of dysplasia in SSLs was estimated through a nationwide study of individuals undergoing colonoscopy in the Netherlands (2014-2022). Out of 186 427 SSLs, 17 456 showed dysplasia, yielding a frequency of 9.4%. (ii) A national audit evaluating diagnostic practices and interobserver variability revealed diagnostic discrepancies in 11% of SSLd cases, while ancillary immunohistochemistry (IHC) was used by only 20% of participating laboratories. (iii) The additional value of biomarkers (MLH1, p16, p53, beta-catenin and c-myc) was assessed using retrospective (n = 213) and prospective (n = 348) SSL cohorts. MLH1 emerged as the only useful biomarker for identifying dysplasia among SSLs, increasing SSLd diagnoses from 33 to 41 cases in the retrospective cohort (P = 0.008) and from 35 to 43 cases in the prospective cohort (P = 0.013). (iv) Misdiagnosis of SSLd among conventional adenomas was investigated using BRAF IHC in a cohort of 1572 advanced adenomas and was found to be very rare, occurring in only 2 cases.

The diagnosis of SSLd appears to have good reproducibility among pathologists and positive diagnostic trends that are observed in recent years. MLH1 is the only IHC marker with robust clinical utility to identify SSLd that do not meet the morphologic criteria for overt dysplasia but should be used only in selected cases due to its low prevalence.