Comparative validation of assessment criteria for Crohn-like lymphoid reaction in colorectal carcinoma

Aims Crohn-like lymphoid reaction (CLR) in colorectal carcinoma (CRC) is associated with a favourable prognosis and microsatellite instability-high (MSI-H) status. However, there is a lack of consensus on optimal criteria for CLR assessment. The aim of this study was to comparatively validate traditional and novel assessment criteria for CLR. Methods CLR status in 212 MSI-H CRCs was assessed independently by two pathologists using three different criteria: (1) traditional semiquantitative criteria (Graham–Appelman criteria), (2) the largest lymphoid aggregate (LA) size-based criteria (Ueno criteria) and (3) LA density-based criteria (Vayrynen–Makinen criteria). Results Among the three criteria, the Vayrynen–Makinen criteria-based CLR assessment showed the best interobserver agreement (κ value, 0.71; intraclass correlation coefficient, 0.76). Pathologically, intense CLR (grade 2) by Graham–Appelman criteria, active CLR (largest LA size ≥1 mm) by Ueno criteria and high-density CLR (≥0.38 LAs/mm) by Vayrynen–Makinen criteria significantly correlated with an early cancer stage (stage I/II). In Kaplan–Meier analysis, both CLR statuses determined by Ueno criteria and Vayrynen–Makinen criteria were associated with significant differences in disease-free survival in MSI-H CRC patients (p=0.005 and p=0.001, respectively). In multivariable analysis, both active CLR and high-density CLR proved to be independent favourable prognostic factors in MSI-H CRC (HR, 0.47; 95% CI 0.24 to 0.9 for active CLR and HR, 0.5; 95% CI 0.28 to 0.89 for high-density CLR). Conclusions Our study confirms that the two recently suggested criteria (Ueno criteria and Vayrynen–Makinen criteria) for CLR assessment are fairly reproducible methods and can serve as superior prognosticators in CRC.