Histopathological and Molecular Features of Adenomatous and Serrated Colon Adenomas, Characteristics and Overlapping Features, Challenges in the Nomenclature

Abstract

Objective: Colorectal cancer develops from precursor epithelial polyps, including tubular adenomas, villous or tubulovillous adenomas, sessile serrated lesions, and traditional serrated adenomas. Although diagnostic criteria for these lesions have been established, overlapping features often complicate classification. This study aimed to define the characteristics and shared features of colorectal adenomas. Material and Methods: A total of 140 adenomas were evaluated, comprising 71 conventional adenomas, 34 sessile serrated lesions, and 35 traditional serrated adenomas. Hematoxylin and eosin-stained slides were reviewed. Macroscopic features, including sessile or polypoid structure, were documented from pathology and endoscopy reports. Histopathological features were assessed first as present or absent, and then by extent using a four-tiered scale (0: less than 10%, 1: 10-25%, 2: 25-75%, 3: more than 75%). Sixteen adenomas with overlapping features were classified as hybrid or unclassified. Molecular studies, including mutation analysis of KRAS, NRAS, and BRAF, as well as microsatellite instability and MLH1 promoter methylation, were performed in 50 cases. Results: No gender predominance was identified. Sessile morphology was most common in sessile serrated lesions and hybrid adenomas. Conventional adenomas showed serration in 50% of cases and ectopic crypts in 23%, though usually involving less than 25% of the lesion. Adenomatous dysplasia was present in most traditional serrated adenomas and nearly half of sessile serrated lesions, while serrated dysplasia occurred in a minority of conventional adenomas. KRAS mutations predominated in conventional (55%) and hybrid adenomas (80%), whereas BRAF mutations were most frequent in sessile serrated lesions (60%) and traditional serrated adenomas (40%); MLH1 promoter methylation was observed across all types, while no NRAS mutations or microsatellite instability were detected. Conclusion: Histopathological features overlapped among all adenoma types, and no single feature was lesion-specific. Applying quantitative thresholds may improve diagnostic accuracy and reduce interobserver variability.