Traditional serrated adenoma: an update

Area of Science:

• Gastroenterology
• Oncology
• Pathology

Background:

• Traditional serrated adenomas (TSAs) have been recognized for 25 years but remain debated diagnostically and biologically.
• Recent advancements have enhanced understanding of TSA morphology and molecular characteristics.

Purpose of the Study:

• To clarify diagnostic criteria for traditional serrated adenomas (TSAs).
• To elucidate the molecular pathways and precursor lesions associated with TSAs.
• To differentiate TSAs from sessile serrated adenomas with dysplasia.

Main Methods:

• Morphological analysis including ectopic crypt foci (ECFs), cytology, and serration patterns.
• Molecular profiling to determine BRAF and KRAS mutation status.
• Analysis of genetic alterations such as TP53, CDKN2A, and mismatch repair enzyme function.

Main Results:

• Ectopic crypt foci (ECFs) combined with specific cytology and serrations improve TSA diagnostic reproducibility.
• TSAs can arise from precursor lesions like hyperplastic polyps and sessile serrated adenomas, particularly BRAF-mutated types.
• Molecularly, TSAs are divided into BRAF-mutated and KRAS-mutated groups, with dysplasia linked to TP53 mutations and Wnt pathway activation.

Conclusions:

• TSAs are distinct from sessile serrated adenomas with dysplasia.
• Despite genetic alterations accompanying dysplasia, mismatch repair enzyme function is retained in TSAs.
• Traditional serrated adenomas (TSAs) represent a significant precursor pathway to aggressive colorectal carcinoma.