Clinicopathological and molecular analysis of serrated lesions of the appendix

Abstract

A clinicopathological and molecular analysis of serrated lesions of the appendix and the prevalence of incidentally detected serrated lesions of the appendix seen in the Division of Anatomical Pathology, National Health Laboratory Services, Johannesburg, over a five-year period, was performed. To date, there is limited data on the molecular events in serrated proliferations of the appendix, with most data being extrapolated from studies on colorectal serrated proliferations.

The demographics of the patients and the histopathologic characteristics of the serrated lesions were evaluated. Molecular characterisation included immunohistochemistry, polymerase chain reaction and sequence analysis.

A total of ten cases were identified over a period of five years. Sessile serrated lesions/sessile serrated adenomas were seen in 0.14% of all the appendixes received over the five-year study period. All ten cases had characteristic morphological features consistent with a sessile serrated lesion/sessile serrated polyp. The molecular findings were inconclusive, with no definitive association with either BRAF V600E or KRAS codon 12 and 13 mutations. A single case contained a well-described KRAS codon 12 mutation. MLH-1 expression by immunohistochemistry was retained in all ten cases. Two of the ten patients showed microsatellite instability low (MSI-L), with both cases showing a dual peak at the BAT-25 locus. One of the sessile serrated lesions with the MSI-L also had associated BRAF mutations at nucleotide position 1732 (C>Y) and 1798 (A >W).

An overall higher occurrence of sessile serrated lesions compared to other serrated proliferations of the appendix was found. This study highlights the importance of alterations in the MAP Kinase pathway and subsequent microsatellite instability in the pathogenesis of serrated proliferations in the appendix.