Diagnostic Reproducibility of Sessile Serrated Lesions: Histopathological Criteria and Immunohistochemical Correlation with BRAF and Annexin A10 Using a Proposed Scoring System

Abstract To evaluate diagnostic of serrated colorectal lesions using standardized histopathological criteria and immunohistochemical markers (BRAF V600E and Annexin A10) integrated into a proposed morphologic-immunohistochemical scoring system. We performed a retrospective, blinded review of colorectal serrated lesions from institutional archives. Cases were re-evaluated by three gastrointestinal pathologists according to 2019 World Health Organization (WHO) criteria. Morphologic variables (crypt architecture, basal dilation, serration extent, mucinous differentiation, lesion size, and presence of dysplasia) were recorded. Immunohistochemistry for BRAF V600E (VE1 clone) and Annexin A10 was performed when material was available. Associations between markers, morphology and lesion size were tested using chi-square or Fisher's exact test as appropriate. A composite diagnostic score was developed combining morphology, lesion size (> 5 mm) and immunopositivity patterns of the aforementioned markers. Reclassification according to 2019 WHO criteria and application of the composite score showed to be a diagnostic tool in cases of suspicion, considering the actual panorama of morphological assessment alone. BRAF V600E immunopositivity and Annexin A10 expression were significantly associated with lesions of the serrated pathway. Integration of selected morphological features with BRAF and Annexin A10 immunohistochemistry into a structured scoring system enhances may improve diagnostic accuracy for serrated colorectal lesions.