Small Colonic Microsatellite Unstable Adenocarcinomas and High-Grade Epithelial Dysplasias in Sessile Serrated Adenoma Polypectomy Specimens

Department of Anatomic Pathology, William Beaumont Hospital, Royal Oak, MI 48073, USA.
American Journal of Clinical Pathology (Impact Factor: 2.51). 02/2006; 125(1):132-45. DOI: 10.1309/V8Q9-KDD5-AJ9L-NBAG
Source: PubMed


Eight sessile serrated adenoma (SSA), right colon polypectomies with focal invasive adenocarcinoma or high-grade dysplasia were studied to identify features indicating a high risk of transformation and characterize the morphologic features of serrated dysplasia; 6 cases had invasive adenocarcinoma; 2 were high-grade dysplasia. All 8 were microsatellite unstable-high and had absent hMLH1 nuclear immunoreactivity. The mean patient age at polypectomy was 69.5 years (range, 57.1-83.9 years). Mean polyp maximum dimension was 8.5 mm (range, 6-12 mm). The majority of each polyp was nonmalignant SSA. All 8 cases had an abrupt transition from benign to high-grade in situ or invasive malignancy. In the 6 invasive adenocarcinomas, the neoplasm extended directly down into the submucosa without lateral intramucosal spread. The mean maximum dimension of the invasive adenocarcinoma was 2.9 mm (range, 2-4 mm). All 8 cases had high-grade serrated-type dysplasia. The nonmalignant SSAs had marked expansion of the proliferative zone. Crypts adjacent to malignancy had moderately enlarged nuclei, irregular nuclear membranes, and overly prominent nucleoli. SSA crypts were lined by a variety of gastric-type cells; no cell type predominated. Foci of adjacent crypts had similar cytologic features. Small proximal SSAs can transform into adenocarcinoma without a component of adenomatous dysplasia.

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    • "Immunohistochemical staining of SSA with MSI-H and SSA-related cancer tissues indicated a significant loss of MLH1 expression in the SSA-associated high-grade dysplasia region or intra-mucosal carcinoma regions (22). The expression of the mismatch repair gene was lost in SSA adjacent to the cancer tissues or dysplasia regions (23). MGMT is a DNA repair gene, and its methylation and loss of expression have been detected in sessile and traditional serrated pathways, particularly in traditional serrated pathway-associated lesions, such as TSA (24). "
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