[Superficial serrated adenoma: a clinicopathological analysis of ten cases]

Objective: To investigate the clinicopathological features, immunophenotype and molecular genetics of superficial serrated adenoma (SuSA), and to characterize their diagnostic features. Methods: Ten SuSA cases diagnosed at the First Affiliated Hospital with Nanjing Medical University, Nanjing, China from January 2023 to June 2025 were collected. Their histological morphology was examined. The expression of CK7, CK20, Ki-67, β-catenin, C-MYC and mismatch repair (MMR) proteins, including PMS2, MLH1, MSH2 and MSH6, was assessed using immunohistochemistry, while KRAS and BRAF mutations were studied in 10 cases by using amplification retardation mutation system PCR. Relevant literature was also reviewed. Results: Among the 10 patients, 5 were male and 5 were female, aged 62.0 (53.5, 72.3) years. The tumors were located in sigmoid colon (7 cases), rectum (2 cases), and descending colon (1 case). There were 9 cases of isolated SuSA that had no synchronous colonic lesions, and 1 case of SuSA with synchronous traditional serrated adenoma (TSA). Endoscopically, isolated SuSA was usually presented as small sessile polyps or large flat lateral lesions. Histologically, it showed a characteristic "double-story building" structure, with serrated changes on the surface and adenomatous structures in the deep. The SuSA with synchronous TSA showed TSA-like changes on the surface/tip of the tumor. The serrate region of the surface layer was positive for CK20 and negative for Ki-67, while the adenomatous region of the middle and lower layers showed high expression of C-MYC and Ki-67, nuclear staining of β-catenin, and no expression of CK7 and CK20. The expression of all MMR proteins (MMR intact phenotype) was found in all cases. Molecular profiling of 10 cases showed that 9 tumors harbored KRAS mutations and 1 tumor harbored a BRAF mutation. Conclusions: SuSA is a rare serrated colorectal lesion that predominantly arises in the left colon. It shares overlapping histological features with hyperplastic polyps, TSA and sessile serrated lesions. It is characterized by superficial serration and deep adenomatous changes, which easily lead to misdiagnosis and missed diagnosis. Understanding its histological features and immunohistochemical profile facilitates its diagnosis and differential diagnosis, including CK20 positivity and Ki-67 negativity in the superficial layer, and high Ki-67 expression with negative CK20 staining in the deep layer. KRAS gene mutation is also an important diagnostic feature.