Abstract
<title>Abstract</title> <p>Background: Superficial non-ampullary duodenal epithelial tumors (SNADETs) are rare neoplasms whose progression remains poorly understood. While tuft cells, identified by POU domain class 2 transcription factor 3 (POU2F3) expression, have been implicated in gastrointestinal epithelial homeostasis and tumorigenesis, their role in SNADETs remains unclear. Methods: We retrospectively analyzed endoscopically and surgically resected SNADETs. Tuft cells were quantified as the total number of POU2F3-positive epithelial cells in five high-power fields. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value for predicting high-grade lesions. Associations between histological grade (Vienna classification), tuft cell count, and mucin phenotype were assessed, and multivariable logistic regression analysis was performed. Results: Among 100 identified SNADETs, 93 were analyzed after excluding seven with inadequate histological evaluation. Tuft cell count was significantly lower in high-grade histology (categories 4/5) than in low-grade histology (category 3) (p < 0.001). ROC analysis identified two tuft cells as the optimal cutoff for predicting high-grade histology (area under the curve = 0.88), with low tuft cell count (< 2 cells) significantly associated with high-grade histology (p < 0.001). Gastric mucin phenotype was also associated with high-grade histology (p < 0.01). In multivariable analysis, low tuft cell count (odds ratio [OR]: 91.0, p < 0.001) and gastric mucin phenotype (OR: 24.9, p = 0.0077) were independently associated with high-grade histology. The association between low tuft cell count and high-grade histology persisted after excluding gastric-type phenotype. Conclusions: Decreased tuft cell count was independently associated with high-grade histology in SNADETs, regardless of mucin phenotype. Tuft cells may serve as histological markers reflecting tumor grade and aid risk stratification.</p>