Objectives: The differential diagnosis of ameloblastoma and odontogenic keratocyst is essential for surgical planning and patient counseling. While deep learning (DL)-based methods show promising potential in this domain, their clinical translation remains challenging due to insufficient interpretability. This study aims to introduce segmentationguided preprocessing approaches to provide support for the clinical implementation of computer-aided diagnosis systems. Methods: This study evaluated the performance of an InceptionV3 model on 128 pathologically confirmed CBCT scans (AME: 64; OKC: 64) by 5-fold cross-validation. Four experimental inputs were compared: (1) Original slice; (2) Bounding-box ROI; (3) Precise segmentation ROI; and (4) Moderately expanded ROI. All models were trained under the same settings. Assessment was conducted on both the slice and patient levels, incorporating accuracy, recall, precision, F1-score, and the area under the receiver operating characteristic curve (AUC). Grad-CAM visualization and confidence curve analysis were employed to verify models’ attention patterns and diagnostic confidence. Results: All models based on segmentation-guided ROI significantly outperformed models based on original slice. The moderately expanded ROI achieved optimal performance. The bounding-box ROI provided competitive performance with higher recall. Grad-CAM confirmed improved attention localization, while confidence curve analysis showed more consistent and reliable prediction patterns across slices. Conclusions: Segmentation-guided preprocessing represents an effective and clinically relevant approach for jaw lesion diagnosis and enhances interpretability.
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