Rare Malignancies: Appendix Cancer: AI- Driven Histopathology and Molecular Biomarker Integration in Biopsy, Chemotherapy, and Immunotherapy Trajectories

Rare appendix malignancies, such as mucinous adenocarcinoma, goblet cell adenocarcinoma, signet-ring cell carcinoma, and appendiceal neuroendocrine tumors, are rare gastrointestinal cancers with diagnostic and treatment challenges due to their histological and molecular diversity. This study presents an explainable Artificial Intelligence (AI)-based approach that integrates digital histological biopsy images, molecular markers, and patient data to enhance disease classification and prediction of response to treatment. A quantitative methodology was used, based on an anonymized dataset of 200 patients with rare appendix malignancies. The performance of machine learning algorithms, such as Logistic Regression, Random Forest, XGBoost, and LightGBM, was compared using Accuracy, Precision, Recall, F1 score, and ROC-AUC metrics, while SHAP and Grad-CAM methods increased model interpretability. LightGBM outperformed all other methods and achieved the highest accuracy (96.2%), F1-score (95.5%), and ROC-AUC (0.987). KRAS, Ki-67, and TP53 were determined to be the most significant predictors from the biomarker analysis and the overall treatment response prediction accuracy of the combined model was found to be 95.1%. These results show that combining digital histopathology, biomarkers, and explainable AI (XAI) can enhance diagnosis accuracy, treatment response predictions, and clinical decision-making in rare appendiceal malignancies.