TAM-Chain: Multi-Scale Thyroid Cytology Classification via Absorbing Markov Chains and Shannon Entropy Uncertainty Quantification for False-Negative Suppression and Domain-Shift Adaptation

Background: Deep learning models can classify thyroid nodules on ultrasound, but reliable clinical decision support also requires calibrated probabilities, uncertainty estimation, and selective referral, particularly under dataset shift. Methods: We developed a calibrated deterministic five-member deep ensemble for ROI-based thyroid nodule classification and selective image-based triage. TN5000 was used for model development, five-fold cross-validation, member-wise vector-scaling calibration, and fold-specific threshold selection. TN3K served as an independent external dataset-shift evaluation. The framework used ConvNeXt-Tiny with squeeze-and-excitation attention, ensemble-mean malignancy probability, and mutual information (MI) as an ensemble-disagreement score. A three-tier policy assigned images to No-FNA suggestion, FNA recommendation, or radiologist review. Results: On pooled out-of-fold TN5000 predictions, the ensemble achieved AUC-ROC 0.9395, AP 0.9715, ECE 0.0088, and Brier score 0.0813. At 50% nominal MI retention, 7.2% of cases received a No-FNA suggestion, 39.9% an FNA recommendation, and 52.9% radiologist review, with 98.3% No-FNA NPV and 99.83% malignancy capture. On TN3K, AUC-ROC decreased to 0.7870, AP to 0.7254, ECE increased to 0.1899, and Brier score to 0.2281. The frozen TN5000 policy assigned 83.7% to review, 1.0% to No-FNA, and 15.3% to FNA recommendation. No malignant image entered the No-FNA pathway, but FNA-recommendation PPV fell to 76.6%. Conclusion: The framework showed strong internal discrimination and calibration, but limited external threshold transportability. Selective prediction may help identify images unsuitable for automated triage, but local recalibration, threshold validation, and prospective clinical evaluation are required before deployment.

We introduce an in-domain supervised pipeline designed to counter the out-of-distribution performance drop that hampers supervised biomedical NLP models, a problem observed when models trained on pathology reports are moved across cancer registries. Our contribution is a reproducible recipe for training a supervised classifier from routinely collected cancer registry data. It describes how to build the in-domain training set and a production-matched holdout, and to choose operating points that keep the false-negative rate (FNR) very low while keeping reviewer workload manageable. The pipeline standardizes data curation with facility-stratified sampling and separate handling of reports linked to registry cases, and includes a blinded manual audit to estimate positive-case prevalence and label noise. On a 418k-report holdout set, the Kentucky model achieved FNR 0.003 and false-positive rate (FPR) 0.097, improving over the Seattle-trained MOSSAIC OncoID baseline (FNR 0.010, FPR 0.183) and raising F1 from 0.860 to 0.922. In a blinded manual review of 600 reports, estimated positive prevalence declined from 0.500 to 0.398, indicating substantial label noise with errors concentrated in rare primary sites.

Thyroid ultrasound diagnosis requires coordinated lesion localization, measurement, risk stratification and reporting, yet most AI systems address these tasks in isolation and provide limited support for clinical review. We present ThyroidXAgent, a clinician-interactive agentic AI system that coordinates specialized diagnostic tools and stores their outputs as an auditable case-level evidence record. The system was developed using OpenThyroidDB, a multicentre, multitask resource integrating approximately 0.3 million ultrasound images and 24,000 paired reports, and was evaluated on 28,458 non-overlapping test cases, including 8,721 cases from 35 centres in the private NHC-MISD-TUS cohort. Across heterogeneous datasets, ThyroidXAgent achieved a mean Dice score of 87.21 percent for nodule segmentation and a mean AUROC of 0.9466 for benign-malignant classification. The same workflow supported lymph-node metastasis prediction and follicular versus papillary thyroid carcinoma classification, with AUROCs of 0.864 and 0.805, respectively. For report generation, evidence-grounded assembly outperformed multimodal language-model baselines across three cohorts. ThyClinScore, a lesion-level clinical semantic metric introduced here, showed the strongest correlation with a location-aware language-model judge. ThyroidXAgent improved physician classification accuracy, increased report diagnostic consistency from 70.3 percent to 86.2 percent, and reduced segmentation and reporting time by 35.9 percent and 27.4 percent, respectively. These findings support auditable, clinician-correctable agentic AI for thyroid ultrasound diagnosis and reporting.