C2LUE: Clinically Aligned Patient-Level Ultrasound Diagnosis via Evidence-Aware Multi-Instance Learning

Patient-level ultrasound diagnosis demands not only high predictive accuracy but also clinically aligned mitigation of asymmetric diagnostic risks. While Multi-Instance Learning (MIL) effectively models routine multi-view exams, standard aggregators often dilute heterogeneous diagnostic cues and optimize solely for global accuracy. This frequently yields undesirable sensitivity-specificity trade-offs. To bridge this gap, we propose C2LUE, a novel MIL framework coupling evidence aware aggregation with risk-aligned regularization. To preserve evidence heterogeneity and prevent unimodal attention collapse, C2LUE employs a multi-query cross-attention mechanism built upon a LoRA-adapted DINOv3 backbone. Multiple latent queries explicitly extract and disentangle diverse morphological patterns from the ultrasound sequence. Furthermore, to improve clinical risk alignment, we introduce a dynamic trade-off regularization objective that penalizes sensitivity-specificity imbalance during training. Rather than leaving the clinical trade-off entirely to post-hoc threshold adjustment, this objective encourages the learned score distribution toward a more balanced operating region. Extensive evaluations on patient-level, biopsy-proven thyroid and breast ultrasound datasets demonstrate that C2LUE consistently outperforms prior alternatives. By uniting strong discrimination with a balanced error profile, C2LUE provides a promising solution for real-world ultrasound screening and diagnosis.