High-sensitivity pan-cancer AI assessment of lymph node metastasis via uncertainty quantification

The histological heterogeneity of primary tumors across the pan-cancer spectrum poses a formidable barrier to accurate lymph node metastasis assessment, often causing AI systems to make “overconfident errors” on rare variants that lead to missed diagnoses. To address this, we present UPATHLN, a unified diagnostic platform that synergizes a pathology foundation model-based encoder with a decoupled uncertainty estimation mechanism. We developed and validated the system using a large-scale multicentre dataset of 26,229 lymph nodes from 14 distinct primary origins. In internal validation, UPATHLN achieved an area under the curve (AUC) of 0.986. Crucially, the uncertainty module functioned as a decisive fail-safe: by flagging potential false-negative predictions for mandatory pathologist review, it intercepted all missed diagnoses, securing 100% conditional sensitivity across both the development and independent test cohorts—even for tumors from seven unseen primary origins. Concurrently, this mechanism reduced the review burden on negative lymph nodes by 73.2%. Ultimately, UPATHLN sets a new benchmark for safety-critical AI, demonstrating that explicitly modeling uncertainty is key to unlocking reliable, workload-efficient diagnostics at the pan-cancer scale.