Rare-Disease Diagnosis on the ZebraMap Multimodal Case Report Dataset: A Hybrid Pipeline with Grounded Explainability.

Rare-disease diagnosis is difficult because clinicians must identify plausible conditions from a large, severely imbalanced disease space using evidence distributed across clinical narratives, structured findings, and image-linked descriptions. This paper presents a hybrid pipeline with caption-mediated multimodal fusion for ranked rare-disease diagnosis and grounded explanation, developed and evaluated on the ZebraMap multimodal case-report dataset (69,146 structured cases; 1727 diseases). Grouped train-validation-test splitting by source article was applied to prevent leakage, and a sequential pipeline was constructed combining BM25 lexical retrieval, a class-balanced TF-IDF classifier, MedCPT dense retrieval and cross-encoder reranking, caption-based image-aware late fusion, and post hoc grounded explanation generation. The final pipeline achieved test MRR 0.3905 and Recall@10 0.5507 (nDCG@10 0.4273), while the strongest individual component, the class-balanced TF-IDF classifier, reached MRR 0.4200 and Recall@10 0.6279; the hybrid pipeline therefore integrates ranking with grounded explanation rather than maximizing single-metric diagnostic accuracy. On 256 explained cases, the explanation module achieved citation coverage 0.7334 and usefulness 3.8734, exposing a tradeoff between diagnostic accuracy and explanation richness. These results indicate that a hybrid retrieval-and-classification approach can support ranked rare-disease differential diagnosis and that grounded explanation quality can be evaluated quantitatively, extending computational support for the prolonged rare-disease diagnostic process.