PPGL-Swarm: Integrated Multimodal Risk Stratification and Hereditary Syndrome Detection in Pheochromocytoma and Paraganglioma

Hereditary polyposis syndromes can be precursor lesions to colorectal cancer and are associated with a broad spectrum of extracolonic tumors. Early identification and accurate classification of these syndromes are essential for timely diagnosis, individualized patient management, and targeted surveillance strategies for affected families. However, public endoscopic datasets are largely organized around the individual sporadic polyp, and none links the polyposis phenotype to histopathology and germline findings at the patient level. Here, we present ERCPMP-Gx, an endoscopic, histopathological, and genomic dataset developed to support the application of artificial intelligence (AI) in the recognition, characterization, and classification of colorectal polyposis. Most procedures were performed using the Olympus EVIS X1 system with white-light endoscopy (WLE), narrow-band imaging (NBI), magnifying NBI (M-NBI), and NBI with near focus modes, yielding 160 images and accompanying video clips. Approximately eighty percent of cases represent clinically and/or genetically confirmed hereditary polyposis syndromes (PG), including familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome (PJS), juvenile polyposis syndrome (JPS), and ganglioneuroma syndrome (GNS), while the remaining twenty percent comprise non-hereditary polyps and polyp-mimicking lesions with overlapping morphological features (Non-PG), included to support differential classification. Each released record is linked, where available, to standardized endoscopic annotations, representative histopathology, and clinically reported germline findings, forming an AI-ready, patient-level annotation framework. The dataset is publicly accessible at Mendeley (https://doi.org/10.17632/nzyfc544bx.2). For the latest updates and further information, readers are referred to the DataBioX website: https://databiox.com.

Disease severity classification for genetic conditions is subjective and labor-intensive, creating bottlenecks in genomic screening, where commercial panels vary widely in size and overlap. We developed an autonomous AI agent integrating Reasoning and Acting (ReAct) with Retrieval-Augmented Generation (RAG) to classify 10,211 Human Phenotype Ontology terms. It uses American College of Medical Genetics (ACMG)-endorsed severity guidelines and American College of Obstetricians and Gynecologists (ACOG) quality-of-life criteria to retrieve PubMed literature, generate interpretable reasoning chains, and independently verify claims. At the phenotype level, using expert-curated cohorts, the agent achieved 93.55% accuracy (MCC 0.9237) with 82.6% to 91.4% of claims supported by direct evidence or valid inferences. Gene-level severity was aggregated across 8,738 pairs, identifying 3,283 autosomal recessive pairs with severe or profound presentations. External validation showed 95.2% concordance with Mackenzie's Mission gene list. This system enables standardized panel design by providing reliable, automated classification supported by direct evidence.

The pathological diagnosis of gestational trophoblastic disease(GTD) takes a long time, relies heavily on the experience of pathologists, and the consistency of initial diagnosis is low, which seriously threatens maternal health and reproductive outcomes. We developed an expert model for GTD pathological diagnosis, named GTDoctor. GTDoctor can perform pixel-based lesion segmentation on pathological slides, and output diagnostic conclusions and personalized pathological analysis results. We developed a software system, GTDiagnosis, based on this technology and conducted clinical trials. The retrospective results demonstrated that GTDiagnosis achieved a mean precision of over 0.91 for lesion detection in pathological slides (n=679 slides). In prospective studies, pathologists using GTDiagnosis attained a Positive Predictive Value of 95.59% (n=68 patients). The tool reduced average diagnostic time from 56 to 16 seconds per case (n=285 patients). GTDoctor and GTDiagnosis offer a novel solution for GTD pathological diagnosis, enhancing diagnostic performance and efficiency while maintaining clinical interpretability.