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

TL;DR

PPGL-Swarm is an AI-driven diagnostic system that automates and enhances risk stratification and hereditary syndrome detection in PPGL tumors, addressing limitations of current manual methods and providing an interpretable, comprehensive report.

Contribution

The paper introduces PPGL-Swarm, a novel agentic system that automates GAPP scoring, incorporates genotype information, and offers an interpretable diagnosis process for PPGLs.

Findings

Automates GAPP scoring with quantified features

Integrates genotype risk alerts into diagnosis

Provides an auditable, multimodal report

Abstract

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors, of which 15-25% develop metastatic disease with 5-year survival rates reported as low as 34%. PPGL may indicate hereditary syndromes requiring stricter, syndrome-specific treatment and surveillance, but clinicians often fail to recognize these associations in routine care. Clinical practice uses GAPP score for PPGL grading, but several limitations remain for PPGL diagnosis: (1) GAPP scoring demands a high workload for clinician because it requires the manual evaluation of six independent components; (2) key components such as cellularity and Ki-67 are often evaluated with subjective criteria; (3) several clinically relevant metastatic risk factors are not captured by GAPP, such as SDHB mutations, which have been associated with reported metastatic rates of 35-75%. Agent-driven diagnostic systems appear promising, but most lack traceable reasoning for decision-making and do not incorporate domain-specific knowledge such as PPGL genotype information. To address these limitations, we present PPGL-Swarm, an agentic PPGL diagnostic system that generates a comprehensive report, including automated GAPP scoring (with quantified cellularity and Ki-67), genotype risk alerts, and multimodal report with integrated evidence. The system provides an auditable reasoning trail by decomposing diagnosis into micro-tasks, each assigned to a specialized agent. The gene and table agents use knowledge enhancement to better interpret genotype and laboratory findings, and during training we use reinforcement learning to refine tool selection and task assignment.