Advances in laboratory diagnostic studies of pheochromocytoma and paraganglioma

Pheochromocytoma (PCC) and paraganglioma (PGL), collectively referred to as pheochromocytomas and paragangliomas (PPGLs), are rare neuroendocrine tumors characterized by marked genetic susceptibility and substantial biological heterogeneity. Given that all PPGLs are considered to have metastatic potential, early and accurate diagnosis is critical for optimizing therapeutic strategies and improving clinical outcomes. This review summarizes recent advances in the laboratory diagnosis of PPGL. For biochemical testing, plasma free metanephrines measured by liquid chromatography tandem mass spectrometry (LC-MS/MS) are recommended by international guidelines as the preferred first-line screening biomarkers. However, strict control of preanalytical conditions, including patient posture, fasting status, and the standardization of laboratory reference intervals, is essential to ensure diagnostic accuracy. Molecular genetic testing covering more than 20 susceptibility genes, such as SDHx, VHL, and RET, enables molecular classification and risk stratification. Emerging biomarkers, including protein expression profiles, epigenetic alterations, immunohistochemical features, tumor microenvironment characteristics, and multiparametric prediction models, further expand the assessment of tumor aggressiveness and treatment-oriented decision making. In the future, laboratory-test driven integration of multiomics data and artificial intelligence assisted models may facilitate precise diagnosis, dynamic monitoring, and personalized management of PPGLs.