Identification of predictors of metastatic potential in paragangliomas to develop a prognostic score (PSPGL)

Abstract Context Paragangliomas (PGLs) are rare tumors in adrenal and extra-adrenal locations. Metastasis are found in approximately 5-35% of PGLs and there are no reliable predictors of metastatic disease. Objective To develop a prognostic score of metastatic potential in PGLs. Methods Retrospective analysis of clinical data of a cohort with PGL and tumor histological assessment. Patients were divided into metastatic PGL (presence of metastasis) and non-metastatic PGL (absence of metastasis ≥96 months of follow up) groups. Univariate and multivariate analysis were performed to identify predictors of metastatic potential. A prognostic score was developed based on coefficients of multivariate analysis. Kaplan Meier curves were generated to estimate Disease Specific Survival (DSS). Results Out of 263 patients, 35 patients had metastatic PGL and 110 patients had non-metastatic PGL. In multivariate analysis, four features were independently related to metastatic disease and composed the Prognostic Score of Paragangliomas (PSPGL): presence of central or confluent necrosis (33 points), > 3 mitosis/10 high power field (HPF) (28 points), extension into adipose tissue (20 points) and extra-adrenal location (19 points). PSPGL ≥24 showed similar sensitivity with higher specificity than Pheochromocytoma of the Adrenal gland Scaled Score (PASS) and Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP). PSPGL ≤ 20 was associated with risk of metastasis of ∼10% whereas PSPGL ≥ 40 was associated with ∼80%. The presence of metastasis and Ki-67 ≥ 3% were related to lower DSS. Conclusion PSPGL, composed of four easy-to-assess parameters, demonstrated good performance in predicting metastatic potential and good ability in estimate metastasis risk.