SAT308 An Assessment Of Prognostic Markers To Predict Metastatic Pheochromocytoma/Paraganglioma

Abstract

Abstract Disclosure: M.D. Lundholm: None. E. Berber: None. P.P. Rao: None. Introduction: Pheochromocytoma/paraganglioma (PCC/PGL, or PPGL) are rare neuroendocrine tumors arising from chromaffin cells. Early identification of PPGL with metastatic potential is a diagnostic challenge. More data are needed on features and scoring markers used to predict PPGL metastasis. Methods: A single-center, retrospective observational study was performed of consecutive patients with pathology-confirmed PPGL from 2005 to 2022. Features associated with metastasis were identified and Pheochromocytoma of the Adrenal gland Scaled Score (PASS), Age, Size, Extra-adrenal location and Secretory type (ASES) score, and Size, Genetic, Age, and PASS (SGAP) score were calculated. Results: We identified 371 patients with PPGL (251 PCC, 120 PGL), age 52.2±15.4yrs, 60.6% female, 69.8% incidental. Metastatic disease was reported in 13.2% (N=49; 30 PCC, 19 PGL) associated with younger age (47.3 vs 53.0yrs, p=0.029), larger tumor size (6.3 vs 4.0cm, p<0.001), histologic findings of necrosis (26% vs 2.5%, p<0.001) and vascular invasion (42.1% vs 19.6% p=0.038), hyperadrenergic symptoms at diagnosis (38.8% vs 22.0%, p=0.038), norepinephrine-only secreting tumors (59.6% vs 30.1%, p<0.001), extra-adrenal location (51.0% vs 32.0%, p=0.009), presence of genetic mutations (72.4% vs 38.5%, p<0.001), particularly SDHx (31.0% vs 12.2%, p=0.020) and VHL mutations (24.1% vs 3.8%, p=0.001). There were no significant differences by gender, race, other histologic criteria from PASS, or other mutations such as RET or NF-1. ASES was positive (≥2) in 27.2% (N=100/371) with sensitivity (SN) 79.6%, specificity (SP) 81.1%, positive predictive value (PPV) 39.0%, and negative predictive value (NPV) 96.3% for predicting metastatic disease. PASS and SGAP could only be applied to patients with PCC: PASS was positive (≥4) in 29.7% (N=55/185) with SN 60.0%, SP 73.9%, PPV 21.8%, and NPV 93.8%. SGAP was positive (≥5) in 27.6% (N=32/116) with SN 56.3%, SP 77.0%, PPV 28.1%, and NPV 91.7%. Discussion: Metastatic PPGL is associated with age, tumor size and location, select histologic findings, symptomatic presentation, hormone-secreting pattern, and select genetic mutations. PPGL scoring markers ASES, PASS, and SGAP were all effective at identifying cases with low likelihood of metastasis, but had poor PPV. ASES outperformed PASS and SGAP in test metrics and practicality as the only clinically-derived marker which could be applied to all cases of PPGL. ASES can also be used pre-operatively. Most histologic features and genetic mutations included in PASS and SGAP were not strongly correlated with metastasis, though limited by lower prevalence in the study population. Conclusion: Our data supports the use of ASES alongside data on necrosis, vascular invasion, SDHx and VHL mutations where available to fine-tune our prediction of metastatic potential for PPGL. Presentation: Saturday, June 17, 2023