SAT-493 Comparison of Clinical Features of Pheochromocytoma, Sympathetic Paraganglioma, and Parasympathetic Paraganglioma

Abstract Disclosure: M.D. Lundholm: None. P.P. Rao: None. Introduction: Paragangliomas (PGLs) are neuroendocrine tumors originating from neural crest cells: pheochromocytomas (PCCs) arise from the adrenal medulla, sympathetic chain PGLs (sPGLs) are extra-adrenal in the thorax, abdomen, or pelvis, and parasympathetic chain PGLs (pPGLs) are located in the skull base or neck. We compare clinical features of these rare PGL types. Methods: A single-center retrospective observational study was performed of consecutive patients with pathology-confirmed PGL from 2005 to 2022. Clinical features were obtained by chart review. Comparison of results is ordered (PCC vs sPGL vs pPGL). Results: We identified 371 patients with PGL (67.7% N=251 PCC, 18.7% N=47 sPGL, 19.7% N=73 pPGL). The mean age was 52.2 ± 15.4 yrs and 75.2% were white without significant difference between PGL types. The majority of patients were female in all PGL types, with the greatest percentage in pPGL (58.2% vs 53.2% vs 74.0%, p=0.028). PCC and sPGL tumors were similar in size and larger than pPGL (4.7 ± 2.8 vs 4.6 ± 2.5 vs 2.7 ± 1.8 cm, p<0.001). Overall, a minority (24.3%) had hyperadrenergic symptoms regardless of tumor type, most often with PCC but absent with pPGL (33.1% vs 14.9% vs 0%, p<0.001). The majority of PCC were functional, while pPGL rarely secreted catecholamines (92.9% vs 57.4% vs 8.2%, p<0.001). Of those tested, 43.8% of patients with any PGL type had a positive genetic result. There was a trend toward a higher percentage of hereditary tumors with sPGL, followed by pPGL, then PCC (38.8% vs 60.0% vs 48.7%, p=0.12). With a median of 6.7 yrs of follow up (IQR 4-12 yrs), metastatic disease was significantly more common in sPGL than PCC and pPGL (12.0% vs 29.8% vs 6.8%, p<0.001). Discussion: Over 17 years, most PGL tumors were discovered despite the absence of hyperadrenergic symptoms (>75%), and there was a high prevalence of associated mutations (>40%) underscoring the need for genetic testing in this population. PGLs are a varied group of tumors with distinct clinical features: PCCs were the largest of the PGL tumors and most likely to secrete hormones with hyperadrenergic symptoms, while sPGL and pPGL were more often associated with mutations, and less likely to produce catecholamines or symptoms. While sPGL and pPGL collectively had a higher metastatic risk than PCC (as reflected in many PGL prognostic scoring calculators), it is critical for prognosis and surveillance to distinguish sPGL from pPGL given a greater than 4-fold higher metastatic disease rate in the former. pPGL had the lowest rates of metastasis, just over half of what was seen in PCC. Conclusion: PGL represents a diverse group of tumor types (PCC, sPGL, and pPGL) varying in location, size, hormone production, symptoms, and metastatic rates. sPGL and pPGL are conventionally grouped as “extra-adrenal PGL,” but to do so misses significant features of these diseases, including a clinically relevant difference in metastatic rates. Presentation: Saturday, July 12, 2025