SUN-269 Spontaneous Regression Of Multiple Paragangliomas

Abstract Disclosure: A. Todd: None. L. Needleman: None. F. Moradi: None. J.P. Annes: None. Background: Paragangliomas (PGL) are hypervascular neuroendocrine tumors that arise from chromaffin cells. While spontaneous PGL regression (SR) is very uncommon, the few published reports almost universally describe only a single lesion with resolution, reduction in tumor volume, or decreased functionality following a clinically distinguishable event such as hemodynamic instability, tumor hemorrhage and/or necrosis, radiation therapy, chemotherapy, or radionuclide therapy. Here, we report a case of multiple PGLs exhibiting spontaneous regression in a patient who did not have any preceding tumor-directed therapy or significant clinical events. Clinical Case: A now 74-year-old woman was diagnosed with hereditary pheochromocytoma/paraganglioma syndrome in 1996 after developing malignant hypertension post-partum. The diagnostic workup at the time revealed bilateral jugular and vagal tumors which were resected via infratemporal craniotomy, and a right carotid body tumor (CBT) which was deemed unresectable but underwent embolization. The patient then presented to our institution in 2022 with worsening hypertension, night sweats, and tachycardia. She also had a history of osteoporosis and began treatment with denosumab six months prior to symptom onset. Subsequent germline sequencing, 4 months after symptom onset, revealed a pathogenic variant in a PGL susceptibility gene, succinate dehydrogenase subunit D (SDHD). Biochemical testing for urine and plasma catecholamine metabolites (including metanephrines) were within normal limits. Functional imaging with PET/CT DOTATATE in 2023 demonstrated the persistence of the right CBT (1.9 x 2.1cm, SUV 28.9), as well as a new mediastinal mass (5.0 x 3.8 cm, SUV 10.3), subcarinal lymphadenopathy, and a new sub-centimeter pulmonary nodule. MRI measurements of the mediastinal mass and CBT were 3.7 x 4.7 x 3.2 cm and 2.2 x 2.1 x 4.6 cm, respectively. The patient preferred nonsurgical management and elected observation with MRI, PET/CT DOTATATE, CBC, and metanephrines measured at regular intervals. A subsequent PET/CT DOTATATE scan in 2024 showed markedly reduced size and reduced uptake across all sites of disease (CBT:∼1.2 cm, SUV 7.3, mediastinal:∼1 cm, SUV 4.6), with complete resolution of uptake in the lymph nodes. MRI confirmed diminished size of the mediastinal mass (2.1 x 1.2 x 1.9 cm) and CBT (1.9 x 1.2 cm). Conclusion: This case might be attributed to immune-mediated SR given the regression of multiple primary tumors and possible metastatic disease. Exploration of mechanisms that explain spontaneous PGL regression could provide insight into SDHD-related tumor homeostasis and aid in the development of novel therapeutic strategies for PGL patients. Presentation: Sunday, July 13, 2025