OR08-04 Paradigm Shift In SDHAF2-Related Familial Paraganglioma Syndrome
Authors: Fernandez-Pombo Antia , Rodriguez-Carnero Gemma , Mato Noelia Otero , Cameselle Teijeiro Jose Manuel , Loidi Lourdes , Seoane Zulema Nogareda , Nunez Virginia Pubul , Martinez Olmos Miguel Angel , Cabezas Agricola Jose Manuel 
Published: October 2023

Disclosure: A. Fernandez-Pombo: None. G. Rodriguez-Carnero: None. N. Otero Mato: None. J. Cameselle Teijeiro: None. L. Loidi: None. Z. Nogareda Seoane: None. V. Pubul Nunez: None. M. Martinez Olmos: None. J. Cabezas Agricola: None.

Introduction: The recommendations of the clinical practice guidelines regarding the management of SDHAF2-related familial paraganglioma syndrome are based on what is described in the literature in relation to two carrier families of the p.Gly78Arg variant in this gene. To date, among other characteristics, paragangliomas (PGLs) have been thought to occur exclusively in the head and neck, with no metastatic disease observed. Objective: To describe the clinical profile of SDHAF2-related familial paraganglioma syndrome in order to increase knowledge of this disorder. Subjects and Methods: A total of 64 individuals were evaluated after the detection of 7 index cases with the same pathogenic variant (p.Gly78Arg) in the SDHAF2 gene. The clinical data of the 46 patients found to be carrying this variant were collected. In addition to the molecular study, these patients underwent a biochemical evaluation, as well as anatomical imaging. PET with 68Ga-DOTA- TOC and 18F-DOPA were also carried out. The surgical specimens were analyzed. Results: A total of 27 patients developed the disease, with a mean age of 37.0 ± 17.2 years at diagnosis (59.2% women). Inheritance in affected patients was of paternal origin in all known cases. All patients manifested PGLs in the head and neck (96.3% carotid bifurcation, 25.9% jugulotympanic and 14.8% glomus vagale), with a high frequency of multifocality (85.2%). Six patients also manifested mediastinal PGLs (retrocardiac, paraaortic, epicardial, paratracheal, phrenic nerve) and two normetanephrine-secreting pheochromocytomas. All extraadrenal PGLs were non-functioning, with the exception of one case with hypersecretion of 3-methoxytyramine. Throughout the follow-up, three patients manifested distant metastasis (bone and lung metastases). Surgical treatment occurred in 85.1% of cases, radiotherapy in 29.6%, radiosurgery in 14.8% and sunitinib in one case, and 58.3% patients reported some type of complication. 68Ga-DOTA-TOC PET was superior to 18F-DOPA PET in identifying extraadrenal PGLs and metastatic involvement, with an overall detection rate of 100% in the case of 68Ga-DOTA-TOC PET (SUVmax 87.6 ± 60.3 g/ml) and 61.0% in the case of 18F-DOPA PET (SUVmax 19.0 ± 16.2 g/ml), p &lt;0.0001. Regarding the immunohistochemical analysis, no positivity for SDHB was observed and Ki-67 index was &lt;3% in all cases. Conclusions: Certain phenotypic variations have been observed in the current study regarding SDHAF2-related familial paraganglioma syndrome, which have not previously been described and which will contribute to modifying the management of this disease.

Presentation: Friday, June 16, 2023