AD05 Case report: A rare H3F3A gene mutation causing recurrent paragangliomas and giant cell tumours of the spine

Abstract

Somatic mutations in the H3F3A gene are most commonly implicated in the pathogenesis of giant cell tumours of bone but have also been associated with the development of bilateral pheochromocytomas and bladder and para-aortic paragangliomas. Due to the rarity of this mutation, evidence guiding clinical management remains limited. A 55-year-old asymptomatic man was referred to the endocrinology department following the incidental discovery of a right adrenal lesion. His medical history included polymyalgia rheumatica and recurrent giant cell tumours of the spine. An incidental bladder lesion was identified and resected by transurethral resection of bladder tumour (TURBT). Following local recurrence, repeat surgery confirmed bladder paraganglioma on histopathological examination. Metaiodobenzylguanidine (MIBG) scintigraphy demonstrated successful treatment of the bladder lesions but persistent uptake within both adrenal glands. Plasma metanephrines and urinary metadrenalines remained within the reference range, indicating non-functioning lesions. Initial R223 genetic testing was negative; however, further evaluation by the clinical genetics service identified a mosaic H3F3A mutation. Following multidisciplinary discussion within the local neuroendocrine tumour team, surveillance with 6-monthly flexible cystoscopy, annual plasma metanephrines, and whole-body magnetic resonance imaging every 2–3 years was recommended. The coexistence of recurrent giant cell tumours and multifocal paragangliomas should raise suspicion for rare genetic syndromes, even when initial targeted genetic testing is negative. Mosaic H3F3A mutations represent an uncommon cause of hereditary predisposition and may require comprehensive genetic evaluation for diagnosis. This case highlights the importance of considering H3F3A mutations in patients with recurrent giant cell tumours and multifocal paragangliomas. Additional case reports and multicentre experience are needed to improve understanding of the natural history of this rare condition and to establish evidence-based recommendations for surveillance and individualized management.