A 58-year-old gentleman who was otherwise well presented with urinary symptoms. As part of his investigation for this he underwent a CT scan which showed an incidental 6 cm right adrenal mass compressing the inferior vena cava and superior pole of the right kidney with a 6-mm pulmonary nodule. He was subsequently found to have a raised urinary normetanephrine of 48.81 (normal range 03.3) suggestive that the mass was a pheochromocytoma. Retrospectively he reported episodes of flushing, sweating, headaches and diarrhoea. Examination was unremarkable with a blood pressure of 136/84 and he did not take any medications including anti-hypertensives. An MIBG scan showed uptake within the adrenal mass. Having been established on phenoxybenzamine he underwent a radical adrenalectomy with right nephrectomy as there was invasion into the perinephric fat. On histological review the excision appeared complete and the tumour cells strongly expressed CD56, chromogranin, synaptophysin and NSE and S100 highlighted sustentacular cells, all of which supported a diagnosis of pheochromocytoma. The Ki-67 proliferation index was <2% suggesting low mitotic activity within the tumour. However, the tumour showed focal extension through the capsule and into the perinephric fat with lympho-vascular invasion within the large vessels of the perinephric fat and within the surrounding fibrous capsule. This histology gave an overall PASS of 6/20 with a score of <4 indicating a tumour will behave in a benign fashion. A gene panel test was performed which revealed a variant of unknown significance in the SDHA gene. Immunostaining showed loss of SDH expression suggesting this was pathogenic. Post-operatively he has had follow-up CT scans with 24 hour urinary normetanephrine and gut hormone measurements at 2 months and 1 year. These have shown no evidence of residual or recurrent disease and stable appearance of the 6mm pulmonary nodule. He reports complete resolution of his symptoms.
Conclusions: Genetic predisposition to pheochromocytomas and paragangliomas is well recognised. The SDHA gene codes for one of the four subunits of the succinate dehydrogenase enzyme which converts succinate to fumarate. It is a tumour suppressor gene and alterations in this gene have been associated with pheochromocytomas and paragangliomas. The particular variant in this case has not previously been reported so it is therefore uncertain whether this alteration is associated with an increased risk of tumour development, however loss of immunostaining suggests it is pathogenic. This case also suggests that SDHA mutation associated pheochromocytoma can exhibit malignant behaviour.
16 - 18 Apr 2018
Society for Endocrinology