A case of metastatic paraganglioma on a background of SDHB mutation

LD Boyle1, Y Du2, AR Sankey3, DL Morganstein1,2

1Department of Endocrinology and Metabolic Medicine, Chelsea and Westminster Hospital NHS Foundation Trust

2Department of Nuclear Medicine and PET/CT, The Royal Marsden NHS Foundation Trust

3Department of Trauma and Orthopaedics, Chelsea and Westminster Hospital NHS Foundation Trust

Abstract: We present the case of an SDHB mutation carrier with metastatic paraganglioma, which exemplifies the importance of multidisciplinary working when faced with diagnostic uncertainty.

This 55 year old lady (with a PMH of HTN with white coat effect, T2DM & dyslipidaemia) underwent surgical resection of a retroperitoneal functional paraganglioma in September 2010. Post-op urinary catecholamines and fasting gut hormone profile were normal.

In 2014 urinary normetadrenaline was marginally elevated (2.34 μmol/24h), raising the suspicion of recurrence or a second paraganglioma. Neither MIBG nor MRI were suggestive of recurrence, although there was signal change adjacent to the right ovary – subsequent pelvic US showed normal ovaries but one 25x24x21mm focal posterior fundal subserosal fibroid. HTN continued to be managed by standard approaches. By December 2016 normetadrenaline was 3.79 μmol/24h.

She experienced back pain while gardening, and MRI spine in February 2017 demonstrated some oedema at L5, thought secondary to disc degeneration. Given SDHB mutation status, Ga-68 DOTATATE PET/CT was arranged in July 2017. There was DOTATATE uptake at L5 and in the right humerus. Plain radiographs of the humerus were normal, and our expert musculoskeletal radiologist felt appearances on subsequent serial MRI scanning of her spine were not typical of metastasis.

During 2018 normetadrenaline climbed to 5.9 μmol/24h and she was discussed in both the Royal Marsden Neuroendocrinology MDT and Spinal MDT at St George’s. Repeat Ga-68 DOTATATE PET/CT showed stable L5 disease, but a new aortocaval node. The L5 soft mass was biopsied in June 2018 and confirmed a metastatic NET. By then an MRI humerus was also suspicious for a mass in the humeral diaphysis, but she was asymptomatic with Mirels’ score <9 when reviewed by T&O.

In February 2019, the Spine Clinic noted that the L5 tumour had grown from 21 to 29mm, was intruding into the spinal canal, and may have been largely responsible for a plasma normetanephrine of 3792 pmol/L, consistent with urinary normetadrenaline levels at 2-3 times the upper limit of normal. Her L5 disease was resected, and metastatic paraganglioma with low proliferation index confirmed. Her BP normalised to the extent that antihypertensive therapy could be withdrawn. With no evidence of residual disease in L5, after discussion at the CyberKnife MDT, stereotactic body radiotherapy was commenced in July 2019.

In April 2020 a DOTATATE PET scan showed mild progression at the known sites of disease, and she was commenced on Lanreotide, with a dose reduction to 60mg monthly due to side effects. A repeat DOTATATE PET in November 2020 has shown minor progression at T6 with the other sites stable.

This case illustrates a number of challenges in long term follow up of patients with paraganglioma, including interpreting the significance of imaging findings and distinguishing metastatic disease from other non-paraganglioma pathology. We will also discuss the available therapeutic options.