EP1222 - ECE_2023 - Multifocal paraganglioma in Von Hippel-Lindau syndrome: a diagnostic conundrum unfolded through multimodal investigation
TL;DR
A 42-year-old female with no personal or family history of PPGL presented with flank pain and urinary symptoms, and further evaluation revealed a unifying diagnosis of Von Hippel-Lindau (VHL) syndrome, a rare autosomal dominant disorder associated with multifocal neuroendocrine tumours.
Abstract
We present a diagnostically complex case of multifocal phaeochromocytoma and paraganglioma (PPGL), initially suggestive of metastatic disease. Further evaluation revealed a unifying diagnosis of Von Hippel-Lindau (VHL) syndrome. A 42-year-old female with no personal or family history of PPGL presented with flank pain and urinary symptoms. CT imaging revealed a 4.3 cm atypical right adrenal lesion. Endocrinology review noted episodic hypertension, sweating, and palpitations. Biochemistry showed elevated plasma normetadrenaline (5.51 nmol/L) and metadrenaline (0.34 nmol/L). Alpha blockade with doxazosin was initiated. Functional imaging (MIBG, FDG PET, somatostatin receptor scintigraphy) confirmed pheochromocytoma. Additional lesions included a 1 cm left para-aortic mass, a non-avid left adrenal nodule (likely adenoma), and a right retrothyroidal neck lesion—all showing uptake on functional imaging. Thyroid ultrasound revealed a U5 lesion, raising concern for metastatic PPGL. Cytology of the neck lesion confirmed a head and neck paraganglioma. Further imaging identified benign liver haemangioma and bilateral renal parapelvic cysts, prompting genetic testing. Genetic analysis revealed a heterozygous pathogenic VHL mutation: NM_000551.3:c.250G>A; p.(Val84Met), confirming the diagnosis of VHL syndrome. A heterozygous pathogenic VHL mutation was found, making multifocal PPGL more likely. However, the distribution of neuroendocrine lesions was still concerning for metastatic PPGL. Patient underwent uncomplicated laparoscopic right adrenalectomy. Histology confirmed pheochromocytoma with classic Zellballen architecture, chromogranin and synaptophysin positivity, and a low Ki-67 index (<2%), consistent with benign behaviour. Persistently elevated normetanephrines led to excision of the left para-aortic lesion, with histology confirming paraganglioma and biochemical normalization. Surveillance imaging remains unremarkable, excluding metastatic disease. VHL syndrome is a rare autosomal dominant disorder associated with multifocal neuroendocrine tumours. Though sporadic VHL mutations are rare, clinical awareness can aid diagnosis. PPGL in VHL mostly presents as benign multifocal disease but in rare cases can be metastatic.