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Thank you for visiting nature. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser or turn off compatibility mode in Internet Explorer. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Adult and paediatric patients with pathogenic variants in the gene encoding succinate dehydrogenase SDH subunit B SDHB often have locally aggressive, recurrent or metastatic phaeochromocytomas and paragangliomas PPGLs.
PPGLs with SDHB pathogenic variants are often less differentiated and do not produce substantial amounts of catecholamines in some patients, they produce only dopamine compared with other hereditary subtypes, which enables these tumours to grow subclinically for a long time. In addition, SDHB pathogenic variants support tumour growth through high levels of the oncometabolite succinate and other mechanisms related to cancer initiation and progression.
As a result, pseudohypoxia and upregulation of genes related to the hypoxia signalling pathway occur, promoting the growth, migration, invasiveness and metastasis of cancer cells. These factors, along with a high rate of metastasis, support early surgical intervention and total resection of PPGLs, regardless of the tumour size. The treatment of metastases is challenging and relies on either local or systemic therapies, or sometimes both.
The adrenal medulla is the main hormonal unit of the autonomic nervous system and it arises from neural crest-derived Schwann cell precursors. The Schwann cell precursors migrate along the preganglionic autonomic fibres until they reach their final destination 1 , 2.