ESPE Abstracts

Introduction: Paragangliomas are rare neuroendocrine neoplasms, that derive from the chromaffin cells of the neural crest. They originate from the extra-adrenal paraganglia and are divided into sympathetic and parasympathetic. They are classified into three different molecular clusters, depending on the underlying gene mutations, in any of at least 20 identified genes: cluster I Pseudo-hypoxia, cluster II Kinase signaling, cluster III Wnt signaling. Half of these cases are caused by mutations of cluster 1 succinate dehydrogenase (SDHx) genes. According to W.H.O. paragangliomas should be treated as potentially metastatic diseases.

Case presentation: A 17-year-old female patient, presented with sudden, periumbilical abdominal pain, that reflected in the right iliac fossa. Magnetic resonance imaging (MRI) revealed a 2cm para-aortic mass with characters suggestive of lymph node. During surgical excision of the mass, the patient had a hypertensive spike that was treated with an increase in anesthesia. The postoperative course was completely satisfactory. However the biopsy revealed a malignant paraganglioma with score GAPP 7. The patient came to our department for further evaluation and follow-up. Clinical examination revealed no symptoms of catecholamine hypersecretion, nor she reported anything remarkable in the past, except for occasional headaches attributed to an intensive study program. Laboratory testing for catecholamines was within normal range, but due to her young age additional histological immunohistochemistry testing was requested, that revealed complete absence of staining for the SDHB subunit. Genetic analysis carried out employing Exome Sequencing identified the novel heterozygous variant c.201-2A>G in the SDHB gene, maternally inherited. This variant affects the intron2/exon3 splice site of the SDHB gene and was classified as Pathogenic according to ACMG criteria and SDHB variant classification recommendations. Six asymptomatic family members were also found to be carriers of the mutation, sugesting low penetrance. The patient is currently free of disease, according to laboratory and imaging tests and monitored according to guidelines.

Conclusions: We report a novel SDHB gene pathogenic variant in a young patient with paraganglioma. Hereditary paragangliomas frequency is the highest among all types of neoplasms. Genetic testing provides information on the diagnostic and therapeutic approach, while planning the follow-up program for the risk of recurrence and metastases after initial treatment. In children and adolescents with paraganglioma due to the SDHB gene pathogenic variants, the likelihood of developing metastases in the first 5 years from initial diagnosis is extremely increased, with a greater proportion of these occurring in bones and lifelong follow-up is recommended.