Mediastinal paragangliomas related to SDHx gene mutations

Abstract

IntroductionParagangliomas (PGLs) related to hereditary syndromes are rare mediastinal tumors. Paragangliomas are caused by mutations in genes encoding subunits of succinate dehydrogenase enzyme (SDH).AimTo evaluate clinical, anatomical and functional characteristics of mediastinal paragangliomas related to SDHx gene mutations.Material and methodsRetrospective analysis of 75 patients with confirmed SDHx gene mutations (24 patients with SDHB, 5 SDHC, 46 with SDHD mutations) was performed. Patients underwent evaluation using computed tomography (CT), somatostatin receptor scintigraphy (SRS) (99mTc-[HYNIC,Tyr3]-octreotide), 123I mIBG scintigraphy and urinary excretion of total methoxycatecholamines.ResultsOut of 75 patients, 16 (21%) patients (1 SDHB, 15 SDHD mutations) had 17 PGLs localized in the mediastinum. Fourteen PGLs were localized in the middle mediastinum (intrapericardial) and 3 PGLs in the posterior mediastinum. The median diameter of paragangliomas measured on the axial slice was 24.3 mm (interquartile range (IQR): 14.7–36.6), and the median volume was 2.78 ml (IQR: 0.87–16.16). Twelve out of 16 patients (75%) underwent SRS, and 11 of them (92.3%) had pathological uptake of the radiotracer. Eleven (68.75%) out of 16 patients underwent 123 I mIBG, with only 3 positive results. Symptoms of catecholamine excretion were observed in 3 patients with PGLs localized in the posterior mediastinum. All PGLs were benign except in 1 patient with the SDHB mutation and PGL detected in the posterior mediastinum, who had a metastatic disease.ConclusionsMost mediastinal paragangliomas were related to SDHD gene mutations. They were asymptomatic, localized in the medial mediastinum, intrapericardially.

Update on Adrenal Tumours in 2017 World Health Organization (WHO) of Endocrine Tumours

“…Sympathetic paraganglioma could be seen in retroperitoneum around the adrenal/renal area, around the organ of Zuckerkandl or in the urinary bladder [75,80]. The other sympathetic paragangliomas are noted in the thorax, heart and other locations [81][82][83]. Sympathetic paragangliomas are more likely to be functioning when compared to head & neck paragangliomas [84].…”

Succinate: An initiator in tumorigenesis and progression

“…Although succinate is known as a classic “housekeeping gene”, SDH mutations are commonly found in a series of neoplasms and different subunit mutations can lead to different types of tumors. It is noteworthy that most mediastinal paragangliomas (PGLs) were related to SDHD gene mutations [ 33 ], whereas germline mutations of SDHB and SDHC play a minor role in sporadic head and neck paraganglioma [ 34 ]. To date, the genomics research on PGL/PCC has demonstrated that mutations of SDHD and SDHC cause PGL1 and PGL3, while PGL4, PGL5, and PGL2 are associated with mutations in the large subunit genes SDHB, SDHA and SDHAF2, respectively [ 35 ].…”

Challenges in the surgical treatment of undiagnosed functional paragangliomas

“…Complications associated with extremely high BP include cerebrovascular hemorrhage, heart failure, arrhythmias, and myocardial infarction. [ 8 ] Notably, 50% to 80% of patients with PGs are asymptomatic and the diagnosis is usually incidental or related to wider effects caused by the tumor. [ 9 – 11 ] Although the current patient had symptoms of hypertension and cerebral hemorrhage, the possible involvement of a mediastinal tumor had not been considered during preoperative diagnosis or treatment.…”