Rare and complicated functional posterior mediastinal paraganglioma

Background

Mediastinal paragangliomas (PGs) are highly vascular, neuroendocrine tumours originating from chromaffin tissue in extra-adrenal sympathetic ganglia. PGs account for 0.3% of mediastinal tumours.1 Functional PGs, that is, catecholamine-secreting PGs, are even more rare with only approximately 50 reported cases in literature.2 Patients with functional PGs present with hypertension, diaphoresis, palpitations and/or headaches with elevated levels of norepinephrine and normetanephrine.3 A single-stage open resection is often used in patients with functional PGs due to the risk of intraoperative catecholamine surges (ICS) during tumour manipulation.3 However, the involvement of major blood vessels and invasion into surrounding structures can complicate resection, and presurgical embolisation of the tumour’s blood supply can help decrease intraoperative bleeding.4 5

Moreover, only a few cases to date have used robotic-assisted thoracoscopy (RAT) for the resection of posterior mediastinal masses. These cases, however, were non-functional PGs6 or did not report major blood vessel involvement.2 We report a unique case of a patient with a functional, subcarinal PG with arterial supply from large branches of the right coronary artery (RCA) and bronchial arteries, and mass effect on the left atrium. We successfully implemented a multidisciplinary and multistage approach involving preoperative embolisation and RAT tumour mobilisation.

Case presentation

An African American man in his 30s presented to the emergency department (ED) with chest pain, seizure-like event, diaphoresis, tongue-biting, incontinence and sudden loss of consciousness. The patient had no history of seizure-like events and was seen 1 week prior in the ED for self-resolving headache, vomiting and elevated blood pressure with unremarkable neurology workup and imaging. On initial examination, the patient’s blood pressure was 142/94 mm Hg, and his cardiovascular and neurological examinations were unremarkable. His family history was significant for migraines and cerebrovascular events.

Investigations

Initial laboratory analysis showed normal complete blood count, metabolic panel and thyroid stimulating hormone levels. ECG revealed prolonged QT interval and cardiac biomarkers were normal. Chest X-ray showed no evidence of acute cardiopulmonary disease. CT angiography (CTA) of the chest showed a 5.7 cm hypervascular middle mediastinal mass with central necrosis and mass effect on the left atrial roof, with no signs of mediastinal metastasis (figure 1A,B). The mass was supplied by hypertrophied bronchial arteries and a large aberrant branch of the proximal RCA. Cardiac MRI showed that it was a mediastinal tumour growing towards the heart without appreciable invasion or obstruction of pulmonary veins and pericardium. Urine and blood chemistry analysis revealed significant elevation (>3× upper limit of normal) in norepinephrine, normetanephrine, dopamine and chromogranin A levels, which were diagnostic of functional PG. To confirm the diagnosis and look for metastatic disease, a PET GA68 Dotatate scan was performed. It showed intense radiotracer uptake associated with the subcarinal mass as well as a periaortic abdominal mass (figure 2).

Differential diagnosis

Differential diagnosis for the patient included neurological aetiology (migraine, stroke, seizure), endocrine abnormalities (hyperthyroidism, hypoglycaemia, carcinoid syndrome, phaeochromocytoma/paraganglioma), cardiovascular disease (ischaemic heart disease, arrhythmia) and panic attack. Emergent neurological and cardiovascular aetiologies, hypoglycaemia and hyperthyroidism were lower on the differential diagnosis list given the unremarkable (1) cardiovascular and neurological physical examination, (2) thyroid stimulating hormone and triiodothyronine (T3)/ thyroxine (T4) levels, (3) metabolic panel and (4) chest X-ray, cardiac biomarkers and ECG. Additionally, the patient was seen in the ED for headache, nausea and hypertension 1 week prior to this visit, and 6 months prior patient presented with headache, photophobia, nausea, vomiting and dizziness. This increased our suspicion for endocrine abnormalities, namely carcinoid syndrome or phaeochromocytoma/paraganglioma. Further imaging and labs showed that the patient had a mediastinal mass with intense radiotracer uptake of GA68, and had elevated urine and blood levels of norepinephrine, normetanephrine, dopamine and chromogranin A levels. This led to our diagnosis of a catecholamine-secreting functional paraganglioma, which was confirmed on tumour biopsy following resection.

Treatment

A multidisciplinary approach to resection was established: (1) alpha and beta blockade to control tumour-related catecholamine symptoms and minimise risk of ICS, (2) embolisation of RCA branch by interventional cardiology to protect the RCA, (3) embolisation of bronchial arteries by interventional radiology to block tumour vascular supply and minimise intraoperative bleeding and (4) RATs for mobilisation/resection of the mass by thoracic surgery immediately after artery embolisation to minimise risk of ICS from tumour manipulation. Procedures were scheduled 2.5 months after the initial visit to allow adequate time for alpha/beta blockade.

The patient first underwent an RCA angiogram (figure 3A), and its branch supplying the mass was successfully coil and particle embolised (figure 3B) as demonstrated by no residual tumour blush. The posterior origin and high-grade stenosis of the right bronchial artery ostium prevented its successful catheterisation and thus embolisation was aborted.

The patient was then transported to the operating room. Once the robotic ports were placed, the lung was retracted anteriorly, and the mass was mobilised from the mainstem bronchi to the bottom of the carina. Multiple subcarinal lymph nodes were removed. The tumour was found to be more firmly adhered to the pericardium than suspected based on preoperative imaging. The inferior pulmonary ligament was mobilised to gain better visualisation of the inferior pulmonary vein, and there was no definitive plane between the vein and the mass. A different approach from the superior aspect of the tumour was tried and the mass was separated from the carina and airway. Additionally, most of the bronchial artery arcade was controlled and divided. However, given the high risk of potentially injuring the left atrium, it was decided that using cardiopulmonary bypass (CPB) would be safer. The removed lymph nodes were negative for metastatic disease.

The next day, a midline sternotomy was made and CPB was instituted. The previous robotic mobilisation greatly facilitated tumour exposure. The mass was adherent to the roof of the left atrial wall and appeared to infiltrate it without providing a clear plane for separating the two structures. Following cardioplegic arrest of the heart, the mass was seperated from the left atrium, taking a 1 cm margin of left atrial wall in the form of en bloc resection. The remaining bronchial arteries were ligated posteriorly. The tumour was successfully removed and was completely encapsulated (figure 4A). No evidence of tumour was left behind as detected by visual inspection. The left atrium was large enough to be closed primarily, taking care not to stenose the pulmonary veins. He was seperated from CPB easily but haemostasis was tedious. The sternotomy could not be closed primarily due to haemodynamic instability. Seven days later, sternotomy closure was performed.

Outcome and follow-up

Histological examination showed a well-circumscribed tumour composed of medium-sized cells with round nuclei, granular chromatin, abundant eosinophilic cytoplasm, indistinct cell borders and vascularised thin stromal septae. Cytologic atypia was generally mild with no evidence of tumour necrosis or increased mitotic activity. Tumour cells were positive for synaptophysin, chromogranin and S100 while negative for cytokeratin AE1/AE3 (figure 4B–E). None of the surrounding lymph nodes showed metastatic disease.

Postoperatively, the patient displayed haemodynamic instability and required respiratory support. He made a complete recovery and was discharged 17 days after sternotomy closure. At 4-month follow-up, his catecholamine levels were within normal ranges, and he did not have any tumour/catecholamine-related symptoms.