Cardiac paraganglioma in a pediatric patient

We present a case of a rare cardiac tumor, predominantly found in adults, in a pediatric patient who presented with persistent hypertension caused by a cPGL and underwent surgical resection. Informed consent from the legal guardian and institutional review board approval (7934, August 30, 2022) were obtained.

A 12-year-old male patient with familial history of hypertension presented with sweating, nocturnal diaphoresis, and headache. He denied chest pain, distress, or symptoms of angina. Average 24-hour blood pressure measured 167/105 mm Hg. The patient commenced treatment with beta-adrenoreceptor blockers with limited effect. Magnetic resonance imaging of the abdomen and pelvis as well as ultrasound of the kidneys and prostate were normal. Radionuclide angiography with captopril revealed a smaller right kidney but failed to explain the increased blood pressure. Examination of urinary output demonstrated elevated noradrenaline, metanephrine, and normetanephrine. Based on the urinary sample, he received additional alpha-adrenoceptor blockers.

The patient was subsequently referred to the Hospital General de Niños “Dr. Pedro de Elizalde”. Positron emission tomography-computed tomography scan showed a 49 × 41 × 47 mm intrapericardial lobulated mass on the right atrium with increased metabolic activity, compatible with cPGL (Figure 1). Echocardiography confirmed the presence of a mass extending from the right anterior region of the heart from the tricuspid valve to the apex (Video 1). The mass had a close relation to the tricuspid and the aortic valves, with uncompromised blood flow through these structures. The right coronary artery (RCA) was observed in relation to the mass, with uncompromised blood flow. Cardiac magnetic resonance imaging confirmed a soft tissue mass anterior and superior in the atrioventricular groove with blood supply from the RCA (Figure 2). Coronary catheterization revealed collateral blood supply from the RCA through two proximal branches and one distal branch.

After detailed analysis, surgical resection of the tumor was planned. The mass measured 4 cm, had an ovoid shape, and rubbery consistency. Its color was very similar to the normal surrounding cardiac muscle. It was located in the right atrioventricular groove infiltrating the medial free wall of the right atrial appendage, part of the free wall of the right ventricle, and the right anterior aspect of the aortic root. The mass was carefully approached from the periphery. A critical aspect in this procedure is to identify the limits between the mass and the normal tissue. Although there was no clear dissection plane, there was a thin membrane in some areas that allowed resection without leaving remnant tumoral tissue. First, the mass was separated from the aortic root, where there was no deep infiltration of the arterial wall. This part was relatively easy because the consistency and macroscopic characteristics of the tumor and the aortic wall were quite different. Then, the tumor was approached from the right side. The atrial wall is a thin structure. Therefore, it is advisable to resect the part of it that is in close contact with the tumor to avoid leaving residual tumor cells. Following this concept, we resected a portion of the medial wall of the right atrial appendage along with the mass. At the bottom of the atrioventricular groove, the RCA was found to be almost completely surrounded by the tumor (Video 2). Identification of the vital anatomical structures in relation to the tumor and whose integrity must be preserved at all costs is another key step in the procedure. Highly vascularized masses like these are usually nurtured by several feeding arteries. In this case, these arteries attached the tumor to the most vital structure involved, the RCA, and were identified by imposing gentle traction on the tumor toward the surgeon. Ligation with clips of these vessels allowed complete separation of the RCA from the tumor. Then, the mass was approached from the left side. The important structures involved here were the anterior free wall of the right ventricle and the annulus of the tricuspid valve. To allow an acceptable safety margin, excision was performed by dissecting through the ventricular cardiac muscle. At a certain point, the right ventricular wall was disrupted. The tricuspid valve apparatus could easily be seen through the ventriculotomy. No annulus or valve damage was observed. Finally, complete excision of the tumor was achieved. Integrity of the RCA was confirmed by administration of cardioplegic solution. Reconstruction of the atrium was performed with running suture and a small autologous glutaraldehyde-treated pericardium patch was used to reconstruct the ventricle (Video 2). The procedure was technically demanding and required an aortic crossclamping time of 153 minutes.

Pathology confirmed the diagnosis of cardiac paraganglioma positive for chromogranin A, synaptophysin, and S100. Genetic report disclosed 4 variants in the succinate dehydrogenase D (SDHD) gene, concluded to be benign or probably benign. On 9-month follow-up, the patient is doing well with normalized blood pressure, in sinus rhythm, and medication free. There was no tumor recurrence on surveillance positron emission tomography-computed tomography.

cPGLs are a subset of PGL. PGLs are rare neuroendocrine tumors that arise from chromaffin cells located outside of the adrenal gland. They can occur in the chest, abdomen, and pelvis or in the head and neck, being of sympathetic or parasympathetic origin, respectively. cPGLs can occur anywhere in the heart but are often found in the roof of the left atrium or in association with the aortic root. Our patient presented with a tumor in the right atrioventricular groove in relation to the RCA.

Symptoms of cPGLs are influenced by the metabolic profile because they can be hormonally active or inactive. Hormonally active PGLs have 3 phenotypes: noradrenergic, adrenergic, and dopaminergic. Our patient presented with hypertension, sweating, diaphoresis, and headache in accordance with the diagnosed noradrenergic profile of the tumor. Depending on the tumor location and infiltration, pressure symptoms such as shortness of breath, chest pain, or distress may be present. Coronary steal syndrome in the form of angina may also occur. Children with either pheochromocytoma or PGLs tend to have sustained hypertension, whereas adults exhibit paroxysmal hypertension.

Meticulous preoperative planning in multidisciplinary teams is paramount to achieve optimal treatment outcome. Surgery can be technically challenging due to the high degree of vascularity of these tumors and their proximity to vital structures. The RCA seems to be the common artery for tumor blood supply. In our case, we managed to preserve the RCA when removing the mass. However, others have had to perform venous bypass grafts.

There are few reports on pediatric cPGLs. In one of them, a 16-year-old patient was found with irregular heart rhythm during recovery from a surgically repaired orbital fracture. The cPGL was located in the base of the aortic and pulmonary roots. Surgical resection was uneventful. Another adolescent presented with headaches, hypertension, and a positive test for urinary norepinephrine. During resection, the sinoatrial nodal artery had to be sacrificed with subsequent postoperative sinus node dysfunction. Finally, an 8-year-old girl had a medical history of shortness of breath, fatigability, exertional dyspnea, tachycardia, and chest tightness. Imaging revealed a highly vascularized tumor at the origin of the left coronary artery. Because catecholamine levels were normal, a biopsy was performed, causing the patient to become hemodynamically unstable. The tumor was deemed unresectable and she was listed for heart transplant. These cases show that this disease is hard to diagnose and treatment can be very challenging.

There is a genetic association with germ line mutations of succinate dehydrogenase (SDH -B, -C, or -D) gene in 25% of these tumors. The incidence of malignant cPGL is estimated at 6% and is mostly associated with mutations in the SDHB gene. Our patient had benign mutations in the SDHD gene. Due to the risk of malignancy, he will undergo annual clinical and imaging follow-up.