Cardiac Paraganglioma Discovered Incidentally

Abstract

Background

Paragangliomas are rare neuroendocrine tumors, arising from neural crest cell lines in the autonomic system. The increased detection of these tumors in recent years can be attributed to advances in imaging techniques.

Case Summary

A 59-year-old man, presenting for a routine primary care evaluation, was incidentally noted to have a 2/6 diastolic murmur. Echocardiography and cardiac magnetic resonance characterized a large, circumscribed mass within the atrioventricular groove of the right ventricle. Coronary angiography demonstrated that this mass was highly vascularized, supplied by the right coronary artery. Serologic work-up revealed significantly elevated serum epinephrine and urinary dopamine levels. DOTATATE-positron emission tomography/computed tomography confirmed the diagnosis of a cardiac paraganglioma.

Discussion

Cardiac paragangliomas are associated with significant morbidity due to catecholamine secretion and rarely malignant potential. Cardiac paragangliomas can also be asymptomatic, making diagnosis challenging. Given their rarity, there is a paucity of evidence-based guidelines regarding diagnostic and management strategies for these tumors.

Take-Home Messages

Cardiac paragangliomas require a combination of serological and imaging tests for diagnosis. Multidisciplinary evaluation is essential for developing effective management strategies.

Graphical Abstract

History of Presentation

A 59-year-old man with a history of well-controlled hypertension, HIV (with an undetectable viral load on efavirenz/emtricitabine/tenofovir), syphilis, and treated prostate cancer presented to a primary care clinic for a new-patient evaluation. On physical examination, he was incidentally found to have a 2/6 diastolic murmur, which he recalled having been told about during his twenties. Apart from brief episodes of dizziness when leaning forward or standing during exercise, he denied any other symptoms.

A transthoracic echocardiogram was recommended, which discovered a 5.7 × 5.9 cm echogenic mass in the atrioventricular (AV) groove creating a mass effect/narrowing of the tricuspid annulus. Right ventricular pressure was determined to be within normal ranges.

Family History

The patient has a paternal history of aortic aneurysm and a maternal history of unspecified valvular disease.

Differential Diagnoses

The echocardiogram raised concern for a cardiac tumor, but the origin—whether primary or metastatic—remained undetermined. This tumor was not within the cavity of the right ventricle (RV), or right atrium, but instead in the AV groove, which creates a unique differential diagnosis of masses and pseudomasses, including angiosarcomas, lymphomas, thymomas, paragangliomas, schwannomas, and lymphangiomas. Metastatic diseases, such as those arising from a melanoma or from breast cancer, were considered as rarer etiologies of a cardiac tumor.^1,2

Investigations

A prospective electrocardiogram-gated computed tomography (CT) scan of the chest revealed a highly vascular, intrapericardial mass (6.0 × 7.7 cm) anterior to the right atrium and RV, with vascular supply from the right coronary artery (RCA). Subsequently, a cardiac magnetic resonance scan showed a large, 6 to 7 cm in diameter, well-circumscribed mass, which originated with a wide base from the RV myocardium and moved with the RV during the cardiac cycle without independent motion (Figure 1). RV size and function were normal. First pass perfusion demonstrated increased vascularity, likely from the RCA (Video 1). T1- and T2-weighted sequences were suggestive of a cardiac paraganglioma, with alternative differential diagnoses including a cardiac lymphangioma or a venolymphatic malformation (Figure 1).

Figure 1.

Magnetic Resonance Images

(A) Short-axis projection: dark blood, T1-weighted fast spin echocardiogram without fat saturation. Slight hypertense T1 signal with scattered hypointense cavitations within the mass that likely represent vascularity or small areas of necrosis. (B) Short-axis projection: dark blood, T2-weighted fast spin echocardiogram with fat saturation. Areas of hyperintense T2 signal with areas of hypointense cavitations. (C) Delayed hyperenhancement using the single-shot phase-sensitive inversion recovery technique after 0.2 mmol/kg of gadolinium contrast demonstrated heterogeneous delayed hyperenhancement within the mass and along the rim of the mass.

As found by a coronary angiogram, there was an engorged acute marginal branch feeding the highly vascular mass, and the RCA was small, which caused a small posterior descending artery and small right posterolateral branch. Filling pressures were normal, and no significantly obstructive coronary artery disease was noted.

Given these findings and the suspicion for a cardiac paraganglioma, a multidisciplinary team including cardiology, cardiothoracic surgery, endocrinology, and oncology was organized.³

Serologic work-up was initiated, which was notable for an elevated serum epinephrine level (335 pmol/L). In addition, the 24-hour urinary dopamine level was found to be elevated (831.5 μg/TV), while the 24-hour urinary catecholamine/metanephrine levels were normal. Given these findings, a DOTATATE-positron emission tomography (PET)/CT scan was performed, which confirmed the presence of a cardiac paraganglioma. Genetic work-up did not reveal any succinate dehydrogenase (SDH) mutations. Between a quarter and one-third of pheochromocytoma/paraganglioma cases have familial etiology; this includes syndromes such as von Hippel-Lindau, multiple endocrine neoplasia type 2, neurofibromatosis type 1, and SDH mutation–related tumors.⁴

On a DOTATATE-PET/CT scan, other incidentalomas were noted, concerning for extracardiac foci of disease. There was uptake in a 1.7-cm left adrenal nodule and a 7-mm left thyroid nodule. Urine cortisol levels were found to be elevated, indicating possible hypercortisolism. A dedicated thyroid ultrasound did not find a nodule in the left thyroid but instead found a 1.2-cm right upper lobe TR4 nodule.

Management

The diagnosis of a functionally active paraganglioma prompted a multidisciplinary approach. Although surgery is the preferred treatment option, given that the patient was asymptomatic and the chronicity of the mass was unclear, consideration was given to a variety of therapeutic options, including radiation therapy and cytoreduction, systemic chemotherapy, sunitinib, somatostatin receptor analog therapies, Lutathera (lutetium Lu 177 DOTATATE), or high-specific-activity iobenguane I-131 (I-131 MIBG). Surgical excision was ultimately chosen. After preoperative alpha-1 receptor blockade with doxazosin was initiated, the tumor was excised, followed by reconstruction of the AV groove and free wall with an autologous pericardial patch (Figure 2). A concurrent great saphenous vein to distal RCA coronary artery bypass graft was performed because of concern for tumor mass erosion into the RCA.

Figure 2.

Gross Specimen of Paraganglioma Mass Immediately After Excision

Outcome and Follow-Up

Postexcision transesophageal echocardiography demonstrated a left ventricular ejection fraction of 65% and normal RV function with no new RV regional wall motion abnormalities. There were no complications during the patient’s postoperative hospital course, and he was discharged home on postoperative day 5. Subsequent outpatient transthoracic echocardiography was performed 1 month after surgery, with no new significant findings. He is planning to continue a course of dual-antiplatelet therapy for 1 year given coronary artery bypass graft and subsequent lifelong antiplatelet monotherapy. Otherwise, he has continued to experience an uncomplicated postresection recovery.

He continues to follow up with endocrinology and cardiology for postoperative monitoring. He will have yearly 24-hour urine catecholamine, metanephrine, and dopamine measurements for routine monitoring. Notably, in the first endocrinology follow-up, his hypercortisolism resolved.

Discussion

Cardiac paragangliomas, though exceedingly rare, present significant clinical challenges due to their heterogenous presentation and potential for catecholamine secretion. These neuroendocrine tumors typically arise from the sympathetic paraganglia of the heart and have an incidence of <1% of all cardiac tumors.⁵ Although most of these tumors occur sporadically, they are also linked to genetic syndromes such as von Hippel-Lindau (VHL) disease, neurofibromatosis type 1 (NF1), and mutations in SDH genes, which predispose patients to multiorgan paragangliomas.⁶ A key feature of cardiac paragangliomas is their ability to secrete catecholamines, which can result in symptoms ranging from paroxysmal hypertension and palpitations to anxiety and diaphoresis. However, these tumors are increasingly incidentally discovered on routine imaging in otherwise asymptomatic cases.⁷

Formal diagnosis of these tumors is based on a combination of serological and imaging tests. Current National Comprehensive Cancer Network guidelines recommend biochemical work-up based on elevated levels of 24-hour urine or free plasma metanephrine, and if work-up is suspicious, DOTATATE-PET should directly be performed for targeted imaging. Finally, given the increasing understanding of these tumors as part of a hereditary genetic syndrome, patients are often recommended to undergo genetic evaluation testing for common germline mutations, such as RET, NF1, VHL, and SDH.⁸

There have been several cardiac imaging modalities described in the literature to have utility in identifying cardiac paragangliomas. Typically, a hybrid PET/CT or PET/magnetic resonance imaging protocol has been used to characterize these masses. Initially, CT-angiography highlights the characteristically highly vascular, pericardial nature of these tumors. Simultaneously, radiotracer scans, such as DOTATATE-PET, are used because of their ability to localize neuroendocrine tumors by binding to somatostatin receptors. 18-fluoro-L-3,4-dihydroxyphenylalanine PET scanning has been described to also detect pathologic regions of uptake. Alternatively, the Octreoscan (CT-single-photon emission computed tomography with indium In-111 pentetreotide, somatostatin receptor scintigraphy) has been described to characterize suspected neuroendocrine tumors, but DOTATATE-PET is the most commonly used imaging technique.⁹

Given their rarity, these tumors have been reported to have a mean time to diagnosis of up to 10 years, during which time they can cause both local ischemia or mass effect and systemic cardiovascular abnormalities that increase mortality.⁵ The literature regarding optimal management strategies is limited, based on smaller case reports or a series of a few dozen to a few hundred patients, but suggests a surgical treatment, with preoperative alpha-1 receptor blockade as the most effective treatment.^5,10 For locally irresectable tumors, there is ongoing study into a variety of different treatment protocols, including radiation and limited surgical cytoreduction, high-specific-activity iobenguane I-131 or other iodine-131-MIBG therapy, somatostatin receptor–focused therapies, and peptide receptor radionuclide therapies. However, even with successful surgical excision, current estimated 5-year survival rates have been estimated at around 78%, possibly due to sequelae of delayed diagnosis.⁸

Conclusions

Cardiac paragangliomas are rare but clinically significant tumors with complex diagnostic and management challenges. The growing availability of advanced imaging techniques and biomarkers, combined with a multidisciplinary approach, has significantly improved the detection and management of these tumors. Despite advances, much remains to be learned about the optimal management strategies, particularly in cases where the tumor is not amenable to surgical resection. Early diagnosis, genetic screening, and personalized treatment plans are crucial to improving outcomes and minimizing morbidity in patients with this rare and potentially life-threatening condition.

Funding Support and Author Disclosures

The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Take-Home Messages

• •Diagnosis of cardiac paragangliomas involves a combination of biochemical evaluation for elevated catecholamine, metanephrine, and dopamine levels and specialized cardiac imaging techniques, such as DOTATATE, positron emission tomography/computed tomography, or positron emission tomography/magnetic resonance imaging.
• •A multidisciplinary approach is key for the management of these tumors; it often requires surgical resection, with consideration toward additional therapies depending on the local resectability in cases of malignant masses.

Appendix

Video 1

Cardiac Magnetic Resonance

First pass perfusion using gadolinium contrast demonstrates high vascularity