Shu-Yu MENG ,Li-Qun WANG ,Hao-Dan DANG ,Lin ZHANG ,Sheng-Li JIANG ,Bo-Han LIU,?

1.Department of Ultrasound Diagnosis,the First Medical Center,Chinese PLA General Hospital,Beijing,China;2.Department of Nuclear Medicine,the First Medical Center,Chinese PLA General Hospital,Beijing,China;3.Department of Pathology,the First Medical Center,Chinese PLA General Hospital,Beijing,China;4.Department of Cardiovascular Surgery,the First Medical Center,Chinese PLA General Hospital,Beijing,China

Paragangliomas,also known as pheochromocytomas (1–9 cases per million),arise in the paraganglia.[1]Pheochromocytomas occur in the adrenal glands,while paragangliomas occur elsewhere.[2]Paragangliomas originate from paraganglion cells,which are derived from the neural ectoderm of the nerves and migrate along both sides of the median axis from the base of the skull to the pelvis during embryonic development.As a result,they can occur in a wide range of sites,most commonly in the head,neck,retroperitoneum,and mediastinum.The majority of thoracic paragangliomas,which account for 1%–2% of all paragangliomas,are located in the posterior mediastinum.A much rarer subgroup is primary cardiac paraganglioma(PCP).[2]This case report presents our experience of characterizing a tumor using multimodal cardiac imaging in a patient with PCP,as well as the diagnosis and treatment process for this rare tumor.

A 54-year-old woman was discovered to have a cardiac mass in an occasional examination by echocardiography in local hospital over five months ago without any symptoms,and she was referred to our hospital to further diagnosis and treatment.At the age of 17,she had previously received a diagnosis of “right atrial and right ventricle hypertrophy” and in 2011,she was diagnosed with “hypertension” without receiving any treatment.To determine the nature and extent of this mass to plan future cardiac surgery,this patient received multimodality cardiac imaging tests.

Transthoracic echocardiography identified a mixed echogenic mass at the upper part of the right atrium displaying speckled strong echogenicity as a first-line test.The mass was about 5.4 cm × 5.1 cm × 5.3 cm in dimensions as viewed through the short-axis view of the aorta,the four-chamber view,and the subxiphoid double atrial view (Figure 1).The tumor appeared to be infiltrating and taking up space within the right atrium,with an indistinct boundary between the atrial wall and partially involving the interatrial septum and the outlet of superior vena cava.There was no evidence of a significant flow signal within the tumor using color Doppler flow imaging.The initial transthoracic echocardiography scan indicated that the tumor located within the right atrial cavity firmly adherent to the atrial wall(Figure 1),but the full view of this tumor was not delineated clearly.Additionally,the patient received contrast echocardiography,contrast-enhanced computed tomography (CT),and positron emission tomography/computed tomography (PET/CT) imaging to determine the tumor extent and characteristics for making the surgical plan.

Figure 1 Two-dimensional echocardiogram images of the cardiac mass.(A): The parasternal short-axis view of the mass.The cardiac mass was observed in the right atrium with an indistinct boundary with the atrial wall and septum (red arrow) in the short-axis view of the aorta;(B): the apical four-chamber view of the mass.In this view,the tumor was measured as 5.4 cm × 5.1 cm,firmly attaching to the atrial wall and septum with speckled strong echogenicity inside the tumor (red arrow);and (C): the subcostal two atrium chamber view of the mass.The outlet of the superior vena cava showed a tendency to be occupied by the tumor in this view.And the entry of the inferior vena cava into the right atrium was not occupied by this tumor (red arrow).

Contrast echocardiography can enhance the visualization of intra-cavity structures by assessing the vascularization of the mass.The mass exhibited a general hypo-enhancement with some strip-like hyper-enhancement at the central region (Figure 2).Contrast echocardiography revealed that the mass may be a benign tumor with characteristics indicative of major feeding vessels but no significant improvement of solid components.However,the features of infiltration into the cardiac wall without a discrete capsule may raise the complexity of dissecting it directly during surgery.In addition,the characteristics of the tumor as observed through various echocardiography techniques need to be additionally confirmed by another cardiac modality,like CT or PET/CT.

Figure 2 Contrast echocardiography showed the tumor with generalized hypo-enhancement but some strip-like hyperenhancement in the core (red arrow).

Contrast-enhanced CT showed a right atrial mass(5.8 cm × 4.9 cm) with a valvular obstruction extending into the superior vena cava,which had a mixed density with irregular calcified foci and cystic hypointense areas (Figure 3A).Contrast injection into the left circumflex coronary artery highlighted the rich vascularity of the mass,with a CT value of 41 HU on plain scan and 170 HU on enhancement.The patient then underwent PET/CT,which showed enhanced uptake at the edge of the mass (SUVmax=6.3),sparse internal uptake,and no apparent metabolic abnormalities in the rest of the body or brain (Figure 3B).PET/CT is particularly useful in providing preoperative information on the presence and extent of unanticipated metastases,but it cannot provide accurate information on local extent and perfusion.

Figure 3 The other enhanced cardiac images showed the features of the mass. (A): The transverse section of contrast-enhanced computed tomography image.Contrast-enhanced computed tomography identified the mass had a mixed density including irregular calcification foci and cystic hypointense areas;and (B): the images of positron emission tomography/computed tomography imaging showed enhanced radioactive uptake on the edge of the mass and sparse internal radioactive uptake.

Intraoperative transesophageal echocardiography(TEE) was performed to maintain surveillance on tumor resection effect and cardiac function during surgery.Before cardiopulmonary bypass,the mid-esophagus bicaval view of TEE showed that the tumor in the right atrium was approximately 4.5 cm × 4.2 cm × 4.2 cm in size,with multiple speckled strong echoes accompanied by posterior acoustic shadows,with unclear borders and still regular morphology,partially involving the interatrial septum and superior vena cava orifices (Figure 4).Rich blood flow signals were seen by color Doppler flow imaging,showing a low-velocity,low-resistance venous-like spectrum,and a flow velocity of 0.31 m/s was measured by pulse wave Doppler imaging.

Figure 4 Intraoperative transesophageal echocardiography showed better resolution than transthoracic echocardiography,which revealed multiple scattered strong echoes accompanied by posterior acoustic shadows,with unclear borders and still regular morphology,partially involving the interatrial septum and superior vena cava orifices.

Based on the above multimodal cardiac imaging features,surgeons also tend to diagnose that the tumor is likely to be a benign lesion,so the tumor should be removed as far as possible to avoid tumor residues.However,due to the close relationship between the tumor and the surrounding structure,it is necessary to avoid damaging the atrial wall,which could cause massive bleeding during resection,so preparation for right atrial reconstruction should be taken into account.During the operation,after incising the right atrium,the surgeon found this right atrial mass,which was approximately 5.0 cm × 4.0 cm × 4.0 cm in size,hard and involved the right atrial free wall,the interatrial septum and part of the left atrium,but not the pulmonary vein orifices,so it was decided intraoperatively to perform a radical resection under cardiac arrest.After freeing the margins of the mass,the mass and the above structures involved were excised and sent for pathological examination,confirming that no residual tumor tissue was seen at the margins.A 10.0 cm × 10.0 cm bovine pericardial patch was then taken and 4–0 proline sutures were placed continuously to reconstruct the left atrial wall and septum.After the heart resumed beating,a 6.0 cm × 8.0 cm bovine pericardial patch was taken and the right atrium was reconstructed with continuous 4–0 proline sutures.Immediately after surgery,TEE showed no abnormal echoes in the original area,no fluid in the pericardium,and visual left ventricular ejection fraction was 58%.The post-operative course was uneventful and the patient was discharged from the Intensive Care Unit on postoperative day 3.

Postoperatively,the gross specimen of this right atrial mass measured 8.0 cm × 6.5 cm × 5.5 cm (Figure 5A),with a greyish yellow to greyish brown cross-section,medium texture,some areas of calcification,and hardness.Microscopically,it was a nested arrangement of epithelioid tumors with abundant blood vessels and basophilic cytoplasm (Figure 5B).The immunohistochemistry was CgA+,CD56+,Syn+,S-100 partially+,Ki-67 index(+3%) (Figure 5C).The final pathological diagnosis was PCP.

Figure 5 The pathological findings of the tumor.(A): The gross specimen of this right atrial mass.This removed mass was measured 8.0 cm × 6.5 cm × 5.5 cm;(B): the × 20 image of H&E staining.Microscopically,the tumor was a nested arrangement of epithelioid tumors with abundant blood vessels and basophilic cytoplasm;and (C): the positive findings of the immunohistochemistry.The immunohistochemistry was CgA+,CD56+,Syn+,S-100 partially+,Ki-67 index (+3%),which could finally diagnose the tumor as primary cardiac paraganglioma.

PCP is rare and often originates from the left atrial visceral paraganglia,coronary arteries,and paraganglia at the main pulmonary window.[3]PCP is most commonly found in the left atrium,the visceral autonomic paraganglia,or the aortic body arising from branchiomeric paraganglia.[4]In our case,however,PCP was found in the atrium and involved the interatrial septum and part of the left atrium,which was easily seen on echocardiography.The localization and diagnosis of PCP rely on a variety of cardiac imaging modalities.Echocardiography has unique advantages in the diagnosis of intracardiac and pericardial tumors and is the method of choice for cardiac tumor screening and a common tool for postoperative assessment.Echocardiography is the most common initial test for any structural abnormality in the heart,which in our case suggested a cardiac tumor.CT is usually the next imaging test obtained,which could be good for delineating tumor anatomy with excellent special resolution.Paragangliomas are all highly vascular with extensive early perfusion seen on enhanced CT or contrast echocardiography.All enhanced imaging modalities found that highly vascular signals were presented in the tumor,orientating from the left circumflex artery.

Depending on whether catecholamines are secreted or not,paragangliomas are categorized as functional or non-functional.The non-functional ones are mostly due to the enlargement of the tumor causing compression symptoms in adjacent organs (superior vena cava syndrome,etc.) and hemodynamic abnormalities (blockage of blood vessels or valve openings).[5]Sweating,palpitations,and headache triad symptoms are the most frequently reported.[6,7]In a review of 30 cases,[1]the most common presentation of PCP was hypertension,with dyspnea occurring in only 3 cases.Although our patient had no symptoms at the time of presentation,her history prompted a detailed examination and echocardiography whether the hypertension was secondary to any reason,including rare cases,like PCP.

Qualitative diagnosis relies mainly on laboratory tests,24-hour urinary catecholamines are generally high in paragangliomas,but laboratory tests could be normal in PCP.[8]This tumor can be hormonally active,so perioperative medical management is important to avoid serious complications.Fortunately,no serious complications occurred during surgery in our case.Compared to adrenal pheochromocytoma,thoracic paragangliomas are often non-secretory or dopamine-secreting tumors.[9]It is important to determine the secretory phenotype.Manipulation of the tumor can cause marked hypertension,even with preoperative alpha and beta-blockade.Wilson,et al.[10]described systolic blood pressures greater than 300 mmHg when a PCP was resected via right thoracotomy without bypass.In a review of 25 patients,four deaths were described,all due to massive hemorrhage.Liu,et al.[11]reported on 17 patients with cardiac paragangliomas who underwent resection,16 patients of whom had metabolically active tumors.The reasons for these differences in hormonal activity between these populations are unknown but may be due to differences in referral patterns between our centers.Surgeons should recognize this tumor and be aware of the risk before surgery,which may require careful manipulation during surgery.

A cardiac tumor can be found in either the left or right atrium and is supplied with blood from the coronary artery.It might be identified through and mixed ultrasound signals in an echocardiogram or density in contrast-enhanced CT,and may contain components of calcification and cystic areas.In our case,these diagnostic results were unusual,similar to PCP.PCP presents interesting diagnostic and therapeutic dilemmas.Although rare,it can be treated and cured in over 90% of cases.Multimodal cardiac imaging may aid in preoperative tumor extent and characterization for further surgical planning.