Cystic tumor of atrioventricular node: a narrative systematic review

Authors

Abstract

Aim Cystic tumor of atrioventricular node (AVN) is a very rare bening cardiac tumor-the silent cause of suddent death. This study aimed to review all studies and summarize literature knowledge of cystic tumor of AVN in addition with recent case reports.
Material and Methods It was performed a systematic analysis based on MEDLINE/PubMed, WOS, Researchgate, Google scholar databases. 67 studies with a confirmed pathological diagnosis of cystic tumor of AVN were included.140 patients diagnosed with cystic tumors of AVN were listed. 24 patients were diagnosed antemortem. Following exclusion of duplicated patients, 116 postmortem patients were evaluated.
Results After adding new cases, the mean age was found to be 39.89, and the expected female-to-male ratio was 1.8:1. Dyspnea and palpitation were the most commonly reported symptoms. Third-degree AV block was the most common ECG finding. The tumors were mostly located in the AVN region. In most patients’ medical history, previous congenital heart block in various degrees existed; it might be a relation with cystic tumor of AVN and misdiagnosed ‘con- genital’ heart block.
Discussion It has been advised to take a routine section of the AVN during autopsy in all cases of sudden death. This is the largest review on cystic tumors of AVN in the literature so far.

Keywords

Introduction

Cystic tumor of atrioventricular node (AVN) is a rare primary congenital cardiac tumor and comprises of 2.7% of cardiac tumors and is the most common primary cardiac tumor causing sudden death [1–9]. It was first described in 1911 as a lymphangioendothelioma [10, 11].
Various terms have been used, such as angioendothelioma, mesothelioma of the AVN, celothelioma, benign mesothelioma of Mahaim, lymphangioma, endothelioma, inclusion cyst, polycystic tumor, endodermal heterotopia, endodermal rest, dysontogenetic endodermal tumor, a remnant of the truncus arteriosus division, hamartoma, epithelial inclusion, chronic lymphangitis proliferans, adenoma-like tissue malformation of the serosal epithelium, heterotopic epithelial replacement of the AVN, congenital endodermal heterotopia, Tawarian node, and Tawarrioma [11].
Cystic tumor of AVN is known to be benign and has a histologically cystic nature [12]. It is typically located at the base of the right atrium, in a similar area of AVN within the Koch’s triangle [1]. Clinical presentations are sudden death, syncope attack, complete heart block or lethal arrhythmia in general [13]. It is sometimes found in an autopsy incidentally [12].
This review aimed to investigate recent clinical studies; clinical presentation, relation with different congenital heart diseases, surgical treatment, medical follow-up, prognosis, and summarize the literature knowledge of cystic tumor of AVN, in addition to recently published case reports in the literature.
Etiology
It is believed that the cystic tumor of AVN originates from congenital rests of endodermal origin [4, 9]. A recent study suggested that the origin of this tumor may be solid cell nests of the thyroid tissue [14]. The tumor has been thought to be a dilatation of a cyst instead of a tumor enlargement [15, 16].
Presentation
A cystic tumor of AVN is a congenital benign mass. First case report- a postmortem diagnosis- was published by Armstrong and Monckeberg in 1911 [10]. The mean age of diagnosis is 38 years with a range from birth to 96 years, and the majority of patients are female [1, 15, 17]. Associated diseases are congenital heart diseases such as atrial septal defect (ASD), ventricular septal defect (VSD), patent ductus arteriosus (PDA); hypoplastic left heart syndrome (HLHS); pulmonary hypoplasia; and transposition of great arteries (TGA); thyroglossal duct cysts, cysts in the ovaries and breasts, encephalocele; and Emery-Dreifuss muscular dystrophy [9, 18].
The main presentation of cystic tumors of AVN is particularly related to conduction system pathologies [15]. Most common symptoms are palpitation, chest pain, shortness of breath, dizziness, syncope, and sudden cardiac death [9, 19]. Other events are heart attack, stroke [9].
The most common arrhythmia is complete atrioventricular (AV) block, which is predominantly relevant to sudden cardiac death [19]. Other rhythm disturbances are 1st or 2nd degree heart blocks, bradicardia, intraatrial conduction defect, paroxysmal atrial arrhythmia, junctional escape rhythm, and spontaneous intermittent preexcitation [1, 13, 20, 21].
Diagnosis and Differential Diagnosis
Regarding literature knowledge, on physical examination, an obvious oscultation evidence of right-sided valves due to an oclusive effect of the cystic tumor of AVN is not encountered. In most cases, patients suffer from different degrees of heart block or palpitation. Frequently, in patients’ medical history, a relevant cardiac arrhythmia occurs in early ages or a few years previously before the cystic tumor of AVN has been diagnosed [13]. Electrocardiogram (ECG) and Holter monitoring determine various degrees of arrhythmia. Magnetic resonance imaging (MRI) and computed tomography (CT) provide detailed information about tumor size, anatomical structures in close proximity, and the exact location of the tumor [1]. Coronary angiography is not necessary unless the patient requires additional examination for co-morbid coronary artery disease; however, with the aid of a selective angiogram, a demonstration of a ‘tumour flush’ or an abnormality of the course of this artery may suggest the existence of an AVN tumour in an alternative way [22].
In differential diagnosis for cardiac cysts, bronchogenic cysts, and mesothelial cysts should be investigated. In addition, teratoma and histiocytoid cardiomyopathy should be suspected for pediatric patients [3, 23]. Bronchogenic cyst develops on the epicardial surface and includes mesoderm and endoderm layers [9]. Mesothelial cyst develops on the surface of the heart and includes mesoderm and endoderm layers, and is larger than a cystic tumor of the AVN [9]. Teratoma includes endoderm, mesoderm, and ectoderm [24].
Management
Because of a limited number of cystic tumors of AVN in the literature- most of them were diagnosed postmortem- a standard management or surgical resection and therapeutic concepts have not been established, and it’s still controversial [21]. Most authors have advocated surgical resection since the exact diagnosis is made [21, 25, 26]. Ojha et al. reported a permanent pacemaker implantation to palliate complications of complete AV block and inhibit -clear and imminent danger- sudden death for their 55-year-old patient who didn’t accept surgical resection [20]. Guilliano et al. suggested close follow- up for elderly asymptomatic patients diagnosed incidentally [27]. Similarly, according to their experience with a 42-year-old asymptomatic patient except a 3rd degree AV block diagnosis, Alrashidi et al. advised close follow-up [28].
Surgical Approach
Two different approaches have been suggested in the literature:
1. A total resection of the tumor [29]. 2. A partial resection in case of patients in poor preoperative condition or a huge tumor [3, 5, 25]. The majority of surgical treatments were realized by standard median sternotomy under cardiopulmonary bypass (CPB); on the other hand, there are only two patients operated on with a minimally invasive approach without cross-clamping of the aorta [13, 26].
Histopathological Characteristics
Tumor size may be in a range of visually unnoticeable size to macroscopic size [1]. This tumor seems to imitate a thickening of the basis of the interatrial septum (IAS), sometimes noticeable only in a routine pathological examination in autopsy, to understand the exact reason for the patient’s sudden death [6, 9]. The exact address of the tumor is similar to AVN, in other words, in Koch’s triangle, which is framed by the ostium of the coronary sinus in the right atrium to the membranous septum, anulus of the tricuspid valve septal leaflet and tendon of Todaro [1]. Only one case has been published in the thyroid gland [30].
Prognosis and Recurrence
Clinical manifestation of cystic tumor of AVN varies. The majority of cases were diagnosed postmortem, and it has been shown that the tumor has a relationship with fatal cardiac dysrhythmia, even with first-degree to complete heart block, and sudden cardiac death is not a surprising result, even though it is accepted as a benign congenital pathology [3, 31]. The majority of postmortem pathological investigations showed that the effect of arrhythmia due to the AVN invaded tumor is independent of tumor size, as proven by microscopic-sized tumors found in autopsy series.

Materials and Methods

A keyword search of MEDLINE/PubMed and Web of Science, researchgate, Google scholar was performed to identify the relevant case reports and case series in English using the following terms: angioendothelioma, mesothelioma of the AVN, celothelioma, benign mesothelioma of Mahaim, lymphangioma, endothelioma, inclusion cyst, polycystic tumor, endodermal heterotopia, endodermal rest, dysontogenetic endodermal tumor, a remnant of the truncus arteriosus division, hamartoma, epithelial inclusion, chronic lymphangitis proliferans, adenoma- like tissue malformation of the serosal epithelium, heterotopic epithelial replacement of the AVN, congenital endodermal heterotopia, Tawarian node and Tawarrioma. The PRISM flowchart is shown in Figure 1.
Ethical Approval
This study did not require ethical approval according to the relevant guidelines.

Results

The present study revealed that the expected female-to- male ratio was 1.8:1 and a mean age of 39.89 years. A total of 140 patients were investigated. Twenty-four patients were diagnosed antemortem. Nineteen of them were female, highlighting the female dominance. In general, antemortem diagnosed alive patients had mostly cardiac symptoms such as palpitation, heart block in various degree. Almost all of them were investigated first via ECG and transthoracic echocardiogram. Computed tomography and MRI were the second-choice diagnostic modalities. The most encountered additional congenital cardiac pathology was ASD. Only in one patient, a VSD was detected.
Characteristics of tumors in antemortem diagnosed patients and preferred treatments were collected and summarized. The tumor localizations were in the region of Koch’s triangle in general. In some cases, tumors were localized in the basal portion of IAS. Among them, only five patients had a partial resection so as not to trigger a complete heart block [3, 25, 26, 35, 37]. Ten patients required new-onset permanent pacemaker implantation. Long-term follow-up data were not found in the literature for all of the cohorts. Only a 5-year follow-up period of one patient is available in the literature [4]. Data from patients with postmortem diagnosis in autopsy were collected from the literature. Some of the patients had been documented in different series belonging to various authors. After excluding duplicated patients, 116 postmortem diagnosed patients were evaluated. All postmortem patients were investigated during the autopsy to understand the exact reason for sudden death. Therefore, due to the fact that the previous symptoms of patients were not fully documented in all literature studies, these data weren’t fully found. Additional congenital heart defects were as follows: 1 VSD, PDA; 1 unknown congenital heart anomaly; 1 VSD with mitral insufficiency (MI); 1 HLHS; 1 pulmonary hypoplasia; and 1 TGA with PDA.
The detailed data are provided in Supplementary Tables S1, S2, S3.

Discussion

Cystic tumor of AVN is an extremely rare congenital tumor. It typically presents in adulthood at a mean age of 38 years, ranging from newborns to 96 years, with a female-to-male ratio of 3:1 according to previous studies [12, 15, 53]. In our study, with the additional new cases, the expected female-to- male ratio was found to be 1.8:1, and the mean age was 39.89 years. Even though being a benign neoplasm, it is an evident reason for sudden death, which is always evaluated in autopsy due to its relevant fatal arrhythmias.
Symptoms, Clinical Manifestation, and Arrhythmia
Clinical manifestations of this tumor varie. Many patients are asymptomatic. Other clinical manifestations are dyspnea, dizziness, unconsciousness, or, in a majority of cases, sudden death. In various cases, patients present with bradycardia, various degrees of heart block in their previous medical history, sometimes since their childhood. When postmortem cases are evaluated, majority have a previous diagnosis of heart block, congenital heart block or permanent pacemaker implantation history. However, some postmortem case reports were about only pathological reports. Therefore, their previous clinical manifestation were not reported. In conclusion, it is difficult to estimate the exact ratio of anticipant arrhythmia.
Most cases introduce a previous permanent pacemaker implantation due to the early onset bradycardia or various degrees of heart block. Before the invention of the pacemaker device, these patients were treated with conservative medical treatment for any reason of heart block. Since permanent pacemaker implantation has become possible, symptomatic improvement has become possible. On the other hand, a permanent pacemaker doesn’t prevent patients’ fateful death. In some cases of sudden death, permanent pacemakers were still working appropriately at the time of postmortem diagnosis at autopsy [59, 62]. This dilemma should be investigated in detail. How important AVN cells or HIS are for a permanent pacemaker to properly stimulate the heart remains unanswered. This answer could also contribute to future pacemaker technology.
Diagnostic Methods
All antemortem diagnosed patients had ECG and transthoracic echocardiogram first due to palpitation symptoms. In addition, for further investigation, transesophageal echocardiogram (TEE), CT, and MRI were preferred imaging tests [26]. Only one patient had a coronary angiography test to eliminate coronary artery disease [34]. In addition, Bharati et al. have suggested using coronary angiography, which might determine the supplying artery of the AVN for a suggestive clue about the probable existence of a cystic tumor of AVN [22].
In most cases, echocardiography alone is insufficient for establishing the diagnosis because of the small size of the tumor [29]. To date, only one single case has been described in the literature in which a successful tumor biopsy was performed using stereotactic guidewires under TEE guidance by Alrashidi et al [28]. Alrashidi et al. used a three-dimensional (3D) TEE to determine an appropriate condition for taking a biopsy. During the patient’s follow-up over 18 months, they also used serial 3D echocardiography [28].
Size of Cystic Tumor of AVN
Symptoms were not related to the size of the cystic tumor of AVN. Particularly in postmortem pathological examinations for suddenly dead patients, most of the tumors were of microscopic size. The largest tumors were reported by Anderson (8 cm in diameter) in a postmortem investigation and Leiballi (7 cm in diameter) in a living patient [1, 40].
Histopathological Characteristics
Although this tumor was previously named mesothelioma of the AVN, primarily based on ultrastructural studies showing its derivation from mesothelial lineage, the exact embryogenesis is still controversial [6]. Cameselle-Teijeiro et al. studied 10 solid cell nests of the thyroid and a case of cystic tumor of AVN of the heart. They remarqued similar cellular features which were proving the hypothesis about the cystic tumor of AVN of the heart and the solid cell nestle of the thyroid are identical structures. To the best of our knowledge, cystic tumor of AVN, originates from ultimobranchial tissue- which is originated form foregut per se- that constitutes cardiac neural crest cells in cardiac development [14].
Cyst which is a remnant structure from embriological period, is described for producing a yellowish cystic fluid in literature [26]. The more fluide increases the more cyst volume becames obvious and easy to be diagnosed.
Differential Diagnosis
The differential diagnosis of the cystic tumor of AVN includes several neoplastic and non-neoplastic entities that may involve the central fibrous body or conduction system region. These primarily comprise papillary fibroelastoma, cardiac myxoma with atypical septal attachment, rhabdomyoma, fibroma, and inflammatory or degenerative cystic lesions such as blood cysts, congenital inclusion cysts, and bronchogenic cysts. In addition, non-neoplastic causes of AV conduction disturbance, including sarcoidosis, amyloidosis, and post-inflammatory or postsurgical fibrosis, may mimic the clinical presentation; however, they typically lack a discrete cystic mass on imaging [35].
Regarding malignant pathologies, metastatic tumors, particularly from lung or breast carcinoma, and primary malignant cardiac tumors such as sarcoma, malignant fibrous histiocytoma, leiomyosarcoma, rhabdomyosarcoma, fibrosarcoma, primary cardiac lymphoma, although exceedingly rare in this location, should be considered in the differential diagnosis. However, all these diseases and malignant tumors can be excluded easily from the cystic tumor of AVN, with a careful correlation of echocardiographic, cardiac MRI, cardiac CT, and histopathological findings is essential to distinguish a cystic tumor of AVN, given its unique predilection for causing complete heart block and sudden cardiac death. The cystic tumor of AVN is generally very small in size and is found to be in a very specific region in the lower part of the IAS or in the region of Koch’s triangle.
First of all, among these pathologies, metastatic carcinoma should be excluded. To ensure, the surgeon’s opinion about the intraoperative view of the mass and the patient’s history of previous cancer should be considered. Conversely, tumors that appear benign and do not contain atypia or mitotic figures may indicate that they are not metastatic carcinoma. Bronchogenic cysts that have larger and single cysts with a muscular wall usually occur on the epicardial surface far from Koch’s triangle. Myxoma, the most encountered cardiac tumor, is generally located in the endocardium of the atrial septum near the fossa ovalis. The cells may be arranged in cords or in vasoformative ring structures and cytokeratin stain negative [35].
Female Dominance and Eustrogene
Regarding previous studies concluding the cystic tumor of AVN is encountered with a dominant female patient frequency, such as a female-to-male ratio of 3:1, Ichimata et al. investigated sex hormone receptors on tumor cells [12, 15, 53, 66]. Their study exhibited that tumor cells had prostate‐like histological architectures and prostate‐like immunohistochemical features. In their investigation, some tumors had glandular epithelium of a subset of cystic tumors of AVN. In a female patient’s tumor, androgen receptor and estrogen receptor were negative; progesterone receptor was focally positive in both the inner and outer cells. In their second and third male patients, the androgen receptor showed intermediate positivity in the inner cells; the estrogen receptor and progesterone receptor were positive in the outer cells. Positive expression of both prostate‐specific antigen and prostate‐specific acid phosphatase were found in the inner cells of both male patients. Ichimata et al. concluded that cystic tumors of AVN may originate from ectopic hindgut‐ related tissue, which is derived from the primitive endoderm urogenital sinus, similar to the foregut [66]. In the literature, there is no clear evidence of a relation between female dominance and estrogen receptor positivity in cystic tumors of AVN. Differently, in the current study, the female-to-male ratio was found to be 1.8:1.
Follow Up in Regard to Complete or Partial Excision
Treatment options for cystic tumors of AVN are controversial due to their rarity, and there is no clear consensus or established guideline. Sudden death risk, although a permanent pacemaker or implantable cardioverter-defibrillator (ICD), still remains [26]. A few investigators have published their works in which they used partial resection for the removal of tumors [3, 25, 26]. For instance, Cheng et al. reported that although the patient underwent partial resection, they required a permanent pacemaker [26]. There is no long-term follow-up regarding tumor recurrence [26].
Fukui et al. reported their experience with partial resection to avoid complete heart block for their patient who had been diagnosed with first-degree heart block at the time of preoperative investigation [25]. Their patient didn’t require a permanent pacemaker implantation. After a one year of follow- up via strict echocardiography investigation every two months, no recurrence was observed [25].
Paniagua et al. used partial resection of the tumor to avoid the complete heart block [3]. However, the patient developed atrial flutter, various degrees of heart block with a slow ventricular rate; therefore, the patient required a permanent pacemaker finally [3]. However, a long-term follow-up report is required.
Li et al. reported their experience with partial resection of a cystic tumor of AVN [35]. The patient’s long-term follow-up wasn’t mentioned.
Stopyra-Początek used partial resection in a patient who had previously received a permanent pacemaker [37]. In the same operation, mitral valve repair was performed due to a mitral valve prolapse. Six months later, the patient was monitored via echocardiography, and no recurrence was found. Unfortunately, long-term follow-up data were not reported.
Follow Up Regarding Surgical Technique: Standard Sternotomy or Minimally Invasive Technique
As mentioned above, there is no clear consensus about the surgical treatment of cystic tumors of AVN. A few case studies provide experiences about minimally invasive surgical techniques. In general, conventional sternotomy and bicaval venous cannulation are still preferred.
The first case under minimally invasive operation circumstances was published by Careddu et al. [13]. Under minimally invasive surgery conditions, without cross-clamping the aorta, the cystic tumor of AVN was excised completely. Following the surgery, a first-degree heart block was observed. On the postoperative 2nd day, a transient complete heart block was observed for a limited time, and nodal rhythm was sustained. Due to the relatively good condition, no pacemaker implantation was made, and after cardiac rhythm was restored spontaneously. However, a persistent complete heart block occurred then, and compulsatory permanent pacemaker implantation was performed [13]. The long-term follow-up data is required.
Cheng et al. reported a minimally invasive technique in the surgery of cystic tumors of AVN in moderate hypothermia by using Del Nido cardioplegia [26]. A multi-septated mass was excised, and the remaining edges of the cyst were marsupialized, finally [26]. The patient was discharged in good condition without a permanent pacemaker. Unfortunately, the long-term follow-up data is required.

Limitations

There are several limitations in the current review. First, the data sources primarily relied on retrospective observational studies on the web. Certain parameters, such as patients’ age, pre-diagnostic symptoms, histopathology, tumor invasiveness, and the extent of resection, postoperative long-term follow-up data could not be obtained from each included study as they were not reported. Therefore, an exact statistical comparison couldn’t be provided in the current review.

Conclusion

In most patients’ medical history, previous congenital heart block in various degrees exists, which might be related to AVN tumor and misdiagnosed as early onset ‘congenital’ heart block. Therefore, it should be kept in mind that this probability exists in heart blocks of childhood. In addition, for bradycardic patients -such as professional athletes- further imaging tests should be made or more specific imaging methods should be developed, whether the patient is asymptomatic about cystic tumor of AVN [21]. For instance, special intracardiac ultrasound to detect the cystic tumor of AVN in case of unknown cause early onset arrhythmia might be a desired method for diagnosis in the future.
It has been advised to take a routine section of the AVN during autopsy in all cases of sudden death, because the cystic tumor of AVN is still one of the most common and silent causes of sudden death [1].
Even though this tumor is a benign congenital tumor, a close co-existence with a congenital heart defect was not observed in the literature.
For diagnostic methods, echocardiography, CT, and MRI should be performed with a focus on the AVN.
To monitor in mid-term follow-up, it is recommended a strict regular echocardiogram every 6 months for the first postoperative year and annually for 3 years.

Figures

View Fullscreen

Figure 1. Flow diagram of the study

References

1. Luc JGY, Phan K, Tchantchaleishvili V. Cystic tumor of the atrioventricular node: a review of the literature. J Thorac Dis. 2017;9(9):3313-8. doi:10.21037/jtd.2017.08.101.
   Article PubMed Google Scholar
2. Sarjeant JM, Butany J, Cusimano RJ. Cancer of the heart: epidemiology and management of primary tumors and metastases. Am J Cardiovasc Drugs. 2003;3(6):407-21. doi:10.2165/00129784-200303060-00004.
   Article PubMed Google Scholar
3. Paniagua JR, Sadaba JR, Davidson LA, Munsch CM. Cystic tumour of the atrioventricular nodal region: report of a case successfully treated with surgery. Heart. 2000;83(4):E6. doi:10.1136/heart.83.4.e6.
   Article PubMed Google Scholar
4. Saito S, Kobayashi J, Tagusari O, et al. Successful excision of a cystic tumor of the atrioventricular nodal region. Circ J. 2005;69(10):1293-4. doi:10.1253/circj.69.1293.
   Article PubMed Google Scholar
5. Kaminishi Y, Watanabe Y, Nakata H, Shimokama T, Jikuya T. Cystic tumor of the atrioventricular nodal region. Jpn J Thorac Cardiovasc Surg. 2002;50(1):37-9. doi:10.1007/BF02913485.
   Article PubMed Google Scholar
6. Sharma G, Linden MD, Schultz DS, Inamdar KV. Cystic tumor of the atrioventricular node: an unexpected finding in an explanted heart. Cardiovasc Pathol. 2010;19(3):e75-8. doi:10.1016/j.carpath.2008.10.011.
   Article PubMed Google Scholar
7. Evans CA, Suvarna SK. Cystic atrioventricular node tumour: not a mesotelioma. J Clin Pathol. 2005;58(11):1232.
   PubMed Google Scholar
8. Tran TT, Starnes V, Wang X, Getzen J, Ross BD. Cardiovascular magnetics resonance diagnosis of cystic tumor of the atrioventricular node. J Cardiovasc Magn Reson. 2009;11(1):13. doi:10.1186/1532-429X-11-13.
   Article PubMed Google Scholar
9. Burke AP, Anderson PG, Virmani R, James TN, Herrera GA, Ceballos R. Tumor of the atrioventricular nodal region. A clinical and immunohistochemical study. Arch Pathol Lab Med. 1990;114(10):1057-62.
   PubMed Google Scholar
10. Travers H. Congenital polycystic tumor of the atrioventricular node: possible familial occurrence and critical review of reported cases with special emphasis on histogenesis. Hum Pathol. 1982;13(1):25-35. doi:10.1016/s00468177(82)80135-4.
    Article PubMed Google Scholar
11. Basso C, Rizzo S, Valente M, Thiene G. Prevalence and pathology of primary cardiac tumors. Cardiovasc Med. 2012;15(1):18. doi:10.4414/cvm.2012.01638.
    Article PubMed Google Scholar
12. Law KB, Feng T, Nair V, Cusimano RJ, Butany J. Cystic tumor of the atrioventricular node: rare antemortem diagnosis. Cardiovasc Pathol. 2012;21(2):120-7. doi:10.1016/j.carpath.2011.05.004.
    Article PubMed Google Scholar
13. Careddu L, Pantaleo A, Savini C, Di Eusanio M, Leone O, Di Bartolomeo R. Cystic atrioventricular node tumor excision by minimally invasive surgery. Ann Thorac Surg. 2013;96(5):1873-5. doi:10.1016/j.athoracsur.2013.03.036.
    Article PubMed Google Scholar
14. Cameselle-Teijeiro J, Abdulkader I, Soares P, Alfonsín-Barreiro N, MoldesBoullosa J, Sobrinho-Simões M. Cystic tumor of the atrioventricular node of the heart appears to be the heart equivalent of the solid cell nests (ultimobranchial rests) of the thyroid. Am J Clin Pathol. 2005;123(3):369-75. doi:10.1309/GWT2PY0T-77PB-BA1A.
    Article PubMed Google Scholar
15. Ford SE. Congenital cystic tumors of the atrio-ventricular node: successful demonstration by an abbreviated dissection of the conduction system. Cardiovasc Pathol. 1999;8(4):233-7. doi:10.1016/s1054-8807(99)00013-7.
    Article PubMed Google Scholar
16. Thorgeirsson G, Liebman J. Mesothelioma of the AV node. Pediatr Cardiol. 1983;4(3):219-23. doi:10.1007/BF02242259.
    Article PubMed Google Scholar
17. Jones JSP, Lund C, Planteydt HT. Colour atlas of mesothelioma: Springer Science & Business Media; 2012. p.187.
    PubMed Google Scholar
18. Strøm EH, Skjørten F, Stokke ES. Polycystic tumor of the atrioventricular nodal region in a man with Emery-Dreifuss muscular dystrophy. Pathol Res Pract. 1993;189(8):960-4. doi:10.1016/S0344-0338(11)81113-1.
    Article PubMed Google Scholar
19. Cavanaugh J, Prahlow JA. Sudden cardiac death due to arrhythmogenic right ventricular cardiomyopathy and cystic tumor of the AV node. Forensic Sci Med Pathol. 2013;9(3):407-12. doi:10.1007/s12024-013-9434-6.
    Article PubMed Google Scholar
20. Ojha V, Pandey NN, Sharma G, Jagia P. Cystic tumor of the atrioventricular node in a patient with intermittent complete heart block. BMJ Case Rep. 2021;14(6):e244442. doi:10.1136/bcr-2021-244442.
    Article PubMed Google Scholar
21. Guo J, Zuo S, Lin C, Ji Y. Surgical treatment of a giant cystic tumor of the atrioventricular nodal region. Interact Cardiovasc Thorac Surg. 2009;8(5):592-3. doi:10.1510/icvts.2008.191866.
    Article PubMed Google Scholar
22. Bharati S, Bicoff JP, Fridman JL, Lev M, Rosen KM. Sudden death caused by benign tumor of the atrioventricular node. Arch Intern Med. 1976;136(2):224-8. doi:10.1001/archinte.1976.03630020078017.
    Article PubMed Google Scholar
23. Pan Y, Chen JL, Li ZJ et al. Cystic tumour of the atrioventricular node: a case report and review of the literature. Chin Med J (Engl). 2012;125(24):4514-6. doi:10.3760/cma.j.issn.0366-6999.2012.24.034.
    Article PubMed Google Scholar
24. Ali SZ, Susin M, Kahn E, Hajdu SI. Intracardiac teratoma in a child simulating an atrioventricular nodal tumor. Pediatr Pathol. 1994;14(6):913-7. doi:10.3109/15513819409037687.
    Article PubMed Google Scholar
25. Fukui S, Mitsuno M, Yamamura M, Ryomoto M, Hao H, Miyamoto Y. Partial resection of cystic tumor of atrioventricular node. Ann Thorac Surg. 2014;98(6):2223-6. doi:10.1016/j.athoracsur.2014.02.061.
    Article PubMed Google Scholar
26. Cheng KM, Law PS, Chen TM, Amin NHM, Lee FW, Khamis AY. A rare case of atrioventricular node cystic tumor. Sch J Med Case Rep. 2025;13(6):1329-34. doi:10.36347/sjmcr.2025.v13i06.007.
    Article PubMed Google Scholar
27. Giuliano K, Scully B, Etchill E, Lawton J. Cystic tumor of the atrioventricular node. Glob Cardiol Sci Pract. 2020;2020(2):e202028. doi:10.21542/gcsp.2020.28.
    Article PubMed Google Scholar
28. Alrashidi M, Adhya S, Monaghan M, Gall N, Murgatroyd F. Real-time three-dimensional transoesophageal echocardiography during stereotactic needle biopsy of complex atrioventricular nodal tumour. Eur J Echocardiogr. 2011;12(8):638. doi:10.1093/ejechocard/jer080.
    Article PubMed Google Scholar
29. Balasundaram S, Halees SA, Duran C. Mesothelioma of the atrioventricular node: first successful follow-up after excision. Eur Heart J. 1992;13(5):718-9. doi:10.1093/oxfordjournals.eurheartj.a060242.
    Article PubMed Google Scholar
30. Duray PH, Mark EJ, Barwick KW, Madri JA, Strom RL. Congenital polycystic tumor of the atrioventricular node. Autopsy study with immunohistochemical findings suggesting endodermal derivation. Arch Pathol Lab Med. 1985;109(1):304.
    PubMed Google Scholar
31. Muramatsu H, Asakura K, Hosoya T, Kurosu A. Variations in subtle cystic tumors of the atrioventricular node: five autopsy cases. Cardiovasc Pathol. 2024;69:107607. doi:10.1016/j.carpath.2024.107607.
    Article PubMed Google Scholar
32. Nojima Y, Ishibashi-Ueda H, Yamagishi M. Cystic tumour of the atrioventricular node. Heart. 2003;89(2):122. doi:10.1136/heart.89.2.122.
    Article PubMed Google Scholar
33. Suzuki K, Matsushita S, Suzuki H et al. Cystic tumor of the atrioventricular node: computed tomography and magnetic resonance imaging findings. J Thorac Imaging. 2014;29(6):W97-9. doi:10.1097/RTI.0000000000000111.
    Article PubMed Google Scholar
34. Ueda K, Tagusari O, Kasao M. Cystic tumour of the atrioventricular node: can an electrophysiological study predict sudden death? Europace. 2016;18(9):1334. doi:10.1093/europace/euw123.
    Article PubMed Google Scholar
35. Li Z, Li G, Jiang X, Fu X. Intraoperative frozen pathological diagnosis of cystic tumor of the atrioventricular node: a case report and review of the literature. Int J Clin Exp Pathol. 2018;11(4):2165-9.
    PubMed Google Scholar
36. Velasco A, Goldstein DJ, Slipczuk L, Di Biase L, Manheimer ED. Cystic tumor of the atrioventricular node causing rapid-onset and reversible complete heart block. JACC Case Rep. 2022;7:101700. doi:10.1016/j.jaccas.2022.101700.
    Article PubMed Google Scholar
37. Stopyra-Początek M, Kustrzycka-Kratochwil D, Gemel M, et al. An incidental finding of an atrioventricular node tumor during standard hospitalization years after pacemaker implantation. Kardiol Pol. 2025;83(7-8):918-20. doi:10.33963/v.phj.105346.
    Article PubMed Google Scholar
38. Zgrablich C, Roger V, Del Percio H et al. Cystic tumor of the atrioventricular node: a case report. Rev Argent Cir Cardiovasc. 2025;23(1):19-24. doi:10.55200/raccv.v23.n1.0090.
    Article PubMed Google Scholar
39. Manion WC, Nelson WP, Hall RJ, Brierty RE. Benign tumor of the heart causing complete heart block. Am Heart J. 1972;83(4):535-42. doi:10.1016/00028703(72)90046-4.
    Article PubMed Google Scholar
40. Anderson WA, Dmytryk ET. Primary tumor of the heart containing epitheliumlike elements. Am J Pathol. 1946;22(2):337-49.
    PubMed Google Scholar
41. Willis RA. Some unusual developmental heterotopias. Br Med J. 1968;3(5613):267-72. doi:10.1136/bmj.3.5613.267.
    Article PubMed Google Scholar
42. Lafargue RT, Hand AM, Lev M. Mesothelioma (coelothelioma) of the atrioventricular node. Chest. 1971;59(5):571-4. doi:10.1378/chest.59.5.571.
    Article PubMed Google Scholar
43. Lewman LV, Demany MA, Zimmerman HA. Congenital tumor of atrioventricular node with complete heart block and sudden death. Mesothelioma or lymphangio endothelioma of atrioventricular node. Am J Cardiol. 1972;29(4):554-7. doi:10.1016/0002-9149(72)90448-1.
    Article PubMed Google Scholar
44. Chitwood WR Jr. Cardiac neoplasms: current diagnosis, pathology, and therapy. J Card Surg. 1988;3(2):119-54. doi:10.1111/j.1540-8191.1988.tb00232.x.
    Article PubMed Google Scholar
45. Ibarra-Perez C, Korns ME, Edwards JE. Mesothelioma of the atrioventricular node. Chest. 1973;63(5):824-7. doi:10.1378/chest.63.5.824.
    Article PubMed Google Scholar
46. Wanless IR, Mielke BW, Jugdutt B, Rossall RE. “Mesothelioma of the atrioventricular node” with long-standing complete heart block. Report of a case. Am J Clin Pathol. 1975;63(3):377-83. doi:10.1093/ajcp/63.3.377.
    Article PubMed Google Scholar
47. Ross MJ. Heart block, sudden death, and atrioventricular node mesothelioma. Am J Dis Child. 1977;131(11):1209-11. doi:10.1001/archpedi.1977.02120240027005.
    Article PubMed Google Scholar
48. Fenoglio JJ Jr, Jacobs DW, McAllister HA Jr. Ultrastructure of the mesothelioma of the atrioventricular node. Cancer. 1977;40(2):721-7. doi:10.1002/10970142(197708)40:2<721::aid-cncr2820400220>3.0.co;2-a.
    Article PubMed Google Scholar
49. Linder J, Shelburne JD, Sorge JP, Whalen RE, Hackel D. Congenital endodermal heterotopia of the atrioventricular node: evidence for the endodermal origin of so-called mesoteliomas of the atrioventricular node. Human Pathol. 1984;15(11):1093-8. doi:10.1016/s0046-8177(84)80255-5.
    Article PubMed Google Scholar
50. Kawano H, Okada R, Kawano Y et al. Mesothelioma in the atrioventricular node. Case report. Jpn Heart J. 1994;35(2):255-61. doi:10.1536/ihj.35.255.
    Article PubMed Google Scholar
51. Monzón Muñoz FJ, Aguilera Tapia B, Martínez-Peñuela Virseda JM, Oliva Aldamiz H. Heterotopía endodérmica poliquística del nódulo auriculoventricular [Polycystic endodermal heterotopy of the atrioventricular node]. Med Clin (Barc). 1995;104(7):257-61.
    PubMed Google Scholar
52. Declich P, Sironi M, Isimbaldi G, Bana R. Atrio-ventricular nodal tumor associated with polyendocrine anomalies. Pathol Res Pract. 1996;192(1):54-9. doi:10.1016/S0344-0338(96)80130-0.
    Article PubMed Google Scholar
53. Arai T, Kurashima C, Wada S, Chida K, Ohkawa S. Histological evidence for cell proliferation activity in cystic tumor (endodermal heterotopia) of the atrioventricular node. Pathol Int. 1998;48(11):917-23. doi:10.1111/j.1440-1827.1998.tb03862.x.
    Article PubMed Google Scholar
54. Suárez-Mier MP, Sánchez-de-León S, Cohle SD. An unusual site for the AV node tumor: report of two cases. Cardiovasc Pathol. 1999;8(6):325-8. doi:10.1016/s1054-8807(99)00022-8.
    Article PubMed Google Scholar
55. Agaimy A, Mandl L. Papilläres fibroelastom der aortenklappe koinzident mit zystischem tumor des atrioventrikularknotens [Papillary fibroelastoma of the aortic valve coincident with a cystic tumor of the atrioventricular node]. Pathologe. 2000;21(3):250-4. doi:10.1007/s002920050396.
    Article PubMed Google Scholar
56. Cohle SD, Suarez-Mier MP, Aguilera B. Sudden death resulting from lesions of the cardiac conduction system. Am J Forensic Med Pathol. 2002;23(1):83-9. doi:10.1097/00000433-200203000-00018.
    Article PubMed Google Scholar
57. Wong J, Ball RY. Endodermal heterotopia of the atrioventricular node associated with transposition of the great arteries. Cardiovasc Pathol. 2003;12(3):159-62. doi:10.1016/s1054-8807(03)00032-2.
    Article PubMed Google Scholar
58. Song Y, Yao Q, Liu C, Laaksonen H, Saukko P, Zhu J. Morphological observations of tumors in cardiac conduction system. J Geriatr Cardiol. 2007;4(3):164-7.
    PubMed Google Scholar
59. Maujean G, Tabib A, Malicier D, Fanton L. Sudden death due to a cystic atrioventricular node tumour. J Forensic Leg Med. 2010;17(8):437-8. doi:10.1016/j.jflm.2010.08.009.
    Article PubMed Google Scholar
60. Oost E, Vermeulen T. Cystic tumour of the atrioventricular node: a case report. Pathology. 2012;44(5):487-9. doi:10.1097/PAT.0b013e3283559e12.
    Article PubMed Google Scholar
61. Kasper F, Ylijoki-Sørensen SM, Lundemose JB, Pedersen LM. Cystisk tumor i atrioventrikulærknuden som dødsårsag hos en niårig pige [Cystic tumour of the atrioventricular node in a nine year-old girl]. Ugeskr Laeger. 2012;174(14):947-8.
    PubMed Google Scholar
62. Patel J, Patel S, Sheppard MN. Benign cardiac tumours associated with sudden death. Europace. 2014;16(6):855-60. doi:10.1093/europace/eut378.
    Article PubMed Google Scholar
63. Abuzeid W, Myers RBH. Cystic tumour of the atrioventricular node: treatment dilemma. BMJ Case Rep. 2017;2017:bcr2017219314. doi:10.1136/bcr-2017219314.
    Article PubMed Google Scholar
64. Farkašová Iannaccone S, Farkaš D, Ginelliová A et al. Sudden death due to cystic tumor of the atrioventricular node and fibromuscular dysplasia ınvolving branches of the coronary arteries. Am J Forensic Med Pathol. 2018;39(1):46-9. doi:10.1097/PAF.0000000000000356.
    Article PubMed Google Scholar
65. Cohle SD. Cystic tumour of the atrioventricular node: case report and literature review. Forensic Sci Res. 2019;4(3):287-9. doi:10.1080/20961790.2019.1595349.
    Article PubMed Google Scholar
66. Ichimata S, Hata Y, Yajima N, Katayama Y, Nomoto K, Nishida N. Sexdependent expression of prostatic markers and hormone receptors in cystic tumor of the atrioventricular node: a histopathological study of three cases. Pathol Int. 2021;71(2):141-6. doi:10.1111/pin.13052.
    Article PubMed Google Scholar
67. Nogueira R, Marinho-Cardoso B, Gomes M, Amorim G. Fetal cystic and solid tumor of the atrioventricular node: autopsy diagnosis at 12 weeks of gestational age. Cardiovasc Pathol. 2024;68:107586. doi:10.1016/j.carpath.2023.107586
    Article PubMed Google Scholar

Declarations

Additional Information

Publisher’s Note
Bayrakol MP remains neutral with regard to jurisdictional and institutional claims.

Rights and Permissions

Creative Commons License

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License (CC BY-NC 4.0). To view a copy of the license, visit https://creativecommons.org/licenses/by-nc/4.0/

View full license details →

About This Article