Cystic Tumor of the Atrioventricular Node
Synonyms and keywords:Mesothelioma of the AV node, AV node tumor

# Overview
Cystic tumor of the atrioventricular (AV) node is a rare benign congenital tumor. The origin of the cystic tumor of the AV node is still controversial. Although it is called mesothelioma of the AV node, it appears to have endodermal origin. The size of the tumor ranges from 0.5 mm to 30 mm and size of the tumor is not correlated with the occurrence of fatal arrhythmias. On gross pathology, small multiocular cysts are characteristic findings of the cystic tumor of the AV node. On microscopic examination, solid cell nests and cystic structures lined by flattended cuboidal and squamous epithelium mixed with rare neuroendocrine cells (C cells) are characteristic findings of the cystic tumor of the AV node. The immunohistochemical staining of the cystic tumor of the AV node is in favor of the epithelial differentiation of the tumor. Cystic tumor of the AV node is most commonly diagnosed postmortem in individuals died due to sudden cardiac death. Fatal arrhythmias including ventricular tachycardia or ventricular fibrillation may occur despite pacemaker placement. Only a few cases of cystic tumor of the AV node has been diagnosed antemortem. Imaging modalities including echocardiography and MRI are helpful in making the diagnosis. Histopathological examination of the resected tumor provides the definitive diagnosis. Because of the critical location of the tumor and its unfavorable prognosis, surgical excision is the mainstay of treatment for cystic tumor of the AV node. Anti-arrhythmic drugs and lifelong pacemaker placement may be necessary after excision to manage any post-surgical AV block.

# Historical Perspective
Cystic tumor of the atrioventricular (AV) node was first reported by Armstrong and Monckeberg in 1911. 

# Classification
There is no established system for the staging of the cystic tumor of the AV node.

# Pathophysiology
The cystic tumor of the AV node is a benign congenital tumor. Although it is also called mesothelioma of the AV node, it appears to be a misnomer. The origin of the cystic tumor of the AV node is still controversial. It is believed that it has endodermal origin, derived from congenital rests during embryogenesis.   One study suggested that cystic tumor of the AV node and solid cell nests of the thyroid have similar structures and may share the same developmental process; therefore it is assumed that cystic tumor of the AV node is an ultimobranchial heterotopia. 
On gross pathology, small multiocular cysts are characteristic findings of the cystic tumor of the AV node. The tumor may be invisible from the endocardial surface of the heart. Therefore, sectioning through the infero-medial tricuspid annulus might be required.    The size of the tumor ranges from 0.5 mm to 30 mm and the size of the tumor is not correlated with the occurrence of fatal arrhythmias. 
On microscopic histopathological analysis, solid cell nests and cystic structures lined by flattened cuboidal or squamous epithelium mixed with rare neuroendocrine cells (C cells) are characteristic findings of the cystic tumor of the AV node.   
On immunohistochemical staining, the main tumor cells stain positive for: 
- Cytokeratin CAM5.2
- Cytokeratin AE1/AE3
- Cytokeratin 34E12
- Cytokeratin 5/6 (CK5/6)
- Cytokeratin 7 (CK7)
- Epithelial membrane antigen (EMA)
- Carcinoembryonic antigen (CEA)
- Carbohydrate antigen (CA)19.9
- p63
- bcl2
- Galectin-3
The neuroendocrine cells of the lesion stain positive for:   
- CAM5.2
- Pan-keratin (AE1/AE3)
- CEA
- Calcitonin
- Chromogranin
- Synaptophysin
- hyroid Transcription Factor 1 (TTF1)
The tumor stains negative for:   
- Keratin 20 (CK20)
- p53
- Bcl-2
- Cyclin D1
- Cytokeratin 20 (CK20)
- Vimentin
- CD31
- Factor VIII related antigen
- Estrogen receptor
- Progesterone receptor
- Thrombomodulin
- Wilms tumor 1
- Calretinin
However, true mesothelium stains positive for thrombomodulin, Wilms tumor 1, calretinin and negative for PAS. 
The immunohistochemistry staining of the cystic tumor of the AV node is in favor of the epithelial differentiation of the tumor and supports the labeling of this tumor as an endodermal heterotopia. 

# Causes
The cause of the cystic tumor of the AV node has not been identified. Other mid-line developmental defects are seen in 10% of the patients. It suggests that a genetic defect might involve migration of embryological tissues and cardiac neural crest cell development   with possible familial predisposition.  Considering the absence of mitoses in the tumor, it is suggested to be resulted from a dilatation of cystic spaces rather than true neoplasm.  

# Differentiating Cystic Tumor of the AV node from Other Diseases
Cystic tumor of the AV node must be differentiated from other cardiac tumors.

# Epidemiology and Demographics
Primary cardiac tumors are rare with an incidence of 0.0017% to 0.03% of all autopsies.   Cystic tumor of the AV node accounts for 2.7% of cardiac tumors and it is the most common primary cardiac tumor that causes sudden death.  
There is no racial or ethnic predilection to the cystic tumor of the AV node.
Women are more commonly affected by the cystic tumor of the AV node than men. The female to male ratio is approximately 3 to 1. 
The cystic tumor of the AV node is usually diagnosed in the fourth decade of life. 

# Risk Factors
There are no established risk factors for the cystic tumor of the AV node.

# Screening
There is insufficient evidence to recommend routine screening for the cystic tumor of the AV node.

# Natural History, Complications, and Prognosis
Cystic tumor of the AV node is most commonly diagnosed postmortem in individuals died due to sudden cardiac death.  Fatal arrhythmias including ventricular tachycardia or ventricular fibrillation may occur despite pacemaker placement.  

# Diagnosis

## Diagnostic Study of Choice
There are no established criteria for the diagnosis of cystic tumor of the AV node. Only a few cases of cystic tumor of the AV node has been diagnosed antemortem. Imaging modalities including echocardiography and MRI are helpful in making the diagnosis.  Histopathological examination of the resected tumor provides the definitive diagnosis. 

## History and Symptoms
The presentation of the cystic tumor of the AV node can range from being asymptomatic to sudden cardiac death.  
Typical symptoms are:   
- Palpitations
- Dyspnea
- syncope
- Dizziness
Patients may also present with partial or complete heart block.   

## Physical Examination
Physical examination of patients with cystic tumor of the AV node is usually unremarkable.

## Laboratory Findings
There are no diagnostic laboratory findings associated with cystic tumor of the AV node.

## Electrocardiogram
An ECG may be helpful in the diagnosis of cystic tumor of the AV node. ECG might show partial or complete heart block. 

## X-ray
There are no x-ray findings associated with cystic tumor of the AV node.

## Echocardiography or Ultrasound
Echocardiography may be helpful in the diagnosis of cystic tumor of the AV node, showing a mass at the site of the tumor.   

## CT scan
Only a few cases of cystic tumor of the AV node have been reported antemortem. Therefore, the data regarding the imaging findings are limited. Reports have shown either a high-attenuation  or low-attenuation lesions on CT images. 

## MRI
Cardiac MRI may be helpful in the diagnosis of the cystic tumor of the AV node. High-signal intensity lesion on T1-weighted   and T2-weighted MRI  or low signal intensity on T2-weighted MRI  have been reported.

## Other Imaging Findings
There are no other imaging findings associated with cystic tumor of the AV node.

## Other Diagnostic Studies
There are no other diagnostic studies associated with cystic tumor of the AV node.

# Treatment

## Medical Therapy
There is no medical treatment for the cystic tumor of the AV node.

## Surgery
Because of the critical location of the tumor and its unfavorable prognosis, surgical excision is the mainstay of treatment for cystic tumor of the AV node. Anti-arrhythmic drugs and lifelong pacemaker placement may be necessary after excision to manage any post-surgical AV block.  

## Primary Prevention
There are no established measures for the primary prevention of the cystic tumor of the AV node.

## Secondary Prevention
There are no established measures for the secondary prevention of the cystic tumor of the AV node.