Cystic tumour of the atrioventricular node (CTAN) is a rare, primary cardiac tumour located in the atrioventricular nodal region. CTAN can be found incidentally at autopsy, causing sudden death associated with complete heart blockage.1 The tumour is benign and congenital, but it is the smallest tumour capable of developing sudden death.2,3 The precise diagnosis of this tumour is based on its macroscopic presence and detailed examination of the cardiac conduction system. Here, we present the case of an unexpected death from cystic tumour in the atrioventricular node detected after detailed histological and immunohistochemical examination during autopsy.
A man aged 42 years, after quarrelling with others, suddenly died. He had no history of palpitation, syncope, amaurosis fugax, hypertension, atherosclerosis or other heart diseases. A complete postmortem study was performed with detailed pathological observations, followed by several panels of immunohistochemical markers staining. At autopsy, all of the systemic organs were macroscopically normal, except small cystic lesions (6 mm×8 mm) found in atrioventricular nodal region when dissecting the cardiac conduction system in series.
Microscopic examination suggested a cystic tumour consisting of small and large cystic spaces and tubular structures lined by two or more layers of flat, cuboidal or squamous epithelial cells (Figure 1). In some areas, there were solid nests of epithelioid cells resembling sebaceous glands with compact dark cells on the periphery and larger pale cells in the centre (Figure 2). In addition, loosely arranged spindle cells scattered in the stroma. The tumour cells extensively penetrated into the atrioventricular nodal region, destroyed the nodal structure and partially infiltrated into the atrial muscles. However, the tumour cells displayed neither anaplasia nor mitotic figures. Amorphous eosinophilic material was found in the cystic lumina, which was positive for PAS staining (Figure 3).
Immunohistochemical staining showed that the tumour cells were strongly positive for pan-keratin (AE1/AE3), epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA) (Figure 4), cytokeratins CK5/6 and CK7, but negative for calretinin, HBME-1, Wilms' tumor 1, factor VIII, chromogranin, synaptophysin or smooth muscle actin. Thus, it was pathologically diagnosed as cystic tumour of the atrioventricular node.
Cystic tumour of the atrioventricular node was firstly described by Armstrong and Monckeberg in 1911 in a 5-year-old boy.4 CTAN is a very uncommon, primary cardiac tumour located in the region of the atrioventricular node and associated with sudden cardiac death. It also has been termed “lymphangioma” and “mesothelioma of atrioventricular node”.4,5 More than 70 cases have been reported, and majority of diagnoses were based upon postmortem examination.3,6,7 Only six recent cases have been diagnosed in living patients, including one in China.6–10 Among all of the reported cases, females were more often involved than males. The patient's age ranged from newborn to 86 years old,7,11 while most died before age 40 years. Clinically, the tumour can initially cause variable degrees of heart block and then gradually evolve to complete heart blockage. Ventricular tachycardia or ventricular fibrillation may be the main reasons for patient's sudden death.3 Tumour size varies from 0.5 mm to 30 mm in diameter and statistically is not associated significantly with lethal arrhythmia.6,11,12 Differential diagnoses of cystic epithelioid tumours in the region of the atrioventricular node include bronchogenic cysts, ectopic thyroid (struma cordis) and teratoma metastatic adenocarcinomas.10 The clinicopathological features of this case is similar to those previously described (Table 1).
The origin of these atrioventricular node tumours has not been clearly explored until now. Possible histogenetic origins include lymphangio-endothelial, epithelial, endodermal and mesothelial cells. Many authors believed in a mesothelial origin, so “mesothelioma of the atrioventricular node” had been widely accepted since 1960's. However, recent studies using immunocytochemical methods demonstrated positive staining of these atrioventricular node tumours for cytokeratin, EMA and CEA but negative staining for mesothelial markers such as calretinin, thrombomodulin, Wilms' tumour 1 or HBME-1 and also negative for factor VIII, p53, Bcl-2, cyclinD1, CK20, and TTF-1. These results suggest a possible endodermal origin of the lesions. In our case, the tumour epithelium showed positive staining for EMA, CEA, AE1/AE3, cytokeratin CK5/6 and CK7, but negative for calretinin, HBME-1, Wilms' tumor 1, factor VIII, chromogranin, synaptophysin and smooth muscle actin. This staining pattern suggested that the tumour had an endodermal origin rather than a mesothelial origin, consistent with some reports.5,15 All of the reported tumours have been located in the atrioventricular area: the lesion probably represents endodermal foregut tissue that was displaced during embryogenesis.2 Furthermore, its benign histological appearance and the immunohistochemical profile undermine a neoplastic aetiology, but support a congenital endodermal heterotopia of the atrioventricular node capable of slow proliferation. Complete heart blockage because of the lethal arrhythmia arising from this cystic tumour may be the direct reason for our patient's death. However, the detailed mechanisms need to be further investigated.
Two cases of postmortem diagnosed “mesothelioma of the atrioventricular node” and one case of antemortem diagnosed “cystic tumour of atrioventricular nodal region” have been reported in China.9,16,17 This case has the most detailed pathological analyses, and so far as we know, we are the first Chinese group to suggest using the term of “cystic tumour of the atrioventricular node”. In summary, antemortem diagnosis of a cystic tumour of the atrioventricular node region is difficult, but should be considered as a differential diagnosis in patients with electrocardiographic evidence of heart block limited to the atrioventricular node, both in children and young adults, particularly in women. Because subsequent pacemaker implantation may not prevent patient's death,3 it still remains as a question whether the cyst should be resected completely from the base of the interatrial septum after diagnosis.
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