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Cystic tumor of the atrioventricular node: rare antemortem diagnosis
Cardiovascular Pathology 21 (2012) 120 – 127
Review Article
Cystic tumor of the atrioventricular node: rare antemortem diagnosis Kelsey B. Law a , Tianshu Feng a , Vidhya Nair b , Robert James Cusimano c,d , Jagdish Butany a,⁎ a
Department of Pathology, Toronto General Hospital/University Health Network, Toronto, Canada b Department of Pathology and Laboratory Medicine, McMaster University, Hamilton, Canada c Faculty of Medicine, University of Toronto, Toronto, Canada d Division of Cardiac Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Canada Received 24 September 2010; received in revised form 12 May 2011; accepted 26 May 2011
Abstract Background: The cystic tumor of the atrioventricular node (TAV) is a rare, congenital cardiac tumor, typically located at the base of the atrial septum. Histologically benign, this multicystic mass is a tumor of the conduction system and is considered the smallest tumor capable of causing sudden and unexpected death. TAV has shown a predilection for women with a mean age at presentation of 38 years. The majority of cases are diagnosed incidentally at autopsy, while antemortem surgical excision is rare, with ours being the firth and sixth reported cases in the medical literature. Methods: We present two cases, in 33- and 29-year-old women who were admitted for complaints of dyspnea, dizziness, palpitation or numbness, along with a review of the literature. One was known to have complete congenital heart block and ventricular septal defect, where an intraoperative transesophageal echocardiogram revealed a right atrial mass. The other patient had a right atrial mass visible on magnetic resonance imaging, which led to surgical resection and permanent pacemaker insertion. Results: Histopathological examination revealed a tumor composed of cysts, some lined by squamous epithelium, and others by transitional epithelium. Irregular proliferation of glandular structures with squamoid nests within a fibrous stroma, with sebaceous-type differentiation, was also observed. A chronic inflammatory component with secondary lymphoid follicles was also noted. Conclusion: These cases are presented, along with a review of the four previously reported cases of TAV diagnosed antemortem. Awareness regarding this lesion could improve gross and microscopic characterization of TAV and increase antemortem diagnoses. © 2012 Elsevier Inc. All rights reserved. Keywords: Cardiac tumors; Cystic tumor of the atrioventricular node; Antemortem diagnosis
1. Introduction Cystic tumor of the atrioventricular (TAV) node is a rare [1–8] and congenital [9,10] primary cardiac tumor. Histologically benign [1,2,5,8,11,12], this multicystic mass [5,8,10] is located at the base of the atrial septum, in the region of the atrioventricular (AV) node [5,6,8–11]. Being a tumor situated in or around the AV node (conduction system), TAV is considered the smallest tumor capable of Competing interests: None. Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Guest Editor: Dr John Veinot. ⁎ Corresponding author. Department of Pathology, Toronto General Hospital, 11th floor, 200 Elizabeth St., Toronto ON, Canada M5G 2C4. Tel.: +1 416 340 3008; fax: +1 416 340 4213. E-mail address: [email protected] (J. Butany). 1054-8807/11/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2011.05.004
causing sudden and unexpected death [1,2,4,6,7,11–13], typically due to severe AV block or ventricular arrhythmia [1,8,14]. Although classically referred to as a tumor, TAV has a debatable histogenesis. Since there is, however, a vast amount of evidence supporting an endodermal nature, it may be time for an alternative descriptor, using terms such as pseudotumor or lesion. About 70 cases of TAV have been reported in the literature, with the majority diagnosed incidentally at postmortem. Antemortem diagnoses with successful excision are rare, with only four reported cases in the literature [3,5,6,13], ours being the fifth and sixth such cases. Presenting symptoms in both our cases include syncopal attacks related to various degrees of heart block [6]. The diagnoses were made antemortem, and both had successful excisions, at up to 4-months' follow-up. There have been no further clinical events in either case.
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Fig. 1. Case 1. (A) Four-chamber TEE view with a mass (arrowhead) at the base of the IAS between the mitral valve MV and TV. (B, C) Modified 4-chamber view showing cystic-like features within the mass (arrows). IAS, interatrial septum; MV, mitral valve; TV, tricuspid valve.
2. Case report
appeared to be multicystic. The subaortic VSD was repaired at the same operation.
2.1. Case 1 2.2. Case 2 A 33-year-old woman with both a congenital subarterial ventricular septal defect and congenital heart block presented for an epicardial dual-chamber pacemaker due to symptoms related to her bradycardia. An intracardiac mass was noted at the time of epicardial atrial lead placement. A transesophageal echocardiogram (TEE) confirmed its presence and location at the base of the interatrial septum (Fig. 1A). Postoperative cardiac, chest, abdomen, and head computed tomography scans failed to further delineate a lesion or demonstrate “metastatic” lesions, and she was reoperated for excision of the primary lesion, which measured 26×27 mm. At operation, a hard mass in the triangle of Koch was found. In order to remove the lesion, the tricuspid and mitral valves were temporarily detached from their respective annulae. The resultant defect, essentially the septum primum, was reconstructed with pericardium, and the leaflets were reattached. During the excision, the lesion was entered. A grayish material reminiscent of toothpaste emanated from the lesion, which essentially, clinically, now
A 29-year-old woman known to have spina bifida occulta, Meckel's diverticulum, Wolf–Parkinson–White syndrome and atrial septal defect (ASD) underwent ablation for the Wolf– Parkinson–White. She was subsequently sent for percutaneous closure of the ASD. A magnetic resonance imaging (MRI) demonstrated a hitherto unknown lesion in the area of the triangle of Koch measuring 14×19 mm. Five months later, a TEE revealed that the mass had grown to 25×20 mm and extended from the aortic root toward the orifice of the inferior vena cava (Fig. 2C). After a negative metastatic workup, an operation was undertaken, both to close the ASD and to resect the mass lesion in the heart. She had also complained of numbness of the left thumb, with a negative workup. At operation, a smaller but similar lesion to the first case was found, along with the same material inside the lesion. It, too, was within the triangle of Kock. Repair was similar to the first case. The patient was given a dual-chamber pacemaker postoperatively for persistent junctional rhythm.
Fig. 2. Case 2. (A) Four-chamber TEE view with a mass (arrowhead) at the base of the IAS (⁎). B, Mass in modified 4-chamber view with speckled appearance and a mobile strand (arrow) attached on the right atrium (RA) surface. (C) Biplane view of a mass at 0° (left) and 90° (right) extending from the aortic root to the orifice of the IVC (arrow). IAS, interatrial septum; IVC, inferior vena cava.
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Both lesions were initially very hard but became soft when the contents came out.
3. Histopathological examination 3.1. Case 1 On gross examination, the excised tissue was a pale yellow-white mass with endocardium on one surface and fibrotic epicardium on the other (Fig. 3A). This specimen had maximum dimensions of 21 mm in length and 25 mm across, with a thickness from 3 to 12 mm. The cut surface
showed small cystic spaces (Fig. 3B). Histological sections revealed inflammatory infiltration (Fig. 3C), with an irregular proliferation of glandular structures and squamoid nests within a fibrous stroma (Fig. 3D). Some areas suggested sebaceous-type differentiation. Many of the glandular structures were cystically dilated with protein-rich granular secretions, histiocytes, and occasional corpora amylacea-like concretions. Focal calcification was noted (Fig. 3E). The stroma demonstrated a moderate to marked chronic inflammatory component including lymphoid follicles. There was no cytological atypia or appreciable mitotic activity. The lesion was moderately circumscribed but was present at the margin of excision.
Fig. 3. Gross and histopathology of case 1. (A) The block of excised tumor that was later cut into vertical slices. (B) The sliced pieces show smaller cystic spaces within the tumor. (C) A low-magnification view shows epicardial fat and atrial wall (top left) in relationship to the tumor cells. There are multiple cystic structures as well as significant inflammatory infiltration (hematoxylin and eosin, ×2.5). (D) The tumor is composed of varying sized cysts. The cyst linings vary from cuboidal to squamoid or glandular appearances. Some larger cysts are filled with necrotic cells and debris; solid cords of epithelial cells are also visible (hematoxylin and eosin, ×5). (E) A large cyst contains proteinaceous fluid and focal areas of calcification (arrow; hematoxylin and eosin, ×10). Immunohistochemical stains show both EMA (F; ×10) and CEA-positive cells (G) at the cyst linings. The cells inside the cysts are also positive for CEA (×10).
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3.2. Case 2 On gross examination, the mass was soft to firm, tan in color, with endocardium on one surface and epicardium on the other (Fig. 4A). The specimen showed an overlying moderately thickened endocardium with underlying myocardium. The maximum dimension of this specimen was 24×12×12 mm. Sections showed a tumor composed of cysts of varying sizes. Sections through it showed cystic spaces filled with necrotic, pale brown, purulent looking material, suggestive of abscesses (Fig. 4B). The diameter of the cysts ranged from 1.0 to 5.0 mm. Histologically, some papillary fronds were observed extending into the cyst cavity (Fig. 4C).
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The cysts were lined by varigated epithelium. Some were lined by squamous looking epithelium, while others were lined by transitional epithelium. Many of the cysts were fluid filled, while some contained periodic-acid Schiff-positive, diastase resistant material. Sebaceous cell-type differentiation with cells having large clear cytoplasm vacuoles was also noted (Fig. 4D). Focal areas showed lymphocytic aggregation. In some areas, small cords of these cells were seen extending into the adjacent myocardium. In the marginal areas, the cords of cells could be seen invaginating between cardiac muscle fibers (Fig. 4E). This, however, does not constitute invasion, as no mitoses were seen in either case. Perhaps, the increase in size of the mass was related to increasing size of the cystic structures.
Fig. 4. Gross and histopathology of case 2. The block of excised tumor (A), which was sliced vertically, and the smaller pieces (B) shows numerous cystic spaces filled with necrotic fluid. (C) A low-magnification view shows papillary fronds extending into the cyst cavities (hematoxylin and eosin, ×2.5). (D) A large cyst, lined with transitional epithelium, contains large, clear cytoplasm-filled cells with a sebaceous appearance. The maturation of epithelial cells at the cyst lining into sebaceous looking cells is apparent as the cells extend inward (hematoxylin and eosin, ×20). (E) There is no fibrous capsule that separates tumor cells and normal tissue as in other benign tumors. The tumor cells can be seen extending into the myocardial fibres, although this is not indicative of invasion (hematoxylin and eosin, ×20). Immunohistochemical staining shows the cyst linings positive for both EMA (F; ×10) and CEA (G). The cells inside the cysts are also positive for CEA (×10).
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12], or “tumor of the AV nodal region” [11,12] are also being used.
Table 1 Immunohistochemistry profile of TAV Antibody CEA EMA CKs (CK5/6, CK7) CK20 Vimentin Calretinin p63 Calponin
Past studies a, b, c
+ + a, b, c + a, b, c −b −c − a, b +c
Case 1
Case 2
+ + + + + − + +
+ + + + + − + +
CK, cytokeratin + and - indicate positive and negative staining, respectively. a b c
Indicates a result from Sharma et al. [6]. Indicates a result from Evans et al. [7]. Indicates a result from Cameselle-Teijeiro et al. [12].
3.2.1. Immunohistochemistry Extensive immunohistochemistry staining was performed on both cases (Table 1). These stains confirmed that the lining of the cystic spaces and the solid cords of cells were endodermal in origin, as epithelial membrane antigen (Figs. 3F and 4F), carcinoembryonic antigen (CEA; Figs. 3G and 4G), and vimentin stains were all positive, and that there was no suggestion of a mesothelial origin (negative for calretinin). The immunohistochemical stains were negative for calcitonin, chromogranin, synaptophysin, Wilm's tumor 1, and S100. Previous studies reported negative stains for human mesothelial cell marker HBME, thyroid transcription factor-1, and thromobomodulin, but reactivity for pankeratin (AE1, AE3), B72.3, galectin-3, and carbohydrate antigen 19.9 was noted [6,7,12]. Stains for macrophages (CD68) and lymphocytes (CD45) were positive in the inflammatory component. Stains for MIB-1, an antibody against Ki-67 (a cellular marker for proliferation), were also positive. 4. Discussion 4.1. Synonyms TAV was first described in 1911 as a lymphangioendothelioma due to a postulated lymphatic origin [11]. Since then, the origin and histogenesis have been hotly debated, and various terms have been used to describe the tumor, including angioendothelioma [1], mesothelioma of the AV node [3,9–12,14], benign mesothelioma of Mahaim [10], lymphangioma [3,9,10,14], lymphangioendothelioma [12], endothelioma [9,10], inclusion cyst [9,10,12], polycystic tumor [14], endodermal heterotopia [10,14], endodermal rest [10], dysontogenetic endodermal tumor, a remnant of the truncus arteriosus division (hamartoma), hamartoma, epithelial inclusion, chronic lymphangitis proliferans, adenoma-like tissue malformation of the serosal epithelium, heterotopic epithelial replacement of the AV node, congenital endodermal heterotopia [12], and Tawarian node [10]. Due to its presently known benign and histologically cystic nature, terms similar to ‘benign congenital polycystic tumor of the AV node region’ [10–
4.2. Clinical features TAV is a rare tumor often detected incidentally at autopsy [1–4,11,12] after sudden death [2,11,12,15], which is typically due to syncopal attacks [6,12,15], with the majority related to complete/fatal heart block [3,5,6,9,11,12] (although partial heart block has been reported) [7], AV block [3], and arrhythmias [3,5,6,9]. TAV typically presents in adulthood [16] at a mean age of 38 years [1,2,6,9,10,15], ranging from newborns to 86 years [3,6,10,15], with a female-to-male ratio of 3:1 [1,2,9–11,13,16]. The mass itself arises from the right atrium and the interatrial septum [3] and is located at the base of the atrial septum, in the region of the AV node [5,6,9–12]. It involves the conduction system [3] and tends to completely or partially replace the AV node [15]. Although typically detected postmortem, those that are detected antemortem are generally seen with TEE or MRI [6]. Congenital TAV can occur in patients possessing congenital heart block, or those with complex congenital heart disease and other organ malformations, such as thyroglossal duct cysts, coexisting cysts in the ovaries and breast, polycystic ovaries, ventricular septal defect, nasal septal defect, Dandy–Walker anomaly, encephalocele, thinning of corpus callosum, absent septum pellucidum, Meckel diverticulum, hyperplasia of the islets of Langerhans, thymic hyperplasia, adrenal tissue heterotopia, clear cell adenomatosis in the kidney, and/or Emery–Dreifuss muscular dystrophy [12]. There is also a question of whether or not TAV has a familial connection. It has been proposed that there is a genetic predisposition for dilated cardiomyopathy and for TAV [12,15]. A possible familial occurrence, associated with midline defects and other congenital lesions, suggests a genetic defect involving migration of embryologic tissues [12]. Cameselle-Teijeiro et al. [12] suggest that TAV represents an ultimobranchial heterotopia, with a histogenesis involving an alternation in cardiac neural crest cell development. This hypothesis is supported by numerous gene mutations associated with neural crest-related defects existing in mammalian models with TAV [12]. However, the exact mechanism of this is unknown and is not yet proven. 4.3. Review of the literature To the best of our knowledge, approximately 70 cases of TAV have been published in the literature since 1911, with ours being only the fifth and sixth cases diagnosed antemortem [3,5,6,13]. All TAV cases diagnosed antemortem involved females, with a mean age of 41 years. Balasundaram et al. [13] were the first authors to report on a case of TAV successfully resected. In their case from 1992, a 21-year-old female with a history of palpitations, dyspnea on moderate exertion, and a heart murmur was presented.
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Electrocardiogram (ECG) revealed first-degree AV block, and a two-dimensional echocardiogram (ECHO) demonstrated an ostium secundum ASD. A mass only 0.5 mm in diameter was discovered during surgery in the interatrial septum in the area of the triangle of Koch, between the coronary sinus and the AV node. The mass was excised completely. Paniagua et al. [3] reported the first case of TAV discovered preoperatively by ECHO and MRI. In 2000, their 59-year-old female patient presented with palpitations. ECG and 24-hour Holter monitoring revealed sinus rhythm and various degrees of heart block. An ECHO and MRI revealed a right atrial cystic lesion with a broad connection within the interatrial septum. During surgery, the mass was seen to be 30 mm in its greatest dimension, lying within the interatrial septum. The cyst was successfully incised and deroofed from the right atrial surface. Postoperatively, the patient developed atrial flutter with various degrees of AV block and a slow ventricular rate, for which a permanent pacemaker was inserted. Kaminishi et al. [5] reported the case of a 66-year-old woman who presented with a 1-year history of exertional dyspnea and palpitation. A resting ECG and 24-hour Holter monitoring revealed sinus rhythm and various degrees of heart block. A routine ECHO revealed an intracardiac tumor, with a TEE and computed tomography scan demonstrating a right atrial cystic lesion with a broad connection to the interatrial septum. During surgery, a right atriotomy revealed a mass, 30 mm in its greatest dimension, lying within the interatrial septum in the area of the triangle of Koch. Kaminishi et al. were able to successfully prevent heart block by leaving the cyst wall attached to the base of the interatrial septum when removing the mass. Sharma et al. [6] reported the first case of TAV diagnosed in an explanted heart specimen. Their 19-year-old patient had a history of congenital heart block, for which a permanent pacemaker was inserted at age 12 years. She presented with shortness of breath, second-degree AV block, and lipomatous hypertrophy of the interstitial septum. Diagnosed with congestive heart failure, the patient underwent cardiac transplant. On gross examination of the explanted heart, sections from the AV node region revealed a lesion that was diagnosed as TAV, based on morphological and immunohistochemical findings. 4.4. Histopathological features The gross findings for AV are very subtle, with most being first identified on microscopic examination of the conduction system [16]. Nonetheless, TAV typically appears as a cyst-like structure [1,9,16], or as an area of thickening [16] with small, fluid-filled cysts [1,6,16] in the AV nodal region that are often barely perceptible [9,10].The tumor size varies, as the majority are between 2 and 20 mm in diameter [5,9,10,16]. However, sizes as small as 0.5 mm and as large as 30 mm have been reported [4]. Since TAV lacks draining channels to epicardium or endocardium, any change in size
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brought about by secretory functions of the lining cells can directly affect the AV node [6]. Microscopically, TAV is a benign, multicystic tumor devoid of smooth muscle [3]. The tumor tends to arise in the inferior interatrial septum and respects the boundaries of the central fibrous body, excluding involvement of the ventricular myocardium or the valves [9,10]. The tumor cells occur in nests [10] and are embedded in the vascular fibrous stroma [11,16]. These nests can replace myofibers within the inferior interatrial septum [9] and are composed of epithelial cells, which may be squamous, sebaceous, cuboidal, or transitional [3,10,16]. The cysts often form two cell layers: the inner (or luminal) one being cuboidal and the deeper consisting of transitional cells [1,9]. A two-cell population may also form, as sebaceous cells can occasionally be found interspersed among cuboidal cells [9]. Dense fibrosis is often seen surrounding the cysts of cell nests with a lymphocytic reaction [9]. Interestingly, the epithelium can flatten causing the cysts to assume tortuous shapes, which may explain why TAV was previously thought to have an endothelial origin [9]. Electron microscopy examination reveals two cell types, including (1) cells that form solid nests, have a well-formed basement membrane, possess cytoplasmic tonofilaments, and are joined by desmosomes, and (2) cells that line spaces (forming glands) and are connected by desmosomes that have short microvilli, and may contain electron dense material [9,10]. 4.5. Histogenesis The debate of the origin of TAV has recently focused on endodermal versus mesothelial, with the majority favoring a foregut endodermal origin [10], in which the tumor arises from rests of foregut endodermal cells entrapped during fusion of the AV septum [16]. Histochemical, ultrastructural, and immunohistochemical studies support the postulated endodermal origin [1,6,14], as staining qualities of secretory products and immunohistochemical cell expression of cytokeratin and epithelial membrane antigen (EMA) demonstrate epithelial differentiation [7,9], and the expressions of CEA and B72.3 all demonstrate an endodermal origin [9–11]. In particular, CEA and B72.3 are strongly positive in most cases, are known to be commonly found in embryonic or neoplastic glandular epithelium, and are generally absent in mesothelial cells [9]. Arai et al. [14] tested for thrombomodulin, which is a marker for mesothelioma, and had a negative reaction. Also, histochemistry showed Alcain blue and periodic-acid Schiff staining that resisted hyaluronidase and diastase digestion, which is characteristic of an endodermal origin [14]. In addition, there has been a report of endocrine cells being interspersed among the lining cells of the tumor that stain for calcitonin and serotonin, also supporting an endodermal and not mesothelial origin [9,10]. However, the exact embryogenesis is still controversial. It has been postulated that the tumors are not true
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neoplasms [14] and likely represent a “misplaced embryologic tissue” [1], capable of slow proliferation [7]. Since TAV can be seen in cases of patients with other midline defects (about 10%) [10], lesions may represent embryologic tissue [4,9]. Furthermore, Arai et al. [14] identified mitoses and nuclear fragments, which resembled apoptotic bodies, and were recognized as a marker of cell proliferation and loss, respectively. The presence of mitosis in tubules indicates cell renewal, where the imbalance between cell proliferation and cell loss could cause alteration in size and shape of the mass [14]. The fact that there is evidence of cell proliferation may explain the diagnosis occasionally being made in advanced years and why patients may live for decades with complete heart block [15]. Due to the debatable histogenesis of TAV, it may be time for an alternative descriptor, using terms such as pseudotumor or lesion, as opposed to tumor. 4.6. Differential diagnosis Bronchogenic cysts, unlike TAV, are typically larger, single cysts with a muscular wall and tend to occur on the epicardial surface, remote from the atrial septum [9]. Teratomas may have a similar localization to TAV but are differentiated by the presence of neural and other ectodermal structures [9]. Mesothelial cysts tend to be larger and unilocular and are localized to the surface of the heart [9]. Metastatic carcinoma demonstrate cellular pleomorphism [9]. Myxomas have an extensive myxoid background and intracavitary growth, which is otherwise absent in TAV [9]. 4.7. Future guidelines and treatment Although the majority of TAVs are diagnosed incidentally and at autopsy, there are some cases diagnosed antemortem. The use of cardiovascular magnetic resonance and computed tomography has been useful in identifying tumors such as TAV that occur in the intra-atrial septum and the AV nodal region [8]. Also, patients (particularly women) with electrocardiographic evidence of heart block with narrow QRS complexes limited to the AV node should be suspected of TAV [3,4], with follow-up testing to confirm. Typically, surgical resection of the mass will be performed, and a pacemaker inserted following resection [1]. The degree of persistent damage to the conduction system (in relation to surgical resection) is, however, controversial. It has not been determined whether or not the cyst should be completely resected from the intra-atrial septum base. Saito et al. [4] suggests that since TAV can result in sudden death due to ventricular tachycardia or fibrillation, complete resection is pivotal, regardless if a pacemaker is required following resection. In addition to pacemaker implantation, antiarrhythmic drugs are often used to suppress ventricular tachycardia [9]. This combination does not always prevent terminal arrhythmias;
however, and electrical pacing has been suggested to precipitate arrhythmias [9]. 5. Conclusion In summary, we present the fifth and sixth reported cases of TAV diagnosed antemortem with successful surgical excision. Two female patients aged 33 and 29 years had presented with nonspecific symptoms including dyspnea, dizziness, palpitations, and numbness. MRI and intraoperative TEE were both useful in identifying TAV, leading to resection and insertion of permanent pacemakers. Histopathological examination revealed a tumor composed of cysts, some lined by squamous epithelium, and others by transitional epithelium. Irregular proliferation of glandular structures with squamoid nests within a fibrous stroma, with sebaceous-type differentiation, was observed. A chronic inflammatory component with secondary lymphoid follicles was also noted. Awareness about this lesion would improve our knowledge of gross and microscopic characteristics of TAV and ultimately increase antemortem diagnoses. References [1] 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. [2] Butany J, Nair V, Naseemuddin A, Nair GM, Catton C, Yau T. Cardiac tumours: diagnosis and management. Lancet Oncol 2005;6(4):219–28. [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. [4] Saito S, Kobayashi J, Tagusari O, Bando K, Niwaya K, Nakajima H, Yamagishi M, Yagihara T, Kitamura S. Successful excision of a cystic tumor of the atrioventricular nodal region. Circ J 2005;69(10):1293–4. [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. [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. [7] Evans CA, Suvarna SK. Cystic atrioventricular node tumour: not a mesothelioma. J Clin Pathol 2005;58(11):1232. [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;11:13. [9] Burke A, Virmani R. Tumors of the heart and great vessels. Atlas of tumor pathology. Washington (DC): Armed Forces Institute of Pathology, 1996. p. 112. [10] Burke AP, Araoz PA. Cystic tumour of atrioventricular node. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, editors. World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press, 2004. [11] 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. [12] Cameselle-Teijeiro J, Abdulkader I, Soares P, Alfonsín-Barreiro N, Moldes-Boullosa 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.
K.B. Law et al. / Cardiovascular Pathology 21 (2012) 120–127 [13] 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. [14] 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.
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[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. [16] Gulino SP. Examination of the cardiac conduction system: forensic application in cases of sudden cardiac death. Am J Forensic Med Pathol 2003;24(3):227–38.
Review Article
Cystic tumor of the atrioventricular node: rare antemortem diagnosis Kelsey B. Law a , Tianshu Feng a , Vidhya Nair b , Robert James Cusimano c,d , Jagdish Butany a,⁎ a
Department of Pathology, Toronto General Hospital/University Health Network, Toronto, Canada b Department of Pathology and Laboratory Medicine, McMaster University, Hamilton, Canada c Faculty of Medicine, University of Toronto, Toronto, Canada d Division of Cardiac Surgery, Peter Munk Cardiac Centre, Toronto General Hospital, Toronto, Canada Received 24 September 2010; received in revised form 12 May 2011; accepted 26 May 2011
Abstract Background: The cystic tumor of the atrioventricular node (TAV) is a rare, congenital cardiac tumor, typically located at the base of the atrial septum. Histologically benign, this multicystic mass is a tumor of the conduction system and is considered the smallest tumor capable of causing sudden and unexpected death. TAV has shown a predilection for women with a mean age at presentation of 38 years. The majority of cases are diagnosed incidentally at autopsy, while antemortem surgical excision is rare, with ours being the firth and sixth reported cases in the medical literature. Methods: We present two cases, in 33- and 29-year-old women who were admitted for complaints of dyspnea, dizziness, palpitation or numbness, along with a review of the literature. One was known to have complete congenital heart block and ventricular septal defect, where an intraoperative transesophageal echocardiogram revealed a right atrial mass. The other patient had a right atrial mass visible on magnetic resonance imaging, which led to surgical resection and permanent pacemaker insertion. Results: Histopathological examination revealed a tumor composed of cysts, some lined by squamous epithelium, and others by transitional epithelium. Irregular proliferation of glandular structures with squamoid nests within a fibrous stroma, with sebaceous-type differentiation, was also observed. A chronic inflammatory component with secondary lymphoid follicles was also noted. Conclusion: These cases are presented, along with a review of the four previously reported cases of TAV diagnosed antemortem. Awareness regarding this lesion could improve gross and microscopic characterization of TAV and increase antemortem diagnoses. © 2012 Elsevier Inc. All rights reserved. Keywords: Cardiac tumors; Cystic tumor of the atrioventricular node; Antemortem diagnosis
1. Introduction Cystic tumor of the atrioventricular (TAV) node is a rare [1–8] and congenital [9,10] primary cardiac tumor. Histologically benign [1,2,5,8,11,12], this multicystic mass [5,8,10] is located at the base of the atrial septum, in the region of the atrioventricular (AV) node [5,6,8–11]. Being a tumor situated in or around the AV node (conduction system), TAV is considered the smallest tumor capable of Competing interests: None. Funding: This research received no specific grant from any funding agency in the public, commercial or not-for-profit sectors. Guest Editor: Dr John Veinot. ⁎ Corresponding author. Department of Pathology, Toronto General Hospital, 11th floor, 200 Elizabeth St., Toronto ON, Canada M5G 2C4. Tel.: +1 416 340 3008; fax: +1 416 340 4213. E-mail address: [email protected] (J. Butany). 1054-8807/11/$ – see front matter © 2012 Elsevier Inc. All rights reserved. doi:10.1016/j.carpath.2011.05.004
causing sudden and unexpected death [1,2,4,6,7,11–13], typically due to severe AV block or ventricular arrhythmia [1,8,14]. Although classically referred to as a tumor, TAV has a debatable histogenesis. Since there is, however, a vast amount of evidence supporting an endodermal nature, it may be time for an alternative descriptor, using terms such as pseudotumor or lesion. About 70 cases of TAV have been reported in the literature, with the majority diagnosed incidentally at postmortem. Antemortem diagnoses with successful excision are rare, with only four reported cases in the literature [3,5,6,13], ours being the fifth and sixth such cases. Presenting symptoms in both our cases include syncopal attacks related to various degrees of heart block [6]. The diagnoses were made antemortem, and both had successful excisions, at up to 4-months' follow-up. There have been no further clinical events in either case.
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Fig. 1. Case 1. (A) Four-chamber TEE view with a mass (arrowhead) at the base of the IAS between the mitral valve MV and TV. (B, C) Modified 4-chamber view showing cystic-like features within the mass (arrows). IAS, interatrial septum; MV, mitral valve; TV, tricuspid valve.
2. Case report
appeared to be multicystic. The subaortic VSD was repaired at the same operation.
2.1. Case 1 2.2. Case 2 A 33-year-old woman with both a congenital subarterial ventricular septal defect and congenital heart block presented for an epicardial dual-chamber pacemaker due to symptoms related to her bradycardia. An intracardiac mass was noted at the time of epicardial atrial lead placement. A transesophageal echocardiogram (TEE) confirmed its presence and location at the base of the interatrial septum (Fig. 1A). Postoperative cardiac, chest, abdomen, and head computed tomography scans failed to further delineate a lesion or demonstrate “metastatic” lesions, and she was reoperated for excision of the primary lesion, which measured 26×27 mm. At operation, a hard mass in the triangle of Koch was found. In order to remove the lesion, the tricuspid and mitral valves were temporarily detached from their respective annulae. The resultant defect, essentially the septum primum, was reconstructed with pericardium, and the leaflets were reattached. During the excision, the lesion was entered. A grayish material reminiscent of toothpaste emanated from the lesion, which essentially, clinically, now
A 29-year-old woman known to have spina bifida occulta, Meckel's diverticulum, Wolf–Parkinson–White syndrome and atrial septal defect (ASD) underwent ablation for the Wolf– Parkinson–White. She was subsequently sent for percutaneous closure of the ASD. A magnetic resonance imaging (MRI) demonstrated a hitherto unknown lesion in the area of the triangle of Koch measuring 14×19 mm. Five months later, a TEE revealed that the mass had grown to 25×20 mm and extended from the aortic root toward the orifice of the inferior vena cava (Fig. 2C). After a negative metastatic workup, an operation was undertaken, both to close the ASD and to resect the mass lesion in the heart. She had also complained of numbness of the left thumb, with a negative workup. At operation, a smaller but similar lesion to the first case was found, along with the same material inside the lesion. It, too, was within the triangle of Kock. Repair was similar to the first case. The patient was given a dual-chamber pacemaker postoperatively for persistent junctional rhythm.
Fig. 2. Case 2. (A) Four-chamber TEE view with a mass (arrowhead) at the base of the IAS (⁎). B, Mass in modified 4-chamber view with speckled appearance and a mobile strand (arrow) attached on the right atrium (RA) surface. (C) Biplane view of a mass at 0° (left) and 90° (right) extending from the aortic root to the orifice of the IVC (arrow). IAS, interatrial septum; IVC, inferior vena cava.
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Both lesions were initially very hard but became soft when the contents came out.
3. Histopathological examination 3.1. Case 1 On gross examination, the excised tissue was a pale yellow-white mass with endocardium on one surface and fibrotic epicardium on the other (Fig. 3A). This specimen had maximum dimensions of 21 mm in length and 25 mm across, with a thickness from 3 to 12 mm. The cut surface
showed small cystic spaces (Fig. 3B). Histological sections revealed inflammatory infiltration (Fig. 3C), with an irregular proliferation of glandular structures and squamoid nests within a fibrous stroma (Fig. 3D). Some areas suggested sebaceous-type differentiation. Many of the glandular structures were cystically dilated with protein-rich granular secretions, histiocytes, and occasional corpora amylacea-like concretions. Focal calcification was noted (Fig. 3E). The stroma demonstrated a moderate to marked chronic inflammatory component including lymphoid follicles. There was no cytological atypia or appreciable mitotic activity. The lesion was moderately circumscribed but was present at the margin of excision.
Fig. 3. Gross and histopathology of case 1. (A) The block of excised tumor that was later cut into vertical slices. (B) The sliced pieces show smaller cystic spaces within the tumor. (C) A low-magnification view shows epicardial fat and atrial wall (top left) in relationship to the tumor cells. There are multiple cystic structures as well as significant inflammatory infiltration (hematoxylin and eosin, ×2.5). (D) The tumor is composed of varying sized cysts. The cyst linings vary from cuboidal to squamoid or glandular appearances. Some larger cysts are filled with necrotic cells and debris; solid cords of epithelial cells are also visible (hematoxylin and eosin, ×5). (E) A large cyst contains proteinaceous fluid and focal areas of calcification (arrow; hematoxylin and eosin, ×10). Immunohistochemical stains show both EMA (F; ×10) and CEA-positive cells (G) at the cyst linings. The cells inside the cysts are also positive for CEA (×10).
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3.2. Case 2 On gross examination, the mass was soft to firm, tan in color, with endocardium on one surface and epicardium on the other (Fig. 4A). The specimen showed an overlying moderately thickened endocardium with underlying myocardium. The maximum dimension of this specimen was 24×12×12 mm. Sections showed a tumor composed of cysts of varying sizes. Sections through it showed cystic spaces filled with necrotic, pale brown, purulent looking material, suggestive of abscesses (Fig. 4B). The diameter of the cysts ranged from 1.0 to 5.0 mm. Histologically, some papillary fronds were observed extending into the cyst cavity (Fig. 4C).
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The cysts were lined by varigated epithelium. Some were lined by squamous looking epithelium, while others were lined by transitional epithelium. Many of the cysts were fluid filled, while some contained periodic-acid Schiff-positive, diastase resistant material. Sebaceous cell-type differentiation with cells having large clear cytoplasm vacuoles was also noted (Fig. 4D). Focal areas showed lymphocytic aggregation. In some areas, small cords of these cells were seen extending into the adjacent myocardium. In the marginal areas, the cords of cells could be seen invaginating between cardiac muscle fibers (Fig. 4E). This, however, does not constitute invasion, as no mitoses were seen in either case. Perhaps, the increase in size of the mass was related to increasing size of the cystic structures.
Fig. 4. Gross and histopathology of case 2. The block of excised tumor (A), which was sliced vertically, and the smaller pieces (B) shows numerous cystic spaces filled with necrotic fluid. (C) A low-magnification view shows papillary fronds extending into the cyst cavities (hematoxylin and eosin, ×2.5). (D) A large cyst, lined with transitional epithelium, contains large, clear cytoplasm-filled cells with a sebaceous appearance. The maturation of epithelial cells at the cyst lining into sebaceous looking cells is apparent as the cells extend inward (hematoxylin and eosin, ×20). (E) There is no fibrous capsule that separates tumor cells and normal tissue as in other benign tumors. The tumor cells can be seen extending into the myocardial fibres, although this is not indicative of invasion (hematoxylin and eosin, ×20). Immunohistochemical staining shows the cyst linings positive for both EMA (F; ×10) and CEA (G). The cells inside the cysts are also positive for CEA (×10).
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12], or “tumor of the AV nodal region” [11,12] are also being used.
Table 1 Immunohistochemistry profile of TAV Antibody CEA EMA CKs (CK5/6, CK7) CK20 Vimentin Calretinin p63 Calponin
Past studies a, b, c
+ + a, b, c + a, b, c −b −c − a, b +c
Case 1
Case 2
+ + + + + − + +
+ + + + + − + +
CK, cytokeratin + and - indicate positive and negative staining, respectively. a b c
Indicates a result from Sharma et al. [6]. Indicates a result from Evans et al. [7]. Indicates a result from Cameselle-Teijeiro et al. [12].
3.2.1. Immunohistochemistry Extensive immunohistochemistry staining was performed on both cases (Table 1). These stains confirmed that the lining of the cystic spaces and the solid cords of cells were endodermal in origin, as epithelial membrane antigen (Figs. 3F and 4F), carcinoembryonic antigen (CEA; Figs. 3G and 4G), and vimentin stains were all positive, and that there was no suggestion of a mesothelial origin (negative for calretinin). The immunohistochemical stains were negative for calcitonin, chromogranin, synaptophysin, Wilm's tumor 1, and S100. Previous studies reported negative stains for human mesothelial cell marker HBME, thyroid transcription factor-1, and thromobomodulin, but reactivity for pankeratin (AE1, AE3), B72.3, galectin-3, and carbohydrate antigen 19.9 was noted [6,7,12]. Stains for macrophages (CD68) and lymphocytes (CD45) were positive in the inflammatory component. Stains for MIB-1, an antibody against Ki-67 (a cellular marker for proliferation), were also positive. 4. Discussion 4.1. Synonyms TAV was first described in 1911 as a lymphangioendothelioma due to a postulated lymphatic origin [11]. Since then, the origin and histogenesis have been hotly debated, and various terms have been used to describe the tumor, including angioendothelioma [1], mesothelioma of the AV node [3,9–12,14], benign mesothelioma of Mahaim [10], lymphangioma [3,9,10,14], lymphangioendothelioma [12], endothelioma [9,10], inclusion cyst [9,10,12], polycystic tumor [14], endodermal heterotopia [10,14], endodermal rest [10], dysontogenetic endodermal tumor, a remnant of the truncus arteriosus division (hamartoma), hamartoma, epithelial inclusion, chronic lymphangitis proliferans, adenoma-like tissue malformation of the serosal epithelium, heterotopic epithelial replacement of the AV node, congenital endodermal heterotopia [12], and Tawarian node [10]. Due to its presently known benign and histologically cystic nature, terms similar to ‘benign congenital polycystic tumor of the AV node region’ [10–
4.2. Clinical features TAV is a rare tumor often detected incidentally at autopsy [1–4,11,12] after sudden death [2,11,12,15], which is typically due to syncopal attacks [6,12,15], with the majority related to complete/fatal heart block [3,5,6,9,11,12] (although partial heart block has been reported) [7], AV block [3], and arrhythmias [3,5,6,9]. TAV typically presents in adulthood [16] at a mean age of 38 years [1,2,6,9,10,15], ranging from newborns to 86 years [3,6,10,15], with a female-to-male ratio of 3:1 [1,2,9–11,13,16]. The mass itself arises from the right atrium and the interatrial septum [3] and is located at the base of the atrial septum, in the region of the AV node [5,6,9–12]. It involves the conduction system [3] and tends to completely or partially replace the AV node [15]. Although typically detected postmortem, those that are detected antemortem are generally seen with TEE or MRI [6]. Congenital TAV can occur in patients possessing congenital heart block, or those with complex congenital heart disease and other organ malformations, such as thyroglossal duct cysts, coexisting cysts in the ovaries and breast, polycystic ovaries, ventricular septal defect, nasal septal defect, Dandy–Walker anomaly, encephalocele, thinning of corpus callosum, absent septum pellucidum, Meckel diverticulum, hyperplasia of the islets of Langerhans, thymic hyperplasia, adrenal tissue heterotopia, clear cell adenomatosis in the kidney, and/or Emery–Dreifuss muscular dystrophy [12]. There is also a question of whether or not TAV has a familial connection. It has been proposed that there is a genetic predisposition for dilated cardiomyopathy and for TAV [12,15]. A possible familial occurrence, associated with midline defects and other congenital lesions, suggests a genetic defect involving migration of embryologic tissues [12]. Cameselle-Teijeiro et al. [12] suggest that TAV represents an ultimobranchial heterotopia, with a histogenesis involving an alternation in cardiac neural crest cell development. This hypothesis is supported by numerous gene mutations associated with neural crest-related defects existing in mammalian models with TAV [12]. However, the exact mechanism of this is unknown and is not yet proven. 4.3. Review of the literature To the best of our knowledge, approximately 70 cases of TAV have been published in the literature since 1911, with ours being only the fifth and sixth cases diagnosed antemortem [3,5,6,13]. All TAV cases diagnosed antemortem involved females, with a mean age of 41 years. Balasundaram et al. [13] were the first authors to report on a case of TAV successfully resected. In their case from 1992, a 21-year-old female with a history of palpitations, dyspnea on moderate exertion, and a heart murmur was presented.
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Electrocardiogram (ECG) revealed first-degree AV block, and a two-dimensional echocardiogram (ECHO) demonstrated an ostium secundum ASD. A mass only 0.5 mm in diameter was discovered during surgery in the interatrial septum in the area of the triangle of Koch, between the coronary sinus and the AV node. The mass was excised completely. Paniagua et al. [3] reported the first case of TAV discovered preoperatively by ECHO and MRI. In 2000, their 59-year-old female patient presented with palpitations. ECG and 24-hour Holter monitoring revealed sinus rhythm and various degrees of heart block. An ECHO and MRI revealed a right atrial cystic lesion with a broad connection within the interatrial septum. During surgery, the mass was seen to be 30 mm in its greatest dimension, lying within the interatrial septum. The cyst was successfully incised and deroofed from the right atrial surface. Postoperatively, the patient developed atrial flutter with various degrees of AV block and a slow ventricular rate, for which a permanent pacemaker was inserted. Kaminishi et al. [5] reported the case of a 66-year-old woman who presented with a 1-year history of exertional dyspnea and palpitation. A resting ECG and 24-hour Holter monitoring revealed sinus rhythm and various degrees of heart block. A routine ECHO revealed an intracardiac tumor, with a TEE and computed tomography scan demonstrating a right atrial cystic lesion with a broad connection to the interatrial septum. During surgery, a right atriotomy revealed a mass, 30 mm in its greatest dimension, lying within the interatrial septum in the area of the triangle of Koch. Kaminishi et al. were able to successfully prevent heart block by leaving the cyst wall attached to the base of the interatrial septum when removing the mass. Sharma et al. [6] reported the first case of TAV diagnosed in an explanted heart specimen. Their 19-year-old patient had a history of congenital heart block, for which a permanent pacemaker was inserted at age 12 years. She presented with shortness of breath, second-degree AV block, and lipomatous hypertrophy of the interstitial septum. Diagnosed with congestive heart failure, the patient underwent cardiac transplant. On gross examination of the explanted heart, sections from the AV node region revealed a lesion that was diagnosed as TAV, based on morphological and immunohistochemical findings. 4.4. Histopathological features The gross findings for AV are very subtle, with most being first identified on microscopic examination of the conduction system [16]. Nonetheless, TAV typically appears as a cyst-like structure [1,9,16], or as an area of thickening [16] with small, fluid-filled cysts [1,6,16] in the AV nodal region that are often barely perceptible [9,10].The tumor size varies, as the majority are between 2 and 20 mm in diameter [5,9,10,16]. However, sizes as small as 0.5 mm and as large as 30 mm have been reported [4]. Since TAV lacks draining channels to epicardium or endocardium, any change in size
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brought about by secretory functions of the lining cells can directly affect the AV node [6]. Microscopically, TAV is a benign, multicystic tumor devoid of smooth muscle [3]. The tumor tends to arise in the inferior interatrial septum and respects the boundaries of the central fibrous body, excluding involvement of the ventricular myocardium or the valves [9,10]. The tumor cells occur in nests [10] and are embedded in the vascular fibrous stroma [11,16]. These nests can replace myofibers within the inferior interatrial septum [9] and are composed of epithelial cells, which may be squamous, sebaceous, cuboidal, or transitional [3,10,16]. The cysts often form two cell layers: the inner (or luminal) one being cuboidal and the deeper consisting of transitional cells [1,9]. A two-cell population may also form, as sebaceous cells can occasionally be found interspersed among cuboidal cells [9]. Dense fibrosis is often seen surrounding the cysts of cell nests with a lymphocytic reaction [9]. Interestingly, the epithelium can flatten causing the cysts to assume tortuous shapes, which may explain why TAV was previously thought to have an endothelial origin [9]. Electron microscopy examination reveals two cell types, including (1) cells that form solid nests, have a well-formed basement membrane, possess cytoplasmic tonofilaments, and are joined by desmosomes, and (2) cells that line spaces (forming glands) and are connected by desmosomes that have short microvilli, and may contain electron dense material [9,10]. 4.5. Histogenesis The debate of the origin of TAV has recently focused on endodermal versus mesothelial, with the majority favoring a foregut endodermal origin [10], in which the tumor arises from rests of foregut endodermal cells entrapped during fusion of the AV septum [16]. Histochemical, ultrastructural, and immunohistochemical studies support the postulated endodermal origin [1,6,14], as staining qualities of secretory products and immunohistochemical cell expression of cytokeratin and epithelial membrane antigen (EMA) demonstrate epithelial differentiation [7,9], and the expressions of CEA and B72.3 all demonstrate an endodermal origin [9–11]. In particular, CEA and B72.3 are strongly positive in most cases, are known to be commonly found in embryonic or neoplastic glandular epithelium, and are generally absent in mesothelial cells [9]. Arai et al. [14] tested for thrombomodulin, which is a marker for mesothelioma, and had a negative reaction. Also, histochemistry showed Alcain blue and periodic-acid Schiff staining that resisted hyaluronidase and diastase digestion, which is characteristic of an endodermal origin [14]. In addition, there has been a report of endocrine cells being interspersed among the lining cells of the tumor that stain for calcitonin and serotonin, also supporting an endodermal and not mesothelial origin [9,10]. However, the exact embryogenesis is still controversial. It has been postulated that the tumors are not true
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neoplasms [14] and likely represent a “misplaced embryologic tissue” [1], capable of slow proliferation [7]. Since TAV can be seen in cases of patients with other midline defects (about 10%) [10], lesions may represent embryologic tissue [4,9]. Furthermore, Arai et al. [14] identified mitoses and nuclear fragments, which resembled apoptotic bodies, and were recognized as a marker of cell proliferation and loss, respectively. The presence of mitosis in tubules indicates cell renewal, where the imbalance between cell proliferation and cell loss could cause alteration in size and shape of the mass [14]. The fact that there is evidence of cell proliferation may explain the diagnosis occasionally being made in advanced years and why patients may live for decades with complete heart block [15]. Due to the debatable histogenesis of TAV, it may be time for an alternative descriptor, using terms such as pseudotumor or lesion, as opposed to tumor. 4.6. Differential diagnosis Bronchogenic cysts, unlike TAV, are typically larger, single cysts with a muscular wall and tend to occur on the epicardial surface, remote from the atrial septum [9]. Teratomas may have a similar localization to TAV but are differentiated by the presence of neural and other ectodermal structures [9]. Mesothelial cysts tend to be larger and unilocular and are localized to the surface of the heart [9]. Metastatic carcinoma demonstrate cellular pleomorphism [9]. Myxomas have an extensive myxoid background and intracavitary growth, which is otherwise absent in TAV [9]. 4.7. Future guidelines and treatment Although the majority of TAVs are diagnosed incidentally and at autopsy, there are some cases diagnosed antemortem. The use of cardiovascular magnetic resonance and computed tomography has been useful in identifying tumors such as TAV that occur in the intra-atrial septum and the AV nodal region [8]. Also, patients (particularly women) with electrocardiographic evidence of heart block with narrow QRS complexes limited to the AV node should be suspected of TAV [3,4], with follow-up testing to confirm. Typically, surgical resection of the mass will be performed, and a pacemaker inserted following resection [1]. The degree of persistent damage to the conduction system (in relation to surgical resection) is, however, controversial. It has not been determined whether or not the cyst should be completely resected from the intra-atrial septum base. Saito et al. [4] suggests that since TAV can result in sudden death due to ventricular tachycardia or fibrillation, complete resection is pivotal, regardless if a pacemaker is required following resection. In addition to pacemaker implantation, antiarrhythmic drugs are often used to suppress ventricular tachycardia [9]. This combination does not always prevent terminal arrhythmias;
however, and electrical pacing has been suggested to precipitate arrhythmias [9]. 5. Conclusion In summary, we present the fifth and sixth reported cases of TAV diagnosed antemortem with successful surgical excision. Two female patients aged 33 and 29 years had presented with nonspecific symptoms including dyspnea, dizziness, palpitations, and numbness. MRI and intraoperative TEE were both useful in identifying TAV, leading to resection and insertion of permanent pacemakers. Histopathological examination revealed a tumor composed of cysts, some lined by squamous epithelium, and others by transitional epithelium. Irregular proliferation of glandular structures with squamoid nests within a fibrous stroma, with sebaceous-type differentiation, was observed. A chronic inflammatory component with secondary lymphoid follicles was also noted. Awareness about this lesion would improve our knowledge of gross and microscopic characteristics of TAV and ultimately increase antemortem diagnoses. References [1] 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. [2] Butany J, Nair V, Naseemuddin A, Nair GM, Catton C, Yau T. Cardiac tumours: diagnosis and management. Lancet Oncol 2005;6(4):219–28. [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. [4] Saito S, Kobayashi J, Tagusari O, Bando K, Niwaya K, Nakajima H, Yamagishi M, Yagihara T, Kitamura S. Successful excision of a cystic tumor of the atrioventricular nodal region. Circ J 2005;69(10):1293–4. [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. [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. [7] Evans CA, Suvarna SK. Cystic atrioventricular node tumour: not a mesothelioma. J Clin Pathol 2005;58(11):1232. [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;11:13. [9] Burke A, Virmani R. Tumors of the heart and great vessels. Atlas of tumor pathology. Washington (DC): Armed Forces Institute of Pathology, 1996. p. 112. [10] Burke AP, Araoz PA. Cystic tumour of atrioventricular node. In: Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC, editors. World Health Organization classification of tumours. Pathology and genetics of tumours of the lung, pleura, thymus and heart. Lyon: IARC Press, 2004. [11] 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. [12] Cameselle-Teijeiro J, Abdulkader I, Soares P, Alfonsín-Barreiro N, Moldes-Boullosa 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.
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