"Mesothelioma of the Atrioventricular Node" with Long-standing Complete Heart Block Report of a Case I. R. W A N L E S S , M.D.,

CM.,

B. W. M I E L K E , M.D.,

F . R . C . P A T H . (C),

B. J U G D U T T , M.B., C H . B., AND R. E. ROSSALL, M.D., F.R.C.P. Departments of Pathology and Medicine, University of Alberta Hospital, Edmonton, Alberta, Canada

ABSTRACT

OCCASIONALLY, complete heart block is associated with a benign tumor of the heart, the tumor being remarkable for its constant location in the region of the atrioventricular node. Owing to slight differences in histologic appearance, various theories regarding the origin of the tumor cells have been put forward, and the tumor has been described as a lymphangioendothelioma, a mesothelioma of the node, or an endodermal inclusion tumor of the heart. About 39 cases of mesothelioma of the A-V node have been reported so far 2-5'7'8'10-13'15'17'18>21-24 Report of a Case A 55-year-old male Caucasian linotype operator was admitted in July 1973, with chest pain and severe dyspnea. At the age Received May 13, 1974; received revised manuscript September 26, 1974; accepted for publication September 26, 1974. Address reprint requests to Dr. B. W. Mielke, Department of Pathology, University of Alberta Hospital, Edmonton, Alberta, Canada. 377

of 21 years, in 1939, he had not been accepted for military service because of a "slow heart and a murmur." There was a previous history of scarlet fever and tonsillectomy. In 1952, at the age of 35 years, abdominal pain and feelings of unreality had developed, and he had had one major seizure, but than he had remained well until 1958, when he had a second seizure. Temporal lobe epilepsy was diagnosed and anticonvulsant therapy was begun (diphenylhydantoin and primidone). Elevated urinary lead excretion of 0.56 mg. per 1. was thought to be related to the patient's occupation, and no specific therapy was instituted. During this investigation the heart rate was recorded between 30 and 60 per min. He was also found to have hypertrophic gastritis, duodenitis, and cholelithiasis. In 1961 the patient was seen because of dizziness, confusion, and feelings of unreality, none of which was related to exertion. Clinical examination revealed a regu-

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Wanless, I. R., Mielke, B. W., Jugdutt, B., and Rossall, R. E.: "Mesothelioma of the atrioventricular node" with long-standing complete heart block. Report of a case. Am J Clin Pathol 63: 3 7 7 - 3 8 3 , 1975. A case of mesothelioma of the atrioventricular node is presented. T h e patient had complete heart block for many years before death. T h e origin of the tissue in this apparently congenital tumor is discussed with reference to the literature. (Key words: Cardiac neoplasm; Heterotopic tissue; Mesothelioma of the atrioventricular node; Complete heart block.)

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By 1966, the dizzy spells were becoming more frequent, and in 1967, the patient was seen because of increasing fatigue, exertional dyspnea, and syncopal episodes, as well as minor seizures characterized by sucking and swallowing. A permanent right ventricular transvenous pacemaker was inserted. Neurologic investigations (skull x-ray, brain scan, cerebral angiography, pneumoencephalography and ventriculography) suggested atrophy in the right temporal region. T h e patient was maintained on salt and fluid restriction, digoxin, furosemide, diphenylhydantoin, and primidone. He remained in good health until April 1973, when he developed congestive heart failure following surgery for a perirectal abscess. Recurrent pulmonary edema necessitated a further three admissions. At his final admission in July 1973, pulmonary edema was successfully treated and pacemaker capture of the ventricle was complete (72 per min.), but the patient suddenly collapsed on the fifth hospital day. Following a D.C. shock, d u r i n g resuscitation, idioventricular rhythm was slow. Neither a transthoracic nor a transvenous pacemaker "captured" the ventricle, and the patient died.

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Postmortem Findings There was evidence of systemic and p u l m o n a r y congestion. T h e heart weighed 580 Gm. T h e coronary arteries were severely compromised by atheromas, and the left ventricle had severe patchy fibrosis. The aortic valve was tricuspid. Massive calcification involved the cusps and the aortic ring, rendering the value rigid with a probe-patient orifice only. The other valves were unremarkable. T h e only abnormality visible in the region of the AV-node was a poorly defined area slightly paler than the adjacent tissue (Fig. 1). The brain weighed 1,360 Gm. T h e hemispheres were symmetrical, with no evidence of atrophy. T h e white matter of the right occipital lobe contained a small area of phlebectasia with focal gliosis adjacent to the termination of the posterior ventricular horn. T h e only other alteration consisted of sclerosis of the tips of the cerebellar tonsils, indicative of former herniation. Sections of m y o c a r d i u m revealed patchy fibrosis. T h e region of the A-V node was excised and a dozen sections from this area were examined. Several of these showed a well-defined lesion that m e a s u r e d 1 5 x 1 2 x 3 m m . It was situated in the right atrial wall, covered only by endocardium and an occasional muscle bundle. The tumor extended 15 mm. in the interatrial septum from the orifice of the coronary sinus to the proximity of the aortic ring, bounded below by the fibrous A-V ring. A portion of the tumor extended through the interatrial septum to the root of the mitral valve. The tumor was composed of cords of epithelial-like cells, as well as ducts and sinuses lined by epithelial-like cells, embedded in a vascular fibrous stroma of moderate density containing scattered foci of lymphocytes (Fig. 2).The margins of the tumor were not circumscribed, with single

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lar heart rate of 44 per min. and a blood pressure of 130/80 mm. Hg. T h e A and V waves in the jugular veins were independent. T h e r e was cardiomegaly with a displaced left ventricular apex. A systolic thrill was present, and a grade IV/VI ejection systolic murmur was heard in the aortic area. There was no sign of cardiac failure. T h e electrocardiogram showed complete heart block, left ventricular hypertrophy, a ventricular rate between 48 and 60 per min., and a QRS duration of 0.08 sec. Cardiac fluoroscopy revealed cardiomegaly, a hyperactive aortic root, a hypoactive aortic arch, and a calcified aortic valve. A presumptive diagnosis of congenital complete heart block with calcific aortic stenosis was made.

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tubules situated between muscle bundles some distance from the main tumor A Masson's trichrome preparation revealed scant remnants of A-V node tissue in the central region of the tumor, characterized by narrow striated fibers with multidirectional orientation. T h e cells lining the sinuses were polygonal, usually in one or two imperfectly arranged layers (Fig. 3). The cytoplasm was often poorly defined and scant at the basement membrane, but increased in quantity in the desquamated intraluminal cells, with a granular and eosinophilic appearance. The nuclei were oval or round, sometimes with angulated margins, occasionally with a longitudinal groove lending a "coffeebean" appearance. The chromatin pattern

was open and coarsely granular. T h e nuclei of desquamated cells were often pyknotic. The epithelial-like cells of the cords and tubules were stratified cuboidal cells resembling transitional urothelium (Fig. 4). No mitoses, intercellular bridges, cilia or goblet cells were seen. T h e granules within desquamated cells were PAS-positive and muci-carminenegative. These granules were associated with large concentrically laminated concretions which were also PAS-positive (Fig. 3). Discussion A review of the previously described cases reveals that complete heart block

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FIG. 1. Vertical section through the atrioventricular junction, showing gross appearance. Coronary sinus (C.S.), left atrium (L.A.), mitral valve (M.V.), interventricular septum (I.V.S.) and borders of tumor are indicated (arrows).

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FIG. 2 (upper). Photomicrograph of tumor. Hematoxylin and eosin. x50. FIG. 3 (lower). Gland-like sinuses containing desquamated cells. Note laminated concretion. Hematoxylin and eosin. X300.

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FIG. 4. Cords and ducts resembling transitional urothelium. Hematoxylin and eosin. x300.

was present in nearly all. T h e patients ranged from an eight-month fetus to 86 years of age. As in our patient, complete heart block was usually present for years before death. Of the 39 patients known to us, 27 were female. Coincident calcific aortic stenosis was present in one patient, believed to have suffered rheumatic fever.18 T h e tumors have usually been less than 20 mm. in their largest dimension and often have not been grossly visible. They have not been in locations other than the A-V node region. All have been benign. The histology varied considerably from case to case, but cystic or tubular spaces lined by epithelial-like cells have been a constant feature. The lining cells have been flat to columnar, simple, pseudostratified, or stratified. Several cases have had goblet cells, ciliated columnar cells, or stratified squamous cells with intercellular

bridges and keratin. Concentric concretions and desquamated cells and debris have been found in other cases.18 Some of these tumors may fulfill the criteria to be called "teratomas." Indeed, we are aware of five cases of teratoma of the interatrial and interventricular region, including both benign and malignant examples. 6,23 However, teratomas tend to be larger than most "mesotheliomas," and have not been associated with complete heart block. Heterotopic rests occur in the heart remote from the interatrial septum, but these are almost invariably simple cysts with ciliated columnar epithelium, usually deeply embedded in left ventricular muscle adjacent to a papillary muscle. These do not cause symptoms, are incidental findings at autopsy, and should not be confused with "mesothelioma." 19 A single case of heterotopic renal tissue, including glomeruli and tubules situated in the

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T h e second theory of mesothelial origin is supported by the morphologic similarity of these cells to those of the mesothelial rests found in the peritoneal cavity and in so-called "pericardial milk spots," 13 the intimate relation of the myoepicardial mantle to the A-V node region of the embryo, 14 and the tinctorial similarity of the mesothelioma of the pleural surface and this benign tumor. 9 Lowry and McKee 16 present a case of primary osteogenic sarcoma of the interatrial septum and list five other cases, all arising in the region of the fibrous rings of the heart. This suggests to them metaplasia from the mesenchymal elements of the cardiac skeleton. If the "mesothelioma" likewise is metaplastic from the same elements, the confinement

to the A-V node region would not be expected. We do not feel that the above evidence is sufficient to establish the histogenesis of these lesions. There is a similarity of this example to the glands and ducts of the patient's prostate gland, particularly in areas of autolysis with desquamation of the lining cells. T h e resemblance is not complete, however, as the cardiac lesion does not show intact columnar gland epithelium. Clinical appreciation of this lesion will allow a suspicion of its presence in those patients with intractable heart block, extant from an early age and with no other explanatory etiology. However, treatment will probably remain symptomatic and diagnosis a postmortem exercise. Acknowledgment. Drs. R. Amy and D. R. Alonso gave helpful advice. Miss Rose Marie Limberger provided technical assistance.

References 1. Andrews GS: T h e histology of the human fetal and prepubertal prostates. J Anat 85:44-54, 1951 2. Armstrong H: Lymphangioendothelioma of the A-V node causing heart block. Liverpool Med C h i r J 33:100, 1913 3. Baroldi G: Ital Cardiol 2:44, 1972 4. Barr JR, Pollock P: Inclusion cyst of the myocardium in a patient with complete heart block. Can Med Assoc J 9 8 : 5 2 - 5 3 , 1968 5. BurucuaJE, Vazquez ST, CasasJG, et al: Bloques auriculoventricular completo por inclusion epithelial endodermica en el nodulo. Rev Argent Med Int 3:16, 1972 6. Cabanas VY, Moore WM: Malignant teratoma of the heart. Arch Pathol 96:399-402, 1973. 7. Case Record, Case 6-1973 N Engl J Med 288:308-315, 1973 8. Fine G, Morales AR: Mesothelioma of the atrioventricular node. Arch Pathol 9 2 : 4 0 2 408, 1971 9. Fisher ER, Hellstrom HR: T h e periodic acidSchiff reaction as an aid in the identification of mesothelioma. Cancer 13:837-841, 1960 10. H a m m o u J C , Perie G, Gay J, et al: Mesotheliome du noeud de Tawara, une observation anatomique. Arch Anat Pathol (Paris) 19:289-291, 1971 11. Hopkinson JM, Newcombe CP: Heart block due to epithelial heterotopia. J Pathol 104:218220, 1971

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epicardial fat of the right ventricle, has been reported. 20 The origin of the epithelial-like cells of the "mesothelioma" is not known. It has been postulated that (1) they arise from sequestered endodermal elements from the primitive foregut during cardiac organogenesis 22 and (2) they arise from the epicardial mesothelium. 17 The first theory is supported by the constant location in the A-V node area. This would be anticipated by the finding of endodermal cysts within the mesocardium, which is attached to the posterior endocardial cushion within which the A-V node develops. 24 If they arose from the epicardial mesodermal tissue a more random intramyocardial location would seem likely, as seen with the ciliated cysts described above. T h e presence of glandular squamous and ciliated cells has been considered strong support for the first theory. 15 It should be mentioned that the coelomic mesothelium is the origin of the ciliated and glandular cells of the paramesonephric system. Similarly, stratified squamous "metaplasia" is a normal finding in the newborn prostatic urethra. 1

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12. Ibarra-Perez C, Korns ME, Edwards J E : Mesothelioma of the atrioventricular node. Chest 63:824-827, 1973 13. Kaminsky NI, Killip T, Alonso DR, et al: Heart block and mesothelioma of the atrioventricular node. Am J Cardiol 20:248-254, 1967 14. Kindred JE: A cyst in the primordium of the tricuspid valve of an abnormal human embryo. Am J Pathol 33:167-176, 1957 15. Lewman LV, Demany MA, Zimmerman HA: Congenital tumor of atrioventricular node with complete heart block and sudden death. Am J Cardiol 29:554-557, 1972 16. Lowry WB, McKee EE, Primary osteosarcoma of the heart. Cancer 30:1068-1073, 1972 17. Mahaim I: Le coelotheliome tawarien benin: Un tumeur sui generis du noeud de Tawara avec bloc du coeur. Cardiologia 6:57-82, 1942

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18. Manion WC, Nelson WP, Hall RJ, et al: Benign tumor of the heart causing complete heart block. Am Heart J 83:535-542, 1972 19. Marshall FC: Epithelial cyst of the heart. Arch Pathol 64:107-110, 1957 20. Milliser RV, Greenberg SR, Neiman BH: Heterotopic renal tissue in the human heart. J Urol 108:21-24, 1972 21. Morris AW, Johnson IM: Epithelial inclusion cysts of the heart. Arch Pathol 77:36-40, 1964 22. Rezek P: Uber eine primare epitheliale Geschwulst in der Gegund des Reizleitungssystems beim Menschen. Virchows Arch [Pathol Anat] 301:305-320, 1938 23. Soloman R: Malignant teratoma of the heart. Arch Pathol 52:561-568, 1951 24. Sopher IM, Spitz WU: Endodermal inclusions of the heart. Arch Pathol 92:180-186, 1971

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"Mesothelioma of the atrioventricular node" with long-standing complete heart block. Report of a case.

A case of mesothelioma of the atrioventricular node is presented. The patient had complete heart block for many years before death. The origin of the ...
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