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Benign tumor of the heart causing complete heart block
Benign tumor of the heart complete heart block William C. Manion, M.D.* William P. Nelson, Lieutenant Robert J. Hall, M.D.**” Robert E. Brierty, M.D. Washington, D. C.
causing
Colonel, MC,
C
omplete atrioventricular (A-V) block is occasionally congenital, but its more common cause is coronary arteriosclerotic heart disease, or sclerotic calcific degeneration of the A-V node accompanying annulus calcification of the mitral or aortic valves. Infectious myocarditis (especially diphtheritic), parasitic diseases, inflammatory lesions, fibrosis, malformations, and trauma can cause both acute and chronic complete heart block.4~10~15~18 Space occupying lesions, including both primary and secondary tumors, fatty infiltration, abscesses, tubercles, and gummata are infrequently the cause of interruption of A-V conduction.1~15~22*24~27 A patient in which a lymphangioendothelioma of the A-V node induced chronic A-V block is the subject of this report. Case report A 53-year-old married school teacher was in good health until age 18, when a diagnosis of rheumatic fever was made following a two month illness of fever and arthralgia. Although no difficulties were encountered during her first pregnancy at age 34,
USA**
a heart murmur was detected in the course of her second pregnancy at age 38. An electrocardiogram (ECG), her first, revealed complete A-V block. However, she remained asymptomatic until the age of 44, when she noted mild exertional dyspnea, but she was never significantly limited. She was observed periodically; murmurs and chronic complete heart block were both construed to be the consequence of rheumatic heart disease. She appeared to tolerate a heart rate between 50 and 60 beats per minute without difficulty. On the day of hospitalization, she had two episodes of unconsciousness, pallor, and shallow respiration, each of 10 to 15 minutes’ duration. On admission, she was hysterical, combative, and disoriented. Examination disclosed no evidence of congestive heart failure. The heart rate was regular at 50 beats per minute. A basal and apical Grade 2 ejection murmur and a variable third sound at the apex were heard. An ECG revealed complete heart block with narrow QRS complexes, suggesting the pacemaker focus to be in the bundle of His. The tracings were unchanged from the previous ECG’s, dating to 1955 (Fig. 1). Three hours after admission, she had a brief spell of weakness and was begun on continuous ECG monitoring. A recurrence several hours later was accompanied by ECG documentations of ventricular flutter fibrillation which terminated spontaneously after 30 seconds (Fig. 2). Thereafter, these recurred
From the Armed Forces Institute of Pathology, Washington, D. C. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Received for publication Oct. 26, 1970. Reprint requests to: The Director, Armed Forces Institute of Pathology, Editorial Office, Washington, D. C. 20305. *Former Chief, Cardiovascular Pathology Branch, Armed Forces Institute of Pathology, Washington, D. C. Deceased since article was submitted. **Chief, Cardiology Service, Fitzsimons General Hospital, Denver, Cola. ***Medical Director, Texas Heart Institute. Houston. Texas.
Vol. 63, No. 4, pp. 535-542
April, 1972
American Heart Journal
535
536
Manion
Am. Heart .I. Afwil, 1972
et al.
Fig. 1. ECG revealing complete bundle of His. -
A-V
block
with
narrow
with increasing frequency and duration, requiring repeated electrical defibrillation. In spite of the administration of intravenous lidocaine, and efforts at external electrical pacing, the ventricular fibrillation continued to recur, and the patient expired 18 hours after admission.
Autopsy
Pertinent autopsy findings were limited to the cardiovascular system. On gross examination the heart weighed 450 grams. The epicardial surface was smooth and glistening and the epicardial fat, yellow in color and of an average amount. There was evident dilatation of all chambers. On cut section, the musculature was dark red in color and firm in consistency. There was no evident fibrosis present. The coronary arteries \vere two in number and arose normally from the aorta and had the expected distribution. On cut section, they
QRS
complexes
suggesting
pacemaker
locus
in the
were relatively free from atheromatous change. The endocardial surface was smooth and glistening throughout all heart cavities. The tricuspid and pulmonary valves appeared normal and measured 12.5 cm. and 6.5 cm. in circumference, respectively. The chordae tendineae of the mitral valve leaflets were minimally shortened, and thickened, measuring 11.5 cm. in circumference. The orifice of the aortic valve was stenotic. The cusps were thickened and focally calcified at the base. The margins of the cusps were adherent in the region of their insertion. The valve measured 6.0 cm. in circumference. Inspection of the interatrial septum revealed a few small nodules, confined to the lower portion of the septum immediately above the atrioventricular ring, in the region of the junction of the anterior septal leaflet of the tricuspid valve (Fig. 3, A).
Volume Number
83 4
Benign
Palpation of this area revealed an illdefined, irregularly shaped cystic nodular mass occupying the region of the atrioventricular node and appearing to extend both above and below the expected limit of that structure (Fig. 3, B and C). Cut section through the mass revealed a multicystic structure composed of a large central cystic cavity with many small cysts surrounding it, some of which appeared to be incorporated in the wall of the large cyst, while a few were present in the adjacent tissue. The largest cyst contained a small amount of rusty fluid and measured approximately 3 cm. in the greatest diameter. The cysts, which varied both in size and shape, appeared to be confined to the right side of the atria1 septum and extended both upward into the septum toward the base of the heart as well as in an anterior and posterior direction. The evident bulge into the right atria1 cavity can be seen immediately above the septal leaflet of the tricuspid valve in Fig. 3, C. Microscopic examination confirmed the gross observation, revealing a multicystic structure with a large empty central cyst, in the wall of which were numerous small, variable size cysts, occasionally tubular in form. Many of the small peripheral cysts appeared to be in communication with the large central cyst. The endocardial surface of the right atrium over the cysts was intact and separated from the central cystic cavity by a thin, variable thickness of cardiac muscle in which several small tubular cysts were present (Fig. 3, 0). In some fields, the cysts were separated by only two or three muscle fibers from the endocardium. The central cyst was lined by a layer of endothelial cells which in most fields was single layered; focally, however, multilayered areas were present (Fig. 3, F). The lining cells were uniform without cytologic atypia. In most fields the endothelial lining appeared to rest on myocardial fibers focally; however, dense fibrous connective tissue was present immediately beneath the cyst lining (Fig. 3, G). The smaller cysts varied in size and shape; often connecting channels between adjacent cysts were present. All of the small cysts had a lining of endothelium that, in most instances, appeared to be multilayered (Fig. 3, E). In some fields, often at the periphery
heart tumor causing complete heart block
537
Fig. 2. Continuous recording of Lead 3 shows the appearance of multiple extrasystoles which increase in number and culminate in a burst of ventricular flutter fibrillation. After 30 seconds the spontaneous reversion to idioventricular rhythm is seen.
538
Manion
et al.
Am. Heart 1. Afiril, 1972
Fig. 3. A, Right side of the heart opened. Note the nodular area of thickening of the lower portion of the interatria1 septum immediately above the atrioventricular ring in the region of the junction of the anterior and septal leaflet of the tricuspid valve (see arrow). B, Cut section of the gross heart through the area showing the large cyst. C, Section through another area showing the multiple small cysts surrounding the larger cyst. Note the bulging into the atria1 cavity. (Hematoxylin and eosin. X8x.) D, Section showing multiple small cysts adjacent to the larger cyst, many containing a small amount of amorphous material. The strand of heart muscle separating the cyst from the endocardium can be seen. (Hematoxylin and eosin. X 11.) E, Photomicrograph of a section from another area of the lesion showing the multilayered lining of some of the small cysts, the communication between some of the cysts, the variable nature of the cystic contents, and the small concentric variable staining masses present in some spaces (see arrow). (Hematoxylin and eosin. X50.) F, Photomicrograph of a section showing an area of stratification of the cyst lining. (Hematoxylin and eosin. X130.) G, Photomicrograph of a section showing an area of fibrous tissue in one area of the cyst wall. (Hematoxylin and eosin. X 130.) H, Photomicrograph of a section showing the solid nest-of cells present in some area of the lesion. (Hematoxylin and eosin. X37.) AFIP Neg. No. 62-6563.
of the lesion, small solid nests of endothelial cells were present (Fig. 3, H). The cysts, while restricted to the right of the atria1 septum, could be found deep in the septum adjacent to the fibrous body; they appeared to extend both above and below this structure and to involve and compress the bundle on the right side. They appeared
to occupy much of the area of the A-V node. In the area where the lining cells were stratified, a cell boundary was often evident and a large leptochromatic centrally located nucleus, surrounded by acidophilic cytoplasm, was seen. Intercellular bridges were not seen, nor were mitotic figures present. The large cyst was empty;
Volume Number
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Benign heart tumor causing complete heart block
539
Fig. 3, F-H. For legend see opposite page. some of the small cysts, however, contained variable amounts of loosely arranged, slightly basophilic, coarsely granular material, while others contained a more dense, deeper-staining material which often was in the form of small concentric masses or spherules. These masses which varied in both size and number in the cysts stained irregularly, and both acidophilic and basophilic staining bodies were present. In a few cysts, desquamated endothelial cells and macrophages were present, in addition to the amorphic material (Fig. 3, D and E). The material in the cyst was para-aminosalicyclic acid (PAS) positive, stained with alcian blue, and was faintly stained with mucicarmine; however, it did not stain like epithelial mucin (red). The cysts were separated from one another by variable-sized strands of tissue which in some instances were chiefly fibrous tissue, while others were muscle fibers. Elastic fibers were quite prominent in the tissue surrounding some of the cysts. In a few fields these strands were lightly infiltrated with leukocytes, chiefly lymphocytes with a few plasma cells. In rare instances the cysts were surrounded by leukocytes. The lesion of the heart in this case is consistent with lesions of the A-V node region considered by Armstrong and Mijnckeberg2s3 as a lymphangioendothelioma and by Mahaiml’ as a benign coelothelioma. It is remarkable that the size of the lesion appears to be greater than any previously reported. Also, in addition to the tumor and valve changes noted, the heart showed focal fatty infiltration of the
interatrial septum the myocardium.
and
focal
fibrosis
of
Discussion The cardiac tumor discovered in our patient is of interest not only because of its rarity but also because of the implication of therapy which is presently available. The strategic location of the tumor causing interruption of the A-V conducting tissue makes it a potentially lethal tumor, despite its small size and benign nature. Indeed, it has been identified as, “the smallest tumor which causes sudden death.“30 The implantation of a permanent cardiac pacemaker would successfully offset the conduction disturbance and obviate the arrhythmias known to accompany complete heart block. This has been done successfully in one of the reported cases and also in one of the cases in the files of the Armed Forces Institute of Pathology. Unfortunately pacemakers were not available when this patient had her final attack. The diagnosis of a tumor of this type can only be suspected during life, and its confirmation by the pathologist represents the clinician’s failure. To date, there are 26 similar cases that we are aware of; the patients ranged in age from newborn to 86 years. Pertinent data on these cases are summarized in Table I. It can be seen that the majority had complete heart block with a significant occurrence of Stokes-Adams attacks and death due to disturbance of rhythm. In many of the patients, death occurred in youth or in the prime of life, and it is in such cases
540
Manion
Tuble I. Summurized
No.
Year
I
1. 2. 3. 4. 5. 6. 7.
1911-1913 1929 1932 1934 1937 1942 1948
8. 9. 10.
1948 1948 19.50
11. 12. 13. 14. 15. 16. 17.
1956 1957 1963 1964 1964 1965 1965
18.
1967
19. 20. 21. 22. 23. 24. 25. 26.
Am. Heart J. Afir& 1972
et al.
data from 26 similar
Author/Case
I
cases*
1
Armstrong and Miinckeberg Lloyd DeChatel Perry and Rogers Rezek (AFIP 859462) Mahaim Rabson and Thill (AFIP 865628) Leicher (Case 1) Leicher (Case 2) Leighton, Hurst, and Crawford (AFIP 864403) Calzavara Ovary, Pinter, and Leovy Meesen and Poche Rossi Morris and Johnson Wolf and Bing Haraszti, Gyarmati, and Sallay (AFIP 1237631) Kaminsky, Killip, Alonso, and Hagstrom Barr and Pollock (AFIP 1273342) Picoff and Petenyi AFIP 1056884 AFIP 1106963 AFIP 1234567 AFIP 1247011 AFIP 1287721 AFIP 1325755
Age
)
Sex
)
%g
/
?%!?
5 39 Newborn 26 71 24 29
M F F F F F F
CHB 1” CHB CHB CHB CHB
SA
24 34 6 mo.
1; F F
CHB CHB None
SA SA
8 mo. 75 3 wk. 78 86 67 8
F F F F F M M
CHB CHB 1” CHB CHB
CHF SA
75
M
CHB
-
49
F
CHB
SA
21 53 23 11 mo. 62 69 8
F F F M M M F
CHB CHB 2" CHB 1” -
SA, VF -
that currently available implanted pacemakers would be most gratifying. Adequate rate control in these individuals without other significant cardiac disease would be anticipated to significantly improve cardiac function and prolong life. This interesting but rare heart lesion is found under several designations in the literature. The terms used seem to be based on the authors’ interpretation of the nature of the lesion, and are as follows: lymphangioendothelioma,z~3~*6~z3~26 epidermoid cyst of the heart,’ benign coelotheepithelium-like
inc1usion,5,1g~25
epi-
thelial hamartoma,13 squamous epithelial l4 a remnant of the truncus arteriosus cyst, division (hamartoma) ,21 chronic lymphangitis proliferans,28s2g primary mesothelioma,11,24J0 and an adenoma-like tissue
‘z%of R R
-
R Other Other RHD
SA, VF -
R -
:HD CHF Ci CVA R R SUD
-
*Abbreviations: AFIP. Armed Forces Institute of Pathology; CHB, complete heart block; SA. Stokes-Adams tricular fibrillation; CHF, congestive heart failure; R. rhythm disturbance cause of death; RHD. rheumatic congenital heart disease’ CVA, cerebrovascular accident: SUD, sudden unexpected death.
lioma,6*i7
(
SUD R SUD SUD SUD SUD
syndrome; VF, venheart disease; CHD,
malformation of the serosal epitlleliun~.g The diversity of the terms applied to the lesion probably indicates not only an uncertainty as to the nature of the tumor but also some variation in the histologic findings in the lining of the cystic structures. The use of the terms “epidermoid,” “epithelium-like,” “squamous,” and “epithelial hamartoma,” indicates that the observers felt that the cyst lining was epithelial in nature. Certainly the findings of “cornified stratified squamous epithelium” and “intercellular protoplasmic bridges,” would support this assumption. The case in question did not show these changes in the cyst lining; however, other cases in our files showed changes of the type indicated by other authors. Discussion of this problem is beyond the scope of this paper; however,
Benign
it is our feeling, that the difference in the histologic findings in the various cases would not necessarily indicate two different types of lesions but might be explained on the basis of a metaplastic change of the lining cells. The presence of inflammatory cells in association with the cysts might be considered as support for the possibility that this is the result of a chronic lymphangiitiszg; however, the constant location of the lesion, the finding of it in a fetus, a newborn, and in the young infant and child would, we feel, support the assumption that this is a unique congenital tumor. The presence of a stratification and intercellular bridge noted in some of the cases would be against the assumption that the tumor is a mesothelioma or the consequence of entrapment of serosal cells in this area during the early development of the heart, unless we assumed that these were the result of metaplasia. Priority is usually given to Armstrong and Mijnckeberg2 for the first description of this lesion in 1911. Their’s was a report of a 5-year-old boy and their findings were supported by an ECG study (this procedure had just been introduced into clinical medicine). A case reported by Hadden in 188g8 would appear compatible with this lesion; it does not appear to be supported by the limited histologic study, even though the clinical history would support this assumption. At the present time, we are aware of 26 cases of this lesion. Table I includes all reports in the literature that we are aware of and those accessioned in the files of the Registry of Cardiovascular Pathology, Armed Forces Institute of Pathology. The case of Klein and Kinzn has been omitted from this study; they describe a malignant tumor of this type that metastasized to the vertebrae; however, the histologic findings of the tumor are not consistent with the diagnosis, and it would appear that this is another type of malignant tumor. Reports of epithelial inclusions are present in both the literature and in our files; however, these are not located in the interatria1 septum and apparently do not interfere with conduction of the heart. Hence, these are excluded from this study. Interestingly, of the 26 reports listed here, 19
heart tumor callsing complete heart block
541
were in women while only 7 were in men. One of the reports concerned an S-monthold fetus, one a newborn, and three in the first year of life. Six were under 10 years of age, six between 21 and 30 years old, and five over 70 years of age when death occurred. In 20 of the 26 cases, heart blocks of various degrees were recorded during life. In two instances, pacemakers were inserted because of the clinical symptomatology and, in one instance, this possibility was considered. Certainly, then, this tumor should be kept in mind when evaluating heart block, particularly in a young individual. In addition to this type of tumor, angiomas may arise in this area producing heartblock as a consequence of encroachment on, or destruction of, the A-V node.‘*15 While our report is concerned with tumors involving the A-V node, it should be pointed out that Nadas and his co-workers20 made a study of 41 cases of paroxysmal tachycardia in infants and children in 1952 and reported two cases in which thickening of the tissue at the caval-auricular junction was found at postmortem examination; both were interpreted as hamartomas of the S-A node. In view of these findings, it is important to stress careful examination of both the S-A and A-V node regions. Summary
A case is presented in which a benign cystic tumor disrupted the continuity of the A-V conducting pathway, resulting in complete heart block. Despite 15 years of stable chronic A-V block, the patient developed ventricular arrhythmias that led to her death. Such tumors, although rare, represent a significant cause of complete heart block and are important because of the implications of pacemaker therapy available today. REFERENCES 1. von Albertini, A.: Histologische Geschwulstdiagnostik, Stuttgart, 1955, Georg Thieme Verlag. 2. Armstrong, H., and MGnckeberg, J. G.: Herzblock, bedingt durch primgren Herztumor, bei einem 5 jlhrigen Kind, Arch. Klin. Med. 102:144, 1911. 3. Armstrong, H.: Lymphangioendothelioma of the AV node, causing heart-block, Liverpool Med. Chir. J. 33:100, 1913. 4. Sotelo-Avila, C., Rosenberg, H. S., and Mc-
542
5.
6.
10.
11.
12.
13.
14.
15.
16.
Munion
Am. Heart J. April, 1972
et ul.
Namara, D. G.: Congenital heart block due to a lesion in the conduction system, Pediatrics 45:640, 1970. Barr, J. R., and Pollock, P.: Inclusion cyst of the myocardium in a patient with complete heart block, Canad. Med. Ass. J. 98:52, 1968. Calzavara, F.: Celotelioma del cuore, Riv. Anat. Pat. Oncol. 13:845, 1958. De Chatel. A.: Koneenitale Eoidermoid-Cvste des Herzens, Frankfurt. Z.’ Path. 44:426, 1932-33. Hadden, W. B.: Cyst of the heart, Trans. Path. Sot. London 39:79, 1888. Haraszti, A., Gyarmati, M., and Sallay, E.: Adenomartige Gewebsmissbildung des Herzens mit atrioventrikularem Herzblock, Zbl. Allg. Path. 107:542, 1965. Hoekenga, M. T.: Complete heart block in an infant associated with multiple congenital cardiac malformations, Amer. J. Dis. Child. 69:231, 1945. Kaminsky, N. I., Killip, T., Alonso, D. R., and Hagstrom, J. W. C.: Heart block and mesothelioma of the atrioventricular node, Amer. J. Cardiol. 20:248, 1967. Klein, R., and Kinz, J.: iiber ein metastasierendes sogenanntes Lymphangioendotheliom des Herzens, Oest. Z. Kinderheilk. 9:289, 1953. Leicher, F.: Zur Pathogenese der primaren epithelialen Tumoren im Reizleitungssystem des Menschen, Z. Kreislaufforsch. 37:105, 1948. Leighton, J., Hurst, J. W., and Crawford, J. D.: Squamous epithelial cysts in the heart of an infant with coincident cystic changes in the ovaries and breasts. Arch. Path. (Chicago)50:632, 1950. Linder, E., Landtman, B., Tuuteri, L., and Hjelt, L.: Congenital complete heart block, histology of the conduction system, Ann. Paediat. Fenn. ll:ll, 1965. Lloyd, P. C.: Heart block due to primary lymphangioendothelioma of atrio-ventricular node, Johns Hopkins Med. J. 44:149, 1929.
17.
Mahaim, I.: Le coelothelioma tawarien benin? Cardiologia 6:57, 1942. 18. Meesen, H., and Poche, R.: Pathomorphologie des myokard, in Bergmann, W., and Doerr, W., editors: Das Herz des Menschen, vol. 2, Stuttgart, 1963, Georg Thieme Verlag, p. 726. 19. Morris, A. S., and Johnson, I. M.: Epithelial inclusion cysts of the heart, Arch. Path. (Chicago) 77:44, 1964. 20. Nadas, A. S., Daeschner, C. W., Roth, A., and Blumenthal, S. L.: Paroxysmal tachycardia in infants and children, Pediatrics 9:167, 1952. 21. Ovary, I., Pinter, L., and Leovey, A.: Atrioventricularis blockhoz vezetij primaer szivtumor, Orv. Hetil. 98:826, 1957. 22. Papp, C.: Sindrome di Adams-Stokes da lipomatosi de1 nodo de tawara, Policlinico [Med.] 39:253, 1932. 23. Perry, C. B., and Rogers, H.: Lymphangioendothelioma of the heart causing complete heart block, J. Path. Bact. 39:281, 1934. 24. Picoff, R. C., and Petenyi, C.: Primary mesothelioma of the atrioventricular node, Arch. Path. 89:84, 1970. 2.5. Rabson, S. M., and Thill, L. J.: Epitheliumlike inclusions in the heart, Amer. J. Path. 24:655, 1948. 26. Rezek, Ph.: tiber eine primare epitheliale Geschwulst in der Gegend des Reizleitungssysterns beim Menschen, Virchow. Arch. Path. Anat. 301:305, 1938. 27. Rossi, L., and Levy, A.: Atteinte du noeud sinusal et du systeme neuro-ganglionaire atria1 par une tumeur primitive maligne du pericarde (Mesotheliome), Arch. Mal. Coeur. 54:807, 1961. 28. Rossi, I,.: Complete heart-block, Brit. Med. J. 1:121, 1964. 29. Rossi, L.: Case of cardiac lymphangitis with atrioventricular block, Brit. Med. J. 2:32, 1965. 30. Wolf, P. L., and Bing, R.: The smallest tumor which causes sudden death, J.A.M.A. 194:674 1965.
causing
Colonel, MC,
C
omplete atrioventricular (A-V) block is occasionally congenital, but its more common cause is coronary arteriosclerotic heart disease, or sclerotic calcific degeneration of the A-V node accompanying annulus calcification of the mitral or aortic valves. Infectious myocarditis (especially diphtheritic), parasitic diseases, inflammatory lesions, fibrosis, malformations, and trauma can cause both acute and chronic complete heart block.4~10~15~18 Space occupying lesions, including both primary and secondary tumors, fatty infiltration, abscesses, tubercles, and gummata are infrequently the cause of interruption of A-V conduction.1~15~22*24~27 A patient in which a lymphangioendothelioma of the A-V node induced chronic A-V block is the subject of this report. Case report A 53-year-old married school teacher was in good health until age 18, when a diagnosis of rheumatic fever was made following a two month illness of fever and arthralgia. Although no difficulties were encountered during her first pregnancy at age 34,
USA**
a heart murmur was detected in the course of her second pregnancy at age 38. An electrocardiogram (ECG), her first, revealed complete A-V block. However, she remained asymptomatic until the age of 44, when she noted mild exertional dyspnea, but she was never significantly limited. She was observed periodically; murmurs and chronic complete heart block were both construed to be the consequence of rheumatic heart disease. She appeared to tolerate a heart rate between 50 and 60 beats per minute without difficulty. On the day of hospitalization, she had two episodes of unconsciousness, pallor, and shallow respiration, each of 10 to 15 minutes’ duration. On admission, she was hysterical, combative, and disoriented. Examination disclosed no evidence of congestive heart failure. The heart rate was regular at 50 beats per minute. A basal and apical Grade 2 ejection murmur and a variable third sound at the apex were heard. An ECG revealed complete heart block with narrow QRS complexes, suggesting the pacemaker focus to be in the bundle of His. The tracings were unchanged from the previous ECG’s, dating to 1955 (Fig. 1). Three hours after admission, she had a brief spell of weakness and was begun on continuous ECG monitoring. A recurrence several hours later was accompanied by ECG documentations of ventricular flutter fibrillation which terminated spontaneously after 30 seconds (Fig. 2). Thereafter, these recurred
From the Armed Forces Institute of Pathology, Washington, D. C. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or as reflecting the views of the Department of the Army or the Department of Defense. Received for publication Oct. 26, 1970. Reprint requests to: The Director, Armed Forces Institute of Pathology, Editorial Office, Washington, D. C. 20305. *Former Chief, Cardiovascular Pathology Branch, Armed Forces Institute of Pathology, Washington, D. C. Deceased since article was submitted. **Chief, Cardiology Service, Fitzsimons General Hospital, Denver, Cola. ***Medical Director, Texas Heart Institute. Houston. Texas.
Vol. 63, No. 4, pp. 535-542
April, 1972
American Heart Journal
535
536
Manion
Am. Heart .I. Afwil, 1972
et al.
Fig. 1. ECG revealing complete bundle of His. -
A-V
block
with
narrow
with increasing frequency and duration, requiring repeated electrical defibrillation. In spite of the administration of intravenous lidocaine, and efforts at external electrical pacing, the ventricular fibrillation continued to recur, and the patient expired 18 hours after admission.
Autopsy
Pertinent autopsy findings were limited to the cardiovascular system. On gross examination the heart weighed 450 grams. The epicardial surface was smooth and glistening and the epicardial fat, yellow in color and of an average amount. There was evident dilatation of all chambers. On cut section, the musculature was dark red in color and firm in consistency. There was no evident fibrosis present. The coronary arteries \vere two in number and arose normally from the aorta and had the expected distribution. On cut section, they
QRS
complexes
suggesting
pacemaker
locus
in the
were relatively free from atheromatous change. The endocardial surface was smooth and glistening throughout all heart cavities. The tricuspid and pulmonary valves appeared normal and measured 12.5 cm. and 6.5 cm. in circumference, respectively. The chordae tendineae of the mitral valve leaflets were minimally shortened, and thickened, measuring 11.5 cm. in circumference. The orifice of the aortic valve was stenotic. The cusps were thickened and focally calcified at the base. The margins of the cusps were adherent in the region of their insertion. The valve measured 6.0 cm. in circumference. Inspection of the interatrial septum revealed a few small nodules, confined to the lower portion of the septum immediately above the atrioventricular ring, in the region of the junction of the anterior septal leaflet of the tricuspid valve (Fig. 3, A).
Volume Number
83 4
Benign
Palpation of this area revealed an illdefined, irregularly shaped cystic nodular mass occupying the region of the atrioventricular node and appearing to extend both above and below the expected limit of that structure (Fig. 3, B and C). Cut section through the mass revealed a multicystic structure composed of a large central cystic cavity with many small cysts surrounding it, some of which appeared to be incorporated in the wall of the large cyst, while a few were present in the adjacent tissue. The largest cyst contained a small amount of rusty fluid and measured approximately 3 cm. in the greatest diameter. The cysts, which varied both in size and shape, appeared to be confined to the right side of the atria1 septum and extended both upward into the septum toward the base of the heart as well as in an anterior and posterior direction. The evident bulge into the right atria1 cavity can be seen immediately above the septal leaflet of the tricuspid valve in Fig. 3, C. Microscopic examination confirmed the gross observation, revealing a multicystic structure with a large empty central cyst, in the wall of which were numerous small, variable size cysts, occasionally tubular in form. Many of the small peripheral cysts appeared to be in communication with the large central cyst. The endocardial surface of the right atrium over the cysts was intact and separated from the central cystic cavity by a thin, variable thickness of cardiac muscle in which several small tubular cysts were present (Fig. 3, 0). In some fields, the cysts were separated by only two or three muscle fibers from the endocardium. The central cyst was lined by a layer of endothelial cells which in most fields was single layered; focally, however, multilayered areas were present (Fig. 3, F). The lining cells were uniform without cytologic atypia. In most fields the endothelial lining appeared to rest on myocardial fibers focally; however, dense fibrous connective tissue was present immediately beneath the cyst lining (Fig. 3, G). The smaller cysts varied in size and shape; often connecting channels between adjacent cysts were present. All of the small cysts had a lining of endothelium that, in most instances, appeared to be multilayered (Fig. 3, E). In some fields, often at the periphery
heart tumor causing complete heart block
537
Fig. 2. Continuous recording of Lead 3 shows the appearance of multiple extrasystoles which increase in number and culminate in a burst of ventricular flutter fibrillation. After 30 seconds the spontaneous reversion to idioventricular rhythm is seen.
538
Manion
et al.
Am. Heart 1. Afiril, 1972
Fig. 3. A, Right side of the heart opened. Note the nodular area of thickening of the lower portion of the interatria1 septum immediately above the atrioventricular ring in the region of the junction of the anterior and septal leaflet of the tricuspid valve (see arrow). B, Cut section of the gross heart through the area showing the large cyst. C, Section through another area showing the multiple small cysts surrounding the larger cyst. Note the bulging into the atria1 cavity. (Hematoxylin and eosin. X8x.) D, Section showing multiple small cysts adjacent to the larger cyst, many containing a small amount of amorphous material. The strand of heart muscle separating the cyst from the endocardium can be seen. (Hematoxylin and eosin. X 11.) E, Photomicrograph of a section from another area of the lesion showing the multilayered lining of some of the small cysts, the communication between some of the cysts, the variable nature of the cystic contents, and the small concentric variable staining masses present in some spaces (see arrow). (Hematoxylin and eosin. X50.) F, Photomicrograph of a section showing an area of stratification of the cyst lining. (Hematoxylin and eosin. X130.) G, Photomicrograph of a section showing an area of fibrous tissue in one area of the cyst wall. (Hematoxylin and eosin. X 130.) H, Photomicrograph of a section showing the solid nest-of cells present in some area of the lesion. (Hematoxylin and eosin. X37.) AFIP Neg. No. 62-6563.
of the lesion, small solid nests of endothelial cells were present (Fig. 3, H). The cysts, while restricted to the right of the atria1 septum, could be found deep in the septum adjacent to the fibrous body; they appeared to extend both above and below this structure and to involve and compress the bundle on the right side. They appeared
to occupy much of the area of the A-V node. In the area where the lining cells were stratified, a cell boundary was often evident and a large leptochromatic centrally located nucleus, surrounded by acidophilic cytoplasm, was seen. Intercellular bridges were not seen, nor were mitotic figures present. The large cyst was empty;
Volume Number
83 4
Benign heart tumor causing complete heart block
539
Fig. 3, F-H. For legend see opposite page. some of the small cysts, however, contained variable amounts of loosely arranged, slightly basophilic, coarsely granular material, while others contained a more dense, deeper-staining material which often was in the form of small concentric masses or spherules. These masses which varied in both size and number in the cysts stained irregularly, and both acidophilic and basophilic staining bodies were present. In a few cysts, desquamated endothelial cells and macrophages were present, in addition to the amorphic material (Fig. 3, D and E). The material in the cyst was para-aminosalicyclic acid (PAS) positive, stained with alcian blue, and was faintly stained with mucicarmine; however, it did not stain like epithelial mucin (red). The cysts were separated from one another by variable-sized strands of tissue which in some instances were chiefly fibrous tissue, while others were muscle fibers. Elastic fibers were quite prominent in the tissue surrounding some of the cysts. In a few fields these strands were lightly infiltrated with leukocytes, chiefly lymphocytes with a few plasma cells. In rare instances the cysts were surrounded by leukocytes. The lesion of the heart in this case is consistent with lesions of the A-V node region considered by Armstrong and Mijnckeberg2s3 as a lymphangioendothelioma and by Mahaiml’ as a benign coelothelioma. It is remarkable that the size of the lesion appears to be greater than any previously reported. Also, in addition to the tumor and valve changes noted, the heart showed focal fatty infiltration of the
interatrial septum the myocardium.
and
focal
fibrosis
of
Discussion The cardiac tumor discovered in our patient is of interest not only because of its rarity but also because of the implication of therapy which is presently available. The strategic location of the tumor causing interruption of the A-V conducting tissue makes it a potentially lethal tumor, despite its small size and benign nature. Indeed, it has been identified as, “the smallest tumor which causes sudden death.“30 The implantation of a permanent cardiac pacemaker would successfully offset the conduction disturbance and obviate the arrhythmias known to accompany complete heart block. This has been done successfully in one of the reported cases and also in one of the cases in the files of the Armed Forces Institute of Pathology. Unfortunately pacemakers were not available when this patient had her final attack. The diagnosis of a tumor of this type can only be suspected during life, and its confirmation by the pathologist represents the clinician’s failure. To date, there are 26 similar cases that we are aware of; the patients ranged in age from newborn to 86 years. Pertinent data on these cases are summarized in Table I. It can be seen that the majority had complete heart block with a significant occurrence of Stokes-Adams attacks and death due to disturbance of rhythm. In many of the patients, death occurred in youth or in the prime of life, and it is in such cases
540
Manion
Tuble I. Summurized
No.
Year
I
1. 2. 3. 4. 5. 6. 7.
1911-1913 1929 1932 1934 1937 1942 1948
8. 9. 10.
1948 1948 19.50
11. 12. 13. 14. 15. 16. 17.
1956 1957 1963 1964 1964 1965 1965
18.
1967
19. 20. 21. 22. 23. 24. 25. 26.
Am. Heart J. Afir& 1972
et al.
data from 26 similar
Author/Case
I
cases*
1
Armstrong and Miinckeberg Lloyd DeChatel Perry and Rogers Rezek (AFIP 859462) Mahaim Rabson and Thill (AFIP 865628) Leicher (Case 1) Leicher (Case 2) Leighton, Hurst, and Crawford (AFIP 864403) Calzavara Ovary, Pinter, and Leovy Meesen and Poche Rossi Morris and Johnson Wolf and Bing Haraszti, Gyarmati, and Sallay (AFIP 1237631) Kaminsky, Killip, Alonso, and Hagstrom Barr and Pollock (AFIP 1273342) Picoff and Petenyi AFIP 1056884 AFIP 1106963 AFIP 1234567 AFIP 1247011 AFIP 1287721 AFIP 1325755
Age
)
Sex
)
%g
/
?%!?
5 39 Newborn 26 71 24 29
M F F F F F F
CHB 1” CHB CHB CHB CHB
SA
24 34 6 mo.
1; F F
CHB CHB None
SA SA
8 mo. 75 3 wk. 78 86 67 8
F F F F F M M
CHB CHB 1” CHB CHB
CHF SA
75
M
CHB
-
49
F
CHB
SA
21 53 23 11 mo. 62 69 8
F F F M M M F
CHB CHB 2" CHB 1” -
SA, VF -
that currently available implanted pacemakers would be most gratifying. Adequate rate control in these individuals without other significant cardiac disease would be anticipated to significantly improve cardiac function and prolong life. This interesting but rare heart lesion is found under several designations in the literature. The terms used seem to be based on the authors’ interpretation of the nature of the lesion, and are as follows: lymphangioendothelioma,z~3~*6~z3~26 epidermoid cyst of the heart,’ benign coelotheepithelium-like
inc1usion,5,1g~25
epi-
thelial hamartoma,13 squamous epithelial l4 a remnant of the truncus arteriosus cyst, division (hamartoma) ,21 chronic lymphangitis proliferans,28s2g primary mesothelioma,11,24J0 and an adenoma-like tissue
‘z%of R R
-
R Other Other RHD
SA, VF -
R -
:HD CHF Ci CVA R R SUD
-
*Abbreviations: AFIP. Armed Forces Institute of Pathology; CHB, complete heart block; SA. Stokes-Adams tricular fibrillation; CHF, congestive heart failure; R. rhythm disturbance cause of death; RHD. rheumatic congenital heart disease’ CVA, cerebrovascular accident: SUD, sudden unexpected death.
lioma,6*i7
(
SUD R SUD SUD SUD SUD
syndrome; VF, venheart disease; CHD,
malformation of the serosal epitlleliun~.g The diversity of the terms applied to the lesion probably indicates not only an uncertainty as to the nature of the tumor but also some variation in the histologic findings in the lining of the cystic structures. The use of the terms “epidermoid,” “epithelium-like,” “squamous,” and “epithelial hamartoma,” indicates that the observers felt that the cyst lining was epithelial in nature. Certainly the findings of “cornified stratified squamous epithelium” and “intercellular protoplasmic bridges,” would support this assumption. The case in question did not show these changes in the cyst lining; however, other cases in our files showed changes of the type indicated by other authors. Discussion of this problem is beyond the scope of this paper; however,
Benign
it is our feeling, that the difference in the histologic findings in the various cases would not necessarily indicate two different types of lesions but might be explained on the basis of a metaplastic change of the lining cells. The presence of inflammatory cells in association with the cysts might be considered as support for the possibility that this is the result of a chronic lymphangiitiszg; however, the constant location of the lesion, the finding of it in a fetus, a newborn, and in the young infant and child would, we feel, support the assumption that this is a unique congenital tumor. The presence of a stratification and intercellular bridge noted in some of the cases would be against the assumption that the tumor is a mesothelioma or the consequence of entrapment of serosal cells in this area during the early development of the heart, unless we assumed that these were the result of metaplasia. Priority is usually given to Armstrong and Mijnckeberg2 for the first description of this lesion in 1911. Their’s was a report of a 5-year-old boy and their findings were supported by an ECG study (this procedure had just been introduced into clinical medicine). A case reported by Hadden in 188g8 would appear compatible with this lesion; it does not appear to be supported by the limited histologic study, even though the clinical history would support this assumption. At the present time, we are aware of 26 cases of this lesion. Table I includes all reports in the literature that we are aware of and those accessioned in the files of the Registry of Cardiovascular Pathology, Armed Forces Institute of Pathology. The case of Klein and Kinzn has been omitted from this study; they describe a malignant tumor of this type that metastasized to the vertebrae; however, the histologic findings of the tumor are not consistent with the diagnosis, and it would appear that this is another type of malignant tumor. Reports of epithelial inclusions are present in both the literature and in our files; however, these are not located in the interatria1 septum and apparently do not interfere with conduction of the heart. Hence, these are excluded from this study. Interestingly, of the 26 reports listed here, 19
heart tumor callsing complete heart block
541
were in women while only 7 were in men. One of the reports concerned an S-monthold fetus, one a newborn, and three in the first year of life. Six were under 10 years of age, six between 21 and 30 years old, and five over 70 years of age when death occurred. In 20 of the 26 cases, heart blocks of various degrees were recorded during life. In two instances, pacemakers were inserted because of the clinical symptomatology and, in one instance, this possibility was considered. Certainly, then, this tumor should be kept in mind when evaluating heart block, particularly in a young individual. In addition to this type of tumor, angiomas may arise in this area producing heartblock as a consequence of encroachment on, or destruction of, the A-V node.‘*15 While our report is concerned with tumors involving the A-V node, it should be pointed out that Nadas and his co-workers20 made a study of 41 cases of paroxysmal tachycardia in infants and children in 1952 and reported two cases in which thickening of the tissue at the caval-auricular junction was found at postmortem examination; both were interpreted as hamartomas of the S-A node. In view of these findings, it is important to stress careful examination of both the S-A and A-V node regions. Summary
A case is presented in which a benign cystic tumor disrupted the continuity of the A-V conducting pathway, resulting in complete heart block. Despite 15 years of stable chronic A-V block, the patient developed ventricular arrhythmias that led to her death. Such tumors, although rare, represent a significant cause of complete heart block and are important because of the implications of pacemaker therapy available today. REFERENCES 1. von Albertini, A.: Histologische Geschwulstdiagnostik, Stuttgart, 1955, Georg Thieme Verlag. 2. Armstrong, H., and MGnckeberg, J. G.: Herzblock, bedingt durch primgren Herztumor, bei einem 5 jlhrigen Kind, Arch. Klin. Med. 102:144, 1911. 3. Armstrong, H.: Lymphangioendothelioma of the AV node, causing heart-block, Liverpool Med. Chir. J. 33:100, 1913. 4. Sotelo-Avila, C., Rosenberg, H. S., and Mc-
542
5.
6.
10.
11.
12.
13.
14.
15.
16.
Munion
Am. Heart J. April, 1972
et ul.
Namara, D. G.: Congenital heart block due to a lesion in the conduction system, Pediatrics 45:640, 1970. Barr, J. R., and Pollock, P.: Inclusion cyst of the myocardium in a patient with complete heart block, Canad. Med. Ass. J. 98:52, 1968. Calzavara, F.: Celotelioma del cuore, Riv. Anat. Pat. Oncol. 13:845, 1958. De Chatel. A.: Koneenitale Eoidermoid-Cvste des Herzens, Frankfurt. Z.’ Path. 44:426, 1932-33. Hadden, W. B.: Cyst of the heart, Trans. Path. Sot. London 39:79, 1888. Haraszti, A., Gyarmati, M., and Sallay, E.: Adenomartige Gewebsmissbildung des Herzens mit atrioventrikularem Herzblock, Zbl. Allg. Path. 107:542, 1965. Hoekenga, M. T.: Complete heart block in an infant associated with multiple congenital cardiac malformations, Amer. J. Dis. Child. 69:231, 1945. Kaminsky, N. I., Killip, T., Alonso, D. R., and Hagstrom, J. W. C.: Heart block and mesothelioma of the atrioventricular node, Amer. J. Cardiol. 20:248, 1967. Klein, R., and Kinz, J.: iiber ein metastasierendes sogenanntes Lymphangioendotheliom des Herzens, Oest. Z. Kinderheilk. 9:289, 1953. Leicher, F.: Zur Pathogenese der primaren epithelialen Tumoren im Reizleitungssystem des Menschen, Z. Kreislaufforsch. 37:105, 1948. Leighton, J., Hurst, J. W., and Crawford, J. D.: Squamous epithelial cysts in the heart of an infant with coincident cystic changes in the ovaries and breasts. Arch. Path. (Chicago)50:632, 1950. Linder, E., Landtman, B., Tuuteri, L., and Hjelt, L.: Congenital complete heart block, histology of the conduction system, Ann. Paediat. Fenn. ll:ll, 1965. Lloyd, P. C.: Heart block due to primary lymphangioendothelioma of atrio-ventricular node, Johns Hopkins Med. J. 44:149, 1929.
17.
Mahaim, I.: Le coelothelioma tawarien benin? Cardiologia 6:57, 1942. 18. Meesen, H., and Poche, R.: Pathomorphologie des myokard, in Bergmann, W., and Doerr, W., editors: Das Herz des Menschen, vol. 2, Stuttgart, 1963, Georg Thieme Verlag, p. 726. 19. Morris, A. S., and Johnson, I. M.: Epithelial inclusion cysts of the heart, Arch. Path. (Chicago) 77:44, 1964. 20. Nadas, A. S., Daeschner, C. W., Roth, A., and Blumenthal, S. L.: Paroxysmal tachycardia in infants and children, Pediatrics 9:167, 1952. 21. Ovary, I., Pinter, L., and Leovey, A.: Atrioventricularis blockhoz vezetij primaer szivtumor, Orv. Hetil. 98:826, 1957. 22. Papp, C.: Sindrome di Adams-Stokes da lipomatosi de1 nodo de tawara, Policlinico [Med.] 39:253, 1932. 23. Perry, C. B., and Rogers, H.: Lymphangioendothelioma of the heart causing complete heart block, J. Path. Bact. 39:281, 1934. 24. Picoff, R. C., and Petenyi, C.: Primary mesothelioma of the atrioventricular node, Arch. Path. 89:84, 1970. 2.5. Rabson, S. M., and Thill, L. J.: Epitheliumlike inclusions in the heart, Amer. J. Path. 24:655, 1948. 26. Rezek, Ph.: tiber eine primare epitheliale Geschwulst in der Gegend des Reizleitungssysterns beim Menschen, Virchow. Arch. Path. Anat. 301:305, 1938. 27. Rossi, L., and Levy, A.: Atteinte du noeud sinusal et du systeme neuro-ganglionaire atria1 par une tumeur primitive maligne du pericarde (Mesotheliome), Arch. Mal. Coeur. 54:807, 1961. 28. Rossi, I,.: Complete heart-block, Brit. Med. J. 1:121, 1964. 29. Rossi, L.: Case of cardiac lymphangitis with atrioventricular block, Brit. Med. J. 2:32, 1965. 30. Wolf, P. L., and Bing, R.: The smallest tumor which causes sudden death, J.A.M.A. 194:674 1965.