Congenital blood cysts of the heart valves

Congenital Blood Cysts of the Heart Valves KENT G. ZIMMERMAN, MD,* SAMUEL H. PAPLANUS, MD, t S. DONG, MS,t AND RAYMOND B. NAGLE, MD, PhD w and are often mnltilocular. These lesions have been observed in fetuses and infants front the sixth month of gestation up to several years of age and are found. most commonly on the mitral and tricuspid valves. The reported prevalence among atttopsied fetuses and infants has varied front 25 to 100 per cent. Because of their prevalence, these lesions need to be recognized and their significance, if any, understood. Blood cysts were first described by Els,isser in 1844 (as cited by LuschkaS). Various theories of the origin and caustive factors in the development of these lesions have been reviewed by Levinson and Learner. 4 The most popular theory is that the cysts are connected to the ventricle via small infoldings in the ventricular surface of the valve leaflet. Tiffs view was developed first by Haushalter and Thiry 6 and e x p a n d e d by others.7.8Jonsson 9 made models of the cysts using wax plate reconstructions from serial sections and showed that the cysts had projections that opened on the ventriculai- surfaces of the atrioventricular valves. More recently, however, investigators have been urj.ab!e to demonstrate these connections by routine [ight microscopic examination.L3 A photomicrograph.by Mills'-'showed an "endothelial bar" withottt an apparent lumen connecting the ventricle and cyst. Similar-appearing blood cysts in calves and other cattle have been shown to have endotlteliunl-lined connections with the ventricles. l0

Congenital blood cysts of the heart valves are found most commonly on the tricuspid and mitral valves of fetuses and infants. Hearts available following 38 random autopsies of fetuses and infants 2 years of age or younger were examined. Blood cysts were found in 18 cases (47 per cent) in which ages ranged from 26 weeks of gestation to 11 months. The cysts varied in diameter, from microscopic to 3 mm. Affected valves had from one to 20 cysts. Light microscopic examination of serially sectioned paraffin-embedded tissue and plastic-embedded tissue and scanning electron microscopic examination revealed connections between the cyst lumens and ventricles via small endothelium-lined channels. The cyst structure suggested formation from ventrieular endothelial infoldings in the valve leaflet base, which bulged into the atrium because of the pressure gradient present during valve closure. Blood cysts are a common finding in neonates dying of various causes and probably have no clinical significance. There is no association with asphyxia as previously described. Blood cysts may persist and enlarge to form giant cysts of the heart valves. HUM PATtlOL 14:699--703, 1983.

Congenital blood cysts of the heart valves are thinwalled, blood-filled cysts that have diantcters ranging from microscopic to 3 mm and are found along the closure lines of the valves, t--4 Histologically, the cysts are spaces lined by flattened endothhelium and filled with n o n - o r g a n i z e d blood. When large, the cysts project abov~ the atrial surface of the valve leaflet

Received May 20, 1982, from the Department of Pathology, Arizona Health Sciences Center, Tucson, AZ 85724. Revision accepted for publication August 18, 1982. * Resident. t Professor. * Research Assistant. Professor. Address correspondene and reprint requests to Dr. Paplanus.

MATERIALS AND METHODS T h e hearts of 38 fetuses and infants 2 years of age and yotmger, on whom random atttopsies were

TABLE 1. Major Diagnoses in Eighteen Cases of Congenital Blood Cysts on Heart Valves Age/Sex Case Case Case Case Case Case Case Case Case Case Case Case Case Case Case Case Case Case

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18

26 wk (GA)/M 30 wk (GA)/M 31 wk (GA)/M 32 wk (GA)/M Term/F I day/M 2 days/M 2 days/M 9 days/M 10 dayslM 13 days/M 13 days/M 14 days/M 3 wk/M 6 wk/M 2 mo/M 10 mo/M 11 mo/F

Valve Mi, T Mi, T Mi, 'F Mi Mi, T Mi Mi, T, P, A T Mi, T

T Mi, T Mi, T T Mi, T Mi Mi T T

Major Diagnoses I'rematnrity Infant respiratory distress Bronchopneun~onia, congestive heart failure Intrauterine fetal demise (fetus stillborn) tloloprosencephaly, hydrocephalus (fetus stillborn) Infant respiratory distress Meningitis, multiple cerebral developmental defects Pubuonary hypoplasia tlypovolemic shock and disseminated intravascular coagnlol)athy llepatic infarct, puhnonary hemorrlmge Meconium aspiration Congenital heart disease (transposition of great vessels) Congenital heart disease (hypoplastic left ventricle) Acute enterocolitis Congenital heart disease (endocardial cushion defect) Congenital heart disease (pulmonic valve stenosis) Bronclmpneumonia, pseudomembranous coloproctitis Medulloblastoma, bronchopneumonia

ABBREVIATIONS: GA = estimated gestational age; Mi = mitral; T = tricuspid; P = pulmonic, A = aortic.

699

HUMAN PATHOLOGY

Volume 44, No. 8 (August 4983]

tion, and tissue was fixed in I0 per cent b u f f e r e d formalin. Tissue processed for histologic examination was e m b e d d e d in paraffin or glycol methacrylate (Polysciences, Inc., W a r r i n g t o n , Pa.). Sections e m b e d d e d in paraffin were cut at 6 - F m intervals, a n d the sections e m b e d d e d in glycol methacrylate were serially sectioned at 2-~m intervals with glass knives. All sections were stained with h e m a t o x y l i n - e o s i n stain. Material for scanning electron microscopic examination was bisected with a razor blade, rinsed in 0.1 xI sodium cacodylate b u f f e r to r e m o v e blood from the lumen, t h e n post-fixed in 1 p e r cent osmium tetroxide for o n e hour. Following post-fixation, the tissues were d e h y d r a t e d in g r a d e d alcohols, critically point dried with liquid carbon dioxide substitution in a Pelco H m o d e l critical point drier, and coated with g o l d - p a ladium using a T e c h n i c s H u m m e r I s p u t t e r i n g device. Specimens were e x a m i n e d with an E T E C Autoscan electron microscope.

FIGURE 1, Blood cysts on the tricuspid valve of a 40-month-old child who died of bronchopneumonia and pseudomembranous coloproctitis. The cysts are located near the closure line of the valve and project above the offial surface. The scale af the right is graduated in millimeters.

RESULTS

9 :i/l

..-,.-:._-,~

:

.

..

O f the 38 hearts e x a m i n e d , 18 (47 p e r cent) were f o t m d to have blood cysts on at least one heart valve. T h e age r a n g e was f r o m 26 m o n t h s o f gestational age to 11 months. T h e lesions were seen p r e d o m i n a n t l y on the tricuspid and mitral valves and u n c o m m o n l y on the aortic and pulmonic valves (table 1). T h e largest lesions were 2 m m in d i a m e t e r , but most were less than t ram. T h e cysts were p~e~ent along the closure lines o f the valves; those o n the atrioventricular valves projected into the atria; those on the senfihmar valves projected into the ventricles (fig. 1). Often, only single cysts were present on the affected valves, but as many as 20 were seen o n some valves. A variety o f causes o f d e a t h were associated with these lesions; in n o n e o f the cases was t h e r e m o r p h o l o g i c evidence o f asphyxia, such as petechial h e m o r r h a g e s over the thoracic portion o f the thymus. Only two o f 18 cases with cysts involved female patients, c o m p a r e d with seven o f the 20 cases without cysts. This finding is not significant (P > 0.1). P a r a f f i n - e m b e d d e d sections s h o w e d n o n - o r g a -

,

:.:~:..'.:'!';::..

..... .

_

.-: .:....,. : ~ : - ] ';-"-:.,.~..... :., . -~- ." .,... ~, - 9 .~,.. . -,, . %..'r +, , , - . . . .- .- - . . .. :.~-...':-..., {.~ , ( ; . . . . .,, 9 .,

-

. . . - . -.. , .

- ..: -~.,:~..;~, : ' . - . . . .

, -

.... ::..'. : *~;:

FIGURE 2. Blood cyst showing non-organized blood filling an endofhelium-lined lumen. The cyst bulges above the atrial surface of the valve leaflet [top]. [Hematoxylin-eosin stain, x 30.]

p e r f o r m e d at the Arizona Health Sciences Center, were studied. In 18 o f the 38, at least one grossly evident blood cyst was p r e s e n t on a h e a r t valve. T h e blood cysts were r e m o v e d for microscopic examinaf:',

-i L''~-

:"..

"~:'.-."

9

:<" " " "" ,:"

"J"

"

- :

~"

t

'

"

~ : : ; " "' ~ ' --.::,*

&

..

.~

\

/z

.... ':.ii!i' :! .% ---'-'

~k'

,.-

..~

"

",

. . . .,. .'.2 , .--"

i . ~

":..

~..-:

-- ;.-.;, - ' -

.... . "-"

.

"

X

~

":,~,,d~lL,~

. . . . 9 ,~;", : e . ~ -

-"- - ~ .'"..... ..-~ . . - ' ~ - ~ . -.

FIGURE 3. Glycol-methacrytate-embedded 2-v.m serial sections of a cyst showing the endothelium-l[ned channel the cyst lumen [C] and an infolding of the ventricular surface of th.e leaflet [V]. [ x 430.] 700

..

[arrows] connecting

CONGENITAL BLOOD CYSTSOF HEARTVALVES [Zimmerman et al.)

FIGURE 4. Top,cross-section of a valve with a blood cyst, after the blood was removed from the lumen [ ~ . The upper part of the cyst WQ[[, which projects into the otriat lumen, has colIapsed and is partJaIIy raided over. The ven~Ticular lumen is below. The inner surface of the lumen is lined by endothelium, which as a cobblestone-like appearance. (x 420.) Boffom, enlargement shows details of a channel opening into the cyst lumen. ( x 800.)

701

HUMANPATHOLOGY Volume"14,No. 8 (August'i983] TABLE 2.

Case 19 Case 20 Case 21 Case 22 Case 23 Case 24 Case 25 Case 26 Case 27 Case 28 Case 29 Case 30 Case 31 Case 32 Case 33 Case 34 Case 35 Case 36 Case 37 Case 38

Major Diagnoses Twenty Cases In Which Congenital Blood Cysts Were Not Present Age/Sex

Major Diagnoses

24 wk (GA)/M 29 wk (GA)tM 30 wk (GA)/F 32 wk (GA)/F 32 wk (GA)/F 32 wk (GA)/F 32 wk (GA)/F 34 wk (GA)/M 34 wk (GA)/M 36 wk (GA)IM 1 day/M 9 days/M 3 wk/M 3 mo/M 9 mo/M 11 mo/M 11 mo/M 15 mo/M 2 yr/F 2 yr/F

Congenital heart disease (hypoplastic pulmonic valve and pulmonary artery) Multiple congenital anomalies including heart (stillborn) Multiple congenital anomalies including heart Intrauterine fetal demise Intrauterine fetal demise Hemolytic disease of the newborn Trisomy 13 with muhiple congenital anomalies including heart Congenital heart disease (transposition of great vessels) Intrauterine fetal demise (stillborn) Intrauterine fetal demise (stillborn) Congenital heart disease (aortic stenosls) Disseminated herpes simplex with intravascular coagulation Congenital heart disease (hypoplasia of right venticle) Necrotizing enterocolitis Meningitis, cerebral abscess and aspiration pneumonitis Malnutrition Trisomy 21 and congenital heart disease (eudocardial cushion defect) Bronclmpneumonia, reual dysplasia Progranulocytic leukemia, sepsis and pseudomembranous colitis Bronchopulnmnary dysplasia

ABBREVIATIONS:GA = estimated gestational age.

nized blood filling an endothelium-lined space (fig. 2). Some cysts were multilocular, with endothelial partitions dividing the cyst lumens. In two of tile 18 cases, hemosiderin was present in the loose connective tissue adjacent to the cyst walls. Numerous irregular infoldings of tile ventricular endocardium were present along the leaflets. Some o f these cleft-like spaces were continuous with the lumen of the cyst (fig. 3). T h e connections were short and less than 15 ~m in diameter. Scanning electron micrographs of the lesions demonstrated tile inner lining of the cysts to have a cobblestone-like appearance typical of an endothelial surface (fig. 4, top). Channels in the base of the cysts were seen in direct apposition to the ventricular surface of the valve (fig. 4, bottom). DISCUSSION T h e prevalence of blood cysts (47 per cent) and their common location on the atrioventricular valves parallel the findings of others, l-q The morphologic studies reveal that the numerous infoldings along tim ventricular surface of the valve, which are normally present, are connected with the cyst lumens. These findings s u p p o r t the theories o f H a n s h a l t e r and Thiry G and othersl-4, 7-9 suggesting a possible mechanism of formation related to pressure across fi valve when closed. T h e cross-sectional thickness o f fetal heart valves is often less than 100 i.tm, and the valves are composed mainly of loose collagenous tissue covered on each side by thin endocardium. When an atrioventricular valve is closed d u r i n g systole, the pressure gradiant across the valve leaflet would cause bulging of tile clefts and infoldings of ventricular efidothelium to form a cyst (diverticulum). T h e top of the cyst would project into the atrial lumen, as we have observed. T h e cysts on the semilunar valves would be formed by a similar mechanism, presum702

ably during diastole when the semilunar ,~a(,:es are closed. During diastole the low-pressure side of the valve would be on tile ventricular surface. Indeed, blood cysts on the semilunar valves are found on the ventricular surfaces. When the valvesare open, the cysts probably empty o f bloods, at least partially, and are filled again as the valve doses and the pressure gradient rises. T h e filling aild. emptying would explain why thrombosis of the lumen has not been observed. It has been suggested that the presence of blood cysts indicates asphyxia as a manner of death--a concept that has made its way into cardiovascular and fetal pathology textbooks, i 1-13T h e original investigators cited in these texts provide no historical or pathologic support of tile association between blood cysts and asphyxia, and the cases reported here cannot support tiffs concept (table I). There was a wide range of major diagnoses in our cases and no definite morphologic evidence of asphyxia. The cases without cysts encompassed a similar spectrum of diseases and diagnoses at death (table 2). T h e presence of hernosiderin in tile wall of the cyst; would indicate that they existed for some time; the hemosiderin presumably had come from breakdown o f erythrocytes that had extravasated from the cyst lumen into the surrounding connective tissue. It is not known what happens to the cysts after infancy. Evidence of transition of a cyst, such as organization and sclerosis of the lumen, has not been observed by us. Wegelin 14 suggested that collapse of the cyst, adhesion o f apposite endothelium, and fibrosis constitute the natural history. We observed a small focus o f mild fibrosis, hemosiderin deposition, and scattered lymphocytes adjacent to a cyst. This may have indicated the site of a cyst that had ruptured and resolved. Giant blood cysts of the cardiac valves, usually the pulmonic valve, IS-Is have been described in children and adults. In these patients par-

CONGENITAL BLOOD CYSTSOF HEARTVALVES [Zimmerman et aLI

tial obstruction of blood flow occurs, and the cysts require surgical removal, since they may be up to 4 cm in diameter. The basic morphologic features of the giant cysts are reminiscent of those of the previously m e n t i o n e d congenital blood cysts in that a channel connects with the htmen from the high-pressure side of the valve. T h e lumens of these large cysts are often filled with organized thrombus. Perhaps a persisting congenital blood cyst slowly enlarges during life and gives rise to a giant cyst that eventually causes obstruction. Although we use the term blood cyst, as have previous investigators, the lesions described here are truly diverticttla. We have sttown that congenital blood cysts form from infoldings of the valvttlar ventricular endothelium that bulge into the atria because of the transvalvular pressure. We propose that these cysts have no dentonstrated clinical significance and are a fairly common finding on the heart wdves of neonates. One should not presume that asphyxia was the cause of death when these lesions are found. These lesions form apparently because o f the immature structure of the heart valve and disappear as the heart valve becomes thicker and comes to consist of more dense collagen later in life.

REFERENCES 1. BeggJG: Blood-filled cysts in the cardiac valve cusps in fetal life and infancy. J Pathol Bacteriol 87:177, 1964 2. Mills SD: The occurrence of blood filled cysts on the cardiac valves in" infancy. J Pediatr 6:51, 1935

3. Boyd TAB: Blood cysts oll heart valves of infants. A m J Pathol 25:757, 1949 4. Levinson SA, Learner A: Blood cysts on the heart valves of newborn infants. Arch Pathol 14:810, 1932 5. Luschka H: Die Blutergiisse in Gewebe der tterzklappen. Virchows Arch [Pathol Anat] 11 : 144, 1857 6. Haushalter P, Thiry C: l~tnde sur les h6matonaes des valvules auriculo-ventriculaires dans renfance. Arch Med Exper Anat Pathol 10:558, 1898 7. Meinhardt H: l~lber die Entstehnng der Herzklappenhfimatome bei N e u g e b o r e n e n . Virchows Arch [Pathol Anat] 192:521, 1908 8. Wegelin C: Uber die Blutkn6tchen an den Herzklappen der Neugeborenen. Frankfllrt Z Pathol 2:411, 1908 9. Jonsson S: Uber Blutzysten an der Herzklappen Neugehorener. Virchows Arch [Pathol Anat] 222:345, 1916 10. Smith RB, Taylor IN: Blood cysts on the cardiac valves of calves and cattle. Cardiovasc Res 5:132, 1971 I 1. Potter EL, Craig JM: Pathology of the fetus and infant, 3rd Ed. Chicago, Year Book Medical Publishers, 1975, p 244 12. Pomerance A: Rarities and endocardial abnormalities. In The Pathology of the fteart. Oxford, Blackwell Scientific Publications, 1975, p 485 13. Hudson REB: Cardiovascular pathology, 3rd Ed, vol 2. London, Edward Arnold Ltd, 1965, p 1980 14. Wegelin C: Weitere Beitrfige zur Kennmis der Blutkn6tchen and Endothelkan~le der Herzklappen. Frankfurt Z Pathol 9:97, 1912 15. Miles VN, Favara BE, Morriss JH, et ali Giant blood c)st and congenital pulmonic stenosis. Am J Dis Child .129:1079, 1975 16. Jim6n6z-Martinez M, Franco-V:izquez S, Angulo-tternfindez O, et ah Blood cysts of the pulmonary valve producing pulmomc stenosis: a successful surgical treatment. J Thorac Cardiovasc Surg 56:165, 1968 17. Zwart HH, Jenson CB, Knight JA,.et al: Blood-filled cysts on heart valves. J Pediatr Surg 8:333, 1973 18. Galluci V, Stritoni P, Fasoli G, ~ ' a l : Giant blood cyst of tricuspid valve: successful excision.in an infant. Br Heart J 38:990, 1976

703