- Email: [email protected]
Cardiac fibroma: Clinicopathologic correlates and surgical treatment
Cardiac fibroma: Clinicopathologic correlates and surgical treatment The clinicopathologic findings of 23 patients with cardiac fibroma are presented. The mean patient age was 13 years, with a range of 1 day to 56 years. The presenting symptoms included heart failure, arrhythmias, sudden death, cyanosis, and chest pain. Some patients had no symptoms, and one patient had Gorlin's syndrome. Echocardiography and magnetic resonance imaging were very sensitive in diagnosis. Nineteen patients underwent tumor resection or biopsy, and four tumors were diagnosed at cardiac transplantation or autopsy on explanted hearts. In five surgical cases, complex operations were necessary, including pericardial or synthetic patches, valve replacement, or coronary artery grafting. Two operative deaths occurred in patients with surgical resections and four operative deaths in patients who at the time of the operation were deemed to have inoperable disease and only biopsy was performed. All deaths but one were in patients younger than 2 years of age. Four patients with subtotal resections did well after the operation. Dense collagen was more frequent in tumors in older patients. We conclude that fibromas are congenital tumors that are frequently discovered in adolescents and adults. Surgical treatment is generally successful, and imaging techniques are helpful in preoperative assessment. (J THoRAc CARDIOVASC SURG 1994;108:862-70)
Allen P. Burke, MD,a Melissa Rosado-de-Christenson, MD,b Philip A. Templeton, MD,c and Renu Virmani, MD, Washington, D.C., and Baltimore, Md.
Cardiac fibroma is a rare benign tumor of the heart that occurs primarily in infants and children. Despite a number of recent reports of single patients or small numbers of patients.I" no large series of these lesions have been published that allow a better characterization of the pathology and the clinical, radiologic, and surgical outcome of these lesions. The purpose of this study is to describe 23 previously unreported cardiac fibromas that have been pathologically documented, with emphasis on clinical findings, histologic features, and radiologic diagnOSIS. From theDepartments of Cardiovascular Pathology" and Radiologic Pathology," Armed Forces Institute of Pathology, Washington, D.C., and theDepartment of Radiology," University ofMaryland Medical System, Baltimore, Md. The opinions orassertions contained herein arethe private views ofthe authors and arenot tobeconstrued asofficial orreflecting the views oftheDepartment ofthe Army, theDepartment oftheAirForce, or the Department of Defense. Received for publication Jan. 6, 1994. Accepted for publication April 19, 1994. Address for reprints: Allen P. Burke, MD, Department ofCardiovascular Pathology, Armed Forces Institute ofPathology, Washington, D.C. 20306-6000. 12/1/57165
862
Materials and methods We retrospectively reviewed the files of the Armed Forces Instituteof Pathology for cases of fibrous tumors of the heart between 1967 and 1993. Twenty-three cases ofcardiacfibroma withpathologic materialwere identified. Thediagnosis dependedon the finding of a discrete, bulging massinoneor more ventricles or atria, which histologically wascomposed primarily of fibroblasts or collagen. Excluded from the diagnosis were tumors that contained myofibroblasts and histiocytic cells (inflammatory pseudotumors) ortumors ofendocardial location with luminal growth (papillary fibroelastoma, myxoma with fibrosis). The clinical information wasbased on material submitted at the timeofconsultation supplemented byfollow-up information requested fromthe treatinginstitution at the timeofthisstudy. Fourteen cases weresubmitted as part ofa radiologic-pathologic correlation course; for these, detailed radiologic evaluation was included with the pathologic materials. Sections of tumors were studied with hematoxylin-eosin stains and Movat's pentachrome stain for collagen, elastic tissue,and acidmucopolysaccharides. Thedegree ofcollagen and the cellularity wereestimated blindly on an arbitraryscale of I to 3+. Results Patient data. The mean age at the time of diagnosis was 13 years; the age range was 1 day to 56 years. More than one third of the patients were younger than I year
The Journal of Thoracic and Cardiovascular Surgery Volume 108, Number 5
Burke et al.
863
Fig. 1. Cardiac fibroma. The specimen is a gross heart from a 3-month-old boy who died suddenly without previous medical history. A, External surface of heart. B, Opened heart demonstrates fleshy mass replacing much of the interventricular septum and ventricular mass. .
of age at the time of diagnosis. No sex or race predominance was apparent. Clinical findings. Symptoms related to cardiac fibroma were related primarily to heart failure, arrhythmias, sudden death, and chest pain. One patient had a persistent pericardial effusion that was at first ascribed to collagen vascular disease; one patient whose tumor obstructed the pulmonary outflow had syncope; two tumors were incidental findings. Of the latter patients, one was being evaluated for multiple mandibular cysts and was noted to have multiple digits of the hands and an enlarged cardiac silhouette. A diagnosis of the Gorlin syndrome was subsequently made. The other patient with an incidental tumor was first investigated after a murmur was auscultated during a routine physical examination. Little correlation exists between the type of initial symptom and the location of the tumor in the heart. Arrhythmias were common in patients with tumors in the interventricular septum, right ventricle, and left ventricle. Patients with heart failure had large, bulky tumors in either ventricle that were difficult to excise. Although tumors in the ventricular septum were usually symptomatic, a calcified mass in the ventricular septum was first noted during coronary artery bypass grafting in a 56-year-old man. Gross findings. The site of cardiac fibroma was the ventricle or interventricular septum in 21 cases and the
right atrium in two cases. The left ventricle was more frequently involved than the right (12:8); in three cases the tumor was predominantly in the interventricular septum. The gross appearance of the tumors was typically described as fibrous, white, and whorled (Fig. 1). An exact size was available for resected or autopsy specimens. The mean size was 5 em, with a range of 2.5 to 8 em. The tumors were described at operation or autopsy as circumscribed in 10 cases and infiltrative in 13. Surgical outcome. Thirteen patients had surgical resections of cardiac fibroma; the mean age of this group was 16 years. In eight patients (Table I, mean age 12 years), simple surgical excision was done; in four of these patients (mean age 7 years), the resection was considered subtotal by the surgeon. In five patients (Table II), complex operations were performed, including patching of the myocardial defect, valve replacement, or coronary artery bypass grafting. The mean age of these patients was 22 years. Only two patients died as a result of surgical complications; one was a I-day-old infant with a large tumor, and the other was a 28-year-old patient in whom valve replacement and coronary artery bypass grafting were necessary. The other patients were well at the time ofmost recent follow-up study (Table 11). Six patients underwent biopsy without an attempt at resection (Table III). Five ofthese patients were younger
The Journal of Thoracic and Cardiovascular Surgery November 1994
8 6 4 Burke et al.
Table I. Clinical findings: Simple surgical excisions Age, race, sex
Clinical
Extent of resection
I day, W, F
Cardiac failure, cyanosis, Apgar score 5/6
Partial
4 mo, B, F
Fever, irritability, murmur as neonate, ?VSD
Partial
4 yr, W, F
Ventricular tachycardia
Partial
4 yr, L, F
Ventricular tachycardia
Total
II yr, W,M
Asymptomatic murmur
Total
II yr, B, F
Incidental murmur
Total
24 yr, W, F
Chest pain, arrhythmias
90% Total
40yr, W, M
Gross
Follow-up
Huge 4.9 em mass infiltrating RV, RVOT, RA Largely circumscribed RV multilobated 4 em mass Infiltrating 5 em LV mass Circumscribed 5 cm LV mass Infiltrating 3 cm LV mass Circumscribed 4.2 cm RV mass Anterior R V wall, 6 ern circumscribed mass LV, PV, RA circumscribed mass
Operative death
Well 4 yr
Well 4 yr Well 2 yr Well (athletic) 5 yr Weill mo Well 2 yr Well 2 yr
W, White; B, black; L, latin; F, female; M, male; VSD, ventricular septal defect; RV, right ventricle; RVOT, right ventricular outflow tract; RA, right atrium; LV, left ventricle; PV, pulmonary valve.
Table II. Clinical findings: Complex surgical resections Age, race, sex
Clinical
6 mo, W, F
Cyanosis
8 yr, W, M
28 yr, W, M
Pericardial effusion treated with aspirin, steroids Chest pain Syncope
48 yr, W, M
Palpitations
25 yr, W, F
Procedure
Gross
B-T shunt (I rno), resection and pericardia I patch (6 mo) Resection and pericardial patch
Infiltrating RA, IVC, SVC, stretched foramen ovale Circumscribed RA mass, into SVC Circumscribed 4 em mass, IVS RV mass, RVOT
Resection and Dacron patch Resection, TVR, CABG to RCA Resection and PTFE graft
Circumscribed mass, anterolateral LV, splayed CAs
Follow-up WellS mo Well 10 yr Well 3 yr Operative death Well 3 yr
W, White; F, female; M, male; B- T, Blalock-Taussig; RA, right atrium; IVC, inferior vena cava; SVC, superior vena cava; IVS, interventricular.septum; TVR, tricuspid valve replacement; CABG, coronary artery bypass graft; RCA, right coronary artery; RVOT, right ventricular outflow tract; LV, left ventricle; CAs, coronary arteries.
than 2 years old (mean age 9 months); in these cases, resection was considered impossible because of the extent of tumor at the time of the operation. Five of these six patients died as a result of surgical complications; one remained well 1 month after the operation. The sixth patient in this group was a 19-year-old man with a circumscribed tumor; in this patient, it was elected to obtain a biopsy specimen of the tumor for diagnostic purposes only and observe the patient without further surgical intervention. In four patients the diagnosis was made first at autopsy or cardiac transplantation (Table IV). Imaging data. Radiologic studies were reviewed in
nine cases, and the reports of radiologic studies were reviewed in an additional five cases (Table V). Cardiomegaly was identified in 10 radiographs. Three exhibited a focal cardiac bulge and three demonstrated focal cardiac calcification. One radiograph showed no abnormalities and one demonstrated congestive heart failure. In 11 of 12 echocardiograms, the mass was identified. Two masses were described as echogenic and three were of complex echogenicity, one with the suggestion of central cystic areas. Two unenhanced chest computed tomograms (CTs) demonstrated the cardiac mass and both identified focal
The Journal of Thoracic and Cardiovascular Surgery Volume 108, Number 5
Burke et al.
865
Table III. Clinical findings: Biopsies without resection Age, race, sex
Clinical
2 wk, A, M 8 wk, W, F
Tachypnea,acralcyano~s
6mo, W, M
Diaphoresis, murmur, mild heart failure Cardiac failure
10 mo, W, F 19 mo, W, F 19 yr, W, M
Dyspnea
Persistent cold, mild heart failure Ventricular tachycardia
Gross
Follow-up
Infiltrating RA and RV Infiltrating LV and PA, PA obstruction 2.5 em LV mass infiltrating, extending into LV cavity Infiltrating pulmonary veins LV, RA,LA Infiltrating LVFW, IVS
Weill mo Died postop.
Died postop.
Circumscribed LV near apex 6 em
Well 2 wk
Died postop. Died postop.
A, Asian; W, white; M, male; F, female; RA, right atrium; RV, right ventricle; LV, left ventricle; PA, pulmonary artery; LA, left atrium; LVFW, left ventricular free wall; IVS, interventricular septum
Table IV. Cardiac fibroma: Pathologic diagnosis made at autopsy or explantation Age. race. rex
Clinical
19 days, L, F
Sudden death, normal birth
3 mo, B, M
Sudden death, no medical history Found during investigation of Gorlin syndrome Angina, ventricular fibrillation
17yr,W,F 56 yr, W, M
Gross Circumscribed 5 em mass, LV, RV 8 ern mass infiltrating IVS, LV, RV Huge mass involving 60% of LV, bosselated Circumscribed 7 ern mass in IVS
Follow-up Not applicable Not applicable Well 2 yr after cardiac transplantation Died suddenly 2 yr after CABG; tumor noted at operation
L, Latin; B. black; W, white; F, female; M, male; LV, left ventricle; RV, right ventricle; IVS, interventricular septum; CABG, coronary artery bypass graft.
central calcifications in the lesions (Fig. 2). Three intravenous contrast-enhanced chest CT scans were available for review. Homogeneous enhancement of the tumor was seen in one case and heterogeneous enhancement in one case; in the third case the mass was not visualized prospectively. The reports of three additional CT studies (imaging technique not specified) described homogeneous masses in two and a nondiagnostic report in one. Two chest CT scans demonstrated pericardial effusions. Magnetic resonance imaging (MRI) studies were available in four cases (Figs. 3 and 4). All had Tl-weighted spin echo images and three used multiple imaging planes. The reports of two additional MRI studies (unknown imaging parameters) were also reviewed. Three masses were isointense to skeletal muscle and of homogeneous signal intensity. Two were heterogeneous and predominantly hyperintense to skeletal muscle. One study was performed after administration of intravenous gadolinium and showed heterogeneous enhancement of the lesion. Cardiac catheterization was performed in seven patients. Three patients had right heart catheterization only. In one, a pressure gradient across the right ventric-
ular outflow tract was noted, corresponding to a right ventricular mass detected on echocardiography. The second patient had a right atrial mass, and catheterization demonstrated a right-to-left shunt at the foramen ovale with severe right ventricular inflow obstruction. The third patient with right heart catheterization had a pulmonary artery injection with left ventricular follow-through that demonstrated a left ventricular mass with displacement of the intraventricular septum into the right ventricle. In four patients, right and left heart catheterization was performed. Displacement of the left anterior descending coronary artery was noted in two, and ventriculograms demonstrated a mass in the ventricle in each case. Thallium scans, performed on two patients, demonstrated photopenic defects at the tumor site. Histologic findings. The histologic appearance was essentially as previously described." However, the amount of collagen increased with age, whereas the degree of cellularity decreased with age (Table VI). Occasional mitoses were present in three cellular tumors of patients less than 5 months of age, and occasional perivascular aggregates oflymphocytes and histiocytes were observed in two
The Journal of Thoracic and Cardiovascular Surgery November 1994
8 6 6 Burke et al.
Table V. Cardiac fibroma: Radiologic findings in 14 cases CXR
2-D echocardiogram
CT/MRI
I. Cardiomegaly; calcification
Echogenic mass, pericardial effusion, mass effect RA, RY
2. Cardiomegaly 3. Initially normal; cardiomegaly
Normal Echogenic mass, RY
4. Cardiomegaly
RA mass into IYC, SYC Complex mass with cystic areas, LYFW
5. Calcified mass, RY
LY mural mass involving IYS
6. Cardiomegaly 7. Cardiomegaly
LV mass Large tumor of lateral LY wall
CT: mass with focal calcification Contrast: heterogeneous enhancement Not performed MRI (TI): homogeneous mass of RY free wall isointense to muscle Not performed CT: heterogeneous mass of LYFW, with focal calcification; heterogeneous contrast enhancement CT: nondiagnostic MRI: heterogeneous hyperintense to muscle Not performed
8. Calcification
RY mass
9. Cardiomegaly
Large posterior pericardial effusion Complex mass with mass effect
10. Cardiomegaly II. Normal
Echogenic apical mass, RY dilatation
12. Calcification
Apical LY mass
13. Cardiomegaly
Mass with mass effect
14. Abnormal cardiac contour
Not performed
MRI: heterogeneous mass compressing RYOT; hyperintense to muscle, enhances post-gadolinium image
Angiogram
Not performed
Filling defect, LY lateral wall Not performed
R-L shunt at FO, RA mass Not performed
RYOT mass, splayed CA
Posterolateral L VFW mass LYFW posterolateral mass, splayed CAs; heterogeneous decreased ventricular contractility Splayed CAs
Anterolateral LY mass CT: mass LYFW with focal calcification CT: mass distal IYS, increased attenuation MRI: mass hypointense to muscle MRI (Tl): 3.5 em mass, apical LY, hyperintense to muscle MRI (Tl): homogeneous isointense to skeletal muscle with mass effect MRI (TI) homogeneous isointense to skeletal muscle
Splaying of CAs around tumor Mass
CXR, Chest radiograph; 2-D, two-dimensional; CT, computed tomography; MRI, magnetic resonance imaging; RA, right atrium; RV, right ventricle; LV,Ieft ventricle; IVC, inferior vena cava; SVC, superior vena cava; R-L, right-to-left; FO, foramen ovale: LVFW, left ventricular free wall; IVS, interventricular septum; RVOT, right ventricular outflow tract; CA, coronary artery.
cellular tumors. Sparse chronic inflammation was present primarily at the junction of the tumor and uninvolved myocardium in seven cases. Prominent elastic fibers were present in only four cases. Calcification was present in tumors of patients of all ages but was somewhat more common in older individuals. A focal myxoid background was present in two patients.
Discussion Cardiac fibroma is considered a tumor of infancy and childhood." Although a majority of patients in this study
were younger than 10 years of age, a substantial proportion (10/23) were 10 years of age or older. The diagnosis of cardiac fibroma should be considered, therefore, even in adolescents and adults with mass lesions in the heart. The propensity for cardiac fibroma to cause arrhythmias is becoming increasingly evident.f Nine patients in this report had documented arrhythmias, had symptoms most likely related to arrhythmias, or died suddenly. This report includes a patient with cardiac fibroma and Gorlin syndrome (multiple nevoid basal cell carcinomas, jaw cysts, and bifid ribs), corroborating the association
The Journal of Thoracic and Cardiovascular Surgery Volume 108, Number 5
Burke et al.
867
Fig. 2. Newbornterm femaleinfant with respiratorydistress at birth. A, Unenhancedchest CT scan shows a large rightventricular mass (arrows) with focalcentral calcifications (arrowheads). Note the large pericardialeffusion (e). B, Contrast enhancedchest CT scan shows heterogeneous enhancement of the lesion and mass effecton the right ventricle (v) and right atrium (a).
that has been established between these two entities.' The prevalence of Gorlin syndrome in patients with cardiac fibromas may be higher than 1 in 23, because many patients were infants in whom manifestations of this syndrome may not yet have appeared. The presence of multiple neural midline defects has been described in a patient with cardiac fibroma/; no such abnormalities were present in patients in our series. The optimal treatment of children and adults with cardiac fibroma has not yet been determined, although reports of successful resection have been published.v 6, 7 In this series, surgery was successful in all but one patient
who had severe symptoms. This patient died after a complex operation that included valve replacement and coronary revascularization. Therefore, surgery appears to be the optimal treatment in patients with symptomatic resectable tumors. The role of surgery in patients with asymptomatic tumors is less clear. 5 Cardiac fibromas can remain dormant for many years and even regress.!? The only patient in our series who died suddenly and who was older than 3 months had concomitant severe coronary artery disease; therefore, the cause for the fatal arrhythmia may have been unrelated to the cardiac tumor. It may thus be reasonable to observe some symptom-free patients
The Journal of Thoracic and Cardiovascular Surgery November 1994
8 6 8 Burke et al.
Fig. 3. Previously healthy 19-year-old man in whom arrhythmias developed during a nasal septal operation. A, Coronal cardiac gated TI-weighted MR image (TR 1090jTE II) showsa round homogeneous mass (arrows) of the left ventricular apex which is isointense to skeletal muscle. The lesionis well circumscribed and causes mass effect on the left ventricle.
Table VI. Cardiac fibroma: Histologic findings Age
1 day 2 wk 1 rno 2 rna 3 rna 4 rno
6 rna 6 rna 10 rna 19 rna 4 yr 4 yr 8 yr 11 yr 11 yr 17 yr 19 yr 24 yr 25 yr 28 yr 40 yr 48 yr 56 yr
Cellularity
Collagen
3+
1+ 1+ 1+ 2+
2+
3+ 1+ 3+ 3+ 3+ 1+ 3+ 2+
2+ 1+ 1+ 1+ 1+
1+ 1+ 1+ 0 0 1+ 0 0
H-
1+ 2+ 2+
1+ 3+ 3+ 3+ 3+ 3+ 3+ 3+ 2+
4+ 4+ 4+ 4+ 4+ 4+
without risking cardiac surgery. Most symptom-free patients in our series, however, had a successful operation, one going on to competitive athletic pursuits in high school. The good surgical outcome of patients in our series
Inflammation
0 0 + 0 0 0 + + 0 0 0 + + 0 + 0 0 0 0 0 + 0 0
Elastosis
0 3+ 0 0 0 1+ 0 3+ 0 3+ 3+ 0 0 0 0 0 1+ 0 0 0 0 2+
3+
Calcification
0 +
O. + 0 0 0 0 0 0 +. + 0 0 0 0 0 0 0 0 0 + +
who were older than the age of 2 years indicates that even in symptom-free patients, tumors that are amenable to resection should probably be removed, especially if optimal cardiac function is to be preserved. Because two
The Journal of Thoracic and Cardiovascular Surgery Volume 108, Number 5
Burke et at. 8 6 9
Fig. 4. Woman, 48years old, with severe nocturnal palpitation. A,Axial cardiac gated Tl-weighted MRimage (TR 882jTE 12)shows a round focal leftventricular mass (m) that is hyperintense to skeletal muscle. B,Axial gadolinium-enhanced Tl-weighted MR image shows enhancement ofthemass. Thenonenhancing areas(arrowheads) likely correspond to the calcifications seen on the chest radiographs. infants in our series died suddenly without any previous symptoms, surgical treatment for cardiac fibroma is most likelyindicatedin this age group to avoidthe development of lethal arrhythmias. The data accumulated in this study support the previous imaging findings of cardiac fibroma.v 11 We have demonstrated that CT has a high sensitivity for the detection of intralesional calcification. MRI is an excellent modality for demonstrating the anatomic location of theselesions and the extent of the mass, which is usually isointense to hyperintense when compared with skeletal
muscle on TI -weighted spin echo images and are of homogeneous or heterogeneoussignal. Because one case in this study imaged after intravenousgadolinium administration exhibited enhancement of the mass, gadolinium may be helpful in evaluating the extent of these lesions beforethe operation. T2-weighted MR images in casesof cardiac fibroma may further characterize the fibrous nature of these tumors, because fibrous tissue characteristically has low signal intensity in T2-weighted MRI studies. Cardiac fibroma is part of the spectrum of soft tissue·
The Journal of Thoracic and
8 7 0 Burke et al.
lesions that embraces soft tissue fibromas and fibromatoses. Many of the latter tumors are considered aggressive lesions with the capacity for local invasion and growth.'? In contrast to fibromatosis, cardiac fibromas do not appear to continue to grow and proliferate after I or 2 years of age. The degree of fibrosis increases with age, and the degree of cellularity decreases with age. Surgical approach must be tailored to the individual case; however, the surgeon can, with some degree of certainty, advise the patient after the operation that the tumor is not likely to recur and that short-term and mid-term prognosis is excellent.
Cardiovascular Surgery November 1994
5. 6.
7.
8.
9. I. 2.
3.
4.
REFERENCES Coffin CM. Congenital cardiac fibroma associated with Gorlin syndrome. Pediatr PathoI1992;12:255-62. de Leon GA, Zaeri N, Donner RM, Karmazin N. Cerebral rhinocele, hydrocephalus, and cleft lip and palate in infants with cardiac fibroma. J Neural Sci 1990;99:27-36. Brown IW, McGoldrick JP, Robles A, Curelly GW, Gula G, Ross DN. Left ventricular fibroma: echocardiographic diagnosis and successful surgical excision in three cases. J Cardiovasc Surg (Torino) 1990;31:536-40. Ceithaml E, Midgley FM, Perry LW, Dullum MK. Intra-
10.
II.
12.
mural ventricular fibroma in infancy: survival after partial excision in 2 patients. Ann Thorac Surg 1990;50:471-2. Tahernia AX, Bricker JT, Ott DA. Intracardiac fibroma in an asymptomatic infant. Clin Cardiol 1990;13:506-12. Otsuka T, Asano K, Murota Y, Fukuda S, Hada Y, Fujii J. Successful removal of a cardiac fibroma in an elderly patient. J Cardiovasc Surg (Torino) 1990;31:55-7. Yamaguchi M, Hosokawa Y, Ohashi H, Imai M, Oshima Y, Minamiji K. Cardiac fibroma: long-term fate after excision. J THORAC CARDIOVASC SURG 1992;103:140-5. Filiatrault M, Beland MJ, Neilson KA, Paquet M. Cardiac fibroma presenting with clinically significant arrhythmias in infancy. Pediatr Cardiol 1991;12:118-20. McAllister HA Jr. Primary tumors and cysts of the heart and pericardium. Curr Probl Cardiol 1979;4:2-51. Lee YC, Singleton RT, Tang CK. Benign mesenchymal tumor of the heart: spontaneous regression and disappearance of pulmonary artery stenosis. Chest 1982;82:5035. Parmley LF, Salley RK, Williams JP, Head GB III. The clinical spectrum of cardiac fibroma with diagnostic and surgical considerations: noninvasive imaging enhances management. Ann Thorac Surg 1988;45:455-65. Burke AP, Sobin LH, Shekitka KM. Mesenteric fibromatosis. Arch Pathol Lab Med 1990;114:832-5.
Allen P. Burke, MD,a Melissa Rosado-de-Christenson, MD,b Philip A. Templeton, MD,c and Renu Virmani, MD, Washington, D.C., and Baltimore, Md.
Cardiac fibroma is a rare benign tumor of the heart that occurs primarily in infants and children. Despite a number of recent reports of single patients or small numbers of patients.I" no large series of these lesions have been published that allow a better characterization of the pathology and the clinical, radiologic, and surgical outcome of these lesions. The purpose of this study is to describe 23 previously unreported cardiac fibromas that have been pathologically documented, with emphasis on clinical findings, histologic features, and radiologic diagnOSIS. From theDepartments of Cardiovascular Pathology" and Radiologic Pathology," Armed Forces Institute of Pathology, Washington, D.C., and theDepartment of Radiology," University ofMaryland Medical System, Baltimore, Md. The opinions orassertions contained herein arethe private views ofthe authors and arenot tobeconstrued asofficial orreflecting the views oftheDepartment ofthe Army, theDepartment oftheAirForce, or the Department of Defense. Received for publication Jan. 6, 1994. Accepted for publication April 19, 1994. Address for reprints: Allen P. Burke, MD, Department ofCardiovascular Pathology, Armed Forces Institute ofPathology, Washington, D.C. 20306-6000. 12/1/57165
862
Materials and methods We retrospectively reviewed the files of the Armed Forces Instituteof Pathology for cases of fibrous tumors of the heart between 1967 and 1993. Twenty-three cases ofcardiacfibroma withpathologic materialwere identified. Thediagnosis dependedon the finding of a discrete, bulging massinoneor more ventricles or atria, which histologically wascomposed primarily of fibroblasts or collagen. Excluded from the diagnosis were tumors that contained myofibroblasts and histiocytic cells (inflammatory pseudotumors) ortumors ofendocardial location with luminal growth (papillary fibroelastoma, myxoma with fibrosis). The clinical information wasbased on material submitted at the timeofconsultation supplemented byfollow-up information requested fromthe treatinginstitution at the timeofthisstudy. Fourteen cases weresubmitted as part ofa radiologic-pathologic correlation course; for these, detailed radiologic evaluation was included with the pathologic materials. Sections of tumors were studied with hematoxylin-eosin stains and Movat's pentachrome stain for collagen, elastic tissue,and acidmucopolysaccharides. Thedegree ofcollagen and the cellularity wereestimated blindly on an arbitraryscale of I to 3+. Results Patient data. The mean age at the time of diagnosis was 13 years; the age range was 1 day to 56 years. More than one third of the patients were younger than I year
The Journal of Thoracic and Cardiovascular Surgery Volume 108, Number 5
Burke et al.
863
Fig. 1. Cardiac fibroma. The specimen is a gross heart from a 3-month-old boy who died suddenly without previous medical history. A, External surface of heart. B, Opened heart demonstrates fleshy mass replacing much of the interventricular septum and ventricular mass. .
of age at the time of diagnosis. No sex or race predominance was apparent. Clinical findings. Symptoms related to cardiac fibroma were related primarily to heart failure, arrhythmias, sudden death, and chest pain. One patient had a persistent pericardial effusion that was at first ascribed to collagen vascular disease; one patient whose tumor obstructed the pulmonary outflow had syncope; two tumors were incidental findings. Of the latter patients, one was being evaluated for multiple mandibular cysts and was noted to have multiple digits of the hands and an enlarged cardiac silhouette. A diagnosis of the Gorlin syndrome was subsequently made. The other patient with an incidental tumor was first investigated after a murmur was auscultated during a routine physical examination. Little correlation exists between the type of initial symptom and the location of the tumor in the heart. Arrhythmias were common in patients with tumors in the interventricular septum, right ventricle, and left ventricle. Patients with heart failure had large, bulky tumors in either ventricle that were difficult to excise. Although tumors in the ventricular septum were usually symptomatic, a calcified mass in the ventricular septum was first noted during coronary artery bypass grafting in a 56-year-old man. Gross findings. The site of cardiac fibroma was the ventricle or interventricular septum in 21 cases and the
right atrium in two cases. The left ventricle was more frequently involved than the right (12:8); in three cases the tumor was predominantly in the interventricular septum. The gross appearance of the tumors was typically described as fibrous, white, and whorled (Fig. 1). An exact size was available for resected or autopsy specimens. The mean size was 5 em, with a range of 2.5 to 8 em. The tumors were described at operation or autopsy as circumscribed in 10 cases and infiltrative in 13. Surgical outcome. Thirteen patients had surgical resections of cardiac fibroma; the mean age of this group was 16 years. In eight patients (Table I, mean age 12 years), simple surgical excision was done; in four of these patients (mean age 7 years), the resection was considered subtotal by the surgeon. In five patients (Table II), complex operations were performed, including patching of the myocardial defect, valve replacement, or coronary artery bypass grafting. The mean age of these patients was 22 years. Only two patients died as a result of surgical complications; one was a I-day-old infant with a large tumor, and the other was a 28-year-old patient in whom valve replacement and coronary artery bypass grafting were necessary. The other patients were well at the time ofmost recent follow-up study (Table 11). Six patients underwent biopsy without an attempt at resection (Table III). Five ofthese patients were younger
The Journal of Thoracic and Cardiovascular Surgery November 1994
8 6 4 Burke et al.
Table I. Clinical findings: Simple surgical excisions Age, race, sex
Clinical
Extent of resection
I day, W, F
Cardiac failure, cyanosis, Apgar score 5/6
Partial
4 mo, B, F
Fever, irritability, murmur as neonate, ?VSD
Partial
4 yr, W, F
Ventricular tachycardia
Partial
4 yr, L, F
Ventricular tachycardia
Total
II yr, W,M
Asymptomatic murmur
Total
II yr, B, F
Incidental murmur
Total
24 yr, W, F
Chest pain, arrhythmias
90% Total
40yr, W, M
Gross
Follow-up
Huge 4.9 em mass infiltrating RV, RVOT, RA Largely circumscribed RV multilobated 4 em mass Infiltrating 5 em LV mass Circumscribed 5 cm LV mass Infiltrating 3 cm LV mass Circumscribed 4.2 cm RV mass Anterior R V wall, 6 ern circumscribed mass LV, PV, RA circumscribed mass
Operative death
Well 4 yr
Well 4 yr Well 2 yr Well (athletic) 5 yr Weill mo Well 2 yr Well 2 yr
W, White; B, black; L, latin; F, female; M, male; VSD, ventricular septal defect; RV, right ventricle; RVOT, right ventricular outflow tract; RA, right atrium; LV, left ventricle; PV, pulmonary valve.
Table II. Clinical findings: Complex surgical resections Age, race, sex
Clinical
6 mo, W, F
Cyanosis
8 yr, W, M
28 yr, W, M
Pericardial effusion treated with aspirin, steroids Chest pain Syncope
48 yr, W, M
Palpitations
25 yr, W, F
Procedure
Gross
B-T shunt (I rno), resection and pericardia I patch (6 mo) Resection and pericardial patch
Infiltrating RA, IVC, SVC, stretched foramen ovale Circumscribed RA mass, into SVC Circumscribed 4 em mass, IVS RV mass, RVOT
Resection and Dacron patch Resection, TVR, CABG to RCA Resection and PTFE graft
Circumscribed mass, anterolateral LV, splayed CAs
Follow-up WellS mo Well 10 yr Well 3 yr Operative death Well 3 yr
W, White; F, female; M, male; B- T, Blalock-Taussig; RA, right atrium; IVC, inferior vena cava; SVC, superior vena cava; IVS, interventricular.septum; TVR, tricuspid valve replacement; CABG, coronary artery bypass graft; RCA, right coronary artery; RVOT, right ventricular outflow tract; LV, left ventricle; CAs, coronary arteries.
than 2 years old (mean age 9 months); in these cases, resection was considered impossible because of the extent of tumor at the time of the operation. Five of these six patients died as a result of surgical complications; one remained well 1 month after the operation. The sixth patient in this group was a 19-year-old man with a circumscribed tumor; in this patient, it was elected to obtain a biopsy specimen of the tumor for diagnostic purposes only and observe the patient without further surgical intervention. In four patients the diagnosis was made first at autopsy or cardiac transplantation (Table IV). Imaging data. Radiologic studies were reviewed in
nine cases, and the reports of radiologic studies were reviewed in an additional five cases (Table V). Cardiomegaly was identified in 10 radiographs. Three exhibited a focal cardiac bulge and three demonstrated focal cardiac calcification. One radiograph showed no abnormalities and one demonstrated congestive heart failure. In 11 of 12 echocardiograms, the mass was identified. Two masses were described as echogenic and three were of complex echogenicity, one with the suggestion of central cystic areas. Two unenhanced chest computed tomograms (CTs) demonstrated the cardiac mass and both identified focal
The Journal of Thoracic and Cardiovascular Surgery Volume 108, Number 5
Burke et al.
865
Table III. Clinical findings: Biopsies without resection Age, race, sex
Clinical
2 wk, A, M 8 wk, W, F
Tachypnea,acralcyano~s
6mo, W, M
Diaphoresis, murmur, mild heart failure Cardiac failure
10 mo, W, F 19 mo, W, F 19 yr, W, M
Dyspnea
Persistent cold, mild heart failure Ventricular tachycardia
Gross
Follow-up
Infiltrating RA and RV Infiltrating LV and PA, PA obstruction 2.5 em LV mass infiltrating, extending into LV cavity Infiltrating pulmonary veins LV, RA,LA Infiltrating LVFW, IVS
Weill mo Died postop.
Died postop.
Circumscribed LV near apex 6 em
Well 2 wk
Died postop. Died postop.
A, Asian; W, white; M, male; F, female; RA, right atrium; RV, right ventricle; LV, left ventricle; PA, pulmonary artery; LA, left atrium; LVFW, left ventricular free wall; IVS, interventricular septum
Table IV. Cardiac fibroma: Pathologic diagnosis made at autopsy or explantation Age. race. rex
Clinical
19 days, L, F
Sudden death, normal birth
3 mo, B, M
Sudden death, no medical history Found during investigation of Gorlin syndrome Angina, ventricular fibrillation
17yr,W,F 56 yr, W, M
Gross Circumscribed 5 em mass, LV, RV 8 ern mass infiltrating IVS, LV, RV Huge mass involving 60% of LV, bosselated Circumscribed 7 ern mass in IVS
Follow-up Not applicable Not applicable Well 2 yr after cardiac transplantation Died suddenly 2 yr after CABG; tumor noted at operation
L, Latin; B. black; W, white; F, female; M, male; LV, left ventricle; RV, right ventricle; IVS, interventricular septum; CABG, coronary artery bypass graft.
central calcifications in the lesions (Fig. 2). Three intravenous contrast-enhanced chest CT scans were available for review. Homogeneous enhancement of the tumor was seen in one case and heterogeneous enhancement in one case; in the third case the mass was not visualized prospectively. The reports of three additional CT studies (imaging technique not specified) described homogeneous masses in two and a nondiagnostic report in one. Two chest CT scans demonstrated pericardial effusions. Magnetic resonance imaging (MRI) studies were available in four cases (Figs. 3 and 4). All had Tl-weighted spin echo images and three used multiple imaging planes. The reports of two additional MRI studies (unknown imaging parameters) were also reviewed. Three masses were isointense to skeletal muscle and of homogeneous signal intensity. Two were heterogeneous and predominantly hyperintense to skeletal muscle. One study was performed after administration of intravenous gadolinium and showed heterogeneous enhancement of the lesion. Cardiac catheterization was performed in seven patients. Three patients had right heart catheterization only. In one, a pressure gradient across the right ventric-
ular outflow tract was noted, corresponding to a right ventricular mass detected on echocardiography. The second patient had a right atrial mass, and catheterization demonstrated a right-to-left shunt at the foramen ovale with severe right ventricular inflow obstruction. The third patient with right heart catheterization had a pulmonary artery injection with left ventricular follow-through that demonstrated a left ventricular mass with displacement of the intraventricular septum into the right ventricle. In four patients, right and left heart catheterization was performed. Displacement of the left anterior descending coronary artery was noted in two, and ventriculograms demonstrated a mass in the ventricle in each case. Thallium scans, performed on two patients, demonstrated photopenic defects at the tumor site. Histologic findings. The histologic appearance was essentially as previously described." However, the amount of collagen increased with age, whereas the degree of cellularity decreased with age (Table VI). Occasional mitoses were present in three cellular tumors of patients less than 5 months of age, and occasional perivascular aggregates oflymphocytes and histiocytes were observed in two
The Journal of Thoracic and Cardiovascular Surgery November 1994
8 6 6 Burke et al.
Table V. Cardiac fibroma: Radiologic findings in 14 cases CXR
2-D echocardiogram
CT/MRI
I. Cardiomegaly; calcification
Echogenic mass, pericardial effusion, mass effect RA, RY
2. Cardiomegaly 3. Initially normal; cardiomegaly
Normal Echogenic mass, RY
4. Cardiomegaly
RA mass into IYC, SYC Complex mass with cystic areas, LYFW
5. Calcified mass, RY
LY mural mass involving IYS
6. Cardiomegaly 7. Cardiomegaly
LV mass Large tumor of lateral LY wall
CT: mass with focal calcification Contrast: heterogeneous enhancement Not performed MRI (TI): homogeneous mass of RY free wall isointense to muscle Not performed CT: heterogeneous mass of LYFW, with focal calcification; heterogeneous contrast enhancement CT: nondiagnostic MRI: heterogeneous hyperintense to muscle Not performed
8. Calcification
RY mass
9. Cardiomegaly
Large posterior pericardial effusion Complex mass with mass effect
10. Cardiomegaly II. Normal
Echogenic apical mass, RY dilatation
12. Calcification
Apical LY mass
13. Cardiomegaly
Mass with mass effect
14. Abnormal cardiac contour
Not performed
MRI: heterogeneous mass compressing RYOT; hyperintense to muscle, enhances post-gadolinium image
Angiogram
Not performed
Filling defect, LY lateral wall Not performed
R-L shunt at FO, RA mass Not performed
RYOT mass, splayed CA
Posterolateral L VFW mass LYFW posterolateral mass, splayed CAs; heterogeneous decreased ventricular contractility Splayed CAs
Anterolateral LY mass CT: mass LYFW with focal calcification CT: mass distal IYS, increased attenuation MRI: mass hypointense to muscle MRI (Tl): 3.5 em mass, apical LY, hyperintense to muscle MRI (Tl): homogeneous isointense to skeletal muscle with mass effect MRI (TI) homogeneous isointense to skeletal muscle
Splaying of CAs around tumor Mass
CXR, Chest radiograph; 2-D, two-dimensional; CT, computed tomography; MRI, magnetic resonance imaging; RA, right atrium; RV, right ventricle; LV,Ieft ventricle; IVC, inferior vena cava; SVC, superior vena cava; R-L, right-to-left; FO, foramen ovale: LVFW, left ventricular free wall; IVS, interventricular septum; RVOT, right ventricular outflow tract; CA, coronary artery.
cellular tumors. Sparse chronic inflammation was present primarily at the junction of the tumor and uninvolved myocardium in seven cases. Prominent elastic fibers were present in only four cases. Calcification was present in tumors of patients of all ages but was somewhat more common in older individuals. A focal myxoid background was present in two patients.
Discussion Cardiac fibroma is considered a tumor of infancy and childhood." Although a majority of patients in this study
were younger than 10 years of age, a substantial proportion (10/23) were 10 years of age or older. The diagnosis of cardiac fibroma should be considered, therefore, even in adolescents and adults with mass lesions in the heart. The propensity for cardiac fibroma to cause arrhythmias is becoming increasingly evident.f Nine patients in this report had documented arrhythmias, had symptoms most likely related to arrhythmias, or died suddenly. This report includes a patient with cardiac fibroma and Gorlin syndrome (multiple nevoid basal cell carcinomas, jaw cysts, and bifid ribs), corroborating the association
The Journal of Thoracic and Cardiovascular Surgery Volume 108, Number 5
Burke et al.
867
Fig. 2. Newbornterm femaleinfant with respiratorydistress at birth. A, Unenhancedchest CT scan shows a large rightventricular mass (arrows) with focalcentral calcifications (arrowheads). Note the large pericardialeffusion (e). B, Contrast enhancedchest CT scan shows heterogeneous enhancement of the lesion and mass effecton the right ventricle (v) and right atrium (a).
that has been established between these two entities.' The prevalence of Gorlin syndrome in patients with cardiac fibromas may be higher than 1 in 23, because many patients were infants in whom manifestations of this syndrome may not yet have appeared. The presence of multiple neural midline defects has been described in a patient with cardiac fibroma/; no such abnormalities were present in patients in our series. The optimal treatment of children and adults with cardiac fibroma has not yet been determined, although reports of successful resection have been published.v 6, 7 In this series, surgery was successful in all but one patient
who had severe symptoms. This patient died after a complex operation that included valve replacement and coronary revascularization. Therefore, surgery appears to be the optimal treatment in patients with symptomatic resectable tumors. The role of surgery in patients with asymptomatic tumors is less clear. 5 Cardiac fibromas can remain dormant for many years and even regress.!? The only patient in our series who died suddenly and who was older than 3 months had concomitant severe coronary artery disease; therefore, the cause for the fatal arrhythmia may have been unrelated to the cardiac tumor. It may thus be reasonable to observe some symptom-free patients
The Journal of Thoracic and Cardiovascular Surgery November 1994
8 6 8 Burke et al.
Fig. 3. Previously healthy 19-year-old man in whom arrhythmias developed during a nasal septal operation. A, Coronal cardiac gated TI-weighted MR image (TR 1090jTE II) showsa round homogeneous mass (arrows) of the left ventricular apex which is isointense to skeletal muscle. The lesionis well circumscribed and causes mass effect on the left ventricle.
Table VI. Cardiac fibroma: Histologic findings Age
1 day 2 wk 1 rno 2 rna 3 rna 4 rno
6 rna 6 rna 10 rna 19 rna 4 yr 4 yr 8 yr 11 yr 11 yr 17 yr 19 yr 24 yr 25 yr 28 yr 40 yr 48 yr 56 yr
Cellularity
Collagen
3+
1+ 1+ 1+ 2+
2+
3+ 1+ 3+ 3+ 3+ 1+ 3+ 2+
2+ 1+ 1+ 1+ 1+
1+ 1+ 1+ 0 0 1+ 0 0
H-
1+ 2+ 2+
1+ 3+ 3+ 3+ 3+ 3+ 3+ 3+ 2+
4+ 4+ 4+ 4+ 4+ 4+
without risking cardiac surgery. Most symptom-free patients in our series, however, had a successful operation, one going on to competitive athletic pursuits in high school. The good surgical outcome of patients in our series
Inflammation
0 0 + 0 0 0 + + 0 0 0 + + 0 + 0 0 0 0 0 + 0 0
Elastosis
0 3+ 0 0 0 1+ 0 3+ 0 3+ 3+ 0 0 0 0 0 1+ 0 0 0 0 2+
3+
Calcification
0 +
O. + 0 0 0 0 0 0 +. + 0 0 0 0 0 0 0 0 0 + +
who were older than the age of 2 years indicates that even in symptom-free patients, tumors that are amenable to resection should probably be removed, especially if optimal cardiac function is to be preserved. Because two
The Journal of Thoracic and Cardiovascular Surgery Volume 108, Number 5
Burke et at. 8 6 9
Fig. 4. Woman, 48years old, with severe nocturnal palpitation. A,Axial cardiac gated Tl-weighted MRimage (TR 882jTE 12)shows a round focal leftventricular mass (m) that is hyperintense to skeletal muscle. B,Axial gadolinium-enhanced Tl-weighted MR image shows enhancement ofthemass. Thenonenhancing areas(arrowheads) likely correspond to the calcifications seen on the chest radiographs. infants in our series died suddenly without any previous symptoms, surgical treatment for cardiac fibroma is most likelyindicatedin this age group to avoidthe development of lethal arrhythmias. The data accumulated in this study support the previous imaging findings of cardiac fibroma.v 11 We have demonstrated that CT has a high sensitivity for the detection of intralesional calcification. MRI is an excellent modality for demonstrating the anatomic location of theselesions and the extent of the mass, which is usually isointense to hyperintense when compared with skeletal
muscle on TI -weighted spin echo images and are of homogeneous or heterogeneoussignal. Because one case in this study imaged after intravenousgadolinium administration exhibited enhancement of the mass, gadolinium may be helpful in evaluating the extent of these lesions beforethe operation. T2-weighted MR images in casesof cardiac fibroma may further characterize the fibrous nature of these tumors, because fibrous tissue characteristically has low signal intensity in T2-weighted MRI studies. Cardiac fibroma is part of the spectrum of soft tissue·
The Journal of Thoracic and
8 7 0 Burke et al.
lesions that embraces soft tissue fibromas and fibromatoses. Many of the latter tumors are considered aggressive lesions with the capacity for local invasion and growth.'? In contrast to fibromatosis, cardiac fibromas do not appear to continue to grow and proliferate after I or 2 years of age. The degree of fibrosis increases with age, and the degree of cellularity decreases with age. Surgical approach must be tailored to the individual case; however, the surgeon can, with some degree of certainty, advise the patient after the operation that the tumor is not likely to recur and that short-term and mid-term prognosis is excellent.
Cardiovascular Surgery November 1994
5. 6.
7.
8.
9. I. 2.
3.
4.
REFERENCES Coffin CM. Congenital cardiac fibroma associated with Gorlin syndrome. Pediatr PathoI1992;12:255-62. de Leon GA, Zaeri N, Donner RM, Karmazin N. Cerebral rhinocele, hydrocephalus, and cleft lip and palate in infants with cardiac fibroma. J Neural Sci 1990;99:27-36. Brown IW, McGoldrick JP, Robles A, Curelly GW, Gula G, Ross DN. Left ventricular fibroma: echocardiographic diagnosis and successful surgical excision in three cases. J Cardiovasc Surg (Torino) 1990;31:536-40. Ceithaml E, Midgley FM, Perry LW, Dullum MK. Intra-
10.
II.
12.
mural ventricular fibroma in infancy: survival after partial excision in 2 patients. Ann Thorac Surg 1990;50:471-2. Tahernia AX, Bricker JT, Ott DA. Intracardiac fibroma in an asymptomatic infant. Clin Cardiol 1990;13:506-12. Otsuka T, Asano K, Murota Y, Fukuda S, Hada Y, Fujii J. Successful removal of a cardiac fibroma in an elderly patient. J Cardiovasc Surg (Torino) 1990;31:55-7. Yamaguchi M, Hosokawa Y, Ohashi H, Imai M, Oshima Y, Minamiji K. Cardiac fibroma: long-term fate after excision. J THORAC CARDIOVASC SURG 1992;103:140-5. Filiatrault M, Beland MJ, Neilson KA, Paquet M. Cardiac fibroma presenting with clinically significant arrhythmias in infancy. Pediatr Cardiol 1991;12:118-20. McAllister HA Jr. Primary tumors and cysts of the heart and pericardium. Curr Probl Cardiol 1979;4:2-51. Lee YC, Singleton RT, Tang CK. Benign mesenchymal tumor of the heart: spontaneous regression and disappearance of pulmonary artery stenosis. Chest 1982;82:5035. Parmley LF, Salley RK, Williams JP, Head GB III. The clinical spectrum of cardiac fibroma with diagnostic and surgical considerations: noninvasive imaging enhances management. Ann Thorac Surg 1988;45:455-65. Burke AP, Sobin LH, Shekitka KM. Mesenteric fibromatosis. Arch Pathol Lab Med 1990;114:832-5.