Download Papillary fibroelastoma of the pulmonary valve

Rom J Morphol Embryol 2014, 55(2):463–467
CASE REPORT
RJME
Romanian Journal of
Morphology & Embryology
http://www.rjme.ro/
Papillary fibroelastoma of the pulmonary valve: a case report
ADRIAN MOLNAR1), SVETLANA ENCICĂ2), EMESE KOVÁCS3), SIMONA MANOLE4), DIANA SĂCUI1),
IOAN MUREŞAN1), TRAIAN SCRIDON1)
1)
Clinic of Cardiovascular Surgery, “Niculae Stăncioiu” Heart Institute, Cluj-Napoca, Romania
2)
Department of Pathology, “Niculae Stăncioiu” Heart Institute, Cluj-Napoca, Romania
3)
Clinic of Cardiology, “Niculae Stăncioiu” Heart Institute, Cluj-Napoca, Romania
4)
Clinic of Radiology, Emergency County Hospital, Cluj-Napoca, Romania
Abstract
Papillary fibroelastoma is a rare, benign cardiac tumor typically found on the heart valves, which is usually discovered incidentally on
echocardiography. The clinical presentation of cardiac papillary fibroelastoma varies from no symptoms to severe embolic sequelae. We
report the case of a 55-year-old female patient, with a suspicion of pulmonary embolism one year before, presently admitted to the hospital
for mild respiratory symptoms; the trans-esophageal echocardiography (TEE) revealed a 10/10 mm tumoral mass attached on the pulmonary
valve, confirmed also by the contrast-enhanced magnetic resonance imaging (MRI). Considering the embolization risk, we decided surgical
removal, with favorable outcome. The pathologic exam of the removed tumor established the diagnosis of papillary fibroelastoma. The clinical
and imaging assessment one month after surgery were within normal limits. The surgical removal of the papillary fibroelastoma of the pulmonary
valve is mandatory for the elimination of embolization risk. The intervention is relatively secure, with low rates of morbidity and mortality.
Keywords: papillary fibroelastoma, pulmonary valve, echocardiography, cardiac magnetic resonance.
 Introduction
Primary tumors of the heart are rare, ranging from
0.002% to 0.02% in prevalence, according to large
autopsy series.
Papillary fibroelastoma is the third most common
primary cardiac tumor (after myxoma and lipoma),
accounting for 7% to 9% of benign primary tumors [1, 2].
It usually involves the aortic or mitral valve, and less
frequently the pulmonary or tricuspid valve; fibroelastoma
can also develop from the papillary muscles, chordae
tendineae, ventricular septum, or endocardial surface.
Men and persons older than 40-year-old are chief among
those who are diagnosed with papillary fibroelastoma;
however, this tumor has also been described in neonates
with congenital cardiac abnormalities [1].
In some surgical series, papillary fibroelastoma was
classified as the second benign tumor of the heart in
order of incidence. Even if it can be found anywhere on
the endocardium surface, it is most frequent location
is on the cardiac valves, usually on the aortic valves;
the localization on the pulmonary valve is rare, in the
literature being described in 13% of cases [3].
As described in some studies, most of them arise in
the left heart, and the vast majority are clinically silent;
though occasionally such lesions when on the aortic
valve may produce symptoms of myocardial or cerebral
ischemia. None has been known to cause symptoms when
in the right side of the heart [4].
Most patients with this tumor are asymptomatic.
Clinical presentation varies, depending upon which side
of the heart is involved. Right-side papillary fibroelastomas are asymptomatic and rarely cause pulmonary
embolism [1].
ISSN (print) 1220–0522
We present a rare case of pulmonary valve tumor in
an adult patient, with good results after surgical removal.
 Patient, Methods and Results
A 55-year-old woman was admitted to the hospital
for frequent episodes of mild dyspnea and reduced
compliance to moderate physical activity. A year ago,
she was clinically diagnosed with pulmonary thromboembolism, and accordingly treated with oral anticoagulants; however, this diagnosis was afterwards infirmed by
the thoracic CT-angiography. The patient had a medical
history of stage III hypertension, and dyslipidemia; also,
she presented a first grade obesity, with a body mass index
(BMI) of 32.5 kg/m2. Due to persistence of respiratory
symptoms, the decision for further investigation was
taken.
The trans-thoracic echocardiography (TTE) showed
no pathologic changes, but the trans-esophageal echocardiography (TEE) revealed a 10/10 mm hyperechogenic
mass attached on the ventricular side of pulmonary valve,
on the aortic adjacent cusp, prolapsing in the RVOT
(right ventricular outflow tract), but not interfering with
the valve function (pulmonary valve without stenosis
and with first grade regurgitation) (Figures 1 and 2).
These findings leaded to the recommendation to
perform a cardiac magnetic resonance, in order to
improve both the structural and functional diagnosis.
The contrast-enhanced MRI showed a well-described,
polylobate, hypercaptant tumoral lesion on the right
anterior pulmonary cusp, without pulmonary stenosis or
regurgitation, and without alteration of cardiac function
(Figures 3–6).
ISSN (on-line) 2066–8279
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At this point, considering the embolization risk, the
indication for surgical removal of the tumor was
established. We performed the excision of the entire mass
after opening the pulmonary artery trunk; the procedure
required 35 minutes of cardiopulmonary bypass, and
aortic cross-clamping for 25 minutes (Figures 7 and 8).
Following tumor removal, the pulmonary valve function
and structure remained unaffected.
After surgery, the patient was hemodinamically stable
with minimal inotropic support, interrupted 24-hours postoperatively. The control trans-thoracic echocardiography
revealed a systolic pressure in the pulmonary artery of
35–40 mmHg, with a vmax of 2.3 m/s. The patient was
discharged nine days later, with an uncomplicated postoperative course.
At the pathologic exam, the removed mass had the
characteristics of a papillary fibroelastoma. Macroscopically, the tumor resembled a sea anemone when viewed
under water (Figure 9). It was whitish, it measured 1.5/
1.0/0.5 cm outside the water, and it was attached to the
endocardial surface by a single, thin pedicle.
The mass was fixed in 10% formalin, embedded in
paraffin and cut serially into cross-sections (5 μm thick).
Sections were stained with Hematoxylin–Eosin,
Masson’s trichrome and Taenzer–Unna Orcein.
Immunohistochemmistry was performed in paraffinfixed tumor sections using LSAB DAKO system. Endogenous peroxidase was blocked with H2O2 3%. Immunohistochemical staining for CD31, CD34 and vimentin
were made with DAKO primary monoclonal antibodies
in dilution 1/20 for CD31, 1/50 for CD34 and 1/100 for
vimentin (clone 9). Finally, the tissues sections were
reacted with 3,3’-diaminobenzidine and counterstained
with Hematoxylin.
Microscopic aspect of the papillary fibroelastoma
is characterized by numerous branches, with a dense
collagen core surrounded by a myxoid mantle (Figure 10a).
The Masson’s trichrome stain (Figure 10b) and Taenzer–
Unna Orcein stain (Figure 10c) showed some fragmentary
elastic fibers and collagen fibers; each branch had CD31positive endothelial cells on the surface (Figure 10d).
On routine follow-up 30-days after discharge, the
ECG and thoracic X-ray were within normal limits, and
the trans-thoracic echocardiography showed no signs of
pulmonary valve dysfunction (Figure 11).
Figure 1 – Trans-esophageal echocardiography in long axis view at
1400 showing a mobile echogenic
mass in the right ventricle.
Figure 2 – Trans-esophageal echocardiography in the mid-esophageal view of
right ventricular outflow at 1030 showing
that the echogenic mass is attached to the
right leaflet of the pulmonary valve, on
its ventricular side. The mass measures
10×10 mm in diameter and is mobile – it
prolapses in the right ventricular outflow
tract, but it does not interfere with the
function of the pulmonary valve (no
evidence of pulmonary regurgitation or
stenosis was found).
Figure 3 – Cardiac MR. HASTE
axial sequence showing nodular
tumoral structure with a diameter
of 7 mm attached to the pulmonary
valve, in the intermediate segment
T1.
Figure 4 – Cardiac MR. Tru-FISP
axial sequence at the pulmonary
valve level showing the attachment
of the nodular structure to the
pulmonary valve.
Figure 5 – Cardiac MR. PSIR T1
axial sequence post-contrast.
Figure 6 – Cardiac MR. Tru-FISP
sagittal sequence at the level of
pulmonary artery trunk.
Papillary fibroelastoma of the pulmonary valve: a case report
Figure 7 – Intra-operative image
showing the location and aspect
of the tumor.
Figure 8 – Tumor aspect and dimensions, after surgical removal.
465
Figure 9 – Macroscopic aspect of the
tumoral mass, which resembled a sea
anemone when viewed under water.
Figure 10 – Microscopic aspect of the papillary fibroelastoma – a bundle of avascular branches, covered by endocardial
tissue, and containing a collagen core, rich in proteoglycans and elastic fibers: (a) Dense core surface lining endothelial
cells (arrows), HE staining, ×100; (b) Dense collagen lining with endothelial cells (arrows): dense core collagen branches
with myxoid mantle on surface with endothelial cells, Masson’s trichrome staining, ×100; (c) Multiple fronds with
fragmented elastin fibrils (arrows), Taenzer–Unna Orcein staining, ×100; (d) Endothelial cells (arrows), CD31 immunohistochemical staining, ×200.
Figure 11 – Postoperative transthoracic echocardiography: in
the parasternal
short axis view,
at the level of the
aortic valve, no
pulmonary valve
dysfunction was
found.
 Discussion
Papillary fibroelastomas are benign endocardial
papillomas that mainly affect the cardiac valves and
account for approximately 75% of all cardiac valvular
tumors [5]. A papillary fibroelastoma situated at the
level of a cardiac valve is a serious condition that may
ultimately determine emboli formation followed by
subsequent migration in any body segment; particularly
from the pulmonary valve, these emboli can migrate into
the lungs, with serious consequences for vital functions.
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Adrian Molnar et al.
Therefore, any of these intracardiac papillary fibroelastomas should be resected by urgent indication [6].
The majority (over 55%) of papillary fibroelastomas
are diagnosed at an average age of 60 years [7], ranging
between 6 and 92 years [3]. They can be situated anywhere
on the endocardium, and rarely there are multiple sites
of the tumor [8]. Most frequently papillary fibroelastomas
are found on the cardiac valves (90%), mainly on the aortic
valve (29% of cases) and mitral valve (25% of cases), as
shown by some studies; other unusual localizations are
the tricuspid valve (17% of cases) and pulmonary valve
(13% of cases) [3]. Usually (69.5% of the patients), the
tumor appears on affected valves: rheumatic disease and
calcific fibrosis are documented in 37.8% and 62.2% of
cases, respectively. Beside cardiac valves, papillary fibroelastoma can be found on rete Chiari, coronary ostia, and
the atrial or ventricular free wall. They are attached by a
single pedicle (rarely by multiple pedicles) on the surface
endocardium, and their dimensions range between 2 and
50 mm, usually being smaller than 10 mm [9].
Histogenesis
The tumor resembles to Lambl excrescences, but it
is quite different. The Lambl excrescences appear at
advanced age, on the semilunar valves at the Arantius
nodules level, on the valve closing line and the free
edges of the valve cusps; on the atrio-ventricular valves,
they are situated on the atrial surface of the closing line.
The Arantius nodules are also age-dependent and appear
as thick masses situated in the centre of the semilunar
valves, at the closing line and free edge junction, in
contrast to papillary fibroelastomas, which are localized at
greater distance from the valve closing line. Also, unlike
Lambl excrescences, papillary fibroelastoma can reach
bigger dimensions, and can be found on any valve surfaces
or in any endocardial tissue. The average dimensions are
of approximately 1 cm, but there are reports of papillary
fibroelastomas with a diameter of 5 cm [10].
In time, it was developed the idea that papillary fibroelastomas are organized thrombi, due to their contents
of fibrin, hyaluronic acid, and elastic fibers; however,
their localization in areas with low hemodynamic stress
leaded to abstention from the organized thrombi theory
[10].
The histological aspect that suggests a proliferation
of miniature chordae tendinea, and the existence of
possible congenital cases with the onset if symptoms at a
young age, leaded to the formulation of hamartomatous
theory.
A recent study [9] showing the presence of dendritic
cells and of the cytomegalovirus in the intermediate
structures in some papillary fibroelastomas, suggested
the idea of a possible connection between these tumors
and chronic viral endocarditis.
The repeated hemodynamic trauma can contribute to
papillary fibroelastoma appearance, as shown in some
studies that correlate the tumor with rheumatic valve
disease, hypertrophic cardiomyopathy, or the mitral valve
prolapse.
As described by some studies [7], the endocardium
seems to react to the flow stress or congenital factors in
a unique way. At least a subset of these tumors (18%)
develops in relation with iatrogenic factors as radiation
therapy, or open-heart surgery; the relationship with these
conditions determined the concept that papillary fibroelastoma can be a reactive degenerative process, but the
histogenesis remains still unclear. Unlike sporadic cases
of papillary fibroelastoma, the iatrogenic tumors are
usually multiple and seem to appear outside the cardiac
valves, close to the predisposing factor (e.g., near the
incised chamber).
Structurally, the tumor seems to contain elastic fibers
more prominent in the core and rare or even absent in
the distal part of the papillae; the mantle is made up of
lax tisuue composed by hyaluronic acid, proteoglycans,
smooth muscle cells, dendritic cells, and fibroblasts [9].
The expression of vimentin, CD34 and CD31 in the
tumoral endothelium cells is lower than in the normal
cardiac endothelium. Into the dense core, the type IV
collagen is positive [7, 9]. The endothelial cells that cover
the papillary branches are in continuity with endocardial
endothelial cells. The structure of papillary branches is
microscopically similar to chordae tendinea [7]. This
reduced expression of endothelial markers is thought to
be linked to a trauma or an endothelial dysfunction; also,
the presence of acute or chronic thrombosis can modify
the macroscopic aspect of the tumor. Usually, the vast
majority (80–90%) of papillary fibroelastomas are unique,
but the ones linked to iatrogen conditions can be multiple,
varying between two and 40 in the literature [9].
The confusion over the pathogenesis of papillary
tumors of valves is reflected in the number of names,
which they have been given [10–12]: myxofibroma,
papilloma, papillary fibroma, hamartoma, fibro-angiomyxoma and hemangio-elastomyxoma. Accordingly, the
surgical removal of these masses should be performed
as soon as possible.
The differential diagnosis [11] should be made with
cardiac myxoma, Lambl excrescences, infectious endocarditis vegetations, and marantic endocarditis.
Papillary ‘tumors’ arise most often on the left side of
the heart, frequently in association with hypertension,
but have been observed on all valves. They are usually
asymptomatic incidental findings at post mortem or,
increasingly often, at cardiac surgery [10–13]. Rarely,
when on the aortic valve they may cause angina by
occluding the coronary ostia. Emboli into the coronary
arteries and cerebral arteries have also been described
[5, 14].
Cardiac tumors can present a significant diagnostic
challenge causing symptoms and signs that mimic other
cardiac diseases. Main symptoms include breathlessness,
fever, weight loss, syncope, hemoptysis, and sudden death.
Cardiac tumors may also cause embolization, arrhythmias
(atrioventricular block and ventricular tachycardia), or
obstruction of the outflow tracts. Diagnosis depends on
a high index of suspicion and can almost always be
made by echocardiography [12, 15–18]. In the detection
of papillary fibroelastoma, the sensitivity and specificity
of TTE are 88.9% and 87.8%, respectively, when the
tumor is larger than 2 mm. However, when the tumor is
smaller, the overall sensitivity of TTE is only 61.9%,
compared with 76.6% for TEE. Newer imaging techniques,
such as contrast echocardiography, can help to better
Papillary fibroelastoma of the pulmonary valve: a case report
delineate cardiac masses [1, 12, 14]. Over the last 10
years, the development of newer pulse sequences and
applications in new clinical areas has enabled cardiovascular magnetic resonance (CMR) to emerge as a
powerful tool for the physician to both diagnose and
guide treatment of various cardiac pathologies [13].
In our patient, the symptoms were non-specific and
mild, and the trans-thoracic echocardiography was nonconclusive, therefore more sensitive and specific tests
were necessary in order to establish the correct diagnosis.
The trans-esophageal echocardiography managed the
primary diagnosis of the existence of the tumoral mass
at the level of pulmonary valve, whereas the cardiac
MR was helpful in the tumoral mass characterization
(dimensions, localization, delimitation, mobility, vascularization), and cardiac function evaluation; however, the
final diagnosis was made only by the pathologic exam
of the resected tumor.
Papillary fibroelastomas are treated curatively by
surgery, whether there are preexisting embolic symptoms
or a lesion is incidentally discovered [12]. Depending
on the intraoperative findings, the resection of the tumor
should be sufficient if the cardiac valve is unaffected (as
happened in the reported case), but in the case of altered
function, the valve replacement should be considered.
Benign tumors normally carry a good prognosis with
normal life expectancy after resection. Patients who have
had benign tumors resected are usually followed up with
regular echocardiography and cardiologic supervision
[12]. Re-growth of the tumor after resection has not been
reported, and it requires long-term TEE follow-up studies
to confirm [14].
 Conclusions
We consider that surgical removal of the papillary
fibroelastoma of the pulmonary valve is mandatory in
order to prevent the embolization risk. The intervention
is relatively secure, with low rates of morbidity and
mortality.
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Corresponding author
Adrian Molnar, Assistant Professor, MD, Clinic of Cardiovascular Surgery, “Niculae Stăncioiu” Heart Institute, 19–
21 Moţilor Street, 400001 Cluj-Napoca, Romania; Phone +40264–591 941/220, e-mail: [email protected]
Received: December 14, 2013
Accepted: April 23, 2014