Fibroelastic papilloma: A not-so-benign cardiac tumor

Cadiovasc

Pathol Vol.

April-June

1992:161-I66

I. No. 2 I61

Fibroelastic Papilloma: A Not-so-Benign Cardiac Tumor Marialuisa

Valente,*

Cristina

Basso,’ Gaetano

Patrizia

Cocco,*

Thiene,*

and Giuseppe

Marta

Bressan,+

Paolo

Stritoni,+

Fasoli’

Departments of *Pathology and ‘Cardiology, University of Padua Medical School, Padua, Italy

Six fibroelastic papillomas, ranging in size from 2 to 17 mm, were diagnosed among 106 benign cardiac tumors observed at our institute since 1970. Two were incidental autopsy findings, and involved the pulmonary and aortic semilunar valves, respectively; four were surgically removed specimens from the left side of the heart. Clinical diagnosis was achieved in two young subjects, aged 25 and 3 1 years, by 2D-echo examination, following an episode of acute myocardial infarction precipitated during a soccer game; the tumor was related to the mitral valve apparatus in both cases, and a coronary embolism, either neoplastic or thrombotic, was the most likely cause of myocardial infarction. Thus, cardiac left-side fibroelastic papilloma should be considered a potentially lifethreatening tumor in hemodynamic terms. Like myxoma, this tumor entails the risk of systemic embolism that may also occur in the coronary arterial tree, precipitating myocardial infarction and sudden cardiac arrest,

Fibroelastic papilloma, a small intracavitary endocardial tumor also known as papillary fibroelastoma, has long been considered an incidental autopsy finding. In his necropsy review on heart tumors in 1951, Pritchard (1) listed 28 fibroelastic papillomas, none of which had given signs during life. More recently, however, symptomatic cases have been detected in vivo by cardiac imaging techniques, thus enabling surgical removal of the tumor (2-16). Moreover, the albeit rare occurrence of embolization has also been recognized (3,8,1O-13,15,17-19). In a series of 114 primary heart tumors, part of which was previously reported (20,21), we diagnosed 6 cases of fibroelastic papilloma. Four specimens had been obtained at surgery, and in two of these cases, the abrupt and lifethreatening clinical onset was due to coronary embolism.

Materials and Methods Since 1970, 114 primary cardiac tumors from 112 patients were studied at this Institute; 106 were benign lesions (82

Manuscript received August 8, 1991; accepted November 15, 1991. Address for reprints: Marialuisa Valente, MD, Istituto di Anatomia Patologica, Via A. Gabelli, 61, I-35121 Padova, Italy.

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by Elsevier

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Inc.

myxomas, 7 pericardial cysts, 6 fibroelastic papillomas, 3 fibromas, 2 giant hematic cysts, 2 celotheliomas, 1 pericardial teratoma, 1 rhabdomyoma, 1 hamartoma, 1 lipoma), and 8 were malignant (2 “myxosarcomas,” 3 pericardial mesotheliomas, 1 fibrosarcoma, 1 angiosarcoma, 1 rhabdomyosarcoma). Of 114, 98 (85%) were surgical specimens, and consisted of 91 benign and 7 malignant tumors. Thus, in our experience, 6% of all benign cardiac tumors were fibroelastic papillomas, and these were found in five patients, four males and one female, ranging in age from 25 to 83 years (mean, 53) (Table 1). Two tumors were casually found during postmortem investigation. In these cases (nos. 1 and 2), aged 77 and 83 years, death was due to ruptured abdominal aortic aneurysm and lung carcinoma, and the tumors were found on the ventricular surface of the semilunar pulmonary and aortic noncoronary cusps, respectively. The other four tumors were surgical specimens. A 49year-old patient (no. 3) had two fibroelastic papillomas, one on the left side of the ventricular septum and the other on the mural leaflet of the mitral valve. These lesions were casual 2D-echographic and intraoperative findings, respectively, during clinical evaluation and subsequent prosthetic replacement of a prolapsing mitral valve with chordal rupture. Tumors were detected in patients 4 and 5, aged 3 1 and 25 years, 10%8807/92/$5.00

VALENTE

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PAPILLOMA

Table 1. Tumor-related Symptoms and Patient 1

Age, Sex II

M

Diagnosis

Circumstances

Surgery

Casual at autopsy*

Location Pulmonary valve

Size (mm) 10 x 8 x 4 Pedicle

2

83 F

-

Casual at autopsy*

Aortic valve, noncoronary cusp

3

49 M

(a) Casual during

Tumor excision

Ventricular septum

ZD-echo Mitral valve replacement

Mitral valve, mural leaflet

surgery 31 M

ZD-echo and angle

25

M

2D-echo and angio

Myocardial

infarction

Tumor excision

Myocardial

infarction

Tumor exclaion

during soccer game

*Cause

of death: ruptured aortic aneurysm (patient no.

I ) and

2X2X3

Mitral valve. anterior

17 x

papillary muscle

Pedicle

Mitral valve. anterior leaflet

10 x

I6 x

I.5

IO x 3

Sessile

lung carcinoma (patient no. 2)

respectively during 2D-echo evaluation following an episode of ECG and enzymatic proven acute myocardial infarction precipitated by effort during a soccer game (Fig. 1); thrombolysis was attempted in patient 5. The fibroelastic papillomas were located at the base of the anterior papillary muscle of the mitral valve in patient 4 (Fig. 2), and on the

Figure 1. Patient no. 4. A Normal ECG recorded 5 years before the episode of acute myocardial infarction. B ECG recorded 14 days after the acute event; note the Q waves in L2, L3, and aVF

with inverted T waves.

is x 8 x 4

Sessile

during soccer game 5

Pedicle

Sessile

(b) Casual during

4

5X5X3

anterior leaflet of the mitral valve in patient 5 (Fig. 3). Two months after the acute episode, angiocardiographic examination detected a localized hypokinesia of the left ventricle, thus confirming the myocardial infarction; a filling defect within the left ventricular cavity was only seen in patient 4 (Fig. 2B). The major coronary trunks appeared patent at selective coronary angiography, and tumor was successfully excised in both cases. The tumors were photographed. Formalin-fixed tissues were paraffin-embedded, and 5-pm-thick sections were stained according to the hematoxlyin-eosin, Alcian pas,

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VALENTE ET AL. FIBROELASTIC PAPILLOMA

163

D

C

Azan, and Weigert-Van Gieson procedures. Small blocks of tumor from two cases were also immediately fixed in 2% glutaraldehyde, and processed for transmission and scanning electron microscopy (SEM) study.

Figure 2. Patient no. 4. A 2D-echo apical four chamber view shows a round mass attached to the anterior papillary muscle of the mitral valve (arrow). B Left ventricular angiogram shows an intracavitary filling defect (arrows) in the antero-lateral wall. C The gross appearance of the excised mass with short pedicle. D At histology, note the fronds branching out from the stalk. Weigert-Van Gieson X 6.

lary core. Thrombus

Results The size of the tumors ranged from 2 x 2 x 4 mm to 17 x 16 x 15 mm (Table 1); three were sessile, and three had a short pedicle (Fig. 2C). At gross examination, all six were white, gelatinous, finely villous masses. Histologic study revealed multiple fronds branching out from the collagen stalk or pedicle, consisting of a fibroelastic core surrounded by a myxoid Alcian-positive substance in which a few elongated cells were scattered [Figs. 2(D) and 3(B)]. Each frond was covered by endothelial lining [Fig. 3(B)]; no vascular structures were present in the papil-

or fibrin lining was never detected on the tumor surface. SEM showed that the papillae had a variable thickness, and were covered by endothelial cells, most of which exhibited microvilli (Fig. 4). Ultrastructural studies demonstrated that the endothelial cells lining the papillae had oval, at times irregularly indented nuclei. The cytoplasm was particularly rich in randomly oriented, intermediate filaments (10 pm thick), and showed occasional pinocytotic vesicles and a few microvilli (Fig. 5); basement membrane was frequent. A few interstitial cells in the papillary stroma were both elongated and stellate-shaped (Fig. 6A); like the lining cells, these were

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VALENTE ET AL. FIBROELASTIC PAPILLOMA

Figure 3. Patient no. 5. A 2D-echo long axis parastemal view: note a small sessile mass attached to the anterior leaflet of the mitral valve. B Histology shows fibroelastic, myxoid fronds covered by endothelial cells. Azan X 75.

rich in intermediate filaments, and occasionally contained rough endoplasmic reticulum. These cells were enmeshed in a finely granular material, and at times appeared in close relationship to collagen bundles. The collagen fibrils were regularly banded, variably oriented, and scattered among the elastic fibers (Fig. 6B).

Figure 4. Patient no. 5. Scanning electron microscopy of the papillary surface shows a continuous lining of endothelial cells, some of which exhibit microvilli. x 1.500.

Discussion Fibroelastic papilloma is generally believed to be a benign lesion, even when it is located in the left side of the heart. Indeed, unlike myxoma, it never reaches a size that causes obstruction. Moreover, its consistency differs from that of friable villous myxoma. In fact, at the light and electron microscope, we and others (2,22) observed a conspicuous amount of collagen and elastic fibers; this finding explains the fii consistency of the papillae and why their fragmentation and embolization is considered unlikely. A fibroelastic papilloma located in the coronary aortic cusp is an exception to this rule, as it may prolapse and abruptly occlude the coronary ostia, leading to cardiac arrest and sudden death (23). Nonetheless, a review of the literature of the last three decades (Table 2) disclosed cases of neurologic defects,

Figure 5. Patient no. 5. At the transmission electron microscope, an endothelial cell on the papillary surface shows an elongated nucleus, a remarkable amount of randomly oriented, intermediate filaments, and cytoplasmic short fingerlike projections. X 16,000.

Cardiovasc Pathol Vol. I. No. 2

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April-June 1992:161-166

Figure 6. Patient no. 5. A A stellate-shaped cell in the core of the tumor, full of intermediate filaments, and enmeshed in a low electron dense ground substance in which both collagen and elastic fibers are interspersed. X 8,000. B Close-up of the stroma, with scattered collagen and elastic fibers enmeshed within the groundsubstance. x 18,000.

strokes, angina, myocardial infarction, and sudden death in which autopsy or in vivo 2D-echo findings of fibroelastic papillomas in the left heart constituted the most plausible explanation for the clinical picture through systemic embolization or coronary ostial obstruction (3,4,6-8,1&13,1519,23-26). Our two young patients (nos. 4 and 5) had experienced overt myocardial infarction, and a fibroelastic papilloma was found attached to the mitral valve apparatus. In both cases, the episode had been precipitated by effort during a soccer match. Because the major coronary arteries of both patients were angiographically patent 2 months after this event, we postulate the presence of an angiographically un-

detectable neoplastic microembolization of the coronary arterial tree, or an embolism from a superimposed thrombosis, with subsequent spontaneous or pharmacologic lysis. Indeed, although the embolism source in patients with symptomatic fibroelasic papillomas seems to be the tumor itself, a neoplastic embolic character was demonstrated only in a

Table 2. Case No.

Reference

Age, Sex

Circumstances

Tumor Location

1 2 3 4 5 6 7 8 9 10 II 12 13 14 15 16 17 18 19 20 21 22

24 25 17 18 23 26 3 4 6 7 7 8 10 11 12 12 19 13 1.5 16 Present report Present report

45 F 67 M 62 M 64M 50 M 77 F 35 M 41 M 71 F 61 M 66 M 24 M 27 M 41 M 43 F 52 F 9F 39 M 77 F 50 F 31 M 25 M

Angina pectoris Angina, AM1 Sudden death Stroke AMI Renal infarction Stroke, AM1 Angina pectoris TIA AMI AMI Stroke Stroke TIA TIA Stroke Angina pectoris Angina pectoris Stroke AM1 AM1 AM1

Aortic valve Aortic valve Aortic valve Papillary muscle Aortic valve Aortic valve Mitral valve Aortic valve Posterior LV free wall Aortic valve Aortic valve Mitral valve Mitral valve Mitral valve Mitral valve Mitral valve Mitral valve Mitral valve Mitral valve Aortic valve LV papillary muscle Mitral valve

Abbreviations:

AMI, acute myocardial

infarction;

165

TIA, transient ischemic attack.

Diagnosis Autopsy Autopsy Autopsy Autopsy Autopsy 2D-echo 2D-echo 2D-echo 2D-echo Autopsy Autopsy ZD-echo ZD-echo ZD-echo 2D-echo 2D-echo Autopsy 2D-echo 2D-echo Angiocardiography 2D-echo ZD-echo

166

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PAPILLOMA

single case (17). Descriptions of fibrin or thrombotic deposition on the fibroelastic papilloma surface, probably as a consequence of blood flow trauma, and endothelial damage and detachment (3), instead suggest the potential thrombotic nature of the emboli. Notwithstanding the neoplastic or thrombotic nature of the embolization, we are now aware that even a small fibroelastic papilloma may precipitate embolic events that may be catastrophic when they occur in the systemic circulation. This issue is not purely academic, as fibroelastic papilloma may be detected in vivo by means of 2D_echocardiography, and open-heart surgery may be performed with very little risk, even in elderly patients. In view of the potential risk of thrombotic superimposition, anticoagulant therapy was suggested (10). Although this approach may be appropriate, not only while the patient is on the waiting list for surgery, but also if intervention is contraindicated for various reasons, we did not find gross or histologic evidence of thrombous formation on any tumor surface. Myocardial infarction occurred in two young subjects during a soccer game, thus showing that effort may precipitate an embolic event; athletic activity, therefore, is strictly contraindicated. In conclusion, a fibroelastic papilloma located in the left side of the heart must be considered a potentially life-threatening tumor in a hemodynamic sense, because, like myxoma, it entails the risk of fatal complications through systemic embolism. This work was supported by Ministery of Education, 40% Funds, and by National Council for Research, Target Project FAT.MA., Rome, Italy.

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