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Cardiac Metastasis From Uveal Melanoma
Arch Ophthalmol. 2001;119:139-140.
Ruiz and coworkers1 recently described
an elderly woman who developed cardiac metastasis from choroidal melanoma
and died of a ruptured myocardium. Because of a scarcity of other reports,
they concluded that cardiac metastasis from uveal melanoma was extremely rare,
perhaps with the exception of patients with widespread micrometastases that
might go undetected without autopsy.1 In
our experience, macroscopically detectable metastasis from uveal melanoma
to the heart is not uncommon, although it is true that it has seldom been
reported in the literature. We are aware of 4 reports of cardiac metastasis
from uveal melanoma in 14 patients.1-4
A fifth article mentions 2 patients with cardiac metastasis from an ocular
primary melanoma, but it does not specify whether the primary site was the
uvea or conjunctiva.5 The purpose of the
present report is to describe 5 patients with cardiac metastasis and to estimate
the frequency of metastasis to the heart from uveal melanoma.
Report of Cases
To get a reliable estimate of the spectrum and frequency of cardiac
metastasis, we reviewed clinical and autopsy data of a consecutive series
of 167 patients who had an eye enucleated between 1972 and 1981 because of
a choroidal or ciliary body melanoma.6 These
patients have complete, validated follow-up data. By December 1999, tumors
had disseminated in 80 patients (48%). Autopsy had been performed on 27 (34%)
of these 80 patients, who all died of disseminated uveal melanoma. Sites of
metastases that were identified clinically or by macroscopic examination at
autopsy were recorded. Metastases that were detected only incidentally by
microscopy, including 1 in the heart, were disregarded. Statistical analysis
was based on exact probability distributions (StatXact-3; Cytel Software,
Cambridge, Mass).
Five patients (Table 1)
had cardiac metastases, all of which were clinically asymptomatic. Macroscopic
autopsy reports gave the following descriptions: Case 1. Three pigmented metastases in the left ventricular wall. Case 2. Multiple pigmented metastases 2 to 3 mm in diameter in the
left ventricular epicardium and myocardium, and a subendocardial metastasis
2 mm in diameter in the anterior papillary muscle. Case
3. Multiple, small metastases in the pericardium, epicardium, and myocardium
(Figure 1) in the apex of the heart. Case 4. One pigmented myocardial metastasis 1 cm in diameter
in the posterior wall of the heart, together with several endo- and pericardial
metastases 2 to 3 mm in diameter. Case 5. A solitary
metastasis in the epicardium.
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Clinical Characteristics of 5 Patients With Malignant Uveal Melanoma*
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Figure 1. Epithelioid melanoma cells infiltrate
within the myocardium (A) diffusely (hematoxylin-eosin, original magnification
x225) and (B) as small nodules (hematoxylin-eosin, original magnification
x360) (case 3).
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The frequency of cardiac metastasis at autopsy was 19% (5 of 27 cases)
(95% confidence interval [CI], 6%-38%). This finding is essentially identical
to that of a 1963 population-based Danish study, which reported pericardial
and myocardial metastases in 9 (24%) of 38 patients who were autopsied (95%
CI, 11%-40%).2 The frequency of cardiac
metastasis in the entire series of 167 patients who had an eye enucleated
was thus 3.0% (95% CI, 1%-7%), and the frequency of symptomatic cardiac metastasis
was 0% (95% CI, 0%-2%). We recognize the limitations of our study in that
the autopsy rate was not high and patients were not selected for autopsy at
random. Autopsies were done on an individual basis according to the preference
of the attending physician and the relatives of the deceased.
Retrospective evidence did not suggest any obvious bias regarding selection
of patients for autopsy. Of the 27 patients who underwent autopsy, 5 were
autopsied without suspicion of metastasis, which argues against selection
for autopsy of patients with known widespread dissemination. Furthermore,
no difference between autopsied and nonautopsied patients who died of disseminated
uveal melanoma was observed in the age at enucleation (P = .25, Mann-Whitney test), the presence of metastatic symptoms (P = .16, Pearson  2 test), or the time from
enucleation to the onset of symptoms and signs of metastatic disease (P = .96, log-rank test). Comparison of the number of clinically
known metastases at the time of death between autopsied and nonautopsied patients
indicated no statistically significant difference between groups (mean, 1.3
vs 1.7, respectively; P = .18, Mann-Whitney test).
Presence of cardiac metastasis was statistically significantly associated
with a large number of macroscopic metastatic sites detected at autopsy (Figure 2) (P<.001,
Pearson 2 test). None (95% CI, 0%-17%) of the 20 patients
who had 3 or fewer metastatic sites had cardiac metastases, whereas 5 (71%;
95% CI, 29%-96%) of 7 patients with 4 or more metastatic sites had cardiac
metastases. Presence of cardiac metastases among the 80 patients who died
of disseminated uveal melanoma was not associated with the age at diagnosis
of uveal melanoma (P = .47, Mann-Whitney test) or
with the time from enucleation to death (P = .82,
log-rank test).
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Figure 2. Number of macroscopic metastatic
sites detected in 27 autopsied patients with metastatic uveal melanoma. Except
for one patient with cerebral metastasis, 10 of the 11 patients who had only
one metastatic site had hepatic metastases. The 5 patients who had cardiac
metastases had a higher number of metastatic sites than those who did not
(P<.001, Pearson 2 test). Bar indicates median.
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Comment
Based on our data, we estimate that cardiac metastasis from uveal melanoma
is found in approximately one fifth of patients who die of this tumor. It
is possible that the ability to spawn widespread visceral metastasis, often
with cardiac involvement, is a property developed by a subset of uveal melanomas,
as opposed to being the result of longer survival time that would allow more
extensive dissemination. Such metastases, however, seldom cause clinical symptoms.
In addition to the case report of Ruiz and coworkers,1
we are aware of one lethal cardiac metastasis from uveal melanoma.4 This 69-year-old man developed an atrioventricular
block and atrial fibrillation and died of cardiac arrest. At autopsy, he was
found to have metastases in the heart, liver, pancreas, adrenal gland, and
lymph nodes. The cardiac metastases involved the atrioventricular node and
left and right bundle branches.4 On the
other hand, patients who die of uveal melanoma are generally 56 years or older,
and many of them have concurrent heart disease, which may obscure the origin
of cardiac symptoms or of electrocardiographic findings related to metastatic
uveal melanoma.
Since submission of the manuscript, Rosario et al7
recently described a woman who experienced syncope attacks because of endocardial
and left ventricular metastasis from choroidal melanoma. She died of complications
during cardiac surgery.
AUTHOR INFORMATION
Teemu Mäkitie, MD;
Tero Kivelä, MD
Helsinki, Finland
Corresponding author and reprints: Teemu Mäkitie, MD, Ophthalmic
Pathology Laboratory, Department of Ophthalmology, Helsinki University Central
Hospital, Haartmaninkatu 4 C, PL 220, FIN-00029 HUS, Helsinki, Finland (e-mail: teemu.makitie{at}huch.fi).
REFERENCES
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1. Ruiz RS, El Harazi S, Albert DM, Bryar PJ. Cardiac metastasis of choroidal melanoma. Arch Ophthalmol. 1999;117:1558-1559.
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2. Jensen OA. Malignant melanomas of the uvea in Denmark 1943-1952: a clinical, histopathological,
and prognostic study. Acta Ophthalmol. 1963;75(suppl):1-220.
3. Einhorn LH, Burgess MA, Gottlieb JA. Metastatic patterns of choroidal melanoma. Cancer. 1974;34:1001-1004.
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4. Matturri L, Nappo A, Varesi C, Rossi L. Metastasi cardiache di melanoma maligno. Pathologica. 1993;85:97-102.
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5. Glancy DL, Roberts WC. The heart in malignant melanoma: a study of 70 autopsy cases. Am J Cardiol. 1968;21:555-571.
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6. Mäkitie T, Summanen P, Tarkkanen A, Kivelä T. Microvascular loops and networks as prognostic indicators in choroidal
and ciliary body melanomas. J Natl Cancer Inst. 1999;91:359-367.
FREE FULL TEXT
7. Rosario RT, DiMaio DJ, Lapham RL, Sweeney M, Smalling R, Barasch E. Metastatic ocular melanoma to the left ventricle inducing near-syncope
attacks in an 84-year-old woman. Chest. 2000;118:551-553.
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ABSTRACT
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Cardiac Metastasis From Uveal Melanoma
Makitie et al.
Chest 2001;120:2115-2116.
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