ARTICLE
Malignant melanomas rarely involve the orbit, and they usually develop
as a result of either secondary extension of intraocular melanomas or
orbital metastasis of cutaneous melanomas [1, 2]. Since orbital involvement
presents ophthalmological signs and symptoms such as exophthalmos, loss
of visual acuity, and impairment of the eyeball movement [2], orbital
melanomas basically require ophthalmological management. However, they
could give rise to dermatological concerns because it is the responsibility
of the dermatologist to search for a cutaneous melanocytic lesion as a
potential source of orbital metastasis. In this communication, we report
a case of ocular melanoma presenting unilateral exophthalmos as its initial
clinical manifestation. Thorough physical and radiological examination
of the whole body failed to disclose any cutaneous or visceral melanoma,
but detected a clinically silent, ocular melanoma on the contralateral
side, suggesting development of a primary intraocular melanoma and subsequent
metastasis to the opposite orbit where exophthalmos occurred. This is
the first report where a clinically silent, ocular melanoma was discovered
by metastasis to the contralateral orbit. The case deserves to be reported
in the dermatological literature because dermatologists should be aware
of the rare possibility that, besides cutaneous melanomas, intraocular
melanomas can metastasize to the contralateral orbit.
Case report
Progressive, left exophthalmos developed in a 76-year-old Japanese woman
two weeks prior to her consultation. She had been operated on for peritonitis
resulting from gangrenous cholecystitis at the age of 35, but otherwise
had been in excellent health. She had completely lost her right vision
as a result of vitreous hemorrhage from a choroidal hematoma of unknown
etiology in 1981, which had been treated in another hospital. In 1992,
she suddenly developed severe pain in the right eye and consulted the
ophthalmological department of our hospital. Slit-lamp examination of
the right eye showed highly injected conjunctivae, chemosis, and corneal
opacity. Infectious endophthalmitis was suspected and it was successfully
treated with a two-week administration of topical and systemic antibiotics.
The causative organism was not identified. Her best corrected visual acuity
in the left eye at this time was 20/100. Ophthalmoscopic examination of
the left fundus only showed age-related, macular degeneration. Since then
she had occasionally undergone ophthalmological examination in our hospital,
but no significant abnormality had been found in the left eye. Forty-two
months after the episode of right endophthalmitis, proptosis and gradual
deterioration of the left visual acuity developed. Measurement of proptosis
with a Hertel exophthalmometer showed 15 mm OD and 22 mm OS. The left
visual acuity had decreased to 20/200 and her intraocular tension was
25 mm. The left fundus examination showed retinal and choroidal folds
with a pigmented retrobulbar mass pushing the fundus forward (not shown).
The abduction of the left eyeball was impaired. An open surgical tumor
biopsy was carried out. Macroscopically the retrobulbar tumor on the left
side was a soft, fragile, easily-bleeding black mass, and on histological
examination showed massive infiltration of atypical epithelioid cells
containing numerous pigmented granules. It was rich in sinusoidal vessels
which were surrounded by the tumor cells oriented in a perpendicular array
around them (Fig. 1).
Both macro- and microscopic findings of the left retrobulbar tumor readily
proved it was a malignant melanoma. Thorough physical examination of the
whole body surface, the oral and vaginal mucosa did not show the presence
of any pigmented lesion suggestive of a primary cutaneous or mucosal melanoma.
The patient had no vitiligous lesions nor had had any previous episode
of spontaneous regression or excision of a pigmented
lesion. Laboratory examinations were insignificant including the liver
enzymes, complete blood cell count, lactate dehydrogenase and erythrocyte
sedimentation rate. Chest X-ray, whole body CT scan, 67Ga scintigraphy,
and ultrasonographic examination of the abdominal and pelvic cavity in
search of primary visceral melanoma failed to disclose any suspicious,
tumoral lesion. Unexpectedly, the CT scan showed bilateral, nonhomogeneous,
retrobulbar masses as well as an atrophic, calcified right eye ball (Fig.
2). These masses showed nonhomogeneous, high signal intensities
on T1-weighed MR images and low signal intensities on T2-weighed MR images,
which was compatible with melanoma (only T1-weighed images are presented
in the following figures). The mass on the right side showed indistinct
margins and appeared to originate from the right eye and to invade the
right optic nerve as shown by MR studies (Fig.
3A). The left retrobulbar mass showed sharp margins and was largely
confined within the orbital muscle cone (Fig.
2) without involvement of the left optic nerve (Fig.
3B), but invaded a portion of the greater wing of the left sphenoidal
bone (not shown). Although the left eyeball was displaced markedly forward,
it was not invaded by the tumor (Fig.
2), as suggested by fundoscopic examination. The right retrobulbar
tumor could not be investigated histologically, and opacity of the vitreous
body prevented detailed ophthalmological examination of the right fundus.
Three months after the initial consultation, however, a black mass was
seen invading the right palpebral conjunctivae, and concomitant right
exophthalmos developed, confirming that the right retrobulbar mass was
also a melanoma (Fig. 4).
We concluded that a primary, uveal melanoma had developed in the right
eye and had metastasized to the contralateral orbit. The tumors did not
respond to combined treatment with dacarbazine, cisplatin, vincristin,
and radiation. She refused further treatment and was lost to further follow-up.
At the time of discharge from hospital, the patient did not show signs
of distant metastasis.
Discussion
Malignant melanomas rarely involve the orbit, and orbital melanomas
usually develop as a result of either secondary extension of intraocular
melanomas or orbital metastasis of cutaneous melanomas [1, 2]. When metastatic
orbital melanoma is suspected therefore, dermatologists should search
for a cutaneous or mucosal melanocytic lesion as a potential source of
the metastasis. The present case, however, is exceedingly unusual because
unilateral exophthalmos due to orbital metastasis was the initial manifestation
of the contralateral intraocular melanoma.
We do not have direct evidence that a primary, intraocular melanoma
had developed on the right side. Any detailed ophthalmological examination
of the right eye was impossible because of the complete opacity of the
right vitreous body. Nevertheless, all the clinical, radiologic, and laboratory
data indicated the right eye as the primary site of the metastatic melanoma.
CT and MR studies indicated the metastatic nature of the left retrobulbar
tumor while suggesting an intraocular origin of the right retrobulbar
tumor (Figs. 2
and 3). The left retrobulbar tumor was histologically
rich in sinusoidal vessels which were surrounded by melanoma cells oriented
in a perpendicular array (Fig.
1), a characteristic feature described both in metastatic and
primary uveal melanomas [3, 4], but not in metastatic ocular tumors from
cutaneous melanomas [2, 5, 6]. A case of localized metastatic melanoma
from an unknown primary site has been reported [7]. However, bilateral
orbital metastases from an occult extraocular melanoma is quite unlikely
because ocular metastases are usually accompanied by concomitant dissemination
[2, 5, 6]. Since uveal melanomas often present inflammatory ocular lesions
and intraocular hemorrhage as their initial manifestations [8], the previous
episode of vitreous hemorrhage of unknown eatiology in the right eye was
probably caused by a uveal melanoma. The most plausible scenario in our
case is that a primary uveal melanoma developed in 1981 as suggested by
the episode of right vitreous hemorrhage. The slowly growing tumor remained
unnoticed because of atrophic degeneration of the right eye. After invasion
into the right optic nerve and retrobulbar space, the tumor finally metastasized
to the contralateral orbit and formed the retrobulbar mass producing left
exophthalmos.
The liver, lung, bone and skin were involved
in 87, 46, 29, and 17%, respectively, of the metastases of uveal melanomas
[9]. Metastasis to the contralateral orbit is extremely rare and there
are only three reported cases in the English literature [3, 4, 10]. In
these cases, the metastases occurred approximately four and nine years
after excision of primary uveal melanomas, indicating their slow growth
rate and delayed metastasis. It is not surprising, therefore, that overt
metastasis occurred more than a decade after development of primary uveal
melanoma in our case.
The route of metastasis to the contralateral orbit remains entirely
unknown, and has never been seriously discussed. Hematogenous metastasis
is the least likely in our case because no distant metastases including
the hepatic metastasis, which is the commonest site for hematogenous dissemination
of uveal melanomas, could be detected even four months after development
of the left exophthalmos. Thorough evaluation of the radiologic findings
failed to disclose the route of metastasis to the contralateral orbit.
Since the tumor apparently invaded the right optic nerve (Fig. 3A),
the tumor cells probably extended along the optic nerve, reaching the
contralateral middle cranial fossa. Since the left optic nerve remained
intact as shown in figure 3B,
continuous tumor cell infiltration from the right optic nerve across the
optic chiasma into the left optic nerve is not likely. It is of note that
metastatic orbital melanomas are primarily confined within the orbital
muscle cone without involving the optic nerve as in the previous cases
[3, 4] as well as the present one. Considering the well-confined location
of the left metastatic tumor within the orbital muscle cone, tumor cells
must have gained access to the contralateral orbit along either the abducent
or oculomotor nerve because these cranial nerves pass through the orbital
muscle cone. In terms of anatomical proximity of the oculomotor nerve
to the root of the optic nerve, the oculomotor nerve appears to be the
more likely candidate rather than the abducent nerve for the passage of
tumor cells into the orbital muscle cone. The patient, however, showed
no ocular signs or symptoms relevant to impaired function of the oculomotor
nerve, as did the previous cases [3, 4, 10]. In none of these cases, was
the formation of the metastatic focus within the middle cranial fossa
near the origin of these cranial nerves reported. Certain uveal melanoma
cells may show a preference for peripheral nerves, and once reaching the
root of the cranial nerves, they may readily invade the contralateral
orbit along these cranial nerves. Such a peculiar mode of tumor growth
is feasible because malignant melanomas occasionally show neurotropism
[11].
No matter what the actual route of metastasis might be, our case reminds
both ophthalmologists and dermatologists that an intraocular melanoma
is a rare, but potential source of a contralateral orbital metastatic
melanoma.
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