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Aggressive Primary Orbital Melanoma in a Young White Man With No Predisposing Ocular Features
Arch Ophthalmol. 2004;122:118-121.
Primary orbital melanoma is an exceedingly rare tumor1 that probably develops from congenital rests of neural crest cells in the orbit.2 It represents less than 1% of primary orbital neoplasms and usually occurs in the presence of clinical or histological evidence of ocular melanosis or blue nevus syndrome.2 Although orbital melanoma in general carries a poor prognosis, our case was unusual for its extremely aggressive clinical course that resulted in the death of the patient 6 months after presentation.
Report of a Case
A 40-year-old white man was first seen by us in July 1998 with a painless 3-mm proptosis of the left eye of 6 months' duration. There was no clinical evidence of ocular melanosis or blue nevus syndrome. A computed tomographic scan of the orbits revealed a well-defined intraconal mass that was discrete from the optic nerve and the horizontal rectus muscles (Figure 1). In the following 6 weeks, the proptosis enlarged, progressing from 3 mm to 8 mm. There was associated conjunctival exposure with ulceration, marked global restriction of movement, and transient visual obscurations. Optic nerve function was preserved, with Snellen visual acuity retained at 6/5, normal color vision, and intact pupillary reactions. A lateral orbitotomy with excision biopsy was performed in September 1998. A large pigmented mass was removed, histological analysis of which showed the lesion to be an orbital melanoma. A cilioretinal artery occlusion occurred postoperatively, reducing the left visual acuity to light perception.
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Figure 1. Axial computed tomographic scan obtained at presentation shows a left intraconal mass, causing a mild left proptosis.
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Histologically, it is not possible to differentiate a primary from a metastatic orbital melanoma; therefore, we performed a thorough systemic evaluation for a primary source. Detailed clinical examination augmented with liver function tests; liver ultrasonography; computed tomographic imaging of the brain, chest, and abdomen; and a bone scan showed no evidence of systemic melanoma. Ocular B-scan ultrasonography, performed to look for an intraocular primary tumor, suggested a possible small anterior ciliary body lesion with a collar-stud appearance and measuring 1.4 mm.
Five weeks after the excision biopsy, there was an alarmingly rapid recurrence of the left proptosis (Figure 2 and Figure 3). Magnetic resonance imaging revealed local tumor regrowth occupying the inferior aspect of the left orbit and extending superiorly as far as the superior rectus muscle. There was no evidence of spread beyond the orbit. A left exenteration with preservation of the eyelids was carried out in November 1998. Postoperative radiotherapy, to be followed by chemotherapy and adjunctive interferon treatment, was planned. However, 3 days before the commencement of radiation treatment, a firm swelling was noted at the lateral aspect of the left orbit. Results of fine-needle aspiration biopsy confirmed the presence of malignant melanoma cells, indicating that surgical clearance had not been achieved.
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Figure 2. Resolution of left proptosis after lateral orbitotomy and excision biopsy.
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Figure 3. Preexenteration photograph shows aggressive tumor recurrence only 5 weeks after excision biopsy, with a large mass filling the left orbit and causing massive proptosis and conjunctival prolapse.
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The patient's clinical course rapidly deteriorated, with massive and disfiguring growth of the melanoma within the exenteration cavity. Magnetic resonance images showed that the extensive melanoma deposit was causing huge soft tissue expansion, with extension into the paranasal sinuses and left temporal fossa and destruction of the anterior aspect of the sphenoid wing (Figure 4). In December 1998, there was evidence of metastatic disease with distant dissemination to the anterior chest wall and the liver. Treatment with subcutaneous interferon alfa-2a, 20 mIU given on alternate days, failed to alter the course of the disease, and the patient died 2 weeks later.
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Figure 4. Axial magnetic resonance image demonstrates extensive melanoma recurrence, causing huge and disfiguring soft tissue expansion with direct invasion of the left temporal fossa and erosion through to the left maxillary antrum.
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Histopathological Findings
A dark irregular mass measuring 23 mm x 32 mm was excised. Sections showed a partly necrotic, partly pigmented mass consisting of spindle cells (Figure 5). There were frequent mitoses, considerable nuclear pleomorphism, and large numbers of small microvessels, indicating a vascular tumor. The pigment, which was patchy, was negative for iron (Perls test). The tumor cells stained positively for NKIC3 antibody, S100 protein, and melanoma-associated antigen (HMB45), indicating their melanocytic nature.
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Figure 5. Excision biopsy specimen shows an area of mainly spindle-shaped melanoma cells (hematoxylin-eosin, original magnification x180).
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Exenteration Specimen
The exenteration specimen (Figure 6) showed extensive infiltration of the orbital fibrofatty tissue by a high-grade malignant melanoma. The tumor was now formed from clusters of medium to large epithelioid cells (Figure 7), but with a staining pattern similar to that of the excision biopsy. There was a high mitotic rate (more than 50 mitoses per 10 x 40 objective fields) and geographic areas of necrosis. There was no evidence of congenital melanosis oculi. Biopsy specimens taken from the margins of excision showed that the skin from the left lateral eyelid and inferior orbital rim was clear, but residual tumor was found at the inferior orbital rim adjacent to the left infraorbital nerve and at the left orbital apex. Ten-micrometer histological sections were made of the entire globe (with every 10th section submitted for staining and examination) and demonstrated no pathological evidence of an intraocular or ciliary-body melanoma as was suggested on ultrasonography.
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Figure 6. Macroscopic view of the left orbital exenteration specimen shows preservation of the normal architecture of the eye but widespread infiltration of the retrobulbar fibrous and adipose tissue by melanoma. No evidence of congenital melanosis oculi is seen.
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Figure 7. Exenteration specimen shows an area composed of mainly epithelioid melanoma cells (hematoxylin-eosin, original magnification x200).
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We found no histological evidence of any predisposing disease, either in the form of blue nevi or ocular melanosis in the excision biopsy or exenteration specimen. The overall conclusion was, therefore, of a highly aggressive malignant melanoma that, in the absence of an intraocular or systemic primary tumor, appeared to have arisen de novo within the orbit.
Comment
Primary orbital melanoma is a rare condition that is histopathologically similar to uveal melanoma.2 It is primarily seen in white adults who seek care most commonly for painless proptosis and has an average age at onset of 42 years.2 Predisposing ocular features are present in most cases. In the series by Tellado et al,2 47.5% of the patients had clinical evidence of some form of congenital melanosis. Intraorbital blue nevus was recognized histologically in 90%. The case presented herein is remarkable for the absence of both. Had there been any evidence of ocular melanosis, this patient would probably have proceeded, after orbital computed tomography, to excision biopsy sooner than actually occurred, as clinical suspicion would have been greater.
It is possible to miss small foci of pigmentation, both clinically and histologically, that may represent ocular, oculodermal, or orbital melanocytosis. Detailed inspection of the gross specimens of both the excision biopsy and the exenteration took place to look for minute areas of pigmentation that could have predisposed to the development of melanoma. This was augmented by a thorough intraoperative examination of the orbital periosteum, with multiple biopsy specimens taken from suspicious areas of grey, brown, or black pigmented areas, specifically at the orbital apex and the lateral orbital rim. No evidence of melanocytosis was found. We accept, however, as no autopsy was performed, that it is possible (although unlikely) that an isolated area of melanocytosis from which the melanoma could have arisen may have been overlooked.
B-scan ultrasonographic examination suggested that the orbital mass represented spread from an anterior ciliary primary melanoma, tumors that are known to behave more aggressively than more posteriorly located lesions.3 Histological examination confirmed that this was not the case. The B-scan had been performed the day after excision biopsy, suggesting that the "lesion" observed represented a postoperative artefact, as it would be unlikely that our method of histopathological sampling could have missed a lesion picked up on ultrasonography 5 weeks earlier and estimated to be at least 1.4 mm.
Although primary orbital melanoma carries a poor prognosis, with a 4.5-year mortality of 38%,2 our case represents a particularly aggressive lesion. The best approach to treatment of orbital melanoma is not scientifically known.1 In our case, an active multidisciplinary approach to tumor control was taken. Surgical excision and local radiotherapy to the orbit followed by chemotherapy and adjunctive interferon treatment was considered the combination most likely to achieve success. However, the very active nature of tumor recurrence, following both the excision biopsy and exenteration, was suprising, and the likelihood of radiotherapy or chemotherapy controlling such macroscopic disease was remote.1, 4-6 Radical skull base surgery, which entails an intraoperative mortality rate of several percent, was considered. However, it was highly improbable that even this kind of surgery could have successfully eradicated the tumor, and the patient declined further intervention.
This unusual case report of a rare but life-threatening condition illustrates that primary orbital melanoma should be considered in cases of rapidly progressing proptosis in young white patients, even where no predisposing ocular disease is present.
AUTHOR INFORMATION
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Yvonne M. Delaney, FRCOphth;
Susan Hague, FRCOphth;
Brendan McDonald, FRCPath
Oxford, England
Corresponding author: Susan Hague, FRCOphth, Radcliffe Infirmary, Oxford Eye Hospital, Woodstock Road, Oxford OX2 6HE, England (e-mail: y.delaney{at}virgin.net)
REFERENCES
1. Polito E, Leccisotti A. Primary and secondary orbital melanomas: a clinical and prognostic study. Ophthal Plast Reconstr Surg. 1995;11:169-181.
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2. Tellado M, Specht C, McLean IW, Grossniklaus HE, Zimmerman LE. Primary orbital melanomas. Ophthalmology. 1996;103:929-932.
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3. Rummelt V, Folberg R, Woolson RF, Hwang T, Pe'er J. Relation between the microcirculation architecture and the aggressive behaviour of ciliary body melanomas. Ophthalmology. 1995;102:844-851.
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4. Agarwala SS, Kirkwood JM. Interferons in melanoma. Curr Opin Oncol. 1996;8:167-174.
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5. Russell-Jones R. Interferon alpha therapy for melanoma. Clin Exp Dermatol. 2000;25:1-6.
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6. Philip PA, Flaherty LE. Biochemotherapy for melanoma. Curr Oncol Rep. 2000;2:314-321.
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SECTION EDITOR: W. RICHARD GREEN, MD
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