The Treatment of Advanced Choroidal Melanoma With Massive Orbital Extension

Frank J. Rini, M . D . , Frederick A. Jakobiec, M . D . , Albert Hornblass , M . D . , Barry L. Beckerman, M . D . , and Richard L. Anderson, M . D .

Four patients, each with a history of choroi­dal melanoma for more than ten years, became increasingly proptotic secondary to massive extraocular extension of their tumors. Because no metastases were detected during thorough systemic examinations, two patients under­went orbital exenteration. These patients suf­fered fulminant local orbital regrowth of their tumors at three and six months after surgery and died of distant metastases within ten months of exenteration. A third patient, who underwent a biopsy of the orbital mass via a lateral orbitotomy and received postoperative radiotherapy, died two years afterward. A fourth patient who refused any surgical treat­ment was followed up for five years after massive orbital disease developed. She died of disseminated disease. The patients who sur­vived the longest had minimal or no surgery.

THE TREATMENT OF localized intraocular mel­anoma is controversial,1,2 and no agreement has been reached on the best clinical treatment of choroidal melanoma with transscleral exten­sion into the orbit. Some investigators have recommended exenteration as a palliative as well as a curative treatment,35 whereas others have found that this disfiguring surgery does not enhance overall survival.6"10 Herein we de-

Accepted for publication Sept. 3, 1987. From the Department of Ophthalmology, Manhattan

Eye, Ear and Throat Hospital, New York (Drs. Rini, Jakobiec, and Hornblass); the Department of Ophthal­mology, Columbia-Presbyterian Medical Center, New York (Drs. Rini and Jakobiec); and the Department of Ophthalmology, University of Utah, Salt Lake City (Dr. Anderson). Dr. Beckerman is in private practice in Mt. Kisco, New York. This study was supported in part by a grant from the Zelda Radow Weintraub Foundation, Inc., New York.

Reprint requests to Frederick A. Jakobiec, M.D., Man­hattan Eye, Ear, and Throat Hospital, 210 E. 64th St., New York, NY 10021.

scribe four patients with late-stage, neglected malignant melanoma in whom the orbital ex­tension overshadowed the intraocular compo­nent.

Case Reports

Case l An 83-year-old woman was referred in April

1984 with a diagnosis of a choroidal melanoma in her left eye, known for at least 15 years, for which she had refused any treatment. During the early years of her disease she had been relatively asymptomatic, with the exception of a decrease in visual acuity in the affected eye. By August 1983 there was obvious extrascleral extension into the orbit and a painful, totally blind eye. Her left globe was markedly prop-tosed, with keratinization of the prolapsed con­junctiva (Fig. 1). A dense cataract prevented visualization of the fundus. Visual acuity was 20/100 in her right eye, with moderate nuclear sclerosis and peripapillary atrophy. An x-ray of the orbit and computed tomography demon­strated that the mass had enveloped the globe, with extension to the orbital apex and erosion into the left antrum (Fig. 2). Results of liver function tests, liver-spleen scan, bone scan, and chest x-ray were negative for metastases. In May 1984 the patient underwent exentera­tion of the left orbit with complete removal of the periorbita and the orbital floor, including the portion of the tumor that had invaded the roof of the antrum. During the procedure it was noted that portions of the medial, lateral, and inferior orbital walls were focally eroded by the mass. Copious amounts of pus and necrotic tissue were removed from the left an­trum. The tissue was irrigated and debrided. The antral and orbital cavities were packed with petrolatum gauze and absorbable colla-

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Vol. 104, No. 6 Choroidal Melanoma and Orbital Extension 635

Fig. 1 (Rini and associates). Case 1. The upper eyelid is tensed against the upwardly displaced globe by spread of melanoma into the inferior and retrobulbar regions of the orbit. Note the massively chemotic inferior conjunctiva.

gen, and the skin flaps were attached to the periosteum. The patient tolerated the proce­dure well. Cultures of the antral pus grew Staphylococcus aureus, and she was treated with intravenous antibiotics. Her hospital course was uneventful and she was discharged on a regimen of oral antibiotics.

Pathologic study of the surgical specimens showed a flat choroidal malignant melanoma of mixed epithelioid and spindle cell composition, with extrascleral extension (Fig. 3). The mela­noma cells infiltrated most of the retrobulbar tissue and invaded the optic nerve. The tumor was focally present at the apical margins of the surgical resection.

Fig. 3 (Rini and associates). Case 1. The exen-terated orbital contents show massive replacement of the inferior orbital tissues by extraocular spread of melanoma. Note that the intraocular component (arrow) is flat and diffuse, a type of choroidal mela­noma frequently associated with extraocular exten­sion (hematoxylin and eosin, x4).

Fig. 2 (Rini and associates). Case 1. Axial comput­ed tomography shows extension of tumor (arrow) into the superior antrum.

Her immediate postoperative course was un­eventful and her orbit and antrum healed well. In early August 1984 a palpable preauricular nodule had developed on the left side. By late August 1984 the patient complained of swell­ings of her temporal socket with minimal focal discharge. Three weeks later the swellings be­came better defined as nontender, hyperpig-mented nodules along the lateral aspect of the orbital rim (Fig. 4). The patient was lost to follow-up but it was confirmed that she had died six months later, in February 1985.

Case 2 An 88-year-old woman, with a 15-year histo­

ry of choroidal melanoma of her left eye, had refused treatment because of her age. During

Fig. 4 (Rini and associates). Case 1. Two and one-half months after the exenteration was per­formed, nodules appeared in the orbital wall. Note the opening between the socket and the antrum.

636 AMERICAN JOURNAL OF OPHTHALMOLOGY December, 1987

Fig. 5 (Rini and associates). Case 2. The left globe is displaced downward and there are 11 mm of left proptosis. Epibulbar extension of melanoma was noted in the superotemporal quadrant of the globe.

late 1985 her internist noted that her left eye was becoming proptosed with complete loss of vision. She was referred in January 1986 with a nonpainful, blind left eye that was 11 mm exophthalmic (Fig. 5). Intraocular pressure in the left eye was 33 mm Hg, with conjunctival injection and moderate keratopathy. There was a pigmented mass subconjunctivally near the insertion of the lateral rectus muscle. The left pupil was fixed. Severe rubeosis iridis, periph­eral anterior synechiae, and a moderate ante­rior uveitis were noted. A cataractous lens prevented visualization of the fundus. System­ic examination showed no distant metastases. When she returned in February for a follow-up examination, the proptosis had become more prominent, with increased conjunctival vascu-larity and a mildly painful eye. Computed to­mography disclosed a large temporal and retro-bulbar orbital tumor together with an intraocular tumor (Fig. 6). Results of biopsy performed through a superotemporal skin inci­sion in late February 1986 demonstrated malig­nant melanoma.

In March 1986 the patient underwent exen-teration of the left orbit. The mass was found to be grossly contained within the periorbita, but during the procedure, the tumor oozed through the superotemporal anterior skin inci­sion of the earlier biopsy site. Gloves and in­struments were changed several times while working in this quadrant of the orbit, and the peeled away, deep periorbital membrane re­mained intact during the entire procedure. The contents of the orbit were extracted in toto and apical bleeding sites were electrocauterized. The superotemporal planes of dissection (the skin flaps, subcutaneous tissue, and orbital rim) were thoroughly irrigated and cryosurgery was performed, using a double freeze-thaw

Fig. 6 (Rini and associates). Case 2. The tumor has filled the temporal and retrobulbar orbital spaces. Note the extension of the tumor laterally beyond the orbital rim. The intraocular tumor is large (arrow), but dwarfed by the extraocular extension.

technique. The orbital cavity was packed and she was treated with topical antibiotics. The patient tolerated the procedure well and was discharged four days later after an uneventful postoperative course. The microscopic diagno­sis was an infiltrating choroidal melanoma with massive orbital extension (Figs. 7 and 8). Many of the tumor cells were epithelioid in nature and had large, round nuclei with prominent nucleoli. Fewer cells had fusiform nuclei with nucleoli. The tumor was focally present at the posterior aspect of the specimen.

Fig. 7 (Rini and associates). Case 2. The exen-terated orbital contents demonstrate a circumscribed retrobulbar tumor. The periorbita is present posteri­orly but attenuated (arrow). The intraocular tumor has artifactitiously fragmented (hematoxylin and eosin, x4).

Vol. 104, No. 6 Choroidal Melanoma and Orbital Extension 637

Fig. 8 (Rini and associates). Case 2. Extension of the intraocular tumor on the right into the orbital tissues on the left through a scleral vascular emissary (hematoxylin and eosin, xllO).

The patient was seen one month postopera-tively and was comfortable. The orbit was heal­ing well without infection, necrosis, or pig-mented masses. The patient returned three months later, with two massive nontender, fixed, yascularized, nonfriable pigmented masses (Fig. 9). Results of biopsy disclosed recurrent malignant melanoma. Computed to­mography demonstrated recurrence of the tumor involving the entire socket, with exten­sion into the antrum down to the region of the hard palate as well as into the left side of the masseter muscle. Results of systemic examina­tion for metastases were again negative. In August 1986 she began palliative radiation therapy at a local medical center. She received a total dose of 6,000 rads (60 Gy) of x-radiation therapy. The tumor continued to infiltrate the orbit, antrum, and mandible. The patient re­mained free of known metastases until late January 1987, ten months postoperatively, when she was admitted to the hospital. She died shortly thereafter of widespread pulmo­nary and hepatic metastases.

Case 3 An 84-year-old woman was examined in

April 1981. For six days she had had blurred vision in her left eye associated with ocular pain, conjunctival redness, and swelling. Her right eye, which was blind from ocular trauma at age 2 years, had been treated with pilocar-pine eyedrops for glaucoma for approximately 16 years. Visual acuity was 20/70 in her left eye; her right eye was atrophied. There was moder­ate swelling of her left upper and lower eyelids, conjunctival injection, restriction of extraocular

Fig. 9 (Rini and associates). Case 2. Four months after orbital exenteration, the orbit is rilled with recurrent tumor. Two nodules orignate from the medial and lateral orbital walls.

motility, and a nuclear cataract. There was a moderate uveitis. Ophthalmoscopy, made dif­ficult by a vitritis, showed choroidal folds and an indistinct pigmented mass. Ultrasonograph-ic examination disclosed a 17 x 26-mm super-otemporal orbital mass continuous through a scleral defect with a solid, vascularized intraoc­ular tumor. The mass, which was of low to medium reflectivity, was 4 mm in height. A diagnosis of choroidal malignant melanoma with orbital extension and orbital inflammation secondary to tumor necrosis was considered. The patient was admitted and a regimen of oral corticosteroids was started; she responded promptly to the therapy. Ophthalmoscopic ex­amination of the posterior segment disclosed a pigmented choroidal tumor and choroidal folds. The choroidal folds regressed as the inflammation subsided. Over the course of the next year, her visual acuity remained stable at 20/40. There was no ophthalmoscopic or ultra -sonographic change in the tumor.

In August 1982 the patient was readmitted for recurrent ocular pain, orbital inflammation, and visual loss to 20/400. Ophthalmoscopy demonstrated a recurrence of the retinal and choroidal striae. Ultrasonographic studies showed an increase in size of the orbital tumor to 20 x 30 mm. Computed tomography demon­strated a superotemporal orbital mass adjacent

638 AMERICAN JOURNAL OF OPHTHALMOLOGY December, 1987

to the globe with central radiolucency. An orbi-totomy using a Kronlein approach disclosed a densely pigmented mass. The biopsy specimen showed a melanoma composed of spindle cells. Over the course of the next month, 4,500 rads (45 Gy) was delivered to the ocular and orbital tumor in ten doses. In December 1983 her visual acuity was stable at 20/200 and the tumor appeared unchanged in size. Skeletal and he­patic metastases were noted during bone and liver scans. Barium enema demonstrated a co-Ionic lesion. The patient died in July 1984 of metastatic melanoma. The eye and left orbital contents were removed; histopathologic stud­ies showed orbital and intraocular malignant melanoma, which was markedly necrotic.

Case 4 A 53-year-old woman examined in July 1974

had a one-year history of painless, progressive visual loss in her right eye and increasing pain in that eye and orbit of at least three weeks' duration. On ocular examination, visual acuity was R.E.: light perception without projection and L.E.: 20/25. Her right eye was painful, tender, and inflamed. The conjunctiva of the right eye had 2+ to 3+ injection; rubeosis iridis and chamber angle had caused a secondary angle-closure glaucoma. Intraocular pressure was R.E.: 65 mm Hg and L.E.: 20 mm Hg. Ophthalmoscopy of the right eye showed a bullous retinal detachment over a large choroi-dal mass. Ultrasonographic examination dem­onstrated a huge, subretinal, highly vascular-ized mass consistent with malignant melanoma. There was evidence of extraocular extension of the tumor, and further systemic examination was suggested. The patient, how­ever, refused all forms of therapy and was lost to follow-up.

In January 1979 the patient's clinical appear­ance progressed to what resembled a marked orbital cellulitis. She had beefy red, edematous right upper and lower eyelids, a violaceous right conjunctiva, marked purulence over the cornea, and severe proptosis. She gave a histo­ry of protrusion of that eye for at least two years. Hertel exophthalmometry readings were R.E.: 28 and L.E.: 20. The patient refused exam­ination of her left eye. She was admitted and intravenous antibiotic therapy was started. Ul-trasonography showed a necrotic intraocular malignant melanoma with extensive extrascle-ral extension and orbital invasion. The family and patient were consulted about the necessity

for exenteration, but the patient refused any form of surgical intervention, radiotherapy, or chemotherapy. She was discharged less than a week after becoming afebrile on a regimen of intravenous antibiotic therapy. She returned in January 1980. Ultrasonography at that time showed that the tumor had filled the entire globe, with a complete absence of scleral ech­oes at the posterior pole. The tumor also com­pletely filled the orbit. The patient again re­fused any form of therapy. On April 12, 1982 the family brought the patient back. She had a partially necrotic subconjunctival extension of tumor (Figs. 10 and 11) and severe shortness of breath, increased abdominal girth, and de­creased bowel movements. There were multiple hard nodules over her liver, stomach, and left flank, and a distended abdomen. Routine chest x-rays showed an extensive pleural effusion. She agreed only to have a thoracic paracentesis to relieve the extensive fluid and was trans­ferred to the medical service. She died six weeks later in early June 1982. An autopsy demonstrated massive orbital extension of in­traocular melanoma, which was microscopical­ly composed of epithelioid cells.

Discussion

The value of exenteration in prolonging life in patients in whom there are minimal or mod­erate degrees of extraocular extension of a cho-

Fig. 10 (Rini and associates). Case 4. A 63-year-old woman with an eight-year history of extraocular extension of choroidal melanoma.

Vol. 104, No. 6 Choroidal Melanoma and Orbital Extension 639

Fig. 11 (Rini and associates). Case 4. The globe has been displaced into the superior orbit by a fungating subconjunctival tumor with multiple areas of hemor-rhagic necrosis.

roidal melanoma is uncertain.3'510 The efficacy of exenteration is questioned because patient mortality is usually caused by widespread me-tastases and rarely by local orbital recurrence. The extraocular extension itself is a poor prog­nostic sign, indicating a highly malignant tumor with a much greater than average poten­tial for metastasis.1116 To date, no one has ad­dressed the issue of whether any surgery is advisable in the much rarer subset of patients whose advanced orbital extensions overshad­ow the intraocular components of their tumor.

Our four cases represent a unique subset of cases of choroidal melanoma with extraocular extension. Unlike most of the previously re­ported cases, the orbits of our patients were almost completely filled with tumor and the extrabulbar volume dwarfed that of the intraoc­ular component. Our four patients had extra-scleral extension and an orbit filled with tumor, the latter possibly representing the biologic equivalent of a delayed recurrence.10 This type of case is rarely encountered in contemporary practice.

In our first two patients, who underwent exenteration, fulminant local recurrence and rapid death occurred in their tenth postopera­tive month. Despite having had their tumors for up to 15 years, neither of these two patients was found before surgery to have disseminated

disease. Given their clinical histories, the local regrowth and metastatic spread of these tu­mors was much more rapid after the exentera-tions were performed than before. The periorbita was grossly intact in the exenteration specimens, corresponding to where clinical re­currences subsequently developed in the orbit­al bone. The outgrowth of the tumor nodules from the orbital walls or into the antrum indi­cates that there must have been focal breaching of the periorbita with subclinical involvement of the cancellous bone at the time of surgery. This may explain the local recurrence of the tumors, but it does not explain the fulminant nature of the regrowth or why the patients died so soon after surgery. In contrast to these two patients, our third patient, who underwent a biopsy via a lateral approach (a less traumatic procedure as compared to exenteration) fol­lowed by orbital radiotherapy, lived for two years before dying of widespread metastases. Our fourth patient, who refused all treatment, survived for five years after the development of massive orbital melanoma before dying of dis­seminated metastases.

Since radical surgery alone in two of our patients was unsuccessful and may actually have accelerated the fatal outcome of the dis­ease, we believe that patients should be fol­lowed up conservatively for as long as possible once they have allowed their orbital disease to progress to an advanced stage. That our long­est survivor after the development of massive orbital extension underwent no surgery sup­ports this conclusion. The spread of tumor from surgical trauma, the interruption of local anatomic barriers during exenteration, or the upsetting of immunologic restraints on the tu­mor's growth may have hastened the death of our first two patients.1419 When surgery is un­avoidable (because of a painful blind eye, ne­crosis, infection, intolerable propfosis, or hem­orrhage), adjunctive radiation therapy should be considered. In this situation, we recommend up to 5,000 to 6,000 rads (50 to 60 Gy) of immediate preoperative or postoperative exter­nal beam radiation before any evidence of local recurrence or distant metastases is discovered. This approach will probably not cure the pa­tient but may retard the local and systemic course of the disease.

ACKNOWLEDGMENT The data for Patient 3 were provided by Joel

Glaser, M.D., and Victor Curtin, M.D.

640 AMERICAN JOURNAL OF OPHTHALMOLOGY December, 1987

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