Ipsilateral orbital metastasis following enucleation of intraocular ciliochoroidal melanoma: a rare occurrence

Abstract

This case report demostrates an unusual occurence of orbital metastasis along with liver metastasis 5 years following enucleation for ciliochoroidal melanoma with no extraocular extension. It exemplifies that metastasis of the tumour can occur in the ipsilateral orbit after enucleation. Importance of close clinical follow-up after enucleation for choroidal melanoma, careful socket examination, and regular systemic metastatic workup is demonstrated. To the best of our knowledge, this is the first case report of uveal melanoma with ipsilateral orbital metastasis.

Background

Uveal melanoma is the most common primary intraocular tumour in adults.¹ Melanomas involving the ciliary body are more at risk of metastasis than melanomas involving the choroid and hence, are associated with a worse prognosis.² The tendency of ciliary body melanomas to form vascular networks is associated with increased risk of metastasis.³ Ciliary body melanomas also tend to be larger than choroidal melanomas and have a predeliction for monosomy 3 and 8q gain which contribute to their relative poorer prognosis.⁴

Orbital recurrences due to residual tumour in the orbit are more common than orbital metastasis from uveal melanoma. Early distant metastasis from uveal melanomas are the usual observation, but both orbital recurrences and contralateral orbital metastasis have been reported to occur many years after enucleation for primary uveal melanoma,^5–11 the longest disease-free interval documented in literature being forty years after enucleation for a choroidal melanoma.⁶

Metastatic melanoma to the orbit accounts for 5%–20% of all orbital metastasis, with the majority of the primary tumours being cutaneous melanomas^{12 13} and rarely, uveal6–8 14 15 or conjunctival melanomas.¹⁶ Herein, we describe a rare occurrence of ipsilateral orbital metastasis following enucleation in a case of ciliochoroidal melanoma without any evidence of extraocular extension. Patient consent has been obtained for publishing identifiable photographs.

Case presentation

A 30-year-old Indian woman presented to us with painless decrease in vision in her left eye of 1-month duration. On examination, her right eye was unremarkable with 20/20 vision. Her left eye had a vision of 20/50 and a shallow anterior chamber. On dilated examination, an elevated, pigmented ciliochoroidal lesion was noted, extending from anterior (figure 1A) to the mid vitreous cavity, from 10:00 to 2:00 clock hours associated with subretinal fluid.

Figure 1.

Patient with intraocular ciliochorodal melanoma. (A) Slit lamp photograph showing a large pigmented lesion in the superior quadrant of the left eye. (B) Ultrasound B scan showing a well-defined acoustically solid intraocular lesion with minimal back shadowing. (C) Photomicrograph of the enucleated eyeball showing cilio-choroidal mass (H&E stain; scanner view). (D) Photomicrograph showing lesion in the stroma of the ciliary body with non-pigmented and pigmented epithelium overlying it (H&E; 10× magnification).

Investigations

Ultrasound B scan of the left eye showed a large mushroom shaped ciliochoroidal lesion with low to moderate internal reflectivity and internal heterogeneity extending from the anterior to the mid vitreous cavity. The tumour basal diameter was 16.74 mm and tumour thickness was 13.23 mm (figure 1B). There was an associated ciliochoroidal excavation and orbital shadowing.

Differential diagnosis and treatment

The clinical picture and ultrasonography B-scan findings confirmed the diagnosis of left eye ciliochoroidal melanoma. The left eye of the patient was enucleated and a polymethyl methacrylate implant was placed in the enucleated socket.

Outcome and follow-up

Gross inspection of the enucleated specimen showed a pigmented mass arising from the ciliary body and choroid with retinal detachment (figure 1C). The anterior chamber was narrowed with closed angles. Microscopic examination revealed a lesion predominantly composed of spindle cells with vesicular nuclei and intracytoplasmic pigment deposition. Nuclei showed mild anisonucleosis with small nucleoli. Mitoses were rare. There was no scleral or extrascleral tumour extension. Vortex veins and Schlemm’s canal did not show any tumour deposits (figure 1D). Based on histopathology, the diagnosis of intraocular ciliochoroidal melanoma was confirmed.

Baseline systemic screening with chest X-ray, ultrasound abdomen, and liver function tests revealed no evidence of systemic metastasis. The patient was kept on close follow-up: every 6 months in the first year and thereafter yearly. Socket examination and metastatic workup was performed at every follow-up visit.

On the fourth year follow-up visit, left socket was healthy and ultrasonography of the abdomen showed lesions in the liver, the largest being 2.7 cm × 2.6 cm in size. The patient was referred to an oncologist and ultrasound-guided fine needle aspiration cytology was done from the liver lesion which revealed metastatic deposit of malignant melanoma. The patient was started on immunotherapy with intravenous pembrolizumab. Eight months after the detection of liver metastasis, the patient complained of inability to retain her ocular prosthesis.

On clinical examination, right eye was unremarkable. Left socket examination revealed a firm mass in the lacrimal gland region and the implant had migrated anteriorly beyond the orbital rim (figure 2A, B), and the ocular prosthesis was unstable. A CT scan of the orbits revealed a relatively well-defined, heterogenous lesion measuring 33.3×25.3× 27.9 mm in the superolateral left orbit involving the mid and posterior orbital spaces. An anterior and inferior migration of the orbital implant was noted (figure 2C). A diagnosis of left orbital metastasis was made. A whole-body positron emission tomography-CT (PET-CT) scan revealed a mass in the left superolateral orbit along with the liver metastasis (figure 2D). There was no evidence of metastasis elsewhere in the body. The patient underwent exenteration of the left orbit.

Figure 2.

Patient with orbital metastasis. (A) Left proptosed anophthalmic socket. (B) Worm’s view showing prominent proptosis of left socket. (C) CT of the orbits showing a homogenous mass in the superolateral orbit with inferior migration of the orbital implant. (D) Positron emission tomography scan of the liver showing multiple FDG-avid lesions. (E) Photomicrograph of the exenterated specimen showing fibrous capsule of the anophthalmic socket (black arrow) with lesion posterior to it (H&E stain; 2× magnification). (F) Photomicrograph showing lesional cells with large vesicular nuclei and prominent nucleoli and intracytoplasmic pigment (H&E; 20× magnification).

On histopathology, the exenterated specimen revealed a pigmented lesion posterior to the fibrous capsule of the anophthalmic socket (figure 2E). Lesional cells were spindled with focal epithelioid cells arranged in a fascicular and lobular pattern separated by thin fibrous septae. There was moderate pleomorphism with large vesicular nuclei with prominent large nucleoli and intracytoplasmic pigment (figure 2F). Apical tissue did not reveal any microscopic tumour deposits. Histopathology confirmed the diagnosis of orbital melanoma.

Based on the clinical and histopathology findings, we made a final diagnosis of left orbital metastatic melanoma in a treated case of ciliochoroidal melanoma. The patient is currently continuing immunotherapy for liver metastasis.

Discussion

The incidence of metastasis in cases with uveal melanoma is 32% at 5 years, 50% at 15 years, and 62% at 35 years.¹⁷ The common sites of metastasis are liver (89%), lung (29%), bone (17%), skin and subcutaneous tissues (12%), and lymph nodes (11%).^{18 19} Orbital metastasis of uveal melanoma is rare. In a study of 645 space-occupying lesions of the orbit, direct extension of melanoma to the orbit from eyelid/conjunctiva/uvea has been reported in 22 (3%) cases, and metastatic tumours from distant sites have been noted in 16 (2%) cases, of which none were from ocular melanomas.¹³

Though orbital tumour recurrence has been reported in eyes with microscopic or gross extraocular tumour extension,^9–11 orbital metastasis in uveal melanoma is very rare. In our case, there was no evidence of microscopic or gross extrascleral tumour extension, and the lesion manifested 5 years after the enucleation. Based on these findings, we ruled out orbital tumour recurrence and made a diagnosis of ipsilateral orbital metastasis. Orbital metastasis of uveal melanoma is usually associated with concurrent generalised metastasis, similar to our case and the prognosis is poor.

There have been isolated case reports on uveal metastasis to the contralateral orbit. Shields et al reported a case of metastasis of choroidal melanoma to the contralateral orbit, choroid and eyelid 5 years after enucleation of the primarily affected eye.¹⁴ The patient had liver metastasis preceding the orbital metastasis and the patient died of liver failure a year after the diagnosis orbital metastasis.¹⁴ Of the 20 metastatic ocular/orbital melanomas reported by Zografos et al, one patient had uveal melanoma of the contralateral eye.¹⁵ Gupta et al reported a case of contralateral orbital metastasis 10 years after treatment of a choroidal melanoma with plaque brachytherapy and argon laser photocoagulation. The primary tumour had been noted to be completely resolved into a flat scar at the end of treatment.⁸ Coupland et al reported the longest interval of forty years between enucleation and melanoma metastasis to the contralateral orbit. This patient also had widespread metastasis to the abdomen and lung at the time of orbital metastasis.⁶ Bowling et al also reported a similar case of choroidal melanoma metastasizing to the contralateral orbit seventeen years after enucleation of the globe with the primary tumour. Around the same time of detection of orbital metastasis, a lung lesion suggestive of thoracic metastasis was also diagnosed.⁷ Our patient had liver metastasis at the time of diagnosis of orbital metastasis. However, our patient had metastatic melanoma in the ipsilateral orbit, while the contralateral orbit was normal.

Based on literature review, there are no reports of metastatic ciliochoroidal melanoma to the ipsilateral orbit, which makes this case uniquely interesting in addition to adding to the sparse number of cases of uveal metastasis to the orbit.

Learning points.

• Orbital metastasis can occur following enucleation in an eye with ciliochoroidal melanoma without extraocular extension or optic nerve tumour invasion.

• It is important to closely examine the enucleated socket and compare its appearance at every subsequent visit.

• Periodic metastatic workup is warranted in all cases with uveal melanoma.

• Systemic metastasis commonly present at the time of orbital metastasis of uveal melanoma.