Iris melanoma in children: Current approach to management.

Iris melanoma usually affects middle aged, Caucasian patients with light colored eyes. Pediatric iris melanoma is rare. A 15-year-old Caucasian male presented with 1-month history of a brown nodule in the inferotemporal aspect of his left eye. Iris nevus was diagnosed, and the patient was observed. Nearly 2 years later the lesion had grown in basal diameter and thickness, and the tumor was excised by partial lamellar scleral flap and sector iridectomy. Histopathology confirmed spindle cell iris melanoma. Two years post-operatively, tumor recurrence with anterior chamber angle involvement and secondary glaucoma developed. He was then treated with custom designed Iodine(125) plaque radiotherapy. This case demonstrates the recurrence of iris melanoma despite proper initial surgical management, and outlines current management options for pediatric iris melanoma.

Introduction

Iris melanoma is a rare condition, comprising 4% of uveal melanoma and having prevalence of 5.1 cases per million population in the United States.[1] The mean age of presentation is 40–47 years, which is approximately 10–20 years younger than patients with other uveal melanomas.[2] Most patients are Caucasian (97.8%) with blue or green irides (97%), and males and females are affected equally.[134] Iris melanoma typically presents as a nodular pigmented lesion in the inferior iris with a mean basal dimension of 6 mm and 2.3 mm thickness.[134] The challenge in diagnosis of iris melanoma is in its differentiation from benign iris nevus, a tumor that can manifest with similar features of nodularity, pigmentation, and involve full thickness iris.[1] Features that help to distinguish iris melanoma from iris nevus include larger tumor size, tumor seeding on the adjacent iris or in the trabecular meshwork, presence of secondary glaucoma, and documented enlargement.[13-5] Herein, we report a case of iris melanoma in a child with secondary glaucoma that required both surgical resection and later plaque radiotherapy.

Case Report

A 15-year-old Caucasian male noticed a brown nodule in the inferotemporal aspect of his left eye (OS) for 1 month [Figure 1a]. On examination, visual acuities were 20/20 in both eyes (OU) with intraocular pressures (IOP) of 11mm Hg OU. The right eye (OD) was unremarkable except for a single iris freckle. In the left eye, a pigmented nodular iris lesion was noted in the five o’clock meridian, extending to the pupillary margin and measuring 3.0 mm in basal diameter and 1.3 mm in thickness. Intrinsic vascularization, feeder vessels, corectopia and ectropion irides were present. There was a light dusting of pigment on the anterior iris surface. The anterior chamber angle showed no sign of tumor or tumor-related seeds. Subtle scleral and choroidal melanocytosis was present OS. The differential diagnosis included iris nevus versus iris melanoma and conservative observation for growth was advised.

Figure 1

A 15-year-old Caucasian male with a pigmented iris lesion. The iris lesion was small at presentation (a) and showed growth over 2 years (b) Visible on gonioscopy (c) and anterior segment optical coherence tomography (d) The lesion was excised by partial lamellar scleral flap and sector iridectomy (e) Later tumor recurrence in the anterior chamber angle with elevated intraocular pressure necessitated Iodine125 plaque radiotherapy (f)

Nearly 2 years after initial presentation, the lesion had enlarged to 3.5 mm in basal diameter and 3.0 mm in thickness [Figure 1b–d]. IOP was 10 mm Hg OD and 12 mm Hg OS. Iris melanoma was diagnosed, and the tumor was surgically excised by partial lamellar scleral flap and sector iridectomy [Figure 1e]. Histopathology confirmed the diagnosis of spindle iris melanoma.

Over 2 years, following iridectomy the patient developed elevated IOP OS of 37mm Hg. Gonioscopy disclosed lightly pigmented tumor invasion of the trabecular meshwork for 360 degrees and melanoma recurrence was suspected. This finding was managed with custom designed Iodine125 plaque radiotherapy, delivering transcorneal radiation to the entire anterior segment, including the entire trabecular meshwork [Figure 1f]. The only other alternative was enucleation.

Discussion

The differential diagnosis of iris melanoma includes primary iris cyst (38%), iris nevus (31%), essential iris atrophy (5.7%), iris foreign body (4.5%), peripheral anterior synechiae (2.5%), and iris metastasis (2.5%).[5] Iris melanoma in children is characterized by smaller tumors, less seeding, and fewer cases of secondary glaucoma compared to adults.[1] Iris melanomas are associated with a better prognosis than other uveal melanomas, probably due to the ease of earlier detection at a smaller size. Metastasis is seen from iris melanoma at a rate of 0.5%, 4%, and 7% at 3, 5, and 10 years respectively.[6] In comparison, metastatic rates from choroidal melanoma are 8%, 15%, and 25% at 3, 5, and 10 years, respectively.[6]

Management options for iris melanoma includes local resection, plaque brachytherapy, proton beam radiation, enucleation and observation.[14] Local resection is reserved for smaller tumors (three to four clock hours or less) and those without evidence of seeding.[4] The goals of surgery are to totally resect the tumor and avoid leaving viable tumor cells that could lead to recurrence or metastasis. Residual tumor is estimated to be present after resection in 3% to 7% of reported cases.[4] Local tumor recurrence after resection in patients with iris melanoma ranges from 2% to 14%, depending on the surgeon and surgical technique. The median time from resection to recurrence is 45 months.[4] Metastasis after local iris melanoma resection occurs in 0% to 9% of reported cases.[47] Older age, involvement of the anterior angle elevated IOP and extraocular extension are all risk factors for metastasis.[7]

Primary plaque brachytherapy for iris melanoma successfully controls melanoma in 92% of patients.[48] Plaque brachytherapy following resection controls iris melanoma in 87% of patients with up to 6 years follow-up.[4] In an analysis by Shah and associates on iris melanoma, it was noted that the reasons for post-resection plaque radiotherapy included clinically evident tumor recurrence visible at follow-up examination (63%), positive margins on histopathology indicating microscopic residual tumor (28%), and clinically evident residual tumor after resection (9%).[4] Following tumor resection for iris melanoma, enucleation is ultimately required in 5%–25% of cases.[4] In our patient, plaque radiotherapy was indicated for suspected tumor recurrence in the anterior chamber angle, the source of secondary glaucoma.

The presence of glaucoma in eyes with iris melanoma complicates treatment. Iris melanoma associated with glaucoma (compared to iris melanoma without glaucoma) is more likely to be thicker, involve the angle, and demonstrate iris stromal seeding.[8] However, the presence of glaucoma does not increase the risk of local recurrence, enucleation or metastasis in patients with iris melanoma.[8] Despite high tumor control, there are radiation-related side effects of plaque radiotherapy, as evidenced by Kaplan-Meir 6-year percentages of radiation-related cataract (53%), glaucoma (19%), corneal epitheliopathy (6%), and radiation maculopathy (6%).[4]

Proton beam radiation has been described as an alternative treatment modality for iris melanoma. At 2 years follow-up, iris melanoma was reduced to flat scar in 6%, stable mass in 19%, and partially regressed mass in 75% of patients.[9] Side effects include cataract (45%), raised IOP (15%), anterior or posterior synechia (10%), uveitis (5%), keratitis (5%), and hyphema (5%).[9] Enucleation is often indicated for tumor recurrence or secondary complications such as intractable glaucoma.[1478] Finally, in some patients with significant co-morbidities or short life expectancy, observation may be the most appropriate management.

In conclusion, we present a young boy with iris melanoma initially treated with resection that eventually required plaque brachytherapy for tumor recurrence. Resection and plaque radiotherapy for iris melanoma have remarkable local success rates but complications of therapy can lead to visual damage.