Iris nevi and melanomas are the most common primary tumors of the iris, with an incidence ranging from 50-70% of all iris tumors; of these, 10-24% may be melanomas. Melanomas arise from malignant proliferation of the neuroectodermally derived iris stromal melanocytes, which replaces the normal iris stromal architecture. While melanoma is the most common primary malignancy of the iris, it comprises only 3%-10% of all uveal melanomas. Considerable controversy exists regarding the histopathologic classification and the malignant potential of iris melanomas.
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Most iris melanomas are believed to arise from active growth in preexisting nevi. Epidemiologic studies suggest that sunlight exposure plays a role in their pathogenesis. Chromosomal mutations may be involved.
Secondary glaucoma in iris melanomas may result from several different mechanisms, including the following:
Clinical and histopathologic studies show that only 13%-25% of all suspected iris melanomas actually meet the criteria for melanomas. Rates of transformation of a suspicious iris nevus to melanoma are reported at 4% in 10 years and 11% by 20 years.
The average age at diagnosis is 40-50 years; however, persons of any age can be affected. There is no predilection for sex or laterality of eye. In a study surveying 3680 iris tumors based on patient age at presentation, Shields et al found that nevus (42%), iris pigment epithelium (IPE) cyst (19%), and melanoma (17%) were the most common specific diagnoses at all ages.
Iris melanomas are more common in whites and in people with light-colored irides than in people of Asian or African descent.
Many patients provide a history of a nevus existing since childhood that has suddenly undergone rapid growth. Patients may present because of cosmetic concerns. Some patients may experience pain as a result of increased intraocular pressure.
Iris melanomas may be circumscribed or diffuse. Circumscribed melanomas have a nodular shape, and almost 80% arise in the inferior half of the iris. They are typically yellow, tan, or brown in color with a flat or rounded anterior contour. They can grow anteriorly into the anterior chamber or posteriorly into the posterior chamber, usually being limited by the lens and giving a “lion’s paw” appearance on ultrasonographic biomicroscopy (UBM).
Diffuse melanomas present differently from circumscribed melanomas, usually as a unilateral dark iris (acquired heterochromia) without focal thickening. Diffuse melanoma may also be associated with glaucoma. This glaucoma tends to respond poorly to medical management and causes severe disc cupping and functional loss. Diffuse melanomas also tend to be of the epithelioid cell type and carry a higher risk of metastasis than circumscribed melanomas do. A 2002 study by Demirci et al reported distant metastasis in 13% of patients with diffuse iris melanomas.
Ring melanomas involve more than two thirds of the angle and have associated glaucoma. Tapioca melanomas are multifocal nodules projecting into the anterior chamber that may be associated with glaucoma.
According to Shields, criteria for a clinical diagnosis of melanoma are as follows:
Ciliary body involvement is associated with a higher incidence of malignancy. Medial location and pigment dispersion onto the iris or the angle structures are associated with tumor growth.
Shields et al described clinical features predictive of growth from iris nevus to iris melanoma based on evaluation of 1611 eyes at an ocular oncology center. They state that the risk factors for growth may be identified by the following:
A thorough ophthalmologic examination, including transillumination and indirect examination with scleral depression, is essential for differentiating among iris cysts, primary iris tumors, and primary ciliary body melanomas.
Gonioscopy and UBM of the entire ciliary body must also be performed to rule out involvement before any therapeutic decisions are made.
Potential complications of iris melanoma include the following:
Other problems to consider include the following:
Sequential predilation photographs of iris lesions are extremely helpful for monitoring the lesions’ size and growth.
Ultrasonographic biomicroscopy (UBM) can be extremely helpful in differentiating solid iris masses from iris cysts. Melanomas involving the anterior chamber angle can also invade the ciliary body. Thus, in these tumors, gonioscopy and UBM of the ciliary body is critical. The anterior chamber angle can also be viewed, and ciliary body involvement can be evaluated. Nodular melanomas with posterior extension delimited by the lens may show a “lion’s paw” appearance on UBM. UBM has recently been used to help monitor the characteristics of these lesions after brachytherapy.
B-scan ultrasonography is recommended only if a ciliary body tumor is suspected. Fluorescein angiography may show irregular vascular channels with late filling. However, this modality is rarely helpful and is usually not done in clinical practice.
Diagnostic procedures include the following:
A multicenter study by Khan et al gathered information on biopsy-proven melanoma of the iris. The study found that the melanomas were most often brown and located in the inferior quadrants of patients with light irides. Commonly associated with angle blunting and spindle cell histopathology, melanomas are usually small and unifocal.
In a 2012 study, liver function testing was not helpful for the early diagnosis of metastatic uveal melanoma, although the high negative predictive value of such tests suggests that they might allow clinicians to reassure patients when test results are negative.
Malignant melanocytic stromal proliferation disrupts the normal iris stromal architecture. The Callender classification divides iris melanomas into spindle A (benign) and spindle B (fascicular, mixed, epithelioid, and necrotic) types. The Jakobiec and Silbert classification categorizes the lesions as spindle cell melanoma, spindle and epithelioid melanoma, or epithelioid melanoma. More than half of all iris melanomas reported in the literature are diagnosed as spindle cell melanoma.
Patients are observed through periodic examinations, photographic documentation, and ultrasonographic biomicroscopy (UBM). Glaucoma can be controlled by medication if no tumor infiltration of the angle structures is present.
The treatment of choice for growing lesions has typically been excision. However, reports in the literature have described the successful treatment of these lesions with brachytherapy and proton beam irradiation.
Excision is recommended if the lesion is impinging on the pupillary margin and interfering with vision or if secondary glaucoma is not controlled with medication. Excision should be considered if the lesion grows rapidly or encroaches on the chamber angle or if the fine-needle aspiration biopsy specimen shows malignant histology. Excision must be complete—that is, either a sector iridectomy or an iridocyclectomy, if the lesion encroaches on the chamber angle.
Glaucoma filtration procedures should not be attempted in the setting of a potential iris melanoma, because they may lead to seeding of the tumor cells and metastases.
Plaque radiation therapy with palladium 103 (103 Pd) has been used for these patients. Preliminary results show a high rate of success, with the most common complication being cataract formation in more than 75% of phakic patients.
Consultation with an oncologist is helpful if a metastatic lesion is suspected. After surgery, patients must be monitored at least every 6 months for metastatic development.
Patients should receive follow-up care as needed. They need to be monitored periodically for lesion recurrence and metastatic development as warranted.
Exposure to ultraviolet light should be minimized.
Most primary tumors of the iris are benign. Iris melanomas are considered to be much less aggressive than melanomas of the choroid and the ciliary body.
Prognosis is generally good in terms of survival. The mortality rate ranges from 0%-11%, depending on the cell type, the presence or absence of metastases, and ciliary body involvement; in the absence of ciliary body involvement, the rate is 0%-3%. Metastatic rate according to cell type are 2.6% for spindle cell, 10.5% for mixed cell, and 6.9% for epithelioid cell type.
Metastases occur in 2%-10% of all iris melanomas; a higher rate of metastasis is observed in cases of ciliary body involvement. Clinical features that may predict metastasis from iris melanoma include the following: