Iris Melanoma

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Overview

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. Considerable controversy exists regarding the histopathologic classification and the malignant potential of iris melanomas.

Go to Ciliary Body Melanoma, Choroidal Melanoma, and Conjunctival Melanoma for complete information on these topics.

Pathophysiology and Etiology

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:

Epidemiology

Although iris melanomas are the most frequent primary malignancy of the iris, they form only a small proportion (3-13%) of all uveal melanomas. Clinical and histopathologic studies show that only 13-25% of all suspected iris melanomas actually meet the criteria for melanomas.

The average age at diagnosis is 40-50 years; however, persons of any age can be affected. No known sexual predilection exists. 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.[1]

Iris melanomas are more common in whites and in people with light-colored irides than in people of Asian or African descent.

Clinical Presentation

Patient history

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.

Physical examination

Iris melanomas may be circumscribed or diffuse. Circumscribed melanomas have a nodular shape and are more common in the inferior iris. 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). 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.

Diffuse melanomas cause acquired heterochromia and are 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.

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:[2]

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.

Many of these traditional signs of malignancy are being challenged by new studies. However, even though many of these features may be more common in benign tumors than in malignant melanomas, their presence should alert the ophthalmologist to closely monitor the lesion.

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.

Complications

Potential complications of iris melanoma include the following:

Differential Diagnosis

The differential diagnosis includes the following:

Leiomyoma, Iris

Other problems to consider include the following:

Imaging Studies

Sequential photography

Sequential predilation photographs of iris lesions are extremely helpful for monitoring the lesions’ size and growth.

Ultrasonographic biomicroscopy

Ultrasonographic biomicroscopy (UBM) can be extremely helpful in differentiating solid iris masses from iris cysts. 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.[3]

Other studies

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

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.[4]

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.[5]

Histologic Findings

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.[6]

Treatment & Management

Medical care

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.

Surgical care

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.

Consultations

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.

Further outpatient care

Patients should receive follow-up care as needed. They need to be monitored periodically for lesion recurrence and metastatic development as warranted.

Deterrence/prevention

Exposure to ultraviolet light should be minimized.

Prognosis

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% to 11%, depending on the presence or the absence of metastases and ciliary body involvement; in the absence of ciliary body involvement, the rate is of 0-3%.

Metastases occur in 2-10% of all iris melanomas; a higher rate is observed in cases of ciliary body involvement.

Author

Nadia K Waheed, MD, Assistant Professor of Ophthalmology, Tufts University School of Medicine

Disclosure: Nothing to disclose.

Coauthor(s)

C Stephen Foster, MD, FACS, FACR, FAAO, Clinical Professor of Ophthalmology, Harvard Medical School; Consulting Staff, Department of Ophthalmology, Massachusetts Eye and Ear Infirmary; Founder and President, Ocular Immunology and Uveitis Foundation, Massachusetts Eye Research and Surgery Institution

Disclosure: Nothing to disclose.

Specialty Editors

Russell P Jayne, MD, Consulting Vitreoretinal Surgeon, The Retina Center at Las Vegas

Disclosure: Nothing to disclose.

Simon K Law, MD, PharmD, Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Disclosure: Nothing to disclose.

Christopher J Rapuano, MD, Professor, Department of Ophthalmology, Jefferson Medical College of Thomas Jefferson University; Director of the Cornea Service, Co-Director of Refractive Surgery Department, Wills Eye Institute

Disclosure: Allergan Honoraria Speaking and teaching; Allergan Consulting fee Consulting; Alcon Honoraria Speaking and teaching; RPS Ownership interest Other; EyeGate Pharma Consulting fee Consulting; Bausch & Lomb Honoraria Speaking and teaching; Bausch & Lomb Consulting; Merck Honoraria Speaking and teaching

Chief Editor

Hampton Roy Sr, MD, Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Disclosure: Nothing to disclose.

References

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  2. Shields JA, Sanborn GE, Augsburger JJ. The differential diagnosis of malignant melanoma of the iris. A clinical study of 200 patients. Ophthalmology. Jun 1983;90(6):716-20. [View Abstract]
  3. Torres VL, Allemann N, Erwenne CM. Ultrasound biomicroscopy features of iris and ciliary body melanomas before and after brachytherapy. Ophthalmic Surg Lasers Imaging. Mar-Apr 2005;36(2):129-38. [View Abstract]
  4. Khan S, Finger PT, Yu GP, et al. Clinical and pathologic characteristics of biopsy-proven iris melanoma: a multicenter international study. Arch Ophthalmol. Jan 2012;130(1):57-64. [View Abstract]
  5. Mouriaux F, Diorio C, Bergeron D, Berchi C, Rousseau A. Liver function testing is not helpful for early diagnosis of metastatic uveal melanoma. Ophthalmology. Aug 2012;119(8):1590-5. [View Abstract]
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