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Differentiating Iris Pigmented Lesions: a Primer

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Differentiating Iris Pigmented Lesions: a Primer ONCOLOGY CLINICAL UPDATE Differentiating Iris Pigmented Lesions: A Primer hat do you do when a 1 2 patient walks in with a pig- Wmented lesion on the iris? The first thing that likely runs through your mind is: “What exactly am I look- ing at, and what risk does it carry?” Melanocytic growths represent 70% of iris lesions.1 The six most common types that comprehensive ophthalmol- ogists might see in their offices on any 3A 3B given day, according to Carol L. Shields, MD, are: freckle, nevus, Lisch nodules, melanocytoma, melanocytosis, and melanoma. “The last three are the ones to worry about,” said Dr. Shields, at Wills Eye Hospital in Philadelphia. Iris Freckle 3C 3D Iris freckles tend to rest on the iris sur- face like a flat pancake and are typically multifocal, bilateral, and mostly affect blue and green irides (Fig 1).2 “They are not actual masses—just increased melanin pigments associated with UV exposure—so they look very different from benign or malignant tumors in the KNOW YOUR LESIONS. (1) Iris freckles. (2) Lisch nodules. (3A) Pigmented nevus, iris,” said Alison H. Skalet, MD, PhD, (3B) nonpigmented nevus, (3C) corectopia, (3D) ectropion. at the Casey Eye Institute in Portland, Oregon. associated with an increased risk of tends to manifest by age 5. It can be a Iris freckles are not typically a pre- cutaneous melanoma.3 “I don’t worry marker for neurofibromatosis type 1 cursor to iris melanoma, and patients about these patients in terms of risk for (NF1). Lisch nodules typically are a with freckles don’t need additional iris melanoma, but I do refer them to a tan color (even on a brown iris), follow-up from an ophthalmic stand- dermatologist,” said Dr. Skalet. bilateral, multifocal, and about 1 mm point, according to Dr. Skalet. But a in diameter with tiny seeds around recent Australian study showed that Lisch Nodule them (Fig. 2). “You want to check the having three or more iris freckles is This is a hereditary condition that patient’s skin for neurofibromatosis features and ask about neurofibroma- tosis in the family,” said Dr. Shields. BY GABRIELLE WEINER, MS, CONTRIBUTING WRITER, INTERVIEWING Lisch nodules can be associated with TIMOTHY S. FULLER, MD, CAROL L. SHIELDS, MD, AND ALISON H. SKALET, choroidal freckling. They do not turn Courtesy of Carol L. Shields, MD of Carol Courtesy MD, PHD. into melanoma. EYENET MAGAZINE • 33 Iris Nevus 4A 4B The chubbier cousin of the iris freckle, an iris nevus appears as a pigmented (Fig. 3A) or nonpigmented (Fig. 3B) spot, typically about 3 mm in diameter and with an inferior clock-hour posi- tion. They penetrate the iris stroma, of- ten distorting its architecture, and may be associated with corectopia (pulling 5A 5B on the pupil, altering its shape; Fig. 3C) or iris ectropion (Fig. 3D), according to Dr. Skalet. If you see corectopia or iris ectropion, it must be a nevus or something worse, she said. A 2009 meta-analysis found that iris nevus has a 1.53 odds ratio for associ- ation with uveal melanoma.4 “It is a MANIFESTATIONS. (4A, B) Iris melanocytoma. (5A, B) Iris melanocytosis marker that tells us we should dilate these patients at least once a year to is a congenital condition in which the Clinical features. Iris melanomas check the back of the eye for melano- uvea gets too much pigmentation, are typically larger and more vascular ma,” said Timothy S. Fuller, MD, at putting the eye at risk for melanoma, than nevi. Depending on location, they Texas Retina Associates in Dallas. said Dr. Shields. Melanocytosis can be may be associated with ectropion uveae complete (Fig. 5A) or sectoral (Fig. or sectoral cataract, according to Dr. Iris Melanocytoma 5B) and is characterized by mammilla- Skalet. When she sees seeding on the A “bigger and badder” subtype of iris tions, appearing as tiny micronodules surface of the iris stroma or within the nevi is melanocytoma, said Dr. Shields. within the pigmented area. Scleral and angle (especially if associated with in creas- This tends to have a dark brown, homo- uveal pigmentation are hallmarks and ed intraocular pressure), extra scleral geneous appearance with a granular sometimes there is skin pigmentation extension, or progressive growth, she surface and often a little bit of seeding around the eye. “Make sure you lift the worries about the melanoma spread ing. around it. It can be very large, espe- lids and check if the patient has scleral “In addition to the nodular pattern cially in children (Figs. 4A, B) and is pigmentation; that will nail the diagno- of growth, comprehensive ophthalmol- associated with secondary glaucoma sis,” Dr. Shields said. ogists need to be aware that thin, diffuse (11% at five years).5 “Melanocytoma Melanocytosis carries a 1 in 400 iris melanomas exist and carry risk for carries only a small risk for growth into risk for melanoma among Caucasians, spread outside the eye. These tumors melanoma, but it is frequently mistaken according to Dr. Shields. Melanoma can are often associated with elevated intra- for melanoma,” she said. develop in the uvea, the orbit, or the ocular pressure,” said Dr. Skalet. meninges, so patients need to be mon- To biopsy or not? Melanoma is Iris Melanocytosis itored in all those sites. “The best way some times confirmed with fine-needle When a patient walks in with one green is to get magnetic resonance imaging aspiration biopsy, but most ocular mela- iris and one brown iris, or one light (MRI) of the head and orbit, but no nomas are diagnosed clinically; it’s not brown and one dark brown, the darker one has established guidelines on how standard to do a needle biopsy for diag- iris could have melanocytosis, which frequently to do so. In our office, we do nosis of iris melanoma, said Dr. Skalet. an MRI every three to five years,” said Biopsies can be tricky and carry a Dr. Shields. risk of bleeding and potentially seeding ABCDEF Guide the tumor. “Even when biopsy is per- Iris Melanoma formed by a skilled ocular oncologist To predict iris nevus growth into mela- who sees these cases regularly, it’s not Clinical factors predictive of nevus noma, Dr. Fuller relies on the ABCDEF unusual to get a nondiagnostic read growth to melanoma: Guide (at left).6 “I highly recommend because the lesions tend to be fairly A Age ≤40 years posting the guide in your exam rooms small,” Dr. Fuller explained. B Blood in the anterior chamber for reference. If your patient meets even That said, for cases in which it’s C Clock-hour inferior just one of those criteria, your index of difficult to make a clinical diagnosis, a D Diffuse configuration suspicion for melanoma should go way biopsy can be helpful for two reasons. E Ectropion up,” said Dr. Fuller. The three strongest First, cytology indicates whether the F Feathery margins predictors are diffuse configuration fol- tumor is a nevus or melanoma. Second, SOURCE: Shields CL et al. Ophthalmology. lowed by clock-hour inferior and blood molecular prognostic testing—when 6 2013;120(4):766-772. in the anterior chamber. it is a melanoma—helps predict how L. Shields, MD of Carol Courtesy 34 • FEBRUARY 2020 aggressive the cells in the tumor might could spare the patient from radiation, be. “The gene expression profiling test monitoring the lesion closely instead. was developed for tumors in the back “Taking photographs and getting An Iris Lesion May Be of the eye, so we’re extrapolating when imaging is critical. Notes are not as Melanoma If . we use it for tumors in the iris,” said Dr. reliable as an image. You need concrete Skalet, “but there is an ongoing study evidence of what the lesion looked like • there is evidence of growth that includes iris melanomas, and the at point A so that you can refer back to • the tumor has intrinsic vessels researchers are looking at the outcomes it at point B if you become concerned • there is seeding on the iris or in for patients based on the gene expres- that it has grown,” said Dr. Skalet. the angle sion profile result.” Imaging starts with slit-lamp mea- • the tumor is more than 3 clock surements. If there is any appearance hours Mission Critical: Get Baseline of dimension or depth to the lesion, • the tumor is invading the ciliary Images it’s advisable to perform ultrasound body “When a comprehensive ophthalmol- biomicroscopy to precisely measure the • there is elevated intraocular pres- ogist sees a patient with a pigmented size of the lesion, check for ciliary body sure or seeding in the angle iris lesion, I can’t stress enough how involvement, and look for spontaneous important it is to get a good photo to vascular movement, which would sug- serve as a baseline,” Dr. Fuller said. He gest melanoma—as well as doing goni- recently had a female patient in her 60s oscopy to check for any pigment in the other cancers we deal with, size mat- with a very large pigmented iris lesion. angle, which further suggests melanoma, ters!” said Dr. Shields. “Ocular oncolo- When she was examined at the slit lamp, said Dr. Skalet. gists are familiar with all the risk factors he was sure she had a melanoma that and can pick up on a melanoma when needed treatment. But, thankfully, the Monitoring Schedule it’s still tiny, hiding out as a nevus.” patient had a slide from the 1970s when Monitoring depends on how long a the spot was first seen by a diligent oph- lesion has been there.
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