Advances in Diagnosing and Treating Iris Melanoma

Podcast Transcript

Dale Shepard, MD, PhD: Cancer Advances. A Cleveland Clinic podcast for medical professionals exploring the latest innovative research and clinical advances in the field of oncology.

Thank you for joining us for another episode of Cancer Advances. I'm your host, Dr. Dale. Shepard, a medical oncologist here at Cleveland Clinic directing the Taussig Early Cancer Therapeutics Program and Co-Director of the Cleveland Clinic Sarcoma Program.

Today, I'm happy to be joined by Dr. Arun Singh, Director of the Department of Ophthalmic Oncology. He has been a guest here for three previous episodes of this podcast, and those episodes are still available. He's here today to talk to us about iris melanoma. Welcome.

Arun Singh, MD: Well, thanks for having me.

Dale Shepard, MD, PhD: Maybe you can remind us a little bit about what you do here at Cleveland Clinic.

Arun Singh, MD: Well, I run eye oncology, or ophthalmic oncology service, which is to deal with all ocular tumors, some benign, some malignant, some simulating conditions, primary, secondary, metastatic. All kinds. Any tumor-related things affecting the eyes ... They come to me. I run the service.

Dale Shepard, MD, PhD: Excellent. We're going to talk about iris melanoma today. Tell us a little bit about iris melanoma. A lot of different people might be listening in. Might not be really familiar with that. They think melanoma, and they think skin. And tell us a little bit about this as a disease.

Arun Singh, MD: Skin melanoma is, of course, the most common kind of skin melanoma. And uveal melanoma ... The melanoma of the uvea of the eye is the second common site. And within it, we have iris. That's the blue part or the brown part of the eye. And then you have the choroid and the ciliary body. Those are the inner parts of the eye. Iris is what people will call the colored part of the eye. Most of in the US is blue or light brown in color, and rarely you can get melanoma in that structure. That's the iris melanoma.

Dale Shepard, MD, PhD: And how common is that?

Arun Singh, MD: I would say it's the least common kind of uveal melanoma. And uveal melanoma we say about six per million. And this would be about maybe one R per million population. It's the rare kind of uveal melanoma, but it's the most visible one because it's the external one. You can see it because cornea is transparent. You can see whatever's happening to the iris.

Dale Shepard, MD, PhD: Gotcha. Are there any particular risk factors? Who's at risk of getting this?

Arun Singh, MD: We see ... Generally, I've seen in light-colored irises, people with blue iris, a light brown iris, North European ancestry. That's most of the US population. Some risk maybe with sunlight exposure, but very minimal. Not really very strong risk from that. And no real occupational risk. Just basically your race.

Dale Shepard, MD, PhD: And so, when we think about melanoma in the skin, there's a whole education about sunscreen and things like that. But with this, not necessarily anything that one can do.

Arun Singh, MD: Not really. First of all, it's very rare, and we don't have very strong data to say that it's related to sunlight exposure because, if it was, then many more people would get it.

Dale Shepard, MD, PhD: Right. When we think about this as a disease, how is this typically managed?

Arun Singh, MD: It's initially diagnosed with somebody noticing some spot on the iris, or you go for a normal eye exam, routine eye exam, and your optician or doctor, ophthalmologist, will notice a spot on the iris and then photograph it or take a note of it. And eventually, it starts to grow. And that's how you figure it out that it's actually melanoma. It's by examination more than anything else.

Dale Shepard, MD, PhD: And so, are most of these ... You mentioned with exams and things. Is this mostly something that we catch early? As you notice, people see it, or they get an eye exam, and you notice it? Or is this something sometimes people get away from them, and it's later?

Arun Singh, MD: No, the iris melanoma on the whole is detected early because of its location and the prominence. Everybody looks at their own eyes 50 times a day. Iris melanoma tend to be very small. We say about three to four millimeter in size in general by the time we diagnose them. Compared to skin or other parts of the body, it's actually very small. And also, it reflects, therefore, the lower risk of metastasis, et cetera, because you're catching it early. Catching it small.

Dale Shepard, MD, PhD: When we think about from a treatment standpoint, these are things ... As you mentioned, you catch them small. Surgical intervention, primarily?

Arun Singh, MD: Primarily surgical, which is excision of the iris. And then we are ways to recreate the pupil. We cannot recreate iris. Iris doesn't heal. If you cut it, that part is missing. It'll always be missing. You can pull it and stitch it together, but you can recreate the pupil. If it's a bigger area, then the pupil cannot be recreated. You have a big defect there. And of course radiation is the alternative. And we like we do for other melanomas of the eye. We can also use the radiation for it. It works very well.

Dale Shepard, MD, PhD: And then I think, as I recall in a previous episode, we talked about uveal melanoma and some newer therapies. It sounds like this isn't something, as you mentioned, metastasized, so we don't really have to think about iris melanoma as much for those kinds of therapies?

Arun Singh, MD: Yeah. Overall, we think ... We estimate the risk of metastasis is about 1% in five years. We have had about 100-some-20 cases over many years, and we haven't had one metastasis from it. The treatment is really focused more on the local cure. And if you can achieve that local control, then I think we are achieving a cure in this case.

Dale Shepard, MD, PhD: And so, in terms of outcomes, if we find it, and we treat it, good outcomes?

Arun Singh, MD: Very good outcomes. Local recurrence rates 1% to 5%. After surgical excision, after radiation, may close to 1%. Systemic metastasis 1%. We're talking about 99% of local control. Freedom from metastasis. Very good outcomes.

Dale Shepard, MD, PhD: I mean, first off, I'm jealous because I treat sarcomas. When we think about this ... Not common. Somebody finds this. Oftentimes, I'm guessing it might be a community ophthalmologist. From the standpoint of management, should patients come to a place where their ophthalmologist has seen that somebody like yourself?

Or is this really, being small, something that could be taken care of in a community setting?

Arun Singh, MD: I think the first thing really to do is to take a photograph of it because, if it's small, very likely it's benign because we have nevi in the iris. Freckles in the iris. That a lot more common. Diagnosis becomes tricky. You have benign things that are a lot more common, and you have the rare malignant things scattered between it. And how do you figure this out? We'll talk about that later, perhaps.

But let's say it's a small spot that has been detected. The smartest thing is to take a photograph of it. At least, we know objectively over time if there's a change or not because, if you're not sure, many times we'll just observe it. And if you have a photograph from baseline, that helps a lot.

Dale Shepard, MD, PhD: And so, you mentioned a few things that might be mimics for things that are more problematic. Maybe if you can elaborate on that just so people ... They happen to look in, and see something abnormal. Sounds like this is relatively rare. What are those more common things that they may be experiencing?

Arun Singh, MD: Just like in skin, you have freckles. We have freckles on the iris. They tend to be very tiny, small, smudgy-like spots. And then you have nevi that are more confluent, more solid looking, and that also are quite common in the iris.

You really can't tell from the first look whether it's really a long-standing nevus versus new melanoma. If somebody has ... Many people will see something new popping up. If they do, then it's very likely to be something more sinister. But if something that's been there for years and years and nothing has changed, that's likely to be benign and nevus. History and some kind of a documentation helps us a lot.

Dale Shepard, MD, PhD: And I guess things like nevi and freckles are things that oftentimes have been there, again, like you say, for long periods of time. That time factor sounds important-

Arun Singh, MD: Is important.

Dale Shepard, MD, PhD: Right. When we diagnose these ... Let's just kind of think about diagnosis. Currently, how are these diagnosed? Certainly, observation. Do you only get biopsied? Or where do we go from a diagnostic standpoint?

Arun Singh, MD: The diagnosis is generally clinical. We can look at the lesion or the tumor itself and figure out a few things. We say with the size. If it's bigger than three millimeters, for example, in any dimension, then we would say it's very likely to be melanoma. If it's bleeding or causing seeding, breaking into little flakes or pigment, then that's very likely or, I would say, suddenly a melanoma because nevus wouldn't cause bleeding, and nevus wouldn't cause flaking.

Then other things also gives us, like any satellite lesions. And more recently, we figured out any kind of feeder vessels. If it's a melanoma, it would have vessels feeding into it, and we can see them, exam eyes, or by angiography. We can do angiogram of the iris to see the iris vasculature. And if you can find vessels, then we would say that it's very, very likely to be melanoma.

Dale Shepard, MD, PhD: Gotcha. What would you describe as the biggest challenges in the current way a diagnosis is made? And then we'll talk about how that might be improved.

Arun Singh, MD: In the baseline, we say nevi are common. Many people have it. And then you have a melanoma, which is rare. Among all the rare things, we have this one tumor that can be a serious one. A malignancy is a malignancy. It can certainly spread within the eye, and there are eyes that even come to a nucleation, rarely, if it's neglected. It's not a tumor is minor in the sense. It's minor if it's treated correctly. But like any cancer, it can be a difficulty later on.

The biggest challenge is a clinical diagnosis without invasive techniques, without biopsy, without cutting. How we can make a diagnosis by looking at it. To me, that's the biggest challenge, and we try to focus on that.

Dale Shepard, MD, PhD: And again, given the rarity, most ophthalmologists, if they're doing routine exams, aren't going to see many of them. What kind of ways have you been working to try to improve the ability to diagnose these?

Arun Singh, MD: When it's a photograph, of course we take a photograph. And from there, we can see if there's any change from prior exams or not. That's very useful. I mentioned angiogram.

We also do OCT scans, which are laser-based scans, about the thickness and the depth of it. We also do ultrasonographic scans of the iris to see, again, the depth, the shape, and how deep it goes to the stroma and how big it is. We have kind of tools by which we can measure it accurately.

Dale Shepard, MD, PhD: And then I guess we ... If you look at some other things, like breast mammograms, we've gotten into more computerized analysis of imaging and things like that. Tell us a little bit about ways that we can improve diagnosis through those kinds of techniques.

Arun Singh, MD: We have been recently getting into that aspect of it because of images, right? Ophthalmology or oncology or iris, particularly, is all images. We can see everything. We can document everything. We can measure everything. We try to use machine learning. We have patients, say, with nevi. 100-plus one of those. And we observe 100 patients that are biopsy-proven melanomas. And we have photographs of all of them. And we try to figure out statistically, mathematically, what are the features that are different between the two groups.

And you're able to create a predictive model that can, if you have certain features ... You say we are 85%, 89% correct or accurate in predicting that it's a melanoma rather than a nevus just by looking at it and detecting all the features on it.

Dale Shepard, MD, PhD: Is that to a point where there's something available that you can take a picture and then, sort of in a clinical sense, make those recommendations in terms of just observation or surgery?

Or are we too early in the process?

Arun Singh, MD: Right now, this isn't image-based in the sense that it's not AI analysis of the image, per se, yet, but it is the analysis of the attributes of the image. Somebody has to look at the image and draw out inferences and then put it into a model and figure out the predictability.

But we are hoping to get into this business where you just have the image directly put in and nevus versus melanoma and then let the computer tell you whether it's nevus or melanoma. We haven't gone in there yet. But again, in a situation like this, you need thousands of cases. You need large number of cases, and we don't have these cases. This is a rare disease. I'm not sure if we'll ever get there in a robust way, but we're trying.

Dale Shepard, MD, PhD: And is that something that you collaborate with other institutions and sort of gather as much information? Or how are we going about doing that?

Arun Singh, MD: We are open to collaboration, but again, it comes down to whether the diagnosis of melanoma was based by biopsy. If you did make a biopsy of the tumor, then we don't know what somebody treated. We have to be very clear on the inclusion in our groups, whether it's nevus versus melanoma, based on what? Based on biopsy. I think it's the way to go. It's hard to find biopsy-proven cases because many times people just treat without biopsying the tumor. Then we never know what it was because it's already been treated.

Dale Shepard, MD, PhD: Right. When we think about patients and people who might be listening in, who should come to a specialized center and be seen by somebody like yourself who sees tumors of the eye?

Arun Singh, MD: I would say that, if you go for a checkup, and they look at your eye, and you're told that you have a growth or a nevus that wasn't there before or looks odd or something that the doctors haven't seen before, I think that those should be the warning signs that you need to come to a more specialized center.

Dale Shepard, MD, PhD: Makes sense. In terms of eye exams, how often should people be getting eye exams?

Arun Singh, MD: There are certain guidelines from American Academy of Ophthalmology. You say that somewhere in adulthood between 20 to 40 you should have one exam so you know that it's kind of all normal. And after that, maybe every five years or so. And then above age 65, they start to make it into once or every two years kind of exam.

But if you have some other risk factors, like diabetes, then obviously once a year. If you have some other family history, like glaucoma or macular degeneration, then you go once a year. But if you're otherwise, maybe every two years is probably reasonable.

Dale Shepard, MD, PhD: Well, it sounds like that there's some potential, get enough data, that maybe we have a good way to come up with some better ways to diagnose this other than observation, but it sounds like we have some more details to come up with, and maybe we'll be getting some updates along the way. Huh?

Arun Singh, MD: There are always room for improvement.

Dale Shepard, MD, PhD: There you go.

Arun Singh, MD: Thank you, sir.

Dale Shepard, MD, PhD: Well, appreciate you being with us.

Arun Singh, MD: Thank you so much.

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