Dr. Geva Mannor discusses the risk and relation of melanoma of the eye as a stand-alone diagnosis and how it relates to the cutaneous manifestation.
So our next presentation is by jeeva manner on ocular and peri ocular melanoma, Jeeva has been a friend of this course since the 90s. He's very accomplished with numerous publications and on the editorial board of optimal logic pathology and clinical optimal logic publications. So we will hear from him now on ocular and peri ocular melanoma. Hello everybody. Can you hear me? Yes thank you terry. Thank you for the wonderful introduction dr ross is always a hard act to follow but I'll do my best. I want to thank the course directors Dr barrett Dr Greenway, I want to thank the organizers, Carrie and Megan and the people behind the scenes at broadcast dot com sky. Justin Donna and the rest of the team will switch gears and talk a little bit about ocular and peri ocular melanoma. I have no conflicts of interest to disclose in looking at A. Q. And peri ocular melanoma. The first thing that's important to realize is that ocular and periodically melanoma is much less frequent than the entire spectrum of cutaneous melanoma. And a ratio between 50-1. The incidents of ocular melanoma is stable and not necessarily increasing risk factors and need ideologies include ultraviolet radiation, irish color, skin color age and an internal actually melanomas welding. Looking at the various types or subtypes of a common peri ocular melanoma is the most common at about 83% is quarried. That would be an intraocular melanoma. Inside the eyeball. Uh the chlorine is part of the U via which is the inner lining of the excuse me, The middle lining of the eyeball. And what would be usually managed by retinal surgeons or specialists in ophthalmic oncology. It's beyond the scope of this course. Well we'll concentrate about are the island melanomas which about 10% of the whole total of peri ocular and ocular melanomas. And we consider them extra ocular and that they're not part of the eyeball. Well, briefly touch based on conjuring title melanomas which are considered extractor and they occur on the superficial layer of the eyeball. The transparent layer. One thing to keep in mind when you're looking at skin melanomas near the cheeks and browse is that these melanomas can creep towards the islets and the eyelid margins. So the slide on the your image on the left reminds me to flip the upper lids and look on the inside of the lower lids. And for example on the image on top of the right here there's a little dark melanoma just on this top of this clara here, just behind the cornea. And this same patient. When the upload was flipped over, you could see melanoma here, this image is reversed with the upper lid down. It's a surgeon's view. Let's go back now to the annual incidents of actual empirical melanoma in the United States versus California versus san Diego. And at the top of this table, you can see that the internal melanomas d'Youville or corridor melanomas are the majority. At about 2500 patients each year. In the United States, We estimate that there's about 750 Patients a year in the United States. It will develop island melanomas and you can see the breakdown of those 750 in the state of California and the county of San Diego. What I'd like to highlight just at the bottom of the graph. And this line here is the ratio between again Cutaneous Melanomas and Melanomas in the island. And that ratio is 266- one. Pain and vision loss are usually late symptoms with eyelid melanomas. A melodic variants exist. Gene expression profiling is an emerging technology for island melanomas but has been around for quite a while for Kuroyedov melanomas. But it's again beyond the scope of our talk. In looking at data from databases, cancer databases, comparing island melanomas and head neck melanomas. Here's a study from 2019 And they found that Allah melanomas represent no more than 2% of head neck melanomas. They found that island melanomas are likely to present earlier in stage one or zero compared to head neck melanomas possibly because they're just more visible as compared to a scalp melanoma. Alan melanomas are more common than females. I don't know. Numbers are more common in patients older than 50. Let's skip that last line there. Another database study that should be published in your journal the Blue journal Jad looked at 13 years of this uh in this database and divided island melanomas and to incite to and invasive and found that the five year survival and 10 year survival are slightly better in L. A. Melanoma is inside to compared to island melanoma that are invasive and compared to head neck melanomas. How are these numbers are fairly low. And even when you look at these total numbers together for Isla Melanomas, they're less than 2000 patients over a 13 year study Review. And remember the previous slides suggested that there should be about 750 patients that you developed island melanomas and toto. So we would expect that this is capturing no more than 1/5 of perhaps the 7500 patients that we would see over 10 years with island melanomas. So these database studies are only as good as the data that's input. But it still gives us some interesting information. For example, The medium bristle depth of the headache Melanomas was 0.9 mm, a little thicker than the median Arezzo death. For the Alabama was 0.7 mm possible. Regional lymph node status was the strongest independent Predictor of worse survival. With a hazard ratio of eight Distant metastases and blood cell thickness greater than two. was also related to survival. Let's review 11 studies comprising 201 patients with peri ocular melanomas. That was reviewed in a meta analysis in 2019 in the ophthalmic literature Of these 201 patients. The majority presented in the lower lid at more than half with reports stating that up to two thirds of patients develop their island melanomas in the lower lids. You can see the further breakdown in locations here. Fortunately melanomas in the media campus are rare. The mean area is 2.123.3 cm in these studies. Which to you I'm sure seems very small and I'm sure to dr galas and dr ross but to an island surgeon seems very large. Here's the breakdown with the pathology as reported in these studies. The mean Breslow depth needs 201 patients was 1.36 mm. And the work up included looking at lymph notes both clinically and through testing evaluating the bony status with an orbit ct soft tissues with the head, neck MRI and systemic evaluations as well. There'll be other talks data that will go into this further. About 5% of these patients died. It's not clear from all these starters whether that was for melanoma or not. Now let's look at some of the clinical evaluation of patients with pigmentation along the eyelids. This is an image of an right i this is the lower lip here. The applet here, inner aspect in a corner, outer corner and here's the pigmentation here. The majority of patients with pigmentation along the eyelids will wind up being benign. Nevertheless it's perfectly reasonable and in fact judicious for you to use your A. B. C. D. E. F. Rules your gut instincts. Other information about the specific patient to refer to an ophthalmologist. For consideration of evaluation, diagnostic testing and biopsies. Biopsies are done in the office and they're straightforward. They're painless. They don't affect the patient's vision and they don't harm the iron. Anyway and this patient was relieved to find out that this was a genius. Here's a lesion that turned out to be an eyelid margin melanoma. I would consider this uh subtle presentation. Here's a more Nigel or melanoma both pigmented on the left image and a melon arctic on the right image. If I saw this patient and the right my first thought would be basil cell. Here's a patient referred by Brett moore in the division of the dermatology and one of the satellites comma valley to Dr Greenway. And this turned out to be a melanoma. You can use your A. B. C. D. E. F. Rules and everything else you know about the patients to decide whether you need to biopsy or not. But I wanted to show you a clinical example. Here's another clinical example of a patient had cardiac transplantation was immuno compromised and had multiple prior skin cancers, basal cell squamous cell melanomas on the face. Prior surgeries on the eyelids as well for a variety of reasons and you're facing him now. So this is his right side and his left side. You can see the areas that dr Greenway circle and he boxed it all of these areas, fortunately the only area that came back positive was this one here, the largest circle which is on the lateral fear portion of the left lower lid at the chief junction. Here's another such patient refer to back to Greenway. You can see the image here and then closer images. The bottom one on the right. This was at the lateral left upper lid at the edge of the brow and turned out to be positive. And here's a patient with more advanced melanoma. She was unable to access healthcare for a number of years. And you can see two images when I first saw her and I didn't know the diagnosis, I would have assumed. This was a screen myself. You can see some pigmentation there. I just want to give you a spectrum of some of the clinical presentations in terms of local treatment for island melanomas. Margin controlled excision is the gold standard. However there is no evidence based margin guidelines and practice for island and periodical melanomas. It's hard to apply some of the uh uh recommendations from studies from other sites of the bodies. So here's some studies from both Australia. This one here. This one here. One from the plastic reconstructive societies. The general plastic reconstructive and aesthetic surgery. One from the actual plastic society survey and one from M. D. Anderson And my distort of this is that it's about 5-10 mm of margin with per millimeter of Brazil death. But of course I defer to people more experience than me like Dr. Greenway and his other staff in in the most clinic in terms of the the size of the margin there standing and things like that sentinel lymph node biopsy is an emerging option. My colleague dismally at MD. Anderson and dr ross knows well has probably more they experience than many other people in the country. I'm gonna skip this and I'm going to talk about the result of margin controlled excision for peri ocular melanoma. Here's some studies recently at the top here is out of M. D. Anderson from vita is molly the one right here in this room here is also out of the M. D. Anderson a couple here. This one here and this one here are from Australia and the one in blue at the bottom is Doctor Greenways personal experience at Scripps Clinic. You'll note that most of these studies have no more than 44 patients and the follow up is no more than three years and you can see the recurrence rate varied between 7% to 25% Interestingly Dr. Greenway Study which was published more than 10 years ago, had a follow up That was minimum of five years and a mean follow up of 94 months. And his recurrence rate is very satisfactory when compared to other studies, here's some typical cases. This is one from uh many years ago when I first started at the clinic patient here. And the image on the left. You can see pigmentation on the medial portion of the right island, inferior and lateral. And this close up here shows that some of the pigmentation is already onto the lid margin and lateral here. You can't see but was on the inner aspect of lived as well as here she was referred to dr green wig from new Mexico. Here's a wood's lamp image of the clinical extent of the cutaneous pigmentation. Here's the patient on the image on the left. She was treated with cereal most excisions and repairs here. The medial aspect of the upper lid should be the lateral aspect of the upper lid, lateral load ladder campus had been excised by mose and reconstructive leaving the media for another time here in the middle. She had the medial done. You can see she had various flaps and graphs reconstructed by me many years later. She presented again. Unfortunately with a little recurrence. I kept in touch with her and her family for about 10 years and at that point she was doing well and I'm pretty sure she did not die of melanoma. Is this patient that we saw before Dr Greenways cardiac transplantation patient from the past year. And I remind you that this is the area here on the left, lower lid that was positive. Here's the patient on the image on the left after dr Greenway did his most surgery and excision with the upper lid marked by me for a possible skin graft. Here's the patient a few months afterwards. You can see that the skin is healed fairly good. He still has persistent pigmentation on the cheek. He is happy because his vision did not reduce. He retained his vision. The comfort of the I was the same. We offered him another stage reconstruction uh revision or touch up but he declined. He'd had multiple numerous surgeries on his eyelids laterally here securely and fairly for all kinds of conditions. Here's the other patient that I want to show recently who had melanoma on the brow here lift up the lid and the tail of the left row. Here's the patient after Dr Greenway did the most excision here. Here's the patient a few months after I reconstructed him. Here's our patient had melanoma in situ of the lateral right low lid margin. You can see a close up here. He was missing the entire full thickness of the lower lid here. This is muscle that's actually at the level of the cheek, not the lid margin and some more skin that's missing here. He is again after the excision. And then after the reconstruction a few months later this photo was taken two months ago. He has retained his vision. He's comfortable he's able to go back to work. Here's the patient that we showed also earlier with the abnormal pigmentation louder portion of the right lower lid. Here he is in the middle. After dr greenly cleared his melanoma with most surgery. And here's a close up on this on the right you can see the entire full thickness left low lit including margin is gone. The lateral campus is gone and they allowed a portion of the right upper lip is gone. The most was done in late december of this past year. We have to blame a while because of covid concerns. I repair this by taking a Tasha countertop, a flat from the upper lid to the lower lid. He had no vision in that eye. For a few weeks two weeks ago I took him back to the r to open it. Hopefully next year I will give you some post op photos I want to mention also the contract travel. I want to uh will now move to the contract of melanomas and contract table melanomas are very very rare. We saw before and I want to remind you that the majority of contract title pigmentation is will be benign. This is a patient referred to me for a pigmentation here. This is the right i this is the inner corner of the right eye. This area here is called canonical and this area here is called the placa. This is where he had his pigmentation and this is part of the contract of oh I don't know if you can see it but you can kind of see that in front of the whites. Clara is a little reflection and that's a transparent contact. Eva fortunately we were able to biopsy it and confirm that this was benign again. A. B. C. D. E. F. Rules can apply to these lesions as well as individualizing patient care depending on their previous clinical characteristics. In terms of when to refer to my doctors, here's what's in the literature. These are two studies from two articles from your literature. The one on the bottom is he published in your Blue Journal. And in terms of referral to eye doctors usually the concern is about an internal melanoma inside the eye in the U. V. A. What you would call the in the retina. And this is what's recommended in the literature for patients to be referred patients with this plastic for new unusual are uncommon tv with these syndromes. Patients with your normal pigmentosa, patient with detainee small number that starts to be metastatic from an unknown primary and patients with actual general mental psychosis of soda should be referred to have the inside of the eye evaluated by enough images or retina surgeon to make sure that they do not have melanoma and the you via the corridor. The retina. Uh fortunately the pickup rate by the ophthalmologist is very rare. So this is not a very common occurrence. But this is what's in the literature. Patients with nervous about a can also have melanomas in the corporate and then the cns and I'll skip over the counter and tower because that's very unusual. So despite these recommendations in the literature, the actual number of patients who have both detainees in Accra melanoma is not that frequent. In a prior study, hubert one of dr greenways. Former fellows reviewed the world literature and found only 268 such patients. So while the literature says to refer and that's a good idea and it's appropriate and judicious fortunately in clinical practice it doesn't occur that often. I'd like to summarize again the talk so periodically melanoma Is much much much less common than cutaneous melanoma. No more than 2% of head, neck melanomas and much less than 2% of the toilet. Cutaneous melanomas melanomas that occur in the cheek and the brow can extend inside of the lid in the contract. IVA. Therefore if you're looking at such patients, remember to look on the inner aspect of the conjunctivitis or inner aspect of the islands of both the upper and lower lids margin controlled excision. Imperial feminism is a gold standard of all the patients with pigmentation on the Contact Eva. Less than 2% of the melanomas. But again utilize your A. B. C. D. E. F. Rules clinical judgment, gut instinct and other information and refer them as often as you would like for evaluation by ophthalmologists for diagnostic evaluation and possible biopsy communication between skin specialist. Skin cancer specialists and I docks is crucial to allow us to give our patients the best possible care. I thank you for your attention and it's an honor to speak at your course. Thank you Dr manner. If you have questions, please send the man and we will ensure that you get responses from DR manner.
