 So, like I said, I'm Mason Schmitz. I'm from here originally attending school at Boston University in fourth year. And I just wanted to thank everybody for this opportunity to present to you. I'm going to present on conjunctival melanoma rising from primary acquired melanosis. So this case is actually a case that I encountered working in Dr. Mamelis' lab, a tissue sample that came into us. But it was Mr. S, an 89-year-old male who was referred for evaluation for a left conjunctival neoplasm. The story was that he had noticed some bumps on his left eye several months ago. And the bumps were accompanied by redness, irritation, tearing. I'm sorry, this was white type before. So let me just try to, I'm just going to switch this. The bumps were on his left eye. He'd noticed them for a few months. And it was causing him some irritation, some redness, and some blurriness in his vision. He had initially presented to an outside ophthalmology clinic. And they saw him. They gave him some eye drops. The symptoms didn't resolve. And three months later, they'd noticed not only that the symptoms hadn't resolved, but also that he, that they'd seemed, that these bumps had seemed to have grown. So they decided to do a conjunctival biopsy. And that initial path readout was read as suspicious for invasive squamous cell carcinoma. As a result, this patient was referred to, to this institution here, where Dr. Mifflin saw him for further evaluation. On presentation here, this is kind of what his patient history looked like. I'll just kind of jump through a few pieces here. The conjunctival neoplasm, he had cataracts in both of his eyes. A few medical conditions you can see there. And the medications he was taking correspond with those, with those medical conditions. The only ocular medications that he was on was Tobridex and azacyte after the conjunctival biopsy. His exam is 2050 in his right eye, 2200 in his left eye. His intraocular pressures were good. And his pupils were equal around it with no afferent pupillary defect. On, on further exam in the right eye, there was some moderate blepharitis and a moderate cataract. But on the left side is where the real interesting pathology was. He, in addition to the moderate blepharitis also here, he had some conjunctival thickening here in the, in the canthus, lateral canthus. Also kind of inferiorly and then infronasally here. This was more of a pigmented lesion, especially here with some pigment kind of extending down right there. So this is a picture of that infronasal lesion that was taken. As you can see, it's pigmented, it's round, it looks a little bit raised. So it was, it was decided that they would obtain an MRI of his orbit face and neck to see if there was any further progression of this, of this neoplasm. And then because of the location of this, of these lesions in the, in the fornic's kind of lateral canthus and involving the inferior lid, it was decided to refer this patient to Dr. Patel for surgery. So here's a picture of the MRI's, you can see. And the conjunctival thickening, let me just actually zoom it up a little bit here. And that kind of loses some of the quality. But you can see there's some conjunctival thickening kind of on the lateral side. It extended laterally into the fornic's. It didn't appear to involve any of the extraocular muscles, in particular the lateral erectus. And no extension intracranially also. It was determined that there was no evidence of this MRI of metastatic disease. So the surgery was performed in the excision of all of these neoplasms in the fornic's superior and inferiorly. And there was a removal of the, of the lesion on the lid with a reconstruction, stage one reconstruction of that lid. Also the conjunctival tumor infranasally was removed with conjunctival plasty and cryotherapy was done around the tumor edges. So now the histopathology came back and it was read as malignant melanoma of the orbit arising from a preexisting primary acquired melanosis. Because there was this question of squamous cell carcinoma versus now this, what they were reading is primary acquired melanosis. The sample was also sent for special immunohistochemistry, HMB45 and S100. This isn't the actual histology of the patient but it's representative. So here you see these atypical melanocytes that are extending throughout the epithelium and into beyond the basement membrane. Here is an HMB45 stain which is stained for melanocytes and the S100 stain which indicated this was indeed melanocytic in nature. Yep. Yeah, there were seven, initially they did two biopsies, one kind of laterally on the conjunctiva, nasally and one temporally. Removed all the, this was the pathology for red for all of them, uh-huh. So what is primary acquired melanosis? It's a flat noncystic pigmented lesion. It arises in the conjunctiva of the cornea, the caruncal and it needs to be distinguished from the more common localized nevus and racial melanosis. Especially in people with dark skin, racial melanosis needs to be ruled out and it's usually, it's also flat but it's usually bilateral. The histology can also be further differentiated as having, as being with or without atypia. So let's show some of what that atypia is. This is without atypia. You see these benign melanocytes here that are confined to the basal layer of the epithelium and that's typical of without atypia. Now with mild atypia, again it's confined to this basal layer, not extending past the basement membrane or really too much into the epithelium but you see that they're kind of more atypical with condensed chromatins at times and some nucleoli. Now PEM with severe atypia, it is now extending, these atypical melanocytes are now extending into the epithelium, still not going past the basement membrane at which point it would be considered melanoma. You also see epithelioid cells which can be typical of PEM with severe atypia. The epidemiology of primary acquired melanocytes is it's more common in Caucasians, women and at an average age of around mid-50s is what I saw in most of the literature but however can affect all races and genders and the incidence has also been sub varied accounts of how common this was. One study by Glorin and Alexandricus where they saw thousands, over a thousand samples in their institution, they thought the institution was around, or the incidence was around 36%. Others think this may even be higher because of the asymptomatic nature of primary acquired melanocytes, oftentimes it doesn't present. So the clinical features is usually unilateral, distinguishing it from racial melanocytes, it's flat, pigmented in the locations we talked about previously. The average diameter is in one of the studies I saw was about 8 millimeters per lesion and on average there were around two of these lesions per eye when it was seen. Almost always asymptomatic, sometimes some redness and mild irritation and these do grow or have the potential to grow. There's also the potential for progression of PAM to conjunctival melanoma and this is what you worry about. It is estimated that about 50 to 75% of conjunctival melanoma arises from primary acquired melanocytes. The other main player that gives rise to conjunctival melanoma is anivis and those give rise to about 20 to 25% of conjunctival melanomas, otherwise it can also arise de novo. Here you see a patient here who had some PAM on here in the inferior fornix and kind of going into the cancer and this patient had this excise with cryotherapy and then was lost to follow-up and here you see this patient returning five years later after he was lost to follow-up with this melanoma that had been developed. Here are other examples of primary acquired melanosis giving rise to melanoma and in this case you see an amelanotic lesion actually of melanoma which PAM can also give rise to. So I wanted to highlight a study that was done by Shields at all at the Wills Eye Institute. They had a study where they had 311 eyes they were looking at retrospectively that had primary acquired melanosis. The initial determination for treatment was 194 of these were just observed, thought that they were looked by nine of them that they could be observed and 107 were biopsied initially. Of those that were observed at an average of 32 months, 16% of these showed growth with no progression to melanoma, 5% of these showed growth with progression to melanoma at an average time of 56 months. Of the biopsied lesions, 27% of those recurred at an average time of 19 months and 3% of those recurred progressing to melanoma at an average time of 39 months. So in determining what predictive factors there were in looking at the initial PAM lesion of its progression and recurrence, they determined that the main predictive factor was clock hours or how many clock hours the initial lesion occupied. In a lesion that occupied one to two clock hours, it was less likely to progress and also less likely to recur after excision. However, a lesion that occupied more than four clock hours was more likely 6.8 times more likely to progress to melanoma and a lesion that occupied 12 clock hours was over 20 times more likely to progress to melanoma than a one clock hour lesion. The other predictive factor they found is the degree of atypia determined your progression to melanoma. So PAM without atypia and PAM with mild atypia were both determined in this study and other studies to have no progression to melanoma. Now this PAM with severe atypia was determined to have the potential to progress to melanoma and there are varying accounts here. In the SHIELD study, they noticed 13%. Other studies have noted progression as high as 50 to 70%. So the overall progression from this study of primary choir melanosis to melanoma was determined to be 3%. So what are the management strategies? One of the most important things I saw is that it's really important to do a detailed exam initially detailing how many clock hours and making good large detailed drawings of these lesions and it was actually in a couple of studies I saw actually the drawings was more reliable than the pictures in determining your next step in moving on to surgery or not. Here's just a way that the SHIELD papers set it out and they're thinking about how they would proceed with surgery or other treatment. They determined that those lesions that had less than one clock hour from their sample looked like most of those didn't progress and they determined that those could be followed just observed one to two times a year. Over the lesions that were kind of in the one to two clock hour range it was now this murky range where it could go either way and they gave the patient the option of surgery or no surgery but once it passed two clock hours that determined the surgical excision with cryotherapy was the best method and above five clock hours a wider incisional biopsy with cryotherapy. Whenever there's a fear that this may already be melanoma and no touch technique where you don't actually manipulate the lesion but making wider incisions and then switching your instruments at the time of excision and switching when you close is the method that they recommended and others recommended. For diffuse primary choir melanosis map biopsies with some cryotherapy and then adjuvant therapy based on histology and for corneal lesions alcohol epitheliacs seem to work pretty well on topical mydomyosin C. Mydomyosin C was something that I saw in several places some people are using it. It seems for more extensive lesions it's not as helpful but it does show some promise for especially these corneal lesions. Now just very briefly not extensively the melanoma management strategies important to do a more extensive work up for this CT blood test et cetera to determine the extent of systemic disease and then a complete excision with cryotherapy using that no touch technique that I talked about. Also radiotherapy is used frequently proton external beam brachytherapy at times is used and oftentimes exeneration is necessary. So back to our case Mr. S was referred to radiation oncology during the time that of his surgery to the time he was presented to radiation oncology. You'd notice some increased blurry vision had also developed some double vision especially in lateral gaze and over the past few months he noted at this time that he had had significant weight loss. So what they were thinking is they were considering proton therapy they thought mydomyosin C and the brachytherapy were maybe less ideal in this situation given the location and extent of the lesions and currently they're planning on presenting this to the melanoma tumor board and proceeding from there based on their recommendations. So here's some of my references and a special thank you to Dr. Manless and Warner whose lab I've been working in for the past month and to Dr. Mifflin and Patel for their work up of this patient. Any questions Dr. Manless? Initially like I showed on the MRI they didn't see from that MRI that there had been metastasis but definitely that 40 pound weight loss speaks to something dangerous. Any more questions? Yes. So PAM is by definition a flat lesion and it is impossible to tell just by gross examination the difference between PAM with atypia and without atypia and so biopsy is necessary. If you were suspicious I think that and especially if this lesion is extending like I showed those clock hours, more clock hours then biopsy is probably the better out to go. Any more questions? Thank you very much.